Metabolic Consequences of Supplemented Methionine in a Clinical Context.

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of Met may result in hyperhomocysteinemia (HHcy), which is a risk factor for cardiovascular disease. This review discusses the evidence generated in preclinical and clinical studies on the importance and potentially harmful effects of Met supplementation and elaborates on potential clinical applications of supplemental Met with reference to clinical studies performed over the past 20 y. Recently acquired knowledge about the NOAEL (no observed adverse effect level) of 46.3 mg · kg-1 · d-1 and the LOAEL (lowest observed adverse effect level) of 91 mg · kg-1 · d-1 of supplemented Met will guide the design of future studies to further establish the role of Met as a potential (safe) candidate for nutritional supplementation in clinical applications.

Açaí (Euterpe oleracea Mart.) beverage consumption improves biomarkers for inflammation but not glucose- or lipid-metabolism in individuals with metabolic syndrome in a randomized, double-blinded, placebo-controlled clinical trial.

Açaí (Euterpe oleracea Mart.) berries, characterized by high polyphenol concentrations (predominantly anthocyanins), have demonstrated anti-inflammatory and anti-diabetic activities. The study objective was to determine the modulation of lipid and glucose-metabolism, as well as oxidative stress and inflammation, by an açaí-beverage (containing 1139 mg L-1 gallic acid equivalents of total polyphenolics) in 37 individuals with metabolic syndrome (BMI 33.5 ± 6.7 kg m-2) who were randomized to consume 325 mL twice per d of a placebo control or açaí-beverage for 12 weeks. Anthropometric measurements, dietary intake, and blood and urine samples were collected at baseline and after 12 weeks of consumption. Two functional biomarkers, plasma level of interferon gamma (IFN-γ) and urinary level of 8-isoprostane, were significantly decreased after 12 weeks of açaí consumption compared to the placebo control (p = 0.0141 and 0.0099, respectively). No significant modification of biomarkers for lipid- and glucose-metabolism was observed in this study. Findings from this small pilot study provide a weak indication that the selected dose of açaí polyphenols may be beneficial in metabolic syndrome as only two biomarkers for inflammation and oxidative stress were improved over 12 weeks. Follow-up studies should be conducted with higher polyphenol-doses before drawing conclusions regarding the efficacy of açaí polyphenols in metabolic syndrome.

Tolerance to increased supplemented dietary intakes of methionine in healthy older adults.

Background: l-Methionine (Met) is an essential amino acid for humans and is important for protein synthesis and the formation of polyamines and is involved in the synthesis of many metabolites, including homocysteine. Free-Met supplements have been claimed to have multiple positive effects; however, it remains unclear what the exact tolerance level is. With aging, Met metabolism changes, and increased plasma homocysteine is more apparent. High plasma concentrations of homocysteine are assumed to be associated with a high risk of developing atherosclerosis.Objective: We estimated the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL) of supplemented, oral, free Met in healthy older adults by examining the increase in plasma homocysteine as the primary determinant.Design: We provided capsules with free Met to 15 healthy older adult subjects for 4 wk at climbing dosages of, on average, 9.2, 22.5, 46.3 and 91 mg · kg body weight-1 · d-1 with washout periods of 2 wk between each intake. Before, at 2 and 4 wk during, and 2 wk after each dosage, we studied a complete panel of biochemical blood variables to detect possible intolerance to increased Met intake. Plasma homocysteine and body composition were measured, and tolerance, quality of life, and cognitive function were assessed via questionnaires.Results: Plasma homocysteine was elevated with the highest dose of supplemented Met. The estimated NOAEL of supplemented Met was set at 46.3 mg · kg body weight-1 · d-1, and the estimated LOAEL of supplemented Met was set at 91 mg · kg body weight-1 · d-1 (on the basis of the actual intakes) in subjects independent of sex. No signs of intolerance were observed via questionnaires or other blood variables at the LOAEL. There were no meaningful changes in body composition.Conclusions: On the basis of plasma homocysteine, the NOAEL of supplemented Met intake is 46.3 and the LOAEL is 91 mg · kg body weight-1 · d-1 in healthy older adults. Both the NOAEL and LOAEL are not associated with meaningful effects on health and wellbeing. This trial was registered at clinicaltrials.gov as NCT02566434.

Effects of powdered Montmorency tart cherry supplementation on acute endurance exercise performance in aerobically trained individuals.

BACKGROUND: The purpose of this study was to determine whether short-term supplementation of a powdered tart cherry supplement prior to and following stressful endurance exercise would affect markers of muscle damage, inflammation, oxidative stress, and/or muscle soreness. METHODS: 27 endurance-trained runners or triathlete (21.8 ± 3.9 years, 15.0 ± 6.0 % body fat, 67.4 ± 11.8 kg) men (n = 18) and women (n = 9) were matched based on average reported race pace, age, body mass, and fat free mass. Subjects were randomly assigned to ingest, in a double-blind manner, capsules containing 480 mg of a rice flour placebo (P, n = 16) or powdered tart cherries [CherryPURE®] (TC, n = 11). Subjects supplemented one time daily (480 mg/day) for 10-d, including race day, up to 48-hr post-run. Subjects completed a half-marathon run (21.1 km) under 2-hr (111.98 ± 11.9 min). Fasting blood samples and quadriceps muscle soreness ratings using an algometer with a graphic pain rating scale were taken pre-run, 60-min, 24 and 48-h post-run and analyzed by MANOVA with repeated measures. RESULTS: Subjects in the TC group averaged 13 % faster half-marathon race finish times (p = 0.001) and tended to have smaller deviations from predicted race pace (p = 0.091) compared to P. Attenuations in TC muscle catabolic markers were reported over time for creatinine (p = 0.047), urea/blood urea nitrogen (p = 0.048), total protein (p = 0.081), and cortisol (p = 0.016) compared to P. Despite lower antioxidant activity pre-run in TC compared to P, changes from pre-run levels revealed a linear increase in antioxidant activity at 24 and 48-h of recovery in TC that was statistically different (16-39 %) from P and pre-run levels. Inflammatory markers were 47 % lower in TC compared to P over time (p = 0.053) coupled with a significant difference between groups (p = 0.017). Soreness perception between the groups was different over time in the medial quadriceps (p = 0.035) with 34 % lower pre-run soreness in TC compared to P. Over the 48-h recovery period, P changes in medial quadriceps soreness from pre-run measures were smaller compared to TC. CONCLUSION: Results revealed that short-term supplementation of Montmorency powdered tart cherries surrounding an endurance challenge attenuated markers of muscle catabolism, reduced immune and inflammatory stress, better maintained redox balance, and increased performance in aerobically trained individuals.

Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance.

BACKGROUND: Creatine monohydrate (CrM) and nitrate are popular supplements for improving exercise performance; yet have not been investigated in combination. We performed two studies to determine the safety and exercise performance-characteristics of creatine nitrate (CrN) supplementation. METHODS: Study 1 participants (N = 13) ingested 1.5 g CrN (CrN-Low), 3 g CrN (CrN-High), 5 g CrM or a placebo in a randomized, crossover study (7d washout) to determine supplement safety (hepatorenal and muscle enzymes, heart rate, blood pressure and side effects) measured at time-0 (unsupplemented), 30-min, and then hourly for 5-h post-ingestion. Study 2 participants (N = 48) received the same CrN treatments vs. 3 g CrM in a randomized, double-blind, 28d trial inclusive of a 7-d interim testing period and loading sequence (4 servings/d). Day-7 and d-28 measured Tendo™ bench press performance, Wingate testing and a 6x6-s bicycle ergometer sprint. Data were analyzed using a GLM and results are reported as mean ± SD or mean change ± 95 % CI. RESULTS: In both studies we observed several significant, yet stochastic changes in blood markers that were not indicative of potential harm or consistent for any treatment group. Equally, all treatment groups reported a similar number of minimal side effects. In Study 2, there was a significant increase in plasma nitrates for both CrN groups by d-7, subsequently abating by d-28. Muscle creatine increased significantly by d-7 in the CrM and CrN-High groups, but then decreased by d-28 for CrN-High. By d-28, there were significant increases in bench press lifting volume (kg) for all groups (PLA, 126.6, 95 % CI 26.3, 226.8; CrM, 194.1, 95 % CI 89.0, 299.2; CrN-Low, 118.3, 95 % CI 26.1, 210.5; CrN-High, 267.2, 95 % CI 175.0, 359.4, kg). Only the CrN-High group was significantly greater than PLA (p < 0.05). Similar findings were observed for bench press peak power (PLA, 59.0, 95 % CI 4.5, 113.4; CrM, 68.6, 95 % CI 11.4, 125.8; CrN-Low, 40.9, 95 % CI -9.2, 91.0; CrN-High, 60.9, 95 % CI 10.8, 111.1, W) and average power. CONCLUSIONS: Creatine nitrate delivered at 3 g was well-tolerated, demonstrated similar performance benefits to 3 g CrM, in addition, within the confines of this study, there were no safety concerns.

Effects of powdered Montmorency tart cherry supplementation on an acute bout of intense lower body strength exercise in resistance trained males.

BACKGROUND: The purpose of this study was to examine whether short-term ingestion of a powdered tart cherry supplement prior to and following intense resistance-exercise attenuates muscle soreness and recovery strength loss, while reducing markers of muscle damage, inflammation, and oxidative stress. METHODS: Twenty-three healthy, resistance-trained men (20.9 ± 2.6 yr, 14.2 ± 5.4% body fat, 63.9 ± 8.6 kg FFM) were matched based on relative maximal back squat strength, age, body weight, and fat free mass. Subjects were randomly assigned to ingest, in a double blind manner, capsules containing a placebo (P, n = 12) or powdered tart cherries [CherryPURE(®)] (TC, n = 11). Participants supplemented one time daily (480 mg/d) for 10-d including day of exercise up to 48-h post-exercise. Subjects performed ten sets of ten repetitions at 70% of a 1-RM back squat exercise. Fasting blood samples, isokinetic MVCs, and quadriceps muscle soreness ratings were taken pre-lift, 60-min, 24-h, and 48-h post-lift and analyzed by MANOVA with repeated measures. RESULTS: Muscle soreness perception in the vastus medialis (») (p = 0.10) and the vastus lateralis (») (p = 0.024) was lower in TC over time compared to P. Compared to pre-lift, TC vastus medialis (») soreness was significantly attenuated up to 48-h post-lift with vastus lateralis (») soreness significantly lower at 24-h post-lift compared to P. TC changes in serum creatinine (p = 0.03, delta p = 0.024) and total protein (p = 0.018, delta p = 0.006) were lower over time and smaller from pre-lift levels over time compared to P Significant TC group reductions from pre-lift levels were found for AST and creatinine 48-h post-lift, bilirubin and ALT 60-min and 48-h post-lift. No significant supplementation effects were observed for serum inflammatory or anti-inflammatory markers. None of the free radical production, lipid peroxidation, or antioxidant capacity markers (NT, TBARS, TAS, SOD) demonstrated significant changes with supplementation. Changes in TC whole blood lymphocyte counts (p = 0.013) from pre-lift were greater compared to P, but TC lymphocyte counts returned to pre-lift values quicker than P. CONCLUSION: Short-term supplementation of Montmorency powdered tart cherries surrounding a single bout of resistance exercise, appears to be an effective dietary supplement to attenuate muscle soreness, strength decrement during recovery, and markers of muscle catabolism in resistance trained individuals.

Consumption of polyphenol-rich peach and plum juice prevents risk factors for obesity-related metabolic disorders and cardiovascular disease in Zucker rats.

Polyphenols from fruits have been implied in the prevention of risk factors for cardiometabolic disorders and cardiovascular disease. The purpose of this study was to investigate if the consumption of peach and plum juice has a protective effect against obesity and metabolic disorders that promote the development of cardiovascular diseases. Obese Zucker and lean rats were fed with peach, plum juice ad libitum or placebo. Body weight gain, biochemical markers and molecular markers for inflammation and cardiovascular disease in heart tissue were quantified. Results show that peach and plum juice consumption protected against a combination of obesity-induced metabolic disorders including hyperglycemia, insulin and leptin resistance, dyslipidemia and low-density lipoprotein oxidation. This was accompanied by a decreased expression of pro-atherogenic and pro-inflammatory biomarkers in plasma and heart tissues including intercellular cell adhesion molecule-1, monocyte chemotactic protein-1, NF-κB and foam cell adherence to aortic arches. In addition, peach and plum juice consumption decreased the levels of angiotensin II in plasma and its receptor Agtr1 in heart tissues, suggesting a role of peach and plum polyphenols as peroxisome proliferator-activated receptor-γ agonists. Furthermore, only plum juice significantly prevented body weight gain and increased the ratio high-density lipoprotein cholesterol/total cholesterol in plasma. This effect is most likely attributed to the plum's higher content of polyphenols (three times that of peach). Altogether, these results imply that cardioprotective effects can be achieved by replacing drinks high in sugar content with fruit juice rich in polyphenols in a diet.