The metabolic roles, pharmacology, and toxicology of lysine.

Flodin, Nestor W.

doi:10.1080/07315724.1997.10718644

Cited by 80 publications

(81 citation statements)

References 91 publications

(92 reference statements)

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“…The safety record of Lys use in humans is established (47), with most supplemental Lys being used to suppress herpes simplex (48) and to raise the biological value of dietary protein (10,49). Although it is too early to leap from rodent studies to the implications in humans, our data propose a therapeutic use of Lys in the treatment of stress-related intestinal disorders, in which 5-HT sensitization and concurrent anxiety disorder are diagnosed.…”

Section: Discussionmentioning

confidence: 99%

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

Smriga

Torii

2003

Proc. Natl. Acad. Sci. U.S.A.

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S tress and stress-induced anxiety play a major role in functional intestinal disorders (1). The stimulation of intestinal contraction and colonic transit are the most consistent patterns in the motility response of the intestinal tract to acute stress (2, 3); however, the stress-gut interactions are enormously complex (1). Both stress-induced anxiety and intestinal disorders are traced, from among other molecular pathologies, to the inappropriate responses of the central and͞or peripheral serotonin (5-HT) system (4, 5). Among the 5-HT receptors, the 5-HT 4 receptor plays a ''prostress'' role in the gut and throughout the body by mobilizing energy and facilitating behavioral, gastrointestinal, and cardiovascular stress responses (6, 7).5-HT 4 receptors are located within the cells and neurons of the gastrointestinal tract (6,8). Agonists on the 5-HT 4 receptor increase cholinergic transmission (9) and thus contract the smooth muscle in the rat and guinea pig ileum † and the human colon (11). Antagonists on the 5-HT 4 receptor do not affect normal, healthy gut function (12) but prevent the disturbances caused by stress (4) or high 5-HT activity (13). Thus, 5-HT 4 receptor antagonists are promising targets for the treatment of diarrhea-predominant irritable bowel syndrome (12). In addition to their effect on the gastrointestinal tract, 5-HT 4 antagonists block corticosteroid secretion in the adrenal cortex (14), 5-HTinduced tachycardia (15, 16), and stress-induced anxiety (17).However, the 5-HT receptor system is heterogeneous (18), and direct receptor targeting often causes side effects, such as diarrhea, gastric bleeding, and anxiety (19). Therefore, it is not surprising that few satisfying pharmacological treatments of stress-triggered, 5-HT-mediated intestinal disorders exist and that other therapeutic approaches, namely nutritional ones, are sought (20)(21)(22)). An interesting candidate to include in ''nutritional management'' of stress-related gastrointestinal disorders would be an essential amino acid, L-lysine (Lys). Lys blunted stress-induced anxiety in rats (23), whereas a dietary deficiency of Lys increased stress-induced colonic transit and anxiety, because of an enhanced transmission of 5-HT in the amygdala (24).Because the effects of Lys overlap with the ''antistress'' effects of the 5-HT 4 receptor antagonists (4), we hypothesized that dietary Lys could act as a partial antagonist on the 5-HT 4 receptors. The present study examined whether the provision of oral L-lysine might result in the blockage of 5-HT-mediated pathologies linked to stress exposure and͞or 5-HT sensitization in rats. Ileum contractions, stress-induced fecal excretion, diarrhea, anxiety, and tachycardia were monitored. The fractions obtained were washed once by centrifugation with 10-fold volume of the buffer, and the microsomal fraction was stored as receptor at Ϫ80°C until use. To determine the binding degree, the inhibition rate of Lys and a positive reference substance were calculated from binding of a tracer to a receptor. D...

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Section: Discussionmentioning

confidence: 99%

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

Smriga

Torii

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, the effective Lys dosage and even very high dietary Lys concentrations (up to 8.6 %) have obviously no adverse effects on arginine metabolism and on health of cats (Maggs et al, 2003;Fascetti et al, 2004). Also in humans high doses of L-Lys (1 -3 g d -1 ) seem to be effective against herpes simplex infections (Kagan, 1974); however, the results obtained in clinical studies are inconsistent (Thein and Hurt, 1984;Flodin, 1997).…”

Section: Recommendationsmentioning

confidence: 73%

“…Therefore, dietary lysine supplementation reduces stress-induced anxiety and diarrhea symptoms in rat but not heart rate and corticosterone levels, probably because in the rat the cardiovascular effects of 5-HT are mediated by 5-HT2 receptors (Centurion et al, 2002). (Flodin, 1997) In the cat, high doses of L-lysine (0.4 -0.5 g additional L-Lys per day; i.e. increase of around 0.5 -0.6 % of dietary lys) seem to reduce severity of conjunctivitis caused by feline herpes virus type 1 (FHV-1) and virus shedding (Maggs et al, 2000(Maggs et al, , 2003Stiles et al, 2002).…”

Section: Recommendationsmentioning

confidence: 99%

Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the safety and efficacy of L-lysine sulphate (Vitalys®Liquid and Dry) for all animal species

2007

EFSA Journal

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SUMMARYThe European Food Safety Authority (EFSA) received a request from the European Commission for an opinion on the safety and efficacy of Vitalys ® , an additive that consists of L-lysine sulphate and by products produced by fermentation by a specific strain of Corynebacterium glutamicum. The product is formulated as a liquid (minimum 25 % L-lysine) and a solid (minimum 44 % L-lysine).All the studies submitted have been made with Vitalys products which were not demonstrated to be identical to the product that is proposed to be placed on the market.The FEEDAP Panel concludes that Vitalys in both application forms (dry or liquid) contains bioavailable lysine. Vitalys is therefore considered a lysine source for all animal species.The applicant has provided two in vitro studies with Vitalys which may be considered to give sufficient reassurance that the product possesses no genotoxic potential in vitro. However, a 90-day study in rats has identified, in high dose treated animals, proliferative lesions in the urogenital tract which are not satisfactorily explained. In the absence of such an explanation the carcinogenic potential of the product cannot be excluded. Therefore the FEEDAP Panel is not in a position to conclude on the safety of Vitalys for the consumer.Although nothing in the data provided on the use of Vitalys in pigs and poultry suggested that Vitalys would pose a risk when used to satisfy lysine requirements, the data from the 90-day rat study does raise concerns for target animal safety. Safety and efficacy of L-lysine sulphate for all animal speciesThe EFSA Journal (2007) 522, Both dry and liquid Vitalys are presumed to be potential respiratory sensitizers. The evidence of dermal sensitisation by dry Vitalys confirms the potential for user risk. Both the dry and the liquid Vitalys are required to be labelled as an irritant and marked "Xi". Both products show no evidence of short term toxicity by inhalation. Without further data on the effects seen in rats after 90-days exposure, the potential for carcinogenicity cannot be excluded and the product should be handled accordingly.The FEEDAP Panel concludes that the use of Vitalys as feed additive is not expected to present a risk to the environment. The FEEDAP Panel recommends: i) that the Register entry should contain, under description, the exact strain (DSM 14764) of the Corynebacterium glutamicum used for fermentation; ii) that since the specification of the product tested in the 90-day study is within that of the product already authorised, the safety of that product should be reconsidered.

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“…Generally, deficiency in lysine may be due to several phenomena. It could be either an insufficient intake of lysine-rich diet, which is mostly the case in many developing countries, poor absorption, liver disease, and/or increased lysine utilization or loss in urine during acute and chronic infection (Flodin, 1997), or a lack of signal transduction in vision color. This defect is related to the level of vitamin A (Bhagavan and Ha, 2015).…”

Section: Discussionmentioning

confidence: 99%

Lysine and threonine plasma concentrations in Ivorian patients living with human immunodeficiency virus

Boyvin¹,

SÃ©ri²,

AkÃ³

et al. 2017

J. AIDS HIV Res.

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Côte d'Ivoire is one of the most affected countries in West Africa with HIV/AIDS, with a prevalence of 3.4%. Essential amino acids are needed by the organism as they play key roles in the immune system and they are supplied through diet. The objective of this study was to determine the plasma lysine and threonine status for better medical and nutritional management of patients living with HIV. This study involved 254 individuals: 127 HIV positive and 127 HIV negative (serving as controls) after confirmation of their HIV status through an HIV test (test DETERMINE® and GENIE II). Lysine and threonine were assayed using high performance liquid chromatography (HPLC) on plasma and CD4 lymphocyte count by the method of flow cytometry (FacsCalibur) from whole blood containing EDTA. This study showed that deficiency of lysine was more observed in male HIV infected individuals (66.7%) and threonine deficiency in female HIV infected individuals (17.1%) as compared to the controls subject. The amino acid concentrations as a measure of the degree of immunosuppression was significant for lysine (P = 0.0006) and not significant for threonine (P = 0.8640). The deficiency observed in HIV infected patients taking antiretrovirals is therefore probably due to viral infection and insufficient lysine intake in diet. The threonine concentration depends on the health condition of the subject.

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The metabolic roles, pharmacology, and toxicology of lysine.

Cited by 80 publications

References 91 publications

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the safety and efficacy of L-lysine sulphate (Vitalys®Liquid and Dry) for all animal species

Lysine and threonine plasma concentrations in Ivorian patients living with human immunodeficiency virus

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