Have their been studies that suggested that there is a deficit in the availability of methyl groups when they are needed?
[. . .]
If it does have a net increase, however, SAMe should increase the methylation equally through out the body. Wouldn't that be introducing a random effect into the regulation of all of the methylation regulatory mechanisms which are active at the time you take SAMe? Perhaps that would even cause a minor case of "dysdifferentiation".
Supplementation with the methyl group donor trimethylglycine helps. And I would hope that the body has control mechanisms to prevent harmful use of spare methyl groups. The second abstract says that the local hypermethylation found in tumor cells is preceded by global hypomethylation caused by inadequate nutrition. I searched for "global hypermethylation" and got 6 hits, none related to supplementation. One cause is breathing airborne particulates. Still, to be safe I'd only take enough TMG to get my homocysteine into the desired range. Mine was actually flagged as being too low last time, so I cut back to 500 mg. I think I was taking either 2 or 3 g at the time.
J Nutr. 2006 Jan;136(1):34-8.
Erratum in: J Nutr. 2007 Apr;137(4):1124.
Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans.
Schwab U, Törrönen A, Meririnne E, Saarinen M, Alfthan G, Aro A, Uusitupa M.
Department of Clinical Nutrition, University of Kuopio, Finland. Ursula.Schwab@uku.fi
Betaine, i.e., trimethylglycine, is linked to homocysteine metabolism. A 3-mo daily betaine supplementation decreased even normal plasma total homocysteine (tHcy) concentrations in humans. The pharmacokinetic characteristics and metabolism of betaine in humans have not been investigated in detail. The aim of this study was to assess the pharmacokinetics of orally administered betaine and its acute effect on plasma tHcy concentrations. Healthy volunteers (n = 10; 3 men, 7 women) with normal body weight (mean +/- SD, 69.5 +/- 17.0 kg), 40.8 +/- 12.4 y old, participated in the study. The betaine doses were 1, 3, and 6 g. The doses were mixed with 150 mL of orange juice and ingested after a 12-h overnight fast by each volunteer according to a randomized double-blind crossover design. Blood samples were drawn for 24 h and a 24-h urine collection was performed. Orally administered betaine had an immediate and dose-dependent effect on serum betaine concentration. Single doses of 3 and 6 g lowered plasma tHcy concentrations (P = 0.019 and P < 0.001, respectively), unlike the 1-g dose. After the highest dose, the concentrations remained low during the 24 h of monitoring. The change in plasma tHcy concentration was linearly associated with betaine dose (P = 0.006) and serum betaine concentration (R2 = 0.17, P = 0.025). The absorption and elimination of betaine were dose dependent. The urinary excretion of betaine seemed to increase with an increasing betaine dose, although a very small proportion of ingested betaine was excreted via urine. In conclusion, a single dose of orally administered betaine had an acute and dose-dependent effect on serum betaine concentration and resulted in lowered plasma tHcy concentrations within 2 h in healthy subjects.
PMID: 16365055
Exp Biol Med (Maywood). 2004 Nov;229(10):988-95.
DNA methylation, cancer susceptibility, and nutrient interactions.
Davis CD, Uthus EO.
Nutritional Sciences Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, Suite 3159, Rockville, MD 20892-7328, USA. davisci@mail.nih.gov.
DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation processes. These nutrients include folate, vitamin B(12), vitamin B(6), methionine, and choline. However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine) deficiency in combination causes decreased tissue S-adeno-sylmethionine, global DNA hypomethylation, hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen treatment. Other dietary components such as vitamin B(12), alcohol, and selenium may modify the response to inadequate dietary folate.
PMID: 15522834
