Fibromyalgia & Classical Homeopathy
A double-blind, randomized, parallel-group, placebo-controlled pilot study (Rheumatology. 2004; 43: 577-582) "demonstrated that individualized homeopathy is significantly better than placebo in lessening tender point pain and improving the quality of life and global health of persons with fibromyalgia." Sixty-two people with physician-confirmed fibromyalgia took part in the six-month study. Each was assessed by two experienced classical homeopaths at a clinic in Phoenix, Arizona. The homeopaths were instructed to agree on one homeopathic remedy (with a confidence rating of at least seven out of ten) for the patient to take daily. The research team hoped having two homeopaths agree on a treatment would increase the likelihood that the correct remedy was chosen for each patient. An inaccurately chosen remedy will have no effect (i.e., work like a placebo), reducing the number of participants who receive active treatment and skewing the results toward a negative finding. Patients in this study received either the prescribed remedy (liquid LM potencies) or an indistinguishable placebo, according to a randomization code. Hahnemann Laboratories in California dispensed the remedies and placebos directly to the patients. A split sample research bottle was sent directly to the research pharmacist. During the study, only the methodologist in Tucson and Hahnemann's pharmacist had access to the randomization code.

Patients visited the homeopaths at baseline, two months, four months, and six months. Homeopaths were permitted to change remedies and potencies whenever clinically indicated throughout the trial. Patients also traveled to the University of Arizona (Tucson) for laboratory assessment at baseline, three months, and six months. There, all patients completed questionnaires and had a physical exam by a conventional provider who rated trigger point pain. Patients were also given electroencephalographic (EEG) and electrocardiographic tests that recorded their responses to double-blind, olfactory-administered test doses of their treatment solution and the solvent. Interestingly, EEG responses differentiated between the homeopathic remedy and the placebo (solvent) and identified exceptional clinical responders from other patients.

Bell IR, Lewis DA, II, Brooks AJ, et al. Improved clinical status in fibromyalgia patients treated with individualized homeopathic remedies versus placebo. Rheumatology. 2004;43:577-582. Available at: http://rheumatology.oxfordjournals.org/cgi/reprint/keh111v1. Accessed July 5, 2006.

Williams M. Individualized homeopathy helps fibromyalgia sufferers. Available at: http://bastyrcenter.org/content/view/420/&page=1. Accessed July 5, 2006.

Polycarbonate Plastic Bottles & Bisphenol A
A few years ago, I bought a polycarbonate plastic bottle (i.e., Nalgene) for drinking water. I was told that polycarbonate plastic does not leach chemicals into the liquid it holds. Then, I noticed a response to a letter in Co-op America Updates (March/April 2006) that sent me searching online for information to support or refute my assumption that polycarbonate is the best choice. I learned that polycarbonate plastic – used in drinking bottles, baby bottles, microwave ovenware, as a coating in metal cans, and as a plastic coating for children's teeth to prevent cavities – releases bisphenol-A (BPA). BPA has several negative health effects, especially for children and pregnant women.

Industry uses over 6.4 billion pounds of this compound each year, according to Frederick S. vom Saal and Claude Hughes. In a commentary that calls for a new risk assessment for BPA (Environmental Health Perspectives. August 2005), vom Saal and Hughes state that 94 of 115 in vivo studies, published as of December 2004, reported significant effects from low-dose exposure to BPA. In 31 of these studies, effects occurred below the "safe" or reference dose of 50 micrograms/kg/day. Chemical manufacturers contest these findings; industry-funded studies report no significant effects from low doses of BPA. In contrast, over 90% of government-funded studies have detected significant negative effects, according to vom Saal and Hughes.

Many of the effects are due to BPA's hormonal properties. Bisphenol A is among the chemicals that Dr. Theo Colburn, co-author of Our Stolen Future, identifies as "weakly" estrogenic compounds. In vitro experiments have demonstrated that BPA disrupts cell function at 10-12 M or 0.23 ppt. Like other "weak" estrogenic compounds, bisphenol A is "as powerful as estrogen at increasing calcium influx into cells and stimulating prolactin secretion." A January 2006 study in Environmental Health Perspectives says that BPA's estrogenic effect disrupts pancreatic ß-cell function and induces hyperinsulinemia and insulin resistance in mice. BPA also has shown negative effects on prostate development in mice, including "susceptibility to adult-onset precancerous lesion and hormonal carcinogenesis." In addition, low-dose bisphenol A causes aneuploidy (chromosome abnormalities) in mice. Aneuploidy in humans produces birth defects and miscarriages. A small study by Japanese researchers found that women with a history of repeated spontaneous miscarriages had higher BPA levels.

BPA has also been linked to changes in brain structure and altered behavior. Female mice exposed to low levels of BPA (one-fifth the amount considered safe) spent less time nursing and more time out of the nest and away from the offspring. The brains of male rats that have been exposed to "safe" BPA levels show an increase in the size of the locus ceruleus. Part of a major norepinephrine pathway, the locus ceruleus, believed to be a fear/anxiety center, is normally larger in females than in males. This pattern reverses when rats are exposed to BPA.

High heat, alkalinity, and repeated use are known to increase the amount of BPA that leaches from polycarbonate containers. But a recent study from the University of Missouri found that polycarbonate releases BPA at room temperature and neutral pH. The researchers compared BPA levels in purified water that sat in animal cages, made from different materials, for one week. They found: "Significant estrogenic activity, identifiable as BPA by [gas chromatography/mass spectrometry] (up to 310 micrograms/L), was released from used polycarbonate animal cages. Detectable levels of BPA were released from new polycarbonate cages (up to 0.3 micrograms/L) as well as new polysulfone cages (1.5 micrograms/L), whereas no BPA was detected in water incubated in glass and used polypropylene cages." Polysulfone has a higher temperature and chemical tolerance than polycarbonate and is supposed to leach BPA less readily, according to manufacturers. The University of Missouri researchers warn that the use of BPA-leaching equipment can compromise the accuracy of experiments investigating estrogenic chemicals.

Pregnant women and children may be particularly vulnerable to the widespread use of polycarbonate plastics. Vom Saal and Hughes state that "the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice." The information on www.ourstolenfuture.org has encouraged me to return to using glass, steel, or polypropylene bottles.

Alonso-Magdalena P, Morimoto S, Ripoli C, et al. The estrogenic effect of bisphenol a disrupts pancreatic b-cell function in vivo and induces insulin resistance. Environmental Health Perspectives. 2006;114: 106-112.

Howdeshell KL, Peterman PP, Judy BM, et al. Bisphenol A is released from used polycarbonate animal cages into water room temperature. Environmental Health Perspectives. 2003;111:1180-1187. Available at: www.ehponline.org/members/2003/5993/5993.pdf. Accessed June 22, 2006.

"Is Polycarbonate Really Dangerous?" Co-op America Updates. March/April 2006.

Our Stolen Future. Background on BPA. Available at: www.ourstolenfuture.org/NewScience/oncompounds/bisphenola/bpauses.htm. Accessed June 22, 2006

Vom Saal FS, Hughes C. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment (Abstract). Environmental Health Perspectives. 2005;113:926-933. Available at: www.ehponline.org/doc/2005/7713/abstract.html. Accessed June 22, 2006

Systematic Reviews & Evidence-Based Medicine
Systematic reviews, derived from individual studies, are part of the move towards evidence-based medicine. Using the principles of research synthesis, researchers find and assess studies that relate to specific questions, such as "Does black cohosh relieve hot flashes?" The studies are then summarized and synthesized so that the researchers can provide an overall interpretation that responds to the question. This interpretation may change as new studies arise, so systematic reviews should be updated periodically. To reduce subjectivity and bias, at least two researchers should independently select and access pertinent studies for a systematic review, using an explicit, reproducible method. Systematic reviews help people make treatment decisions based on the volumes of studies being conducted; but like the studies themselves, systematic reviews have some shortcomings.

Individual studies, used in systematic reviews, vary in quality and study design. Although randomized, double-blind, placebo-controlled studies usually top the "hierarchy of evidence" list, this study design is not useful for determining rare side effects. In addition, these studies are usually short-term, making it impossible to evaluate long-term effects. M.G. Myriam Hunink, professor of clinical epidemiology and radiology in Rotterdam, The Netherlands, wrote that a case control or observational study is better for identifying rare side effects of a treatment and that cohort studies provide the best evidence for causes of illnesses and prognoses.

Drug studies showing a positive effect are more likely to be published that those that show a neutral or negative effect, and industry-funded or affiliated studies are more likely to show a greater response than those performed by independent researchers. For this reason, systematic reviewers try to find unpublished studies, including adverse reports and post-marketing studies. Otherwise, they risk creating a review that overestimates a treatment's effectiveness and underestimates its negative effects. Hilda Bastian of Cologne, Germany, describes "the first of many experiences of being led down the garden path by a systematic review because of absent or weak information on adverse effects" in the British Medical Journal (October 30, 2004).

Systematic review methodology is also susceptible to conscious or unconscious biases. The criteria that researchers chose for evaluating relevant studies influences the results of a systematic review. "There are many different scales for assessing the strength and quality of a study that may be included in a review," journalist Roy Moynihan explains in his Milbank Memorial Fund report Evaluating Health Services: A Reporter Covers the Science of Research Synthesis. "Like the whole science of research synthesis, these scales are evolving." As an example, Moynihan refers to a 1999 JAMA study conducted by Peter Juni and colleagues (JAMA. 282:1054-60). The team used the 17 trials from a published meta-analysis (a type of systematic review) that compared low-molecular-weight heparin to standard heparin as prevention for deep vein thrombosis, but the team evaluated the trials' quality with a variety of scales. Some of the resulting meta-analyses indicated that low-molecular-weight heparin was more effective than standard heparin. Other analyses showed the exact opposite. As a unit, the 25 meta-analyses, conducted by Juni and colleagues, showed no overall difference in the effectiveness of the two treatments. Moynihan says that "part of the controversy surrounding the systematic review of mammography screening for breast cancer, published in The Lancet in 2001, arose because different researchers have different views on the quality and strength of the original studies that were reviewed."

Despite the limitations of systematic reviews, health care insurers, hospitals, and government agencies are depending upon them to clarify the haze generated by a flood of research studies. Moynihan lists several organizations that produce good quality systematic reviews: Canadian Coordinating Office for Health Technology Assessment, Cochrane Collaboration, National Health Service Center for Reviews and Dissemination, National Institute for Clinical Excellence, Scottish Intercollegiate Guidelines Network, and United States Preventive Services Task Force. It is important to remember that these reviews are works-in-progress.

Bastian H. Learning from evidence-based mistakes. BMJ. 2004; 329:1053. Available at: http://bmj.bmjjournals.com/cgi/content/full/329/7473/1053. Accessed July 5, 2006.

Hunink MGM. Does evidence based medicine do more good than harm? BMJ. 2004;329:1051. Available at: http://bmj.bmjjournals.com/cgi/content/full/329/7473/1051. Accessed July 5, 2006.

Juni P, Witschi A, Bloch R, et al. The hazards of scoring the quality of clinical trials for meta-analysis (Abstract). JAMA. 1999;282:1054-60. Available at: http://jama.amaassn.org/cgi/content/abstract/282/11/1054. Accessed July 31, 2006.

Moynihan R. Evaluating Health Services: A Reporter Covers the Science of Research Synthesis. New York: Milbank Memorial Fund, 2004. ISBN 1-887748-56-3.

Genes & Chemical Sensitivity
Genetic differences may explain why some people develop multiple chemical sensitivity (MCS) and others do not, according to a 2004 International Journal of Epidemiology study. Epidemiologist Gail McKeown-Eyssen of University of Toronto (Canada) led a study that investigated variations in five genes – CYP2D6, NAT1, NAT2, PON1, and PON2—among 365 Caucasian women (203 with MCS and 162 controls). These genes govern the body's production of drug-metabolizing enzymes.

The researchers found that women with MCS were more likely to have more active forms of CYP2D6 and NAT2. Women with higher CYP2D6 activity were more than three times as likely to be chemically sensitive than those with inactive CYP2D6. Enzymes governed by CYP2D6 break down chemicals that include neurotransmitters, central nervous system medications (e.g., various antidepressants, stimulants, and codeine), and procarcinogens (substances that break down into reactive, carcinogenic compounds). Women with a rapid metabolizing form of NAT2 were four times more likely to be chemically sensitive than those with those with slow-metabolizing NAT2. Women with active forms of both genes were 18 times more likely than controls to have chemical sensitivity, a finding that McKeown-Eyssen views with caution. The original study design did not include analyses for such an interaction, and the number of participants with this gene combination was very small.

The researchers hypothesize that people with these active gene forms may be metabolizing chemicals faster than the body can eliminate the resulting toxic byproducts, creating the varied symptoms of MCS.

McKeown-Eyssen G, Baines C, Cole DEC, et al. Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR. International Journal of Epidemiology. 2004; 33:971-978. Available at: http://ije.oxfordjournals.org/cgi/content/short/33/5/971. Accessed on June 22, 2006.

Spivey A. Genes and sensitivity. Environmental Health Perspectives. 2005;113: A157.

Chemical Intolerance & Addiction
Chemical intolerance may be the "flipside" of chemical addiction, according to Claudia S. Miller, professor of environmental and occupational medicine at the University of Texas Health Science Center (San Antonio). "Addicted individuals seek repeated hits of a substance," she explained [in an article for Chemical & Engineering News], "while the chemically intolerant shun many of the same substances. But the reason for these seemingly opposite behaviors may well be the same — to avoid unpleasant withdrawal symptoms." Miller says that addiction and chemical intolerance may also have a similar neurotransmitter pathway and pathophysiology. Miller organized a 2005 joint meeting of the National Institute of Environmental Health Sciences (NIEHS) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) so that researchers from the two specialties could share information and research methods.

One of the speakers at the conference was Barbara A. Sorg, professor of neuroscience at Washington State University (Pullman). Sorg has used rats to investigate the involvement of the limbic system in chemical sensitivity. Researchers know that repeated doses of cocaine sensitize the mesolimbic dopamine pathway in the rat's brain, leading to addiction. Using rats that had never been exposed to cocaine, Sorg repeatedly exposed them to low levels of formaldehyde vapor. Later, when she administered cocaine to these rats, they responded as if they had been previously sensitized to cocaine, suggesting that the mesolimbic pathway may have been sensitized by the formaldehyde exposure.

Another speaker, David H. Overstreet, has developed a strain of rats that could be used as an animal model for chemical intolerance. Overstreet is a professor of psychiatry at the University of North Carolina (Chapel Hill). Flinders Sensitive Line (FSL) rats, like people who are chemically sensitive, react negatively to organophosphate pesticides, such as diisopropyl fluorophosphate (DFP). FSL rats and chemically intolerant people also react to nicotine, ethanol, and many drugs, including serotonin agonists and dopamine antagonists. When exposed to egg protein, FSL rats exhibit increased gut permeability and airway reactivity. Food intolerance and asthma are among the symptoms reported by chemically sensitive people. FSL rats also show signs of depression, including inactivity, disinterest in eating, and intermittent sleep. Depression is another common complaint of people with chemical intolerance.

Chemical intolerance disables or compromises the life quality of three-to-six percent of the US population. Organizers of the conference hope that collaboration between the two specialties will lead to preventive and treatment strategies for chemical intolerance.

Hileman B. Chemical intolerance. Chemical & Engineering News. October 10, 2005; 83;(41):24-29. Available at: http://pubs.acs.org/email/cen/html101005155844.html. Accessed June 22, 2006.

Treatment Ratings for Multiple Chemical Sensitivity
Researchers at James Madison University (Harrisonburg, Virginia) gathered information from 917 people with self-reported multiple chemical sensitivity (MCS) concerning their experience with various treatments. Respondents to this survey reported using over 101 treatments, including environmental medicine techniques, holistic therapies, individual nutritional supplements, detoxification techniques, body therapies, Eastern-origin techniques, prescription items, and others. The researchers hoped the survey would give patients, many of whom rely on disability or worker's compensation for income, a way to evaluate possible treatments. Clinical studies that evaluate MCS treatment are very limited.

The survey, published in Environmental Health Perspectives (Sept. 2003), gives the number of people who tried each treatment, the respondents' ratings for the treatment, and a help:harm ratio (the number of people who reported the treatment helpful compared to the number reporting it harmful). "Treatments with the highest help:harm ratios have more positive and fewer negative effects, according to respondents' perceived efficacy ratings," the authors explain. Creating a chemical-free living space, chemical avoidance, and prayer had the highest help:harm ratios. Of the 820 people who had created a chemical-free living space, 94.8% said it was helpful, 4.5% said it had no effect, and 0.6% found it harmful. This intervention, however, was quite expensive; respondents spent a mean of $57,000 to create a safe home. Of the 875 who used chemical avoidance, 94.5% found it helpful, 4.7% reported no effect, and 0.8% experienced a negative effect. Using air filters to prevent exposure was also rated helpful by 82.1% of the 786 who tried them. Of the 609 people who sought help through prayer, 64.2% said it helped, 34.4% reported no effect, and 1.4% reported harm. Rotation diet, personal oxygen to cope with exposures, acupressure, reflexology, and moving to a safe location all had help:harm ratios over 10, meaning ten times as many people rated it helpful as rated it harmful. Pharmaceuticals (including antidepressants) and provocation-neutralization testing for chemicals with preservative drew the highest negative response.

The researchers write: "Many people noted in the qualitative comments that it was only the combination of treatments that helped them improve. Many reported that it was necessary to do environmental controls, a correctly tailored program of nutritional supplements, and a number of other interventions that addressed their own unique constellation of symptoms."

Gibson PR, Elms ANM, Ruding LA. Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity. Environmental Health Perspectives. 2003;111:1498-1504. Available at: www.ehponline.org/members/2003/5936/5936.pdf. Accessed July 5, 2006.

Magnetic Resonance Imaging Evidence of Fibromyalgia
A study, published in Arthritis & Rheumatism (May 2002), used functional magnetic resonance imaging (fMRI) to provide evidence that 16 people diagnosed with fibromyalgia (FM) showed greater sensitivity to pain than 16 healthy, matched controls. The researchers used a 1-cm3 hard rubber probe attached to a hydraulic piston to apply controlled, repeatable pressure of five-second duration to the left thumbnail beds of each participant. As the pressure gradually increased from 0.45 kg/cm2 to 9 kg/cm2 or to tolerance, participants described their experience of pain and unpleasantness using a numerical analog descriptor scale. fMRI patterns were similar in patients and controls when the pain/unpleasantness rating was the same, but controls required more pressure to elicit the same pain rating given by FM patients. Earlier studies have shown that people with FM and those without it tend to notice sensory stimulation (electrical, thermal, mechanical) at the same levels, but those with FM report painful or unpleasant sensations at lower stimulation levels

This fMRI experiment also found that mild pressure activated only two areas of the brain in control subjects compared to 12 areas of activation in the patients. Eight of those 12 areas became active in control subjects when stimulation pressure reached higher levels. Hypervigilance and anticipation of pain are known to activate sensory areas of the brain, but the study's authors rule out both factors because they found a pattern of decreased activity in the anterior cingulate cortex. This area of the brain becomes more active during anticipation and attention, not less. Decreased activity in this area occurs during hypnotic analgesia (insensitivity to pain). The study's authors view their findings as support for the hypothesis that "FM is characterized by cortical or subcortical augmentation of pain processing."

Richard H. Gracely, PhD, one of the study's authors told WebMD, "What [this study] shows is that the brain response is consistent with what the patients report verbally….Being believed is an extremely important issue for these people. Now these physical findings are emerging, it is gratifying for these patients [sic]….The general public doesn't realize that pain can be very severe – and sometimes untreatable – in a person who does not seem to be injured."

DeNoon D. Brain scan proves what sufferers have always known. WebMD Medical News. Available at: www.webmd.com/content/article/48/39261.htm. Accessed on July 5, 2006.

Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis & Rheumatism. 2002;46: 1333-1343.

Marshall Protocol for Sarcoidosis
Trevor G. Marshall, PhD, affiliated with Autoimmunity Research Foundation (Thousand Oaks, California), has developed a therapy to treat sarcoidosis. Marshall characterizes sarcoidosis as a Th1 inflammatory disease caused by pleomorphic intracellular bacteria. Marshall says that the bacteria infect phagocytes, triggering a cytokine release that leads to a "runaway immune reaction." The bacteria are also present in the blood of healthy people, but this disease develops in people with susceptible alleles on the HLA-DRB1 gene. Marshall and colleagues believe that overproduction of 1,25-dihydroxyvitamin D is another predisposing factor. Vitamin D controls the TH1 immune response, according to Marshall, and is nearly always elevated in people with sarcoidosis. Sarcoid inflammation can affect several organs including the lungs, spleen, liver, skin, heart, and brain.

Moscovic first discovered acid-fast, Cell Wall Deficient (CWD) bacteria in biopsy specimens from sarcoidosis patients in 1978. Since then, Borrelia, Mycobacterium, Rickettsia, and Propionibacterium have been found in sarcoidosis patients. Pleomorphic bacteria transform into cell wall-deficient microbes as a defense against hostile environments within the body and as a defense against antibiotics that attack the bacterial cell wall.

The Marshall Protocol (MP) uses long-term antibiotic therapy to weaken these bacteria so that the immune system can destroy them. The protocol begins with no more than 25 mg of minocycline every 48 hours. Patients experience Jarisch-Herxheimer Shock (JHS) as the bacteria die off and release toxins. If the microbes are killed too quickly, patients can die. Consequently, doctors must monitor patients carefully and prescribe a dosage that produces JHS reactions that the patient finds tolerable. Marshall's team has observed that "patients who do not experience significant JHS are not killing the bacteria at a rate fast enough to induce remission of their sarcoid inflammation." Skin reactions, breathing difficulties, and bradycardia are among the common reactions to the therapy.
The protocol calls for a gradual increase in minocycline over the first three months of treatment. When a patient tolerates 100 mg of minocycline every 48 hours, one quarter of a 250 mg azithromycin tablet (˜62 mg) once a week is added to their regimen. Over several months, the azithromycin dosage gradually increases to 250 mg/week. With both antibiotics at "full dosage," a little sulfamethoxazole/trimethoprim can be taken with the minocycline to boost its effectiveness against resistant bacteria.

More information about the Marshall Protocol is available at http://AutoimmunityResearch.org. In addition, www.MarshallProtocol.com has a forum for medical professionals only, and www.SarcInfo.com has papers for physicians and patient tutorials.

Autoimmunity Research Foundation. The Marshall Protocol. Available at: http://AutoimmunityResearch.org/phase1.pdf. Accessed June 22, 2006.

Marshall TG, Fenter BJ, Marshall F. Antibacterial therapy induces remission in sarcoidosis. Journal of Independent Medical Research. 1957 (October 26, 2005). Available at: www.joimr.org/phorum/read.php?=2&i=107&t=107. Accessed June 22, 2006.

Marshall TG, Marshall FE. Sarcoidosis succumbs to antibiotics - implications for autoimmune disease. "Autoimmunity Reviews." 2003;3(4):295-300. Available at: http://yarcrip.com/sarcoidosissuccumbs-preprint.htm. Accessed June 22, 2006.

Vitamin D Recommendations
New knowledge about vitamin D's role in preventing several serious conditions is propelling the Institute of Medicine to re-examine the recommended daily allowance (RDA). Vitamin D deficiency has been linked to common cancers, autoimmune diseases, type 1 diabetes, heart disease, and osteoporosis. Because muscle pain and aching bones are common signs of vitamin D deficiency, it is often misdiagnosed as fibromyalgia or chronic fatigue syndrome, according to Michael F. Holick, PhD, of Boston University School of Medicine.

Humans make vitamin D when ultraviolet B (UVB) rays from sunlight reach our skin. Reduced exposure to sunlight and the use of sunscreen inhibit the amount of vitamin D that we produce. Oily fish (salmon, sardines, mackerel) and cod liver oil also provide D, but few people in the US consume these regularly. Dark skin, aging, and obesity are other causes of low serum levels. To help offset vitamin D deficiency, milk, packaged cereals, and some yellow spreads are supplemented with vitamin D2 or vitamin D3. Dr. Laura Armas from Creighton University (Omaha, Nebraska) and colleagues found that a single 50,000 IU dose of D3 results in higher blood levels of vitamin D and 25-hydroxyvitamin D (a biologically active form of D made in the liver) than does the same dose of D2, and levels remain high for a longer period. D3 supplements, however, are manufactured in a process that uses lanolin, a concern for vegetarians.

The Adequate Intake (AI), set by the Food and Nutrition Board of the Institute of Medicine in 1997, is 200 IU/day for infancy through age 50, 400 IU for people 51-70, and 600 IU for those over 70 years. Holick and other vitamin D experts recommend a minimum of 1000 IU/day, according to an article on RedOrbit News. However, people with primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma need to consult a qualified practitioner before supplementing with vitamin D because of the risk of hypercalcemia (high blood levels of calcium). Hypercalcemia is also characterized by muscle pain and weakness and can lead to calcification of organs if left untreated for a long period. Concerns about inducing hypercalcemia have kept vitamin D intake recommendations low. Jane Higdon, PhD, at the Linus Pauling Institute (Portland, Oregon), says: "Research published since 1997 suggests that the UL [upper intake level] for adults is likely overly conservative and that vitamin D toxicity is very unlikely in healthy people at intake levels lower than 10,000 IU/day. Vitamin D toxicity has not been observed to result from sun exposure."

Higdon J. Vitamin D. Available at: http://lpi.oregonstate.edu/infocenter/vitamins/vitaminD/index.html. Accessed July 6, 2006.

Vitamin D deficiency: common cause of many ailments. RedOrbit News. February 10, 2005. Available at: www.redorbit.com/modules/news/tools.php?tool=print&id=126369. Accessed July 5, 2006.