You have it backwards. The Made-in-China, synthetic folic acid is far more powerful than the form that is found in food. Even people who don’t have methylenetetrahydrofolate reductase mutation are harmed by the synthetic. Taking a supplement and eating foods containing the synthetic causes chronic diseases.

For years, decades, I’ve been like a car running on fumes. Every once in a while, I may feel good, energetic, happy, (like once a year) but overall, I mostly experience fatigue and negative feelings. I’ve tried everything, but the kitchen sink, to address the anxiety, depression, low energy, lack of positive feelings. (When someone hugs me, I feel nothing. A hug has to be about 30 seconds, for me to feel warm and fuzzy.) Because I’ve not felt positive feelings for so long, I think I just learned to fake it. Sad, but true. What else does one do, when joy doesn’t just bubble up from within?

Add to that growing anxiety, panic attacks, anxiety that was off the charts, severe depression, I was losing hope.

After being on the above supplements for one week, I actually feel pretty good. My mind isn’t racked with worries, I feel more comfortable in my own skin, I actually feel tired inside and out (after 10pm), some happy memories and songs came to mind this week, I feel less anxious as each day passes, and I even had a great laugh with a new friend, so I’m hopeful. (I usually have a good laugh every 2-5 years. :/ No joke. This is the truth. No exaggeration.)

I’m only taking 800 mcg of L Methylfolate each day. Maybe Deplin is overkill?

Sally, please provide even ONE research study from Pubmed or even Google Scholar to back up your claim that ‘methylfolate stimulates the production of adrenaline’ and ‘ increases the breakdown rate of serotonin.

At the time I found out BC/BS would not cover the then $3000 DNA test unless you were a woman and had 3 miscarriages. I was lucky and came across one of the studies that did the DNA test near the $85 real cost if you allowed them to use the results in the study.

Once diagnosed BC/BS covered the L-Methylfolate with B12 that the doctor prescribed. I and those around me quickly noticed the improvements to my health.

But a couple years later BC/BS dropped the coverage for the supplement. And sadly they are one of the insurances with the best coverage.

This is where the problem started. The market price at the time was quite high (about $150-200 for a one month supply). Soon after I gave up on it.

I am wondering if with the increased medical evidence insurance coverage has come back, or whether non-prescription prices have dropped into an affordable range. Does anybody know?

There are other nuances this post misses.

I propose downloading and reviewing Yasko diagrams on the topic.

For one, it’s not accurate to say methyl folate is responsible for methylation.

The methhylfolate cycle works with MB12 to help recycle spent methyl donors used in the primary methyl cycle. Think of two spinning particle fields thousands of times a second interacting at intracellular level.

MB12 help recycle MF which in turn replenish spent methyl donors eg homecysteine that was once choline/DMG/TMG/SAM-e->methionine which donate their methyl molecules for methylation as well as to the transsulfuration cycle which drives taurine to glutathione production, after which a spent methyl donee that is homecysteine becomes a reactant that needs to be replenished.

There are many papers that talk about the import of various cholines (CDP, AGPC, etc.) and methyl donors (TMG, DMG, SAM-E) and how they help spare Methylfolate and vice versa, but they are *not* co-equivalent substitutes.

Methylfolate if anything is more key to driving the BH4BH2 cycle that is precursors to the three horsemen neurotransmitters cited above which is related to methylation insofar as methylated serotonin transforms into melatonin for example.

I would review methylation diagrams and include that in these posts. I think visually, and translate math and physics into cause and effect process diagrams, while also mastering the equations. Depending on how one is wired, the right diagram(s) will help make these complex concepts more precise as words are too easily overloaded.

I continue to rely on Yasko diagrams and consider them central to any supplementation regime. Genetic mutations are static decision points. Biology is a dynamic flow and should be discussed thusly.

You are missing the point.  People should throw out their multi-vitamins because the cheap synthetic folic acid in the vitamins build up in the body, so it can cause major health problems- birth defects, cancer, cardiovascular disease, and dementia because most people have a reduced ability or can not methylate cheap synthetic folic acid or folate into methylfolate because they have a MTHFR gene defect copy.

Keep in mind that a deficiency of the good stuff- methylfolate, causes side effects- including stomach problems and inflammation, hair loss, anemia, and high homocysteine levels which are linked to heart disease, vascular dementia, erectile dysfunction, depression, and cancer. Doctors can give you a prescription of Metanx or buy Life Extension 2 Per Day Vitamins or similar vitamins that have methylfolate, plus buy betaine, or buy methylfolate also known as 5-MTHF plus betaine also known as TMG.  The reason- You also need betaine or TMG with the methylfolate to reduce homocysteine levels as methylfolate alone does not reduce homocysteine. Do not eat vitamin supplements with folic acid- the bad stuff. It causes cancer! Throw out your vitamins. Do not eat foods fortified with extra folic acid found in bread, cereal, flour, cornmeal, pasta, rice, and other grain.  It is so bad that as little as 5 mg a day of folic acid for 90 days increases serum unmetabolized folic acid which causes reduced natural killer cell cytotoxicity which causes cancer and reduces defenses against virus infections in humans.  

MTHFR mutation which up to 85% of us may have, increases the risk of cardiovascular disease and vitamin B deficiencies due to high homocysteine levels. Those with an MTHFR mutation are at risk for poor MTHFR enzyme efficiency. Consequently, folate and folic acid cannot be efficiently converted into their active form, known as 5-MTHF or L-methylfolate. So, those who have a MTHFR gene defect  (which most of us in the whole world have) can not process folate and especially folates in the form of cheap synthetic folic acid found in normal vitamins into methylfolate. Do not underestimate how important proper methylation is and how sick and closer to death we get if we are deficient our whole life long. Methylation is needed to stop high levels of homocysteine for cardiovascular health, vascular dementia, and erectile dysfunction. Methylation is needed to decrease inflammation for every disease we do not want to get. Methylation is needed for DNA stabilization in DNA replication, so we are reproducing healthy cells needed to regenerate our bodies. Methylation is needed to keep telomeres long and to keep us from aging rapidly. Methylation is needed to make neurotransmitters like serotonin, dopamine and norepinephrine to stop neurodegeneration, dementia and prevent psychiatric illnesses. Methylation is needed to make hormones in our mitochondria which mitochondria are the power house of every cell.http://www.gbhealthwatch.com/GND-Cardiovascular-Diseases-MTHFR.php
Two common variants of the MTHFR gene, 677C>T and 1298 A>C, lead to reduced enzyme activity and increased risk for hyperhomocysteinemia, cardiovascular diseases and cancer. The distributions of these two variants are quite high, with frequencies between 13 to 57% depending on ethnic group (Table 1). Overall, about 85% OF THE GENERAL POPULATION CARRIES AT LEAST ONE OF THESE MTHFR VARIANTS.  In addition, functional interaction between these two variants results in an additive effect on MTHFR enzyme activity. The compound heterozygous genotype, which refers to people carrying both variants is found in between 14% and 23% of people within most ethnic groups (Table 1) and can reduce enzyme activity by up to 48%. (Note: your articles only uses the 14% and 23% figures and saying it wrong with the MTHR C667 gene mutation, so your conclusion has no impact.)
https://www.ncbi.nlm.nih.gov/pubmed/27012626 “High folic acid reduces natural killer cell cytotoxicity in aged mice.” note: Low natural killer cell number or function in elderly individuals is associated with increased mortality risk and increased incidence of severe infections, supporting the role of natural killer cells in the defense against infections in the elderly.
https://www.ncbi.nlm.nih.gov/pubmed/23482308 “Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?” Yes. Methylfolate is better than folic acid.
https://www.ncbi.nlm.nih.gov/pubmed/28895788 “Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods.”
https://www.ncbi.nlm.nih.gov/pubmed/20727555 “Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults.”
https://www.ncbi.nlm.nih.gov/pubmed/25733468 “Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults.”
https://www.ncbi.nlm.nih.gov/pubmed/28724658 “A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610948/ “Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis.”

This article should stress the importance of methylation. This article should actually be a wake up call to the supplement industry to reformulate vitamins to take out folic acid which kills natural killer cells that reduce defenses against viruses and causes cancer, and replace folic acid with methylfolate; otherwise Life Extension vitamins will take away all of their business and doctors will be prescribing Metanx instead.  This article should be a wake up call to the pharmaceutical industry that their drugs inhibit methylation and change our epigenetics in deleterious and permanent ways with tragic and enduring side effects.  Drugs should be taken off the market by the FDA if they cause more diseases than they cure.

http://www.medicinabiomolecular.com.br/biblioteca/pdfs/Nutrigenomica/nutrig-0043.pdf “Epigenetic side effects of common pharmaceuticals: a potential new field in medicine and pharmacology.” Epigenetics refers to DNA and chromatin Here is something to add. Alcohol and these drugs may stop methylation because they inhibit folic acid absorption in the stomach, reduce absorption of B vitamins, inactivate B vitamins, may make you deficient in B vitamins, elevate homocysteine, cause folate deficiency, can inhibit expression of the reduced folate carrier and decrease the hepatic uptake and renal conservation of circulating folate,  etc.  In other words, alcohol and these listed drugs below can stop methylation which is important for DNA replication and mitochondrial function. They can affect hormone synthesis in mitochondria, affect your body’s ability to make neurotransmitters, increase inflammation in our bodies, cause high homocysteine, heart disease, erectile dysfunction, dementia, neurodegeneration and psychiatric disorders. Alcohol and drugs that detrimentally affect methylation for those with the MTHFR defect: Antacids, proton pump inhibitors, histamine blockers, anti-depressants/SSRIs, statins, cholesterol lowering medications, amalgram fillings, fluoride, acetaminophen, fish oil, asthma medications-Theophylline, albuterol and prednisone, Anticonvulsants, Cyclosporine, Methotrexate, Dilantin, Neuroleptics Colchine, Oral diabetic medications-Metformin, Ethionamid, Cycloserine, Aminosalicylic acid, Antibiotics, phenytoin, fosphenytonin, phenobarbital, cobalt, chlorpromazine, methylprednizone, synthetic hormone birth control, levodopa, antihypertensives, methotrexate. Asthma medications-Theophylline, albuterol, prednisone.

This article should stress the importance of methylation. This article should actually be a wake up call to the supplement industry to reformulate vitamins to take out folic acid which kills natural killer cells that reduce defenses against viruses and causes cancer, and replace folic acid with methylfolate; otherwise Life Extension vitamins will take away all of their business and doctors will be prescribing Metanx instead.  This article should be a wake up call to the pharmaceutical industry that their drugs inhibit methylation and change our epigenetics in deleterious and permanent ways with tragic and enduring side effects.  Drugs should be taken off the market by the FDA if they cause more diseases than they cure.

http://www.medicinabiomolecular.com.br/biblioteca/pdfs/Nutrigenomica/nutrig-0043.pdf “Epigenetic side effects of common pharmaceuticals: a potential new field in medicine and pharmacology.” Epigenetics refers to DNA and chromatin Here is something to add. Alcohol and these drugs may stop methylation because they inhibit folic acid absorption in the stomach, reduce absorption of B vitamins, inactivate B vitamins, may make you deficient in B vitamins, elevate homocysteine, cause folate deficiency, can inhibit expression of the reduced folate carrier and decrease the hepatic uptake and renal conservation of circulating folate,  etc.  In other words, alcohol and these listed drugs below can stop methylation which is important for DNA replication and mitochondrial function. They can affect hormone synthesis in mitochondria, affect your body’s ability to make neurotransmitters, increase inflammation in our bodies, cause high homocysteine, heart disease, erectile dysfunction, dementia, neurodegeneration and psychiatric disorders. Alcohol and drugs that detrimentally affect methylation for those with the MTHFR defect: Antacids, proton pump inhibitors, histamine blockers, anti-depressants/SSRIs, statins, cholesterol lowering medications, amalgram fillings, fluoride, acetaminophen, fish oil, asthma medications-Theophylline, albuterol and prednisone, Anticonvulsants, Cyclosporine, Methotrexate, Dilantin, Neuroleptics Colchine, Oral diabetic medications-Metformin, Ethionamid, Cycloserine, Aminosalicylic acid, Antibiotics, phenytoin, fosphenytonin, phenobarbital, cobalt, chlorpromazine, methylprednizone, synthetic hormone birth control, levodopa, antihypertensives, methotrexate. Asthma medications-Theophylline, albuterol, prednisone.

This article should stress the importance of methylation. This article should actually be a wake up call to the supplement industry to reformulate vitamins to take out folic acid which kills natural killer cells that reduce defenses against viruses and causes cancer, and replace folic acid with methylfolate; otherwise Life Extension vitamins will take away all of their business and doctors will be prescribing Metanx instead.  This article should be a wake up call to the pharmaceutical industry that their drugs inhibit methylation and change our epigenetics in deleterious and permanent ways with tragic and enduring side effects.  Drugs should be taken off the market by the FDA if they cause more diseases than they cure.

http://www.medicinabiomolecular.com.br/biblioteca/pdfs/Nutrigenomica/nutrig-0043.pdf “Epigenetic side effects of common pharmaceuticals: a potential new field in medicine and pharmacology.” Epigenetics refers to DNA and chromatin modifications that persist from one cell division to the next, despite a lack of change in the underlying DNA sequence. The “epigenome” refers to the overall epigenetic state of a cell, and serves as an interface between the environment and the genome. The epigenome is dynamic and responsive to environmental signals not only during development, but also throughout life; and it is becoming increasingly apparent that chemicals can cause changes in gene expression that persist long after exposure has ceased. Here we present the hypothesis that commonly-used pharmaceutical drugs can cause such persistent epigenetic changes. Drugs may alter epigenetic homeostasis by direct or indirect mechanisms. Direct effects may be caused by drugs which affect chromatin architecture or DNA methylation. For example the antihypertensive hydralazine inhibits DNA methylation. An example of an indirectly acting drug is isotretinoin, which has transcription factor activity. A two-tier mechanism is postulated for indirect effects in which acute exposure to a drug influences signaling pathways that may lead to an alteration of transcription factor activity at gene promoters. This stimulation results in the altered expression of receptors, signaling molecules, and other proteins necessary to alter genetic regulatory circuits. With more chronic exposure, cells adapt by an unknown hypothetical process that results in more permanent modifications to DNA methylation and chromatin structure, leading to enduring alteration of a given epigenetic network. Therefore, any epigenetic side-effect caused by a drug may persist after the drug is discontinued. It is further proposed that some iatrogenic diseases such as tardive dyskinesia and drug-induced SLE are epigenetic in nature. If this hypothesis is correct the consequences for modern medicine are profound, since it would imply that our current understanding of pharmacology is an oversimplification. We propose that epigenetic side-effects of pharmaceuticals may be involved in the etiology of heart disease, cancer, neurological and cognitive disorders, obesity, diabetes, infertility, and sexual dysfunction. It is suggested that a systems biology approach employing microarray analyses of gene expression and methylation patterns can lead to a better understanding of long-term side-effects of drugs, and that in the future, epigenetic assays should be incorporated into the safety assessment of all pharmaceutical drugs. This new approach to pharmacology has been termed “phamacoepigenomics”, the impact of which may be equal to or greater than that of pharmacogenetics. We provide here an overview of this potentially major new field in pharmacology and medicine.

http://suzycohen.com/articles/methylation/ “Medicine Messes Up Your Methylation.”

http://drhyman.com/blog/2011/02/08/maximizing-methylation-the-key-to-healthy-aging-2/

http://www.drkendalstewart.com/wp-content/uploads/2011/09/Methylation-Overview-for-Professionals-10.11.pdf

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=2441&path%5B%5D=4386 “Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells.”  (p53 is the tumor suppressor gene.)

http://www.nature.com/scitable/topicpage/The-Role-of-Methylation-in-Gene-Expression-1070 (Not all genes are active at all times. DNA methylation is one of several epigenetic mechanisms that cells use to control gene expression.)

Also, in your section…Methylfolate is responsible for many methylation reactions all throughout the body. ….The last sentence- You say, “A large part of the United States population has these mutations with 10-15% of Whites and 25% of Hispanics carrying the mutation MTHFR C667T, one of the more common mutations [R].”   It should say MTHFR C677, not 667.  However, your source says these statistics are only actually for one small particular variant with a double allele. I quote instead from your referenced ncbi source of what it actually says, “More than 25% of Hispanics and around 10-15% of North America Caucasians are estimated to be homozygous for the “thermolabile” variant (TT genotype) (4). The TT genotype is least common in individuals of African descent (6%) (5, 6).”    So you are quoting this completely wrong, plus drawing wrong conclusions.

Corrections.
Under….  SIDE EFFECTS AND RISKS OF METHYLFOLATE….. It says, “Furthermore, over-consumption of L-methylfolate (>148 pmol/L in the blood) has been linked to cancer, depression, and other cognitive disorders [R].”  Please re- Read that your source actually says folic acid, not methylfolate……Your source actually says, “…unmetabolized synthetic folic acid with regard to cancer, depression, and cognitive impairment. With all these concerns, early data suggest supplementation with l-methylfolate rather than folic acid may mitigate these risks.”

However the reference that you gave for that clearly states “Also, concerns have been raised about the potentially untoward effects of unmetabolized synthetic folic acid with regard to cancer, depression, and cognitive impairment.”

Clearly unmetabolized synthetic folic acid has these issues, not methylfolate. All the more reason not to take the synthetic folic acid,