Stepping into a drugstore, natural market, or Costco reveals a vibrant selection of supplements claiming to enhance mental clarity, boost immunity, calm nerves, and harmonize hormones. With the increasing popularity of these products, many consumers are left wondering whether they genuinely deliver on their promises.
A 2023 survey indicates that approximately 75% of U.S. adults take at least one dietary supplement. A significant number report using these products to address health issues that remain unresolved by conventional medicine.
However, most nutraceuticals—supplements intended for medical benefits—lack rigorous scientific backing. Peer-reviewed studies on branded supplements are uncommon, and when available, often have limitations that hinder their interpretability. The National Institutes of Health cautions against assuming that supplements can reverse disease progression.
This situation raises a critical question: should the lack of evidence lead us to conclude that these products do not work?
The absence of robust trials for nutraceuticals is concerning. I recently attempted to develop such a trial when a supplement company sought an exhaustive, randomized controlled trial (RCT) for a promising botanical extract. They required a limited budget, restricted participant numbers, and a lengthy list of secondary endpoints, including both biomarkers and functional assessments. As the plan evolved, it became evident that achieving all these goals would necessitate substantial compromises and a dramatic reduction in my investigator fee.
This experience shed light on the broader issues within the nutraceutical sector. I identified five recurring tensions that highlight the obstacles hindering meaningful research.
Tension 1: Public Demand for Evidence vs. a System That Discourages It
In the pharmaceutical industry, patent protections help offset the costs of clinical trials, which is rarely the case for botanical supplements. Ingredients sourced from nature, such as turmeric, ashwagandha, and elderberry, are generally difficult to patent, making it unappealing for a company to invest heavily in trials only for competitors to benefit from the findings without any costs. Consequently, the financial justification for conducting trials becomes challenging.
Compounding this issue is the soaring cost of investigational product research, a result of rising evidentiary standards, increasingly intricate trial designs, and operational inefficiencies that have persisted over the years. This has led to a landscape where well-funded biopharmaceutical companies can afford exhaustive clinical development, while many nutraceutical firms are effectively barred from undertaking rigorous trials.
Tension 2: Realistic Costs vs. Design Quality
Many companies assume that running a clinical trial is as simple as gathering a few volunteers, administering surveys, and comparing results. However, credible trials require validated outcomes, safety monitoring, skilled personnel, participant support, statistical expertise, and ethical reviews. These elements can quickly accumulate costs. Even modest randomized controlled trials often soar past $150,000—an amount that may seem exorbitant to a nutraceutical sponsor. When budgets are tight, the first items to be cut are sample sizes or follow-up duration. However, small sample sizes can only identify large effects, and brief trials often fail to capture the gradual benefits of natural compounds. Underpowered studies can miss significant findings simply because they lack sufficient data.
Numerous manufacturers, including nutraceutical companies, have begun adopting decentralized trials—conducting studies in home or community settings using apps and wearable devices. While these may be perceived as cost-saving, the reality is that costs simply shift rather than disappear. In on-site trials, research staff oversee consistency and proper conduct. In decentralized settings, every participant functions as a micro-site, necessitating additional training, equipment troubleshooting, and adherence monitoring from a central research team. Measurement variability increases when assessments are conducted in diverse environments, such as living rooms or parks, necessitating increased oversight to ensure data quality.
While decentralized trials offer benefits like improved access and participation, they do not alleviate the demand for expertise and effort required to conduct rigorous studies.
Tension 3: Strength of the Research Question vs. Regulatory Limitations
Companies cannot legally claim that their supplements prevent, diagnose, treat, or cure diseases. If a supplement sponsor conducts a trial targeting clinical endpoints or disease mechanisms, the FDA may interpret that as an intent akin to pharmaceuticals. As a result, researchers often opt for softer inquiries, such as “Does this help maintain daily energy levels among generally healthy adults?”
This slight shift in language fundamentally alters scientific inquiry. Populations become more varied, and outcomes transition from clinical assessments to wellness metrics that prove challenging to validate. Biomarkers are relegated to exploratory status rather than serving as definitive proof. Companies often seek the rigor associated with pharmaceuticals without crossing into drug regulation, requiring a careful balance that many nutraceutical sponsors may not have fully considered.
Tension 4: An RCT Alone Does Not Comprise the Full Body of Evidence
Randomized controlled trials are recognized as the gold standard for determining a product’s efficacy. However, an RCT is merely one component of a comprehensive evidence package. Vital previous knowledge about how the body interacts with the substance (both pharmacokinetics and pharmacodynamics), the optimal and toxic doses, and potential interactions with food, medication, or other supplements is essential.
Acquiring this information often requires systematic reviews of existing literature or new studies involving cells, tissues, animals, or small human cohorts. Rushing straight into a pivotal RCT without addressing these knowledge gaps can lead to wasted resources on a trial that is unlikely to succeed.
Tension 5: Research Timelines vs. Commercial Timelines
Even rudimentary studies require months of preparation, while supplement companies are under pressure to innovate rapidly. New formulations and claims frequently change every quarter, pushing sales teams to demand clinical results within months rather than years. This mismatch in timelines often results in predictable shortcuts: shorter follow-up periods, reduced rigor, and a focus on producing publishable results, rather than conclusive findings. When research is driven by marketing goals instead of a quest for knowledge, consumers ultimately suffer.
The five tensions outlined illustrate that the challenge lies not in a lack of interest about the efficacy of supplements but rather in a system weighed down by economic constraints, regulatory pressures, and research realities.
Yet, this predicament is not insurmountable. The industry could adopt several innovative models to enhance evidence generation:
- Shared-cost trials across multiple brands within a given product category.
- Platform designs that evaluate ingredients collectively for the benefit of all.
- Collaborative efforts to establish and validate significant biomarkers fit for their intended purpose.
- Partnerships between academia and industry focused on research questions rather than marketing claims.
- Clear communication on the actual costs associated with high-quality evidence.
- Open registration of trials and disclosure of results, even for null outcomes.
While these strategies do not eliminate the need for investment, they promote smarter, fairer, and more impactful funding.
Supplements are here to stay, with millions relying on them each day. To move beyond debates about whether specific supplements are effective or safe, we must cultivate a research environment capable of providing clear, rigorous, and sustainable answers.
Elise Felicione is an independent clinical research scientist and principal investigator specializing in operations innovation, health technology in clinical research, and evidence generation strategies.
