The world of Nutrigenomic research has been advancing, giving medical providers the opportunity to take individualized medicine to a whole new level. This is especially meaningful during pregnancy, a very delicate period of time when we take every precaution to support the best possible outcomes for mother and baby.
An important nutritional discovery took place in 1965, when we acknowledged the importance of adequate folate (Vitamin B9) for healthy fetal neurological development.
Folate is a nutrient needed for building neurotransmitters, DNA and for “methylation reactions,” a process involved in many physiological functions including DNA synthesis and repair, producing myelin for healthy brain and nerve cells, red blood cell production, and much more!
It’s not hard to see why these activities are crucial to growing a healthy fetus, and why optimal folate levels are important for a healthy pregnancy. For more information about folate, see our folate handout on our website: www.naturespathfamilywellness.com/handouts.
The genes involved in folate metabolism include:
DHFR
MTHFD1
MTHFR
MTRR
MTR
FOLR1
FOLR2
SLC19A1
MTHFS
SHMT
MTHFR is the most well-known and researched gene. More than a 1/3rd of the US population carries a genetic variant or Single Nucleotide Polymorphism a.k.a “SNP,” in one of these genes. These SNPs slow the enzymes that break down folate into a form that the body can use. For example, individuals with SNPs in their MTHFR gene can have almost 75% less available active folate (5-MTHF) due to having a slow acting MTHFR enzyme.
SNPs that affect folate processing and methylation have been shown to influence pregnancy and may increase the risk of pregnancy related conditions including preeclampsia, HELLP Syndrome, eclampsia, uteroplacental insufficiency, intrauterine growth restriction, recurrent pregnancy loss, gestational hypertension, placental abruption, neural tube defects, Down syndrome, subfertility, and miscarriage.
The relationship between these genetic SNPs and Preeclampsia is of particular interest because this condition is a major cause of maternal and perinatal mortality. Preeclampsia is a disorder that occurs during the second half of pregnancy and is characterized by constriction of maternal blood vessels, which causes high blood pressure and potential damage to maternal organs, including the placenta.
*A key sign of organ damage is protein loss through the urine (proteinuria), something your doctor or midwife will look for.
Research shows a hereditary component to preeclampsia that comes from both the maternal and paternal genes, both men and women born of a preeclamptic pregnancy are more likely to have a preeclamptic pregnancy of their own. Mothers with the MTHFR C677T genetic variant may have up to 5 times the risk of developing preeclampsia when compared to mothers without the genetic variant.
(FYI: This risk increases dramatically in areas of high air pollution!)
A clue to understanding why defects with folate processing may contribute to preeclampsia is by diving deeper into how we think preeclampsia occurs in the first place…
The basic idea is that early on in pregnancy the placenta doesn’t develop well and poorly attaches to the wall of the uterus. This leads to poor blood flow from mother’s uterus to the placenta, which causes the distressed placenta to release inflammatory chemicals. These chemicals are damaging to the mother’s own blood vessels, and cause her vessels to constrict, which decreases the blood flow to the mother’s body and organs, including the placenta. Decreased blood flow to the placenta perpetuates this cascade that we call preeclampsia.
It is a vicious cycle and it is very dangerous for both mother and baby!
So what does the process of preeclampsia have to do with folate?
Folate helps keep blood vessels wide and open through a chemical called nitric oxide, therefore a folate deficiency can affect how well blood vessels dilate and allow for healthy blood flow.
Additionally, the amino acid Homocysteine requires folate to be broken down. If folate is deficient, homocysteine will become elevated which leads to the production of toxic "free radicals." These free radicals cause inflammation and a nasty process called "endothelial dysfunction," which causes decreased placental growth.
Together, these processes may explain the connection between how genetic variants that decrease available folate can contribute to the process of preeclampsia.
Some other folate related “SNPs” that are associated with preeclampsia:
The genetic variant MTR A2756G in either mother or fetus increases the likelihood of developing preeclampsia and Intrauterine Growth Restriction, however this risk goes down significantly when mothers supplement with adequate folate (yay!).
Mothers with 2 copies (homozygous) of the MTHFD1 G1958A SNP may have increased risk of developing intrauterine growth restriction, which is associated with preeclampsia.
MTRR SNPs may be associated with Preeclampsia, as placentas from preeclamptic pregnancies can have 50% less expression of the MTRR gene when compared to normal pregnancies.
Nutritional and supplemental folate to support genes and reduce risk of pregnancy complications:
Eat plenty of natural folate containing foods such as: Fresh green leafy vegetables, legumes (lentils, chickpeas, pinto beans, black-eye peas, peas, black beans, edamame, tofu), avocados, asparagus, broccoli sprouts, beets, non-fortified brewer’s yeast, liver and kidney, nuts and seeds, and fruits (oranges, papaya, mango, pomegranate, kiwi, strawberry).
Supplement with at least 400 mcg of folate in the forms of 5-mthf and calcium folinate (not folic acid!) for at least 4 weeks before trying to conceive and continued supplementation until at least 12 weeks after conception (we recommend supplementing throughout the entire pregnancy!).
It may be advantageous to supplement with methylated folate, the most usable form that doesn’t require the body’s enzymes to process.
One study showed that women with a history of preeclampsia from a previous pregnancy, who supplemented with methyl-folate had half the rates of recurrent preeclampsia!. (we recommend supplementing throughout the entire pregnancy!).
References:
1.Williams PJ, Broughton Pipkin F. The genetics of pre-eclampsia and other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011. doi:10.1016/j.bpobgyn.2011.02.007
2.Valenzuela FJ, Pérez-Sepúlveda A, Torres MJ, Correa P, Repetto GM, Illanes SE. Pathogenesis of preeclampsia: The genetic component. J Pregnancy. 2012. doi:10.1155/2012/632732
3. Wu X, Yang K, Tang X, et al. Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis. J Assist Reprod Genet. 2015. doi:10.1007/s10815-014-0408-8
4. Haram K, Mortensen JH, Nagy B. Genetic aspects of preeclampsia and the hellp syndrome. J Pregnancy. 2014. doi:10.1155/2014/910751
5. Nagy B, Hupuczi P, Papp Z. High frequency of methylenetetrahydrofolate reductase 677TT genotype in Hungarian HELLP syndrome patients determined by quantitative real-time PCR. J Hum Hypertens. 2007. doi:10.1038/sj.jhh.1002122
6. Khidri FF, Waryah YM, Ali FK, Shaikh H, Ujjan ID, Waryah AM. MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: A case control study. BMC Med Genet. 2019. doi:10.1186/s12881-019-0905-9
7. Zhang Y, He X, Xiong X, et al. The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes. Prenat Diagn. 2019. doi:10.1002/pd.5396
8. Yang YL, Yang HL, Shiao SPK. Meta-prediction of MTHFR gene polymorphisms and air pollution on the risk of hypertensive disorders in pregnancy worldwide. Int J Environ Res Public Health. 2018. doi:10.3390/ijerph15020326
9. Osunkalu VO, Taiwo IA, Makwe CC, Quao RA. Methylene tetrahydrofolate reductase and methionine synthase gene polymorphisms as genetic determinants of pre-eclampsia. Pregnancy Hypertens. 2020. doi:10.1016/j.preghy.2020.02.001
10. Furness DLF, Fenech MF, Khong YT, Romero R, Dekker GA. One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency. Am J Obstet Gynecol. 2008. doi:10.1016/j.ajog.2008.06.020
11. Seremak-Mrozikiewicz A, Bogacz A, Bartkowiak-Wieczorek J, et al. The importance of MTHFR, MTR, MTRR and CSE expression levels in Caucasian women with preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2015. doi:10.1016/j.ejogrb.2015.03.009
12. Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet. 2018. doi:10.1007/s10815-018-1225-2
13. Tsang B, Cordero A, Marchetta C, et al. Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism on blood folate concentrations: a systematic review and meta‐analysis of trials and observational studies (LB311). FASEB J. 2014. doi:10.1096/fasebj.28.1_supplement.lb311
14. Servy E, Menezo Y. The Methylene Tetrahydrofolate Reductase (MTHFR) isoform challenge. High doses of folic acid are not a suitable option compared to 5 Methyltetrahydrofolate treatment. Clin Obstet Gynecol Reprod Med. 2017. doi:10.15761/cogrm.1000204
15.Obeid R, Holzgreve W, Pietrzik K. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? J Perinat Med. 2013. doi:10.1515/jpm-2012-0256
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17. Yan J, Jiang X, West AA, et al. Pregnancy alters choline dynamics: Results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women. Am J Clin Nutr. 2013. doi:10.3945/ajcn.113.066092
18. Drews K, Różycka A, Barlik M, et al. Polymorphic variants of genes involved in choline pathway and the risk of intrauterine fetal death. Ginekol Pol. 2017. doi:10.5603/GP.a2017.0039
19. Gorelova V, Ambach L, Rébeillé F, Stove C, Van Der Straeten D. Folates in plants: Research advances and progress in crop biofortification. Front Chem. 2017. doi:10.3389/fchem.2017.00021
20. Lamers Y, Prinz-Langenohl R, Brämswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006. doi:10.1093/ajcn/84.1.156
21.Ferrazzi E, Tiso G, Di Martino D. Folic acid versus 5- methyl tetrahydrofolate supplementation in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2020. doi:10.1016/j.ejogrb.2020.06.012
دور شيخ روحاني في المجتمع
يلعب شيخ روحاني دورًا محوريًا في حياة الناس، حيث يساهم بشكل كبير في توجيههم نحو النمو الروحي والارتقاء بحياتهم الروحية. يقوم الشيخ الروحاني بتقديم النصائح والإرشادات التي تساعد الأفراد على فهم أعمق لدينهم وتحقيق السلام الداخلي. من خلال التواصل المستمر مع الأفراد، يساعد شيخ روحاني في حل المشكلات الروحية والنفسية التي قد تواجههم.
تتمثل أهمية شيخ روحاني في المجتمع في كونه مرشدًا وموجهًا يساهم في نشر القيم الروحية والدينية. من خلال خطبه ودروسه، يعزز الشيخ الروحاني من روح المحبة والتعاون بين الناس، مما يساهم في بناء مجتمع قوي ومتماسك. إن دوره لا يقتصر فقط على تقديم النصائح، بل يتعدى ذلك إلى كونه مصدر إلهام للأفراد في رحلتهم الروحية.
تأثير شيخ روحاني على النمو الروحي
يعد النمو الروحي عملية…