Micro Nutrient Metabolism

Dementia and Serum Levels of Homocysteine and Folate

Russell Sage College
Elizabeth Chevrette

Micro Nutrient Metabolism

Dementia and Serum Levels of Homocysteine and Folate

The article Serum Homocysteine and Folate Levels are Associated With Late-life
Dementia in a Korean Population, was published by Elsevier Journal in Science Direct in the
year 2010. This study, performed by Ju Hee Song, MS, Moon Ho Park, MD, Changsu Han, MD,
Sangmee A. Jo, PhD, and Kyungsook Ahn, PhD, aimed to determine if serum levels of
homocysteine (Hcy) and the biological determinants folate and vitamin B12 are related to the
decline in cognitive function that is seen so often in the elderly population. This study involved
samples from 424 cognitively normal control patients, 382 mildly cognitive impaired (MCI), and
56 dementia patients all over the age of 60 years old from Ansan Geriatric (cognitive functions
were measured by the Consortium to Establish a Tegistry for Alzheimers disease
neuropsychological battery). Serum blood sample concentrations of Hcy, folate, and vitamin B12
were measured in these three groups.
Low serum levels of folate has been found to correlate with both structural and functional
brain abnormalities including but not limited to cerebral cortex atrophy and dementia. The
brains metabolic functions are maintained in part thanks to one-carbon transfer reactions which
are carried out through the actions of Hcy, vitamin B12, and folate. Hcy accumulation can be
found in those with folate and vitamin B12 deficiencies. Elevated blood Hcy has been found to
correlate with dementia and Alzheimers disease (AD). In the body, the essential amino acid
methionine is demethylated to form Hcy and can then be remethylated within the body. The
metabolism of methionine depends on the presence of vitamin B12 (cobalamin), pyridoxine
(vitamin B6), and folic acid (vitamin B9). Folate is necessary for the remethylation of Hcy to
form methionine and without adequate folate, Hcy will accumulate in the body. Deficiencies in
these can lead to homocysteinemia in the body from the lack of proper metabolic function being
performed.

Micro Nutrient Metabolism

Folate and vitamin B12 are both water soluble vitamins. Unlike folate and many other
water soluble vitamins, vitamin B12 is able to be stored in the body, mostly in the liver, for up to
3-5 years. This makes it difficult to catch vitamin B12 deficiencies early on. Folate is many times
ingested in polyglutamate form and must be deconjugated by the enzyme folylpoly glutamate
carboxypeptidases before it can become monoglutamate. Folate is taken up into the intestinal
cells through proton-coupled folate transporter and is used in the cytosol and mitochondria of
cells as a coenzyme involved in the accepting and donating of one-carbon units, a reaction that is
curtail in synthetic reactions involving amino acids including methionine. Folate is needed in the
form of 5-methyl tetrahydrofolate (THF) before it can be used in the conversion of Hcy. Folate
becomes 5-methyl THF through the action of the enzyme serine hydroxymethyl-transferase
converting THF to 5,10-methylene THF, which is then further converted to 5-methyl THF by
methylene THF reductase. The reaction turning THF to 5,10-methylene THF is a reversible
reaction but the change to 5-methyl THF is an irreversible conversion that must be converted
back to THF with the help of cobalamin. Because of this sequence, if vitamin B12 is unavailable
for the reaction, folate may be irreversibly converted and become stuck in the methyl folate trap.
Folate becomes trapped by being continuously converted to 5-methyl THF without adequate
vitamin B12 to react with. When this occurs, serum folate levels increase while intracellular
folate concentrations decrease. This also causes methionine levels to decrease and Hcy levels to
build up which can lead to homocystenemia.
Upon ingestion, vitamin B12 is released from its protein source by pepsin and
hydrochloric acid in the stomach. It is carried to the small intestines by intrinsic factor (IF) where
it is then released and absorbed by the body. Folate and vitamin B12 are both irreplaceable
contributors in the reaction required for methionine synthesis. In this reaction, vitamin B12 binds
to the enzyme methionine synthase and takes up a methyl group from 5-methyl THF. This
reaction binds methylcobalamin, methionine synthase, and THF together. Methionine synthase
can then transfer the methyl group from methylcobalamin to Hcy and will produce methionine
and vitamin B12.
In this study, blood samples were taken from all participants in order to assess their levels
of Hcy concentration, while serum folate and vitamin B12 levels were assessed by using

Micro Nutrient Metabolism

competitive binding assays. Significantly increased Hcy serum concentrations and significantly
lower levels of serum folate and vitamin B12 concentrations were found in patients with
dementia when compared to the levels that were found in the patients of the control group. No
significant differences were found in Hcy levels when comparing the MCI group to the controls,
but folate and vitamin B12 levels were found to be lower in the MCI group than in the control.
Patients found to have intermediate hyperhomocystenemia were also found to be at a much
higher risk for acquiring dementia than those that were found to have moderate
hyperhomocystenemia.
More research is needed in this area to acquire more concrete results, and other factors
including smoking and alcohol use should be accounted for in further studies on this topic. High
Hcy levels have been found to correlate with decreased brain volume, and this study shows
correlations between elevated Hcy, decreased folate levels, decreased vitamin B12 levels, and a
higher risk for the onset of dementia. The findings of this study could support the
recommendation for higher requirements of folate and vitamin B12 for adults over the age of 50
to help prevent the onset of dementia later in life. Supplements of folate and vitamin B12 in the
middle aged to senior populations could possibly help to reduce the risk for homocystenemia,
and in turn, dementia.

Micro Nutrient Metabolism

5
Works Cited

1. Song, MS, & Park, MD, & Han, MD, & Jo, PhD, & Ahn, PhD. (Oct. 10, 2010). Serum
Homocysteine and Folate Levels are Associated With Late-life Dementia in a
Korean Population. Elsevier. 1 (1), 17-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766893/pdf/main.pdf

2. Gropper, S. S., & Smith, J. L. (2013). Advanced Nutrition and Human Metabolism. 6th
edition. Belmont, CA: Wadsworth Cengage Learning.