Low Energy Availability and Increased Risk of Relative Energy Deficiency in Sport (RED-S) During a 3767-km Thru-Hike on the Pacific Crest Trail: A Case Study.

Long-distance "thru-hiking" has extraordinary physical demands and has become increasingly popular. This report describes a man (55 y) who thru-hiked the Pacific Crest Trail in 2021 and was at risk of developing the relative energy deficiency in sport (RED-S) syndrome. Hiking distance was 3767 km over 128 d. Eighty-eight days (69%) were full days of hiking, covering 38±8 km/d (mean±SD) in 7.9±1.6 h/d. Exercise energy expenditure above rest (heart rate vs indirect calorimetry regression method) was 2834±1518 kcal/d, total energy expenditure was 5702±1323 kcal/d, and energy intake was 4141 kcal/d. Body mass decreased by 9%, and fat mass (dual-energy X-ray absorptiometry) decreased by 46%. Energy availability (energy intake minus exercise energy expenditure) was 19.3 kcal/d/kg fat-free mass, indicating low energy availability (defined as <30 kcal/d/kg). Dual-energy X-ray absorptiometry-measured spine bone mineral density (BMD) decreased by 8.6%, with little to no decrease in total hip (-1.0%) and femoral neck (-1.5%) BMD. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides increased by 24, 39, and 57%, respectively. Within 8 mo after the hike, BMD and serum lipids nearly or fully returned to baseline. No changes in high-density lipoprotein cholesterol, glycemia, or blood pressure were observed. According to guidelines, these observations are consistent with a moderate risk of RED-S, and a medical evaluation and treatment plan are advisable in order to avoid clinical manifestations (eg, stress fractures, anemia, psychological disturbances). To minimize RED-S risk, it may be prudent for thru-hikers to optimize energy availability by moderating daily hiking distances and/or increasing food intake.

Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Short-Term Mediterranean Diet Improves Endurance Exercise Performance: A Randomized-Sequence Crossover Trial.

Objective: Healthful dietary patterns have constituents that are known to improve exercise performance, such as antioxidants, nitrates, and alkalizing effects. However, ergogenic effects of such diets have not been evaluated. We hypothesized that a short-term Mediterranean diet results in better exercise performance, as compared to a typical Western diet. Methods: Eleven recreationally active women (n = 7) and men (n = 4) (body mass index, 24.6 ± 3.2 kg/m2; age 28 ± 3 years) were studied in a randomized-sequence crossover study, in which they underwent exercise performance testing on one occasion after 4 days of a Mediterranean diet and on another occasion after 4 days of a Western diet. A 9- to 16-day washout period separated the two trials. Endurance exercise performance was evaluated with a 5-km treadmill time trial. Anaerobic exercise performance tests included a Wingate cycle test, a vertical jump test, and hand grip dynamometry. Results: Five-kilometer run time was 6% ± 3% shorter (faster) in the Mediterranean diet trial than in the Western diet trial (27.09 ± 3.55 vs 28.59 ± 3.21 minutes; p = 0.030) despite similar heart rates (160 ± 5 vs 160 ± 4 beats/min; p = 0.941) and ratings of perceived exertion (14.6 ± 0.5 vs 15.0 ± 0.5; p = 0.356). No differences between the diet conditions were observed for anaerobic exercise tests, including peak and mean power from the Wingate test (both p ≥ 0.05), the vertical jump test (p = 0.19), and the hand grip strength test (p = 0.69). Conclusions: Our findings extend existing evidence of the health benefits of the Mediterranean diet by showing that this diet is also effective for improving endurance exercise performance in as little as 4 days. Further studies are warranted to determine whether a longer-term Mediterranean diet provides greater benefits and whether it might also be beneficial for anaerobic exercise performance and muscle strength and power.

Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women.

The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m(-2)) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might facilitate better training adaptations and exercise adherence. Key pointsSeven days of 3000 mg/day supplementation with algae-derived docosahexaenoic acid (DHA) attenuates the delayed onset muscle soreness and stiffness, and protects against the loss of joint range of motion that is caused by strenuous eccentric exercise.This benefit was observed in women, and supports the findings from other studies that were conducted on men or a combination of men and womenThe benefits from algae-derived DHA appear to be similar to those reported in other studies that used a combination of DHA and eicosapentaenoic acid (EPA) derived from fish oilThe findings of better recovery from strenuous exercise with DHA supplementation, paired with other research which demonstrated that DHA and EPA protect against chronic diseases suggest that DHA is an attractive optionThese findings have relevance to athletic populations, in that DHA would be expected to facilitate recovery and allow for better performance during training and competition. However, DHA supplementation might also benefit non-athletic populations, such as individuals starting new exercise programs and patient populations that are prone to muscle soreness (e.g. physical therapy patients).

Micronutrient Deficiencies in Patients With Heart Failure: Relationships With Body Mass Index and Age.

BACKGROUND: It is conceivable that lean patients (body mass index 18.5-24.9 kg/m(2)) with heart failure (HF) have low body weight due to low food consumption and that this may contribute to micronutrient deficiencies and to their poorer prognosis compared with overweight/obese patients. We hypothesized that lean patients have a greater number of inadequate micronutrient intakes (<50% of recommendations) than overweight/obese patients and that this also depends on age. METHODS AND RESULTS: Lean (n = 15) and overweight/obese (n = 49) patients underwent 24-hour diet and physical activity recall interviews. Inadequate essential micronutrient intakes were ubiquitous (intakes of 13 ± 1 of 27 micronutrients were inadequate) and did not depend on race, status, or access to supermarkets. Younger (40-64 y) lean patients had inadequate intakes of 20 ± 2 micronutrients, which was more than the other weight/age subgroups (all P < .01). Physical activity levels did not differ across weight and age groups. CONCLUSIONS: Patients with HF may be at risk of malnutrition due to numerous inadequate micronutrient intakes; younger lean patients may have an especially high risk. Future studies are needed to confirm these preliminary findings and to investigate the possibility that incorporating a micronutrient-dense meal plan will improve patient outcomes.

Effects of oral sodium supplementation on indices of thermoregulation in trained, endurance athletes.

Guidelines recommend the consumption of sodium during exercise to replace losses in sweat; however, the effects of sodium on thermoregulation are less clear. To determine the effects of high-dose sodium supplementation on indices of thermoregulation and related outcomes, 11 endurance athletes participated in a double-blind, randomized-sequence, crossover study in which they underwent 2-hrs of endurance exercise at 60% heart rate reserve with 1800 mg of sodium supplementation (SS) during one trial and placebo (PL) during the other trial. A progressive intensity time-to-exhaustion test was performed after the 2-hr steady state exercise as an assessment of exercise performance. Sweat rate was calculated from changes in body weight, accounting for fluid intake and urinary losses. Ratings of perceived exertion (RPE) and heat stress were assessed using verbal numeric scales. Cardiovascular drift was determined from the rise in HR during the 2-hr steady state exercise test. Skin temperature was measured with an infrared thermometer. Dehydration occurred in both SS and PL trials, as evidenced by substantial weight loss (2.03 ± 0.43% and 2.27 ± 0.70%, respectively; p = 0.261 between trials). Sweat rate was 1015.53 ± 239.10 ml·hr(-1) during the SS trial and 1053.60±278.24 ml/hr during the PL trial, with no difference between trials (p = 0.459). Heat stress ratings indicated moderate heat stress ("warm/hot" ratings) but were not different between trials (p = 0.825). Time to exhaustion during the SS trial was 6.88 ± 3.88 minutes and during the PL trial averaged 6.96 ± 3.61 minutes, but did not differ between trials (p = 0.919). Cardiovascular drift, skin temperature, and RPE did not differ between trials (all p > 0.05). High-dose sodium supplementation does not appear to impact thermoregulation, cardiovascular drift, or physical performance in trained, endurance athletes. However, in light of the possibility that high sodium intakes might have other adverse effects, such as hypertension, it is our recommendation that athletes interpret professional recommendations for sodium needs during exercise with caution. Key pointsBased on current professional recommendations to replace sodium losses in sweat during exercise, some endurance athletes consume salt or other electrolyte supplements containing sodium during training and competition, however the effects of sodium on thermoregulation are less clear.High-dose sodium supplementation does not appear to impact thermoregulation, cardiovascular drift, or physical performance in trained, endurance athletes.The possibility remains that high sodium intakes might have other adverse effects. It is our recommendation that athletes interpret professional recommendations for sodium needs during exercise with caution.

Effects of dietary Acid load on exercise metabolism and anaerobic exercise performance.

Dietary acid load, quantified as the potential renal acid load (PRAL) of the diet, affects systemic pH and acid-base regulation. In a previous cross-sectional study, we reported that a low dietary PRAL (i.e. alkaline promoting diet) is associated with higher respiratory exchange ratio (RER) values during maximal exercise. The purpose of the present study was to confirm the previous findings with a short-term dietary intervention study. Additionally, we sought to determine if changes in PRAL affects submaximal exercise RER (as a reflection of substrate utilization) and anaerobic exercise performance. Subjects underwent a graded treadmill exercise test (GXT) to exhaustion and an anaerobic exercise performance test on two occasions, once after following a low-PRAL diet and on a separate occasion, after a high-PRAL diet. The diets were continued as long as needed to achieve an alkaline or acid fasted morning urine pH, respectively, with all being 4-9 days in duration. RER was measured during the GXT with indirect calorimetry. The anaerobic performance test was a running time-to-exhaustion test lasting 1-4 min. Maximal exercise RER was lower in the low-PRAL trial compared to the high-PRAL trial (1.10 ± 0.02 vs. 1.20 ± 0.05, p = 0.037). The low-PRAL diet also resulted in a 21% greater time to exhaustion during anaerobic exercise (2.56 ± 0.36 vs. 2.11 ± 0.31 sec, p = 0.044) and a strong tendency for lower RER values during submaximal exercise at 70% VO2max (0.88 ± 0.02 vs. 0.96 ± 0.04, p = 0.060). Contrary to our expectations, a short-term low-PRAL (alkaline promoting) diet resulted in lower RER values during maximal-intensity exercise. However, the low-PRAL diet also increased anaerobic exercise time to exhaustion and appears to have shifted submaximal exercise substrate utilization to favor lipid oxidation and spare carbohydrate, both of which would be considered favorable effects in the context of exercise performance. Key pointsShort-term (4-9 days) changes in the acid or alkaline promoting qualities of the diet, quantified as potential renal acid load (PRAL), alter systemic pH, as evidenced in the present study by changes in fasted morning urine pH. Low-PRAL (alkaline promoting) diets are characterized by high intakes of vegetables and fruits with limited consumption of meats, cheeses, and grains while high-PRAL diets are characterized by the opposite dietary pattern.An alkaline promoting (low-PRAL) diet increases anaerobic exercise performance, as evidenced by greater time-to-exhaustion during high-intensity treadmill running.Preliminary evidence suggests that an alkaline promoting (low-PRAL) diet increases lipid oxidation and may have a carbohydrate-sparing effect during submaximal endurance exercise, although further studies are needed.In contrast to what has been observed in response to habitual/long-term dietary patterns, a short-term low-PRAL diet does not increase maximal exercise respiratory exchange ratio and even appears to lower it. This suggests that short-term and long-term alterations in PRAL have different physiologic effects on this parameter.

Benefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus risk.

In the United States, life expectancy has markedly increased during the past century, and population ageing is expected to double within the next 25 years. The process of ageing in a population is associated with the development of chronic diseases, such as type 2 diabetes mellitus, that can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. The evidence to date, consolidated by the numerous epidemiological studies and clinical trials conducted, suggests that caloric restriction is an effective nutritional intervention for preventing most of these age-related conditions. At a metabolic level, caloric restriction with adequate nutrition has been shown to improve insulin sensitivity, reduce fasting glucose and insulin concentration and prevent obesity, type 2 diabetes, hypertension and chronic inflammation. The purpose of this article is to review current knowledge of the metabolic and clinical implications of caloric restriction with adequate nutrition for the prevention of type 2 diabetes and cardiovascular disease.

Caloric restriction: powerful protection for the aging heart and vasculature.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Research has shown that the majority of the cardiometabolic alterations associated with an increased risk of CVD (e.g., insulin resistance/type 2 diabetes, abdominal obesity, dyslipidemia, hypertension, and inflammation) can be prevented, and even reversed, with the implementation of healthier diets and regular exercise. Data from animal and human studies indicate that more drastic interventions, i.e., calorie restriction with adequate nutrition (CR), may have additional beneficial effects on several metabolic and molecular factors that are modulating cardiovascular aging itself (e.g., cardiac and arterial stiffness and heart rate variability). The purpose of this article is to review the current knowledge on the effects of CR on the aging of the cardiovascular system and CVD risk in rodents, monkeys, and humans. Taken together, research shows that CR has numerous beneficial effects on the aging cardiovascular system, some of which are likely related to reductions in inflammation and oxidative stress. In the vasculature, CR appears to protect against endothelial dysfunction and arterial stiffness and attenuates atherogenesis by improving several cardiometabolic risk factors. In the heart, CR attenuates age-related changes in the myocardium (i.e., CR protects against fibrosis, reduces cardiomyocyte apoptosis, prevents myosin isoform shifts, etc.) and preserves or improves left ventricular diastolic function. These effects, in combination with other benefits of CR, such as protection against obesity, diabetes, hypertension, and cancer, suggest that CR may have a major beneficial effect on health span, life span, and quality of life in humans.

The Effect of Omega-3 Fatty Acid Supplementation on the Inflammatory Response to eccentric strength exercise.

Omega-3 fatty acids (omega-3) have anti-inflammatory properties. However, it is not known if omega-3 supplementation attenuates exercise-induced inflammation. We tested the hypothesis that omega-3 supplementation reduces inflammation that is induced by eccentric arm curl exercise. Healthy adult men and women (n=11; 35 ± 10 y) performed eccentric biceps curls on two occasions, once after 14d of dietary omega-3 restriction (control trial) and again after 7d of 3,000 mg/d omega-3 supplementation (omega-3 trial). Before and 48 h after eccentric exercise, signs of inflammation was assessed by measuring soreness ratings, swelling (arm circumference and arm volume), and temperature (infrared skin sensor). Arm soreness increased (p < 0.0001) in response to eccentric exercise; the magnitude of increase in soreness was 15% less in the omega-3 trial (p = 0.004). Arm circumference increased after eccentric exercise in the control trial (p = 0.01) but not in the omega-3 trial (p = 0.15). However, there was no difference between trials (p = 0.45). Arm volume and skin temperature did not change in response to eccentric exercise in either trial. These findings suggest that omega-3 supplementation decreases soreness, as a marker of inflammation, after eccentric exercise. Based on these findings, omega-3 supplementation could provide benefits by minimizing post-exercise soreness and thereby facilitate exercise training in individuals ranging from athletes undergoing heavy conditioning to sedentary subjects or patients who are starting exercise programs or medical treatments such as physical therapy or cardiac rehabilitation. Key pointsDietary supplementation with omega-3 fatty acids has been shown to reduce inflammation in numerous inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and Chrohn's disease.Although strenuous exercise is known to cause acute increases in inflammation, it is not clear if omega-3 fatty acid supplementation attenuates this adverse response to exercise.Our research demonstrates that 3000 mg·d-1 omega-3 fatty acid supplementation minimizes the severe, delayed-onset muscle soreness that results from strenuous eccentric strength exercise.This information, along with a plethora of information showing that omega-3 fatty acid supplementation has other health benefits, demonstrates that a readily available over the counter nutritional supplement (i.e. omega-3 fatty acids) reduces delayed-onset soreness caused by strenuous strength exercise.This information has obvious relevance to athletic populations but also to other groups such as physical therapy patients and newly admitted cardiac rehabilitation patients, as muscle soreness, if left unchecked, can slow the progress in adapting to a new exercise program.Furthermore, as inflammation is known to be involved in the pathogenesis if numerous diseases, including heart disease, cancer, and diabetes, it is likely prudent for individuals to use inflammation-attenuating interventions, such as omega-3 supplementation, to keep inflammatory responses to physical activity at a minimum.

Effect of Huperzine A on Cognitive Function and Perception of Effort during Exercise: A Randomized Double-Blind Crossover Trial.

Huperzine A has shown the ability to acutely improve cognitive function in certain populations, and therefore is commonly added to pre-workout supplements. However, its effects have not been studied in exercise-trained individuals. OBJECTIVE: We hypothesized that acute consumption of huperzine A would improve cognitive function during exercise, which may be beneficial for exercise performance. METHODS: From January to April, 2018, 15 exercise-trained individuals (11 women [height 166 ± 2 cm, weight 60.5 ± 3.0 kg] and 4 men [height 173 ± 4 cm, weight 82.0 ± 11.0 kg], BMI 23.5 ± 1.4 kg/m2, age 30.4 ± 3.6 years) were studied in a double blind randomized-sequence cross-over study, in which they underwent tests for cognitive function (digit span, verbal/word fluency, and Stroop), neuromuscular performance (sharpened Romberg and dart throwing), and exercise performance (estimated aerobic capacity, hand-grip strength, vertical jump, and push-up) after acute ingestion of huperzine A (200 mcg) or placebo. One week separated the two trials. RESULTS: No measures of cognitive function differed between placebo and huperzine A trials (all p ≥ 0.296). Heart rates (157 ± 4 vs. 158 ± 4 bpm; p = 0.518) and ratings of perceived exertion (13.7 ± 0.56 vs. 13.9 ± 0.61; p = 0.582) did not differ between placebo and huperzine A trials, respectively. Ratings of subjective difficulty post-exercise (0-10 scale) were significantly higher (5.7 ± 0.38 vs. 6.8 ± 0.38; p = 0.002) in the huperzine A trial than the placebo trial. No differences were observed for neuromuscular or exercise performance measures between groups (all p ≥ 0.497). CONCLUSIONS: Huperzine A does not enhance cognitive function during exercise despite it being marketed as a cognitive enhancer. Because of its inability to enhance cognitive function, its inclusion in pre-workout supplements warrants reconsideration. Other more practical and effective strategies should be considered.

Short Term High-Repetition Back Squat Protocol Does Not Improve 5-km Run Performance.

The purpose of this study was to evaluate the hypothesis that a novel high-repetition, low-resistance back squat training protocol, designed to stimulate high-intensity interval training, improves 5-km run performance. Fifteen runners [4 male, 11 female; 150 + minutes of endurance exercise/week; age = 22.7 ± 2.0 y; 21.5 ± 2.2 kg/m2 BMI] in this single-group test-retest design completed two weeks of back squats consisting of three sets of 15-24 repetitions at 60% of estimated one-repetition max (1RM), three times per week (1-2 days of rest between sessions). Outcome tests included a 5-km outdoor timed run, laboratory indirect calorimetry to quantify substrate oxidation rates during steady-state submaximal exercise (60% and 70% heart rate max (HRmax)), and estimated 1RM for back squats. Back squat estimated 1RM increased by 20% (58.3 ± 18.5 to 70.2 ± 16.7 kg, P < 0.001). However, 5-km run times due to the back squat protocol did not significantly change (Pre-Squats: 23.9 ± 5.0 vs. Post-Squats: 23.7 ± 4.3 minutes, P = 0.71). Likewise, the squat training program did not significantly alter carbohydrate or lipid oxidation rates during steady-state submaximal exercise at 60% or 70% of HRmax (P values ranged from 0.36 - 0.99). Short term high-repetition back squat training does not appear to impact 5-km run performance or substrate utilization during submaximal exercise.

Correction: The Effect of Protandim® Supplementation on Athletic Performance and Oxidative Blood Markers in Runners.

[This corrects the article DOI: 10.1371/journal.pone.0160559.].

Large-for-gestational-age infants of type 1 diabetic mothers: an effect of preprandial hyperglycemia?

OBJECTIVE: To determine how the frequency, timing and magnitude of hyperglycemia are associated with large-for-gestational-age (LGA) infants in pregnancies complicated by type 1 diabetes. METHODS: Charts from pregnant women with type 1 diabetes (n = 70) were reviewed. Indices of maternal glycemic control were determined for seven gestational periods (weeks 7-10, 11-15, 16-19, 20-24, 25-28, 29-32 and 33-38) and compared between women who delivered LGA infants and appropriate-for-gestational-age (AGA) infants. RESULTS: Of the 70 pregnancies, 57% of the infants were LGA (4.3 +/- 0.4 kg) and 43% were AGA (3.2 +/- 0.4 kg). Total maternal weight gain and rate of weight gain were significantly higher in mothers with LGA infants. The glycemic variables associated with an LGA infant were percentage of preprandial values above target for weeks 11-15, 25-28 and 29-32, and percentage of all values above target for weeks 33-38. For the entire pregnancy, the strongest predictors of an LGA infant were percentage of preprandial blood glucose values above target during weeks 29-32 and maternal weight gain. CONCLUSIONS: In pregnant women with type 1 diabetes, frequent episodes of preprandial hyperglycemia in the third trimester significantly impact the development of LGA infants.

Low-carbohydrate, ketogenic diet impairs anaerobic exercise performance in exercise-trained women and men: a randomized-sequence crossover trial.

BACKGROUND: Low-carbohydrate, ketogenic diets cause mild, subclinical systemic acidosis. Anaerobic exercise performance is limited by acidosis. Therefore, we evaluated the hypothesis that a low-carbohydrate, ketogenic diet impairs anaerobic exercise performance, as compared to a high-carbohydrate diet. METHODS: Sixteen men and women (BMI, 23±1 kg/m2, age 23±1 years) participated in a randomized-sequence, counterbalanced crossover study in which they underwent exercise testing after 4 days of either a low-carbohydrate, ketogenic diet (LC; <50 g/day and <10% of energy from carbohydrates) or a high-carbohydrate diet (HC; 6-10 g/kg/day carbohydrate). Dietary compliance was assessed with nutrient analysis of diet records, and with measures of urine pH and ketones. Anaerobic exercise performance was evaluated with the Wingate anaerobic cycling test and the yo-yo intermittent recovery test. RESULTS: The diets were matched for total energy (LC: 2333±158 kcal/d; HC: 2280±160 kcal/d; P=0.65) but differed in carbohydrate content (9±1% vs. 63±2% of energy intake; P<0.001). LC resulted in lower urine pH (5.9±0.1 vs. 6.3±0.2, P=0.004) and the appearance of urine ketones in every participant. LC resulted in 7% lower peak power (801±58 watts vs. 857±61 watts, P=0.008) and 6% lower mean power (564±50 watts vs. 598±51 watts, P=0.01) during the Wingate Test. Total distance ran in the yo-yo intermittent recovery test was 15% less after LC diet (887±139 vs. 1045±145 meters, P=0.02). CONCLUSIONS: Short-term low-carbohydrate, ketogenic diets reduce exercise performance in activities that are heavily dependent on anaerobic energy systems. These findings have clear performance implications for athletes, especially for high-intensity, short duration activities and sports.

The historical context and scientific legacy of John O. Holloszy.

John O. Holloszy, as perhaps the world's preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy's outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.

Caloric restriction but not exercise-induced reductions in fat mass decrease plasma triiodothyronine concentrations: a randomized controlled trial.

Caloric restriction (CR) decreases circulating triiodothyronine (T(3)) concentration. However, it is not known if this effect is due to body fat mass reductions or due to CR, per se. The purpose of this study was to test the hypothesis that plasma T(3) concentration decreases with CR-induced reductions in fat mass but not in response to similar decreases in fat mass that are induced by exercise. Sedentary, nonobese 50- to 60-year-old men and women with no clinical evidence of cardiovascular or metabolic disease and not taking thyroid medications were randomly assigned to 12 months of caloric restriction (n = 18) or exercise-induced weight loss (n = 17) or to a control group (n = 9). Body weight and composition and plasma concentrations of the thyroid hormones T(3), thyrotropin (TSH), thyroxine (T(4)), and free thyroxine (FT(4)) were measured at baseline and 12 months. Fat mass changed significantly in the CR (-6.3 +/- 1.0 kg) and exercise (-5.5 +/- 1.0 kg) groups but not in the control group (-0.6 +/- 1.4 kg). The changes were not significantly different between the CR and exercise groups. Plasma T(3) concentration decreased in the CR group (-9.8 +/- 2.0 ng/dL, p < 0.0001) but not in the exercise (-3.8 +/- 2.1 ng/dL, p = 0.07) or control (-1.3 +/- 2.8 ng/dL, p = 0.65) groups. TSH, T(4), and FT(4) did not change in any of the study groups. Twelve months of CR decreased circulating T(3) concentrations in middle-aged adults. This effect does not appear to be attributable to changes in body fat mass because a comparable decrease in T(3) concentration was not observed in response to an exercise-induced fat mass reduction.

Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans.

Excessive adiposity is associated with increased oxidative stress and accelerated aging. Weight loss induced by negative energy balance reduces markers of oxidation in experimental animals and humans. The long-term effects of weight loss induced by calorie restriction or increased energy expenditure induced by exercise on measures of oxidative stress and damage have not been studied in humans. The objective of the present study was to compare the effects of 20% caloric restriction or 20% exercise alone over 1 year on oxidative damage to DNA and RNA, as assessed through white blood cell and urine analyses. Eighteen men and women aged 50 to 60 years with a body mass index (BMI) between 23.5 to 29.9 kg/m(2) were assigned to one of two conditions--20% CR (n = 9) or 20% EX (n = 9)--which was designed to produce an identical energy deficit through increased energy expenditure. Compared to baseline, both interventions significantly reduced oxidative damage to both DNA (48.5% and 49.6% reduction for the CR and EX groups, respectively) and RNA (35.7% and 52.1% reduction for the CR and EX groups, respectively) measured in white blood cells. However, urinary levels of DNA and RNA oxidation products did not differ from baseline values following either 12-month intervention program. Data from the present study provide evidence that negative energy balances induced through either CR or EX result in substantial and similar improvements in markers of DNA and RNA damage to white blood cells, potentially by reducing systemic oxidative stress.

Adropin: An endocrine link between the biological clock and cholesterol homeostasis.

OBJECTIVE: Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. METHODS: Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models. RESULTS: In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis of hepatic Enho expression in male mice suggests control by the biological clock. Expression is rhythmic, peaking during maximal food consumption in the dark correlating with transcriptional activation by RORα/γ. The nadir in the light phase coincides with the rest phase and repression by Rev-erb. Plasma adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001 and the 7-oxygenated sterols 7-ß-hydroxysterol and 7-ketocholesterol, or the Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells. Consumption of high-cholesterol diets suppress expression of the adropin transcript in mouse liver. However, adropin over expression does not prevent hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor mutations. CONCLUSIONS: In humans, associations between plasma adropin concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse studies suggest that the relationship between adropin and cholesterol metabolism is unidirectional, and predominantly involves suppression of adropin expression by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and oxysterols by the RORα/γ ligand-binding domain suggests a plausible functional link between adropin expression and cellular lipid metabolism. Furthermore, the nuclear receptors RORα/γ and Rev-erb may couple adropin synthesis with circadian rhythms in carbohydrate and lipid metabolism.