Is Nicotine Really Non-Carcinogenic as Tobacco Companies Claim?

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Is Nicotine Really Non-Carcinogenic as Tobacco Companies Claim?

Tobacco products sold always contain nicotine. Tobacco companies claim that “nicotine is not carcinogenic” and that it does not cause tobacco-related diseases. But is this really true?

Is Nicotine Really Non-Carcinogenic as Tobacco Companies Claim?

What is Nicotine?

Nicotine is a common substance found in tobacco products, including new types of heated tobacco. It is a plant-based alkaloid found in the nightshade family, to which tobacco belongs. Alkaloids are toxic defensive substances evolved by plants to deter insects and herbivores. For example, tomatine in green tomatoes and solanine in the green sprouts of potatoes are both toxic alkaloids with strong cytotoxicity.

In contrast, cultivated plants like eggplants, tomatoes, peppers, and potatoes have been bred to contain very low levels of these alkaloids or to reduce their toxicity. These cultivated plants are generally safe unless consumed in excessive amounts. On the other hand, tobacco has been selectively bred to increase nicotine levels, enhancing its addictive properties.

As a plant-based alkaloid, nicotine is inherently toxic. The lethal dose for adults is estimated to be 1–13 mg of nicotine per kg of body weight, meaning a 90 kg adult can reach a lethal dose with just 5 mL of a 1.8% nicotine solution.

Tobacco also contains tobacco-specific nitrosamines (TSNAs), compounds with a nitroso group (N=O) known to be carcinogenic, causing conditions such as esophageal cancer and liver damage. TSNAs are recognized as significant carcinogens in tobacco smoke.

Evidence of Nicotine’s Carcinogenicity

After harvesting, tobacco leaves undergo drying and fermentation, during which TSNAs are chemically formed from tobacco alkaloids. For example, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a carcinogen linked to lung cancer, is a chemical transformation product of nicotine.

Research directly investigating the health effects of nicotine itself has been limited. However, since the late 1990s, studies have suggested that nicotine may transform into carcinogenic TSNAs within the bodies of smokers and those exposed to secondhand smoke. Experimental studies on animals, such as mice and hamsters, have shown that exposure to nicotine can induce cancer. Recent research indicates that nicotine and its metabolite cotinine may be carcinogenic, potentially causing lung, cervical, colon, stomach, pancreatic, breast, liver, bladder, and head and neck cancers.

So, does nicotine have a relationship with cancer? The answer is “yes.” Nicotine exhibits multiple functions on cellular receptors, promoting chromosomal and genetic mutations, DNA damage, and oxidative stress, all of which can lead to cancer development and progression. Additionally, nicotine can promote cancer metastasis and hinder cancer treatment. For instance, a 2021 study by a U.S. research group concluded that nicotine could facilitate the metastasis of breast cancer to the lungs.

The Desperate Denial by Tobacco Companies

Tobacco products invariably contain nicotine. These research findings pose a serious threat to tobacco companies. In response, companies like Japan Tobacco (JT) and Philip Morris International (PMI) consistently claim that nicotine is not carcinogenic and does not cause tobacco-related diseases, downplaying its dangers.

For tobacco companies, nicotine is essential for retaining loyal customers and attracting new ones. As a result, heated tobacco products and e-cigarettes are carefully designed to include controlled amounts of nicotine, ensuring that users remain addicted. Nicotine’s addiction potential is comparable to cocaine, and its strong dependency keeps smokers from quitting, leading to the continuous intake of harmful substances and resulting in diseases such as cancer and chronic obstructive pulmonary disease (COPD). Nicotine is a substance that clearly causes substance dependence, with tobacco products serving as the delivery mechanism.

Tobacco products sold domestically must display nicotine and tar content, but there are no regulations on the amounts. Currently, there is no requirement to label the nicotine content in heated tobacco products, although the government is considering implementing such requirements.

Nicotine concentrations in heated tobacco products vary by country and region. A study published in February 2024 found that sticks sold in Japan had the highest nicotine concentration, while those sold in South Africa had the highest levels of TSNAs.

Nicotine pouches, another form of tobacco product, also vary in nicotine content and are not regulated in Japan. These pouches have been found to contain significant amounts of carcinogenic TSNAs.

While the nicotine content needed to satisfy smokers varies, it is generally consistent among individuals. However, the nicotine content in different tobacco products varies, with heated tobacco typically containing less nicotine than traditional cigarettes. This variability, controlled by tobacco companies, makes it challenging to assess the health impacts of nicotine and smoking.

What About Nicotine Replacement Therapies for Smoking Cessation?

Nicotine replacement therapies (NRTs), such as nicotine patches and gums, are used in smoking cessation treatments. These products contain minimal TSNAs and are not harmful to health. Unlike inhaled tobacco smoke, which delivers nicotine rapidly to the brain, causing addiction, NRTs provide a slower absorption through the skin or oral mucosa, reducing dependency. Consequently, they are used to support smoking cessation.

These products are intended only for smoking cessation and are not needed once the individual successfully quits smoking. Their slower and lower nicotine absorption rates prevent the continuous, long-term use typical of smoking. However, nicotine patches have contraindications for non-smokers, pregnant or breastfeeding women, people with heart disease, and those recovering from cerebrovascular accidents.

Understanding these contraindications underscores nicotine’s toxicity. Nicotine poses teratogenic risks and toxicity to fetuses and infants, and can cause vasoconstriction and increased blood pressure, adversely affecting the heart, brain, and blood vessels. Nicotine is classified as a highly toxic substance under the Pharmaceutical and Medical Device Act and requires strict management for use and sale.

In summary, nicotine in tobacco products is carcinogenic and poses risks of promoting cancer metastasis and hindering cancer treatment. Nicotine is a highly addictive drug, and new tobacco products containing nicotine share these risks. The claims made by tobacco companies are misleading and do not consider the health of smokers and those exposed to secondhand smoke.