How Does MTHFR Affect Weight Gain?

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.

MTHFR genetic mutations have been linked to both weight gain and difficulty losing weight.

This may be partly due to nutritional deficiencies that result from impaired methylation in the body.

Methylation is required for numerous metabolic processes, including the conversion of homocysteine to methionine. Numerous studies have investigated whether the MTHFR genetic mutation and homocysteine affects 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. 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. These findings suggest a genetic and biochemical link between MTHFR C677T, elevated homocysteine levels, and increased obesity risk.¹

• High homocysteine and MTHFR weight problems
  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). These modifications can affect whether certain genes are expressed (switched on) or silenced (switched off).
  DNA methylation and histone modification help to control the way genes work without changing the genetic code. Several studies have shown that elevated homocysteine can disrupt the expression of genes involved in fat storage and metabolism, potentially increasing the risk of weight gain and obesity.
  Elevated homocysteine can also disrupt metabolic processes linked to metabolic syndrome. Individuals with the homozygous MTHFR mutation are also more likely to be affected by obesity, hypertension, insulin resistance or type 2 diabetes, and/or lipid disorders (e.g. high triglycerides, low HDL).²

• Estrogen and weight maintenance
  Impaired methylation due to a MTHFR mutation can reduce the activity of COMT, an important enzyme required for detoxifying estrogen metabolites like 4-OH-E2, a potentially harmful estrogen metabolite.³ Low COMT activity can allow these toxic metabolites to accumulate.
  COMT is also required for synthesising 2-methoxyestradiol (2MeOE2), an estrogen metabolite that can help to protect against obesity and restore insulin sensitivity.⁴
  Reduced COMT activity and 2MeOE2 levels have been linked to the development of obesity and insulin resistance, as well as hypertension.⁵
  Increased estrogen may also promote the accumulation of subcutaneous fat.⁶
  Genetic profiling can help women to take preventative measures regarding weight gain or breast cancer risk.

MTHFR is unlikely to be the main cause of weight problems. Excess weight is most often linked to poor diet and lack of exercise, although medical conditions and lack of sleep can also contribute.

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.

If you have MTHFR and you are overweight, it’s a good idea to have your homocysteine levels tested, as high homocysteine may be impacting your health and your weight loss efforts. Reducing homocysteine requires methylfolate, the bioidentical, active form of folate that converts homocysteine to methionine. Many people with MTHFR and high homocysteine are low in methylfolate, but this can be restored by supplementing with a quality methylfolate product.

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.

Methylfolate is critical for methylation processes involved in the production of neurotransmitters (such as serotonin and dopamine), which can play a major role in motivation and mood.⁷

Proper methylation may also improve estrogen clearance.⁸

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.⁹

Restoring your gut microflora should also be considered. Poor digestive function and dysbiosis (imbalance of gut bacteria) can contribute to inflammation and sluggish metabolism.¹⁰ Supplementing with probiotics, prebiotics, and eating plenty of fermented foods can help to support a healthy microbiome.