Astaxanthin supplementation enhances metabolic adaptation with aerobic training in the elderly.

Endurance training (ET) is recommended for the elderly to improve metabolic health and aerobic capacity. However, ET-induced adaptations may be suboptimal due to oxidative stress and exaggerated inflammatory response to ET. The natural antioxidant and anti-inflammatory dietary supplement astaxanthin (AX) has been found to increase endurance performance among young athletes, but limited investigations have focused on the elderly. We tested a formulation of AX in combination with ET in healthy older adults (65-82 years) to determine if AX improves metabolic adaptations with ET, and if AX effects are sex-dependent. Forty-two subjects were randomized to either placebo (PL) or AX during 3 months of ET. Specific muscle endurance was measured in ankle dorsiflexors. Whole body exercise endurance and fat oxidation (FATox) was assessed with a graded exercise test (GXT) in conjunction with indirect calorimetry. Results: ET led to improved specific muscle endurance only in the AX group (Pre 353 ± 26 vs. Post 472 ± 41 contractions), and submaximal GXT duration improved in both groups (PL 40.8 ± 9.1% and AX 41.1 ± 6.3%). The increase in FATox at lower intensity after ET was greater in AX (PL 0.23 ± 0.15 g vs. AX 0.76 ± 0.18 g) and was associated with reduced carbohydrate oxidation and increased exercise efficiency in males but not in females.

The effect of dietary nitrate on exercise capacity in chronic kidney disease: a randomized controlled pilot study.

BACKGROUND: Chronic Kidney Disease (CKD) patients exhibit a reduced exercise capacity that impacts quality of life. Dietary nitrate supplementation has been shown to have favorable effects on exercise capacity in disease populations by reducing the oxygen cost of exercise. This study investigated whether dietary nitrates would acutely improve exercise capacity in CKD patients. METHODS AND RESULTS: In this randomized, double-blinded crossover study, 12 Stage 3-4 CKD patients (Mean ± SEM: Age, 60 ± 5yrs; eGFR, 50.3 ± 4.6 ml/min/1.73 m2) received an acute dose of 12.6 mmol of dietary nitrate in the form of concentrated beetroot juice (BRJ) and a nitrate depleted placebo (PLA). Skeletal muscle mitochondrial oxidative function was assessed using near-infrared spectroscopy. Cardiopulmonary exercise testing was performed on a cycle ergometer, with intensity increased by 25 W every 3 min until volitional fatigue. Plasma nitric oxide (NO) metabolites (NOm; nitrate, nitrite, low molecular weight S-nitrosothiols, and metal bound NO) were determined by gas-phase chemiluminescence. Plasma NOm values were significantly increased following BRJ (BRJ vs. PLA: 1074.4 ± 120.4 µM vs. 28.4 ± 6.6 µM, p < 0.001). Total work performed (44.4 ± 10.6 vs 39.6 ± 9.9 kJ, p = 0.03) and total exercise time (674 ± 85 vs 627 ± 86s, p = 0.04) were significantly greater following BRJ. Oxygen consumption at the ventilatory threshold was also improved by BRJ (0.90 ± 0.08 vs. 0.74 ± 0.06 L/min, p = 0.04). These changes occurred in the absence of improved skeletal muscle mitochondrial oxidative capacity (p = 0.52) and VO2peak (p = 0.35). CONCLUSIONS: Our findings demonstrate that inorganic nitrate can acutely improve exercise capacity in CKD patients. The effects of chronic nitrate supplementation on CKD related exercise intolerance should be investigated in future studies.

The gender dependent influence of sodium bicarbonate supplementation on anaerobic power and specific performance in female and male wrestlers.

The aim of this study was the assessment of progressive low-dose sodium bicarbonate (NaHCO3) supplementation on the anaerobic indices in two bouts of Wingate tests (WT) separated by wrestling-specific performance test and assessing the gender differences in response. Fifty-one (18 F) wrestlers completed a randomized trial of either a NaHCO3 (up to 100 mg·kg-1) or a placebo for 10 days. Before and after treatment, athletes completed an exercise protocol that comprised, in sequence, the first WT1, dummy throw test (DT), and second WT2. The number of completed throws increased significantly in males from 19.3 ± 2.6 NaHCO3pre to 21.7 ± 2.9 NaHCO3post. ΔWT2-WT1 improved particularly in the midsection of 30-s WT on NaHCO3. However, no significant differences were found in peak power (PP), power drop (PD) and average power (AP) (analyzed separately for each WT), and ΔWT2-WT1 in PP and PD. Interaction with gender was significant for AP, PP and PD, every second of WT1 and WT2, as well as DT test. In conclusion, our study suggests that the response to NaHCO3 may be gender-specific and progressive low-dose NaHCO3 supplementation allows the advantageous strengthening of wrestling-specific performance in males. It can also lead to maintenance of high anaerobic power mainly in the midsection of the 30-s Wingate test.

Milk-Fat Globule Membrane Plus Glucosamine Improves Joint Function and Physical Performance: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

Care of the musculoskeletal system, including the muscles, joints, and bones, is important for a healthy life expectancy in today's aging society. The aim of this randomized, double-blind, placebo-controlled study was to investigate the effect of consumption of milk-fat globule membrane (MFGM) and glucosamine on joint function and physical performance. Participants were healthy Japanese men and women, aged 60-74 y, with a history of mild knee or low back pain at rest. They were randomized to receive tablets containing MFGM 1.0 g+glucosamine 1.5 g or placebo tablets for 8 wk. We assessed passive range of motion, active range of motion (self-reported VAS score), JKOM and JLEQ, and physical performance. Data were available for analysis for 25 participants in the active treatment group and 28 in the placebo group. The active group showed significant improvements in passive range of motion at the knee and active range of motion at both the knee and low back. The active group also showed significant improvements in some physical performance, including obstacle walking speed and speed of ascending stairs. The findings of this study suggest that consumption of a combination of MFGM and glucosamine may improve joint function and physical performance.

Exercise and resveratrol increase fracture resistance in the 3xTg-AD mouse model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) and osteoporosis are progressive diseases that affect the elderly population. Both conditions are associated with fracture risk that is greater than twice that of the healthy population. Resveratrol and exercise are two treatments that have been linked with attenuation of age-related diseases, including the risk of bone fractures. In this study, we test the hypothesis that these treatments improve fracture resistance in a mouse model representative of the AD condition. METHODS: Three-month-old male 3xTg-AD mice were treated for 4 months with resveratrol or exercise or both combined, and compared with wild type mice. Exercise training was performed on a treadmill at 15 m/min for 45 min/day, 5 days/week. Resveratrol was given at 4 g/kg diet in the form of pellets. Three-point bending, cross-sectional geometric, and fluorescence analyses were conducted on tibias and compared by treatment group. RESULTS: Tibias of 3xTg mice exhibited signs of diminished bone quality and fracture under less force than age-matched wild type mice (P < 0.05). Treatment with both resveratrol and exercise improved indicators of fracture resistance and bone quality in AD mice to levels comparable to that of wild type mice (P < 0.05). CONCLUSIONS: The 3xTg mouse model of AD is at elevated risk for limb bone fracture compared to wild type controls. Treatment with resveratrol, exercise, or both in combination improves fracture resistance and cross-sectional geometric indicators of bone strength.

Effects of lipoic acid on walking performance, gait, and balance in secondary progressive multiple sclerosis.

BACKGROUND: Gait and balance impairment is common in secondary progressive multiple sclerosis (SPMS). Lipoic acid (LA), an over-the-counter antioxidant, is effective in MS animal models and may improve walking speed, but effects on mobility are unreported. OBJECTIVE: Examine the effects of 1200 mg daily oral dose of LA versus placebo (PLA) on gait and balance in a 2-year, randomized, double-blind pilot study. METHODS: 134 participants were screened for eligibility before assignment to LA (n = 28) or PLA (n = 26). Included here were, 21 participants with SPMS who took LA (N = 11) or PLA (N = 10) capsules for 2 years (enrolled May 2, 2011 - August 14, 2015) and completed all tasks without the use of an assistive device. Participants completed the Timed Up and Go (TUG) and quiet standing tasks every 6 months while wearing inertial sensors (APDM Opals) to quantify mobility. RESULTS: LA had a medium effect on time to complete TUG at 2 years (g = 0.51; 95% CI = -0.35, 1.38). In a subset of 18 participants with less disability (EDSS < 6, no use of ambulatory device), turning time was significantly shorter with LA (p = 0.048, Δ= 0.48 s). No differences in balance metrics were found between groups. CONCLUSIONS: LA had an effect on walking performance in people with SPMS, particularly in those with lower baseline disability. TRIAL REGISTRATION: Lipoic Acid for Secondary Progressive Multiple Sclerosis https://clinicaltrials.gov/ct2/show/NCT01188811?term=spain+lipoic+acid&rank=1 NCT0118881.

Clinical efficacy and safety of nuanxin capsule for chronic heart failure: A systematic review and meta-analysis.

BACKGROUND: Chronic heart failure (CHF), the final phase of various heart diseases, is a serious public health problem resulting in high hospitalization rates, mortality, and increasing health care costs. Nuanxin capsule (NXC), a Chinese herbal formula, has been widely used in the treatment of CHF. However, the safety and efficacy of NXC used in patients with CHF has been uncertain and there has been no standard clinical trial published to confirm this. Thus, we conduct a study to evaluate the safety and efficacy of NXC for CHF. METHODS: The reference lists of randomized controlled trials and 8 electronic databases will be independently and systematically searched by 2 review authors in May 2018. Four English databases (EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature [CINAHL], and Cochrane Central Register of Controlled Trials [CENTRAL]) and 4 Chinese databases (Chinese Biomedical Literature Database [CBM], Chinese National Knowledge Infrastructure [CNKI], Wanfang Database, and VIP Database) will be included. The primary outcomes will be assessed according to the function classification of New York Heart Association (NYHA). Data synthesis will be precisely computed using the RevManV5.3 software when a data-analysis is allowed. Methodological quality will be assessed according to Cochrane Handbook. RESULTS: This study will provide a high-quality synthesis of current evidence of NXC for CHF from different aspects including the mortality, the function classification of NYHA. CONCLUSION: The conclusion of this systematic review will provide evidence to prove whether NXC is an effective therapeutic intervention for patient with CHF.PROSPERO registration number: PROSPERO CRD42018090003.

Effects of a Commercial Supplement of Ophiocordyceps sinensis and Ganoderma lucidum on Physiological Responses to Maximal Exercise in Healthy Young Participants.

Cordyceps sinensis (=Ophiocordyceps sinensis) and Ganoderma lucidum are 2 medicinal mushrooms that have been suggested to have the potential to enhance exercise capacity. We used a commercial supplement combining a traditional Chinese medicine and G. lucidum and tested its effects on human physical, aerobic, and anaerobic capacities. Physical education students (n = 96; 43 women, 53 men; mean ± standard deviation age, 26.3 ± 3.21 years) were randomly divided into 3 groups: low-dose treatment, high-dose treatment, and placebo. Participants received the supplement or the placebo for 28-33 days. Both before and after the intervention, the participants performed a graded maximum oxygen consumption (Vo2max) test on a treadmill and a Wingate anaerobic cycle test (on a different day). The following parameters were measured and recorded during the maximal graded treadmill test: heart rate, oxygen consumption, respiratory exchange ratio, and ventilation. The following parameters were calculated from the Wingate anaerobic cycle test: maximal anaerobic power, mean anaerobic power, and fatigue index. The supplements did not affect Vo2max or the physiological responses upon maximal exercise during the graded treadmill test. In a similar way, they had no effect on peak or mean power, or fatigue index, as measured by the Wingate anaerobic test. A borderline interaction indicated a somewhat lower heart rate at rest after treatment; however, post hoc analysis did not reveal any further statistically significant differences (P = 0.047; F = 3.169). The findings indicate that dual supplementation with C. sinensis and G. lucidum had no effect on Vo2max, on physiological responses at peak exercise load during a graded maximal treadmill test, or on the parameters of anaerobic capacity.

Metabonomic analysis of serum reveals antifatigue effects of Yi Guan Jian on fatigue mice using gas chromatography coupled to mass spectrometry.

Yi Guan Jian (YGJ), one of the most commonly used traditional Chinese medicines, has been reported to possess significant antifatigue effects. However, the mechanisms underlying its antifatigue effects remain largely unresolved. In this study, a metabonomics approach, involving gas chromatography coupled to mass spectrometry and a multivariate statistical technique, was developed to estimate the extent to which YGJ alleviated the exhausting swimming-induced fatigue of mice. High-dose treatment with YGJ significantly extended the swimming time of fatigued mice. Significant alterations of metabolites involving amino acids, organic acids and carbohydrates were observed in the serum of fatigued mice, which were reversed by YGJ treatment while biochemical indexes returned to normal. These metabolic changes suggest that the antifatigue effect of YGJ is associated with the impairement of amino acid, organic acids and carbohydrates. It also appears that YGJ can induce significant metabolic alterations independent of the exhausting swimming-induced metabolic changes. The significantly altered metabolites induced by YGJ intervention include l-2-amino-acetoacetate, taurine, fumaric acid, malic acid, oxoadipic acid and l-aspartate, all of which are associated with antifatigue properties. This suggests that YGJ exerts chemopreventive effects via antifatigue mechanisms.

Effects of dietary supplementation with a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) on joint mobility, comfort, and functional capacity in healthy overweight subjects: a randomized placebo-controlled clinical trial.

BACKGROUND: Joint and connective tissue integrity, comfort and function are paramount to optimal performance in exercise, recreational and occupational activities. The fruit of Terminalia chebula has been used extensively in various traditional health systems for different ailments, with additional preclinical and clinical data demonstrating antioxidant and anti-inflammatory potential. The aim of this study was to evaluate the effects of a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) dietary supplementation on joint mobility, comfort, and functional capacity in healthy overweight subjects. METHODS: One-hundred and five (105) overweight, apparently healthy male and female subjects (35-70 years of age) were pre-screened and randomized to one of three groups for 84 days: placebo, AyuFlex1 (250 mg twice daily) or AyuFlex2 (500 mg twice daily) in a randomized, double-blind, placebo-controlled design. A two-week placebo lead-in period was used to improve data quality/validity. All subjects had no knee joint discomfort at rest, but experienced knee joint discomfort only with activity/exercise of at least 30 on 100 mm Visual Analog Scale (VAS). Primary outcome measures included symptoms of joint health and function as measured by modified-Knee Injury & Osteoarthritis Outcomes Score (mKOOS) global & modified-Western Ontario and McMaster Universities Arthritis Index (mWOMAC) subscales (discomfort, stiffness and function). Secondary outcomes included VAS questionnaires on overall/whole-body joint health, low back health, knee mobility, willingness and ability to exercise, 6-min walk test for distance and range of motion (ROM) of pain-free knee flexion/extension. Tertiary outcome measures included inflammatory (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α) and extracellular matrix (ECM)/Connective Tissue (COMP) biomarkers, and safety (vital signs and blood markers) & tolerability (Adverse Event (AE)/ side effect profiles). RESULTS: Compared to placebo, at day 84 AyuFlex® treatment significantly: 1) improved mKOOS global scores in AyuFlex1 + AyuFlex2 (P = 0.023), and improved total and physical function subscale of mWOMAC relative to baseline, 2) improved VAS scores for Knee Discomfort with activity/exercise in AyuFlex1 + AyuFlex2 (P = 0.001) relative to baseline, 3) improved VAS scores for whole-body joint function in AyuFlex1 + AyuFlex2 (P < 0.029) relative to baseline, 4) improved VAS score for decreased knee joint soreness following leg extension challenge for AyuFlex1 (P = 0.022) and AyuFlex2 (P = 0.043) relative to baseline, 5) improved 6-min walk performance distance covered (P = 0.047) and VAS discomfort (P = 0.026) post-6 min walk in AyuFlex1 + AyuFlex2 relative to baseline, 6) and tended to decrease COMP levels in AyuFlex1 + AyuFLex2 (P = 0.104) relative to baseline. All biomarkers of safety remained within normative limits during the study. Low back health tended to improve in the AyuFlex1 and AyuFlex2 group, but failed to reach significance relative to placebo group. CONCLUSIONS: AyuFlex® improved mKOOS global scores, knee joint discomfort with activity/exercise, 6-min walk test distance covered and discomfort post-6 min walk test, overall whole-body joint function, knee soreness following leg extension resistance exercise in a healthy, overweight population, without AE. Differences between 250 mg/BID and 500 mg/BID were non-significant for most of the outcome measures, validating the efficacy of the lower dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02589249 ; October 26, 2015.

The effects of dietary nitrate supplementation on the adaptations to sprint interval training in previously untrained males.

OBJECTIVES: Dietary nitrate can improve repeated high-intensity and supramaximal exercise performance, although the effect on adaptations to training has received limited attention. The purpose of this study was to investigate the effects of dietary nitrate on the response to 3-weeks of sprint interval training (SIT). DESIGN: Randomized control trial. METHODS: Twenty-seven untrained males (Age: 28±7 y, V⋅O2Max: 42±7mlkg-1min-1) completed an incremental exercise test at the beginning and end of the study. Participants were matched for V⋅O2Max and randomly assigned to a control group (CON; n=8), SIT+placebo group (PLA; n=10), or SIT+nitrate group (NIT; n=9). The SIT comprised 4-6 repeated 15 s all out sprints on a cycle ergometer, interspersed with 4min active recovery, 3-times per week. Approximately 2.5h prior to exercise, participants consumed gels containing ∼0.1mmol (PLA) or ∼8mmol nitrate (NIT). RESULTS: Following SIT, V⋅O2Max (PLA: 5%, p=0.057, d=0.34; NIT: 6.3%, p=0.041, d=0.34) and ventilatory threshold (VT) increased to a similar extent in both SIT groups. Maximum work rate tended to increase to a greater extent in NIT (8.7%, d=0.55) compared to PLA (4.7%, d=0.31, p=0.073). Fatigue index, calculated by the change in mean power from the first to the last sprint, tended to be reduced following SIT in NIT compared to PLA (PLA: 7.3±7.4%, NIT: 0.5±7.1%, p=0.058). CONCLUSIONS: While dietary nitrate supplementation does not augment improvements to V⋅O2Max and VT following SIT, it may improve WRmax and indices of repeated high-intensity exercise.

Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction.

Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.

Effects of dietary almond- and olive oil-based docosahexaenoic acid- and vitamin E-enriched beverage supplementation on athletic performance and oxidative stress markers.

Functional beverages based on almonds and olive oil and enriched with α-tocopherol and docosahexaenoic acid (DHA) could be useful in modulating oxidative stress and enhancing physical performance in sportsmen. The aim of this work was to evaluate the effects of supplementation with functional beverages on physical performance, plasma and erythrocyte fatty acids' and polyphenol handling, oxidative and nitrative damage, and antioxidant and mitochondrial gene expression in young and senior athletes. Athletes performed maximal exercise tests before and after one month of dietary supplementation and blood samples were taken immediately before and one hour after each test. The beverages did not alter performance parameters during maximal exercise. Supplementation increased polyunsaturated and reduced saturated plasma fatty acids while increasing the DHA erythrocyte content; it maintained basal plasma and blood polyphenol levels, but increased the blood cell polyphenol concentration in senior athletes. Supplementation protects against oxidative damage although it enhances nitrative damage in young athletes. The beverages enhance the gene expression of antioxidant enzymes in peripheral blood mononuclear cells after exercise in young athletes.

Caffeine Ingestion Increases Estimated Glycolytic Metabolism during Taekwondo Combat Simulation but Does Not Improve Performance or Parasympathetic Reactivation.

OBJECTIVES: The aim of this study was to evaluate the effect of caffeine ingestion on performance and estimated energy system contribution during simulated taekwondo combat and on post-exercise parasympathetic reactivation. METHODS: Ten taekwondo athletes completed two experimental sessions separated by at least 48 hours. Athletes consumed a capsule containing either caffeine (5 mg∙kg-1) or placebo (cellulose) one hour before the combat simulation (3 rounds of 2 min separated by 1 min passive recovery), in a double-blind, randomized, repeated-measures crossover design. All simulated combat was filmed to quantify the time spent fighting in each round. Lactate concentration and rating of perceived exertion were measured before and after each round, while heart rate (HR) and the estimated contribution of the oxidative (WAER), ATP-PCr (WPCR), and glycolytic (W[La-]) systems were calculated during the combat simulation. Furthermore, parasympathetic reactivation after the combat simulation was evaluated through 1) taking absolute difference between the final HR observed at the end of third round and the HR recorded 60-s after (HRR60s), 2) taking the time constant of HR decay obtained by fitting the 6-min post-exercise HRR into a first-order exponential decay curve (HRRτ), or by 3) analyzing the first 30-s via logarithmic regression analysis (T30). RESULTS: Caffeine ingestion increased estimated glycolytic energy contribution in relation to placebo (12.5 ± 1.7 kJ and 8.9 ± 1.2 kJ, P = 0.04). However, caffeine did not improve performance as measured by attack number (CAF: 26. 7 ± 1.9; PLA: 27.3 ± 2.1, P = 0.48) or attack time (CAF: 33.8 ± 1.9 s; PLA: 36.6 ± 4.5 s, P = 0.58). Similarly, RPE (CAF: 11.7 ± 0.4 a.u.; PLA: 11.5 ± 0.3 a.u., P = 0.62), HR (CAF: 170 ± 3.5 bpm; PLA: 174.2 bpm, P = 0.12), oxidative (CAF: 109.3 ± 4.5 kJ; PLA: 107.9 kJ, P = 0.61) and ATP-PCr energy contributions (CAF: 45.3 ± 3.4 kJ; PLA: 46.8 ± 3.6 kJ, P = 0.72) during the combat simulation were unaffected. Furthermore, T30 (CAF: 869.1 ± 323.2 s; PLA: 735.5 ± 232.2 s, P = 0.58), HRR60s (CAF: 34 ± 8 bpm; PLA: 38 ± 9 bpm, P = 0.44), HRRτ (CAF: 182.9 ± 40.5 s, PLA: 160.3 ± 62.2 s, P = 0.23) and HRRamp (CAF: 70.2 ± 17.4 bpm; PLA: 79.2 ± 17.4 bpm, P = 0.16) were not affected by caffeine ingestion. CONCLUSIONS: Caffeine ingestion increased the estimated glycolytic contribution during taekwondo combat simulation, but this did not result in any changes in performance, perceived exertion or parasympathetic reactivation.

Combination of Cilostazol and L-Carnitine Improves Walking Performance in Peripheral Arterial Disease Model Rats.

Cilostazol and L-carnitine have been used as a first-line drug and supplement, respectively, in patients with peripheral arterial disease with intermittent claudication. In this study, the effect of the combination of cilostazol and L-carnitine has been investigated in rats with unilateral hindlimb ischemia. For 28 days, cilostazol and L-carnitine were administrated separately or as a combination. The distance walked before gait disturbance developed was measured using a treadmill for 5 days a week. The capillary density of the ischemic hindlimb was evaluated by immunohistochemical staining at days 7, 14, 21, and 28. Angiogenic gene expression was measured by real-time RT-PCR at days 7 and 28. The greatest increase in the distance was observed in the combination therapy group when compared to the other groups. The capillary density in the adductor muscles of rats treated with cilostazol alone and combination therapy increased at day 28. Angiopoietin-2/Angiopoietin-1 expression ratios were higher, suggesting the promotion of angiogenesis, with cilostazol alone and combination therapy at day 7. This is the first study to show functional improvement of the hind limb following combination therapy with cilostazol and L-carnitine in experimental animals. This study also revealed that cilostazol promotes angiogenesis, and L-carnitine additively contributes to functional improvement via a non-angiogenic mechanism.

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

Behavioral and cognitive effects of tyrosine intake in healthy human adults.

The amino acid tyrosine is the precursor to the catecholamine neurotransmitters dopamine and norepinephrine. Increasing tyrosine uptake may positively influence catecholamine-related psychological functioning. We conducted a systematic review to examine the effects of tyrosine on behavior and cognition. Fifteen studies were reviewed. All studies except one involved tyrosine loading during a single test session. In most behavioral studies, there were no significant effects of tyrosine on exercise performance. In contrast, cognitive studies employing neuropsychological measures found that tyrosine loading acutely counteracts decrements in working memory and information processing that are induced by demanding situational conditions such as extreme weather or cognitive load. The buffering effects of tyrosine on cognition may be explained by tyrosine's ability to neutralize depleted brain catecholamine levels. There is evidence that tyrosine may benefit healthy individuals exposed to demanding situational conditions. For future research we recommend moving from studying the acute effects of a single tyrosine load in small samples to studying the behavioral and cognitive effects of tyrosine in larger groups over multiple weeks.

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy.

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

Impact of polyphenol antioxidants on cycling performance and cardiovascular function.

This investigation sought to determine if supplementation with polyphenol antioxidant (PA) improves exercise performance in the heat (31.5 °C, 55% RH) by altering the cardiovascular and thermoregulatory responses to exercise. Twelve endurance trained athletes ingested PA or placebo (PLAC) for 7 days. Consecutive days of exercise testing were performed at the end of the supplementation periods. Cardiovascular and thermoregulatory measures were made during exercise. Performance, as measured by a 10 min time trial (TT) following 50 min of moderate intensity cycling, was not different between treatments (PLAC: 292 ± 33 W and PA: 279 ± 38 W, p = 0.12). Gross efficiency, blood lactate, maximal neuromuscular power, and ratings of perceived exertion were also not different between treatments. Similarly, performance on the second day of testing, as assessed by time to fatigue at maximal oxygen consumption, was not different between treatments (PLAC; 377 ± 117 s vs. PA; 364 ± 128 s, p = 0.61). Cardiovascular and thermoregulatory responses to exercise were not different between treatments on either day of exercise testing. Polyphenol antioxidant supplementation had no impact on exercise performance and did not alter the cardiovascular or thermoregulatory responses to exercise in the heat.

A single dose of beetroot juice enhances cycling performance in simulated altitude.

INTRODUCTION: Increasing nitric oxide bioavailability via supplementation with nitrate-rich beetroot juice (BR) has been shown to attenuate the negative effect of hypoxia on peripheral oxygen saturation and exercise tolerance. PURPOSE: We investigated the effects of a single dose of concentrated BR on the physiological responses to submaximal exercise and time trial (TT) performance in trained cyclists exposed to moderate simulated altitude (approximately 2500 m). METHODS: Nine competitive amateur male cyclists (age, 28 ± 8 yr; V˙O2peak at altitude, 51.9 ± 5.8 mL·kg·min) completed four exercise trials consisting of an initial graded test to exhaustion and three performance trials on a cycle ergometer. The performance trials comprised 15 min of submaximal steady-state exercise at 60% maximum work rate and a 16.1-km TT. The second and third trials were preceded by ingestion of either 70 mL of BR or nitrate-depleted BR (PLA) 3 h before exercise. RESULTS: Plasma nitrate (PLA, 39.1 ± 3.5 µM; BR, 150.5 ± 9.3 µM) and nitrite (PLA, 289.8 ± 27.9 nM; BR, 678.1 ± 103.5 nM) measured immediately before exercise were higher after ingestion of BR compared with that after PLA (P < 0.001, P = 0.004). V˙O2 during steady-state exercise was lower in the BR trial (2542 ± 114 mL·min) than that in the PLA trial (2727 ± 85 mL·min, P = 0.049). TT performance was significantly faster after BR (1664 ± 14 s) than that after PLA (1702 ± 15 s, P = 0.021). CONCLUSION: A single dose of BR lowered V˙O2 during submaximal exercise and enhanced TT performance of trained cyclists in normobaric hypoxia. Consequently, ingestion of BR may be a practical and effective ergogenic aid for endurance exercise at altitude.