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It has been estimated that nearly 60% of the population could have at least one MTHFR genetic mutation affecting the way these individuals utilize folic acid and thereby methylate. This is important because methylation takes place in nearly every cell in the human body and is involved in numerous biochemical process. Having just one mutation has been associated with a 20-40% reduction in methylation activity (depending on where the mutation is on the gene). Having two mutations at the same location has been associated with a 40-70% reduction in activity.

This reduced methylation ability can impact weight gain in several ways.


MTHFR mutations can play a role in various mood disorders because folate is needed 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 lack of folate) can result in increased appetite and cravings. (1) (2)


When the body breaks down protein it produces something called homocysteine. Under normal circumstances, vitamin B12, vitamin B6, and folate break down homocysteine. These convert it to other substances your body needs so that little remains in the bloodstream. If this doesn’t happen and homocysteine levels stay high, heart and blood vessel disease, hardening of the arteries and blood clots, increasing the risk of blood vessel blockages. (3) (4)


MTHFR mutations can lead to oestrogen-dominance with high oestrogen concentration cycles. This is because the body needs to be able to methylate estrogen to clear it efficiently. Without this ability, you may experience hormone weight. Additionally, folate is crucial to prevent pregnancy complications and miscarriages. High homocysteine levels caused by inadequate B vitamins and poor methylation can also impact insulin levels, even contributing to insulin resistance and PCOS (polycystic ovarian syndrome). (5)


Besides B9 (folate), other B vitamins are also cofactors that play an important role in energy metabolism and studies suggest deficiencies can lead to weight gain. (6) B1 is important in glucose metabolism as well as ATP energy synthesis. B2, B3, B7 are important in carbohydrate, lipid, and protein metabolism. B5 is involved in the synthesis of fats, cholesterol, and neurotransmitters. B6 functions to release glucose from glycogen. B12 necessary for the breakdown of fat and protein.


Because people with MTHFR mutations cannot properly metabolize folic acid, it could result in the accumulation of unusable folic acid in the blood. This could lead to higher fat accumulation. 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. (7)


Phase 2 of the liver detoxification process involves methylation. Methylation transforms various toxins from insoluble compounds to water-soluble compounds. That way, they can be purged from the body in urine, sweat and bile. If the body cannot methylate properly, these toxins can build up in the body.

What’s more, the fats and cholesterol we eat are transported to the liver, and MTHFR mutations can hinder the processing of these fats causing them to accumulate in the liver. This accumulation then can result in fatty liver disease. (8) High alcohol consumption can also decrease folate levels further impacting liver health.


If you struggle with poor methylation and low folate because of MTHFR genetic mutations, that doesn’t mean you’re doomed. Talk to your doctor about taking a methylated and USABLE form of folate like that found in the Plexus xFactor Plus™ multivitamin.

xFactor Plus™ has the most-bioactive and most-bioavailable forms of vitamins, for better absorption, including the already methylated and usable form of B9, L-methylfolate. That means even those with an MTHFR gene mutation can utilize it. If you are already taking a supplement that says it contains “folic acid” and you suspect you might have this gene mutation, I highly suggest switching to a methylated form like xFactor Plus™. Otherwise, you might just be flushing your money down the toilet (quite literally, as unused B vitamins often are secreted via urine.)

In addition, xFactor Plus also contains other vitamins and minerals that are needed to make and use other hormones. For example, it has 100% of the DV of Pantothenic acid (vitamin B5) which is needed to make both sex hormones and stress hormones, 150% of the DV of selenium which is needed to convert T4 into T3 and assist the adrenal glands, 500 mcg of boron which is needed for the body to use estrogen and testosterone, and 7000% of vitamin B12, which is needed for the adrenal system, nervous system, cardiovascular system, hormonal balance, enzyme production, and DNA synthesis.


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