Reply To: MTHFR


Hello Tina (and colleagues),

I wanted to chime in on the MTHFR conversation. I have spent the past year extensively studying the metabolic complexity of this mutation. This is a very important conversation to have on this list serve because it is impacting a large percentage of people we treat. At least 25% of the population is at least heterozygous (see below) for this mutation.

To answer your questions:

1. MVI (already answered) – stop immediately! Unmethlyated folic acid to someone with MTHFR is a cellular toxin that only perpetuates their metabolic stress.

2. Future lab work – checking T-Hcy may yeild a positive test, but how it is treated will be based upon whether the client has other elevated tests. It is also important to note that if HCY is WNL, that does not mean there is not a serious nutritional problem. It is very similiar to the paradox in the eating disorder world where labs are “normal,” but we (RDN’s) know there are serious hepatic, GI, and cardiac issues at play. The main one I would recommend to look at is MMA (methylmalonic acid) – The reason this is important is that when the folic acid cycle is impaired at reducing homeocysteine, B12 will come in and “save the day.” Think back to the folate-methyl trap what you learned in your MNT class…read it again, it will be fascinating in this context!

3. Vitamin recommendations: this is my personal one because it gets at the B12, pyridoximine (B6), and folic acid that are being stressed with this mutation.

Additional background
WARNING – metabolism and science get me really excited so my ability to talk about this topic can span for days. However, for all who are interested in grasping the importance of looking into this issue, I will be brief and not use too many inappropriate analogies 🙂

Consuming food has the primary purpose of helping our bodies gain access to carbon subunits (2 and 3 carbon are preferred) to support the production of ATP. This is our energetic currency. The breakdown of carbohydrates (mainly 5 and 6 carbon units), fatty acids (primarily 3 chains of >10 carbon units), and proteins (they vary…messy buggers!) all undergo methylation. This is when a CH3 (methyl group) changes the original structure (CHO, FAT, etc.), allowing access to the bonds (e.g, covalent, hydrostatic, disulfide…) that keep the molecule glued together. This process is normal and required.

When someone has the MTHFR (methylene tetrahyrofolate reductase) mutation, there is a broken “switch” in the folic acid cycle of metabolism that makes the reduction (TRANSFORMATION) of homocysteine (THINK BAD GUY!!!!) into a methionine (GOOD GUY). Methionine is an essential amino acid that can safely cruise around the body looking for points of entry into the metabolic cycles when ATP is needed. Homocysteine is not something you want lingering around because it erodes cellular walls and causes distress. I like to think of homocysteine as the original metabolic gang member armed with many cans of spray paint and nothing to lose!

As this relates to mental health, our bodies are innately wired to maintain homeostasis. If homocysteine is unable to get reduced by folic acid using the MTHFR pathway, other pathways and vitamins will get drained to make this metabolic predator go away. Mainly we are talking about B12 and B6. A deficiency in B12 already has established clinical data and understanding to mimic psychosis. Here is more info –

Where do you go from here? Know that it is a very complex system and it is normal to be overwhelmed. Here are the key take clinical takeaways and personal thoughts on how to help patients navigate this process.
Determine if client homozygeous (2 broken swtiches) or heterozygous (1 broken switch) for MTHFR mutation. Think about your renal rotations. Does the person have at least one functional kidney and must learn how to adjust their eating to prevent unnecessary burden on the functional organ or do they need to be on dialysis?
Affirm client and self that this is not too much to manage. They have been “functioning” in their lives until the awareness of this dx. Consciousness has the power to create panic because of the need to FIX the problem. Take a deep breath and know that time and the realization that it is time to make nutritional adjustments is a gift. It is an upgrade to their current level of metabolic efficiency.
Get synthetic folic acid OUT (completely) of the diet. All fortified foods (cereals, crackers, breads, etc.) and supplements need to go away. There is a lot of grief and anger that may come out. As a nutrition therapist, you may spend months helping your clients develop alternatives for their ‘normal’ way to living. Be patient and sit with them in this process. It is painful to let go of something that you have always thought was “good” for you.
Keep dietary folic acid in the diet! Food based. The will need the methyl donors as the body recalibrates to having less cellular toxins to process.
For you…dig out your biochem book, Krause, or any basic metabolic book and start learning about the integrative process of how nutrients communicate with each other. *For all my fellow metabolism nerds on the EML, we are talking abou molecular and cellular nutritional epigenetics. It has ties into cytochrome metabolism, RNA remodeling, and calcium channel activation for excitation of neurons.
Lastly, the next steps in your clinical assistance with this mutation is to help your client find a balance with how much protein/what type is tolerated as it relates to the ratio of methyl donors they consume (i.e., how many servings of fruits and vegetables do they need to eat each day and what colors are needed to keep the homocysteine from building up and causing problems?). This is personalized, will change with time, hormones, stress, and vacillate throughout the lifespan. My suggestion for you as a clinician to be a food-based translator for the symptoms that come their way as they explore this change in reality. Nutritional science is always changing and what we know today may change tomorrow. Do your best and most importantly, just be with them during this transition.
For anyone who is still reading…thank you for allowing me the space to share my knowledge. It brings me great joy to help out my colleagues!

Have a great weekend,