I think there's an extreme important link between methylation and histamine. I personally was born with Asian glow gene, deficient of alcohol breakdown enzyme known as aldehyde dehydrogenase (ALDH2). Please see the excerpt below. In the body, alcohol is metabolized into a substance called acetaldehyde, which is broken down by the enzyme known as aldehyde dehydrogenase (ALDH2). For those who get Asian glow, there’s a genetic change in this enzyme that metabolizes alcohol more quickly but breaks down acetaldehyde less efficiently—which means that acetaldehyde accumulates in the body. When that happens, you essentially become drunk, with symptoms like nausea, vomiting, and headache. But this same enzyme is also responsible for processing histamine—the chemical involved in allergic reactions that allows more blood flow to areas of your body like your face, causing a flush. That means that if you have a genetically changed ALDH2, you don’t break down histamines as quickly, either. That’s where the glow comes in. When the enzyme works overtime to try to process the alcohol, histamine builds up and causes extreme flush. Source: http://www.mochimag.com/article/asian-glow-why-how-it-happens-does-pepcid-ac-zantac-work-safe-risks I feel like one step closer to solving this big puzzle. My body is genetically incapable of breaking down histamine easily. This is one of the reasons why I get body rashes everywhere when I take mb12. 1,000 mcg can drive me nuts and break out everywhere with rashes. Other forms of B12, cyb12 and hyb12 can be tolerated better. According to Dr. Ben Lynch, usually, there's an inverse relationship between methylation and histamine levels. Since people with ALDH2 mutation (Asian glow people) have high histamine level, this means that they are more prone to undermethylation. Breaking out in rashes, hives, or what not is a symptom of releasing toxin builtups that have occurred in the past. Toxin can be a result of anything, and can be both intercellular and extracellular. Vague, I know So, I do think that people who get itchiness, rashes, hives, and other skin conditions from mb12 are the ones that need most methylation support, but the protocol these people cannot be as harsh as other people in the beginning. I get instant flare ups from 1,000 mcg of mb12 and even 500 mcg gives me difficult times. As suggested by @Sherpa, @caledonia, it would be beneficial for Asian glow group to start very slowly, or even inactive forms of B12. I am still doing some research on folate/methylfolate, and I definitely want to become more knowledgeable before I make any decision for myself.