Why natural medicines often lack large clinical trials
Understanding the evidence gap in oncology
Throughout this hub, you will see phrases such as “human evidence is limited” or “most research is preclinical”.
These statements describe where the research stands. They do not, by themselves, explain why it stands there.
For many natural compounds, the gap between promising laboratory findings and well-designed human trials reflects more than scientific uncertainty.
It also reflects the
cost of research,
commercial incentives
difficulties producing consistent products and
the priorities of those who fund studies.
Oncology researchers have explicitly identified all of these barriers.
Understanding this context helps us avoid two opposite mistakes:
1) dismissing a potentially useful compound simply because it remains under-researched, or
2) treating promising early findings as proof that it works in people.
Research follows funding—not just potential benefit
A laboratory experiment and a large clinical trial are very different undertakings.
Testing a compound in cancer cells can provide valuable information about its biological activity.
Testing it in people requires much more: a reliable product, a suitable dose, safety monitoring, recruitment, clinical staff, and follow-up.
Large trials cost considerably more than laboratory studies.
Someone must pay for that work.
For a pharmaceutical company, patent protection can provide a period of commercial exclusivity. That creates an opportunity to recover research costs through sales of a successful treatment.
For a widely available natural compound, the financial calculation may be less attractive. If competitors can sell essentially the same substance, the company paying for the research may have little opportunity to recover its investment.
A review by Johns Hopkins oncology researchers identifies this lack of patent protection as a major obstacle to funding large natural-product trials.
In plain language: a treatment’s potential value to patients and its potential value to investors are not necessarily the same thing.
“Natural compounds cannot be patented” is too simple
Patent protection is not an all-or-nothing distinction between natural medicines and pharmaceuticals.
A substance as it occurs in nature may offer limited opportunities for patent protection, while a new formulation, manufacturing process or modified version may offer more. The oncology review describes this distinction using a specialised formulation of paclitaxel as an example.
This helps explain why investment may favour developing a proprietary product rather than testing a readily available preparation.
It also explains why “natural” and “pharmaceutical” are not opposing categories. Established cancer medicines such as paclitaxel and vinblastine came from plant-derived compounds. Their development shows that nature can provide useful medicines—but it does not establish that the original plant, an extract and the finished drug are interchangeable.
From green tea to a drug candidate: the EGCG example
EGCG, a naturally occurring compound in green tea, offers a useful example of how researchers reshape a natural molecule for pharmaceutical development. Its biological activity has attracted considerable interest, but researchers are finding it difficult to deliver consistent amounts to the tissues researchers want to target.
One approach is Pro-EGCG, a chemically modified version designed to protect the molecule until enzymes inside cells release the active EGCG. Researchers are also developing nanoparticle delivery systems to improve its stability, absorption and delivery.
This development with EGCG illustrates both sides of the funding discussion: changing a natural compound can address genuine scientific problems, while a new formulation or modified molecule may also offer opportunities for patent protection and commercial investment that the original substance does not. The plant supplies the starting point; the proprietary version may offer a stronger business case for further development.
Why promising findings can remain in the laboratory
Researchers may identify an interesting effect in the natural compound without having the resources to take it through the next stages of testing.
A 2025 article on natural products and cancer highlights this persistent problem: thousands of preclinical studies have explored anticancer activity, but progress into human trials has remained limited.
Public funding, universities, charities and philanthropy can help bridge the gap. Natural-product research does receive support outside the pharmaceutical industry, including dedicated clinical-trial funding programmes across several countries. That means commercial incentives are an important part of the explanation—not the entire explanation.
The useful question is therefore not just, “Why hasn’t this been proven?”
It is also, “Has it received the funding and development work needed to test it properly?”
There are practical scientific barriers too
Financial barriers do not remove the genuine challenges of studying natural medicines.
Researchers need a consistent product
A plant’s chemical composition can vary with growing conditions, harvesting and processing. Different parts of the same plant may contain different amounts of relevant compounds.
Researchers need to know what participants are receiving and whether it remains consistent throughout the trial. Otherwise, it becomes difficult to interpret the results—or apply them to another product sold under the same name.
A laboratory effect may require an exposure people cannot achieve
Cancer cells in a laboratory may be exposed directly to a compound at high concentrations for long periods.
A person taking that compound orally may absorb only a small amount, break it down rapidly, or never achieve comparable concentrations in the relevant tissue. This is one reason researchers study absorption, metabolism and dosing before moving to larger trials.
The question being tested matters
“Does this help with cancer?” is not one research question.
A study might investigate whether a product:
affects tumour growth;
reduces a particular treatment side effect;
improves quality of life;
changes the amount of a cancer medicine circulating in the body.
These are different outcomes. Evidence for one should not be presented as evidence for another. Natural-product oncology trials investigate both cancer-related outcomes and supportive-care outcomes, as well as interactions with treatment.
What “limited clinical evidence” actually means
Uncertainty needs to be described accurately.
There is an important difference between:
“There are no suitable human studies answering this question.”
“Small human studies suggest a possible benefit, but the result needs confirmation.”
“A well-designed trial found no meaningful benefit for this use.”
These statements should not be collapsed into a single dismissive label.
An untested approach and an approach that has performed poorly in a good trial are not in the same position. Equally, encouraging early studies may be overturned by better-controlled research. The oncology review illustrates this with pomegranate research, where promising early findings did not translate into a demonstrated benefit in a later placebo-controlled trial.
A funding gap can explain why an answer is missing. It cannot supply the missing answer.
Commercial pressures exist in the supplement industry too
The imbalance in research funding deserves scrutiny—but supplement businesses are also commercial businesses.
Manufacturers may be able to sell a product using laboratory findings or small studies without paying for the larger trials that would clarify its clinical value. The Johns Hopkins review (below) identifies this as another reason promising early research may not progress to definitive testing.
That is why each deep dive in this hub unpacks the underlying studies rather than treating either pharmaceutical marketing or supplement marketing as a substitute for evidence.
The same questions apply to both: What was tested? In whom? Against what comparison? What actually changed?
How this hub approaches the evidence
Our aim is to make the research understandable without dismissing possibilities or overstating findings.
For each natural medicine, we aim to separate:
what laboratory and animal studies suggest;
what human studies have actually shown;
whether the research concerns cancer control, symptom relief or another outcome;
whether the preparation and dose studied match the product being discussed;
what remains unknown.
When we say “clinical evidence is limited”, we are describing the present evidence—not making a judgement that the compound has no value.
The position taken throughout this hub is straightforward: promising findings deserve fair consideration, evidence gaps deserve context, and claims of benefit should remain proportionate to what has actually been demonstrated.
Further reading
Core anchor paper
Challenges of Conducting Clinical Trials of Natural Products to Combat Cancer
Paller CJ, Denmeade SR, Carducci MA. Clinical Advances in Hematology & Oncology. 2016;14(6):447–455.
The foundation of this page—how limited patent protection and commercial incentives can restrict research funding, alongside practical challenges such as manufacturing, contamination and product consistency. This oncology-focused review also discusses the limitations of early clinical findings and why supplement manufacturers may have little incentive to fund definitive trials.
The gap between laboratory research and clinical testing
Natural products and cancer: The urgent need to bridge the gap between preclinical and clinical research
Rojas A, González I, Morales MA. World Journal of Gastrointestinal Oncology. 2025;17(4):100484.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11995318/
The discussion on how promising natural compounds remaining in the preclinical stage despite years of research, and the authors’ call for greater funding and coordinated efforts to bring suitable candidates into cancer clinical trials. This is a commentary calling for action—not a clinical trial or proof that the compounds discussed improve patient outcomes.
Funding the steps needed before large trials
Finding Funding for the Building Blocks of Natural Product Clinical Trials
National Center for Complementary and Integrative Health. NCCIH Research Blog. 17 October 2024.
Explains why a large trial needs a foundation of smaller studies first—how the product is absorbed, what dose produces a measurable biological effect, whether that effect can be reproduced, and whether the proposed trial methods are workable. The article explicitly acknowledges that researchers have historically struggled to find funding for these preliminary steps. It concerns natural-product research generally, rather than oncology alone.
What public funding can—and cannot—cover
Building a Foundation for Clinical Trials of Natural Products
Weber WJ. National Center for Complementary and Integrative Health. NCCIH Research Blog. 27 September 2016.
Expplains that public funding for natural-product research exists, but comes with specific priorities and eligibility requirements. It also explains why researchers need evidence of absorption, biological activity and suitable dosing before larger efficacy trials. Importantly, the particular funding programmes described in this historical article excluded trials testing natural products for cancer treatment or prevention—so it should not be presented as evidence that those programmes funded anticancer trials.