Dimethylglycine Abstracts 1

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Alterations in DNA methylation: a fundamental aspect of neoplasia.
            (Baylin et al., 1998)  Download
Neoplastic cells simultaneously harbor widespread genomic hypomethylation, more regional areas of hypermethylation, and increased DNA-methyltransferase (DNA-MTase) activity. Each component of this "methylation imbalance" may fundamentally contribute to tumor progression. The precise role of the hypomethylation is unclear, but this change may well be involved in the widespread chromosomal alterations in tumor cells. A main target of the regional hypermethylation are normally unmethylated CpG islands located in gene promoter regions. This hypermethylation correlates with transcriptional repression that can serve as an alternative to coding region mutations for inactivation of tumor suppressor genes, including p16, p15, VHL, and E-cad. Each gene can be partially reactivated by demethylation, and the selective advantage for loss of gene function is identical to that seen for loss by classic mutations. How abnormal methylation, in general, and hypermethylation, in particular, evolve during tumorigenesis are just beginning to be defined. Normally, unmethylated CpG islands appear protected from dense methylation affecting immediate flanking regions. In neoplastic cells, this protection is lost, possibly by chronic exposure to increased DNA-MTase activity and/or disruption of local protective mechanisms. Hypermethylation of some genes appears to occur only after onset of neoplastic evolution, whereas others, including the estrogen receptor, become hypermethylated in normal cells during aging. This latter change may predispose to neoplasia because tumors frequently are hypermethylated for these same genes. A model is proposed wherein tumor progression results from episodic clonal expansion of heterogeneous cell populations driven by continuous interaction between these methylation abnormalities and classic genetic changes.

A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder.
            (Bolman and Richmond, 1999)  Download
As the treatability of the syndrome of autism becomes more possible there is a great deal more interest in the effectiveness of various therapies. Although the very influential nonmedical literature cited in the Autism Research Review International Newsletter finds that dimethylglycine (DMG) is regarded as more effective than the usual psychopharmacologic drugs, there have been no studies of DMG using the currently accepted research methodology. We report a double-blind, placebo-controlled, crossover pilot study of low dose DMG and placebo in a sample of eight autistic males ranging in age from 4 years 5 months to 30 years 8 months, who completed the full 3 1/2-month study consisting of drug-free baseline periods at the beginning, end, and in-between two, 1-month double-blind trials in which DMG or placebo was given. Measures included the Campbell-NIMH rating scale, an experimental rating scale, and an individualized scale created for each child. Analysis of all three scales revealed no statistically significant differences, and parent reports were equally distributed. The major methodologic weaknesses of the study are thought to be the low dosage of DMG and the small sample size.

Effects of commercial preparations of pangamic acid (B15) on exercised rats.
            (Dohm et al., 1982)  Download
Exercise endurance and metabolic patterns were determined in rats that had been administered commercial preparations of “pangamic acid,” dimethylglycine, or diisopropylamine subcutaneously. None of these sub- stancesaffected (a) the time required to reach exhaustion by treadmill running, (b) the specific activities of succinate dehydrogenase of liver and muscle, (c) the capacity of liver mitochondria for oxidative N-de-methylation, (d) the content of mitochondria in liver, (e) the ratios of soluble to membranous protein of the liver mitochondria, or (f) the level of urinary excretion of creatinine. The concentrations of glycogen in muscle and liver were not increased. These results do not substantiate previous reports by Russian investigators on whose work many athletes base their practice of consuming pangamate to improve performance.

N,N dimethylglycine and epilepsy.
            (Gascon et al., 1989)  Download
Nineteen institutionalized patients with frequent seizures (group average two to three per day; seizure types--generalized, akinetic/myoclonic), were treated randomly with either placebo or N,N dimethylglycine (DMG) for 28 days. Dosage was 300 mg/day for the first 14 days and then 600 mg/day. Plasma levels were measured at baseline, days 2, 5, 8, 15, 22, 30, and 1 and 2 weeks after the study ended. No differences in seizure frequency were noted between placebo and DMG or between baseline and test conditions. No toxicity was noted.

Immunomodulating properties of dimethylglycine in humans.
            (Graber et al., 1981)  Download
Dimethylglycine (DMG), a tertiary amino acid, has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. Its potential as an immunoadjuvant has also been suggested by a study of an analog of DMG, calcium pangamate. A double-blind study in 20 human volunteers showed a fourfold increase in antibody response to pneumococcal vaccine in those receiving DMG orally as compared with controls (P less than 0.01). Production of leukocyte inhibitory factor in response to concanavalin A was similar in the two groups, but those taking DMG tablets had a significantly highr mean response of leukocyte inhibition factor to streptokinase-streptodornase (P less than 0.001). The in vitro responses of lymphocytes from patients with diabetes and those with sickle cell disease to phytohemagglutinin, convanavalin A, and pokeweed mitogen were increased almost threefold after addition of DMA. These results suggest that DMG enhances both humoral and cell-mediated immune responses in humans.

B15: Myth or Miracle?
            (Gray and Titlow, 1982b)  Download
In brief B15, a mixture of calcium gluconate and N, N-Dimethylglycine (DMG), is widely used by amateur and professional athletes because they believe it lowers blood lactic acid, stabilizes blood sugar during exercise, and reduces the effects of fatigue. In general, Russian studies report increased oxygen efficiency, but they are not properly controlled. Some American studies support the claims of reduced lactic acid and increased performance, but others show no measurable effects. The authors say further studies are needed, but it is illegal to sell B15 as a dietary supplement or a drug.

The effect of pangamic acid on maximal treadmill performance.
            (Gray and Titlow, 1982a)  Download
The effect of pangamic acid (calcium gluconate and N, N-Dimethylglycine) ingestion was examined during short-term maximal treadmill performance on 16 male track athletes. The study was conducted as a double-blind experiment with an experimental group (E) whose members each ingested six 50-mg pangamic acid tablets per day and a control group (C) whose members each ingested six placebo tablets per day for three weeks. The placebo tablets were identical to the pangamic acid tablets in appearance. Subjects were tested by using the Bruce treadmill protocol before and after treatment. The following parameters were examined: maximal heart rate (HR), treadmill time (TM), recovery HR at minutes 1 and 3, and pre-test and post-test blood glucose and lactate levels. Pre-treatment data were 183 bpm (E) and 194 bpm (C) for maximal HR, 16.99 min (E) and 16.49 min (C) for TM, 132.13 mg% (E) and 133.38 mg% (C) for post-test glucose, and 64.63 mg% (E) and 76.13 mg% (C) for post-test lactate. Post-treatment data were 181 bpm (E) and 194 bpm (C) for maximal HR, 17.21 min (E) and 16.83 min (C) for TM, 138.88 mg% (E) and 139.13 mg% (C) for post-test glucose, and 70.88 mg% (E) and 66.58 mg% (C) for post-test lactate. Multivariate analysis of variance (MANOVA) revealed no significant differences (P greater than 0.05) between groups after treatment. It was concluded that ingestion of pangamic acid does not produce significant changes in short-term maximal treadmill performance.

Pangamic acid ("vitamin B15").
            (Herbert, 1979)  Download
“Vitamin B15” is the latest rage in health food stores in the United States (1). Numerous articles have appeared in lay publications and on radio and television extolling this substance. Yet, according to the Food and Drug Administration (2), vitamin B15 is “not an identifiable substance ... not a vitamin nor a provitamin . . . no accepted scientific evidence establishing any nutritional properties of the substance or any deficiency . . . in man or animal . . . no medical, nutritional, or other usefulness for these substances has been established.”

Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder.
            (Kern et al., 2001)  Download
N,N-dimethylglycine, a dietary supplement, has been reported to be beneficial in children with autism and pervasive developmental disorder. We examined the effectiveness of dimethylglycine in children with autism and pervasive developmental disorder in a double-blind, placebo-controlled study. Thirty-seven children between 3 and 11 years of age with a diagnosis of autism and/or pervasive developmental disorder were gender and age matched and randomly assigned to receive either placebo or dimethylglycine for 4 weeks. All children were assessed before and after treatment on two behavioral measures, the Vineland Maladaptive Behavior Domain and the Aberrant Behavior Checklist. Standardized neurologic examinations before and after treatment on 33 children showed no change. An overall improvement on all behavioral measures was observed for both the placebo and the dimethylglycine groups. However, the improvement among the children who received dimethylglycine was not statistically different from the improvement observed among the children who received the placebo. The children who participated in this study were a heterogeneous group, and their apparent responses to the dimethylglycine varied. Some children appeared to respond positively to the dimethylglycine, and there was a smaller proportion of negative changes in the dimethylglycine group, but the quantitative changes in the dimethylglycine behavioral assessments were not significantly different from what was observed among children who received placebo.

Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus.
            (Lawson et al., 2007)  Download
BACKGROUND:  Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel Perna canaliculus (Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses. METHODS:  In our initial studies, we treated lipopolysaccahride (LPS) stimulated THP-1 monocytes in vitro with increasing concentrations of Perna extract or DMG. Additionally, we treated rat peripheral blood neutrophils with increasing concentrations of Perna extract and measured superoxide burst. In subsequent in vivo experiments, CIA was induced by administration of type II collagen; rats were prophylactically treated with either Perna or DMG, and then followed for disease severity. Finally, to test whether Perna and/or DMG could block or inhibit an ongoing pathologic disease process, we induced CIA in mice and treated them therapeutically with either of the two immunomodulators. RESULTS:  Following LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-alpha and IL-12p40 production in Perna treated cultures. DMG treatment, however, showed significant increases in both of these cytokines in the range of 0.001-1 microM. We also demonstrate that in vitro neutrophil superoxide burst activity is dose-dependently reduced in the presence of Perna. Significant reductions in disease incidence, onset, and severity of CIA in rats were noted following prophylactic treatment with either of the two immunomodulators. More importantly, amelioration of mouse CIA was observed following therapeutic administration of Perna. In contrast, DMG appeared to have little effect in mice and may act in a species-specific manner. CONCLUSION:  These data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.

The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: a double-blind randomized crossover clinical trial.
            (Liet et al., 2003)  Download
OBJECTIVE:  To study the effectiveness of dimethylglycine (DMG) on oxygen consumption (VO(2)) in children with Saguenay-Lac-Saint-Jean cytochrome-c oxidase (SLSJ-COX) deficiency (OMIM 220111). STUDY DESIGN:  In a crossover randomized double-blind clinical trial, 5 children with SLSJ-COX deficiency, who were stable and old enough to comply with VO(2) measurement, were treated with placebo or DMG for 3 days, and with the alternate treatment after a 2-week washout period. VO(2) was measured by indirect calorimetry before and after treatment. Dietary caloric intake was calculated for 3 days before each measurement. Mean caloric intakes per day were 1562 and 1342 kcal x m(-2) before and during placebo, 1,336 and 1,380 before and during DMG, respectively. RESULTS:  DMG was well tolerated and, in all cases, resulted in markedly increased blood DMG levels (617 + 203 mmol x L(-1)), versus 0 to 2 mmol x L(-1) without treatment. Mean VO(2) was lower after administration of either DMG (-1 +/- 3 mL x min(-1) x m(-2)) or placebo (-6 +/- 4), but neither difference was statistically significant. There was no detectable effect of DMG treatment on blood levels of lactate, pyruvate, bicarbonate, or pH. VO(2) values of patients (range, 101-135 mL x min(-1) x m(-2)) were lower than published norms (150-160 mL x min(-1) x m(-2)). CONCLUSION:  This study suggests that treatment with DMG does not substantially change VO(2) in children with SLSJ-COX deficiency.

The metabolism of dimethylglycine by liver mitochondria.
            (Mackenzie and Frisell, 1958)  Download
Dimethylglycine is metabolized stoichiometrically by liver mitochondria in the absence of added cofactors. Both of the active formaldehyde molecules can condense with glycine to produce a high yield of serine or, alternatively, they can be converted to ordinary formaldehyde. Exogenous formaldehyde, however, cannot re- place active formaldehyde as a source of the P-carbon of serine in this system. he conversion of dimethylglycine to serine completes a cyclic series of reactions in which methyl groups are oxidized and l-carbon compounds are generated. The metabolic significance of this l-carbon cycle is discussed.

Dimethylglycine Deficiency and the Development of Diabetes.
            (Magnusson et al., 2015)  Download
Experimental studies have suggested possible protective effects of dimethylglycine (DMG) on glucose metabolism. DMG is degraded to glycine through a DMG-dehydrogenase (DMGDH)-catalyzed reaction, and this is the only known pathway for the breakdown of DMG in mammals. In this study, we aimed to identify the strongest genetic determinant of circulating DMG concentration and to investigate its associations with metabolic traits and incident diabetes. In the cohort with full metabolomics data (n = 709), low plasma levels of DMG were significantly associated with higher blood glucose levels (P = 3.9E(-4)). In the genome-wide association study (GWAS) of the discovery cohort (n = 5,205), the strongest genetic signal of plasma DMG was conferred by rs2431332 at the DMGDH locus, where the major allele was associated with lower DMG levels (P = 2.5E(-15)). The same genetic variant (major allele of rs2431332) was also significantly associated with higher plasma insulin (P = 0.019), increased HOMA insulin resistance (P = 0.019), and an increased risk of incident diabetes (P = 0.001) in the pooled analysis of the discovery cohort together with the two replication cohorts (n = 20,698 and n = 7,995). These data are consistent with a possible causal role of DMG deficiency in diabetes development and encourage future studies examining if inhibition of DMGDH, or alternatively, supplementation of DMG, might prove useful for the treatment/prevention of diabetes.

Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome.
            (Mahmoud and Ali, 2019)  Download
DNA methylation is an epigenetic mechanism that is essential for regulating gene transcription. However, aberrant DNA methylation, which is a nearly universal finding in cancer, can result in disturbed gene expression. DNA methylation is modified by environmental factors such as diet that may modify cancer risk and tumor behavior. Abnormal DNA methylation has been observed in several cancers such as colon, stomach, cervical, prostate, and breast cancers. These alterations in DNA methylation may play a critical role in cancer development and progression. Dietary nutrient intake and bioactive food components are essential environmental factors that may influence DNA methylation either by directly inhibiting enzymes that catalyze DNA methylation or by changing the availability of substrates required for those enzymatic reactions such as the availability and utilization of methyl groups. In this review, we focused on nutrients that act as methyl donors or methylation co-factors and presented intriguing evidence for the role of these bioactive food components in altering DNA methylation patterns in cancer. Such a role is likely to have a mechanistic impact on the process of carcinogenesis and offer possible therapeutic potentials.

Therapeutic Use Of Vitamin B-15
            (Navarro, 1954)  Download
A new vitamin of the B complex, tentatively assigned the number 15, was isolated by Krebs and Krebs from rice bran and polishings. Vitamin B15 or pangamic acid sodium is widely distributed in nature.

Stimulation of the immune response by dimethylglycine, a nontoxic metabolite.
            (Reap and Lawson, 1990)  Download
The immunomodulating capacities of dimethylglycine (DMG) were examined in a rabbit model. Female New Zealand white rabbits were immunized on day 0 and were given booster inoculations on day 9 with either killed influenza virus or Salmonella typhi vaccine. Experimental animals were force fed 20 mg/kg body weight of DMG daily beginning 14 days prior to the first inoculation and continuing throughout the experiment. Control animals were force fed daily only distilled water. Blood was obtained on day 0, day 9, and day 30. Hemagglutination inhibition assays showed a more than fourfold increase in mean antibody titer to influenza antigen in the DMG-treated animals (p = 0.0006) after the first inoculation, and a fourfold increase in mean titer after the booster inoculation (p = 0.1000). A standard agglutination test for Salmonella typhi O (somatic) and H (flagella) antigens was performed on all sera from animals receiving the typhoid vaccine. Mean antibody titers to the O antigen were significantly higher (more than threefold) after the first inoculation (p = 0.0302) and more than fivefold higher after the booster inoculation (p = 0.0047) in DMG-treated animals. Mean antibody titers to the H antigen were also higher in DMG-treated animals compared with controls after both the first and second inoculation. Lymphocyte transformation assays on cells taken from DMG-treated animals immunized with the influenza vaccine showed a tenfold increase in mean proliferative response (p = 0.0024). Lymphocytes from DMG-treated animals immunized with the typhoid vaccine showed a fourfold increase (mean values) in thymidine uptake (p = 0.0180). No toxicity or adverse effects were observed at any time during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

N,N-dimethylglycine for epilepsy.
            (Roach and Carlin, 1982)  Download
Although no definite conclusions can be drawn from a single patient’s response to DMG, we think further study is warrented.

Failure of N,N-dimethylglycine in epilepsy.
            (Roach and Gibson, 1983)  Download
Five patients with refractory seizures were studied. After the initial observation period, each subject be- gan a regimen of three daily doses of either 270 mg of DMG or an identical-looking placebo. At the end of 30 days, the DMG or placebo was exchanged and the tablet was con- tinued for another 30 days. There was no apparent improvement in seizure frequency in any of the five patients, and none of the patients had notable deterioration of definite side-effects. Although no benefit was demonstrated in these refractory seizure patients, DMG might still be of benefit in other, less difficult patients. Furthermore, the possibility remains that the originally de- scribed patient had an isolated defect in his metabolism that was circumvented by DMG, analogous to the treatment of pyridoxine dependency with high doses of vitamin Bb. These reservations aside, our small pilot study failed to demonstrate any benefit of D M G in the routine management of refractory seizure patients.

Methyl donors in the diet and responses to chemical carcinogens.
            (Rogers, 1995)  Download
Dietary deficiency of labile methyl donors (choline and methionine) increases spontaneous and chemically induced hepatocarcinogenesis in rats. Chemical carcinogenesis in the colon, mammary gland, esophagus, and pancreas also may be increased. The mechanism of the dietary effect is not known but may be related to reduced methylation of DNA and RNA, hyperplasia of target cells, increased peroxidative damage, and altered carcinogen or promoter metabolism. Folate deficiency also is associated with increased carcinogenesis, an effect that may be mediated through participation in methyl metabolism; this has been less extensively studied. Deficiency of these three nutrients also may play a role in the elevated cancer risk in humans that is associated with ethanol intake.

Studies on the chemical identity and biological functions of pangamic acid.
            (Schneider et al., 1999)  Download
Pangamic acid (6-O-(dimethylaminoacetyl)-D-gluconic acid) has been detected 1938 and described as a natural, universally occurring substance with multiple biological and medical functions. In this respect pangamic acid has been worldwide on the market since decades as a drug stimulating cellular respiration. In addition to the natural pangamic acid, diisopropylammonium dichloroacetate (DIPA), a synthetic product not found in biological material, is on the market requesting similar biological functions. In commercially available drugs on the German market declared as pangamic acid three separate substances can be found by chemical identification of pangamic acid, namely: gluconic acid, glycine and diisopropylamonium dichloroacetate. As biological functions have been found in vitro inhibition of Cu-dependent LDL oxidation by glycine due to chelation of Cu2+ ions and deterioration of mitochondrial respiratory control due to an increased state IV oxygen consumption rate at high concentrations of DIPA.

Dimethylglycine supplementation does not affect plasma homocysteine concentrations in pre-dialysis chronic renal failure patients.
            (Slow et al., 2004)  Download
OBJECTIVE:  To determine whether daily dimethylglycine supplementation affects plasma homocysteine concentrations. DESIGN AND METHODS:  A randomized, blinded, crossover design was used. Seven pre-dialysis chronic renal failure patients consumed 400 mg of dimethylglycine or placebo daily for 28 days. Fasting blood samples and 12-h urine samples were collected at baseline and at the end of each treatment period for analysis. RESULTS:  No significant differences were observed in plasma homocysteine (P = 0.624), glycine betaine (P = 0.452) and methionine (P = 0.457) concentrations between dimethylglycine and placebo treatments. CONCLUSION:  Daily supplementation with dimethylglycine does not affect plasma homocysteine.

Methyl groups in carcinogenesis: effects on DNA methylation and gene expression.
            (Wainfan and Poirier, 1992)  Download
Lipotrope-deficient (methyl-deficient) diets cause fatty livers and increased liver-cell turnover and promote carcinogenesis in rodents. In rats prolonged intake of methyl-deficient diets results in liver tumor development. The mechanisms responsible for the cancer-promoting and carcinogenic properties of this deficiency remain unclear. The results of the experiments described here lend support to the hypothesis that intake of such a diet, by causing depletion of S-adenosylmethionine pools, results in DNA hypomethylation, which in turn leads to changes in expression of genes that may have key roles in regulation of growth. In livers of rats fed a severely methyl-deficient diet (MDD), lowered pools of S-adenosylmethionine and hypomethylated DNA were observed within 1 week. The extent of DNA hypomethylation increased when MDD was fed for longer periods. The decreases in overall levels of DNA methylation were accompanied by simultaneous alterations in gene expression, yielding patterns that closely resembled those reported to occur in livers of animals exposed to cancer-promoting chemicals and in hepatomas. Northern blot analysis of polyadenylated RNAs from livers of rats fed control or deficient diets showed that, after 1 week of MDD intake, there were large increases in levels of mRNAs for the c-myc and c-fos oncogenes, somewhat smaller increases in c-Ha-ras mRNA, and virtually no change in levels of c-Ki-ras mRNA. In contrast, mRNAs for epidermal growth factor receptor decreased significantly. The elevated levels of expression of the c-myc, c-fos, and c-Ha-ras genes were accompanied by selective changes in patterns of methylation within the sequences specifying these genes. Changes in DNA methylation and in gene expression induced in livers of rats fed MDD for 1 month were gradually reversed after restoration of an adequate diet. In hepatomas induced by prolonged dietary methyl deficiency, methylation patterns of c-Ki-ras and c-Ha-ras were abnormal. Although human diets are unlikely to be as severely methyl deficient as those used in these experiments, in some parts of the world intake of diets that are low in methionine and choline and contaminated with mycotoxins, such as aflatoxin, are common. Even in industrialized nations, deficiencies of folic acid and vitamin B12 are not uncommon and are exacerbated by some therapeutic agents and by substance abuse. Thus, it seems possible that interactions of diet and contaminants or drugs, by inducing changes in DNA methylation and aberrant gene expression, may contribute to cancer causation in humans.

DNA methylation in senescence, aging and cancer.
            (Xie et al., 2019)  Download
In response to genotoxic stresses, cells are programmed to trigger senescence, involving metabolic slowdown and proliferation arrest, to contain deleterious effects of the damaged genetic material [1]. Two forms of senescence processes are relevant in this context: (a) Replicative Senescence (RS) in response to telomere shortening and/or reactive oxygen species (ROS) that occur during aging; (b) Oncogene Induced Senescence (OIS) in response to oncogenic mutations, such as oncogenic RAS mutations. Failure to trigger senescence can lead to tumorigenesis. Epigenetic alterations play important roles during both senescence and tumor initiation. During senescence, epigenetic alterations play important roles in stably silencing proliferation-promoting genes [2], while in tumorigenesis the epigenetic changes function in suppressing tumor suppressor genes. Here we summarize recent advances in understanding the relation and origins of senescence and tumor epigenomes, and its implications for tumorigenesis.

 


References

Baylin, SB, et al. (1998), ‘Alterations in DNA methylation: a fundamental aspect of neoplasia.’, Adv Cancer Res, 72 141-96. PubMed: 9338076
Bolman, WM and JA Richmond (1999), ‘A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder.’, J Autism Dev Disord, 29 (3), 191-94. PubMed: 10425581
Dohm, GL, S Debnath, and WR Frisell (1982), ‘Effects of commercial preparations of pangamic acid (B15) on exercised rats.’, Biochem Med, 28 (1), 77-82. PubMed: 7150274
Gascon, G, et al. (1989), ‘N,N dimethylglycine and epilepsy.’, Epilepsia, 30 (1), 90-93. PubMed: 2463912
Graber, CD, et al. (1981), ‘Immunomodulating properties of dimethylglycine in humans.’, J Infect Dis, 143 (1), 101-5. PubMed: 6163829
Gray, ME and LW Titlow (1982a), ‘The effect of pangamic acid on maximal treadmill performance.’, Med Sci Sports Exerc, 14 (6), 424-27. PubMed: 7162387
——— (1982b), ‘B15: Myth or Miracle?’, Phys Sportsmed, 10 (1), 107-12. PubMed: 29267114
Herbert, V (1979), ‘Pangamic acid (”vitamin B15”).’, Am J Clin Nutr, 32 (7), 1534-40. PubMed: 377937
Kern, JK, et al. (2001), ‘Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder.’, J Child Neurol, 16 (3), 169-73. PubMed: 11305684
Lawson, BR, et al. (2007), ‘Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus.’, BMC Complement Altern Med, 7 20. PubMed: 17562016
Liet, JM, et al. (2003), ‘The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: a double-blind randomized crossover clinical trial.’, J Pediatr, 142 (1), 62-66. PubMed: 12520257
Mackenzie, CG and WR Frisell (1958), ‘The metabolism of dimethylglycine by liver mitochondria.’, J Biol Chem, 232 (1), 417-27. PubMed: 13549430
Magnusson, M, et al. (2015), ‘Dimethylglycine Deficiency and the Development of Diabetes.’, Diabetes, 64 (8), 3010-16. PubMed: 25795213
Mahmoud, AM and MM Ali (2019), ‘Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome.’, Nutrients, 11 (3), PubMed: 30871166
Navarro (1954), ‘Therapeutic Use Of Vitamin B-15’, Sto Tomas J Med, 9 (5), 376-78. PubMed:
Reap, EA and JW Lawson (1990), ‘Stimulation of the immune response by dimethylglycine, a nontoxic metabolite.’, J Lab Clin Med, 115 (4), 481-86. PubMed: 1691258
Roach, ES and L Carlin (1982), ‘N,N-dimethylglycine for epilepsy.’, N Engl J Med, 307 (17), 1081-82. PubMed: 6181403
Roach, ES and P Gibson (1983), ‘Failure of N,N-dimethylglycine in epilepsy.’, Ann Neurol, 14 (3), 347. PubMed: 6195957
Rogers, AE (1995), ‘Methyl donors in the diet and responses to chemical carcinogens.’, Am J Clin Nutr, 61 (3 Suppl), 659S-65S. PubMed: 7879734
Schneider, D, et al. (1999), ‘Studies on the chemical identity and biological functions of pangamic acid.’, Arzneimittelforschung, 49 (4), 335-43. PubMed: 10337453
Slow, S, et al. (2004), ‘Dimethylglycine supplementation does not affect plasma homocysteine concentrations in pre-dialysis chronic renal failure patients.’, Clin Biochem, 37 (11), 974-76. PubMed: 15498524
Wainfan, E and LA Poirier (1992), ‘Methyl groups in carcinogenesis: effects on DNA methylation and gene expression.’, Cancer Res, 52 (7 Suppl), 2071s-7s. PubMed: 1544143
Xie, W, SB Baylin, and H Easwaran (2019), ‘DNA methylation in senescence, aging and cancer.’, Oncoscience, 6 (1-2), 291-93. PubMed: 30800716