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The racetam class of nootropics enjoy unmatched popularity among online aficionados of cognitive enhancement. While they are little studied, the better-understood racetam piracetam is thought to marginally improve human cognition by affecting the cholinergic system of the brain. But what is the cholinergic system, and are the racetams our best bet towards enhancing it?
This series of blog posts will introduce the reader to the cholinergic system, beginning with the essential nutrient that is choline. We will review choline’s role in the brain, particularly its role in cognitive decline and depression, before we discuss the three ways the cholinergic system is manipulated: through the inhibition of acetylcholinesterase, through the agonizing of muscarinic receptors, and through the agonizing of nicotinic receptors.
CHOLINE: THE VITAL AMINE
If you’re interested in genetics or cognitive enhancement, you’ve probably heard of choline before. Choline intake is a frequent topic of discussion in the genetics community because polymorphisms at the ‘methylation genes’ produce some of the largest common variations in human nutritional needs. Their biggest impact is on choline requirements. In the nootropics community, an online community dedicated to improving human condition mostly through the use of cognitively enhancing molecules, alpha-GPC (formally, L-alpha glycerylphosphorylcholine) is among the popular supplements, in addition to, and often coupled with, the racetams.
Since the advent of nutritional sciences in the early 20th century, micronutrients (nutrients that we consume in small amounts) have only been considered essential if a known ‘deficiency disease’ arose from its exclusion from a diet. The nutritional compound choline was discovered to be necessary for our health in the early 1990’s, mainly through the work of the research physician Alan Buchman at the University of Chicago.
THE LIVER DEPENDS ON CHOLINE
Observing patients receiving intravenous total parenteral nutrition in 1992, Buchman found that many of his patients quickly developed nonalcoholic steatohepatitis (NASH, an advanced form of liver disease). Critically, he discovered that NASH was a deficiency disease of choline. In initial studies, Buchman learned that he could cure patients’ NASH with just 4 weeks of choline supplementation. He showed that after 10 weeks of removing the choline component of their diet, NASH would again present in a segment of the patients, further confirming its vital role in the diet. Later, placebo-controlled trials indicated that NASH could be induced even in healthy people through a choline deficient diet, within 10 weeks.
The discoveries of the 1990’s showed that, like vitamin C deficiency caused scurvy, vitamin B1 deficiency caused beriberi, and vitamin D deficiency caused rickets, choline deficiency caused liver disease (and DNA damage, but that was discovered later). Choline came to be called a vital amine (the origin of the word vitamin) and was officially recognized as an essential nutrient by the American Institute of Medicine in 1998. But why was this learned so late?
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