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Understanding Folate, Folic Acid, Folinic Acid and Methylfolate

Depression, Heart, Mental Health, Pregnancy | August 20, 2018 | Author: Naturopath

Brain, cancer, heart, pregnancy, mental health, depression

Understanding Folate, Folic Acid, Folinic Acid and Methylfolate

Folate, or vitamin B9 is a water-soluble vitamin that is involved in several biochemical pathways required for health and wellbeing. This includes the prevention of neural tube defects in the early weeks of pregnancy, heart health, reduced cancer risk, healthy mood and cognition. But like most vitamins and minerals folate has many different forms including folic acid, folinic acid and methylfolate. So, which one is best for you?

Folate

Folate is the natural form of vitamin B9 which is found in the diet. Animal products are notoriously poor sources (unless you are eating organ meats like liver or kidney) and this is why deficiency can easily occur if you’re not eating enough fresh fruits and vegetables.

FolateRich sources of folate include legumes, nuts and fresh green leafy vegetables, such as spinach and cabbage, broccoli, sprouts, mushrooms and asparagus. Cooking, processing and freezing foods can reduce the content of folic acid—meaning we still may not be getting enough.

Folate deficiency

Folate is essential in the diet as we cannot synthesise it ourselves. A deficiency in folate can occur due to:

  • low dietary intake
  • poor absorption of ingested folate
  • alteration of folate metabolism due to genetic defects
  • taking certain medications such as methotrexate or the oral contraceptive pill

A deficiency in folate has been linked to increased risk of neural tube defects, cardiovascular disease, cancer and cognitive function.

Folate benefits

Folate is essential for the following:

  • production of DNA and RNA. This is essential for cell division and repair of genetic material.
  • production of the active form of B12
  • reduction of homocysteine levels for cardiovascular health
  • synthesis of SAMe for healthy mood and joints
  • amino acid metabolism
  • important methyl donor

In order for all these benefits, folate must be converted to the active from 5-MTHF.

In clinical practice folate can be used to help depression, prevent neural tube defects, cognitive decline, Alzheimer’s disease, high homocysteine levels and to support healthy methylation.

Folic acidFolic acid

Folic acid is the synthesized version of folate which is added to fortified foods and taken as a supplement. Since fortifying bread flour with folic acid, the rate of neural tube defects in Australia has nearly halved.

Folic acid is the common supplemental form which can be found individually or in a multivitamin.

Active folate

The active form of vitamin B9 is a folate known as levomefolic acid or 5-methyltetrahydrofolate (5-MTHF). In the digestive system, the majority of dietary folate is converted into 5-MTHF before entering the bloodstream.

Isn’t folic acid good enough?

Unlike most folate, the majority of folic acid is not converted to the active form of 5-MTHF in the digestive system. Instead, it needs to be converted in the liver or other tissues.

Unfortunately, this process is slow and inefficient and after taking a folic acid supplement, it takes time for the body to convert all of it to 5-MTHF.

Even a small dose, such as 200–400 mcg per day, may not be completely metabolized until the next dose is taken. This problem is even worse when fortified foods are eaten alongside folic acid supplements.

As a result, un-metabolized folic acid is commonly detected in people's bloodstreams, even during fasting.

This is a common finding in people who have MTHFR gene mutations. MTHFR stands for Methylenetetrahydrofolate reductase, which is an enzyme responsible for converting folate into the active form. Therefore, people with MTHFR defects have a reduced ability to convert folate into 5-MTHF.

This is worrying, since high levels of un-metabolized folic acid have been associated with several health issues including masking a deficiency in vitamin B12.
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5-methyltetrahydrofolate (5-MTHF)

The first obstacle in choosing a 5-MTHF supplement is understanding the various names that are used for this ingredient and what they mean. The most common versions you will see are: 5-MTHF, methylfolate, and 5-methyl tetrahydrofolate. Naturally occurring 5-MTHF has important advantages over synthetic folic acid as it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects. Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B12 deficiency, reduces interactions with certain folate antagonist drugs and overcomes metabolic defects caused by MTHFR polymorphism. 5-MTHF supplements prevents the potential negative effects of unconverted folic acid in peripheral circulation.

Folinic acid

Folinic acid appears to be a more metabolically active form of folate and is an immediate precursor to 5,10-METHF, which in turn is rapidly metabolised to produce active folate (5-MTHF).

Supplementation with folinic acid alleviates the need for the certain enzymes and steps that are required with folic acid supplementation. Bioavailability of folinic acid appears to be high, with human absorption studies showing a bioavailability of 92%. Folinic acid is often used to support healthy DNA and to reduce the side-effects and toxicity from medications such as methotrexate (a medication used to treat rheumatoid arthritis).

Folinic acidFolinic acid supports DNA-based production. 

This is very important. Everything on us from our hair to the lining in our digestive tract contains cells that are constantly dividing and repairing.

In fact, nearly every single cell in our body contains DNA—making folinic acid a nutrient that is in high demand.

Folate side-effects

Doses higher than 5mg per day may cause abdominal cramps, nausea, skin rashes, diarrhoea, flatulence, irritability and excitability. Use of folate supplements can mask a B12 deficiency state and allow the condition to remain undetected. It is recommended that patients are screened for a B12 deficiency.
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References

Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide, 3rd ed. Sydney: Churchill Livingstone Elsevier, 2010.

https://www.mthfrsupport.com.au/what-is-mthfr/

Kim YI. Folic acid fortification and supplementation--good for some but not so good for others. Nutr Rev 2007;65(11):504-511

Scaglione F, et al. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014 May;44(5):480-8

https://www.ncbi.nlm.nih.gov/pubmed/24494987

R Prinz-Langenohl, et al. [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C→T polymorphism of methylenetetrahydrofolate reductaseBr J Pharmacol. 2009 Dec; 158(8): 2014–2021

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807663/

Shea B, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis.

https://www.ncbi.nlm.nih.gov/pubmed/23728635

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