Ly7.0

L-Lysine Research

41 peer-reviewed studies · Evidence score: 7/10

Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis "Nutra NMA SCZ"

Fornaro M et al. • Molecular psychiatry (2025)

The Author(s), under exclusive licence to Springer Nature Limited.

Change (Standardized Mean Difference = SMD) in total symptomatology and acceptability (Risk Ratio = RR) were co-primary outcomes.
High heterogeneity (tau2 = 0.10, I2 = 55.9%) and global inconsistency (Q = 40.79, df = 18, p = 0.002) emerged without publication bias (Egger's test, p = 0.42).
Sarcosine improved negative symptoms (SMD = -0.65, 95%CI = -1.10; -0.19).

Meta-Analysisn=50

DOI

Metabolomics in Diabetic Retinopathy: A Systematic Review

Hou XW et al. • Investigative ophthalmology & visual science (2021)

This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.

This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.
Further research warranted to confirm findings

Systematic Review

DOI

The Impact of Amino Acids on Postprandial Glucose and Insulin Kinetics in Humans: A Quantitative Overview

Sloun BV et al. • Nutrients (2020)

The extracted information is publicly available and can serve multiple purposes such as computational modeling.

Oral ingestion of most individual AAs induced an insulin response, but did not alter glucose concentrations in healthy participants.
Specific AAs (i.e., leucine and isoleucine) co-ingested with glucose exerted a synergistic effect on the postprandial insulin response and attenuated the glucose response compared to glucose intake alone in healthy participants.
Oral AA ingestion as well as intravenous AA infusion was able to stimulate an insulin response and decrease glucose concentrations in T2DM and obese individuals.

Systematic Reviewn=55

DOI

Safety assessment of L-lysine oral intake: a systematic review

Hayamizu K et al. • Amino acids (2019)

Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96-1.07; p = 0.49); thus, no significant increase was observed. (UMIN000028914).

Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96-1.07; p = 0.49); thus, no significant increase was observed. (UMIN000028914).
The dose range of L-lysine in the selected studies was 16.8-17,500 mg/day, and the range of dosing period was 1-1095 days.
The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea.

Systematic Reviewn=71

DOI

Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review

Lakhan SE et al. • Nutrition journal (2010)

Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects.

Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence.
Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects.
There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders.

Systematic Reviewn=2,619

DOI

Comprehensive Safety Assessment of l-Lysine Supplementation from Clinical Studies: A Systematic Review

Hayamizu K et al. • The Journal of nutrition (2020)

The provisional no-observed-adverse-effect level in healthy human subjects was based on gastrointestinal symptoms and identified at 6.0 g/d.

The observed adverse events were mainly subjective gastrointestinal tract symptoms; however, the risk analysis for incidence of gastrointestinal symptoms was not statistically significant (risk ratio of 1.02).
The provisional no-observed-adverse-effect level in healthy human subjects was based on gastrointestinal symptoms and identified at 6.0 g/d.
The review protocol was registered at umin.ac.jp as UMIN000028914 before the beginning of the study.

Systematic Review

DOI

Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence

Mailoo VJ et al. • Integrative Medicine (2017)

Doses >3g/day improved patients' subjective disease experience; <1g/day was ineffective.

Higher doses (>3g) more effective
Low doses (<1g) ineffective
Best combined with low-arginine diet

Systematic Review

Effects of additional oral fosravuconazole l-lysine ethanolate therapy following inadequate response to initial treatment for onychomycosis: A multicenter, randomized controlled trial

Naka W et al. • The Journal of dermatology (2024)

A high complete cure rate is possible without additional F-RVCZ treatment when nail involvement decreases by ≥55% at week 24; however, when the reduction is <55% at week 24, additional F-RVCZ treatment should be considered to improve the cure rate.

Fosravuconazole l-lysine ethanolate (F-RVCZ), a fourth-generation azole antifungal agent with potent antifungal activity and few drug interactions, was highly effective in a clinical trial, with a complete cure rate of 59.4% at 48 weeks after treatment initiation.
Patients who demonstrated ≥55% reduction in nail involvement ratio at week 24 were included in Group X and followed up.
Patients with <55% reduction were randomly assigned to follow-up (Group A) or additional treatment (Group B) groups.

RCTn=318

DOI

Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study

Watanabe S et al. • The Journal of dermatology (2018)

The Journal of Dermatology

The efficacy and safety of F-RVCZ, compared with a placebo, were investigated in a multicenter, double-blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail.
The primary end-point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36-week post-treatment visit).
The complete cure rate at week 48 was significantly higher with F-RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001).

RCTn=153

DOI

A Dietary Supplement in the Management of Patients with Lumbar Osteochondrosis: A Randomized, Double-Blinded, Placebo-Controlled Study

Laky B et al. • Nutrients (2024)

In conclusion, this multi-nutrient supplement might not only stabilize the progression of lumbar osteochondrosis, but it might also potentially even increase IVD volumes as detected on MRIs.

Despite no significance regarding the distribution of Pfirrmann grade changes (improvement, no change, worsening; p = 0.259), in the supplement group, one patient achieved a three-grade improvement, and worsening of Pfirrmann grades were only detected in the placebo group (9.1%).
Disc degeneration according to Pfirrmann classifications remained stable during the 3-month intervention in both groups.
Furthermore, in-depth evaluations of MRIs showed significantly higher 3D-measured volume changes (increase) in the supplement (+740.3 ± 796.1 mm3) compared to lower 3D-measured volume changes (decrease) in the placebo group (-417.2 ± 875.0 mm3; p < 0.001).

RCT

DOI

Metabolic plasticity of the gut microbiome in response to diets differing in glycemic load in a randomized, crossover, controlled feeding study

Hullar MA et al. • The American journal of clinical nutrition (2025)

In healthy humans, diet impacts microbial metabolism and enzymatic activity but not the overall diversity of the gut microbiome.

Overall community structure measured by alpha and beta diversity was not significantly different across the diets, although diet did significantly increase the abundance of 13 of 161 genera (Padj < 0.05) and 5 species in the LGL diet and 7 species in the HGL diet.
In healthy humans, diet impacts microbial metabolism and enzymatic activity but not the overall diversity of the gut microbiome.
This emphasizes the relevance of dietary components in activating expression of specific bacterial genes and their impact on host metabolism.

Crossovern=69

DOI

A novel nutritional supplement containing amino acids and chromium decreases postprandial glucose response in a randomized, double-blind, placebo-controlled study

Östman E et al. • PloS one (2020)

Future studies should clarify, whether regular consumption of the supplement improves markers of disease or could play a role in a diet aiming at preventing the development of diabetes.

In the intention-to-treat-analysis (n = 60) the supplement resulted in a decreased venous blood glucose iAUC0-120min compared to placebo, mean (SE) of 68.7 (6.6) versus 52.2 (6.8) respectively, a difference of -16.5 mmol/L•min (95% CI -3.1 to -30.0, p = 0.017).
The Cmax for venous blood glucose for the supplement and placebo were 6.45 (0.12) versus 6.10 (<0.12), respectively, a difference of -0.35 mmol/L (95% CI -0.17 to -0.53, p<0.001).
In the per protocol-analysis (n = 48), the supplement resulted in a decreased Cmax compared to placebo from 6.42 (0.14) to 6.12 (0.14), a difference of -0.29 mmol/L (95% CI -0.12 to -0.47, p = 0.002).

RCTn=60

DOI

Dietary Intervention With a Targeted Micronutrient Formulation Reduces the Visual Discomfort Associated With Vitreous Degeneration

Ankamah E et al. • Translational vision science & technology (2021)

The findings of this study indicate improvements in vision-related quality of life and visual function of patients suffering from vitreous floaters after supplementation with a formulation of antioxidative and antiglycation micronutrients.

After supplementation, the active group reported a significant decrease in their visual discomfort from floaters (P < 0.001), whereas the placebo group had no significant change in their visual discomfort (P = 0.416).
At 6 months, there was a significant decrease in vitreous opacity areas in the active group (P < 0.001) and an insignificant increase in vitreous opacity areas in the placebo group (P = 0.081).
Also, there was a significant improvement in photopic functional contrast sensitivity with positive contrast polarity in the active group after supplementation (P = 0.047).

RCTn=61

DOI

Efficacy of a mouthwash containing ε-poly-L-lysine, funme peptides and domiphen in reducing halitosis and supragingival plaque: a randomized clinical trial

Shen S et al. • BMC oral health (2024)

The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe.

After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group.
Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P < 0.01).
The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe.

RCT

DOI

Pilot study of the effects of lisdexamfetamine on cocaine use: A randomized, double-blind, placebo-controlled trial

Mooney ME et al. • Drug and alcohol dependence (2015)

LDX did not significantly reduce cocaine use compared to PBO in the randomized sample.

Retention rates were higher though not significantly different in the PBO (71.4%) than the LDX condition (57.1%).
Compared to those in the PBO condition, those receiving LDX were more likely to report experiencing (ps<0.05) diarrhea (45.5% vs. 14.3%), headaches (45.5% vs. 9.5%), and anxiety (31.8% vs. 4.8%).
LDX did not significantly reduce cocaine use compared to PBO in the randomized sample.

RCTn=21

DOI

L-lysine as an adjunct to risperidone in patients with chronic schizophrenia: a double-blind, placebo-controlled, randomized trial

Zeinoddini A et al. • Journal of psychiatric research (2014)

Iranian registry of clinical trials (www.irct.ir): IRCT201202201556N33.

Clinical trial examining L-Lysine efficacy
Further research warranted to confirm findings

RCTn=72

DOI

Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise

Tsikas D et al. • International journal of molecular sciences (2022)

Plasma nitrite concentration turned out to be a more discriminant marker of NaNO3 ingestion than plasma nitrate (area under the receiver operating characteristic curve: 0.951 vs. 0.866, p < 0.0001 each).

At the end of the study, the plasma concentrations of homoarginine (hArg; by 24%, p = 0.0001), citrulline and ornithine (Cit/Orn; by 16%, p = 0.015), and glutamine/glutamate (Gln/Glu; by 6%, p = 0.0003) were higher in the NaNO3 group compared to the NaCl group.
The plasma concentrations of sarcosine (Sarc; by 28%, p < 0.0001), tyrosine (by 14%, p = 0.0051), phenylalanine (by 8%, p = 0.0026), and tryptophan (by 8%, p = 0.0047) were lower in the NaNO3 group compared to the NaCl group.
The plasma Kgaa/KhArg ratio was lower in the NaNO3 group compared to the NaCl group (1.57 vs. 2.02, p = 0.0034).

RCTn=8

DOI

Bioavailable Lysine Assessed Using the Indicator Amino Acid Oxidation Method in Healthy Young Males is High when Sorghum is Cooked by a Moist Cooking Method

Paoletti A et al. • The Journal of nutrition (2022)

Although the bioavailability of lysine in sorghum is high, its lysine content is limiting.

The bioavailability of lysine from sorghum was 94%.
Upon complementation with lentils, there was a decline in the oxidation of L-[1-13C] phenylalanine by 19% (P < 0.0495), reflecting an improvement in available lysine in the mixed meal due to increased lysine intake.
Although the bioavailability of lysine in sorghum is high, its lysine content is limiting.

RCTn=5

DOI

Steroids and L-Lysine Aescinate for Acute Radiculopathy Due to a Herniated Lumbar Disk

Oros M et al. • Medicina (Kaunas, Lithuania) (2019)

Among patients with acute radiculopathy due to a herniated lumbar disk a short course of IV dexamethasone or L-lysine aescinate resulted in pain improvement at 15th and 30th day.

Among patients with acute radiculopathy due to a herniated lumbar disk a short course of IV dexamethasone or L-lysine aescinate resulted in pain improvement at 15th and 30th day.
Dexamethasone may be preferable if a longer-term analgesic effect is needed.
Taking into account side effects of dexamethasone, a solution of L-lysine aescinate can be used to relieve pain symptoms.

RCTn=90

DOI

Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women

Bihuniak JD et al. • The Journal of nutrition (2014)

Larger and longer clinical trials are needed to clarify the possible benefit of arginine and lysine on calcium absorption.

There was no difference in calcium absorption between the diet supplemented with CaSR-AAAs (22.9 ± 2.0%) and the control diet (22.3 ± 1.4%) (P = 0.64).
However, calcium absorption tended to be greater during the DAA supplementation period (25.2 ± 1.4%) compared with the control diet period (22.3 ± 1.4%) (P < 0.10).
Intestinal calcium absorption was measured between days 5 and 6 using dual-stable calcium isotopes ((42)Ca, (43)Ca, and (44)Ca).

RCTn=14

DOI

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