Fish Oil and MTHFR, What Is The Link?

We’ve all heard about fish oils and omega3 fatty acids for so many incredible reasons. They are strongly anti-inflammatory and perform almost as well as non-steroidal anti-inflammatory tests for pain relief, without side effects. 

They have been most strongly studied for heart disease and show an almost unbelievable array of benefits. Fish oils reduce the risk of sudden death from cardiac arrhythmias, reduce all-cause mortality in patients with known cardiac disease, and help to treat high cholesterol (hyperlipidemia) and high blood pressure (hypertension.) All of this, without significant side effects or drug interactions

Studies have also shown that countries with higher intake of omega-3 fatty acids have lower rates of depression. Fish oils have also shown beneficial effects in both research and clinical practice for diabetes, Alzheimer’s disease, stroke, and autoimmune disease. 

What about Fish Oil and MTHFR?

Most studies aren’t MTHFR-specific.  But, fish oil has benefits for so many of the long-term consequences of unbalanced methylation in MTHFR, that it makes sense that there would be some link.  What reserach has found is some kind of synnergy between fish oil and B vitamins, in which the combination works better than either therapy alone.

Omega-three fatty acids and B vitamins for cognitive decline

A randomized placebo-controlled  trial of people with mild cognitive impairment found that treatment with B vitamins lowered homocysteine and slowed the rate of cognitive decline. Researchers went back and re-analyzed the data from this study to see if baseline levels of omega-three fatty acids interacted wtih the results in any way. The study involved mental testing over the course of two years.They found that for all outcome measures, higher concentrations of DHA significantly enhanced the effects of B vitamins, while the levels of EPA had less of an impact.

Not only that, when omega-3 fatty acid levels are low, B vitamin treatment has no effect on cognitive decline, but when omega threes are in the high-normal range, B vitamin treatment becomes effective. There is some synnergy happening here that needs further investigation to fully understand, but since omega-three fatty acids are good for so many things and truly haven’t shown negative consequences it makes sense to add them in as a no-risk measure for seniors with cognitive decline.

Omega-three fatty acids and homocysteine

The methylation process itself seems to be involved in the metabolism and distribution of these polyunsaturated fats through your body, which means that MTHFR and omega-3s are intimately linked. Also, it has been theorized that omega-three fatty acids actually have expression control on enzymes within the methylation cycle, so effectively MTHFR controls omega-threes, which control MTHFR. There is not a big enough body of research yet to draw firm conclutions, but the evidence is pointing in this direction.  For MTHFR folks, the most important thing to understand is that using fish oils and B vitamins together produces a great reduction in homocysteine levels than using either one alone. 


This research suggests that omega-3 fatty acids (referred to here as PUFA or polyunsaturated fatty acids) actually stimulates the action of the MTHFR enzyme, which activates folate to generate SAMe, the methyl donor. PUFA also stimulates the MAT enzyme which converts methionine to SAM, the CCT enzyme which is involved in the conversion of choline to phosphatidylcholine, and the CGL enzyme which is involved in the conversion of Homocysteine to Glutathione. 

Inflammation, heart disease, cognitive decline, and high homocysteine are all problems that happen more frequently in folks who have MTHFR with unbalanced methylation, and since fish oils effectively address these problems, it almost seems like a gimme.

Next week, we’ll talk about a few bits of research being done regarding fish oil and gene expression for MTHFR folks. The research is new, but it’s starting to get good.

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Who Should Care About MTHFR Mutation?

On the internets, it seems like everyone cares about MTHFR right now, but honestly, it isn’t necessarily important for everyone. Not even for everyone with a known mutation.

Just having a polymorphism is not a cause for panic. Having an MTHFR mutation, even one that is considered significant will never have any symptoms, signs, or health risks from the polymorphism. Just having the gene doesn’t mean anything at all in terms of supplements you should take, things you should do, or really anything else. In fact, over supplementing can be as harmful to your health as under supplementing.

This girl thinks you should care about MTHFR mutations.

Two Main Factors Make MTHFR Matter

  1. Your circumstances
  2. Your symptoms

Let’s review what MTHFR might do, and then we’ll talk more about circumstances and symptoms.

Possible Health Consequences of the MTHFR mutations

MTHFR mutations have been implicated in at least one research study in:

  • Midline Abnormalities: neural tube defects, anencephaly, spina bifida, cleft palate, cleft lip, and facial asymmetries.
  • Cancer: including breast, lung, brain, stomach, head and neck, and kidney.
  • Cardiac disease: including thrombosis (increased tendency to clot), deep vein thrombosis, high homocysteine levels, pre-eclampsia (high blood pressure in and around pregnancy), vascular dementia.
  • Fertility issues: including miscarriages or multiple pregnancy loss, low sperm count, history of children with birth defects.
  • Neurological issues: including migraines, autism, Alzheimer’s dementia.
  • Mood and Psychological issues: including anxiety, depression, obsessive-compulsive traits or tendencies, bipolar disorder, and schizophrenia. Also, reduced reactions to certain medications like SSRIs for depression, and increased tendency toward addictions.
  • Abnormal Reactions to Medications and Therapies – including methotrexate, FOLFOX (a combination chemotherapeutic agent), SSRI medications for depression, some vitamins including folic acid, methyl-B12, betaine, and others.

When Should You Be Concerned?

This is simple. These are the circumstances that matter:

  • Fertility and Pregnancy – if you suspect you or your partner might have an MTHFR issue and you’re considering having a baby, it matters to know so you can get your health right before you build a baby.
  • Treatments for Depression and Anxiety aren’t Working – this is a strong indicator that there is something underlying the issue that isn’t being addressed, and none of the medications out there manage MTHFR issues.
  • You Have a Strong Family History of Early Cardiac Death – it might not be related to MTHFR, but if it is then knowing your MTHFR status gives you something you can work on, instead of waiting for the ax to fall.
  • You Have Three Known Bad Copies of MTHFR – this is three compromised copies of significant MTHFR SNPs (C677T and A1298C) out of four.

Who Should Care about MTHFR Polymorphisms?

These are the symptoms that matter. If you or your genetically related family members have more than three of the following, then your life might get better by addressing your methylation, whether you know about your MTHFR or not.

  • Anxiety
  • Overachieving tendencies
  • Perfectionism
  • Obsessive thoughts
  • Insomnia
  • Cleft lip or cleft palate
  • Spina bifida
  • Abnormal or unexplained clotting
  • Bad reaction to birth control pills
  • Alcohol intolerance
  • Schizophrenia
  • Bipolar disorder
  • Repeat miscarriages
  • Unexplained low sperm count
  • Alzheimer’s dementia
  • Addictions
  • High homocysteine levels
  • Food or chemical sensitivities
  • Intense competitive drive
  • Serum folic acid tests is abnormally high or abnormally low
  • “New car smell” gives you a headache or other symptoms.
  • Taking B vitamins sometimes makes you feel depressed

Who Should Not Be Worried About MTHFR Polymorphisms?

  1. People who know they have no bad copies.
  2. People who know they have one bad copy but have no related symptoms or family histories.
  3. People who don’t know their genetic profile who also don’t have related symptoms or family histories.

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