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Researching Candida-Related Complex

"If you think research is expensive, try disease."
--Mary Lasker

"Chronic candida" in not a conventional medical diagnosis, and has only been the subject of one peer-reviewed clinical trial. The term "chronic candida"(AKA the yeast syndrome, Candida-Related Complex) is used by a small number of patients and practitioners to refer to a cluster of GI and systemic symptoms which defy conventional diagnosis, and respond to anti-candida measures like antifungal medications and dietary elimination of sugar. Most physicians would attribute the same symptoms to IBS, if mild, or the DSM-IV diagnosis of undifferentiated somatoform disorder if more severe(if they gave them a diagnostic label at all).

Why Research Chronic Candida?

The "chronic candida" concept has been around for two decades now. There continue to be books, websites, and products that attest to it's validity. For example, below is a list of books that can be found on this condition at Amazon.com and bn.com. While popularity does not mean a medical concept is scientifically valid, long-term popularity is a sufficient indicator to warrant diligent investigation.

It is not being discredited as a diagnostic label. Whereas research on Gulf War syndrome and CFS has found evidence of physical pathology, there has been no investigation into CRC. It will persist as long as:

The symptoms "chronic candida" refers to have no conventional diagnosis(save for labeling them psychosomatic), and even then no effective treatment. Until there is a better medical understanding of them, patients are likely to look outside of conventional medicine.
There continues to be a steady stream of anecdotal evidence that the treatment is effective; or at least somewhat effective for some of those who employ it.

There is a market for candida treatment

The public response to the description of chronic candida has been substantial. The most popular book on the subject has over 1 million copies in print¹. If the disease is a fiction, it is a popular one. The demand for treatment for this condition has produced a substantial number of books, nutritional supplements, and therapies.

There are over a dozen books in the lay press on the diagnosis and treatment of "chronic candida", and new titles continue to appear^1-12.
There is an entire category of supplements marketed to relieve candida problems(such as caprylic acid, grapefruit seed extract, garlic, and others).
Some practitioners actively solicit clients seeking help with chronic candida. These include alternative/complimentary practitioners such as naturopaths, chiropractors, and nutritionists as well as licensed MDs.

Conventional physicians demand research before they will treat it

Medical authorities have criticized the diagnostic label of "chronic candida". They oppose anti-candida treatment, even if empirically effective, because research support is absent. Hundreds of physicians and thousands of patients consider anti-candida treatment safe, effective, and free of serious side-effect. This is not scientific proof, but it is evidence. When patients are denied the option of anti-candida treatment, they are offered the alternative diagnosis of somatization disorder. This attributes the patients symptoms to psychological causes, not because of proof of mental illness, but lack of medical proof of physical illness. Somatization disorder has no effective treatment, and is often found later to be an undiagnosed physical illness. Patients put in this position may leave their doctors in frustration. If they were emotionally stable before, this change that. Patients may have expectation they would be listened to and believed. This can seem naive in hindsight. Patients I've met who reports benefits from anti-candida treatment expresses confusion and animosity towards the health-care system that denied them access to this treatment.

The scientific proof medical authorities are holding out for does not appear forthcoming. While there is substantial research being done on candida and it's pathogenesis, there is none being done on this syndrome. In the absence of scientific proof, there is only anecdotal/circumstantial evidence to go by. Should a patient have the right to demand an unconventional treatment their doctor opposes? Should a doctor have the right to withhold a reasonably safe treatment a patient demands, because it lacks medical consensus? There are no easy answers, but patients are being left in the lurch. Some know from direct, personal experience that antifungal medications help them, but they cannot get them prescribed.

Perhaps medical opinion will capitulate under the burden of lost revenue due to patients jumping ship in favor of chronic candida proponents. In 1996, the late Dr. Keith Sehnert, who reports treating nearly four thousand CRC patients, wrote⁸:

"Change is occurring. It may seem slow, but it is happening...In the case of CRC, the generation (twenty-five to thirty years) of slow acceptance has passed...It is my firm conviction that this medical paradigm is on the verge of shifting."

In the meantime, research is necessary to prove the physical basis for the symptoms of chronic candida.

There is no effective treatment for somatization disorder

If people with chronic candida, who are diagnosed as suffering from somatization disorder, report improvement from anti-candida treatment, this suggests other patients with somatization might be helped. This is true even if you do not accept the label of chronic candida. You can continue to label it somatization, but if patients report improvement, it ought to be pursued. This is especially true considering there is currently no effective treatment for somatization.

This contradicts the hypothesis that somatization is purely psychological in cause. However, the cause has never been proven. There may more than one subset of somatization patients with unrecognized physical disorders.

Approaches to researching CRC

Epidemiological

There are epidemiological similarities among CRC patients, which make them different from any other group. These are:

A history of antibiotic use prior to developing symptoms,
systemic symptoms of fatigue and "brain fog" or clouded consciousness,
gi symptoms of constipation/diarrhea, bloating, food sensitivities, and possibly others,
an absence of an underlying general medical condition to explain their symptoms,
a history of antibiotic use prior to developing symptoms,
and an empirical response to antifungal medication and the elimination of sugar from the diet.

Some patients who match the above profile report developing symptoms after taking tetracycline long-term for acne. This practice is widespread, but is an off-label use of that drug. It has therefore not been accepted by the FDA as safe and effective, and should be subject to more vigilant post-market surveillance by pharmaceutical epidemiologists.

Seven hundred patients on minocycline treatment for acne were evaluated for side-effects in 1996¹⁴. The mean duration of treatment was 10.5 months(range 2 weeks to 4 years). This study did not evaluate for CRC, but the results might be seen as supportive of it.

Three of the seven hundred reported memory disturbances/poor concentration.
22 reported gastrointestinal symptoms.
9 reported vaginal candidiasis or pityriasis versicolor.

In the March 24, 1973 issue of "The Lancet", Leonard Sadoff and Theodore Eckberg wrote about an unusual cancer in a 16-year old girl taking tetracycline for acne. They closed their letter:

"The wisdom of giving long courses of tetracycline to young people for benign conditions is questioned--in view of the lack of long-term toxicity studies with this class of drugs."

Some toxicity studies have since been completed, but none looked for subjective symptoms, such as fatigue, brain fog, and depression. I would like to make a case for epidemiological research to follow up on the health of people who have taken tetracycline for acne, based on:

Reports of patients being harmed by the long-term use of tetracycline(causing lasting fatigue and the other symptoms of CRC)
The fact this is an off-label use, not approved by the FDA
The lack of research on it's long-term effect on the GI microflora
The growing scientific appreciation of the importance of the GI microflora to gastrointestinal and immune function

A health survey of those who have used tetracycline long-term might identify people who match the profile of CRC, in greater numbers than comparable healthy controls.

Pathophysiological

Biopsies of the duodenum (taken by endoscope) can be evaluated for increased intestinal permeability to intact antigens. This can be caused by GI infection, and is potentially the mechanism for systemic symptoms in CRC. Patients suspected of having CRC could be evaluated for disordered intestinal permeability. This might uncover a physical cause of the disorder.

Clinical trials

Clinical trials of CRC treatments are not possible until the disease can be scientifically defined. However, treatments that have been anecdotally effective can be tried against the individual symptoms attributed to CRC. Antifungals or probiotics could be used to treat gi symptoms in patients who appear to have CRC, for whom conventional measures have failed.

How different groups might benefit from research on CRC

Candida practitioners

Advocates of the CRC diagnostic label have mainly been practitioners who use the diagnosis in their practice. They would be free to openly promote their approach to the condition if it were defined and validated scientifically.

Mainstream physicians

The largest single group of patients seen by GI specialists are those with "functional" disorders, for which the physician can do little. If some of these patients could be helped by anti-candida treatment, it would reduce the frustration felt by these patients and their doctors.

Consumers/the public

Consumers with vague GI and systemic symptoms, which defy diagnosis or cure by conventional medicine, may resort to over-the-counter and alternative therapies which claim to address one or more of their symptoms. Scientifically established diagnostic criteria for CRC could allow those who don't, in fact, have chronic candida to save their money on anti-candida remedies. f CRC were discovered to be a cause of depression, gastrointestinal symptoms, and misdiagnosed somatization disorder(as is being alleged), people currently diagnosed with these disorders might be helped by screening for CRC.

Pharmaceutical and probiotic companies

If CRC is scientifically defined, drug and probiotic companies could begin to conduct clinical trials of proprietary treatments. Prescription antifungals already being marketed could be tested for effectiveness against CRC. A probiotic remedy effective against GI candida overgrowth might also help those at risk of disseminated candidiasis(such as immunocompromised patients). The commercial demand for CRC remedies appears steady, if not growing, even without scientific support.

More Candida Studies 1 Nystatin and Candiasis Research

References

C. Orian Truss MD, "The Missing Diagnosis", The Missing Diagnosis Inc, 1983(ISBN 0961575808)
William Crook, MD "The Yeast Connection: A Medical Breakthrough", Random House Inc, 1983 (ISBN 0394747003)(this book was a bestseller with more than 1 million copies in print)
John Parks Trowbridge, MD, Morton Walker, DPM "The Yeast Syndrome, How to Help your Doctor Identify and Treat the Real Cause of your Yeast-Related Illness", Bantam Books, 1986(ISBN: 0553277510)
Shirley Lorenzani, Ph.D. "Candida: A Twentieth Century Disease", Keats Publishing, 1986(ISBN 0879833750)
William Crook, MD "Chronic Fatigue Syndrome and the Yeast Connection: A Get-Well Guide for People With This Often Misunderstood Illness--And Those Who Care for Them", Professional Books 1992(ISBN: 0933478208)
Stanley Weinberger "Candida Albicans: The Quiet Epidemic", CHC Publishing, 1995(ISBN: 0961618469)
Christine Winderlin, Keith Sehnert MD "Candida-Related Complex, What Your Doctor Might Be Missing", Taylor Publishing Co, 1996(ISBN: 0878339353)
Ray C. Wunderlich "The Candida-Yeast Syndrome; How to Fight an Exploding Epidemic of Yeast-Related Diseases", Keats Publishing 1997(ISBN: 0879836970)
Gill Jacobs "Beat Candida Through Diet : A Complete Dietary Programme for Sufferers of Candidiasis", Trafalgar Square 1997(ISBN: 0091815452)
Leon Chaitow "Candida Albicans : Could Yeast Be Your Problem?", Healing Arts Press, 1998(ISBN: 089281795X)
William Crook MD "The Yeast Connection Handbook", Professional Books, 1999(ISBN: 0933478240)
Gary Carlsen "The Candida Yeast Answer", Candida Wellness Program, 1999(ISBN: 1576360792)
Goulden V, Glass D, Cunliffe WJ "Safety of long-term high-dose minocycline in the treatment of acne" British Journal of Dermatology 134:693-695, 1996