Experts in pathology recently published a review of the evidence for CAM laboratory tests commonly used in the U.S., the U.K., and Australia. Their article, published in the Annals of Clinical Biochemistry: International Journal of Laboratory Medicine (article behind paywall), notes that CAM practitioners, such as naturopaths, “promote and sell a wide range of tests, many of which are of dubious clinical significance.” Some “have little or no clinical utility and are widely discredited.” Others are legitimate lab tests used for unvalidated purposes. The term “CAM testing” is used in the article to describe both types of tests; collectively, those with “little or no clinical benefit that represent a potential risk to patient safety.”
In my view, the authors have contributed an extremely important addition to the medical literature, for three reasons. First, there is far too little in the mainstream medical literature exposing the risks of CAM practices and CAM practitioners like chiropractors, naturopaths, and acupuncturists. Second, the article handily collects the most popular CAM lab testing scams into one convenient reference. Third, it serves as pushback to the infiltration of integrative medicine in the medical literature (also here and here), which treats CAM practitioners as valuable additions to the healthcare team, conveniently eliding the risks posed to patients by their pseudoscience, including dubious diagnostic tests, which, as the article points out,
are often accompanied by extensive clinical interpretations which may recommend, or be used to justify, unnecessary or harmful treatments.
Testing may be “particularly appealing” to CAM practitioners and their unwitting patients for several reasons, according to the authors, two of whom are with the departments of clinical biochemistry in London hospitals; the third is a retired Australian pathologist.
- It adds “an element of science” to the office visit. Patients are aware that conventional medicine relies on diagnostic testing and may erroneously assume CAM testing gives them the benefit of a scientific approach.
- Testing produces data to support a diagnosis, however bogus. CAM tests are “often ordered as large profiles of multiple analytes,” increasing the possibility of getting “abnormal” results purely by chance. CAM practitioners can then build a narrative around these “abnormal” results, especially with chronic conditions (such as chronic fatigue syndrome and fibromyalgia) without a definitive cause and with limited treatment options.
- CAM practitioners make money by selling further testing, dietary supplements, or other treatments based on the “abnormal” lab results.
- CAM practitioners can claim they are offering a unique service unavailable from conventional physicians. This is appealing to patients “with unexplained symptoms for which there are a limited range of evidence-based investigations and treatments available.”
The authors note that there are now labs around the world devoted solely to CAM testing. Some of these operate outside of any regulatory program, others are fully accredited to the same standards as established clinical labs. These labs often promote themselves as environmental, nutritional, natural medicine, or other CAM, specialists. Some sell directly to the public; others require a “health professional” to order a test but will actually accept orders from unlicensed naturopaths and nutritionists, who may order tests inappropriately or misinterpret the results. Some labs issue reports recommending therapies for the “abnormalities” detected by their testing.
The article offers a useful primer on how lab tests are evaluated per the American Association of Clinical Chemistry (AACC) framework (emphasis added):
Analytic validity of a test defines its ability to measure accurately and reliably the component of interest. . . .
Clinical validity defines the ability to detect or predict the presence or absence of an accepted clinical disease or predisposition to such a disease. . . .
Clinical utility refers to the likelihood that the test will lead to an improved outcome. What is the value of the information to the individual being tested and/or to the broader population?
Ethical, legal and social implications (ELSI) of a test. Issues include how the test is promoted, how the reasons for testing are explained to the patient, the incidence of false-positive results and incorrect diagnoses, the potential for unnecessary treatment and the cost-effectiveness of testing.
Their framework is essential to understanding the, in my view, tragically inadequate regulation of lab tests in the U.S., which directly contributes to the explosion of dubious lab tests now made available directly to consumers and via naturopaths, chiropractors, so-called “integrative physicians”, and the like. We’ll return to this topic, including draft legislation to address this regulatory gap now circulating in Congress, in a moment.
The authors reviewed the evidence for over a dozen common CAM lab tests, noting “there are many others not covered in this review.” As is appropriate for a scientific journal and expert review, their analysis is at times highly technical. As a layperson, my summary of their analysis will not be, and I’ll add a few comments of my own.
Live blood cell analysis (or LBA, also known as dark-field video analysis, nutritional blood analysis)
LBA is done is real time, with the practitioner “interpreting” cell morphology and the presence of meaningless features in a sample of “live” blood viewed under a dark field microscope and displayed on a video monitor. The test can supposedly diagnose any number of diseases, from nutritional and energy “imbalances” to cancer. Merely describing this test should be sufficient for all but the most credulous to dismiss it as nonsense, but the authors actually found two studies of LBA. Big surprise: They showed the test lacked reliability, sensitivity, and specificity.
Interestingly, the authors note that labs performing LBA in the U.S. must be CLIA-certified for high complexity testing, which, according to a federal regulatory agency, is “virtually impossible” for a facility offering LBA. In other words, anyone performing LBA is very likely in violation of the certification requirement, which is exactly what the feds found in a 2001 audit of labs offering LBA.
SBM’s Mark Crislip did his own analysis of LBA and found it wanting as well. Yet, in 2014, the Washington State Board of Naturopathy declared that the Bolen Blood Procedure (which is either the same or a very similar type of blood analysis) was within the scope of naturopathic practice.
Leukocytotoxic tests: Bryan’s test, ALCAT test, MELISSA test
Bryan’s Test for allergies, a blood test, was found in controlled studies to have very poor correlation with known allergens, a high-false positive rate, and poor reproducibility, within-individual and inter-operator.
The manufacturer of the ALCAT test, a commercial, mechanized cytotoxic test, “supplies panels of hundreds of foods, environmental chemicals, food colorings, molds, herbs and some drugs.” Studies have found “no credible evidence” to support the test and several medical organizations internationally, including the American Academy of Allergy, Asthma and Immunology, have recommended against using ALCAT for the diagnosis of food intolerance or allergy.
MELISA is an assay used primarily for metal sensitivity and Lyme disease. Researchers independent of the commercial lab providing the test report that “MELISA is so non-specific as to be of no clinical utility.”
Food intolerance testing using food antigen-specific IgG4 antibodies
The authors found that food intolerance or sensitivity testing is widely available direct to consumer (DTC), often as a panel, some containing over 200 food components and often with an interpretive report recommending excluding foods from one’s diet. Advertising suggests that the test can identify foods responsible for a variety of symptoms, including “bloating, abdominal pain, fatigue, depression, irritable bowel and skin complaints.”
As SBM’s Scott Gavura explained (also here) IgG4 antibodies indicate food exposure, not sensitivity or intolerance. As these authors point out, there is no evidence that IgG4 testing is beneficial in determining food intolerance or food allergy, and dietary exclusion based on testing “would result in considerable overtreatment and potential harm from unnecessary dietary restriction, especially in children.” This is why, they note, many professional organizations recommend against IgG4 testing for clinical purposes.
Nevertheless, just last week, the Florida Association of Naturopathic Physicians newsletter touted IgG testing for food “sensitivity” as it can lead to “chronic health problems, including ADHD, digestive disorders, and persistent infection.”
Hair analysis for trace elements and minerals
The authors of this journal article note that quantitation of trace elements in hair is usually offered for individuals with nutritional or toxicological concerns and test reports “often include detailed interpretation highlighting nutritional deficiencies or heavy metal toxicities and further investigations that may be required” and “recommending unnecessary treatments.”
The method is fraught with numerous difficulties, including, according to the CDC, variable collection procedures, sample preparation, and methodology; lack of standards; sample contamination; poor understanding of the biological processes underpinning element incorporation into hair; lack of reference ranges; and lack of correlation between element levels and target tissues. There are also questions over conflicts of interest because many CAM laboratories work in collaboration with CAM practitioners who sell treatments on the basis of “abnormal” hair test results. In sum, there is “little evidence to support the use of hair element analysis in routine nutritional or toxicological assessment.”
CAM laboratories commonly offer assessments of antioxidant status, ranging from a single analyte, such as reduced glutathione, to panels of vitamins or tests for total antioxidant status . . . [They] may claim that free radicals cause or aggravate many ailments, such as cancer, Alzheimer’s disease, heart disease, chronic fatigue syndrome (CFS) and dementia.
While free radicals may have a role in many conditions, the authors say the appropriate question is whether there is any clinical utility in measuring antioxidant status. As it turns out, the answer is “no” according to the only paper they could find addressing this question.
Even though this bogus testing is used to sell antioxidant supplements,
no regulatory authority has approved any antioxidant supplement for the treatment of any condition . . . [and there is] no evidence to support the use of antioxidant supplements in the primary or secondary prevention of chronic diseases or mortality. Supplementation with beta-carotene, vitamin A, and vitamin E may actually increase mortality.
Marketing of this test suggests it is useful in the diagnosis of many conditions, including bipolar disorder, schizophrenia and depression, but this review found no evidence in the mainstream, peer-reviewed literature that it is useful in any of those conditions or any other clinical purpose for that matter.
Mitochondrial function: neutrophil ATP profile
This test, according to the article, is marketed with the claim that its “ATP profile” correlates with physical disability in CFS and is “used to tailor unconventional therapies.” It is based on a study that has never been independently replicated or validated.
This is a popular CAM scam we’ve covered here on SBM. As the this article explains, CAM practitioners claim that low-level colonization with Candida can cause symptoms such as fatigue, muscle weakness, depression, and bloating, a “theory” that is widely discredited. Testing patients with non-specific symptoms “carries a high risk of false positive or clinically irrelevant results.” In addition to unnecessary supplements and dietary modifications, treatments include potent antifungal agents, which has resulted in “severe iatrogenic complications.”
Post-chelator challenge testing [PCCT]
Yet another CAM favorite and the subject of SBM posts (also here and here). As this article explains, agents that bind metallic elements from the body’s tissues (chelators) increases the excretion of these elements in urine. “In-house” laboratory assays, which have not been cleared by the FDA for clinical use, will show elevated metallic elements (e.g., mercury) which are then interpreted by practitioners “as an indication for ‘detoxification,’ sometimes involving powerful chelating agents that can have serious side effects and have caused a number of fatalities.”
Laboratories offering PCCT frequently report post-challenge metal excretion levels against reference intervals derived from unprovoked individuals. This inevitably leads to at least one ‘elevated’ results and opens the door to potential misinterpretation. So far as we are aware validated reference intervals and cut-offs for clinical toxicity do not exist for samples taken post-chelation.
The article points out that, despite being uniformly criticized by health professionals, toxicologists, and regulatory agencies, PCCT remains widely available, especially in the U.S.
Secretory IgA (sIgA) tests using stool and saliva samples are promoted by CAM practitioners “to assess immune health with claims that abnormal results may suggest autoimmune disease, asthma, allergy, infection, inflammatory bowel disease, dental caries and many other conditions.” (This includes the Florida Association of Naturopathic Physicians, which recommended IgA testing in its aforementioned monthly newsletter.) The stool test is also advertised as an alternative test for celiac disease. Yet, there is no convincing evidence, according to this review, that sIgA testing is useful diagnosis of any condition.
Testing using sIgA is likely to lead to further unnecessary investigation, anxiety and possibly inappropriate treatment, such as dietary exclusion. Screening for [celiac disease] using sIgA carries a significant risk of missing a potentially serious diagnosis.
Adrenal stress profile
Saliva samples, collected by patients several times during the day (“collection and sampling handling instructions vary significantly”), are analyzed for cortisol and DHEAS. The test results are often interpreted by CAM labs as adrenal dysfunction and used by CAM practitioners
to support the medically-unrecognized diagnosis of adrenal fatigue . . . [and] claim this poorly-defined adrenal dysfunction is caused by chronic physiological or psychological stress, resulting in a variety of non-specific symptoms. There is no consensus on criteria for diagnosis or recommended treatments, though the diagnosis is often used to justify the prescription of nutritional supplements. . . There are no published data validating the adrenal stress profile for the investigation or diagnosis of any condition.
Possible regulatory reform in U.S.
In sum, the authors of this excellent review say,
The common factor in all these tests is the lack of evidence for clinical validity and utility as used in CAM practice. This should not be surprising since this is true for CAM practice in general.
They find that inadequate regulatory oversight of CAM lab testing in the U.K., Australia and the U.S. is a big cause of the problem and should be remedied. (Of course, I would add that inadequate regulatory oversight of CAM practitioners is a big cause of the problem and should be remedied.)
Here in the U.S., the FDA abandoned its efforts to effectively regulate the use of laboratory-developed tests (LDTs), that is, tests developed and performed at a single laboratory, with all samples sent to that particular lab for testing. Many of the CAM lab tests fall into this category, which has been, and still is, only lightly regulated. While this is an oversimplification, as it now stands, LDTs are required to show only analytical validity, but not clinical validity or clinical utility. And I see no evidence that any CAM lab test manufacturer or marketer has ever thought about the ethical, legal and social implications of their tests, if they even know this consideration exists as part of the AACC framework.
Instead, the FDA, apparently realizing that it lacked the necessary authority to fully address the regulatory issues raised by the exponential growth in lab testing, turned to Congress for a remedy. This resulted in the drafting of a bill, The Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2018, which would overhaul regulation of all in-vitro diagnostic testing, including LDTs. The VALID Act draft, which has bipartisan support, is now circulating in Congress.
Needless to say, stakeholders in the lab industry are not fully on board with a broad reworking of the lab testing regulatory scheme and, due to their lobbying, the draft will undoubtedly undergo substantial revision. We’ll have to wait to see what effect, if any, these efforts will have on CAM testing. In the meantime, CAM practitioners will continue to bamboozle patients into unnecessary and possibly dangerous therapies based on the results of dubious lab tests, which can themselves cause injury.