Anatabine is an alkaloid compound found in tobacco and plants in the nightshade family, which includes eggplant and peppers. Anatabine possesses anti-inflammatory properties but further research is needed to determine if supplementation is practical.
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Primary Information, Benefits, Effects, and Important Facts
Anatabine is an alkaloid found in tobacco and other plants in the nightshade family.
Anatabine is being researched for its anti-inflammatory properties. Preliminary evidence suggests it may be useful to treat autoimmune diseases and Alzheimer’s disease.
Unfortunately, current research uses doses that are significantly higher than the anatabine supplements available on the market. Oral studies tend to use a dose of 1.6mg/kg of bodyweight for people, which translates to dose between 68-110mg for a 150lb person. One human study even failed to find anti-inflammatory effects at a dose that was 6 – 12 times higher than the doses found in today’s anatabine supplements.
Anatabine’s main mechanism works by inhibiting the signal transducer and activator of transcription 3 protein (STAT3), which inhibits a protein responsible for DNA transcription, called nuclear factor kappa-light-chain-enhancer of activated B cells (nF-kB). Both Boswellia serrata and Feverfew have a similar mechanism.
Due to limitation of anatabine supplements on the market, it is not a practical anti-inflammatory supplement.
Animal research on anatabine used an oral dose of 12.5 – 20mg/kg of bodyweight in mice, for the purpose of autoimmune diseases. This suggests a preliminary human dose of:
• 70-110 mg for a 150lb person
• 90-150 mg for a 200lb person
• 110-180 mg for a 250lb person
These dosages are based on preliminary animal evidence, not human studies. Anatabine supplementation cannot be recommended at this time due to a lack of human evidence for its effects.
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects anatabine has on your body, and how strong these effects are.
Grade
Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
?
The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome
Magnitude of effect
?
The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
?
Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Anatabine is an alkaloid found in tobacco and the solanaceae family of plants. This alkaloid is structurally similar to nicotine, and is an analogue of both nornicotine and anabasine (other alkaloids in the same plant family).[1]
It is found in:
Tobacco in the range of 927-1390μg/g[2] or on average 554μg per cigarette (range of 130-1120μg; American cigarettes containing 500-550μg)[1]
Anatabine is a tobacco alkaloid similar to nicotine, and is found in the same plants
1.2. Structure and Properties
Anatabine is an alkaloid with structural similarity to nicotine, and closer structure similarity to anabasine (which is anatabine without the double bond in the right ring pictured below).
2Neurology
2.1. Cholinergic Neurotransmission
In vitro, anatabine has been noted to have bind to the α3β4 receptor with similar affinity as nicotine.[3]
May interact with nicotinic cholinergic receptors, although this is not well researched
2.2. Alzheimer's Disease
Anatabine has been found to reduce Aβ production (both Aβ1–40 and Aβ1–42) with an IC50 of around 640µg/mL, and it appeared to mostly inhibit β-cleavage of APP.[4] As this is known to occur with NF-kB inhibition[5][6] anatabine was then tested on the protein and it was found to inhibit NF-kB activation from TNF-α with a similar IC50 value[4] and nicotine was found to be inactive at the same concentrations tested. It has been noted elsewhere that this inhibitory effect on NF-kB is secondary to inhibiting STAT3 phosphorylation at 600-800µg/mL[7] although concnetrations as low as 10µg/mL can inhibit LPS-induced NF-kB activity and 400µg/mL can fully abolish IL-1β secretion induced by LPS.[7]
Nicotine has been found to inhibit Aβ production by regulating BACE-1 transcription in cells that express its receptor (α4β2 nicotinic acetylcholine receptor)[8] and anatabine has also been found to downregulate BACE-1 mRNA, which was credited to NF-kB inhibition (known to regulate BACE-1[9]). Activation of the nicotinic receptors can inhibit NF-kB[10] via STAT3[11] but nicotine seems to require a cholinergic receptor whereas anatabine does not.[4]
When injected into mice at 0.5-2mg/kg, only the higher dose was able to reduce brain and plasma Aβ concentrations to near control levels (in plasma) and by about 25% (brain)[4] and this dose has been noted to exert anti-inflammatory effects by reducing C-reactive protein[4] as well as IL-1β, IL-6, and TNF-α.[7]
Anatabine is a STAT3 inhibitor, which then inhibits NF-kB and exerts an anti-inflammatory effect. This appears to be active following injections of anatabine and may be of therapeutic benefit to Alzheimer's Disease
3Cardiovascular Health
3.1. Blood Pressure
Anatabine has structural similarity to nicotine, and since nicotine is able to acutely increase heart rate and blood pressure[12] anatabine has been investigated for its ability to do the same; it has since failed to significantly influence blood pressure or heart rate.[13]
Currently no significant interactions between anatabine and cardiovascular function are known
4Inflammation and Immunology
4.1. Mechanisms
Incubation of macrophages with 250-350μM was able to inhibit an IFN-γ and LPS induced increases in iNOS and COX-2 mRNA levels, suggesting antiinflammatory effects.[14]
May have general antiinflammatory properties at moderately high concentrations
4.2. Autoimmune Diseases
Despite the large amount of adverse health effects associated with tobacco smoking, both ulcerative colitis[15][16] and autoimmune (Hashimoto's) thyroiditis[17][18] have noted benefits associated with smoking. This is currently thought to be due to the antiinflammatory properties of nicotine via the α7 nicotinic receptor[19] (inhibits STAT3 and then NF-kB), but anatabine is also being tested.
In mice inflicted with experimental autoimmune thyroiditis and concurrently supplemented orally with approximately 12.5mg/kg anatabine, occurrence of thyroiditis and the antibody response were significantly reduced.[14] Autoimmune encephalomyelitis (research model for Multiple sclerosis) also sees clinical benefit in response to 20mg/kg anatabine in mice, although antibodies were not affected in this study.[20]
Appears to be beneficial for rodents with autoimmune diseases in high oral doses
5Physical Exercise and Skeletal Muscle
5.1. Muscle Soreness and Damage
Supplementation of 6-12mg anatabine (via lozenges that also conferred 834-1668IU vitamin A and 66-132IU Vitamin D) for ten days prior to physical exercise testing in otherwise healthy young men failed to outperform placebo (which contained the vitamins) in reducing muscle soreness or power output when measured over the next three days.[13]
The lone study in humans assessing the antiinflammatory properties of anatabine failed to find any significant influence of supplementation
