Beware of Piracetam-Containing Dietary Supplements Touting Unproven Brain Benefits

Taking dietary supplements — which include substances such as amino acids, enzymes, herbs and minerals — often provides no health benefits and may cause harm. Importantly, but unknown to many people, the Food and Drug Administration (FDA) does not evaluate the risks and benefits of these products before they are marketed.

Brain enhancement supplements and drugs known as nootropics or “smart drugs” have been promoted to enhance cognitive performance (including improved memory, attention and processing of information), mood, sleep and longevity.[1] The alleged benefits of these products often are promoted with little or no evidence of effectiveness. Despite concerns related to safety and effectiveness, the popularity of nootropics has grown substantially in recent years, and their global sales are expected to approach six billion dollars by 2024.[2] To generate such large sales, nootropic manufacturers often prey on vulnerable individuals with cognitive impairments due to Alzheimer’s disease, other types of dementia or stroke, falsely claiming that their products treat these conditions.

Due to the unscrupulous nature of such promotions, the FDA in December 2018 issued 12 warning letters and five online advisory letters to foreign and domestic product manufacturers for making unfounded claims on their websites that their products cure or prevent Alzheimer’s disease and other serious medical conditions.[3] The FDA warned that these misbranded or unapproved drugs, which come in tablet, capsule or oil forms, may be ineffective and unsafe and may divert patients from seeking proper medical attention.[4]

Among the nootropic manufacturers cautioned by the FDA were two companies[5],[6] that marketed the prohibited substance piracetam and other similar products as brain-enhancing drugs. Notably, in 2004 the agency determined that piracetam may not be marketed as a dietary supplement because there was insufficient evidence establishing that it was safe.[7] These companies also made false claims regarding piracetam products by indicating that they have “neuro protection” properties and can protect the brain after injury or stroke and that they are a “prescription drug for Alzheimer’s” or can improve its symptoms. The FDA has not approved piracetam for these or any other medical uses.

Consumers need to beware of piracetam because a recent study published online on Nov. 25, 2019, in the Journal of the American Medical Association (JAMA) Internal Medicine showed that this substance is commonly present in high doses in cognitive enhancement dietary supplements, despite the FDA’s prohibition of such products.

The JAMA Internal Medicine study[8]

The researchers for this study sought to examine whether piracetam is available for sale in the U.S. as a dietary supplement. Therefore, they conducted a Google search using the keywords “dietary supplements” and “piracetam.” They found five different brands of dietary supplements that met their search criteria and were available for purchase. The researchers obtained two samples of each of these brands and analyzed the powder form of these samples to test for the presence and amount of piracetam in each sample.

The researchers found that eight of the ten samples contained piracetam. The amount of piracetam detected in the samples ranged from approximately 830 to 1,500 milligrams (mg) per serving size. Following some of the manufacturers’ recommendations for these brands could expose consumers to doses that could have been as high as 11,300 milligrams of piracetam per day. The researchers noted that such doses would have been extremely high even compared with piracetam-containing products in Europe, which are available by prescription and commonly formulated in doses that range from 2,400 to 4,800 mg per day, with dosage adjusted based on renal function.

Therefore, the researchers concluded that the piracetam supplement brands available in the U.S. may unwittingly expose consumers to high amounts of this illegal drug, thereby significantly increasing the risk of adverse events such as drowsiness, depression, insomnia and anxiety. One of the study researchers cautioned in an interview with News Medical that the adverse effects of high doses of this drug on the elderly can be “catastrophic” because their kidneys are not capable of metabolizing such doses.[9]

Piracetam’s exclusion from pharmacy compounding

In September 2014, piracetam was nominated by the pharmacy compounding industry to be placed on the list of drug substances that may be used in pharmacy compounding.[10] However, FDA experts opposed this nomination in January 2015 after an extensive review of the literature regarding this substance.[11]

The FDA experts noted that most of the previous studies that suggested piracetam was effective for improving cognitive impairment had significant flaws, were poorly designed or executed, and did not demonstrate adequate evidence of effectiveness.[12]

They also noted that the evidence for the purported benefits of piracetam was evaluated in four systematic reviews conducted by the Cochrane Collaboration.[13] These reviews showed that clinical trials of this substance neither included detailed safety information nor emphasized the potential risks associated with this drug. These reviews deemed the evidence not supportive of the use of piracetam for treating several conditions, including dementia or cognitive impairment[14] and stroke.[15]

Furthermore, the single well-designed placebo-controlled clinical trial testing piracetam, which was conducted by a manufacturer of the drug, showed that it was no more effective than placebo for treating mild cognitive impairment after 12 months of follow-up.[16]

In February 2015, the FDA’s Pharmacy Compounding Advisory Committee voted nine to one in favor of excluding piracetam from the list of drug substances that may be used in pharmacy compounding, affirming the agency’s position.[17] After nearly four years, in February 2019, the FDA issued a final rule excluding piracetam from the list of drugs approved for use in pharmacy compounding.[18]

What You Can Do

Do not use dietary supplements to improve your cognitive health because there is a lack of evidence that they are effective or safe. You should not use piracetam either alone or in combination with any other drug to treat any medical condition. Also, check your dietary supplements to make sure they do not include piracetam. Talk to your doctor about safe and effective ways to maintain cognitive health.
 

References

[1] Froestl W, Muhs A, Pfeifer A. Cognitive enhancers (nootropics). Part 1: drugs interacting with receptors. J Alzheimers Dis. 2012;32(4):793-887.

[2] Zion Market Research. Global nootropics market will reach USD 5,959 million by 2024: Zion Market Research. January 11, 2019. https://www.globenewswire.com/news-release/2019/01/11/1690384/0/en/Global-Nootropics-Market-Will-Reach-USD-5-959-Million-By-2024-Zion-Market-Research.html. Accessed February 5, 2020.

[3] Food and Drug Administration. Unproven Alzheimer’s Disease products. December 22, 2018. https://www.fda.gov/consumers/health-fraud-scams/unproven-alzheimers-disease-products. Accessed February 5, 2020.

[4] Food and Drug Administration. FDA takes action against 17 companies for illegally selling products claiming to treat Alzheimer’s disease. February 11, 2019. https://www.fda.gov/news-events/press-announcements/fda-takes-action-against-17-companies-illegally-selling-products-claiming-treat-alzheimers-disease. Accessed February 5, 2020.

[5] Food and Drug Administration. Warning Letter: Peak Nootropics LLC aka Advanced Nootropics. February 5, 2019. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/peak-nootropics-llc-aka-advanced-nootropics-557887-02052019. Accessed February 5, 2020.

[6] Food and Drug Administration. Warning Letter: Pure Nootropics, LLC. February 5, 2019. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/pure-nootropics-llc-565425-02052019. Accessed February 5, 2020.

[7] Food and Drug Administration. Letter to Mr. David Tolson. January 9, 2004. https://www.regulations.gov/document?D=FDA-2004-S-0571-0127. Accessed February 6, 2020.

[8] Cohen PA, Zakharevich I, Gerona R. Presence of piracetam in cognitive enhancement dietary supplements. JAMA Intern Med. 2020;180(3):458-459.

[9] Mandal A. Piracetam - an unapproved drug, found in brain supplements. News-Medical. November 26, 2019. https://www.news-medical.net/news/20191126/Piracetam-an-unapproved-drug-found-in-brain-supplements.aspx. Accessed February 6, 2020.

[10] Food and Drug Administration. FDA briefing document: Pharmacy Compounding Advisory Committee (PCAC) meeting. February 23-25, 2015. PDF pg. 787. https://wayback.archive-it.org/7993/20170405230436/https:/www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/UCM433804.pdf. Accessed February 5, 2020.

[11] Ibid. PDF pg. 793

[12] Ibid. PDF pgs. 13-14

[13] Ibid. PDF pg. 798

[14] Flicker L, Grimley Evans J. Piracetam for dementia or cognitive impairment. Cochrane Database Syst Rev. 2001; 2(CD001011).

[15] Greener J, Enderby P, Whurr R. Pharmacological treatment for aphasia following stroke. Cochrane Database Syst Rev. 2001; 4(CD000424).

[16] UCB Pharma SA. Clinical study summary for piracetam (Nootropil). September 7, 2007. https://www.ucb.com/_up/ucb_com_patients/documents/N01001_CSS_20070907.pdf. Accessed February 5, 2020.

[17] Food and Drug Administration. Summary minutes of the Pharmacy Compounding Advisory Committee meeting. February 23-24, 2015. https://wayback.archive-it.org/7993/20170404155246/https:/www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/UCM500989.pdf. Accessed February 5, 2020.

[18] 84 FR 4696-4710.