The Case:  Pam is dealing with brain fog, poor concentration, and fatigue. Tests revealed that she was low in Folate and Vitamin B12. Weeks of taking Vitamin B Complex didn’t help her symptoms at all. A little more research helped Pam understand that not all B vitamins are the same - some are synthetic while other options are natural and in methylated forms. Inspecting the B Complex vitamin she’d been taking, she discovered that the B12 was in the cyanocobalamin form and the folic acid was also synthetic. You might think the mystery was solved at this point, but after finding a methylated B Complex at the local health food store, and taking it for several weeks, her symptoms persisted. She increased her dosage, but after several weeks, she felt even worse.  Her labs showed that she was deficient in B vitamins, so why weren’t her supplements working?   The Investigation This is something I commonly see and while B vitamins are wonderful, they come in many forms but they are not ‘one size fits all.’ And there is another misconception - people believe that because B vitamins are water soluble, they can’t hurt anyone because the body will expel what it doesn’t use. This isn’t the whole story.    How Methylation Works The body has a process called methylation. This is a biochemical process where there is a transfer of four atoms - one carbon atom and three hydrogen atoms (CH3) from one substance to another. This process happens all the time, every second. When its optimal it has a significant positive impact on many biochemical reactions in the body that regulate all types of activities. Methylation is needed for neurotransmitter production, detoxification, histamine metabolism, estrogen metabolism, fat metabolism, cellular energy, eye health, and immune balancing. Essentially, if you think of the body as a machine, then methylation (and demethylation) are the gears that trigger the different systems in the body.  Two important methyl donors (nutrients that keep methylation moving) are methylated folate (also known as methyltetrahydrofolate or 5 MTHF) and methylcobalamin (methylated B12). It’s worth noting that there is a gene called the MTHFR gene (which we’ve talked about in Episode 34) which makes it harder to convert folic acid from foods or supplements into active form.    Understanding the Role of the MTHFR Gene in Methylation The process of methylation is quite complex. We have about 30 enzymes that are part of the methylation cycle pathway. The MTHFR gene is only one piece of the puzzle. And, while the MTHFR being off can cause issues with methylation, those other enzymes can also be a factor (sometimes a major factor).   Balancing Methylation You may have heard that methylation is all about taking methyl folate or methyl B12 but there is so much more to it.  Think of methylation (and methyl donors, specifically) as a bell shaped curve. You want to be somewhere at the top of the curve to be in balance. If you are lower on the left side of the curve, that is considered less methylation or being an under methylator. If you are lower on the right side of the curve, that would be considered too much methylation or being an over methylator. So many doctors don’t realize this and think more is better. More is not always better, balanced is what you want to aim for.   Symptoms of Unbalanced Methylation When you are not in balance (in either over methylation or under methylation) you can experience symptoms. And, taking more B vitamins (especially the wrong kind) may make things worse - even if you’re taking methyl folate and methyl B12 (considered to be the best). There are tons of issues with sub optimal methylation and some can actually be the same when you are an over or an under methylator Anxiety Itchy skin Brain fog Mood changes Fatigue Jitteriness Allergies Immune challenges Environmental sensitivities  And many more…   How to know if you are an over or an under methylator? Looking at genetics can help but genetics don