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Getting the Lead Out for Optimal Health

Posted By Administration, Tuesday, June 8, 2010
Updated: Friday, April 18, 2014

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Sensible steps for purging lead and other toxic metals can have profound health implications for people of all ages.
 

by John Pittman, MD, and Mark N. Mead, MSc

 

Lead is a toxic metal with an ancient relationship to public health.  The Greek physician Hippocrates, considered the “father of Western Medicine”, is thought to have written the first case report of lead poisoning in 600 BC. In ancient Rome, lead’s extensive use in cooking utensils, cosmetics, wine vessels, aqueducts and water pipes may have contributed to widespread toxic effects—possibly even accounting for imperial madness, infertility, and miscarriage rates that kept the ruling class from replacing themselves.  The bones from Roman graves show high concentrations of lead.  It seems ironic that the powerful empire may have been defeated more primarily by its lack of environmental health awareness than by any opposing army per se.  

Our recent history has again boosted the lead count, but by very different means. Three industrial centuries have greatly increased the mining and smelting of lead, resulting in its widespread dispersal in air, water, and soil. In the 1970s, when leaded gasoline was in vogue, automobiles were the number one contributor to lead pollution here in the United States.  Thankfully, this form of gasoline was phased out, and blood lead levels dropped as a consequence.  Other preventive strategies such as eliminating lead as an additive from paint and as a component of lead solder in food cans have resulted in further lowering of blood lead levels among U.S. children.  (Note:  Lead from solder leaches more readily into acidic foods, like tomatoes and citrus, than into nonacid and dry foods.  Tests of canned tomato products in the late 1980s found that about one quarter of the cans tested contained lead-soldered seams.) 

Despite these important public health measures, lead continues to be a problem today. Modern body burdens of lead are still hundreds of times higher than those natural, prehistoric levels with which we evolved.  The metal is used in construction, for decorations, in pottery glazes, and even as a food additive. Lead soldering in old water supply pipes results in some lead leaching into drinking water supplies. Imported toys and other children’s products may be a major source of lead exposure for U.S. children.   In 2007, tests on more than 1,200 children’s products found that 35 percent contain lead—many with levels far above the federal recall standard used for lead paint, according to the Michigan-based Ecology Center along with the national Center for Health, Environment and Justice and groups in eight other states. 

Much of the concern about lead’s harmful effects has focused on younger people.  An estimated 310,000 U.S. children younger than five years have elevated blood lead levels, according to a 2009 estimate by the Centers for Disease Control and Prevention.  Unfortunately, younger brains are uniquely susceptible to the toxic effects of lead.   By the same token, however, many children with elevated blood lead levels show huge improvements in their health and behavior when we take the proper steps to “get the lead out.”   

 A Threat to Adults as Well 

It’s not just young people who are at risk of lead-related health effects.  We now know that lead promotes hypertension and boosts the risk of dying from cardiovascular disease.  For example, in the October 2006 issue of Environmental Health Perspectives, researchers reported on a 12-year study of nearly 9,800 adults, all over age 40, who were part of the Third National Health and Nutrition Examination Survey, or NHANES III.  Those people with blood lead levels higher than 10 µg/dL were 59% more likely to die from cardiovascular disorders compared with people who had blood lead below 5 µg/dL. 

Another NHANES III-based study looked into the connection between blood lead levels and overall mortality over a 12-year period. Reporting in the medical journal Circulation on September 26, 2006, the researchers concluded that blood lead levels as low as 2 µg/dL—a level deemed safe by the U.S. Centers for Disease Control—were linked with a significantly increased risk of overall mortality and an increased risk of dying from both coronary heart disease and stroke.  Given that nearly 40% of U.S. adults have a 2 µg/dL blood lead level, the public health implications of these findings are immense.  Yet another study from NHANES found that people with higher blood lead levels were nearly three times more likely to have chronic kidney disease, and twice as likely to have peripheral arterial disease, as reported in the 10 October 2005 Archives of Internal Medicine. 

These research findings prompt the question: How many people seeking mainstream medical treatment for these conditions never get their lead levels checked and therefore end up taking costly medications for the rest of their lives?  How many people are going in for costly cardiac drugs and surgery without realizing that metal toxicity may be a critical underlying cause or promoting factor?  Imagine how health care could be improved by addressing this common yet widely unrecognized biological insult. 

Long-term effects of lead on the brain have also been identified.  A recent look at data from the Nurses Health Study found a significant link between cognitive deficits in the elderly and higher lead levels in the tibia or “shinbone” (a leg bone that records long-term lead exposure). Several studies have now shown that memory loss and other kinds of psychological deterioration are associated with the tibia lead levels in older people.  In the January 2009 issue of Neuropsychology, experts reported that bone lead levels predicted cognitive decline in people over age 55. Also, hypertension could play a mediating role in the relationship between lead exposure and age-related cognitive decline, as reported online in the 27 May 2009 issue of Neurotoxicology. 

It’s important to remember that the development of senile dementia is most likely preceded by small and often subtle decreases in cognitive functioning over time.  In this regard, adults are at risk of “silent” toxicity from low-level lead exposures that gradually damage the brain over decades.  Thus, the brain-toxic effects of lead may be very hard to perceive or sort out in the context of the aging process. 

How Low Can You Go?

Overt symptoms of lead toxicity are rare at blood lead levels of less than 70 µg/dL.  But much lower levels are still toxic to the brain, and as we just noted above, lead can alter brain function in a gradual, silent manner, whereby the cognitive and behavioral changes are themselves so gradual as to be almost imperceptible.  For very young people, however, the effects of lead exposure are more readily seen in the form of reduced test scores, spelling ability, reading comprehension, and attention span—all outcomes that have been significantly correlated with blood lead levels. 

The U.S. Centers for Disease Control has set a safe blood lead level for children at 10 µg/dL.  Any lead level above 10 µg/dL may promote hyperactivity, distractibility, memory loss, hearing loss, and low IQ scores. But new research indicates that even lower lead levels—on the order of 3 to 5 µg/dL—may compromise one’s cognitive ability.  For infants and young children, there currently appears to be no safe threshold for lead exposure, especially if other brain-toxic pollutants (e.g., mercury and all pesticides on the market) and poor dietary habits are thrown into the mix. 

Just how bad is the problem of lead exposure in the general population? A study in the March 2, 2009 issue of Pediatrics concludes that, although blood lead levels have dropped since the 1970s, they continue to be higher for low-income children, non-Hispanic black children, and children living in older housing (built before 1950).  Some of the children with high blood lead levels have been exposed to lead from consumer products, imported toys, imported traditional medicines, and house wares.  And children whose parents work with lead are confronted with “take-home” lead exposure. 

The authors of the above-mentioned Pediatrics report recommended more aggressive efforts to identify sources of lead, and to measure blood lead levels in those children most at risk.  In this regard, North Carolina was among the first states to institute such proactive strategies.  In the 1980s, public health officials suspected a link between high lead levels and the state’s low national ranking in SAT scores.  All NC property owners were required by law to begin eliminating lead hazards such as peeling paint or contaminated soil in places where younger children (under age 6) spend time.  The state’s Childhood Lead Poisoning Prevention Act, which went into effect on July 1, 1990, was designed to detect and correct high-lead situations prior to exposing the children. 

Nutritional Keys and the Calcium Connection

Lead’s health effects also bear a close relationship to calcium.  Like various radioactive elements, most of the lead we absorb is eventually stored in our bones, where over 99% of the body’s calcium is also stored.  Scientists once thought the bone’s lead deposits were relatively harmless; however, when calcium leaves the bones, lead is released simultaneously, and this results in a rise in the blood lead level. 

Whenever the blood’s calcium level is low, calcium is drawn from the bones to function in more essential body processes like nerve transmission and heartbeat. Such losses are most dramatic when people consume diets high in meats and other protein-rich foods, and high-fat foods and caffeine can further exacerbate the losses. For woman, bone-calcium losses occur naturally during pregnancy, lactation, and menopause—a process further amplified by the dietary habits just mentioned. 

People who minimize these dietary habits and consume plenty of dark leafy greens—which are rich in calcium—will be less likely to experience the lead-calcium time bomb.  Taking a high-quality calcium supplement is also recommended, ideally one that contains either calcium citrate or hydroxyapatite. 

A substantial amount of today’s lead exposure happens through the food chain—from airborne lead that falls on agricultural areas. Such fallout has resulted in major increases in the lead content of rice, oats, lettuce, cabbage, and other vegetable foods. Once lead enters the food chain, it becomes increasingly concentrated in animal flesh, which is yet another reason to avoid a heavy meat diet.  EPA officials estimate that U.S. adults consume, on average, about 30 to 40 micrograms of lead each day through food, the major route for adult exposure. 

Successful Removal of Toxic Metals

Since lead has an obvious potential to promote hypertension, hamper learning ability, and disrupt other aspects of behavior and personality, it behooves us to find ways to pull the lead out of our bodies.  At this time, chelation therapy is the only established way to do eliminate toxic metals.  The word chelation derives from the Greek word “chele”, which refers to the claw of a crab or lobster.  The “claw” in chelation therapy is the chelator itself, a substance that binds to toxic metals, essentially pulling them out of the body through the urine and feces.   

Among the oldest of these “claws” is the synthetic amino acid disodium ethylenediamine tetra-acetic acid (EDTA).  When given intravenously, EDTA binds ionic calcium, trace elements and other divalent cations and transports these bound components out of the body in the urine.  The standard approach to EDTA chelation is to mix the compound with antioxidant nutrients in an intravenous solution that is administered repeatedly over weeks to months.  Between chelation sessions, high oral doses of antioxidant vitamins and mineral supplements are typically recommended. 

Chelation therapy with EDTA and/or DMSA has long been used for the treatment of lead poisoning.  The U.S. Food and Drug Administration has approved both drugs as a treatment for lead and heavy metal poisoning.  Some physicians only recommend chelation therapy when the blood lead level reaches 45 μg per dL (2.17 μmol per L) or greater, as reported in the 15 March 2010 American Family Physician.  However, this high blood level usually only reflects an acute lead exposure.  Repeated or chronic low-level exposures are more common and result in accumulations of lead in the bones.   Thus, it is possible to have a much lower blood level, on the order of 10 μg per dL or lower, yet still have a high body burden of lead. 

To assess your child’s overall body burden—and to get some sense of how much of the metal might be stored in the bones—the urinary chelation challenge test should be used in addition to the blood test.  The challenge test involves giving EDTA and then measuring how much lead comes out in the urine.  If findings from the challenge test indicate a high body burden, then the chelation approach can be very beneficial.  (Note:  Another method entails the use of Kappa x-ray fluorescence, which measures lead in bone, usually in the tibia and patella.) 

If your child’s lead count is unacceptably high, oral or intravenous EDTA, along with natural chelating agents, can be used to draw the lead out of the tissues and blood before sending it on to the kidneys and being excreted in the urine.  When properly administered, such chelation sessions may help safeguard your child’s intellectual potential. For example, kids with either ADHD or Autism Spectrum Disorders who have high lead levels often show substantial improvements in their overall behavior when the lead levels are brought down. 

Similarly, adults with high lead levels will generally experience a gradual improvement in symptoms after a series of chelation treatments and an extended period whereby their blood lead level remains low.  Those with very high lead levels will show greater improvements after chelation, including better cognitive function.  But in most cases, the improvements will lag behind the decline in blood lead levels, probably because of the relatively slower removal of lead from the brain and central nervous system. The pace of improvement can be highly variable from one individual to the next, ranging from weeks to a year or more depending on the magnitude of the lead burden as well as the individual’s overall nutritional status. 

Many people only show the neuro-cognitive benefits when chelation therapy is used in the context of comprehensive nutritional support and other forms of treatment, such as cognitive rehabilitation and occupational therapy.  It’s important to note that short-term improvements in cognitive functioning following a decline in the blood lead level may not be able to override or reverse the harmful effects of long-term cumulative lead exposures. 

This is why getting the lead out at an earlier stage of life is so critical, and why preventing or minimizing lead exposures is always the top priority.  There is a critical time period—less than 3 years of age—during which lead and other toxic metals can have a profound long-range impact on IQ, attention span, and antisocial behaviors.  Chelation therapy’s ability to impact neurobehavioral development is clearly greatest in these early years.  But older children, too, can benefit from appropriate removal of lead and other metals.  In many cases, we find that children with ADHD, learning disabilities, or Autism Spectrum Disorders will not respond well to other biological therapies or to behavioral approaches until their toxic metal burden has been substantially reduced. 
 

An Integrative Approach is Essential 

Chelation is clearly the best treatment against metal poisoning, but it must be performed correctly in order to be effective.   Research reviewed in the October 2008 issue of the Indian Journal of Medical Research indicates that chelation therapy is most effective when combined with specific antioxidants and nutritional factors that support the body as it attempts to eliminate the toxic metals. Along these same lines, research reported in the 15 April 2007 issue of Cellular & Molecular Biology confirms the value of chelation therapy for reversing a situation of toxic overload with lead and arsenic.  The authors of this paper, titled “Arsenic and lead-induced free radical generation and their reversibility following chelation”, emphasized the importance of judicious chelation therapy in combination with specific antioxidant nutrients and herbals to support optimal detoxification. 

Our own clinical experience at the Raleigh-based Carolina Center for Integrative Medicine suggests, similarly, that chelation is most effective when accompanied by supportive strategies such as selenium, zeolites, herbal chelators, and glutathione-boosting nutritional strategies.  The lack of inclusion of these supportive measures in randomized clinical trials may explain why the few trials completed to date have not demonstrated any major benefits.  You can have the most rigorous clinical study design on the planet, but if your intervention is bogus, so too will be the results of the study.  

If lead-laced wine did indeed cause the madness of Caesars and bring the Roman Empire to ruin, then the rising tide of toxic metal pollution means that our society’s sanity and intelligence may be at stake.  Unless we clean up our act and fast, we may be putting our brains at risk for the indefinite future.  Using chelation therapy within the framework of integrative medicine—that is, coupled with individually tailored nutritional and herbal support—is our best hope for turning the biological tide in a body already burdered with lead, mercury, cadmium, and other toxic metals.  

 

To reach the authors or schedule a consultation, or to obtain more information on how to optimize the removal of toxic metals, contact the Carolina Center for Integrative Medicine in Raleigh, NC at 919-571-4391, or visit the website at www.carolinacenter.com.

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Clinical Aspects and Management of Fibromyalgia Syndrome

Posted By Administration, Friday, May 21, 2010
Updated: Friday, April 18, 2014

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Abstract 

Fibromyalgia syndrome (FMS) is a chronic and debilitating musculoskeletal pain disorder of unknown aetiology with usual accompanying features of fatigue, sleep disturbances and stiffness. Its place in medical textbooks was controversial with rheumatologists holding the helm of its management for many years. Over the last decade, abnormalities have been identified at multiple levels in the peripheral, central, and sympathetic nervous systems as well as the hypothalomo-pitutary-adrenal axis stress response system. With the elucidation of these pathways of pain, FMS is known more as a central sensitivity syndrome. This led to tremendous increment in interest in both pharmacological and non-pharmacological treatment of FMS. The United States Food and Drug Administration (FDA) has also successively approved 3 drugs for the management of fibromyalgia – pregabalin, duloxetine and milnacipran. Non-pharmacological modalities showed aerobic exercise, patient education and cognitive behavioural therapy to be most effective. Overall, management of FMS requires a multi-disciplinary approach. 

                                                        Ann Acad Med Singapore 2009;38:967-73 

Key words: Aetiology, Fibromyalgia-Fibromyositis Syndromes, History, Pain syndrome

Introduction 

Fibromyalgia syndrome (FMS) has been referred to as a medically unexplained syndrome; a rheumatological entity described in rheumatology textbooks and taught to all training rheumatologists,and lately with newer development in research particularly in neurophysiology, as a central sensitivity syndrome. Due to its lack of objective findings on physical examination, laboratory and imaging modalities, FMS was once dismissed by physicians and the public as a psychological disorder. It was thought to be a society-driven disorder, whereby expressions of the distressed patient’s problems are made into a “disease”, hence becoming more legitimate for equal social support and sympathy from the medical community. Whether this is actual social or economic medicalisations, there are real patients suffering real symptoms. 

Background 

FMS is a chronic musculoskeletal pain disorder of unknown aetiology, characterised by chronic widespread pain and muscle tenderness and the presence of tender points on examination. Patients experience both allodynia (pain from a normally nonpainful stimulus) and hyperalgesia (inappropriately intense pain from a normally painful stimulus). Other common accompanying features are fatigue, sleep disturbances, stiffness, paraesthesias, headaches, Raynaud’s like symptoms, depression and anxiety. FMS is much more than widespread pain as it overlaps substantially with other central sensitivity syndromes such as chronic fatigue syndrome, irritable bowel syndrome, chronic pelvic pain syndrome/ primary dysmenorrhoea; temporomandibular joint pain, multiple chemical sensitivity, restless legs syndrome and interstitial cystitis. In 1990, the American College of Rheumatology (ACR) published the classification criteria of Fibromyalgia. Patients who fulfilled these criteria must have firstly, pain for at least 3 months involving the upper and lower body, right and left sides, as well as axial skeleton, and secondly, pain in at least 11 of 18 tender points on digital examination. The second criterion requires these tender points to be digitally palpated with about 4 kg per unit area of force. Although the criteria provided a sensitivity of nearly 88% and specificity of 81% in distinguishing FMS, it is important to exclude other causes of chronic musculoskeletal pain.

Systemic diseases, such as hypothyroidism, systemic lupus erythematosus (SLE) and malignancies, can mimic FMS and have to be excluded. The classifi cation criteria initially drew considerable criticisms of over-relying on tender points, referring fibromyalgia as a discrete entity rather than a cut-point along a pain-distress continuum and under- emphasising on central symptoms of the syndrome, has now gained wide recognition in the medical community. Presumably, one understands that like most ACR criteria for other rheumatic diseases, it is developed for research purpose and over the years, it has aided our understanding of FMS in both research and clinical settings. 

History in Brief 

Clinical description of fibromyalgia has been reported since mid-1800s. In 1904, Sir William Gowers created the term “fibrositis” when he was actually referring to regional pain syndrome. The term “fibrositis” hence was a misnomer and no longer used as studies have shown that there were no inflammation within the connective tissues. “Fibromyalgia” was first introduced in 1976 in an editorial to the section on non-articular rheumatism in the 22nd “Rheumatism Review” of the American Rheumatism Association (currently known as ACR). Derived from both Latin (fi bra – fi ber) and Greek words (myo-muscle and algos –pain), it literally means “pain in the muscle and fibrous tissues”. Since then, the studying of fibromyalgia has gathered momentum. A Medline literature review found that the total number of medical articles dealing with fibromyalgia/FMS has increased 5-fold during this past decade,with non rheumatology journals publishing substantially more articles compared to a decade ago. 

Fibromyalgia Syndrome and Rheumatology 

Rheumatologists tend to be ambivalent about FMS though the condition has been traditionally perceived to be an entity from the rheumatology specialty due to the presence of physical pain and body tenderness. With the development of the ACR criteria in 1990 and the World Health Organization (WHO) providing Fibromyalgia ICD code, it has been conferred a “diagnosis” status. The general perception amongst rheumatologists is that patients with FMS takes up too much time for a busy clinical practice and having little success in managing these patients, most find FMS difficult to treat. Literature also showed FMS symptom measurements, such as pain, global severity, fatigue, sleep disturbance, anxiety, depression and health status, can remain unsatisfactory despite years of therapy. In the last 2 years, some even questioned whether FMS should be cared for by the rheumatologists at all as latest evidence showed FMS to be a pain syndrome centred in the nervous system. Although there was a recent study which showed that family physicians could be trained to diagnose FMS correctly in 70% of patients, there were many factors such as physician training, ethnicity and cultural biases which can affect the outcome of that study. Historical clinical evidence showed FMS can mimic autoimmune diseases, which was why its diagnosis was a constant challenge even to the rheumatologists. FMS patients can display symptoms suggestive of SLE such as peripheral neuropathy or manifest with low titre ANA levels ranging from 8.8% to 30% in FMS patients. Furthermore, FMS patients often present with bodily ache and joint pain but physical examination shows no objective evidence of synovitis. In addition, immunoglobulin depositions without complement fixations in the skin were documented in the skin of FMS patients. Sicca symptoms such as dry eyes and mouth which are characteristic of Sjorgren’s syndrome has been demonstrated in FMS patients. Despite these mimics, a retrospective analysis with long-term follow-up of FMS patients however showed no increased probability of FMS patients developing into any connective tissue disease.24 Nonetheless, FMS is the second most common musculoskeletal disorder which takes up the second most amount of time in rheumatologists’ offi ces. FMS can co- exist and affect management of other rheumatic diseases. It was estimated that 20% of patients with rheumatoid arthritis and 50% of patients with SLE suffer from fibromyalgia. 

 


Local Perception of Fibromyalgia Syndrome 

Local studies are however lacking. In 1999, a study in Singapore showed that fibromyalgia patients exist amongst our patients. Looking into 101 patients randomly selected from medical clinics and using dolorimeter to confirm the tender points, 6 patients (5.99%) fulfilled the ACR criteria for fibromyalgia. These patients had mean tender point count of 14.17 as compared to 5.58 from a sample population. Eighteen patients (17.8%) had 11 or more tender points but did not satisfy the criteria of widespread pain of more than 3 months’ duration. A survey on the awareness and perceptions of FMS in Malaysia and Singapore showed more than 90% of rheumatologists surveyed believed that FMS is a distinct entity, an illness rather than a disease, involving medical and psychological realms, and is confirmed by excluding other well-defined clinical diseases through a combination of clinical evaluation and screening tests. A more recent survey (personal communication – Feng PH. Short survey on fibromyalgia. August 2009) of Singapore rheumatologists/rheumatology trainees was undertaken in 2009. Although less than half responded, those responded believe FMS exists, do see FMS patients, use the ACR criteria for diagnosis, and treat FMS patients via a multi-disciplinary methods by co-managing these patients with pain specialists, psychiatrists, rehabilitation physicians, physiotherapists, psychologist and medical social workers. Majority are also of the opinion that they can play a role in managing FMS patients although some think that other specialists are more suited to managing FMS patients. Indeed, there were a few responders who believed that the diagnosis of FMS need not be a diagnosis of exclusion but it is imperative to exclude certain systemic diseases such as autoimmune diseases, malignancies or metabolic diseases. Literature evidence shows FMS patients underwent unnecessary operations thus consumed unnecessary healthcare resources. Positive diagnosis of FMS, on the other hand, is associated with reduced healthcare utilisation and reduction in investigations. Unfortunately, there is still no gold standard for diagnosis of fibromyalgia. The presence of ACR criteria, however, has inadvertently made the diagnosis of fibromyalgia simply to be “the blessing” of the rheumatologists. 

Epidemiology of FMS 

FMS is a very common condition, estimated to affect 2% to 4% of the population although local epidemiologic study is lacking. It has a prevalence of 3.4% in women versus only 0.5% in men with a female-to-male ratio of approximately 9:1. Usually diagnosed between 20 to 50 years of age, it increased with age until aged 70 after which it decreased slightly. FMS can also occur in children at prevalence rate of 1.2% and 1.4%. The prevalence of FMS is considerably higher in rheumatology clinic at 12% to 20% of new patients seen whereas it occurs in 5% to 6% of adult patients presenting at general medical and family practice clinics. 

Aetiology and Pathogenesis 

It is beyond the scope of this article to discuss the various aetiologies and pathogenesis of FMS. The exact aetiology of FMS is unknown and no single factor can lead to all the symptoms of FMS. Stress and medical illness can trigger FMS. Early studies showed there was no peripheral damage or infl ammation within the muscles or tissues. Focus then shifted for alternative explanations. Investigations have focused upon central pain processing systems such as disturbances in neurotransmitter and neuroendocrine regulations, reduced levels of biogenic amines, increased concentrations of excitatory neurotransmitters, including substance P, and dysregulation of the hypothalamic- pituitary-adrenal axis. FMS patients experience pain differently; they have allodynia, hyperalgesia as well as lower pain threshold as compared to normal. Sleep disruption has been implicated in FMS39,40 and over 90% of FMS patients complain of sleep problem. Fibromyalgia-like symptoms were reproduced in normal volunteers by depriving them of deep sleep. Evidence using functional brain imaging allow visualisation of structures involved in pain processing further suggest central cause of pain. Patients with FMS are thought to develop functional changes in the central nervous system (CNS) that result in central pain sensitisation that is manifested as increased excitability of neurons, enlargement of their receptive fields, reduction in pain threshold and recruitment of novel afferent inputs. Abnormalities have been identified at various levels in the peripheral, central, and sympathetic nervous systems, as well as the hypothalamo-pitutary-adrenal axis stress- response system. Despite evidence that emphasises the role of sensory and CNS abnormalities for the chronic pain associated with FMS, psychosocial factors also play an important role in the development and course of FMS. These include exposure to negative life events and chronic stress, increased focus on bodily symptoms and passive pain-coping mechanisms. A recent family study also found that FMS coaggregates with mood disorders in families, suggesting the possibility of shared pathophysiologic factors in FMS and mood disorders. 

Management of Fibromyalgia 

Numerous literatures are available on the management of fibromyalgia. Most FMS patients have been evaluated by different specialists and undergone multiple tests. The approach is to establish a correct diagnosis, to exclude differentials and to explain the implications of the diagnosis to the patients. The goals of therapy are to improve symptoms, function and emotional well-beings. Empathetic listening and acknowledgment that the patient is indeed experiencing pain would go a long way to validate the patient’s illness and establish rapport for further treatment. Prior to prescribing any form of treatment, it is imperative to assess any possible causal or perpetuating factors, including attention to psychological and sociocultural factors. Concomitant treatment of any possible nociceptive pain from an apparent pathology is important, for example, treating the pain from an infl amed bursitis or degenerative spondylosis. Excessive investigations or testings if not indicated should be discouraged. Physicians are also reminded to avoid comments such as “It’s all in your mind” or “I cannot find anything wrong with you”. Besides management of clinically relevant symptoms such as fatigue, depression, rigidity and sleep disorders; physical and emotional stress may aggravate FMS and needs to identified and treated appropriately. Evidence has shown that multi-disciplinary rehabilitation helps at least in the short term but effort needed to maintain long-term benefits.

Pharmacological Treatment 

A range of medical therapeutics, such as anti-infl ammatory like symptoms were reproduced in normal volunteers by depriving them of deep sleep. Evidence using functional drugs, opioids, muscle relaxants, antidepressants, sedatives and antiepileptics, have been used to treat FMS. With newer understanding of the neurophysiology of the FMS pointing to a central pain processing, research into drugs has intensified. This led to drugs being approved by the United States Food and Drug Adminstration (FDA). In June 2007, pregabalin became the first treatment approved by the FDA for the treatment of FMS. Currently there are 3 FDA-approved drugs for FMS. They are Pregabalin (Lyrica; Pfi zer, Inc), Duloxetine (Cymbalta; Eli Lily and Company) and Milnacipran (Savella; Forest Laboratories and Cypress Bioscience). Market survey showed the most frequent drugs used for treatment of FMS is non-steroidal anti-inflammatory drugs (NSAIDS) and since FMS is largely devoid of infl ammation, it is of little wonder that these treatment failed. 

Alpha-2-delta ligands such as gabapentin and pregabalin were used in the treatment of many pain conditions such as painful diabetic neuropathy and postherpetic neuralgia. As a α 2δ calcium-channel antagonist that acts by limiting the neuronal release of excitatory neurotransmitters, it can decrease pain, decrease sleep latency and modify sleep architecture by improving slow-wave sleep. Pregabalin was approved by the FDA for fi bromyalgia after demonstrating effi cacy in 3 published trials. Generally starting at lower doses, it should reach doses such as 600 mg daily. Most patients who discontinue pregabalin do so because of somnolence and dizziness especially with higher doses. However, a meta-analysis58 showed pregabalin at 150 mg daily was generally ineffective hence higher doses (such as 300 mg, 450 mg or 600 mg) were required. Gabapentin with the same mechanism of action has also been effective in the treatment of FMS.

Anti-depressants such as tricyclic anti-depressants (TCA), selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, citalopram and paroxetine as well as dual receptor inhibitors serotonin-norepinephrine reuptake inhibitors (SNRIs) have been found to be helpful in relieving symptoms of fibromyalgia. However, it was the SNRIs which provide more benefit as compared to pure serotonergic drugs. Initial trials with the first available SNRI, venlafaxine, showed conflicting results in the management of FMS. In June 2008, another SNRI duloxetine was approved by the FDA for the management of FMS. Duloxetine was previously approved for the treatment of peripheral neuropathic pain, depression and generalised anxiety disorder. This new approval was based on data from 2 pivotal double-blind, fixed-dose, randomised, phase-3 clinical trials of 12 weeks’ duration. A subsequent 6-month multi-centre, randomised, double-blind placebo-controlled trial showed reduction in pain severity and global assessments at 3 and 6 months, irrespective of depression status. The recommended dose of duloxetine is 60 mg once daily and no additional benefit was observed in patients receiving 120 mg once daily. Treatment should be initiated at 30 mg once daily for 1 week to allow patients to adjust to the medication before increasing to 60 mg once daily dosing. Improvement in pain can be felt as early as the first week and this benefit persisted throughout the study period. The common side effects of duloxetine were nausea, dry mouth, constipation, decreased appetite, somnolence, hyperhidrosis and agitation. 

Another SNRI, milnacipran, was approved in January 2009 for the management of fibromyalgia after its efficacy was established in 2 pivotal US phase 3 trials. Milnacipran was found to have greater efficacy than placebo for pain relief, improvement in global well-being and physical function. The recommended dose of milnacipran is 100mg or 200 mg daily. Adverse effects of milnacipran such as nausea, headache and constipation are the main reasons for discontinuation of treatment. Milnacipran is not available in Singapore at this point of time. 

In practice, patients often respond to combination of pharmacological treatments, although studies of combination pharmacotherapy are still limited. A α 2δ calcium-channel antagonist gabapentin in combination with SNRI venlafaxine was found to be more effective in improving symptoms of pain, fatigue, mood disturbance and insomnia in patients with neuropathic pain who did not respond to gabapentin monotherapy. Combinations of TCA and SSRI have also been proven more effective than either medication used alone. 

Other SSRIs (fluoxetine, fluvoxamine, citalopram and paroxetine ) and TCA (amitriptyline, desipramine) have all been studied for treatment of FMS but most showed modest effi cacy at best. A 2009 meta-analysis of 18 randomised, placebo-controlled studies of a variety of anti-depressants showed strong evidence for efficacy of anti-depressants for pain relief, fatigue, depressed mood, sleep disturbance and in improving health-related quality of life. 

As there is no inflammation present in FMS patients, anti-inflammatory drugs such as NSAIDS and steroids, are not effective. However, they have a role if there is concomitant inflammation condition which serves as a nociceptive trigger. Paracetamol helps pain relief but often insuffi cient when taken alone. Paracetamol in combination with tramadol, a narcotic that combines μ-opioid agonist- antagonist and SNRI activities may be helpful. Common side effects of tramadol are nausea, constipation and pruritis. However, the risk of abused and dependence with tramadol is low as compared to other opioids. 

Other pharmacologic modalities included use of human growth hormone, dehydroepiandrosterone (DHEA), 5-hydroxytryptophan, topisetron and pramipexole remain under investigation. Most of these drugs attempt to combat fatigue, rigidity, insomnia or poor sleep.

Non-pharmacological Treatment 

Non-pharmacolgical treatment modalities, including aerobic exercises, physical therapy, cognitive behavioural therapy (CBT), massage and acupuncture can be helpful. Few of these approaches have been demonstrated to have clear-cut benefi ts in randomised controlled trials. 

The role of aerobic exercise has been supported by systematic review. It was postulated that aerobic exercises can stimulate endogenous analgesic systems, increase time spent in deep sleep and increase a sense of well-being and control. The challenge is to start and maintain FMS patients in a structured exercise programme and the key here is to encourage exercise according to fitness level. Low impact exercise may be tailored to individuals with musculoskeletal problems. 

Adjunctive CBT will be indicated for patients with prominent psychosocial stressors, and/or difficulty coping, and/or difficulty functioning. CBT has also been proven on metaanalysis to improve FMS. CBT addresses the various aspect of the biopsychosocial model of FMS and can decrease depression and pain.Patient education as a modality has been found to have therapeutic effect with patient undergoing education intervention having had signifi cantly more improvement than controls but improvements are short-term. Appropriate patient selection may improve efficacy. More research is needed to confirm the effectiveness and to determine the best match of treatment components to particular sets of FMS symptoms. 

Other modalities include acupuncture, trigger point or tender point injections, EMG-biofeedback, chiropractic or massage. There is increased interest to develop more effective non-pharmacological treatment modalities in FMS as our ability to accurately measure effect of treatment has improved. The multifaceted nature of FM suggests that multimodal individualised treatment programmes may be necessary to achieve optimal outcomes in patients with this syndrome. 

Conclusion 

Management of fibromyalgia requires knowledge of its broad spectrum of symptomatology that goes beyond addressing simple complaint of pain. While diagnostic criteria do exist, they were originally developed for research purposes and need further refinement as understanding of fibromyalgia has evolved. Although diagnosis can be difficult, new treatments, better understanding of the pathophysiology and greater involvement of different specialities can pave the way for improvement in the diagnosis of FMS. Often, a multidisciplinary healthcare setting is required to address the multidimensional nature of FMS. Outcome measures borrowed from clinical research in pain, rheumatology, neurology and psychiatry enable treatment response in specifi c symptoms domains. Managing FMS patients encompass an art of practising medicine as much as knowing its scientific basis. 

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Mercury Induces Inflammatory Mediator Release from Human Mast Cells

Posted By Administration, Friday, May 7, 2010
Updated: Friday, April 18, 2014

Background 

Heavy metals such as mercury result in neurological injury that may lead to developmental defects, peripheral neuropathies, and enhanced neurodegenerative changes. Mercurials may be found in various drugs, in bleaching creams, antiseptics, disinfectants, as preservatives in cosmetics, tooth pastes, lens solutions, vaccines, contraceptives and immunotherapy solutions, fungicides, herbicides and in dental fillings, as well as in fish such as tuna due to water pollution. Mercury can cause immune, sensory, neurological, motor, and behavioral dysfunction similar to those associated with Autism Spectrum Disorders (ASD). The possible role of mercury used as preservative in vaccines has been debated extensively, but most epidemiological studies do not support a causal association between vaccines and autism. However, 87% of children included in the US Vaccine Adverse Event Reporting System (VAERS) had ASD. Moreover, a paper based on computerized medical records in the Vaccine Safety Data-link concluded there was "significantly increased rate ratios for ASD with mercury exposure from thiomerosal-containing vaccines." Mercury has been shown to induce proliferation and cytokine production from T lymphocytes. Mercuric chloride (HgCl2) in nontoxic doses induces the release of histamine and cytokines, such as IL-4 and tumor necrosis factor-alpha (TNF-α), from a murine mast cell line and from mouse bone marrow-derived cultured mast cells. HgCl2 (100 μM) also enhances immunoglobulin E-mediated mediator release from human basophils, and histamine release from a rat basophil cell line (RBL-2H3). 

We, therefore, investigated whether HgCl2 could stimulate human mast cells, an action that could be enhanced in subjects who already have an atopic background.  

Methods 

HgCl2 was obtained from Fluka Chemical Corp. (Milwaukee, WI) and was diluted in Dulbecco's phosphate buffered saline (DPBS, GIBCO, Grand Island, NY) on the day of the experiments. 

Human mast cell culture 

LAD2 and human umbilical cord blood-derived cultured mast cells (hCBMCs) were cultured as previously described. Umbilical cord blood was collected as approved by the Tufts Medical Center's (Boston, MA) Investigation Review Board in tubes containing 10 U/ml heparin, blood was diluted 1:2 with DPBS, GIBCO) containing 2 mM ethylenediaminetetraacetic acid (Sigma, St. Louis, MO). Non-phagocytic mononuclear cells were separated by density-gradient centrifugation using Lymphocyte Separation Medium (LSM) from Organon Teknika Corp. (Durham, NC). The isolation of hematopoietic stem and progenitor cells (CD34+) was performed by positive selection of AC133-expressing cells by magnetic-associated cell sorting (MACS) using an AC133 cell isolation kit (Milltenyi Biotec, Auburn, CA) as reported previously [15,16]. CD34+ cells were suspended in AIM-V Medium (GIBCO BRL), supplemented with 100 to 200 ng/ml recombinant human stem cell factor (rhSCF, Amgen, Thousand Oaks, CA), 50 ng/ml IL-6 (Millipore, Temecula, CA) and cultured for 12 to 16 weeks. During this culture period, the cells were washed with DPBS every week and resuspended using fresh culture medium. The purity of hCBMCs was evaluated by immunocytochemical staining for tryptase as previously described. Mast cell viability was determined by Trypan blue (0.3%) exclusion method. LAD2 cells cultured over 10 days and hCBMCs cultured over 12 weeks were used for the experiments. 

Histamine assay 

LAD2 or hCBMCs cells were washed with DPBS and mast cell media, once in each. Cell suspensions (5 × 104 cells per tube, 500 μl/sample) were preincubated with either the neuropeptide substance P (SP, 0.1-2 μM) or anti-IgE (10 μg/ml) as positive controls, or HgCl2 (1-10 μM) for 30 min. After the reaction, the cells were centrifuged and the supernatant fluid was collected. 

Histamine levels were assayed using EIA histamine kit (# IM2015; Immunotech, Beckman Coulter Company, France) as per the directions. Histamine release was calculated as percent of total. 

β-Hexosaminidase assay 

β-Hexosaminidase release, as an index of mast cell degranulation, was assayed using a fluorometric assay as previously reported. Briefly, β-hexosaminidase activity in the supernatant fluid and cell lysates (LAD2 cells, 0.5 × 105/tube, were lysed with 1% Triton X-100 to measure residual cell-associated β-hexosaminidase) were incubated with substrate solution (p-nitrophenyl-N-acetyl-β-D-glucosaminide from Sigma, St Louis, MO) in 0.1 M citrate buffer (pH 4.5) for 60 min at 37°C. The reaction was terminated by the addition 0.2 M NaOH/0.2 M glycine. Absorbance was read at 405 nm in an enzyme-linked immunosorbent assay reader, and the results are expressed as the percentage of β-hexosaminidase activity released over the total. 

Cytokine assay 

LAD2 cells or hCBMCs were washed with DPBS, sterile Tyrode's buffer, and plain culture medium, once in each, and were suspended in complete culture medium without IL-6 (for hCBMCs). The LAD 2 cells or hCBMCs (2 × 105 cells/well/200 μl) were plated in 96-well, flat-bottom Falcon cell culture plates (Becton Dickinson) and were pre-incubated for 15 min at 37°C in a 5% CO2 incubator. The cells were then incubated with either neuropeptide SP (0.1-2 μM) or HgCl2 (1-10 μM) for 24 hours at 37°C. Control cells were treated with equal volumes of only the respective culture medium. After the reaction time, plates were centrifuged and the supernatant medium was gently collected from the wells and stored at -80°C until the cytokines were measured by enzyme-linked immunosorbent assay (ELISA) using a commercial kit (Quantikine, R&D Systems, Minneapolis, MN), as reported previously. The minimum detectable levels of VEGF and IL-6 were 5 pg/ml. Cell viability was assessed at 1 hour and at 24 hours using the Trypan blue exclusion method. 

Statistical analysis 

All conditions were performed in triplicate, and all experiments were repeated five times (n = 5). Results are presented as mean ± SD. Data from two conditions, such as stimulated and control samples, were compared using the Unpaired 2-tailed Student's t-test. Significance of comparisons is denoted by p < 0.05.   

Results 

Effects of HgCl2 on mast cell viability 

LAD2 mast cells and hCBMCs were incubated with HgCl2 for 1 hour or for 24 hours in their respective media, and cell viability was assessed by Trypan blue exclusion. HgCl2 reduced viability of LAD2 mast cells in culture medium only slightly (10%), only at concentration of 10 μM, and only after 24 hours of incubation. HgCl2 reduced viability of hCBMCs by 25% at concentration of 10 μM after 24 hours of incubation. 

Effects of HgCl2 on LAD2 mast cell histamine release 

We first tried to study the effect of HgCl2 on mast cell histamine release. We assayed histamine release from LAD2 mast cells and hCBMCs after incubation with HgCl2 (1-10 μM) for another 30 min at 37°C in Tyrode's buffer. Addition of HgCl2 for 30 min induced statistically significant histamine release from hCBMCs, compared to control cells, at HgCl2 concentrations of 0.1 and 1 μM. However, as the results were inconsistent due to interference of HgCl2 with the histamine assay, we do not present them. Instead, we investigated the effect of HgCl2 on the release of β-hexosaminidase, another secretory granule marker that is released in parallel with histamine. Only 10 μM HgCl2 was able to induce a 2-fold increase in β-hexosaminidase release. 

Effects of HgCl2 on LAD2 mast cell VEGF release 

We then investigated whether HgCl2 could stimulate release of proinflammatory mediators from mast cells. LAD2 mast cells released significantly more VEGF at HgCl2 concentrations of 0.1 and 1 μM (311 ± 32 pg/106 cells and 443 ± 143 pg/106 cells, respectively, compared to 227 ± 17 pg/106 cells for control cells, p < 0.05, Fig. ​Fig.2B).2B). HgCl2 (0.1 μM) had a statistically significant synergistic effect on LAD2 mast cell VEGF release (693 ± 102 pg/106 cells) when added with SP (0.1 μM). Combinations of higher concentrations of HgCl2 and SP did not induce any additional VEGF release. 

Effects of HgCl2 on hCBMC VEGF and IL-6 release 

HgCl2 (1 μM) also induced release of significantly more VEGF (182 ± 57 pg/106 cells) from hCBMCs (n = 5, p < 0.05) compared to control cells (360 ± 100 pg/106 cells).

LAD2 mast cells cannot synthesize IL-6. We, therefore, investigated the effect of HgCl2 on IL-6 release from hCBMCs. HgCl2 (0.1 and 1 μM) significantly induced IL-6 release (466 ± 57 pg/106 cells and 204 ± 47 pg/106 cells, respectively) compared to untreated control cells (13 ± 25 pg/106 cells, n = 5, Fig. ​Fig.3B).3B). SP (5 μM), used as a positive control, also significantly increased IL-6 release (609 ± 57 pg/106 cells) from hCBMCs. Addition of HgCl2 (0.1) with SP (5 μM) further increased IL-6 release to 745 ± 117 pg/106 cells.   

 


Discussion 

This is the first report to our knowledge showing that inorganic mercury in concentrations as low as 0.1 μM can induce VEGF and IL-6 release from human cultured mast cells. We also report for the first time that mercury has a significant synergistic effect with SP (0.1 μM) on VEGF release; this amount of VEGF release is higher than what has previously been reported for hCBMCs. One paper has reported that HgCl2 can induce release of histamine from primary lung and human leukemic mast cells (HMC-1 cells), but only at toxic levels of 0.33 mM. Here we show that HgCl2 induces β-hexosaminidase release, but only at a concentration of 10 μM. Mercury (10 μM) has previously been shown to induce release of β-hexosaminidase, IL-4 and TNF-α from a murine mast cell line and from mouse bone marrow-derived cultured mast cells; the secretion of cytokines mediated by HgCl2 is additive to that which follows FcepsilonRI-induced mast cell activation. In contrast, HgCl2 does not have an effect on its own on release of histamine and IL-4 from human basophil, but only enhances allergic release at concentrations of 1 and 10 μM. This is also true for IL-4 release from rat mast cells. Clinical symptoms of mercury poisoning may be expected at blood levels of 1 μM. However, brain mast cells may react to lower mercury concentrations, especially in vulnerable patient subpopulations. 

Mast cells, by virtue of their location in the skin, respiratory tract, and gastrointestinal system are potential targets for environmental agents with immunotoxic effects. Mast cells are critical not only for allergic reactions, but also important in both innate and acquired immunity, as well as in inflammation. In view of the fact that a subgroup of ASD patients have allergy symptoms that do not appear to be triggered by IgE, it is noteworthy that mast cells can be stimulated by non-allergic triggers originating in the gut or the brain, especially neuropeptides such as SP and neurotensin (NT). Once activated, mast cells secrete numerous vasoactive, neurosensitizing and proinflammatory molecules that are relevant to ASD; these include histamine, proteases, VEGF, prostaglandin D2, as well as cytokines such as IL-6. In particular, mast cells can secrete VEGF, an isoform of which is vasodilatory and is over expressed in delayed hypersensitivity reactions. In fact, mast cells can release VEGF, IL-6 and other mediators "selectively" without degranulation. Such mediators could disrupt the gut-blood and blood-brain barriers (BBB) permitting brain inflammation. It is important to note that mercury can cross the BBB through a transport mechanism that can lead to significant brain concentrations, and that can persist for prolonged periods of time. Activated brain mast cells can disrupt the BBB and further increase brain mercury levels. 

The mechanisms of heavy metal neurotoxicity are not fully understood. Mercury increases cytosolic calcium levels in PC12 cells, and thimerosal does so in thymus lymphocytes. Mercury may also increase cellular oxidative stress since neurons are highly susceptible to reactive oxygen species (ROS) and neuronal mitochondria are especially vulnerable to oxidative damage. In fact, the primary dietary source of neurotoxic mercury compounds is via the ingestion of methylmercury from fish, which has been previously linked to neurological damage. 

Mercury's activation of mast cell inflammatory mediator release may enhance allergic reactions in atopic individuals and exacerbate IgE-dependent diseases. Allergic symptomatology is often present in ASD patients, and a survey of children with ASD in Italy reported that the strongest association was with a history of allergies. Moreover, a recent study reported increased atopic diseases, as well as elevated serum IgE and eosinophils in Asperger patients. In a National Survey of Children's Health, parents of autistic children reported symptoms of allergies more often than other children, with food allergies showing the greatest difference. A case series study also reported higher rate of food allergies in ASD children. In one study, 30% of autistic children (n = 30) had a history of atopy as compared to 2.5% of age-matched "neurologic controls" (n = 30), but there was no difference in serum IgE or in skin prick tests to 12 common antigens, implicating triggers other than IgE. In another study, ASD patients did not have increased incidence of allergic asthma or allergic dermatitis, but this study included only ASD patients that were positive to RAST/skin testing. Finally, a preliminary report indicated that the prevalence of ASD may be 10-fold higher than the general population (1/100 children) in mastocytosis patients, characterized by increased number of hyperactive mast cells in many tissues, with symptoms that include allergies, food intolerances and "brain fog." 

Some epidemiological studies have failed to find a significant relationship between mercury exposure from vaccines and autism. Nevertheless, 87% of children included in the US Vaccine Adverse Event Reporting System (VAERS) have ASD. Moreover, a paper based on computerized medical records in the Vaccine Safety Datalink concluded there was "significantly increased rate ratios for ASD with mercury exposure from Thimerosal-containing vaccines." Also, there are a series of epidemiological studies conducted in the USA that have found significant associations between environmental sources of mercury exposure and ASDs. In addition, patients with severe ASD have evidence of significantly increased urinary porphyrins consistent with mercury intoxication. Mercury toxicity may also affect critical methylation pathways in vulnerable cells. 

ASD are a group of pervasive developmental disorders that include autistic disorder, Asperger's disorder, and atypical autism - also known as pervasive developmental disorder-not otherwise specified (PDD-NOS). These are neurodevelopmental disorders diagnosed in early childhood. They are characterized by various degrees of dysfunctional communication and social skills, repetitive and stereotypic behaviors, as well as attention, cognitive, learning and sensory defects. ASD cases have increased more than 10-fold during the last decade to a prevalence of 1/100 children. However, there is no known distinct pathogenesis, there are no biomarkers, and there is no effective treatment. 

ASD may result from a combination of genetic/biochemical susceptibility and epigenetic exposure to environmental factors, including reduced ability to excrete mercury and/or exposure to mercury at critical developmental periods. A number of papers have suggested that ASD may be associated with immune dysfunction, while a recent review made the case that ASD may be a neuroimmune disorder involving mast cell activation. 

Conclusions 

The results of the present study support the biological plausibility of how mercury could contribute to ASD pathogenesis by inducing VEGF and IL-6 release from mast cells, and as a result disrupt the BBB and thus permit brain inflammation. Further studies should investigate the effect of mercury and thimerosal alone or together with allergic and non-immune triggers. 

Abbreviations 

ASD: Autism Spectrum Disorders; (DPBS): Dulbecco's phosphate buffered saline; hCBMCs: human umbilical cord blood-derived cultured mast cells; ELISA: enzyme-linked immunosorbent assay; HgCl2: mercury chloride; PDD-NOS: pervasive developmental disorder-not otherwise specified; (NT): neurotensin; (SP): Substance P; rhSCF: recombinant human stem cell factor; VAERS: Vaccine Adverse Event Reporting System; VEGF: vascular endothelial growth factor. 

Competing interests 

TCT is on the Scientifc Advisory Board of The Mastocytosis Society. TCT is the inventor of US patents No. 6,624,148; 6,689,748; 6,984,667 and EPO 1365777, which cover methods and compositions of mast cell blockers in neuroinflammatory conditions, as well as US patent application No.12/534,571 for diagnosis and treatment of ASD. 

Authors' contributions 

This study is based on an original idea of TCT. TCT and DK wrote the manuscript. DK and SA carried out the cytokine, β-hexosaminidase and histamine assays. JH, AM, BZ carried out the viability assays and some mediator assays. EP provided umbilical cord blood. All authors have read and approved the manuscript. 

Acknowledgements 

This work was funded in part by the Safe Minds (Huntington Beach, CA) and the Defeat Autism Now Coalition (San Diego, CA), as well as Theta Biomedical Consulting and Development Co., Inc. (Brookline, MA). Christos Damianos Kalogeromitros participated in some aspects of this work as part of his IB project at Athens College, Greece.   

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Source: Duraisamy Kempuraj, Shahrzad Asadi, Bodi Zhang, Akrivi Manola, Jennifer Hogan, Erika Peterson, and Theoharis C Theoharides. J Neuroinflammation. 2010; 7: 20. Published online 2010 March 11. doi: 10.1186/1742-2094-7-20.

Tags:  human mast cells  inflammatory mediator  mercury 

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The Second Brain: The Gut and Serotonin

Posted By Administration, Thursday, May 6, 2010
Updated: Friday, April 18, 2014

 

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by Zina Kroner, DO

This is not the “shock and awe” study of the year, but it elucidates an excellent medical phenomenon.  A recent study in the American Journal of Gastroenterology showed that St. John’s Wort, an herb used to treat mild depression, was less effective than placebo at treating irritable bowel syndrome (IBS).  Improvements in quality of life were similar in both placebo and the herb treated groups.  Gastroenterologists have been treating IBS with anti-depressants for quite some time.   I would like to bring to light the theory behind it, as this may have clinical implications beyond the use of medication.

The gut, often referred to as the second brain due to the powerful enteric nervous system that it houses, is tightly connected to serotonin, the feel good neurotransmitter.   Dr. Michael D. Gershon, the chairman of the department of anatomy and cell biology at Columbia has brought this to light in his book entitled “The Second Brain.” 

We have all felt a twinge in the stomach prior to a major exam or a public speaking event.  It is quite common for my patients with a psychiatric disorder to have a concomitant gastrointestinal issue. 

There are several reasons why stress or anxiety can cause irritable bowel syndrome.  First, with any fight or flight response, cortisol, a stress hormone, is released. Cortisol fires up the sympathetic nervous system and makes the parasympathetic nervous system less efficient.  It is the parasympathetic nervous system that we need in order to maintain bodily homeostasis, such as breathing, digestion,etc.  Therefore, with a cortisol surge, digestion becomes ineffective and irritable bowel syndrome can kick in.

Second, it is important to note that serotonin has a profound effect on gastrointestinal function, being that 95% of the body’s serotonin is cradled in the gut.  At the start of digestion, it is the enterochromaffin cells that release serotonin into the gastrointestinal tract, which houses many serotonin receptors.  The receptors then initiate a process via nerve cells that starts the flow of digestive enzymes. 

Serotonin then relays messages up to the brain, letting it know what is happening.  Therefore, certain foods may elicit a feeling of nausea, etc.  Once serotonin is released in the gastrointestinal tract and the process of digestion is stimulated, normally, it is cleared out of the way by SERT, a serotonin transporter. 

These transporters are found in the gut walls.   Often, those with IBS, may not have an appropriate level of functioning SERTs, and they are therefore unable to clear out the serotonin cells.  This can stimulate diarrhea. Once the serotonin receptors are supersaturated, the effect is constipation, thus the infamous Irritable Bowel Syndrome.  Therefore, medications as well as supplements such as St. Johns Wort which manipulate the serotonin may potentially help IBS symptoms. It is no wonder that in this recent study, placebo was quite beneficial in IBS.  This shows how much mind and body are connected.  Focusing on stress management is key as well. 

A third contributor to IBS as it related to the enteric nervous system is allergens.  Often, the barrier of the gut becomes damaged and certain allergens, etc, may enter the bloodstream, triggering the brain to send a message to the gut to increase the production of histamines and other inflammatory cells in order to try to get rid of the allergens.  This inflammatory process may trigger the neurons in the enteric nervous system (in the gut) to become hyperactive and therefore contribute to diarrhea. 

The challenge now is to optimize the efficiency of the gastrointestinal tract by preventing unnecessary cortisol surges so not to disrupt the sympathetic and parasympathetic nervous system harmony, to maintain a healthy serotonin and SERT level, and to prevent unnecessary allergens from entering the GI tract so not to trigger the inflammatory process involved in diarrhea.  The gut really is the Second Brain! 

Citation:  Saito YA et al. A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome. Am J Gastroenterol 2010 Jan; 105:170.

Tags:  gut health  inflammatory bowel disease 

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Role of Diet in the Management of Inflammatory Bowel Disease

Posted By Administration, Friday, April 30, 2010
Updated: Friday, April 18, 2014

ABSTRACT

Many studies have looked at connections between diet, etiology, signs and symptoms associated with inflammatory bowel disease (IBD). Although these connections are apparent to clinicians, they are difficult to prove qualitatively or quantitatively. Enteral feeding and polymeric diets are equally effective at bringing about remission in Crohn’s disease (CD). Parenteral feeding is also effective, although none of these methods is as effective as corticosteroid therapy. However, enteral feeding is preferred in the pediatric population because linear growth is more adequately maintained via this route. Exclusion diets in patients brought into remission using an elemental diet have been shown to maintain remission for longer periods. Studies that aim to isolate culpable food groups have shown that individuals react differently on exposure to or exclusion of various foods. The commonly identified food sensitivities are cereals, milk, eggs, vegetables and citrus fruits. Studies that have looked at gut mucosal antigen behavior have shown higher rectal blood flow, in response to specific food antigens, in those with CD over healthy subjects. Exclusion of sugar shows little evidence of amelioration in CD. Omega 3 fatty acids show promise in the treatment of IBD but await larger randomized controlled trials. Patients frequently notice that specific foods cause aggravation of their symptoms. Whilst it has been difficult to pinpoint specific foods, with advances in the laboratory tests and food supplements available, the aim is to prolong remission in these patients using dietary measures, and reduce the need for pharmacotherapy and surgical intervention.

INTRODUCTION

The etiology of inflammatory bowel disease (IBD) is considered multifactorial. Genetic, infective and environmental theories exist, as well as those centered around host immunity, intraluminal gut flora, food allergies and hypersensitivity.

Whilst pharmacological therapy plays a major role, many patients prefer to control their symptoms by the most conservative means possible. Our aims in IBD therapy are to downregulate inflammation, and reduce the incidence of relapse and the healing time.

Dietary therapy encompasses dietary modifications suggested by physicians and those that patients make autonomously. The putative mechanisms of action are due to bowel rest, provision of nutrients, alteration of bowel flora or alteration of antigenic stimuli. The gastrointestinal flora and its interaction with nutritional factors has a huge impact on the environment, especially in genetically predisposed individuals. Nutrients as components of cell structure or antigens can induce inflammatory mediator expression and suboptimal levels of nutrients, which may have an impact on tissue repair and other cellular processes. Other reviews have concluded that nutrients that tend to affect the immune responses of the host (n-3 fatty acids, antioxidants) are likely to play a role in the treatment of IBD.

In this review, we examine the literature for dietary interventions in IBD, such as exclusion/elimination diets, enteral nutrition and total parenteral nutrition (TPN), and review the evidence that they induce and/or maintain remission in patients with IBD.

METHODOLOGY

Elemental/polymeric diets

Elemental diets were chanced upon as a therapeutic option for CD patients when they were used to bolster their nutritional status and reduce inflammation. Liquid feeds are thought to work by reducing mucosal antigen exposure, partly due to the nature of the feed and partly to faster transit times. They also alter the fecal flora, which causes local immunomodulation downscaling, which enhances nutritional status and allows relative bowel rest.

Compliance may be poor as elemental diets are not known for their palatability and are often delivered via a nasogastric tube, whereas the polymeric drinks are far more palatable. Several trials and meta-analyses have shown no significant difference in the efficacy of elemental diets over polymeric diets.

Elemental diets offer a cheaper way of bringing about remission and without the side effect profile of TPN. In both adult and pediatric populations, elemental and polymeric feeds have been shown to be as effective as corticosteroid therapy in treating active CD. However, a Cochrane review by Zachos et al has shown, in a meta-analysis, that enteral nutrition is not as effective as steroid therapy for inducing remission.

However, enteral therapy for CD has its role in selected cases, in particular, in children in whom steroids may cause growth retardation. Food exclusion with liquid diet is very difficult to maintain, therefore, these are rarely long-term solutions. Unfortunately, a staged return to normal feeding often leads to relapse.

Exclusion diets

The East Anglia Multicentre Controlled Trial showed that various food intolerances were perceived in individual patients, and among the more common were cereals, dairy produce and yeast. This work looked at the use of exclusion diets as an intervention in active CD. The exclusion diet was based around daily reintroduction of a single food type. If it caused diarrhea or pain, it was eliminated. All patients were treated initially with an elemental diet, and those who attained remission followed a reduced prednisolone course or the exclusion diet pathway. Jones et al have shown that maintenance of remission, by identification and avoidance of food intolerances, is possible, often without pharmaceutical adjuncts. Testing for these sensitivities has proven difficult, because testing shows a large number of sensitivities in unselected populations, which are of doubtful clinical significance. Jones et al have tested a diet rich in unrefined carbohydrate against an exclusion diet. Seven out of 10 patients on the exclusion diet stayed in remission for 6 mo, while none of those on the carbohydrate-rich diet remained in remission. Pearson et al have conducted a study of 42 CD patients after induction of remission by elemental diet. Single foods were investigated using open and double blind rechallenge over 5 d. Fourteen patients dropped out due to flare-ups that were thought to be unrelated to food, and caused by inability to comply with the regimen. Twenty of the remaining patients identified food intolerances and eight did not. This research group has concluded that food intolerance is not as frequent as claimed in other studies, and that it is variable in its intensity and occurrence.

Parenteral feeding in CD

TPN allows bowel rest while supplying adequate calorific intake and essential nutrients, and removes antigenic mucosal stimuli. However, TPN is expensive, invasive and has a number of side effects. TPN has been shown to bring about remission in CD. Müller et al have found that, in 30 consecutive complicated CD patients, 3 wk of TPN as an inpatient followed by an additional 9 wk at home, during which time, no medication or oral intake was allowed, 25 patients avoided surgery. These patients returned to work and needed no further medication and ate normal meals subsequently. In a prospective randomized controlled trial (RCT), 51 patients with active CD refractory to medical treatment were treated with TPN and nil by mouth, defined formula diet via a nasogastric tube, or partial parenteral nutrition. Clinical remission was obtained in 71% of the patients on TPN, 58% on enteral feeding, and 60% on partial parenteral feed.

Enteral vs parenteral feeding

There has been controversy regarding the enteral vs parenteral route for feeding in patients with IBD. Comparison of TPN against elemental diet in a group of 36 patients showed no significant difference in the number of days to remission, the drop in Crohn’s disease activity index (CDAI) score, the erythrocyte sedimentation rate (ESR), or albumin. However, in other studies that have agreed with this finding, neither was proven to be as beneficial as corticosteroids, except one study in a pediatric population. In that study, Sanderson et al entered 17 children into an RCT, in which eight were given an elemental diet for 6 wk via a nasogastric tube, and seven were given adrenocorticotrophic hormone injections and oral prednisolone and sulfasalazine. The elemental diet was equally effective at improving the Lloyd-Still disease activity index scores, C-reactive protein (CRP), ESR and albumin. The elemental diet was markedly better at maintaining linear growth. Whilst strong evidence exists supporting the primary use of enteral feeding in children with CD, it is not commonplace in the treatment of adults.

Omega-3 fatty acids

Shoda et al have noted that the gradual replacement of n-3 polyunsaturated fatty acids with n-6 polyunsaturated fatty acids results in an increased incidence of CD. This implies that there is the potential to modulate immune responses by altering the ratio of polyunsaturated fatty acids in favor of n-3 rather than n-6. Meister and Ghosh have shown that fish-oil-enriched enteral diet, when incubated with intestinal tissue from 11 subjects with IBD and four controls, reduced inflammation modestly in CD and significantly in UC. Inflammatory improvement was assessed by analyzing the interleukin (IL)-1 receptor antagonist/IL-1β ratio. The greater the ratio, the less inflamed the tissue. A systematic review of the effects of n-3 fatty acids in IBD by MacLean et al has identified 13 controlled trials that investigated the effects of n-3 fatty acids. The results were mixed but in the three studies that looked at steroid requirements, this was found to be reduced. However, this was statistically significant in just one of these studies.

 

MAINTENANCE OF REMISSION IN CD

Exclusion diets

Jones has looked at exclusion diets for the maintenance of remission of CD and has shown that, in personalized exclusion diets, 62% of the patients maintained remission at 2 years and 45% at 5 years, with no other medical intervention. This was compared to the European Cooperative Crohn’s Disease Study in 1984 in which the placebo arm of the study had no patient who maintained remission after 2 years of follow-up.

A Cochrane review of the maintenance of remission in CD has suggested that larger, high-powered controlled trials are required to confirm current hypotheses relating to diet and maintenance of remission. Trials of diet against azathioprine and infliximab also have been suggested to investigate quantitative effects of nutritional supplements and their impact on cost-effectiveness and quality of life.

Enteral feeding

Enteral feeding has been shown to have a role in preventing relapse in inactive CD patients (predominantly in children), but the effect has also been observed in a Japanese study of adult CD patients. Esaki et al have demonstrated in a trial of 145 patients with CD (mostly induced into remission with TPN) that, under maintenance with elemental/polymeric nutrition, the risk of recurrence was lower in those with small bowel rather than large bowel involvement.

 

DIETARY MANAGEMENT IN UC

Maintenance of remission in UC

UC does not seem to be ameliorated by bowel rest and elemental diets in the same way as CD is. However, patients still express concern about specific food types, and there does appear to be an association with a western diet. In a study that has investigated self-reported food intolerance in chronic IBD, patients with CD and UC have reported that they felt intolerant to specific dietary triggers and restricted their diet accordingly. The same study has shown that the pattern and frequency of food intolerance did not differ between CD and UC patients. This has been reinforced by work from our own group that has investigated food intolerances detected by measuring IgG4 antibodies to specific food antigens. There is no evidence to support the use of elemental/polymeric feeding in the treatment of UC.

Omega-3 fatty acids

Omega-3 fatty acids derived from fish oils have been shown to be of benefit in a double-blind RCT that looked at patients with distal UC. That study found that the group treated with 3.2 g eicosapentaenoic acid or 2.4 g docosahexaenoic acid daily had significantly better clinical and sigmoidoscopic scores compared with the control group who took sunflower oil, after 3 and 6 mo. This supports the idea that omega-3 oils suppress natural cytotoxicity.

 

ADDITIONAL DIETARY FACTORS

Fiber

Dietary fiber has been investigated as a means of increasing short-chain fatty acid (SCFA) production. IBD has been linked with impaired SCFA production. SCFAs are mainly produced by the anaerobic bacterial fermentation of undigested carbohydrates and fiber polysaccharides. In 1995, Galvez et al reviewed a number of studies that concluded that dietary fiber confers clinical benefits in patients with IBD because it maintains remission and reduces colonic damage. This is thought to occur by increasing SCFA production and by altering the gut flora towards predominantly non-pathogenic bacteria.

Fats

The properties of omega-3 fatty acids have been discussed elsewhere in this review. Other studies have revealed an inverse correlation between the percentage of energy derived from long-chain triglycerides and the efficacy of enteral feeds in achieving remission.

Sugars

A high intake of sugar has been shown to be linked to CD in a number of trials, hence its possible etiological role has led to therapeutic trials of sugar avoidance. Most of these trials also have promoted a high fiber intake. The only trial to look solely at sugar avoidance has shown no statistically significant benefit.


 

ANTIGENIC RESPONSE TO FOOD

 

Van den Bogaerde et al have published a trial in which the reactivity of peripheral lymphocytes to food, yeast and bacterial antigens was studied. They found that 23 out of 31 patients with CD responded to one or more antigens, compared to five out of 22 in the control group. They also correlated in vitro sensitization and in vivochanges with histological and blood flow changes. Skin testing and rectal exposure to six food antigens and saline were tested in 10 patients and 10 controls. The results showed that CD patients demonstrated in vitro and in vivo sensitization to food antigens and this was gut specific.

Levo et al have shown that patients with IBD have higher serum concentrations of IgE. They also have shown that the levels are higher still in those with active disease over those in remission. However, this difference is not statistically significant. In 1998, another study was performed to investigate food-specific IgE as well as IgG, and IgE anti-IgE autoantibodies using serum from normal subjects, patients with CD and those with food allergies. They found that food-specific IgE was not detected at all in the CD group but they did have higher levels of IgG and IgE anti-IgE autoantibodies. They concluded that, even if IgE is an autoantigen in CD, it is not thought to take part in the pathophysiology of the adverse food reactions commonly reported by the patients.

Western diets are more strongly associated with CD. There are several theories as to whether this may relate to the increased intake of sucrose, refined carbohydrate, and omega-6 fatty acids, and reduced intake of fruit and vegetables. Urban diets contain large quantities of microparticles such as natural contaminants like dust, and food additives which may be antigenic. CD patients allocated to a low microparticle diet experienced a reduction in disease activity and in steroid requirement compared to a control group on a normal diet.

SUMMARY

Although many studies have looked at diet therapy and IBD, mixed opinions exists as to the importance that food intolerance plays in the pathophysiology of IBD. In those that have looked at food sensitivity, this was done using different methods. Riordan et al have observed sensitivity to corn in seven patients; wheat, milk and yeast in six; egg, potato, rye, tea and, coffee in four; and apples, mushrooms, oats and chocolate in three. Ballegaard et al have found sensitivity, using questionnaires, to vegetables (particularly onions and cabbage), fruits (apples, strawberries, and citrus fruits) and to meat (especially beef). Van den Bogaerde et al have shown in a case-control study using lymphocyte proliferation that, out of 31 CD patients, 16 reacted to cabbage and peanuts, 14 to cereals, 13 to milk, and nine to citrus fruits.

As observed by Hunter, epidemiologists tend to look at statistical relationships that lead to studies of sugar, sweet, coke and chocolate intake because patients with CD eat and drink more of these substances than control subjects. Clinicians focus on the foods that patients associate with their symptoms and therefore avoid. As a result, exclusion diets have tended to concentrate more on dairy products, cereals and yeast. Other work is being carried out on polyunsaturated fatty acids, especially omega-3 oils, and their anti-inflammatory effects.

Current elemental and polymeric diets have a role to play in the management of CD, particularly in children. Exclusion diets are of use particularly for maintenance of remission. TPN is of value and has been shown to be as effective as elemental diets, but none have proven as effective as corticosteroid therapy. However, TPN remains a crucial method for administering nutrition in patients with severe disease, who are not able to tolerate enteral feeding.

Despite early ideas about the involvement of sugars in the etiology of CD, the omission of sugar has not been found to be of benefit. Omega oil has shown promising results, particularly in reducing inflammation in UC, and to a lesser degree, in CD.

CONCLUSION

IBD has a multifactorial etiology but food sensitivity/intolerance appears to play a role, and the culpable foods vary on an individual basis. Techniques to identify food intolerance require refining. Progress has been made by looking at factors such as IgG4 responses to food antigens, but a large expanse of work exists in trying to determine people’s food sensitivities and the degree to which these affect disease activity. Without further research, it remains unclear whether dietary manipulation will continue to have a role solely in symptom control, or whether complete remission may be possible using these methods in combination with pharmacological agents.

 

FOOTNOTES

 

Peer reviewer: Wallace F Berman, MD, Professor, Division of Pediatric GI/Nutrition, Department of Pediatrics, Duke University Medical Center, Duke University School of Medicine, Durham, Box 3009, NC 27710, United States

S- Editor Tian L L- Editor Kerr C E- Editor Ma WH

 

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Source: Nirooshun Rajendran and Devinder Kumar. 

World J Gastroenterol. 2010 March 28; 16(12): 1442–1448.

Published online 2010 March 28. doi: 10.3748/wjg.v16.i12.1442

 

 

 

 

Tags:  diet  inflammatory bowel disease 

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Black Cohosh May Reduce Side Effects of Clomid/Clomiphene

Posted By Administration, Thursday, April 15, 2010
Updated: Friday, April 18, 2014

 

 

by Fiona McCulloch, ND

Clomid is one of the most commonly used pharmaceuticals in the treatment of fertility concerns today.  It is often the first therapy used.  Clomid (also known as clomiphene) binds to estrogen receptors, inhibiting the action of estrogen (which is produced by developing follicles) on the hypothalamus in the brain.   As a result, the pituitary gland perceives estrogen levels to be low (when they actually are not), and it responds by producing increased levels of both LH and FSH.  This causes increased follicle production by the ovaries, and stimulation of ovulation.pregnancy with clomid therapy

As effective as this therapy can be at inducing ovulation, studies have indicated fertility specific side effects of clomiphene, many of which are caused by its antagonism to estrogen. The major fertility related side effects are: 1) thinning of the endometrial lining and 2) reduction of cervical mucous required for entry of sperm into the uterus.

One of the isomer forms of clomiphene has a slow excretion rate from the body (it can take more than 6 weeks to be excreted).  If clomiphene therapy is used for longer than two months, side effects can be more pronounced, resulting in greater thinning of the endometrial lining which is needed for healthy implantation. In women over 40, endometrial lining thins naturally, and perhaps this is why clomiphene is often not an effective treatment in this group of patients.

For many women, the ovulation induction produced by this medication can be the answer to ovulation difficulties however therapy often must be stopped after a short period due to side effects over time. Estrogen therapy has been studied in conjunction with Clomid presumably to offset the anti-estrogenic effects of the medication, with mixed results.  Some studies have found giving additional estrogen to women to be helpful, and others have found it to be of no benefit.

Recently, two studies have been completed on combining black cohosh (also known as Cimicifuga racemosa) with clomiphene in patients seeking treatment for infertility.  Cimicifuga is a botanical therapy, often used in womens health to treat menopausal conditions such as hot flashes.  Estrogenic effects of black cohosh remain highly debated, with early studies indicating that it  directly affects estrogen receptors, and more recent studies showing that the effect of the plant may occur from an entirely different mechanism.  Without yet knowing the exact mechanisms through which black cohosh works, several convincing studies have indicated it to be beneficial in the clinical treatment of hormonal disorders.  A recent study has indicated that black cohosh may reduce proliferative effects of estrogens on tissues, which is in line with the effect of many phytoestrogens, however the mechanism for this remains to be elucidated.

In the first study conducted in 2008, black cohosh was found to significantly increase estradiol and LH concentrations in patients taking clomiphene therapy.   Endometrial thickness, serum progesterone and clinical pregnancy rate in patients were significantly higher in the black cohosh group as compared to control.

The second study was completed in 2009. In this study of patients taking clomiphene, black cohosh given in the follicular phase was compared to estrogen therapy, presumably in order to determine which could reduce side effects more effectively. The black cohosh group needed significantly fewer days for healthy follicular development, had a thicker endometrial lining and had higher estradiol concentration at the time of HGG ovulation trigger when compared to the estrogen replacement therapy group.  Clinical pregnancy rate was 14.0% in the estrogen replacement group versus 21.1% in the black cohosh group. Although this did not reach clinical significance, it appears that the black cohosh group did display many benefits overall when compared to the estrogen replacement group. When results from the previous study are also considered, it appears that this therapy may warrant serious consideration and further study for those undergoing clomiphene treatment.

More studies will need to be conducted in order to determine the mechanisms of this herbal medicine’s benefits for patients undergoing modern assisted reproductive technology therapies.

References:

Homburg, I.  Clomiphene citrate—end of an era? a mini-review.  Human Reproduction 2005 20(8):2043-2051

Insler, V MB, BCh; Zakut, H MD; Serr, D M MB, ChB. Cycle Pattern and Pregnancy Rate Following Combined Clomiphene-Estrogen Therapy. April 73 (4) 4

Massai et al.  Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment.  Fertil Steril. 1993 Jun;59(6):1179-86

Osmers et al. Efficacy and Safety of Isopropanolic Black Cohosh Extract for Climacteric Symptoms. Obstetrics & Gynecology:  May 2005 – Volume 105 – Issue 5, Part 1 – pp 1074-1083

Sandro Gerli, Hossein Gholami, Antonio Manna, Antonio Scotto Di Frega, Costantino Vitiello, Vittorio Unfer, Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study, Fertility and Sterility, Volume 73, Issue 1, January 2000, Pages 85-89

Shahin AY, Ismail AM, Shaaban OM. Supplementation of clomiphene citrate cycles with Cimicifuga racemosa or ethinyl oestradiol–a randomized trial. Reprod Biomed Online. 2009 Oct;19(4):501-7.

Shahin, Ahmed Y.1; Ismail, Alaa M.1; Zahran, Kamal M.1; Makhlouf, Ahmad M.1 Adding phytoestrogens to clomiphene induction in unexplained infertility patients – a randomized trial. Reproductive BioMedicine Online, Volume 16, Number 4, April 2008 , pp. 580-588(9)

Tags:  black cohosh  clomid  clomiphene  side effects 

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The Relationship Between Alzheimer's Disease and Diabetes: Type 3 Diabetes?

Posted By Administration, Friday, April 9, 2010
Updated: Friday, April 18, 2014

Zina

Published in Alternative Medicine Review, Volume 14, Number 4 2009

by Zina Kroner, DO

 

 

 

Abstract 

In recent years, Alzheimer’s disease (AD) has been considered to be, in part, a neuroendocrine disorder, even referred to by some as type 3 diabetes. Insulin functions by controlling neurotransmitter release processes at the synapses and activating signaling pathways associated with learning and long-term memory. Novel research demonstrates that impaired insulin signaling may be implicated in AD. Post-mortem brain studies show that insulin expression is inversely proportional to the Braak stage of AD progression. It was also demonstrated that neurotoxins, coined amyloid beta-derived diffusible ligands (ADDLs), disrupt signal transduction at synapses, making the cell insulin resistant. ADDLs reduce plasticity of the synapse, potentiate synapse loss, contribute to oxidative damage, and cause AD-type tau hyperphosphorylation. Diabetes and AD have signs of increased oxidative stress in common, including advanced glycation end products (AGEs), when compared to normal subjects. Diabetic patients appear to have an increased risk for AD because AGEs accumulate in neurofibrillary tangles and amyloid plaques in AD brains. This research should encourage a more proactive approach to early diagnosis of diabetes and nutritional counseling for AD patients. (Altern Med Rev 2009;14(4):373-379) 

Introduction 

The epidemic of insulin resistance/prediabetes and type 2 diabetes may be associated with the emergence of higher rates of Alzheimer’s disease (AD). New research delineates a direct correlation between sugar imbalance and AD. AD is associated with consistent pathological findings, including neurofibrillary tangles, amyloid-beta deposits, and signs of oxidative stress. No common link among the proposed pathological processes has been identified. Novel evidence demonstrates that impaired insulin signaling may significantly contribute to the pathogenesis of AD, contributing to the idea that it is actually a neuroendocrine disease. Neurotoxins called amyloid beta-derived diffusible ligands (ADDLs) have been implicated as a cause of impaired insulin signaling. Advanced glycation end products (AGEs) are found in higher concentration in both hyperglycemia and AD, contributing to oxidative stress and cell damage. These AGEs are known to be further modified to reactive advanced glycation end products, (RAGEs), which can generate oxidative injury. 

Understanding the mechanism of action of this neuroendocrine disorder, termed type 3 diabetes by some, may shed light on new tools for diagnosing and treating AD and for the need for early intervention in obese patients with insulin resistance. 

The Clinical Link: Diabetes and AD 

The research linking diabetes and AD has its roots in the groundbreaking Rotterdam study. Of 6,370 elderly subjects studied for 2.1 years, 126 developed dementia; 89 of these were specifically diagnosed with AD. Type 2 diabetes doubled the risk of a patient having dementia and patients on insulin had four times the risk.As rates of insulin resistance and diabetes in the senior population are both increasing, this landmark study, conducted almost a decade ago, has been getting more attention in recent years since further studies have solidified the connection between diabetes and AD.

Since type 2 diabetes is reaching epidemic proportions and is under-diagnosed, and AD may be associated with hyperglycemia, more attention should be drawn to early diagnosis of diabetes. The Gertner Institute for Epidemiology and Health Policy Research in Israel, in a recently published 25-year, cross-sectional study of 623 adults, demonstrated that approximately 13 percent of the studied population had undiagnosed type 2 diabetes. This study reinforces the importance of early diagnosis of type 2 diabetes by identifying patients with risk factors, including hypertension, hypertriglyceridemia, and a large waist circumference (males: ≥40 inches [102 cm], females: ≥35 inches [88 cm]) – factors seen in metabolic syndrome. These results encourage early detection via screening methods targeting those with traits of metabolic syndrome in otherwise healthy adults.

Another study demonstrating the high prevalence of diabetes showed almost one-third of elderly patients in a sample of 7,267 subjects had diabetes, and three-fourths had impaired fasting glucose (glucose lev- els >99 but <126) or diabetes.

Elevated body mass index (BMI), adiposity, impaired fasting glucose, and diabetes increase the risk of AD substantially. The latest study, utilizing data on 2,322 participants in the Baltimore Longitudinal Study of Aging, shows the incidence of AD increased in men who gained weight between the ages of 30 and 45 and in women with a BMI >30 at ages 30, 40, and 45.7 This suggests more emphasis should be placed on early weight-loss strategies for preventing AD. 

A 2008 Swedish study showed a statistically significant increase in the risk of developing AD in men who develop type 2 diabetes in midlife. The researchers followed 2,269 men for 32 years and found that those with low insulin production at age 50 were 150-percent more likely to develop AD than those with adequate insulin production. This association was greatest in patients who did not have the apolipoprotein E4 (ApoE4) genetic predisposition to AD (which renders individuals less efficient at breaking down beta-amyloid plaques), thereby making diabetes a possible independent risk factor for AD. This study illustrates the importance of maintaining healthy blood glucose control in middle-aged men as a possible means of preventing AD later in life. 

A recent investigation suggests that AD is associated with metabolic syndrome. After studying 50 patients diagnosed with AD and comparing them to 75 cognitively normal controls, the AD patients had a greater waist circumference, higher triglyceride and glucose levels, and lower high-density lipoprotein cholesterol. Patients with metabolic syndrome are diagnosed with AD at a younger age than AD patients without metabolic syndrome.

Type 3 Diabetes: Is It Actually a Unique Condition? 

The term type 3 diabetes was coined in 2005 by Suzanne de la Monte, MD, MPH, Associate Professor of Pathology and Medicine and neuropathologist at Brown Medical School. Her team, examining postmortem brain tissue of AD patients, found that AD may be a neuroendocrine disease associated with insulin signaling. The team termed it type 3 diabetes because it harbors elements of both types 1 and 2 diabetes, since there is both a decrease in the production of insulin and a resistance to insulin receptors.

The team analyzed 45 postmortem brains of patients of varying Braak stages of AD neurodegeneration and found that insulin expression was inversely proportional to the Braak stage, with an 80-percent decrease in the number of insulin receptors in AD patients compared to normal subjects. In addition, the ability of insulin to bind to the receptors was compromised. There was a reduced level of mRNA corresponding to insulin, insulin-like growth factor-1 (IGF-1) and -2 polypeptides, and their receptors. The research team also noted a reduction in the tau protein, which is regulated by insulin and IGF-1. This phenomenon ultimately could lead to neuronal cell death and AD exacerbation.  

The postmortem studies inspired a rat study in which intracerebral injection of streptozotocin resulted in a chemical depletion of insulin and an alteration of IGF-signaling mechanisms together with oxidative injury. The combination of alterations resulted in neurodegeneration, including reduction in brain size and other neurological changes seen in AD.

AD is characterized by a reduction in the utilization of glucose, and treatment with insulin has been associated with improved memory. Insulin, important in memory processing, crosses the blood-brain barrier and is even produced in brain tissue itself. AD patients have less insulin and fewer insulin receptors than non-AD patients, and correction of insulin levels improves cognition. Insulin binds to insulin receptors in the brain, most of which are located in the cerebral cortex, olfactory bulb, hippocampus, cerebellum, and hypothalamus. Since there are more insulin receptors in the cognitionpertinent areas of the brain, it is logical to consider the association between insulin and cognition.

Several studies utilizing intranasal, intravenous, and intracerebral administration of insulin demonstrate improved cognition. A study utilizing intranasal insulin showed that its administration enhanced verbal recall in normoglycemic adults with early AD or cognitive impairment. In the study, 25 participants were randomly assigned to receive either placebo (n=12) or 20 IU intranasal insulin (n=13) twice daily. After 21 days of treatment, changes in cognition were measured. The fasting plasma glucose and insulin levels were unchanged with treatment. However, when compared with the placebo treated subjects, the insulin-treated subjects retained more verbal information and displayed superior attention and functional status. 

A study utilizing intravenous (IV) insulin assessed cognitive performance in 22 adults with AD and 15 normal adults receiving five consecutively higher IV doses of insulin resulting in five plasma insulin levels (10, 25, 35, 85, and 135 microU/mL), while plasma glucose levels of ~100 mg/dL were maintained. Cognitive performance was measured after 120 minutes of infusion. AD patients who were ApoE4-positive were found to have improved memory at lower insulin levels of 25 microU/mL, compared to their ApoE4-negative counterparts, who required a higher blood insulin level of 35 and 85 microU/mL before an improvement in memory was noted. Interestingly, normal adults also showed improved memory at insulin levels of 25 and 85 microU/mL. This shows that AD patients who are ApoE4-negative may not be as sensitive to insulin.  

A study utilizing intracerebroventricular insulin showed that its administration enhanced memory formation in rodents undergoing a step-through passive avoidance task These studies suggest that insulin may have a role in enhancement of cognition and memory. The other implication is that patients with the ApoE4 genetic predisposition to AD may not reap the benefits of improvement in AD by glycemic control. 

Based on a recent epidemiological study, individuals who are ApoE4-positive are not more likely to be insulin resistant than those who are ApoE4-negative. Therefore, insulin resistance and being positive for the ApoE4 allele are independent risk factors for AD; having both may pose an additive risk. 

Pathophysiological Connections between Insulin and AD 

AD is characterized by both low insulin levels and insulin resistance within the central nervous system (CNS), as opposed to type 2 diabetes, which is characterized by high insulin levels and insulin resistance outside of the CNS. Insulin resistance and hyperinsulinemia cause a reduction in brain insulin. Several mechanisms might explain why insulin mediates memory facilitation. As noted, insulin receptors are found in areas of the brain responsible for cognition. Insulin activates signaling pathways associated with learning and long-term memory. According to de la Monte, insulin helps to regulate processes such as neuronal survival, energy metabolism, and plasticity. These processes are required for learning and memory.  Peripheral insulin resistance, therefore, affects cognition.

In addition to regulating blood sugar levels, insulin functions as a growth factor for all cells, including neurons in the brain. Thus, insulin resistance or lack of insulin, in addition to adversely affecting blood sugar levels, contributes to degenerative processes in the brain.

When insulin levels reach an exceedingly high level, the beta-amyloid peptide, the hallmark of AD that accumulates in senile plaques, is modulated. Exaggerated elevation of plasma insulin levels causes amyloid peptide levels in the cerebrospinal fluid to increase, resulting in memory insult.

Amyloid beta-Derived Diffusible Ligands 

A group of researchers at Northwestern University studied why brains of AD patients are both low in, and resistant to, insulin. According to William Klein, PhD, who led the research, amyloid beta-derived diffusible ligands may be responsible for the phenomenon. ADDLs are oligomers similar in morphology and size to prions that have been linked to neurodegenerative disease. ADDLs may contribute to lowered insulin levels and insulin resistance in AD brains. Because the ADDLs are so small, they are more diffusible and therefore more harmful than amyloid. 

In healthy brains, insulin binds to a receptor at a synapse, resulting ultimately in memory formation. Klein’s team found that ADDLs disrupt this mechanism of communication by binding to the synapse and changing its shape, thereby causing dysfunction. Because the shape of the synapse is altered, insulin cannot effectively bind, disrupting signal transduction and resulting in insulin resistance. ADDLs have been shown to reduce the plasticity of the synapse, potentiate synapse loss, cause oxidative damage, and result in AD-type tau hyperphosphorylation, mechanisms linked to AD. Since ADDLs have been shown to affect neuronal insulin receptor signaling, it has been suggested that insulin resistance in the AD brain is a response to  ADDLs, inducing a neurological form of diabetes.  Neurons with no ADDLs show an adequate number of insulin receptors. 

Measuring ADDL levels may potentially be a novel tool for diagnosing AD. In 2005, the ultrasensitive bio-barcode assay was used to measure ADDL concentration in cerebrospinal fluid. Of 30 subjects, ADDL concentrations were found to be higher in those diagnosed with AD compared to non-AD patients. This test is not readily available and less invasive testing is underway. An ADDL vaccine is being studied and ADDL-blocking drugs are being considered by Klein et al.


Insulin and the Cholinergic Hypothesis 

The cholinergic hypothesis that suggests AD is caused by an inadequate production of acetylcholine may also have links to blood sugar abnormalities and insulin resistance. The researchers at Brown point out that insulin also participates significantly in neurological function by stimulating the expression of choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine synthesis. Therefore, suboptimal insulin levels as well as poor insulin receptor sensitivity can ultimately contribute to a decrease in acetylcholine, which further elucidates a possible bio-chemical link between diabetes and AD.

AGEs and Oxidation – Common Thread between Diabetes and AD 

Another mechanism linking diabetes with AD is that both diseases, as mentioned previously, are associated with increased oxidative stress and production of AGEs. Although the association between vascular dementia and AGEs is well established, new research points to a link between AGEs and AD. AGEs are formed by a sequence of events originally identified in 1912 as the end-products of the Maillard reaction, during which reducing sugars can react with the amino groups of proteins to produce cross-linked complexes and unstable compounds. 

AGEs have been found in retinal vessels, peripheral nerves, kidneys, and the CNS of diabetics. AGEs couple with free radicals and create oxidative damage, which in turn leads to cellular injury. Diabetic patients could have an increased risk of AD via AGE production. Oxidative stress on its own also causes AGEs, creating a vicious cycle.

AGEs are also known to modify plaques and neurofibrillary tangles, both implicated in AD. AGEs have been identified in neurofibrillary tangles (consisting of tau protein) and senile plaques (consisting of beta-amyloid protein). Since type 2 diabetes accelerates the production of AGEs, it may be another causative factor in the development of AD. It has been proposed that a potential biomarker for early detection of AD may be measurement of toxic AGEs in the serum or cerebrospinal fluid.

Conclusion 

Understanding that AD has its foundation in neuroendocrinology is persuasive evidence that there should be greater emphasis on early diagnosis of metabolic syndrome, insulin resistance, and type 2 diabetes. Referring to AD as type 3 diabetes has its foundation in the fact that the CNS in AD is characterized by a paucity of insulin and resistance of the insulin receptors. This results in cognitive dysfunction, since insulin is crucial for neurological signaling processes to occur. Insulin also participates in neurological function by stimulating the expression of ChAT, the enzyme responsible for acetylcholine synthesis; acetylcholine is in turn a necessary neurotransmitter for cognition. AGEs, found in greater amounts in diabetic patients compared to controls with normal glucose regulation, have also been found in high concentration in AD brains. 

The links between hyperglycemic states and AD can allow for better future diagnostic strategies. Since ADDLs may contribute to lowered insulin levels and insulin resistance in AD brains, the future of diagnosis may entail the measurement of ADDLs. Measurement of AGEs has also been proposed. 

Treatment strategies utilizing this information require more research. The knowledge that there is a reduction of the sensitivity to insulin in AD patients who are not ApoE4-positive suggests that optimization of blood sugar levels may have therapeutic benefits. Insulin-sensitizing agents may potentially be used in the setting of early AD. 

References 

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2. Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease – is this type 3 diabetes? J Alzheimers Dis 2005;7:63-80. 

3. Viola KL, Velasco PT, Klein WL. Why Alzheimer’s is a disease of memory: the attack on synapses by A beta oligomers (ADDLs). J Nutr Health Aging 2008;12:51S-57S. 

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6. Cowie CC, Rust KF, Ford ES, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006. Diabetes Care 2009;32:287-294. 

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11. de la Monte SM, Tong M, Lester-Coll N, et al. Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. J Alzheimers Dis 2006;10:89-109. 

12. Lester-Coll N, Rivera EJ, Soscia SJ, et al. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. J Alzheimers Dis 2006;9:13-33. 

13. Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 2004;3:169-178. 

14. Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates beta- amyloid in early AD. Neurology 2008;70:440-448. 

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Are Rice and Spicy Diets Good for Functional Gastrointestinal Disorders?

Posted By Administration, Friday, April 9, 2010
Updated: Friday, April 18, 2014

263141343_81f39a201b_oAbstract 

Rice- and chili-containing foods are common in Asia. Studies suggest that rice is completely absorbed in the small bowel, produces little intestinal gas and has a low allergenicity. Several clinical studies have demonstrated that rice-based meals are well tolerated and may improve gastrointestinal symptoms in functional gastrointestinal disorders (FGID). Chili is a spicy ingredient commonly use throughout Asia. The active component of chili is capsaicin. Capsaicin can mediate a painful, burning sensation in the human gut via the transient receptor potential vanilloid-1 (TRPV1). Recently, the TRPV1 expressing sensory fibers have been reported to increase in the gastrointestinal tract of patients with FGID and visceral hypersensitivity. Acute exposure to capsaicin or chili can aggravate abdominal pain and burning in dyspepsia and IBS patients. Whereas, chronic ingestion of natural capsaicin agonist or chili has been shown to decrease dyspeptic and gastroesophageal reflux disease (GERD) symptoms. The high prevalence of spicy food in Asia may modify gastrointestinal burning symptoms in patients with FGID. Studies in Asia demonstrated a low prevalence of heartburn symptoms in GERD patients in several Asian countries. In conclusion rice is well tolerated and should be advocated as the carbohydrate source of choice for patients with FGID. Although, acute chili ingestion can aggravate abdominal pain and burning symptoms in FGID, chronic ingestion of chili was found to improve functional dyspepsia and GERD symptoms in small randomized, controlled studies. 

Keywords: Chili pepper, Rice, Functional gastrointestinal disorder, Capsaicin, TRPV1 receptor 

Introduction 

Complaints of gastrointestinal symptoms after food ingestion are common in patients with functional gastrointestinal disorders (FGID) and are reported in 25-64% of irritable bowel syndrome (IBS) patients.IBS patients often complain of food-related gastrointestinal symptoms secondary to more than one specific food. A recent population-based study in the USA demonstrated that 16.5% and 28.3% of IBS patients had intolerance to 1-2 food items and > 2 items, respectively. These statistics suggest that hyper-sensitivity to the ingestion of foods is common in IBS. Research studies also demonstrate that certain foods, such as chili, fructose or fructan containing foods and fatty foods, can affect gastrointestinal motility and sensation and induce gastrointestinal symptoms more than other foods.This suggests that certain foods, and not just the process of eating foods, can aggravate symptoms in patients with FGID. Therefore, modification of either eating habits (reducing meal size and/or the time of meals) or the composition of meals (avoiding specific food items) may benefit patients with FGID, and studies on the effects of food on gastrointestinal functions and symptoms are important. 

The effects of food ingestion on gastrointestinal symptoms in patients with FGID have been extensively studied, mainly in Western countries and with Western diets. Moreover, information regarding the effects of typical Asian foods on gastrointestinal symptoms of FGID is quite limited. This review will focus on the effects of specific but widely used Asian diets/ingredients, "rice and chili or spicy foods," on gastrointestinal functions and their roles on the symptoms of FGID. 

Characteristics of the Asian Diet 

The Asian diet is characterized by a high-carbohydrate, high-fiber, low-fat, and low-meat protein composition. Typical Asian food generally consists of rice and vegetables as the major source of carbohydrate and fiber. Vegetable oil is a common source of fat, whereas fish, eggs, poultry, and pork are the main sources of protein. This is in contrast to Western diets, which are rich in animal fat and beef protein but lower in carbohydrate and fiber contents. In addition, Asian foods often consist of several ingredients, such as chili, to make the foods tastier. 

 


1. Role of rice and high-carbohydrate diet in FGID 

In general, food can aggravate gastrointestinal symptoms by several mechanisms including: exaggerated physiologic responses of the gastrointestinal tract, food intolerance, allergy, increased intestinal gas,and modification of gut motility and sensation. 

Food with high-carbohydrate content may cause symptoms of functional bowel disorders by both allergic and non-allergic mechanisms. As for the latter, carbohydrate may cause gastrointestinal symptoms because of incomplete absorption in the small bowel, such as lactose mal-absorption. In the allergic mechanism, the protein contents in the carbohydrate sources may cause allergic reactions to the gastrointestinal tract, such as gluten in wheat. 

Major types of carbohydrate in the human diet are: starches, sucrose, and lactose. They have to be digested into monosaccharide before being absorbed through the gut mucosa. If the complex-carbohydrate and monosaccharide are not completely absorbed into the small bowel, then these substances will enter the colon and will be fermented by colonic bacteria to produce gas and short-chain fatty acids, which may contribute to the symptoms reported in patients with FGID such as diarrhea, gas, bloating, and abdominal discomfort and pain. The non-absorbable carbohydrates and their metabolites may induce gastrointestinal symptoms by their effects on gut sensation and gut motility, such as decreased gastric tone, decreased lower esophageal sphincter pressure and accelerated small bowel transit. A recent study in Asia (India) demonstrated that there is a similar prevalence of lactose intolerance in IBS patients and healthy controls. The authors performed lactose hydrogen breath tests in 124 IBS patients and 53 age- and gender-matched healthy controls. They found a similar prevalence of abnormal lactose hydrogen breath tests in IBS patients and healthy volunteers (72% vs. 60%). However, IBS patients developed gastrointestinal symptoms more often than healthy volunteers after ingestion of lactose (56% vs. 34%). This higher rate of gastrointestinal symptoms suggests that there is a role of visceral hypersensitivity in the expression of carbohydrate mal-absorption symptoms and that the completeness of small intestinal absorption of carbohydrate is important in patients with IBS and can associate with their IBS symptoms. 

2. Rice is completely absorbed in the small intestine, producing little gas 

Major sources of complex carbohydrate or starch in the human diet are wheat, rice, oat, potato, and corn. The effects of each complex carbohydrate or starch on gastrointestinal symptoms depend on its fiber content, its allergenicity, and the completeness of the small bowel digestion and absorption. In Western countries, wheat is the major source of carbohydrate. It may cause gastrointestinal symptoms by allergic reaction to gluten, the major protein component of wheat. In a recent meta-analysis of 14 studies, patients who fulfill the criteria of IBS (n = 2,278) have a higher prevalence of celiac disease than controls (n = 1,926). The pooled prevalence of positive IgA-class antigliadin antibody, either positive endomysial antibody or tissue transglutaminase, and biopsy-proved celiac disease in IBS were 4.0%, 1.63%, and 4.1%, respectively. Pooled odds ratios (95% confidence interval) for positive IgA-class antigliadin antibody, either positive endomysial antibody or tissue transglutaminase, and biopsy-proved celiac disease in IBS patients compared with controls were 3.40 (1.62-7.13), 2.94 (1.36-6.35), and 4.34 (1.78-10.6), respecttively. This implies that, in a subgroup of IBS patients, ingestion of a gluten-containing diet may aggravate and avoidance of the diet may improve gastrointestinal symptoms.Furthermore, wheat ingestion produces the highest peak of breath hydrogen compared to other sources of carbohydrate such as corn, oats, potatoes, beans, and rice in healthy humans. This suggests that wheat carbohydrate is not completely absorbed in the small bowel and that it may produce gastrointestinal symptoms, independent of gluten hypersensitivity.

Rice is the major source of carbohydrate in Asian populations. In contrast to wheat and other sources of carbohydrate, rice is completely absorbed in the small bowel and produces very little intestinal gas after ingestion. A previous study demonstrated that the amount of hydrogen, a maker of carbohydrate metabolism by intestinal bacteria, in breath samples after rice ingestion is minimally increased and not significantly different from the fasting period. Furthermore, rice has been shown to have a low allergenicity. Previous studies demonstrated that serum IgG levels produced in reaction to several kinds of food such as wheat, beef, pork, lamb, soybean, shrimp, egg, and crab were increased in IBS patients compared to healthy humans, but the serum IgG levels produced to rice in IBS patients is mild or not increased. A study from China in 37 IBS,  functional dyspepsia, and 20 healthy controls demonstrated that serum IgG antibody titers to rice was similar in IBS (28.7 ± 0.5 U/mL) and functional dyspepsia patients (29.5 ± 0.7 U/mL) compared to healthy controls (28.4 ± 0.5 U/mL). In contrast, the serum IgG antibody titer to wheat was increased in IBS patients (60.6 ± 3.4 U/mL) compared to functional dyspepsia patients (49.4 ± 2.0 U/mL) and healthy controls (48.1 ± 2.0 U/mL). This low production of IgG suggests that rice has a low allergenicity compared to other common foods. 

3. Rice has lowest fiber content compared to other common sources of carbohydrate 

It has been reported that fiber speeds up human gut transit and can improve constipation symptoms. However, its benefit in FGID is limited. Recent meta-analysis studies on the effect of fiber on global symptoms of IBS patients demonstrated conflicting results. In addition, it may worsen abdominal pain and bloating symptoms. In healthy humans, ingestion of fiber (psyllium) can delay intestinal gas transit and cause more gas retention after intestinal gas perfusion. Thus, a high-fiber diet may worsen abdominal bloating and pain by delaying intestinal gas transit and increasing gas production in the colon secondary to bacterial fermentation. In certain parts of Asia, such as in India, healthy controls and patients with IBS have more dietary fiber (51.7 and 52.3 g/day, respectively) than the recommended amount for the general population (20-40 g/day). Therefore, increasing the dietary fiber consumption of functional gastrointestinal disorder patients in certain parts of Asia may not provide any benefit but may worsen the bloating and abdominal pain symptoms. 

Although the Asian diet is rich in fiber, rice - the widely used complex carbohydrate - has the lowest fiber content compared to other kinds of cereal. A previous study demonstrated that the total fiber content (insoluble + soluble fiber) of different kinds of cereal is lowest in rice and highest in wheat (4.1% in rice vs. 12.5% in wheat). As high-fiber may worsen abdominal pain and bloating symptoms, rice may be the most preferable carbohydrate source for functional gastrointestinal disorder patients with predominant symptoms of bloating and abdominal pain. 

4. Clinical studies suggest benefits of rice-base meal in IBS 

Rice has been the major source of carbohydrate in exclusion diets in several clinical studies. These studies demonstrated that the exclusion diet is well tolerated and can improve IBS symptoms in both open and controlled studies. A recent study by King et al. suggests that the rice-based exclusion diet may improve symptoms in IBS by reducing intestinal gas production. The study was performed in 6 female IBS patients and 6 female controls by measuring 24-hour hydrogen and methane production after ingestion of rice-based exclusion diet or standard diet, in a crossover controlled trial, using a whole-body calorimeter. The authors found that after standard diet the gas excretion rate and hydrogen production was higher in IBS patients (2.4 mL/min and 332 mL/24 hr, respectively) than in controls (0.6 mL/min and 162 mL/24 hr). The rice-based exclusion diet reduced hydrogen production compared to standard diet in both IBS (79 vs. 332 mL/24 hr) and controls (95 vs. 162 mL/24 hr). In addition, in IBS patients, the exclusion diet reduced symptoms [symptom score = 8 (5.25-10) vs. 4 (3-7)] and reduced the maximum gas excretion rate compared to the standard diet (0.5 vs. 2.4 mL/min). 

Recently, the very-low-carbohydrate strategy has been shown to improve IBS-D symptoms in a small open study. The authors found that 13 of the 17 patients who were enrolled completed the study. Ten (77%) of the patients who completed the study reported adequate relief of IBS symptoms. Furthermore, the stool frequency, stool consistency, pain scores, and quality of life were significantly improved. 

Because there have been reports of inadequate dietary intake because of food avoidance in IBS patients, the avoidance of poorly-absorbed carbohydrates combined with the consumption of well-absorbed carbohydrates or rice may be more appropriate than the use of very-low-carbohydrate diets in the dietary treatment strategy for IBS patients. 

All together, rice may be the best source of carbohydrate for patients with functional bowel disorder because of its low allergenicity, its nearly complete absorption in the small bowel, and its low fiber content. In addition, a small crossover controlled study supports its benefit in IBS. 

5. Effect of chili on FGID 

Chili and spicy food are common in most Asian countries. The average daily chili consumption in Asian people is 2.5-8 g/person. It is much higher than that of 0.05-0.5 g/person in European and American peoples. Recent studies suggest that acute and chronic ingestion of chili can modify gastrointestinal symptoms in FGID. Whether or not a high prevalence of spicy food modifies gastrointestinal symptoms at the population level is not known. In addition, data on the effect of chili or spicy foods on FGID in Asian countries with a high prevalence of spicy food have been limited. 

6. Capsaicin mediated visceral nociception in FGID 

The active ingredient of chili is capsaicin. Capsaicin can modulate gastrointestinal sensation via capsaicin or TRPV1 receptors. These receptors have been found at different levels throughout the gastrointestinal tract. Capsaicin, acid, and heat can stimulate the TRPV1 receptors and mediate a sensation of burning and pain. Several studies suggested that TRPV1 receptors can mediate sensations of warmth, pressure, cramping, and pain in the human gut. Increases in the number of TRPV1 receptors have been found in the gut mucosa of patients with conditions associated with visceral hypersensitivity, including in the esophagus of patients with non-erosive reflux disease (NERD), in the colon of patients with irritable bowel syndrome and in the rectum of patients with rectal hypersensitivity. Recent studies demonstrated that patients with FGID, including functional dyspepsia and irritable bowel syndrome, exhibit gut hypersensitivity to capsaicin or capsaicin containing chili. Hammer et al. studied the effect of 0.75 mg capsaicin powder ingestion on gastrointestinal symptoms in 54 functional dyspepsia patients and 61 healthy controls. They found that after capsaicin ingestion, nausea, a flutter-like sensation, warmth and abdominal pain scores were higher in functional dyspepsia patients than in healthy volunteers. A recent study in 20 IBS-D patients demonstrated that ingestion of chili-containing meals produces higher abdominal pain and abdominal burning symptom scores than standard meals and when compared to the symptoms reported by healthy volunteers in response to ingestion of chili-containing meals. Studies suggest that abdominal pain and burning symptoms seem to be the typical gastrointestinal symptoms of capsaicin hypersensitivity, whereas abdominal bloating symptoms seems to be independent of the capsaicin pathways. 

Low-grade inflammation in the gastrointestinal tract has been proposed as a major pathogenesis of FGID, especially in irritable bowel syndrome. Up-regulation of TRPV1 pathways resulting in visceral hypersensitivity to mechanical and chemical stimulations has been reported following an induction of colonic inflammation in an animal model. In humans, gut inflammation has been reported to be associated with an increased number of TRPV1-expressing nerve fibers. Thus, hypersensitivity of the TRPV1 pathways in patients with FGID is likely a result of low-grade inflammation and may be an important pathogenesis of gut hypersensitivity, abdominal pain, and abdominal burning symptoms in FGID. 

7. Desensitization of capsaicin receptors, its role on patients' symptom profiles and treatment of FGID 

It has been reported that prior exposure of esophageal mucosa to capsaicin solution do not affect esophageal sensation in response to acid perfusion or to balloon distention. However, the study evaluated the effect of single stimulation of esophageal mucosa by perfusion of capsaicin solution into the esophagus and could not exclude the desensitization effects of capsaicin receptors in the gut mucosa after repeated exposure to capsaicin agonists. 

It has been demonstrated that TRPV1 receptors can be desensitized by repeated exposure to capsaicin. Recent small studies suggested that chronic ingestion of capsaicin containing chili can modify dyspepsia symptoms in functional dyspepsia patients and GERD symptoms in NERD by decreasing dyspeptic and GERD symptoms, respectively. Bortolotti et al.randomized 30 functional dyspepsia patients to receive 2.5 g/day of red pepper powder or placebo in a double-blind manner for 5 weeks. They found that red pepper significantly improved overall symptom scores, epigastric pain, fullness, and nausea scores relative to placebo. The overall symptom scores decreased from 3.3 ± 0.6 at baseline to 1.7 ± 0.2 at the end of week 5 for red chili treatment compared to from 3.4 ± 0.7 to 2.5 ± 0.3 for placebo treatment. In a preliminary study in 8 patients with NERD, red chili ingestion for 6 weeks significantly improved total GERD, heartburn, and regurgitation symptom scores compared to placebo. The authors found that, at baseline, total GERD scores, heartburn, and regurgitation scores were similar comparing between chili and placebo capsules (chili vs. placebo: 7.6 ± 3.7 vs. 4.7 ± 2.8, 4.6 ± 2.3 vs. 3.2 ± 2.1, and 2.9 ± 2.4 vs. 1.5 ± 1.6, respectively). At the end of week 6, red chili significantly decreased GERD symptom scores (chili vs. placebo: 0.9 ± 1.2 vs. 4.9 ± 2.4), heartburn symptom scores (0.4 ± 0.6 vs. 3.7 ± 1.6), and food regurgitation symptom scores (0.5 ± 0.8 vs. 1.3 ± 1.6) compared to placebo. The effects of chili ingestion on functional dyspepsia and GERD symptoms were observed after the 2nd week of treatment in both studies. The similar effects of chronic ingestion of red chili in functional dyspepsia and NERD patients suggests that capsaicin receptors play role on the development of both functional dyspepsia and NERD symptoms and is consistent with previous reports of visceral hypersensitivity to capsaicin in functional dyspepsia54 and increase TRPV1 receptors in NERD.42 In contrast, a previous study in 12 healthy volunteers reported that chronic chili ingestion induce more gastroesophageal refluxes. However, the duration of chili ingestions was too short (≤ 1 week) in relative to the other studies, which showed the desensitization effect of chili (5-6 weeks). These limited data suggest that the natural capsaicin agonist (chili) may have a therapeutic role for pain and burning symptoms in FGID and more research studies are needed to confirm this hypothesis. 

The effect of spicy food, which is frequently eaten in Asia, on the gastrointestinal symptom profiles in FGID at population level is not clearly known. Studies of GERD symptoms in Asian patients have reported a lower prevalence of heartburn compared to Western patients. A study of GERD symptoms in German patients who underwent 24-hour esophageal pH monitoring showed that both heartburn and acid regurgitation are the main typical GERD symptoms, whereas a similar study in an Asian country (Thailand) with a high prevalence of spicy food reported only acid regurgitation, but not heartburn, as the main GERD symptom (Fig. 1). Furthermore, epidemiologic studies in Asian countries, including China, Iran, and Thailand, demonstrated lower heartburn/regurgitation symptom prevalence ratios compared to Western or developed countries with a low prevalence of spicy food. However, the low heartburn/regurgitation symptom prevalence ratio was not observed in Korea. In Turkey, an European country with a high prevalence of spicy food, the prevalence of heartburn in the population is much lower than the prevalence of acid regurgitation (weekly heartburn vs. acid regurgitation: 10% vs. 15.6%, respectively).71 When the studies that reported the prevalence of annual regurgitation and heartburn symptoms were included, studies of the American population reported a heartburn/regurgitation prevalence ratio of 0.91-0.94, whereas studies in China reported a lower ratio of 0.34. There has been no study that directly compares GERD symptom profiles between Asian and Western peoples or patients in the area of high and low prevalence of chili in the diet. However, the collective results of the available studies imply that acid or gastric content regurgitation into the esophagus in people in certain regions of Asia is not perceived as heartburn symptoms by the esophagus in the same way that heartburn symptoms are perceived by Western people. The high prevalence of spicy food may play a role in this finding, but this hypothesis has not been proven. The low prevalence of heartburn symptoms is not likely to be a misinterpretation of acid reflux symptoms in Thai people because acid perfusion tests produce no symptoms in most Thai GERD patients (GI Motility Research Unit, Chulalongkorn University, Thailand, un-published data). However, the heartburn/regurgitation symptom prevalence ratio is not lower in Mexico, where the prevalence of spicy food is high. This inconsistency suggests that not only spicy food, but also other factors, may influence the sensitivity of esophagus to gastro-esophageal reflux contents at the population level.   

In summary, capsaicin or TRPV1 receptors are involved in the pathogenesis of burning and pain symptoms of the gastrointestinal tract. Recent small studies suggest that the chronic use of capsaicin-containing chili can decrease heartburn and abdominal pain in GERD and dyspepsia, respectively. In addition, the ratio of the prevalence of heartburn/regurgitation symptoms in the population is lower in several parts of Asia; this lower rate may be related to the high prevalence of chili or spicy food. 

Conclusion 

Rice seems to be the most preferable source of carbohydrate in patients with FGID. It has a low allergenicity and fiber content; it is also completely absorbed in the small bowel and produces little gas after ingestion. Therefore, it should be advocated as a major source of carbohydrate for patients with IBS and those with other functional GI disorders. 

There has been increasing evidence to support the role of capsaicin receptors in the pathogenesis of symptoms of FGID. Preliminary studies support the role of desensitization of capsaicin receptors by chili, a natural capsaicin receptor agonist, for the treatment of functional dyspepsia and NERD. However, more research studies are needed to confirm this hypothesis. 

Footnotes 

Financial support: This review was supported by the Ratchadapisek Sompotch Endowment Fund (GI Motility Research Unit grant). Conflicts of interest: None. 

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Source: J Neurogastroenterol Motil. 2010 April; 16(2): 131-138. Published online 2010 April 27. doi: 10.5056/jnm.2010.16.2.131. By, Sutep Gonlachanvit MD.

Tags:  food and drink  gastrointestinal disease 

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Low Testosterone Linked to Heart Disease

Posted By Administration, Thursday, March 25, 2010
Updated: Friday, April 18, 2014

3227286803_3cbf819f60_m Low levels of testosterone have been associated with increased body weight, insulin resistance (a precursor to diabetes and a risk factor for heart disease), and poor cholesterol levels.  These metabolic factors ultimately lead to cardiovascular disease.   

A noteworthy overview of androgen deprivation therapy and its tight link to cardiovascular disease has been published in the journal Circulation.  In it, a group that included members of prominent heart, cancer and urological societies, issued a well-researched position stating that prostate cancer patients who are on androgen deprivation therapy (ADT) are at an elevated risk for getting heart disease.  

Evidence shows that when one’s androgen levels are lowered, a metabolic syndrome ensues.  This does not necessarily mean that patients should not be on ADT, but does pave the way to new screening strategies for metabolic syndrome for those on ADT.   

Most importantly, this brings to light, again, the negative effect that low testosterone has on insulin sensitivity and the heart.  Metabolic syndrome and cardiovascular disease can potentially be prevented via the optimization of testosterone levels.  

For males, it is important to understand what your “total” and “free” testosterone levels are, and to perform a thorough workup that focuses of deciphering the cause of why the levels are low (or high) in the first place.  Then, a treatment strategy should ensue.  This should focus on addressing the cause, first and foremost.  Thereafter, treating the cause is key.  

There are many options for patients with low testosterone.  Lifestyle changes should ensue as they are often significant contributors to low testosterone levels.  Supplements and/or medication that can boost testosterone levels can also be judiciously utilized.  There are also supplements and medications that can work on preventing the aromatization of testosterone (conversion of testosterone into estrogen in fatty tissue).  Those patients on intentional ADT in the setting of prostate cancer cannot be on androgen replacement therapy.   

- Zina Kroner, DO
 

Tags:  heart disease  testosterone 

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Have We Abandoned Our Children to Toxins?

Posted By Administration, Friday, March 19, 2010
Updated: Friday, April 18, 2014

Many of us are aware of the recent Centers for Disease Control (CDC) report indicating that 1 in every 110 children has some form of autism. Fewer know the work of Dr. Philip Landrigan, of Mt. Sinai Medical School, who was quoted in a February 25, 2010, New York Times editorial by Nicholas Kristof: "Do Toxins Cause Autism?"  According to Landrigan, 1 in 6 American children is currently learning or behaviorally disabled. childwithmaskAnother excellent resource is the work of ACAM member, Dr. Kenneth Bock, chronicled in his recent book Healing the New Childhood Epidemics: Autism, ADHD, Asthma and Allergies The Groundbreaking Program for the 4-A Disorders.

As the following, recent news stories indicate, our nation’s children live in an environment that is increasingly toxic:

  • Studies show danger of even small amounts of lead in children's blood
  • Dust bunnies tainted with toxins? Household dust consists of a potpourri that can include lead, arsenic, and other potentially harmful substances
  • Phthalates (plastics softeners used in children's products) predispose mice to allergies

Add to these the fact that our children are exposed to more vaccinations than ever before. In 1985, children were vaccinated for seven diseases; that number has swelled to 16. And vaccinations are grouped together solely to make children more likely to get them, even though the risks increase to an unknown degree.

Parents deserve to know that vaccines are neither 100 percent effective nor 100 percent safe. A 16-year old girl lost her vision following vaccination against the HPV virus. Do we have to wait until most children are autistic or otherwise damaged before we try to do something about this situation?

Published March 16, 2010 at ANH-USA.org. Have We Abandoned Our Children to Toxins?

Tags:  toxins 

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Aging Gracefully Now

Posted By Administration, Thursday, March 18, 2010
Updated: Friday, April 18, 2014

4016109413_10fc490c33_m Aging in the West conjures up images of people in nursing homes, unable to enjoy the few remaining years in their lives and totally dependent on other people for some of the basic things in life such as eating or bathing themselves. Who wants to have a long life if this would be the eventual outcome for anyone? How many people live independently and abundantly into their senior years? How can someone make sure that they could enjoy their lives free from chronic disease or infirmities?

That’s where the concept of holistic preventive care comes in. Preventive care unfortunately, usually just involves early detection and screening in allopathic medicine. It’s the advice given to women about annual Pap’s smears and mammograms or PSA testing for men at a certain age. There’s more to prevention however than getting yearly tests. Prevention should be done on a daily basis by taking care of the body’s needs, primarily through clean food, water and air. Then, there are also important things such as sleep, exercise, stress reduction, detoxification and intake of nutritional supplements.

Our health is very closely related to that of the health of our environment. Just as clean air and water are necessary for the survival of the earth, they are also needed for our survival as a species.

There’s a concept called “internal milieu.” Dr. Louis Pasteur, on his deathbed, admitted that “the microbe is nothing, the terrain is everything.” What this means is that for instance, if several people were exposed to the same germ/pathogen, not everybody gets sick. Some people may be more resistant to illness because of genetics as well as other factors that influence their immune system (diet, presence of toxins.) If I may borrow one of my colleague’s analogies, “Our genes are like a loaded gun, our environment pulls the trigger.”

The major medical systems in the world, such as Chinese medicine, Tibetan medicine and Ayurveda, all emphasize the important role that food plays in prevention of illness as well as influencing the course of illness. Unfortunately, this is not the case in other medical systems where people are told that they can eat anything after a certain diagnoses. Ever wonder why there are fast food joints that sell deep fried or highly refined foods at major medical centers?

Anyway, in more practical terms, what are the factors that could cause premature aging?

Among the different reasons behind aging there are hormonal imbalances, nutritional deficiencies, oxidative stress, chronic inflammation and toxicities. Just like doing maintenance work on our cars is imperative to make them work more efficiently, we need to do the same thing to our bodies. Let’s start with the basics. The food we give our bodies could be compared to the things we do to maintain our cars. Again, to borrow another analogy, carbohydrates could be compared to the fuel system, fats to the oil used to lubricate the car and protein to the actual skeleton/frame of the car. Neglect one of these and it could lead to eventual breakdown of our cars and in this case, our bodies.

Regarding food, I believe that everybody is different and therefore, have different food requirements. One of my mentors taught me that we in North America, actually don’t have a traditional diet unlike peoples from Asia, Africa or the Mediterranean. The Standard American Diet (SAD) of meat and potatoes in general doesn’t give us adequate nutrition to prevent illness. What I would recommend for one person may be different from what I recommend to another.

For instance, for Asians in general, a typical meal of fish with rice and vegetables should suffice. However, for a Caucasian, I may recommend food combining with protein and vegetables without any starches during a meal.

There are many diets available out there. These include the blood type diet, the South Beach diet, raw food diet, etc. In general, I would recommend eating organic foods. Having greater portions of vegetables and fruits in the diet and a limited amount of meat would work for most people. As far as meat is concerned, free-range chicken or grass-fed beef would be a better choice than regular chicken or beef.

Then, there’s concern about fish or seafood. The higher you go up on the food chain, the greater the chances of mercury toxicity. I would recommend smaller fish such as anchovies or sardines.

There’s the timing of meals that’s also equally important. I would recommend small, frequent meals rather than three “square meals a day.” Not eating after 6 pm ideally would be best, but if necessary, at least keeping it light at night would be advisable.

Nutrition is a very touchy subject because of the different recommendations you get from authorities. What I would recommend in general is to only eat when hungry and only eat as natural as possible. Any food adulterated by man (boxed cereal grains, “low-fat” TV dinners) could cause more problems long-term. Just a quick note, fat is what tells our satiety centers that we’re full. Thus, a low-fat meal won’t really curb someone’s appetite or help with weight loss.

- Joel Lopez, MD, CNS

Tags:  anti-aging 

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Integrated Medicine for Neurologic Disorders

Posted By Administration, Tuesday, March 9, 2010
Updated: Friday, April 18, 2014

Imgres Integrated Medicine for Neurologic Disorders is a book which addresses herbal and holistic medicine for brain health and neurological disorders such as Alzheimer’s Disease, Parkinson’s Disease, Multiple Sclerosis, Stroke, Migraine, and Seizures. This book can help patients and medical practitioners to integrate Western medicine with herbal and holistic medicine to reduce symptoms and slow disease progression.

Sheryl Shook, Ph.D., a physiology professor with a Ph.D. in neuroscience, co-authored the book with Dr. Sidney Kurn. They have combined their expertise to work in the community educating about improving health by integrating the benefits of mainstream medicine with the rich and valuable practices from many cultures that rely on plants, nutrition, and lifestyle for healing. 

“Keeping your body healthy is an expression of gratitude to the whole cosmos - the trees, the clouds, everything.” Thich Nhat Hanh 

As one of the oldest medical subspecialties, neurology has a long history of clinical observation and theoretical development. The extreme complexity and inaccessibility of the nervous system continues to challenge researchers, compared with the rapid, technological development of other specialties such as cardiology or nephrology. Until the last 20 years, even drug treatments were rather limited. Neurologists have witnessed a rapid growth in our pharmacopoeia, including drugs for disorders previously untreatable such as ALS and Alzheimer’s disease.

 Most exciting is the seminal breakthrough in seeing an underlying order involving a few abnormal processes that manifest variably as Parkinson’s disease in one patient, Alzheimer’s disease in another, and so on. Numerous articles report on studies revealing inflammation, excitotoxicity, oxidation, genetic predilection, nutrient deficiencies and environmental toxicity in the onset and development of neurologic disorders. Disorders as disparate as stroke and multiple sclerosis, share these underlying processes. The contribution of each process, the particular positive feedback loops, and particularly the genetic predilection appear to determine the particular disease in any one individual. Even the fields of neuroprotection and system theory, generally not part of mainstream neurology, are receiving attention with numerous articles in peer-reviewed journals (1). 

Unfortunately, despite these important developments in clinical neuroscience, patients continue to suffer the symptoms of neurologic illness. Our drugs are not as effective as we would like, illnesses continue to progress, and the chronicity of some diseases overwhelm our best efforts. As patients and clinicians, we are committed to being pragmatic, finding what works, even if usage is based on tradition without good double-blind, placebo-controlled trials. Large randomized trials are expensive, and for natural herbs and nutrients, do not necessarily lead to a patentable product. Numerous studies on supplements exist and appear regularly in peer-reviewed journals. Studies may not rise to the level of large randomized trials necessary for FDA approval. The absence of this type of evidence is not proof of lack of efficacy. In regards to toxicity, the long history of usage provides ample information, and new interactions are reported on a regular basis. The “gold standard” of clinical drug usage, the Physician’s Desk Reference (PDR), has its second addition on herbs and nutrients. The standard pharmacist’s reference on herbs, nutrients and their interactions has also been re-edited. These texts, plus innumerable Medline references help guide the judicious use of supplements in clinical practice, or, what I call, clinical supplementation.

 Integrated Neurology is the practice of neurology utilizing all appropriate measures to alleviate suffering in an individual patient with a neurologic disorder. This may involve drugs, herbs, nutrients, acupuncture and a large group of bodywork modalities. It is an “open system”, drawing information as needed from science, medicine and the more traditional healing arts. It is “evidence based”, from large randomized trials, millennial long traditional usage as well as anecdotal evidence. The principle of “do no harm”, applies to Integrated Neurology as it does to medicine in general. Even though herbs and nutrients are generally much less toxic than drugs, known side effects, toxicities and drug interactions exist and require careful consideration. Integratedneurology.net offers the reader an introduction to Integrated Neurology including basic principles, treatment suggestions, references and appropriate linkages. Feedback is welcome on the E-mail site. 

“The wisest mind has something yet to learn.”  George Santayana 

          - Sidney Kurn, MD

References:

1. Albergina L and Colangelo AM The modular systems biology approach to investigate the control of apoptosis in Alzheimer’s disease neurodegeneration. BMC Neurosci. 2006 Oct 30;7 Suppl 1:82 (Epub ahead of print)

Tags:  integrative medicine  neurology 

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Soy and Fertility in Men

Posted By Administration, Thursday, March 4, 2010
Updated: Friday, April 18, 2014

There is so much controversy about the effect of soy foods on men’s fertility.  With each study that is released, a news article follows declaring it to be either safe or harmful for men’s fertility.   I would like to go through some of the studies in this area and review the significance of them before drawing a conclusion based on the current evidence.  Soy is well-known for its health benefits for men, including the reduction of risk for both cardiovascular disease and prostate cancer.  Due to these benefits, it has become a larger part of the North American diet than it ever has been in the past so it is important to fully understand its impact on hormones and fertility.

Effects of Soy on Infants and During Pregnancy on Adult Male Fertility

The following studies investigate reproductive effects on men who were given soy products either through infant formula, or while their mothers were pregnant.  This is a very sensitive time of development for the reproductive organs, so much concern remains about the possibility of permanent negative effects.

Soy Formula in Infant Male Marmoset Monkeys causes no Adverse Effects
This study concluded that infant feeding with soy formula has no major adverse reproductive effects in male marmoset monkeys. Although it did not appear to affect fertility, soy infant formula did alter testis size and cell composition.

Again I would like to mention here that both rats and monkeys produce much higher levels of equol (an estrogen like substance which is much stronger than soy isoflavones) in their intestines than humans in general.  The equol is produced through fermentation of isoflavones by bacteria which reside in the intestine.  It’s hard to compare humans directly with rats or monkeys especially when it comes to estrogenic effects.  Studies investigating the effects of phytoestrogens on the fertility of different animal species have been very inconsistent. This indicates that soy has very species specific effects on fertility and highlights the need for more studies on humans before we can draw definitive conclusions.

Study on Vegetarian Mothers and Hypospadias in Infants
This famous study investigated the difference between vegetarian and omnivorous women and the likelihood of a condition known as hypospadias in their newborns.  Hypospadias is a condition (which is currently on the rise) where the urethral opening is in a lower position.  This study found that significantly more of the vegetarian mothers had babies with hypospadias.  As vegetarians have a greater exposure to phytoestrogens than do omnivores, the researchers concluded that phytoestrogens may have a negative effect on the developing male reproductive system. However, this study was not specific for soy, it only examined whether or not vegetarians tended to have more infants with hypospadias. Other factors cannot be excluded for example, vegetarians could be more likely to be deficient in other vitamins or nutrients such as B12, and could also be consuming a larger amount of estrogenic pesticide 
Soy Infant Formularesidue, and this study did not question participants about consumption of organic foods.   It was also found that the vegetarian mothers who did not take iron supplements had more infants with hypospadias.  In Japan, there are 1/10th the number of infants born with hypospadias as there are in North America and yet there is a much higher level of phytoestrogen consumption.  Therefore, this study is not fully conclusive that phytoestrogens are the cause of this developmental condition since there are too many unaccounted for variables.

Study on Soy Formula in Infants and Reproductive Outcome In Young Adulthood
This study on 811 men and women, who were fed either soy or cow milk formula as infants were assessed in young adulthood for their pubertal maturation, menstrual and reproductive history, height/weight, and current health.  It concluded that exposure to soy formula does not appear to lead to different general health or reproductive outcomes than exposure to cow milk formula in infancy. This study did not go into details asking about length of time to conceive. Also, no reproductive health markers were reported for male subjects with the exception of sexual maturation. Although men were questioned about pregnancy outcomes in partners the results were not reported.

In conclusion on the subject of male reproduction and feeding of infant soy formula, it appears that overall there may be a risk for some long-term reproductive developmental changes, however, the full effects of this are unknown and may not go so far as to cause fertility concerns.  However, as we know from so much current data, breast milk is a far superior nutrition method for infants, and avoids any of the risks that soy formula may hold.

Studies on Male Adult Animals

Phytoestrogenic Plant given to Adult Male Mice – Some Effects on Reproduction
A phytoestrogenic plant(pueraria mirifica) was given in two doses, one high and one low,  to a group of adult male mice. Neither treatment had effect on testicular weight, sperm count, LH, FSH or testosterone. However the high (100mg/kg) dose reduced the weight of epididymis, seminal vesicle and sperm motility.  There were no effects on fertility. This effect was seen to be reversible after the phytoestrogen was stopped. However, this plant, though it does contain some of the same components as soy, is not identical to soy.

Acute Exposure of Adult Male Rats to Dietary Phytoestrogens Causes Temporary Reduction in Fertility
This study found that lipid peroxidation damage of sperm was increased in rats fed a high phytoestrogen diet for 3 days.   No such changes were noted in low phytoestrogen group.  As in the previous study, this effect was temporary, with fertility returning to control levels by day 12. Rats who were fed the phytoestrogens for longer than 6 days did not show this reduction in fertility and in fact showed no change in any reproductive parameters.

Phytoestrogens cause no Negative Effects on Fertility of Rhesus Monkeys
In this study, phytoestrogens were given to rhesus monkeys at the age of puberty.  They had no adverse effects on the reproductive systems of male or females as evaluated by hormone concentrations.  Cardiovascular benefits were observed in the monkeys receiving the phytoestrogens.

Studies on Adult Men

Soy Products Related with Slightly Lower Testosterone and Lower Estradiol in Japanese MenMale Symbol

This study on Japanese men investigated the relationship between soy product intake and serum testosterone and estrogen concentrations.  The results found that blood levels of estradiol concentration were significantly lower with increased soy product intake, and blood estrone levels were not related to soy intake.  Testosterone levels were also lower with increased soy intake but this effect was so slight it did not reach significance in the study.  This study also concluded that this may be part of the reason soy reduces risk of prostate cancer in men.

Soymilk Given to Japanese Men Results in Lower Estrogen Concentrations

This  second study on Japanese men investigates the effects of drinking 400 mL daily soymilk on serum estrogen and testosterone concentrations.  In contrast to the previous study, the results of this study indicate that soymilk consumption is associated with lower levels of the estrone form of estrogen.  In this study there was no effect of soymilk on any of the other hormones measured including testosterone, estradiol, and sex hormone binding globulin.

These two studies indicate that soy can affect serum estrogen levels.  It is known from other research that estrogen is required for proper formation of sperm, but also, that elevated levels of estrogen can interfere with fertility (especially if testosterone to estrogen ratios are altered).  So, what we can say is that a good level of balance of estrogen is required for optimal male fertility, and the real question is, does soy interfere with the balance of estrogen enough to impact actual fertility parameters in males.  These two studies do not answer this question, so we need to look more to studies on soy consumption and the end result on adult male fertility.

Soy Food Intake Related to lower Sperm Concentration Among Men from an Infertility Clinic
This very well-known study took a group of men from a fertility clinic and evaluated the relationship between soy food intake and sperm quality and count.  It found that there was a relationship between the intake of soy foods and the reduction of sperm concentration.  72% of men in this study were either overweight, or obese according to their BMI levels.  The relationship was more pronounced in the men who had the highest sperm concentration and among overweight or obese men. Soy foods did not reduce sperm motility, sperm morphology, or ejaculate volume.  This suggests that because androgens are converted into estrogen in fatty tissue,  this may increase tissue sensitivity to phytoestrogens in those who have higher amounts of body fat.   This study did not consider that those who eat more soy could be exposed to more estrogenic pesticides (it did not ask about consumption of organic versus non organic soy).  It also did not account for the addition of soy in many foods that may not have been reported by the participants (such as soy based additives in baked goods, processed foods and so forth).  Therefore, although this study is quite interesting, it not conclusive.   
Couple preparing a healthy mealThis study does however,  make an important association between elevated body mass index, and effects of soy on fertility in men.

Healthy Adult Men of Normal BMI: Soy Isoflavones have No Negative Effect on Sperm Parameters

This new study from the University of Guelph which involved healthy adult men with a healthy body mass index investigated the effects of isoflavones on sperm parameters.  In this study, men were given a daily serving of soy isoflavones in low concentration, high concentration, and then isoflavone free milk protein isolate.  The different substrates were given for 57 days each separated by a 28 day ‘break period’.  The study showed no significant effect of soy isoflavones on sperm concentration, motility and morphology of the men.  This study adds to the evidence that soy has a much lesser effect on semen parameters in men of healthy body mass index.

Summary

In summary, more research needs to be done before we can have any conclusive answers about the impact of soy on male fertility.  There are many conflicting studies on this subject, which indicates we need to investigate further.  There are a few points though that we can learn from the current research which can probably be protective to male fertility, and also allow men to have some of the health benefits that soy foods can provide.

1)  Soy can have a temporary, acute effect on adult male reproductive parameters if taken in high quantities, especially if not normally included in the diet.  Therefore, it would not be a good idea to consume large amounts of soy directly around the time when your partner is ovulating.

2)  Soy appears to reduce sperm concentration in males who are overweight or obese, so if you are overweight, try to achieve a healthy BMI.  In cases where BMI is high, soy foods might not be the best staple for the diet while trying to conceive.

3)  It is probably likely that small amounts of organic soy have little negative effect on reproduction in males of healthy body mass index and can provide health benefits such as improvement of cardiovascular profiles, and reduction of risk for prostate cancer.  More research still needs to be done in order to truly understand the impact of soy fertility of healthy adult males.

- Fiona McCulloch, ND


References

Anthony et al. J Nutr. 1996 January; 126(1): 43–50. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys.Beaton et al. Soy protein isolates of varying isoflavone content do not adversely affect semen quality in healthy young men. Fertility Sterility in press

 

Chavarro et al. Hum Reprod. 2008 November; 23(11): 2584–2590Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic

Eddy et al. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 1996 137 4796 – 4805.

A Glover et al. Acute exposure of adult male rats to dietary phytoestrogens reduces fecundity and alters epididymal steroid hormone receptor expression. J Endocrinol. 2006

Hess RA. Estrogen in the adult male reproductive tract: a review. Reprod Biol Endocrinol 2003; 1: 52.

Jaroenporn S et al. Effects of pueraria mirifica, an herb containing phytoestrogens, on reproductive organs and fertility of adult male mice. Endocrine 30(1) August 2006.
Jay et al. Aromatase Inhibitors for Male Infertility. The Journal of Urology – February 2002 (Vol. 167, Issue 2, Part 1, Pages 624-629)

Karen et al. Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood. Hum. Reprod. 21: 896-904.

Nagata et al. Nutr Cancer. 2000; 36(1): 14–18. Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men.

Nagata et al. Cancer Epidemiol Biomarkers Prev. 2001 March; 10(3): 179–184. Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men.

North et al. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. BJU Int. 2000 January; 85(1): 107–113.

Rozman et al. NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Soy Formula. Birth Defects Res B Dev Reprod Toxicol. 2006 August; 77(4): 280–397.

Strom et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 2001 August 15; 286(7): 807–814.

 

Tags:  fertility  soy 

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My Path to Integrative Medicine

Posted By Administration, Monday, February 22, 2010
Updated: Friday, April 18, 2014

 

Get to know ACAM member Stuart H. Freedenfeld, MD, and his passion for Integrative Medicine in his essay, My Path to Integrative Medicine.

 

I was a rebellious youth, born in the forties and inspired by the awareness movements of the sixties. Having aspired to scientific research since my earliest memories, it was during my last year in college that I shifted focus and came to know that my passion was to devote my life to the healing profession. Having excelled in high school and college, I felt drawn to the more glorious pursuits of the surgical subspecialties especially neurosurgery. While working in the inner city free clinics, which are training centers where inexperienced doctors-in-training practice their new skills on the areas poor and uninsured, I realized that my inspiration came from the people that I served and not from the skills that I had to offer them. Family Practice seemed the only area where I could devote myself to the patient rather than the procedure.

After completing my residency in Family Practice, I entered private practice with Kirk Seaton, MD, who had been the director of the Phillips Barber Family Health Center where I had trained. Together we formed Stockton Family Practice. After only two years he decided to return to academic medicine. For the next four years I was the solo physician at SFP. I worked six days per week including two evenings and every Saturday. I was taking call and even delivering babies seven days per week, fifty-two weeks per year. I still get excited with the memories of delivering over 500 babies during my medical career and am thrilled to have been present at the beginnings of so many new families.

These were exhausting years. So when Sal D'Angio knocked on my office door saying he was just finishing his residency training and wondered if I would consider letting him join SFP, I was more than eager to learn about this new physician. He told me about his background and how he had also studied homeopathy, acupuncture and herbal medicine. It intrigued me as it was a far different medical experience than I had had.

Medical school is a place for learning, but it is also a place for conforming. My training had not expanded my horizons, rather it had narrowed my focus. Now this new doctor reinvigorated my passion for learning and my natural tendency to think outside the box. We established a collaborative relationship as we each learned what the other had to offer. But this was not easy for me. Sal understood and taught his skills in ethereal terms but I was a scientist at heart and needed to understand healing in biochemical terms. In a sense, my early studies in these "alternative" approaches were like studying poetry in a foreign language in which I had only limited knowledge. I could say the words but could not grasp the intricacies of meaning. I could see that alternative therapies worked but I could not relate to them in terms that made sense to me.

My great awakening occurred in 1989. Three of my patients in one year had very poor outcomes related to conventional treatments for their coronary artery disease. One 54 year old died during the angiogram study, another died immediately after his bypass surgery and the third, a 79 year old woman had successful bypass but suffered terribly for a year with various complications. None of these individuals had severe symptoms and none had immediately life threatening disease, but each one suffered from standard medical care. I felt obligated to learn more about alternatives. I had heard about chelation therapy for cardiovascular disease but had no personal experience so I went to a 5-day conference on chelation and other aspects of complimentary medicine sponsored by ACAM (The American College for Advancement in Medicine).

I was blown away. Not only was there science behind chelation, but I found myself at a conference taught by world leading scientists, discussing their own particular area of research. Until then, all medical conferences that I had attended were taught by doctors discussing pharmaceutical treatments and presenting the research that was bought and paid for by the pharmaceutical industry. This same industry was also paying their speaker fees. How refreshing to hear information from people who held my own passion for research and shared their knowledge for the sake of healing rather for the sake of selling. Suddenly hawthorn, coenzyme Q 10, L-carnitine and magnesium took on whole different perspectives.

I was so overwhelmed with this abundance of information that I literally could not sleep for the entire five days of this conference. The speakers spoke of alternative medicine and they spoke in my own language, the language of science.

That five-day conference was my epiphany, Since then I have never lost my enthusiasm for learning or my zeal for the healing arts. In the years since 1989 I have continued to pursue knowledge for the sake of my patients with a driving passion that still gives me exhausted evenings and sleepless weekends. I wonder at the universe of knowledge and am humbled by the vastness of the unknown. My enthusiasm comes from the needs of symbiotic fashion, I am nourished by those that I nurture. I learn from those that I teach. I am healed by those I attend.

For the past 15 years Stockton Family Practice has been devoted to integrating the finest aspects of healing arts from around the world and throughout time. Our goal is to be able to provide the safest and most effective approaches to health and healing for those that come to learn and be well. There is no retirement from this pursuit, only gratification. And so to all of you who give me strength, I say thank you.

Dr

Dr. Freedenfeld is the medical director of Stockton Family Practice. He received his Bachelor of Science Degree with Distinction from the University of Rochester in 1970 and received his Medical Degree, with honors, from the College of Medicine and Dentistry of New Jersey in 1975.

He has become recognized as one of the leading experts on the integration of multiple forms of healing. He offers consultation on the most complex and challenging problems of our day. His forte is in the areas of autism, chronic fatigue, chronic pain, allergy, autoimmune disease, colitis, cancer, heart and cardiovascular diseases, diabetes, detoxification, longevity and health maintenance. He believes there is a vast array of routes to health and healing, and teaches the integration of the routes most appropriate to the individual.

For more information on Dr. Freedenfeld or the Stockton Family Practice, please visit www.stocktonfp.com

 

 

 



Tags:  integrative medicine 

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Shivering

Posted By Administration, Tuesday, February 9, 2010
Updated: Friday, April 18, 2014

As many parts of the United States endure a winter chill, researchers at the University of California, Davis, researchers have published noteworthy findings in the current Journal of Nutrition. Their study suggests increasing the current recommended vitamin D intake by at least a factor of five (5). The new study states that in order to achieve vitamin D sufficiency (i.e., at least 75 nm/liter), someone of European ancestry needs 1,300 IU of vitamin D a day. People of African descent require 2,100-3,100 IU daily. Many experts consider that 25(OH)D levels less than 50 nmol/liter indicate vitamin D deficiency.

2096907196_1e72a36290 A pooled analysis published in the British Medical Journal found that the combination of vitamin D and calcium reduced fractures by 8 percent and hip fractures by 16 percent.

The call by Bill Faloon of Life Extension Foundation to test hospital patients for vitamin D status grows in importance as vitamin D deficiency is linked to the following:

  • osteopenia and osteoporosis
  • muscle weakness and chronic pain
  • fractures
  • common cancers
  • autoimmune diseases including type I diabetes
  • infectious disease
  • cardiovascular or heart diseases

Of those aged 50-70 enrolled in a Chinese study, 94 percent tested vitamin D deficient. Vitamin D deficiency is also now linked to metabolic syndrome or insulin resistance. Given the approximately 2,900 studies published to date and the growing awareness of vitamin D deficiency among those who live in the United States, why no public-health action?

From ANH-USA. Published on January 26, 2010.

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What's New in Regenerative Orthopaedics?

Posted By Administration, Monday, February 8, 2010
Updated: Friday, April 18, 2014

Platelet Rich Plasma (PRP)

Many people in this country are suffering needlessly from chronic pain. Whether it be back pain, neck pain, rotator cuff injuries, headaches, sports injuries, pain from automobile accidents, often patients will suffer for years with their pain. They search for causes, see numerous specialists, and occasionally have surgery, but still go on with pain. What could be wrong? Is it really in their head?

More often than not, the pain is not in their head (unless they have head and neck issues) but is caused by damage to the soft tissue of the joints such as ligament or tendon tissue. The ligaments and tendons of our body support nearly every joint, and also send the brain information of proprioception (the position of our body in space), and nociception (pain). If a ligament or tendon is damaged, it can cause both local pain and referred pain such as sciatica, or numbness down an arm, or into the head. The ligament and tendon damage is often not seen on MRI, CT scan, nor X-ray and needs to be found on a careful physical examination by a physician who is skilled in musculoskeletal injuries. Occasionally, ultrasound may be used to diagnose the problem.

Fortunately, we have a new method to make damaged ligaments and tendons heal - Platelet Rich Plasma (PRP). Our body has the ability to heal, and contains growth factors to regenerate damaged tissue. We have learned in recent years on how to harness that ability and concentrate it into a damaged area. With PRP, after a proper diagnosis has been established, a small amount of blood is extracted from the patient. The blood is then processed and the platelets and growth factors are extracted from the blood. Under appropriate guidance, it is directly and precisely injected into the damaged area. The injection will cause a scaffold to form around the damaged area, impregnated with growth factors, and will incite the healing response. After a series of treatments, the areas will heal, and the pain will end. Since PRP is regenerating joint damage, not just treating pain, the response will often be permanent, and normal activities can be resumed - then the patient can live happily ever after!!!

- Scott Greenberg, MD


Greenberg-61 Dr. Greenberg is a practicing physician at the Magaziner Center for Wellness and a long time member of ACAM. He specializes in natural approaches to family practice problems with a distinctive emphasis on nutrition, cancer, preventive medicine, anti-aging strategies and the use of  PRP and prolotherapy for pain management. Dr. Greenberg personally performs about 100 PRP treatments per month and 4000 prolotherapy treatments per year. For more information on the Magaziner Center for Wellness and PRP please visit: www.drmagaziner.com

Tags:  orthopaedics 

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Psychotherapy: What's Metaphyscial Got to Do With It?

Posted By Administration, Friday, February 5, 2010
Updated: Friday, April 18, 2014

ABSTRACT

Clinicians have a number of treatment options for dealing with the emotional ills of patients, including psychoeducation, psychotherapy, and pharmacotherapy. However, after years of experience in the clinical field, we have recognized that these treatment options may not be sufficient to adequately address the problems of some patients. We have found that adding a metaphysical/spiritual component may be helpful, particularly for those patients with histories of childhood trauma. In this edition of The Interface, we discuss four metaphysical techniques for facilitating patient healing—1) refocusing on the present, 2) reframing adversity, 3) practicing surrender, and 4) meditation. These approaches can be mutually integrated and compliment a psychological treatment in either the psychiatric or primary care setting, regardless of whether or not the patient has formal religious beliefs.

INTRODUCTION

In working with patients for more than 25 years, we have relied on the cornerstones of our psychiatric/family-medicine training for the treatment of psychiatric disorders—psychoeducation, psychotherapy, and psychopharmacology. We candidly acknowledge that these three therapeutic approaches have been invaluable in treating many patients with emotional difficulties. However, despite this cache of clinical interventions, a number of patients continue to emotionally struggle. Something in the overall treatment strategy appears to be missing. We have long noted that these struggling patients oftentimes have histories of childhood adversity. In our earnest endeavors to address this enigmatic deficit and to enhance patient care, we began to explore additional therapeutic options and found some possible answers in the metaphysical/spiritual literature. Collectively, these metaphysical techniques seem to offer a spiritual component to the treatment of emotionally complex patients.

While novel for some healthcare professionals, the addition of a spiritual component to the preceding three conventional therapeutic components was described long ago by Native Americans. These pioneers developed the medicine wheel and its four key areas-of-life emphasis: the intellectual (i.e., psychoeducation), the emotional (i.e., psychotherapy), the physical (i.e., pharmacotherapy), and the spiritual (i.e., the metaphysical). In this edition of The Interface, we discuss this fourth component—the metaphysical/spiritual—and describe four techniques from this literature that may offer additional therapeutic support to patients.

THE IMPORTANCE OF THE "NOW"

A number of contemporary metaphysical authors stress the importance of “living in the present.”17 They pragmatically emphasize that the present is the only experiential space in which we realistically can live. This perspective essentially requires one to relinquish, to some degree, compulsive preoccupations with the past and the future. Neither past nor future allows one to experience the only reality that an individual can ever actually experience, which is the present.

Without reasonable anchorage in the present, one is left with the vicissitudes of the past and future, which at times may be entrapping through compulsive preoccupation. Indeed, Eckhart Tolle describes these mental past/future machinations as being “trapped in time [with] the compulsion to live almost exclusively through memory and anticipation.”8 This metaphysical emphasis on the present does not exclude the necessity of healthy reflection and realistic future planning in one’s life, but rather confronts the ongoing churning of distressing past/future mental movies.

Living in the past. For many of our patients, it is reflexive to emotionally anchor in the past, especially for those with traumatic life histories. Childhood adversities, particularly sexual, emotional, and physical abuses as well as physical neglect and observing repetitive violence, tend to be powerful and influential psychological material upon which to obsess. At its extreme, in some tragic cases, repeated victimization in childhood (i.e., genuine victim status) morphs into an artificial “victim” identity in adulthood, replete with its chronic self-defeating behaviors and continual re-enactments of self-destructive relationships. Such extreme mind identification with the past effectively defeats the genuine unfolding of the individual’s true identity in the present, leaving him or her trapped in a monotonous and robotic life script. In the aftermath, ongoing preoccupation with the losses and abuses of the past, which distracts from the experience of the present, may unintentionally precipitate intensely negative feelings, which may lead to clinical depression in susceptible individuals.

Living in the future. Like the past, the future is also fertile ground for mind play in a variety of forms. One common example is excessive and/or neurotic planning to avert some imaginary disaster, which behaviorally reaches a crest in the phobic patient. Another common example is the excessive mental activity focused upon “getting somewhere”—i.e., achieving a highly desirable endpoint (e.g., completing an education, closing a business deal, achieving the prescribed retirement nest egg). Granted, it is necessary to do a reasonable degree of planning for the future, but compulsive rumination about the future may set the stage for impatiently waiting for an imaginary future life to unfold—all at the expense of being able to experience the reality of the present.

As a corollary, many people seem to over-value the outcome of an experience and the foreshadowed rewards or relief that it may bring, rather than “experiencing the experience.” In this regard, American culture including the media tends to play an active role in nurturing these mental preoccupations with the future. We are constantly bombarded with futuristic formulas for success. Children have to get into the right private schools. Particular clothes, make-ups, fragrances, bodies, neighborhoods, and cars will ultimately garner social success and happiness—once one has accumulated the extensive financial resources to afford them. Happiness awaits when one moves into the big house. The folly of these cultural myths may seem self-evident, but for young patients and those with poor or absent mentoring (i.e., patients with deficient parental mentoring, whom we so commonly encounter in those with histories of childhood adversity), this cultural dogma may function as the only life guidance for scripting “success.” On an emotional level, this excessive preoccupation with the future may unintentionally reinforce worry and tension, which may lead to clinical anxiety states in susceptible individuals.


Case example 1. Regina described the situation exactly as she had experienced it. “I just sat there…thinking to myself over and over that the flight was going to be cancelled. After sitting for an hour on the tarmac, they started pulling off the luggage because of weight requirements. Then, after another hour of sitting on the plane, they started pulling people off. I just knew that I would never make my connecting flight in Atlanta. I just knew it! I would have to stay in a hotel overnight in Atlanta and get into town the next day. I hate unnecessary overnights! Then, I would never make my business appointments. I wondered if I should call work and cancel my appointments.”

Therapist: “What happened?”

Regina replied, “The plane took off two and half hours late, but I made my connection.”

Case example 2. Ben was working very hard as a first-year resident in the internal medicine program. “I’m working 80 hours a week, studying all the time, and I don’t get to spend much time with my family, but it will all pay off when I finish. I’m going to have a great salary, nice house, club membership…you know…that’s all I think about…I’m really going to have made it!”

Living in the present. Granted, the metaphysical principle of staying present appears to be a very easy concept—stay in the present and avoid an excessive focus on the past (depressogenic) or the future (anxiogenic). However, putting this principle into actual spiritual practice can be a frank challenge.

At this juncture, we wish to emphasize that the importance of living in the present is hardly a new concept. Indeed, “being present” appears to have its early roots in Buddhism and is described in the Third Noble Truth. Likewise, living in the present is not a novel concept in psychiatry. Cognitive behavioral therapy attempts to curb futuristic thinking (e.g., the endless “what ifs”) as well as the self-imposed constraints that have consolidated through past experience (e.g., “yes, but…”) by confronting unhealthy cognitive patterns. However, the importance of routinely sensing and being aware of what time frame one mentally experiences appears to be relatively novel to the field of psychiatry.

How can the clinician approach the patient who demonstrates compulsive preoccupation with either the past or the future? The initial intervention would seem to be psychoeducation. We believe that patients need to understand and accept (intellectually and emotionally) that their automatic and unattended mental activities are contributing to their overall life dissatisfaction. After explaining the benefits of present-minded thinking to the patient, we suggest several techniques that seem to promote better anchoring in the present.

One initial technique is simply beginning to recognize and be aware of past/future compulsive thinking. “Watch your thinking, observe it, witness it.” This alone may begin to result in the disruption of compulsive patterns of thought. This exercise needs to be undertaken in a nonjudgmental manner (i.e., neutral self-observation) and continually practiced.

A second technique is the immediate cueing on the environment. This technique entails using the five senses to instantaneously experience the immediate environment. “I want you to see, touch, smell, and hear your world…in the moment.” This practice relates to the principle of “mindfulness” or simply being aware. This form of mindfulness practice may be particularly helpful in a number of clinical situations. For example, in an individual with binge eating disorder, the clinician may augment the patient’s experiential tasting through mindfulness practice. “I want you to really experience, savor, and fully taste your meal. Focus solely on the food…it’s texture, color, and taste. This means no distractions, eating slowly, and fully concentrating on your eating.”

Another time-honored technique is focused attention on one’s breathing. Breathing is obviously a physiological experience that is very much “in the moment.” “I want you to concentrate on your breathing, as you breathe in and out. Observe and experience each breath.” This can be undertaken in conjunction with meditation practice.

A final technique is having the patient examine the world through the eyes of a newborn baby. “I want you to see the world in its wholeness and not focus on its parts. See the forest, not the trees. See the world as if it were the very first time you had ever seen it. Like a baby might see it.”

Again, we wish to emphasize that the shift from past/future to present-minded thinking is far easier said than done. It seems to require a consistent and authentic desire to retool one’s thinking processes and ongoing frames of experience. Like any skill, present-mindedness requires continual practice, so we frame this technique to patients as a lifestyle change. At the same time, just as any skill, it becomes easier with practice and more automatic with time.

THE ADVERSITY PARADIGM

Adversity—it sounds onerous—hardship, misfortune, difficulties. No one is immune to life’s obstacles. Yet, a number of metaphysical authors emphasize that all things happen for a reason.2,6,9 For some individuals, this proposition may require the proverbial “leap of faith.” How could all things happen for a reason? Certainly, bad things don’t purposefully occur. Whether the position that all-things-happen-for-a-reason is causally valid or not, believing so may improve mental health functioning by facilitating the patient’s adaptation to adverse circumstances.

How does reframing adversity promote patient adaptation? First, we must illustrate the differences between perceiving adversity as a random event versus perceiving adversity as an event by design. If the patient perceives adversity as a random event, then a series of well-honed cognitions are likely to follow—such as “I got screwed,” “I’m a loser,” and “Why me?” These distressing cognitions naturally result in negative feelings, such as helplessness, demoralization, and a sense of victimization, and may culminate in the troubling behaviors of either acting out or internalizing. However, by accepting that all things happen for a reason, the patient is actively challenged around determining what is to be learned from this adverse experience. There is a shift from random victim to psychological explorer. As an example, perhaps an impulsive son (the adversity) is there to remind an impulsive father to keep on his spiritual path of growth and not get side-tracked in his own impulsive behaviors. Perhaps an emotionally vacant mother (the adversity) is there to reinforce to the daughter the importance of being a good mother to her children.

Usually it is possible to construct a positive interpretation of most adverse events. Of course, this approach does not exclude the validation of the patient’s pain and sense of loss with such events. However, helping the patient to refocus in this way seems to redirect them from “stuckness” toward more productive problem-solving and self-awareness. This approach consistently promotes the development of responding rather than reacting to adverse situations. But, again, this reframing requires a spiritual leap of faith—that all things are in ongoing order and that nothing is left to random design.

SURRENDER

Surrender is an emotionally charged concept in our culture. Yet, surrender is a word that has very different meanings when viewed from Western versus Eastern perspectives. From a Western perspective, surrender is associated with giving in, admitting defeat, submitting, or capitulating. The connotation is blatantly negative and implies weakness. However, in Eastern thought, surrender entails the relinquishing of unrealistic fantasies of controlling others or events. It is the active acceptance of what is. In other words, it reflects a positive mindset.

To be clear, surrender is not the equivalent of resignation. It is not the commonplace attitude of “whatever” that we so often encounter in adolescents. Surrender is about acknowledging one’s own internal resistance to a situation and relinquishing the belief that in resistance resides one’s strength. Surrender is an action that relates to truly and genuinely accepting what is. It is about not opposing the course of life. Perhaps another way to think about surrender is that it is simply and genuinely accepting one’s path at any given time, yet understanding that choice is always a part of that path.

As an example, this metaphysical concept is particularly useful in helping patients to deal with their seemingly unending comparisons with others. We all tend to look at others and compare ourselves. People around us may seem far more gifted or more fortunate than ourselves. By assessing ourselves in this way, however, we fall into a hazardous comparison trap. Realistically, there is always someone who is more accomplished, talented, attractive, well liked—we can rarely triumph. As a result, comparison tends to generate bad feelings about one’s self. At this juncture, the metaphysical intervention would entail encouraging the patient to accept his or her unique and personal current path as highly relevant and necessary to his or her overall life course, whatever that may be (i.e., surrender), while empowering him or her around active choices. From a pragmatic perspective, comparing one’s path with the paths of others is unproductive and redirects the patient away from his or her own individualized life course.

Case example 3. Danne, a female patient with an eating disorder (ED), commented, “I can’t believe this! Here I am in this ED unit, and these girls are all thinner than me, have more money, and are prettier! Why can’t I be like them?”

Therapist: “Danne, focusing on the other patients only distracts you from the work that you have to do. Everybody has a unique path in life. You cannot have their path and they cannot have your path. Each path is uniquely valid. I encourage you to accept the idea that your path, while distasteful to you, is your path. Stay focused on the inner and be careful about being caught up in the outer.”

As so eloquently summed up by Eckhart Tolle, “Surrender is the simple but profound wisdom of yielding rather than opposing the flow of life.”10 Indeed, opposing the flow of life is likely to precipitate profound negative emotional states.

MEDITATION

Meditation is a structured mind/body experience that seems to transcend the thinking mind by allowing one to enter into a heightened state of relaxation and awareness. The techniques for undertaking meditation are numerous, but most, if not all, entail a relaxed sitting position in a quiet place and begin with a focus on breathing. The focus on breathing promotes relaxation as well as a sense of presentness. Following focused breathing, meditation practices may diverge into a variety of different directions. For example, some practitioners meditate to heighten relaxation. Some initiate auto-suggestion, which may be particularly effective in this relaxed state. Others seek a different level of consciousness, sometimes referred to as a fourth dimension. Yet others use meditation to broach and focus upon major life questions, hoping that the heightened sense of clarity in this unique state will facilitate a response (i.e., an intuitive “knowingness”). Whatever the reason, meditation is a strongly espoused spiritual practice by the metaphysical community, and certainly our patients may potentially benefit from any of the preceding functions. We do not espouse a particular meditation technique, but underscore with the patient the following: 1) the potential value of meditation, 2) the importance of meditating in a calm environment in a relaxed position, 3) the initiation of this experience with paced and focused breathing, and 4) the use of simple words (a mantra) for promoting focus. After continued practice, the patient will find it easier to “calm the mind” and contain intrusive thoughts. Note that meditation may be undertaken as a practice for mindfulness and present-moment awareness.

MINDFULNESS

An interconnecting theme in the preceding metaphysical approaches is the practice of mindfulness. Mindfulness is simply being aware. This means being both internally and externally attuned, without the filters of judgment, the emotions, or the culture. Note that in each of the preceding techniques, there is an element of being present—i.e., being in a mindful and aware state. For example, dealing with adversity entails being mindful of the obstacle from the perspective of “here by design.” The technique of surrender requires one to experience and accept the nowness of the path. Finally, meditation and its attendant focus on breathing is clearly an exercise in mindfulness. Mindfulness seems to be the fabric that supports the metaphysical design in the presented techniques.

WHAT ABOUT RELIGION?

Religious beliefs are not, per se, a limitation to using any of the preceding metaphysical approaches. Nor is a religious orientation necessary to use them. However, religious belief may temper some interventions such that “by design” is easily interpretable as God determined. In addition, meditation may be translated as “prayer” or “spending time with God.”

CONCLUSION

The modern era has certainly provided clinicians with an invaluable array of psychotherapeutic tools to address the emotional difficulties experienced by patients. These tools include psychoeducation, psychotherapy, and psychopharmacology. Yet, for a number of patients, these approaches fall short of providing a satisfying resolution to their inner turmoil, particularly among those individuals with histories of childhood trauma. In our search to compliment these contemporary approaches to treatment, we have integrated a number of metaphysical/spiritual techniques that have the potential to offer comfort and peace to many patients. While we have only presented four specific techniques, there are others that can be gleaned from the recommended reading list in the sidebars. We are all pilgrims on this planet. We are all seeking inner harmony. Why not benefit from the centuries of wisdom that have preceded us?

From: Psychiatry (Edgmont). 2009 December; 6(12): 26–31. Randy A. Sansone, MD and Lori A. Sansone, MD.

CONTRIBUTOR INFORMATION

Randy A. Sansone, Dr. R. Sansone is a professor in the Departments of Psychiatry and Internal Medicine at Wright State University School of Medicine in Dayton, Ohio, and Director of Psychiatry Education at Kettering Medical Center in Kettering, Ohio;

Lori A. Sansone, Dr. L. Sansone is a family medicine physician (government service) and Medical Director of the Primary Care Clinic at Wright-Patterson Air Force Base. The views and opinions expressed in this column are those of the authors and do not reflect the official policy or the position of the United States Air Force, Department of Defense, or US government;

REFERENCES

1.Davis J. The Diamond Approach. Boston, MA: Shambala; 1999. p. 24.

2.Tolle E. Tolle E. Oneness With All Life. New York, NY: Penguin Group; 2008. The power of the present moment; pp. 21–35.

3.Almaas AH. The Unfolding Now. Boston, MA: Shambala; 2008.

4.Bodian S. Bodian S. Wake Up Now. New York, NY: McGraw Hill; 2008. The practice of presence; pp. 79–98.

5.Batchelor S. Batchelor S. Buddism Without Beliefs. New York, NY: Riverhead Books; 1997. Awareness; pp. 57–66.

6.Jacobson L. Journey into Now. La Selva Beach, CA: Conscious Living Publications; 2007.

7.Brown M. The Presence Process. New York, NY: Namaste Publishing; 2005.

8.Tolle E. Practicing the Power of Now. Novato, CA: New World Library; 1999. p. 31.

9.Richo D. The Five Things We Cannot Change. Boston, MA: Shambala; 2006. p. 27.

10.Tolle E. Practicing the Power of Now. Novato, CA: New World Library; 1999. p. 115.

 

Tags:  metaphysical  psychotherapy 

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Enzymes for Health

Posted By Administration, Thursday, January 28, 2010
Updated: Friday, April 18, 2014

 

 

2752472918_e2926279ea_mOne of the processes that first decline as we age is the production of digestive enzymes. That’s the reason why one of the most popular drugs in the 20-40 year old age group are the antacids or proton pump inhibitors. It usually presents itself as heart burn, indigestion or flatulence. This decline in enzyme production is part of normal aging but dietary and lifestyle influences could actually hasten its occurrence.

For instance, eating primarily cooked, devitalized food could make the process of digestion harder. Eating rapidly or on-the-go (like most busy people) can also affect the digestive process. The normal response to having dyspepsia is to give medications to suppress the symptoms. However, this approach sometimes doesn’t address issues  like Helicobacter pylori (or other pathogens that may affect digestion) or chronic elevation of cortisol from prolonged stress. If a person has a documented ulcer by endoscopic procedure, then it’s okay to give these proton-pump inhibitors for a certain period but to take these drugs indefinitely is not a good idea. These medications could actually deplete the body of nutrients such as vitamin B12, D, folic acid, calcium, iron, zinc and protein.

What are enzymes anyway? Enzymes are complex proteins that facilitate chemical reactions in the body. They’re found in digestive juices where they act upon food, breaking it down into simpler molecules that the body can use for energy. Enzymes could be either derived from plants or animals. Popular plant enzymes include bromelain and papain from pineapples and papaya, respectively. Animal enzymes are usually derived from porcine sources. They closely resemble human digestive enzymes. They’re more sensitive to pH changes. Thus, they need to be taken at least 30 minutes prior to meals.

- Dr. Joel Lopez

Tags:  enzyme 

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Thyroid and Fertility

Posted By Administration, Wednesday, January 20, 2010
Updated: Friday, April 18, 2014

Fiona 021e website size  Thyroid problems are extremely common, and because they can be asymptomatic, it can be difficult to know if a condition is present.  The thyroid is absolutely essential for healthy fertility.  Dysfunction can cause ovulatory disorders, menstrual irregularity, and recurrent miscarriage.  The thyroid gland is key to support ovarian function. If thyroid function is low, the eggs will not mature fully and, ovulation can be either delayed or prevented.  Surprisingly, 5-20 percent of women in their reproductive years have a thyroid condition.

Autoimmune thyroid disease is one major cause of many thyroid conditions. Women who test positive for thyroid antibodies will generally develop hypothyroidism at a rate of 20% per year.  Often times, when a fertility general health screening is done, the only test completed for the thyroid is TSH (Thyroid Stimulating Hormone).  TSH is a useful test to screen for hypo or hyperthyroidism, however it does not detect autoimmune conditions.  Autoimmune thyroid antibodies can be present with no symptoms of hypothyroidism at all.  In autoimmune thyroiditis, TSH levels are often normal so it is important to complete a full thyroid panel. This can determine if there is a risk of developing hypothyroidism which could threaten a pregnancy.  When a woman becomes pregnant, there are widespread hormonal changes in the body, including an increased demand for thyroid function. If autoimmune antibodies are present, this can trigger miscarriage due to inability of the thyroid to compensate normally for pregnancy. Many cases of recurrent miscarriage or premature birth are related to thyroid disease so this is a very important part of fertility screening in those who suffer from miscarriages. One of the protective functions of pregnancy is a decrease in immunity, so it is unlikely that a new flare up of Grave’s disease (an autoimmune disease which causes symptoms of hyperthyroidism and goitre) will occur during pregnancy, however often we see worsening of hypothyroidism.

Another condition which can be present in those with thyroid disease is primary ovarian failure.  This is caused by autoantibodies to the ovary and is associated with autoantibodies to the thyroid.  This condition, although not common, can be devastating for women.

In men, hypo- or hyper- thyroidism can cause poor development of sperm, so for all men with sperm quality concerns, the thyroid should be screened.   Although thyroid disease is more common in women, it can still happen for many men and go undetected.

Symptoms of Hypothyroidism:

fatigue, weakness, weight gain, dry skin or hair, feeling cold, constipation, irritability, depression, muscle cramps, menstrual irregularities.

Symptoms of Hyperthyroidism:

anxiety, feeling hot, insomnia, heart palpitations, weight loss, hunger, sweating, trembling

To optimize fertility the following lab testing for thyroid should be done.  Explanation of thyroid lab values and normal ranges are included.

TSH – Thyroid Stimulating Hormone.

This is a hormone released by the pituitary gland (in the brain) which stimulates the thyroid to release thyroid hormones.  It is controlled by feedback mechanisms, when thyroid hormone is low in the bloodstream, the pituitary gland will increase its output of TSH to stimulate more release of thyroid hormones.

Normal Levels :  0.4 – 4 mIU/L.   If levels are above 2, and especially if thyroid antibodies are present with signs and symptoms of hypothyroidism, this is suspect of “subclinical hypothyroidism” and may present risks for fertility.

Free T4 – Thyroxine.

A thyroid hormone produced by the thyroid gland.  This is the most abundant thyroid hormone in the body.  It is also the weaker of the thyroid hormones.  It represents 80% of the thyroid hormones in the body, and its major function is to be converted into the stronger T3 hormone.  This is a measure of the T4 which is not bound to carrier proteins.

Normal Levels:   8.5-15.2 pmol/L

Free T3 – Triiodothyronine.

A thyroid hormone produced from the conversion of T4 by enzymes.  This is a much stronger thyroid hormone and has powerful effects on the body’s metabolism.  It represents 20% of the total thyroid hormones in the body. The conversion of T4 into T3 can also be impaired, so this is important to investigate.  This is a measure of the T3 which is not bound to carrier proteins.

Normal Levels:  3.5 – 6.5 pmol/L

Reverse T3

When there is sufficient T3, the body will convert excess T4 into a compound known as reverse T3.  This compound is inactive, and serves to protect the body from excessive overstimulation by thyroid hormone. It can bind to receptors where T3 would normally bind, however it does not stimulate the receptor as T3 would. In some cases, the body may actually convert T4 excessively into reverse T3, which can result in metabolic abnormalities. This condition should be screened for whenever signs and symptoms (including low body temperature) are present in fertility patients.

Normal Levels:  200-300 pmol/L

Thyroid peroxidase antibodies

These are antibodies against an enzyme known as Thyroid Peroxidase.  Thyroid peroxidase is involved in the conversion of T4 to T3.  If antibodies exist, this can cause a conversion disorder which results in hypothyroidism.

Normal Levels: <35

Antithyroglobulin antibodies

These are antibodies directed against a protein known as Thyroglobulin.  Thyroglobulin is present in the thyroid gland and is essential for the production of thyroid hormones.  These antibodies can trigger destruction of the thyroid gland.

Normal Levels:  <20

Treatment for thyroid conditions can involve thyroid hormones, nutritional supplements, amino acids and herbal medicines, depending on which type of thyroid condition is present.  Naturopathic treatment for thyroid is often integrated with conventional thyroid medications when needed to optimize response for fertility concerns.

- Dr. Fiona McCulloch

Reference:  Mosby’s Manual of Diagnostic and Laboratory Tests

Tags:  Infertility  thyroid 

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Anti-Aging Medicine

Posted By Administration, Thursday, January 14, 2010
Updated: Friday, April 18, 2014

Images There is no question that the horizons of longevity have already been extended. This has come about largely through the efforts, not of doctors, but of plumbers. By this I mean that improvements in sanitation over the past few centuries have vastly reduced the incidence of infectious diseases that used to dispatch many individuals in the prime of life. The average life span of people during the Middle Ages in Europe was around 40 years. Today, it is around 75 years. According to Scientific American magazine, "the centenarian population grew by 160 percent in the U.S. during the 1980s. Many demographers predict that 20 million to 40 million people will be aged 85 or older in the year 2040, and 500,000 to four million will be centenarians in 2050. the economic burden of caring for people older than 85 could be vast, especially if a huge percentage of them need special care."

The concern, of course, is that while longevity has been extended, quality of life, by and large, has not. Far too many Americans are living well beyond the medieval life expectancy only to encounter decades of chronic pain, immobilization, mental deterioration, and prescription drug dependency.

The approach to life extension has been, until lately, one of targeting the major killer-diseases for eradication. Thus the search for hi-tech approaches to heart disease and cancer have dominated the arena of medical research, consuming billions annually. At first, this may seem a logical way of promoting longevity, but biostatisticians have pinpointed a remarkable fact: even as dramatic an innovation as a universally successful cancer cure would have a minimal impact on life span. Remarkably, eliminating cancer as a cause of death would extend the average longevity by a mere 2 years!

Evidently, the conclusion to be drawn is that it is not disease, but the aging process itself that is responsible for the death of most Americans. Yet the National Institutes of Health allocate to cancer research twenty times the amount of money that they allocate to anti-aging research. A re-balancing of national priorities is clearly in order.

Perhaps part of the problem is a lack of rational resolve. Policy-makers in this area lack a clear vision of what enhanced longevity might bring. Perhaps they fear that active promotion of anti-aging research might threaten the fabric of society by creating a huge elderly population, sustained only via expensive technological support, inundating Social Security and Medicare, and devastating pension programs. A vast army of disabled and senescent oldsters would prove an unacceptable burden to 21st Century America.

While partly justified, fears of this scenario may be exaggerated. First, our approach to longevity need not prioritize just numerical survival; it must also emphasize quality aging. Languishing for years on sophisticated life-support systems in the critical care unit of the hospital of the future just does not constitute acceptable life extension.

Secondly, the anti-aging movement, while embracing sophisticated high-tech innovations, aligns itself mostly with economical lifestyle modifications like diet, exercise, modest stress reduction, and the use of anti-aging "nutraceuticals." Drugs and hormone therapies are envisioned as low-cost interventions to forestall more costly medical and surgical catastrophes.

Finally, research suggests that, if critical barriers to longevity are removed, older individuals can remain healthy and unencumbered by serious debility well past ninety, until they naturally "drop off the end of the aging curve." There is evidence that the incidence of medically-costly and debilitating illness actually decreases once an individual surpasses certain key aging milestones. According to Thomas T. Perls, M.D., a geriatrician at Harvard: "People in their late nineties or older are often healthier and more robust than those 20 years younger. Traditional views of aging may need rethinking."

What actually is aging? Here, a distinction must be made between chronological and biological aging. A person's age in years correlates only roughly with the rate at which his or her bodily systems age. In the rare hereditary medical condition argyria, for example, aging is markedly accelerated, to the point where children afflicted with the disease take on the appearance of elderly dwarves.

Conversely, others seem to cheat Father Time by maintaining youthful appearance and vitality well into their mature years.

Consequently, anti-aging researchers have proposed a series of "biomarkers" to better delineate the aging process. A few of these appear below:

  • muscle mass

  • Muscle strength

  • Post-exercise time

  • Reflex speed

  • Joint mobility

  • Breathing capacity

  • Endurance

  • Short-term memory

  • Problem-solving skills

  • Balance

  • Liver function

  • Skin elasticity

  • Wound healing capability

  • Hormone levels

  • Sleep quality

  • Immune function

  • Cancer markers

  • Free radical defenses

  • Fat to lean ratio

  • Glucose/insulin tolerance

  • Lipid profile

  • Susceptibility to blood clots

No doubt, other biomarkers may merit inclusion in this list. The routine preventive physical exam of the future may derive more relevance from a biological age assessment based on such objective parameters. The technology is already here.


Several scientific theories attempt to explain the aging process, and provide insights into how we might retard it. Among the most popular is the Free Radical Theory of Aging, first promulgated by Denham Harmon. This concept has recently gained influence from an ingenious experiment comparing fruit flies with or without bioengineered adoptive antioxidant protection: the free radical-shielded flies lived up to 20% longer, and remained physically active far longer into old age. The implication for humans is that, via consumption of antioxidant-rich supplements or foods, aging can be delayed.

Indeed, lifestyle influences have been linked to a variety of disease processes that curtail longevity. Smoking, poor diet, excessive (but not moderate) alcohol consumption, illegal drug use, unsafe sex, reckless driving, exposure to environmental and occupational pollutants, and firearms hasten the demise of many Americans who should otherwise reach an advanced age. Therefore, a rational approach to life-extension is predicted on fundamental lifestyle intervention.

Another mechanism of aging is via a process called "protein cross-linking." A simple analogy is the way foods "brown" while baking: heat induces changes in protein structure called cross-links which render the food cooked. Similarly, in biological systems, the aging process results in a steady accumulation of dysfunctional cross-linked proteins, culminating in deterioration and death. Ingenious strategies are being investigated which slow the cross-linking cascade.

Other theories hold that human aging results from fundamental changes in immune function. Immune surveillance declines with age, resulting in greater susceptibility to cancer, infectious disease, and auto-immune conditions. Administration of thymic extracts or specifically bioengineered monoclonal antibodies might help buttress a flagging immune function.

Maladaptive reactions to stress have also been shown to accelerate the aging process. They do so by increasing the production of catecholamines, stress hormones that include adrenaline, the well-known "fight-or-flight hormone." Elevated levels of catcholamines have been shown to impair immunity, promote high blood pressure, diabetes, and heart disease; as well as to impair memory, and worsen allergic diseases. Most individuals who survive into their 80s or 90s embody personal traits of resilience and stress-coping that have sheltered them from the adverse effects of rampaging catecholamines.

Evidence also suggests a role for hormones in the process of aging. Deft manipulation of estrogen, progesterone, testosterone, thyroid, growth hormone, and melatonin

 --all of which decline with age--may preserve certain aspects of youthful vigor. By contrast, levels of insulin tend to rise in response to dietary excess and sedentary lifestyle. The resultant "Syndrome x" is a major precipitant of premature disease.

It is also clear that certain aspects of aging are genetically programmed. For example, the presence of a gene called Apo-E4 predicts susceptibility to Alzheimer's Disease. Through the genetic engineering of the future, doctors may be able to selectively "edit out" deleterious genes, or modify the expression of genes already encoded. Specific growth factors may be available to "turn on" the mechanisms for organ repair, or "turn off" the harmful proliferation of tissue that occurs in certain degenerative diseases like arthritis, arteriosclerosis, or cancer.

"Smart drugs" are already available that crudely modulate levels of neurotransmitters in the brain. Among the most popular is Deprenyl, a prescription medication used to slow the progression of Parkinson's disease. It is held by some anti-aging researchers that Deprenyl and other drugs can be used to halt the decline in mental functioning that is the hallmark of aging. The advent of better "smart drugs" may provide a breakthrough in enhancing the quality of our later years.

Cosmetic aspects of rejuvenation deserve attention here, too. Conscientious application of improved techniques of dermatology and plastic surgery (always used in conduction with appropriate lifestyle modification,) can create a meaningful anti-aging "makeover." Newer less invasive techniques such as laser surgery and natural skin treatments now enhance the repertoire of longevity specialists.

Finally, high-tech advances such as exquisitely-modeled miniature micro-processor seeing and hearing devices may eventually reduce the debilitation now suffered by many of the aging. New techniques of locomotion utilizing robotics and virtual reality could eventually resuscitate failing motor skills. Remarkable progress in organ transplantation and artificial organ technology may also ultimately transform the search for longevity.

Nevertheless, the zeal for life extension must be tempered with a healthy recognition of our ultimate limitations. We live in a dazzlingly youth-oriented culture which places a premium on beauty, fitness, hedonistic indulgence, and sexuality. We need to acknowledge the importance of maturity, even debility, illness, pain and death. Our efforts to extend life and to improve the quality of our newly-attained longevity must be tempered with respect for our humble biological origins, and the spiritual connectedness our lives embody.

- Dr. Ronald Hoffman

Tags:  anti-aging 

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Interested in Detoxing?

Posted By Administration, Monday, January 4, 2010
Updated: Friday, April 18, 2014

Images ACAM is excited about the upcoming release of ACAM member, Dr. Gerald Wootan's new book, Detox Diets for Dummies. 

This guide to making informed choices about cleansing your body and mind safely and conveniently will be released on March 1, and is currently available for pre-order on amazon.com.

The book discusses how our bodies accumulate toxins from everyday exposure to different chemicals and the ways we can rid them from our systems. A screening quiz is also included to help decipher which plan is most suitable for each individual.

Detox Diets For Dummies also discusses chelation therapy, which detox programs cause more harm than good, plans for quitting smoking and drinking, fighting allergies, losing weight, calming stress and anxiety, increasing your energy, and revitalizing your spirit, as well as over 35 recipes for safe cleansing of toxins and other harmful agents.

Whether you are motivated by weight loss, disease prevention, metal purification, or physical revival-Read Detox Diets For Dummies for a variety of detox programs that are all natural and fit every lifestyle. 

Check ACAM's IM Blog often for more exciting news from ACAM members.       

Tags:  detoxification 

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Case Studies on Mesothelioma and Non-Traditional Therapies

Posted By Administration, Saturday, January 2, 2010
Updated: Friday, April 18, 2014

Patients who have been diagnosed with mesothelioma—an unusual cancer which is associated with asbestos exposure—have been particularly receptive to trying alternative and complementary therapies. One of the reasons for their willingness to look outside of conventional medicine for treatment is the fact that mesothelioma, generally an incurable cancer which is often diagnosed in advanced stages, usually renders traditional therapies ineffective. Other patients pursue an integrative approach, using holistic methods to ameliorate the side effects of chemotherapy and/or radiation.

Although mesothelioma is considered a fatal cancer, there is one man who has become something of a legend due to how long he has lived with the disease. Paul Kraus was diagnosed with the rare subtype peritoneal mesothelioma, which affects the lining of the abdominal cavity, in 1997. Now, thirteen years later, he is alive and well—against all odds, since fewer than 10 percent of all mesothelioma patients live more than two years after diagnosis. Kraus credits a radical lifestyle change, including an extremely healthful diet and a regimen of nutritional supplements, for his remarkable survival. He also meditated, visualized, received intravenous Vitamin C infusions, and underwent a treatment called ozone therapy, in which extra oxygen was added to his blood.

Soy-whey-protein-diet  After embracing the idea that our bodies are equipped with powerful capabilities for self-healing, if we can only tap into and support them, Kraus began juicing—beet juice, carrot juice, and various green juices. He drank fresh juice several times a day, supplementing his diet with high-fiber, vegetarian and mostly raw foods. Additionally, he exercised and began taking vitamins, minerals, homeopathic remedies and amino acids. Although admitting that these changes were extremely difficult, Kraus also knew that they were necessary for his survival and his overall health. Today, he is in his mid-sixties and doing well. In order to help others who may be facing a similar diagnosis and who wish to heal their cancer using holistic methods, he has written a book entitled “Surviving Mesothelioma and Other Cancers: A Patient's Guide.”

In a 2005 interview, Kraus summed up his philosophy. “The mind-body connection is very important for healing. They are inextricably linked. If one has the wrong attitude one cannot be a survivor of mesothelioma or any form of cancer.”

Another odds-defying survival story is that of Marie Augustine, a Canadian woman who was diagnosed with malignant pleural mesothelioma three years ago. Augustine was given only six months to live, but  she was determined to attend her 50th wedding anniversary, which was seven months away. Too weak to be a good candidate for either radiation or chemo, Augustine decided to look at alternatives. She worked with a practitioner of Traditional Chinese Medicine and tried other holistic treatments, with varying results. Then she stumbled upon pawpaw, a tree whose fruit and bark have been shown in laboratory tests to have potent anticancer effects. Pawpaw has been studied at Purdue University, and although there are as yet no published studies on its efficacy for mesothelioma patients, this is a treatment that bears watching.

Augustine calls her experience with pawpaw “miraculous.” Within a month of taking pawpaw capsules,Pawpaw-fruit   she noticed a difference in her energy level and endurance. Once nearly bedridden, and unable to venture outside of her house, Augustine is now able to take walks around the neighborhood, to drive, and to attend community events.

The memoir “They Said Months, I Chose Years: A Mesothelioma Survivor's Story” chronicles the courageous fight of another mesothelioma survivor, James “Rhio” O'Connor against this deadly cancer. Diagnosed in 2001 with mesothelioma and given less than a year to live, O'Connor went on to survive for over seven years, astounding his family and the medical community. Like Kraus, O'Connor established for himself a nutritional regimen consisting of over 100 supplements per day and changed his eating habits. On his website, O'Connor quotes Hippocrates, whose belief in the practice of mind-body medicine is summed up by the expression, “Let food be thy medicine and medicine be thy food.”

The conviction that nutrition, supplements such as minerals, vitamins, enzymes, and amino acids can actually help a patient overcome something as serious as cancer is often seen as a radical one, but O'Connor did his research, and his book cites almost one hundred medical articles that support this view. 

James “Rhio” O'Connor, whose oncologist encouraged him to take his wife on a cruise, then to return home and enter hospice care—in other words, to succumb to the mesothelioma and get ready to die—fought the traditional paradigm of treatment, and succeeded in his battle against cancer for over seven years. Yet he did not eschew traditional therapies, admitting that if chemotherapy could have effected a cure, he would have been the first to sign up. Indeed, it was probably the fact that his cancer was inoperable, due to the position of the tumor, that sent him to seek answers from alternative modalities in the first place.

O'Connor died on July 11, 2009, more than seven years later than anticipated, leaving behind a legacy that speaks to the success of integrative medicine, just as the lives of Marie Augustine and Paul Kraus continue to do.

Tags:  mesothelioma 

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Chelation

Posted By Administration, Thursday, November 19, 2009
Updated: Friday, April 18, 2014

Meetdr4_12_5 by Ronald Hoffman, MD       

The most common and toxic heavy metals that can poison our systems and lead to fatigue and illness are iron, lead, cadmium, and mercury. Iron is by far the most common of the heavy metals that predisposes individuals to heart disease. It promotes free radical activity and thereby leads to accelerated arterial damage. Lead and cadmium are common industrial pollutants that also foster free radical activity and poison critical enzymes which repair tissue. Mercury is found in some kinds of seafood and in dental fillings. Its toxicity can depress the immune system and cause an array of symptoms. Even too much iron, such as occurs in the hereditary disease hemochromatosis, can hasten degenerative disease and damage the heart, hastening free radical damage.

One of the most reliable approaches to determining heavy metal toxicity is to test a person with a chelator--a substance that tends to pull metals and minerals out of the body. You simply give the person two urine tests--one before chelation and one after chelation. If, between the two tests, metals in the urine increase dramatically, toxicity is almost certain. Chelation tests can detect lead toxicity in people who have stored high levels of lead in their bone, even though blood levels may be "safe."

Getting the iron, lead, cadmium, and mercury out can be accomplished with chelation therapy, which both prevents and can reverse heart disease, atherosclerosis, and the other problems mentioned above.

How does chelation therapy work? For most of these metals, an intravenous solution of vitamins, minerals, and the chelator EDTA is prepared. EDTA is a substance known for its ability to pull heavy metals out of the body. This is infused into the bloodstream through a vein. EDTA leaves the body in the same form by which it entered, but on its way out, it chelates metals and minerals from the body. Patients usually undergo between 10 and 20 chelation treatments over a period of weeks or months. Each treatment lasts several hours, during which patients can read or watch a movie.

I've seen patients with mysterious, low-level, chronic fatigue feel absolutely rejuvenated after a series of chelation treatments. The spring is back in their walk, the energy back in their lives. Circulation is improved, and the body no longer has to work overtime to carry its load of toxic metals.

Chelation therapy must be performed by an experienced practitioner. Because EDTA is excreted by the kidneys, the possibility of kidney damage is a concern and must be closely monitored. Minerals and nutrients may also bind with EDTA, so their levels must be carefully checked and controlled through supplementation. Chelation must be done slowly over a period of three to four hours. Too much fluid at too rapid a rate might cause an increase in blood volume and a fluid overload, which could be problematic, particularly in patients with serious heart disease. Oddly enough, the magnesium in the chelation bottle might cause the opposite--a drop in blood pressure. That's why all patients must be closely supervised.

To safeguard against possible problems, blood and urine tests are taken before chelation to check kidney function. Cardiac function is evaluated, through a stress test and a noninvasive heart test called an echocardiogram. After every few chelations, blood work is repeated. The patient is advised to eat a good meal before the treatment, and blood pressure is monitored before and after each infusion. To flush the kidneys, at least 16 ounces of water must be drunk during the treatment.

If high levels of mercury have been detected in the body's cells, two other chelating agents called DMSA (also known as succimer) and DMPS can help pull the mercury out. If mercury levels are high, either DMSA or DMPS can be used as chelators. Another chelator, which sometimes causes allergic side effects, is known as D-penicillamine (or Depen.) In addition, the following nutrients are known to chelate mercury in the body: the amino acid L-cysteine, the antioxidant glutathione, the mineral selenium, and vitamin C. Garlic is rich in the sulfhydryl groups that help chelate mercury. Selenium, in particular, competes with mercury for binding sites in the cell. The other nutrients grab on to mercury and help the cells release it.

Beyond its effects on heavy metals, chelation with EDTA also helps to remove inappropriate accumulations of calcium from tissue. Calcium gravitates to atherosclerotic plaque in blood vessels, leading to arterial narrowing and blockage. Chelation gently and gradually mobilizes calcium from plaque, restoring elasticity and flow to blood vessels.

While controversial (chelation for cardiovascular disease reversal has few adherents among orthodox cardiologists), several thousand physicians practice chelation throughout North America and the world.

Tags:  chelation therapy 

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Zinc and Copper Levels Are Key Factors in ADHD/ADD

Posted By Administration, Saturday, October 10, 2009
Updated: Friday, April 18, 2014

Research has found that many children and young adults with ADHD/ADD are deficient in zinc. Zinc is found in the brain's hippocampus and interacts with other chemicals to send messages to the sensory brain center, enhancing memory and thinking skills. It has a significant effect on visual memory, learning, emotional and behavioral state and overall cognitive function. A deficiency may result in learning impairments, poor memory and emotional and behavioral problems.

A study carried out on 135 males aged between 3 and 20 with a history of aggressive behavior found that many of the subjects were likely to have high levels of copper and low levels of zinc compared with non-aggressive people. Zinc and copper compete for absorption. Because of this inverse relationship, zinc supplements can be effective for lowering copper levels. Proper mineral balance is essential for the production of chemical signals in the brain that influence behavior. Both copper and zinc tend to be concentrated in the hippocampus of the brain, which is the area known to be associated with stress response.

Since it usually takes two to three months to overcome a copper-zinc imbalance, treatment with zinc supplements should be continued for a minimum of four months before determining effectiveness. Zinc deficiency can result from exposure to heavy metal toxins, such as cadmium (usually from exposure to cigarette smoke) and lead, which prevent its absorption. Poor dietary habits such as excessive consumption of sugar or carbohydrates are also known to reduce zinc absorption.

--
Doc Howard

Dr.  Julie Howard is CEO of The Howard Clark Corporation and founder/director of Youth Essential Solutions, Head Out Rehabilitation Camp, and Texas Preparatory Academy. For more information visit, http://docjhoward.com/. 

 

Tags:  ADD/ADHD  ADHD/ADD 

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Integrative Mesothelioma Treatment Modalities Emerging

Posted By Administration, Saturday, October 3, 2009
Updated: Friday, April 18, 2014

Mesothelioma is a rare but aggressive cancer that is almost exclusively linked to an exposure to theImages-2 building and insulating material, asbestos. During the course of manufacturing, installing, or break-down of asbestos-containing materials, a fine particulate – composed of microscopic and needle-like fibers – may be released into the surrounding air. After being inhaled or ingested, those fibers can embed themselves deep into the mesothelium, which is a membranous lining that protects the lungs, heart and stomach, and which also lines the thoracic and abdominal cavities. The fibers can cause irritation, lung scarring (asbestosis) and eventual malignancy, known as malignant mesothelioma.

One of the most unfortunate hallmarks of mesothelioma is the fact that it is often asymptomatic, remaining undiagnosed for an astonishing 20 to 50 years. By the time the cancer is diagnosed, it has usually reached Stage III or Stage IV, and is often not receptive to traditional treatment. Curative surgery is only feasible in Stage I mesothelioma, and such early detection is very rare. In later stages, surgery may be attempted to remove some of the cancer, usually in combination with radiation therapy and chemotherapy. Clinical studies have shown that a trimodal approach to mesothelioma treatment is generally most effective, but most patients still have a life expectancy of only 18 months after diagnosis. In later stages, many mesothelioma patients find that the benefits of palliative chemotherapy and radiotherapy do not outweigh the side effects and discomfort that accompany these treatments, and therefore opt not to pursue conventional methods of cancer treatment.

For these reasons, homeopathic and other alternative treatments have been proven popular with mesothelioma patients. Alternative approaches can be used as stand-alone treatments to reduce the pain and symptoms of the disease, or as complementary therapy intended to help ease the side effects of more conventional therapies.

Some of the most popular alternative therapies include massage, yoga, acupuncture and acupressure Images-3 (including reflexology), traditional Chinese medicine (TCM), use of select herbs as a nebulizer, nutritional regimens, supplements, meditation or hypnosis, and aromatherapy. TENS therapy, or transcutaneous electrical nerve stimulation, is also becoming popular. This therapy involves no drug interactions, is non-invasive, and has no known harmful side effects. In TENS therapy, pain relief is achieved by attaching electrodes to specific areas on the patient's skin and administering an electrical current. TENS is believed by some to stimulate the body's natural production of endorphins, which are analgesics.

Images-5 Acupuncture, similarly, is used to relieve pain, as well as to ameliorate some of the side effects,  including nausea, commonly experienced by patients undergoing chemotherapy and radiation. The same is true of meditation and hypnosis, which some patients claim can help them alleviate their pain. Other therapies, such as aromatherapy, massage and practicing the ancient exercise of yoga, help primarily by relaxing the patient and improving their overall mind-body wellness. Herbal treatments are gaining in popularity and efficacy as well, as they become better understood, and evidence is emerging that certain herbs, such as licorice root, American ginseng and oldenlandia can ameliorate advanced lung cancer symptoms. Nutritional approaches, such as supplements, herbal teas or tinctures, and a change in diet can help improve the patient's overall health as well as targeting both specific symptoms of mesothelioma and the side effects of its conventional treatments.

An increasing number of physicians and oncologists are recognizing the value of alternative therapies, and integrating them into the treatment plan. Each treatment program is individually tailored, in order to best address the individual patient's needs, symptoms, advancement of disease, and wishes. Integrative medicine, as the combination of traditional cancer treatments and more holistic approaches has come to be known, is considered by many health care professionals to be the best path to superlative patient care. Indeed, the incorporation of proven alternative therapies into a standard medical treatment regimen can yield more satisfying results for patients and their caregivers than can reliance upon conventional modalities alone, and it is likely that future preferred mesothelioma treatment methods will be integrative in nature.

Tags:  mesothelioma 

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Integrative Boot Camp 101: The Fundamentals of Integrative Medicine

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