Dietary Supplement Clinical Trials

Dietary supplements are common support therapy and have been shown to improve energy, protein, micronutrients intake, maintain or improve nutritional status. Clinical research enthusiasm fuels a burgeoning development in dietary supplements for management of many chronic disorders, which can unlock incredible market opportunities for dietary supplements through clinical trials. 

It is important to understand the clinical trial process for dietary supplements so that you know what to expect when conducting clinical research for your product.

What Is A Clinical Trial?

A clinical trial is carefully designed to closely monitor people’s progress, which can be an essential component for substantiating health claims for foods, food constituents and supplements.  When properly conducted, they provide the highest level of scientific evidence into a cause-and-effect relationship. (1)

Many critical factors must be considered in the design of a well-controlled dietary supplement trial  to ensure that the objectives of the study will be met and to ensure that the results collected will be relevant to the proposed health claim. Also, Good Clinical Practice (GCP) guidelines should be followed to ensure the credibility of clinical study data and the protection of study subjects.

Under FDA regulations, an Institutional Review Board (IRB) is group that has been formally designated to protect the rights, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup.(2) IRBs can also be called Independent Ethics Committees (IECs).

Best practices dictate the use a double-blind placebo controlled (the gold standard) clinical trial encompassing a wide diversity of population and age groups. These studies are expensive and time consuming, but offer the most reliable and verifiable data for the efficacy of a substance with regard to other testing methods.  

Supplements Generally Considered Safe Through Historic Use

According to the Food and Drug Administration (FDA) Dietary Supplement Health and Education Act (DSHEA) of 1994 (3), all supplements include vitamins, minerals, amino acids, herbs, and other botanicals are considered safe until they are proven unsafe.  Furthermore, anything prior to 1994 was not regulated. Thus, any and all supplements generally found on the shelves of your local supermarket or pharmacy is generally considered safe.   In general, the FDA recommends avoiding:

· Products that claim to work like prescription drugs—anything that claims to treat an illness or cure a medical condition.

· Products that are advertised through mass e-mails.

· Products marketed mainly in a foreign language.

· Products that promise weight loss, body-building, or enhanced sexual performance.

· Products that say they are a legal alternative to anabolic steroids

as they have been known to be tainted with potentially dangerous additives. (4)

A dietary supplement is considered “new” if it contains an ingredient not recognized as a food substance, unless it was sold as a supplement before October 1994. If it is new, the manufacturer must provide the FDA with reasonable evidence that the new ingredient is safe before the supplement is marketed to the public. (4)

Advantages of Clinical Trials for Dietary Supplements

All prescription and non-prescription drugs are regulated in the United States by the FDA. But dietary supplements are treated more like special foods.  In 1994, the DSHEA defined dietary supplements as a category of food, which put them under different regulations than drugs. They are considered safe until proven otherwise. The DSHEA says that dietary supplements cannot contain anything that may have “a significant or unreasonable risk of illness or injury” when the supplement is used as directed on the label, or with normal use if there are no directions on the label.

Due to these guidelines, it is very advantageous for any company bringing a new (or old, but repurposed) dietary supplement ingredient to market to perform some form of study to prove the substance is not unsafe.  The most complete way to do this is by way of a clinical trial. Any material which has already undergone rigorous testing will not face nearly as many hurdles during its market life than those which have little to no testing before going to market.

Current dietary supplements which have already undergone clinical trials (worldwide) include: (5) (6)

1. Bifidobacterium Longum 1206: A probiotic to aid in IBS (Irritable Bowel Syndrome)

2. A study by Proctor & Gamble on various plant extracts in the aid of natural colds.

3. The study of Inorganic Nitrite on cardiac and skeletal muscle health.

1. Do High Doses of Protein Supplements Affect Serum Lipid Profiles?

4.  Effects of Genetic Variations in the Response to Brazil Nut Supplementation (SUBRANUT)

5.   And more…

Effective Use of Supplements in Modern Medicine

It is important to note that at the time of this article, no dietary supplements have been shown to have any efficacy in treating COVID-19.  There is no scientific data to suggest that dietary supplements have any effect on the virus or its symptoms.  However, a double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy of the Manremyc® food supplement to prevent SARS-CoV-2 infection in healthcare workers is ongoing.

While many doctors view the use of dietary supplements skeptically for the treatment of many conditions, supplements are used for the betterment of general health.  Anyone who has been told to take a daily multivitamin is being counseled to use a dietary supplement.  For instance, patients with heart disease are often prescribed a regiment of magnesium and potassium supplements along with the addition of Omega-3 either through krill or fish oil.  It has been well established that an increase of vitamin C, when combined with other medicinal regiments can aid in the treatment of many ailments, from the common cold to certain cancers.    

With a recent acceptance, CBD has become a near panacea, however, it has shown promise as an inflammation-reducing agent as well as a way to easy certain forms of seizures.  

Future of Clinical Trials for Supplements

Due to the resources needed to conduct a clinical trial,  contract research organization (CROs) are going to be the path for companies to utilize in the future as CROs tend to be specialized in, or are able to readily sub-contract the various parts of the trial. Furthermore, the same tried and tested mechanisms used in the pharmaceutical sector can be used for dietary supplement trial data analysis. They can then compile the data and present the customer with a well put together project documentation.  As they are already subject to FDA oversight, confidence can be had in their results as they are less likely to include errors, or omit important data.  As more development into supplements progresses, it will be increasingly important for companies to provide proof that their product is not “unsafe” as defined by the FDA.  

Currently, many healthcare supply companies use independent laboratory tests, such as the United States Pharmacopeia (USP), but these tests provide data that is considered more or less subpar by published FDA standards and are more for marketing purposes than anything else.  Therefore, future endeavors should include data from reputable sources, utilizing well-defined methods as established by the FDA’s protocols regardless if the supplement might become subject of an audit or not.

References

1.  Intertek. (2020) “Food and Supplement Clinical Trial Services” https://www.intertek.com/food/consulting/clinical-trials/

2.  https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/institutional-review-boards-irbs-and-protection-human-subjects-clinical-trials)

3.  Dietary Supplement Health and Education Act of 1994. Public Law 103-417, 25. October 1994.

4.  American Cancer Society. (2015). “FDA regulation of drugs versus dietary supplements” https://www.cancer.org/treatment/treatments-and-side-effects/complementary-and-alternative-medicine/dietary-supplements/fda-regulations.html

5.  EU Clinical Trials Register. “Clinical trials for dietary supplements”.  https://www.clinicaltrialsregister.eu/ctr-search/search?query=dietary+supplements

6.  https://clinicaltrials.gov/ct2/show/NCT03111355?cond=Dietary+supplements&draw=2&rank=9

About the Author:

Lin Zhang, M.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.