6 replies to this topic

[magnelectro]

Surely I'm reading this wrong...

High consumption of potatoes and butter, cheese and margarine was associated with lower risk of gastric cancer with hypermethylation of the hMLH1 promoter. In contrast, consumption of vegetables was associated with higher risk of gastric cancer with hypermethylation of the hMLH1 promoter. High intake of mushrooms and fruits and low intake of cereals and butter, cheese and margarine were associated with higher risk of gastric cancer without hypermethylation of the hMLH1 promoter (Table 4).

Effects of dietary intake and genetic factors on hypermethylation of the hMLH1 gene promoter in gastric cancer
ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 2005 July 7;11(25):3834-3841
http://www.ncbi.nlm....8?dopt=Abstract

Among men, we observed strong positive associations between folate and BRAF-mutated tumors (RR = 3.04 for the highest versus lowest tertile of intake, Ptrend = 0.03) and between vitamin B6 and tumors showing MLH1 hypermethylation (highest versus lowest tertile: RR = 3.23, Ptrend = 0.03). Among women, the relative risks of tumors with BRAF mutations or MLH1 hypermethylation were also increased in the highest tertiles of folate and vitamin B6 intake, respectively, but these did not reach statistical significance. The positive associations between folate intake and tumors harboring BRAF mutations and between vitamin B6 intake and those showing MLH1 hypermethylationwere most pronounced among men and may suggest that these vitamins enhance colorectal cancer risk through genetic as well as epigenetic aberrations.

Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer
Carcinogenesis 2008 29(9):1765-1773; doi:10.1093/carcin/bgn074
http://carcin.oxford...abstract/bgn074

Could somebody please explain what I'm missing here?

[RighteousReason]

Odd. What is hypermethylation of the hMLH1 promoter?

Edited by RighteousReason, 15 December 2009 - 10:04 PM.

[kismet]

Odd. What is hypermethylation of the hMLH1 promoter?

Methylation is simply a mechanism used to control gene expression.

Could somebody please explain what I'm missing here?

The fact we're talking certain types of colorectal and gastric cancer, responsible for low levels of all-cause mortality. It is an irrelevant curiousity until negative effects on all-cause mortality or a net increase in cancer incidence are replicated (read: probably never). Some of the biggest cohorts found no risk from vegetables, fruits, etc. That's probably it.

The folate cancer connection is an old friend, but there's no reason to overly worry about dietary intake.

Edited by kismet, 15 December 2009 - 10:20 PM.

[niner]

hMLH1 (or MLH1 as it's more commonly called) is a DNA repair gene. If its promoter is methylated, then you get less expression of the gene, thus less DNA repair, thus more cancer. This is probably a good example of why megadosing random vitamins might not be such a good idea. Another inverted U... As kismet pointed out, you don't really want to take home a "vegetables are bad" message from this. It's more of a curiosity. If you you took home a "don't megadose with methyl donors" message, that might be right.

[magnelectro]

I know! Everybody from Atkins to Ornish loves vegetables, right? Lightly steamed, non-starchy, fresh picked organic vegetables, that is. But many ImmInst members take methyl donors for a variety of reasons—from cognitive enhancement to reduction of homocysteine. And the studies aren’t talking about megadoses. The amounts found in an ordinary diet are minuscule compared to typical supplement doses. I’ve come across several sites advocating 20g of MSM per day for everything from acne to joint problems! And methyl donors have additive effects. For example, choline supplementation reduces the need for folate and vice versa. I’m not worried about vegetables, or even the folate in my multivitamin. I’m just looking for a greater understanding of how dietary methyl donors can impact health through epigenetics.

[brunotto]

"The level of B6 in cancer patients is lower than that of healthy subjects, suggesting that administration of B6 maybe usefull"..

"The anti-tumor effect of vitamine B6 is not limited to liver cancer alone... Application of supraphisiologicaldoses of B6 as an anthineoplasti therapy is promising area of furrther research"

http://journals.camb...l...&aid=607128

Maybe b6 causes other troubles...

[magnelectro]

"The level of B6 in cancer patients is lower than that of healthy subjects, suggesting that administration of B6 maybe usefull"..

"The anti-tumor effect of vitamine B6 is not limited to liver cancer alone... Application of supraphisiologicaldoses of B6 as an anthineoplasti therapy is promising area of furrther research"

http://journals.camb...l...&aid=607128

Maybe b6 causes other troubles...

I know that B6 is generally necessary and beneficial but I'm wondering how much is too much? Where is the peak of the dose/benefit curve?

I ran across these studies looking for a connection between dietary methyl donors (ie folate, choline, TMG, MSM, etc.) and DNA methylation (ie epigenetic modification of gene expression). Ultimately, I wanted to find out if an increase in dietary methyl donors can cause an increase in DNA methylation. Evidently, it can by pushing the methionine/homocysteine pathway towards the production of S-adenosyl methionine (SAM) which is the substrate of DNA methyl transferase (DNMT). What this means for health and longevity at this point is unclear to me.

Methylated DNA is transcriptionally repressed. It seems that DNMTs have varying degrees of selectivity in the genes they methylate, but global hypermethylation can't be a good thing. Might we be randomly shutting down gene transcription by supplementing with methyl donors? I don’t think so. My feeling is that sufficient methyl donors are necessary to maintain adequate methylation and if provided in excess the body uses what it needs and flushes the rest out. I would really appreciate any evidence to indicate whether this is or isn’t the case.

I've also read that methylation is used to suppress the transcription of viral DNA and oncogenes and there are many studies demonstrating the detrimental health effects from a lack of dietary methyl donors (for example, spina bifida from folate deficiency). But is when methyl donors are in excess, even if these 'bad' genes are methylated first, is there a mechanism to prevent the methylation and suppression of 'good' genes?