Are smokers’ health dietary supplements legit?

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Smokers’ health and smoking cessation products have proliferated in recent years. This growth has prompted regulators to issue warning letters. While smoking cessation products like nicotine gum are classified as over-the-counter (OTC) drugs, emerging dietary supplement companies are targeting smokers with products claiming to help smokers quit, to mitigate the harmful health effects of smoking, or to reverse the cardiovascular damage that smoking causes.

Some of these claims and applications verge on pharmaceutical territory. In 2019, the Center for Science in the Public Interest (CSPI; Washington, DC) asked FDA to take enforcement action against 15 companies selling smoking cessation dietary supplements. CSPI claimed that several of the products in question contained Lobelia inflata or other ingredients from the Lobelia genus; FDA banned the use of Lobelia in OTC smoking cessation products in 1993, citing a lack of efficacy data.

While ineffective products in this market are common, some ingredients do indeed have scientific backing validating their ability to support smokers’ health. Still, is there a real-world opportunity for ingredients that work? Can supplement brands make anyclaims about smoking without running afoul of regulators? Or is pursuing pharmaceutical drug status the only path into this market? And which natural ingredients have demonstrated proven efficacy in improving smokers’ health? Here are some of the ingredients and situations that have us asking: Where there’s smoke, can there possibly be dietary supplements?

Antioxidant Ingredients May Hold Promise

While there are relatively few studies on supplements that can support smokers’ health, antioxidants are perhaps the ingredients with the most validation. David Foreman, RPh, president of Herbal Pharmacist Media (Oceanside, CA), says that carotenoids specifically could help support smokers’ health, although more research is certainly needed.

“There aren’t any studies specific to smokers,” Foreman says. “Smoking is definitely a free radical nightmare to the lungs. If I were to suggest the best antioxidants, I would go with the carotenoids.”

One independent 2021 research review¹ examined the plasma antioxidant profiles of smokers and the available literature on antioxidant-based diet and supplementation strategies for improving smokers’ overall health. This review found that relative to nonsmokers, smokers consume significantly fewer fruits and vegetables and have lower levels of beta-carotene. Four of the studies profiled in this literature review found that even after correcting for dietary antioxidant consumption, the action of smoking causes depletion of vitamin C and possibly beta-carotene. Additionally, plasma concentrations of vitamin A, vitamin E, cysteine, and glutathione tend to be lower in smokers than in nonsmokers. Given that smokers tend to be deficient in antioxidants, antioxidant support supplements could be a natural fit for the smokers’ health market.

Vitamin K2 Supports Cardiovascular Health

The cardiovascular risks of smoking have been established since 1964, when then-U.S. Surgeon General Luther Terry released his landmark report on the issue. Subsequent studies, like a May 2000 secondary analysis² of data from the Finnish Adult Health Behavior surveys from 1978 to 1991, have further confirmed these risks. That analysis was conducted by researchers at the National Public Health Institute Department of Health and Disability, which at the time was a branch of the government of Finland. The study found that after adjusting for age, education, and period and chronic morbidity, occasional smoking in men was associated with a 1.6-times higher risk of cardiovascular-related premature death.

It stands to reason that if smoking poses cardiovascular risks, then nutrients that support cardiovascular health may help mitigate some of the damage smoking causes. Kate Quackenbush, communications director for Gnosis by Lesaffre subsidiary NattoPharma (Edison, NJ), says vitamin K2’s cardiovascular effects make it a key supplement for supporting smokers’ health.

“Smoking influences cardiovascular disease, resulting in accelerated atherosclerosis and vascular calcification,” Quackenbush says. “A 2020 study that was completed with NattoPharma’s support found that vitamin K2 ameliorated nicotine-induced intracellular oxidative stress, EV [extracellular vesicles] secretion, and calcification.”

The study³ in question, an ex vivo micro-CT study of 62 carotid lesions collected from 15 smokers and 15 nonsmokers, assessed the degree of calcification, prevalence of reactive oxygen species, and expression of enzymes p22phox, NOX1, NOX2, NOX4, and NOX5. While NattoPharma did not directly fund the study, one of the study’s authors receives research grants from NattoPharma.

The study found that nicotine consumption increases concentrations of intracellular calcium ions, and smoking specifically is associated with a 17-fold increase in the number of microcalcifications found in atherosclerotic lesions. Additionally, the study determined that pre-administration of vitamin K2 to the vascular smooth muscle cells reduced oxidative stress and calcification.

“It is important to understand that this study was not initiated to explore K2 as a smoking cessation agent,” Quackenbush explains. “Rather, this specific population was targeted due to the detrimental effects smoking has on cardiovascular health and to build on the body of evidence that vitamin K2 is an important nutrient for supporting heart health.”

Drug or Supplement?

While there is credible science to support the validity of certain supplements as playing various roles in smokers’ health, the area of smoking cessation is one that FDA vigilantly polices. In 2002, FDA banned nicotine-infused water after determining that Nico Water, a bottled water product infused with nicotine that was manufactured by Quick Test Five (Westlake Village, CA), constituted an unapproved pharmaceutical drug.⁴ The National Institute on Drug Abuse classifies substance addiction of any kind as a form of disease⁵; therefore, any product that claims to help a consumer quit smoking is, by definition, treating a disease, whether it is an FDA-authorized drug or not.

At least one supplement manufacturer understands this distinction and is directing its ingredient to the drug market. CV Sciences (San Diego, CA), a hemp-derived-cannabidiol (CBD) supplier and manufacturer, received a patent in 2020 for a new pharmaceutical drug (CVSI-007) containing nicotine and CBD.⁶ This new drug is undergoing development as a treatment for smokeless tobacco addiction.

A 2021 preclinical study⁷ that CV Sciences sponsored and conducted in partnership with Scripps Research and the University of California San Diego assessed whether CBD could prevent withdrawal symptoms in 84 nicotine-addicted Wistar rats. Dependency was induced via osmotic administration of 3.15 mg/kg of MilliporeSigma’s (St. Louis, MO) nicotine hydrogen tartrate in saline per day for two weeks. After one week, the rats were injected with 7.5, 15, or 30 mg/kg of Noramco (Wilmington, DE) CBD dissolved in sesame oil per day for two weeks, while the nicotine administration continued. The study featured three control groups: One group consisted of rats with nicotine pumps that were injected with sesame oil; the second group contained rats with saline pumps that received sesame oil; and the third group of rats was administered 30 mg/kg/day of CBD but no nicotine. After two weeks, the study authors removed the minipumps to induce nicotine withdrawal.

Withdrawal symptoms such as blinking, jumping, teeth chattering, and paw tremors were measured in 30-minute spans at intervals of 24 hours and 7 days post-withdrawal. The study authors also took blood samples at baseline, during nicotine or saline administration, during withdrawal, and after the acute withdrawal phase. During withdrawal, CBD administration reduced withdrawal symptoms like hyperalgesia and tremors. While this is a preclinical study, and human trials are required, the study authors concluded that CBD may be useful in reducing the symptoms of nicotine withdrawal during smoking cessation.

Smokers’ Health Market Fraught with Regulatory Issues

Smokers’ health supplements represent a unique challenge. The National Institute on Drug Abuse and the FDA adhere to the disease model of substance addiction, which stipulates that addiction to any chemical substance is, by definition, a medical condition. This means that any new product aiming to help smokers quit is, by definition, a pharmaceutical drug.

While smoking cessation products are classified as pharmaceutical drugs, other products that help to support cardiovascular health or improve antioxidant profile may be viable as dietary supplements to support smokers’ health. Natural product brands looking to enter this space will want to invest in proactive regulatory compliance or consider pursuing pharmaceutical drug status.

References

1. Astori E et al. “Antioxidants in smokers.” Nutrition Research Reviews. Published online April 30, 2021.
2. Luoto R et al. “Occasional smoking increases total and cardiovascular mortality among men.” Nicotine & Tobacco Research, vol. 2, no. 2 (May 2000): 133-139
3. Petsophonsakul P et al. “Nicotine promotes vascular calcification via intracellular CA2+-mediated, Nox5-induced oxidative stress, and extracellular vesicle release in vascular smooth muscle cells.” Cardiovascular Research. Published online July 17, 2021.
4. Kaufman M. “Nicotine Water Is Drug, FDA Ban Says.” The Washington Post. Published July 3, 2002.
5. National Institute on Drug Abuse webpage. “Drug Abuse and Addiction: One of America’s Most Challenging Public Health Problems.” Published online June 2005.
6. CV Sciences press release. “CV Sciences, Inc. Receives Formal Notice of Patent Issuance from USPTO for Proprietary Cannabidiol (CBD) and Nicotine Formulation for Treating Smokeless Tobacco Addiction.” Posted May 20, 2020.
7. Smith LC et al. “Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats.” Psychopharmacology, vol. 238, no. 8 (August 2021): 2201-2211