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Lysine

Lysine is an amino acid commonly paired with Vitamin C in many supplements. While an essential amino acid it does not hold much promise as a supplement beyond reducing the symptoms of herpes simplex.

Our evidence-based analysis on lysine features 41 unique references to scientific papers.

Kamal Patel
Research analysis led by .
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Examine.com Team
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How to Take Lysine

Recommended dosage, active amounts, other details

To supplement Lysine to reduce symptoms of herpes simplex, take up to 2g of lysine daily in divided doses with meals. It should be noted that ingesting supplemental L-arginine at this time will be counterproductive for this purpose and, if the diet is modified to increase lysine intake, then L-arginine should be controlled.

Scientific Research on Lysine

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1Sources and Structure

1.1Sources

Lysine initially saw usage not as a dietary supplement but, rather, a food additive. Vegetarian diets high in grains but low in legumes (a source of methionine) may run the risk of having suboptimal lysine intake and as such it was explored as a food additive for cereal grains as well as usage in farm animal feed.[2]

1.2Biological Significance

Lysine is an essential amino acid that serves as a building block for proteins in the body; as lysine cannot be synthesized in the body it must be consumed through the diet or supplementation. It is considered a dibasic amino acid alongside amino acids such as arginine, cysteine, and ornithine due to having a second basic group.

1.3Recommended Intake

According to a joint report from the World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO), and United Nations University (UNU) the basic level of lysine required for human health is 30mg/kg bodyweight;[3] or approximately 2.1 grams for a 70kg individual.

1.4Deficiency

Lysine is not a common deficiency as, among the essential amino acids, lysine appears to be the most well conserved in the body[2] based on rat studies where a lysine deficient diet produced the least overall nitrogen loss.[4][5]

1.5Formulations and Variants

Lysine monohydrochloride is a form of lysine that is sometimes used as a food additive in snacks as the addition of either lysine or Cysteine can reduce acrylamide formation during heating.[6]

2Pharmacology

2.1Absorption

Lysine is known to bind to some minerals such as Copper allowing easier transport into intestinal cells, as evidenced by a study using copper sulphate and finding presence of copper-lysine conjugates and allowing transport via amino acid transporters in vitro; that being said, efflux from the intestinal cells back into the gut was also noted to a high degree.[7]

When tested in rats, supplementation of lysine (1.5% of rat feed) does not appear to interfere with the absorption of either copper or iron when at normal dietary levels in one study where overall protein content was average (20% of rat feed)[8] despite a previous study noting an inhibitory effect of lysine on absorption of these two minerals in rats fed half the protein.[9] Zinc appeared to not be affected by lysine under the conditions where it affected copper and iron.[9]

Studies comparing the bioavailability of copper using either a lysine conjugate (copper-lysine) versus a more basic form (copper sulphate) have mixed effects in various tested animal species as to whether lysine aids in the absorption[10][11] or if the two are equally effective,[12][13] potentially related to how copper-lysine seems to form passively in intestinal cells from free copper.[7]

While Lysine appears to interact with some trace minerals to allow them easier access into intestinal cells, it does not appear to have consistent evidence as to whether the inclusion of lysine with these minerals (ex. copper or iron) increases their absorption or if there is no effect

2.2Neurological Distribution

Lysine appears to be transported across the blood brain barrier by cationic amino acid transporters (system y+) with a KM of 470 +/- 106μM in a manner that is voltage dependent but not sodium dependent. Lysine seems to use this transporter almost exclusively since uptake is blocked with this transporter and b0,+ seems to play no role. [14] This transporter is also used by the other cationic amino acids, arginine and ornithine, and in the presence of sodium chloride both alanine and serine.[14] It is the major transporter for lysine and arginine.[15] 

While at normal physiological concentrations competition between amino acids seems unlikely, saturating the transporter with lysine an inhibit the uptake of arginine[16] subsequently reducing nitric oxide production;[17] this was hypothesized to be a potential mechanism for how lysine supplementation could affect neurological function.[18]

Lysine is taken up into the brain by the same transporter that takes arginine into the brain, and it is thought that high doses of lysine could hinder the ability of arginine to produce nitric oxide in this tissue and thus indirectly influence cognition

3Neurology

4Interactions with Glucose Metabolism

4.1Insulin

When 0.1% lysine is added to the drinking water of diabetic rats, it failed to influence insulin concentrations despite affecting other parameters of glucose metabolism.[19]

4.2Insulin Sensitivity

In a metabolic ward study comparing a low lysine diet, defined as between 25-40mg/kg bodyweight (similar to the 30mg/kg requirement from the World Health Organization) versus a high lysine diet of 80mg/kg in adult males, it was found that the addition of extra lysine to the diet did not further increase insulin sensitivity when compared to the low lysine diet despite having a small positive effect on skeletal muscle tissue function.[20]

4.3Glycation

Glycation (non-enzymatic glycosylation) refers to the process of adding a sugar molecule onto a protein or lipid. This process can modify the function of proteins and is relevant to conditions with high blood sugar such as diabetes as it contributes to numerous complications.[21] Lysine is investigated for its role in glycation as it is claimed to be a molecular chaperone,[19] a group of molecules with various actions of which include stabilizing proteins.[22] Numerous small amino acids, methylamines, and sugars may have these properties secondary to being osmolytes.[22]

When testing lysine, the enzyme known as lysozyme experiences less glycation when incubated in the presence of lysine[1] and the glycation of albumin appeared to be reduced in diabetic rats given 0.1% lysine in their drinking water.[19]

Lysine shows preliminary promising in limiting glycation seen during states of high blood glucose, but the precise mechanism and potency relative to other options is unknown

4.4Type II Diabetes

When supplementation of lysine (1.5g twice daily) was given to type II diabetic patients who were also given Metformin and glibenclamide over three months it was found that the addition of lysine to these two drugs showed benefit in reducing fructosamine, AGEs, and fasting blood sugar while improving the content and activity of lysozyme slightly.[1]

5Inflammation and Immunology

5.1Virology

Lysine is protective against the symptoms of the herpes simplex (HSV) due to being an analogue of Arginine. Arginine is considered a nutrient to HSV and promotes replication[23] while the presence of lysine works in the opposite manner and can prevent replication by preventing the virus from using arginine.[24]

Lysine has been tested a few times as an oral supplement in subjects with recurrent herpes simplex (without any other major immunological conditions) with both failures[25][26] and success in reducing the frequency and intensity of flare-ups;[27][28] potentially a dose-related issue as one study finding success with 1,248mg of lysine monohydrochloride failed to find benefits with half the dose while the other successful study used 3,000mg daily.[27] Two studies on recurrent herpes labialis both using 1,000mg found a success[29] and a failure with secondary analysis finding less recurrences in some patients.[30] This effect does not appear to be curative as, when benefits are noted, these benefits dissipate within a week or two of stopping the lysine supplementation.[27][28]

One study did note that recurrence rates of symptoms appeared to be related to the amount of lysine in serum, with those above the predetermined threshold (165μM/L) having less recurrence than those below this threshold.[29]

Lysine appears to have a relation to recurrence, severity, healing time when it comes to herpes flare-ups. This appears to be somewhat related to the amount of lysine in your body and supplementation exceeding 2g a day seems to be associated with benefits. Increasing lysine in the diet also appears effective but requires Arginine to be limited

6Other Medical Conditions

6.1Schizophrenia

One study assessing the effects of lysine supplementation in schizophrenia found that supplementation of 6g lysine daily for four weeks alongside their prescribed medication resulted in a reduction in positive symptoms (assessed by PANSS, particularly the subscales for delusions and suspiciousness) with no significant effect on negative symptoms; there also appeared to be a benefit to problem solving skills and cognitive flexibility according to WCST compared to placebo.[18]

7Nutrient-Nutrient Interactions

7.1Arginine

L-arginine is an essential amino acid, and appears to be synergistic with L-lysine for increasing growth hormone.

1200mg of lysine (as hydrochloride) paired with 1200mg arginine (as 2-pyrrolidone-5-carboxylate) was able to increase secretion of insulin and somatotropin which promoted growth hormone secretion (peak value was 90 minute after ingestion and reached 7.94-fold baseline levels; there was no placebo for comparison), it was said to be synergistic as either agent alone at the same dose failed to promote growth hormone secretion, and measurements lasted 120 minutes.[31] 

A later study using 3g of L-arginine paired with 3g L-lysine twice daily (12g total) for 12 days in both youth and elderly men has failed to find appreciable increases in 24 hour AUC measurements of growth hormone[32] and this failure has been replicated in a study using 2g of the three amino acids L-Arginine, L-Ornithine, and L-Lysine in weight trained men.[33]

Although technically they appear to be synergistic (based on one study without a placebo control, so it has its flaws), this synergism is only acute and has failed to manifest in day-long GH measurements. Despite the synergism, the combination still may not be an appreciable way to increase growth hormone.

7.2Calcium

Lysine is thought to increase calcium absorption in humans. While some amino acids are capable of doing this through the calcium-sensing receptor (CASR) which can be acted upon by the likes of tryptophan, phenylalanine, and histidine (thought to partially explain why dietary protein improves calcium absorption[34][35]) lysine itself does not appear overly effective in this manner.[36] Lysine may be more effective practically, as one study supplementing a low protein diet (0.7g/kg) with a large amount of the dibasic amino acids lysine and arginine was able to increase calcium absorption and elimination to a greater degree than a diet with mixed amino acids or the aforementioned three that act on CASR.[37]

Studies assessing the effects of lysine find that adding 400mg of lysine to 3g calcium chloride in both healthy and osteoporotic women[38]

8Safety and Toxicology

8.1General

Supplementation of 25-40g lysine (as monohydrochloride) over 3-5 days, in studies using the supplement with mercurial diuretics, has found no major side-effects with only mild diarrhea and cramping being reported; these symptoms dissipated when the dosage was lowered and likely due to most lysine not being absorbed from the intestines.[39][40] 

While fatty liver has been noted in rats fed 5% lysine in the diet[41] it has been noted[27][28] that this equates to 90-100 times greater than combined normal supplementary doses (assumed 2g) and human diet. An LD50 value could not be reached after oral ingestion although an LD50 of 4mg/kg has been found to intravenous injection.[18][2]

Overall, oral supplementation of lysine appears to be highly safe. Large doses (25 grams or more over the course of a day) may cause intestinal distress and diarrhea which is alleviated by lowering the dose

References

  1. ^ a b c Mirmiranpour H et al.. The Preventive Effect of L-Lysine on Lysozyme Glycation in Type 2 Diabetes. Acta Med Iran. (2016)
  2. ^ a b c Flodin NW. The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr. (1997)
  3. ^ FAO/WHO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition. . (2007)
  4. ^ Gahl MJ et al.. Use of a four-parameter logistic equation to evaluate the response of growing rats to ten levels of each indispensable amino acid. J Nutr. (1991)
  5. ^ Said AK, Hegsted DM, Hayes KC. Response of adult rats to deficiencies of different essential amino acids. Br J Nutr. (1974)
  6. ^ Claeys WL, De Vleeschouwer K, Hendrickx ME. Effect of amino acids on acrylamide formation and elimination kinetics. Biotechnol Prog. (2005)
  7. ^ a b Gao S et al.. Amino acid facilitates absorption of copper in the Caco-2 cell culture model. Life Sci. (2014)
  8. ^ Bertinato J et al.. l-Lysine supplementation does not affect the bioavailability of copper or iron in rats. J Trace Elem Med Biol. (2016)
  9. ^ a b Mitchell GV, Jenkins MY. Effect of excess L-lysine on rat growth and on plasma and tissue concentrations of copper, iron and zinc. J Nutr Sci Vitaminol (Tokyo). (1983)
  10. ^ Aoyagi S, Baker DH. Copper-amino acid complexes are partially protected against inhibitory effects of L-cysteine and L-ascorbic acid on copper absorption in chicks. J Nutr. (1994)
  11. ^ Rabiansky PA et al.. Evaluating copper lysine and copper sulfate sources for heifers. J Dairy Sci. (1999)
  12. ^ Apgar GA, Kornegay ET. Mineral balance of finishing pigs fed copper sulfate or a copper-lysine complex at growth-stimulating levels. J Anim Sci. (1996)
  13. ^ Kegley EB, Spears JW. Bioavailability of feed-grade copper sources (oxide, sulfate, or lysine) in growing cattle. J Anim Sci. (1994)
  14. ^ a b O'Kane RL et al.. Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+. Am J Physiol Endocrinol Metab. (2006)
  15. ^ White MF, Gazzola GC, Christensen HN. Cationic amino acid transport into cultured animal cells. I. Influx into cultured human fibroblasts. J Biol Chem. (1982)
  16. ^ Closs EI et al.. Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B. Nitric Oxide. (1997)
  17. ^ Carter BW Jr, Chicoine LG, Nelin LD. L-lysine decreases nitric oxide production and increases vascular resistance in lungs isolated from lipopolysaccharide-treated neonatal pigs. Pediatr Res. (2004)
  18. ^ a b c Wass C et al.. L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study. BMC Med. (2011)
  19. ^ a b c Jafarnejad A et al.. The improvement effect of L-Lys as a chemical chaperone on STZ-induced diabetic rats, protein structure and function. Diabetes Metab Res Rev. (2008)
  20. ^ Unni US et al.. The effect of a controlled 8-week metabolic ward based lysine supplementation on muscle function, insulin sensitivity and leucine kinetics in young men. Clin Nutr. (2012)
  21. ^ Younus H, Anwar S. Prevention of non-enzymatic glycosylation (glycation): Implication in the treatment of diabetic complication. Int J Health Sci (Qassim). (2016)
  22. ^ a b William J. Welch, C. Randell Brown. Influence of molecular and chemical chaperones on protein folding. Cell Stress Chaperones. (1996)
  23. ^ Tankersley RW Jr.. Amino Acid Requirements of Herpes Simplex Virus in Human Cells. J Bacteriol. (1964)
  24. ^ Griffith RS, DeLong DC, Nelson JD. Relation of arginine-lysine antagonism to herpes simplex growth in tissue culture. Chemotherapy. (1981)
  25. ^ Simon CA et al.. Failure of lysine in frequently recurrent herpes simplex infection. Arch Dermatol. (1985)
  26. ^ DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Arch Dermatol. (1984)
  27. ^ a b c d Griffith RS et al.. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. (1987)
  28. ^ a b c McCune MA. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis. (1984)
  29. ^ a b Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg Oral Med Oral Pathol. (1984)
  30. ^ Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol. (1980)
  31. ^ Isidori A, Lo Monaco A, Cappa M. A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin. (1981)
  32. ^ Corpas E, et al. Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men. J Gerontol. (1993)
  33. ^ Fogelholm GM, et al. Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters. Int J Sport Nutr. (1993)
  34. ^ Dawson-Hughes B et al.. Comparative effects of oral aromatic and branched-chain amino acids on urine calcium excretion in humans. Osteoporos Int. (2007)
  35. ^ Busque SM et al.. L-type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. Am J Physiol Gastrointest Liver Physiol. (2005)
  36. ^ Arthur D. Conigrave et al.. L-Amino acid sensing by the extracellular Ca2+-sensing receptor. PNAS. (1999)
  37. ^ Bihuniak JD et al.. Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women. J Nutr. (2014)
  38. ^ Civitelli R et al.. Dietary L-lysine and calcium metabolism in humans. Nutrition. (1992)
  39. ^ Rubin AL et al.. The use of L-lysine monomydrochloride in combination with mercurial diuretics in the treatment of refractory fluid retention. Circulation. (1960)
  40. ^ Lasser RP et al.. L-lysine monohydrochloride. A clinical study of its action as a chloruretic acidifying adjuvant to mercurial diuretics. N Engl J Med. (1960)
  41. ^ Hevia et al.. Serum lipids of rats fed excess L-lysine and different carbohydrates. J Nutr. (1980)
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This page features 41 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page.

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