Nickel (Ni)

Ni – Nickel is found in igneous rocks at 75 ppm; shale at 68 ppm; sandstone at 2 ppm; limestone at 20 ppm; fresh water at 0.01 ppm; sea water at 0.0054 ppm; soils at 40 ppm (higher in soils derived from serpentine); marine plants at 3 ppm; land plants at 3 ppm (accumulated by Alyssum bertalonii); marine animals at 0.4-25ppm and land animals at 0.8 ppm (accumulates in RNA).

Symptoms of Nickel Deficiency in the rat

  • Poor growth
  • Lower hematocrit (anemia)
  • Depressed oxidative ability of the liver
  • High newborn mortality
  • Rough/dry hair coat
  • Dermatitis
  • Delayed puberty
  • Poor zinc absorption

Less than 10 % of ingested metallic nickel is absorbed. Nickel deficiency was first reported in 1970.

Nickel functions as a cofactor for metalloenzymes and facilitates gastrointestinal absorption of iron and zinc. Optimal tissue levels of B12 deficiency results in an increased need for nickel by animals and man.

Nickel is a trace mineral nutrient. Nickel is now known to be an essential trace mineral nutrient of all higher plants, including cereal grains and legumes, which require nickel for seeds to grow (germinate). Nickel helps plants liberate nitrogen from soil and absorb IRON. Nickel also seems to be a trace mineral nutrient for some animal species, though its function is unknown. Diets that exclude nickel slow growth in sheep, goats, cows and rats. Nickel deficiency decreases red blood cell production in these animals as well. Nickel-deficient chickens develop abnormally. Human requirements, if any, are unknown. A typical American diet supplies an estimated 0.3 to 0.6 mg of nickel daily.

Like many trace minerals, minute amounts may be essential nutrients, though high-level exposure is hazardous. Because nickel is an industrial waste, it has emerged as an environmental pollutant. The toxicity of high doses of nickel is well documented; for example, nickel carbonyl is a hazardous industrial chemical, and exposure in the workplace is regulated. Nickel allergies are linked to jewelry; once a person is sensitized, nickel allergies are long lasting.

Selected reported deficiency signs

Depressed growth and reproductive performance in rats, minipigs, and goats; altered distribution and functioning of other nutrients including calcium, iron, Zinc, and vitamin B12 in goats and rats.

Possible function

Cofactor for an enzyme that affects the propionate pathway of branched-chain amino acid and odd-chain fatty acid metabolism.

Dietary need and sources

Human requirement most likely less than 100 mcg/day; rich food sources include chocolate, nuts, dried beans and peas, and grains.

J Nutr 1975 Dec;105(12):1620-1630

Nickel deficiency in rats.
Nielsen FH, Myron DR, Givand SH, Zimmerman TJ, Ollerich DA

Nickel deficiency was produced in rats fed diet (containing 2-15 ng of nickel/g) based on dried skim mile, acid-washed ground corn, EDTA-extracted soy protein, and corn oil. Controls were fed a supplemental 3 mug of nickel/g of diet as NiCl2-6H2O. The rats were raised in plastic cages located inside laminar flow racks. Nickel deprivation resulted in several consistent pathological findings. These included: (1) increased perinatal mortality, (2) unthriftiness in young rats characterized by a rough coat and/or uneven hair development, (3) altered gross appearance (color) of the liver, (4) increased rate of alpha-glycerophosphate oxidation by liver homogenates, (5) decreased liver cholesterol, and (6) ultrastructural changes in the liver with the most obvious difference in the amount and organization of the rough endoplasmic reticulum. Nickel deficiency in rats tended to decrease growth, hematocrits, and liver total lipids and phospholipids.

Biol Trace Elem Res 1995 Jul;49(1):43-52

Distribution of various nickel compounds in rat organs after oral administration.
Ishimatsu S, Kawamoto T, Matsuno K, Kodama Y

Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

In this study, eight kinds of nickel (Ni) compounds were orally administered to Wistar male rats and the distribution of each compound was investigated 24 h after the administration. The Ni compounds used in this experiment were nickel metal [Ni-M], nickel oxide (green) [NiO(G)], nickel oxide (black) [NiO(B)], nickel subsulfide [Ni3S2], nickel sulfide [NiS], nickel sulfate [NiSO4], nickel chloride [NiCl2], and nickel nitrate [Ni(NO3)2]. The solubilities of the nickel compounds in saline solution were in the following order; [Ni(NO3)2 > NiCl2 > NiSO4] >> [NiS > Ni3S2] > [NiO(B) > Ni-M > NiO(G)]. The Ni level in the visceral organs was higher in the rats given soluble Ni compounds; Ni(NO3)2, NiCl2, NiSO4, than that in the rats receiving other compounds. In the rats to which soluble Ni compounds were administered, 80-90% of the recovered Ni amounts in the examined organs was detected in the kidneys. On the other hand, the Ni concentration in organs administered scarcely soluble Ni compounds; NiO(B), NiO(G), and Ni-M were very low. The estimated absorbed fraction of each Ni compounds was increased with the increase of the solubility. These results suggest that the kinetic behavior of Ni compounds administered orally is closely related with the solubility of Ni compounds, and that the solubility of Ni compounds is one of the important factors for determining the health effect of Ni compounds.

Int J Vitam Nutr Res 1976;46(1):96-99

[Absorption and metabolic efficiency of iron in nickel deficiency]. [Article in German]
Schnegg A, Kirchgessner M

Absorption and Metabolic Efficiency of Iron During Ni Deficiency. Ni deficiency leads to reduced iron contents in organs and to greatly reduced hemoglobin levels and erythrocyte counts. Using models it was studied whether this Ni-dependent Fe anemia can be attributed to an impaired absorption of iron or to its metabolic efficiency. An experiment with seven 30-day-old rats from each of two generations were used for this. In Ni deficiency (0.015 ppm dietary nickel) iron absorption was clearly impaired at both 50 ppm and 100 ppm iron in the diet. Compared to the groups given 20 ppm nickel, the amount of iron absorbed fell two-thirds and one-third, respectively. By comparison, the influence on the metabolic efficiency of the iron was relatively small; at high iron supply, however, it was reduced by 8% in the Ni-deficient animals. Therefore, the reduced levels of hemoglobin, erythrocytes and hematocrit must essentially be caused by the impaired absorption.

J Nutr 1996 Oct;126(10):2466-2473

Nickel deficiency alters liver lipid metabolism in rats.
Stangl GI, Kirchgessner M

Institut fur Ernahrungsphysiologie der Technischen Universitat, Munchen-Weihenstephan, Freising, Germany.

The present investigation was designed to examine the effect of nickel deficiency on lipid metabolism in liver and serum lipoproteins of rats. Therefore, a study over two generations was conducted feeding a nickel-deficient diet containing 13 mcg/kg nickel or a nickel-adequate diet supplemented with 1 mg/kg nickel. Male 7-wk-old pups from the second offspring were studied. Pups fed a diet poor in nickel tended to have lower weight gains (P < 0.15), nickel concentrations in liver (P < or = 0.1) and iron levels in serum (P < 0.1) than nickel-adequate rats. They were classified as nickel-deficient on the basis of significantly lower erythrocyte counts, hemoglobin concentrations, hematocrits and nickel concentrations in kidney compared with nickel-adequate rats. Nickel deficiency caused a significant triacylglycerol accumulation in liver, with greater concentrations of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids than nickel-adequate rats. Nickel deficiency had slight but significant effects on the fatty acid composition of liver total lipids and phosphatidylcholine and phosphatidylethanolamine. Moreover, nickel-deficient rats had significantly lower activities of the lipogenic enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme and fatty acid synthase than nickel-adequate rats. Nickel-depleted pups had significantly higher concentrations of triacylglycerols and phospholipids in serum VLDL, and cholesterol in serum LDL than nickel-adequate pups. Most of these alterations in lipid metabolism are similar to those obtained in several iron-deficiency studies. Because nickel deficiency also slightly compromised iron status, it is possible that at least some of the observed alterations are due to the moderate iron deficiency.

Biol Trace Elem Res 1996 Apr;52(1):23-35

Dietary folate affects the response of rats to nickel deprivation.
Uthus EO, Poellot RA

United States Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034, USA.

Because vitamin B12 and Ni are known to interact and because of the similar metabolic roles of vitamin B12 and folate, an experiment was performed to determine the effect of dietary folate on Ni deprivation in rats. A 2 x 2 factorially arranged experiment used groups of nine weanling Sprague-Dawley rats. Dietary variables were Ni, as NiCl(2) 6H(2)0, 0 or 1 mu g/g; and folic acid, 0 or 2 mg/kg. The basal diet, based on skim milk, contained less than 20 ng Ni/g. After 54 d, an interaction between dietary Ni and folate affected several variables including erythrocyte folate, plasma amino acids, and femur trace elements. For example, folate deprivation decreased erythrocyte folate; folate supplementation to the Ni-supplemented rats caused a larger increase in erythrocyte folate concentration than did folate supplementation to the Ni-deprived rats. Also, dietary Ni affected several plasma amino acids important in one-carbon metabolism (e.g., Ni deprivation increased the plasma concentrations of glycine and serine). This study shows that dietary Ni, folate, and their interaction can affect variables associated with one-carbon metabolism. This study does not show a specific site of action of Ni but it indicates that Ni may be important in processes related to the vitamin B12-dependent pathway in methionine metabolism, possibly one-carbon metabolism.

Nickel Summary

Interest in the biochemistry of nickel has been stimulated by recent discoveries of its essentiality to various microorganisms, plants, and animals and of the existence of several nickel metalloenzymes in plants and microorganisms. Signs of nickel deprivation have been described for six animal species–chick, cow, goat, minipig, rat, and sheep. Included among the more consistent signs of deficiency in mammals are depressed growth, unthriftiness characterized by rough hair coat, and an altered iron metabolism leading to depressed hematopoiesis. The predominant sign of nickel deficiency for microorganisms is depressed growth, and for plants is depressed nitrogen utilization. In plants and microorganisms, nickel is known to function in several metalloenzymes including urease, several hydrogenases, and carbon monoxide dehydrogenase. In higher animals, the evidence showing that nickel is essential has not defined its metabolic function. The finding of nickel metalloenzymes in lower forms of life suggests that a similar function for nickel in animals may be found.

Divalent nickel is the apparent important oxidation state in the metabolism of nickel. Ultrafilterable Ni2+ binding ligands, perhaps histidine and cystine, apparently play important roles in the extracellular transport of nickel, intracellular binding of nickel, and excretion of nickel in urine and bile. Two Ni2l binding proteins suggested to have a role in the transport and homeostasis of nickel in serum are albumin and histidine-rich glycoprotein. The transport of nickel across the mucosal epithelium apparently occurs as Ni2+ and is an energy-driven process, rather than one driven by simple diffusion, and is probably connected with the iron-transport system. Only recently another oxidation state of nickel has been indicated to be important in biochemistry. Ni3+ apparently is important for the activity of bacterial hydrogenases.

In conclusion, emerging evidence indicates that nickel is a dynamic trace element in living organisms. However, knowledge of the biochemistry of nickel is very limited. Thus, further research on nickel biochemistry is needed to help evaluate the nature and importance of the physiologic, pharmacologic, and toxicologic actions of nickel.