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Betaine/TMG/methylator supplementation generates endogenous Methionine???

betaine mtor same tmg methylator homocysteine methionine choline inositol cysteine

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#1 ikon2

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Posted 13 November 2014 - 01:48 PM


The evidences surrounding methionine (and somewhat cysteine or any sulfur amino acid) restriction and the resulting longevity seems to be quite strong.  The evidence that we lose methyl group clusters on DNA as we age as a marker of aging and a supplemental methylator such as betaine/TMG or SAMe ameliorating this extends life is also compelling, not to mention the reduction in homocysteine from TMG being a good thing.  But it seems the MOA by which betaine does this is to actually recycle homocystiene into methionine:

 

Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice.
Abstract
BACKGROUND/AIMS:

We previously reported that acute betaine treatment induced significant changes in the hepatic glutathione and cysteine levels in mice and rats. The present study was aimed to determine the effects of dietary betaine on the metabolism of sulfur-containing amino acids.

METHODS/RESULTS:

Male mice were supplemented with betaine (1%) in drinking water for up to 3 weeks. Changes in hepatic levels of major sulfur amino acid metabolites and products were stabilized after 2 weeks of betaine supplementation. Betaine intake increased methionine, S-adenosylmethionine, and S-adenosylhomocysteine levels significantly, but homocysteine and cystathionine were reduced. Methionine adenosyltransferase activity was elevated to three-fold of control. Cysteine catabolism to taurine was inhibited as evidenced by a decrease in cysteine dioxygenase activity and taurine levels in liver and plasma. Despite the significant changes in the transsulfuration reactions, neither hepatic cysteine nor glutathione was altered. Betaine supplementation decreased the hepatotoxicity induced by chloroform (0.5 ml/kg, ip) significantly.

CONCLUSIONS:

Betaine supplementation enhances recycling of homocysteine for the generation of methionine and S-adenosylmethionine while reducing its utilization for the synthesis of cystathionine and cysteine. However, the hepatic levels of cysteine or glutathione are not affected, most probably due to the depression of taurine generation from cysteine.

PMID:  15885362 [PubMed - indexed for MEDLINE]

 

 

This is alarming.  Maybe I'm coming late to the party on this but I was under the impression that many here (myself included) supplement TMG for its marked reduction in homocysteine levels.  Does this not run counter to Me restriction and would it not actually shorten life?  

 

And what does this mean for other lipotropics as well such as choline or inositol, or basically any lipotropic that increases sulfur amino acids endogenously?

 

How do we reconcile the two so that we can lower homocysteine levels via methylators but still observe Me restriction to an appreciable degree?



#2 Darryl

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Posted 13 November 2014 - 03:37 PM

The betaine (and its precursor choline) has no effect on the total pool of (methionine + homocysteine), it just provides methyl groups to shift towards methionine within that pool. Reduced methionine and cysteine intakes, and higher glycine, serine, and to a lesser extent glutamate, histidine, and arginine intakes, appear to reduce the (methionine + homocysteine) pool.

 

There appear advantages to a higher betaine status and lower choline status, and perhaps to foods containing high levels of betaine (spinach and beets) over over foods containing high levels of its precursor choline (eggs). That said, there isn't much in the literature supporting long term intake of betaine supplements, as in trials of betaine as a homocysteine lowering agent it doesn't reduce events, and it appears elevated homocysteine and its association with CVD may mostly be a marker of high methionine status.

 

 

Konstantinova, S. V., Tell, G. S., Vollset, S. E., Nygård, O., Bleie, Ø., & Ueland, P. M. (2008). Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and womenThe Journal of nutrition138(5), 914-920.

 

Multivariate analyses showed that choline was positively associated with serum triglycerides, glucose, BMI, percent body fat, waist circumference (P < 0.0001 for all), and physical activity (P < 0.05) and inversely related to HDL cholesterol (P < 0.05) and smoking (P <0.0001). Betaine was inversely associated with serum non-HDL cholesterol, triglycerides, BMI, percent body fat, waist circumference, systolic and diastolic blood pressure (P < 0.0001 for all), and smoking (P < 0.05) and positively associated with HDL cholesterol (P < 0.01) and physical activity (P < 0.0001). Thus, an unfavorable cardiovascular risk factor profile was associated with high choline and low betaine concentrations. Choline and betaine were associated in opposite directions with key components of metabolic syndrome, suggesting a disruption of mitochondrial choline dehydrogenase pathway.

 

Rajaie, S., & Esmaillzadeh, A. (2011). Dietary choline and betaine intakes and risk of cardiovascular diseases: review of epidemiological evidenceARYA atherosclerosis7(2), 78.

 

Individuals with high plasma choline levels were obese and had elevated plasma triglycerides, HDL and non-HDL cholesterol levels; whereas high plasma betaine levels were inversely associated with these biochemical markers.

 

Troen, A. M., Lutgens, E., Smith, D. E., Rosenberg, I. H., & Selhub, J. (2003). The atherogenic effect of excess methionine intakeProceedings of the National Academy of Sciences100(25), 15089-15094.

 

Mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia without any increase in vascular pathology. Our findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice. Although homocysteine may contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in this model.

Edited by Darryl, 13 November 2014 - 03:55 PM.

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#3 deeptrance

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Posted 13 November 2014 - 10:40 PM

There appear advantages to a higher betaine status and lower choline status, and perhaps to foods containing high levels of betaine (spinach and beets) over over foods containing high levels of its precursor choline (eggs). 

 

Thanks for the interesting article links. The discussion in the first study doesn't indicate any benefit of betaine consumption over that of choline. I'm afraid most readers of this thread will see the correlations and assume that there is an implied causality which suggests that dietary choline should be avoided and betaine should be sought, but the authors point out that dietary choline, relative to betaine, is likely to be higher in healthier diets.

 

So there really isn't a takeaway from that study for users of this forum, because there's nothing prescriptive or even suggestive in their findings. What they uncovered was an association between conditions that points to genetic factors predisposing individuals to set levels of choline-to-betaine conversion, and this is unlikely to be affected by diet. In other words, the underlying genetic factors that contribute to metabolic disorder are also likely to be responsible for the observed correlation between choline serum concentration and negative indicators for metabolic syndrome (and the opposite correlation for betaine.)

 

Also, the second study clearly states that both choline and betaine have beneficial effects, as stated in their conclusion: "Although dietary intakes of choline and betaine were not significantly associated with CVD incidence, the long-term consumption of these nutrients have been shown to prevent CVD mortality by decreasing inflammation and other risk factors."


Edited by deeptrance, 13 November 2014 - 10:59 PM.


#4 Darryl

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Posted 13 November 2014 - 11:09 PM

The same study group found egg intake was the strongest predictor of plasma choline.

 

Konstantinova, S. V., Tell, G. S., Vollset, S. E., Ulvik, A., Drevon, C. A., & Ueland, P. M. (2008). Dietary patterns, food groups, and nutrients as predictors of plasma choline and betaine in middle-aged and elderly men and womenThe American journal of clinical nutrition88(6), 1663-1669.

 

Plasma choline was predicted by egg consumption (0.16 mol/L; P 0.0001) and cholesterol intake (0.16 mol/L; P  0.0001), and betaine was predicted by consumption of high-fiber bread (0.65 mol/L; P 0.0001); high-fat dairy products (0.70 mol/L; P 0.0001); complex carbohydrates, fiber, folate, and thiamine (0.66-1.44 mol/L; P 0.0002 for all); and total energy (0.45 mol/L; P 0.004). Plasma choline was not significantly associated with any identified dietary patterns, whereas betaine was negatively associated with a Western dietary pattern with a high loading for meat, pizza, sugar, and fat (P 0.0001).

 

Perhaps not surprisingly given the egg/plasma choline association and the plasma choline/metabolic syndrome association, there's also a fairly robust egg/diabetes association.

 

Li, Y., Zhou, C., Zhou, X., & Li, L. (2013). Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysisAtherosclerosis,229(2), 524-530.

 

The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02–1.38), 1.83 (95% CI 1.42–2.37), 1.68 (95% CI 1.41–2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03–1.10), 1.40 (95% CI 1.25–1.57), 1.29 (95% CI 1.21–1.37), respectively.

 

The association may not be mediated by choline, as arachidonic acid intake is an equally plausible connection.


Edited by Darryl, 13 November 2014 - 11:10 PM.


#5 Skyguy2005

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Posted 02 December 2014 - 07:54 PM

http://onlinelibrary...02/ptr.3669/pdf

 

Here's a study where Methionine decreased the brain weight of rats. So perhaps there is a connection to diabetes/alzheimers?



#6 Reincarnatian

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Posted 20 January 2016 - 01:57 AM

Ignore wrong topic. 


Edited by Reincarnatian, 20 January 2016 - 01:58 AM.


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#7 Gediminas Jesinas

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Posted 25 August 2021 - 01:59 PM

How necessary it is to take betaine along with let's say 1 g of niacin and how much?







Also tagged with one or more of these keywords: betaine, mtor, same, tmg, methylator, homocysteine, methionine, choline, inositol, cysteine

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