@stridor @Kathevans
Regarding methylation and mercury. I've made an extensive study of methylation, and now in the past year or so, mercury.
The link is that mercury (and lead and possibly aluminum) inhibit the methylation cycle at methionine synthase. Some cycle diagrams show this. This is right where B12 is the co-factor for methylfolate to create methionine and eventually SAMe.
So it's a very important step in the methylation cycle.
So you can either have genetics or epigenetics inhibiting the methylation cycle (or both). So you can have genetic mutations in MTHFR and MTR inhibiting things or you can have toxic metals inhibiting things (or both).
I've seen a lot of people's genetics on here, and most have some form of MTHFR - a lot greater than you would see in the general population. If they don't have that, they have GST (glutathione) mutations. I've only seen a few people who have neither. I've seen a lot of people who have symptoms of metal toxicity.
In my opinion, people with methylation mutations are the "canaries in the coalmine" - they're already not detoxifying well, so when they accumulate metals, they're more likely to get sick than someone without mutations. Then once you've accumulated some metals, your ability to detoxify gets even worse. So you can see how it can become a vicious downward spiral. Of course, it's possible to have no methylation or glutathione mutations, and still have enough toxic metal exposure to become very sick.
We've seen on here that it's possible for some people to take enough folate and B12 to compensate for genetics and even mercury inhibiting the cycle. However, they need to continue to take high dose supplementation, and they may also continue to have various health issues.
There are also people who have chelated out mercury and other metals and get significantly better.
If you had a total block of methylation you would be dead. So there is still some methylation going on even with both the mutations and the metals inhibiting things.
I agree with Stridor about trying to tackle both to the extent that your body allows. Even if it's just a little bit of B12 and folate, or very low doses of a chelator. Both strategies are accomplishing the same thing, which is increasing your methylation capacity. If you're maxed out on how much B12 and folate you can take and you still have issues, it's time to look at metals. Things should get better as the metals come out.
Of course, you can't change your genetics. But, in general, if you didn't have the metals adding an additional burden, you should be able to be healthy with 1, 2 or even 3 MTHFR mutations. Those with 4 mutations (extremely rare) are very sick. Most were never born to begin with.