A study published in Clinical Nutrition (2006; 25(1):60–67) examined 224 patients newly admitted to a psychiatric hospital. These patients had significantly lower serum folate levels than healthy controls. Low serum folate was associated with depression. The same relationship was not observed between serum cobalamin levels and depression; however, serum cobalamin is not always a reliable indicator of overall vitamin B12 status.
Research suggests that serum cobalamin alone may not be the best test for identifying vitamin B12 deficiency. A study published in the American Journal of Hematology (1990; 34:99–107), which reviewed 419 cases of B12 deficiency, found that elevated homocysteine and elevated methylmalonic acid were present in 95% of deficient patients, whereas only 69% had low serum cobalamin levels. In this study, B12 deficiency was defined clinically, based on symptoms affecting the tongue, nervous system, and/or hematopoietic system that responded to vitamin B12. Notably, several patients had clear symptoms of B12 deficiency despite serum cobalamin levels above 200 pg/mL. The authors concluded that measuring homocysteine or methylmalonic acid provides a more sensitive assessment of B12 status than serum cobalamin alone. It should be noted that elevated homocysteine can also result from folate deficiency and may not respond to B12 supplementation alone.
Vitamin B12 levels tend to decline with age, a finding supported by research published in the Archives of Family Medicine (October 1994; 3:918–922). Some cases of depression, cognitive decline, or other mental health concerns in older adults may be related to deficiencies in vitamin B12 or folate. A study published in the European Journal of Clinical Investigation (1994; 24:600–606) evaluated 296 elderly patients diagnosed with mental illness. Measurements included serum folate, homocysteine, and cobalamin. More than 7% of these patients had normal serum cobalamin levels but elevated homocysteine. Treatment with vitamin B12 injections lowered homocysteine levels, and the addition of folic acid further reduced homocysteine in patients with low folate status.
Vitamin B12 has also been examined in relation to cognitive function. A small pilot study published in the Journal of the American Geriatrics Society (February 1992; 40(2):168–172) followed 22 individuals with low serum B12 levels and cognitive impairment. Participants received vitamin B12 injections daily for one week, weekly for four weeks, and then monthly for six months. Cognitive function was assessed using the Mattis Dementia Rating Scale at baseline and after at least six months of treatment. Of the 18 participants who completed the study, 11 showed improvement. The degree of improvement was related to how long symptoms had been present, leading the authors to suggest that there may be a limited window during which cognitive symptoms related to B12 deficiency are reversible and that older adults may benefit from regular screening.
