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Valine is one of the three branched chain amino acids, although infrequently tested in isolation and possibly the least important BCAA for body composition and does not appear to have any known unique benefits associated with it.

Our evidence-based analysis on valine features 27 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Research Breakdown on Valine

1Sources and Structure


Valine is one of the essential amino acids (EAAs), and belongs to the subclass of branched chain amino acids with the other two EAAs leucine and isoleucine; similar to the latter two, valine is in this group due to having a branched side-chain which is common to these three amino acids and no others.


Valine is metabolized reversibly into the alpha-keto derivative known as 2-ketoisovalerate (via the branched-chain aminotransferase enzyme) and then irreversibly into isobutyryl-CoA (via the rate-limiting branched-chain α-keto acid dehydrogenase enzyme).[1]

Valine (both L and D isomers) are also known as a glucogenic amino acid (similar to isoleucine but not leucine) and can be converted into glucose in the liver.[2][3] The methyl carbons of valine appear to be utilized to create glucose and subsequently glycogen, and may produce some carbon dioxide as a byproduct.[4] This oxidation into glucose, similar to isoleucine, is increased following injury to skeletal muscle.[5]

1.3Valine deficiency

As valine is an essential amino acid, it can have a deficiency state.

A dietary elimination of valine in rats is able to induce lipid droplet formation in the liver (indicative of fatty liver formation)[6] with other symptoms of valine depletion including leukopenia, hypoalbuminemia, hair loss, and weight loss.[7] Restricting valine intake in swine tends to reduce food intake, which is aggravated with excess dietary leucine.[8]

However, valine depleted diets have been found to have a role in reducing tumor growth in rats.[7][6] It is thought that delivering a small amount of valine directly to the portal vein of the liver (practical only in clinical settings) may prevent fatty liver.[9]



Due to the link between athletes and Amyotrophic lateral sclerosis (ALS, albeit somewhat unreliable of an association that is still up for debate[10] with both positive[11][12] and null[13] evidence) investigation into agents possibly used by these athletes were conducted and BCAAs suspected.

The epidemiological link between ALS and athletes is somewhat weak and inconsistent, and even then the link between ALS and BCAA supplementation (hypothesized to be more commonly occurring in athletes) is currently unsupported

Valine has been noted to (in vitro) cause dose-dependent hyperexcitability in stimulated neurons (10-300μM incubation for 6 days) which is abolished by rapamycin (mTOR inhibitor) and suppress with Riluzole (sodium channel blocker),[14] and this was similar to the other two BCAAs but not amino acids without a branched side-chain (alanine and phenylalanine). As hyperexcitability of neurons is a pathological feature of ALS in humans[15][16] and of the mouse model which mimicks ALS (the G93A model[17][18]), it was thought that this induced hyperexcitability could be a mechanism of action. BCAA-induced hypersensitivity also appeared to be sodium channel dependent, and occurred in mice (B6SJL strain) raised from birth with 2.5% of the diet as BCAAs (1:1:1 ratio).[14]

Both in vitro and mouse models of BCAA incubation/supplementation fail to find alterations in resting membrane potential.[14]

It is plausible that BCAAs may increase neuronal excitation via mTOR dependent means, but the in vitro evidence used quite high concentrations while the mouse model was conducted from birth (which is usually more sensitive to neurological effects but may not accurately represent a non-infant consuming the agent). More research on this topic is needed

3Interactions with Glucose Metabolism


1mM valine incubated with a muscle cell not in the presence of insulin does not appear to modify glucose uptake,[19] yet oral supplementation of 0.3g/kg in rats prior to a glucose tolerance test causes an elevated level of glucose in serum 30 minutes into the test (but not 60-120 minutes) while leucine caused an increase at 60-120 minutes.[19]

Elsewhere in humans (either with type II diabetes or impaired glucose tolerance) intravenous valine has been noted to reduce fractional clearance rate of glucose.[20]

May induce a transient state of insulin resistance, similar to leucine but quicker acting

Valine has been noted to increase insulin secretion from the pancreas, but is approximately 3-9% (health persons and those with impaired glucose tolerance) as potent as glucose itself and weaker than L-arginine (46-61%), but in type II diabetics increases to 47% (Arginine at 180%).[20]

Valine may increase insulin secretion, but it is fairly weak in doing so


Valine appears to promote glycogen synthesis in muscle cells, but to a lesser degree (about 61% as potent) as leucine supplementation.[19]

4Skeletal Muscle and Performance


A study in neurons where the effects of valine were abolished by rapamycin suggest that valine can activate mTOR[14] and an increased protein content of P90S6K has been noted in these neurons incubated with valine (without rapamycin);[14] this protein is downstream of mTOR and activated when mTOR is activated.[21] 

Other studies in adipocytes have noted either inactivity[22] or activity significantly less potent than leucine in activatin mTOR, where 8mM is required for activation (leucine significantly active at 1mM)[23] and valine possessing an EC50 value of greater than 10mM.[23]

5Inflammation and Immunology


In dendritic cell cultures (antigen presenting cells) removal of BCAAs or valine (but not leucine or isoleucine) from the medium impairs maturation, CD83 receptor expression, and the ability of dendritic cells to stimulate monocytes.[24] 

Supplementation of L-Valine to healthy controls and cirrhotic patients (from hepatitis C) experience increase dendritic cell and monocyte interaction as well as increased IL-12 secretion[24] which has been noted to apply to persons with advanced cirrhosis[25] which is known to have impaired dendritic function.[26]

Valine supplementation is possibly immunostimulatory


One case study exists in a woman with advanced liver cirrhosis associated with hepatitis C where supplemental L-valine (3g a day for four weeks, then increasing sequentially by 3g every four weeks until 12g daily was consumed) was able to suppress serum HCV and α-fetoprotein (AFP); this suggests that valine may have an antiviral role.[27]


  1. ^ Nutraceutical Effects of Branched-Chain Amino Acids on Skeletal Muscle.
  2. ^ FONES WS, SOBER HA, WHITE J. The conversion of D-valine to glycogen in the rat. Arch Biochem Biophys. (1951)
  3. ^ FONES WS, WAALKES TP, WHITE J. The conversion of L-valine to glucose and glycogen in the rat. Arch Biochem Biophys. (1951)
  4. ^ FONES WS, WHITE J. The conversion of L-valine to glycogen and carbon dioxide in rats receiving p-dimethylaminoazobenzene. J Natl Cancer Inst. (1951)
  5. ^ Birkhahn RH, Robertson LA, Okuno M. Isoleucine and valine oxidation following skeletal trauma in rats. J Trauma. (1986)
  6. ^ a b Komatsu H, et al. Effect of valine-depleted total parenteral nutrition on fatty liver development in tumor-bearing rats. Nutrition. (1998)
  7. ^ a b Nishihira T, et al. Anti-cancer therapy with valine-depleted amino acid imbalance solution. Tohoku J Exp Med. (1988)
  8. ^ Gloaguen M, et al. Providing a diet deficient in valine but with excess leucine results in a rapid decrease in feed intake and modifies the postprandial plasma amino acid and α-keto acid concentrations in pigs. J Anim Sci. (2012)
  9. ^ Nishihira T, et al. Prevention of fatty liver and maintenance of systemic valine depletion using a newly developed dual infusion system. JPEN J Parenter Enteral Nutr. (1995)
  10. ^ Armon C. Sports and trauma in amyotrophic lateral sclerosis revisited. J Neurol Sci. (2007)
  11. ^ Chiò A, et al. Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain. (2005)
  12. ^ Belli S, Vanacore N. Proportionate mortality of Italian soccer players: is amyotrophic lateral sclerosis an occupational disease. Eur J Epidemiol. (2005)
  13. ^ Valenti M, et al. Amyotrophic lateral sclerosis and sports: a case-control study. Eur J Neurol. (2005)
  14. ^ a b c d e Carunchio I, et al. Increased levels of p70S6 phosphorylation in the G93A mouse model of Amyotrophic Lateral Sclerosis and in valine-exposed cortical neurons in culture. Exp Neurol. (2010)
  15. ^ Vucic S, Kiernan MC. Cortical excitability testing distinguishes Kennedy's disease from amyotrophic lateral sclerosis. Clin Neurophysiol. (2008)
  16. ^ Zanette G, et al. Changes in motor cortex inhibition over time in patients with amyotrophic lateral sclerosis. J Neurol. (2002)
  17. ^ Pieri M, et al. Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis. Exp Neurol. (2009)
  18. ^ van Zundert B, et al. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J Neurosci. (2008)
  19. ^ a b c Doi M, et al. Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. Biochem Biophys Res Commun. (2003)
  20. ^ a b Fasching P, et al. Insulin production following intravenous glucose, arginine, and valine: different pattern in patients with impaired glucose tolerance and non-insulin-dependent diabetes mellitus. Metabolism. (1994)
  21. ^ Tokunaga C, Yoshino K, Yonezawa K. mTOR integrates amino acid- and energy-sensing pathways. Biochem Biophys Res Commun. (2004)
  22. ^ Fox HL, et al. Amino acid effects on translational repressor 4E-BP1 are mediated primarily by L-leucine in isolated adipocytes. Am J Physiol. (1998)
  23. ^ a b Lynch CJ, et al. Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes. J Cell Biochem. (2000)
  24. ^ a b Kakazu E, et al. Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells. J Immunol. (2007)
  25. ^ Kakazu E, et al. Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis. Hepatology. (2009)
  26. ^ MacDonald AJ, et al. Monocyte-derived dendritic cell function in chronic hepatitis C is impaired at physiological numbers of dendritic cells. Clin Exp Immunol. (2007)
  27. ^ Kawaguchi T, et al. Valine, a branched-chain amino Acid, reduced HCV viral load and led to eradication of HCV by interferon therapy in a decompensated cirrhotic patient. Case Rep Gastroenterol. (2012)