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L-Glutamine Health Benefits and Side Effects

Amino acid expert Dr. Eric Braverman often refers to the interrelated amino acids glutamic acid, gamma-aminobutyric acid (GABA), and glutamine as "the brain's three musketeers."

Although glutamine is usually marketed to bodybuilders, the most dramatic results from glutamine supplementation are usually seen in neurological conditions.

Before we get into why glutamine is not especially important for athletes for may be very important for people who deal with alcoholism, Alzheimer's, anxiety, and overactive appetite as well as intestinal conditions, let's take a closer look at how the body converts these three amino acids back and forth into each other.

Glutamine, Glutamic Acid, and GABA

What is Glutamine?

You probably know the difference between essential amino acids and non-essential amino acids.

Essential amino acids are necessary for the function of the human body and they have to be obtained from food.

Non-essential amino acids are also necessary for the function of the human body, but the body can manufacture then from the essential amino acids through processes that require enzymes, which the body in turn makes with various vitamins and minerals.

Glutamine is one of the amino acids the body can manufacture. In fact, the body has to manufacture glutamine, unless it is provided by supplements, because there is no glutamic acid in food.

The amino acid that we get in food is glutamic acid, which is bound to tissues as glutamate. The body can transform glutamic acid or glutamate into glutamine, and it can also transform glutamine back into glutamic acid or glutamate. The body can also exchange glutamic acid/glutamate back and forth with GABA.

Glutamine is a unique amino acid that contains two atoms of nitrogen instead of just one.

When the body needs to remove ammonia (NH3) from the bloodstream after it has been released during the breakdown of protein, it can transform glutamic acid/glutamate into glutamine.

When it needs the B vitamin niacin, it can release NH3 from glutamine to make the vitamin. Glutamine also forms much of the protein in muscles, and it is the second most abundant amino acid in the brain.

Glutamic Acid and GABA Especially Important to Brain Health

Glutamic acid causes neurons to fire. GABA keeps neurons from firing. Glutamine regenerates glutamic acid, and, indirectly, GABA, and can be used as an alternative fuel for the brain when glucose and ketones (from fat) are not available. All three amino acids play a major role in brain health.

Brain

Glutamic acid is especially abundant in the hippocampus, which organizes memories, and in the cranial nerves, which control muscle movements.

Increasing glutamic acid sometimes enables better movement and better integration of memories. Glutamic acid plays major roles in ADHD, Alzheimer's, autism, Parkinson's disease, and schizophrenia.

About sixty years ago, scientists discovered that GABA was a natural, non-narcotic remedy for anxiety. It is very useful in brain disorders that are accompanied by severe anxiety, such as alcoholism, chronic pain, chronic stress, sleep disorders, and Parkinson's disease.

You can't take a GABA supplement for brain health, because the blood-brain barrier is impermeable to this important chemical. Instead, the brain makes its own GABA from glutamic acid and pyridoxal phosphate, the activated form of vitamin B6. Pharmaceutical science has created nearly identical molecules that do pass through the blood-brain barrier, gabapentin (Neurontin) and tiagabine (Gabatril).

Inside the brain, GABA acts in much the same way as lithium, used for bipolar disorder, or Librium, a common muscle relaxant and tranquillizer. GABA accumulates in high concentrations in the hypothalamus, the "master gland" that controls the function of other endocrine glands.

Accumulation of GABA is especially important for the release of prolactin, the hormone that, in both sexes, increases the sense of satisfaction after sex. (The hormone dopamine stimulates desire for sex, and the hormone prolactin increases satisfaction after sex.)

The hypothalamus also regulates the responsiveness of the pancreas, thymus, and duodenum (the first section of the small intestine, nearest the stomach, which receives "recycling" from the liver) to regulatory signals from the brain.

Glutamine can be used to build proteins, but it can also be used as a fuel source in the brain and muscles. (About 25% of all the protein we eat winds up as amino acids used for fuel.)

There is no more abundant amino acid in the muscles or in the blood. And by regulating the amount of ammonia in the blood, glutamine also helps regulate the body's pH. The kidneys "alkalize" the body (actually, they just prevent acidity) with glutamine and calcium.

Glutamic Acid and Glutamine Can Come From Many Sources

As I mentioned earlier, glutamine is not an essential amino acid, because the body can make it from glutamic acid. But glutamic acid is not an essential amino acid, either. The human body can use arginine, aspartic acid, ornithine, proline, or alpha-ketoglutarate (a product from the breakdown of the antioxidant glutathione) to make glutamic acid.

It really does not make a lot of difference how your body gets its glutamic acid. There is a lot of glutamic acid in "high protein" foods and in certain vegetables, especially asparagus, bok choi, daikon radish, and ripe, red tomatoes. Wheat gluten, casein in dairy products, and gelatin contain even more, although gluten and casein often trigger food sensitivities.

FoodMilligrams Glutamic Acid in 200-Calorie Serving
Swanson Chicken Broth14250
Breaded Fried Chicken Breast (1 piece)8250
Mori-Nu Silken Tofu7695
Cottage Cheese7544
Steamed Shrimp7206
Steamed Lobster7134
Turkey (White Meat Only)7034
Spirulina6768
Breaded Fried Chicken Drumstick6758
Canned Tuna6565
Egg White6458
Chinese Cabbage (Bok Choi)6232
Canned Tomatoes5600
Asparagus5366
Ham5328
Lamb Shanks5098
Beef Sirloin5062
Veggie Burgers (Minus Buns)4167
Parmesan Cheese4035
Sun-Dried Tomatoes4033
Non-Fat Milk4021
Broccoli Raab4012
Sweet Peppers1643
Peas and Carrots1616
Kale1533
Sweet Corn Kernels1479
Green Beans1143
Celery1125
Potato Salad450
Baked Potato with Skin281
Pickle Relish228
Sweet Potato124

US Department of Agriculture Estimates of Glutamic Acid Content per 200-Calorie Serving of Foods Commonly Eaten in the United States

There is no minimum daily requirement of glutamic acid because people who consume enough calories to survive get enough glutamic acid in the process.

It is possible, however, to consume toxic amounts of glutamic acid, enough to cause nausea and vomiting. In the United States, this is most likely to happen at Thanksgiving, when people "stuff themselves" with turkey. It takes a huge amount of turkey, over 3000 calories in turkey alone providing about 100 grams of glutamic acid, to cause a toxic reaction, but many people manage to have it.

There is no glutamine in food, but the body can easily absorb glutamine from supplements. And in doses of up to about 20 grams (20,000 mg) a day, glutamine is helpful in many health conditions.

Glutamine for Alcoholism

In one study, alcoholics were given graduated doses of glutamine over a 90-day period.

  • In the first month, participants in the trial received three 2,000-mg doses of L-glutamine three times a day, totaling 6,000 mg a day.
  • In the second month, participants in the trial received 12,000 mg of L-glutamine a day.
  • In the third month, participants in the trial received 15,000 mg of L-glutamine a day.

Alcoholism

About 75% of alcoholics in the study reported better control over their drinking. Since glutamine can be used as brain fuel, scientists theorize that the extra glutamine helped drinkers think more clearly even when they reduced their consumption of sugar by reducing their consumption of alcohol.

Also, since alcohol is known to deplete the calming chemical GABA in the brain, it is possible that the glutamine supplements helped the brain generate more.

L-Glutamine and Alzheimer's Disease

Elevated levels of glutamic acid are found in autopsies of brains of people who died of Alzheimer's disease. The failure to convert glutamic acid to glutamine is known to cause death of brain cells. Giving supplemental glutamine is not as important as giving vitamin B6 or pyridoxal phosphate to help the brain detoxify glutamic acid into glutamine.

GABA and Anxiety

Chronic diseases make people anxious. On the level of brain chemistry, chronic disease states and chronic stress deplete GABA, which increases the firing of neurons in the brain. Tranquilizers like Xanax (alprazolam) work by increasing the sensitivity of neurons in the brain to the GABA already present in the brain. GABA supplements, on the other hand, bypass the need for tranquilizers and their side effects.

My feedback from readers is that the results GABA supplements can be hit and miss. Sometimes they work and sometimes they don't. When a GABA supplement causes fatigue, it probably is not the GABA itself. It would be inositol used as a secondary ingredient.

Stress

Also, the directions on some GABA supplements say to place the tablet under your tongue and let it dissolve so the GABA travels directly to your brain. I have found that when people have anxiety, they would rather chew the pill than carefully balance it under the tongue until it dissolves. The Life Extension Foundation (LEF) product is made without inositol and is chewable, also releasing GABA to circulation quickly. It may take as much as 4,000 mg a day to make a difference in symptoms.

GABA and Appetite Suppression

GABA has also been used as an experimental treatment for insulin-induced hyperphagia, which is a tendency to overeat when insulin levels are high, as in prediabetes or the early stages of type 2 diabetes.

Of course, if you can get your appetite under control, maybe you can also stop the progression of prediabetes or, with the right diet, even reverse early stages of type 2 diabetes.

There is no solid clinical evidence that GABA will suppress carbohydrate cravings and overactive appetite, but there are numerous anecdotal reports that 2,000 to 4,000 mg a day helps. As with anxiety, I would use the chewable inositol-free LEF product.

GABA, Glutamine, Branched-Chain Amino Acid and Diabetes

Some diabetes experience lowering of blood sugars after taking GABA, probably due to not wanting to eat as much.

The only way to know whether the product works for diabetes is to test blood sugars regularly, and this also protects against the potential for hypoglycemia.

Up to 4,000 mg of GABA per day may be helpful. Do not take this product if you do not test your blood sugars at least once a day.

It may also be helpful for type 2 diabetics to take post-workout drinks combining glutamine and the branched-chain amino acids isoleucine, leucine, and/or valine after weight-lifting or resistance exercise.

This combination of amino acids makes the muscles more responsive to insulin after exercise, and may increase and prolong the blood sugar lowering accomplished by exercise.

It is always possible for diabetics to lower their blood sugar levels too much, so it is best to do a finger stick at least the first time you use the drink and to have a glucometer and test strips handy at all times.

A good post-workout drink for this purpose is Recovery Orange, or just use the Life Extension Product Pure Plant Protein.

Glutamine and Intestinal Injuries

The intestine captures nutrients in villi, tiny pockets of cells that are constantly pushing outward to renew themselves. The intestine regenerates its lining as often as once every 6 days.

The most important amino acid for the proteins the intestine uses to build the villi is glutamine, and it is the first protein needed after a prolonged fast.

Crohn's disease, ulcerative colitis, and ischemic bowel disease cause constant stress on the intestine that may benefit from regular supplementation with 5 to 15 grams of glutamine daily, if cancer is not present. (See Frequently Asked Questions, below, for further information about glutamine and cancer.)

L-Glutamine and Bodybuilding

As I mentioned in my article on L-glutamine and bodybuilding, most bodybuilders don't need supplemental glutamine, because they get enough glutamic acid in their diets.

What About Dosing?

When glutamine is indicated, up to 15 grams per day may be helpful. No one should take more than 6,000 mg of GABA in any one day or more than 3,000 mg of GABA in any one dose.

Overdosing GABA can cause flushing in the face and shortness of breath that goes away in a few minutes. To make sure you don't have these problems, start taking just 500 mg a day and work up to 3,000 mg or your desired dosage.

Frequently Asked Questions

Q. Are there any supplements related to glutamine that you believe are more important than glutamine?

A. The body transforms glutamic acid into glutamine with the help of an enzyme that requires manganese. Farmers actually take care to make sure the soil contains manganese so you will typically get enough in food, but a multivitamin-multimineral supplement including manganese is a good idea.

Also the brain needs vitamin B6 in its active form, pyridoxal phosphate, to make GABA. People who take diuretics such as hydrochlorothiazide (HCTZ) or furosemide (Lasix) or who drink excessively may need supplemental B6.

Q. Are glutamine and monosodium glutamate the same thing?

A. No. You can get nasty gastrointestinal reactions to taking monosodium glutamate, also known as MSG.

Q. Is there glutamine in gluten?

A. Yes, but they are not the same substance.

Q. What about glutamine and cancer? Is it safe to take glutamine if you have cancer?

A. I wouldn't. Glutamine is an alternative energy source for cells all over the body, including cells in cancerous tumors. Aspartic acid can also be used by cancer cells for energy. Enzymes that break down glutamine or aspartic acid are used in some cancer treatments. I would avoid all amino acid supplements if I had active cancer.

Q. Can taking glutamine stimulate release of growth hormone?

A. No.

Q. Is glutamine safe for patients on kidney dialysis?

A. Since the idea of kidney dialysis is to remove excess nitrogen from the bloodstream and glutamine helps clear excess nitrogen from the bloodstream, it probably is-but people on dialysis don't need it. GABA, on the other hand, may help with mental symptoms related to dialysis, but you should talk about this with your nephrologist first.

Q. Do men and women have the same requirements for glutamine?

A. The only differences are due to muscle mass, men typically having greater muscle mass than women. But neither men nor women typically suffer glutamine deficiency.

Selected References:

Andrews FJ, et al. Glutamine: essential for immune nutrition in the critically ill. Br J Nutr 2002 Jan;87 (suppl 1):S3-8.

Antonio J, Ph.D., & Stout J., Ph.D. (Editors). Sports Supplement Encyclopedia Edition 1. Colorado: Nutricia Institute of Sports Science, 2002:132-3.

Ardawi MSM, et al. Glutamine metabolism in lymphocytes of rats. Biochem J 1983 Jun 15;212(3):835-42.

Ardawi MSM, et al. Metabolism in lymphocytes and its importance in the immune response. Essays Biochem 1985;21:1-44.

Atkins, Robert C., M.D. Dr. Atkin's Vita-Nutrient Solution. New York: Simon & Schuster, 1998:167-170.

Castell LM, et al. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol 1996;73(5):488-90

Castell LM. Can glutamine modify the apparent immunodepression observed after prolonged, exhaustive exercise? Nutrition 2002 May;18(5):371-375.

Hankard RG, et al. Effect of glutamine on leucine metabolism in humans. Am J Physiol 1996 Oct ;271 (4 Pt 1): E748-54.

Hendler, Sheldon S., Ph.D., M.D., & Rorvik, David, M.S. (Editors). PDR for Nutritional Supplements. New Jersey: Medical Economics Company, 2001:189-91.

Krebs H. Glutamine metabolism in the animal body. In: Mora J, Palacios R (Editors). Glutamine: metabolism enzymology and regulation. Academic Press, 1980:319-29.

Miller A. Therapeutic considerations of l-glutamine: A review of the literature. Altern Med Rev 1999 Aug;4(4):239-48

Neu J, et al. Glutamine: clinical applications and mechanisms of action. Curr Opin Clin Nutr Metab Care 2002 Jan;5(1):69-75.

Nieman D, et al. Exercise and immune function. Recent developments. Sports Med 1999 Feb;27(2):73-80.

O'Dwer ST, et al. Maintenance of small bowel mucosa with glutamine-enriched parental nutrition. J Parenter Enteral Nutr 1989 Nov-Dec;13(6):579-85.

Parry-Billings M, et al. A communicational link between skeletal muscle, brain and cells of the immune system. Intern J Sports Med 1990 May;11 (suppl 2):S122-8.

Reinaldo A., et al. Branched-chain amino acid supplementation and the immune response of long-distance athletes. Nutrition 2002 May;18(5):376-9.

Rennie MJ, et al. Amino acid transport during muscle contraction and its relevance to exercise. Adv Exp Med Biol 1998;441:299-305.

Rohde T, et al. Effect of glutamine supplementation on changes in the immune system induced by repeated exercise. Med Sci Sports Exerc 1998 Jun;30(6):856-62.

Talbott, Shawn M., Ph.D. A Guide to Understanding Dietary Supplements. New York: The Haworth Press, 2003:414-5.

Vante JP et al. Plasma-amino acid profiles in sepsis and stress. Ann Surg 1989 Jan;209(1):57-62.

Ziegler TR. Glutamine supplementation in bone marrow transplantation. Br J Nutr 2002 Jan;87(suppl 1):S9-15.

 

Written By Robert S. Rister
Robert Rister is the author of Healing without Medication and many other books that have been translated into eight languages. He is a chemist, a formulator of natural products, and a writer of consumer guides to getting the greatest value from natural health care.

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