The Cholinergic Anti-Inflammatory Pathway

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 8 No. 1 • January 2005


The Cholinergic Anti-Inflammatory Pathway

The cholinergic nervous system, acting via the vagus nerve, serves as one of the human body’s natural anti-inflammatory mechanisms to prevent excessive release of inflammatory cytokines in (for example) infection/sepsis or autoimmune diseases, such as rheumatoid arthritis.1

The nicotinic acetylcholine receptor alpha7 subunit has recently been identified as essential to the cholinergic anti-inflammatory effects.1 Nicotine directly activates this nicotinic acetylcholine receptor alpha7 subunit. However, due to nicotine’s addictive and other adverse effects (e.g., it promotes angiogenesis), nobody is very enthusiastic about using it as an anti-inflammatory. The authors suggest that “… it is now reasonable to consider the therapeutic potential for targeting the nicotinic acetylcholine receptor alpha7 subunit to inhibit TNF [tumor necrosis factor, a potent inflammatory cytokine], either by direct pharmacological approaches or through increasing activity in the vagus nerve.”1

We would like to point out that acetylcholine acts as an agonist at the nicotinic and muscarinic acetylcholine receptors. Though it is not selective for the nicotinic receptors, a choline and vitamin B5 supplement does increase acetylcholine synthesis and release2,3 and, hence, can be expected to activate nicotinic acetylcholine receptors. One nice thing about choline and vitamin B5 supplements is that both are very safe to take and will not result in nasty side effects, hitherto unknown, emerging years later, as may occur with highly selective xenobiotic drugs (for example, selective COX-2 inhibitors), especially when used chronically.

Galantamine (extracted from the snowdrop flower bulb) acts as an agonist to nicotinic acetylcholine receptors4 and, hence, should enhance the cholinergic anti-inflammatory pathway. Anti-inflammatories such as curcumin have been shown to protect against Alzheimer’s disease, as does galantamine. See our interview “Maintain Your Brain the Durk Pearson & Sandy Shaw Way” in the May 2004 issue of Life Enhancement (free from Life Enhancement Products at 1-800-543-3873).

  1. Wang et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulatory of inflammation. Nature 421:384-8 (2003).
  2. Wurtman. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurol Sci 15(4):117-22 (1992).
  3. Ulus and Wurtman. Choline increases acetylcholine release. [Letter] Lancet March 14, 1987.
  4. Lloyd and Williams. Neuronal nicotinic acetylcholine receptors as novel drug targets. J Pharmacol Exp Therapeut 292(2):461-7 (2000).

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