LONG-TERM HIGH COPPER INTAKE: EFFECTS ON INDICES OF COPPER STATUS, ANTIOXIDANT STATUS, AND IMMUNE FUNCTION IN YOUNG MEN

Authors: Turnlund, Judith; Jacob, Robert; KEEN, CARL - UNIV.CA.DAVIS NUTR.DEPT.; STRAIN, J. - UNIV. OF ULSTER, NICHE; Kelley, Darshan; Domek, Joseph; Keyes, William; ENSUNSA, JODI - UNIV.CA.DAVIS,NUTR.DEPT.; LYKKESFELDT, JENS - COPENHAGEN, DENMARK; COULTER, JAMES - UNIV.OF ULSTER, NICHE

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/31/2003
Publication Date: 10/31/2003
Citation: Turnlund, J.R., Jacob, R.A., Keen, C.L., Strain, J.J., Kelley, D.S., Domek, J.M., Keyes, W.R., Ensunsa, J.L., Lykkesfeldt, J., Coulter, J. 2004. Long-term high copper intake: effects on indices of copper status, antioxidant status, and immune function in young men. American Journal of Clinical Nutrition. 79:1037-1044.

Interpretive Summary: Short-term high copper intake does not appear to affect indices of copper status or functions related to copper status, but effects of long-term high copper intake are not known. Therefore, we conducted a study in men to determine the effect of long-term high copper intake on indices of copper status, oxidant damage and immune function. Nine men were confined to a metabolic research unit for 18 d and fed a 3-d rotating menu with an average of 1.6 mg/d copper. They continued the study under free-living conditions for 129 d, supplementing their usual diets with 7 mg/d copper. The men returned to the unit for another 18 d with the same diet as the first period, except copper intake was increased to 7.8 mg/d. Copper status, antioxidant status and immune function were evaluated. Copper status. Plasma copper, Cp activity, Cp protein, plasma malondialdehyde (MDA), benzylamine oxidase (BAO) activity, erythrocyte superoxiiide dismutase (SOD), hair copper, urinary copper, and urinary thiobarbituric acid reactive substance (TBARS) were compared in each period. Cp activity, BAO and SOD were significantly higher at the end of the second period than the first. Urinary copper excretion and hair copper concentration were significantly higher during the second period than the first. Antioxidant status. Urine TBARS were significantly higher in the second period. Immune function. Both polymorphonuclear cell (PMN) count and % of white blood cells (WBC), lymphocyte count, and IL-2R, were affected by copper supplementation. Antibody titer for Beijing strain of influenza virus was significantly lower in supplemented subjects following immunization than in unsupplemented controls. The results suggest that under highly controlled conditions, long term high copper intake results in increases in some indices of copper status, alters an index of oxidant stress, and affects several indices of immune function. The physiological implications of these changes are not known.

Technical Abstract: Background: Short-term high copper intake does not appear to affect indices of copper status or functions related to copper status, but effects of long-term high copper intake are not known. Objective: A study was conducted in men to determine the effect of long-term high copper intake on indices of copper status, oxidant damage and immune function. Design: Nine men were confined to a metabolic research unit (MRU) for 18 d and fed a 3-d rotating menu with an average of 1.6 mg/d copper. They continued the study under free-living conditions for 129 d, supplementing their usual diets with 7 mg/d copper. The men returned to the MRU for another 18 d with the same diet as the first period, except copper intake was increased to 7.8 mg/d. Copper status, antioxidant status and immune function were evaluated. Results: Copper status. Plasma copper, Cp activity, Cp protein, plasma malondialdehyde (MDA), benzylamine oxidase (BAO) activity, erythrocyte superoxiiide dismutase (SOD), hair copper, urinary copper, and urinary thiobarbituric acid reactive substance (TBARS) were compared in each MRU period. Cp activity, BAO and SOD were significantly higher at the end of the second MRU period than the first. Urinary copper excretion and hair copper concentration were significantly higher during the second MRU period than the first. Antioxidant status. Urine TBARS were significantly higher in the second MRU period. Immune function. Both polymorphonuclear cell (PMN) count and % of white blood cells (WBC), lymphocyte count, and IL-2R, were affected by copper supplementation. Antibody titer for Beijing strain of influenza virus was significantly lower in supplemented subjects following immunization than in unsupplemented controls. Conclusions: The results suggest that under highly controlled conditions,long term high copper intake results in increases in some indices of copper status, alters an index of oxidant stress, and affects several indices of immune function. The physiological implications of these changes are not known.