I am hearing and experiencing more and more people who are responding poorly to folic acid whether it be folic acid or methylfolate.
Why are people with MTHFR mutations responding poorly to methylfolate!?
It doesn’t make sense right?
People with MTHFR mutations and high homocysteine – especially those who are homozygous MTHFR – should respond favorably to methylfolate.
In researching this and looking closely at the biochemistry, it makes sense why some react poorly to methylfolate, methylcobalamin or folic acid.
(By the way, methylfolate in this case means 5-MTHF or L-5-MTHF.)
Today, I received yet another question about this and I felt it important to share with you.
My husband is + for MTHFR compound heterozygous gene mutation. He reacts very unfavorably to folate supplementation, actually deteriorated while on IV injections of folate. We are trying to get his metabolic MD/neurologist to engage in further testing and having a difficult time in having him understand the problems my husband is having with his prescription Folbic medication.
Thank you for sharing your story. This, unfortunately, is all too common a scenario.
It is VERY important to know which MTHFR mutations he has.
I do not recommend obtaining the L-5-MTHF for your husband. It may make him worse if given right now. From hearing the symptoms, other things have to be addressed first.
I highly recommend you get tested for MTHFR along with your husband’s family members. It is serious and must be addressed. Do not try and get pregnant without being tested for MTHFR and having the possible mutations dealt with.
If you are having trouble obtaining a lab test for MTHFR, you may obtain the test from me as long as you are not living in NY. I can only provide the test for you, I cannot diagnose anyone or prescribe treatment for MTHFR. Your physician has to do that.
IMPORTANT!! Increased methylation may cause – and does cause – neurological symptoms.
Methylation reactions increase in aging, the symptoms of Parkinson’s Disease (PD) are strikingly similar to the neurological and functional changes seen in advanced aging, and Parksinson’s Disease is age-related. For methylation to be regarded as important in PD it means that, along with its biochemical reactions and behavioral effects, increased methylation should also cause specific neuronal degeneration . . . Most of the SAM-induced anatomical changes that were observed in the rat model are similar to the changes that occur in PD, which further support a role of SAM-dependent increased methylation in PD.
and . . .
Increased methylation can deplete dopamine, norepinephrine and 5-HT; increase acetylcholine; and cause hypokinesia and tremors. These effects are similar to changes seen in PD, and interestingly also, they are similar to some of the changes that are associated with the aging process. It is suggested, therefore, that increased methylation may be an inducing factor in parkinsonism. Accordingly, the effects of an increase in methylation in the brain of rats were studied. S-adenosylmethionine (AdoMet), the limiting factor in the methylation process, was injected into the lateral ventricle of rats. Specific behavioral changes that resemble changes seen in PD were investigated. The results showed that AdoMet caused tremors, rigidity, hypokinesia, and depleted DA.
So if your husband’s level of SAMe increases, I would assume his symptoms worsen. Based on what you told me about his negative response to certain foods (very helpful information by the way), I am assuming his methionine is elevated and therefore so is his SAM.
SAMe comes from Methionine and Methionine is highest in these foods:
- Turkey 
These are all the foods which are causing your husband to worsen which makes total sense – if you step back and think about the biochemistry.
If given methylfolate, methylcobalamin or folic acid, your husband’s methionine will increase.
I have a hunch that your husband may do well with Vitamin B6 and magnesium.
Talk with your doctor about stopping Folbic and lowering homocysteine with Vitamin B6 and magnesium.
Magnesium Plus contains active B6 and magnesium. Consider 2 capsules twice a day.
The biochemistry also shows the importance of Vitamin B6.
Vitamin B6 as pyridoxal-5-phosphate actually converts homocysteine into much needed nutrients.
If vitamin B6 is low, the production of these critical nutrients is severely limited. These critical nutrients are absolutely essential in those with neurological disorders as they help with neurological function and protection from neuronal oxidation/damage.
My guess is your husband is quite low in Pyridoxal-5-phosphate and may actually have another mutation which prevents the conversion of inactive Vitamin B6 (pyridoxine HCl to active vitamin B6 (pyridoxal-5-phosphate).
Taking about 20 mg of Niacin twice a day may help as well as this ‘eats up’ excess methyl groups – which may be elevated right now due to taking Folbic.
Do let me know how he does.
In time, he likely will need to get on L-5-MTHF by Seeking Health – or HomocysteX by Seeking Health – but currently, I do not think it is correct – but I am just guessing based on your comment.
Summary for your husband:
- Stop eating foods with methionine!
- Talk with your doctor about stopping vitamin B12 and folic acid immediately
- Lower homocysteine with Pyridoxal-5-Phophate
- Consider taking Nicotonic acid (20 mg) 2 to 3 times a day for a week to remove the excess methyl groups.
It is impossible for me to diagnose, treat or prescribe – so I am not. I am merely providing you information which may be beneficial – or it may not.
Hopefully it is!