NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.

BACKGROUND: Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. OBJECTIVES: We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults. METHODS: A randomized, double-blind, controlled trial was conducted in 14 (female/male: 4/10) community-dwelling, older adults with impaired physical function [age, 72.9 ± 4.0 years; BMI, 25.2 ± 2.3 kg/m2]. Participants were supplemented with 207.5 mg niacin equivalents/day [intervention (INT)] and a control product (CON) that did not contain niacin equivalents, each for 32 days. The primary outcomes tested were mitochondrial oxidative capacity and exercise efficiency, analyzed by means of paired Student's t-tests. Secondary outcomes, such as NAD+ concentrations, were analyzed accordingly. RESULTS: Following supplementation, skeletal muscle NAD+ concentrations [7.5 ± 1.9 compared with 7.9 ± 1.6 AU, respectively] in INT compared with CON conditions were not significantly different compared to the control condition, whereas skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation [INT, 0.098 ± 0.063 compared with CON, 0.025 ± 0.014; P = 0.001], suggesting an increased NAD+ metabolism. Conversely, neither ADP-stimulated [INT, 82.1 ± 19.0 compared with CON, 84.0 ± 19.2; P = 0.716] nor maximally uncoupled mitochondrial respiration [INT, 103.4 ± 30.7 compared with CON, 108.7 ± 33.4; P = 0.495] improved under NAD+-precursor supplementation, nor did net exercise efficiency during the submaximal cycling test [INT, 20.2 ± 2.77 compared with CON, 20.8 ± 2.88; P = 0.342]. CONCLUSIONS: Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This study was registered at clinicaltrials.gov as NCT03310034.

Acute exercise does not decrease liver fat in men with overweight or NAFLD.

Elevated hepatic lipid content (IntraHepatic Lipid, IHL) increases the risk of metabolic complications. Although prolonged exercise training lowers IHL, it is unknown if acute exercise has the same effect. Furthermore, hepatic ATP content may be related to insulin resistance and IHL. We aimed to investigate if acute exercise leads to changes in IHL and whether this is accompanied by changes in hepatic ATP. Twenty-one men (age 54.8 ± 7.2 years, BMI 29.7 ± 2.2 kg/m(2)) performed a 2 h cycling protocol, once while staying fasted and once while ingesting glucose. IHL was determined at baseline, 30 min post-exercise and 4 h post-exercise. Additionally ATP/Total P ratio was measured at baseline and 4 h post-exercise. Compared with baseline values we did not observe any statistically significant changes in IHL within 30 min post-exercise in neither the fasted nor the glucose-supplemented condition. However, IHL was elevated 4 h post-exercise compared with baseline in the fasted condition (from 8.3 ± 1.8 to 8.7 ± 1.8%, p = 0.010), an effect that was blunted by glucose supplementation (from 8.3 ± 1.9 to 8.3 ± 1.9%, p = 0.789). Acute exercise does not decrease liver fat in overweight middle-aged men. Moreover, IHL increased 4 h post-exercise in the fasted condition, an increase that was absent in the glucose-supplemented condition. These data suggest that a single bout of exercise may not be able to lower IHL.

Thirty days of resveratrol supplementation does not affect postprandial incretin hormone responses, but suppresses postprandial glucagon in obese subjects.

AIMS: Resveratrol, a natural polyphenolic compound produced by various plants (e.g. red grapes) and found in red wine, has glucose-lowering effects in humans and rodent models of obesity and/or diabetes. The mechanisms behind these effects have been suggested to include resveratrol-induced secretion of the gut incretin hormone glucagon-like peptide-1. We investigated postprandial incretin hormone and glucagon responses in obese human subjects before and after 30 days of resveratrol supplementation. METHODS: Postprandial plasma responses of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide and glucagon were evaluated in 10 obese men [subjects characteristics (mean ± standard error of the mean): age 52 ± 2 years; BMI 32 ± 1 kg/m(2), fasting plasma glucose 5.5 ± 0.1 mmol/l] who had been given a dietary supplement of resveratrol (Resvida(®) 150 mg/day) or placebo for 30 days in a randomized, double-blind, crossover design with a 4-week washout period. At the end of each intervention period a standardized meal test (without co-administration of resveratrol) was performed. RESULTS: Resveratrol supplementation had no impact on fasting plasma concentrations or postprandial plasma responses (area under curve values) of glucose-dependent insulinotropic polypeptide (11.2 ± 2.1 vs. 11.8 ± 2.2 pmol/l, P = 0.87; 17.0 ± 2.2 vs. 14.8 ± 1.6 min × nmol/l, P = 0.20) or glucagon-like peptide-1 (15.4 ± 1.0 vs. 15.2 ± 0.9 pmol/l, P = 0.84; 5.6 ± 0.4 vs. 5.7 ± 0.3 min × nmol/l, P = 0.73). Resveratrol supplementation significantly suppressed postprandial glucagon responses (4.4 ± 0.4 vs. 3.9 ± 0.4 min × nmol/l, P = 0.01) without affecting fasting glucagon levels (15.2 ± 2.2 vs. 14.5 ± 1.5 pmol/l, P = 0.56). CONCLUSIONS: Our data suggest that 30 days of resveratrol supplementation does not affect fasting or postprandial incretin hormone plasma levels in obese humans, but suppresses postprandial glucagon responses.

Exercise-induced modulation of cardiac lipid content in healthy lean young men.

Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m²) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance spectroscopy (¹H-MRS) at baseline, directly after exercise and again 4 h post-exercise, together with systolic function (by multi-slice cine-MRI) and cardiac energy status (by ³¹P-MRS). Plasma FA concentrations were increased threefold during exercise and ninefold during recovery in the fasted state compared with the glucose-fed state (p < 0.01). Cardiac lipid content was elevated at the end of the fasted test day (from 0.26 ± 0.04 to 0.44 ± 0.04%, p = 0.003), while it did not change with glucose supplementation (from 0.32 ± 0.03 to 0.26 ± 0.05%, p = 0.272). Furthermore, PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4 h post-exercise was higher compared with the low FA state (63 ± 2 vs. 59 ± 2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the fasted state, lead to increased cardiac lipid content, but do not acutely hamper systolic function. Although the lower cardiac energy status is in line with a lipotoxic action of cardiac lipid content, a causal relationship cannot be proven.

Peroxisome proliferator-activated receptors: a therapeutic target in COPD?

Extrapulmonary pathology significantly impairs clinical outcome in chronic obstructive pulmonary disease (COPD). The peroxisome proliferator-activated receptors (PPARs) are implicated in the regulation of several hallmarks of systemic COPD pathology, including cachexia, decreased oxidative muscle metabolism, oxidative stress and systemic inflammation. Recently, expression of PPARs and related cofactors was shown to be reduced in peripheral skeletal muscle of patients with moderate-to-severe COPD and muscle weakness. The current authors hypothesise that impaired peroxisome proliferator-activated receptor signalling may underlie some of the muscular disturbances in chronic obstructive pulmonary disease. Proposed mechanisms will be outlined in the present article, as well as the therapeutic potential of peroxisome proliferator-activated receptor modulation in the treatment of skeletal muscle dysfunction.