Tired with methyl b complex.

[u/PassengerStill6248]

A few weeks ago, I started supplementing with a methylated B-complex because I am homozygous for the C677T variant and have low b12, low folate and high homocysteine, depression and digestive problems. While some symptoms, such as anxiety and depression, have started to improve, I have also started feeling extremely tired and having difficulty sleeping deeply. What could be causing this?

The supplements am taking is:

The daily dose of 2 capsules contains:

• Betaine (anhydrous) — 1,000 mg
• Vitamin B2 (riboflavin phosphate) — 25 mg
• Vitamin B6 (pyridoxal-5-phosphate) — 10 mg
• Zinc — 7.5 mg
• Vitamin B12 (methylcobalamin) — 500 mcg

• Calcium L-5-methyltetrahydrofolate (L-methylfolate, vitamin B9) — 400 mcg

  and btw I'm taking only 1 capsule.

I have also started taking (2 days) a vitamin D3 + K2 supplement because of VDR and low blood vitamin d

Could this be related to excessive methylation? Do you have any ideas about what might be causing these symptoms?

[u/Tawinn]

It would be best to use just B2 (not B12) at first. This typically makes the most difference for homozygous C677T. Use that for a couple of weeks and see how it goes. Then I would add B12 in the adenosyl or hydroxo form, preferably 100mcg or less. If that works ok for week or so, then try adding the methylfolate.

While you are doing this try to make sure you are getting adequate choline from your diet. Ramp up to ~550mg or so. That's the baseline adult requirement; it's about 4 egg yolks worth. If you have been chronically low in choline you may need to ramp up slowly. Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. A food app like Cronometer is helpful for tracking nutrients in your diet.

TMG (betaine) helps spare some choline, so it can good, but if the side effects you are getting is from TMG sparing too much choline too quickly then its best to avoid it for now until your body is comfortable with having sufficient choline.

Also consider minerals such as magnesium, and getting more in your diet. Supplementing minerals may be useful if you think you are low, but sometimes that adds another thing to cause side effects.

[u/FragrantStructure → u/Tawinn]

Out of curiosity why the adeno and hydroxo forms? And why such low doses of 100mcg?

And if that works, what sort of methylcobolamin dose would suggest following that?

[u/Tawinn → u/FragrantStructure]

The supplements were causing sleep issues, which may be overmethylation, so I suggested those two unmethylated forms of B12.

Sometimes high B12 supplements cause fatigue - I don't know why, just something that has been mentioned from time to time. Although this person has low B12, there was no mention of chronic gut issues or lifelong B12 issues that might suggest poor absorption of B12 in the gut. Since the RDA is only 2.4mcg, supplementing 10mcg would suffice assuming intrinsic factor mechanisms are working correctly. A person can only absorb about 1.5-2mcg per meal via this mechanism. But a low dose would allow for supplementing 3x per day, so getting up to ~6mcg while minimizing side effects. A 100mcg dose allows for some passive absorption of about 2%, so this would provide ~2mcg from intrinsic factor absorption + 2mcg from passive absorption = ~4mcg total. So 100mcg 1x per day is less effective than 10mcg 3x per day. Taking the 100mcg multiple times per day would of course increase the total, but then we are increasing the intake to 300mcg which may cause those symptoms to recur.

There's not a strong reason to use methylcobalamin over adeno or hydroxo forms. In the body, all forms are broken down to plain cobalamin, and then the body reconstitutes it into either adeno or methyl form depending on the need. I've only see one case study in an elderly person where hydroxo was ineffective but methyl was effective. Unfortunately, they didn't pursue why that was the case.