Walk into any drugstore, natural market, or Costco and you’ll find a dazzling array of supplements promising everything from sharper thinking and stronger immunity to calmer nerves and balanced hormones.
A 2023 survey showed that around three-quarters of U.S. adults take at least one supplement. Many report using these products to help with health concerns or symptoms unresolved by conventional medicine.
The problem is most nutraceutical products — that is, dietary supplements used for medicinal purposes — are unproven. Peer-reviewed trials are rare for branded products, and when they exist, they are often underpowered, methodologically limited, or uninterpretable. The National Institutes of Health advises consumers against assuming that supplements can reverse the course of disease.
All of this leaves consumers and health experts wondering whether the absence of evidence is evidence of absence.
So why aren’t there better trials for nutraceuticals? I recently tried to design one. A supplement company approached me wanting a publication-quality, randomized controlled trial (RCT) for a promising botanical extract. It also insisted on a compressed budget, a strict limit on participants, and a long wish list of secondary endpoints, including biomarkers and functional assessments. As the design evolved, it became clear that having it all would require both critical design compromises and slashing my investigator fee to something resembling minimum wage.
That experience painted a bigger picture: The nutraceutical sector faces structural barriers that make rigorous research far harder than most stakeholders appreciate. Through this project, I observed five recurring tensions and reflected on what could be a constructive path forward.
Tension 1: Public demand for evidence vs. a system that discourages it
In pharmaceuticals, patent exclusivity helps justify the expense of clinical trials. Botanical supplements rarely have this. Products derived from nature, such as turmeric, ashwagandha, and elderberry, are difficult to patent in ways that block competitors. If one company spends $300,000 proving its product supports sleep or immune function, every other brand using the same ingredient benefits for free. From a business standpoint, investing in trials is hard to justify.
Further compounding the issue is the astronomical cost of investigational product of research, driven upward over decades by escalating evidentiary standards, increasingly complex trial designs, and entrenched operational inefficiencies.
The result is a contemporary research landscape where large biopharmaceutical companies with big budgets can afford full clinical development, while most nutraceutical firms are effectively priced out of conducting rigorous clinical trials.
Tension 2: Realistic costs vs. design quality
Many consumer product companies assume running a clinical trial means recruiting a handful of volunteers, collecting some surveys, and comparing results. But credible trials require validated outcomes, safety monitoring, trained staff, participant support, statistical expertise, and ethics review. These pieces add up quickly. Even small randomized controlled trials can easily exceed $150,000, a number that can feel shockingly high to a nutraceutical sponsor. When money is tight, the first thing to shrink is sample size or follow-up duration. But a small sample can only detect large effects, and short trials are unlikely to demonstrate benefit for natural compounds with gradual effects. Underpowered studies miss signals that matter. The product may work; the study simply can’t show it.
Many manufacturers, including companies that make nutraceuticals, are also embracing decentralized trials (studies conducted in home or community settings using apps and wearable devices) for cost savings purposes, assuming they are cheaper just because there are no research sites.
But in reality, costs don’t disappear — they shift. When a clinical trial takes place on-site, research staff supervise assessments to ensure consistency and correct conduct. Without sites, every participant becomes a “micro-site,” requiring an extra layer of training and instruction, equipment troubleshooting, and adherence monitoring from a central research team. Measurement variability increases across living rooms, backyards, and parks, and protecting data quality requires follow-up from investigators.
Decentralized trials bring many benefits, such as increased access, easier participation, and ecological validity, but they don’t eliminate the workload or expertise required to run a rigorous study.
Tension 3: Strength of the research question vs. regulatory limitations
Companies legally cannot claim that their supplements prevent, diagnose, treat, or cure disease. If a supplement sponsor runs a trial that targets clinical endpoints or disease pathways, the FDA may interpret that as drug-like intent, especially once the results are shared publicly. So instead of asking, “Does this improve clinical fatigue?” researchers ask softer questions like, “Does this help maintain daily energy levels in generally healthy adults?”
It seems like a small shift, but it fundamentally changes the science. Populations become more heterogeneous. Outcomes move from clinical scores to wellness measures that are harder to validate. Biomarkers must be categorized as exploratory hints rather than proof. Companies often want drug-like rigor without crossing into drug regulation, and that balancing act requires careful language and design many nutraceutical sponsors haven’t anticipated.
Tension 4: An RCT alone does not comprise the full body of evidence
Randomized controlled trials are rightly viewed as the gold standard for demonstrating whether a product works. But an RCT is only one part of the evidence package, and much of this additional knowledge is needed to inform the design of the RCT itself. What does the body do to the substance, and what does the substance do to the body (pharmacokinetics and pharmacodynamics)? What dose is optimal, and what dose is toxic? Does it interact with food, medication, or other supplements?
These answers come from review of the peer-reviewed literature or de novo studies done in cells, tissues, animals, or small human cohorts. Skipping these steps and jumping straight into a pivotal RCT when critical knowledge gaps remain increases the risk of wasting precious resources on a trial that is at risk of failure.
Tension 5: Research timelines vs. commercial timelines
Even simple studies take many months, and supplement companies move fast. New formulas and claims often refresh on quarterly cycles. Sales teams want clinical results in months, not years. That mismatch leads to predictable shortcuts: shorter follow-up windows, reduced rigor, and an emphasis on “getting something publishable” rather than getting something conclusive. When research becomes a marketing deliverable instead of a truth-seeking exercise, everyone loses, especially consumers.
As these five tensions demonstrate, the problem isn’t a lack of interest and curiosity about whether supplements work. It’s that the system of economics, regulations, and research realities pose significant barriers.
Yet none of this is inevitable. There are ways to generate better evidence if the industry embraces new models:
- Shared-cost trials across multiple brands within a product category
- Platform designs that evaluate ingredients once for the benefit of all
- Consortia to develop and validate meaningful biomarkers that are fit for purpose
- Academic–industry partnerships grounded in research questions rather than marketing claims
- Transparent expectations about what high-quality evidence costs
- Open registration of trials and publication of results, even if results are null
None of these strategies eliminate the need for investment. But they make investment smarter, more equitable, and more impactful.
Supplements are here to stay. Millions of people use them every day. If we want to stop arguing about whether name-your-supplement works, or if it is safe, and start knowing, we need a research ecosystem capable of answering the question realistically, rigorously, and sustainably.
Elise Felicione is an independent clinical research scientist and principal investigator at the intersection of operations innovation, health technology in clinical research, and evidence generation strategy.
Source: www.statnews.com
