Overweight and obesity have become a serious public health problem worldwide since they increase the risk of chronic diseases and early death. Obesity is a multifactorial disease that involves environmental and genetic factors. While lifestyle choices like diet and exercise are undeniably important, genetics also play a significant role in weight management. The methylenetetrahydrofolate reductase (MTHFR) gene, pivotal in folate metabolism, has garnered attention for its potential association with weight gain and obesity. This article explores the complex relationship between MTHFR gene polymorphisms, folate metabolism, and weight regulation, providing an overview of current research and practical strategies for managing weight in individuals with MTHFR mutations.
Understanding MTHFR
MTHFR stands for methylenetetrahydrofolate reductase. The MTHFR gene contains the DNA code to produce the MTHFR enzyme. The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme is crucial for converting folate (vitamin B9) from food into its active form, 5-methyltetrahydrofolate, which the body can then use. MTHFR is a pivotal enzyme in folate metabolism, since it catalyzes 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Moreover, it regulates the proportional usage of one-carbon units between methylation reactions and nucleic acid synthesis. Methylation is a process that happens in every cell of our body and is absolutely central to our physical, emotional, and mental well-being.
MTHFR Gene Polymorphisms
Variations in the MTHFR gene, known as polymorphisms, are common. The rs1801133 polymorphism (677C>T; A222V) is the most common and majorly studied. These polymorphisms can affect the enzyme's efficiency, with some variants leading to reduced enzyme activity. The 677TT genotype is associated with a reduction in the availability of folate, high homocysteine levels, reduced enzyme activity, and a thermolabile enzyme. Research has shown that homozygous MTHFR leads to significantly reduced function of the enzyme, while the homozygous MTHFR A1298C variant results in 60% of normal enzyme function.
The Link Between MTHFR and Weight: Unpacking the Evidence
The association between MTHFR gene mutations and weight gain or difficulty losing weight has been observed. Numerous studies have investigated whether the MTHFR genetic mutation and homocysteine affect body weight. Although results are generally inconsistent, a 2019 meta-analysis found that the MTHFR C677T genetic variant may be linked to a modestly increased risk of obesity. The link between the MTHFR gene and weight gain was first suggested when it was observed that people who were obese were more likely to have a specific variation of the MTHFR gene. A recent study has suggested the C677T and TT genotypes may increase the risk of obesity by up to 20% although the differences in BMI between genotypes were very small.
Homocysteine and Metabolic Disruption
MTHFR mutations can impair folate metabolism which can then lead to high homocysteine levels. People with MTHFR gene problems often have homocysteine imbalances. Elevated homocysteine can also disrupt metabolic processes linked to metabolic syndrome. High homocysteine has been linked to inflammation and changes to the way the body stores fat, potentially increasing the risk of weight gain and obesity. People with the TT genotype (which produces a less active enzyme) had a 13% higher risk of obesity than those with the CC genotype. Among obese individuals, those with the TT genotype also had higher homocysteine levels. Homocysteine is an amino acid involved in one-carbon metabolism, which plays a key role in DNA methylation. Homocysteine levels can also influence histone modification: the methylation of amino acid residues on histones (the proteins that package DNA). DNA methylation and histone modification help to control the way genes work without changing the genetic code.
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Folate and B Vitamin Deficiencies
MTHFR mutations can also lead to deficiencies in folate and other B vitamins, which are vital for energy metabolism. B vitamins play many essential roles in energy metabolism in the body. 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. 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. Some research has also shown that folate levels are lower in obese people than in healthy people, and that low folate may be associated with higher body mass index and abdominal fat accumulation.
Hormone Imbalances
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 estrogen-dominant women with high estrogen concentration cycles. Studies have shown that high levels of estrogen may increase your risk and progression for cancer. However, genetic mutations may also directly influence hormone concentrations. You need to methylate estrogen to clear it efficiently. Research has found that MTHFR mutations are linked to estrogen dominance with high estrogen concentration cycles.
Appetite, Mood, and Neurotransmitters
Research has found that MTHFR mutations can play a role in various mood disorders as folate is a requirement for the synthesis of neurotransmitters such as serotonin and dopamine. Serotonin is the body’s natural appetite suppressant, so a lack of serotonin (caused by a lack of folate) can result in increased cravings and appetite.
Fat Accumulation
As discussed previously, people with MTHFR mutations cannot properly metabolize folic acid, which can lead to the accumulation of folic acid in the blood. In a study published in Nutrients, scientists 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, i.e. higher fat accumulation.
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.
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Counterarguments and Conflicting Findings
It's important to note that the relationship between MTHFR and weight is not universally agreed upon. Some studies have found no statistical differences about the prevalence of the MTHFR 677C>T polymorphism between normal weight and overweight/obesity individuals, which agrees with the majority of researches.
A study of young individuals found no difference in the distribution of the MTHFR 677C>T polymorphism between individuals with normal weight and overweight/obesity. However, an analysis stratified by gender showed a significant protector effect of the TT genotype against obesity in males and elevated waist circumference in females. These results suggest that the MTHFR 677T polymorphism might not be a risk factor for being overweight/obesity. Rather, on the basis of these results, this variant could be a protector effect.
Strategies for Weight Management with MTHFR Mutations
While you cannot reverse an MTHFR mutation, you can follow the MTHFR diet to manage your symptoms. Even better, we now know that there are things we can do to balance out gene mutations and keep them from causing major problems. This knowledge gives us personal control like never before. Instead of throwing up our hands and accepting your “fate,” you can actively take steps to give your body what it needs to thrive. With all of the potential for nutrient deficiencies that impact how our genes are expressed, I highly recommend that everyone take a high-quality multivitamin as part of their daily routine.
Dietary Recommendations
Knowing your genetics allows you to find the individualized way of eating that will work best for you. There’s no right answer - we are all unique individuals. There are, however, some general rules that I recommend everyone follow - especially those with the MTHFR mutation.
- Folate-rich foods: Folate is an essential nutrient that is crucial to maintaining overall health. Get your folate from natural sources including dark leafy greens like spinach, kale, bok choy, and Swiss chard. Try to eat at least one cup or more of these daily.
- Eat whole, natural foods instead: Avoid processed foods that have synthetic folic acid added to them.
- Foods rich in vitamin B12: Those with a mutation in their MTHFR gene can also experience a deficiency in several other nutrients, such as vitamins B12 and B6. Vitamin B12 supports normal functioning of the brain and nervous system. It is also required for the breakdown of homocysteine. A deficiency in these nutrients can increase homocysteine levels in the body, increasing the risk of cardiovascular disease.
- Foods containing choline and methionine: Choline and methionine are another group of nutrients essential for those with a mutant MTHFR gene.
Supplementation
If you have MTHFR, supporting your body’s folate levels should be a priority. The best way to do this is with methylfolate, the active form of folate that bypasses the MTHFR mutation.
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- 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.
- Methylfolate: Reducing homocysteine requires methylfolate, the bioidentical, active form of folate that converts homocysteine to methionine.
Lifestyle Adjustments
Repairing the digestive system and optimizing the flora to correct methylation deficiency.
- Don’t forget to hydrate! Your body needs water to function at its best. If plain water just isn’t your thing, try to jazz it up a bit by infusing with fresh fruit, choose naturally flavored seltzer, or drink a lot of herbal tea.
- Alcohol: It can increase oxidative stress on the body and interfere with folate and vitamin B absorption.
- Coffee: Studies suggest that coffee can increase the homocysteine levels in those with the MTHFR C677T mutation.
Medical Monitoring
- Have your homocysteine levels measured: If your homocysteine levels are high, you may have a methylation issue or a B12/folate deficiency.
- Discovering you have an MTHFR polymorphism: can be a reason to speak with your doctor about options for getting bioavailable folate in your diet.
The Importance of a Holistic Approach
MTHFR is unlikely to be the main cause of weight problems. Weight gain and an inability to lose weight can be lifelong struggles for some women. Weight problems can have many underlying factors, with the most common being poor diet and a sedentary lifestyle. However, genetics are also a major part of the puzzle - including MTHFR.
Effective weight loss begins with eating a healthy diet low in sugar, saturated fats, and processed foods. Exercise for at least 30 minutes a day on most days of the week, and try to get at least 6-8 hours sleep each night. If you are overweight and struggle with eating well or exercising, it may help to speak to a qualified nutritionist and/or weight loss coach.
For far too long, women have thought that there are things they simply can’t control when it comes to their health. While you can’t change which genes you were born with, you can change the way your body responds to these genes. Learn to work with your genes instead of against them.
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