How the MTHFR genetic mutation could be contributing to weight gain or stopping your weight loss attempt

If you have an MTHFR genetic mutation you may be experiencing a number of different symptoms, including ineffective weight loss. Other symptoms include chronic fatigue, histamine intolerance, chronic pain, mental health disorders, amongst many others which vary in seriousness.

There is also a link between MTHFR genetic mutations and weight gain or the inability for weight loss. In fact, many people being diagnosed with MTHFR gene mutations are discovering that this has been a major contributing factor to their weight gain for years.

So, what exactly is MTHFR?

In some respects, methylation is actually very simple, in that it’s really just a biochemical process. But it’s also a very intricate process that is absolutely central to our physical, emotional, and mental well-being. (1)

MTHFR stands for methylenetetrahydrofolate reductase. The MTHFR gene contains the DNA code to produce the MTHFR enzyme. This enzyme converts the folate you eat (DHF – dihydrofolate) into the active form (5-Methyltetrahydrofolate) in order to be used by the body.

If you have a mutation in the MTHFR gene, it will affect how much active folate you have available.

Methylation is a process that happens in every cell of our body. Here are some of the ways we use methylation:

Cell division and renewal
Healthy immune cells
Synthesizing and clearing adrenaline
Detoxification in the liver (and elsewhere)
Producing energy for cells to use in chemical reactions
Clearing out excess estrogens and histamine
Regulating how our genes get expressed (2)

Find out more about MTHFR here.

MTHFR genetic mutation and weight gain

The most common signs that your weight gain could be attributed to a mthfr genetic mutation include:

You accumulate fat around the abdominal area first

Being more likely have a larger BMI (body mass index) and a larger hip to waist ratio which means that more fat and weight is being collected around the waistline
You have fatty liver – many people who test positive for MTHFR genetic mutation have a fatty liver that leads to weight gain. When you consume and digest foods, the fats and cholesterol are transported to the liver. They are then packaged into low-density proteins for transport through the blood to all the tissues that require the fats for good health. When you have MTHFR gene problems these fats get stuck in the liver and build up to cause fatty liver. The reduction in the MTHFR enzyme can’t keep up with the processing of the fats so they end up being stored.
You have signs of cardiovascular disease (high blood pressure)
Struggling to obtain good results from dieting and exercise
You are unable to lose weight
A family history of weight problems
Obesity
You have a slow metabolism (3)

There are a number of contributing factors to how MTHFR contributes to weight gain, including:

Storing high levels of unmetabolised folic acid

As MTHFR variations cause the body to not be able to process folic acid and folates into the active and usable form of methylfolate, your body will store higher levels of unmetabolised folic acid, resulting in weight gain or the ability to not be able to lose weight.

A study published in the Nutrients Open access journal examined the effects of folic acid on rats that were fed a high fat diet. Results concluded that excess levels of folic acid caused increased lipid storage and weight gain. (4)

The importance of B vitamins impacting MTHFR and weight loss

B vitamins play many essential roles in energy metabolism in the body. The B vitamins include:

B-12
biotin
folate
B-6
pantothenic acid or B-5
niacin or B-3
riboflavin or B-2
thiamine or B-1

Deficiency in one of the B vitamins can affect other B vitamins, which can disrupt a person’s metabolism. B-12 is essential for the metabolism of proteins and fats. It needs B-6 and folate to work correctly. B-6 also helps metabolize protein. Thiamine helps the body metabolize fat, protein, and carbohydrates.

The ability to process fats, proteins, and carbohydrates is essential. A healthy metabolism ensures that the body uses these nutrients for energy rather than storing them as fat.

Researchers discovered, in two large cohorts of people, significant interactions between the DNA methylation–associated HIF3A single nucleotide polymorphism and intake of B vitamins on 10-year changes in BMI.

A genetic association with a smaller increase in BMI was observed in the subgroup with lower intake of vitamin B2, vitamin B12, and folate, whereas the association with a greater increase in BMI was observed in the subgroup with higher deficiency of vitamin B2, vitamin B12, and folate. The findings support the hypothesis that DNA methylation may causally affect weight gain. (5)

People must regularly eat foods that contain B vitamins to meet their daily needs.

Good choices of foods that contain B vitamins include:
lean meats and seafood
whole grains, including barley and brown rice
dairy products
eggs
some fruits, such as bananas, apples, grapes, and watermelon
nuts and seeds
some vegetables, including spinach, potatoes, and squash

B-12 is present only in animal products, meaning vegetarians and vegans may have difficulty consuming enough of this vitamin.

In addition to dairy products, the following foods may contain B-12:

fortified plant-based milk
nutritional yeast
fortified breakfast cereals
meat substitutes
some spreads, such as Vegemite and Marmite (6)

MTHFR and the clearance of estrogen for weight loss

Methylation issues can also result in hormone imbalances. Certain MTHFR mutations harshly affect the methylation cycle and therefore lead to hormone imbalances – such as in oestrogen-dominant women with high oestrogen concentration cycles. Studies have shown that high levels of oestrogen may increase your risk and progression for cancer. However, genetic mutations may also directly influence hormone concentrations. (7)

You need to methylate estrogen to clear it efficiently. Without this ability, you are likely to struggle to lose weight.

High homocysteine levels

Homocysteine is an amino acid produced when proteins are broken down. A high homocysteine level, also called hyperhomocysteinemia, can contribute to arterial damage and blood clots in your blood vessels.

People with MTHFR gene problems often have homocysteine imbalances. High homocysteine levels usually indicate a methylation issue and a deficiency in vitamin B 12 or folate. Higher homocysteine levels cause fat accumulation, impacting insulin and resulting in further weight gain.

What you can do to reverse weight gain cause by a gene mutation

Genetic testing and weight loss

There are options to help with weight loss caused by a gene mutation. The first step is to get a comprehensive gene test.

Your diet, environment and lifestyle can have a significant effect on how your genes are expressed. Finding out if you have the MTHFR gene defect will allow you to find out your genetic strengths and weaknesses and start to address any issues you may have, including managing your weight.

At Advanced Functional Medicine, our team can help you interpret your genetic data and guide you in how best to lose weight, according to your genetic make-up.

Managing your gene mutation through diet

Once we have all the information about your genes, we can work on creating a diet plan to help you lose weight.

Some of the strategies that may work well for you include:

Repairing the digestive system and optimizing the flora to correct methylation deficiency. This includes treating candida because of the toxins it releases, inhibiting proper methylation.

Adhering to a comprehensive diet which may include supplementing your diet with a daily dose of activated folate such as methylfolate

Check your supplements. If any of them has folic acid added, we recommend you stop taking the supplement or switch brands to that use active forms of folate.. Your body won’t process high amounts of folic acid well, particularly if you have a MTHFR polymorphism, and it can build up inside you blocking your folate receptor sites. We will prescribe more suitable supplements to assist in returning you to optimal health, whilst also helping you to lose weight.

Avoid processed foods that have synthetic folic acid added to them. These include most commercial cereal and grains in Australia.
Get your folate from natural sources including dark leafy greens like spinach, kale, bok choy, and Swiss chard. You should aim for at least 1 cup or more of dark greens every day.
Have your homocysteine levels measured. If your homocysteine levels are high, you may have a methylation issue or a B12/folate deficiency. If so, supplement with methylcobalamin (Vit B12), Vitamin B2, Vitamin B6 and 5-MTHF may be indicated.
Eat hormone free, grass-fed meats, grass-fed butter or ghee, and organic free-range eggs.

By following the above diet guidelines and prescribing effective supplements, in addition to an exercise program, many of our patients have experienced significant weight loss success, many without even trying too hard.

Get in touch with us and find out more

Advanced Functional Medicine have expeience addressing health issues associated with MTHFR genetic polymorphisms and methylation issues.

We provide advice on factors such as diet, lifestyle and supplemental recommendations.

Through the analysis of your genetic predisposition to certain biochemical imbalances and understanding your biochemistry, we look to get to the root of the problem.

MTHFR: Genetic mutation may be an underlying cause of weight gain or prevent weight loss