Cyclic Glycine-Proline

Cyclic glycine-proline, or cGP, is a tiny peptide built from only two amino acids joined into a closed ring, and the human body already makes it on its own. It turns up naturally in blood, in breast milk, and in the fluid that bathes the brain and the spinal cord; it comes about when the body breaks apart a growth-related hormone called IGF-1. Researchers mainly use it as a laboratory tool for studying how much of that hormone is available to act.

What it is

Cyclic glycine-proline, often shortened to cGP, is a small ring-shaped molecule built from just two amino acids, glycine and proline, joined end to end into a closed loop. Chemists place it in a family of compounds called cyclic dipeptides. Unlike many research peptides, the human body makes cGP on its own, and it can be measured in blood, in breast milk, and in the fluid that bathes the brain and the spinal cord.

cGP comes into being naturally as the body dismantles insulin-like growth factor 1, also called IGF-1, a hormone tied to growth and metabolism. Researchers describe it as a kind of built-in regulator: it competes with IGF-1 for a carrier protein called IGFBP-3, which controls how much of that hormone is free to act on tissue. Because of this relationship, much of the published interest in cGP centers on how it might help keep IGF-1 activity in a normal range rather than acting as a hormone in its own right.

How it is studied

Research on cGP includes work in laboratory mice, most of it from one New Zealand research group, alongside a smaller body of work measuring cGP levels in people who already have a health condition of interest, such as stroke or Parkinson disease. One small human study gave people a blackcurrant extract that naturally contains cGP rather than the purified peptide itself. There is no large program of controlled human trials giving people the purified peptide directly; most human data so far comes from measuring the amount the body already produces.

What studies report

In mice bred to develop Alzheimer disease brain changes, a course of cGP improved performance on a spatial memory task and lowered the amount of amyloid plaque, a sticky brain buildup linked to Alzheimer disease, compared with untreated mice. [arora-2023]
In a small group of stroke patients followed for three months, those with a lower ratio of cGP to IGF-1 in their blood soon after the stroke tended to have worse neurological scores later on, and the ratio rose over time as patients recovered. [fan-2019-stroke]
In older adults without Parkinson disease, a higher ratio of cGP to IGF-1 in blood was linked to better memory and thinking scores; this link was not seen in a separate group of people who already had Parkinson-related memory loss. [fan-2020-parkinson]
In eleven men with Parkinson disease, taking a blackcurrant extract that naturally contains cGP for twenty-eight days raised cGP levels in the fluid that surrounds the brain and the spinal cord, though it did not change IGF-1 levels there. [fan-2018-blackcurrant]

What is not known

No published study has given people purified cGP directly and measured a clinical outcome; the closest human work so far has either measured cGP levels the body already makes or used a food extract that happens to contain the molecule alongside many other compounds. Because of that, it is not known whether cGP itself, given on its own, would produce the same associations seen in these observational studies. Whether the mouse findings on memory and amyloid plaque would carry over to people has also not been tested.

Regulatory status

No national medicines regulator anywhere, the United States Food and Drug Administration included, has approved cyclic glycine-proline for use in people, and it is not included among the substances the World Anti-Doping Agency has placed on its prohibited list. It remains a substance studied mainly by measuring what the body already produces, not an approved medicine.