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Anatabine

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.

Our evidence-based analysis on anatabine features 20 unique references to scientific papers.

Kamal Patel
Research analysis led by Kamal Patel.
All content reviewed by the Examine.com Team. Published:
Last Updated:

Summary of Anatabine

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.

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Things To Know & Note

Primary Function:

Also Known As

Anatabloc (Brand Name)

Caution Notice

Examine.com Medical Disclaimer

How to Take Anatabine

Recommended dosage, active amounts, other details

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.

Human Effect Matrix

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.
Notes
grade-c
Blood Pressure
- - See study
6-12mg anatabine does not appear to significantly influence blood pressure in otherwise healthy persons.
grade-c
Heart Rate
- - See study
There is no significant influence on heart rate seen with 6-12mg anatabine in otherwise healthy persons
grade-c
Muscle Damage
- - See study
The progression of recovery after a novel workout (when measured over three days) was unaffected by 6-12mg anatabine
grade-c
Muscle Soreness
- - See study
Perceived muscle soreness and pain from a workout was unaffected by anatabine supplementation.
grade-c
Power Output
- - See study
Strength recovery over the course of three days recovery was not significantly improved by 6-12mg anatabine

Scientific Research on Anatabine

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1Sources and Structure

1.1Sources

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

1.2Structure 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

2.1Cholinergic 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

2.2Alzheimer'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

3.1Blood 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

4.1Mechanisms

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

4.2Autoimmune 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

5.1Muscle 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

References

  1. ^ a b Wu W, Ashley DL, Watson CH. Determination of nicotine and other minor alkaloids in international cigarettes by solid-phase microextraction and gas chromatography/mass spectrometry. Anal Chem. (2002)
  2. ^ Lisko JG, et al. Application of GC-MS/MS for the analysis of tobacco alkaloids in cigarette filler and various tobacco species. Anal Chem. (2013)
  3. ^ Screening of Tobacco Smoke Condensate for Nicotinic Acetylcholine Receptor Ligands using Cellular Membrane Affinity Chromatography Columns and Missing Peak Chromatography.
  4. ^ a b c d e Paris D, et al. Anatabine lowers Alzheimer's Aβ production in vitro and in vivo. Eur J Pharmacol. (2011)
  5. ^ Paris D, et al. Inhibition of Abeta production by NF-kappaB inhibitors. Neurosci Lett. (2007)
  6. ^ Paris D, et al. Reduction of beta-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer's disease. J Neuroinflammation. (2010)
  7. ^ a b c Paris D, et al. Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation. Eur J Pharmacol. (2013)
  8. ^ Nicotine decreases beta-amyloid through regulating BACE1 transcription in SH-EP1-α4β2 nAChR-APP695 cells.
  9. ^ Buggia-Prevot V, et al. NFkappaB-dependent control of BACE1 promoter transactivation by Abeta42. J Biol Chem. (2008)
  10. ^ Yoshikawa H, et al. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol. (2006)
  11. ^ Peña G, et al. Unphosphorylated STAT3 modulates alpha 7 nicotinic receptor signaling and cytokine production in sepsis. Eur J Immunol. (2010)
  12. ^ Haass M, Kübler W. Nicotine and sympathetic neurotransmission. Cardiovasc Drugs Ther. (1997)
  13. ^ a b Jenkins ND, et al. The effects of anatabine on non-invasive indicators of muscle damage: a randomized, double-blind, placebo-controlled, crossover study. J Int Soc Sports Nutr. (2013)
  14. ^ a b Caturegli P, et al. Anatabine ameliorates experimental autoimmune thyroiditis. Endocrinology. (2012)
  15. ^ Boyko EJ, et al. Effects of cigarette smoking on the clinical course of ulcerative colitis. Scand J Gastroenterol. (1988)
  16. ^ Calabrese E, et al. Low-dose smoking resumption in ex-smokers with refractory ulcerative colitis. J Crohns Colitis. (2012)
  17. ^ Belin RM, et al. Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. (2004)
  18. ^ Pedersen IB, et al. Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum: a population study. Eur J Endocrinol. (2008)
  19. ^ Bencherif M, et al. Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases. Cell Mol Life Sci. (2011)
  20. ^ Paris D, et al. Amelioration of experimental autoimmune encephalomyelitis by anatabine. PLoS One. (2013)

This page is regularly updated, to include the most recently available clinical trial evidence.

Each member of our research team is required to have no conflicts of interest, including with supplement manufacturers, food companies, and industry funders. The team includes nutrition researchers, registered dietitians, physicians, and pharmacists. We have a strict editorial process.

This page features 20 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page.

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