The Science of the Placebo Effect: Why Most Supplements Don’t Work Dr.

By Dr. Rick Cohen, M.D.

Most Supplements Don’t Work — and That’s Exactly Why You Feel Better

After two decades studying human performance, recovery, and longevity, here’s the truth almost nobody in the industry will say:
Most supplements don’t work.

Not because they’re fake, or because science hasn’t found the right molecule yet — but because the part that actually works isn’t the capsule, the powder, or the compound.
It’s you.

On average, about 54% of the overall treatment effect in clinical trials is attributable to placebo (contextual) effects.

Read that again!

When you spend money, commit to a new ritual, and believe it might help, your physiology responds. Focus increases. Behavior shifts. Attention changes. The nervous system moves from passive to participatory. That internal activation — not the product — is what drives much of the benefit.

That’s called the placebo effect, and it’s not a side note in medicine. It’s one of the most replicated, measurable, and misunderstood forces in all of science.

The Science Everyone Pretends to Ignore

Across hundreds of controlled studies, the placebo effect consistently produces real biological change — not just “feelings.”

Meta-research of 186 randomized trials found that ~54% of the total measured treatment benefit came from contextual or placebo mechanisms, not the active intervention itself.

In depression research, placebo response rates hover around 35–40%, meaning nearly half of all “improvement” happens from expectation alone.

In pain and chronic-disease trials, placebo responses routinely range from 39–56%. Brain imaging confirms the same neural pathways light up during a placebo response as during real pharmacologic treatment.

When people think a treatment is expensive or advanced, their body responds more. One review found that “premium” placebos outperformed “generic” ones — simply because value amplifies belief, and belief directs biology.

Science has quietly proven it for decades: meaning and context change measurable physiology.

The Mechanism vs. the Experience

Even the most “biochemically sound” supplements show how wide the gap can be between a plausible mechanism and real-world effect. Let's see how that works with a few common examples:

Supplement / Modality	Mechanistic Credibility	Human Clinical Evidence	Placebo / Contextual Contribution	Marketing Gap
Coenzyme Q10	High — part of mitochondrial electron transport chain.	Mixed: Some improvement in fatigue and heart-failure markers; limited general benefit for healthy users.	Moderate-high (20–50%).	Market claims “mitochondrial fix” far exceed typical human effect size.
Curcumin / herbal anti-inflammatories	Moderate — antioxidant, NF-κB modulation.	Weak-moderate: marker shifts, inconsistent clinical improvements.	High (>50%).	Perceived as systemic “anti-inflammatory cure” despite low bioavailability and limited real-world outcomes.
Blue-light blocking glasses	Low-moderate — plausible photochemical link to melatonin.	Weak: minimal effect on sleep, eyestrain in most RCTs.	Very high (>70%).	Marketed as mitochondrial/circadian rescue; benefits mostly expectation and behavior change.

Even where the molecule does something in an isolated "study or "Petri dish", it rarely translates cleanly in the body. The typical user’s improvement often matches or even exceeds what would be expected from placebo alone or is way worse — because the ritual is doing the heavy lifting.

Paying Attention Is the Active Compound

The reason you often “feel something” after taking a new supplement isn’t necessarily because the molecule is rewiring your mitochondria. It’s because you’re paying attention.

You’ve activated the part of your nervous system that tracks sensation and meaning. You’ve attached value to a future outcome and begun orienting your biology around it. That’s not imaginary — that’s the same top-down neuroendocrine signaling that drives healing and adaptation.

If someone secretly slipped your “miracle supplement” into your drink without telling you, you probably wouldn’t feel anything. Because your awareness wasn’t engaged.

The pill isn’t the cure; your engagement with it is.

The Industry’s Quiet Dependency on Placebo

Every major supplement brand rides on this mechanism — the unspoken fuel of belief. They dress it in scientific language, promise clinical precision, but underneath it all, they’re selling focus loops. Ritual, repetition, investment, identity.

And the irony? It works — but not for the reasons they claim.

When people spend more, they feel more. When they track progress, they notice more. When they believe, they mobilize. This is biology, not hype. The placebo effect isn’t weakness or delusion — it’s proof that awareness can steer biochemistry.

The Real Supplement Is You

So yes, most supplements don’t “work” in the mechanistic sense. But the reason you sometimes feel better after taking them isn’t an illusion — it’s participation.

That’s why you can’t dismiss placebo; you have to harness it. It’s the difference between outsourcing your health to a molecule and reclaiming it through attention, expectation, and coherence.

When you buy something to improve yourself, you’re not just purchasing a formula — you’re funding your own focus. The payment, the ritual, the awareness — that’s the actual catalyst.

If you truly want a supplement that works, start by realizing this:
You are the active ingredient.

And if you want a supplement that provides enough actual active compounds — so that even if someone slipped it into your drink while you slept, you’d still feel the difference when you woke up — that’s PureClean Performance.
Because we do it right.

References (condensed)

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The Science of the Placebo Effect: Why Most Supplements Don’t Work Dr. Rick Cohen, M.D.