***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The study of Cu metabolism is hampered by a lack of sensitive and specific biomarkers of status and suitable isotopic labels , but limited information suggests that Cu homeostasis is maintained through changes in absorption and endogenous loss . The aim of the present study was to employ stable-isotope techniques to measure Cu absorption and endogenous losses in adult men adapted to low , moderate and high Cu-supplemented diets . Twelve healthy men , aged 20 - 59 years , were given diets containing 0.7 , 1.6 and 6.0 mg Cu/d for 8 weeks , with at least 4 weeks intervening washout periods . After 6 weeks adaptation , apparent and true absorption of Cu were determined by measuring luminal loss and endogenous excretion of Cu following oral administration of 3 mg highly enriched (65)Cu stable-isotope label . Apparent and true absorption ( 41 and 48 % respectively ) on the low-Cu diet were not significantly different from the high-Cu diet ( 45 and 48 % respectively ) . Endogenous losses were significantly reduced on the low- ( 0.45 mg/d ; P<0.001 ) and medium- ( 0.81 mg/d ; P=0.001 ) compared with the high-Cu diet ( 2.46 mg/d ) . No biochemical changes result ing from the dietary intervention were observed . Cu homeostasis was maintained over a wide range of intake and more rapidly at the lower intake , mainly through changes in endogenous excretion A double-blind study was done giving 10 mg of copper/day as copper gluconate or placebo capsules for 12 wk . The seven subjects receiving copper gluconate  had no change in the level of copper in the serum , urine , or hair . There was also no change in the levels of zinc or magnesium . There was also no significant change in levels of hematocrit , triglyceride , SGOT , GGT , LDH , cholesterol , or alkaline phosphatase . The side effects of nausea , diarrhea , and heartburn were the same in the subjects receiving copper gluconate and subjects receiving placebo capsules We examined the effects of low-copper diets on indexes of immune response of 11 healthy men ( aged 21 - 32 y ) during a 90-d metabolic suite study . Daily copper intake for the first 24 d , next 42 d , and the last 24 d of the study was 0.66 , 0.38 , and 2.49 mg , respectively . Feeding the diet with 0.38 mg Cu/d was associated with a significant ( P < or = 0.05 ) decrease in the proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin , Concanavalin A , or pokeweed , and an increase in the percentage of circulating B cells ( CD 19 + ) , but had no effect on the concentration of serum interleukin 2 receptor , the percentage of peripheral monocytes , neutrophils , CD3 + , CD4 + , or CD8 + T cells ; or on the neutrophil phagocytic activity . Feeding 2.49 mg Cu/d for 24 d prevented further decreases in the indexes affected by the low-copper diet but did not restore them to the pre study concentrations , even though plasma copper and ceruloplasmin concentrations were restored to normal The effects of calcium supplementation ( as calcium citrate malate , 1000 mg elemental Ca/d ) with and without the addition of zinc ( 15.0 mg/d ) , manganese ( 5.0 mg/d ) and copper ( 2.5 mg/d ) on spinal bone loss ( L2-L4 vertebrae ) was evaluated in healthy older postmenopausal women ( n = 59 , mean age 66 y ) in a 2-y , double-blind , placebo-controlled trial . Changes ( mean + /- SEM ) in bone density were -3.53 + /- 1.24 % ( placebo ) , -1.89 + /- 1.40 % ( trace minerals only ) , -1.25 + /- 1.46 % ( calcium only ) and 1.48 + /- 1.40 % ( calcium plus trace minerals ) . Bone loss relative to base-line value was significant ( P = 0.0061 ) in the placebo group but not in the groups receiving trace minerals alone , calcium alone , or calcium plus trace minerals . The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals ( P = 0.0099 ) . These data suggest that bone loss in calcium-supplemented , older postmenopausal women can be further arrested by concomitant increases in trace mineral intake A study was conducted in young men to evaluate the effect of a low-copper diet on copper absorption , excretion , and retention .  Eleven young men were confined to a metabolic research unit for 90 d. The study was divided into three periods , with dietary copper as the only variable . Dietary copper intake was 0.66 mg/d for 24 d , 0.38 mg/d for 42 d , and 2.49 mg/d for 24 d. The stable isotope 65Cu was fed to five of the subjects once during the first and last dietary period and twice , early and late , in the second period to determine copper absorption . 65Cu was infused into an arm vein of the other six subjects once during each dietary period to estimate excretion of endogenous copper . Total copper and 65Cu were determined by isotope dilution with thermal-ionization mass spectrometry . Fractional absorption was significantly higher during the low-copper period than in either period with higher dietary copper and excretion of the infused isotope was significantly lower in the low-copper period . Subjects were in negative balance early in the first two periods but achieved balance by the end of those periods . They retained copper during the highest dietary copper period ( third period ) . The results suggest that endogenous copper excretion is a major point of regulation of the body 's copper stores . Regulation of absorption and of endogenous excretion in response to dietary copper intake helps to protect against deficiency and toxicity . However , this regulation was not sufficient to maintain copper status at the lowest intake of dietary copper , 0.38 mg/d Red cell superoxide dismutase ( SOD ) activity was evaluated as a biochemical index of copper nutrition in a double-blind study of 17 infants recovering from malnutrition and receiving marginal copper intakes . Children were paired on admission by sex , birth weight , nutritional status and antecedents of diarrhea and breast feeding . Nine served as controls receiving a copper sulfate supplement ( 80 micrograms/kg daily for 120 d ; eight received a placebo and were supplemented only if plasma copper levels dropped below 90 micrograms/dl or on d 90 for at least 30 d. After copper supplementation there was a significant rise ( paired t-test ; P less than 0.05 ) in plasma copper ( 96 vs. 165 micrograms/dl ) ; ceruloplasmin ( 33 vs. 50 mg/dl ) and SOD ( 1073 vs. 1371 U/g Hb ) . After supplementation these values were similar to those of the controls . SOD was correlated with plasma copper ( r = 0.78 ; P less than 0.001 ) and not with weight-for-age or weight-for-length . Addition of copper in vitro did not modify the SOD activity . Red cell SOD is a good marker of copper nutrition in humans and correlates well with plasma copper BACKGROUND Numerous studies have examined the effect of low and adequate intakes of copper on absorption and retention , but little information is available on the regulation of absorption and retention of copper when intake is high . OBJECTIVE A study was conducted in men to determine the effect of long-term high copper intake on  copper absorption , retention , and homeostasis . DESIGN Nine men were confined to a metabolic research unit ( MRU ) for 18 d and were fed a 3-d rotating menu containing an average of 1.6 mg Cu/d . They continued the study under free-living conditions for 129 d , supplementing their usual diets with 7 mg Cu/d . They then returned to the MRU for 18 d and consumed the same diet as during the first period , except that copper intake was 7.8 mg/d . The stable isotope (63)Cu was fed to 3 subjects and infused into the other 6 on day 7 of each MRU period , and complete urine and stool collection s were made throughout the study . Total copper and (63)Cu were determined by inductively coupled plasma mass spectrometry . Copper absorption , excretion , and retention were calculated on the basis of dietary , urinary , and fecal copper and (63)Cu . RESULTS Results were as follows when comparing the high copper intake with the usual intake : fractional copper absorption was significantly lower , but the amount absorbed was significantly higher ; excretion of the infused (63)Cu was significantly faster ; and total retention was significantly higher . CONCLUSIONS Homeostatic regulation of copper absorption and retention helped to minimize the amount of copper retained with high copper intake but was not sufficient to prevent retention of > 0.6 mg Cu/d Western diets containing suboptimal Cu concentrations could be widespread . A link between marginal Cu deficiency and CVD has been suggested . The objective of the present study was to investigate the effect of Cu supplementation on both Cu status and CVD risk factors in healthy young women . Sixteen women with a mean age of 24 ( sd 2 ) years participated in a r and omised crossover study of three 4-week periods with 3-week washouts between periods . During each intervention period , subjects received 0 , 3 or 6 mg elemental Cu/d as CuSO4 in addition to their habitual diet . Blood sample s were taken to assess the effect of supplementation on putative markers of Cu status . The content of plasma lipids , lipoprotein ( a ) , apo and certain haemostatic factors , as putative indices of CVD , was also analysed . Daily supplementation with 3 mg Cu significantly increased ( P < 0.05 ) serum Cu concentration and the activity of erythrocyte superoxide dismutase , although there was no further significant increase after an intake of 6 mg Cu/d . The concentration of the fibrinolytic factor plasminogen activator inhibitor type 1 was significantly reduced ( P < 0.05 ) by about 30 % after supplementation with 6 mg Cu/d . No other marker of Cu status or CVD risk factor was affected by Cu supplementation . The results indicate that supplementation with 3 or 6 mg Cu/d may improve Cu status in these healthy young women . Increased Cu intake could reduce the risk of CVD and atherosclerosis in man by promoting improved fibrinolytic capacity In rats , copper deficiency leads to low copper metalloenzyme activity , high serum cholesterol , and cardiovascular lesions . In humans , moderately low copper intake may be common , but the consequences remain largely uncertain . The present study examined the effects of copper supplementation ( 2 mg/d for 4 weeks in a copper/placebo crossover design ) in 20 adult men with moderately high plasma cholesterol . End-point measurements were three copper enzyme activities , erythrocyte superoxide dismutase ( SOD ) , plasma ceruloplasmin ( Cp ) , and plasma diamine oxidase ( DAO ) , and three parameters related to the risk of cardiovascular disease ( CVD ) , plasma cholesterol , plasma lipoprotein ( a ) [ Lp(a ) ] , and lag times for very-low-density lipoprotein ( VLDL ) and low-density lipoprotein ( LDL ) oxidation in vitro . Although copper had no significant effects on any parameter for the entire study group , it did significantly increase two enzyme activities ( SOD and DAO ) , as well as lipoprotein oxidation lag times , in 10 subjects in the lower half of a median split for precopper values . Thus , copper supplementation appeared to influence some types of measurements in subjects beginning with less than median values No sensitive functional index is currently available to assess Cu status in healthy human population s. This study evaluated the effect of Cu supplementation on putative indices of Cu status in twelve women and twelve men , aged between 22 and 45 years , who participated in a double-blind placebo controlled crossover study . The study consisted of three 6-week supplementation regimens of 3 mg CuSO4 , 3 mg Cu-glycine chelate and 6 mg Cu-glycine chelate , each separated by placebo periods of equal length . Women had significantly higher caeruloplasmin oxidase activity ( P < 0.001 ) , caeruloplasmin protein concentration ( P < 0.05 ) , and serum diamine oxidase activity ( P < 0.01 ) at baseline than men . Erythrocyte and leucocyte superoxide dismutase activity , leucocyte cytochrome c oxidase activity , and erythrocyte glutathione peroxidase activity did not respond to Cu supplementation . Platelet cytochrome c oxidase activity was significantly higher ( P < 0.01 ) , after supplementation with 6 mg Cu-glycine chelate in the total group and in women but did not change in men . Caeruloplasmin 
    Output:
    
Data for serum copper suggested its value as a biomarker , reflecting changes in status in both depleted and replete individuals , although these changes were smaller in the latter .
Total ceruloplasmin protein is related to copper status but reflects changes in highly depleted individuals only .
Erythrocyte superoxide dismutase and urinary deoxypyridinoline are not useful biomarkers , but there were insufficient data to draw firm conclusions about plasma , erythrocyte , and platelet copper ; leukocyte superoxide dismutase ; erythrocyte , platelet , and plasma glutathione peroxidase ; platelet and leukocyte cytochrome-c oxidase ; total glutathione ; diamine oxidase ; and urinary pyridinoline .
Despite limited data , serum copper appears to be a useful biomarker of copper status at the population level .