Oral L-lysine Research Articles

Oral L-lysine Treatment Ameliorates Proximal Tubular Damage in Mice with Alport Syndrome

Oral L-lysine Treatment Ameliorates Proximal Tubular Damage in Mice with Alport Syndrome

The effect of L-Lysine in recurrent herpes labialis: pilot study with a 8-year follow up

ABSTRACT Several treatments for recurrent herpes labialis have been tested, including intradermal snake venom, camphor compresses, psychiatric treatments, vitamin C and other vitamin complexes. Nowadays, topical and systemic retroviral drugs such as acyclovir, valacyclovir and vadarabina are the drugs of choice. However they are only effective for symptoms minimization of existing lesions, without eliminating the virus permanently. In this study an alternative treatment with oral L-lysine is presented. This is one of the eight essential not manmade amino acids which should be acquired through feeding since they are important for protein synthesis and organism development. It was observed a significant effect on the annual incidence reduction of recurrent herpes in 12 patients with 8-year follow up.

Multifactorial modulation of susceptibility to l-lysine in an animal model of glutaric aciduria type I

Glutaric aciduria type I is an inherited defect in l-lysine, l-hydroxylysine and l-tryptophan degradation caused by deficiency of glutaryl-CoA dehydrogenase (GCDH). The majority of untreated patients presents with accumulation of neurotoxic metabolites – glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) – and striatal injury. Gcdh−/− mice display elevated levels of GA and 3-OH-GA but do not spontaneously develop striatal lesions. l-lysine-enriched diets (appr. 235mg/d) were suggested to induce a neurological phenotype similar to affected patients. In our hands 93% of mice stressed according to the published protocol remained asymptomatic. To understand the underlying mechanism, we modified their genetic background (F1 C57BL6/Jx129/SvCrl) and increased the daily oral l-lysine supply (235–433mg). We identified three modulating factors, (1) gender, (2) genetic background, and (3) amount of l-lysine. Male mice displayed higher vulnerability and inbreeding for more than two generations as well as elevating l-lysine supply increased the diet-induced mortality rate (up to 89%). Onset of first symptoms leads to strongly reduced intake of food and, thus, l-lysine suggesting a threshold for toxic metabolite production to induce neurological disease. GA and 3-OH-GA tissue concentrations did not correlate with dietary l-lysine supply but differed between symptomatic and asymptomatic mice. Cerebral activities of glyceraldehyde 3-phosphate dehydrogenase, 2-oxoglutarate dehydrogenase complex, and aconitase were decreased. Symptomatic mice did not develop striatal lesions or intracerebral hemorrhages. We found severe spongiosis in the hippocampus of Gcdh−/− mice which was independent of dietary l-lysine supply. In conclusion, the l-lysine-induced pathology in Gcdh−/− mice depends on genetic and dietary parameters.

Is Dietary L-Lysine Effective for Treatment of Feline Ocular Disease Caused by Feline Herpesvirus-1?

Since the early 2000s, oral supplementation of L-lysine has been used to treat ocular disease in cats that was attributable to feline herpesvirus (FHV). Local (ocular) signs of disease that included conjunctivitis, blepharospasm, and ocular discharge were felt to improve when oral supplementation with a 250 or 500 mg bolus was administered once to twice daily. FHV-1 is considered the most common pathogen among other infectious agents, i.e., feline calicivirus and Chlamydophila felis, to cause ocular disease as well as infectious upper respiratory disease. It is felt that FHV-1 may establish a lifelong neural latency in 80% of infected cats. Early studies proposed that oral bolus administration of L-lysine reduced replication of FHV-1 by approximately 80% via antagonism of arginine, an essential amino acid for FHV-1 replication. Arginine is an essential dietary need for normal cat immune function. Studies evaluating serum arginine levels following oral L-lysine dose trials have found no adverse diminished levels of arginine. L-lysine is commercially available over the counter for treatment of the common cold sore in people that is caused by herpes simplex virus type 1. This formulation may be used for treatment of feline ocular disease by administering pills orally or by adding the contents of capsules to the diet. The generally recommended dose is a bolus of 500 mg, per os, twice per day in adult or average sized cats. Younger or smaller cats are typically fed 250 mg, twice per day. It has been shown that diets fortified with L-lysine that are consumed gradually throughout the day may not provide the immunologic effect necessary to reduce ocular disease and, specifically, infectious upper respiratory disease. Since the emergence of L-lysine as an effective and safe, long-term therapeutic for FHV-1 treatment, a number of commercially available products have become available on the veterinary market. By using palatable gels and treat products, administering a consistent and effective dosage regimen has become less problematic.

Characterization of proteinuria and tubular protein uptake in a new model of oral L-lysine administration in rats

Intravenous infusion of basic amino acids is used experimentally and pharmacologically to prevent renal proximal tubular uptake of filtered proteins. Intravenously injected L-lysine is rapidly cleared from plasma and the effect on tubular protein reabsorption is transient. To obtain a more sustained effect, we developed a model of oral L-lysine administration and characterized this model by analyzing urinary protein excretion and proximal tubule uptake of filtered proteins. Rats placed in metabolic cages were treated with 20 mmol/kg/6 h of L-lysine, glycine, or water. Urines were analyzed for proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and radioimmunoassay. Proximal tubule uptake of proteins and expression of apical membrane receptors were investigated by immunocytochemistry. In vitro uptake and receptor expression were studied using a yolk sac cell line. L-lysine administration produced increased urinary excretion of a large number of proteins while the effect on tubular accumulation of selected proteins was variable. L-lysine treatment induced changes in the localization of two receptors responsible for tubular endocytosis of filtered proteins. In conclusion, oral L-lysine treatment induced proteinuria, in particular albuminuria, as efficiently as previous reports on intravenous infusion. The effect on tubular protein accumulation was variable suggesting differential effects on tubular reabsorption and degradation of filtered proteins. Changes in tubular protein handling were accompanied by changes in the localization of the endocytic receptors, megalin, and cubilin. In vitro experiments supported the in vivo observations. The findings suggest that L-lysine may affect receptor trafficking in addition to possible effects on the direct binding of ligands to the receptors.

Metabolic interactions between restraint stress and L-lysine: the effect on urea cycle components.

We studied the effects of L-lysine on wrap-restraint stress-induced changes in ureagenesis. An exposure to wrap-restraint stress did not affect the plasma concentration of L-lysine, but did decrease plasma urea and arginine. Oral L-lysine (1 g/kg) blocked the effect of stress on ureagenesis, and enhanced the effect of stress on L-arginine. No influence of L-lysine were found in controls. The results imply a stress-specific, ureagenesis-stimulating effect of L-lysine, and suggest an increased requirement for L-arginine during the above conditions.

A molecular abnormality of keratin in ectodermal dysplasia

A 14-year-old Negro male was admitted to the hospital eleven times because of crises of abdominal pain, vomiting, ptyalism, profound muscle weakness, and lethargy. The diagnosis of pancreatitis was suggested by clinical findings and an elevated serum amylase and lipase and was supported by operative findings, including a pancreatic ductogram. Plasma and 24 hour urinary lysine on 8 separate occasions over a 2 year period were determined by ion-exchange column chromatography. The 24 hour urinary lysine output ranged from 288 to 1,144 rag. which is 6 to 20 times the upper limit of controls. The range for plasma lysine concentration was 2.4 to 7.1 nag. per cent in comparison to 1.2 to 4.6 mg. per cent obtained from 12 controls. Moderately elevated blood ammonia was also found during the crises. An oral L-lysine loading test (150 mg. per kilogram body weight) showed a rise from a value of 5.07 mg. at fasting level to 5.20 at 1 hour, 14.64 at 2 hours, 7.33 at 4 hours, and 6.7 mg. at 6 hours. In 2 controls the lysine values rose from a fasting level of 0.2, 1.6, to 4.9, 7.9 at 1 hour, 5.5, 7.2 at 2 hours, 3.5, 4.4 at 4 hours, and 1.4, 3.3 mg. per cent at 6 hours. Two hours and 45 minutes after the lysine load, the patient experienced a crisis identical to the previously described crises. The profound muscle weakness responded to a tensilon test. An exceptional opportunity for genetic study was provided by the remarriage of each parent and the resulting offspring. Fourteen members of the family were studied, of whom 6 showed abnormal findings. The present findings indicate that the disturbance in lysine metabolism is genetically determined. Hyperlysinemia, in turn, probably triggers the crisis as manifested by profound muscle weakness, ptyalism, and abdominal symptoms consistent with pancreatitis.