Bicarbonate Unlocks the Ergogenic Action of Ketone Monoester Intake in Endurance Exercise.

PURPOSE: We recently reported that oral ketone ester (KE) intake before and during the initial 30 min of a 3 h 15 min simulated cycling race (RACE) transiently decreased blood pH and bicarbonate without affecting maximal performance in the final quarter of the event. We hypothesized that acid-base disturbances due to KE overrules the ergogenic potential of exogenous ketosis in endurance exercise. METHODS: Nine well-trained male cyclists participated in a similar RACE consisting of 3 h submaximal intermittent cycling (IMT180') followed by a 15-min time trial (TT15') preceding an all-out sprint at 175% of lactate threshold (SPRINT). In a randomized crossover design, participants received (i) 65 g KE, (ii) 300 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON), together with consistent 60 g·h-1 carbohydrate intake. RESULTS: KE ingestion transiently elevated blood D-ß-hydroxybutyrate to ~2-3 mM during the initial 2 h of RACE (P < 0.001 vs CON). In KE, blood pH concomitantly dropped from 7.43 to 7.36 whereas bicarbonate decreased from 25.5 to 20.5 mM (both P < 0.001 vs CON). Additional BIC resulted in 0.5 to 0.8 mM higher blood D-ß-hydroxybutyrate during the first half of IMT180' (P < 0.05 vs KE) and increased blood bicarbonate to 31.1 ± 1.8 mM and blood pH to 7.51 ± 0.03 by the end of IMT180' (P < 0.001 vs KE). Mean power output during TT15' was similar between KE, BIC, and CON at ~255 W but was 5% higher in KE + BIC (P = 0.02 vs CON). Time to exhaustion in the sprint was similar between all conditions at ~60 s (P = 0.88). Gastrointestinal symptoms were similar between groups. DISCUSSION: The coingestion of oral bicarbonate and KE enhances high-intensity performance at the end of an endurance exercise event without causing gastrointestinal distress.

Exogenous Ketosis Impairs 30-min Time-Trial Performance Independent of Bicarbonate Supplementation.

PURPOSE: We recently demonstrated that coingestion of NaHCO3 to counteract ketoacidosis resulting from oral ketone ester (KE) intake improves mean power output during a 15-min time trial (TT) at the end of a 3-h cycling race by ~5%. This ergogenic effect occurred at a time when blood ketone levels were low, as ketosis was only induced during the initial ~2 h of the race. Therefore, in the current study, we investigated whether performance also increases if blood ketone levels are increased in the absence of ketoacidosis during high-intensity exercise. METHODS: In a double-blind crossover design, 14 well-trained male cyclists completed a 30-min TT (TT30') followed by an all-out sprint at 175% of lactate threshold (SPRINT). Subjects were randomized to receive (i) 50 g KE, (ii) 180 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON). RESULTS: KE ingestion increased blood d-ß-hydroxybutyrate to ~3-4 mM during the TT30' and SPRINT (P < 0.001 vs CON). In KE, blood pH and bicarbonate concomitantly dropped, causing 0.05 units lower pH and 2.6 mM lower bicarbonate in KE compared with CON during the TT30' and SPRINT (P < 0.001 vs CON). BIC coingestion resulted in 0.9 mM higher blood d-ß-hydroxybutyrate (P < 0.001 vs KE) and completely counteracted ketoacidosis during exercise (P > 0.05 vs CON). Mean power output during TT30' was similar between CON and BIC at 281 W, but was 1.5% lower in the KE conditions (main effect of KE: P = 0.03). Time to exhaustion in the SPRINT was ~64 s in CON and KE and increased by ~8% in the BIC conditions (main effect of BIC: P < 0.01). DISCUSSION: Neutralization of acid-base disturbance by BIC coingestion is insufficient to counteract the slightly negative effect of KE intake during high-intensity exercise.

Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress.

There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus ß-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague-Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% ß-alanine (HFba), as ß-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine-4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine N(ε)-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.

Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.

The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a double-blind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTT(R)), a 30-min cycling bout at ~75% VO(2max), and another OGTT after exercise (OGTT(EX)). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTT(R). Blood samples were collected before (t0) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTT(EX) an additional 75-g oral glucose bolus was administered at t60. In OGTT(R), OFI administration reduced the area under the glucose curve (AUC(GLUC)) by 26%, mainly due to lower blood glucose levels at t30 and t60 (p < .05). Furthermore, a higher serum insulin concentration was noted after OFI intake at baseline and at t30 (p < .05). In OGTT(EX), blood glucose at t60 was ~10% lower in OFI than in PL, which resulted in a decreased AUC(GLUC) (-37%, p < .05). However, insulin values and AUC(INS) were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

No effects of lifelong creatine supplementation on sarcopenia in senescence-accelerated mice (SAMP8).

Oral creatine supplementation can acutely ameliorate skeletal muscle function in older humans, but its value in the prevention of sarcopenia remains unknown. We evaluated the effects of lifelong creatine supplementation on muscle mass and morphology, contractility, and metabolic properties in a mouse model of muscle senescence. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 wk. Soleus and extensor digitorum longus muscles were tested for in vitro contractile properties, creatine content, and morphology at weeks 25 and 60. Both muscle types showed reduced phosphocreatine content at week 60 that could not be prevented by creatine. Accordingly, age-associated decline in muscle mass and contractility was not influenced by treatment. Aged soleus muscles had fewer and smaller fast-twitch glycolytic fibers irrespective of treatment received. It is concluded that lifelong creatine supplementation is no effective strategy to prevent sarcopenia in senescence-accelerated mice.

Acute Rhodiola rosea intake can improve endurance exercise performance.

PURPOSE: The purpose of this study was to investigate the effect of acute and 4-week Rhodiola rosea intake on physical capacity, muscle strength, speed of limb movement, reaction time, and attention. PHASE I: A double blind placebo-controlled randomized study (n= 24) was performed, consisting of 2 sessions (2 days per session). Day 1: One hour after acute Rhodiola rosea intake (R, 200-mg Rhodiola rosea extract containing 3% rosavin + 1% salidroside plus 500 mg starch) or placebo (P, 700 mg starch) speed of limb movement (plate tapping test), aural and visual reaction time, and the ability to sustain attention (Fepsy Vigilance test) were assessed. Day 2: Following the same intake procedure as on day 1, maximal isometric knee-extension torque and endurance exercise capacity were tested. Following a 5-day washout period, the experimental procedure was repeated, with the treatment regimens being switched between groups (session 2). PHASE II: A double blind placebo-controlled study (n = 12) was performed. Subjects underwent sessions 3 and 4, identical to Phase I, separated by a 4-week R/P intake, during which subjects ingested 200 mg R/P per day. PHASE I: Compared with P, acute R intake in Phase I increased (p <.05) time to exhaustion from 16.8 +/- 0.7 min to 17.2+/- 0.8 min. Accordingly, VO2peak (p <.05) and VCO2peak (p<.05) increased during R compared to P from 50.9 +/- 1.8 ml x min(-1) x kg(- )1 to 52.9 +/- 2.7 ml x min(-10) x kg(-1) (VO2peak) and from 60.0 +/- 2.3 ml x min(-1) x kg(-1) to 63.5+/- 2.7 ml x min(-1) x kg(-1) (VCO2peak). Pulmonary ventilation (p =.07) tended to increase more during R than during P (P: 115.9+/- 7.7 L/min; R: 124.8 +/- 7.7 L/min). All other parameters remained unchanged. PHASE II: Four-week R intake did not alter any of the variables measured. CONCLUSION: Acute Rhodiola rosea intake can improve endurance exercise capacity in young healthy volunteers. This response was not altered by prior daily 4-week Rhodiola intake.

Effect of muscle creatine content manipulation on contractile properties in mouse muscles.

The effects of muscle creatine manipulation on contractile properties in oxidative and glycolytic muscles were evaluated. Whereas control mice (NMRi; n = 12) received normal chow (5 g daily), three experimental groups were created by adding creatine monohydrate (CR group; 5%, 1 week; n = 13); beta-guanidinoproprionic acid, an inhibitor of cellular creatine uptake (beta-GPA group; 1%, 2 weeks; n = 12); or CR following beta-GPA (beta-GPA+CR group; n = 11). Total creatine (TCr) and the contractile properties of incubated soleus and extensor digitorum longus (EDL) muscles were determined. For the soleus, compared with control, TCr increased in the CR group (+25%), decreased in beta-GPA group (-50%), and remained stable in the beta-GPA+CR group, whereas, for the EDL, TCr was similar in the CR, and lower in the beta-GPA (-40%) and beta-GPA+CR (-15%) groups. None of the experimental groups (CR, beta-GPA, or beta-GPA+CR) showed changes in peak tension (P(peak)), time to peak tension, or relaxation in soleus or EDL during twitch or tetanic stimulation. For the soleus, fatigue reduced P(peak) to approximately 60% of initial P(peak); 5 min of recovery restored P(peak) to values approximately 15% higher in CR than in controls. P(peak) recovery was not affected by beta-GPA or beta-GPA+CR in the soleus or any treatment in the EDL. Thus, peak tension recovery is enhanced by creatine intake in oxidative but not glycolytic muscles. This may be implicated in the beneficial action of creatine loading.

Effects of creatine supplementation and exercise training on fitness in men 55-75 yr old.

effect of oral creatine supplementation (CR; 5 g/day) in conjunction with exercise training on physical fitness was investigated in men between 55 and 75 yr of age (n = 46). A double-blind randomized placebo-controlled (PL) trial was performed over a 6-mo period. Furthermore, a subgroup (n = 20) completed a 1-yr follow-up. The training program consisted of cardiorespiratory endurance training as well as moderate resistance training (2-3 sessions/wk). Endurance capacity was evaluated during a maximal incremental bicycle ergometer test, maximal isometric strength of the knee-extensor muscles was assessed by an isokinetic dynamometer, and body composition was assessed by hydrostatic weighing. Furthermore, in a subgroup (PL: n = 13; CR: n = 12) biopsies were taken from m. vastus lateralis to determine total creatine (TCr) content. In PL, 6 mo of training increased peak oxygen uptake rate (+16%; P < 0.05). Fat-free mass slightly increased (+0.3 kg; P < 0.05), whereas percent body fat slightly decreased (-1.2%; P < 0.05). The training intervention did not significantly change either maximal isometric strength or body weight. The responses were independent of CR. Still, compared with PL, TCr was increased by approximately 5% in CR, and this increase was closely correlated with initial muscle creatine content (r = -0.78; P < 0.05). After a 1-yr follow-up, muscle TCr was not higher in CR than in PL. Furthermore, the other measurements were not affected by CR. It is concluded that long-term creatine intake (5 g/day) in conjunction with exercise training does not beneficially impact physical fitness in men between 55 and 75 yr of age.