Healthy aging: The link between homocysteine, dementia, and B vitamins

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Do not go gentle into that good night,

Old age should burn and rave at close of day;

Rage, rage against the dying of the light.

—Dylan Thomas, Poet

According to the World Health Organization¹, dementia is one of the common conditions of aging. While this fact isn’t likely to come as a surprise to anyone reading this article, what you may not be aware of is that homocysteine, often implicated as a risk factor in cardiovascular disease, is also implicated in dementia.

Defining Homocysteine

Homocysteine is a by-product of normal protein metabolism, formed via conversion from methionine. Given that high levels of homocysteine are not good for our health, our bodies have a metabolic process that partially converts it back into methionine and other beneficial, nontoxic amino acids. Unfortunately, this process may be out of whack, resulting in a buildup of homocysteine in bodily fluids and tissues, resulting in ramifications for dementia.

Alzheimer’s Disease and Vascular Dementia

A causative link has been established between high homocysteine and both Alzheimer’s disease and vascular dementia in old age. Research² shows that individuals with Alzheimer’s disease and vascular dementia have higher homocysteine levels than controls. In a variety of clinical studies³, the relative risk of dementia in elderly people with moderately raised homocysteine (within the normal range) ranges from 4.3% to 31%. So, what can be done to lower risk?

B Vitamins, Homocysteine, and Dementia

Although B vitamins have been used in dietary supplements for a long time and are not among the sexier of the nutraceuticals, they can nonetheless have a profound effect on reducing homocysteine levels and dementia risk.

Let’s start with the fact that, among elderly, deficiency of vitamin B12, B6, and folate is known to affect cognitive functioning and is accompanied by depressive symptoms prevalent among older adults.^4,5 B vitamin deficiency—particularly B6, B12, and folate deficiency—is associated with increased serum homocysteine levels, which, as noted, increases the risk of dementia and is very common among this age group. Increasing the intake of these vitamins can lower the risk of developing these disorders by reducing the levels of plasma homocysteine.

The National Health and Nutrition Examination Survey has shown that about 6% of elderly (age >70 years) are severely deficient in vitamin B12, and more than 20% of elderly (age >60 years) are mildly deficient.⁶ According to recent studies, more than 20% of the elderly population is at risk of vitamin B12 deficiency.⁷ The prevalence of this deficiency is due to insufficient food intake and malabsorption of vitamin B12 due to degenerative digestive conditions. Also consider: Data from the Framingham Offspring Study on elderly people revealed elevated plasma gastrin levels in 24% of those aged 60-69 years and in 37% of those 80 years old and older. The altered digestive function elevates the gastrin levels, which in turn causes malabsorption of the vitamin.^7,8 Meanwhile, the prevalence of vitamin B6 deficiency among the European institutionalized elderly population ranges between 1%-75%.⁹

A group of experts reviewed literature evidence over the past 20 years. Their consensus statement concluded that “elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer’s disease in older persons. Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline. The findings are consistent with moderately raised plasma total homocysteine (>11 µmol/L), which is common in the elderly, being one of the causes of age-related cognitive decline and dementia. Thus, the public health significance of raised [total homocysteine] tHcy in the elderly should not be underestimated, since it is easy, inexpensive, and safe to treat with B vitamins.”

Conclusion

High homocysteine levels are implicated in the development of cognitive decline, dementia, and Alzheimer’s disease in older persons. The supplemental use of folate, vitamin B12, and vitamin B6 constitutes an established strategy for modifying risk. Of course, there are other nutraceutical strategies for lowering homocysteine and potentially helping to lower dementia risk (e.g., ingredients like betaine anhydrous, also known trimethylglycine or TMG), but that is a topic for another article.

About the Author

Gene Bruno, MS, MHS, RH (AHG), is a certified nutritionist and registered herbalist with 44 years of dietary supplement industry experience. With a master’s degree in nutrition and a second master’s degree in herbal medicine, he has a proven track record of formulating innovative, evidence-based dietary supplements. In addition, Bruno also serves as a professor of nutraceutical science at Huntington University of Health Sciences.

References

1. Ageing and Health. World Health Organization. Published October 1, 2022. Accessed April 19, 2023. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health#:~:text=Common%20conditions%20in%20older%20age,conditions%20at%20the%20same%20time
2. Ho, R.C.M.; Cheung, M.W.L.; Fu, E.; et al. Is High Homocysteine Level a Risk Factor for Cognitive Decline in Elderly? A Systematic Review, Meta-Analysis, and Meta-Regression. Am J Geriatr Psychiatry. 2011, 19 (7): 607-617. DOI: 10.1097/JGP.0b013e3181f17eed
3. Smith, A.D.; Refsum, H.; Bottiglieri, T.; et al. Homocysteine and Dementia: An International Consensus Statement. J Alzheimers Dis. 2018, 62 (2), 561-570. DOI: 10.3233/JAD-171042
4. Beydoun, M.A.; Shroff, M.R.; Beydoun, H.A.; Zonderman A.B. Serum Folate, Vitamin B-12 and Homocysteine and Their Association with Depressive Symptoms Among U.S. Adults. Psychosom Med. 2010, 72 (9), 862-873. DOI: 10.1097/PSY.0b013e3181f61863
5. Kennedy, D.O. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review. Nutrients. 2016, 8 (2), 68. DOI: 10.3390/nu8020068
6. Pfeiffer, C.M.; Caudill, S.P.; Gunter, E.W.; Osterloh, J., Sampson, E.J. Biochemical Indicators of B Vitamin Status in the US Population After Folic Acid Fortification: Results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr. 2005, 82 (2), 442-450. DOI: 10.1093/ajcn.82.2.442
7. Sturtzel, B.; Dietrich, A.; Wagner, K.H.; Gisinger, C.; Elmadfa, I. The Status of Vitamins B6, B12, Folate, and of Homocysteine in Geriatric Home Residents Receiving Laxatives or Dietary Fiber. J Nutr Health Aging. 2010, 14 (3), 219-223. DOI: 10.1007/s12603-010-0053-6
8. Allen, L.H. How Common Is Vitamin B-12 Deficiency? Am J Clin Nutr. 2009, 89 (2), 693S-696S.DOI: 10.3945/ajcn.2008.26947A
9. Kjeldby, I.K.; Fosnes, G.S.; Ligaarden, S.C.; Farup PG. Vitamin B6 Deficiency and Diseases in Elderly People--A Study in Nursing Homes. BMC Geriatr. Published online February 8, 2013. DOI: 10.1186/1471-2318-13-13