Evidence review of nicotine information for use in clinical practice. July 2023

Dr Jomana Karim

By Dr Jomana Karim

Dr Jomana Karim is an experienced General Practitioner. She completed her medical education at the University of St Andrews & the University of Manchester. After obtaining her medical degree she completed further medical training to become a member of the Royal College of General Practitioners. During her training, Dr Karim worked in several large teaching hospitals in multiple specialities. After completing her post graduate training, she worked as a physician in one of Manchester’s busiest emergency departments as well as working in other private and NHS general practice roles. Dr Karim is involved in providing smoking cessation advice on a daily basis as part of routine primary care services.

Evidence review of nicotine information for use in clinical practice. July 2023


What is the current perception of nicotine and common questions asked in clinic?

The composition of nicotine and its effects on the general public are not well-understood. Nicotine is mistakenly believed to be the primary cause of cancer, heart attacks, and COPD. Negative associations are also commonly associated with the use of Nicotine replacement therapy (NRT). This perspective is widespread among healthcare professionals, leading to under-prescribing of nicotine replacement therapy (NRT).

What does the evidence say about nicotine and cancer?

The relationship between nicotine and cancer is intricate because nicotine is typically not consumed in its pure form. Instead, nicotine enters the body through various tobacco and non-tobacco products, and its metabolism is complex due to the involvement of different enzymes and the variability of nicotine-containing products available. However, it is generally agreed upon that regulated nicotine-containing products, such as nicotine replacement therapy, which provide controlled doses of nicotine, can help cigarette smokers gradually reduce their nicotine dependence and minimise their exposure to carcinogens. Currently, the International Agency for Research on Cancer (IARC) does NOT classify nicotine as a carcinogen. The carcinogens associated with traditional smoking arise from the combustion of tobacco, with tobacco-specific nitrosamines (TSNAs) being one of the most significant groups of carcinogens found in tobacco products. https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono83.pdf )(https://cancer-code-europe.iarc.fr/index.php/en/ecac-12-ways/tobacco/199-nicotine-cause-cancer)

 What does the evidence say about nicotine and heart disease?

Nicotine does not pose a significant health hazard for individuals without heart conditions. However, it can be problematic for those with existing heart disease, as its effects can contradict the goals of most treatments that aim to reduce blood pressure and heart rate. (https://www.bhf.org.uk/informationsupport/heart-matters-magazine/news/e-cigarettes)  People with cardiovascular disease who smoke tobacco products containing nicotine face an increased risk of myocardial infarction, cerebrovascular accident, and other serious vascular events. Some studies published as recently as 2001 suggested a potential link between Nicotine Replacement Therapy (NRT) and cardiac and vascular adverse events. Nevertheless, randomised controlled studies have failed to support the association between nicotine patch therapy and acute cardiovascular events, even in patients who continue to smoke. The Mayo Clinic Proceedings have highlighted that the benefit of NRT in enhancing successful tobacco smoking cessation efforts and reducing the burden of cardiovascular disease is clear and convincing.


What does the evidence say about nicotine and COPD?

There is now evidence that the majority of tobacco smokers develop some form of respiratory impairment due to COPD. According to a recent study addressing this issue, 50% of smokers eventually develop COPD, as defined by the guidelines set forth by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). This finding holds significant clinical importance as it provides a scientific basis for advising smokers that if they continue to smoke throughout their lives, they have at least a 50% chance of developing COPD.


Cigarette smoke contains an extremely high concentration of oxidants, which generate reactive oxidant substances that induce inflammation in the lungs and airways. Smoking causes an inflammatory process in the central airways, peripheral airways, and lung parenchyma, even among smokers with normal lung function. Quitting smoking is the most effective and cost-effective treatment for COPD. NRT products can assist in smoking cessation. However, there is currently insufficient long-term data to confirm whether the prolonged use of electronic smoking devices leads to COPD. Since vaping is still relatively new to the market, its safety remains uncertain.

What does the evidence say about how to best quit nicotine and harm reduction from smoking?

Effective stop smoking methods include:

  1. Using nicotine replacement therapies (NRT) or e-cigarettes increases the likelihood of success by one and a half times.
  2. Using stop smoking medications prescribed by healthcare professionals doubles a person’s chances of quitting.
  3. Combining stop smoking aids with expert support from local stop smoking services makes someone three times more likely to successfully quit smoking


 Prescription tablets

There are two prescription-only stop smoking medicines available: Varenicline (Champix) and Bupropion (Zyban). Varenicline significantly increases the chances of long-term success in quitting smoking by 2 to 3 times when compared to attempts without the use of a stop smoking aid. Research indicates that individuals using Varenicline have higher success rates in quitting compared to those using other first-line pharmacotherapies for treating tobacco dependence.


Bupropion, on the other hand, helps reduce cravings and withdrawal symptoms associated with smoking. The likelihood of maintaining a smoke-free status using this medication is similar to that of nicotine replacement therapy.


Nicotine Replacement Therapy

Nicotine Replacement Therapy (NRT) is a medication that offers users nicotine without the harmful substances found in tobacco smoke, such as tar, carbon monoxide, and other poisonous chemicals. It is designed to help reduce withdrawal symptoms associated with tobacco use, including irritability and cravings. According to high-certainty evidence, using a combination of NRT methods, as opposed to a single-form NRT, and opting for higher doses (e.g., 4 mg nicotine gum instead of 2 mg), can significantly increase the chances of successfully quitting smoking (source: Different doses, durations, and modes of delivery of nicotine replacement therapy for smoking cessation – PubMed (nih.gov)).


An e-cigarette offers users the ability to inhale nicotine through vapor instead of smoke. These devices come in various models and operate by heating a solution, known as e-liquid, which typically contains nicotine, propylene glycol, vegetable glycerin, and flavorings. Prominent health and public health organizations in the UK, such as the RCGP, BMA, and Cancer Research UK, now concur that while not entirely risk-free, e-cigarettes are significantly less harmful than traditional smoking. Based on an evaluation of available international peer-reviewed evidence, PHE and the RCGP estimate that e-cigarettes can potentially reduce harm by at least 95% compared to smoking. Additionally, it is worth noting that nicotine replacement products can be used in conjunction with e-cigarettes. (https://www.gov.uk/government/publications/health-matters-stopping-smoking-what-works/health-matters-stopping-smoking-what-works)

What does the evidence say about using nicotine for harm reduction from smoking?

While there may be some conflicting messages, the current consensus is that the potential harm from long-term nicotine use is still considered minimal when compared to the harm caused by long-term tobacco use. The concept of harm reduction aims to provide smokers with the nicotine they are addicted to, while eliminating the tobacco smoke responsible for the majority of smoking-related harm.


Ideally, non-tobacco nicotine products should be used for a limited duration to assist tobacco smokers in quitting. Short-term use of nicotine does not result in clinically significant harm. Recognizing this, the UK Medicines and Healthcare products Regulatory Agency (MHRA) recently extended the indication of Nicotine Replacement Therapy (NRT) to include ‘harm reduction’, defined as using NRT as a substitute or partial substitute for smoking tobacco, both for those attempting to quit and those not currently planning to quit, without any specified limitation on the duration of use. Guidelines on harm reduction approaches to smoking from the National Institute for Health and Care Excellence (NICE) further state that it is safer to use licensed nicotine-containing products than to smoke, and there is reason to believe that lifetime use of such products will be considerably less harmful than smoking. (https://www.rcplondon.ac.uk/projects/outputs/nicotine-without-smoke-tobacco-harm-reduction)

How do you respond to a patient claiming that shisha smoking is safe?

Shisha smoke, like cigarette smoke, contains nicotine, tar, carbon monoxide and high levels of thousands of toxicants. A study comparing the health effects of shisha and cigarette smoking among young adults in Kuwait suggested that shisha smoking is not safer than cigarette smoking, except for certain complaints like cough, chest pain, and rapid heart rate. Individuals who smoke both shisha and cigarettes may experience worse health effects, including frequent respiratory infections, persistent cough, rapid heartbeat, and sleep disturbance. https://oneyousurrey.org.uk/quit-smoking-with-one-you-surrey/ 

According to research conducted by the World Health Organization (WHO), a one-hour shisha smoking session is estimated to be equivalent to smoking between 100 and 200 cigarettes.


Another study published in the British Journal of General Practice suggested a more cautious estimate of 10 cigarettes equivalence in a 45-minute shisha session. While there may be variations in the specific equivalence, there is sufficient evidence to conclude that shisha smoking is not harmless (source: Shisha guidance for GPs: eliciting the hidden mystery – PubMed (nih.gov)).

What if patients slip up and smoke while using the NRT?

Patients can continue to use Nicotine Replacement Therapy (NRT) while maintaining their resolution to quit smoking. Remaining on NRT increases the likelihood of patients staying on track with their quitting journey. Although not recommended, it is not considered unsafe to smoke while using NRT. A large study examining the effects of preloading patients with NRT prior to their smoking cessation attempt demonstrated that it is safe to use a nicotine patch while smoking, with the majority of individuals not experiencing any side effects. This study aligns with previous research indicating the safety of smoking while using NRT and supports the decision made by the UK medicines regulator in 2005 to remove warnings against smoking while using nicotine patches (source: “Preloading – Wearing a Nicotine Patch for Four Weeks Before Quitting” – Nuffield Department of Primary Care Health Sciences, University of Oxford).

My patient says they tried NRT but they still had cravings. 

It is important that they are using NRT correctly. The nicotine patch is available in three strengths: 7 mg, 14 mg, and 21 mg. The appropriate dose for each patient depends on their smoking habits. If a patient smokes more than 10 cigarettes per day, it is advisable to start them on a 21 mg patch. Over time, typically after 8 to 12 weeks, they should gradually decrease the dose with the goal of eventually stopping the use of the patch altogether.

For nicotine gums and lozenges, they usually come in two strengths: 2 mg and 4 mg. Patients should be advised to use one piece of gum or lozenge every 1-2 hours during the first 6 weeks of their quit attempt. It is important to explain to patients that nicotine gum is different from regular chewing gum, and they should follow the specific directions for chewing for it to be effective.

Patients should be aware that they may still experience withdrawal symptoms or cravings while using NRT. It is common for most individuals to find withdrawal symptoms particularly challenging during the first week or two after quitting. However, using NRT can help make these withdrawal symptoms less intense. (https://smokefree.gov/stay-smokefree-good/stick-with-it/slips-relapses)

What about patients who ask about smokeless products such as vaping products?

There is a wide variety of vaping products available, making it a challenge to be an expert in all of them. Like NRT, the selection of nicotine strength for e-liquids depends on the patient’s current smoking habits. Here are some general guidelines:

  • Light smokers who consume half a pack or less per day may opt for a low nicotine product, typically with a nicotine strength of 2% and below.
  • Average smokers who consume half a pack to one pack (10-20 cigarettes) per day may consider using a medium strength nicotine product, typically ranging from 2% to 3.5%.
  • Heavy chain smokers who consume 20 or more cigarettes per day may require a higher nicotine strength, typically found in 4.5% to 5% options. In this case, using 1-2 pods per day might be necessary.

Patients can gradually reduce the nicotine strength of the e-liquid, transitioning to devices with lower nicotine concentrations. This allows for a gradual tapering down of nicotine intake.

How is the nicotine oral inhaler different than an e-cigarette?

There are important distinctions between the nicotine inhaler and e-cigarettes. The nicotine inhaler has received FDA approval as a quit-smoking medicine for over 20 years. It is a regulated product, and scientific studies have demonstrated its safety and efficacy. The nicotine inhaler is specifically designed to deliver nicotine to the mouth and throat area for absorption, rather than being inhaled into the lungs. As a result, nicotine plasma peak and curve is lower for nicotine inhaler than that of e-cigarette. In a recent clinical trial comparing the two products, the e-cigarette was more acceptable and provided more satisfaction. Latest Cochrane Review finds high certainty evidence that nicotine e-cigarettes are more effective than traditional nicotine-replacement therapy (NRT) in helping people quit smoking (https://www.cochrane.org/news/latest-cochrane-review-finds-high-certainty-evidence-nicotine-e-cigarettes-are-more-effective).

What are the health policy implications of smoking usage in Saudi Arabia? Answer by Dr Ahmed

The magnitude of the problem is indicated by its prevalence among the population. According to reports, the smoking rate in Saudi Arabia in 2020 was nearly 14.5%, which represents a 0.1% increase compared to 2019. On average, individuals in Saudi Arabia start smoking at the age of 19, with males starting around age 19 and females tending to start at higher ages. Overall, approximately 30% of individuals started smoking before the age of 15, and about 61% began smoking before the age of 18. Additionally, around 11% of smokers consume cigarettes daily, averaging 15 cigarettes per day. Approximately 11% of Saudis also smoke shisha (hookah) daily, with 21% of males and about 1.5% of females engaging in this habit.

Furthermore, aside from the health damage caused to the smokers themselves, it is reported that a significant percentage of people in Saudi Arabia smoke at home, thereby exposing their families to the harmful effects of second-hand smoke. Sadly, many groups, such as children and older individuals, are put at risk due to the ignorance of certain smokers. Among smokers, approximately 50% have attempted to quit smoking within the last 12 months. Additionally, around 55% of smokers reported receiving advice from their doctors or healthcare professionals to quit smoking during any visit within the last 12 months. However, the level of advice provided to quit smoking falls short of what is needed to address the problem.

In the United Kingdom, professional reports and literature state that smoking is the leading preventable cause of illness and premature death, resulting in the deaths of around 75,000 people in England in 2019. In the same year, there were an estimated 5,600,000 smoking-related hospital admissions in England, which is equivalent to approximately 1,400 admissions per day. In Saudi Arabia, it is estimated that 70,000 people die annually from smoking-related diseases. The cost of tobacco use in Saudi Arabia is approximately $20 billion, representing around 0.2% of the GDP.

When it comes to healthcare service utilisation, there is valuable data available from the UK NHS. I encourage healthcare professionals to conduct further research on the burden of smoking in the healthcare system, including both financial and non-financial burdens, as well as health service utilization. Reports indicate that smokers utilize GP services 35% more than non-smokers, and one in four patients occupying hospital beds are smokers at the secondary healthcare level. Therefore, it is evident that quitting smoking directly leads to shorter hospital stays, reduced complications, higher survival rates, improved wound healing, decreased infections, and fewer readmissions after surgery.

Which country would you recommend that KSA look at as an example to be inspired with? Answer by Dr Ahmed

The UK has announced its commitment to make England a smoke-free society in England by 2030. This is divided as adult smoking prevalence of 5% or less. The plan sets out several ambitions:

  1. Reducing the uptake of smoking in young people.
  2. Reducing the prevalence of smoking in pregnancy.
  3. Supporting people with mental health conditions to quit smoking.
  4. Using evidence-based innovation to help people quit smoking.

To achieve these ambitions, certain critical recommendations have been identified, among many is education on the potential benefits of vaping as a less harmful alternative to tobacco smoking.

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