Although nickel-specific enzymes have yet to be identified in higher animals, nickel can activate or inhibit a number of enzymes that usually contain other elements. The production or action of some hormones (prolactin, adrenaline, noradrenaline, aldosterone) responds to changes in nickel concentration. Within cells, nickel alters membrane properties and influences oxidation/reduction systems. Nickel has great affinity for cellular structures such as chromosomes and ion channels, but its influence on them at normal tissue concentrations is not known.

Deficiencies: It is difficult to induce a deficiency because the requirement is low and nickel comes from a variety of sources. Feeding a low nickel diet has reduced the growth of several species of animals. At the cellular level structures become disorganized and membrane properties change. Nickel deficiency has been linked to low blood glucose levels, abnormal bone growth, poor absorption of ferric iron, and altered metabolism of calcium, vitamin B-12 and energy nutrients.

Diet recommendations: Based on animal experiments, the human requirement for nickel probably does not exceed 100 �g/day. Nickel content of Western self-selected and institutional diets ranges from 60 to 260 �g/day. Adequacy of the lower intakes may depend on the bioavailability of nickel (the nickel compounds ingested and foods consumed with them).

Food sources: Rich food sources of nickel include oatmeal, dried beans and peas, nuts, and chocolate. The apparent absorption from test meals is about 1%. Up to 27% is absorbed from water but the daily intake of water provides only 1-2 �g Ni. Absorption is influenced by the amount fed, the acidity of the gut, and the presence of various binding agents (as phytate) or competing substances. In particular, the levels of other minerals such as iron, magnesium, zinc and calcium may alter nickel absorption from the gut.

Toxicity: Toxicity has occurred in workers exposed to nickel dust or nickel carbonyl formed in refining. Increased risk of nasal and lung cancers was linked to occupational nickel exposure before current workplace safety standards were set. Environmental sources of lower levels of nickel include tobacco, dental or orthopedic implants, stainless-steel kitchen utensils and inexpensive jewelry. Repeated exposures may lead to asthma and contact dermatitis, symptoms of which may worsen if the diet is high in nickel. The oral toxic dose is about 1000 times the amount consumed in food. Different chemical forms vary widely in toxicity. Excessive nickel in tissues is pro-oxidant (damaging chromosomes and other cell components) and alters hormone and enzyme activities, movement of ions through membranes, and immune function. These effects can change glucose tolerance, blood pressure, response to stress, growth rate, bone development and resistance to infection. Under some conditions, large amounts of nickel may precipitate magnesium deficiency or cause accumulation of iron or zinc.

Recent research: Additional information is needed to establish more precisely an intake/exposure range that is both adequate and safe, and to account for other factors that affect the need and tolerance for nickel.