Folate, also known as vitamin B9 and folacin,] is one of the B vitamins. “Folates” are a family of nutrients related to folic acid obtained from natural sources. In contrast, the term “folic acid” is given to the manufactured form used as a dietary supplement. 

The term “folic” is from the Latin word folium (meaning “leaf”) because it is found in dark-green leafy vegetables, among other foods. Folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage.

Folate was discovered between 1931 and 1943 and is on the World Health Organization’s List of Essential Medicines. In 2019, it was the 89th most commonly prescribed medication in the US.  

Folate is needed by the body to produce DNA and RNA and metabolize amino acids necessary for cell division. As humans cannot make folate, it must be in the diet or taken as a pill. It occurs naturally in many foods. If levels are low, people can suffer from anemia. 

Folic acid is also used as a supplement by pregnant women pregnancy to reduce the risk of neural tube defects (NTDs) in the baby. Low levels in early pregnancy are believed to cause more than half of babies born with NTDs. More than 80 countries use either mandatory or voluntary fortification of certain foods with folic acid to decrease the rate of NTDs.

The recommended adult daily folate intake is 400 micrograms from foods or dietary supplements. Besides dark green leafy vegetables (such as turnip greens, spinach, romaine lettuce, asparagus, Brussels sprouts, and broccoli), it is also found in peanuts, beans, sunflower seeds, liver, fresh fruits, and whole grains. 

Now, an American-Israeli team of researchers has discovered that low levels of folate (vitamin B9) in the blood may be linked to a higher risk of dementia and death from any cause in older people, 

The study was published under the title “Serum folate deficiency and the risks of dementia and all-cause mortality: a national study of old age in the BMJ’s journal Evidence-Based Mental Health. 

The researchers were psychiatrist Dr. Anat Rotstein of the Icahn School of Medicine at Mount Sinai Medical Center in New York (formerly of the University of Haifa) and Prof. Stephen Levine of the community mental health department at the University of Haifa.  

Anemia symptoms may include feeling tired, heart palpitations, shortness of breath, open sores on the tongue, and skin or hair color changes. 

Levels should be routinely monitored, and deficiencies corrected in older age, especially given that blood levels of folate tend to tail off with age, with up to one in five older adults believed to be folate deficient, said the researchers.  

The evidence to date suggests that folate deficiency affects cognition and nerve signaling in the brain, making it a possible risk factor for subsequent dementia. But the few studies that have looked at this have included small numbers of participants and produced mixed results. 

The American-Israeli team found that folate concentrations in the blood may function as a biomarker used to modify the risks of dementia and mortality in old age. The implications for public health policy appear to be to reliably monitor serum concentrations of folate in older adults and treat deficiency for preventative measures and/or as part of implemented therapeutic strategies while regularly reviewing patients’ clinical outcomes.

Because of the time it takes for dementia to develop, it’s been difficult to rule out reverse causation, whereby folate deficiency could be a consequence of pre-clinical dementia rather than its cause, they added.

They wanted to see if serum folate deficiency might be linked to the risks of incident dementia and death from any cause in a large national sample of older adults and to include the potential role of reverse causation.

They drew on the medical records of 27,188 people served by one Israeli health maintenance. All the participants were aged between 60 and 75 and had had no pre-existing dementia for at least ten years before blood folate checks began in 2013. Their records were monitored for a diagnosis of dementia or death up to the end of 2017.

Some 3,418 (just under 13%) participants were folate deficient, defined as levels below 4.4 ng/ml. Folate deficiency was associated with a substantially heightened risk of dementia and death from any cause.

Among those who were folate deficient, the incidence of dementia was estimated at 7.96 per 10,000 person-years, while death from any cause was estimated at 19.20 per 10,000 person-years. This compares with an estimated dementia incidence of 4.24 and of death from any cause of 5.36 per 10,000 person-years among those who weren’t folate deficient.

In percentage terms, rates of dementia were almost 3.5% and of death from any cause just under eight percent among those with folate deficiency. This compares with dementia rates of just over three percent and of death from any cause of almost four percent among those who weren’t folate deficient. 

After accounting for potentially influential factors, including co-existing diabetes, depression, cognitive decline, vitamin B12 deficiency, smoking, and the use of folic acid supplements, the folate-deficient were 68% more likely to be diagnosed with dementia and nearly three times as likely to die from any cause. 

It’s possible that folate deficiency could affect homocysteine levels and, therefore, the vascular risk of dementia and/or compromise DNA repair of neurons, making them vulnerable to oxidative damage, which might speed up brain cell aging and damage explain.

The authors concluded that erum concentrations of folate in the blood could function as a biomarker used to modify the risks of dementia and mortality in old age, adding that older adults should be screened routinely for folate deficiency.