Nootropics for Dummies #4: What’s the Difference Between a Supplement and a Drug?

8 min readMay 20, 2019

In this multi-part, opinionated, skeptic’s guide to the world of nootropics and supplements at large, I attempt to offer some context and perspective on a broad, controversial topic. This is part 4: What’s the Difference Between a Supplement and a Drug? If you didn’t read parts 1–2–3, consider doing that before reading on.
Necessarily, in the interest of expedience, some of this will be a gloss. Hence the ‘dummies’ bit in the title. I don’t think you’re a dummy — it’s a figure of speech. Please do read on, regardless of your self-assessed intelligence.

Supplements v Drugs: According to the FDA

The Food and Drug Administration is the segment of the US government responsible for regulating both supplements (food) and drugs, as the name may have suggested to you.

The Food, Drug, and Cosmetic Act of 1938 is the law that stipulates that the FDA regulates food separately from drugs. Under this rule, drugs are defined as products used for medical purposes, whereas foods have nutritional purposes, and food is the category supplements fall under. Drugs are for treating, preventing, diagnosing, or curing diseases, and thus, by exclusion, supplements can’t be marketed with claims to do any of those things.

Another important distinction: drugs, in the eyes of the FDA, are unsafe until proven safe. That means in the drug approval process, drugmakers need to prove via ‘substantial evidence’ that the drug is both safe and effective through a series of clinical trials. This applies to both prescription and over-the-counter drugs.

To the converse, supplements, like food, are considered safe until proven unsafe. According to David Kessler, commissioner of the FDA when the Dietary Supplement Health and Education Act of 1994 (DSHEA) was approved:

“The 1994 Dietary Supplement Act does not require that dietary supplements … be shown to be safe or effective before they are marketed. The FDA does not scrutinize a dietary supplement before it enters the marketplace. The agency is permitted to restrict a substance if it poses a ‘significant and unreasonable risk’ under the conditions of use on the label or as commonly consumed…Congress has shown little interest in protecting consumers from the hazards of dietary supplements, let alone from the fraudulent claims that are made, since its members apparently believe that few of these products place people in real danger. Nor does the public understand how potentially dangerous these products can be.”

Woof. Scary stuff, right?

Supplement regulations distinct from those on foods do exist — lots of them, in fact, but, taken in aggregate, the upshot is that the regulation of supplements is significantly lighter than it is on drugs, and that means that, as with your regular diet, the onus is on you, the consumer, to make informed decisions about supplements.

That also means that supplement manufacturers, distributors, and marketers can sell things that have no effect, have poorly understood effects, have many side effects without carrying a warning, interact with other supplements or drugs, are known to be poorly tolerated, or are even stronger than advertised.

I don’t want to give the impression that it’s entirely the wild west out there — in the rule (21 CFR 111), supplement manufacturers are required to self-report to the FDA any complaints of Serious Adverse Events they receive from customers, and companies that routinely fail to comply with this (or are routinely filing SAE reports) are liable to eventually be fined or shut down by the FDA.

Nonetheless, the fact remains that almost every rule in the code relies on companies to self-report, self-police, self-inspect, and self-document, with only the threat of inspection to keep them honest. The FDA simply does not have the resources to properly police the industry.

The majority of regulatory scrutiny is directed at the manufacturers, who have to comply with cGMPs (current Good Manufacturing Practices, a topic outside the scope of this series), but for distributors and marketers, who are, in most cases, the authors of the formula and arbiters of the claims made to consumers, compliance is enforced only when the FDA takes notice via a direct complaint.

I’ll continue to discuss enforcement as a theme woven through other topics in this series, but if you want to know more about the history of the issues surrounding the lack of regulation, safety standards, and oversight in the supplement and vitamin industry, check out Do You Believe In Magic?: The Sense and Nonsense of Alternative Medicine by Paul A Offit, MD. It’s a great survey of the history of the industry and how we got to the regulatory state we’re in.

Spoiler alert: there’s little evidence that supplementing vitamin C benefits immunity unless you have scurvy — deceptive vitamin C marketing could be considered the ‘original sin’ of the modern supplements industry. Sorry if that comes as a shock. Also there’s no tooth fairy.

If Supplements Work, Why Aren’t They Drugs?

In addition to — and because of — the regulations on drugs, there are market forces that shape this decision on a per-ingredient basis. The short answer is that it’s fabulously expensive to develop a drug, in large part because most fail on their way to market, but there’s more to it than cost.

Let’s go back to the underlying distinctions between supplements and drugs: supplements cannot be marketed to treat, prevent, or cure any disease, and the inverse must be true of drugs. In the category of nootropics, we’re looking at things that are, well, supplemental — they’re intended to improve the functioning of already-healthy individuals, not to cure disease.

But even if they were meant to treat diseases, and makers were successfully marketing them surreptitiously, in a bit of a winking way, as being ‘good for people with a certain condition’ (as is actually the case with the marketing of many supplements), the supplement in question may not be viable as a drug.

Why is that? One reason is that in the case of many herbs, we’re not entirely sure exactly how they work, or even what chemical constituent (or constituents) of the herb is responsible for the effects we see.

You may find that surprising, but there are more than a few drugs on the market whose mechanisms we don’t understand, either— including some you’re probably quite familiar with, like acetaminophen, penicillin, and lithium. In those cases we’ve nailed it down to a specific molecule whose effects, side effects, dosage, scheduling, contraindications, etc. we know well enough for it to be, in the case of acetaminophen (aka Tylenol), both over-the-counter and the most commonly-used painkiller in the U.S, but we’re still not exactly sure what’s going on ‘under the hood’, so to speak.

With that being the case, it looks quite expensive from the perspective of a drugmaker to take an herb that has some effect, first isolate the active components, figure out how to produce those in a pure way, in quantity, reliably, and then take them through FDA approval, including all the many expensive trials required, when they could simply just sell the whole plant, or an extract (more on the difference later in this series), and get the effect they’re after.

Image by Lizanne Koch, public domain, Wikipedia

But in the case of herbs, why would one bother trying to isolate the active components at all when the whole plant works? Well, with a few exceptions, you can’t patent a (naturally-occurring) plant. You’d need to patent the active chemical or the process used to isolate it (or both) in order to hope to begin to recoup the enormous cost (call it ~$600 million) of bringing a drug to market — otherwise you could expect competitors to quickly begin to offer generic versions of your drug and undercut your bottom line, as they don’t have development costs to recover.

The Takeaway, and a Personal Note

In the eyes of the law, supplements are only subject to slightly more regulation than food, and at that, much of the compliance is expected to be self-policed and self-enforced. This is in part due to lax regulatory law and lack of enforcement resources.

There are many in the supplement industry that would like to see stricter laws and more enforcement, and of these, many operate at a higher standard than the law requires, despite that it is costly and often invisible to the end consumer. They do this because they believe it’s the right way to do business.

As a member of that group, I can tell you from personal experience that you have to hunt to find partners that think this way. When I was just starting out, I went through months of talks with multiple manufacturers only to find that my insistence on rigorous testing protocols (more on this in a later post) were ‘overboard’ for them, and that they were only interested in getting product to market as quickly and cheaply as possible.

They weren’t suggesting I break any laws — only that my voluntary quality control protocol, above and beyond cGMP and 21 CFR 111, which I was suggesting I undertake entirely at my expense and risk, was unnecessarily rigorous.

I even had one manufacturer derisively tell me, ‘you know what? You should do your own clinical study. Because that’s the only thing that’s gonna satisfy you.’ He meant that as an insult, if you can believe that.

It took me more than 2 years to find a manufacturer who understood my insistence on additional testing and QC (again, more in a later post on what I mean by that) and who was happy to comply with my requests because they knew I was intent on making a well-understood, controlled, high-quality product.

With that warning in mind, the purpose of this series of articles is to give you the tools to weed out the ‘brain-zap guys’, as I call them, who rush products to market with only sales potential and profitability in mind, and to use those tools to discern from what information is available exactly who shares your concern for your own health in mind and body.

The Outro

This concludes part 4 of Nootropics for Dummies, because I’m gonna keep these (relatively) bite-sized. Not because you’re a dummy — I just know you’re busy.

Read on for Part 5: How to Read a Supplement Label for what is easily the most immediately practical and useful advice in this series about how to interpret the information on the label of every supplement you pick up.

Give me an example / Just tell me what to take / The Shortcut

I get it. With the regulation and the laws and so on and you were here because you’re overwhelmed already. I felt the same way at one point, and I’m flattered you already want my opinion.

I suppose it won’t be a spoiler to say that I figured out something that works for me, and that, nearly 3 years later, it’s now available for anybody, whether or not they want to read the rest of this article. It’s called Plato, it’s exactly what I’ve been taking for 2.5 years†, and you can hit that link to get it.

† I’m not Rain Man now but more on that soon.††

†† More like The Lawnmower Man, a recurring joke I think you’ll continue to enjoy throughout this series.