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WARNING LETTER

UNITED PARCEL SERVICE SIGNATURE REQUIRED

May 4, 2022

RE: 622405

Dear Sir or Madame:

This letter concerns your products Shredded-AF, Charged-AF, Alpha-AF, 3-EPI-Andro, Focused-AF, and Amped-AF, which are labeled as dietary supplements. As explained further below, introducing or delivering these products for introduction into interstate commerce violates the Federal Food, Drug, and Cosmetic Act (the FD&C Act) because the products are adulterated dietary supplements. You can find the FD&C Act through links on FDA’s website at https://www.fda.gov/regulatory-information/laws- enforced-fda/federal-food-drug-and-cosmetic-act-fdc-act and the FDA regulations at https://www.ecfr.gov/current/title-21.

Adulterated Dietary Supplement: Unsafe Food Additive

The label of your product Shredded-AF declares hordenine HCl as a dietary ingredient. The label of your product Charged-AF declares higenamine HCl as a dietary ingredient. The label of your product Alpha- AF declares 5-alpha-hydroxy-laxogenin as a dietary ingredient and the label of your product 3-EPI-Andro declares 5a-hydroxy laxogenin, a shortened name for 5-alpha-hydroxy-laxogenin,1 as a dietary ingredient. However, hordenine HCl, higenamine HCl, and 5-alpha-hydroxy-laxogenin are not dietary ingredients.

Under section 201(ff)(1) of the FD&C Act [21 U.S.C. § 321(ff)(1)], 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 the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of the preceding substances. Hordenine HCl, higenamine HCl and 5-alpha-hydroxy- laxogenin do not qualify as dietary ingredients under section 201(ff)(1) of the FD&C Act because they are not a vitamin; a mineral; an amino acid; an herb or other botanical; a dietary substances for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any of the preceding dietary ingredient types.

If a substance is not generally recognized as safe (GRAS) by qualified experts for its intended use in food and does not qualify for any of the other exemptions from the food additive definition, it is a food additive. Food additives require premarket approval based on data demonstrating safety. Any food additive that has not been approved for its intended use in food is deemed to be unsafe and causes the food to be adulterated under section 402(a)(2)(C)(i) of the FD&C Act [21 U.S.C. § 342(a)(2)(C)(i)].
Adulterated foods cannot be legally imported or marketed in the United States.

Section 201(s) of the FD&C Act [21 U.S.C. § 321(s)] exempts dietary ingredients used in dietary supplements from the food additive definition. However, non-dietary ingredients intended for use in dietary supplements, such as the hordenine HCl, higenamine HCl, and 5-alpha-hydroxy-laxogenin used in your products, are not exempt from the food additive definition and must meet the same requirements as substances added to conventional foods. In other words, a non-dietary ingredient added to a dietary supplement must be used in accordance with a food additive regulation or be GRAS for its intended use, unless it qualifies for another exception to the food additive definition.

Hordenine HCl, higenamine HCl, and 5-alpha-hydroxy-laxogenin are not generally recognized as safe under their conditions of use in your dietary supplement products. Because hordenine HCl, higenamine HCl, and 5-alpha-hydroxy-laxogenin do not qualify as dietary ingredients and are not GRAS or otherwise exempt from the food additive definition, your products Shredded AF, Charged-AF, Alpha-AF, and 3- Epi-Andro are adulterated under section 402(a)(2)(C)(i) of the FD&C Act because they contain an unsafe food additive. The introduction or delivery for introduction into interstate commerce of any food that is adulterated is a prohibited act under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].

Adulterated Dietary Supplement: New Dietary Ingredient

The label of your Focused-AF product declares higenamine as a dietary ingredient. The label of your product Amped-AF declares hordenine as a dietary ingredient. Higenamine is a “dietary ingredient” under section 201(ff)(1)(F) of the FD&C Act [21 U.S.C. § 321(ff)(1)(F)] because it is a constituent of aconite, asarum, lotus, and other botanicals. Hordenine is a “dietary ingredient” under section 201(ff)(1)(F) of the FD&C Act [21 U.S.C. § 321(ff)(1)(F)] because it is a constituent of barley and other botanicals. As explained below, higenamine and hordenine are also “new dietary ingredients” (i.e., a dietary ingredient not marketed in the United States before October 15, 1994) under section 413(d) of the FD&C Act [21
U.S.C. § 350b(d)].

Under section 413(a) of the FD&C Act [21 U.S.C. § 350b(a)], a dietary supplement that contains a new dietary ingredient shall be deemed adulterated under section 402(f) of the FD&C Act [21 U.S.C. § 342(f)] unless it meets one of two requirements:

1.    The dietary supplement contains only dietary ingredients that have been present in the food supply as an article used for food in a form in which the food has not been chemically altered; or

2.    There is a history of use or other evidence of safety establishing that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe and, at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides FDA with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe.

To the best of FDA’s knowledge, there is no information demonstrating that higenamine and hordenine were lawfully marketed as dietary ingredients in the United States before October 15, 1994, nor is there information demonstrating that higenamine and hordenine have been present in the food supply as articles used for human food in a form in which the food has not been chemically altered. Therefore, higenamine and hordenine are subject to the premarket new dietary ingredient notification requirement in section 413(a)(2) of the FD&C Act [21 U.S.C. § 350b(a)(2)] and 21 CFR 190.6. FDA has not received any NDI notifications pertaining to the use of higenamine or hordenine have in dietary supplements. Products for which the manufacturer or distributor is required to submit a new dietary ingredient notification under section 413(a)(2) and 21 CFR 190.6, but for which the required notification has not been submitted, are adulterated under sections 402(f) and 413(a) of the FD&C Act [21 U.S.C. §§ 342(f) and 350b(a)].

Moreover, based on our evaluation of the relevant safety evidence, there is no history of use or other evidence of safety establishing that higenamine and hordenine will reasonably be expected to be safe when used as a dietary ingredient. Therefore, even if a new dietary ingredient notification had been submitted, dietary supplements containing higenamine or hordenine would still be adulterated under sections 402(f) and 413(a) of the FD&C Act [21 U.S.C. §§ 342(f) and 350b(a)]. In the absence of adequate information to provide reasonable assurance that higenamine and hordenine do not present a significant or unreasonable risk of illness or injury, dietary supplements containing higenamine or hordenine are adulterated under section 402(f)(1)(B) of the FD&C Act [21 U.S.C. § 342(f)(1)(B)]. The introduction into interstate commerce of dietary supplements that are adulterated under sections 402(f) and 413(a) of the FD&C Act is prohibited under sections 301(a) and (v) of the FD&C Act [21 U.S.C.
§ 331(a) and (v)].

This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.

This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and injunction.

Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps you have taken to address these matters. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration.
 

Your written reply should be directed to Aaron Dotson, Compliance Officer, via email at CFSANResponse@fda.hhs.gov. If you have any questions, you may also email at CFSANResponse@fda.hhs.gov.
 
Sincerely,
/S/
Ann M. Oxenham Director
Office of Compliance
Center for Food Safety and Applied Nutrition
Food and Drug Administration

• 1. Chemists commonly use “a” as an abbreviation for “alpha.”