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Miscarriage:  Why are rates skyrocketing?
By: Keith Vrbicky, MD

Those of us caring for women in the reproductive age group have noticed an alarming increase in the rate of miscarriages.  The New England Journal of Medicine recently published a report estimating that 30% of pregnancies result in miscarriage, making it the most common adverse outcome of pregnancy.  In fact, miscarriage rates are rising at approximately 1% per year according to this 2018 study.  Odds are you or someone you know has experienced a miscarriage.

Many strategies are used to attempt to prevent miscarriages, such as proper nutrition, clean water, stress management, positive affirmations, and continuing to consume prenatal vitamins.  Most miscarriages do occur in the first trimester (less than 14 weeks’ gestation); however, episodes of unexplained bleeding in the second or third trimester can also occur without any obvious reason.  The mystery of these unexplained bleeding episodes and recurrent miscarriages appears to possibly be related to the MTHFR gene variants.  The MTHFR gene produces the MTHFR enzyme, which is short for methylenetetrahydrofolate reductase.  This enzyme turns folate (vitamin B9) into methylfolate, which is the form of folate that is usable by your body.  Methylfolate donates methyl group to other compounds in the body.  That process is called methylation.  Methylation is required for proper functioning of nearly all processes in your body, such as:  Regulating gene expression; repairing damage cells; creating neurotransmitters that influence mood, sleep, behavior, cognition, and memory; building immune cells; antioxidant production; processing hormones, such as estrogen; producing energy; and detoxifying the body.  Additionally, methylation is critical during pregnancy because it is required for making new RNA, DNA, fats, and proteins.  It is required for the creation of new cells in the growing baby as well as the placenta.  Consequently, if the methylation pathway is down regulated, it can lead to miscarriage.

Blood testing is available that can screen for genetic variants of the MTHFR gene.  If this is positive, the body has a decreased ability to clear toxins.  It also explains a reason for repetitive miscarriages.  A decreased ability to methylate is an often overlooked explanation for miscarriage.  It is not commonly discussed among medical doctors, yet, it is estimated that up to 40% of the population has a variant of the MTHFR gene.

When you have a variant of the MTHFR gene, the enzyme made from that gene does not work as efficiently.  The result is anywhere from 30%-70% reduction in enzyme activity.  This results in significantly less production of methylfolate than someone who does not have the genetic variant.  The degree of impairment depends on the specific gene variant as well as individual factors.  Impairment of the methylation process can also occur due to the deficiencies in certain micronutrients, stress level, and overall toxic burden from chemicals in the water and food.  It is critically important to recognize that reduced ability to methylate has a profound impact on health including increased risk of miscarriage.

To potentially aggravate matters, when a woman desires to become pregnant, she is usually instructed by her clinician to consume high doses of folic acid in the supplemental form in order to prevent neural tube defects.  Unfortunately, the potential problem with that advice is twofold: first, folic acid is the synthetic form of vitamin B9.  The body does not metabolize synthetic folic acid in the same manner as natural occurring folate.  Furthermore, synthetic folic acid may compete with natural sources of folate, such as folate derived from green leafy vegetables and liver.  This consequently can block the methylation process.  Therefore, the same supplements that are being recommended to prevent neural tube defects could be contributing to miscarriages in women who have a variant of the MTHFR gene.  Secondly, it appears that neural tube defects are not the result of folic acid deficiency.  It appears they are in fact the result of a methylation deficiency.  Therefore, folic acid supplementation may actually be harmful to some women and unborn babies that have an MTHFR variant. All women should be taking vitamins with L-methylfolate, the active form of folic acid.

Some studies are showing that severe nausea (hyperemesis) early in the pregnancy may be a symptom of poor methylation.  Knowing this, we would recommend consideration to compensate for the reduced ability to methylate by:  Prior to trying to conceive, a functional blood test to determine possible nutrient deficiencies and the MTHFR mutation.  This will help modify the diet and possible supplements of the missing nutrients.  Increasing consumption of foods naturally rich in folate that include organic leafy green vegetables such as spinach, kale, mustard greens, collard greens, turnip greens, and romaine lettuce as well as small amounts of liver.  If possible, choosing whole foods instead of processed foods with every meal.  Many of them are also high in the unhealthy sugars-fructose, sucrose, and glucose. 

Lastly, checking the nutritional label of the prenatal vitamins.  If folic acid is listed, consider using a vitamin that contains the active form of folic acid-5, methylenetetrahydrofolate, which is the form of this vitamin that the body can readily use.

Credit: Dr. Sina McCallough, who holds a doctorate in Nutrition from the University of California-Davis.