Methylfolate Benefits for Mood

Our mood has a powerful influence on our daily life and function. Mood is defined as a pervasive and sustained feeling that is experienced internally and that impacts nearly all aspects of a person’s thoughts and behavior. Mood disorders can involve distinctive emotional disruptions, including severe lows (depression) or highs (mania). 

Moods can last for hours, days, or even weeks, sometimes without the affected individual person knowing why they feel that way. Mood can influence perception, motivation, decision-making, social interactions, and even memory and attention.

Although mood can be influenced by particular experiences or events, on a physiological basis these experiences are communicated to brain cells via neurotransmitters serotonin, dopamine, and norepinephrine. Imbalances in the levels of these neurotransmitters have been linked to depression, anxiety, and the incidence of various psychiatric disorders. [1] The biosynthesis of these neurotransmitters depends upon an individual’s levels of active folate, known as methylfolate.

This article will cover the wide range of l-methyl folate supplementation benefits and how this vitamin functions in the brain and body. 

The Difference Between Folate, Folic Acid, and Methylfolate

• Folate is a water-soluble B-vitamin (B9) found naturally in foods such as leafy green vegetables, citrus fruit, and legumes. Folate is best known for its role in the synthesis and repair of DNA and the re-methylation of homocysteine to produce methionine. [2]

• Folic acid is not natural folate, but a synthetic (man-made) form that is used in supplements and added to fortified foods such as bread and cereals. Folic acid is also commonly prescribed by doctors. However, it should be noted that those who have the MTHFR polymorphism are unable to metabolize folic acid and will not benefit from it. In addition, unmetabolized folic acid syndrome has become more common since folic acid was added to foods, even among people who are not taking a supplement. [3]

• Methylfolate (also known as 5-methyltetrahydrofolate, 5-MTHF, or L-methylfolate) is the only folate that can cross the blood-brain barrier. Most importantly, methylfolate is the form necessary for the proper biosynthesis of the neurotransmitters. It is also required for the proper conversion of homocysteine into methionine, which is then required for the production of S-adenosylmethionine (SAMe), the body's major methyl donor. SAMe is involved in numerous biochemical methyl donation reactions, including those involved in supporting healthy mood. [4]

Benefits of Methylfolate

As well as supporting healthy mood, the many benefits of methylfolate include its role in daily cognitive function, sleep, and even in our ability to learn new skills. 

• Supports brain health

Methylfolate is essential for several crucial cellular processes, including DNA synthesis, amino acid conversion, various methylation reactions, and ultimately, normal cell division and growth. Low folate and vitamin B12 status and function lead to reduced S-adenosylmethionine levels and elevated plasma total homocysteine and S-adenosylhomocysteine. Healthy homocysteine levels are linked to good brain and cardiovascular health. This is in turn associated with hypomethylated DNA altered gene expression, and poor DNA stability, which affects the synthesis of various brain molecules including neurotransmitters. Impaired folate metabolism is associated with several neurodegenerative and neuropsychiatric diseases. [5]

• Ease depression

It has been shown that up to 70% of people with depression have a gene mutation of the MTHFR (methylenetetrahydrofolate reductase) enzyme that impairs their ability to convert folic acid to l-methylfolate. [6]

Unlike folic acid, methylfolate is the biologically active form of folate that readily crosses the blood-brain barrier. L-methylfolate is a cofactor in the production of monoamines serotonin, dopamine, and norepinephrine, which regulate mood and assist in the activity of antidepressants. Supplementation of L-methylfolate in patients with MDD can improve response to antidepressants, particularly in those patients who do not respond adequately to such medication. In fact, studies show that L-methylfolate in the treatment of SSRI-resistant depression is highly effective and is now recommended by many health professionals.

• Enhances the benefits of SAMe (s-adenosyl-methionine)

Methylfolate assists in creating methionine for the production of SAMe (s-adenosyl-methionine), the downstream metabolite of methionine. Without methylfolate, in this process, SAMe and neurotransmitter levels decrease significantly, contributing to the onset of depression.

While SAMe supplementation has been shown to improve depressive symptoms, methylfolate supplementation is also found to either enhance production of tetrahydrobiopterin (BH4) or act as a substitute. BH4 is also an essential cofactor in neurotransmitter biosynthesis and therefore the maintenance of healthy mood. [7]

• Promotes healthy production of melatonin

Melatonin is the hormone responsible for inducing sleep and normal circadian rhythm. The brain releases melatonin in response to darkness. However, melatonin production decreases as we get older.

One of the many neurochemicals that requires L-methylfolate for its production. The final step of melatonin synthesis involves the methylation of N-acetyl-serotonin, in which SAMe acts as a methyl donor. This can only occur if L-methylfolate is adequate. [8]

• Supports mood, memory, cognition, and behavior.

Methylfolate assists in monoamine synthesis and production of tetrahydrobiopterin (BH4). BH4 is a critical cofactor in neurotransmitter synthesis and reduced levels can alter the bioavailability of serotonin and dopamine. [9] Serotonin is linked with memory, neuroplasticity, and learning processes, with recent studies showing that serotonin neurons can modulate reinforcement learning rates. [10] Dopamine has a major role in the modulation of behavior and cognition; motivation; punishment and reward; sleep, improved mood; attention; working memory; and learning. [11]

Folate-rich Foods

A good many fruits and vegetables are naturally rich in folate. Adding these foods to the diet can help to support folate levels. However, it should be noted that those requiring therapeutic levels of this nutrient are advised to supplement. Check out some of the best methylfolate supplements at Methyl-Life®. 

Citrus fruits (oranges in particular)

Citrus fruit juices are a particularly good source of both vitamin C and folate. The total folate content of orange juice is around 32 μg/100 g and 22 μg/100 g juice stored at ambient or chilled temperature. [12]

Avocado

Avocados contain 27 μg folate and 0.09 mg vitamin B-6 per 30 g, plus a wide range of other nutrients including fiber, vitamins, minerals, and antioxidants. [13]

Beans

Beans are an excellent source of folate, providing roughly 70% of the recommended dietary allowance (RDA) per 1 cup serving. [14]

Peanuts

Peanuts are a legume, and a great source of folate and other B vitamins. A 100 g serving of dry roasted peanuts provides around 240 μg of folate, or up to 60% of the RDA, as well as 75% of the RDA of niacin, and 53% RDA of thiamin. [15]

Sunflower seeds

Sunflower seeds provide around 326.88 mcg of folate per cup, or 17% of the RDA in a one-ounce serving.  [16] This amount also provides 11% of the RDA for pantothenic acid (B6) and 6% for thiamin. [17]

Broccoli

Cooked broccoli contains around 44-72 µg/100 g of folate, which is a similar content to peppers, spinach, soybean sprouts, and coriander. [18]

Beets

Beets are an excellent source of folate, with raw beets providing around 109 ug per 100 g, and cooked providing 80 ug. [19]

Beef Liver

Beef liver is rich in folate and other nutrients. Just three ounces of liver provides around 215 mcg of folate, along with more than 100% of the RDA for vitamin A, vitamin B12, and copper. [20]

Dark leafy greens (especially spinach, romaine, and turnip greens)

Spinach and other leafy greens such as romaine lettuce and turnip greens are especially high in folate. One cup of raw spinach provides around 58 mcg folate, while a half-cup of cooked spinach provides around 131 mcg. [21] One cup of romaine lettuce contains around 63.92 mcg, while turnip greens contain around 170 mcg. [22]

Brussel sprouts

Like other green vegetables, Brussels sprouts are an excellent source of B vitamins and folate. Just half a cup of cooked Brussels sprouts provides around 47 mcg of folate or 12% of the RDA. [23]

Asparagus

Just four spears of cooked asparagus contains about 89 mcg of folate.  [24]

Supplementing with methylfolate

While these foods can certainly provide natural folate, it should be noted that the amount of folate obtained from these foods will not be at therapeutic levels, and also that dietary folate must still be processed by the MTHFR enzyme in order to be converted to methylfolate. Those with MTHFR mutations are unable to do this adequately. Essentially, high dosages of methylfolate are only possible via supplementation. 

While there are many brands offering methylfolate products, one of the best-known is Methyl-Life®. Methyl-Life® provides a range of supplements designed specifically to support mood, including methylfolate 10 mg and 15 mg. 

The takeaway

Methylfolate is an essential nutrient that plays numerous biochemical roles in the body. Clinical studies show that methylfolate benefits go well beyond supporting mood and alleviating depression. Methylfolate is also involved in healthy cognitive function, melatonin production, and normal behavior. Low methylfolate levels can have a significant impact on quality of life. For these reasons, supplementation may be necessary for those who are already affected by depression. 

References

1. https://www.frontiersin.org/articles/10.3389/fpsyt.2021.637863/full

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648733/

3. https://pubmed.ncbi.nlm.nih.gov/20573790/

4. https://pubmed.ncbi.nlm.nih.gov/18950248/

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844834/

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869616/

7. https://pubmed.ncbi.nlm.nih.gov/18950248/

8. https://pubmed.ncbi.nlm.nih.gov/12221245/

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968318/

10. https://www.nature.com/articles/s41467-018-04840-2

11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684895/

12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264544/

13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664913/

14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915747/

15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711439/

16. https://www.uhhospitals.org/health-information/health-and-wellness-library/article/nutritionfacts-v1/seeds-sunflower-seed-kernels-dried-1-cup

17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500752/

18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723199/

19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947971/

20. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

21. https://www.uhhospitals.org/health-information/health-and-wellness-library/article/nutritionfacts-v1/lettuce-cos-or-romaine-raw-1-cup-shredded

22. https://nutritiondata.self.com/facts/vegetables-and-vegetable-products/2704/2

23. https://healthyeating.sfgate.com/health-benefits-eating-brussels-sprouts-4461.html

24. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/