Sep 27, 2019 Dimethylglycine has been used to improve immune function and to manage autism and seizures, but evidenced is mixed or lacking. Dimethylglycine (DMG) is an amino acid found naturally in plant and animal cells and in many foods such as beans, cereal grains, and liver.
What is DMG?
Dimethylglycine is a highly unusual supplement, in that it is extremely popular despite the fact that all of its touted effects have largely been refuted by clinical and laboratory testing. Dmg 2 iso windows 7 download. It is most widely used as a performance enhancer by athletes, and in dogs and horses that are bred for racing purposes. Specifically, DMG is thought to be able to reduce lactic acid build up that might otherwise contribute to muscle fatigue. There is no immediately obvious reason why DMG should be able to achieve this, given its role in the body as a metabolite of betaine and a source of glycine. Reports of an ability of DMG to enhance athletic performance first appeared in the popular literature in the 1980's. Controlled studies involving treadmill horses, male athletes, and patients prone to lactic acid build up due to a cytochrome oxidase deficiency fail to support these earlier claims. Other common uses of DMG which have been refuted by clinical research include the treatment of autism and idiopathic epilepsy.
'..all of its touted effects have largely been refuted by clinical and laboratory testing.'
DMG is also touted as an immune stimulant, although it has no role in the body that could directly account for this effect. A double blind study in the early 1980's showed increased immune function (both humoral and cell-mediated) in humans following supplementation with DMG. Another study suggested this increased immune response could translate into a protective effect against cancer. A comprehensive study in 1992 failed to demonstrate any immune enhancing properties of DMG in cats.
What is the function of DMG?
DMG is a metabolite of betaine, which is used to help promote the production of methionine from homocysteine. Abnormal homocysteine levels are associated with autism and with coronary artery disease, but DMG does not stimulate reactions that reduce homocysteine, but is a by-product of them. DMG may also eventually be converted into two very vital compounds, phosphatidylserine and glutathione, but a direct effect has not been demonstrated. Indeed, in one study, DMG supplementation actually reduced glutathione levels.
'DMG does appear to function as an antioxidant, and has been shown to have a protective effect against gastric ulceration.'
DMG does appear to function as an antioxidant, and has been shown to have a protective effect against gastric ulceration.
Why recommend the administration of DMG to my pet?
Despite the lack of supportive research, DMG is used to enhance athletic performance in dogs and horses. It may also function as an antioxidant, and be of some benefit in reducing inflammation. DMG may also be recommended for the treatment of immune deficiency disorders, cancer, epilepsy and cognitive disorders, although research support for these uses is lacking.
How much experience is there with the use of DMG in pets?
DMG has been used for over 20 years in humans, racing dogs and horses. While not necessarily clinically effective, DMG is at least extremely well tolerated and very safe, which is not surprising given that it is a metabolite already present in the body. No toxicity has been reported to DMG supplementation. It is important to note that practitioners who use DMG are convinced of its efficacy, and report positive clinical outcomes, despite the lack of research support. Mavericks 10.9.4 dmg download free.
Where do I get DMG and do I need a prescription?
Pet owners are cautioned against buying supplements without knowledge of the manufacturer, as supplements are not highly regulated and some supplements may not contain the labelled amount of ingredients. Your veterinarian may have preferred supplements that he or she will recommend. A prescription is not needed for DMG.
Published online 2016 Feb 11. doi: 10.1262/jrd.2015-149
PMID: 26875568
This article has been cited by other articles in PMC.
Abstract
The antioxidant effect of N, N-dimethylglycine (DMG) on in vitro-produced (IVP) bovineembryos was examined. After in vitro fertilization, presumptive zygotes were cultured with orwithout 0.1 μM DMG under different oxygen tensions. The percentage of embryos developing to the blastocyststage was lowest under a 20% oxygen concentration without DMG, and it was significantly increased (P <0.05) by applying a 5% oxygen concentration. Under the 20% oxygen concentration, supplementation of the mediumwith DMG significantly improved blastocyst development, which was nearly equal to that achieved under 5%oxygen without DMG. Furthermore, a tendentious increase (P = 0.06) in blastocyst cell numbers was observedwhen DMG was applied. In the second experiment, addition of H2O2 (0.5 mM) to the culturemedium significantly (P < 0.01) reduced the percentage of embryos developing to the blastocyst stage.However, DMG supplementation prevented this reduction. In conclusion, DMG enhanced thein vitro development of IVP bovine embryos by acting as an antioxidant.
Keywords: Antioxidant, Bovine embryo, DMG, In vitro fertilization, N, N-Dimethylglycine
In vitro-produced (IVP) bovine embryos at early developmental stages are known to be sensitiveto reactive oxygen species (ROS) []. Under oxidative stress, ROS canaccumulate in embryos, causing DNA damage and developmental arrest [, ]. Oxygen in air contributes to oxidative stress in embryos during culture.Reducing the oxygen concentration in the incubator from 20% to approximately 5% during culture has been reportedto improve the development of IVP embryos in several mammal species including cattle [,].
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N, N-Dimethylglycine (DMG) (also known as vitamin B15 or pangamic acid) acts as an antioxidant, extending thelifespan of animal cells through protection from oxidation [,]. DMG is presumably involved in thebetaine pathway, the metabolism of homocysteine and glutathione synthesis [, ]. In a previous report, addition of 0.1 μM DMG to a culturemedium prompted the development of early IVP bovine embryos [].
However, to clarify whether or not DMG promotes in vitro development of bovine embryos by actingas an antioxidant, the embryos must be exposed to oxidized in vitro culture (IVC) conditions.This study was conducted to demonstrate the antioxidant effect of DMG on bovine embryos for the first time. Forthis purpose, two experiments were performed.
In Experiment 1, the effect of addition of 0.1 μM DMG and no DMG (+DMG and –DMG, respectively) to a culturemedium on in vitro development of IVP bovine embryos was examined under both 20%(20O2) an oxygen concentration of and 5% (5O2) oxygen concentrations. Embryos were culturedin the presence or absence of DMG under 20% (5% CO2 in air) or 5% (5% CO2, 5% O2and 90% N2) as described below (+DMG/20O2, +DMG/5O2, –DMG/20O2 and–DMG/5O2 groups, respectively). Without DMG addition to the medium, blastocyst development wassignificantly lower under the 20% oxygen concentration conditions (–DMG/20O2 group) than that obtainedunder 5% oxygen (–DMG/5O2 group); however, they had similar cleavage rates (Table 1). When DMG was added to the culture medium under the 20% oxygen concentration conditions(+DMG/20O2 group), embryo development to the blastocyst stage increased significantly to a levelsimilar to that of embryos cultured without DMG under 5% oxygen (–DMG/5O2 group) (Table 1). Moreover, when DMG was added to the medium and 5% oxygen was used(+DMG/5O2 group), the highest blastocyst formation rate was obtained among all the groups (P <0.05) (Table 1). Also, when cultured under the 20% oxygenconcentration conditions, a trend (P = 0.06) was found for higher numbers of total cells per blastocyst in favorof DMG-treated embryos (+DMG/20O2 group) compared with non-treated embryos (–DMG/20O2 group)(Table 2).
Table 1.
Effect of N, N-Dimethylglycine (DMG) addition to the IVC medium* on development of bovine IVP embryoscultured under different oxygen concentrations
Values with different superscripts are significant (P < 0.05). * SOF1: mSOFaa supplemented with 0.3%BSA, 10 μl/ml ITS, 1 ng/ml TGFb1 and 10 ng/ml FGF was used during 0–96 h of IVC. SOF2: SOF1 supplementedwith 1.5 mM glucose (BSA was replaced with 5% FBS) was used after 96 h of IVC. ** Rates of cleavage anddevelopment to the blastocyst stage were assessed 48 h and 8 days, respectively, after insemination. Fivereplicates were performed for experiments on embryo development.
Dmg N N-dimethylglycine Side Effects In WomenTable 2.
Effect of N, N-Dimethylglycine (DMG) addition to the IVC medium* on cell number of bovine IVP embryoscultured under different oxygen concentrations
* SOF1: mSOFaa supplemented with 0.3% BSA, 10 μl/ml ITS, 1 ng/ml TGFb1 and 10 ng/ml FGF was used during0–96 h of IVC. SOF2: SOF1 supplemented with 1.5 mM glucose (BSA was replaced with 5% FBS) was used after 96h of IVC. The experiment was replicated three times. ICM, inner cell mass; TE, trophectoderm.
Experiment 2 demonstrated the antioxidant actions of DMG. In vitro culture of IVP bovine embryosat the 8- to 16-cell stage was conducted using the culture medium either in the absence (control group) orpresence of 0.5 mM hydrogen peroxide (H2O2). In another group, bothH2O2 and 0.1 μM DMG were added to the culture medium. As described below, IVP embryos werecultured to the blastocyst stage. Table 3 shows that the addition of H2O2 significantly (P < 0.01) reduced blastocystdevelopment compared with the control group (65.0% and 14.3%, respectively). However, when DMG was added to theH2O2-containing medium, the blastocyst formation rate improved significantly (P < 0.01)to a level (57.1%) equivalent to that obtained in the control group (Table3), demonstrating that DMG exerted a strong antioxidant effect by counteracting exogenous oxidativestress in embryos.
Table 3.
In vitro development of 8- to 16-cell stage bovine embryos to the blastocyst stage inthe presence of H2O2 and DMG
H2O2: hydrogen peroxide, DMG: N, N-Dimethylglycine. Base medium: SOF1/SOF2. SOF1:mSOFaa supplemented with 0.3% BSA, 10 μl/ml ITS, 1 ng/ml TGFb1 and 10 ng/ml FGF was used during 0–96 h ofIVC. SOF2: SOF1 supplemented with 1.5 mM glucose (BSA was replaced with 5% FBS) was used after 96 h of IVC.The experiment was replicated three times. SOF2: SOF1 supplemented with 1.5 mM glucose (BSA was replacedwith 5% FBS) was used after 96 h of IVC. Values with different superscripts are significant (P <0.01).
The concentration of oxygen in the body is lower than that in the atmosphere. Previous studies have demonstratedthat the oxygen concentration in the oviduct and uterus is approximately one-fourth of that in the atmosphere[]. Embryo development has reportedly been improved by adjusting theoxygen concentration to approximately 5% in in vitro culture of early embryos []. Our results confirm that a 5% oxygen concentration, which is presumed toapproximate the oxygen concentration in the body, is effective as a culture condition for early embryos and thatthe level of oxidative stress is involved in determining the quality of embryos, such as the number of cells.Oxygen present in the culture medium changes into free radical or nonradical molecular species. Previous reportshave described that ROS affects fertilization of in vitro maturation (IVM) oocytes and theirsubsequent cleavage [, ].Differences attributable to the concentration of oxygen have also been demonstrated in the invitro production of embryos in cattle, including the IVM and in vitro fertilization(IVF) of oocytes and IVC of early embryos []. Results of previous studieshave shown that decreasing the oxygen concentration to 5% during maturation improved embryo development andchanged the expression of genes related to oocyte competence and glucose metabolism [] and that the addition of antioxidants to the culture medium for IVF oocytes affects theirpronucleus formation rate in cattle []. However, exceedingly low oxygenconcentrations might adversely affect development, as the proliferative capacity was decreased and apoptosis wasincreased under a markedly low oxygen concentration of 1% in human and mouse stem cells [].
Although the blastocyst formation rate of embryos cultured under an oxygen concentration of 5% was found to besignificantly higher even without DMG (–DMG/5O2 group) than that of embryos cultured without DMG underthe 20% oxygen concentration conditions (–DMG/20O2 group), the development rate improved significantlywhen DMG was added to the culture medium and embryos were cultured, even under the 5% oxygen concentrationconditions (+DMG/5O2 group); the highest blastocyst formation rate was obtained in the+DMG/5O2 group among all the group. Furthermore, cells in the prepared embryos were slightly morenumerous with the addition of DMG. There are two possible explanations for these phenomena; it is possible that(1) even under 5% oxygen the embryos still suffer from oxidative stress to some degree or (2) DMG might improveembryo development not only by neutralizing oxidative stress but also via another, currently unknown, way. Furtherresearch will be necessary to clarify this point. Based on the findings presented above, we conclude that 0.1 μMDMG apparently exerted an antioxidant effect on bovine embryos produced invitro,increasing blastocyst formation rates and tending to increase the number of cells in resultant embryos.
Methods
Reagents were obtained from Sigma Chemical (St. Louis, MO, USA) unless otherwise specified.
The protocol was approved by the Ethics Committee for Experimentation with Animals of the Akita PrefecturalExperiment Station.
Oocytes were collected from follicles (2–5 mm in diameter) of bovine ovaries collected at a meat processingplant by aspirating follicular fluid containing cumulus–oocyte complexes (COCs) with a 5-ml syringe equippedwith an 18G needle. The IVM medium was 25 mM HEPES-buffered TCM-199 (TCM-199; Gibco, Thermo Fisher Scientific,Waltham, MA, USA) supplemented with 0.4% (w/v) bovine serum albumin (BSA, Fraction V), 100 μM cysteamine, 50ng/ml epidermal growth factor, 100 ng/ml transforming growth factor α, 0.05 IU/ml human menopausal gonadotropin(Serono Laboratories, Tokyo, Japan) and 10 μg/ml gentamicin (Gibco) [].The COCs with two or more layers of adhered cumulus cells were washed three times with IVM medium. They werethen placed in IVM medium covered with paraffin oil at a ratio of 5 μl/COCs (15–20 COCs/culture drop) usingRepro C-1 plates (Research Institute for the Functional Peptides, Yamagata, Japan). They were incubated for 20 hunder gaseous-phase conditions of 38.5°C, 5% CO2, 95% air and saturated humidity.
Frozen semen from one Japanese black bull was thawed in hot water heated at 38°C and was washed twice with theBrackett and Oliphant (BO) solution [] containing 10 mM caffeine(Caff-BO solution) by centrifugation (500 × g for 5 min). The supernatant was removed from thesperm pellet. The Caff-BO solution was then added to achieve a final sperm concentration of 1 ×107/ml. Then the same volume of BO solution supplemented with 20 mg/ml BSA (Fraction V) (BSA-BOsolution) and 10 IU/ml heparin (Novo-Heparin; Mochida Pharmaceutical, Tokyo, Japan) was added to achieve a finalsperm concentration of 5 × 106/ml. This suspension was used as the IVF medium. After IVM of COCs,oocytes with adhered cumulus cells were washed three times with the BSA-BO solution. They were then transferredinto IVF medium covered with paraffin oil at a ratio of 5 μl/oocyte using Repro C-1 plates and were incubatedunder gaseous-phase conditions of 38.5°C, 5% CO2, 95% air and saturated humidity.
After 6 h of IVF, cumulus cells and spermatozoa were removed from the surface of the zona pellucida by gentlepipetting with a fine glass pipette. The putative zygotes were then washed three times in SOF1 medium, which wasSOFaa medium supplemented with 3 mg/ml BSA (Fraction V), 10 μl/ml insulin-transferrin-selenium (Gibco), 1 ng/mltransforming growth factor β1 and 10 ng/ml fibroblast growth factor [].Twenty zygotes per Repro C-1 plate were placed in 100 μl of SOF1 medium covered with paraffin oil and culturedwith or without 0.1 μM DMG at 38.5°C under gaseous conditions of 5% CO2, 5% O2 and 90%N2 or 5% CO2, 95% air and saturated humidity. After 96 h of culture, the embryos werethen transferred to SOF2 medium, which was SOF1 medium supplemented with 1.5 mM glucose and 5% (v/v) fetalbovine serum in place of BSA [21], and cultured with or without 0.1 μMDMG under the same gaseous conditions. We changed the IVC medium based on a report by Matsumoto etal. [21] and performed IVC using the culture mediasupplemented with glucose thereafter because it was shown that the addition of glucose to the IVC mediumimmediately after IVF until 96 h of IVC is detrimental to bovine embryo development, although it is necessarylater for embryo hatching [].
The embryonic cell number was assessed using double staining. Embryos were treated with 0.2% Triton X-100-PBSsupplemented with 0.1 mg/ml propidium iodide for 1 min. They were then transferred into 99.5% ethanolsupplemented with 25 μg/ml Bis-benzimide (33342; Hoechst). Embryos were stained at 4°C for 3 h and protectedfrom light. They were then washed with Vectashield (Vector Laboratories, Burlingame, CA, USA). The treatmentsolution containing embryos was dropped onto a slide glass. A cover slip was added to flatten the embryos.Observations were conducted using a fluorescence microscope (IMT-2, Olympus, Tokyo, Japan). The inner cell mass(blue) and trophectoderm (pink) cells were counted.
In one experiment, embryos at the 8-cell to 16-cell stage were used to examine the antioxidant effect of DMG.The test was conducted with three groups: a group cultured with H2O2 (0.5 mM), a groupcultured with H2O2 (0.5 mM) and DMG (0.1 μM) and a control group cultured withoutH2O2 and DMG. The embryos were cultured in SOF1 medium and then in SOF2 medium until Day8 (Day 0 = the day of IVF), and the development rate was examined.
The StatView software was used for statistical analyses. After all percentage data were subjected to arcsinetransformation, significance was tested using a one-way analysis of variance (ANOVA) and the Tukey-Kramer test.Differences with P < 0.05 were regarded as significant.
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