PCOS and MTHFR: Miscarriage, Insulin Resistance and Heart Health
PCOS | POSTED April 23, 2019
Miscarriage and cardiovascular disease are related to each other – and unsurprisingly, they both affect women with PCOS frequently. Let’s take a look at one of the areas that increases risk for both of these concerning risks in PCOS: MTHFR.
MTHFR stands for “stands for methylenetetrahydrofolate reductase”: an enzyme that’s responsible for an important process known as methylation.
Methylation a term that has become immensely popular in recent years. It is a process where “methyl” groups are added to DNA, causing a change in the activity of the DNA segment. Methylation typically causes DNA to be “silent” in its activity, downregulating the “actions” of that particular segment of DNA.
In the case of cardiovascular and circulatory health, methylation is a very important process. When methylation is impaired, there can be the accumulation of the wrong types of cellular byproducts – types that are associated with inflammation, and clotting. When methylation is impaired, there can also be low levels of key components like phosphatidylcholine that are needed for cell membrane function, and for keeping the liver strong and healthy. Since methylation is involved in so many processes, it goes without saying that an impairment in methylation can wreak havoc.
Genetic testing has not found that women with PCOS actually have MTHFR any more than is found in the typical population. However, MTHFR has a strong effect on cardiovascular health, and miscarriage and is relatively common.
A new study set to find out exactly how MTHFR status could impact a woman with PCOS.
Genetic SNPs (or small, single changes in genes ) in the MTHFR gene cause a substance called homocysteine to increase in the blood. This is an even more significant issue if the person has a folate or vitamin B12 deficiency (folate and B12 are used to recycle homocysteine and reduce its levels) .
MTHFR and Insulin Resistance in PCOS
Homocysteine has been found to be associated with both cardiovascular disease and inflammation.
Few studies have looked into MTHFR and its relationship to insulin resistance to date until this one. In particular, researchers haven’t delved into its effect on women with PCOS. 
This study included 200 women with PCOS who had insulin resistance, and 200 without it.
Researchers created a cut off for the Diagnosis of Insulin resistance.
The Homeostasis Model Assessment of IR (HOMA-IR) was calculated based on following formula (21):
HOMA−IR: Fasting serum insulin (μU/ml) × Fasting plasma glucose (mg/dl)/ 405. The HOMA-IR cut-off levels were 2.07 (22).
The study actually found a surprising result. Frequencies for the CC (healthy), CT(mild), and TT(severe)MTHFR 677C>T gene polymorphism genotypes were, respectively, 46%, 48%, and 6% in PCOS women without insulin resistance.
Compare this to 28%(healthy), 53%(mild), and 19%(severe) in PCOS women with insulin resistance.
This study shows clearly that the women who had the more problematic MTHFR gene snp were also significantly more likely to have insulin resistance. Additionally, this research also confirmed another study, not on women with PCOS. That study found the T genotypes were more common in patients with insulin resistance.
Benefits of Knowing your MTHFR Status
High levels of homocysteine and other inflammatory products typically found in patients with this gene’s T variations can cause dysfunction of blood vessels’ inner lining. This in turn can promote the development of insulin resistance.  Interestingly, the cardiovascular system is often where the first signs of insulin resistance begin.
For women with PCOS of all age ranges, this is key information – since insulin resistance and inflammation aggravate so many elements of PCOS – we can’t ignore our methylation status in our overall health.
For women with PCOS who are trying to conceive, increased clotting, inflammation and insulin resistance is associated with miscarriage, ovulatory dysfunction and lower egg quality. Improving methylation status can increase the health of the baby during development by exposing them to less inflammation and insulin resistance.
Overall, women with PCOS—especially with insulin resistance—would benefit from knowing their MTHFR status. This knowledge can have a major impact on their metabolic and cardiovascular health as they age.
Key nutrients for those with the MTHFR snp includes Vitamins such as B6, methylB12 and methylfolate, trimethylglycine (TMG), anti-inflammatory or anticoagulant support.
Testing for MTHFR is available at:
Once you have your results, download the raw data and then upload it into pages such as Strategene or Prometease.
1. M N AA, Abd-El Fatah AH, Ahmed HS. Genetic polymorphism of
Methylenetetrahydrofolate reductase is associated with insulin resistance in
Egyptian women with polycystic ovary syndrome. J Gene Med. 2019 Feb 11:e3076
2. Choi SW1, Gu BH, Ramakrishna S, Park JM, Baek KH. Association between a single nucleotide polymorphism in MTHFR gene and polycystic ovary syndrome.Eur J ObstetGynecolReprod Biol.(2009);145, 85–88.