How Does Folate Prevent Heart Disease?

When it comes to heart disease, the first thing that comes to mind for most people is cholesterol and with good reason; we’ve been hit over the head with the diet AND the lipid hypotheses of cardiovascular disease, including heart disease/heart attacks, for decades. In a nutshell, it goes like this: Saturated fat [diet theory] increases cholesterol levels in the blood and, in turn, high cholesterol levels [lipid theory] are associated with cardiovascular disease.

This highly over-simplified theory is not only largely out-dated, it’s essentially wrong and is primarily maintained by the manufacturers of cholesterol-lowering medications. For more on this, read my other posts 5 Reasons Why I Am Not Worrying About Saturated Fat, and Heart Health Is More Than Just Lowering LDL “Cholesterol”, and 9 Ways To Love Your Heart (and brain) With Food.


Inflammation Not Cholesterol Is The Culprit

Elevated blood cholesterol in and of itself isn’t the culprit. We are now moving towards seeing heart disease (and other vascular diseases such as dementia and stroke) as diseases of inflammation, and inflammation can be caused by many things including elevated blood sugar (as seen in insulin resistance, per-diabetes and diabetes), bacterial and viral infections, excessive alcohol, sugar and refined carbohydrate consumption, smoking, and oxidized [damaged] LDL cholesterol all of which promotes plaque formation.

Another driver of inflammation is elevated homocysteine. Lowering inflammation is, or rather should be, the primary goal of any medication, lifestyle, diet or supplement-based strategy to lower the risk for cardiovascular disease. From a medication point of view, benefits from statins are/can be attributed to mechanisms that have nothing to do with their cholesterol-lowering effects, not the least of which is lowering inflammation1.


When it comes to diet, one of the unsung heroes when it comes to cardiovascular/blood vessel health is the B vitamin folate, or vitamin B9.

Folate And Cardiovascular Disease

The terms folate and folic acid are used interchangeably but they are different and should be treated as such. Folate is the form of vitamin B9 that is found naturally in plant foods whereas folic acid is the synthetic form found in most supplements (except for higher quality brands) and is the form used to fortify foods.


While they do share similar metabolic activities, they are slightly different. Regardless, both folate and folic acid need to be converted into the metabolically active (usable) form of the B-vitamin called 5-MTHF (5-methyl-tetra-hydro-folate). This conversion is directed by a gene that produces an enzyme called MTHFR, BUT many people have ‘defects’ (mutations) in this gene and are therefore “poor converters”.

About 66% of us have at least 1 mutation resulting in a 40% reduction of enzyme activity. These folks will only produce about 60% of the possible 5-MTHF from a given amount of dietary folate or supplemental folic acid. Another 30% or so of us have 2 mutations which leads to a 70% reduction in enzyme activity which results in only 30% of possible 5-MTHF being made compared to those without the mutations.


Less 5-MTHF being produced means less to go round; the body must prioritize where it goes, so some systems will suffer.

Folate, Vascular Function And Cardiovascular Disease Risk

Folate, and more precisely, its usable form 5-MTHF, improves vascular health in several ways by:


1. Endothelial Function

Folate has been shown to improve and maintain endothelial function or the ability of blood vessels to expand (vasodilate) and contract (vasoconstrict) in a healthy way. Endothelial dysfunction refers to the impaired ability of blood vessels to expand optimally resulting in decreased blood flow, increased blood pressure, and blood vessel damage.

Endothelial dysfunction is recognized as a marker for, and associated with, a higher incidence of cardiovascular disease risk and the progression of atherosclerosis.


2. Homocysteine

Both higher intakes of dietary folate, as well as, randomized controlled studies using supplements of synthetic folic acid or the active form 5-MTHF, have been shown to not only lower levels of elevated homocysteine but homocysteine levels that are already in the normal range.

While homocysteine levels increase inflammation and are associated with cardiovascular disease, simply lowering homocysteine levels hasn’t always lead to decreased disease. It may be that a folate deficiency (due to low dietary intake or lower blood levels and/or lower amounts of the usable form due to reduced MTHFR activity) is the primary cause of vascular disease and elevated homocysteine is simply a maker of low/poor folate status.


3. Antioxidant Actions

Ample evidence shows that oxidative stress and free radicals are involved in the development of cardiovascular disease. Studies have shown that folate and its metabolites have antioxidant potential, albeit, lower than what’s seen with more well-known antioxidants such as vitamins C and E, beta-carotene, lycopene, and other phytonutrients/polyphenols.

But folate may lend to the antioxidant bottom line; every little bit helps.

4. Enhancing Nitric Oxide Production

Folate and its metabolites interacts with the enzyme eNOS which is needed to produce nitric oxide, a gas that blood vessels produce which enables optimal endothethial function. Higher intakes of folate and its conversion into the active/usable form 5-MTHF enhances the production of nitric oxide which enables blood vessels to expand and relax in a healthy manner.

Do We Need To Increase Our Folate Intake?

The answer is a qualified yes; the overall available data strongly suggests that getting more folate from both diet and supplements means better health when it comes to reducing all manner of cardiovascular disease.

Studies also show that many of us don’t get the recommended daily intake of 400 mcg to start with which is only meant to prevent overt or clinical deficiencies and does not take into account the amount of folate needed to promote optimal health. Even if we did, we know that the majority of us will have a 180% increased risk for lower blood levels and have some difficulty converting the folate into its active form.

To help overcome any genetic limitations, you could just endeavor to just eat more folate-rich foods2 and/or take a supplement that ideally has folate in the active form 5-MTHF versus synthetic folic acid (some research suggests synthetic folic acid may increase the risk for some cancers especially in those with MTHFR mutation). You could also take a genetic test to see if you have the MTHFR mutation.

Mutation or not, taking the active form of folate, 5-MTHF, is something everyone can do.