Methylfolate and Aging: Can It Slow Down the Clock

Methylfolate and Aging: Can It Slow Down the Clock?

Aging is a natural, gradual process. The speed at which we age varies significantly from person to person, largely depending on their health history. 

Unlike chronologic age, biologic age is affected by diet, lifestyle, environment, stress, and many other external factors that affect the physiological condition of our cells and tissues.

The aging process is increased by oxidative stress damage to biomolecules, especially DNA. 

Certain vitamins are important in preventing age-related diseases, and micronutrient deficiencies are also associated with greater susceptibility to illness and aging - particularly folate. 

Folate is essential for cell growth and reproduction. Methylated folate plays a pivotal role in DNA methylation and therefore in maintaining genomic integrity.

This article will discuss the potential benefits of methyl folate supplementation for healthy aging. 

What is methylfolate? 

Methylfolate is the active form of folate. It functions as a methyl donor in many metabolic reactions, including the biosynthesis of DNA precursor molecules. 

DNA methylation controls gene expression, cell proliferation, and differentiation, among a variety of important functions. Methylfolate is also required for the conversion of homocysteine into methionine, which is then used to produce SAMe (S-adenosylmethionine), the universal methyl donor for methylation. [1]

Folate coenzymes are essential to the formation of DNA and RNA and proper cell replication. 

If this process is impaired, DNA strand breaks can occur, along with an inability to repair other DNA damage. These issues can be contributing factors to the development of many diseases. [2]

How does aging affect folate metabolism? 

Folate metabolism supports a wider set of processes known as one-carbon metabolism. Folate is required for a number of steps in these processes that contribute to DNA synthesis and homocysteine remethylation. Essentially, folate metabolism is one of the most crucial elements of aging and disease. It is also a process that becomes less efficient as we age, for several reasons.

Impaired folate metabolism affects both methylation and DNA synthesis. The availability of methylfolate is dependent on the availability of dietary intake of folate and folic acid and the function of the MTHFR enzyme. 

Lack of dietary folate is also shown to decrease folate levels in both old and young, and folic acid intake among older people is generally well below the recommended dietary intake. [3]  Animal studies comparing aspects of folate metabolism between young and aged rats have also found that aging affects serum folate levels by around 50%. [4]

Reduced folate intake also leads to increased homocysteine levels, one of the symptoms of poor methylation. This is also associated with increased risk of dementia. Even moderately increased homocysteine or poor folate and vitamin B12 can increase the risk of vascular disease and neurocognitive disorders. [5]

Methylfolate and oxidative stress

DNA has the most highly developed biomolecule repair process in the body. However, certain factors may affect this process. The speed at which we age is linked to damage in DNA, which in turn is caused by defects in the DNA repair process, as well as oxidative stress. [6]

Oxidative stress occurs when there is an imbalance between reactive free radical generation and antioxidant defenses. ROS are involved in a wide spectrum of diseases, including chronic inflammation. 

Free radicals and reactive oxygen species (ROS) cause strand breaks, resulting in mutagenesis (changes in the DNA sequence) and genomic instability (defects in processes that control the way cells divide). [7]

In addition to its essential role in growth and development, methylfolate also has an antioxidant effect including free radical scavenging and activation of cellular antioxidant defense. Several animal studies have shown that folic acid supplementation can reduce oxidative stress caused by hyperhomocysteinemia. [8]

Folate is a well-known antioxidant that can protect cells from oxidative degradation. Methylated folate deficiency is positively correlated with DNA damage. Studies have noted that once folate is deficient, damage to nuclear and mitochondrial DNA increases. [9]

However, studies in diabetic patients show that methylfolate supplementation resulted in significantly higher protection (over folic acid) from high glucose-induced oxidative stress and inflammation. [10]

The link between methylfolate and inflammation 

Oxidative stress is known to cause inflammation and neurodegenerative diseases, leading to reduced life quality and expectancy. Individuals with lower antioxidant status are more vulnerable to oxidative stress. [11]

Inflammation caused by oxidative stress also depletes neurotransmitter levels, which can then contribute to the development of depression. Tetrahydrobiopterin (BH4) is a critical enzyme cofactor that is involved in the production of serotonin, dopamine, and norepinephrine. The presence of inflammation or oxidative stress can lead to the degradation of BH4, which is irreversible. 

Numerous studies have shown a high incidence of folic acid deficiency symptoms in adults, which may contribute to mental issues, especially depression and cognitive decline. [12]

However, L-methylfolate plays an important role in increasing the bioavailability of BH4 and may be a solution for patients affected by inflammation and neurotransmitter imbalance. [13]

Another study has noted that higher dietary intake of folate intake in obese and overweight women with the MTHFR C677T polymorphism has been shown to reduce levels of inflammatory biomarkers, indicating that folate may help reduce inflammation. Researchers have also suggested that patients affected by inflammation may benefit from taking methylfolate alongside antidepressants. [14]

The evidence on methylfolate and healthy aging

Aging is associated with oxidative stress damage in biomolecules, especially DNA. Methylfolate plays a pivotal role in maintaining genomic integrity. Folate deficiency contributes to aging of the brain and increases the risk of neurodegenerative disorders such as Alzheimer's disease and vascular dementia. 

Increasing evidence indicates that folate deficiency increases the risk for Alzheimer’s disease, while sufficient intake of folate may protect against it. A large meta analysis found that folic acid supplementation can slow cognitive decline and brain atrophy in patients with mild cognitive impairment, indicating that sufficient folate intake is preventive against Alzheimer’s. [15]

Folate has high antioxidant activity and can improve the bioavailability of BH4, which is required for healthy neurotransmitter production. Researchers have shown that supplementation with methylfolate may help protect against oxidative stress and inflammation, both of which can speed the aging process. Mood and some cognitive functions are also related to the methylation process. [16]

How to supplement with methylfolate

Supplementing with methylfolate may help to protect against homocysteine-related disease and the neurodegenerative effects of aging. Methylfolate is generally considered safe with most medications, but it’s important to discuss any methylation supplements with your health professional first. 

It’s also important to check the quality and quantity of the ingredients. Only products made with pure, certified methylfolate should be considered, such as the range by Methyl-Life®. 

Those new to methylfolate or who are taking other methylation supplements may choose to start with a low-dose option - Purest Active L-Methylfolate 2.5 mg. 

For comprehensive methylation support, the Methylfolate 7.5 mg + Active B12s supports homocysteine metabolism and healthy cognitive function, 

The Chewable Methylated Multivitamin is a convenient option for supporting overall wellbeing alongside healthy methylation. It contains both methylfolate and active B12 plus a wide range of vitamins, minerals, antioxidants and other cognitive nutrients. 

The takeaway

Folate is known to be linked to the aging process due to its important role in homocysteine metabolism, neurotransmitter function, and vascular support. Low folate levels - especially in older people - can contribute to depression, vascular disease, and dementia. In other words, low folate may speed the aging process. 

Methylfolate is not only required for healthy methylation but can function as a potent antioxidant that may reduce oxidative stress and inflammation associated with damage to DNA. Supplementing with methylfolate is a natural and effective means of supporting healthy aging and potentially reducing the risk of age-related disease.

References 

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961567/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062306/

3. https://pubmed.ncbi.nlm.nih.gov/15103481/

4. https://www.mdpi.com/2073-4409/11/2/214

5. https://pubmed.ncbi.nlm.nih.gov/15103481/

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062306/

7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062306/

8. https://www.mdpi.com/2076-3921/11/6/1046

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062306/

10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179225/

11. https://pubmed.ncbi.nlm.nih.gov/25874023/

12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123448/

13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442361/

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

15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123448/

16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123448/