CHELATION AND MISC

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A SCIENTIFIC LOOK AT ALTERNATIVE MEDICINE

Chelation Therapy;

Allergy and Arthritis Treatments; Other Miscellaneous Topics

Thomas J. Wheeler, Ph.D.

Associate Professor (retired), Department of Biochemistry and Molecular Biology,

University of Louisville School of Medicine, Louisville KY

thomas.wheeler@louisville.edu

Revised 2018

This material was originally part of a handout for an elective course given to medical students at the University of Louisville.

DISCLAIMER: The material presented here is not medical advice. It represents the author's summary of scientific evidence concerning various topics. For medical advice, see your physician.

CONTENTS

Chelation therapy

Allergy treatments

Arthritis treatments

"Chronic Lyme disease"

Clinical ecology

Controversial diseases and syndromes (adrenal fatigue, candidiasis sensitivity, chronic fatigue, fibromyalgia, “leaky gut,” Morgellons)

Devices

Magnets

Mercury amalgam and other topics in dentistry

Oxygenating therapies

Stem cells

Other miscellaneous topics (alkaline diet, anti-aging treatments, applied kinesiology, bee venom therapy, behavioral vision therapy, bioidentical hormones, biological terrain assessment, Buteyko Breathing Technique, cold temperature treatments, colloidal silver, colonic irrigation, detoxification, detoxifying foot baths, ear candling, earthing, full body scans, genetic testing, hair analysis, HGH, hypoglycemia, intravenous nutrient therapy, Kinesio taping, live cell analysis, low level laser therapy, multiple sclerosis, neural therapy, progesterone and yam creams, prolotherapy, provoked challenge urine testing, testosterone supplementation, thermography, ultraviolet blood treatment, water, whole-body vibration)

CHELATION THERAPY

Principles. Ethylenediamine tetraacetic acid (EDTA) binds strongly with metal ions having two positive charges (it chelates them). There is a legitimate use in removing heavy metals like lead in cases of metal toxicity (approved by FDA for heavy metal poisoning and for Wilson's disease, in which there is excess copper storage). By extension, alternative practitioners use it to remove supposed toxic metals underlying other conditions.

An early rationale was to remove Ca2+ from calcified plaques in arterial disease, as well as deactivation of calcium channels to prevent hypertension. "The lowering of serum calcium during and immediately after a treatment stimulates the release of parathyroid hormone, resulting in the partial removal of metastatic calcium deposits, including those from atherosclerotic plaque" (Chappell 1997. Altern Med Rev. 2(6):426-32).

A newer rationale sees free radicals as being responsible for most chronic illnesses. EDTA is supposed to prevent this. It also is alleged to lower LDL and VLDL, inhibit platelet aggregation, and relax vascular tone.

Practice and scope. Intravenous injection is used to administer EDTA (thus, the practice is limited to physicians and others under their supervision who are allowed to give IV's. Note that physicians can use approved drugs for unapproved purposes!). Disodium EDTA has been the preferred form used by chelationists, whereas sodium calcium EDTA is used with heavy metal poisoning (if chelationists believed the free radical hypothesis, one might think they would prefer this form).

It is claimed to be effective in a wide range of diseases, including heart disease, kidney disease, arthritis, Parkinson's disease, Alzheimer's disease, diabetes, emphysema, and multiple sclerosis, as well as the aging process itself. It is also claimed to help 75% to over 90% of patients.

110,000 patients in the U.S. used chelation therapy in 2007.

Compounds to be taken orally or applied transdermally are also marketed as alleged chelating agents. Cohen and others found that the chelator 2,3-dimercaptopropane-1-sulfonate (DMPS), approved in Europe for oral or intravenous use, was ineffective when applied transdermally as is done by some alternative practitioners (J Med Toxicol. 2013 Mar;9(1):9-15).

Use of chelation is supported by anecdotal evidence, studies in obscure medical journals, and nondocumented studies described in books

Provoked challenge urine testing employs chelating agents to test for metals. This is discussed below under Miscellaneous Topics.

Scientific evaluation:

Basic science: There is no way for EDTA to remove "bad" but not "good" calcium.

"This rationale [deblocking of arteries] is (at best) based on an outdated understanding of artherogenesis. There is reason to believe that proponents of chelation therapy adhere to pathophysiological models of arteriosclerosis, which are in overt discordance with our present knowledge." (Ernst 1997 Aug 5. Circulation. 96(3):1031-3.)

There is no evidence that EDTA prevents free radical damage. Free radicals are produced as a side-product of normal metabolic reactions, and removing the metals that cause these would prevent vital cellular processes. Moreover, while iron is bound to EDTA and still in the circulation, it remains capable of forming free radicals.

Clinical trials: A randomized, double-blind trial for ischemic heart disease found no benefits (Knudtson et al. 2002 Jan 23-30. JAMA. 287(4):481-6). A clinical trial for intermittent claudication (a problem of circulation to the legs) showed no effect (1992).

The TACT Trial. In 2002, the National Center for Complementary and Alternative Medicine (NCCAM) and the National Heart, Lung, and Blood Institute announced a $30 million, 5-year study of chelation therapy, to include 2400 patients at 100 sites. In part this appears to have been in response to pressure from Rep. Dan Burton, a prominent advocate of alternative medicine. The trial tested chelation with or without an oral high dose vitamin and mineral supplement.

Many criticisms of the study were raised by scientists. As a result, the study was temporarily suspended in 2008. Some of the criticisms were:

• Lack of a plausible rationale for why chelation should work

• Potential dangers

• Previous trials showed no benefit.

• More than a dozen of the doctors involved had "trouble with federal regulators, state medical boards, and even, in some cases, the law" (Tsouderos 2011 Dec 12. Chicago Tribune).

• Patients were not given adequate informed consent.

• "Only 12 of the 110 TACT study sites were academic medical centers. Many of the study sites were highly dubious clinics touting highly dubious therapies" (Gorski 2012 Nov 5. Science-Based Medicine blog)

• "...blinding of the study groups to local investigators was likely to be faulty" (ibid).

Results of the trial were announced in November, 2012, and published in March, 2013 (Lamas et al. 2013 Mar 27. JAMA. 309(12):1241-50) with additional analysis published in July, 2014 (Lamas et al. 2014 Jul. Am Heart J. 168(1):37-44.e5; Mark et al. 2014 Jul. Circ Cardiovasc Qual Outcomes. 7(4):508-16). The results indicated a small positive effect for a "primary composite end point" of five separate outcomes. According to Atwood (2012 Nov 4. Science-Based Medicine blog), "Although that result may seem intriguing, it becomes less so when the data are examined more carefully. First, it barely achieved the pre-ordained level of statistical significance, which was P=.036. Second, none of the individual components of the composite endpoint achieved statistical significance, and most of the absolute difference was in coronary revascularization – which is puzzling..."

He further noted, "It’s ironic, then, that the TACT results are informative in an important way that its authors seem to have overlooked: it convincingly demonstrates that the claims of chelationists have been bogus all along. That’s because those claims have been far more dramatic than even the small effect that the TACT may appear to support. Typically, chelationists, including those involved in the TACT, claim 'improvement' or even 'marked improvement' in 80-90% of patients with ischemic heart disease or other vascular disease."

Another point made was that there were many more dropouts in the placebo group, suggesting that patients found out that they were only getting placebo. There was no effect on the quality of life, and the benefits were only seen for the subgroup with diabetes.

In editorials accompanying the publication of the main results, Bauchner et al. (2013 Mar 27. JAMA. 309(12):1291-2) wrote, "these findings do not support the routine use of chelation therapy as secondary prevention for patients with previous myocardial infraction and established coronary disease. Whether chelation therapy may have any role in the prevention and treatment of cardiovascular disease remains to be determined," while Nissen (2013 Mar 27. JAMA. 309(12):1293-4) wrote, "Given the numerous concerns with this expensive, federally funded clinical trial, including missing data, potential investigator or patient unmasking, use of subjective end points, and intentional unblinding of the sponsor, the results cannot be accepted as reliable and do not demonstrate a benefit of chelation therapy. The findings of TACT should not be used as a justification for increased use of this controversial therapy."

In 2016, it was announced that a followup trial (TACT2) will be funded for $37 million. This will focus on the subgroup that appeared to show benefits, patients with diabetes and previous heart attacks.

Reviews: Meta-analysis by Ernst (2000 July. Am Heart J. 140(1):139-41): “The most striking finding is the almost total lack of convincing evidence for efficacy...Given the potential of chelation therapy to cause severe adverse effects, this treatment should now be considered obsolete.”

Review by Dans et al. (2002 21 Oct. Cochrane Database Syst Rev. (4):CD002785): “At present, there is insufficient evidence to decide on the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of patients with atherosclerotic cardiovascular disease.”

Review by Seely et al. (2005 Nov 1. BMC Cardiovasc Disord. 5:32): “The best available evidence does not support the therapeutic use of EDTA chelation therapy in the treatment of cardiovascular disease.”

Side effects: Chelation is dangerous if it is used instead of proper medical treatment for these diseases.

"Furthermore, the serious side effects of EDTA chelation are worrisome. Toxic effects include renal toxicity, cardiac arrhythmias, bone marrow depression, exfoliative dermatitis, histamine-like reactions, insulin shock, and thromboemboli. Fortunately, few adverse effects have been reported when the guideline of 50 mg/kg per infusion is used, as specified by the American College of Advancement in Medicine." (Elihu et al. 1998 Feb. J Clin Pharmacol. 38(2):101-5).

Guldager et al. (1993 Nov. Dan Med Bull. 40(5):627-30) found that EDTA treatment was accompanied by bone loss.

In 2005, a 5-year-old died after chelation therapy for treatment of autism.

Other points: Chelation is expensive (about $100 per treatment; typically 30 weekly treatments are given, followed by additional treatments less often), and usually is not covered by insurance.

The treatment may also include exercise and diet, which could lead to improvement being attributed to chelation.

The American College of Advancement in Medicine (ACAM) is an organization of "integrative medicine" physicians, and has served as the major group advocating chelation therapy. "Chelation therapists in the United States have set up certifying boards so they can call themselves 'board certified.' The American Board of Chelation Therapy (ABCT) was founded in 1982...The American Board of Clinical Metal Toxicology (ABCMT) was founded in 2003...Neither is recognized by the American Board of Medical Specialties (ABMS), which sets the certification standards for in the United States" (Barrett. 2009. Be wary of 'board certification" in clinical metal toxicology. Quackwatch). At one point ACAM estimated that there were 800,000 chelation visits per year.

In 1998, the FTC reached a consent agreement with ACAM, prohibiting it from “representing that EDTA chelation therapy is an effective treatment for atherosclerosis without possessing and relying upon competent and reliable scientific evidence to substantiate the representations.”

In 2010 the FDA issued warnings to eight companies for promoting over-the-counter chelation products for autism and other conditions.

ALLERGY TREATMENTS

About 20% of Americans suffer from allergies, making it a profitable area for alternative treatments. “In 2005, 18% of patients seen in United States food allergy clinics reported using CAM for treatment of their food allergies” (Wisniewski and Li. 2012 Feb. Immunol Allergy Clin North Am. 32(1):135-50).

A survey of websites of Canadian alternative practitioners (Murdoch et al., BMJ Open. 2016 Dec 16;6(12):e014028) found that "Naturopath clinic websites have the highest rates of advertising at least one of diagnosis, treatment or efficacy for allergy or sensitivity (85%) and asthma (64%), followed by acupuncturists (68% and 53%, respectively), homeopaths (60% and 54%) and chiropractors (33% and 38%)...Of the interventions advertised, few are scientifically supported; the majority lack evidence of efficacy, and some are potentially harmful."

Food allergies - These are relatively rare (5 percent of children, 2 percent of adults) (they should not be confused with food intolerance, which is much more common), but are frequently "diagnosed" by mail order labs and some allergists.

“Common skin-prick tests, in which a person is scratched by a needle coated with proteins from a suspect food, produce signs of irritation 50 to 60 percent of the time even when the person is not actually allergic” (Shell. 2015 Nov 3. Sci Am. 313(5):28-9).

Invalid methods of diagnosis and treatment include:

1. Provocation and neutralization - food extract is injected in the arm or placed under the tongue, and symptoms such as drowsiness or fatigue are looked for. A weaker neutralizing dose is then used to treat the disorder (either before or after an episode with the offending food). However, double-blind studies show that provocation and neutralization methods are invalid.

2. Cytotoxic testing (Bryan's test) - leukocytes are mixed with suspected allergens in vitro and examined under microscope for changes.

3. Urine autoinjection - uses preparation from the patient's own urine. This has potentially dangerous complications.

4. Sublingual testing - foods are placed under tongue.

5. Applied kinesiology - see below (Other Miscellaneous Topics)

6. Nambudripad’s Allergy Elimination Technique (NAET). According to Stephen Barrett’s critique (2017 May 13. Nambudripad's Allergy Elimination Technique (NAET) and its variants. Chirobase), “NAET is a bizarre system of diagnosis and treatment based on the notion that allergies are caused by ‘energy blockage’ that can be diagnosed with muscle-testing and permanently cured with acupressure and/or acupuncture treatments.”

7. IgG testing for food allergies. “Serum IgG4 testing is the most common unconventional diagnostic test performed in the United States to diagnose allergies. IgG4 to a variety of foods and allergens can be measured, but the presence or absence is not involved with the known immunologic mechanism of atopic disease. IgG to certain foods is a common postprandial finding and can not be used to diagnose allergy” (Shah and Greenberger. 2012 May-Jun. Allergy Asthma Proc. 33 Suppl 1:S100-2). “Moreover, the measurement of food-specific IgG levels in blood as a diagnostic tool for food allergy has been disproved by double-blind placebo-controlled food challenge (DBPCFC), where no correlation was found between symptoms resulting from ingestion of the food antigens and levels of food-specific IgG or IgG4 antibodies” (Wisniewski and Li. 2012 Feb. Immunol Allergy Clin North Am. 32(1):135-50).

8. Vegatest - see below (“Devices”)

9. Halotherapy - patients sit in salt caves. There are no controlled trials demonstrating benefits.

A National Institute of Allergy and Infectious Diseases (NIAID) sponsored expert panel “recommends not using any of the following nonstandardized tests for the routine evaluation of IgE-mediated FA [food allergy]:” basophil histamine release/activation, lymphocyte stimulation, facial thermography, gastric juice analysis, endoscopic allergen provocation, hair analysis, applied kinesiology, provocation neutralization, allergen-specific IgG4, cytotoxicity assays, electrodermal test (Vega), mediator release assay (LEAP diet) (Boyce et al. 2010 Dec. J Allergy Clin Immunol. 126(6 Suppl):S1-58).

Silvers and Bailey (2014 Apr. Ann Allergy Asthma Immunol. 112(4):280-5) reviewed CAM methods for allergy and asthma, and concluded:

1. Supplementation with antioxidants "has had variable outcomes in disease modification or prevention."

2. Supplementation with vitamin D has been helpful for children with low vitamin D levels.

3. "There is conflicting evidence regarding the efficacy of supplemental vitamin C."

4. Research with probiotics "is still in its infancy and there is no proven role for probiotics for treatment or prevention of allergy at this time."

5. "A Cochrane review of marine fatty acids for asthma determined that there was little evidence to recommend supplementation with fish oil."

6. "Some data suggests choline, magnesium, and Pinus pinaster pine bark (Pycnogenol) may be helpful in managing asthma."

7. "Butterbur (Petasites hybridus) has been studied as a treatment for AR [allergic rhinitis] with variable results."

8. "A Cochrane review of treatment of AR with capsaicin stated that stated that there was insufficient evidence to evaluate its review."

9. "There is variability in the studies on the effect of yoga on asthma."

10. "There may be added benefit with the Buteyko Breathing Technique [see below, "Other Miscellaneous Topics"] and with the Papworth Method (a combined breathing and relaxation program)."

11. "A review of relaxation therapies for asthma, including progressive muscle relaxation, hypnotherapy, autogenic training, biofeedback training, and transcendental meditation, did not reveal conclusive benefit for asthma treatment."

12. "A Cochrane review of manual therapy for asthma indicated that there was insufficient evidence to support its use."

FAH-2 is a combination of herbs, based on traditional Chinese medicine; it has undergone clinical testing for treatment of food allergies.

A review found that the most popular complementary and alternative methods for asthma patients were breathing techniques, herbal products, homeopathy, and acupuncture (Slader et al. 2006 Jul. Respirology. 11(4):373-87). A meta-analysis by Kohn and Paudyal (Eur Respir Rev. 2017 Jan 31;26(143)) found that "Overall, there was limited evidence on the effectiveness of CAM in adult asthma as most CAMs were only assessed in a single trial. CAMs with multiple trials provided null or inconsistent results. Many of the trials were rated as having high risk of bias.The existing evidence is insufficient to recommend any of the oral and topical CAMs in the management of asthma in adults."

A study of CAM use in children with asthma (Adams et al. 2007 Nov. J Asthma. 44(9):775-82) found that "Positive parental beliefs about CAM were significantly associated with greater risks for nonadherence and poorer asthma control."

ARTHRITIS TREATMENTS

About 40 million Americans suffer from arthritis, many of them having frequent pain. Thus, this is another popular area for alternative remedies. A 2009 survey found that more than 80% "had tried at least 1 complementary therapy for arthritis symptoms" (Callahan et al. 2009. Chronic Dis. 6(2):A44). Annual costs of alternative treatments have been estimated to be $1 to $3 billion.

A study of rheumatology patients (Rao et al. 2003 Oct. Arthritis Rheum. 49(5):619-25) found that the most popular CAM therapies were dietary supplements, herbs, special diets, chiropractic, electrical stimulators, and vitamins and minerals. Other remedies that have been popular include copper bracelets, magnets, golden raisins soaked in gin, bee venom (also promoted for multiple sclerosis) [see below, "Other Miscellaneous Topics"], acupuncture, massage, biofeedback, mud pack therapy, and lubricants.

A National Center for Complementary and Integrative Health [NCCIH] report (2016 May 4. Rheumatoid Arthritis: In Depth) stated "In general, there is not enough scientific evidence to prove that any complementary health approaches are beneficial for RA, and there are safety concerns about some of them. Some mind and body practices and dietary supplements may help people with RA manage their symptoms and therefore may be beneficial additions to conventional RA treatments, but there is not enough evidence to draw conclusions." "Some patients with RA claim that symptoms improve with the elimination of certain foods, but scientific support has been sparse" (Dunn and Wilkinson. 2005. Mod Rheumatol. 15(2):87-90).

Trials found that magnetic and copper bracelets provided no benefit for osteoarthritis (Richmond et al. 2009 Oct.-Dec. Complement Ther Med. 17(5-6):249-56) and rheumatoid arthritis (Richmond et al. 2013 Sep 16. PLoS One. 8(9):e71529).

Acupuncture for arthritis is discussed in the article on Eastern approaches.

Glucosamine and chondroitin sulfate; and methylsulfonylmethane (MSM) are discussed in the article on dietary supplements. Other dietary supplements and herbs taken for arthritis include vitamin E, fish oil, gamma linolenic acid, ginger, turmeric, Thunder God root (a Chinese herbal product), devil’s claw, boswellia, avocado/soybean nonsaponifiables, rose-hip, hyaluronic acid, soy protein, cat's claw, white willow, green tea, and propolis.

"So far there is insufficient reliable evidence on the effectiveness of ginger, turmeric and ananas. Pomegranate and green tea only have preclinical evidence of efficacy due to the lack of clinical data. In vivo and clinical studies are required to understand their targets and efficacy in OA. Limited in vitro and in vivo evidence is available for cat's claw and Indian olibaum. More extensive studies are required before long-term controlled trials of whole cat's claw and Indian olibaum extracts, or isolated active compounds, are carried out in patients with OA to determine their long-term efficacy and safety. Devil's claw has not been rigorously tested to determine its antiarthritic potential in in vitro and in vivo models. There is strong clinical evidence of the effectiveness of devil's claw in pain reduction. However, high-quality clinical trials are needed to determine its effectiveness" (Akhtar and Haqqi 2012 Jun. Ther Adv Musculoskelet Dis. 4(3):181-207).

"The results from clinical trials for products containing avocado/soybean unsaponifiables, Indian frankincense or rosehip suggest some efficay, and these herbs appear to cause few unwanted effects, but more robust data are needed. The UK Medicines and Healthcare products Regulatory Agency has approved traditional Herbal Registrations for several herbal medicinal products containing devil's claw for rheumatic symptoms, but the trial results for this herb are equivocal. There is little conclusive evidence of benefit from other herbs commonly used for symptoms of osteoarthritis, such as cat's claw, ginger, nettle, turmeric and willow bark" (no author listed. 2012 Jan. Drug Ther Bull. 50(1):8-12).

According to a Cochrane Collaboration review, "There is moderate-quality evidence that in people with osteoarthritis Boswellia serrata slightly improved pain and function...There is moderate-quality evidence that avocado-soybean unsaponifiables (ASU) probably improved pain and function slightly, but may not preserve joint space...We are uncertain whether other oral herbal products improve osteoarthritis pain or function, or slow progression of joint structure damage because the available evidence is limited to single studies or studies that cannot be pooled, and some of these studies are of low to very low quality" (Cameron and Chrubasik 2014 May 22. Cochrane Database Syst Rev. (5):CD002947).

A review of supplements for osteoarthritis by Liu et al. (Br J Sports Med. 2018 Feb;52(3):167-17) concluded: "Of 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract, Curcuma longa extract, Boswellia serrata extract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance, Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term Similar results were found for physical function."

DMSO (dimethylsulfoxide) - has local analgesic properties, but results on overall effectiveness are conflicting. There is potential toxicity. (It is also used as cancer treatment). "DMSO and MSM, as with many alternative medicines and nutraceuticals, appear not to cause harm but there is not much credible published evidence that they work" (Ely and Lockwood 2002 Nov 9; Pharmaceut J 269:685-687). "The most common side effect of DMSO therapy is a garlic-like taste and odor on the breath that occurs within 5 minutes of administration and interferes with the double-blind nature of any study of its effectiveness" (Rothenstein 1999 Nov. Rheum Dis Clin North Am 25(4):900-918).

Flavocoxid (Limbrel) is a bland of bioflavonoids, classified as a medical food and available only by prescription. It was found to be capable of causing significant liver injury (Chalasani et al. 2012 Jun 19. Ann Intern Med. 156(12):857-60, W297-300).

Black Pearl (Chinese Black Balls, chuifong tuokuwan) - contains several powerful (and dangerous) drugs. It is illegal in the U.S., but is sold surreptitiously.

There is some evidence that dietary administration of proteins may be effective in treating rheumatoid arthritis and other autoimmune diseases. Antibiotic therapy has also been supported by some studies. A study indicated reduction of symptoms with a Mediterranean diet. Fish oil, with omega-3 fatty acids, may be beneficial. "Daily ingestion of ω-3 fish oils has been consistently shown to reduce the number of tender joints on physical examination and the amount of morning stiffness in RA patients, when 3 g of EPA and DHA acids are taken in combination with medication, although benefits are not apparent until at least 12 weeks" (Dunn and Wilkinson 2005. Mod Rheumatol. 15(2):87-90).

"Results from single trials with moderate risk of bias indicate that both fasting followed by a vegetarian eating plan and a Cretan Mediterranean eating plan may improve pain when compared to an ordinary diet. However, no effects were found for physical function, stiffness, or other important outcomes. The effects of vegan and elimination eating plans are uncertain. Higher dropout rates and weight loss in the groups with dietary manipulations indicate that potential adverse effects should not be ignored" (Smedslund et al. 2010 May. J Am Diet Assoc. 110(5):727-35).

In prolotherapy, "Doctors inject an irritant such as glucose into the knee, which may stimulate the body to call healing cells to the site...'I don't see there's evidence that shows it works,' says Dr. [Eric] Berkson [Massachusetts General Hospital], 'it may not work and it has a risk of infection. I think it's a consideration if everything else has failed, but I don't promote it" (anon. 2012 Nov. Harv Health Lett. 38(1):4).

Periods of remission are a natural feature of the disease; if one of these corresponds to the time of use of an alternative therapy, it might be given credit.

"CHRONIC LYME DISEASE"

Introduction. Lyme disease is a genuine disorder, caused by the bacterium Borrelia burgdorferi and transmitted by ticks. Characteristics include a bulls-eye rash (erythema migrans), musculoskeletal pain, and joint inflammation. Treatment with antibiotics usually cures the disease. Some treated patients may later suffer symptoms (post-treatment Lyme disease syndrome). However, multiple clinical trials "show that patients with well-documented Lyme disease who have residual nonspecific symptoms after treatment do not benefit from additional treatment, even with extended courses of intravenous antibiotics" (Shapiro et al. 2017 Jul. Am J Med. 130(7):771-772).

In contrast to genuine Lyme disease, "a belief system has emerged for some activists over the past 20 years—that Lyme disease can cause disabling subjective symptoms even in the absence of objective signs of disease, that diagnostic tests for extracutaneous manifestations of Lyme disease are often falsely negative, and that treatment with antibiotics for months or years is necessary to suppress the symptoms of the disease, which often recur despite prolonged antibiotic therapy" (Auwaerter et al. 2011 Sep. Lancet Infect Dis. 11(9):713-9). This is referred to as "chronic Lyme disease" (also known as alternatively diagnosed chronic Lyme syndrome, ADCLS). Patients "receive a diagnosis on the basis of the presence of nonspecific symptoms such as fatigue, night sweats, sore throat, swollen glands, stiff neck, arthralgia, myalgia, palpitations, abdominal pain, nausea, diarrhea, sleep disturbance, poor concentration, irritability, depression, back pain, headache, and dizziness. Nonspecific symptoms such as these are common, and some occur in more than 10% of the general population, regardless of whether Lyme disease is endemic in the area" (Feder et al. 2007 Oct 4. N Engl J Med. 357(14):1422-30).

"The Centers for Disease Control and Prevention has established highly specific criteria for the diagnosis of Lyme disease: an acknowledged tick bite, the appearance of a bull’s-eye rash, and, for those who don’t live in a region where Lyme is common, laboratory evidence of infection" (Specter 2013 July 1. The Lyme Wars. New Yorker). "... we are using the term [chronic Lyme disease] to refer to patients with persistent, unexplained subjective symptoms, with no documented history of Lyme disease and without credible laboratory evidence – past or present – of infection with Borrelia burgdorferi, the bacterium that causes Lyme disease" (Shapiro et al. op. cit.). "Chronic Lyme disease is the most recent in a continuing series of 'medically unexplained symptoms' syndromes. These syndromes, such as fibromyalgia, chronic fatigue syndrome, and multiple chemical sensitivity, meet the need for a societally and morally acceptable explanation for ill-defined symptoms in the absence of objective physical and laboratory findings" (Sigal and Hassett 2002. Environ Health Perspect. Aug;110 Suppl 4:607-11).

Some patients that are alleged to have Lyme disease have never been exposed to ticks or been to an area with endemic Lyme.

"There is something called 'post-treatment Lyme disease syndrome,' but responsible medical authorities do not equate this syndrome with the nebulous symptoms and unvalidated lab tests of 'chronic Lyme' and specifically reject the utility long-term antibiotic treatment based on well-conducted clinical trials" (Bellamy 2017 Nov. 9. Science-Based Medicine blog).

"Chronic lyme" advocacy. "As with other antiscience groups, some Lyme disease activists have created a parallel universe of pseudoscientific practitioners, research, publications, and meetings, arranged public protests and made accusations of corruption and conspiracy, used harassment and occasional death threats, and advocated legislative efforts to subvert evidence-based medicine and peer-reviewed science. Politicians, the media, and the public have been left trying to discern the scientific facts from the pseudoscientific ones, with many regarding both as equally valid as they try to be fair and balanced" (Auwaerter et al. op. cit.). The major group of "Lyme literate" physicians (or "Lyme literate medical doctors," LLMDs) is the IADS (International Lyme and Associated Disease Society), while a patient-oriented group is the Lyme Disease Association. "Lyme literate" doctors have issued "their own guidelines for the diagnosis and treatment of 'chronic Lyme,' guidelines based on very low levels of evidence that are accepted only by themselves and, in contrast to the IDSA [Infectious Diseases Society of America] guidelines, no other professional medical organization" (Bellamy op. cit.). "Activists have organised their own scientific meetings, published their own journal, and funded research by LLMDs. All this activity has led to the creation of a cadre of doctors and activists with their own institutions, research, and conferences, a dedicated pool of patients, and unorthodox, alternative views of microbiology, immunology, and pharmacology" (Auwaerter et al. op. cit.).

"Several physician members of ILADS—including current and former officers—have been sanctioned by state medical licensing boards or reprimanded by federal agencies...Other LLMDs have been convicted in state and federal courts raising concerns about ethics and professional credibility" (ibid).

Advocates have pushed for state laws requiring insurance coverage for "chronic Lyme." "Politicians are attempting to displace mainstream physicians as diagnosticians in the complex world of Lyme disease by passing legislation that encourages the use of unproven treatments and that requires health insurance companies to pay for unsafe remedies with no documented benefit and well-documented adverse effects... Lyme disease patient advocates have lobbied state legislatures in both Maryland and Virginia to pass laws that require physicians to inform their patients that a negative result from an FDA-approved diagnostic test does not necessarily mean that they do not have Lyme disease" (Shapiro et al. op. cit.).

Testing. "For US Lyme we rely on indirect, two-step testing to determine if the disease is present; first is a screening ELISA followed by a confirmatory western blot. The test we use was validated in patients with culture-proven Lyme, so we know what the false positive and negative rates are, the sensitivity and specificity. The ELISA is a screening test and, like many screening tests in ID, are designed to be overly sensitive. You don’t want to miss a real case of Lyme but it is at the cost of having a positive test that due to other processes...It will pick up Lyme, but a lot of other diseases as well. To get a more specific answer, you do a western blot. The western blot has two flavors, the IgM (for acute disease) and the IgG (for more prolonged disease). IgM is the first antibody to respond to infection, lasting a couple of months and eventually supplanted by IgG, which is lifelong" (Crislip. 2016 Jan. 8. Science-Based Medicine blog). According to the CDC (2015 Mar 4. Lyme Disease), "you should only have an immunoblot (such as an FDA-approved Western Blot or striped blot) test done if your blood has already been tested and found reactive with an EIA [enzyme-linked immunosorbent assay, or ELISA] or IFA [immunofluorescent assay]. Second, the IgM Western Blot test result is only meaningful during the first four weeks of illness. If you have been infected for longer than 4 to 6 weeks and the IgG Western Blot is still negative, it is highly likely that the IgM result is incorrect (e.g., a false positive). This does not mean that you are not ill, but it does suggest that the cause of illness is something other than the Lyme disease bacterium."

"There also have been recent proposals to change the recommended 2-tier algorithm for serologic testing for Lyme disease from the current standard (an ELISA usually is the first-tier assay, followed by a Western immunoblot as the second-tier assay) to one in which a Western blot is not used. Instead, the second-tier assay would also be an ELISA, but a different one from that used as the first-tier assay...However, even if such a change in 2-tier testing were to occur, it is not likely to have a major influence on the problems commonly encountered with use of antibody tests for diagnosis of Lyme disease, which primarily are testing of patients with a low probability of having Lyme disease and misinterpretation of the test results" (Shapiro and Wormser 2018 Aug 21. JAMA. 320(7):635-636).

"Lyme specialty laboratories are favoured by some activists and LLMDs because their non-standard testing methods and interpretation criteria often lead to more positive results than other laboratories that rely on validated methods" (Auwaerter et al., op. cit.). "Health care providers who diagnose chronic Lyme disease question the reliability of 2-tier antibody-based tests for Lyme disease approved by the Food and Drug Administration (FDA). They espouse the viewpoint that the validity of 2-tier testing is 'no better than that of a coin toss.' This ignores well-recognized features of both the disease process and the intrinsic characteristics of antibody-based tests for the diagnosis of Lyme disease. Because it takes several weeks for antibodies to develop, many patients with Lyme disease will be seronegative early in the illness. However, patients who have been infected by B. burgdorferi for many weeks or months are almost invariably seropositive by 2-tier tests...Fake blood cultures are not the only false tests that have been used to support a misdiagnosis of Lyme disease...The CDC lists several other types of nonvalidated in-house tests, often used by Lyme disease specialty laboratories, which are not recommended for the diagnosis of Lyme disease" (Shapiro et al. op. cit.). Some perform immunoblot tests with synovial fluid or cerbrospinal fluid, which the CDC says is not appropriate.

"Initial research trying to settle the question of whether or not chronic Lyme disease is a real entity focused on trying to find evidence for persistence of the spirochete in patients with symptoms diagnosed as chronic Lyme. Such efforts failed, but did not settle the controversy. Proponents of chronic Lyme just special-pleaded away this negative evidence" (Novella 2016 Apr 6. Science-Based Medicine blog).

Treatments and side effects. There are risks from long-term use of antibiotics, even for those who actually have Lyme. Lantos et al. (2015 Jun 15. Clin Infect Dis. 60(12):1776-82) surveyed unorthodox therapies marketed to treat "chronic Lyme disease." They identified more than 30 treatments "which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorferi to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments....in many cases they are potentially harmful."

Other. A study by Patrick et al. (2015 Oct 1. Clin Infect Dis. 61(7):1084-91) found that "chronic Lyme" patients have symptoms indistinguishable from chronic fatigue syndrome. Specter (op. cit.) quoted Michael Wormser: "We conclude that false-positive serological results from an alternative Lyme specialty laboratory represent the most likely reason for different labels for what is clearly a debilitating illness." "'There is a group of people with aches and pains and medically unexplained symptoms that are being treated for chronic Lyme.' He said these patients often go 'from doctor to doctor' without a satisfactory diagnosis. 'They are suffering and unhappy, and finally they go to a doctor who says, "I know what you have, it’s chronic Lyme." Then they get treated and treated and treated for chronic Lyme. And patients are happy because somebody has finally taken interest in them'.” An earlier study (Hassett et al. 2009 Sep. Am J Med. 122(9):843-50) found that "Psychiatric comorbidity and other psychological factors are prominent in the presentation and outcome of some patients who inaccurately ascribe longstanding symptoms to 'chronic Lyme disease'."

"Acceptance of the diagnosis of chronic Lyme disease provides a number of benefits for these sufferers. It legitimizes the pain, suffering, and disability. It provides a structure by which to understand a very frightening experience. It produces a community with which to identify and from which to draw strength and comfort. It gives the sufferer a means by which to address the suffering on personal and societal levels. Perhaps most important, the diagnosis of Lyme disease denies a psychiatric diagnosis - 'this is NOT in my head, doctor'" (Sigal and Hasssett op. cit.).

The Jarisch-Herxheimer reaction, which may include fever, chills, and other symptoms, is caused by endotoxins released by bacteria killed during antibiotic treatment (including treatment for genuine Lyme disease). However, believers in "chronic Lyme" incorrectly identify superficially similar symptoms as Jarisch-Herxheimer. "When patients diagnosed with chronic Lyme are treated, no matter what happens as a response to the treatment is considered by believers to be evidence in support of the diagnosis. If they get better, then that is evidence that the treatment is working. If they get worse, then that is evidence that the treatment is working and they are experiencing the JHR (or 'herxing' as the community calls it). If nothing happens, they just need more treatment. No matter what happens or doesn’t happen, it’s chronic Lyme" (Novella 2017 Oct. 25. Science-Based Medicine blog).

Chronic Lyme advocates suggest that "Antibiotics are not effective against B. burgdorferi when the organism is intracellular - an untenable argument as a wide variety of intracellular infections are readily treated with the major antibiotics available for Lyme disease" (Lantos et al. 2014 Mar. Clin Infect Dis. 58(5):663-71). "Although B. burgdorferi can develop into cystlike forms in vitro under certain conditions that can be created in the laboratory, there is no evidence that this phenomenon has any clinical relevance. B. burgdorferi may penetrate cells in vitro, but there is no evidence that the organism may be sheltered from antibiotics during an intracellular phase and then disseminate and cause clinical relapse. Indeed, the strategies used by B. burgdorferi to adapt to the vertebrate host and evade host defenses indicate an extracellular existence" (Feder et al. op. cit.).

In response to an investigation by the Connecticut attorney general, an independent panel was established to review the Lyme testing guidelines of the Infectious Disease Society of America (IDSA). The final report "unanimously approved all of the recommendations made in the IDSA's current guidelines. The review panel, which relied on >1000 published scientific papers in making its deliberations, also affirmed that there is no published evidence to indicate that extended antibiotic therapy is beneficial for the treatment of chronic Lyme disease; there is 'no well-accepted definition of post-Lyme disease syndrome'; and there is 'no convincing evidence of symptomatic chronic Borrelia burgdorferi infection among patients given recommended treatment regimens for Lyme disease'." However, "Some Lyme disease activists continue to make the astounding claim that this overwhelming consensus of independent experts is the result of conflicts of interest and/or a vast conspiracy by a cabal to suppress the truth. This is absurd, especially when such claims are made by 'Lyme-literate physicians' who profit immensely from the prolonged treatment of chronic Lyme disease" (Baker 2010 Nov. FASEB J. 24(11):4175-7).

Lipson (2009 May 11. Science-Based Medicine blog) noted, "but if you read these websites, message boards, etc., you see a certain commonality - people aren't getting better. They are still suffering. Much of that suffering is blamed on a heartless medical community, and when they find a 'Lyme literate' doctor, there is a huge sense of relief. But the symptoms often continue."

CLINICAL ECOLOGY, MULTIPLE CHEMICAL SENSITIVITY, ENVIRONMENTAL MEDICINE, ETC.

Hypersensitivity to common foods and chemicals is said to cause "depression, irritability, mood swings, inability to concentrate or think clearly, poor memory, fatigue, drowsiness, diarrhea, constipation, sneezing, runny or stuffy nose, wheezing, itching eyes and nose, skin rashes, headache, muscle and joint pain, urinary frequency, pounding heart, muscle incoordination, swelling of various parts of the body, and even schizophrenia" (Barrett 1992. Skeptical Briefs. 2(4), 5, 7). Standard and nonstandard (e.g., provocation and neutralization) tests are given. Treatments range from simple avoidance of implicated substances to severe life-style changes (moving to a new location, special diet with only organically grown food, and specially constructed housing units). Nutritional supplements, drugs, and other measures may be prescribed. The American Academy of Allergy and Immunology feels that evidence in support of the tenets of clinical ecology is lacking. Many patients may actually suffer from psychosomatic diseases.

However, a meta-analysis (Davidoff and Fogarty 1994 Sep-Oct. Arch Environ Health. 49(5):316-25) found major flaws in studies concluding a psychological basis. Other patients may have respiratory infections, etc., which cause similar symptoms. One paper suggested a genetic link to panic disorder (Binkley et al. 2001 May. J Allergy Clin Immunol. 107(5):887-90).

Another view has been promoted by “physician Claudia Miller...who studies a phenomenon she calls toxicant-induced loss of tolerance (TILT)...TILT, says Miller, is a two-step process: First, a susceptible individual gets sick after toxic exposure or exposures. But then, instead of recovering, the neurological and immune systems remain damaged, and the individual fails to get well. The sufferer begins to lose tolerance to a wide range of chemicals in everyday life...The two-step process of TILT...may be driven by epigenetic changes, which occur when the environment alters the expression of genes without changing the DNA code itself” (Newmark 2013 Nov. Discover 45-51).

Barrett (2016 Nov 23. Adverse court rulings related to clinical ecology theories and methodology. Quackwatch) wrote, “There is now a clear consensus of judicial opinion that the diagnosis and concepts of multiple chemical sensitivity (MCS) have no scientific basis and that expert testimony based on such concepts should not be permitted. Some plaintiffs have attempted to get around this by labeling the patient's condition as something else, but courts have excluded such testimony as well.”

CONTROVERSIAL SYNDROMES AND DISEASES

“A syndrome is a constellation of symptoms and features that tend to occur together. We don’t even know yet if it is real, if it is one or more disorders, and what the pathophysiology might be” (Novella 2017 May 31. Science-Based Medicine blog). "One of the hallmarks of alternative medicine is the 'fake disease.' Fake diseases don’t actually exist – they are invented without any objective evidence showing that they are real. Fake diseases tend to emerge from vague symptoms which can’t be attributed to a specific medical diagnosis. This is not to say what patients are experiencing isn’t real – the issue is the diagnosis, and the practitioner making the call" (Gavura 2017 June 29. Science-Based Medicine blog). This section covers a variety of syndromes and diseases, some not recognized by conventional medicine, some recognized but treated by unscientific methods. Clinical ecology (multiple chemical sensitivity) and “chronic Lyme disease” are discussed above.

Adrenal fatigue - not to be confused with adrenal insufficiency, a genuine medical problem in which the adrenal glands do not produce enough cortisol. In contrast, adrenal fatigue is claimed to occur due to stressful conditions, and includes a variety of common and nonspecific symptoms such as tiredness and trouble sleeping. Supposedly the stressful conditions cause "overuse" of the adrenals in producing hormones. The condition may be diagnosed based on symptoms or on invalid blood or saliva tests. Treatments include corticosteroids, supplements, and lifestyle changes. While patients may feel better after administration of steroids, "corticosteroids promote a sense of wellbeing (usually temporary), regardless of the patient's condition" (Cadegiani and Kater 2016 Aug 24. BMC Endocr Disord. 16(1):48). "If you take adrenal hormone supplements when you don't need them, your adrenal glands may stop working and become unable to make the hormones when you are under physical stress. When these supplements are stopped, a person's adrenal glands can remain 'asleep' for months. People with this problem may be in danger of developing a life-threatening condition called adrenal crisis" (Endocrine Society 2015. Myth vs fact: Adrenal fatigue). Akturk and others (Mayo Clin Proc. 2018 Mar;93(3):284-290) found that over-the counter "adrenal support" supplements all "contained a small amount of thyroid hormone and most contained at least 1 steroid hormone," with risk of serious adverse effects.

Candidiasis hypersensitivity (yeast syndrome) - Candida albicans is often found in the digestive tract and vagina; it is normally harmless, but may cause occasional or chronic vaginal infections (which can be treated with antifungal drugs). However, it has been alleged that many Americans (30%) suffer from various diseases as a result of sensitivity to the normal low levels of the organism. Consequences are said to include fatigue, depression, headaches, infections, weight gain, indigestion, AIDS, arthritis, and multiple sclerosis. It may be diagnosed with a questionnaire rather than a lab test. Treatments include strict diets (no foods made from or containing yeast, as well as many other prohibitions), vitamins, herbs, antifungal drugs, provocation/neutralization and possibly other therapies such as chiropractic or acupuncture. Promoted by C. Orian Truss and by William Crook (author of The Yeast Connection, which sold 800,000 copies).

According to the Executive Committee of American Academy of Allergy and Immunology (1986), "The concept is speculative and unproven." There is a danger of the selection of resistant strains as a result of inappropriate use of oral antifungal drugs.

Chronic fatigue syndrome (also known as myalgic encephalomyelitis and systemic exertion intolerance disease) - whether this is a legitimate medical diagnosis has been controversial. However, by 2007 there was enough evidence to convince the Centers for Disease Control to launch a major public awareness campaign. An Institute of Medicine review in 2015 concluded that it “was an under-studied physiological illness...The US National Institutes of Health (NIH) responded by doubling its planned spending on research into the condition, from about US$6 million in 2016 to $12 million in 2017" (Maxmen 2017 Mar. Nature. 28;543(7647):602). Metabolic disruptions and alterations in the gut microbiome are being investigated.

Fibromyalgia - “Fibromyalgia is a common disorder that involves widespread pain, tenderness, fatigue, and other symptoms. It’s not a form of arthritis, but like arthritis, it can interfere with a person’s ability to perform everyday activities...In addition to pain and fatigue, people with fibromyalgia may have other symptoms, such as cognitive and memory problems, sleep disturbances, morning stiffness, headaches, painful menstrual periods, numbness or tingling of the extremities, restless legs syndrome, temperature sensitivity, and sensitivity to loud noises or bright lights. A person may have two or more coexisting chronic pain conditions. Such conditions can include chronic fatigue syndrome, endometriosis, fibromyalgia, irritable bowel syndrome, interstitial cystitis, temporomandibular joint dysfunction, and vulvodynia. It’s not known whether these disorders share a common cause. The exact cause of fibromyalgia is unclear, but it may be related to injury, emotional distress, or viruses that change the way the brain perceives pain. There’s no diagnostic test for fibromyalgia, so health care providers diagnose it by examining the patient, evaluating symptoms, and ruling out other conditions” (National Center for Complementary and Integrative Health 2016 May. Fibromyalgia: In depth).

Fibromyalgia is “a good example of an alleged disorder that is more commonly accepted within mainstream medicine but is also dubious. It is supposed to be a disorder of chronic myofascial pain without a specific identifiable cause. I think fibromyalgia is fine as a placeholder syndrome label. There are patients with chronic myofascial pain without a known cause, and it’s reasonable to give them a syndrome label while we try to sort out what’s going on. The problem is that the label is often used as if it is an established disorder or even disease. When the diagnostic label was first created it included the criteria that there would be specific trigger points that were especially painful. However, clinicians mostly ignored the trigger points and used the diagnosis as a garbage pail for anyone with unexplained chronic achy pain. So eventually they just dropped the trigger point criterion, now it is officially a garbage pail diagnosis” (Novella op. cit.).

“Approximately 3-6 million people 18 years of age and older in the United States have FMS [fibromyalgia syndrome]...Alternative therapies are commonly used by patients in the treatment of this disorder, perhaps in part due to the limited effect of specific therapy for the syndrome” (Taylor et al. 2009 Jan. J Altern Complement Med. 15(1):15-23). One approach that has been used is Myers Cocktail, an intravenous vitamin and mineral therapy.

A review by Lauche et al. (2015. Evid Based Complement Alternat Med. 2015:610615) stated that "Consistently positive results were found for tai chi, yoga, meditation and mindfulness-based interventions, hypnosis or guided imagery, electromyogram (EMG) biofeedback, and balneotherapy/hydrotherapy. Inconsistent results concerned qigong, acupuncture, chiropractic interventions, electroencephalogram (EEG) biofeedback, and nutritional supplements. Inconclusive results were found for homeopathy and phytotherapy. Major methodological flaws included missing details on data extraction process, included or excluded studies, study details, and adaption of conclusions based on quality assessment...Despite a growing body of scientific evidence of CAM therapies for the management of FMS systematic reviews still show methodological flaws limiting definite conclusions about their efficacy and safety."

According to the NCCIH (op. cit.), ”Although some studies of tai chi, yoga, mindfulness meditation, and biofeedback for fibromyalgia have had promising results, the evidence is too limited to allow definite conclusions to be reached about whether these approaches are helpful. It’s uncertain whether acupuncture is helpful for fibromyalgia pain. Vitamin D supplements may reduce pain in people with fibromyalgia who are deficient in this vitamin. Some preliminary research on transcranial magnetic stimulation (TMS) for fibromyalgia symptoms has had promising results.”

“Leaky gut syndrome” - a supposed disorder involving defective tight junctions in the intestine. “ According to the proponents of leaky gut syndrome, bacteria and toxins enter the bloodstream through these defective tight junctions and wreak havoc throughout the body, causing bloating, gas, cramps, inflammatory bowel disease (IBD), as well as fatigue, food sensitivities, joint pain, moodiness, irritability, sleeplessness, autism, and skin problems like eczema and psoriasis...This is all speculation, as scientific studies do not validate any of these claims...There is a test available that shows whether an individual has intestinal permeability. It works by measuring levels of two indigestible sugars, mannitol and lactose, in the urine. Most physicians do not use this test and research shows that it is not very reliable...The situation becomes especially dangerous when you consider that the symptoms associated with this disorder are present in a number of other illnesses, so a quick diagnosis of leaky gut is more likely to leave patients untreated for what really ails them” (Canadian Society of Intestinal Research 2018. Debunking the myth of ‘leaky gut syndrome’”).

Morgellons - “the informal name of a self-diagnosed, unconfirmed skin condition in which individuals have sores that they believe contain some kind of fibers. Morgellons is poorly characterized but the general medical consensus is that it is a form of delusional parasitosis; the sores are the result of compulsive scratching, and the fibers, when analysed, turn out to originate from textiles” (Wikipedia 2018 Oct 15. Morgellons). Hylwa et al. (2011 Sep. Arch Dermatol. 147(9):1041-5) examined 108 patients diagnosed with delusional skin infestation, and found “neither skin biopsies nor examination of patient-provided specimens provided objective evidence of skin infestation.” Pearson et al. (2012. PLoS One. 7(1):e29908) studied 115 cases of “self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations.” They found “No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin.”

DEVICES

Numerous bizarre electrical and mechanical devices have been marketed for diagnosis and treatment of disease. Often they are used to provide individualized recommendations for nutritional supplements, which allegedly will correct the problems. In general the claims made for these devices are contrary to scientific knowledge of the human body and principles of physics, and are unsupported by reliable evidence.

Stephen Barrett has described an important group of these devices (2018. Regulatory actions related to EAV devices. Quackwatch):

Thousands of practitioners use "electrodiagnostic" devices to help select their recommended treatment. These devices, which are fancy galvanometers, merely measure skin resistance to the passage of electrical current. However, many are claimed to determine the cause of any disease by detecting the "energy imbalance" causing the problem. Some are also claimed to detect whether someone is allergic or sensitive to foods, deficient in vitamins, or has defective teeth. Some operators claim to tell whether a disease, such as cancer or AIDS, is not present. The diagnostic procedure is most commonly referred to as Electroacupuncture according to Voll (EAV) or electrodermal screening (EDS)...

Galvanic skin resistance has no proven or logical relationship to the diagnosis or treatment of any disease. The U.S. Food and Drug Administration classifies "devices that use resistance measurements to diagnose and treat various diseases" as Class III devices, which require FDA approval prior to marketing. No such device can be legally marketed in the United States for diagnostic or treatment purposes. A few companies have obtained 510(k) clearance (not approval) by telling the FDA that their devices will be used for biofeedback or to measure skin resistance, but this does not entitle them to market the devices for other purposes....

The FDA has banned importation of EAV devices into the United States and warned or prosecuted a few marketers.

Products using this type of technology include ZYTO, Ondamed, Electro-Physio-Feedback-Xrroid (EPFX)/Quantum Xrroid Interface System (QXCI), iTOVi, Vegatest, and Vitastiq.

Some other examples of invalid devices:

Bioresonance: “It originates from Germany and uses an instrument that is not dissimilar to the e-meter of scientology (its inventor had links to this cult). This instrument is supposed to pick up unhealthy frequencies from the body, inverses them and thus treats the root cause of the problem” (Ernst 2017 Mar 27. edzardernst.com blog).

EMPpad - allegedly provides low-intensity pulsed electromagnetic fields, which target cells and improve their functions.

Ray Jardine’s Blood Cleaner: “It is a micro electronic device that allegedly kills or disables pathogens in a person’s bloodstream” (Hall 2016 June 14. Science-Based Medicine blog).

Power Balance bracelets: contain embedded holograms that supposedly have frequencies that will restore energy balance, resulting in improved strength, balance, and flexibility. Marketers may use applied kinesiology (see below, "Other Miscellaneous Topics") to demonstrate the effects.

The Rife Frequency Generator supposedly treats cancer by detecting "auras" of bacteria and destroying the bacteria with radio waves of the proper frequency. (See also Hulda Clark’s “Zapper” and “Synchrometer” in the Cancer article).

The Bi-digital O-ring test is a variation of applied kinesiology (see below) combined with a diagnostic device. A related method is Quantum Reflex Analysis.

VoiceBio - “also called Voice BioAnalysis or BioHarmonics - is based on the idea that internal organs communicate with each other through sound waves, with each organ dysfunction being detectable by a computer-assisted analysis of the patient’s voice” (Barrett. 2013. A skeptical look at VoiceBio. Device Watch)

MAGNET THERAPY

Unlike pulsating electromagnetic fields, which may have some medical use, magnets with static fields are marketed for pain relief. A variety of shapes and configurations are available (e.g., to strap on affected parts of the body, or as mattress pads). According to Hall (2017 Mar 7. Science-Based Medicine blog), “magnetic health products are a big business: a billion dollars of sales a year worldwide and $300 million a year in the US.”

Harlow et al. (2004 Dec 18. BMJ. 329(7480):1450-4) found relief of hip and knee pain from magnetic wrist bracelets, but could not rule out placebo effects, while Winemiller (2005 Sep. Mayo Clin Proc. 80(9):1138-45) found no benefits for magnetic insoles. Kuipers et al. (2007 Apr. J Appl Physiol. 102(4):1410-5) found that “acute exposure to static magnetic fields does not alter pain perception, sympathetic function, and hemodynamics at rest or during noxious stimuli.”

A review by Eccles (2005 Jun. J Altern Complement Med. 11(3):495-509)) concluded that “The weight of evidence from published, well-conducted controlled trials suggests that static magnetic fields are able to induce analgesia.” But Pittler, Brown, and Ernst (CMAJ. 2007 Sep 25;177(7):736-42) wrote that "The evidence does not support the use of static magnets for pain relief, and therefore magnets cannot be recommended as an effective treatment." According to the National Center for Complementary and Integrative Health (2017 Dec 27. Magnets for pain), "Research studies don’t support the use of static magnets for any form of pain."

Colbert et al. (2008 Jun. J Altern Complement Med. 14(5):577-82) argued that in many of the studies the “magnetic field exposure at the target tissue could not be characterized...If the SMF dosimetry is inadequate, any inferences drawn from reported negative findings are questionable.”

There are strong reasons for skepticism concerning claimed benefits. The magnets are too weak to have any conceivable effects within tissues, and proposed mechanisms (e.g., increasing blood circulation) are implausible. Nerves and blood vessels are almost randomly oriented, so any directional effects would cancel out. Much larger fields used in MRI seem to have no effects on tissues.

It should be possible to demonstrate relevant effects in laboratory or animal models, but this has not been done in a convincing manner. Several animal studies and two human studies show no effects on circulation. In contrast, Morris and Skalak reported effects on microvascular remodeling in laboratory studies (2007 Aug. J Appl Physiol. 103(2):629-36) and on reducing edema in rat studies (2008 Jan. Am J Physiol Heart Circ Physiol. 294(1):H50-7). Novella (2008 Jan 9. Science-Based Medicine blog) noted that these were contrary to the usual claims of increased blood flow from magnets, and also provided criticisms of the work. Two other studies found effects on bones in rat models (Xu et al. 2007 Mar. Evid Based Complement Alternat Med. 4(1):59-63; Taniguchi and Kanai 2007 Mar. Evid Based Complement Alternat Med. 4(1):99-105.)

A general problem with clinical studies is difficulty in blinding, since it is often possible to tell if a real magnet is being used. As Feingold and Flamm wrote (2006 Jan 7. BMJ. 332(7532):4):

An example is a randomised trial of powerful magnetic bracelets for the relief of hip and knee osteoarthritis, which reports a significant decrease in pain because of the bracelets. The patients given real magnets could detect them because the magnets often stuck to keys in pockets. Perhaps subjects with magnetic bracelets subconsciously detected a tiny drag when the bracelets were near ferromagnetic surfaces (which are ubiquitous in modern life), and this distracted or otherwise influenced the perceived pain. Patients with fibromyalgia detected which sleeping pads were magnetic by their mechanical properties, by “comfort with the firmness” and thus unblinded the study. In a sophisticated postural assay, where magnetic soles were found to decrease swaying, the authors admit that the magnetic soles could have differed in stiffness from the controls.

There is a possible danger of magnets interfering with pacemakers or implantable defibrillators unless these are sufficiently shielded.

MERCURY AMALGAM

Millions of Americans have "silver" dental fillings, which are actually made of an amalgam of silver, copper, tin, and mercury. The mercury is allegedly released in dangerous amounts. Therefore some dentists recommend replacing all such fillings with newer plastic composites (which are more expensive and less durable). Mercury toxicity is claimed to be responsible for multiple sclerosis, immune deficiency, epilepsy, leukemia, arthritis, and other conditions. In my assessment, whether mercury in amalgams is dangerous is a genuine controversy within the scientific community. However, some dangerous and pseudoscientific practices are associated with anti-amalgamist dentists.

The case for toxicity:

1. Mercury is a highly toxic element that can damage the nervous system.

2. Studies showing mercury vapor can be released during chewing.

3. Human and animal studies of dangers of exposure to mercury vapor, such as reproductive problems

4. Despite rejections of the toxicity claims by some experts (see below), some toxicologists and physiologists feel that the amalgams are dangerous, and both sides agree that more study is needed.

5. A review (Lorscheider et al. 1995 Apr. FASEB J. 9(7):504-8) concluded that “Recent research does not support the notion of amalgam safety.”

6. Reportedly causes 2/3 of human body load of mercury.

7. In 2006, a joint panel of FDA advisers said that a report supporting safety “didn’t objectively and clearly present the current state of knowledge about the fillings” (Bridges 2006 Sep 7. Yahoo! News).

8. In 2008 the FDA changed to a more neutral position, stating that mercury in amalgams “may be harmful to pregnant women, children, fetuses and people who are especially sensitive to mercury exposure” (McCullough 2008 June 7. Philadelphia Inquirer). Final regulations issued in 2009 classified dental amalgam as Class II (moderate risk).

The case for safety of amalgam:

1. Mercury in fillings is combined with copper, tin, and silver in an inert state.

2. Amounts released during chewing are extremely small, may not be harmful.

3. An NIH panel concluded that amalgams were not toxic (August, 1991). PHS report (Jan 1993) - no evidence that it is a problem, though more study needed. FDA Consumer Update (Feb 2002): “...no valid scientific evidence has ever shown that amalgams cause harm to patients with dental restorations.” Life Sciences Research Office report (requested by NIH and other agencies) (2004): “...there is little evidence to support a causal relationship between mercury fillings and human health” (though it also stated that “many research gaps existed”).

4. The American Dental Association feels that amalgams are safe. "Since dentists have a much higher exposure to mercury vapor than the general public...it has seemed prudent to look for evidence of increased disease among that population. The American Dental Association (ADA) has collected data on the health and causes of death of American dentists for many years and run voluntary mercury level tests at dental conventions. Their data show that dentists have no higher levels of death or disease than the general public" (Institute for Science in Medicine Policy Statement. Dental Amalgam).

5. Study showing people with mercury-containing fillings had normal blood levels of mercury (though rapid storage in tissues may make blood levels a poor indicator).

6. Two studies from the University of Kentucky found no effect on brain function or Alzheimer’s.

7. Replacing fillings might produce more exposure than leaving them in. Lorscheider (see above) did not recommend removing existing fillings.

8. Review by Clarkson et al. 2003 Oct 30. N Engl J Med. 349(18):1731-7): “Patients who have questions about the potential relation between mercury and degenerative diseases can be assured that the available evidence shows no connection...There is no clear evidence supporting the removal of amalgam.”

9. Retrospective cohort study of Bates et al. (2004 Aug. Int J Epidemiol. 33(4):894-902): “Results were generally reassuring, and provide only limited evidence of an association between amalgam and disease.”

10. Bellinger et al. (2006 Apr 19. JAMA. 295(15):1775-83) and DeRouen et al. (2006 Apr 19. JAMA. 295(15):1784-92) performed randomized, controlled trials with children, and found no effects of amalgam on IQ, other neurological functions, or renal function. (However, in discussing these studies, Needleman (2006 Apr 19. JAMA. 295(15):1835-6) said, “It is predictable that some outside interests will expand the modest conclusions of these studies to assert that use of mercury amalgam in dentistry is risk free. This conclusion would be unfortunate and unscientific. The conclusions that can be extrapolated from these 2 studies are constrained by several factors,” such as limited followup, insufficient statistical power to detect subtle effects, and possible effects on vulnerable subpopulations.)

11. European Union scientific committee (2008) - concluded amalgams posed no risk of systemic disease.

A study found that patients convinced that they were adversely affected by their amalgam fillings had no higher mercury levels than controls (Bailer et al. 2001 Feb. Psychol Med. 31(2):255-63). The authors concluded, “The findings suggest that self-diagnosed ‘amalgam illness’ is a label for a general tendency toward somatization.”

OTHER MISCELLANEOUS TOPICS

Alkaline diet - based on the idea that the modern diet contains an excess of acid-forming foods, and that it is important to eat alkaline promoting foods. Otherwise the body "pulls out alkaline-rich minerals like calcium, phosphorus, and magnesium from the bones, teeth, and organs. They say this leads to osteoporosis and fatigue, and compromises our immune system...people with alkaline urine are said to have a reduced risk of osteoporosis, cancer, and heart disease. The alkaline diet is said to facilitate weight loss and increase energy. It is even used to treat cancer" (Hall 2017. Skeptic 22(2):4-5) (see also the Cancer article). However, the body has a great ability to regulate its pH, and "there is no evidence that the Alkaline Diet is effective for the prevention or treatment of any disease, particularly cancer" (Ernst 2017 Jan 26. edzardernst.com blog). Alkaline water is also sold, with claims that it detoxifies, acts as an antioxidant, enhances the immune system, and provides other benefits.

Anti-aging treatments - include antioxidant supplements and DHEA (see the article on dietary supplements), HGH (see below), bioidentical hormones (see below), chelation therapy (see above), and others. Nicotinamide adenine dinucleotide (NAD) and its precursor nicotinamide riboside are being tested in animal and clinical studies, and marketed as the supplement Basis. It was reportedly a $56 billion industry in 2006. Treatments are not covered by insurance, since aging is not a disease. For physicians, there is a professional group, the American Academy of Anti-Aging Medicine (A4M).

A relatively new development is transfusion of plasma from young donors (known as parabiosis). Research is still in the early stage, but some individuals are paying $8000 to be part of a study. Another approach is calorie restriction, with consumption of little or no food for one or a few days a week. Potential benefits are unclear at this point.

In 2002, 51 leading researchers in the field of aging denounced anti-aging products, noting that none had been shown effective. It was also noted that “two so-called scientific ‘journals’ (Journal of Longevity and The International Journal of Anti-Aging Medicine) that appear on the surface to be traditional refereed publications are in fact little more than advertisements for a pseudoscientific anti-aging industry” (de Grey et al. 2002 Apr 26. Science. 296(5568):656) [they noted that Journal of Anti-Aging Medicine is a legitimate scientific journal]. At its 2009 meeting, the American Medical Association said that long-term use of HGH “can present more risks than benefits...and the AMA says there’s no credible evidence that other hormones, so-called bio-identicals, are safer than traditional estrogen and progesterone products” (Associated Press 2009 June 16). According to a 2011 Chicago Tribune story, the FDA was concerned about the marketing of alleged anti-aging skin creams, and had sent some warning letters to companies that were making drug claims for the creams.

Applied kinesiology - method of diagnosis involving testing of muscle weakness. It may be used to assess condition of internal organs supposedly related to the muscles. Two different rationales: 1. alleged “neurolymphatic reflexes,” with changes in internal organs affecting (via lymphatic drainage) the peripheral nervous system and muscles. 2. connections according to meridian theory in traditional Chinese medicine. Using before and after comparisons, it may be used to test for allergies or nutritional deficiencies when subject holds a food item, places an item under the tongue, etc. The idea that food items can cause immediate changes in muscle strength, especially when merely held in the hand, is absurd. Several studies have demonstrated that it is not a valid diagnostic procedure. A paper in Explore (a journal sympathetic to alternative methods) noted that "The research published by the Applied Kinesiology field itself is not to be relied upon, and in the experimental studies that do meet accepted standards of science, Applied Kinesiology has not demonstrated that it is a useful or reliable diagnostic tool upon which health decisions can be based" (Schwartz et al. 2014 Mar-Apr. Explore (NY)10(2):99-108). It likely involves stage trickery (perhaps unintentional) to make muscle strength appear to respond to the treatment.

“Chiropractors can obtain a diplomate in applied kinesiology (DIBAK) from the International College of Applied Kinesiology by passing a written exam after attending 300 hours of instruction followed by 3 years of [applied] kinesiology practice” (Homola 2018 June 22 Science-Based Medicine blog).

Bee venom therapy (bee sting therapy, apitherapy, bee venom acupuncture) - involves applying live bees to the body for the supposed benefits of the stings. "Bee-sting therapy, as with many unusual medical treatments, is believed to have originated in ancient Greece, where the venom was used to relieve soldiers' muscle fatigue after battle" (Benda 2010 Feb. J Altern Complement Med. 16(2):139-40). It has been promoted for arthritis, other forms of pain, multiple sclerosis, stroke, and other conditions. Injection of diluted bee venom into acupuncture points has also been employed. "After years of research there is still no proven application for bee venom therapy. The most encouraging preliminary data is with pain, and I would not be surprised if a component of bee venom is isolated that is useful for neuropathic (nerve induced) or nociceptive (tissue pain)...There are no neurological uses of BVT that are backed by any reasonable evidence. At this point I think we can say that it is not effective for multiple sclerosis" (Novella 2012 June 20. Science-Based Medicine blog). Novella examined the published evidence again in 2018 (Apr 25. Science-Based Medicine blog). "The pattern is the same regardless of indication - there is scant and low grade evidence suggestive of an effect, but we can't really conclude that it works because of the lack of rigorous data." A fatal allergic reaction was reported in 2018; the patient had been receiving monthly treatments for two years without problems.

Behavioral vision therapy (behavioral optometry) - "a combination of in-office and at-home eye exercises — many of these optometrists claim they can offer significant help for problems that go far beyond the headaches, neck aches, eyestrain and poor posture typically associated with vision problems. According to Visionandlearning.org, a behavioral-optometry Web site, vision therapy can be used to treat reading problems, learning problems, spelling problems, attention problems, hyperactivity, coordination problems; it can also treat a child who experiences 'trouble in sports,' who 'frustrates easily,' displays 'poor motivation,' and 'does not work well on his own' — virtually anything that presents as an 'impaired potential for achievement'...Vision therapy’s critics argue that the published research in its favor is largely anecdotal, often derived from studies in which the practitioners had a vested interest in positive results, where disorders were badly defined and therapies inconsistently practiced and during which children were usually receiving other kinds of therapy...Critics say that behavioral optometry rests upon some very basic misconceptions about the way the brain operates, particularly regarding the processes involved in paying attention and reading. They point out that recent advances in brain imaging have shown that most reading problems are not vision problems but instead involve glitches in language processing in the brain" (Warner 2010 Mar 14. New York Times).

The American Academy of Pediatrics and the American Academy of Ophthalmology issued a joint statement criticizing the method in 2009. "Scientific evidence does not support the efficacy of eye exercises, behavioral vision therapy, or special tinted filters or lenses for improving the long-term educational performance in these complex pediatric neurocognitive conditions. Diagnostic and treatment approaches that lack scientific evidence of efficacy, including eye exercises, behavioral vision therapy, or special tinted filters or lenses, are not endorsed and should not be recommended" (American Academy of Pediatrics, Section on Ophthalmology, Council on Children with Disabilities et al. 2009 Aug. Pediatrics 124(2):837-44).

"Behavioral optometrists often rely on anecdotal evidence to support their claims...the outcomes are highly subjective and susceptible to placebo effects...Essentially there is reasonable evidence for eye exercises to treat convergence insufficiency – which is a disorder of eye movements. This has plausibility, and the evidence is reasonable. There is some evidence for benefit with patients recovering from a stroke or injury, likely due to brain plasticity as it tries to compensate for the damage...All other claims by behavioral optometrists, however, relating to behavior issues and visual problems not caused by eye muscle weakness, lack the kind of evidence necessary to conclude that treatments are effective" (Novella 2018 Jan 31. Science-Based Medicine blog).

Bioidentical hormones - estrogen and progesterone (made synthetically, but identical to human forms) are given in individualized doses by compounding pharmacists. The idea is promoted in books by actress Suzanne Somers. "Somers says these custom-made treatments are natural and not really drugs. That's just not true. Bioidenticals may start out as wild yams or soybeans, but by the time this plant matter has been converted into hormone therapy it is, in fact, a drug" (Wingert and Kantrowitz 2006 Oct. 31 MSNBC.com). They are taken by women who are concerned about risks, or lack of optimum benefits, of standard hormone replacement therapy. "Most sites start with fear tactics and may falsely represent the true risks of pharmaceutical HRT and then state or infer that their pharmacy-mixed hormones have similar or greater benefits, with no risk or no mention of risk" (MacLennan and Sturdee 2006 Feb. Climacteric. 9(1):1-3.) However, there is no evidence that these are less risky. Moreover, saliva tests used to prescribe doses maybe unreliable, and there are concerns over quality control. "...there are no published peer-reviewed data to show that a single or multiple salivary hormone assays can accurately reflect the hormonal status or needs of a woman and, in particular, there has been no validation that they can be used to titrate hormone regimens to give an appropriate hormonal response" (ibid).

MacLennan and Sturdee (op. cit.) further note: "...unlike the strict requirements for registered pharmaceutical products, the bioidentical products can be synthesized and imported without regulatory quality control evidence of purity, dosage, contamination, bioavailability, etc...The cost of the unproven ‘bioidentical hormones’ is usually several times greater than traditional menopausal hormone therapies and the patient often has to pay dearly for the salivary tests. Both the patient and her doctor may receive results of these assays from ‘hormone consultants’, whose qualifications are unknown, who have not seen the patient, and who give unvalidated interpretations of the results..."

The North American Menopause Society (2009) and the Endocrine Society (2016) issued statements in opposition to the use of bioidentical hormones.

Biological terrain assessment - "a computerized analysis of blood, urine and saliva specimens used to recommend nutritional programs, vitamin and mineral supplements, homeopathic products, and/or herbs" (Barrett 2002 Apr. 9. Biological terrain assessment is nonsense. Quackwatch). The pH, resistivity, and oxidation-reduction potential of samples are measured.

Buteyko Breathing Technique - “an alternative breathing technique developed in Russia for the treatment of asthma” (Albietz 2009 Dec 25. Science-Based Medicine blog). Chronic hyperventilation supposedly exacerbates asthma and causes other diseases, due to low levels of carbon dioxide in the blood. Published studies on the method for asthma “imply that BBT can alter a patient’s perception of their symptoms, and perhaps prevent overuse of asthma medications. However, they also provide evidence that BBT does very little to alter the underlying pathophysiology of asthma, and absolutely no evidence to support Buteyko’s claim that BBT can cure asthma...There are no published studies evaluating BBT for any of the other 149 diseases Buteyko claimed to cure” (ibid).

Cold temperature treatments - cold water swims are alleged to provide some health benefits. In addition to the risk of hypothermia, there are also potentially dangerous releases of stress hormones and increases in blood pressure.

More extreme is whole body cryotherapy, which is increasingly being used by athletes and others. “Unlike run-of-the-mill cold therapy, it uses gasified liquid nitrogen to cool the air around recipients who stand in an enclosed chamber to temperatures below -200 degrees F. Although the gas temperature is much colder than ice, the cold from ice applied directly to the body has a better chance of penetrating through layers of skin and fat to reach the target soft tissue than does icy gas that swirls around the skin but is not pressed against it, making chilling of deeper parts of the body harder to achieve...Yet the science behind these devices is decidedly lackluster. In July the U.S. Food and Drug Administration issued a warning stating that there is no evidence these technologies help to ease muscle aches, insomnia or anxiety or provide any other medical benefit. Instead, it said, they may cause frostbite, burns, eye damage or even asphyxiation. In a statement to Scientific American the agency added, ‘The FDA has not approved or cleared any whole-body cryotherapy devices, and we do not have the necessary evidence to substantiate any medical claims being made for these devices.’...Adding insult to injury, cryotherapy is pricey. A package of five two-minute sessions can cost several hundred dollars” (Maron 2017 Jan. Scientific American. 22-23). Four small randomized controlled trials have found no significant evidence of benefits. A more recent study (also quite small) reported benefits for fibromyalgia (Vitenet et al. 2018 Feb. Complement Ther Med. 36:6-8).

Colloidal silver - marketed for both topical and sublingual use. Claimed to be an antibiotic and antiviral agent, as well as a treatment for AIDS, cancer, and numerous other diseases. Danger of argyria (deposits of silver salts in skin, eyes, and other sites), seizures, and kidney damage. Case of myoclonic status epilepticus and coma reported were reported in 2004. In 1999 the FDA declared that OTC silver products are not recognized as safe and effective, with additional actions by FDA and FTC in subsequent years to stop illegal marketing.

Colonic irrigation - based on theory of autointoxication (accumulation of toxins in the colon). It may involve as much as 20 gallons of liquid, possibly pumped in by machine. Other substances (e.g., coffee) may be included to assist in removal of toxins. It is used in some cancer treatments, as well as for other conditions or general maintenance of health (see the Cancer article). Practitioners may call themselves “hydrotherapists” or “colon hygienists.” Colonic irrigation has led to deaths from electrolyte imbalance, bowel necrosis or perforation, toxic colitis, amebiasis, hypokalemia, and sepsis. Dehydration and renal failure have also been produced. In 2003, Texas filed several lawsuits against promoters.

Detoxification (“detox”) - “The basic idea is that modern life results in the accumulation of ‘toxins’ in your body, and every now and then you should have a tune up by flushing those toxins out. The specific toxins are never mentioned. There is also no basic science reason or clinical evidence to support the notion that the methods recommended actually remove any specific toxins from the body...animals evolved mechanisms to process and remove toxins that get into their system. One primary function of our livers, which are giant chemical factories, is to filter anything potentially toxic from the blood, metabolize it, and excrete it. Toxins are also filtered from the blood by the kidneys, and excreted in the urine. A healthy liver and pair of kidneys are all most of us need to sufficiently ‘detox’” (Novella 2017 Jan 4. Science-Based Medicine blog). In addition to the accumulation of environmental “toxins,” it is thought that internally-generated “toxins” accumulate in the colon (autointoxication) and must be dealt with.

“... the belief in ‘detoxification’ resembles a belief common in many religions that sinners (or those who do wrong in the eyes of the deity) are somehow ‘unclean’ and must undergo ritual purification in order to be on the deity’s good side again. The ideas behind ‘detox,’ more than anything else, resemble ideas undergirding those of ritual purification, with unnamed ‘toxins’ rather than sins or impure thoughts and deeds being the cause of the taint producing the unclean state that must be purified” (Novella 2017 Jan 30. Science-Based Medicine blog).

Methods include: colonic irrigation (see above); drinking large amounts of water, which has a possible danger of low sodium levels (hyponatremia); herbal remedies (such as valerian, milk thistle (Silymarin), dandelion, sarsaparilla, burdock root); foods and supplements (such as foods rich in vitamin C, garlic, cilantro, chlorella, alfalfa, modified citrus pectin, probiotics); chelating agents (such as DMSA); detoxifying foot baths (see below); sweat lodges, saunas, etc. to remove “toxins” by sweating; activated charcoal (taken in juices); electromagnetic devices (see above); and ear candling (see below)

Concerning the diagnosis of the need to detox, “All of the listed signs and symptoms [used by a detox practitioner] are non-specific and occur with most diseases. It remains unclear how many of them need to be present or which are obligatory for detoxification to become necessary. If one or two would suffice, nearly every patient who ever consulted clinician would need to be detoxified. It seems that here lies one crucial reason why proponents of AD [alternative detox] advocate their treatments for virtually every person...A recent survey suggested that 92% of US naturopaths use some form of AD” (Ernst 2012. Br Med Bull. 101:33-8).

Ernst (2018 Jan 3. Edzard Ernst blog) wrote: "To the best of our knowledge, no randomised controlled trials have been conducted to assess the effectiveness of commercial detox diets in humans."

Detoxifying foot baths - subjects place feet in a basin of salt water through which electrical current is passed. This allegedly removes “toxins” and balances “energy.” Water discoloration is taken as evidence of the toxins. However, it actually comes from rusting of the electrodes. “Detox” foot pads have also been marketed; one such product was banned by the FDA in 2010.

Ear candling - a candle (a hollow cone about 10 inches long) is placed in ear and lit; this allegedly creates suction that removes wax and other impurities from the ear, sinuses, and even the brain. Drippings are used as evidence of the removed material. They are popular at health expos. Use of ear candles can cause ear injuries (burns, punctures of the eardrum, etc.) and cause delay in receiving needed treatment. The FDA has taken action against distributors.

Earthing (grounding) - based on the premise that the flow of electrons from the Earth through the body neutralizes free radicals and provides health benefits. Promoted by Clinton Ober, Stephen Sinatra, Gaétan Chevalier, and James Oschman. “Among benefits reported are reductions in inflammation and pain, improvement in sleep and energy, a decrease in stress, a reduction in the indicators of osteoporosis, and improvements in peripheral blood flow and glucose metabolism" (Brown 2016 Sep. J Altern Complement Med. 22(9):757-9). It is alleged that the increasing use of rubber soled shoes has prevented grounding, and that people should restore it by walking barefoot, or by using grounding wires or various other products. The concept is also tied with mystical ideas about people losing a connection to nature.

However, the ideas are not scientifically credible. A critique was provided by Novella (2012 May 1 Neurologica blog). Among his points: there is no reason to think that shoes alone could effectively isolate us electrically from the Earth. Moreover, external electrons have nothing to do with antioxidant mechanisms, which use specific molecules within the body as a source of electrons, not external electricity. Free radicals are not the cause of inflammation but rather part of the body's defense. Since they are often useful, "suppressing free radicals may therefore cause more harm than good." Studies claimed to be supportive of the benefits of grounding "are typical of the kind of worthless studies designed to generate false positives - the kind of 'in house' studies that companies sometimes use so that they can claim their products are 'clinically proven.' Reading through the individual studies...you can see that they are small pilot or preliminary studies with atrocious methodology. They are little more than documenting placebo effects, subjective findings, and anomaly hunting. What is lacking are rigorous studies that are designed to establish the basic claims of earthing or to show convincing evidence of a positive clinical effect."

Full body scans - CT and MRI scans are offered to detect diseases in early stages. However, there is not evidence that the benefits outweigh the risks of surgery or further testing to deal with detected abnormalities that may be benign. In addition there is risk from the radiation. Several professional groups have recommended against such screening. According to the FDA, this is an unapproved use for the CT device (it is only approved when there are disease symptoms or other reasons for testing).

Genetic testing - some companies are now performing genetic tests in order to recommend supplements, etc. Pharmacies are also marketing DNA tests. There is legitimate research interest in identifying genetic markers that indicate susceptibility to disease, guide appropriate doses of drugs, etc. However, many of the current tests being marketed are inappropriate, since there is not reliable evidence connecting the genes identified to benefits of the products being sold. In 2013 the FDA took action against the DNA testing company 23andMe, stating that its DNA health reports had not been approved and were illegal. "In barring 23andMe's health reports, the FDA also cited the danger that erroneous interpretations of gene data could lead someone to seek out unnecessary surgery or take a drug overdose" (Anon 2015. Technology Review 118:16, 18).

Investigators have found conflicting results from samples sent to multiple companies. Also, "'The bulk of this information is extremely low,' [geneticist James] Evans told the [House committee] panel...'The risk of U.S. citizen developing Crohn's disease is 1 in 1000...In what way is it useful to know that I am instead at a 1-in-500 risk, or a 1-in-2,000 risk?'" (Walker 2010 July 22. MedPageToday).

"The big mistake among these practitioners is a failure to appreciate the distinction between tests for Mendelian (single gene) disorders — such as sickle cell disease, cystic fibrosis, or Tay-Sachs disease, where absence of a functional gene is diagnostic — versus those for single nucleotide polymorphisms (SNPs), where the presence of a mutation is merely one factor affecting risk. There is a danger of interpreting test results out-of-context from the diagnostic workup needed to pinpoint which tests are appropriate for a patient in the first place. This could distract a clinician from the correct diagnosis, leading to inappropriate treatment" (Warmflash 2018 Feb 28. Genetic Literacy Project).

A currently popular genetic test is for variants in the MTHFR gene, which is related to the conversion of homocysteine to methionine. Such variants are extremely common, but experts have concluded that testing is unnecessary for most people (and if a problem is suspected, measuring blood levels of amino acids is a more direct assessment of effects). However, some "functional medicine" doctors recommend testing and associate the gene variants with a variety of diseases. They then recommend supplements (such as 5-methyltetrahydrofolate, 5-MTHF) to correct the supposed problems.

An area of controversy is genetic testing of age-related macular degeneration (AMD) patients in order to guide the optimum levels of supplements.

Hair analysis - used to diagnose deficiencies or excesses of minerals and deficiencies of vitamins. It may be of some use in screening for heavy metal exposure, but otherwise is unsupported. Problems include lack of correlation of hair levels with tissue levels, unknown normal levels, inaccurate and inconsistent analyses by various labs, and inappropriate interpretations and recommendations. Dyes, shampoos, and other environmental factors can alter mineral levels in hair. An investigation (Seidel et al. 2001 Jan. JAMA. 285(1):67-72) documented numerous problems with commercial hair analysis.

HGH (human growth hormone) - is being injected as an anti-aging remedy (estimated usage, 25,000-100,000, with $1.4 billion in sales in 2011). "Anti-aging HGH regimens vary greatly, with a yearly cost typically ranging from $6,000 to $12,000 for three to six self-injections per week" (Caruso and Donn 2012 Dec 22. Associated Press). However, there are numerous risks associated with elevated IGF-1 levels (which increase in response to GH). Prescription of GH for adults is illegal except for individuals who meet diagnostic criteria for GH deficiency, and it appears that many people who do not meet these criteria are receiving injections.

A 2002 paper reported increased lean body mass and decreased body fat in response to HGH, but there were also significant adverse effects. A 2008 review concluded "Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events" (Liu et al. 2008 May 20. Ann Intern Med. 148(10):747-58). A 2010 paper found improvements in sprinting but not in strength or fitness. Liu et al. (2007 Jan 16. Ann Intern Med. 146(2):104-15) reviewed the use of growth hormone for the elderly. They found that the literature "suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy."

Growth hormone supplements and sprays are also being marketed, but significant absorption is unlikely. Some supplements contain other chemicals alleged to stimulated the release of GH, but effects are likely to be insignificant. The FTC took action against marketers of sprays and other products in 2005 and 2007, and in 2006 acted against illegal imports of growth hormone.

Hypoglycemia - True hypoglycemia is relatively rare; it is primarily due to certain enzyme deficiencies and endocrine disorders. Reactive hypoglycemia (oversecretion of insulin following meal) is also relatively uncommon. However, some practitioners claim that hypoglycemia affects tens of millions of Americans, and causes depression, fatigue, schizophrenia, criminal behavior, and other disorders. Special diets, supplements, and herbs are prescribed.

Intravenous (IV) nutrient (or micronutrient) therapy (IV drips, hydration therapy) - infusions of water, vitamins, and minerals are marketed to healthy individuals for the purpose of recovery from stress (such as after athletic events or illness, or indulgences in alcohol or drugs); to detoxify (see above); to give more energy; to boost immunity; and to help lose weight. They are also marketed for treatment of conditions such as chronic fatigue, fibromyalgia, migraine, and depression. Myers Cocktail contains magnesium, calcium, vitamin C, and B vitamins. Infusions typically cost $100 to $200. Dangers include risk of infection, bruising, and blood clots.

Any benefits are likely placebo effects. There appear to be no controlled studies showing effectiveness for most conditions. Beninger (2011 Mar/Apr. Skeptical Inquirer 49-51) wrote, "There is some evidence that IV therapy with magnesium alone can have beneficial effects in severe acute and chronic cases of asthma...Yet there have also been studies that did not show improvement in individuals with acute asthma..." Overall, "the evidence for IV nutrient therapy is speculative at best..." Gorski (2018 Sep 24. Science-Based Medicine blog) pointed out that "If your malabsorption of nutrients is so poor that you need intravenous vitamins and micronutrients, you probably need total parenteral nutrition (TPN), in which all your nutrient needs are provided intravenously." In 2018 the FTC took action against a marketer of "iV Cocktails" for its claims of being able to treat serious diseases.

Kinesio Taping - developed by Dr. Kenzo Kase in Japan. Special tape is applied directly over and around muscles. "The original purpose was for edema control, soft tissue support, joint protection, and relieving heat produced from active inflammation. Advanced purpose was continuing the effect of manual therapy from clinic to home care and activity of daily living" (Wu et al. 2015. Evid Based Complement Alternat Med. 2015:950519). It supposedly improves lymph flow and provides numerous benefits related to pain and sports injuries. The method became popular after use by an Olympic athlete in 2008. Alleged benefits are likely placebo effects. "For products that have become so popular on and off the playing field, there's surprisingly little evidence that kinesiology tapes actually relieve pain, says Dr. John Wilson, an assistant professor of family medicine at the University of Wisconsin in Madison who specializes in both sports medicine and arthritis treatment...According to Wilson, it's unrealistic to think that a strap of tape on the skin could have any effect on blood flow or lymph drainage" (Woolston 2011 Apr 4. Los Angeles Times). A study by Kamali, Sinaei, and Taherkhani (J Bodyw Mov Ther. 2018 Apr;22(2):540-545), as well as a review by Júnior and others (Spine (Phila Pa 1976). 2018 Jun 26. [Epub ahead of print]) found no benefit of KT for low back pain.

Live cell analysis - invalid diagnostic technique in which blood is viewed with dark field microscope connected to a video display. The appearance of cells and other particles is used to diagnose nutritional deficiencies, allergies, excess fat, presence of yeast or other "parasites," and other conditions. “Darkfield microscopy is a microscopic technique in which light strikes the observed material from the side rather than from underneath and through the material. The background is dark with the observed material highlighted by the lateral light source...Because darkfield is by definition dark, most of the detail that is apparent in brightfield examination is invisible. The use of darkfield techniques in examining live blood for cellular shape and detail is suspect and is not offered by most reputable medical laboratories because it has little diagnostic value...In a typical scenario, the alternative medicine practitioner will have the darkfield microscope set up at a health fair or in his or her office. A video camera is connected to the microscope and feeds a video monitor so that the enlarged image is visible on the screen. For a fee, the practitioner will offer the test to a patient or attendee at a health fair... The problem is that most of these practitioners are not trained medical professionals and are not qualified to examine a blood sample...While reviewing the sample with the customer the practitioner will often observe ‘rouleau’ formations of the red cells. Rouleaux occur when the red cells stack on top of one another and appear like stacks of coins...The rouleaux observed by alternative medicine practitioners are almost always artifacts due to the slight drying of the blood sample around the edges of the coverslip or due to clumping in areas of the slide where there is a large concentration of red cells” (Patterson 2012 Nov/Dec. Skeptical Inquirer 36(6):43-45). Some of the misinterpretations include: rouleaux as indicative of acidic blood; artifacts interpreted as bacteria budding off of red cells, which is impossible; artifacts interpreted as yeasts or other parasites; light spots on the red cells interpreted as “fermentation.”

Low level laser therapy - also known as cold laser, soft laser, low power laser, low intensity laser, or monochromatic infrared light energy (MIRE) therapy. Lasers with wavelengths of 600 to 1000 nm and power of 5 to 500 milliwatts are used to treat various types of pain and for wound healing. Sometimes the laser is directed to acupuncture points (laser acupuncture). "The providers include physicians, chiropractors, physical therapists, and occupational therapists, but devices are also marketed for long-term use at home...The U.S. Food and Drug Administration classifies most LLLT devices as Class II devices as 'lamp, non-heating, for adjunctive use in pain therapy'...Between 2002 and 2016, 44 such devices received 510(k) clearance for marketing for temporary pain relief...Most of the clearances were for symptoms related to wrist pain due to carpal tunnel syndrome, but a few mentioned temporary relief of muscle stiffness, minor arthritis pain, and/or temporary increase in local blood circulation...The scientific consensus is that no LLLT has been proven more effective for pain than standard forms of heat delivery. Some benefits have been reported, but the studies have been too small and/or too short to draw firm conclusions. The best-designed study of diabetic patients with sensory nerve impairment of the feet found that 90 days of Anodyne therapy at home brought about no more improvement in peripheral sensation, balance, pain, or quality of life than sham therapy" (Barrett 2018 Apr 26. A Skeptical look at low level laser therapy. Device Watch).

Multiple sclerosis - “MS's extreme variability makes it a perfect disease for quacks. The only way to know whether a treatment is effective is to follow many patients for years to see whether those who receive the treatment do better than those who do not. Quacks don't bother with this kind of testing, however. They simply claim credit whenever anyone who consults them improves. And since the majority of attacks are followed by complete or partial recovery, persuasive quacks can acquire patients who swear by whatever they recommend” (Barrett 2017 Mar 9. Be wary of multiple sclerosis "cures." Quackwatch). The Therapeutic Claims Committee of the International Federation of Multiple Sclerosis Societies “noted that no nutritional deficiency is known to be a factor in MS, and that no special diet or the addition of vitamins or minerals has been proven to alter its course. Polyunsaturated fatty acids (PUFA) have slight immunosuppressive properties, but studies involving sunflower seed oil, evening primrose oil, safflower seed oil, and fish oils, have produced conflicting results. The committee concluded that other than a possible benefit of PUFA-containing oils, there is no evidence that any dietary change affects MS” (ibid).

Herbs are used by many patients, with evening primrose oil being the most frequent. “Dietary supplements commonly used include n-3 fatty acids, lipoic acid, ginkgo biloba, ginseng, green tea polyphenols, and vitamin D” (Cunningham 2013 July. J Acad Nutr Diet. 113(7):1004). The Swank diet, with low levels of saturated fat, has been used but was lacking in support from controlled trials. Some patients use bee venom (see above), but a 2005 study found no benefit. Procarin (or Prokarin) is a skin cream containing histamine and caffeine, but there is no good evidence that it is effective. Other products and treatments used include removal of amalgam fillings (see above), calcium ethylamino-phosphate (calcium EAP), “coral calcium,” and oxygenating therapies (see above)

A review by Claflin, van der Mei, and Taylor (J Neurol Neurosurg Psychiatry. 2018 Jan;89(1):34-41) concluded, "Overall, we found little evidence of efficacy for CAM treatments of MS and class I [good quality randomized controlled trial with little evidence of bias] evidence was almost universally lacking."

In 2009, an Italian surgeon, Paolo Zamboni, proposed that multiple sclerosis is caused by chronic cerebrospinal venous insufficiency (CCSVI), a narrowing of the veins draining blood from the brain. He developed a therapy “in which balloon angioplasty devices or stents are used to widen narrowed veins in the chest and neck” (Barrett op. cit.), which came to be known as liberation therapy. This aroused considerable skepticism, since multiple sclerosis is largely an autoimmune disease involving inflammation. However, interest spread among patients on social media, and some doctors around the world began offering the therapy. Further investigation showed that there was no association between CCSVI and MS, contrary to Zamboni’s finding. Not only is the therapy ineffective, it has been associated with death, strokes, and other problems, leading to an FDA warning not to use it. A group including Zamboni himself finally performed a study showing that the method is ineffective (JAMA Neurol. 2018 Jan 1;75(1):35-43).

Neural therapy - “Neural therapy is not based on the concepts of anatomy and physiology that are generally recognized by the scientific community. It involves the injection of procaine (a local anesthetic) or other substances into various body tissues. It is based on the notion that trauma can produce long-standing disturbances in the electrochemical function of tissues. Proponents claim that a neural therapy injection often can relieve chronic pain and many types of long-standing illnesses...In addition to procaine, current practitioners may inject vitamins, minerals, homeopathic medications, and/or herbal extracts. The injections are placed into scars, nerves, ganglions (nerve clusters), and/or ‘acupuncture meridians’ claimed to be responsible for the ‘blockages.’...To determine where to inject, many practitioners utilize ‘autonomic response testing (ART),’ in which they test muscle strength by pushing down on the patient's arm or trying to pull apart the patient's fingers (O-ring test) while exposing the patient to stimuli such as a slide or a vial containing a test substance. Some also use ‘electrodermal testing’...” (see above under Devices) (Barrett 2018 Jul 3. Stay away from neural therapy. Quackwatch).

Progesterone creams, yam creams - creams marketed for premenstrual and menopausal symptoms. Such products became more popular with research showing possible dangers of hormone replacement therapy. Some actually contain progesterone (referred to as “natural” because it is the same compound as the natural hormone, even though it is synthetic). To the extent that this is absorbed, it has the same potential for adverse side effects as oral hormone therapy. Some products are based on Mexican wild yams. While a compound in these can be converted to progesterone in the laboratory, this conversion does not occur in humans.

Prolotherapy - injection of fatty acids and other compounds into injured tissues with the aim of stimulating healing of cartilage and ligaments (see above under Arthritis Treatments). “Through the injection of various solutions directly into the joint, inflammation occurs that causes granulocytes, macrophages, and fibroblasts to be drawn to the site along with the secretion of growth factors in the affected tissues. It is this process of inflammation that starts or restarts the repair and growth of these ligaments and/or tendons, thereby increasing tissue and joint stability and causing decreased pain...Three primary types of solutions are used in prolotherapy: (1) irritant, (2) chemotactic, and (3) osmotic solutions. Irritant solutions include phenol, guaiacol, tannic acid, and pumic flour (a type of irritant solution known as a particulate)” (Marlow 2012 Sep. Prim Care. 39(3):533-46). For low back pain, several studies found benefits of prolotherapy when used as an adjunctive to another therapy, but not when used alone.

Provoked challenge urine testing - “Many patients are falsely told that their body has dangerously high levels of lead, mercury, or other heavy metals and should be ‘detoxified’ to reduce these levels...In provoked urine testing, the levels of lead, mercury, and other potentially toxic heavy metals can be temporarily raised by administering a scavenger (chelating agent) such as DMPS or DMSA, which attaches to molecules of these metals in the blood and forces them to be excreted. In other words, some molecules that would normally recirculate within the body are exited through the kidneys, which artificially and temporarily raises their levels in the urine. How much the levels are raised depends on how the test is administered. The standard way to measure urinary mercury and lead levels is by collecting a non-provoked urine sample over a 24-hour period. When testing is performed, the levels are expressed as micrograms of lead or mercury per grams of creatinine (µg/g) and compared to the laboratory's ‘reference range.’ Well-designed experiments have demonstrated how provocation artificially raises urinary output...researchers found that administering DMSA to healthy, symptom-free volunteers multiplied their urinary mercury levels an average of about six times, raising them to levels similar to those reported elsewhere among people who—based on provoked testing—had been diagnosed with mercury toxicity. The researchers concluded: ‘The oral chelation test using DMSA may lead to misleading diagnostic advice regarding potential mercury toxicity’... Neither Mayo Clinic nor any other major laboratory has reference ranges for ‘provoked’ specimens...Very few patients understand what the numbers on provoked urine metal test reports mean. They simply see what looks like a big difference between the measured level and the reference range. The patient is then advised to undergo ‘detoxification’ with chelation therapy, other intravenous treatments, dietary supplements, or whatever else the practitioner happens to sell” (Barrett 2018 Sep 5. How "provoked" urine metal tests are used to mislead patients. Quackwatch).

Testosterone supplementation - a decrease in testosterone occurs normally in men with aging, and also as a result of medicines, illnesses, and other factors. While supplements may be appropriate for some men, low testosterone (referred to as “low T,” “male menopause,” or “andropause”) has been blamed for a wide variety of conditions by some practitioners, who advocate testing and supplementation to restore youthful levels. The growth in questionable use of testosterone supplementation has largely been promoted by major pharmaceutical companies. “At a chain of Low-T centers, a man can walk in, have his blood drawn, and get his first testosterone injection 30 minutes later...An FDA investigation found that fully half of men taking testosterone hadn’t been diagnosed with the disease hypogonadism, and a quarter of them were given hormones without a previous blood test” (Hall 2016 Mar 22. Science-Based Medicine blog).

Several studies of testosterone supplementation had been carried out, with mixed results concerning benefits. A larger series of trials, with 788 older men treated for one year, was subsequently performed (the TTrials). Snyder et al. (2018 Jun 1. Endocr Rev. 39(3):369-386) summarized the results: “Testosterone treatment improved most aspects of sexual function to a moderate degree. Testosterone also improved the walking distance in all men, but only by a small amount, and improved mood and depressive symptoms to a small degree. For the men who were mildly anemic, testosterone corrected the anemia in the men with unexplained anemia and also in the men who had another, identifiable cause. Testosterone increased the surrogate measure of volumetric bone mineral density and estimated bone strength to similar degrees as standard treatments of osteoporosis. Testosterone did not improve any measure of cognitive function...The results of the TTrials have demonstrated that increasing the testosterone levels in older men with low testosterone to those of young men has clear, although modest, benefits.”

In another commentary on the TTrials, Hall (2017 Mar 17. Science-Based Medicine blog) wrote: “The clinical significance of the positive findings is not clear. No major cardiovascular events occurred during the study and there was no reduction in the incidence of fractures, but the trials only lasted a year. The number of subjects in some of the trials was small. Longer, larger trials will be needed to confirm findings. Other studies have reached different conclusions: for instance, a retrospective cohort study found an association of testosterone prescriptions with a reduced risk of cardiovascular events in men over the age of 40 with testosterone levels lower than 300 ng/dL...Testosterone supplementation has both benefits and risks, and the decision to prescribe it should be carefully considered for each individual...But one thing is clear: testosterone supplementation is not an anti-aging panacea.”

Concerning side effects, Hall (ibid) wrote: “Testosterone is not harmless. It can contribute to sleep apnea, cause acne, stimulate benign prostatic growth and prostate cancer, enlarge breasts, cause male pattern baldness, reduce sperm production, shrink testicles, and increase the risk of a blood clot...And some studies have found that it increases the rate of cardiovascular events. The dangers are not limited to the patient. The gel can be transferred from the patient’s body to others by simple contact, affecting children, women, and pets. There have been reports of early puberty and aggressiveness in children, increases in acne and body hair and menstrual irregularity in women, and severe hormonal effects in pets.”

As an alternative to injections, some practitioners advocate various herbs and supplements, dietary changes, and lifestyle modifications to increase testosterone.

Thermography (infrared imaging) - “Thermographic devices portray heat emission from body surfaces as images that the practitioner interprets. The images may be in color or in black and white, and may be accompanied by displays of various calculations. Each color or shade represents a specific temperature level. One type of device converts the radiated heat (infrared energy) into electronic signals that are amplified and transmitted to a monitor and/or videotape. Liquid crystal display devices exist but are not as popular. Some devices produce a printout that can be shown to the patient. An infrared thermographic examination typically costs hundreds of dollars. Chiropractors who use thermography typically claim that it can detect nerve impingements or ‘nerve irritation’ and is useful for monitoring the effect of chiropractic adjustments on subluxations...Thermography is also promoted by the American College of Clinical Thermology (ACCT), which offers training and several ‘certification’ programs in ‘clinical thermography’...The ACCT site also lists 76 alleged ‘indications for thermographic evaluation’ and about 120 ‘approved clinics’ in the United States” (Barrett 2018 Mar 31. A Critical look at the use of thermography by chiropractors. Chirobase).

“The scientific view is that thermography is, at best, a research tool that would not yield useful information for day-to-day chiropractic or medical practice” (ibid.). The American Academy of Neurology, the American College of Radiology, the American Medical Association, and the Agency for Health Care Policy and Research have criticized the inappropriate use of thermography.

“The FDA regulates ‘Telethermographic systems’ as Class I medical devices when used as an adjunct to other methods and as Class III devices when used alone for diagnostic screening...Class I devices require 510(k) clearance, but class III devices require full FDA approval. So far, the FDA has ordered three companies to stop making illegal claims for thermograpy devices” (ibid.).

A popular use for thermography is breast cancer screening. "Some women have sought out thermography because it is painless and doesn't require exposure to radiation" (FDA Consumer Health Information 2017 Oct 27. Breast cancer screening: Thermogram no substitute for mammogram). "The rationale for applying thermography to the detection of breast cancer is that breast cancers tend to induce angiogenesis, which is nothing more than the ingrowth of new blood vessels into the tumor to supply its nutrient and oxygen needs...These blood vessels result in additional blood flow, which results in additional heat. In addition, the metabolism of breast cancer cells tends to be faster than the surrounding tissue, and cancer is often associated with inflammation, two more reasons why the temperature of breast cancers might be higher than the surrounding normal breast tissue and therefore potentially imageable using infrared thermography" (Gorski 2010 Oct 11. Science-Based Medicine blog). "However, regulation of skin temperature is complex and surface (skin) temperature is not a reliable proxy for what is going on in deeper tissues. Thermography was initially investigated as a method for identifying breast malignancies and abnormalities in the 1970s, but scientists found that it showed poor detectability and high false positive rates" (Nilson 2018 Oct. 12. Science–Based Medicine blog).

"The problem is...There aren't any baseline measurements of sensitivity and specificity. There are no widely agreed-upon standards for test performance and interpretation. Even if there were accepted standards, we don't know whether thermography is cost-effective. There is the potential for over-diagnosis and over-treatment if, as promoters claim, lesions are detected 5-10 years before mammography. Even as an adjunct, thermography doesn't provide any information that a breast MRI doesn't provide and provide better" (Bellamy 2017 Apr 27. Science-Based Medicine blog). Because of these deficiencies, "the greatest danger from thermography is that those who opt for this method instead of mammography may miss the chance to detect cancer at its earliest stage" (FDA 2017. op. cit.).

Medicare and other insurers do not cover thermography for breast cancer screening because of insufficient evidence in support. Organizations stating that thermography should not be used for breast cancer screening include the American Cancer Society, American College of Radiology, American College of Obstetricians and Gynecologists, and the FDA. While its use as an adjunct to other methods, is legal, its use as a sole screening method is not, and the FDA has taken action against marketers that imply this application.

Ultraviolet blood treatment - blood is treated with a device inserted into a vein. The method had seen popularity in the 1950s, with the rationale that bacteria and viruses in the blood would be killed by ultraviolet radiation. However, one limitation was the small amount blood that could be treated. Also, most bacteria and viruses would not be in the blood and would not be affected. Currently the approach is advocated by some naturopaths and other practitioners, using a device called UVLrx. "The device delivers an illuminated cocktail of red, green, and ultraviolet wavelengths directly into the bloodstream that is claimed to improve circulation and oxygen saturation, reduce pain, modulate the immune system and lessen inflammation" (Hermes 2016 Sept 26. UVLrx therapy lights up charlatans dealing in medical devices. Forbes). "The UVLrx claims to fix that problem [amount of blood being treated] by placing a laser inside a vein and then treating all the blood as it flows by. This doesn't really fix the problem, however, as the dose will be small to any part of the blood as it quickly flows by the light. There is no evidence that this treatment does what it is supposed to do" (Novella 2016 Sep 28. Science-Based Medicine blog).

Edzard Ernst was quoted by Hermes (op. cit.): "UV treatment of blood has been around for some time, but no proof of efficacy has ever emerged. The claims made for the therapy that it a deactivates pathogens, stimulates the immune system, or increases oxygen saturation are pure fantasy...The implication that it cures any condition is not supported by good evidence...we cannot even be sure that the treatment is safe."

Water - numerous forms of water-related dietary supplements have been marketed. Most of these claim to have features that are scientifically unfounded. Alkaline water is discussed above with alkaline diet. Oxygenated water is discussed with oxygenating therapies. Other products include allegedly magnetized, ionized, acidic, clustered, and energized water. Raw (untreated) water is also being sold, which presents a risk of disease.

Whole-body vibration (vibratory therapy) - "you stand, sit or lie on a machine with a vibrating platform. As the machine vibrates, it transmits energy to your body, forcing your muscles to contract and relax dozens of times each second...Advocates say that as little as 15 minutes a day of whole-body vibration three times a week may aid weight loss, burn fat, improve flexibility, enhance blood flow, reduce muscle soreness after exercise, build strength and decrease the stress hormone cortisol" (Laskowski 2017 Apr 12. Is whole-body vibration a good way to lose weight and improve fitness? Mayo Clinic). Other claimed benefits include reduction in bone loss, improved balance, and benefits for patients with neurological diseases. In general there is a lack of convincing evidence of effectiveness. A 2011 review concluded "Claims about whole-body vibration therapy for the prevention and treatment of osteoporosis cannot be made without further research" (Agency for Healthcare Research and Quality Technical Brief 2011 Nov 15. Whole-body vibration therapy for osteoporosis).

READING

Chelation therapy

Barrett S. 2018. Chelation Watch

Green S. 2013. Chelation therapy: Unproven claims and unsound theories. Quackwatch

FDA Center for Drug Evaluation and Research. 2008. FDA Public Health Advisory: Edetate disodium (marketed as Endrate and generic products). Chelation Watch

Atwood KC, Woeckner E, Baratz RS, Sampson WI. 2008. Why the NIH Trial to Assess Chelation Therapy (TACT) should be abandoned. Medscape J Med. 10(5):115

Barrett S. 2010. FDA attacks oral "chelation therapy" products and heavy metal screening test. Chelation Watch

Tsouderos T. 2011 Dec 12. Troubled study at heart of therapy debate. Chicago Tribune

Barrett S. 2012. Be wary of "board certification" in clinical metal toxicology. Quackwatch

Atwood K. 2012 Nov 4. The Trial to Assess Chelation Therapy: Equivocal as predicted. Science-Based Medicine

Gorski D. 2012 Nov 5. The result of the Trial to Assess Chelation Therapy (TACT): As underwhelming as expected. Science-Based Medicine

Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, Lindblad L, Lewis EF, Drisko J, Lee KL; TACT Investigators. 2013. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: The TACT randomized trial. JAMA. 309(12):1241-50

Bauchner H, Fontanarosa PB, Golub RM. 2013. Evaluation of the Trial to Assess Chelation Therapy (TACT): The scientific process, peer review, and editorial scrutiny. JAMA. 309(12):1291-2

Nissen SE. 2013. Concerns about reliability in the Trial to Assess Chelation Therapy (TACT). JAMA. 309(12):1293-4

Gorski D. 2013 Apr 10. In which Orac gets even more “shrill and brutish” about chelation therapy and TACT. Respectful Insolence

Cohen JP, Ruha AM, Curry SC, Biswas K, Westenberger B, Ye W, Caldwell KL, Lovecchio F, Burkhart K, Samia N. 2013. Plasma and urine dimercaptopropanesulfonate concentrations after dermal application of transdermal DMPS (TD-DMPS). J Med Toxicol. 9(1):9-15

Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, Rozema T, Nahin RL, Terry Chappell L, Lindblad L et al. 2014. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy. Am Heart J. 168(1):37-44.e5

Maron DJ, Hlatky MA. 2014. Trial to Assess Chelation Therapy (TACT) and equipoise: When evidence conflicts with beliefs. Am Heart J. 168(1):4-5

Peguero JG, Arenas I, Lamas GA. 2014. Chelation therapy and cardiovascular disease: Connecting scientific silos to benefit cardiac patients. Trends Cardiovasc Med. 24(6):232-40

Mark DB, Anstrom KJ, Clapp-Channing NE, Knight JD, Boineau R, Goertz C, Rozema TC, Liu DM, Nahin RL, Rosenberg Y et al. 2014. Quality-of-life outcomes with a disodium EDTA chelation regimen for coronary disease: Results from the Trial to Assess Chelation Therapy randomized trial. Circ Cardiovasc Qual Outcomes. 7(4):508-16

Gorski D. 2014 Sep 19. Apologetics for chelation therapy in The Atlantic. Respectful Insolence.

Salzberg S. 2016 Oct 3. NIH will spend $37 million on discredited treatment that may harm patients. Forbes

Allergy treatments - general

Barrett S. 2011. Allergies: dubious diagnosis and treatment. Quackwatch

Slader CA, Reddel HK, Jenkins CR, Armour CL, Bosnic-Anticevich SZ. 2006. Complementary and alternative medicine use in asthma: Who is using what? Respirology 11(4):373-87

Adams SK, Murdock KK, McQuaid EL. 2007. Complementary and alternative medication (CAM) use and asthma outcomes in children: An urban perspective. J Asthma. 44(9):775-82

Engler RJ, With CM, Gregory PJ, Jellin JM. 2009. Complementary and alternative medicine for the allergist-immunologist: Where do I start? J Allergy Clin Immunol. 123(2):309-16

NIAID-Sponsored Expert Panel, Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH et al. 2010. Guidelines for the diagnosis and management of food allergy in the United States: Report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 126(6 Suppl):S1-58

Shah R, Greenberger PA. 2012. Unproved and controversial methods and theories in allergy-immunology. Allergy Asthma Proc. 33 Suppl 1:100-2

Wisniewski JA, Li XM. 2012. Alternative and complementary treatment for food allergy. Immunol Allergy Clin North Am. 32(1):135-50

Ernst E, Posadzki P. 2012. Alternative therapies for asthma: Are patients at risk? Clin Med (Lond). 12(5):427-9

Silvers WS, Bailey HK. 2014. Integrative approach to allergy and asthma using complementary and alternative medicine. Ann Allergy Asthma Immunol. 112(4):280-5

Shell ER. 2015. Overreaction. Sci Am. 313(5):28-9 ["Many children are wrongly diagnosed with food allergies because of inaccurate tests."]

Qiu J, Grine K. 2016. Complementary and alternative treatment for allergic conditions. Prim Care. 43(3):519-26

Murdoch B, Carr S, Caulfield T. 2016. Selling falsehoods? A cross-sectional study of Canadian naturopathy, homeopathy, chiropractic and acupuncture clinic website claims relating to allergy and asthma. BMJ Open. 6(12):e014028

Kohn CM, Paudyal P. 2017. A systematic review and meta-analysis of complementary and alternative medicine in asthma. Eur Respir Rev. 26(143)

Allergy - specific methods

Hall H. 2017 Jul 25. Aller-Varx: A questionable remedy for allergic rhinitis. Science-Based Medicine

Barrett S. 2002. Stay away from cytotoxic testing. Quackwatch

Lewith GT, Kenyon JN, Broomfield J, Prescott P, Goddard J, Holgate ST. 2001. Is electrodermal testing as effective as skin prick tests for diagnosing allergies? A double blind, randomised block design study. BMJ. 322(7279):131-4

Barrett S. 2017. Nambudripad's Allergy Elimination Technique (NAET) and Its variants. Chirobase

Barrett S. 1997. Be wary of provocation-neutralization testing. Quackwatch

Arthritis treatments

National Center for Complementary and Integrative Health. 2016. Rheumatoid arthritis: in depth

Richmond SJ, Brown SR, Campion PD, Porter AJ, Moffett JA, Jackson DA, Featherstone VA, Taylor AJ. 2009. Therapeutic effects of magnetic and copper bracelets in osteoarthritis: A randomised placebo-controlled crossover trial. Complement Ther Med. 17(5-6):249-56Smedslund G, Byfuglien MG, Olsen SU, Hagen KB. 2010. Effectiveness and safety of dietary interventions for rheumatoid arthritis: A systematic review of randomized controlled trials. J Am Diet Assoc. 110(5):727-35

Chalasani N, Vuppalanchi R, Navarro V, Fontana R, Bonkovsky H, Barnhart H, Kleiner DE, Hoofnagle JH. 2012. Acute liver injury due to flavocoxid (Limbrel), a medical food for osteoarthritis: a case series. Ann Intern Med. 156(12):857-60, W297-300

Akhtar N, Haqqi TM. 2012. Current nutraceuticals in the management of osteoarthritis: A review. Ther Adv Musculoskelet Dis. 4(3):181-207

Anon. 2012. Herbal medicines for osteoarthritis. Drug Ther Bull. 50(1):8-12

Ragle RL, Sawitzke AD. 2012. Nutraceuticals in the management of osteoarthritis : A critical review. Drugs Aging. 29(9):717-31

Arthritis Research UK. 2012. Complementary and alternative medicines for the treatment of rheumatoid arthritis, osteoarthritis and fibromyalgia. pdf file available from: https://www.versusarthritis.org/about-arthritis/conditions/rheumatoid-arthritis/

Richmond SJ, Gunadasa S, Bland M, Macpherson H. 2013. Copper bracelets and magnetic wrist straps for rheumatoid arthritis - analgesic and anti-inflammatory effects: A randomised double-blind placebo controlled crossover trial. PLoS One. 8(9):e71529

Cameron M, Chrubasik S. 2014. Oral herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. (5):CD002947

Phang JK, Kwan YH, Goh H, Tan VIC, Thumboo J, Østbye T, Fong W. 2018. Complementary and alternative medicine for rheumatic diseases: A systematic review of randomized controlled trials. Complement Ther Med. 37:143-157Cochrane Database Syst Rev. (5):CD002947

Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. 2018. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 52(3):167-175

Gavura S. 2018 Jul 12. Supplements for osteoarthritis - Evaluating the evidence. Science-Based Medicine

"Chronic Lyme disease"

Feder HM Jr, Johnson BJ, O'Connell S, Shapiro ED, Steere AC, Wormser GP; Ad Hoc International Lyme Disease Group. 2007. A critical appraisal of "chronic Lyme disease." N Engl J Med. 357(14):1422-30

Marques A. 2008. Chronic Lyme disease: A review. Infect Dis Clin North Am. 22(2):341-60

Hassett AL, Radvanski DC, Buyske S, Savage SV, Sigal LH. 2009. Psychiatric comorbidity and other psychological factors in patients with "chronic Lyme disease." Am J Med. 122(9):843-50

Halperin JJ, Baker P, Wormser GP. 2011. Lyme disease: the great controversy. In: Halperin JJ, editor. Lyme disease: An evidence-based approach. CAB International. Link to pdf file: https://www.aldf.com/pdf/Halperin_Book_Chapter_17.pdf

Auwaerter PG, Bakken JS, Dattwyler RJ, Dumler JS, Halperin JJ, McSweegan E, Nadelman RB, O'Connell S, Shapiro ED, Sood SK et al. 2011. Antiscience and ethical concerns associated with advocacy of Lyme disease. Lancet Infect Dis. 11(9):713-9

Specter M. 2013 July 1. The Lyme wars. New Yorker

Centers for Disease Control and Prevention. 2015. Laboratory tests that are not recommended. Lyme disease

Patrick DM, Miller RR, Gardy JL, Parker SM, Morshed MG, Steiner TS, Singer J, Shojania K, Tang P; Complex Chronic Disease Study Group. 2015. Lyme disease diagnosed by alternative methods: A phenotype similar to that of chronic fatigue syndrome. Clin Infect Dis. 61(7):1084-91

Lantos PM, Shapiro ED, Auwaerter PG, Baker PJ, Halperin JJ, McSweegan E, Wormser GP. 2015. Unorthodox alternative therapies marketed to treat Lyme disease. Clin Infect Dis. 60(12):1776-82

Berende A, ter Hofstede HJ, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, van den Hoogen FH, Donders AR, Evers AW, Kullberg BJ. 2016. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. 74(13):1209-20

Shapiro ED, Baker PJ, Wormser GP. 2017. False and misleading information about Lyme disease. Am J Med. 130(7):771-772

Bellamy J. 2018 Mar 15. More political science: Proposed laws protect "Lyme literate" doctors from discipline. Science-Based Medicine

Clinical ecology

Barrett S. 2016. Multiple chemical sensitivity: A spurious diagnosis. Quackwatch

Niemark J. 2013 Nov. Allergic to life. Discover. 45-51

Barrett S. 2016. Adverse court rulings related to clinical ecology theories and methodology. Quackwatch

Controversial syndromes and diseases

Barrett S. 2015. Be wary of "fad" diagnoses. Quackwatch

Novella S. 2017 May 31. Mast cell activation disorder - Yes, it's real. Science-Based Medicine [general discussion of controversial syndromes and diseases]

Cadegiani FA, Kater CE. 2016. Adrenal fatigue does not exist: A systematic review. BMC Endocr Disord. 16(1):48

Hormone Health Network. 2018. Adrenal fatigue

Gavura S. 2017 Jun 29. Adrenal fatigue: A fake disease (updated). Science-Based Medicine

Akturk HK, Chindris AM, Hines JM, Singh RJ, Bernet VJ. 2018. Over-the-counter "adrenal support" supplements contain thyroid and steroid-based adrenal hormones. Mayo Clin Proc. 93(3):284-290

Barrett S. 2005. Dubious "yeast allergies." Quackwatch

National Center for Complementary and Integrative Health. 2018. Fibromyalgia: In depth

Holdcraft LC, Assefi N, Buchwald D. 2003. Complementary and alternative medicine in fibromyalgia and related syndromes. Best Pract Res Clin Rheum 17(4) 667-83

Lauche R, Cramer H, Häuser W, Dobos G, Langhorst J. 2015. A systematic overview of reviews for complementary and alternative therapies in the treatment of the fibromyalgia syndrome. Evid Based Complement Alternat Med. 2015:610615

Perry R, Leach V, Davies P, Penfold C, Ness A, Churchill R. 2017. An overview of systematic reviews of complementary and alternative therapies for fibromyalgia using both AMSTAR and ROBIS as quality assessment tools. Syst Rev. 6(1):97

Stobbe M. 2007 Feb 17. Politics plays a role in disease research. Associated Press. [chronic fatigue]

Crislip M. 2016 Sep 16. Chronic fatigue syndrome/systemic exertion intolerance disease speculcation [sic]. Science-Based Medicine

Maxmen A. 2017. Biological underpinnings of chronic fatigue syndrome begin to emerge. Nature. 543(7647):602

Crislip M. 2015 Jun 12. Leaky Bowel. Science-Based Medicine

GI Society. 2018. Debunking the myth of 'leaky gut syndrome'

Hylwa SA, Bury JE, Davis MD, Pittelkow M, Bostwick JM. 2011. Delusional infestation, including delusions of parasitosis: Results of histologic examination of skin biopsy and patient-provided skin specimens. Arch Dermatol. 147(9):1041-5

Pearson ML, Selby JV, Katz KA, Cantrell V, Braden CR, Parise ME, Paddock CD, Lewin-Smith MR, Kalasinsky VF, Goldstein FC, et al. 2012. Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy. PLoS One. 7(1):e29908

Gorski D. 2012 Jan 26. Still more evidence that Morgellons disease is most likely delusional parasitosis, 2012 edition. Respectful Insolence

Devices

Barrett S. 2018. Device Watch

Barrett S. 2018. Quack "electrodiagnostic" devices. Quackwatch

Bratton RL, Montero DP, Adams KS, Novas MA, McKay TC, Hall LJ, Foust JG, Mueller MB, O'Brien PC, Atkinson EJ, Maurer MS. 2002. Effect of "ionized" wrist bracelets on musculoskeletal pain: A randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 77(11): 1164-8

Berens MJ and Wilmsen C. 2007 Nov 20. "Miracle machine" scams desperately ill. Chicago Tribune

Hall H. 2011. Power Balance products: A skeptical look. Device Watch

Barrett S. 2013. A skeptical look at VoiceBio. Device Watch

Patterson T. 2013. Electrocuting parasites: Cutting edge pseudoscientific technology. Skeptical Inquirer 37(5):49-51

Novella S. 2016 Jun 8. Pulsed electromagnetic field snake oil. Evidence-Based Medicine

Hall H. 2016 Jun 14. The Blood Cleaner: invented by Ray Jardine. Science-Based Medicine

Gorski D. 2016 Sep 13. You, too, can measure your nutrient levels using an iPhone and a giant stylus on your acupuncture points. Respectful Insolence

Barrett S. 2017. The fakery of electrodermal screening. Skeptical Inquirer 41(5):40-3

Barrett S. 2017. Some notes on the bi-digital O-ring test and Quantum Reflex Analysis. Quackwatch

Frost J. 2017. A skeptical look at the Spooky2 Rife system. Device Watch

Barrett S. 2017. iTOVi scanning: Another test to avoid. Device Watch

Ernst E. 2017 Mar 27. Bioresonance cures addictions to alcohol, cocaine, crack, nicotine, heroin, opiates, cannabis, spice, legal highs and other medications? No, it doesn’t! Edzard Ernst

Gorski D. 2017 Jun 23. Gwyneth Paltrow shows that the Quantum Xrroid Consciousness Interface was ahead of its time, as NASA slaps down Goop. Respectful Insolence

Hall H. 2017 Oct 3. Amino Neuro Frequency: Just more “embedded frequencies” silliness. Science-Based Medicine

Barrett S. 2018. Regulatory actions related to EAV devices. Quackwatch

Barrett S. 2018. ZYTO scanning: Another test to avoid. Device Watch

Barrett S. 2018. A skeptical look at the AcuGraph and SimplusPro. Device Watch

Gorski D. 2018 Aug 17. Luminas Pain Relief Patches: Where the words “quantum” and “energy” really mean “magic.” Respectful Insolence

Magnet therapy

National Center for Complementary and Integrative Health. 2017. Magnets for pain

Barrett S. 2008. Magnet therapy: A skeptical view. Quackwatch

Harlow T, Greaves C, White A, Brown L, Hart A, Ernst E. 2004. Randomised controlled trial of magnetic bracelets for relieving pain in osteoarthritis of the hip and knee. BMJ. 329(7480):1450-4

Eccles NK. 2005. A critical review of randomized controlled trials of static magnets for pain relief. J Altern Complement Med. 11(3):495-509

Winemiller MH, Billow RG, Laskowski ER, Harmsen WS. 2005.Effect of magnetic vs sham-magnetic insoles on nonspecific foot pain in the workplace: A randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 80(9):1138-45

Finegold L and Flamm BL. 2006. Magnet therapy. BMJ. 332(7532):4

Pittler MH, Brown EM, Ernst E. 2007. Static magnets for reducing pain: systematic review and meta-analysis of randomized trials. CMAJ. 177(7):736-42

Kuipers NT, Sauder CL, Ray CA. 2007. Influence of static magnetic fields on pain perception and sympathetic nerve activity in humans. J Appl Physiol. 102(4):1410-5

Novella S. 2008 Jan 9. Can magnets heal? Science-Based Medicine

Hall H. 2017 Mar 7. Magnets provide amusement, but not health benefits. Science-Based Medicine

Mercury-amalgam

Barrett S. 2006. The "mercury toxicity" scam: How anti-amalgamists swindle people. Quackwatch

National Council Against Health Fraud. 2002. Position paper on amalgam fillings

Life Sciences Research Organization. 2004. Review and analysis of the literature on the potential health effects of dental amalgams

Institute for Science in Medicine. 2012. Dental amalgam (pdf file)

Lorscheider FL, Vimy MJ, Summers AO. 1995. Mercury exposure from "silver" tooth fillings: Emerging evidence questions a traditional dental paradigm. FASEB J 9(7):504-8

Clarkson TW, Magos L, Myers GJ. 2003. The toxicology of mercury - Current exposures and clinical manifestations. N Eng J Med 349(18):1731-7

Risher JF and Amler SN. 2005. Mercury exposure: evaluation and intervention - The inappropriate use of chelating agents in the diagnosis and treatment of putative mercury poisoning. NeuroToxicology 26(4): 691-9

Needleman HL. 2006. Mercury in dental amalgam–A neurotoxic risk? JAMA. 295(15):1835-6

Bellinger DC, Trachtenberg F, Barregard L, Tavares M, Cernichiari E, Daniel D, McKinlay S. 2006. Neuropsychological and renal effects of dental amalgam in children: A randomized clinical trial. JAMA. 295(15):1775-83

DeRouen TA, Martin MD, Leroux BG, Townes BD, Woods JS, Leitão J, Castro-Caldas A, Luis H, Bernardo M, Rosenbaum G, Martins IP. 2006. Neurobehavioral effects of dental amalgam in children: A randomized clinical trial. JAMA. 295(15):1784-92

Anon. 2006 Apr 19. Studies of dental fillings reassuring. Associated Press

Anon. 2009 July 31. Mercury released by dental amalgam fillings are not high enough to cause harm, FDA finds. ScienceDaily