Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk.

Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51-53 %E) v. lower CHO (39-40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine and γ-butyrobetaine concentrations were higher after the high- v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by high v. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.

Energy substrate partitioning and efficiency in individuals with atherogenic lipoprotein phenotype.

Individuals with an atherogenic lipoprotein phenotype (ALP) characterized by increased levels of small dense low-density lipoprotein (LDL) particles tend to have greater adiposity compared to unaffected subjects. We sought to determine whether this may be related to alterations in energy substrate partitioning or efficiency. These were assessed by indirect calorimetry in men with ALP (ALP(+), n = 7) and unaffected controls (ALP(-), n = 8) during rest (30 min) and exercise (10 min). Gross, net and delta efficiencies were calculated during graded leg-cycle ergometry at workloads of 10 and 50 W. Respiratory exchange ratios (RER) were significantly (P < 0.05) higher in ALP(+) vs. ALP(-) during rest (0.86 ± 0.01 vs. 0.83 ± 0.02) and exercise at 10 W (0.88 ± 0.02 vs. 0.84 ± 0.02) and 50 W (0.92 ± 0.01 vs. 0.87 ± 0.01, respectively) (P < 0.05). Lipid oxidation (kcal/min) was lower in ALP(+) vs. ALP(-) during rest (0.56 ± 0.02 vs. 0.71 ± 0.07) and exercise at 10 W (1.52 ± 0.25 vs. 2.00 ± 0.20) and 50 W (1.28 ± 0.10 vs. 2.32 ± 0.22, respectively) (P < 0.05). Gross and net efficiencies were significantly increased (P = 0.005) in ALP(+) vs. ALP(-) at 10 W. RER was correlated positively with plasma triglyceride during exercise and inversely with high-density lipoprotein (HDL) cholesterol and LDL peak particle diameter during rest and exercise (P < 0.05). These findings suggest that increased muscular efficiency at low exercise intensity and reduced lipid oxidation during rest and exercise may contribute to both dyslipidemia and increased adiposity in individuals with ALP.

Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet.

Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles. We sought to determine whether increases in plasma Lp(a) induced by a low-fat high-carbohydrate (LFHC) diet are related to changes in OxPL and LDL subclasses. We studied 63 healthy subjects after 4 weeks of consuming, in random order, a high-fat low-carbohydrate (HFLC) diet and a LFHC diet. Plasma concentrations of Lp(a) (P < 0.01), OxPL/apolipoprotein (apo)B (P < 0.005), and OxPL-apo(a) (P < 0.05) were significantly higher on the LFHC diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller (P < 0.0001). Diet-induced changes in Lp(a) were strongly correlated with changes in OxPL/apoB (P < 0.0001). The increases in plasma Lp(a) levels after the LFHC diet were also correlated with decreases in medium LDL particles (P < 0.01) and increases in very small LDL particles (P < 0.05). These results demonstrate that induction of increased levels of Lp(a) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.

Plasma triglyceride concentrations are rapidly reduced following individual bouts of endurance exercise in women.

It is known that chronic endurance training leads to improvements in the lipoprotein profile, but less is known about changes that occur during postexercise recovery acutely. We analyzed triglyceride (TG), cholesterol classes and apolipoproteins in samples collected before, during and after individual moderate- and hard-intensity exercise sessions in men and women that were isoenergetic between intensities. Young healthy men (n = 9) and young healthy women (n = 9) were studied under three different conditions with diet unchanged between trials: (1) before, during and 3 h after 90 min of exercise at 45% VO(2)peak (E45); (2) before, during and 3 h after 60 min of exercise at 65% VO(2)peak (E65), and (3) in a time-matched sedentary control trial (C). At baseline, high-density lipoprotein cholesterol (HDL-C) was higher in women than men (P < 0.05). In men and in women, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and LDL peak particle size were unaltered by exercise either during exertion or after 3 h of recovery. In women, but not in men, average plasma TG was significantly reduced below C at 3 h postexercise by approximately 15% in E45 and 25% in E65 (P < 0.05) with no significant difference between exercise intensities. In summary, plasma TG concentration rapidly declines following exercise in women, but not in men. These results demonstrate an important mechanism by which each individual exercise session may incrementally reduce the risk for cardiovascular disease (CVD) in women.

Effects of endurance training on cardiorespiratory fitness and substrate partitioning in postmenopausal women.

We examined the effect of endurance training on energy substrate partitioning during rest and exercise in postmenopausal women. Ten healthy sedentary (55 +/- 1 years old) subjects completed 12 weeks of endurance exercise training on a cycle ergometer (5 d/wk, 1 h/d, 65% peak oxygen consumption [Vo(2)peak]). Whole-body energy substrate oxidation was determined by indirect calorimetry during 90 minutes of rest and 60 minutes of cycle ergometer exercise. Subjects were studied at 65% Vo(2)peak before training and after training at the same absolute exercise intensity (same absolute workload as 65% of pretraining Vo(2)peak) and same relative exercise intensity (65% of posttraining Vo(2)peak). After training, Vo(2)peak increased by 16.3% +/- 3.9% and resting heart rate decreased by 4 beats per minute (P < .05). During exercise at same absolute intensity, mean arterial pressure decreased by 8 mm Hg (P < .05), heart rate decreased by 19 beats per minute (P < .05), energy derived from carbohydrate decreased by 9.6%, and the energy derived from lipid increased by 9.2% (P < .05). Lactate concentration was lower at the same absolute and relative exercise intensities (P < .05). Changes in substrate partitioning during exercise were accomplished without changes in dietary composition, body weight, or body composition. We conclude that endurance training in healthy postmenopausal women who remain in energy balance results in many of the classic cardiopulmonary training effects, decreases the reliance on carbohydrate, and increases lipid oxidation during a given submaximal exercise task without a reduction in body weight.

Training improves the response in glucose flux to exercise in postmenopausal women.

We examined the effects of endurance training on parameters of glucose flux during rest and exercise in postmenopausal women. Ten sedentary, but healthy women (55 +/- 1 yr) completed 12 wk of endurance exercise training on a cycle ergometer [5 days/wk, 1 h/day, 65% peak oxygen consumption (Vo(2peak))]. Flux rates were determined by primed continuous infusion of [6,6-(2)H]glucose (D(2)-glucose) during 90 min of rest and 60 min of cycle ergometer exercise during one pretraining exercise trial [65% Vo(2peak) (PRE)] and two posttraining exercise trials [the power output that elicited 65% pretraining Vo(2peak) (ABT) and 65% posttraining Vo(2peak) (RLT)]. Training increased Vo(2peak) by 16.3 +/- 3.9% (P < 0.05). Epinephrine and glucagon were lower during ABT and lactate was lower during ABT and RLT (P < 0.05), but the apparent insulin response was unchanged. Whole body glucose rate of appearance decreased posttraining during exercise at a given power output (4.58 +/- 0.39 mg.kg(-1).min(-1) during ABT compared with 5.21 +/- 0.48 mg.kg(-1).min(-1) PRE, P < 0.05), but not at the same relative workload (5.85 +/- 0.36 mg.kg(-1).min(-1)). Training resulted in a 35% increase in glucose MCR during exercise at the same relative intensity (7.16 +/- 0.42 ml.kg(-1).min(-1) during RLT compared with 5.28 +/- 0.42 ml.kg(-1).min(-1) PRE, P < 0.05). Changes in parameters of glucose kinetics during exercise were accomplished without changes in dietary composition, body weight, or body composition. We conclude that despite changes in the hormonal milieu that occur at menopause, endurance training results in a similar magnitude in training-induced alterations of glucose flux as seen previously in younger women.

Glucoregulation is more precise in women than in men during postexercise recovery.

BACKGROUND: The regulation of glycemia is challenged in healthy men and women after exercise bouts of substantial energy expenditure. OBJECTIVE: We determined rates of glucose appearance (Ra), disappearance (Rd), and metabolic clearance (MCR) before, during, and after isoenergetic moderate and hard-intensity exercise. DESIGN: Ten men and 8 women received primed-continuous infusion of [6,6-(2)H(2)]glucose tracer to measure glucose kinetics. Participants were studied under 3 different conditions with diet unchanged between trials: 1) before, during, and 3 h after 90 min of exercise at 45% of peak oxygen consumption (VO(2)peak; E45); 2) before, during, and 3 h after 60 min of exercise at 65% VO(2)peak (E65), and 3) in a time-matched sedentary control trial. RESULTS: In men and women, Ra, Rd, and MCR increased above the control trial during exercise and were higher in E65 than in E45 (P < 0.05). Average Ra, Rd, and MCR remained elevated above the control over 3 h of postexercise recovery in men after exercise in E45 and E65 (P < 0.05), and blood glucose concentrations were depressed below the control during recovery (P < 0.05). Glucose concentrations were not depressed in women during 3 h of postexercise recovery, and in contrast with that in men, average Ra and Rd did not remain significantly elevated during postexercise recovery in women, although MCR did remain elevated in E65 (P < 0.05). CONCLUSIONS: After exercise bouts, women are better able to maintain glucose concentrations at sedentary control levels, thus not requiring the counter-regulation of glucose production that is seen in men and requiring less accentuation of lipid metabolism.

Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period.

We sought to determine whether lipolysis, fatty acid (FA) mobilization, and plasma FA oxidation would remain elevated for hours following isoenergetic exercise bouts of different intensities. Ten men and eight women received a primed-continuous infusion of [1,1,2,3,3-(2)H(5)]glycerol and continuous infusion of [1-(13)C]palmitate to measure glycerol and plasma FA kinetics. On Day 1 (D1), participants were studied under one of three different conditions, assigned in random order: (1) before, during and 3 h after 90 min of exercise at 45% V(O2)peak (E45), (2) before, during and 3 h after 60 min of exercise at 65% V(O2)peak (E65), and (3) in a time-matched sedentary control trial (C). For each condition, participants were studied by indirect calorimetry the following morning as well (D2). Rate of appearance (Ra) of glycerol (Ra(GL)) increased above C during exercise in men and women (P < 0.05), was higher in E45 than E65 in men (P < 0.05), and was not different between exercise intensities in women. During 3 h of postexercise recovery, Ra(GL) remained significantly elevated in men (P < 0.05), but not women. FA Ra (Ra(FA)) increased during exercise in men and women and was higher in E45 than E65 (P < 0.05), and remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05), but with a greater relative increase in men than women (P < 0.05). Plasma FA oxidation (Rox) increased during exercise with no difference between intensities, and it remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05). Total lipid oxidation (Lox) was elevated in both sexes (P < 0.05), but more in men during 3 h of postexercise recovery on D1 (P < 0.05) and remained elevated on D2 in men (P < 0.05), but not in women. There were no differences between E45 and E65 for postexercise energy substrate turnover or oxidation in men and women as energy expenditure of exercise (EEE) was matched between bouts. We conclude that the impact of exercise upon lipid metabolism persists into recovery, but that women depend more on lipid during exercise whereas, during recovery, lipid metabolism is accentuated to a greater extent in men.

Retention of intravenously infused [13C]bicarbonate is transiently increased during recovery from hard exercise.

The effects of exercise on energy substrate metabolism persist into the postexercise recovery period. We sought to derive bicarbonate retention factors (k) to correct for carbon tracer oxidized, but retained from pulmonary excretion before, during, and after exercise. Ten men and nine women received a primed-continuous infusion of [(13)C]bicarbonate (sodium salt) under three different conditions: 1) before, during, and 3 h after 90 min of exercise at 45% peak oxygen consumption (Vo(2peak)); 2) before, during, and 3 h after 60 min of exercise at 65% Vo(2peak); and 3) during a time-matched resting control trial, with breath samples collected for determination of (13)CO(2) excretion rates. Throughout the resting control trial, k was stable and averaged 0.83 in men and women. During exercise, average k in men was 0.93 at 45% Vo(2peak) and 0.94 at 65% Vo(2peak), and in women k was 0.91 at 45% Vo(2peak) and 0.92 at 65% Vo(2peak), with no significant differences between intensities or sexes. After exercise at 45% Vo(2peak), k returned rapidly to control values in men and women, but following exercise at 65% Vo(2peak), k was significantly less than control at 30 and 60 min postexercise in men (0.74 and 0.72, respectively, P < 0.05) and women (0.75 and 0.76, respectively, P < 0.05) with no significant postexercise differences between men and women. We conclude that bicarbonate/CO(2) retention is transiently increased in men and women for the first hour of postexercise recovery following endurance exercise bouts of hard but not moderate intensity.