What You Should Know About Alcohol and MTHFR

Alcohol is one of the most common recreational drugs used by adults today. Although widely associated with numerous medical, psychiatric, and social problems, alcohol has a central role in modern culture. 

Among the many health risks associated with chronic alcohol consumption is high homocysteine. Homocysteine is a sulfur-containing amino acid formed in the body that can lead to serious chronic diseases.  

Homocysteine levels are further influenced by a polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. 

Recent studies indicate that the combination of alcohol and the MTHFR polymorphism may be especially harmful to both short- and long-term health. Both alcohol and MTHFR significantly affect the methylation process that is essential for every bodily process, largely due to the impact on folate status and liver function. 

This article will discuss the various ways in which MTHFR and alcohol interact and how alcohol may further impair methylation. We will also examine how MTHFR can increase the risk of some diseases, particularly those related to elevated homocysteine. 

Numerous studies have shown that alcohol can interact with the MTHFR gene polymorphism by increasing the risk of complex diseases such as cardiovascular diseases, diabetes, and several cancers. 

The MTHFR polymorphism has also been linked to decreased enzymatic activity and poor homocysteine regulation. As a result, chronic alcohol consumption may increase the risk of causing/developing elevated homocysteine levels even further, which in turn increases the risk of several disease phenotypes already associated with reduced MTHFR activity.

This is attributed to the one-carbon metabolism pathway, in which the MTHFR C677T polymorphism plays an important role in the breakdown of homocysteine to methionine. Chronic alcohol consumption is also associated with folate deficiency, with around 80% of alcoholics shown to have low folate levels. Deficiency of vitamin B12 and pyridoxal phosphate (B6) also contributes to elevated homocysteine. 

Folate acts as a methyl donor via S-adenosylmethionine (SAM-e), which means that high homocysteine and low folate may further influence DNA methylation rate.

Chronic alcohol exposure impairs folate absorption and methylation by blocking enzyme pathways. Folate deficiency means SAM-e cannot be produced, which is necessary to protect the liver from oxidative stress. A lack of SAM-e further reduces methionine metabolism in the liver, causing DNA damage while promoting alcoholic liver injury.

When liver tissue is exposed to elevated insulin or glucose, the cellular methylation balance can be altered. Sugar is absorbed from alcohol into the bloodstream, triggering the release of insulin. Chronic alcohol abuse can reduce the body's responsiveness to insulin and cause glucose intolerance. As a result, blood sugar levels stay high, and the excess sugar increases advanced glycation end-products (AGEs), causing β-cell damage, oxidative stress (OS), and inflammation.

A small study focusing on a subset of Indian men found that the C677T allele was more prevalent in those with mild alcohol dependence and depression. However, further research is needed to determine the significance of this finding.

The liver plays a central role in the metabolism of methionine and homocysteine. It has been reported that hyperhomocysteinemia alters the metabolism of intracellular lipids and homocysteine, which may then lead to liver damage. There is some evidence that patients with fatty liver disease have significantly higher homocysteine levels than control groups.

High homocysteine is an indicator of poor methylation due to reduced folate levels, which is commonly associated with chronic alcohol use. Hyperhomocysteinemia is a known risk factor for several diseases or disorders, including Neural Tube Defects  (NTDs), Alzheimer’s disease, schizophrenia, pregnancy complications, cardiovascular diseases, non-insulin-dependent diabetes, and end-stage renal disease.

Insulin has also been shown to change the activity of metabolic enzymes involved in the turnover of homocysteine, with studies showing that insulin levels were significantly lower in people with the TT MTHFR mutation than in CC or CT subjects. Insulin resistance can lead to type 2 diabetes and atherosclerotic cardiovascular disease (CVD).

Alcohol intake is also found to significantly increase the risk of breast cancer and colon cancer, although the association appears limited primarily to persons with low folate intake. Alcohol intake and MTHFR C677T may also increase the risk of thyroid cancer.

One of the main risks associated with alcohol intake and low MTHFR function is elevated homocysteine. Homocysteine concentration is twice as high, and plasma B vitamins are lower among chronic alcoholics than among healthy controls. This is most likely due to a combination of poor diet and the direct effects of alcohol intake on folate status.

However, some research suggests that those effects may be overcome by sufficient folate intake.

Folate supplementation effectively decreases homocysteine among all genotypes, although those with the TT genotype may require higher intakes than others. 

Women with both high folate intake and moderate alcohol intake had a significantly lower risk of coronary artery disease (CAD) than nondrinkers with low folate intake. The effect of these interactions between folate intake, alcohol intake, and MTHFR genotype on the risk of CAD is believed to be due to homocysteine. 

In addition, those with the C677T genotype may be more susceptible to colon cancer if their diet is “methyl-poor” - i.e., high in alcohol, low in folate, or both.

Folate and vitamin B12 supplementation may have a therapeutic role in patients with hyperhomocysteinemia. For those with an MTHFR mutation who choose to drink alcohol, supporting the methylation process and liver health is vital. 

The most effective way to improve folate status is through supplementation with methylfolate, especially in the case of an MTHFR polymorphism that inhibits the metabolism of folic acid. Methylfolate is an active form of folate that can bypass the MTHFR mutation. It is already in its metabolized form, which means it is readily absorbed in the body and can be immediately utilized for methylation. 

Some of the most highly recommended methylfolate supplements include the Methyl-Life® product range. These are formulated specifically for those with a heightened need for bioavailable folate due to MTHFR defects, dietary deficiencies, or other conditions in which nutritional absorption is impaired. Taking a methylfolate supplement is highly recommended for those who choose to drink alcohol as it is an effective means of supporting folate status and, therefore, methylation.