A New Perspective on Nicotine

Nicotine is commonly perceived negatively due to its association with smoking or tobacco use. However, nicotine is not the harmful part of cigarettes, it’s the heavy transition metals and tar which are deadly. It is noteworthy that nicotine is present in various foods and can exert a medicinal impact on mitochondrial function through its influence on nicotinamide adenine dinucleotide (NAD+). This effect is particularly notable in muscular function. Some individuals, particularly those facing challenges, may contemplate utilizing nicotine as a bio-hacking tool, a potentially more favourable alternative to coffee. Additionally, it is less known that mammals possess nicotinic receptors located in the neuromuscular junctions of somatic muscles. These receptors may play a role in responding to nicotine, and the supplementation could potentially impact positively neuromuscular function. Supplementing a high-quality nicotine source might be considered for its potential medicinal effects on mitochondrial function, particularly in the context of supporting muscular performance and overall well-being.

Medicinal Applications of Nicotine: Unbranded Summary

• Nicotine is often conflated with the harms of smoking, but evidence shows nicotine itself, separate from tobacco and combustion products, has diverse physiological effects.

• Nicotine’s impact varies significantly depending on dose, delivery method, and individual biology.

What happens when you supplement Nicotine:

1. Nicotine is absorbed through the mucus membranes in the mouth. The absorption into the blood stream is slower than if inhaled,

2. Nicotine binds to nicotinic acetylcholine receptors in the central and peripheral nervous system, leading to the release of neurotransmitters like dopamine. 

3. Nicotine then stimulates the central nervous system, leading to increased alertness and cognitive enhancement.

4. Nicotine enters the mitochondria and stimulates increased mitochondrial function. Thus, nicotine can have metabolic effects, such as increased metabolic rate and suppression of appetite, which may be relevant for weight management.

5. Nicotine affects the autonomic nervous system, leading to changes in heart rate, blood pressure, and respiratory rate. It can activate both the sympathetic and parasympathetic systems, depending on the dose and context.

Nicotine is a mitochondrial stimulant

Nicotine assumes a crucial role in modulating the electron tunnelling process within the mitochondria, specifically at cytochrome/complex 1, involving the NAD+/NADH couple in the tricarboxylic acid (TCA) cycle. Remember NAD is NICOTINamide adenine dinucleotide. By favouring the NAD+ state, nicotine enhances the efficiency of the TCA cycle, leading to a more streamlined quantum movement of electrons and protons, thereby reducing mitochondrial heteroplasmy. Mitochondrial heteroplasmy describes the rate at which mitochondria lose their efficiency at generating energy and functioning well. This is measured by the distance between complex 1 on one side and complex 5 on the other side, when this distance increases heteroplasmy rates rise and mitochondria become less efficient at doing their jobs. Nicotine can help shorten the distance between these complexes and improve mitochondrial efficiency, especially in healthy dark skin individuals. Nicotine, when optimized with adequate oxygen and sunlight exposure, can stimulate beneficial processes like mitophagy (mitochondrial renewal/regeneration), providing a small superoxide pulse that optimizes energy flux and counters elevated heteroplasmy rates.

Tobacco, being a summer plant adapted to equatorial/tropical or subtropical climates, introduces a circadian mismatch when supplemented in wintertime. Interestingly, nicotine, a key component of tobacco, demonstrates reduced efficacy and lower addictive potential in Caucasian populations compared to those with darker skin. This correlation arises from nicotine's intricate link to dopamine in the brain, and individuals with more melanin-rich skin exhibit greater dopamine production, thereby amplifying the effects of nicotine. Notably, as skin darkens with sun exposure, the effectiveness of nicotine increases.

The interplay between nicotine, dopamine, and melanin is rooted in the biochemical transformation of tyrosine, a key amino acid that necessitates UV light for the synthesis of melanin, dopamine, and the optimization of mitochondrial efficiency. It is noteworthy that nicotine functions optimally in the presence of UV light, aligning with the natural habitat of tobacco as a tropical/subtropical plant dependent on strong UV light for growth.

Furthermore, nicotine's mimicry of the neurotransmitter acetylcholine allows for the direct activation of acetylcholine receptors, leading to the induction of catecholamines like adrenaline and dopamine. This dual mechanism underlies both the potential for addiction and the stimulation of fat burning. Additionally, the pyrrolidine ring in nicotine chemically relates it to the racetams, a class of nootropic drugs.

Understanding nicotine's fluorescence properties as a fluorophore protein is integral to comprehending its interaction with light. With an absorption spectrum primarily situated in the ultraviolet range, approximately 260-270 nm, a nuanced grasp of this spectrum is crucial for unravelling the intricate biochemical processes influenced by nicotine's response to light.

Nicotine stimulates the production of Nitric Oxide

1. Nicotinic Acetylcholine Receptors (nAChRs): Nicotine primarily acts on nicotinic acetylcholine receptors (nAChRs) throughout the body, including the vascular endothelium.

2. Stimulation of nAChRs: When nicotine binds to nAChRs, it triggers the release of neurotransmitters, including acetylcholine.

3. Acetylcholine and NO Synthesis: Acetylcholine, in turn, stimulates the production of nitric oxide synthase (NOS), an enzyme responsible for the synthesis of nitric oxide.

4. NO Production: Nitric oxide is then produced from the amino acid L-arginine by NOS. This NO production has several effects, including the relaxation of blood vessels (vasodilation).

Importance for Athletic Performance

Enhanced vasodilation and increased blood flow resulting from NO production can have implications for athletic performance. Improved blood flow means better oxygen and nutrient delivery to muscles, potentially enhancing exercise endurance and performance.

Nicotine impacts both the sympathetic and parasympathetic nervous systems

Nicotine receptors, specifically nicotinic acetylcholine receptors, are present in both the sympathetic and parasympathetic nervous systems. While the parasympathetic system is associated with the calming "rest and digest" response, the sympathetic system is linked to the stress-induced "fight or flight" response. Nicotine's interaction with these receptors can modulate the activity of both systems, potentially contributing to its effects on various physiological responses. Generally, when nicotine is supplemented, it begins by activating the parasympathetic nervous system and then goes on to stimulate the sympathetic nervous system in that order.

Nicotine is present in commonly eaten vegetables.

Nicotine is a natural substance in most peoples every-day diet. It’s nothing to be afraid of but if supplementing it’s wise to go slow to determine a dose that works for you. 4mg is a strong dose, so keeping to this or less to begin would be wise.

Citation:

• https://www.nejm.org/doi/full/10.1056/NEJM199308053290619?fbclid=IwAR2CwtqZAOEn8YO29BC3iUlIFa2UN8VTO19DrtW5Cz62ONIaIBcaLpBEC3A

Cognitive & Neurological Effects

Dopamine & Cognitive Enhancement

• Nicotine stimulates nicotinic acetylcholine receptors (nAChRs), leading to increased dopamine release.

• Enhances cognitive performance, including attention and working memory.

• Potential use in neurodegenerative conditions such as Alzheimer's and Parkinson’s.
  
  

Neuroprotection & Brain Plasticity

• Promotes neuroplasticity — critical for learning, memory, and recovery from injury.

• May reduce cognitive impairment in Alzheimer’s and motor symptoms in Parkinson’s.

• Has potential in stroke and traumatic brain injury contexts due to receptor-mediated neuroprotection.

Mood & Anxiety Regulation

• Modulates serotonin and norepinephrine, similar to certain antidepressants.

• May improve mood and reduce anxiety, particularly in older adults.

Immune & Inflammatory Modulation

Cholinergic Anti-Inflammatory Pathway

• Activates α7 nicotinic acetylcholine receptors (α7-nAChRs), reducing systemic inflammation.

• Demonstrated benefits in conditions such as ulcerative colitis and sepsis.

Immune Regulation

• Downregulates pro-inflammatory cytokines.

• Modulates immune cell activity, with potential implications for autoimmune conditions like multiple sclerosis, rheumatoid arthritis, and lupus.

Metabolic, Pain, and Regenerative Effects

Appetite Suppression & Weight Control

• Influences the hypothalamus to reduce appetite.

• Increases fat metabolism and lowers calorie intake.

Analgesic Properties

• Reduces pain sensitivity and increases pain tolerance.

• Shown to have benefit in neuropathic pain conditions.

Muscle Regeneration & Anti-Fibrotic Potential

• Early-stage research suggests nicotine may support muscle repair and reduce fibrosis, with implications for conditions like muscular dystrophy.

Important notes

• If someone has poor mitochondrial function, i.e. are regularly coughing/sniffing, experience the seasonal flu, do not sleep well, etc, supplementing nicotine regularly can stimulate the over production of free radicals like reactive oxygen species. However, in this case of persistent mitochondrial issues, the introduction of nicotine, methylene blue, coupled with exposure to abundant sunlight, particularly targeting the retinal pigment epithelium (RPE), can be offered as a potential solution.

• Long term nicotine supplementation can adversely impact melatonin function. Be aware that caffeine, nicotine and alcohol encourage sleep disturbances so best not to have them after sunset. Remember the nutrients that support healthy melatonin function are Vit B3, Vit B6, Calcium, L-serine, glycine and Magnesium.

• People who use nicotine regularly have a reduced risk of Parkinson’s Disease (PD) or Alzheimer’s Disease (AD) because in these diseases the nicotine receptor in the parasympathetic system becomes desensitized and sometimes destroyed.

• People who smoke and quit, generally gain weight as more food electrons are needed in the TCA to maintain the same level of energy because the cytochromes are further apart (higher heteroplasmy).

• Certain liver gene mutations such as those on the CYP gene can impact your body’s efficiency at which it metabolises nicotine. Some are fast, some are slower, and some are in the middle depending on the mutations you have in your phase 1 and 2 detoxification pathways.

If Supplementing

Delivery Methods and Pharmacokinetics

• Patches: Slow, steady absorption (16–24 hours); useful for withdrawal and possible neuroprotective applications.

• Gum/Lozenges: Moderate onset; may support cognitive function and appetite suppression.

• Nasal Spray: Rapid absorption; may benefit acute cognitive decline or fatigue.

• Troches/Sublingual Tablets: Slow release with high bioavailability; lower addiction risk, good for nootropic effects.

• Synthetic Nicotine: Free from tobacco-derived impurities; pharmaceutical-grade option for research and therapeutic use.

Usage Guidelines

• It can be used at the end of a plane trip to support mitochondrial biogenesis (mitophagy) as during the flight your mitochondria will be damaged.

• Nicotine is best used during the middle portion of the day or before a physically exertive exercise (game, training, workout, etc).

• If feeling well hydrated and in a healthy state but having a slightly off day when you need to be on mentally. Avoid sequential day use. It’s a tool to be used strategically not dependently.

Dosing Guidelines

• Low Dose (0.5–2 mg/day): Cognitive enhancement, focus, neuroprotection.

• Moderate Dose (2–6 mg/day): Appetite control, mood support, pain modulation.

• High Dose (>6 mg/day): Greater risk for adverse effects and addiction.

Key Scientific Sources

• Nicotine enhances cognition via nAChRs and dopamine modulation .

• Supports memory and neuroprotection in Alzheimer’s and Parkinson’s models .

• Has antidepressant-like effects via serotonergic and noradrenergic pathways .

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