The Role of Folate and Methylfolate in the Aging Process

The Role of Folate and Methylfolate in the Aging Process

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Nare Simonyan - PhD Pharmaceutical Science

Medical Reviewer:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Kari Asadorian - BSN, RN

Edited By:

Kari Asadorian - BSN, RN
Last updated:

Folate and methylfolate requirements in the body by age

Your folate requirements increase throughout life according to different stages of development. These increases often reflect higher rates of cell division, DNA synthesis, and methylation requirements; for example, during adolescence or pregnancy.
According to the National Institutes of Health, the average daily recommended intakes of folate by age groups are as follows:1


Birth to 6 months: 65 mcg
Infants 7–12 months: 80 mcg
Children 1–3 years: 150 mcg
Children 4–8 years: 200 mcg
Children 9–13 years: 300 mcg
Teens 14+/adults: 400 mcg
Pregnant women: 600 mcg
Breastfeeding women: 500 mcg


Note: The bioavailability and metabolism of different forms of folate are not the same. Both natural folate (from food) and synthetic folate (folic acid) must be converted to active methylfolate to be used by the body. Folic acid requires a lengthy conversion process before it can be used.


This conversion is not very efficient, and only a fraction of ingested folic acid will become active folate. This is even lower in people with MTHFR genetic mutations.


Methylfolate, on the other hand, bypasses this entire conversion pathway because it is already active and immediately usable by cells. Because none of the methylfolate dosage is ‘lost’ during conversion, much lower doses are required. This is why even low-dose methylfolate is considered more efficient and more reliable than folic acid.

MTHFR mutation and how the condition changes by age

While the MTHFR mutation doesn't change with age, some research suggests that age can affect how the mutation affects homocysteine levels. The C677T mutation already impairs how efficiently folic acid is converted to methylfolate, which then impacts homocysteine metabolism. But as we age, even more variables may affect the conversion process, such as reduced kidney function, hormonal changes, medications, or other health conditions. Common medications in older adults such as proton pump inhibitors, can interfere with folate or B12 absorption, compounding the effects of MTHFR. This combination of factors can contribute to higher homocysteine levels.2


Current research does not indicate that methylfolate dosages should be adjusted with age. In addition, not everyone with MTHFR mutations will experience elevated homocysteine or related symptoms, especially if they are eating a wholesome diet and/or supplementing with active B vitamins.

Relation of methylfolate to cognitive decline and dementia

Low folate levels are associated with a higher risk of cognitive decline in older adults, particularly those with MTHFR.3


A high homocysteine level (>15 µmol/L), known as hyperhomocysteinemia, is a major risk factor for Alzheimer’s disease, brain atrophy, and damage to the vascular system.4 Studies show that elevated homocysteine levels, along with decreased folate and vitamin B12 levels is common in those with Alzheimer’s.5


Elderly people have the highest rate of folate deficiency, especially those with dementia. Although there is limited research regarding an effective methylfolate dosage for older people, methylfolate may offer protective benefits by reducing homocysteine more efficiently than folic acid, especially in those with MTHFR.6

Is folate an anti-aging treatment or does it cause premature aging?

Folate may help to protect against the effects of aging by supporting cognitive function and cardiovascular health.


Some research has shown that older adults who have higher serum levels of methylfolate also have better physical function. Specifically, people with higher folate levels have reduced disability and fewer difficulties with everyday tasks such as shopping, managing finances, walking, and climbing stairs.7 The benefits of higher folate were most evident in women aged under 80, those with normal body weight, and non-drinkers.


A similar study found that women with higher folate levels had longer telomeres, a marker of slower cellular aging. Shorter telomeres are associated with a higher risk of age-related diseases and earlier mortality. This suggests folate plays an important role in reducing oxidative stress and supports healthy aging in both physical function and at the DNA level.8


Tips for healthy aging if you have MTHFR:

  • Supplement with methylfolate
    For people with MTHFR, maintaining healthy folate levels throughout life is critical. Methylfolate is essential for supporting the brain and physical function as the body ages. It helps to protect against other age-related changes by supporting healthy methylation, which plays a role in DNA repair, neurotransmitter production, and cognitive function. It may also help reduce oxidative stress and inflammation, processes that can accelerate aging. Most importantly, methylfolate helps to reduce homocysteine levels and protect against homocysteine-related diseases, which have been linked to neurodegenerative effects.9

  • Monitor homocysteine levels
    If you have MTHFR, and/or a family history of heart disease, it’s recommended that you check your homocysteine levels regularly. Your health professional can advise you on how often you should do this.

  • Eat a healthy diet
    Along with MTHFR and increasing age, other major contributors to high homocysteine and oxidative stress are smoking, coffee consumption, high cholesterol, and poor diet. Eating a whole food diet with minimal processed foods (especially deli meats) can help to keep homocysteine levels in check.10

Are age spots related to folate?

Age spots are strongly related to chronic sun exposure and the photo damaging effects of ultraviolet rays.11 However, some recent research suggests that folate and vitamin D both support endothelial cells of the vascular system by reducing oxidative stress and inflammation. UV rays can degrade methylfolate in the skin while stimulating vitamin D production. Low folate levels can therefore worsen oxidative stress in the skin and contribute to age-related pigmentation changes like age spots.12


While more research is needed, some studies suggest that folate plays an important role in maintaining healthy blood vessels, which could indirectly affect skin pigmentation by improving nutrient delivery and reducing oxidative stress in skin cells.13

The role of folate and methylfolate in the aging process

Key takeaways

  • Icon MTHFR does not change with age, but we become more susceptible to high homocysteine and reduced folate levels as we get older.
  • Icon Active folate (methylfolate) becomes especially important for older adults due to increased risk of deficiency.
  • Icon Methylfolate may help with healthy aging by supporting cognitive function, reducing homocysteine levels, and protecting against oxidative stress - especially in those with MTHFR.

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  • Bioactive MTHFR Folate, Methylfolate, for Max Absorption
  • Sublingual B12 to Aid B12 Sufficiency via Active Hydroxy Form
  • 3rd-Party Tested for Purity, Potency & Safety
  • 90 Day Supply to Optimize Methylation Pathways

Frequently Asked Questions about methylfolate and healthy aging

Does MTHFR get worse with age?

No, MTHFR does not get worse with age. However, the effects of MTHFR on the body may become more or less significant with age, especially if your levels of specific nutrients (particularly methylfolate and B12) and/or oxidative stress increase. These factors can contribute to higher homocysteine levels, which can in turn increase the risk of heart disease, cognitive decline, and other health conditions. Age-related decline in kidney or liver function can also impair homocysteine conversion.14

Can taking folate increase aging?

No, but taking active folate (methylfolate) has been shown to reduce oxidative stress and high homocysteine, which are both linked to faster aging and age-related health conditions.

Does folate decrease with age?

Yes, folate and many other nutrients decrease with age for several reasons, including reduced intestinal absorption, medications, poor diet, exposure to oxidative stress, and other factors that are more prevalent as we get older.

Why do folate requirements increase with age?

Folate requirements increase with age because the body is less able to absorb and store nutrients. Age-related changes in the gastrointestinal system can reduce the body's ability to absorb nutrients effectively. Certain medications can also interfere with nutrient utilization, and inadequate intake of folate-rich foods can also contribute to deficiencies.15

Why are elderly at risk for folate deficiency?

Folate deficiency is highest among older people, mainly due to reduced dietary intake and/or poor intestinal absorption. Malabsorption issues increase with age as a result of reduced stomach acid production, digestive issues, and/certain medications. These factors can all affect the absorption of nutrients, including folate.16

Why is folate important for elderly?

Folate becomes even more critical with age as it plays a key role in many biological functions that affect the brain and cardiovascular system. Folate helps to convert homocysteine to methionine, which is required for healthy brain function and neurotransmitter production, and also for protecting the body against elevated homocysteine levels. Low folate in older adults has been associated with cognitive decline, dementia and depression.17

References

  1. National Institutes of Health | Office of Dietary Supplements; "Folate"; 2022 Nov

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

  2. Jacques Paul F, Rogers Gail, Ordovas Jose M, Rosenberg Irwin H, Selhub Jacob, Friso Simonetta, Russo Giuseppina T, Cucinotta Domenico, Wilson Peter W.F; "Age and Gender Affect the Relation between Methylenetetrahydrofolate Reductase C677T Genotype and Fasting Plasma Homocysteine Concentrations in the Framingham Offspring Study Cohort"; The Journal of Nutrition; sciencedirect.com; 2003 Nov

    https://www.sciencedirect.com/science/article/pii/S0022316622162206

  3. Yating Tang, Xia Zhou, Jing Cao, Zhiwei Li, Wenwen Yin, Ke Wan, Chaojuan Huang, Wenhao Zhu, Jiabin Yin, Wei Zhang, Xiaoqun Zhu, Zhongwu Sun; "Synergistic effect of folate and MTHFR C677T on hippocampal subfields and perfusion in Alzheimer's disease"; Progress in Neuro-Psychopharmacology and Biological Psychiatry; 2024 Aug

    https://www.sciencedirect.com/science/article/abs/pii/S0278584624001398

  4. Ram Prakash Sah, C S Vidya, Pratibha Pereira, Shubha Jayaram, Anshu Kumar Yadav, P Sujatha; "Elevated Homocysteine Level and Brain Atrophy Changes as Markers to Screen the Alzheimer Disease: Case Series"; Annals of geriatric medicine and research; 2023 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10982442

  5. Ram Prakash Sah, C S Vidya, Pratibha Pereira, Shubha Jayaram, Anshu Kumar Yadav, P Sujatha; "Elevated Homocysteine Level and Brain Atrophy Changes as Markers to Screen the Alzheimer Disease: Case Series"; Annals of geriatric medicine and research; 2023 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10982442

  6. Lorena Carboni; "Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health"; Integrative medicine; 2022 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9380836/

  7. Lujun Ji, Tianhao Zhang, Liming Zhang, Dongfeng Zhang; "Associations between Serum Folate Concentrations and Functional Disability in Older Adults"; Antioxidants; 2023 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10045063/

  8. Larry A Tucker; "Serum and Dietary Folate and Vitamin B12 Levels Account for Differences in Cellular Aging: Evidence Based on Telomere Findings in 5581 U.S. Adults"; Oxidative medicine and cellular longevity; 2019 Oct

    https://pmc.ncbi.nlm.nih.gov/articles/PMC6800923/

  9. Charith U B Wijerathne, Kathy K W Au-Yeung, Yaw L Siow, Karmin O; "5-Methyltetrahydrofolate Attenuates Oxidative Stress and Improves Kidney Function in Acute Kidney Injury through Activation of Nrf2 and Antioxidant Defense"; Antioxidants; 2022 May

    https://pubmed.ncbi.nlm.nih.gov/35739943/

  10. Vijetha Shenoy, Veena Mehendale, Krishnananda Prabhu, Ranjan Shetty, Pragna Rao; "Correlation of serum homocysteine levels with the severity of coronary artery disease"; Indian journal of clinical biochemistry; 2014 Jul

    https://pubmed.ncbi.nlm.nih.gov/24966483/

  11. Wonseon Choi, Lanlan Yin, Christoph Smuda, Jan Batzer, Vincent J Hearing, Ludger Kolbe; "Molecular and histological characterization of age spots"; Experimental dermatology; 2018 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC5342934

  12. S Tony Wolf, W Larry Kenney; "Skin pigmentation and vitamin D–folate interactions in vascular function: An update"; Current opinion in clinical nutrition and metabolic care; 2022 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8789342/

  13. S Tony Wolf, W Larry Kenney; "Skin pigmentation and vitamin D–folate interactions in vascular function: An update"; Current opinion in clinical nutrition and metabolic care; 2022 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8789342/

  14. Yanjun Long, Jing Nie; "Homocysteine in Renal Injury"; Kidney Disease; 2016 Apr

    https://pmc.ncbi.nlm.nih.gov/articles/PMC4947689/

  15. Theodora Kalogerakou, Maria Antoniadou; "The Role of Dietary Antioxidants, Food Supplements and Functional Foods for Energy Enhancement in Healthcare Professionals"; Antioxidants; 2024

    https://www.mdpi.com/2076-3921/13/12/1508

  16. João Ricardo Araújo, Fátima Martel, Nuno Borges, João Manuel Araújo, Elisa Keating; "Folates and aging: Role in mild cognitive impairment, dementia and depression"; Ageing Research Reviews; 2015 Jul

    https://www.sciencedirect.com/science/article/abs/pii/S1568163715000458

  17. Anat Rotstein, Arad Kodesh, Yair Goldberg, Abraham Reichenberg, Stephen Z Levine; "Serum folate deficiency and the risks of dementia and all-cause mortality: a national study of old age"; BMJ Mental Health; 2022 Mar

    https://mentalhealth.bmj.com/content/25/2/63

Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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