All Essential Benefits/Effects/Facts & Information

L-Alanyl-L-Glutamine (alanylglutamine) is a dipeptide molecule, consisting of L-glutamine and L-alanine, two amino acids.

Alanylglutamine is sometimes supplemented before prolonged physical exercise to enhance electrolyte absorption and improve endurance.

Preliminary rodent evidence suggests alanylglutamine is more effective at increasing muscular glutamine content after supplementation than Glutamine itself. This is because glutamine is absorbed by the liver and intestines after supplementation. Since alanylglutamine is a dipeptide molecule, it contains more than one amino acid for the intestines to absorb, allowing glutamine to reach the muscles.

Though alanylglutamine supplementation results in greater glutamine muscular content, this has not been shown to provide a performance enhancing effect.

Current evidence suggests alanylglutamine may be a more effective supplement than glutamine because of its increased stability and water solubility, but more research is needed to determine if it actually has an effect on performance.

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How to Take

Recommended dosage, active amounts, other details

Current studies on L-alanyl-L-glutamine use a dose of 1-3g a day. More research is needed to determine the optimal dose.

L-Alanyl-L-Glutamine supplementation may be similar to Glutamine supplementation, in terms of dose, timing, and purpose.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects alanylglutamine has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Fatigue Minor Very High See study
A possible minor antifatigue effect has been noted with higher doses of alanylglutamine in sports lasting an hour in length
Intestinal Permeability Minor Very High See study
In subjects with HIV who reported diarrhea in the last two weeks, supplementation of alanylglutamine was more effective than placebo (glycine) in reducing intestinal permeability
Plasma Glutamine Minor Very High See 2 studies
Higher doses (0.09-0.2g/kg) of oral alanylglutamine appear to increase plasma glutamine, and when compared to glutamine itself this dipeptide is more bioavailable
Reaction Time Minor Very High See study
A low dose, yet not the higher antifatigue dose, has once been noted to improve reaction time and shooting accuracy following an hour long basketball game
Adrenocorticotropic Hormone - Very High See study
ACTH does not appear to be differentially affected by alanylglutamine compared to water
Aldosterone - Very High See study
Aldosterone during exercise does not appear to be significantly influenced with alanylglutamine relative to water (both used in rehydration protocols)
Anaerobic Running Capacity - Very High See study
In a 75% VO2 max cycle until fatigue, rehydration with alanylglutamine failed to outperform water rehydration in overall time until exhaustion
Blood Glucose - Very High See study
No significant influence on blood glucose relative to control.
Blood Pressure - Very High See study
No significant interaction with blood pressure during exercise has been noted with acute supplementation of alanylglutamine
C-Reactive Protein - Very High See study
C-reactive protein does not appear to be influenced by alanylglutamine
CD4+ Lymphocytes - Very High See study
CD4+ Lymphocyte counts in subjects with HIV are not affected by alanylglutamine supplementation.
Cortisol - Very High See study
Cortisol is not influenced by alanylglutamine relative to water during and after an exercise trial.
Growth Hormone - Very High See study
The kinetics of growth hormone release from exercise are not influenced by alanylglutamine relative to water.
Heart Rate - Very High See 2 studies
No significant influence of alanylglutamine on heart rate during exercise relative to water
Hydration - Very High See study
Parameters of hydration including water retention do not appear to be modified with alanylglutamine when compared to the free amino acids or water.
Interleukin 6 - Very High See study
Interleukin-6 does not appear to be influenced during exercise when alanylglutamine is increased prior as rehydration (relative to water)
Lactate production - Very High See study
Lactate production and serum levels during a cycle to fatigue do not appear to differ between alanylglutamine and water
Lipid Peroxidation - Very High See study
Alanylglutamine does not appear to have any influence on lipid peroxidation (MDA) concentrations during exercise relative to glutamine or water control.
Power Output - Very High See study
When tested after exercise, alanylglutamine is no different than water in jump performance in athletes
Testosterone - Very High See study
Secretion of testosterone the day surrounding an exercise trial are not influenced by alanylglutamine any differently than water.
Vasopressin - Very High See study
Water and alanylglutamine rehydration protocols appear equal in influencing vasopressin kinetics during exercise.
Viral Load - Very High See study
When a high dose is given to subjects with HIV, their viral loads do not appear to be modified.
Weight - Very High See study
10 days supplementation of alanylglutamine in subjects with HIV does not modify overall bodyweight.

Studies Excluded from Consideration

Note: The HEM does not include trials using intravenous Alanylglutamine (used in clinical settings for nutrition)

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Scientific Research

Table of Contents:

  1. 1 Sources and Composition
    1. 1.1 Origin and Composition
    2. 1.2 Physicochemical Properties
  2. 2 Pharmacology
    1. 2.1 Absorption
    2. 2.2 Transportation in Serum
    3. 2.3 Peripheral Distribution
    4. 2.4 Metabolism
  3. 3 Interactions with Glucose Metabolism
    1. 3.1 Glycogen
  4. 4 Skeletal Muscle and Physical Performance
    1. 4.1 Myokines
    2. 4.2 REDOX and Acidity
    3. 4.3 Muscular Endurance
    4. 4.4 Heat Regulation and Hydration
    5. 4.5 Immunological Interactions
  5. 5 Interactions with Hormones
    1. 5.1 Androgens
    2. 5.2 Corticosteroids
    3. 5.3 Growth Hormones
  6. 6 Peripheral Organ Systems
    1. 6.1 Intestines

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1Sources and Composition

1.1. Origin and Composition

L-alanyl-L-glutamine (Alanylglutamine) is a dipeptide consisting of the amino acids L-Glutamine and L-alanine, which can be synthesized using bioengineered bacteria.[1][2] It is often used intravenously in clinical nutrition for tissue repair, since L-glutamine requirements are increased in rapidly dividing cells.[3] Because L-glutamine is readily hydrolyzed to glutamic acid in aqueous solution, dipeptides such as alanylglutamine are often used instead due to their increased stability.[3][4]

In animal models, alanylglutamine has been shown to help increase the absorption of electrolytes more than glutamine.[5]This suggests potential for use as an endurance-enhancing agent during extended cardiovascular exercise where hydration stress is a factor, a hypothesis that has been explored in humans.[6] Alanylglutamine is also better absorbed in the intestines than L-glutamine itself,[4] which underlies claims of increased bioavailability.

Alanylglutamine is a more stable and better orally absorbed form of L-glutamine that is often used intravenously in clinical nutrition.

1.2. Physicochemical Properties

Alanylglutamine is more stable than the free amino acid L-glutamine under acidic conditions and high temperatures. This is an important property for enteral and paternal solutions, where the high temperatures that are often employed for sterilization readily break down free-form L-glutamine.[7] Alanylglutamine also allows for better absorption of electrolytes and water,[5] which could underlie benefits over glutamine in instances of secretory diarrhea.[5] Alanylglutamine is highly water-soluble, (568g/L) greatly exceeding that of free-form glutamine (35g/L at 20°C).[7]


2.1. Absorption

Dipeptides including alanylglutamine are absorbed in the intestines via the proton-dependent dipeptide transporter Pept-1[8][9] which is also expressed to a small degree in colonocytes.[10] While exhibiting increased stability in solution, this dipeptide retains the benefits of free-form glutamine in nutritionally supporting the intestines in the rat.[11][12]

Alanylglutamine is absorbed by the Pept-1 dipeptide transporter in the intestines and colon.

In subjects who ingested either 60 mg/kg of L-glutamine or 89 mg/kg of alanylgutamine (equivalent to 60 mg/kg glutamine) in a fasted state, the average AUC of plasma glutamine was 124% higher than that of L-glutamine over the course of 4 hours post-ingestion, suggesting that alanylgutamine is more readily absorbed than free-form L-glutamine.[4]

In humans under fasted conditions, alanylglutamine is better absorbed than equivalent amounts of L-glutamine.

2.2. Transportation in Serum

When exercising rats given oral alanylglutamine for three weeks (1.5g/kg) were compared to those given a solution containing the free amino acids Glutamine (1g/kg) and L-alanine (0.67g/kg), both groups showed equivalent increases in serum glutamine levels (59-62% relative to water).[13]Similar observations were noted elsewhere in rats both at rest and with exercise when comparing alanylglutamine dipeptide versus the free amino acids[14][15] and when compared to equivalent doses of glutamine alone.[16]

Chronic ingestion studies in rats have noted that equivalent amounts of alanine and glutamine in free-form increase serum glutamine concentrations to a similar extent to alanylglutamine dipeptide.

One study in humans using oral solutions of alanylglutamine in water noted that 0.05g/kg failed to increase plasma glutamine any more than water alone, while a higher dose of 0.2g/kg increased plasma glutamine approximately 45 minutes after consumption (from approximately 700µM to 950µM; data estimated from graph) which was maintained during the estimated 15 minutes of exercise.[6] Elsewhere a peak in serum glutamine levels has been noted under fasting conditions with 0.09g/kg alanylglutamine increasing from 475µM to 735+/-147µM after 15-45 minutes, then returning to baseline after four hours in a time course paralleling that of L-glutamine (0.6g/kg) but reaching a higher Cmax value.[4]

One study has noted that low doses of alanylglutamine (50mg/kg) failed to increase serum glutamine while higher doses (90-200mg/kg) seem to increase glutamine in serum; the one acute comparative study noted better absorption with alanylglutamine but no chronic studies exist (to compare against the rat studies).

2.3. Peripheral Distribution

In exercising rats, orally administered alanlylglutamine (1.5g/kg) for three weeks increased glutamine concentration in the fast-twitch gastrocnemius muscle to a larger degree than a solution of the free amino acids Glutamine (1g/kg) and L-alanine (0.67g/kg).[13] This differential effect was not noted in the soleus or in plasma,[13] where both alanlylglutamine and equivalent amounts of the individual amino acids increased glutamine levels to a similar extent. Other studies have also failed to note any differences in glutamine levels in soleus or gastrocnemius with alanlylglutamine vs. glutamine supplementation,[14] suggesting that both may be effective at increasing tissue glutamine levels.

When compared to glutamine (1g/kg) alone in trained rats who swam to exhaustion, a similar dose of glutamine via the dipeptide (1.5g/kg) has been noted to increase muscular glutamine to a higher level in both soleus and gastrocnemius again with no differences in serum nor exercise performance.[16]

Both free form L-glutamine and alanylglutamine appear to midly increase concentrations of glutamine in the muscle of active rats, with alanylglutamine showing a trend to increase these concentrations slightly more than free glutamine.

Liver glutamine concentrations did not differ between chronic treatment groups.[16] In another study, liver glutamine levels only differed after exercise (where a drop was attenuated with the dipeptide relative to free amino acids[14]) whereas glutamate has been noted to be higher with the dipeptide compared to a combination of L-glutamine (1g/kg) and L-alanine (0.67g/kg) at rest only, the difference fading when exercise is utilized.[14]

The peak concentration of liver glutamine does not appear to differ between alanylglutamine and the free form amino acids when delivered orally in similar amounts. Alanylglutamine may increase glutamine levels to a greater extent than L-glutamine when prolonged exercise is introduced, however.

2.4. Metabolism

In rats exercised to fatigue who previously had three weeks continuous supplementation of either L-glutamine (1g/kg) or alanylglutamine (1.5g/kg), a higher plasma glutamate concentration with the dipeptide was noted,[16] although elsewhere no difference between the dipeptide and free glutamine was observed when L-alanine (0.67g/kg) was also used in the free peptide group.[15] Since glutamate is taken up from the blood and transformed in muscle to glutamine in the glutamine-glutamate cycle[17] via enzymatic conversion by glutamine synthetase,[18] increased glutamate levels with alanylglutamine have been proposed to reflect a higher intramuscular glutamine concentration; with increased tissue levels of glutamine there may be and less of a need for glutamate uptake to support intramusuclar glutamine stores.[16]

There may be an increase in serum glutamate levels secondary to an increased accumulation of glutamine in muscle tissue upon supplementation with alanylglutamine

Infusion of alanylglutamine under fasting conditions in humans appears to reverse a general efflux of glutamine and alanine from the muscle, instead causing a minor influx. While both the kidneys and splanchnic (liver and intestinal) tissues have a role in metabolizing alanylglutamine, it seems that renal elimination is preferred with the dipeptide.[19] This is in contrast to administration of the free amino acids L-glutamine and L-alanine, which are heavily metabolized by splachnic tissue.[19] The preference for renal elimination of the dipeptide is thought to be due to the fact that dipeptidase hydrolysis activity (which breaks alanylglutamine into L-glutamine and L-alanine) is primarily localized to the kidneys.[20][21]

Alanylglutamine appears to be more metabolized by the kidneys than the liver when compared to the free amino acids, which are heavily metabolized by the liver. This is thought to be due to the enzyme that hydrolyzes the dipeptide bond primarily existing in kidneys.

3Interactions with Glucose Metabolism

3.1. Glycogen

Three weeks supplementation of alanylglutamine (1.5g/kg), relative to glutamine itself (1g/kg) or water in rats subject to exhaustive exercise did not influence glycogen content of the gastrocnemius muscle while both amino acid groups noted an increase in liver glycogen relative to water.[16]

Limited animal evidence on glycogen levels in skeletal muscle fail to note any differences between alanylglutamine and the free form amino acids, although liver glycogen stores are increased with supplementation of both the dipeptide and free amino acid.

4Skeletal Muscle and Physical Performance

4.1. Myokines

Rats given either 0.1 or 0.5 g/kg alanylglutamine immediately post-exercise altered muscle cell signalling in a way that theoretically could lead to reduced muscle breakdown, while muscle synthesis pathways were relatively unaltered.[22] Specifically, phosphorylation was reduced for both AMPK and NF-kB p65 at both doses. The latter pathway has been seen to lead to muscle wasting in mice,[23], and the former is a major energy sensor in cells, which can signal muscle breakdown when activated[24].

4.2. REDOX and Acidity

Heat shock proteins are special stress-response proteins that function as molecular chaperones, protecting proteins from toxic aggregation to preserve function during the type of metabolic and oxidative stress[25][26][27][28] that is often experienced during intense exercise[29] In rats subjected to physical training given 1.5g/kg of either alanylglutamine or the free amino acids (1g/kg Glutamine and 0.67g/kg L-alanine) orally for three weeks, supplementation of the dipeptide increased expression of the heat shock proteins (HSP72 and HSP73) more than the free amino acids.[13] Differential effects on HSP subcellular localization were also noted with the dipeptide vs. free amino acids. Whereas the dipeptide increased cytosolic HSP levels, the individual amino acids appeared to be associated with lower cytosolic HSP levels and increased nuclear localization.[13] In the fast twitch gastrocnemius the opposing effects occurred, with the dipeptide causing more nuclear localization than the free amino acids, while both groups improved glutathione status to a similar degree.[13]

Heat shock proteins are special stress-response proteins that function as molecular chaperones, protecting proteins from toxic aggregation during metabolic and oxidative stress. Both alanylglutamine dipeptide and its constituent amino acids in free-form are robust activators of heat-shock proteins. Although potential differential effects on heat shock protein cellular localization have been noted with the dipeptide vs. free amino acids, this requires further investigation to be substantiated.

4.3. Muscular Endurance

Rat studies where the dipeptide was administered at 1.5g/kg for three weeks along with an endurance test failed to note any performance differences when the dipeptide was compared to either an equivalent amount of L-glutamine (1g/kg)[16] or that dose of L-glutamine paired with L-alanine (0.67g/kg).[13][14] A decrease in ammonia has been noted in rats subject to long duration exercise compared to water control, but the dipeptide again performed equally to a mixture of L-glutamine and L-alanine[15] with the only difference being a reduction in plasma glutamate (a serum reserve for glutamine production in muscle cells[17]).

In rodent research there is currently no noticeable improvement in performance seen with alanylglutamine that differs from taking the free forms of the amino acids.

In athletic women playing a competitive basketball game where the provided water included either a low or high concentration of alanylglutamine (1g or 2g per 500mL) it was noted that the inclusion of the low dose of the supplement relative to water improved shooting performance by 11.1% when tested after the game (alongside improved visual reaction time). This effect was not observed with the higher dose, which may be due to the dipeptide's abiliy to enhance rehydration.[30] Notably, self-reported fatigue appeared to be reduced with only the higher dose.[30] In another human study, a 75% VO2 max test to fatigue in trained men did failed to note an increase in time until failure with solutions of alanylglutamine (0.05g/kg and 0.2g/kg) relative to water.[6]

Human studies involving alanylglutamine have had mixed results; a high (but not low) dose of the dipeptide as been noted to reduce self-reported fatigue, with no effect on overall performance. Another study in trained men failed to note any effects on fatigue or otherwise.

4.4. Heat Regulation and Hydration

In a study where trained athletes reported to the lab in a dehydrated state and then rehydrated (over the course of 45 minutes) with either water or one of two solutions containing alanylglutamine (0.05g/kg or 0.2g/kg) it was found that, relative to water alone, alanylglutamine failed to increase performance on a 75% VO2 max test to fatigue.[6] Hormones involved in water regulation (vasopressin and aldosterone), serum electroytes, and overall plasma volume did not differ between groups.[6]

Another study involving trained female basketball players where dehydration was not present at the start of the study, alanylglutamine solutions (1g and 2g per 500mL) failed to increase weight acutely (attributed to water retention) any more than water alone. The low dose of the dipeptide did result in a modest increase in shooting performance, however.[30] Since dehydration has been shown to effect shooting performance in basketball players in several studies,[31][32][33] and alanylglutamine can increase water absorption,[6] it is possible that enhanced rehydration may account for the increased shooting performance in the alanylglutamine group.[30]

Although some studies have noted indirect evidence that is suggestive of a possible hydration-enhancing effect with alanylglutamine, current studies have failed to find any hydration increases over water alone. More evidence is required on this topic.

4.5. Immunological Interactions

A study with rats fed either alanylglutamine (1.5g/kg) or the combination of L-glutamine (1g/kg) with L-alanine (0.67g/kg) for three weeks alongside exercise noted that both groups performed equally in reducing creatine kinase and TNF-α levels in serum, with alanylglutamine reducing PGE2 to a slightly greater extent.[14]

In response to a 75% VO2 max test to fatigue, a rehydration protocol of alanylglutamine (0.05g/kg or 0.2g/kg) failed to differ from water in altering C-reactive protein or interleukin-6 concentrations either immediately after the trial or when tested a day after.[6]

The subtle immunological/antiinflammatory effects of alanylglutamine do not appear to be significant in vivo.

5Interactions with Hormones

5.1. Androgens

The alterations in testosterone concentrations seen during a test (75% VO2 max cycle to fatigue) did not differ in groups given 0.05g/kg or 0.2g/kg alanylglutamine relative to water.[6]

5.2. Corticosteroids

Acute and 24 hour increases in cortisol and its stimulating hormone (ACTH) resulting from a 75% VO2 max cycle to fatigue do not appear to be influenced by 0.05g/kg or 0.2g/kg alanylglutamine relative to water.[6]

5.3. Growth Hormones

The acute spike in growth hormone concentrations resulting from a 75% VO2 max cycle to fatigue does not appear to be influenced by 0.05g/kg or 0.2g/kg alanylglutamine relative to water.[6]

6Peripheral Organ Systems

6.1. Intestines

Oral ingestion of high doses of alanylglutamine (24g) over ten days in HIV-infected subjects appeared to improve intestinal absorption relative to Glycine placebo in subjects who reported diarrhea in the last two weeks.[34]

Scientific Support & Reference Citations


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  2. Tabata K1, Hashimoto S Fermentative production of L-alanyl-L-glutamine by a metabolically engineered Escherichia coli strain expressing L-amino acid alpha-ligase . Appl Environ Microbiol. (2007)
  3. Wernerman J Clinical use of glutamine supplementation . J Nutr. (2008)
  4. Harris RC1, et al L-glutamine absorption is enhanced after ingestion of L-alanylglutamine compared with the free amino acid or wheat protein . Nutr Res. (2012)
  5. Lima AA1, et al Effects of an alanyl-glutamine-based oral rehydration and nutrition therapy solution on electrolyte and water absorption in a rat model of secretory diarrhea induced by cholera toxin . Nutrition. (2002)
  6. Hoffman JR1, et al Examination of the efficacy of acute L-alanyl-L-glutamine ingestion during hydration stress in endurance exercise . J Int Soc Sports Nutr. (2010)
  7. Fürst P New developments in glutamine delivery . J Nutr. (2001)
  8. Adibi SA The oligopeptide transporter (Pept-1) in human intestine: biology and function . Gastroenterology. (1997)
  9. Alteheld B1, et al Alanylglutamine dipeptide and growth hormone maintain PepT1-mediated transport in oxidatively stressed Caco-2 cells . J Nutr. (2005)
  10. Ford D1, Howard A, Hirst BH Expression of the peptide transporter hPepT1 in human colon: a potential route for colonic protein nitrogen and drug absorption . Histochem Cell Biol. (2003)
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  12. Tazuke Y1, et al Alanyl-glutamine-supplemented parenteral nutrition prevents intestinal ischemia-reperfusion injury in rats . JPEN J Parenter Enteral Nutr. (2003)
  13. Petry ER1, et al Alanyl-glutamine and glutamine plus alanine supplements improve skeletal redox status in trained rats: involvement of heat shock protein pathways . Life Sci. (2014)
  14. Cruzat VF1, Rogero MM, Tirapegui J Effects of supplementation with free glutamine and the dipeptide alanyl-glutamine on parameters of muscle damage and inflammation in rats submitted to prolonged exercise . Cell Biochem Funct. (2010)
  15. Cruzat VF1, Tirapegui J Effects of oral supplementation with glutamine and alanyl-glutamine on glutamine, glutamate, and glutathione status in trained rats and subjected to long-duration exercise . Nutrition. (2009)
  16. Rogero MM1, et al Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise . Nutrition. (2006)
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  18. Wagenmakers AJ1, et al Carbohydrate supplementation, glycogen depletion, and amino acid metabolism during exercise . Am J Physiol. (1991)
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  22. Wang W1, et al L-Alanylglutamine inhibits signaling proteins that activate protein degradation, but does not affect proteins that activate protein synthesis after an acute resistance exercise . Amino Acids. (2015)
  23. Cai D1, et al IKKbeta/NF-kappaB activation causes severe muscle wasting in mice . Cell. (2004)
  24. Nakashima K1, Yakabe Y AMPK activation stimulates myofibrillar protein degradation and expression of atrophy-related ubiquitin ligases by increasing FOXO transcription factors in C2C12 myotubes . Biosci Biotechnol Biochem. (2007)
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  30. Hoffman JR1, et al L-alanyl-L-glutamine ingestion maintains performance during a competitive basketball game . J Int Soc Sports Nutr. (2012)
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  33. Baker LB1, et al Progressive dehydration causes a progressive decline in basketball skill performance . Med Sci Sports Exerc. (2007)
  34. Leite RD1, et al Improvement of intestinal permeability with alanyl-glutamine in HIV patients: a randomized, double blinded, placebo-controlled clinical trial . Arq Gastroenterol. (2013)