Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

Assessment of Creatine in Sports Products

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has at the request of the Norwegian Food Safety Authority (Mattilsynet) conducted an assessment of creatine in sports products (e.g. supplements). The evaluation has been performed by an ad hoc group, and assessed by the VKM Panel on nutrition, dietetic products, novel food and allergy. The evaluation of safety and possible risks of creatine supplementation in this opinion is based on previous reports, 23 original papers and 14 reviews from literature searches. Marketing and sales of sport products are increasing in the Nordic countries, with creatine supplements being one of four most common categories. In addition to be used by athletes, the use of creatine supplements seems to increase among general exercisers and young people. Creatine supplements are mainly used for their supposed effects on muscles mass and high intensity and short duration sport performances. Supplementation has been shown to result in higher concentration of creatine phosphate in the muscles, which is the limited substrate. For athletes, it is recommended a loading dose of 10-20 g/day for 4-7 days and a maintenance dose of 2-5 g/day for weeks or months. Some athletes continue the maintenance dose for several years. It is well documented that creatine supplementation has positive effects on muscle mass combined with strength training and performance during maximal exercise. There are however large individual variation in the response, and there are responders and non-responders. The new scientific literature, including long term studies, is in line with the EFSA (European Food Safety Authority) opinion from 2004. VKM Panel on nutrition, dietetic products, novel food and allergy supports the EFSA conclusion that supplementation of creatine in doses below 3 g/day is unlikely to pose any risks if the purity of the creatine compound is adequate. Scientific long-term studies with doses up to 5-10 g/day in adult athletes have shown no harmful effects, but there are no dose-response studies indicating a safe upper limit for creatine. The potential negative effects (impaired kidney function, weight gain and gastrointestinal disturbances) which have been published in non scientific journals and anecdotal reports have not found support in controlled systematic studies on healthy subjects. It has been indicated that individuals with impaired kidney functions should refrain from creatine supplements. Creatine-monohydrate is the most studied form of creatine supplements, and only creatine monohydrate has been included in the scientific investigations on adverse effects.

Creatine Monohydrate Supplementation Increases White Adipose Tissue Mitochondrial Markers in Male and Female Rats in a Depot Specific Manner

White adipose tissue (WAT) is a dynamic endocrine organ that can play a significant role in thermoregulation. WAT has the capacity to adopt structural and functional characteristics of the more metabolically active brown adipose tissue (BAT) and contribute to non-shivering thermogenesis under specific stimuli. Non-shivering thermogenesis was previously thought to be uncoupling protein 1 (UCP1)-dependent however, recent evidence suggests that UCP1-independent mechanisms of thermogenesis exist. Namely, futile creatine cycling has been identified as a contributor to WAT thermogenesis. The purpose of this study was to examine the efficacy of creatine supplementation to alter mitochondrial markers as well as adipocyte size and multilocularity in inguinal (iWAT), gonadal (gWAT), and BAT. Thirty-two male and female Sprague-Dawley rats were treated with varying doses (0 g/L, 2.5 g/L, 5 g/L, and 10 g/L) of creatine monohydrate for 8 weeks. We demonstrate that mitochondrial markers respond in a sex and depot specific manner. In iWAT, female rats displayed significant increases in COXIV, PDH-E1alpha, and cytochrome C protein content. Male rats exhibited gWAT specific increases in COXIV and PDH-E1alpha protein content. This study supports creatine supplementation as a potential method of UCP1-independant thermogenesis and highlights the importance of taking a sex-specific approach when examining the efficacy of browning therapeutics in future research.

Sex- and tissue-dependent creatine uptake in response to different creatine monohydrate doses in male and female Sprague-Dawley rats

Sprague-Dawley rats (n=32) underwent 8-weeks of creatine monohydrate (CM) supplementation (0, 2.5, 5, and 10 g/L). Total creatine concentrations (TCr) in female white fiber-dominant gastrocnemius (WGAS) and cardiac muscle (HRT) were significantly higher compared to males (p<0.05). CM supplementation increased TCr concentrations in female WGAS (p<0.05) and HRT (p<0.01) and in male red fiber-dominant gastrocnemius muscle (RGAS) (p<0.05). Future research should further investigate sex-differences in basal levels of TCr and the response to CM supplementation. Novelty – There is a sex- and tissue-dependant response to CM supplementation in rats.

Analysis of health claims regarding creatine monohydrate present in commercial communications for a sample of European sports foods supplements

Objective:To analyse the information on health claims present in the labelling of creatine monohydrate (CM) products.Design:A descriptive study of a selection of products marketed as CM, with health claims, and that met the inclusion/exclusion criteria, was conducted using the Amazon and Google Shopping websites. The adequacy and compliance of the health claims were evaluated with the European legislative requirements (European Food Safety Authority and European Commission). The results were discussed with scientific evidence criteria from the Academy of Nutrition and Dietetics, International Olympic Committee, and International Society of Sports Nutrition, as well as the systematic review carried out by Mielgo-Ayuso in 2019.Setting:Health claims in the commercial communications of a sample of CM supplements, in relation to current legislation and scientific knowledge.Participant:A total of 554 CM products were obtained.Results:Of the total sample, only 167 met the inclusion/exclusion criteria. Of these, 30·5 % recommended a CM dose of 5·0–5·9 g/d, while 29·9 % recommended 3·0 to 3·9 g/d. As for the health claims, ‘Enhances physical performance’ appeared in 73·1 % of the supplements, in most cases referring to a dosage of 3·0 to 3·9 g/d for these products. The rest of the declarations were not adequate or needed to be modified.Conclusion:Only 25 % of the health claims complied with the criteria established by the scientific reference documents. Most of the declarations must be modified or eliminated, as they could be considered fraudulent and/or misleading for the consumer.

EFFECTS OF CREATINE MONOHYDRATE SUPPLEMENTATION ON ADIPOSE, MUSCULOSKELETAL TISSUE AND PHYSICAL PERFORMANCE OF RATTUS NORVEGICUS

Despite scientific advances and findings on the effects of creatine supplementation, little is known about the use of this supplement and its effects on visceral fat accumulation, as well as on the process of improving muscle endurance associated with stereological factors of muscle tissue. This study aimed to evaluate the effects of creatine monohydrate use on physical valences, stereology of muscle tissue and quantitative aspects of visceral adipose tissue. Twenty-four Wistar rats, aged 15 weeks and under controlled feeding and hydration conditions, were selected. To verify the desired variables, the animals were classified into four groups: control, supplemented, training, and training and supplemented. Creatine supplemented animals were supplemented (via gavage) at dosages of 300mg / kg body mass for nine weeks, and the same period of training as the animals that were trained underwent a program based on Honenberg & Farrar studies. The loads at which the animals performed the series were noted, as well as the number of climbs performed per training session. After the experimental period, the animals were weighed and euthanized, and visceral fat was removed for weighing and comparison between groups and staining in the standard protocol of hematoxylin and eosin for stereological verification of muscle tissue. The observed results indicated time-dependent ergogenic improvements and slight reductions in the visceral fat of the supplemented animals, as well as variations of mononuclear phagocytes present in the tissue of the experimental groups, especially a low amount of these cells in the animals that trained and supplemented. It is concluded that creatine may have effects on visceral fat and the potential modulating effect of the innate immune system, in addition to time-dependent ergogenic effects.

A Survey on Dietary Supplement Consumption in Amateur and Professional Rugby Players

Purpose: the aim of the present study was to analyse the pattern of dietary supplements (DS) consumption on federated rugby players, including the analysis of differences based on the sex and competitive level (professional vs. amateurs). Material and methods: 144 rugby players (83 male and 61 female), of whom 69 were professionals and 75 amateurs, were recruited for the study. All the participants filled out a specific questionnaire about DS consumption including questions related to the consumption of DS and their effects on sport performance and health status. Results: 65.3% of participants declared consuming at least one DS, with a higher prevalence in males than females (77.1% vs. 49.2%) and in professionals thanin amateur players (79.7% vs. 52.0%). The main reason for consumption was to enhance sport performance (62.3%) with differences only based on sex (74.3% males vs. 43.2% females). The most common purchase sites were the Internet (45.6%) and specialised stores (39.8%). As to the moment of ingestion, professionals did this most frequently during competition and training (56.4% vs. 28.2%), whereas amateur players did so only during competition (20.5% vs. 3.6%). Moreover, professional player intake most frequently in post-exercise (65.5% vs. 35.9%), whereas amateur during pre-exercise (30.8% vs. 5.5%). The DS most consumed included whey protein (44%), caffeine (42%), sports drinks (38%), energy bars (34%) and creatine monohydrate (31%), with a higher prevalence in male and professional players of whey protein and creatine monohydrate. Conclusions: The main reason for DS consumption is for enhancing sports performance). Professional players more frequently purchase them on the Internet and consume DS during training and competition period and in the post-exercise, whereas amateur players consume during competition and pre-exercise. Related to the main form of DS consumption, it is observed that a moderate consumption of DS could be considered ergogenic, such as whey protein, sport bar and creatine, while an absence of other DS could be considered ergogenic.