Avoiding the Use of Dietary Supplement Ingredients that Aren't NDI, ODI, or GRAS
An article recently written by Hank Schultz of Nutraingredients-USA.com highlighted the FDA’s recent action in sending warning letters to 10 dietary supplement companies who were using ingredients that were either not established to be allowed dietary ingredients, had cardiovascular risks, or both. Schultz indicated that the ingredients in question included 5-alpha-hydroxy-laxogenin, higenamine, higenamine HCl, hordenine, hordenine HCl, and octopamine.
Naturally, when there is online/social media buzz surrounding the latest hot ingredient, it is tempting to consider incorporating it into your supplement brand. Before doing so, however, you need to do your due diligence and determine if that ingredient is a dietary ingredient allowed for use in a dietary supplement. If it’s not, then you may be the not-so-happy receiver of an FDA warning letter, like the 10 dietary supplement companies mentioned above.
So, how do you know which ingredients are and aren’t allowed? Simply put, to be allowed, it needs to be a New Dietary Ingredient, an Old Dietary Ingredient, or be classified as GRAS.
What is a New Dietary Ingredient?
The term "new dietary ingredient" (NDI) means a dietary ingredient that was not marketed in the United States as a dietary supplement before October 15, 1994.[i] If you want to market an NDI in a dietary supplement, you must be sure that the substance is considered to be a dietary ingredient in the first instance. According to the FDA: "A dietary ingredient is a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any of the above dietary ingredients."[ii]
Furthermore, the product containing the dietary ingredient must be a dietary supplement.[iii] The FDA has clearly defined the term "dietary supplement" to mean a product (other than tobacco) intended to supplement the diet that contains one or more dietary ingredients. A dietary supplement is limited to products that are intended for ingestion in tablet, capsule, powder, softgel, gelcap, liquid, or another form, that is not represented as a conventional food or as the sole item of a meal or of the diet, and that are labeled as dietary supplements.
If you want to submit a dietary ingredient to the FDA to gain its approval as an NDI, that may be done. You should first determine if the dietary ingredient has not been present in the food supply as an article used for food in the same chemical form that you plan to use in your dietary supplement. Then you must show why you consider that the new dietary ingredient will reasonably be expected to be safe under the conditions recommended or suggested in the labeling. Of course, there’s more to it than that, but those are the basics.
What is an Old Dietary Supplement Ingredient?
If the dietary ingredient was marketed in the United States before October 15, 1994, then it may be regarded as "grandfathered" or, more correctly, an old dietary ingredient (ODI). Since there is no authoritative list of dietary ingredients that were marketed in dietary supplements before October 15, 1994, it is up to the manufacturer or distributor to provide evidence that the dietary supplement containing the dietary ingredient was, in fact, marketed before October 15, 1994. I can tell you from experience that this is not always an easy task. Of course, there are many dietary ingredients that easily fall into this category, and which are unlikely to result in a challenge by the FDA. This includes common vitamins and minerals, as well as several herbs and some other nutraceuticals.
What Does GRAS Mean?
Generally recognized as safe (GRAS) is an FDA designation that a chemical or substance added to food is considered safe by experts under the conditions of its intended use.[iv]
GRAS substances are subject to premarket review and approval by FDA and may be used in dietary supplements as well as food. Unlike NDI and ODI classifications, the FDA does have an online database that can be searched for GRAS substances. There are quite a few common dietary substances that can be found there, like calcium carbonate, inositol, alpha-tocopheryl acetate (vitamin E)—and many, many others.
My Recommendation for Dietary Supplement Brand Owners
Clearly, it can be difficult to determine if a given ingredient is NDI, ODI, or GRAS—but you can get into trouble if you don’t know and take the risk of including it in your product. So, how can you mitigate this risk?
My recommendation for a brand owner like you is to do business with a supplement manufacturer that can help you navigate these tricky regulatory waters. NutraScience Labs' staff of account managers, formulators, and quality control professionals possess decades of nutraceutical industry experience and can advise you on what ingredients are allowed for use in a dietary supplement.
[i] See section 413(d) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350b(d))
[ii] See section 201(ff)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C 321(ff)(1)
[iii] See section 201(ff) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321 (ff)
[iv] How U.S. FDA's GRAS Notification Program Works (original January 2006; updated)". US Food and Drug Administration. 9 February 2018. Retrieved 5/11/2022 from https://www.fda.gov/food/generally-recognized-safe-gras/how-us-fdas-gras-notification-program-works.