A study, published in Clinical Nutrition (2006; 25(1): 60-7) looked at 224 patients who were newly admitted to a psychiatric hospital. The patients had significantly lower serum folate levels than healthy controls. Low serum folate correlates with depression. The same correlation did not exist between serum cobalamin levels and depression, but serum cobalamin is not necessarily a good indicator of vitamin B12 status.

Testing for serum cobalamin may not be the best way to check for a B12 deficiency. Research appearing in the American Journal of Hematology (1990;34:99-107) found that elevated homocysteine and elevated methylmalonic acid occurred in 95% of patients with cobalamin deficiency, whereas only 69% of these patients demonstrated a low serum cobalamin. The study reviews 419 cases of B12 deficiency. The subjects were determined to have a B12 deficiency based on symptoms. Vitamin B12 deficiency was determined as a syndrome affecting the tongue, nervous system and/or hematopoietic system that responded to B12. A dozen of the subjects had symptoms of B12 deficiency, but serum cobalamin was higher than 200 pg/ml. The authors of the study concluded that measuring homocysteine or methylmalonic acid is a much better way to determine B12 levels than serum cobalamin. Serum cobalamin is normal in a significant number of patients who are B12 deficient. It should be noted that homocysteine may be elevated due to a folic acid deficiency, and that will not respond to B12 alone.

Vitamin B12 levels tend to decrease with age, this was verified by research appearing in the Archives of Family Medicine (October 1994;3:918-922). Many problems with depression, cognition or other mental issues that are experienced by the elderly may be due to vitamin B12 or folic acid deficiency. One study that appeared in the European Journal of Clinical Investigation (1994;24:600-606), looked at 296 elderly patients diagnosed with mental disease. Serum folate, homocysteine, and cobalamin were measured. Over 7% of these patients had normal serum cobalamin levels, but high homocysteine. Treatment of these patients with vitamin B12 injections reduced homocysteine levels. Addition of folic acid to the treatment also lowered homocysteine in patients with low folate.

Vitamin B12 does seem to help with cognitive function. A small pilot study, appearing in the Journal of the American Geriatric Society (February 1992;40(2):168-172) looked at 22 subjects with low serum B12 levels in conjunction with cognitive dysfunction. The subjects received B12 injections (1000 milligrams) daily for one week, weekly for four weeks then monthly for a period of six months. At the beginning of the study and after at least six months of therapy, the subjects were evaluated with the Mattis Dementia Rating Scale. Of the 18 patients who finished the study, 11 showed improvement. The amount of improvement experienced by the subjects correlated with the amount of time they had exhibited symptoms. The authors of this study believe that there is a narrow window of opportunity to treat patients with cognitive problems due to vitamin B12 deficiency and that elderly patients should be regularly screened.