Effects of HMB on Endurance Performance in a Healthy Population: A Systematic Review and Meta-Analysis.

ABSTRACT: Fernández-Landa, J, Todorovic, N, Santibañez-Gutierrez, A, Ostojic, SM, Calleja-González, J, Sekulic, D, and Mielgo-Ayuso, J. Effects of HMB on endurance performance in a healthy population: a systematic review and meta-analysis. J Strength Cond Res 38(4): e202-e210, 2024-ß-hydroxy-ß-methylbutyrate (HMB) has been used extensively as a dietary supplement for athletes and physically active people. However, the ergogenic effect of HMB supplementation on endurance performance is still unclear. Therefore, this systematic review and meta-analysis (SRMA) aimed to assess HMB supplementation on endurance performance and V̇O 2 max . This SRMA followed PRISMA guidelines. Three electronic databases were searched (PubMed/Medline, Web of Science [WOS], and Scopus) from inception until April 3, 2023. In this SRMA, human experimental trials, controlled with a placebo group, assessing the effect of HMB supplementation on endurance performance in a healthy population were included. The quality of the studies was assessed by the Physiotherapy Evidence Database (PEDro) scale. The study protocol was registered in the Prospective Register of Systematic Review (PROSPERO): CRD42022341790. Eleven studies involving 279 participants met the inclusion criteria. The results displayed a significant improvement on endurance performance (pooled standardized mean difference [SMD] = 0.58 [0.28-0.87]) and V̇O 2 max (pooled SMD = 0.58 [0.21-0.95]) after HMB ingestion. Moreover, after the exclusion of the studies not evenly distributed around the base of the funnel plot, the results continued to be significantly positive in endurance performance (pooled SMD = 0.38 [0.22-0.53]) and V̇O 2 max (pooled SMD = 0.25 [0.09-0.42]). In conclusion, HMB (3 g·d -1 ) ingestion during 2-12 weeks significantly improves endurance performance and V̇O 2 max .

Molecular nutrition in life course perspective: Pinpointing metabolic pathways to target during periconception.

Lifecourse nutrition encompasses nourishment from early development into parenthood. From preconception and pregnancy to childhood, late adolescence, and reproductive years, life course nutrition explores links between dietary exposures and health outcomes in current and future generations from a public health perspective, usually addressing lifestyle behaviours, reproductive well-being and maternal-child health strategies. However, nutritional factors that play a role in conceiving and sustaining new life might also require a molecular perspective and recognition of critical interactions between specific nutrients and relevant biochemical pathways. The present perspective summarises evidence about the links between diet during periconception and next-generation health and outlines the main metabolic networks involved in nutritional biology of this sensitive time frame.

Nutrition in a lifecourse perspective: From molecular aspects to public health approaches.

This Special Issue covers a variety of topics related to nutrition from a lifecourse perspective, addressing diet in sensitive periods (preconception, pregnancy and infancy/toddlerhood), in different contexts, spanning from molecular nutrition to settings and gatekeepers of diet in these sensitive periods. It highlights challenges and research gaps within the field.

Creatine and multiple sclerosis.

Multiple sclerosis (MS) is a complex and debilitating neurodegenerative disease, with unknown cause(s), unpredictable prognosis, and rather limited treatment options. MS is often accompanied by various metabolic disturbances, with impaired creatine metabolism may play a role in its pathogenesis and the clinical course of the disease. This review summarizes human trials describing alterations in creatine levels in the nervous system and other tissues during MS, affects how certain medications for MS affect brain creatine concentrations, and discusses a possible demand for exogenous creatine as an adjunct therapeutic agent in the management of MS. Creatine metabolism seems to be dysfunctional in MS, indicating a low metabolic state of the brain and other relevant organs in this unpredictable demyelinating disease. A disease-driven brain creatine deficit could be seen as a distinctive pathological facet of severe MS that might be approached with targeted therapies in aim to restore creatine homeostasis.

Medium-chain triglycerides may improve memory in non-demented older adults: a systematic review of randomized controlled trials.

BACKGROUND: Ketosis has been exploited for its neuroprotective impact and treatment of neurological conditions via ketone production. Exogenous medium-chain triglyceride (MCT) supplementation may induce nutritional ketosis. The aim of this systematic review is to explore the effects of MCTs on memory function in older adults without cognitive impairment. METHODS: A systematic literature search of PubMed, Cochrane Library, Scopus, and Web of Science was employed from inception until April 2022 for randomized controlled trials (RCTs) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, investigating the impact of MCT oils on components of memory. Risk of bias (RoB2) tool was utilized for quality assessment. RESULTS: Six trials were included for qualitative synthesis, in which two studies examined the effect of MCTs through a ketogenic meal. MCT supplementation compared to controls was associated with improved indices of memory function in 4 out of 6 studies, particularly working memory. A meta-analysis was not employed due to the low number of studies, therefore, a true effect measure of MCT supplementation was not explored. CONCLUSIONS: MCT supplementation may enhance working memory in non-demented older adults. These effects may be more prominent in individuals with lower baseline scores, from short and long-term supplementation. Further studies are warranted to confirm these findings in terms of optimal dose and MCTs composition, which may protect from memory decline during aging.

Cataloguing guanidinoacetic acid content in various foods.

Guanidinoacetic acid (GAA) is a natural amino acid derivative involved in several metabolic pathways across the human body, including creatine biosynthesis, arginine utilization, and neuromodulation. Apart from GAA synthesized internally from glycine and arginine, a total daily exposure to GAA also involves exogenous dietary sources. However, a majority of food databases provide no comprehensive data about the amount of GAA available from various foods. In this report, we summarize information for GAA levels in different food groups, as extracted from the available scientific literature. The content of GAA appears to vary across different foods, with meat-based products contain the highest relative amount of GAA (~50 mg per kg), followed by a dairy group (~0.3 mg per kg), and plant-based foods (~1 µg per kg), with the latter considered to be almost negligible. Although no data are currently available about its requirements in humans, cataloguing GAA amount in various foods could help in more accurate quantification of GAA provision via regular diet in the future.

Nutritional Profiles of US Adults with Suboptimal Dietary Creatine Intake.

INTRODUCTION: Recent population-based studies reported an inadequate dietary intake of creatine, a conditionally essential nutrient that plays an important role in human metabolism. METHODS: We analyzed here the nutritional profiles of US adults with low creatine consumption, using data from the 2017 to 2018 National Health and Nutrition Examination Survey (NHANES). RESULTS: Among 4,004 NHANES adult participants that reported detailed dietary intake information, 2,611 (65.2%) were calculated to have dietary creatine intake below recommended levels of 1.00 g/day. The average daily creatine intake in this subpopulation was 0.52 ± 0.26 g (95% confidence interval, from 0.51 to 0.53). This was accompanied by a significantly lower dietary intake of meat-based protein, as compared to participants whose dietary creatine intake was equal to or above recommended levels (20.1 ± 10.2 g/day vs. 67.1 ± 30.4 g/day; p < 0.001). CONCLUSION: The large-scale rate of suboptimal dietary creatine intake found in this cross-sectional study warrants additional research, and calls for immediate public health measures fostering creatine-rich foods in human nutrition.

Dietary creatine and cognitive function in U.S. adults aged 60 years and over.

OBJECTIVES: Recent clinical trials suggested a potential benefit of dietary creatine on cognitive function for aging individuals. However, the association between creatine consumption from food and cognitive function in the older adults remained undetermined at the populational level. The present study quantified the amount of creatine consumed through a regular diet among U.S. adults aged 60 years and over, and evaluated the link between dietary creatine and cognitive function using data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). METHODS: NHANES 2001-2002 round included a total of 1340 older adults (51.8% women; age 71.4 ± 7.8 years) who provided valid dietary information and cognitive testing measures. Dietary intake information was obtained from the NHANES Dietary Data component through a 24-h in-person dietary recall interview. Cognitive function was assessed using the WAIS III Digit Symbol Substitution Test (DSS) conducted during the household interview. RESULTS: A bivariate model revealed a significant positive correlation between DSS scores and creatine intake across the whole sample (τb = 0.043; P = 0.02). The partial models demonstrated a significant correlation between creatine consumption and DSS score when adjusted for sociodemographic variables (r = 0.062; P = 0.039), and nutritional variables (r = 0.055; P = 0.049). The participants who consumed more than 0.95 g of creatine per day (3rd and 4th quartiles of creatine intake) were found to have higher scores on the cognitive functioning test as compared to their peers with lower creatine intake (1st and 2nd quartiles) (P < 0.05). CONCLUSION: Our findings suggest that creatine from food might be protective against reduced cognitive performance in the older population. Further research is highly warranted to investigate the role of dietary creatine amount in cognitive function in the older adults.

Effects of Rapid Weight Loss on Kidney Function in Combat Sport Athletes.

Even though scientific literature shows numerous heath complications and performance decrements associated with rapid weight loss (RWL), its prevalence remains exceedingly high across various combat sports. The aim of this study was to thoroughly search the existing literature to explore the influence of RWL on kidney function in Olympic and non-Olympic combat sport athletes. PubMed and Web of Science were searched for the relevant studies. Only original articles published from 2005 onwards, written in English, that included healthy males and females who prompted ~5% weight loss within a week or less, were included in the study. Retrieved studies showed that creatinine, blood urea nitrogen and urine specific gravity values were significantly increased after RWL in the majority of the included studies. This observation indicates that RWL caused dehydration and subsequent acute kidney damage despite various degrees of weight lost during the RWL phase, which can lead to adverse events in other body systems. Alternative methods of weight reduction that prioritize athletes' health should be considered.

Hydrotherapy with hydrogen-rich water compared with RICE protocol following acute ankle sprain in professional athletes: a randomized non-inferiority pilot trial.

We analysed the effects of an experimental novel protocol of intensive hydrotherapy with hydrogen-rich water (HRW) on injury recovery in athletic men who suffered an acute ankle sprain (AAS) and compared it with a RICE protocol (rest, ice, compression, elevation). Professional athletes (age 23.7 ± 4.0 years; weight 78.6 ± 5.7 kg, height 182.5 ± 4.3 cm; professional experience 5.9 ± 3.9 years) who incurred AAS during a sport-related activity were randomly assigned immediately after the injury to either hydrogen group (n = 9) or a conventional RICE treatment group (n = 9). Hydrogen group received six 30-min ankle baths with HRW throughout the first 24 h post-injury, with hydrotherapy administered every 4 hours during the intervention period. RICE group stood off the injured leg, with ice packs administered for 20 min every 3 hours, with the injured ankle compressed with an elastic bandage for 24 hours and elevated at all possible times above the level of the heart. HRW was equivalent to RICE protocol to reduce ankle swelling (2.1 ± 0.9% vs. 1.6 ± 0.8%; P = 0.26), range of motion (2.4 ± 1.3 cm vs. 2.7 ± 0.8 cm; P = 0.60), and single-leg balance with eyes opened (18.4 ± 8.2 sec vs. 10.7 ± 8.0 sec; P = 0.06) and closed (5.6 ± 8.4 sec vs. 3.9 ± 4.2 sec; P = 0.59). This non-inferiority pilot trial supports the use of HRW as an effective choice in AAS management. However, more studies are needed to corroborate these findings in other soft tissue injuries.

Guanidinoacetic acid deficiency: a new entity in clinical medicine?

Guanidinoacetic acid (GAA, also known as glycocyamine or betacyamine) is a naturally-occurring derivative of glycine and a direct metabolic precursor of creatine, a key player in high-phosphate cellular bioenergetics. GAA is found in human serum and urine, with circulating GAA likely reflects an equilibrium between its endogenous production and utilization/excretion. GAA deficiency (as indicated by low serum GAA) has been reported in various conditions yet this intriguing clinical entity appears to be poorly characterized as yet, either as a primary deficit or a sequel of secondary disease. This minireview article summarizes the inherited and acquired disorders with apparent GAA deficiency and discusses a possible relevance of GAA shortfall in clinical medicine.

Correlation between biomarkers of creatine metabolism and serum indicators of peripheral muscle fatigue during exhaustive exercise in active men.

Exhaustive exercise induces various disturbances of homeostasis, with impaired bioenergetics often associated with strenuous muscular work. However, no study so far validated serum biomarkers of creatine metabolism vs. traditional markers of exhaustive exercise and fatigue. Here, we investigated how well changes in serum guanidinoacetic acid (GAA), creatine and creatinine correlate with responses in blood lactate, creatine kinase, interleukin-6 and cortisol in 11 young active men (age 23.2 ± 3.7 years; VO2max 49.5 ± 5.4 ml/kg/min) exposed to exhaustive exercise. All participants were subjected to running at individual running speed at anaerobic threshold until exhaustion, with venous blood drawn at baseline and during an exercise session at 5-min intervals. Running-to-exhaustion markedly affected serum GAA and creatine levels, with circulating GAA increased for 5.3 ± 8.5%(95% CI, -0.4 to 11.0), and serum creatine elevated by 33.9 ± 21.8% (95% CI, 19.3 to 48.6) compared to baseline levels (P ≤ 0.05). In addition, moderate-to-strong positive linear correlations were found between exhaustive exercise-induced changes in serum cortisol and GAA levels (r = 0.79; P = 0.03), and cortisol and creatine concentrations (r = 0.81; P = 0.03). This suggests a link between cortisol and heavy exercise-induced impaired bioenergetics, with future studies needed to evaluate a cause-and-effect interconnection between cortisol and GAA-creatine axis.

Benefits and drawbacks of guanidinoacetic acid as a possible treatment to replenish cerebral creatine in AGAT deficiency.

Arginine-glycine amidinotransferase (AGAT) deficiency is a rare inherited metabolic disorder that severely affects brain bioenergetics. Characterized by mental retardation, language impairment, and behavioral disorders, AGAT deficiency is a treatable condition, where long-term creatine supplementation usually restores brain creatine levels and improves its clinical features. In some cases of AGAT deficiency, creatine treatment might be somewhat limited due to possible shortcomings in performance and transport of creatine to the brain. Guanidinoacetic acid (GAA), a direct metabolic precursor of creatine, has recently been suggested as a possible alternative to creatine to tackle brain creatine levels in experimental medicine. AGAT patients might benefit from oral GAA due to upgraded bioavailability and convenient utilization of the compound, while possible drawbacks (e.g. brain methylation issues, neurotoxicity, and hyperhomocysteinemia) should be accounted as well.

Guidelines-Driven Educational Intervention Promotes Healthy Lifestyle Among Adolescents and Adults: A Serbian National Longitudinal Study.

Background and objectives: The effectiveness of short-term focused educational programs to change health behaviors across large populations seems to be poorly described so far. The main aim of the present study was to evaluate an age-specific 45-min educational program, designed in accordance with the current U.S. Department of Health and Human Services and U.S. Department of Agriculture dietary guidelines and physical activity (PA) guidelines, among adolescents and adults. Materials and Methods: We evaluated the health-promoting lifestyle habits by the Health-Promoting Lifestyle Profile (HPLP-II) at baseline and following 6⁻8 weeks post-education in a nationally representative sample of Serbian adolescents and adults (n = 3822). Results: The percentage of adolescents eating 3⁻5 servings of vegetables per day increased at follow-up (20.1% versus 23.1%, p = 0.001), with significantly more adolescents regularly reading food labels (from 12.2% at baseline to 14.2% at follow-up; p = 0.02). Taken together, mean HPLP-II scores in adolescents significantly improved for both diet (0.05 points; p < 0.0001) and PA (0.09 points; p < 0.0001), and for PA in adults (0.08 points; p < 0.0001). Hierarchical multiple regression analysis revealed that our model as a whole (including time of testing as a predictor variable, and age and gender as control variables) explained 3.0% of the variance in mean HPLP-II scores for diet (p = 0.942) and 3.0% for PA (p = 0.285) in adolescents, and 1.1% of the variance in HPLP-II scores for diet (p = 0.781) and 1.9% for PA (p = 0.075) in adults, respectively. Conclusions: It appears that a brief focused education can positively tackle unhealthy lifestyles in promoting good health in general population. Different modes of interactive communication used here appeared to strengthen participants' capacities for lifestyle changes.

Serum creatine is not a reliable marker of muscular fitness in young adults.

PURPOSE: Elevated serum creatine and higher handgrip strength are individually associated with better health profiles yet the link between two variables remains unknown. In this cross-sectional study, we evaluated serum creatine levels in relation to handgrip strength in a cohort of 130 young healthy adults (61 women and 69 men; age 23.3 ± 2.6 years), while controlling for age, gender, fat-free mass and biomarkers of creatine metabolism as effect modifiers. MATERIALS AND METHODS: Serum creatine, creatinine and guanidinoacetic acid (GAA) levels were measured with liquid chromatography-tandem mass spectroscopy, while handgrip strength was assessed with a hydraulic hand dynamometer. RESULTS: Hierarchical multiple regression revealed that our model as a whole explained 79.9% of the variance in handgrip strength (p < 0.001). However, the evaluation of the contribution of each independent variable revealed that gender and free-fat mass make significant contributions (45.4 and 31.8%, respectively) to our model (p < 0.05), while neither age (0.9%) nor serum creatine (4.5%) or any other lab markers made significant contributions to the model (p > 0.05). CONCLUSIONS: Having higher blood creatine appears to be unrelated with better physical performance in young healthy adults. Serum creatine was not a reliable marker of muscular fitness in this population.

Dietary guanidinoacetic acid does not accumulate in the brain of healthy men.

We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations. No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used.

Thinness in young schoolchildren in Serbia: another case of the double burden of malnutrition?

OBJECTIVE: Thinness is rarely highlighted or regularly monitored among children in developed countries although it may be rather frequent and pose a significant risk to children's health. We aimed to describe the prevalence of mild, moderate and severe thinness among young Serbian schoolchildren. DESIGN: Cross-sectional study of schoolchildren aged 6-9 years. Children were assessed for weight, height and BMI as part of the WHO European Childhood Obesity Surveillance Initiative in Serbia. Thinness grades were defined as gender- and age-specific cut-offs for BMI according to the International Obesity Task Force criteria. SETTING: Serbia, September to November 2015. SUBJECTS: Students (n 4861) in grades 2 and 3 (6-9 years, 2397 girls). RESULTS: Overall prevalence of thinness in Serbian schoolchildren was 9·6 %. Mild thinness was clearly the largest category with a prevalence of 7·6 %, moderate thinness was present in 1·7 % of children and severe thinness was found in 0·3 % of children. OR indicated a significant risk of being thin for girls (1·44 times higher compared with boys) and children attending schools with no health-focused educational programme (1·57 times more likely to be thin than peers enrolled in schools with such programmes). In addition, OR for thinness tended to be 1·23 times higher in children living in an economically disadvantaged region of Serbia (P=0·06). CONCLUSIONS: A rather high prevalence of thinness highlights this malnutrition disorder as an emerging health issue that should trigger public health policies to tackle thinness, especially in girls of young age and children living in economically disadvantaged areas.