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Dealing with the heartbreak of a lost pregnancy can leave many people asking – why? While the answers aren’t always known, there are some cases where the parents’ genetic variants can interact with diet and lifestyle to increase miscarriage risk. This article dives into the MTHFR variants and miscarriage risk – with added information.
MTHFR and Miscarriages
There are quite a few studies showing that women carrying certain MTHFR variant combinations are at a somewhat higher risk for recurrent miscarriages. Almost all of these studies point to a small, yet statistically significant increase in miscarriage risk for women carrying MTHFR variants.[ref][ref]
Want to learn all about MTHFR? Check out this article.
Recently, I ran across a study that added a new twist to the topic. It turns out that the father’s MTHFR variants can also play a role in recurrent miscarriages.
This makes sense. Both the DNA in the egg and the DNA in the sperm need to be complete and without significant errors in order to become a baby.
Importance of Dad’s MTHFR Variants in miscarriage
The study from 2015 looked at 225 couples with more than three consecutive pregnancy losses compared with 100 control couples with successful pregnancies. All 225 mothers in the pregnancy loss group carried either compound heterozygous MTHFR C677T and A1298C variants or homozygous C677T or homozygous A1298C. The study defined carrying just one copy (heterozygous) of either C677T or A1298C as being at low risk for miscarriage.
When the researchers looked at the fathers’ MTHFR variants, they found that in the pregnancy loss group, the men were more likely to carry the risk variants.[ref] This backs up the work of other, smaller studies that also found that the male’s MTHFR status, combined with the mother’s MTHFR variants, does seem to statistically increase the risk of miscarriage.[ref]
There are a couple of things that could be going on here
First, fathers who carry the MTHFR variants are likely to pass them on to the baby. There are a couple of studies showing that the baby’s MTHFR variants may play a role in miscarriages. On the other hand, there are quite a few studies showing no effect from the baby’s MTHFR gene. Overall, the meta-analyses that combine all the study data tend to show little to no effect on the baby’s MTHFR status, so this is probably not the reason.[ref]
The second possibility of why the father’s MTHFR variants matter could tie in with the fact that men carrying homozygous MTHFR variants are also at a higher overall risk for infertility.
A meta-analysis pooled the results of 20+ studies and showed that men carrying either the homozygous MTHFR C677T or A1298C variants were at a higher risk for infertility (29 – 63% increase). Statistics here… Keep in mind that this is just the increase in the risk of infertility compared to the normal risk. For example, if the risk of male infertility is 1 in 20, a 69% increase would make the risk 1.69 in 20.[ref]
One of the final steps in sperm creation involves methylation of the DNA and packing it up correctly in the nucleus. Decreased methylation cycle nutrients could be affecting this final step in sperm creation. Alternatively, the methylation cycle and the MTHFR variants impact the way the cells deal with oxidative stress. Excessive oxidative stress can also impact and damage the DNA in the sperm. [ref]
MTHFR Genotype Report
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Lifehacks: Folate for Dads
Dads matter!
In conception, pregnancy, and throughout life! It is easy to see how prospective moms need to clean up their diets, exercise, and sleep well before getting pregnant, but I think these studies are a good reminder that prospective fathers need to pay attention to their own health as well!
Eating more folate
MTHFR variants (read more here) increase the need to ensure adequate folate consumption. This means leafy green veggies, legumes, and other organic food sources of folate need to be eaten daily.
Methyl folate and vitamin B12
If dietary changes aren’t possible, there are methyl folate supplements as well. A quality B12 is also important, and many people find it convenient to take a B-complex to cover all the bases.
Which type of B12? Check your COMT variants
I didn’t find any specific studies looking at men supplementing with folate for recurrent miscarriage, but there are studies showing that it is effective for women. One recent (small) study found that 5mg of methyl folate along with B6 and B12 decreased the risk of miscarriage.[ref]
Folic acid vs. methyl folate
Please note that methyl folate is likely the better form of supplemental folate vs. folic acid,[ref], but some studies show that a folate-rich diet is as effective as either methyl folate or folic acid. [ref]
One reason for methyl folate instead of folic acid is that there have been several recent studies linking high doses of folic acid to things like an increased risk of allergies[ ref] and some epigenetic changes that are a bit of an unknown.[ref]
There are also genetic variants that can impact whether folic acid or methyl folate may work better for you.
Recap of your genes:
| Gene | RS ID | Your Genotype | Notes for Your Genotype | Effect allele | Effect allele frequency |
|---|---|---|---|---|---|
| MTHFR | rs1801133 | — | typicalone copy of MTHFR C677T allele, enzyme function decreased by 40%two copies of MTHFR C677T, enzyme function decreased by 70 – 80% | A | 0.33 |
| MTHFR | rs1801131 | — | typicalone copy of MTHFR A1298C (heterozygous), slightly decreased enzyme function by ~10-20%two copies of MTHFR A1298C (homozygous), decreased enzyme by about 20-30% | G | 0.3 |
| MTHFR | rs2274976 | — | typicalsomewhat increased risk of schizophrenia, cognitive issues possible for seniors with this genotype in conjunction with low vitamin B12associated with cleft lip, neural tube defect, higher homocysteine, and folate deficiency, increased risk of schizophrenia in children, cognitive issues possible for seniors with this genotype in conjunction with low vitamin B12, risk of lower bone mineral density if B12 is also low | T | 0.04 |
| MTHFR | rs4846048 | — | typicalincreased relative risk of cervical cancer through miR-522 interactionincreased relative risk of cervical cancer through miR-522 interaction | G | 0.3 |
| MTHFR | rs9651118 | — | most common genotypedecreased risk of liver cancer, slower cognitive decline in the elderly, lower homocysteine, type 2 diabetes (compared to T/T)decreased risk of lung cancer, lower homocysteine, type 2 diabetes (compared to T/T) | C | 0.2 |
| MTHFR | rs13306560 | — | typicalavg 2.6 mmHg lower diastolic blood pressureavg 5.2 mmHg lower diastolic blood pressure, protective against Parkinson’s | T | 0.05 |
| MTHFR | rs17367504 | — | typicalprotective against hypertension, preeclampsiaprotective against hypertension, preeclampsia | G | 0.14 |
| MTHFR | rs4846049 | — | typicaltypicaldecreased risk of migraines, lower relative risk of cervical cancer | G | 0.61 |
Related Genes and Topics
References:
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