“Natural” Ingredients in Dietary Supplements for Sports Nutrition: Unfounded Assumption of Safety

April 3, 2018 - 8 minutes read

“Natural” Ingredients in Dietary Supplements for Sports Nutrition: Unfounded Assumption of Safety

In 2016, sports nutrition dietary supplements sales in the United States (U.S.) totaled $5.7 billion dollars, which was approximately 13 percent of total dietary supplement sales ($41.16 billion).1 For sports nutrition dietary supplements, athletes are demanding “natural” products with “clean” labels, presuming that “natural” products with “clean” labels and ingredient lists are safe. From where is consumers’, and even manufacturers’, unfounded assumption of safety for these “natural” ingredients originating? Perhaps the assumption of safety stems from “natural” ingredients having a perceived history of (safe) use or a misconception that “chemicals” are only found in laboratory synthesized ingredients. Regardless of the reasoning, athletes are seeking “natural” products with “clean” labels with the erroneous assumption that they are safe and will even support their health, well-being and athletic performance. In response, manufacturers are capitalizing on this misinformation/urban legend and sourcing “natural” ingredients from non-traditional materials and altering manufacturing processes to meet consumers’ demands.

Under the Dietary Supplement Health and Education Act (DSHEA),2 ingredients which were marketed in the U.S. as dietary ingredients (in or as a dietary supplement) before Oct. 15, 1994, are considered pre-DSHEA dietary ingredients — also commonly referred to as “old dietary” ingredients — and are “grandfathered.” Such old dietary ingredients do not require the filing of a pre-market New Dietary Ingredient Notification (NDIN) with the U.S. Food and Drug Administration (FDA), as long as (1) it can be proven as having been used as a dietary supplement prior to Oct. 15, 1994 (with the burden of proof on the manufacturer), and (2) the marketer has evidence of a “reasonable assurance that the ingredient does not present significant or unreasonable risk of illness or injury”.2 Establishing the history of safe use of an old dietary ingredient is critical and primary considerations include, but are not limited to, the source material, the specific part of the source botanical (e.g. leaf, root or stem) from which the active ingredient is extracted, processing techniques, intended use levels and production practices. Any changes, even those seemingly insubstantial may produce a chemically different ingredient mix or active(s), co-extractives or contaminants and, therefore, mandate filing a notification as a “new dietary ingredient.”

Changes in Source Materials
Manufacturers have found traditional sources of natural ingredients are either exhausted or have become too expensive to maintain profit margins. An example is resveratrol, a popular ingredient used in sports nutrition supplements reported to increase endurance. Grapes are arguably most commonly thought of as a source of resveratrol and, consequently, as is wine, with red grapes containing three- to 10-fold more resveratrol than white grapes.4 However, Japanese knotweed (Fallopia japonica) is reported to contain the highest concentrations of resveratrol, with the roots containing greater amounts than the stems and leaves.3 Resveratrol was first isolated from white hellebore (Veratrum grandiforum) almost 80 years ago,4 and other sources include, pistachios, peanuts, plums, tomatoes, mulberries, cranberries, cocoa, apples and grapes.4,5 More recently, microorganisms (e.g. Escherichia coli strains) are being genetically engineered to synthesize resveratrol to reportedly increase the production and purity of resveratrol as compared to botanical sources.6 The takeaway message is that there are many sources of resveratrol, each source containing varying concentrations of the “natural” ingredient in addition to other constituents that may or may not be chemically characterized and/or considered when assessing the potential toxic effects of the resveratrol co-extractives. Important questions to consider are (1) from where is the resveratrol sourced and (2) has the safety of the resveratrol co-extractives been assessed?

Changes in Manufacturing Techniques
Manufacturers may change manufacturing techniques to either increase production, utilize “natural” solvents or target a different chemical constituent within a “natural” source material. There is a trend toward “bio-solvents,” “eco-friendly” or “sustainable” solvents (e.g. ethyl oleate, ethanol, water, supercritical CO2), resulting in a reduction in use of traditional solvents, such as hexane.7 The use of non-traditional solvents presents the potential to produce products with different co-extractives, or, at the very least, products with different ratios of extractants than those produced with traditional solvents.

Beetroot or beet root juice is an example of a traditional “natural” botanical that is now being manufactured to target a specific chemical constituent within the root for use in dietary supplements for athletes. Inorganic nitrate (NO3-) is reported to be the biologically active ingredient in beet roots that increases plasma nitrate concentrations in consumers and supports physiological responses to exercise.8 Although data are limited and results are conflicting, the proposed mechanism of action reported for beetroot is that it, “dilates blood vessels in exercising muscle, reduces oxygen use and improves energy production.”9 With manufacturers producing beet root juice rich in nitrate, the concentrations of nitrates — in addition to other constituents and contaminants — must be taken into consideration when assessing the safety of such dietary supplements.

As manufacturers strive to meet athletes’ demands, “natural” ingredients are being sourced from different source materials and the manufacturing processes are evolving. These and other changes call into question the safety of these newly sourced or newly processed “natural” ingredients, as there is opportunity for variations in the chemical composition as compared to traditional “natural” products. These variations need to be considered when assessing the safety of dietary supplements containing “natural” ingredients. The safety of “naturally” sourced ingredients cannot be assumed on the basis of their “natural” origin or the history of (safe) use of traditional “natural” dietary ingredients that vary in chemical composition.


  1. Nutrition Business Journal, 2017. Supplement Business Report 2016. New York, NY: Penton.
  2. Public Law 103-417
  3. Chen, H., Tuck, T., Ji, X., Zhou, X., Kelly, G., Cuerrier, A., Zhang, J., 2013. Quality Assessment of Japanese Knotweed (Fallopia japonica) Grown on Price Edward Island As a Source of Resveratrol. J. Agric. Food Chem. 61, 6383-6392.
  4. Weiskirchen , S., Weiskirchen, R., 2016, Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy? Adv. Nutr. 7, 706-708.
  5. Dybkowska E., Sadowska, A., Swiderski, F., Rakowska, R., Wysocka, K., 2018. The occurrence of resveratrol in foodstuffs and its potential for supporting cancer prevention and treatment. A review. Rocz Panstw Zakl Hig. 69, 5-14.
  6. Lim, C.G., Fowler, Z.L., Hueller, T., Schaffer, S., Koffas, A.G., 2011. High-Yield Resveratrol Production in Engineered Escherichia coli. Appl Environ Microb. 77, 3451-3460
  7. Lavoine-Hanneguelle, S., Perichet, C., Schnaebele, N., Humbert, M., 2014. Development of New Natural Extracts. Chem. Biodivers. 11, 1798-1820.
  8. Wylie, L.J., Kelly, J., Bailey, S.J., Blackwell, J.R., Skiba, P.F., Winyard P.G., Jeukendrup, A.E., Vanhatalo, A., Jones, A.M., 2013. Beetroot juice and exercise: pharmacodynamics and dose-response relationships. J Appl Physiol. 115, 325-336.
  9. Dietary Supplements for Exercise and Athletic Performance. NIH. Site visited on March 29, 2018.
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