Proline is the third most abundant amino acid in the body, after glutamine and alanine. Nearly every protein the body makes contains at least some proline, but proline is especially important in collagen, the protein found in skin, bone, and connective tissue.
The human body can make proline from glutamic acid, the most abundant amino acid in food. Proline acts in concert with another amino acid, ornithine, in tissue growth. Enzymes that incorporate proline and ornithine into collagen depend on the presence of niacin, pyridoxine (vitamin B6), and vitamin C. When collagen breaks down, the result is a chemical called hydroxyproline. Gelatin (Jell-O or jelly) is prepared from connective tissue from animals, and is especially high in hydroxyproline. Weak or jelly-like connective tissues in humans are also high in hydroxyproline.
Diet and Proline
There is so much proline in a typical diet that nutritionists have never developed a recommended dietary intake for this nutrient. Unlike most other amino acids, there is more proline in dairy foods than in meat; for most amino acids, the opposite is true. There is also a relative abundance of proline in wheat germ. The human body only produces L-proline. The D- form of proline cannot be used.
Proline in the diet reduces requirements for arginine, since the body can transform proline into ornithine and ornithine into arginine. When there is not enough vitamin C in the diet, collagen breaks down as proline turns into hydroxyproline.
|Food||Milligrams Proline in 200-Calorie Serving|
|Fried Pork Skins||2542|
|Roasted Chicken Breast||2210|
Who Benefits from Supplemental Proline?
There are three main groups of people who may benefit from proline supplements.
- People who have spent weeks, months, or years in institutions that provide low-quality diets.
- People who have hard-to-heal wounds.
- People who have fine lines and wrinkles in the skin.
Typically one would take a >proline-only supplement
>proline-only supplementlike the product made by Solgar or maybe a proline and lysine supplement like the product made by Life Extension Foundation (LEF), at least 1,000 mg and up to 5,000 mg a day. The proline and lysine combination supplement by LEF, as I'll explain a little later in this article, has a special application for preventing atherosclerosis.
It does not make sense to take supplemental proline without taking supplemental niacin, vitamin B6, and vitamin C, although the needed amounts of these vitamins are quite low. Taking as little as 100 mg of vitamin C and any "complete B vitamin" supplement would be adequate for the body to make the enzymes it needs to use proline in wound and skin healing.
Any effects of proline supplementation would take at least several weeks.
Who Should Not Take Supplemental Proline?
There are also people who should not take proline supplements.
- People who have chronic kidney failure should not take any amino acid supplement without consultation with their physicians.
- Smokers should avoid proline supplements and foods that are high in proline if they eat foods preserved with nitrates or that release nitrates during the process of pickling such as ham, bacon, sausage, salami, pastrami, cucumber pickles, sauerkraut, and kimchee. In smokers, although not in non-smokers, nitrates can convert proline into the potent carcinogen N-nitrosoproline.
- People who have alcohol-related liver disease should not take proline, because they usually already have high levels of proline in the bloodstream. Chronic liver inflammation interferes with the body's ability to make collagen anywhere except in the liver, where proline is used to form the collagen that forms the fibers that cause cirrhosis of the liver.
- People who have allergies should not use proline supplements, or at least should not take them by mouth. Proline increases levels of histamine in the bloodstream.
- People who have the hereditary iron overload disease hemochromatosis should not take proline supplements, because they raise ferritin levels in the bloodstream.
These concerns are not an issue, however, for the use of proline in skin creams for wrinkles. Proline is never labeled as a separate amino acid on skin care products. It is just listed as "amino acids."
What About the Combination of Proline and Lysine?
As I mentioned earlier in this article, Nobel laureate Linus Pauling believed that a combination of proline and lysine could prevent or even reverse the hardening of the arteries known as atherosclerosis. Understanding why proline and lysine taken together may prevent or reverse atherosclerosis requires revisiting the concept of hardening of the arteries.
Doctors often talk about cholesterol as if somehow it were like the calcium that builds up inside water pipes. It's really nothing like that. Arteries do not harden all over the body. In the early 1950's, a Canadian physician named G. C. Willis made the observation that atherosclerosis most often occurs in the blood vessels nearest the heart, where they are under greatest pressure and where they take the tightest turns to connect with the heart.
This observation undermined the "like a pipe" theory that cholesterol somehow collected on the linings of arteries and hardened. Actually, cholesterol accumulates at the points arteries are injured. In the 1980's, Dr. Linus Pauling, a Nobel prize winning chemist, and his colleague, Dr. Matthias Rath, a physician, theorized that the cholesterol would not accumulate at these sites of arterial injury if the body were provided with two amino acids, lysine and proline.
Cholesterol from the bloodstream has to be captured by the cells that use it. It is electrostatically attracted to receptor sites that bind it at the site of the injury. Then white blood cells infiltrate the lining of the arteries and either remove excess cholesterol, in which case there is no hardening of the artery at that site, or they get stuck in the lining of the artery. Eventually a combination of cholesterol, white blood cells, and calcium blocks the artery, but this does not happen if the cholesterol is never bound to the artery wall.
If there is more lysine and proline in the bloodstream, there is a greater chance that lysine will bind to the arterial wall instead of cholesterol. That keeps plaques from forming. But you don't just want to keep plaques from forming; you also want to heal the injury the arterial wall. Pauling and Rath believed that the combination of lysine and proline, which are used to make collagen, along with vitamin C, niacin, and vitamin B6, would heal the site of injury in the artery so that cholesterol would even cease to be a concern.
This strategy stops the harmful effects of cholesterol in the arteries, Pauling and Rath believed, without the need to change liver chemistry to stop the production of cholesterol. Pauling recommended every adult take 3,000 mg of vitamin C every day along with 2,000 mg of lysine and 2,000 mg of proline to prevent cardiovascular disease, and about 50% more to reverse cardiovascular disease.
Does the Strategy Work?
It wasn't until 2008 that scientists confirmed Pauling and Rath's idea that lysine metabolism provided protection for the linings of arteries and the smooth muscles supporting them. Researchers have been looking at the enzymes that break down collagen proteins as a cause of atherosclerosis and arterial weaknesses that can cause aneurysms, however, rather than looking at lysine and proline supplements as a way of keeping arteries clear. Dr. Rath himself has only experimented with lysine and proline in cultures of artery cells grown in test tubes, and he has spent much of the last 20 years involved in ethical and legal controversies in Europe, South Africa, and the USA. Unfortunately, no one has ever conducted a clinical trial of these ingredients as a treatment for heart disease.
I briefly consulted to the Linus Pauling Foundation, but I have not been able to find any clinical research for their claims. The one doctor I could find who claims to have "reversed heart disease in 10 days" with this combination has also been sued for fraud at least 10 times.
We simply don't know that this treatment will work. There are some people, such as smokers and people who have alcoholic liver disease mentioned above, who should not try it. While most people will not have any adverse reaction to this supplement, it is nearly impossible to measure how well it is working and results would have to be taken on faith.
Ivanov V, Roomi MW, Kalinovsky T, Niedzwiecki A, Rath M. Anti-atherogenic effects of a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea phenolics in human aortic smooth muscle cells. J Cardiovasc Pharmacol. 2007 Mar;49(3):140-5.