It wasn’t until 1973 that the first randomized controlled clinical trial—involving 29 subjects and lasting only six weeks—took place. The participants, all with normal vitamin B12 blood levels, were given either a twice-weekly dose of the vitamin or a placebo for two weeks, followed by a rest period of two weeks, and a final two-week phase in which the vitamin and placebo recipients were secretly switched.
The study was flawed because only the group that received the vitamin first was analyzed. No statistical differences were noted in appetite, sleep patterns, and fatigue, but those initially given vitamin B12 were “happier” and “felt better.”
In another small randomized controlled study from 1989, five people with chronic fatigue syndrome were given a mixture of liver extract, folic acid, and B12, or a placebo, at different phases of the month-long study. Their fatigue levels were the same regardless of which phase they were in.
The role of vitamin B12 has been much better established as replacement therapy for people who are really deficient in the vitamin, which is essential for DNA synthesis, red blood cell development, peripheral nerve integrity, and cognitive function. B12 is not made in our bodies and can be obtained only from animal proteins (or artificially fortified grains). Once it’s ingested, stomach acid is necessary to pry it from food, after which the vitamin combines with something called intrinsic factor, a substance made in the stomach, before eventually being absorbed in the small intestine.