Different methionine to cysteine supplementation ratios altered bone quality of broilers with or without Eimeria challenge assessed by dual energy X-ray absorptiometry and microtomography.

Despite the acknowledged significance of nutrition in bone development, effects of methionine (Met) and cysteine (Cys) on bone quality remain under-researched, particularly during Eimeria challenge. We investigated the effects of different supplemental Met to Cys ratios (MCR) on bone quality of broilers under Eimeria challenge. A total of 720 fourteen-day old Cobb500 broilers were allocated into a 5 × 2 factorial arrangement. Five diets with Met and Cys supplemented at MCR of 100:0, 75:25, 50:50, 25:75, and 0:100 were fed to the birds with or without Eimeria challenge. Body composition was measured by dual energy x-ray absorptiometry, and the femur bone characteristics were assessed by microtomography. Data were analyzed by two-way ANOVA and orthogonal polynomial contrast. The results reaffirmed the detrimental effects of Eimeria challenge on bone quality. On 9 d post inoculation (DPI), significant interaction effects were found for whole body bone mineral content (BMC), lean tissue weight, and body weight (P < 0.05); in the nonchallenged group (NCG), these parameters linearly decreased as MCR decreased (P < 0.05). In the challenged group (CG), body weight and lean tissue weight were unaffected by MCR, and BMC linearly increased as MCR decreased (P < 0.05). For the cortical bone of femoral metaphysis on 6 DPI, bone mineral density (BMD) linearly increased as MCR decreased (P < 0.05). Bone volume to tissue volume ratio (BV/TV) in the CG linearly increased as MCR decreased (P < 0.05). On 9 DPI, BMC and TV linearly increased as MCR decreased (P < 0.05) in the NCG. BMD and BV/TV changed quadratically as MCR decreased (P < 0.05). For the trabecular bone of femoral metaphysis on 9 DPI, BV/TV, and trabecular number linearly increased as MCR decreased (P < 0.05) in the NCG. For the femoral diaphysis, BV, TV, BMC on 6 DPI, and BMD on 9 DPI linearly increased as MCR decreased (P < 0.05). In conclusion, this study showed that both Eimeria challenge and varying supplemental MCR could influence bone quality of broilers.

S-1-Propenylcysteine promotes IL-10-induced M2c macrophage polarization through prolonged activation of IL-10R/STAT3 signaling.

Atherosclerosis is a chronic inflammatory disease that may lead to the development of serious cardiovascular diseases. Aged garlic extract (AGE) has been reported to ameliorate atherosclerosis, although its mode of action remains unclear. We found that AGE increased the mRNA or protein levels of arginase1 (Arg1), interleukin-10 (IL-10), CD206 and hypoxia-inducible factor 2α (HIF2α) and decreased that of CD68, HIF1α and inducible nitric oxide synthase in the aorta and spleen of apolipoprotein E knockout mice. We also found that S-1-propenylcysteine (S1PC), a characteristic sulfur compound in AGE, increased the level of IL-10-induced Arg1 mRNA and the extent of M2c-like macrophage polarization in vitro. In addition, S1PC increased the population of M2c-like macrophages, resulting in suppressed the population of M1-like macrophages and decreased lipopolysaccharide-induced production of pro-inflammatory cytokines. These effects were accompanied by prolonged phosphorylation of the IL-10 receptor α (IL-10Rα) and signal transducer and activator of transcription 3 (STAT3) that inhibited the interaction between IL-10Rα and Src homology-2-containing inositol 5'-phosphatase 1 (SHIP1). In addition, administration of S1PC elevated the M2c/M1 macrophage ratio in senescence-accelerated mice. These findings suggest that S1PC may help improve atherosclerosis due to its anti-inflammatory effect to promote IL-10-induced M2c macrophage polarization.

Harnessing SeN to develop novel fluorescent probes for visualizing the variation of endogenous hypobromous acid (HOBr) during the administration of an immunotherapeutic agent.

By means of the formation of SeN, the ABT-Se and NDI-Se were developed to detect and visualize endogenous hypobromous acid (HOBr) in live cells. Specifically, the upregulation of HOBr was monitored by NDI-Se during the administration of an immunotherapeutic agent.

Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats.

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

A novel dendritic mesoporous silica based sustained hydrogen sulfide donor for the alleviation of adjuvant-induced inflammation in rats.

PURPOSE: S-propargyl-cysteine (SPRC), an excellent endogenous hydrogen sulfide (H2S) donor, could elevate H2S levels via the cystathionine γ-lyase (CSE)/H2S pathway both in vitro and in vivo. However, the immediate release of H2S in vivo and daily administration of SPRC potentially limited its clinical use. METHODS: To solve the fore-mentioned problem, in this study, the dendritic mesoporous silica nanoparticles (DMSN) was firstly prepared, and a sustained H2S delivery system consisted of SPRC and DMSN (SPRC@DMSN) was then constructed. Their release profiles, both in vitro and in vivo, were investigated, and their therapeutical effect toward adjuvant-induced arthritis (AIA) rats was also studied. RESULTS: The spherical morphology of DMSN could be observed under scanning Electron Microscope (SEM), and the transmission electron microscope (TEM) images showed a central-radiational pore channel structure of DMSN. DMSN showed excellent SPRC loading capacity and attaining a sustained releasing ability than SPRC both in vitro and in vivo, and the prolonged SPRC releasing could further promote the release of H2S in a sustained manner through CSE/H2S pathway both in vitro and in vivo. Importantly, the SPRC@DMSN showed promising anti-inflammation effect against AIA in rats was also observed. CONCLUSIONS: A sustained H2S releasing donor consisting of SPRC and DMSN was constructed in this study, and this sustained H2S releasing donor might be of good use for the treatment of AIA.

l-Cysteine Stimulates the Effect of Vitamin D on Inhibition of Oxidative Stress, IL-8, and MCP-1 Secretion in High Glucose Treated Monocytes.

Objective: Vitamin D deficiency is common in the general population and diabetic patients, and supplementation with vitamin D is widely used to help lower oxidative stress and inflammation. The cytokine storm in SARS-CoV2 infection has been linked with both diabetes and Vitamin D deficiency. This study examined the hypothesis that supplementation with vitamin D, in combination with l-cysteine (LC), is better at reducing oxidative stress and thereby, more effective, at inhibiting the secretion of the pro-inflammatory cytokines, Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in U937 monocytes exposed to high glucose concentrations. Methods: U937 monocytes were pretreated with 1,25 (OH)2 vitamin D (VD, 10 nM) or LC (250 µM) or VD + LC for 24 h and then exposed to control or high glucose (HG, 25 mM) for another 24 h. Results: There were significantly greater reactive oxygen species (ROS) levels in monocytes treated with HG than those in controls. Combined supplementation with VD and LC showed a more significant reduction in ROS (46%) in comparison with treatment with LC (19%) or VD (26%) alone in monocytes exposed to HG. Similarly, VD supplementation, together with LC, caused a more significant inhibition in the secretion of IL-8 (36% versus 16%) and MCP-1 (46% versus 26%) in comparison with that of VD (10 nM) alone in high-glucose treated monocytes. Conclusions: These results suggest that combined supplementation with vitamin D and LC has the potential to be more effective than either VD or LC alone in lowering the risk of oxidative stress and inflammation associated with type 2 diabetes or COVID-19 infection. Further, this combined vitamin D with LC/N-acetylcysteine may be a potent alternative therapy for SARS-CoV2 infected subjects. This approach can prevent cellular damage due to cytokine storm in comorbid systemic inflammatory conditions, such as diabetes, obesity, and hypertension.

TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation.

TRMU is a nuclear gene crucial for mitochondrial DNA translation by encoding tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase, which thiolates mitochondrial tRNA. Biallelic pathogenic variants in TRMU are associated with transient infantile liver failure. Other less common presentations such as Leigh syndrome, myopathy, and cardiomyopathy have been reported. Recent studies suggested that provision of exogenous L-cysteine or N-acetylcysteine may ameliorate the effects of disease-causing variants and improve the natural history of the disease. Here, we report six infants with biallelic TRMU variants, including four previously unpublished patients, all treated with exogenous cysteine. We highlight the first report of an affected patient undergoing orthotopic liver transplantation, the long-term effects of cysteine supplementation, and the ability of the initial presentation to mimic multiple inborn errors of metabolism. We propose that TRMU deficiency should be suspected in all children presenting with persistent lactic acidosis and hypoglycemia, and that combined N-acetylcysteine and L-cysteine supplementation should be considered prior to molecular diagnosis, as this is a low-risk approach that may increase survival and mitigate the severity of the disease course.

L-Cysteine Containing Vitamin Supplement Which Prevents or Alleviates Alcohol-related Hangover Symptoms: Nausea, Headache, Stress and Anxiety.

AIMS: Alcohol-related hangover symptoms: nausea, headache, stress and anxiety cause globally considerable amount of health problems and economic losses. Many of these harmful effects are produced by alcohol and its metabolite, acetaldehyde, which also is a common ingredient in alcohol beverages. The aim of the present study is to investigate the effect of the amino acid L-cysteine on the alcohol/acetaldehyde related aftereffects. METHODS: Voluntary healthy participants were recruited through advertisements. Volunteers had to have experience of hangover and/or headache. The hangover study was randomized, double-blind and placebo-controlled. Nineteen males randomly swallowed placebo and L-cysteine tablets. The alcohol dose was 1.5 g/kg, which was consumed during 3 h. RESULTS: The primary results based on correlational analysis showed that L-cysteine prevents or alleviates hangover, nausea, headache, stress and anxiety. For hangover, nausea and headache the results were apparent with the L-cysteine dose of 1200 mg and for stress and anxiety already with the dose of 600 mg. CONCLUSIONS: L-cysteine would reduce the need of drinking the next day with no or less hangover symptoms: nausea, headache, stress and anxiety. Altogether, these effects of L-cysteine are unique and seem to have a future in preventing or alleviating these harmful symptoms as well as reducing the risk of alcohol addiction.

Stability of N-Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of N,N-Diacetylcystine (DAC) Formation.

The ESPGHAN/ESPEN/ESPR-Guidelines on pediatric parenteral nutrition (PPN) recommend the administration of the semiessential amino acid (AA) cysteine to preterm neonates due to their biochemical immaturity resulting in an inability to sufficiently synthetize endogenous cysteine. The soluble precursor N-acetylcysteine (NAC) is easily converted into bioavailable cysteine. Its dimer N,N-diacetylcystine (DAC) is almost unconvertable to cysteine when given intravenously resulting in a diminished bioavailability of cysteine. This study aims to understand the triggers and oxidation process of NAC to DAC to evaluate possibilities of reducing DAC formation in standardized PPN. Therefore, different air volumes (21% O2) were injected into the AA compartment of a standardized dual-chamber PPN. O2 concentrations were measured in the AA solution and the headspaces of the primary and secondary packaging. NAC and DAC concentrations were analyzed simultaneously. The analysis showed that O2 is principally delivered from the primary headspace. NAC oxidation exclusively delivers DAC, depending on the O2 amount in the solution and the headspaces. The reaction of NAC to DAC being containable by limiting the O2 concentration, the primary headspace must be minimized during manufacturing, and oxygen absorbers must be added into the secondary packaging for a long-term storage of semipermeable containers.

A Previously Unknown Drug-Drug Interaction Is Suspected in Delayed Elimination of Plasma Methotrexate in High-Dose Methotrexate Therapy.

Background: High-dose methotrexate (HD-MTX) therapy is widely implemented for leukemia, osteosarcoma, and lymphoma. Although various measures have been taken to avoid toxicity from high serum MTX concentrations, there are many cases of delayed elimination of MTX. Objective: We suspected that delayed elimination of serum MTX was caused by unknown interactions between MTX and concomitant drugs. Methods: Concerning concomitant drugs in the case of delayed elimination of MTX, we performed screening tests in 35 patients who had undergone HD-MTX therapy. We then investigated the risk factors for delayed MTX elimination in 94 patients with leukemia, lymphoma, or osteosarcoma retrospectively. Results: The percentages of concomitant use of Stronger Neo-Minophagen C (SNMC), a glycyrrhizin preparation, and vincristine were higher in the delayed group. The percentage of delayed MTX elimination in patients receiving HD-MTX therapy was 41%. Multiple logistic regression analysis revealed that the concomitant use of SNMC solely was a significant risk factor for delayed MTX (odds ratio = 12.20; 95% CI = 1.06-139.84). Conclusion and Relevance: Concomitant use of SNMC was shown to be related to delayed elimination of serum MTX, and our results suggested a previously unknown drug-drug interaction between MTX and SNMC.

Sulfur-containing amino acid supplementation to gilts from late pregnancy to lactation altered offspring's intestinal microbiota and plasma metabolites.

Maternal nutrition during late pregnancy and lactation is highly involved with the offspring's health status. The study was carried out to evaluate the effects of different ratios of methionine and cysteine (Met/Cys: 46% Met, 51% Met, 56% Met, and 62% Met; maintained with 0.78% of total sulfur-containing amino acids; details in "Materials and methods") supplements in the sows' diet from late pregnancy to lactation on offspring's plasma metabolomics and intestinal microbiota. The results revealed that the level of serum albumin, calcium, iron, and magnesium was increased in the 51% Met group compared with the 46% Met, 56% Met, and 62% Met groups. Plasma metabolomics results indicated that the higher ratios of methionine and cysteine (0.51% Met, 0.56% Met, and 0.62% Met)-supplemented groups enriched the level of hippuric acid, retinoic acid, riboflavin, and δ-tocopherol than in the 46% Met group. Furthermore, the 51% Met-supplemented group had a higher relative abundance of Firmicutes compared with the other three groups (P < 0.05), while the 62% Met-supplemented group increased the abundance of Proteobacteria compared with the other three groups (P < 0.05) in piglets' intestine. These results indicated that a diet consisting with 51% Met is the optimum Met/Cys ratio from late pregnancy to lactation can maintain the offspring's health by improving the serum biochemical indicators and altering the plasma metabolomics profile and intestinal gut microbiota composition, but higher proportion of Met/Cys may increase the possible risk to offspring's health.

A diet rich in taurine, cysteine, folate, B12 and betaine may lessen risk for Alzheimer's disease by boosting brain synthesis of hydrogen sulfide.

The gaseous physiological modulator hydrogen sulfide (H2S) has recently been shown to exert a variety of neuroprotective effects. In particular, the treatment of transgenic mouse models of Alzheimer's disease (AD) with agents that release H2S aids preservation of cognitive function, suppresses brain production of amyloid beta, and decreases tau phosphorylation. The possible physiological relevance of these findings is suggested by the finding that brain and plasma levels of H2S are markedly lower in AD patients than matched controls. Hence, nutraceutical strategies which boost brain synthesis or levels of H2S may have potential for prevention of AD. The chief enzyme which synthesizes H2S in brain parenchyma, cystathionine beta-synthase (CBS), employs cysteine as its rate-limiting substrate, and is allosterically activated by S-adenosylmethionine (SAM). Supplemental taurine has been shown to boost expression of this enzyme, as well as that of another H2S source, cystathionine gamma-lyase, in vascular tissue, and to enhance plasma H2S levels; in rats subjected to hemorrhagic stroke, co-administration of taurine has been shown to blunt a marked reduction in brain CBS expression. Brain levels of SAM are about half as high in AD patients as in controls, and this is thought to explain the reduction of brain H2S in these patients. These considerations suggest that supplementation with cysteine, taurine, and agents which promote methyl group availability - such as SAM, folate, vitamin B12, and betaine - may have potential for boosting brain synthesis of H2S and thereby aiding AD prevention. Indeed, most of these agents have already demonstrated utility in mouse AD models - albeit the extent to which increased H2S synthesis contributes to this protection remains unclear. Moreover, prospective epidemiology has associated low dietary or plasma levels of folate, B12, and taurine with increased dementia risk. Rodent studies suggest that effective nutraceutical strategies for boosting brain H2S synthesis may in fact have broad neuroprotective utility, possibly aiding prevention and/or control not only of AD but also Parkinson's disease and glaucoma, while diminishing the neuronal damage associated with brain trauma or stroke.

Substitution of Dietary Sulfur Amino Acids by DL-2-hydroxy-4-Methylthiobutyric Acid Increases Remethylation and Decreases Transsulfuration in Weaned Piglets.

BACKGROUND: DL-2-hydroxy-4-methylthiobutyric acid (DL-HMTBA), an L-methionine (L-Met) hydroxyl analogue, has been suggested to be a dietary L-Met source. How dietary DL-HMTBA compared with L-Met affects whole-body L-Met kinetics in growing individuals is unknown. OBJECTIVES: We determined to what extent DL-HMTBA supplementation of an L-Met-deficient diet affects whole-body L-Met and L-cysteine (L-Cys) kinetics, protein synthesis (PS), and the L-Met incorporation rate in liver protein (L-MetInc) compared with L-Met and DL-Met supplementation in a piglet model. METHODS: Forty-five, 28-d-old weaned piglets (male, German Landrace) were allocated to 4 dietary groups: L-Met-deficient diet [Control: 69% of recommended L-Met plus L-Cys supply; 0.22% standardized ileal digestible (SID) L-Met; 0.27% SID L-Cys; n = 12] and Control diet supplemented equimolarly to 100% of recommended intake with either L-Met (n = 12; LMET), DL-Met (n = 11; DLMET), or DL-HMTBA (n = 10; DLHMTBA). At 47 d of age, the piglets were infused with L-[1-13C; methyl-2H3]-Met and [3,3-2H2]-Cys to determine the kinetics and PS rates. Plasma amino acid (AA) concentrations, hepatic mRNA abundances of L-Met cycle and transsulfuration (TS) enzymes, and L-MetInc were measured. RESULTS: During feed deprivation, L-Met kinetics did not differ between groups, and were ≤3 times higher in the fed state (P < 0.01). Remethylation (RM) was 31% and 45% higher in DLHMTBA than in DLMET and Control pigs, respectively, and the RM:transmethylation (TM) ratio was 50% higher in DLHMTBA than in LMET (P < 0.05). Furthermore, TS and the TS:TM ratio were 32% lower in DLHMTBA than in LMET (P < 0.05). L-MetInc was 42% lower in DLMET and DLHMTBA than in L-Met-deficient Control pigs, whereas plasma AA and hepatic mRNA abundances were similar among DL-HMTBA-, L-Met-, and DL-Met-supplemented pigs. CONCLUSIONS: In piglets, DL-HMTBA compared with L-Met and DL-Met supplementation increases RM and reduces the TS rate to conserve L-Met, but all 3 Met isomers support growth at a comparable rate.

The impact of different levels of cysteine on the plasma metabolomics and intestinal microflora of sows from late pregnancy to lactation.

Cysteine (Cys) is a semi-essential amino acid that is synthesized from methionine in mammals and affects their physiological state. This study aimed at investigating the effects of different Cys levels on the birth weight and survival rate of piglets as well as the plasma biochemical parameters, intestinal microbial diversity, and plasma metabolome of sows during late pregnancy. The results showed that 0.4% Cys supplementation increased the birth weight of piglets and decreased the calcium, triglyceride, and bilirubin levels in sows, whereas 0.5% Cys supplementation reduced the gamma-glutamyl transpeptidase levels and increased the serum glucose levels in sows at farrowing. Intestinal microbial analysis demonstrated that 0.4% Cys supplementation increased the diversity of fecal and intestinal microbiota compared with 0.5% Cys supplementation. In addition, plasma metabolomics identified 11 differential metabolites among the 0.4% Cys, 0.5% Cys, and control (basal diet) groups. The serum hypotaurine levels in sows increased by 0.4% and 0.5% Cys supplementation, and the serum acetylcysteine levels increased by 0.5% Cys supplementation; however, the differences in hypotaurine and acetylcysteine levels between the 0.4% and 0.5% Cys groups were not significant. Furthermore, Pearson analysis revealed a positive correlation between the hypotaurine levels and the abundance of Lactobacillus or Pseudobutyrivibrio and a negative correlation between the acetylcysteine levels and the abundance of Ruminococcaceae_UCG-014. Overall, the results indicated that 0.4% Cys supplementation increased the birth weight of piglets, increased the differential metabolites beneficial for combating antioxidative stress in embryos enhancing the intestinal microbial abundance in sows, and increased the diversity of fecal microbiota in sows. Thus, these findings suggest that 0.4% Cys supplementation is highly beneficial for maintaining the health of sows during late pregnancy.

High doses of phytase on growth performance and apparent ileal amino acid digestibility of broilers fed diets with graded concentrations of digestible sulfur amino acids.

Two experiments of the same design were conducted to determine the influence of phytase on performance and apparent ileal digestibility (AID) of amino acids in broilers fed graded concentrations of digestible sulfur amino acids (dgM+C). Cobb 400 male broilers were allocated to 1 of 10 diets consisting of 5 basal diets formulated at 75, 82, 89, 96, or 103% of the Cobb 400 dgM+C requirements for each feeding phase. Phytase was included in each basal diet at 0 or 2,000 FTU/kg. In experiment 1, 33 birds/pen from hatch to day 42 were fed a 2-phase feeding program with 10 replicate pens/diet. In experiment 2, there were 26 birds/pen from hatch to day 21 and 8 replicate pens/diet. Data were analyzed as a 5 × 2 factorial and means separated using orthogonal contrasts. In experiment 1, overall (hatch to day 42) feed intake (FI) decreased (linear, P < 0.05), body weight gain (BWG) increased (quadratic, P < 0.05), and feed conversion ratio (FCR) was improved (quadratic, P < 0.05) as dgM+C increased to ≥96% in the diet. Phytase increased (P < 0.05) BWG and improved (P < 0.05) FCR, regardless of the percent dgM+C in the diet. In experiment 2, overall (hatch to day 21) BWG increased (quadratic, P < 0.05), and FCR was improved (quadratic, P < 0.05) as dgM+C increased to ≥96% in the diet. Phytase increased FI (P < 0.05) and BWG (P < 0.05) and improved FCR (P < 0.05), regardless of the percent dgM+C in the diet. In the absence of phytase, the AID of all amino acids was greatest (quadratic, P < 0.05) in birds fed between 89 and 96% dgM+C. However, in the presence of phytase the AID of all amino acids was greatest (quadratic, P < 0.05) in birds fed 82% dgM+C and greater at all levels of dgM+C than birds fed diets without phytase (dgM+C × phytase, P < 0.05). In conclusion, phytase improved AID of all amino acids and improved growth performance regardless of the level of dgM+C in the diet.

Allicin Bioavailability and Bioequivalence from Garlic Supplements and Garlic Foods.

Allicin is considered responsible for most of the pharmacological activity of crushed raw garlic cloves. However, when garlic supplements and garlic foods are consumed, allicin bioavailability or bioequivalence (ABB) has been unknown and in question because allicin formation from alliin and garlic alliinase usually occurs after consumption, under enzyme-inhibiting gastrointestinal conditions. The ABB from 13 garlic supplements and 9 garlic foods was determined by bioassay for 13 subjects by comparing the area under the 32-h concentration curve of breath allyl methyl sulfide (AMS), the main breath metabolite of allicin, to the area found after consuming a control (100% ABB) of known allicin content: homogenized raw garlic. For enteric tablets, ABB varied from 36⁻104%, but it was reduced to 22⁻57% when consumed with a high-protein meal, due to slower gastric emptying. Independent of meal type, non-enteric tablets gave high ABB (80⁻111%), while garlic powder capsules gave 26⁻109%. Kwai garlic powder tablets, which have been used in a large number of clinical trials, gave 80% ABB, validating it as representing raw garlic in those trials. ABB did not vary with alliinase activity, indicating that only a minimum level of activity is required. Enteric tablets (high-protein meal) disintegrated slower in women than men. The ABB of supplements was compared to that predicted in vitro by the dissolution test in the United States Pharmacopeia (USP); only partial agreement was found. Cooked or acidified garlic foods, which have no alliinase activity, gave higher ABB than expected: boiled (16%), roasted (30%), pickled (19%), and acid-minced (66%). Black garlic gave 5%. The mechanism for the higher than expected ABB for alliinase-inhibited garlic was explored; the results for an alliin-free/allicin-free extract indicate a partial role for the enhanced metabolism of γ-glutamyl S-allylcysteine and S-allylcysteine to AMS. In conclusion, these largely unexpected results (lower ABB for enteric tablets and higher ABB for all other products) provide guidelines for the qualities of garlic products to be used in future clinical trials and new standards for manufacturers of garlic powder supplements. They also give the consumer an awareness of how garlic foods might compare to the garlic powder supplements used to establish any allicin-related health benefit of garlic.

S-Allyl-L-cysteine sulfoxide, a garlic odor precursor, suppresses elevation in blood ethanol concentration by accelerating ethanol metabolism and preventing ethanol absorption from gut.

Alcoholic beverages are enjoyed together with meals worldwide, but their excessive intake is associated with an increased risk of various diseases. We investigated whether S-allyl-L-cysteine sulfoxide (ACSO), a sulfuric odor precursor of garlic, suppresses elevation in plasma ethanol concentration by accelerating ethanol metabolism and preventing ethanol absorption from the gut in rats. ACSO and garlic extract with a high ACSO content (Garlic-H) suppressed elevation in concentrations of ethanol and acetaldehyde in plasma and promoted the activities of alcohol dehydrogenase and aldehyde dehydrogenase. However, ACSO and Garlic-H did not affect plasma acetate so much. Furthermore, we examined the change in plasma ethanol concentration by injecting ACSO or Garlic-H into the ligated stomach or jejunum together with ethanol solution. ACSO and Garlic-H suppressed the absorption of ethanol from the stomach and jejunum, but suppression in the jejunum was less than in the stomach. In conclusion, ACSO inhibits ethanol absorption and accelerates ethanol metabolism.

Effects of methionine plus cysteine inclusion on performance and body composition of liquid-fed crossbred calves fed a commercial milk replacer and no starter feed.

This experiment aimed to evaluate the effects of supplying 4 different inclusion levels of Met + Cys to crossbred liquid-fed calves on animal performance and body composition. Thirty-six Holstein-Gyr male calves were separated into 2 age groups: 16 calves, slaughtered at an age of 30 d, representing the physiological phase from 8 to 30 d, and 20 calves, slaughtered at an age of 60 d, representing the physiological phase from 30 to 60 d. At 8 d of age, the animals were randomly distributed among the experimental treatments: 4 Met + Cys inclusion levels (Met + Cys: 8.0, 8.7, 9.4, and 10.2 g/d), provided by an AA supplement added to 1.0 kg (as fed) of commercial milk replacer containing soy protein concentrate and wheat protein isolate reconstituted at 13.8% (dry matter basis). The diet was supplied without allowing leftovers and no starter feed was provided. The experimental diets were supplied without allowing orts, so that the dry matter, crude protein, and ether extract intakes were the same for all animals, independent of Met + Cys level. Total weight gain, average daily gain, gain composition, and body composition were evaluated for both age groups separately. Digestibility of organic matter, crude protein, and ether extract was lower for 8 to 30 d than for 30 to 60 d. The effect of Met + Cys levels on the digestibility of nutrients was not observed; there also was no significant interaction between physiological phase and Met + Cys levels. For the 8 to 30 d group, no responses in performance were observed according to the different Met + Cys levels, which indicates that 8.0 g/d of Met + Cys met the requirements for this physiological phase. The 30 to 60 d group responded positively to higher Met + Cys inclusion in the diet. In conclusion, an optimal Met + Cys dietary level to ensure best performance and protein gain ranges from 8.41 to 9.81 g/d.

Effects of the Usage of l-Cysteine (l-Cys) on Human Health.

This review summarizes recent knowledge about the use of the amino acid l-Cysteine (l-Cys) through diet, nutritional supplements or drugs with the aim to improve human health or treat certain diseases. Three databases (PubMed, Scopus, and Web of Science) and different keywords have been used to create a database of documents published between 1950 and 2017 in scientific journals in English or Spanish. A total of 60,885 primary publications were ultimately selected to compile accurate information about the use of l-Cys in medicine and nutritional therapies and to identify the reported benefits of l-Cys on human health. The number of publications about the use of l-Cys for these purposes has increased significantly during the last two decades. This increase seems to be closely related to the rise of nutraceutical industries and personalized medicine. The main evidence reporting benefits of l-Cys usage is summarized. However, the lack of accurate information and studies based on clinical trials hampers consensus among authors. Thus, the debate about the role and effectiveness of supplements/drugs containing l-Cys is still open.

Digestible methionine+cysteine in the diet of commercial layers and its influence on the performance, quality, and amino acid profile of eggs and economic evaluation.

This work aimed at evaluating the effects of 4 digestible Met+Cys levels on the diet of commercial layers and their influence on the productive performance, quality, and amino acid profile of eggs and economic viability of the activity. A total of 576 white Lohmann LSL-Lite layers was distributed into 6 replicates of 24 birds for each diet. The experimental design was completely randomized, with 4 treatments defined by levels evaluated in the feed (0.465, 0.540, 0.581, and 0.647%). The productive performance was measured for 30 weeks. The quality (34 and 50 wk old) and the amino acid profile of eggs (43 wk old) also were evaluated. A linear positive response was observed at higher Met+Cys levels for feed intake, number of eggs per housed bird, and digestible Met+Cys intake. Egg production, egg weight, egg mass, feed efficiency, and weight gain had their optimal values determined by the quadratic regression model at 0.638, 0.654, 0.647, 0.644, and 0.613% digestible Met+Cys, respectively. In the 34th wk, eggshell thickness decreased linearly at higher Met+Cys levels. In the 50th week, the optimal levels detected for eggshell thickness and percentage were 0.571 and 0.570% digestible Met+Cys, respectively. The percentages of proteins, branched-chain amino acids (leucine, isoleucine, and valine), histidine, and proline in eggs (albumen+yolk) showed a linear negative response in function of higher Met+Cys levels. Higher digestible Met+Cys levels (>0.630%) led to a good performance of layers, while lower Met+Cys levels improved the eggshell quality of layers in peak production. Optimal Met+Cys levels may change according to the price of the synthetic amino acid.