One of the most frequently asked questions on this site is what dosage of vitamin supplements should one take to address MTHFR mutations. The answer to that is as individual as each of us but there are some guidelines put forth by notable practitioners in the field. In today’s guest post Kiki Kish* explores some of these approaches to give you a starting point. Remember that we are not doctors and the information contained in this post is for informational purposes only – you should always check with a doctor or licensed medical practitioner before beginning any sort of supplement regimen.
Supplementing for MTHFR defects requires some research as to approaches as well as some trial and error. One size does not fit all. I liken the right protocol to a favorite family recipe – everyone seems to have their own version that’s the best because they tweaked it over time. It’s the same way with various approaches to supplementing for MTHFR. Learn about them, tweak them to suit you and then perhaps tweak them again as your metabolism changes, conditions improve or as you learn more about other contributing deficiencies. I’m providing an overview of some approaches for supplementing MTHFR and some comments on common nutritional deficiencies that may have a bearing on your MTHFR protocol.
Dr. Ben Lynch’s Approach
MTHFR.net is a good and well-recognized resource of information for MTHFR defects based on Dr. Ben Lynch’s extensive experience. Dr. Lynch provides a protocol for the MTHFR defect C677T here and while he doesn’t also indicate an approach for 1298C, you can assume the protocol is the same. His general recommendation for starting out is to start with B12 for several days at low dosages, and start adding MTHF folate at a ratio that is half the amount of B12, increasing every several days until you feel better or reach the point of overmethylation symptoms. He also notes that MTHFR is not just about folate and suggests a number of other supplements (some of which you can buy on his site) as well as lifestyle recommendations that would benefit anyone. Dr. Lynch is not a fan of large doses of MTHF folate and certainly not a fan of any dose without the accompaniment of B12 among other nutrients and minerals. Like many families including mine, Dr. Lynch’s family of five all have different MTHFR defects, but he says none of them take more than 400mcg of folate per day. Accompanied by double the amount of B12, that is probably a good base recommendation for people without many health concerns who have MTHFR defects. This is similar to the basic recommendation that my local center for integrative medicine recommends of 500mcg of folate and 1mg of B12 daily for anyone with the defects.
Dr. Amy Yasko’s Approach
My previous post provided direction on how to get a number of useful reports from your 23andMe genetic data including Dr. Yasko’s Methylation Pathway Analysis (MPA). The MPA provides a good discussion of methylation, the impact of various SNPs as well as a suggested supplement protocol based on your individual genetics. If you haven’t had your genome mapped yet, you can still access Dr. Yasko’s Simplified Protocol right on the knowyourgenetics home page. Her protocol addresses methylation by first laying groundwork before starting B12 and folate supplementation. The six steps of the protocol include 1) balancing certain supplements including a multi and B complex, 2) providing other shortcut support that supports detox as toxic loads can interfere with methylation protocols 3) balancing lithium levels, 4) determining your ideal form of B12, 5) Implementing the remainder of long route support which includes titrating the amount of MTHF folate you need via drops and 6) additional support based on your particular nutrigenomic profile.
One part of her recommendations that is very important is the type of B12 that is best for you based on two particular genes, COMT and VDR Taq. This table is duplicated below.
Best Type of B12 based on COMT V158M and VDR Taq SNPs
|COMT V158M||VDR Taq||B12 types that should be tolerated|
|– –||++ (TT)||All three types of B12|
|—||+- (Tt)||All three types with less methyl B12|
|—||— (tt)||Hydroxy B12 and Adenosyl B12|
|+-||++||All three types with less methyl B12|
|+-||+-||Hydroxy B12 and Adenosyl B12|
|+-||—||Hydroxy B12 and Adenosyl B12|
|++||++||Hydroxy B12 and Adenosyl B12|
|++||+-||Hydroxy B12 and Adenosyl B12|
|++||—||Mostly Hydroxy B12|
When I first started supplementing for MTHFR, I did not pay much attention to the type of B12. Once I found this table, I tried the recommended combination and it made a big difference for me and also for my husband (COMT – -, VDR Taq ++). His recommended type of B12 is the top line of the table. I further tweaked his B12 as he seemed to do best with adenosyl and methyl. So while I’ve seen sites that have recommended that people try different types of B12 to see which works best, I’m a proponent of this table as a starting point and really appreciate the work that Dr. Yasko and colleagues put in to develop it.
The right type B12 is as important as folate. In fact, a B12 deficiency alone can cause a variety of conditions and ailments that can be as serious as the conditions attributed to MTHFR defects. For this reason, many feel the supplementation of pharmaceuticals (medical foods) like Deplin and others in high amounts without recommending associated B12 or other cofactors is a real mistake that can make many symptoms worse rather than helping.
Just a bit more about B12. There are four forms, the three mentioned in the table above as well as cyanocobalamin. Cyano has to convert to hydroxyl before it can be converted to the methyl and adenosyl forms that the body can use (these forms are sometimes referred to as B12 coenzymes). Hydroxy is supposed to have a longer half life than any other form and adenosyl is the only form stored by the liver.
Recommended Approach Based on Homocysteine Level
One of the generally understood problems of MTHFR defects is that they cause high homocysteine. Homocysteine (Hcy) is a naturally occurring amino acid that is produced as part of the methylation cycle and is an important indicator of how efficiently you are methylating. High Hcy is implicated as a factor that can cause many serious problems from heart disease to Alzheimers. Dr. Brady, author of The H Factor Solution recommends a number of supplements that work synergistically with dosages based on Hcy values shown in the table below. He believes that your Hcy level is the best indication of whether the B vitamins are doing their job as opposed to checking B12 or B6 levels for example.
Daily Nutrient Needs Based on Homocysteine Score
H < 6
|Very High Risk
When I first had my husband’s Hcy measured, it was in the very high risk category at 17.4 (and that was after supplementing him for several months with folate and B12). Four months later, after following a combination of these three approaches, it’s at 11.1. And while there is conflicting research as to whether lowering homocysteine correspondingly lower the risk of heart disease, Alzheimers, etc, he feels a lot better and I anticipate continuing improvement.
The methylation cycle has four key steps that change homocysteine into methionine, methionine into SAMe, and then SAMe back to homocysteine that needs a methyl donor so that it can start the cycle over again. The enzymes that facilitate this metabolic process need the cofactors B6, B12 and folate, the active forms of B vitamins. TMG, also known as betaine, is an important methyl donor and is included in all the protocols discussed here. Many people may be deficient in betaine due to metal toxicity, inflammation and stress. Dr. Brady considers TMG as the best (and most cost-effective) way to generate SAMe in the body, which he calls the “master tuner”. SAMe helps make or activate important neurotransmitters that can help with mood, chronic pain and food cravings. Interestingly, TMG is an FDA-approved treatment for a rare genetic condition (CBS deficiency) that causes high homocysteine because it “methylates” homocysteine, removing it from circulation.
Note that while most other approaches recommend double the amount of B12 in relation to folate, Dr. Brady’s does not. What he does recommend is that as your health improves, you may not need as much of these nutrients as you did initially and can lower your dosage. He also recommends dividing the doses of the B vitamins within the day. B vitamins are water soluble and will leave your body based on your hydration status (yep, that’s the Bs in bright yellow urine). We take sublingual B12 and folate when we wake up and after lunch. That seems to work well for us. I’ve heard some feel well dividing them into three doses. Most people don’t recommend taking them later in the evening because they are energizing and not conducive to sleep.
Why You Need More Than Folate, B12 and B Complex for MTHFR and Health
Dr. Linus Pauling, two-time Nobel Prize winner, said you can trace every sickness, every disease, and every ailment to a mineral deficiency. Without minerals, amino acids and enzymes don`t work and so vitamins and other nutrients don`t get broken down and absorbed properly and we end up with major deficiencies in both vitamins and minerals. In relation to MTHFR, most approaches concur that a full combination of nutrients works much better than any two in isolation. Many are synergistic and don’t work at all without other cofactors. Methylation can’t even take place without a magnesium molecule. B6 is converted to its active form by zinc, so a zinc deficiency would make taking B6 useless. Vitamin B6 has been shown to improve the absorption of magnesium as well as other minerals into cells. Calcium works synergistically with vitamins D and K2 and may actually be harmful if not taken with K2.
People are deficient in many vitamins and minerals due to a number of reasons and it may not simply be diet. The typical advice of eating five servings daily of fruits and vegetables is still the best, but it doesn’t buy you the nutrition that it did in the 1940s due to the nutrient depletion in the soil, the use of chemicals in farming, hormones in livestock and other factors.
Here is a list of the most common critical deficiencies:
- All the B Vitamins, particularly folate, B12, B6 and B2
- Vitamin A
- Essential Fatty Acids
Most of these can be found in a good multivitamin/mineral supplement, but not all of them. Both Dr. Lynch and Dr. Yasko have multivitamin formulas, and they don’t cover all the bases. There are three particular deficiencies that deserve special mention: lithium, iodine and essential fatty acids. Most multivitamin/mineral supplements do not contain these important nutrients.
Lithium, Iodine, and Essential Fatty Acid Deficiencies
Lithium can only be found in water that comes out of the ground, so that would be spring or mineral water and not bottled water labeled as purified or drinking water. Areas that have sufficient lithium in the drinking water have lower rates of crime, homicides, mental illness and suicides and higher rates of longevity (a good discussion can be found here). I can actually go to a spring that’s about a five minute drive away and get spring water right out of the ground (find a spring near you). Water with sufficient lithium would provide about 2mg/day. A safe daily low dose is considered 3-5mg. Lithium is neuroprotective, can help with mood, inhibits beta-amyloid secretion, and also prevents damage caused by beta-amyloid protein once it’s been formed and enhances nerve cell DNA replication. This is obviously beneficial in preventing Alzheimers. Lithium also helps to chelate or remove aluminum from the body. Hair mineral tests on family members, one 19 and one 75, showed they both had harmfully high levels of aluminum indicating that they were not able to detoxify this metal. As you may recall, one of the problems MTHFR creates is an inability to detoxify things like aluminum and other metals; thus, lithium may be beneficial for those of us with the defect. I found a mineral supplement with 4.5mg and both my daughter and I felt a positive effect on mood after taking it. This is far from the amount used in prescriptions for serious mental illness which is typically 300mg.
Iodine is important for thyroid function, breast health, bone marrow, the immune system and mental health. A deficiency can cause weight gain, low energy, depression, cardiovascular disease, cognitive decline, and a variety of cancers. Most experts do not believe that the intake of iodine in iodized table salt is sufficient for good health. Selenium is synergistic with iodine helps the body absorb it. The Japanese have an average daily intake of 12.5mg from their high consumption of sea vegetables as well as fish. Consequently, the Japanese have rates of breast cancer that are 1/3 the incidence for US women. They also have a lower incidence of other types of cancer and heart disease. Iodine-deficient breast tissue also shows alterations in DNA and increases in estrogen receptor proteins. Women with fibrocystic breast disease (FBD) were given iodine in doses between 3 and 6mg and it reduced the symptoms of FBD significantly without side effects. Iodine also suppresses tumor growth and causes cancer cell death in breast cancer in cancer-prone rats, reducing tumor rates 2.5 fold. Although my local women’s hospital told me my risk was low for breast cancer about eight years ago, given that my sister was diagnosed with breast cancer at age 40, and I’ve had three stereotactic biopsies, a lumpectomy, a history of FBD along with estrogen exposure from decades of birth control plus being heterogenous C677T, I’m taking iodine. So I’m guessing when my doctor said there is nothing that can be done for FBD, I doubt she was considering possible beneficial integrative medicine approaches.
Regarding essential fatty acids (EFAs) the Omega 6 to omega 3 ratio in the US is one of the most unhealthy in the world. The average ratio in the US is 15:1 but can be as bad as 50:1. The healthy ratio is 1:1 to 5:1. A healthy ratio will reduce the risk of breast cancer, and reduce the symptoms of arthritis, allergies, cardiovascular disease and depression among many other conditions. Elevated omega 6s contribute to all inflammatory diseases. Probably the worst offender food is omega 6 vegetable oils followed by processed foods. You can fix your ratio by decreasing the omega 6 foods and increasing the omega 3 foods like the oily fish in these recipes, certified pure fish oil supplements containing DHA and EPA, or other foods such as flax, walnuts, cauliflower, brussel sprouts, broccoli, squash and collards. In doing some research on this important ratio, I downloaded a not very user friendly tool called Kim. I tried to input my diet in numerous ways but could not get my ratio down even when eating salmon three times a day. But by adding 1 Tbl of flax oil, my ratio was in the optimal range. So 1 Tbl of flaxoil, preferably organic or ground flax seeds (which go great in oatmeal) is going to have a positive effect of your ratio of these essential oils. I think of EFAs as a brain lubricant and just as important to your brain as oil is in your car. Your brain is the fattest organ in your body, comprised of 60% fat, so make sure it gets enough good fats!
For people with MTHFR defects, the minimum supplements recommended by the approaches reviewed here are folate, B12, B6, magnesium, Zinc and TMG. Due to the positive synergistic effect of all the vitamins and minerals on the B vitamins, the best approach would be to make sure you don’t have any deficiencies by taking a good multi, supplementing to improve your ratio of EFAs and consider supplementing iodine and lithium. Like the advice of Linus Pauling, avoiding these deficiencies would go a long way in avoiding most diseases and improving or resolving many adverse health conditions.
Always add supplements one at a time slowly to assess your tolerance and remember that methylation is a critical metabolic process. Always check with your doctor or a qualified practitioner before starting any methylation related protocol.
About Kiki Kish*
In 1992, my husband, 24 years my senior, was diagnosed with Hepatitis C. Hep C is a serious liver disease without a cure, so I explored alternative medicine. Now at 75, he is the poster child for transplants and health with Hep C, mostly because I became a self-navigating nutritionist, naturopath and now a budding nutrigenomist. In 2001, my son was diagnosed with Autism. Same thing, no cure, but I used supplements and nutrition; he’s in college making As and Bs. These two situations along with a parent with cancer caused me to do two decades of research on alternative therapies. I was often asked if I was in the medical field probably because I did my research to try and make sure that the doctors were doing a good job. I had problems for which I was prescribed medication, but the doctors, as usual, didn’t discuss what might be causing it. I determined I had a histamine intolerance problem, and in researching that for myself, I found that compromised methylation could be a cause. That led to MTHFR (I’m heterozygous for 677C). Once I did the research on it, as an engineer (M.S), I found the statistical prevalence of the defect and the risk of problems and diseases it causes or contributes to astounding. Everyone in my family as well as those in my extended family who have been tested have the defect and have many related conditions. And that’s how I arrived here.
* Name has been changed to protect privacy.