This is prompted by a post from BBruce:
"Stay away from Vitamin B12"
I reviewed the folate-PCa literature 2 years ago. B12 is covered in that post. What seemed lacking in the new thread was context, IMO.
A number of the B vitamins feed into 'one-carbon metabolism' (a term that is usually found in PCa papers that looked at the issue.) I prefer to narrow that down to the SAM cycle, which I simplify as:
... Methionine--->SAM (SAMe)--->Homocysteine--->Methionine ...
Cells have a need for methyl. SAM is the universal methyl donor in the body. SAM obtains its methyl from Methionine. When SAM drops off its methyl load, we are left with homocysteine.
Although there will be some methionine in the diet, there will generally be a need for other dietary methyl donors. Folate (vitamin B9) is the most important. Folic acid is a synthetic form.
With adequate folate and cofactors that include vitamins B6 & B12, homocysteine can be converted back to methionine.
When the supply of methyl is low, cells can become hypomethylated, leading to genetic instability & an increased risk of cancer.
When the supply of methyl is adequate, PCa cells take up way more than normal prostate cells. They become hypermethylated. Most damaging is the silencing of tumor suppressor genes. This occurs by methylation of suppressor gene promotor regions (see CpG island hypermethylation [1]). In normal cells, promoter regions of tumor suppressor genes are never methylated.
So we have a situation where hypomethylation increases cancer risk, but hypermethylation increases the risk of aggressive cancer.
We don't often get to see a poorly thought out experiment conducted on an entire population, but the fortification of flour with folic acid in Chile had terrible consequences for some.
Comparing the periods 1992-1996 with 2001-2004, colon cancer rates increased by a factor of 2.6 in those aged 45-64 years, and 2.9 in those aged 65-79. [2]
And, "a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada." [3]
The health damage done in a country that adopted folic acid fortification depends on the baseline degree of folate insufficiency. In the Chilean population, folate insufficiency was no doubt responsible for many colon cancer cases, but also prevented them from developing. With sufficiency, these cancers were suddenly unmasked.
...
The Chilean experience shows how hypomethylation might work as a strategy when cancer already exists.
For men in North America & in those countries that adopted the FDA mandate of grain fortification, it is difficult to be folate-insufficient. (European & Scandinavian countries have been more cautious.)
One could however target one of the cofactors. Vitamin B12 is easiest. Many aging men have poor uptake of B12. Their stomachs do not produce enough intrinsic factor.
Vegans will find it easy to be B12 deficient [5]. In fact, vegans are often found to be deficient in a number of nutrients. While many respond to a cancer diagnosis by eating a 'healthy' diet, selective insufficiency is a more promising strategy IMO.
To return to the recent thread: vitamin B12 will not cause PCa. It will not even cause aggressive PCa. But insufficiency might lower the risk of aggressive disease.
I forget how many pinheads a lifetime of vitamin B12 will fit on, but we don't need much in the diet. The body also recycles it. One could become vegan today & still not be deficient a year from now, depending on our stores. Deficiency "may not appear for decades." [4]
One must be careful when flirting with B12 deficiency. Some of the potential damage cannot be reversed. What do we fear more than PCa? Dementia, perhaps? B12 is protective. But if PCa mortality is the immediate concern, increased risk might be acceptable.
-Patrick
[1] en.wikipedia.org/wiki/CpG_i...
[2] ncbi.nlm.nih.gov/pubmed/191...
[3] ncbi.nlm.nih.gov/pubmed/280...
Homocysteine, hypermethylation/PCa aggressiveness and MTFHR mutation
