Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome.

[pjoshea13]

New paper below [1]. However, details in the full text.

Great to see a U.S. interest in the subject of aberrant DNA methylation in cancer & the dietary micronutrients that contribute to that.

In my posts I tend to focus on folate (from foliage) & folic acid (from fortified grain products or supplements), as methyl donors. And also the co-factor vitamin B12. The idea is that we can perhaps limit intake & slow or stop unwanted methylation. My posts usually refer to the "SAM cycle".

The new paper promises a broader look at dietary micronutrients.

"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."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/308...

Nutrients. 2019 Mar 13;11(3). pii: E608. doi: 10.3390/nu11030608.

Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome.

Mahmoud AM1,2, Ali MM3,4.

Author information

1

Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, 1919 W. Taylor St. (AHSB), Room 433, Chicago, IL 60612, USA. [e-mail].

2

Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA. [e-mail].

3

Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, 1919 W. Taylor St. (AHSB), Room 433, Chicago, IL 60612, USA. [e-mail].

4

Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA. [e-mail].

Abstract

{text as above}

KEYWORDS: DNA methylation; Vitamin B; betaine; cancer; choline; dietary; folate; methyl donors; methyltransferase; nutrients

PMID: 30871166 DOI: 10.3390/nu11030608

[hansjd]

Thank you Patrick for this posting. "In this review, we focused on nutrients that act as methyl donors or methylation co-factors". It would be good to know what they are. How does one get to see the full article or at least the list? Cheers

[Hidden in reply to hansjd]

here the full article: mdpi.com/2072-6643/11/3/608...

Folic acid: legumes (1 cup lentils 90% DV) , dark leafy greens spinach 1 cup 65%DV) citrus fruits, beets...

[hansjd in reply to Hidden]

Thanks Myriammole !

[Hidden in reply to hansjd]

But I can't really believe that this so healthy food should be avoided, very strange!

[rnewman751]

Hello Patrick, I hope you are well. What is your feeling about elevated homocysteine and the risks it may cause in causing cancer and vascular damage and disease. As you know the only way to lower homocysteine is to intake the methylating nutrients such as B6, B12,

folic acid and TMG. I would appreciate reading your point of view. Best regards, Rob

[pjoshea13 in reply to rnewman751]

Hi Bob,

Interestingly, a Norwegian intervention study to lower homocysteine, although successful, did not lower cardiovascular risk. [1] (2006)

"The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point"

"In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk"

"Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested."

Here is a more recent meta-analysis [2] (2017):

"there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/165...

[2] ncbi.nlm.nih.gov/pubmed/288...

[cjkn2000]

mdpi.com/2072-6643/11/3/608...

link to full article.

[bdriggers]

How does the B12 come into play? In your opinion, is it a good idea to avoid ( if possible) multivitamins That contain folic acid?

[pjoshea13 in reply to bdriggers]

Absolutely! If living in a country that fortifies grain products with folic acid, additional folic acid is unnecessary. If not, correcting a folate deficiency with folic acid may accelerate PCa progression.

B12 is a co-factor in the SAM cycle. If homocysteine is elevated, folate (or another methyl donor) may be needed. But if B12 is insufficient, homocysteine will not be converted back to methionine (& thus to SAM). Both are needed.

-Patrick

[Hidden in reply to pjoshea13]

But do you think we should avoid so healthy foods such as legumes, dark leafy greens?

[pjoshea13 in reply to Hidden]

The SAM system depends on a methyl donor to recycle homocysteine. The most important methyl donor is folate.

A very large proportion of the U.S. population takes a multivitamin & is therefore getting folic acid (synthetic folate). In spite of this, the FDA mandated that it be added to grain products (to prevent neural tube defects.) i.e. the FDA decided that a significant proportion of the population was deficient in folate.

I think that if we could avoid foods 'enriched' with folic acid & multivitamins, we might find that most of us are not getting a lot of folate. I doubt that draconian changes to the diet would be required.

-Patrick

[tom67inMA in reply to pjoshea13]

I have an MTHFR gene defect (as does about half of the US population), and my GP has recommended methylated folate and TMG supplementation to reduce my homocysteine. Does this still make sense post diagnosis?

[pjoshea13 in reply to tom67inMA]

Tom,

I think I should address this in a separate thread. Should be posted by noon.

-Patrick

[Hidden in reply to pjoshea13]

Maybe synthetic folic acid from multivitamins is cancer promoting, whereas folate from food is protective?

[cesanon]

What general dietary and supplement recommendations does anyone have to deal generally with this Methylation issue? And on a relative scale, how important is it?

I am not certain what to do. And it seems like there may be lots of trade offs no matter what you do.

[snoraste]

I thought I include this link as a supplement to what Patrick mentioned. It’s a simple explanation of the process, and a detailed breakdown of types of food:

naturallysavvy.com/eat/are-...

[Hidden]

exactly! I mean very healthy food such as legumes, dark leafy greens, beets, broccoli, citrus fruit, it does not seem very common sense to avoid them!

Maybe synthetic folic acid from multivitamins is cancer promoting, whereas folate from food is protective?

[Hidden]

ok, but for Patrick B12 is also an issue...

[Advo__cate]

Patrick, I was going to ask the same question as Myriam. We use multi-vitamins that are raw food sourced and only contain folate. We gave up the "enriched" foods long ago.

[Lyubov]

Is Folic Acid the culprit to be avoided?

[LeeLiam]

I'm trying to follow this discussion but I find it very confusing. Is this a good multi? lifeextension.com/Vitamins-...

It contains

Folate (as L-5-methyltetrahydrofolate calcium salt) 400 mcg. Is that better than folic acid or just as bad?

[pjoshea13 in reply to LeeLiam]

"Levomefolic acid (INN) (also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6S)-5-methyltetrahydrofolate, and (6S)-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine. It is also the form found in circulation and transported across membranes into tissues and across the blood-brain barrier."

en.wikipedia.org/wiki/Levom...

Nevertheless, I would not supplement unless there was a good reason (as in Nalakrats case).

-Patrick

[Lyubov]

Thanks!

[LeeLiam]

Patrick, Thanks for the quick response. I know Nal posted some B vitamins without folic acid. I'm just trying to find a comparable multivitamin.

[LeeLiam]

I think I will try this one:

amazon.com/Seeking-Health-O...