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The effect of N,N-dimethylglycine on athletic performance at altitude in horses and mules
Abstract
N,N-dimethylglycine (DMG) is widely used to delay fatigue by inhibiting lactate production. DMG effects were examined in a paradigm of moderate exercise intensity that was potentially oxygen-limited. Performance in seven horses and four mules was assessed using blood lactate concentrations and heart rates. The experimental group was administered 2.2 g of DMG twice per day for four days. The exercise tests consisted of two exercise bouts, one starting at an elevation of 2635m and the other at 1960m. Work at the high altitude increased the total number of heart beats and recovery time in both horses and mules. There were no difference for peak heart rate (152±11 vs 141±2, p= 0.32), average heart rate, (99±2 vs 97±3, p=0.40) and blood lactates (0.62±0.05 vs 0.66±0.04 mM, p=0.78) between higher altitude and lower altitude tests, respectively. When data were pooled for species and altitude, DMG reduced blood lactates, (0.60±0.03 vs 0.74±0.06 mM, p=0.03).
... TO THE EDITOR N,N-dimethylglycine (DMG), being part of the endogenous homocysteine pathway, and its sodium salt (DMG-Na) have been widely used in animal husbandry to increase feed/weight ratio, induce fattening, or boost physical performance and were also approved as a safe nonfuel food supplement for humans (Cupp and Tracy, 2003;Greene et al, 1996;Kalmar et al, 2014;Prola et al, 2013). DMG and DMG-Na were also shown to support tissue and cellular functions, for example, by improving antioxidant capacities and oxygen utilization, promoting tissue regeneration, and enhancing immune response/defense (Bai et al, 2016;Feng et al, 2018;Graber et al, 1981;Kalmar et al, 2014). ...
... Considering that (i) DMG is an endogenous intermediate of the choline and betaine metabolism (ii) being present in many tissues, including the skin, as well as (iii) having broad plasma levels, it is expected that generally low total daily dermal use of DMG will not lead to a significant increase in DMG background levels in plasma. Furthermore, as mentioned in the main text, DMG and its sodium salt have been widely used in animal husbandry to increase feed/weight ratio, induce fattening, or boost physical performance and were also approved as a safe nonfuel food supplement for humans (Cupp and Tracy, 2003;Greene et al, 1996;Kalmar et al, 2014;Prola et al, 2013). Additional published clinical studies in adult subjects after oral use of DMG at significantly higher doses than the topical treatment also showed no negative impact or adverse clinical signs related to safety pharmacology (Gascon et al, 1989;Wolfsegger et al, 2021). ...
... N,N-dimethylglycine (DMG) is part of the endogenous homocysteine pathway and is found in several food sources and plants [1,2], and the sodium salt of N,N-dimethylglycine (DMG-Na) has been widely used as a food supplement in animal husbandry to increase the feed/weight ratio, induce fattening, or boost physical performance [2][3][4][5][6][7][8][9][10][11]. Moreover, DMG is also approved as a safe, non-fuel food supplement for human application [2,12,13]. ...
N,N-dimethylglycine (DMG) is a naturally occurring compound being widely used as an oral supplement to improve growth and physical performance. Thus far, its effects on human skin have not been described in the literature. For the first time, we show that N,N-dimethylglycine sodium salt (DMG-Na) promoted the proliferation of cultured human epidermal HaCaT keratinocytes. Even at high doses, DMG-Na did not compromise the cellular viability of these cells. In a scratch wound-closure assay, DMG-Na augmented the rate of wound closure, demonstrating that it promotes keratinocyte migration. Further, DMG-Na treatment of the cells resulted in the upregulation of the synthesis and release of specific growth factors. Intriguingly, DMG-Na also exerted robust anti-inflammatory and antioxidant effects, as assessed in three different models of human keratinocytes, mimicking microbial and allergic contact dermatitis as well as psoriasis and UVB irradiation-induced solar dermatitis. These results identify DMG-Na as a highly promising novel active compound to promote epidermal proliferation, regeneration, and repair, and to exert protective functions. Further preclinical and clinical studies are under investigation to prove the seminal impact of topically applied DMG-Na on relevant conditions of the skin and its appendages.
... Increased DMG levels in rainbow trout exposed to clove oil have been shown to be protective stress responses to anesthetics [38]. Other studies have suggested that dietary DMG could improve athletic performance in horses and mice [37,39]. To demonstrate that Japanese red sea bream has high DMG levels, additional data is required to determine whether it is added in the diet to improve athletic performance or it is produced in response to external stress generated during the distribution process. ...
Red seabream (Pagrus major), a migratory fish, is characterized by high protein levels in the muscle. South Korean and Japanese red seabreams have a general distribution pattern; however, distinguishing them based on their geographical origin is difficult. In this study, we used capillary electrophoresis time-of-flight mass spectrometry (CE-TOF/MS) to analyze the red seabream muscle metabolome to investigate how can distinguish the origin of the fish. The metabolites were extracted using 50% acetonitrile in water. Chromatographic separation was successfully used to classify the metabolite profiles of Japanese and South Korean red seabream. Principal component analysis and hierarchical cluster analysis showed good ability to categorize the samples according to their origin. Amino acids showed the greatest quantitative difference in South Korean and Japanese muscle samples. Specifically, the L-alanine, L-glutamic acid, L-isoleucine, dimethylglycine, and L-valine levels in Japanese red seabream samples were significantly higher than those in South Korean samples. In contrast, the levels of trimethylamine N-oxide and inosine monophosphate in South Korean muscle samples were significantly higher than those in Japanese red muscle samples. The monitored metabolite profiles suggest that South Korean and Japanese red seabreams can be identified on the basis of amino acid levels.
... This result might be attributed to the function of these metabolites as antioxidant in neutralizing the free radicals produced by diazinon. Also, it was recognized that some osmolytes such as N,Ndimethylglycine can used as glycine resource for synthesis of detoxification proteins like glutathione (Tonda and Hart, 1992;Greene et al., 1996;Friesen et al., 2007). ...
... Friesen et al. [12] found that DMG could act as a source of glycine for glutathione synthesis, and thereby, may improve the antioxidant capacity in the body. Other researchers suggested that dietary supplementation with DMG could reduce oxidative stress and improve athletic performance in men [13], dogs [14], and horses [15]. Cupp et al. [16] reported that DMG could be absorbed rapidly and completely through gastric intubation in mice, generally used for the uptake of small water-soluble molecules. ...
In the present study, the free radical scavenging activities (against 1,1-diphenyl-2-pierylhydrazy (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6- sulphonate) (ABTS+), Hydrogen peroxide (H2O2)) of dimethylglycine sodium salt (DMG-Na) were measured and compared with those of Trolox (6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid), a commonly used antioxidant. The radical scavenging activities of DMG-Na were found to be the highest at 40 mg/ml. In Experiment 2, gastric intubation in mice with 12 mg DMG-Na/0.3 ml sterile saline solution significantly increased (P < 0.05) the body weight (BW) (28 d), organ proportion (liver and spleen), and antioxidant capacity in serum and the liver (Superoxide dismutase (SOD), Hydrogen peroxidase (CAT), Glutathione peroxidase (GPx), and Total antioxidant capacity (T-AOC)), and significantly decreased (P < 0.05) the activities of serum Glutamic-pyruvic transaminase (ALT) and Glutamic oxalacetic transaminase (AST) and Methane Dicarboxylic Aldehyde (MDA) contents in the serum and liver. Specifically, the effect of 12 mg DMG-Na/0.3 ml sterile saline solution, which showed the highest antioxidant capacity, was further studied using a mice model. In Experiment 3, the mice CL (CON+ lipopolysaccharide (LPS)) group showed a significant decrease (P < 0.05) in the serum ALT and AST content; hepatic mitochondrial antioxidant capacity (Manganese Superoxide dismutase (MnSOD), Glutathione reductase (GR), GPx, Glutathione (GSH)); MDA and Protein carbonyl (PC) content; Reactive oxygen species (ROS) level, Mitochondrial membrane potential (MMP) level, and expression of liver antioxidant genes (Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase 1 (HO-1), Manganese superoxide dismutase (MnSOD), Glutathione peroxidase 1 (Gpx1), Sirtuin 1 (Sirt1)) relative to the mice CS (CON+ sterile saline) group. The DL (DMG+LPS) group showed a significant decrease (P < 0.05) in serum ALT and AST content, ROS level, and expression of liver antioxidant gene MnSOD, Gpx1, Sirt1 and a significant increase (P < 0.05) in the hepatic mitochondrial antioxidant capacity (MnSOD, GSH, GPx, GR) and MMP level relative to the CL group. These results indicate that DMG-Na could protect against the LPS-induced oxidative stress by enhancing the free radical scavenging capacity, and increasing the activity of antioxidant defense system.
... As methyl donation capacity (Jin et al., 2007) and anti-oxidative action (Lai, 2008) are both associated with increased insulin sensitivity, DMG can possibly influence insulin sensitivity. Other studies report that DMG, used as a dietary supplement, reduces blood lactate level and improves athletic performance in men (Tonda and Hart, 1992), horses (Greene et al., 1996) and dogs (Gannon and Kendall, 1982). Only one study investigated the effect of DMG as a feed additive in livestock production, namely on broiler performance (Kalmar et al., 2010 ). ...
The current pilot study assessed the influence of N,N-dimethylglycine (DMG) on insulin sensitivity, glucose and fat metabolism, nutrient digestibility and reproductive performance of sows in the peripartal period. At day 105 of gestation, 25 sows were randomly assigned to the control (n = 13) or the DMG group (n = 12). Sows from the DMG group were supplemented with 1 g DMG/kg feed until day 3 of lactation. After an overnight fast 1 day after farrowing, a blood sample of each sow was drawn. The plasma was analyzed for insulin, glucose, fructosamine, leptin, thiobarbituric acid reactive substances (TBARS), ferric reducing ability of plasma (FRAP), non-esterified fatty acids (NEFA) and triglycerides (TG) and an oral glucose tolerance test was performed. A rectal feces sample was collected and the apparent fecal digestibility (AFD) of crude fat (CFAT), crude protein (CP) and nitrogen-free extract (NFE) was calculated after proximate analyses. Finally, a colostrum sample was collected from each sow and analyzed for the presence of DMG. Reproductive performance parameters were recorded. The results showed an improvement in the AFD of CFAT, CP and NFE when DMG was supplemented. This beneficial effect confirms the hypothesis that DMG acts as an emulsifying agent. The improvement in digestibility in the DMG group was accompanied by a numerical increase in plasma TG (P = 0.067). Plasma NEFA concentrations were not different between treatment groups. DMG supplementation neither affected glucose clearance nor influenced plasma insulin, glucose, fructosamine or leptin levels. TBARS and FRAP also remained unaffected, despite previously reported anti-oxidative properties of DMG. Furthermore, no significant impact on reproductive performance could be recorded. In conclusion, DMG supplementation significantly improved nutrient digestibility. Possible beneficial effects on energy metabolism and reproductive performance of sows should be tested when DMG is supplemented for a longer period of time or at a higher dose.
... Increased altitude is a poorly studied environmental stressor for 3-day event horses. Previous experiments have described the effects of high altitude on horses (DeAluja et al. 1968;Collins et al. 1969;Wickler et al. 1995) and mules (Riar et al. 1976(Riar et al. , 1980Wickler et al. 1995;Greene et al. 1996) performing packing work or show jumping, but we are unaware of previous reports on the effects of altitude on 3-day eventing. This experiment was undertaken with the hypothesis that increased altitude would have measurable physiological effects on horses competing in 3day events and horse trials when compared to horses competing in similar tests at sea level. ...
Three-day event horses are subject to various external environmental stresses including changes in ambient temperature, humidity, altitude, and test severity. Considerable research on the adverse effects of increased heat and humidity preceded the 1996 Olympic Summer Games in Atlanta, Georgia USA, but no research has been done previously on the effects of altitude on 3-day eventing. Physical and venous blood gas data were collected on horses (n = 24) competing in the High Prairie Preliminary (CCN*) and Intermediate (CCN**) 3-day events and Preliminary Horse Trials in Parker, Colorado (1900 m above sea level). Despite the increased altitude, only post exercise rectal temperature and pH were higher (P < 0.05) whereas heart rate (HR), [K+], and ionized calcium (ICa++) were lower (P < 0.05) in 3-day event horses compared to horse trial horses. All other variables (respiratory rate [RR], PCV, [Hb], PCO2, [tCO2], [HCO3-], BE, and [Na+]) were not different between groups (P > 0.05). When these preliminary horse trial horses in Colorado were compared to those previously studied at preliminary horse trials at sea level in Arizona, post exercise HR and RR were higher (P < 0.05) and pH, PCO2, [tCO2], [HCO3-], BE and [iCa++] were lower (P < 0.05) at altitude. These data show that increased altitude (1900 m above sea level) was more stressful for 3-day event horses, but did not result in the severe physiological changes and inability to complete prescribed exercise tests seen in previous studies with increased heat and humidity. It is clear from these and previous data that increased heat and humidity are the more important environmental stressors in 3-day eventing.
In a crossover study, either a placebo paste or N,N-dimethylglycine was administered orally at a dose rate of 1.2 mg/kg twice daily for five days to six thoroughbred horses, with bodyweights ranging from 424 to 492 kg. Using previously determined regression equations for oxygen uptake (VO2) against speed for each horse, a standardised exercise test was given with speeds equivalent to fixed percentages of the maximum oxygen uptake (VO2max). The test consisted of two minutes at speeds equivalent to approximately 40 per cent and 50 per cent VO2max, and one minute at speeds that produced approximately 60, 70, 80, 90 and 100 per cent VO2max. During the last five seconds of each exercise stage, the values of VO2, carbon dioxide production (VCO2), heart rate, arterial blood and plasma lactate concentrations, arterial blood gases and pH were measured. Before and immediately after the exercise test, muscle biopsies were collected from the middle gluteal muscle to determine the muscle lactate concentrations. The administration of N,N-dimethylglycine produced no significant differences in any of the measured values, and it is concluded that the compound has no beneficial effects on cardiorespiratory function or lactate production in the exercising horse.
Effect of a nutritional supplement containing N,N-dimethylglycine on the racing Standardbred
- Levine S.B.
- Myhre G.D.
- Smith G.L.
- Burns J.G.
- Erb H.