FDA rules Dietary Supplements are not Medicines.

The FDA recently sent warning letters to seven companies selling dietary supplements that claim to prevent, treat, or cure hangovers. Under the federal Food, Drug, and Cosmetic Act (FD&C Act), only FDA-approved drugs can legally make such claims regarding a disease. As the FDA points out:

Unlike drugs approved by the FDA, there has been no FDA evaluation of whether these unapproved products are effective for their intended use, what the proper dosage might be, how they could interact with FDA-approved drugs, or whether they have dangerous side effects or other safety concerns.

In addition to warning marketers to avoid illegal disease prevention and cure claims, the FDA raised an issue of potentially greater importance to the dietary supplement industry: the use of N-acetyl-L-cysteine (NAC), an ingredient in several of the hangover remedies. The FDA takes the position that NAC is never a proper ingredient in any dietary supplement, a point we will return to later.

The warning letters were issued to the colourfully named Vita Heaven LLC (doing business as Hangover Heaven), Happy Hour Vitamins, Mind, Body & Coal LLC, and Purple Biosciences LLC, as well as Double Wood LLC, Ebnsol Inc., and LES Labs.

These companies are part of a burgeoning industry. A 2019 Washington Post article quoted sources estimating there some 2.6 billion hangovers in the U.S. annually, and that was before the pandemic hit. Analysts put the global hangover remedy industry at $1 billion. (The global alcoholic beverages market was valued at $1.4 trillion in 2017.)

But before we go further: What, exactly, is a hangover, from a medical perspective? Here is an explanation from a pharmacy professor:

Hangovers are the result of the unpleasant after-effects of consuming ethanol, the main psychoactive ingredient in alcoholic beverages. They are often characterized by malaise, head and muscle aches, nausea, and lethargy, though the duration of these symptoms can vary.

 The unpleasant feelings from a hangover are attributed to a combination of dehydration, toxic impurities found in some alcoholic beverages (congeners), and toxic byproducts of alcohol metabolism.

Ethanol is a diuretic that can suppress the release of antidiuretic hormone from the pituitary gland and result in excess diuresis. This can lead to the characteristic dry mouth, headache, and irritated eyes commonly associated with a hangover.

Congeners are impure fusel alcohols that are often present in “darker” spirits or red wine and can contribute to hangover symptoms following consumption. Ethanol is metabolized into the toxic metabolite acetaldehyde, which can cause nausea and malaise. Decreased blood sugar and secondary general inflammation from ethanol consumption may also play a role in hangover symptoms.

But is a hangover a “disease”, as the FDA’s warning letters seem to imply? Here is how the agency explains its position:

A hangover can occur after alcohol intoxication. Alcohol intoxication, like all poisonings, causes dose-related dysfunction and damage, ranging from mild impairments to death. Alcohol intoxication causes temporary damage to brain function, causing impairments of judgment, attention, reflexes, and coordination.

In other words, a hangover is a sign or symptom of alcohol intoxication, which is a type of poisoning. Poisoning is a disease. Per federal law, a claim that a product has an effect on a sign or symptom of a specific disease is considered a claim that the product can mitigate, treat, cure, or prevent that disease, which the product cannot do unless it is an FDA-approved drug.

(There is some real buzzkill for you from the federal government: in drinking alcohol, you are poisoning yourself.)

Hangover “cure” ingredients

One of most hyped ingredients in the illegal hangover remedies cited by the FDA is an extract from the Japanese (or Oriental) Raisin Tree (Hovenia dulcis) which one company said has been “used for centuries as an anti-alcohol herb and hangover cure in Asia.” Its active ingredient, dihydromyricetin (DHM), is “a liver detox and hangover prevention ingredient” which, when blended with electrolytes “may reduce hangover symptoms by up to 99%” and will “prevent hangovers after a night of drinking”, “reduce feelings of intoxication while drinking”, or “raise the alcohol intoxication threshold so you can have a few drinks without becoming intoxicated”. In other words, “NEVER SUFFER ANOTHER HANGOVER”.

(The hangover remedy industry appears to rely heavily on ALL CAPS as a sales tool, as you shall see.)

There is, in fact, some evidence that DHM is effective in reducing the ill effects of drinking alcohol. Recent research from the University of Southern California, funded in part by the NIH’s National Institute on Alcohol Abuse and Alcoholism, support the utility of DHM as a dietary supplement to offset acute alcohol-related effects as well as long-term risks. In addition, the [study’s] authors say the substance has wider applications to help people cope with binge drinking, alcoholism and liver damage.

What got these supplement companies in trouble, though, is not the lack of evidence of effectiveness for their DHM-containing products. (Although they undoubtedly went beyond what evidence does exist.) It is, again, that federal law does not permit dietary supplements to make claims that they can prevent or cure disease. There is a legal procedure for allowing dietary supplements to make what are called health claims, that is, a claim that a substance has a particular effect on a disease or health-related condition (e.g., the association between dietary fibre and reduced risk of cancer [PDF]) if the claim meets certain requirements for supporting evidence (“significant scientific agreement among qualified experts”). Otherwise, supplement marketers are limited to claims like “supports liver health”. (Even this sort of “structure/function” claim is supposed to be backed by evidence, but supplement makers do not have to disclose that evidence to consumers or the FDA.)

Other ingredients touted for hangover prevention and cure by the companies cited are milk thistle which “HELPS PREVENT HANGOVER SYMPTOMS” by protecting the liver from damage and, along with kudzu flower powder and artichoke leaf extract, will help “KILL YOUR HANGOVER BEFORE IT EVEN STARTS”. According to WebMD, at this point, there is not enough evidence to say whether milk thistle will help your liver.

Prickly pear cactus, per the supplement marketers, will “help prevent hangover symptoms” and you can say goodbye to the day-after woes! By reducing inflammation associated with a hangover and increasing the ability for your cells to repair themselves after a night of drinking debauchery, you can feel better right away!

According to the Mayo Clinic, there is limited research suggesting prickly pear cactus can lessen the unpleasant effects of a hangover, due to an anti-inflammatory effect, but side effects can include “mild diarrhoea, nausea, increased stool volume, increased stool frequency and abdominal fullness.”

Supplement makers are not required to disclose these adverse effects, leaving consumers in the dark. In my view, these are not side effects one would want to risk while suffering from a hangover. In fact, they sound like a hangover.

One company, the cleverly named Mind, Body & Coal, sells a dietary supplement capsule called Miracoal to “PUT YOUR HANGOVER TO BED”. Miracoal contains organic coconut charcoal with electrolytes “to flush away toxins and impurities in your digestive systems and provide fast detoxifying rejuvenation”.

While it is true, as Mind, Body & Coal claims, that activated charcoal is an effective treatment for poisoning, it should, according to the Mayo Clinic, only be administered for that purpose in a health care facility, where the product is mixed with a liquid and given orally as a drink or via a tube. The capsule form is not used for treating poisoning. Per our pharmacy professor, there is “no definitive evidence showing it does anything to prevent the severity and/or duration of hangovers”.

Four of the companies receiving warning letters are cited for using N-acetyl-L-cysteine (NAC) in their hangover remedies. The FDA takes the position that their products are not legally dietary supplements because supplements cannot contain substances approved as drugs unless the substances were marketed as foods or supplements prior to the drug’s approval. Because the FDA approved NAC for use as a mucolytic drug for the treatment of chronic respiratory disease in 1963, and there is no evidence NAC was marketed as a food or supplement prior to that date, it is not a legal supplement ingredient in the eyes of the FDA.

 This (apparently new) position could cause difficulties for the supplement industry. An article in a supplement industry publication says that NAC has been widely used in finished dietary supplements, frequently as a standalone product. A recent search on Amazon produced more than four hundred products for sale mentioning the ingredient, which is usually positioned as a “cellular antioxidant”, or for liver support. Some major brand names were represented in that search. On the supply end, a search on Alibaba brings up more than 1,000 hits of bulk . . . NAC for sale . . ..

The president of an industry trade group told the publication that “people should be concerned” because the “FDA has suddenly decided to get serious about some of these ingredients that have these drug exemptions, like NAC and, of course, CBD”.

Given the huge liberties afforded the industry by Congress, in the form of the Dietary Supplement Health and Education Act, I doubt a few hangover remedies getting hit by the FDA, or even an FDA crackdown on the drug exemption issue, will cause much of a dent in the $40-billion-plus supplement industry.
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