Vitamin B6 is a water-soluble vitamin, and is readily metabolized and excreted, so it has generally been assumed to have negligible toxicity, although at very high levels of intake it can cause peripheral nerve damage. Nutritional deficiency disease is extremely rare, although a significant proportion of the population shows biochemical evidence of inadequate status, despite apparently adequate levels of intake. The vitamin has been used to treat a wide variety of conditions, which may or may not be related to inadequate intake. In some conditions use of vitamin B6 supplements has been purely empirical; in other conditions there is a reasonable physiological or metabolic mechanism to explain why supplements of the vitamin many times greater than average requirements may have therapeutic uses. However, even in such conditions there is little evidence of efficacy from properly conducted controlled trials.