DNA Methylation, Aging, And Cancer

[Dave Clark]

Maybe the absorption is different, I take notice that almost all methylcobalamin supplements are designed as sublingual, or dissolve-in-the-mouth tablets, to bypass the digestion process.

 

[yerrag]

Maybe the absorption is different, I take notice that almost all methylcobalamin supplements are designed as sublingual, or dissolve-in-the-mouth tablets, to bypass the digestion process.

That's a notable observation. There has to be a good reason for that. Does it have toxic effects the same way that methyl alcohol (of bootleg fame) is toxic (can lead to blindness) and ethyl alcohol isn't?

 

[Texon]

The b12 I usually see in b-complex supplement formulations are of the cyanocobalamin type. Very seldom do I see methylcobalamin used in supplements. Methylcobalamin is used in skin patches, as a topical delivery of b12.

Is it safe to take the cyanocobalamin form of b12, since it's not methylated?

Probably safe although your body needs to detox the cyanide part of the molecule. Btw, hydroxocobalamine is used IV as an antidote to cyanide poisoning. There is another form of B12 (adenosyl), but I don't know much about it. Due to the fact that I am homozygous for 3 COMT polymorphisms, I have to be very careful with overdoing supplemental methyl donors. Methyl folate is particularly difficult to the point that I stay totally away from it, even though I test as needing it.

 

[DaveFoster]

The b12 I usually see in b-complex supplement formulations are of the cyanocobalamin type. Very seldom do I see methylcobalamin used in supplements. Methylcobalamin is used in skin patches, as a topical delivery of b12.

Is it safe to take the cyanocobalamin form of b12, since it's not methylated?

I don't think the danger pertains specifically to methylcobalamin, but Dr. Peat has mentioned hydroxocobalamin for opposing nitric oxide.

 

[BibleBeliever]

Brought back to this thread; people on facebook posting this article all worried about b-vitamin supplements:
Energy-Promising Vitamins Appear to Be Causing Lung Cancer

I think I have read Ray saying b6 is fine at 5mg in the form of p5p, are other forms of b6 considered potentially harmful then?

 

[yerrag]

I don't think the danger pertains specifically to methylcobalamin, but Dr. Peat has mentioned hydroxocobalamin for opposing nitric oxide.

Brought back to this thread; people on facebook posting this article all worried about b-vitamin supplements:
Energy-Promising Vitamins Appear to Be Causing Lung Cancer

I think I have read Ray saying b6 is fine at 5mg in the form of p5p, are other forms of b6 considered potentially harmful then?

This gives me pause when I think about the b-vitamin complexes. I've been eating goat liver regularly as in once a week, in trying to use food for my nutritional needs rather than on supplementation. There's b-complex supplements handy, but I haven't been taking it often. I can't find goat liver nutrition info on the web, but I hope lamb liver is a good approximation: http://nutrition.healthgrove.com/l/44397/Lamb-Liver

There's still a good amount of b12 in a 100g+ serving of raw liver (I eat it cooked, although raw would be more nutritious, like lions eating the liver first before anything else of their prey), but I hope taking b12 as part of a whole food wouldn't be harmful, as nature has a way of balancing things out.

I was surprised liver has enough vitamins b2 and b3, as non-fat soluble vitamins are usually found in plants (with the exception of b12 and vitamin C), but I wonder how much of what's listed would be left after cooking. Vitamin b1, thiamine, seems to me something I would find hard to get from food. The only food I've found that has significant b1 are brans - wheat, rice, oat - but I still have to eat significant quantities that would appear impractical to me. Seems to me if I were to try to satisfy my b-vitamins needs in a practical way through food, the only b-vitamin I would have to take is b1.

Especially on a Peaty fiber-free diet, devoid of bran (white rice, white bread (but bread isn't Peaty)), b1 supplementation would be a must.

Then again, considering I only eat liver once a week, I still have to take some supplementation also of b2 and b3 for my daily needs. Given that these are water-soluble, they don't get stored in the body the same way FSV's are. B2 and B3 , like B1, are also not practical to obtain through food.

 

[mayweatherking]

I think that study is a very good answer to all the questions why I don't have B5, folic acid and B12 in Energin. So, thanks for posting it!
Another reason for not including B5 is that virtually nobody is deficient in it, similar to iodine. It is added to pretty much every processed food, including the "artisan" breads everybody seems to be so fond of lately.

Also @DaveFoster

Isn't B5 depleted in stress?

How sure is nobody deficient in it? RP daily foods, like milk, cheese, OJ, etc. aren't processed so it wouldn't be there. If you are in a chronic stress state, seems like it could be depleted?

 

[DaveFoster]

@mayweatherking Stress depletes all vitamins and minerals.

B5 helped with my mental fuzziness

 

[mayweatherking]

@mayweatherking Stress depletes all vitamins and minerals.

B5 helped with my mental fuzziness

Yes... but I mean, it sounds like you were guys were saying B5 isn't neccessary to get, but if it is depleted in stress is what I was getting at.

 

[DaveFoster]

Yes... but I mean, it sounds like you were guys were saying B5 isn't neccessary to get, but if it is depleted in stress is what I was getting at.

You're correct. CRON-o-meter might be helpful.

 

[Texon]

I find this whole thing concerning and confusing. I have a complicated history with B12 specifically and it has caused me to go back and forth between supplementing and not. I have a history of veganism that have me a wicked deficiency, but I didn't realize it until years after I stopped the diet. Then I did the whole 23 and me thing and discovered a lot of MTHFR mutations. So I started getting b12 blood tests somewhat regularly just to see where I stood and if the mutations were having any effect. In the absence of supplements my b12 is always, always high. I have never gotten a straight forward answer as to why this might be, but a naturopathic doctor told me once that he thought I had a functional deficiency wherein my body can't use b12 efficiently so it doesn't recycle quickly and therefore shows high in my blood. When I supp b12 I do feel more energetic and some other things go away, but the cancer connection is deeply concerning.

@haidut @DaveFoster
TG, like you, I have the same mthfr issues along with comt, mtrr etc. My last B12 blood test registered 2000 (don't know the units offhand). I'm pretty sure I don't utilize the vitamin well, and it is insidious and commonly missed clinically. If the deficiency goes on long
enough, you can wind up in a wheel chair due to nerve damage and there's no way to reverse it. There's a British doc that is well known in treating it. Also, I think there's a comprehensive list of symptoms at a website he runs called b12d.org. I had so many on the list the recommendation was to take immediate action. OTOH homocysteine is a big issue for me also, as I am usually in the 11-12 range, and if I took niacinamide regularly, I know it would be a lot higher.

 

[DaveFoster]

@haidut @DaveFoster
TG, like you, I have the same mthfr issues along with comt, mtrr etc. My last B12 blood test registered 2000 (don't know the units offhand). I'm pretty sure I don't utilize the vitamin well, and it is insidious and commonly missed clinically. If the deficiency goes on long
enough, you can wind up in a wheel chair due to nerve damage and there's no way to reverse it. There's a British doc that is well known in treating it. Also, I think there's a comprehensive list of symptoms at a website he runs called b12d.org. I had so many on the list the recommendation was to take immediate action. OTOH homocysteine is a big issue for me also, as I am usually in the 11-12 range, and if I took niacinamide regularly, I know it would be a lot higher.

"Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate."​

Reference: Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. - PubMed - NCBI

 

[Texon]

"Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate."​

Reference: Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. - PubMed - NCBI

"Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate."​

Reference: Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. - PubMed - NCBI

@haidut Dave, this is very interesting as I suspect I have developed a subclinical low thyroid due to some pretty severe stressors recently. I have a confirmed low gaba high glutamate issue. I have tried several times but cannot tolerate even very low doses of methyl folate supplements. I do take an occasional 650 mgs scoop of tmg when I think of it. Also sublingual B12, niacinamide, thiamine etc. in the same manner. I had a very interesting and painful experience last night that seemed like a severe body wide pain reaction to phenols from a Ecklonia Cava supplement I started about 4 days ago. Or was it a thyroid reaction to too much iodine...I have no idea. Anyway since I also thought it might be some kind of mast cell reaction I tried a half tsp of 2:1 baking soda and k2co3 in water. Within an hour I was 90% better and this morning feel perfectly fine. This is mysterious. I would love any thoughts you guys might have a bout this.

 

[Texon]

"Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate."​

Reference: Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. - PubMed - NCBI

@haidut Another question...do either of you know of a possible way to recover optimal thyroid function without actually having to take the hormone?

 

[DaveFoster]

@haidut Another question...do either of you know of a possible way to recover optimal thyroid function without actually having to take the hormone?

Strong coffee with sugar and milk together with aspirin , as well as other substances that lower inflammation, such as lisuride, cyproheptadine, ashwagandha, antibiotics or carrots and so on can support thyroid function.

 

[Rafe]

It makes sense to me that b vitamins would contribute to cancer growth. If cancer is a regression to a primitive metabolic state in order to adapt to chronic inescapable environmental stress, then cancer cells’ need for massive nutrients of all kinds seems right.

Without cancer the problem is getting some but not too much or the wrong kind just like talking about oxidation.

I just finished trying (again) the wrong kind of b12 for me, methylated. In one kmud segment RP seems to be saying that a main problem with overmethylation is that it produces serotonin (but I don’t yet know how). I tried niacinamide to stop the overmethylation symptoms but it was mild. The symptoms were bizarre. The advice to use nicotinic acid worked immediately for me (but small doses no flushing). Immediate relief. In another older thread a member said they thought “overmethylation” was really copper excess.

I’m interested in the procaine & hydroxycobalamin. I wonder what it is about the methylated b’s that make them so heavily marketed.

 

[Rafe]

The nicotinic acid isn’t an RP recommendation.

 

[Rafe]

Wait. I just listened to the kmud methylation clip (thanks @raypeatclips). Correction: he’s not saying that dna methylation causes higher serotonin. He’s saying it decreases adaptability, which causes learned helplessness.

 

[Amazoniac]

I tried niacinamide to stop the overmethylation symptoms but it was mild. The symptoms were bizarre. The advice to use nicotinic acid worked immediately for me (but small doses no flushing). Immediate relief.

Sir, have you tried nicotinamide riboside?

 

[Rafe]

I have naught. But just earlier I watched Chris Masterjohn [Lite!] on nicotinamide riboside where he recommends that if you must take it [b/c your doc tells you to] then you should also supply tri-methyl-glycine 1:1 mg in order to supply the methyl groups needed to use the NR. "If you are being held captive, here's the stick you bite on."

Which goes to show that supplementing can become a hairy tangle of escalating supplementation if you are taking these as metabolic "insurance." I knew this before the ill-fated methylated b12 experiment, but methylated b12 is the Active Form! And most of the popular info is heavily weighted to undermethylation and worry over SNPs. Which seems very snippy if you are worried well. I fell for it. I keep thinking now about RP saying we are "sandwiched between the sugar energy we get from plants and the carbon dioxide we make as the final product of the energy from the sugar." I mean the "sandwiched between" part is helpful for thinking about b vites, cancer, and health.

I probably will come up with a plan for intermittent niacin/niacinamide. Maybe when eating meat or greens.