Saga of Dietary Supplements: “All Natural”? “Herbal”? “Safe and effective”? Um… Not quite.

Poor wee “All Natural”, “Herbal” dietary supplements — ‘safe and effective’ alternative medical modalities so beloved of the pseudoscience aficionados and woomeisters all over the world: they can’t get a break!

On June 2, the US Food and Drug Administration (FDA) issued a public warning – via its Medication Health Fraud webpage – against 6 over-the-counter products for ‘Sexual Enhancement’, its second-largest single-day set of warning in this particular category. (The largest-yet set was warnings against 7 products in June last year.)

What, you thought those ‘male enhancement’ pills only appeared in spam emails and weird late-night TV commercials, did you?

In these notifications, the FDA advises the consumers not to purchase and use the respective products. As pharmacologist and science communicator par excellence David Kroll has pointed out in a recent Forbes essay on Adulterated Supplements, all the 6 “sexual enhancement” products in the current warnings, many labeled “All Natural” or “Herbal”, are tainted with chemical substances — called PDE5 inhibitors — which are the main ingredients in drugs used commonly to treat Erectile Dysfunction, such as Viagra (sildenafil) and Cialis (tadalafil). Many of the products (with wonderfully evocative names, such as Alpha Male, XZone, Wood-E and SexRx) associated with previous warnings under the same category had the same exact problem.

During sexual stimulation, male erection is achieved by an increased blood flow to a swath of tissue within the penis. The PDE5 inhibitors keep the smooth muscle of blood vessels supplying penile tissue in a relaxed state, thereby maintaining the blood flow and the erection. The supplements containing these chemically-synthesized PDE5 inhibitors and their analogs are, therefore, neither “All Natural” nor “Herbal” as advertised, and the touted efficacy of these supplements may well be attributed to the adulteration with these pharmacologically-active drug molecules.

What is the risk if these substances are present in the supplements? PDE5 inhibitors are metabolized in the liver via an enzyme system, and can potentially interfere with the action of other drugs using the same system, such as alcohol, certain antifungals and antivirals, including HIV medications. But the greatest risk comes from their hypotensive (blood-pressure lowering) mechanism of action; accidental combination with other prescription hypotensives, including those used in treatment of various cardiovascular or metabolic conditions, can drastically lower the blood pressure and result in death.

And Sexual Enhancement is not the only enticement; of the nearly 300 fraudulent products under FDA’s radar, many promise rapid weight loss and assistance in bodybuilding, and many of these contain hidden or deceptively labeled ingredients (sometimes prescription ingredients at a much higher concentration than in regular drugs) associated with significant health risks. This is why the FDA is charged with continually warning consumers about contaminated products fraudulently marketed as dietary supplements; these pose the danger of serious, life-threatening injury. Indeed, the FDA has received numerous reports of harm attributed to such supplements, including stroke and cardiac conditions, liver and kidney injury, and even death.

Supplements

By an Act of Congress (the 1994 Dietary Supplement Health and Education Act, DSHEA) dietary supplements are formally defined as products that are labeled as such, and: (a) supplement the diet, (b) contain one or more dietary ingredients (including vitamins, minerals, herbs or other botanicals, amino acids, and certain other substances) or their constituents (in form of concentrates, metabolites, extracts) alone or in combination, (c) are taken orally. Herbal supplements are supposed to contain parts (such as leaves, flowers or seeds) of one or more plant(s), all of which are required by law to be listed on the label. However, in practice, that may not always be the case, prompting the NIH (via the NCCAM) to push the following warnings:

• Although many dietary supplements (and some prescription drugs) come from natural sources, “natural” does not always mean “safe”.
• A manufacturer’s use of the term “standardized” (or “verified” or “certified”) does not necessarily guarantee product quality or consistency.
• An herbal supplement may contain dozens of compounds and that all of its ingredients may not be known.
• What’s on the label may not be what’s in the bottle: analyses of dietary supplements sometimes find differences between labeled and actual ingredients. For example:
  • An herbal supplement may not contain the correct plant species.
  • Amounts of the ingredients may be lower or higher than the label states.
  • Dietary supplement may be contaminated with other herbs, pesticides, or metals, or even adulterated with unlabeled, illegal ingredients such as prescription drugs.

Some dietary supplements, such as certain vitamins and occasionally minerals, are useful in specific conditions, such as clinically evaluated deficiencies and demonstrated need based on sound scientific principles (e.g. Folate during pregnancy). But such legitimate use pales in comparison with the vast majority of use by “Natural Products” enthusiasts and believers in alternative medicine even in absence of demonstrated efficacy for any specific condition.

Prima facie the Federal Government is responsible for the regulation of these dietary supplements through the FDA; in practice, however, the said regulations for dietary supplements are extremely lax, and not at all comparable to those for real prescription or over-the-counter medications. For instance, the supplement manufacturers are not legally required to provide the FDA with any safety and efficacy data, or indeed, FDA’s approval, prior to marketing. Again, of the three types of efficacy claims that supplement manufacturers may make via the labeling, only health claims (supplement would reduce risk of a disease or some health condition) require scientific evidence, the quality and strength of which is allowed to fall far below the accepted norm for real drugs; nutrient content claims (supplement contains a specific amount of certain supplements) require only proper labeling showing numerical or categorical quantitation, whereas structure/function claims require only general functional statements (e.g. “Calcium helps bone growth”), and a disclaimer that the “product is not intended to diagnose, treat, cure, or prevent any disease”. After a dietary supplement is marketed, the FDA performs post hoc evaluation of safety; if a product is deemed unsafe, FDA may initiate action against the manufacturer and/or distributor, and may issue warning statements about it and require a recall/removal from the market – but it’s much easier for the manufacturer to put the product on the market than for FDA to remove it.

Naturally, in absence of the serious Federal oversight that is de rigueur for the mainstream pharmaceuticals, the dietary supplement industry has rapidly grown; according to a report from last year, it produced “about $32 billion in revenue for just nutritional supplements alone in 2012, [and was] projected to double that by topping $60 billion in 2021…” The NCCAM reports:

According to the 2007 National Health Interview Survey, which included questions on Americans’ use of natural products (not including vitamins and minerals), 17.7 percent of American adults had used these types of products in the past 12 months […] National Health and Nutrition Examination Survey (NHANES) data collected from 2003 to 2006 that covered all types of dietary supplements indicate that 53 percent of American adults took at least one dietary supplement, most commonly multivitamin/multimineral supplements (taken by 39 percent of all adults). Women were more likely than men to take dietary supplements.

In other words, “BigSupplement” is B-I-G, even as its ardent supporters continue to denounce the mainstream pharmaceutical industry as the quintessentially evil, greedy “BigPharma”.

Across the world

And this situation is by no means unique to the United States, but is seen in places where alternative medical systems, especially herbal medicine, are popular – such as India (Ayurvedic and Unani medicine) and China (Traditional Chinese Medicine/TCM), and wherever their diaspora have spread across the globe. Published in the journal Pharamcoepidemiology and Drug Safety in 2000, a screening study carried out in an Indian tertiary care hospital on on 120 samples of alternative medicines used for asthma, arthritis and other conditions (including Ayurvedic, homeopathy, and others) discovered that almost 42% of them were adulterated with corticosteroids. Traditional herbal medicines have been known to be laced with heavy metals, organic toxins, prescription drugs, such as steroids, and so forth; a 2010 review published in the Journal of Forensic Science laid out this situation from a unique perspective, in which problems associated with the use of herbal medicine were seen to negatively impact the determination of causes of death in forensic practice. A recent (2013) meta analysis of systematic reviews, published in the European Journal of Clinical Pharmacology, identified several serious concerns regarding the safety of herbal medications sourced in India or China owing to adulteration and contamination.

The growth of alternative medicine and dietary supplement industry continues unabated, however, driven mostly by crafty peddlers of pseudoscience, who target various vulnerable groups and use sophisticated marketing tactics. Relentlessly educating patients and consumers seems the only way to keep this from becoming a public health disaster.