Folate and MTHFR: How do they affect Pregnancy outcomes?
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1 Folate and MTHFR: How do they affect Pregnancy outcomes? Naturopath and MTHFR Support Australia Founder Carolyn Ledowsky
2 Carolyn Ledowsky
3 MTHFR Gene and pregnancy
4 ARE YOU TRYING TO FALL PREGNANT? What are the key issues affecting you? Have you been trying for a while with no success? Have you never tried and are just wanting to do the right thing to prepare? Do you have the MTHFR gene and are simply overwhelmed by what you should do?
5 MY QUESTIONS TO YOU. MAY 28 Are you are looking to fall pregnant in the next 6 months? Do You Have The MTHFR Gene Mutation?
6 PREGNANCY SOME ISSUES Hormonal imbalances particularly low progesterone, PCOS, endometriosis No ovulation Low healthy cervical fluid Endometrium not healthy Not enough follicles Multiple miscarriage
7 So why? What causes these issues? Genes that affect the proper clearing of hormones allowing estrogen to build up. Lack of folate to help the baby grow and develop Lack of preparation time pre-pregnancy to support good DNA Lack of proper nutrition Build up of toxins Thyroid issues
8 Your Genes Genes that affect hormones Key genes that affect estrogen are CYP 1B1, COMT, SULTS, Affects folate levels Affects homocysteine levels Lower ovarian reserve Egg death Higher AMH levels Lower E2 levels Neural tube defects spina bifida, anencephaly and encephalocele (usually days after conception Thrombophilia and pregnancy loss Recurrent IVF failure Unexplained Infertility DNA damage to sperm Recurrent miscarriage Autism Allergies in the child Low birth rate Spontaneous abortion
9 Lack of Folate A lack of folate is specifically linked to: Neural tube defects (due to a combined effect of low folate and high homocysteine Low quality sperm and DNA issues with sperm Thrombophilia clotting disorder Autism in the child ADD/ADHD /Behavioral issues Allergies Low birth weight
10 Lack of Folate Any period of rapid growth increases the need for healthy DNA production. Increased demand for the production of healthy DNA during pregnancy, due to the intense growth of the fetus. This DNA production is largely governed by: Adequate folate levels And therefore the MTHFR gene.
11 Lack of Folate The DNA health and nutrition stores are passed onto the fetus upon conception, along with MTHFR mutation. Health of both male and female at conception will determine how MTHFR is impacting their body, and to what degree this will then impact the baby. Well controlled/ managed MTHFR will affect the health of a fetus much less than an untreated MTHFR mutation.
12 If you have good Folate levels before you conceive, there will be less Congenital anomalies Folate (L-5MTHF) supplement during preconception reduces anomalies including neural tube defects Anomalies decrease with increasing folate dose
13 What Is MTHFR? MTHFR stands for : methylene-tetrahydrofolate reductase. It is an enzyme that converts folate you eat into the active form (5- Methyltetrahydrofolate). The folate you eat (DHF- dihydrofolate) has to be converted via many steps to the active folate 5-MTHF. The MTHFR enzyme affects this at the last step. So if you have a mutation in the gene then its going to be affecting how much active folate you have available.
14 The folate pathway
15 MTHFR - A Key Aspect of Methylation What is Methylation? It is the transfer of a methyl group (one carbon atom and 3 hydrogen atoms) onto amino acids, proteins, enzymes and DNA in every cell and tissue. Methyl groups are the On-Off switches of the cells activities All genuine healing is within the cell. When the cell and its membrane are healthy the other tissues and organs function properly.
16 MTHFR all part of a bigger pathway
17 MTHFR Polymorphism & Male Infertility
18 MTHFR and Female Fertility If unsupported, the MTHFR gene reduces the amount of methyl groups available for use throughout the body. Methyl groups are needed in the body to: Synthesise choline needed for brain health and development Balance neurotransmitters needed for healthy mood, sleep, digestion Modulate inflammation Keep the immune system strong Metabolise toxins and hormones e.g. oestrogen Crucial for DNA synthesis All of which are needed for to create the environment for a healthy pregnancy.
19 MTHFR and Female Fertility MTHFR Gene variants and high homocysteine levels are associated with: Lower ovarian reserves A diminished response to follicular stimulation Reduced chance of live birth after IVF Egg death Complications with: Egg development Preparation of the endometrium for implantation References available at end of presenta2on
20 MTHFR gene associated with higher AMH Reduced folate level and increased Hcy related to recurrent spontaneous abortion and other pregnancy complications Folic acid supplement & IVF/ICSI: 0.4 mg/d folic acid lower serum estradiol at ovulation and fewer oocytes 0.8 mg/d folic acid the above were compensated in full MTHFR received appropriate supplement: Elevated AMH level
21 MTHFR and Pregnancy: Depression MTHFR C677T variant is associated with a greater depressed mood during the second trimester of pregnancy which then went on to affect the stress and mood of the baby for life. READ MORE
22 MTHFR and Pregnancy In pregnancy, the MTHFR C677T mutation is linked with: Pre-eclampsia, specifically in Caucasian and East Asian populations. Recurrent Pregnancy Loss (RPL) Congenital Heart Defects (CHD) Down s Syndrome Thombophilia (related to MTHFR, Factor 5 Leiden and Prothrombin genes) Thrombophilia further link with hypertension, recurrent abortions and intra-uterine growth retardation. References available at end of presenta2on
23 Folate, MTHFR & Fetal Development MTHFR C677T linked with: Neural Tube Defects Autism Spina bifida, anencephaly and encephalocele. Occurs between 21 and 28 days acer concep2on. In countries without folic acid supplementa2on ASD children found to have higher levels of homocysteine and lower an2oxidant status. References available at end of presenta2on
24 Folate, MTHFR & Fetal Development MTHFR C677T and A1298C linked with: Cleft lip and palate. MTHFR C677T linked with: Low birth weight Allergies in offspring MTHFR A1298C linked with: ADHD Impaired Neurotransmitter synthesis References available at end of presenta2on
25 SO WHAT WILL YOU LEARN TODAY The latest research about the MTHFR gene and pregnancy How you can prepare for pregnancy knowing that you are doing the right thing What are the best strategies for you to take in the lead up to your pregnancy.
26 LATEST RESEARCH Arch Gynecol Obstet Nov 3. [Epub ahead of print] Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation. Yang Y 1, Luo Y 2, Yuan J 2, Tang Y 2, Xiong L 2, Xu M 1, Rao X 3, Liu H 4. Author information Abstract PURPOSE: Numerous studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss (RPL); however, the results remain controversial. The aim of this study is to drive a more precise estimation of association between MTHFR gene polymorphisms and risk of RPL. METHODS: We searched PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and RPL risk. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in the homozygous model, heterozygous model, dominant model, recessive model and an additive model. The software STATA (Version 13.0) was used for statistical analysis. RESULTS: Overall, 57 articles were included in the final meta-analysis. In maternal group the MTHFR C677T polymorphism showed pooled odds ratios for the homozygous comparison [OR = 2.285, 95 % CI (1.702, 3.067)] and the MTHFR A1298C polymorphism showed pooled odds ratios for recessive model [OR = 1.594, 95 % CI (1.136, 2.238)]. In fetal group the MTHFR C677T polymorphism showed pooled odds ratios for dominant model [OR = 1.037, 95 % CI (0.567, 1.894)] and the MTHFR A1298C polymorphism showed pooled odds ratios for dominant model [OR = 1.495, 95 % CI (1.102, 2.026)]. CONCLUSIONS: In summary, the results of our meta-analysis indicate that maternal and paternal MTHFR gene C677T and A1298C polymorphisms are associated with RPL. We also observed a significant association between fetal MTHFR A1298C polymorphism and RPL but not C677T. KEYWORDS: A1298C; C677T; MTHFR; Meta-analysis; Polymorphisms; Recurrent pregnancy loss
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29 J Clin Diagn Res Feb;9(2):BC15-8. doi: /JCDR/2015/ Epub 2015 Feb 1. Evidence of Paternal N5, N10 - Methylenetetrahydrofolate Reductase (MTHFR) C677T Gene Polymorphism in Couples with Recurrent Spontaneous Abortions (RSAs) in Kolar District- A South West of India. Vanilla S 1, Dayanand CD 2, Kotur PF 3, Kutty MA 4, Vegi PK 5. INTRODUCTION: Recurrent spontaneous abortion (RSA) is a multifactorial clinical obstetrics complication commonly occurring in pregnancy. Many research studies have noted the mutations such as C677T in N5, N10 - Methylenetetrahydrofolate reductase (MTHFR)gene which is regarded as RSA risk factor. This study was carried out to determine the occurrence of frequency of C677T of the MTHFR gene mutations with RSA. AIM: The purpose of present study is to determine the frequency of MTHFR C677T polymorphisms in couples with recurrent pregnancy loss and the impact of paternal polymorphisms of MTHFR C677T in recurrent pregnancy loss in population of couples living in Kolar district of Karnataka with RSA. DESIGN: A total of 15 couples with a history of two or more unexplained RSA were enrolled as subjects in the study and a total of 15 couples with normal reproductive history, having two or more children and no history of miscarriages were enrolled as controls. MATERIALS AND METHODS: DNA extraction from samples case and control group couples and its quantification by Agarose gel electrophoresis, assessment of DNA purity, MTHFR C 677T gene mutation detection by PCR-RFLP method. RESULTS: The frequency of C677T genotype showed homozygous wild type CC (80%), heterozygous CT type (13.3%) and homozygous mutation TT type (6.67%) observed in males. Similarly from female's homozygous wild type CC (86.6%), heterozygous type (13.3%), and homozygous type mutations TT (0%) was recorded. In couple control groups, we observed homozygous wild type CC (86.6%), heterozygous CT type (13.3%) and homozygous type mutations TT type (0%). CONCLUSION: We noticed a high frequency of MTHFR specifically T allele associated with paternal side.therefore, the present study indicated the impact of paternal gene polymorphism of MTHFR C677T on screening in couples with recurrent pregnancy loss.
30 Indian J Hum Genet May-Aug; 15(2): doi: / PMCID: PMC MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India Cyrus Cyril, Padmalatha Rai,1 N. Chandra,1 P. M. Gopinath,1 and K. Satyamoorthy1 Author information Copyright and License information BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation. It stems predominantly from the failure of chromosome 21 to segregate normally during meiosis. Despite substantial research, the molecular mechanisms underlying non-disjunction leading to trisomy 21 are poorly understood. CONCLUSION: This first report on MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south Indian population revealed that MTHFR 677CT polymorphism was associated with a risk for Down syndrome. Go to:
31 Folic acid and sperm! Epigenetics involves the way the environment impacts the molecules in! your body which then can impact your genes.
32 ? So what question do you have for me? What do you need to know most?
33 CASE HISTORY KATHERINE Katherine had one child. Was into her 30 s and was desperate for another child, but was told that there was little or no hope. We worked on her methylation and she started to feel better. Still was told IVF probably wouldn t work.
34 CASE HISTORY KATHERINE Fell pregnant with no IVF, no assistance other than her supplements.
35 CASE HISTORY - ANNA Anna came to see me but didn t know she had the MTHFR gene. Had thyroid issues mostly. 1 year later, decided she wanted to fall pregnant.
36 CASE HISTORY - ANNA She fell pregnant first go!
37 Epigenetics Your genetic make up cannot change but epigenetics can change. Epigenetics involves the way the environment impacts the molecules in your body which then can impact your genes.
38 Epigenetics Mum and Dad s genes are involved. Our DNA may not be static, it can be modified because of epigenetics They key modifiable agents are methyl groups. These are affected by diet, stress, smoking, alcohol etc.
39 What Do We Do? Don t already know your MTHFR status? Check it: Genetic testing Local blood pathology ask for both variants i.e.: C677T and A1298C Address any underlying issues i.e.: Gut Allergies Depression and/or anxiety Toxic elements /detoxification issues Hormonal issues
40 Diet & Lifestyle for MTHFR Patients Gluten Free Dairy Free Most MTHFR patients are gluten sensitive. Zonulin, the protein in wheat is responsible for breaking down gap junctions in the gut wall and causing allergies and systemic inflammation. Increases xanthine oxidase a potent creator of ROS, nitric oxide and peroxynitrite & allergies
41 Diet & Lifestyle for MTHFR Patients Whole food and Low processed food - reduce inflammation and burden on detox pathways and systems of elimination No alcohol for either parent in preconception Coffee linked to miscarriage No smoking - either partner Healthy weight Get enough exercise
42 Diet & Lifestyle for MTHFR Patients High in vegetables - alkalizing, natural folate and antiinflammatory action. Modulate stress uses up methyl groups and cortisol shuts off reproductive function Remove all environmental and household toxins Eat organic where possible
43 Diet & Lifestyle for MTHFR Patients All foods should be as fresh and organically grown/fed whenever possible. See the dirty Dozen list - there is the list of the foods that should be bought organic and those with the lowest pesticides. If you can t afford to buy organic all the time then avoid the dirty dozen. Buy organic chicken and eggs. Do not over cook foods. Do not use a microwave for cooking Eat seasonally and follow what the organic/farmers markets are growing and only buy those fruit and vegetables at that season. Eat locally grown. If you are buying oranges all year round then you know that you are buying the 'off season' fruit that has been imported from another country and/or frozen/cold stored for long periods of time.
44 Diet & Lifestyle for MTHFR Patients Avoid saturated fats that are toxic like fried food. Use cold pressed, plant based oils in salads like extra virgin olive oil, flaxseed, nut oils Use coconut oil or grape seed oil or rice bran oil for cooking as they have a high smoke point (don't cook with olive oil) Eat protein at every meal. Protein is essential for both mum and baby Avoid farmed raised fish, choose wild ocean fish. Avoid soy as it may disrupt thyroid function
45 Diet & Lifestyle for MTHFR Patients Avoid delicatessen meats as they are high in fats and contains toxic sulphates and nitrites. Drinks - drink clean filtered water, herbal tea. Exercise but not over exercise (remember they use up methyl groups) Keep a good body weight and avoid obesity or being underweight. You need a minimum of 22% body fat to have good hormonal levels. Most women cannot fall pregnant if body fat levels are below 22%. Keep stress under control - it uses up methyl groups.
46 Nutrients Vital for a Healthy Pregnancy Methyl-folate Optimally taken 4 months prior and throughout pregnancy Needed for rapid cell division & for production of DNA. Dramatically reduces the incidence of birth defects such as Neural Tube defects, cleft lip, cleft palate, cardiovascular disorders, Impaired neurological development in newborns has also been linked to low maternal folate levels. Vitamin B12: Vitamin B6: Rapid cell division Closure of the neural tube during the first month of embryogenesis. Low maternal vitamin B6 status during the early stages of pregnancy has been associated with an increased risk of miscarriage. This may be due to its role in implantation and early placental development, as well as to its role in progesterone synthesis. Co factor for much of the methylation cycle.
47 Supplements for heterozygous mutations and basic for homozygous You need a good pregnancy multivitamin with methylfolate. Only forms to have that are therapeutic are: L-5-MTHF (avoid R forms) Quatrefolic Metafolin L-methylfolate (6S) 5-MTHF You also need this in combination with folinic acid as this will help MTR/MTRR activity. AVOID FOLIC ACID
48 Nutrients Vital for a Healthy Pregnancy Vitamin A Iron: Iodine Zinc Protein Vitamin C Vitamin D Calcium and magnesium Vitamin E Vitamin K Omega 3 s Phosphatidylcholin e Inositol CoQ10 Alpha lipoic acid
49 So What Have We Got? A good multivitamin A good quality prenatal DHA Magnesium Calcium Additional iodine if required A good antioxidant with alpha lipoic acid, co Q10, inositol, vitamin E Phosphatidylcholine An additional B12/folate depending on your presentation.
50 Important Things to Remember Other mutations may require further assistance i.e.: PEMT/BHMT choline BCOM1 vitamin A MTR/MTRR vitamin B12 Homozygous MTHFR C677T may require additional methyl folate/b12. All MTHFR mutations require liver support/ glutathione and antioxidant support in the pre-conception phase. This is a must because your ability to detoxify is compromised. Hormonal balancing is part of this. References available at end of presenta2on
51 Important Things to Remember Side effects of methylfolate i.e.: when are you over methylating: Muscle pain, joint pain Irritability, increased anxiety Decrease in mood, even severe depression Headaches, vomiting, nausea Rash DON T SELF MEDICATE. GET PROFESSIONAL ADVICE IF YOU HAVE ISSUES References available at end of presenta2on
52 IT S A STEP BY STEP GUIDE What you are getting: 8 amazing modules MTHFR gene Blood tests and analysis Supplements to take and at what dose Your diet How to prepare your home
53 IT S A STEP BY STEP GUIDE What you are getting: 8 amazing modules Environmental assessment endocrine disrupting hormones What exercise is best What fertility issues do men and women have? When should you start trying and what's the best time? What next?
54 WHAT YOU LL GET Workbooks Checklists Handouts Video trainings Calendars Bonus videos from experts in the field
55 What are you not going to get? Supplements are not included because these depend on you. You are not getting a quick fix You are not getting a magical pill You are not getting flippant advice You are not getting a superficial course
56 The Course Step by step guide that takes you through all stages of preparing for pregnancy. Including: What MTHFR is How it affects pregnancy Testing and analysis Supplements Nutrition and food Preparing your home Environmental assessment and endocrine disrupting hormones Exercise Fertility issues for men and women The best time to try. Our Price is $797 AUD or $95 per month for 10 months References available at end of presenta2on
57 Course Feedback I rate the course 10/10. I loved everything about it. I ve learned a lot of valuable information that I will use for the rest of my life and I have been able to help family members and friends with passing on this information. I have fallen pregnant!!! Carolyn this has been a fantastic course. Please write another one!! References available at end of presenta2on
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59 So What now? If you are wanting a pre-conception step by step guide then you are in the right place. My pre-conception signature course has just launched so get the launch special price. Bonus will be my interview with Ben Lynch
60 MTHFR Polymorphism & Male Infertility hhp:// hypotheses.com/ar2cle/s (08) /abstract?cc=y=
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