Friday, July 6, 2012

Glutamine

Glutamine is one of my "favorite" supplements just because I can really see the benefits.
Usually at least 4 times a year, I'll go on a specific nutritional cleansing protocal where I'll personally take 80 g. of glutamine for 7 days straight.  I'll talk more about that some other time.


From The Way Up Newsletter

BENEFITS OF THE AMINO ACID L-GLUTAMINE
Physicians with an allopathic approach generally have their favorite armamentarium of medicines with which they are comfortable & achieving predictable results. Likewise holistic physicians have their favorite supplements which work to achieve desired benefits.
In my medical practice , L- Glutamine in one of the most frequently prescribed supplements. This is not surprising since the importance of Glutamine is demonstrated by the fact that it is the most abundant amino acid in circulation . The total body Glutamine levels are in the range of 100,000 mg. In a healthy person, the concentration of Glutamine in the blood is 3-4 times greater than all other amino acids. It is actively transported, & metabolized in nearly all tissue. Glutamine is a major fuel source & therefor energy source for the entire body. It is particularly concentrated in the brain, skeletal muscles, gut lining, lungs, heart, kidneys, & liver where it has multiple & critical functions.
During years of ordering blood tests to determine amino acid status, Glutamine is one of the amino acids most usually below normal. In fact in my patient population of those with either chronic illness or mood & cognitive symptoms it is rare to see normal levels. Amino Acid testing may be obtained from Great Smokies Diagnostic lab at http://www.gsdl.com or from Doctors Data Lab at http://www.doctorsdata.com as well as other labs.
WHERE CAN YOU GET L-GLUTAMINE?
We primarily obtain Glutamine from the conversion of Glutamic Acid from food, though some Glutamine is also in food. The average amount of Glutamine ingested daily in a health diet is from 5,000-8,000 mg. Those foods with the highest content are pork, poultry, eggs, & dairy proteins, wheat germ, oats & avocados. Or you can get it as a free form amino acid supplement.
Much of the dietary Glutamine is derived from the salt form of Glutamic Acid ( Glutamate). This converts to Glutamine with the action of the enzyme Glutamine Synthetase. Proper functioning of this enzyme requires adequate presence of pyridoxal-5-phosphate ( the active form of vitamin B6), manganese, & other vitamin/mineral co-factors. If these are not present in sufficient quantities there can be a Glutamine deficiency even in the presence of adequate dietary protein. Glutamate also converts to GABA. Glutamine can conversely convert back to Glutamate & to GABA with the help of the enzyme Glutaminase. They all can convert among themselves as needed & depending upon the presence of adequate enzymes & co-factors.
GLUTAMINE IMPROVES BRAIN FUNCTIONING
Glutamine, Glutamate, & GABA are all neurotransmitters which means they are chemical messengers in the brain without which the brain could not function. GABA is a calming neurotransmitter, Glutamate is a stimulating neurotransmitter, while Glutamine is a modulator of the inhibitory & excitatory activity of the other two.
Glutamine is highly concentrated in the brain , being 10-15 times more concentrated in the cerebro-spinal fluid than in the blood. It is an important fuel for the brain, & can provide adequate energy in the absence of glucose (the other major brain fuel). For this reason it is helpful with focus, concentration, memory, intellectual performance, alertness, attentiveness, improving mood, & eliminating brain fog & cloudiness. It is one of the first nutrients I prescribe when any of these symptoms are present.
In animal studies an inhibitor of the synthesis of Glutamine produced convulsions, & Alzheimer’s or senile dementia-type changes in the brain.
Research suggests Glutamine may protect the brain cells in situations of decreased oxygen supply. It also helps in the brain to detoxify ammonia.
Those prone to mania need to be careful with high doses of Glutamine for it can trigger mania, as can any antidepressant substance.
STABILIZES BLOOD SUGAR & DECREASES ALCOHOL CRAVINGS
Glutamine does this by several mechanisms. When the blood sugar is low, Glutamine suppresses insulin to stop the further decline of the sugar levels. It also stimulates glycogen (a stored form of glucose) to be released to help increase the blood sugar to normal levels.
Further, Glutamine is a glycogenic amino acid which means it can convert to sugar for energy production, a process called gluconeogenesis. It is the most important such substance.
These blood sugar stabilizing effects may partially explain why it decreases alcohol cravings, as well as sugar cravings. In studies with alcoholics, 2000-3000 mg 3 times daily decreased the desire to drink, decreased anxiety, & improved sleep. It works best given between meals. Has been used for this purpose in daily doses from 6000-15,000 mg in 3 divided doses. Use upon arising, mid-morning & mid-afternoon between meals.
Giving Glutamine to rats decreased their voluntary alcohol consumption by 34%. When the Glutamine was stopped, their alcohol consumption returned to baseline levels.
Additionally, Glutamine supports pancreatic growth & function, increases the production of pancreatic enzymes, increases pancreatic weight, DNA, & protein content. This would also stabilize blood sugar & indirectly improve overall nutritional status..
MAINTAINS HEALTH /FUNCTIONING OF THE LINING OF THE GUT
Glutamine increases the growth & absorptive capacity & is the main fuel source for the cells lining the intestinal tract. It is critical for the maintenance of proper gut metabolism, structure & function. The cells lining the small intestines consume Glutamine at a voracious rate, using up to 30% of the circulatory pool. Glutamine deficiency results in hypoplasia of the intestinal absorptive lining & dysfunction of the intestinal immune system. It helps maintain normal Secretory IgA an immune substance in the gut.
Studies show that Glutamine helps promote healing of impaired gut mucosa , such as with ulcers, ulcerative colitis, & Crohn’s Disease. It enhances bowel function when there has been partial removal of the intestines & improves overall survival in gut originated severe infection.
Certain bacteria, fungi, & parasites can also impair the intestinal lining disrupting the optimal intestinal barrier functioning, & causing increased intestinal permeability ( the leaky gut syndrome). With increased permeability there can be increased allergy reactions to foods, & increased predisposition to autoimmune problems.
Also, the bacteria which live in the GI tract can cross the disrupted mucosal barrier to infect other organs in a process called bacterial translocation, so Glutamine can help prevent this serious process.
IMPORTANT FOR MUSCLE FUNCTION & METABOLISM
The intracellular concentration of Glutamine in muscle is a regulator of muscle protein synthesis or muscle building & supports muscle glycogen accumulation. When there is Glutamine depletion, there is a breakdown in muscle. Studies indicate Glutamine counteracts steroid-induced muscle atrophy.
Skeletal muscle is the largest organ in the body accounting for approximately 30-40% of total body mass. A 150 pound male would ideally have about 60, 000 mg of Glutamine in these muscles. Free stores of Glutamine in muscles exceed those of any other amino acids( alanine & glycine are the other major muscle amino acids).
Surgical & injury trauma , infections, burns, stress, cancer, acidosis, & most major illnesses dramatically deplete & alter the production & interorgan flow of Glutamine causing movement of Glutamine out of the muscle , altering intestinal Glutamine metabolism, & also decreasing Glutamine blood levels. Under these circumstances the net Glutamine consumption exceeds the production & there is a decrease in muscle protein synthesis. This contributes to the muscle wasting in severe illness & trauma. Research has shown a statistically significant correlation between survival in severely infected patients & the muscle intracellular Glutamine concentration. Supplying Glutamine helps the metabolic processes associated with recovery.
HELPS WITH WOUND HEALING
The cells of connective tissue in the body use Glutamine for protein & nucleic acid synthesis & also for 30% of energy needs. These cells are called fibroblasts . Glutamine is required for their proliferation & is therefore critical in wound metabolism & healing.
HELPS MAINTAIN ACID/ALKALINE BALANCE
This is done by the production & metabolism of Glutamine in the kidneys. The more severe the acidosis is as in uncontrolled diabetes, starvation, kidneys disorders, decreased oxygen in the body, fluid & electrolyte loss , the greater the rate of Glutamine metabolism in the kidneys. When controlling acidosis the kidneys consume enormous amounts of Glutamine & deplete muscle & other stores . In acidotic conditions there is low Glutamine, low alanine & an increased production of ammonia.
In studies 2000 mg Glutamine produced a quick increase in plasma bicarbonate( which elevates alkaline reserve) & an increase in growth hormone.
IS CRITICAL IN PROTEIN METABOLISM
Glutamine is used in the liver & kidney to make urea & ammonia which are normal breakdown products of protein, which are then excreted. Glutamine participates in the detoxification of the ammonia.
Excessive Glutamine can elevate rather than decrease ammonia levels, as it should do. Such excessive dose would be in the range of 40,000 mg for a 150 pound person-way above any recommended amount.
GLUTAMINE & CANCER
In the area of tumor growth, the evidence is unclear. Glutamine is highly used by rapidly dividing cells such as blood cells, & those in the GI Tract & cancer cells. It provides the nitrogen precursor for the synthesis of purines & pyramidines essential to cell reproduction & division. So whether Glutamine enrichment in amounts required to maintain normal metabolic balance will accelerate tumor growth is not well known.
Research has provided varying information. One research report suggested Glutamine aggravated muscle tumor( sarcoma) but this was not found in research on fibrosarcoma. Other reports indicated Glutamine not only was beneficial for the patient with the tumor, but did not stimulate tumor growth. It may very well depend upon the type of the tumor.
The fear is that since the immune cells require Glutamine for proper functioning & since an illness such as cancer depletes the body of Glutamine, such depletion will impair immune function & interfere with the body fighting the cancer & associated infections-if Glutamine is not given.
Cancer bearing rats were able to maintain normal immune function when given Alanine-Glutamine enriched nutrition without increasing tumor size. According to Rifat Latifi M.D. in “Amino Acids In Critical Care & Cancer” the general consensus is “that an increased uptake of Glutamine by tumor cells does not necessarily result in an increase in tumor size & the absence of accelerated tumor growth may have been due to the maintenance of cell mediated immune reactions of the host”
As if this weren’t definitive enough, animal studies showed Glutamine enhanced the selectivity of antitumor drugs. It did so by helping to protect normal cells from the chemotherapy while making the tumor cells more sensitive to the chemo. Further, when Glutamine was given to patients undergoing abdominal or pelvic radiation therapy it protected the intestinal mucosa from injury, accelerated the healing of the radiated bowel & modulated the long term consequences of radiation.
So if you have cancer consult with your doctor whether or not Glutamine supplementation would be wise in your type of cancer.
MISCELLANEOUS BENEFITS
Glutamine is important for the synthesis of glutathione( an essential anti-oxidant) in the liver.
• Adequate Glutamine helps to protect the lungs from toxic insult.
• Glutamine is needed for RNA (Genetic messenger material) synthesis
• Essential for the synthesis of Vitamin B3 .
TOXICITY
Studies using high dose Glutamine have failed to demonstrate toxicity. However Glutamine should be avoided in cases of acute liver failure & kidney failure.
DOSAGE
As with any free form amino acid, Glutamine should always be taken with pyridoxal-5-phosphate which regulates the absorption, metabolism & conversion of all amino acids.
The usual dose recommended in my practice is 4000-5000 mg anywhere from 1-3 times daily between meals & not later than 3pm.
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Until next time,
Blessings to you,

Priscilla Slagle M.D

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