FDA Warns Supplement Sellers Over Untested Stimulants and Heart-Disease Cure Claims (2022)

Table of Contents

1. What the FDA Did in 2022
2. May 2022: Letters Over Pre-Workout and Weight-Loss Ingredients
3. The Four Ingredients Named in May
4. A Letter Sent to the Wrong Company
5. June 2022: The “Supplement Your Knowledge” Initiative
6. November 2022: Claims to Treat Heart Disease
7. When a Product Labeled as a Supplement Counts as a Drug
8. What a Warning Letter Is and What Can Follow
9. What These Actions Do Not Do
10. Dates and Legal Status as of October 18, 2026
11. How It Fits Earlier and Later FDA Supplement Actions
12. Primary Documents
13. Key Research Papers
14. Connections
15. Featured Videos

1. What the FDA Did in 2022

The FDA’s “What’s New in Dietary Supplements” page lists the agency’s 2022 supplement actions month by month. Three of them are reported on this page:

• May 9, 2022: “FDA Sends Warning Letters to Multiple Companies for Illegally Selling Adulterated Dietary Supplements” — letters over products containing 5-alpha-hydroxy-laxogenin, higenamine, hordenine and octopamine.
• June 2, 2022: “FDA Launches New Dietary Supplement Education Initiative” — the “Supplement Your Knowledge” materials for consumers, high-school teachers and physicians.
• November 17, 2022: “FDA Issues Warning Letters to Companies Selling Dietary Supplements that Claim to Treat Cardiovascular Disease” — letters to seven companies.

The same FDA page explains what a warning letter is for: “FDA issues Warning Letters to let companies know that they have violated the laws we enforce and to tell them what corrective action they need to take.” Each round was announced in a Constituent Update, a short notice the FDA’s food and supplement program publishes for industry and the public. None of these steps was a rule published in the Federal Register, the government’s daily journal of regulations; they are enforcement and education actions.

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2. May 2022: Letters Over Pre-Workout and Weight-Loss Ingredients

On May 9, 2022 the FDA announced that it had “posted warning letters to multiple companies for selling adulterated dietary supplements.” The update gives two separate reasons the products were considered adulterated (the legal term the FDA uses):

• some contained new dietary ingredients (NDIs) “for which the FDA has not received the required premarket NDI notifications” — that is, the seller had not given the FDA the notice the law requires before a new ingredient is sold in a supplement;
• others contained “unsafe food additives.”

The update adds a third problem for some of the products: “Some of the identified dietary supplements also are drugs, despite lacking approval, because they are intended for use in the cure, mitigation, treatment, or prevention of disease.” The FDA’s summary judgment of the products was that they “could potentially harm consumers.”

The update listed the companies that received letters; after the correction described in section 4, ten companies remained on that list. This page does not name them.

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3. The Four Ingredients Named in May

The May 9 update states that the products “contain one or more of the following ingredients: 5-alpha-hydroxy-laxogenin, higenamine, higenamine HCl, hordenine, hordenine HCl, and octopamine.” (“HCl” means the hydrochloride salt form of the same compound.)

• Higenamine — the one ingredient the update singles out. The agency wrote that it had “previously expressed concern about several of these ingredients for reasons including, for example, the potential adverse effects of higenamine on the cardiovascular system.” Published research describes higenamine as a stimulant with cardiovascular properties; one analysis of U.S. products labeled as containing it is listed under Key Research Papers below.
• Hordenine and octopamine — named by the FDA in the same list; the update gives no ingredient-specific detail for them.
• 5-alpha-hydroxy-laxogenin — named in the same list, again without ingredient-specific detail in the update. A 2019 chemical analysis of supplements sold for muscle building (listed below) reported that this compound had not been isolated from any natural source.

The update does not say which ingredient was in which product, or which products failed for a missing notification and which for an unsafe additive. It also states that the agency “has not evaluated whether the unapproved products subject to the warning letters announced today are effective for their intended use, what the proper dosage might be, how they could interact with FDA-approved drugs or other substances, or whether they have dangerous side effects or other safety concerns.”

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4. A Letter Sent to the Wrong Company

Two days later, on May 11, 2022, the FDA added a correction at the top of the same update. It said one company named on May 9 “was incorrectly identified” and did not sell the two products cited in the warning letter it had been sent on May 4, 2022.

The FDA explained how the error happened: “the website on which the products … are sold incorrectly stated that the site was the property of one of [the company’s] subsidiaries.” The company found the error and notified the agency. The FDA wrote that the letter “has been retracted and the FDA is continuing its investigation to determine the responsible firm and reissue the warning letter,” and added: “The FDA regrets the confusion this error has caused.”

The documents read for this page do not say whether, or to whom, that letter was later reissued.

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5. June 2022: The “Supplement Your Knowledge” Initiative

On June 2, 2022 the FDA announced “a new education initiative titled Supplement Your Knowledge, to broaden public understanding of dietary supplements.” According to the announcement, the fact sheets, videos and curriculum are designed to do three things:

• help consumers “learn more about dietary supplements, including how they are regulated and their potential benefits and risks”;
• help educators equip high-school students “to evaluate the accuracy and credibility of information they see and hear about dietary supplements.” The FDA gave its reason: “Teens are particularly vulnerable targets for misunderstanding what dietary supplements are and the potential benefits and adverse effects they can have on their bodies”;
• help physicians and other health care professionals through a continuing medical education program “developed in collaboration with the American Medical Association,” meant to help physicians understand how supplements are regulated, inform patients about their use, and “recognize and report adverse events to the FDA.”

The initiative’s own page lists the materials: consumer fact sheets in English and Spanish (“Understanding Dietary Supplements,” “Talking to Healthcare Professionals About Dietary Supplements,” “Dietary Supplements: Report Adverse Events to FDA” and “Dietary Supplements: How FDA Helps Keep You Safe”); three short videos on supplements, supplements and medications, and adverse events; videos for health professionals covering how supplements are defined, regulated and labeled and their “potential interactions with other supplements, medications, and laboratory tests,” for which physicians can earn 0.50 continuing-education credit; and a high-school science curriculum titled “FDA’s Science and our Food Supply: Examining Dietary Supplements.”

The June announcement states the agency’s aim in its own words: “The FDA wants consumers to have access to safe, well-manufactured, and appropriately labeled products, as well as the knowledge to make informed decisions about taking dietary supplements.”

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6. November 2022: Claims to Treat Heart Disease

On November 17, 2022 the FDA announced warning letters to seven companies “for illegally selling dietary supplements that claim to cure, treat, mitigate, or prevent cardiovascular disease (or related conditions, such as atherosclerosis, stroke, or heart failure).” The agency described the products as “unapproved new drugs” that “have not been evaluated by the FDA to be safe and effective for their intended use.” The conditions are described on the site’s Atherosclerosis, Stroke and Heart Failure pages.

The update explained why the agency singled out heart claims, citing the Centers for Disease Control and Prevention (CDC): cardiovascular disease is the leading cause of death in the United States, and in 2020 “nearly 700,000 Americans died from cardiovascular disease, accounting for 1 in every 5 deaths.” (The FDA’s text prints the year with a typing error, “202o”; the figure it cites is for 2020.)

The FDA described the risk it saw in reliance on such products: “Consumers who rely on unapproved products claiming to cure, treat, mitigate, or prevent cardiovascular disease or related conditions instead of discussing their symptoms with a health care professional may not receive appropriate treatment and could potentially suffer harm.”

The update listed the seven companies; this page does not name them. The update does not say which ingredients the products contained; the November letters rest on the disease claims made for the products, not on a finding about any ingredient.

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7. When a Product Labeled as a Supplement Counts as a Drug

Both rounds of letters restate the same legal principle under the Federal Food, Drug, and Cosmetic Act (FD&C Act), the main law the FDA enforces: “products intended to diagnose, cure, treat, mitigate, or prevent disease are drugs and are subject to the requirements that apply to drugs, even if they are labeled as dietary supplements.” The May update adds that such products “generally require preapproval from the FDA.”

In plain terms, what decides whether a product is regulated as a drug is the use it is sold for, not the word “supplement” on the label. A product sold with a claim that it treats a disease is, in the FDA’s reading of the law, a drug, and such a drug generally requires FDA approval before it is sold. The products in the November round were cited on this ground alone; some products in the May round were cited on this ground in addition to the ingredient problems.

The November update draws the contrast with approved medicines: “Unlike drugs approved by the FDA, the agency has not evaluated whether the unapproved products … are effective for their intended use, what the proper dosage might be, how they could interact with FDA-approved drugs or other substances, or whether they have dangerous side effects or other safety concerns.”

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8. What a Warning Letter Is and What Can Follow

In both rounds, the FDA “requested responses from the companies within 15 working days stating how they will address these issues, or providing their reasoning and supporting information as to why they think the products are not in violation of the law.”

Both updates describe what can follow if a company does not respond adequately. The May update: “Failure to adequately address this matter may result in legal action, including product seizure and/or injunction.” The November update: “Failure to correct violations promptly may result in legal action, including product seizure and/or injunction.” A seizure is a court action in which the government takes possession of the goods; an injunction is a court order requiring a company to stop or change what it is doing. A warning letter itself is neither: it is a notice from the agency, which the company may answer or dispute.

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9. What These Actions Do Not Do

• They are not recalls, bans or court orders. A warning letter asks a company to correct a violation; it does not by itself remove a product from sale or bind any company other than the one it is addressed to.
• They say nothing about supplements not named in them. The letters covered the products cited; they are not a list of every product containing the four ingredients or making heart claims.
• They do not evaluate the ingredients’ safety. The May letters rest on missing premarket notifications, unsafe-additive status and, for some products, disease claims; the FDA states that it has not evaluated the products’ effectiveness, proper dose, interactions or side effects.
• They do not create a new rule. No regulation was proposed or issued; the letters apply requirements already in the FD&C Act.
• The education initiative does not change any requirement. “Supplement Your Knowledge” is a set of consumer, classroom and professional materials.

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10. Dates and Legal Status as of October 18, 2026

• May 4, 2022: date of the warning letter later retracted (as stated in the FDA’s correction).
• May 9, 2022: the FDA posts warning letters over products containing 5-alpha-hydroxy-laxogenin, higenamine, hordenine or octopamine.
• May 11, 2022: the FDA retracts one letter after finding it misidentified the seller, and says it is continuing its investigation.
• June 2, 2022: the FDA launches the “Supplement Your Knowledge” education initiative.
• November 17, 2022: the FDA announces warning letters to seven companies over claims to treat cardiovascular disease.

Status as of October 18, 2026: advisory letters; no later change found. Warning letters are advisory notices, not final agency orders, and the later status of each company that received one was not checked for this page. A check of the Federal Register through October 18, 2026 found no FDA document mentioning higenamine, hordenine, octopamine or laxogenin. The “Supplement Your Knowledge” page remains on the FDA website, and the FDA’s “What’s New in Dietary Supplements” page, current as of March 3, 2026, still lists all three 2022 actions.

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11. How It Fits Earlier and Later FDA Supplement Actions

The FDA’s “What’s New in Dietary Supplements” page places the 2022 letters in a run of similar warning-letter rounds aimed at supplements sold with disease claims. Among the entries it lists:

• April 2017: “FDA Takes Action Against 14 Companies for Selling Illegal Cancer Treatments.”
• February 2019: action against 17 companies over products claiming to treat Alzheimer’s disease.
• April 2019: “FDA Acts on Dietary Supplements Containing DMHA and Phenibut” and the launch of a Dietary Supplement Ingredient Advisory List.
• July 2020: warning letters to seven companies selling hangover products.
• February 2021: warning letters to 10 companies over claims to treat depression and mental illness.
• May 2021 and September 2021: joint FDA and Federal Trade Commission letters over claims to treat infertility (five companies) and diabetes (10 companies).

The same page lists the other 2022 supplement steps: the FDA’s response to two citizen petitions on NAC (March), draft and final guidance on NAC (April and August; see NAC Supplements Stay on Shelves), and a draft guidance on new-dietary-ingredient enforcement discretion (May). The list continues with the March 2023 launch of a public directory of ingredients used in products marketed as supplements (see FDA Opens a Public Directory of What It Has Said About Supplement Ingredients (2023)), new-dietary-ingredient guidance in 2024 and educational materials on the notification process in 2025, and a March 2026 public meeting on the scope of dietary ingredients (see FDA Public Meeting on What Counts as a Dietary Ingredient (2026)).

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12. Primary Documents

1. U.S. Food and Drug Administration. FDA Sends Warning Letters to Multiple Companies for Illegally Selling Adulterated Dietary Supplements. HFP Constituent Update, May 9, 2022, with correction of May 11, 2022 — fda.gov constituent update, May 2022
2. U.S. Food and Drug Administration. FDA Launches New Dietary Supplement Education Initiative. HFP Constituent Update, June 2, 2022 — fda.gov constituent update, June 2022
3. U.S. Food and Drug Administration. Supplement Your Knowledge: Dietary Supplement Education Initiative. Program page, content current as of May 25, 2022 — fda.gov Supplement Your Knowledge page
4. U.S. Food and Drug Administration. FDA Issues Warning Letters to Companies Selling Dietary Supplements that Claim to Treat Cardiovascular Disease. HFP Constituent Update, November 17, 2022 — fda.gov constituent update, November 2022
5. U.S. Food and Drug Administration. What’s New in Dietary Supplements. Program page, content current as of March 3, 2026 — fda.gov What’s New in Dietary Supplements

None of these actions was published in the Federal Register, so there is no FR citation or docket number. The individual warning letters, which name the companies, are posted on the FDA’s warning-letter pages and are not linked here.

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Key Research Papers

1. Cohen PA, Travis JC, Keizers PHJ, Boyer FE, Venhuis BJ (2019). The stimulant higenamine in weight loss and sports supplements. Clinical Toxicology (Philadelphia) 57(2):125-130 — PubMed PMID: 30188222
2. Hudzik TJ, Patel M, Brown A (2021). β2-Adrenoceptor agonist activity of higenamine. Drug Testing and Analysis 13(2):261-267 — PubMed PMID: 33369180
3. Wen J, Li M, Zhang W, Wang H, Bai Y, Hao J, Liu C, Deng K, Zhao Y (2021). Role of Higenamine in Heart Diseases: A Mini-Review. Frontiers in Pharmacology 12:798495 — PubMed PMID: 35082678
4. Avula B, Chittiboyina AG, Bae JY, Haider S, Wang YH, Wang M, Zhao J, Deuster PA, Khan IA (2019). The power of hyphenated chromatography-Time of flight mass spectrometry for unequivocal identification of spirostanes in bodybuilding dietary supplements. Journal of Pharmaceutical and Biomedical Analysis 167:74-82 — PubMed PMID: 30753977
5. Cohen PA, Avula B, Katragunta K, Khan I (2022). Recalls, Availability, and Content of Dietary Supplements Following FDA Warning Letters. JAMA 328(4):393-395 — PubMed PMID: 35881132
6. Assadourian JN, Peterson ED, McDonald SA, Gupta A, Navar AM (2023). Health Claims and Doses of Fish Oil Supplements in the US. JAMA Cardiology 8(10):984-988 — PubMed PMID: 37610733

The first paper analyzed 24 supplements sold in the United States that were labeled as containing higenamine; it found amounts from trace levels to about 62 mg per serving, and none of the five products that stated an amount was accurately labeled. The second and third are reviews of higenamine’s action on adrenaline-type receptors and of its studied effects on the heart. The fourth is a chemical analysis of twelve muscle-building supplements labeled as containing 5-alpha-hydroxy-laxogenin: five contained none, and the authors report that the compound has not been found in any natural source. The fifth examines how often supplements were recalled, and whether they still contained prohibited drugs, after FDA warning letters. The sixth is a survey of heart-health and other claims printed on fish oil supplement labels in the United States.

PubMed Topic Searches

1. PubMed: higenamine in supplements
2. PubMed: pre-workout supplement adverse events
3. PubMed: dietary supplements and FDA warning letters
4. PubMed: cardiovascular health claims for supplements

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Connections

• FDA Actions of 2022
• FDA and Regulation
• Dangerous Supplements
• Stimulants in Weight-Loss and Energy Products
• How to Verify a Supplement
• Cardiovascular Disease
• Atherosclerosis
• Stroke
• Heart Failure
• Hypertension
• NAC Supplement Enforcement Discretion (2022)
• Dietary Supplement Ingredient Directory (2023)
• Tianeptine Retailer Warning (2024)
• NMN Supplement Status Reversal (2025)
• What Counts as a Dietary Ingredient (2026)

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