Overview of L-Lysine HCl Injection
Dosage Strength of L-Lysine HCl Injection
L-Lysine HCl 100 mg/mL 30 mL Vial
L-lysine is an essential amino acid and is one of the key building block of muscle tissue. Human body is not able to synthesize lysine hence it needs to be acquired through diet or pharmaceutical supplementation. The recommended uptake of lysine in adults for regular biological functions are reported in the range of 12 to 45 mg·kg−1·d−1. Besides being essential for regular growth, this important amino acid participates in various vital biological processes like proteinogenesis, crosslinking of collagen polypeptides, uptake of essential mineral nutrients, and in the production of carnitine.12 Carnitine is established to play a crucial role in energy production by transporting long-chain fatty acids into the mitochondria and generated toxic compounds out from the cell.
A few conflicting studies also suggest its role for enhancement of athletic performance. Some patented preparations to increase growth hormone in the body and for stimulating overall growth, cell repair and regeneration also used L-lysine HCl as a major component.3 Lysine is also been recognised as an important precursor for glutamate synthesis, which works as a neurotransmitter in the vertebrate nervous system.4
L-lysine HCl can improve calcium absorption as well as improvise collagen quality and muscle well-being in general, and has helped patients suffering from osteoporosis. It contributes to a positive calcium balance by boosting intestinal calcium absorption and improving the renal conservation of the absorbed calcium.5 L-lysine HCl has also been suggested to be used in combination with minocycline hydrochloride, and metronidazole to treat reactive arthritis or bursitis.6 With common occurrence in young men and women, this disease can be caused by species of Shigella bacteria, species of Salmonella, genitourinary pathogens, Chlamydia trachomatis, Neisseria gonorrhea, Ureaplasma urealyticum, Streptococcus pyogenes etc.
According to a few research and patented concepts, L-lysine HCl alone or with other active pharma ingredients can be used to treat Herpes simplex I and II infections which are viral by origin.7
Usage of L-lysine HCl independently as well as in compounded form has been reported for nephroprotection when radioactive therapy is conducted especially against cancer. The proximal tubular uptake of radionuclide in the renal pathway is inhibited temporarily due to intravenous infusion of concomitant amino acid like lysine protecting the kidney from the radio toxicity.8
Treatment with L-lysine HCl has also been reported to be well tolerated and showed a significant decrease in positive symptoms of schizophrenia.9
Results have shown that administration by ingestion, especially with food, have much higher safety and lower possibility of adverse effects compared to injections.10
Mechanisms of Action
Among the indispensable amino acids, lysine is most strongly conserved and is less rapidly catabolised.11 Proteins of high biological value invariably have high lysine content. Most of the several essential functions of the lysine residue in cell and body proteins are largely related to its e-amino group. The positively charged lysine residue execute several important functions 10 in protein like;
- Receptor affinity: Lysine-rich regions in LDL particles are essential for their "docking" at hepatic LDL receptors.
- Endoplasmic reticulum retention: Mammalian cytoplasmic proteins at fresh synthesis have Specific lysine-containing motifs present at carboxyl groups which act as identifying tags allowing them to be retained in the endoplasmic reticulum.
- Muscle function: Titin is a large sized muscle protein which appears to control elasticity of different types of muscle. At its center, it contains a lysine-rich motif termed PEVK (abbreviated for proline, glutamate, valine, and lysine) which is believed to provide it the required elasticity acting as a "spring”.
It has a tendency to be stored in muscle tissues where it may act as a binding agent besides playing an important role in collagen formation and wound healing. 12
Lysine competes with other dibasic amino acids like arginine and ornithine for transportation not only in intestinal mucosa and renal tubule but also in mitochondria. 11 It antagonizes arginine by way of the following five mechanisms. Lysine functions as an antimetabolite of arginine. Lysine competes with arginine for reabsorption in the renal tubules thereby increasing arginine excretion in urine. Lysine also competes with arginine for transport into cells and at absorption sites in the intestines. If there is excess concentration of lysine in the gut, then absorption of arginine is decreased. Lastly, lysine induces enzyme arginiase, which degrades arginine.13
Excess lysine in rats has been shown to inhibit liver arginase activity. A study with of 0.5 mmol/kg intravenous infusion of L-lysine monohydrochloride11 caused an increase in plasma concentration of arginine with its increased leakage in urine which was inferred to be due to inhibitory effect of lysine on arginine activity. This allows lysine to control growth of herpes simplex virus which exploits the growth-promoting action of arginine.14 The competing nature of lysine against arginine and ornithine was also shown to interfere with the ammonia cycle and could lead to an increase in urinary ammonia.
Infusion of lysine with a dosage of 0.4 g/kg did not show blood pressure reduction or increase in extracellular fluid volume which are primarily markers of vasodilatation necessary for use against cardiovascular diseases, however, it did lead to an increase in plasma cyclic GMP as well as effected plasma electrolytes and atrial natriuretic peptide concentrations positively. It has also been shown to reduce stress by blocking the stress receptors and improving the cardio vascular response in general.15
L-lysine HCl injection has been reported to induce kaliuresis, i.e. elimination of significant amount of potassium in urine, when injected at a pH of 7.4. It is believed to achieve this by extracellular acidosis and intracellular alkalosis, thereby suppressing the kidney’s ability to secrete H+ ion and facilitating K+ secretion.16
L-lysine HCl has demonstrated effective use against herpes simplex virus. It has also been used prophylactically against the virus.18
Patients suffering from lysinuric protein intolerance suffer from poor physical development and other issues like hepatosplenomegaly, muscle weakness and osteoporosis due to their inability to absorb protein. Oral ingestion of lysine in these patients interferes strongly with their ammonia cycle. However, the intravenous pathway for infusion of lysine has been shown to be well tolerated and not interfere in the ammonia cycle of such patients unlike oral ingestion which leads to hyperammonemia due to absence of arginine and ornithine. 19
Lysine is almost entirely catabolised in the liver where it is utilised either for protein synthesis or oxidative metabolism. The enzyme responsible for its catabolism, lysine-ketoglutarate reductase is responsive to low dietary lysine levels and this essential amino acid is retained longer in the body using this mechanism.
When infused intravenously it tends to disappear rapidly from the blood11 with a good proportion being eliminated via the renal pathway. The remainder is expected to be processed in the liver and catabolized through the metabolic pathways similar to orally ingested lysine.
An increase in blood ammonia and urinary orotic acid was observed due to impaired ammonia disposal via the urea cycle and direct ammonia formation from lysine. The increase in orotic acid is due to competition for membrane transport between lysine and ornithine.
Lysine is a weak basic cationic amino acid and uses a plasma-membrane transport mechanism, called system y+. Lysine catabolism happens through two pathways but one of them which involves pipecolic acid as an intermediate is not known to be of much significance in humans.10 The major pathway involves interaction between ketoglutarate and lysine to form saccharopine which is further metabolised to a-amino adipic semialdehyde and glutamate via the action of enzyme saccharopine dehydrogenase.17 The semialdehyde undergoes oxidation and is finally decarboxylated to form acetoacetyl coenzyme A with carbon dioxide as a by-product which is ultimately eliminated via respiration.
Contraindications / Precautions
L-lysine is broken down in the liver and its supplementation needs an increased elimination of nitrogen from the body. Also, it is known to interference with urea cycle. Patients with impaired hepatic functionality or sensitivity to increase in blood ammonia concentrations are contraindicated for lysine.10
Pregnancy / Breastfeeding
Amino acids are generally recommended during pregnancy as per individual requirement. Study on amino acids requirement during pregnancy has suggested increased requirement of essential amino acids during advanced stage of pregnancy. 20 In a study lysine requirement in healthy pregnant women was determined to be 36.6 mg · kg−1 · d−1 during early stage and 50.3 mg · kg−1 · d−1 during advance stages of gestation.21
There is no evidence indicating ill effect from lysine supplementation during breastfeeding. No specific safety data for L-lysine hydrochloride infusion could be identified. Physician’s advice before use is recommended.
L-lysine HCl may have a nephrotoxic effect and should not be taken with aminoglycoside antibiotics due to the increased risk of nephrotoxicity. 22 L-lysine HCl in large doses can be nephrotoxic and single large doses of aminoglycosides alone are nephrotoxic. When the two are combined, the toxicity was found to be additive.
L-lysine HCl interacts with calcium supplementation. It enhances calcium absorption; hence the prescribed doses need to be revised accordingly.
Adverse Reactions/Side Effects
L-lysine hydrochloride has been proved to be safe as per most clinical studies with only mild side effects. No side effects necessitating the discontinuance of the drug were found during literature survey. However, most of the data available is for oral administration with limited data on injection route. In children between the age of 10-14 years, no serious adverse effect was noted when 14–22 g of L-lysine hydrochloride was infused intravenously to study its effect on urea cycle.11 Patients with cardiovascular or gall bladder disease should exercise caution in supplementation of lysine. Its long-term use can cause arginine deficiency.18
Studies with oral supplementation of lysine showed no significant adverse effects except upset stomach in some cases. Animal studies have shown that more than 3% oral ingestion of lysine lead to accumulation of triglycerides in liver.23
Other side effects of lysine supplementation may include headache, neutropenia, elevated liver enzymes, nausea, abdominal pain, and malaise. Warnings for antiviral drugs containing L-lysine hydrochloride API, generally include hypersensitivity, thrombolic thrombocytopenia purpura, hemolytic uremic syndrome, acute renal failure, and central nervous system involvement.
Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.
- 1. D. Tomé and C. Bos, “Lysine Requirement through the Human Life Cycle,” J. Nutr., vol. 137, no. 6, pp. 1642S-1645S, Jun. 2007.
- 2. E. Volpi, A. A. Ferrando, C. W. Yeckel, K. D. Tipton, and R. R. Wolfe, “Exogenous amino acids stimulate net muscle protein synthesis in the elderly.,” J. Clin. Invest., vol. 101, no. 9, pp. 2000–2007, May 1998.
- 3. S. H. Kim, Y. kyung Chung, J. Y. Chang, S. K. Lee, M. S. Lee, and S. K. Park, “Stable liquid formulation of human growth hormone,” US8409586B2.
- 4. F. Papes, M. J. Surpili, F. Langone, J. R. Trigo, and P. Arruda, “The essential amino acid lysine acts as precursor of glutamate in the mammalian central nervous system,” FEBS Lett., vol. 488, no. 1–2, pp. 34–38, Jan. 2001.
- 5. R. Civitelli, D. T. Villareal, D. Agnusdei, P. Nardi, L. V Avioli, and C. Gennari, “Dietary L-lysine and calcium metabolism in humans.,” Nutrition, vol. 8, no. 6, pp. 400–5.
- 6. E. L. J. Bonner and R. Hines, “Method for treatment of reactive arthritis or bursitis,” US6765000B2, 2004.
- 7. K. Gerzon, “Herpes treatment,” US4415590A, 1983.
- 8. M. Singh et al., “Medicinal Uses of L-Lysine: Past and Future,” Int. J. Res. Pharm. Sci., vol. 2, pp. 637–642, 2011.
- 9. C. Wass et al., “L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study.,” BMC Med., vol. 9, p. 40, Apr. 2011.
- 10. a. b. c. d. N. W. Flodin, “The metabolic roles, pharmacology, and toxicology of lysine.,” J. Am. Coll. Nutr., vol. 16, no. 1, pp. 7–21, Feb. 1997.
- 11. a. b. c. d. e. T. Kato, M. Sano, and N. Mizutani, “Inhibitory effect of intravenous lysine infusion on urea cycle metabolism,” Eur. J. Pediatr., vol. 146, no. 1, pp. 56–58, Jan. 1987.
- 12. S. Guo and L. A. Dipietro, “Factors affecting wound healing.,” J. Dent. Res., vol. 89, no. 3, pp. 219–29, Mar. 2010.
- 13. K. F. Harlow, “L-Lysine Hydrochloride: An Alternative Prophylactic Therapy Reducing the Recurrence Rate of Herpes Labialis,” Pacific University, 2015.
- 14. R. S. Griffith, D. C. DeLong, and J. D. Nelson, “Relation of Arginine-Lysine Antagonism to Herpes simplex Growth in Tissue Culture,” Chemotherapy, vol. 27, no. 3, pp. 209–213, 1981.
- 15. F. Vuvor and T. Ndanu, “Effect of lysine supplementation on cardiovascular response to stressors of households in two peri-urban communities in Ghana,” J. Heal. Res. Rev., vol. 3, no. 3, p. 92, 2016.
- 16. W. G. Walker, H. Dickerman, and L. J. Jost, “Mechanism of lysine-induced kaliuresis,” Am. J. Physiol. Content, vol. 206, no. 2, pp. 409–414, Feb. 1964.
- 18. a. b. V. J. Mailoo and S. Rampes, “Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence.,” Integr. Med. (Encinitas)., vol. 16, no. 3, pp. 42–46, Jun. 2017.
- 19. M. Lukkarinen, K. Näntö-Salonen, K. Pulkki, K. Mattila, and O. Simell, “Effect of lysine infusion on urea cycle in lysinuric protein intolerance,” Metabolism, vol. 49, no. 5, pp. 621–625, May 2000.
- 17. F. C. I. Fellows and M. H. R. Lewis, “Lysine metabolism in mammals,” Biochem. J., vol. 136, no. 2, pp. 329–334, Oct. 1973.
- 20. R. Elango and R. O. Ball, “Protein and Amino Acid Requirements during Pregnancy,” Adv. Nutr. An Int. Rev. J., vol. 7, no. 4, pp. 839S-844S, Jul. 2016.
- 21. M. Payne, T. Stephens, K. Lim, R. O. Ball, P. B. Pencharz, and R. Elango, “Lysine Requirements of Healthy Pregnant Women are Higher During Late Stages of Gestation Compared to Early Gestation,” J. Nutr., vol. 148, no. 1, pp. 94–99, Jan. 2018.
- 22. L. Bumpstead, “Long-term use of supplemental lysine - is it safe?,” J. Aust. Tradit. Soc., vol. 19, no. 4, pp. 228–231, 2013.
- 23. P. J. Garlick, “The Nature of Human Hazards Associated with Excessive Intake of Amino Acids,” J. Nutr., vol. 134, no. 6, pp. 1633S-1639S, Oct. 2004.