Dietary copper and human health: Current evidence and unresolved issues.

Although copper (Cu) is recognized as an essential trace element, uncertainties remain regarding Cu reference values for humans, as illustrated by discrepancies between recommendations issued by different national authorities. This review examines human studies published since 1990 on relationships between Cu intake, Cu balance, biomarkers of Cu status, and health. It points out several gaps and unresolved issues which make it difficult to assess Cu requirements. Results from balance studies suggest that daily intakes below 0.8 mg/day lead to net Cu losses, while net gains are consistently observed above 2.4 mg/day. However, because of an incomplete collection of losses in all studies, a precise estimation of Cu requirements cannot be derived from available data. Data regarding the relationship between Cu intake and potential biomarkers are either too preliminary or inconclusive because of low specificity or low sensitivity to change in dietary Cu over a wide range of intakes. Results from observation and intervention studies do not support a link between Cu and a risk of cardiovascular disease, cognitive decline, arthritis or cancer for intakes ranging from 0.6 to 3mg/day, and limited evidence exists for impaired immune function in healthy subjects with a very low (0.38 mg/day) Cu intake. However, data from observation studies should be regarded with caution because of uncertainties regarding Cu concentration in various foods and water. Further studies that accurately evaluate Cu exposure based on reliable biomarkers of Cu status are needed.

[1]  J. Cerhan,et al.  Antioxidant intake from fruits, vegetables and other sources and risk of non‐Hodgkin's lymphoma: the Iowa Women's Health Study , 2009, International journal of cancer.

[2]  J. Sweeney,et al.  Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery , 2012, International Journal of Obesity.

[3]  D. Medeiros,et al.  Copper supplementation effects on indicators of copper status and serum cholesterol in adult males , 1991, Biological Trace Element Research.

[4]  R. Gibson,et al.  Dietary intakes of adolescent females consuming vegetarian, semi-vegetarian, and omnivorous diets. , 1996, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[5]  L. Klomp,et al.  New developments in the regulation of intestinal copper absorption. , 2009, Nutrition reviews.

[6]  M. Gupta,et al.  Serum Copper in Myocardial Infarction—Diagnostic and Prognostic Significance , 1983, Angiology.

[7]  W. Skinner,et al.  The Occurrence and Incorporation of Copper and Zinc in Hair and their Potential Role as Bioindicators: A Review , 2007, Journal of toxicology and environmental health. Part B, Critical reviews.

[8]  C. Davis Low dietary copper increases fecal free radical production, fecal water alkaline phosphatase activity and cytotoxicity in healthy men. , 2003, The Journal of nutrition.

[9]  L. Klevay,et al.  Effect of copper intake on balance, absorption, and status indices of copper in men , 1990 .

[10]  Gert B. M. Mensink,et al.  Intake of selected nutrients from foods, from fortification and from supplements in various European countries , 2009, Food & nutrition research.

[11]  E. Pinelli,et al.  Bioavailability of Cu and Zn in raw and anaerobically digested pig slurry. , 2009, Ecotoxicology and environmental safety.

[12]  C. Davis,et al.  Low dietary zinc alters indices of copper function and status in postmenopausal women. , 2001, Nutrition.

[13]  J. Turnlund Copper nutriture, bioavailability, and the influence of dietary factors. , 1988, Journal of the American Dietetic Association.

[14]  H. Mcardle,et al.  Iron, copper and fetal development , 2004, Proceedings of the Nutrition Society.

[15]  R Pettersson,et al.  Daily intake of copper from drinking water among young children in Sweden. , 1999, Environmental health perspectives.

[16]  H. Kodama,et al.  Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment , 2012, Current drug metabolism.

[17]  J. Cerhan,et al.  Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. , 2003, American journal of epidemiology.

[18]  S. Bügel,et al.  Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project). , 2000, Free radical biology & medicine.

[19]  W. Buckley,et al.  Analytical variables affecting exchangeable copper determination in blood plasma , 2008, BioMetals.

[20]  M. Linder,et al.  Synthesis and Turnover of Ceruloplasmin in Rats Treated with 17β-Estradiol , 1993 .

[21]  P. Hinsinger,et al.  Copper bioavailability and extractability as related to chemical properties of contaminated soils from a vine-growing area. , 2003, Environmental pollution.

[22]  I. Rodushkin,et al.  Application of double focusing sector field ICP-MS for multielemental characterization of human hair and nails. Part II. A study of the inhabitants of northern Sweden. , 2000, The Science of the total environment.

[23]  G. Brewer Copper toxicity in Alzheimer's disease: cognitive loss from ingestion of inorganic copper. , 2012, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[24]  T. Decsi,et al.  Methods of assessment of zinc status in humans: a systematic review. , 2009, The American journal of clinical nutrition.

[25]  C. Keen,et al.  Copper status and urinary and salivary copper in young men at three levels of dietary copper. , 1990, The American journal of clinical nutrition.

[26]  Y. Schutz,et al.  Copper absorption in elderly men determined by using stable 65Cu. , 1982, The American journal of clinical nutrition.

[27]  J. Dwyer,et al.  Dietary supplement use is associated with higher intakes of minerals from food sources. , 2011, The American journal of clinical nutrition.

[28]  C. Keen,et al.  Copper status of young men consuming a low-copper diet. , 1997, The American journal of clinical nutrition.

[29]  Alberto Costa,et al.  Zinc and copper in breast cancer. A joint study in northern italy and southern france , 1991 .

[30]  B. Mackey,et al.  Effects of low-copper diets on human immune response. , 1995, The American journal of clinical nutrition.

[31]  C. Keen,et al.  Copper, oxidative stress, and human health. , 2005, Molecular aspects of medicine.

[32]  J. Canary,et al.  Effect of copper intake on blood cholesterol and its lipoprotein distribution in men , 1987 .

[33]  M. Hamer,et al.  Redox-modulatory vitamins and minerals that prospectively predict mortality in older British people: the National Diet and Nutrition Survey of people aged 65 years and over , 2010, British Journal of Nutrition.

[34]  H. Allen,et al.  Effect of soil copper content and pH on copper uptake of selected vegetables grown under controlled conditions , 2002, Environmental toxicology and chemistry.

[35]  Manuel Olivares,et al.  Age and copper intake do not affect copper absorption, measured with the use of 65Cu as a tracer, in young infants. , 2002, The American journal of clinical nutrition.

[36]  J. Turnlund Use of enriched stable isotopes to determine bioavailability of trace elements in humans. , 1983, The Science of the total environment.

[37]  J. Strain,et al.  Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men. , 2004, The American journal of clinical nutrition.

[38]  S. Fairweather-Tait,et al.  Adaptive responses in men fed low- and high-copper diets , 2003, British Journal of Nutrition.

[39]  H. Mcardle,et al.  Biomarkers of copper status: a brief update. , 2008, The British journal of nutrition.

[40]  L. Klevay Copper and cognition , 2010, Clinical Neurophysiology.

[41]  P. E. Johnson,et al.  Effects of age and sex on copper absorption, biological half-life, and status in humans. , 1992, The American journal of clinical nutrition.

[42]  S. Jaiser,et al.  Copper deficiency myelopathy , 2010, Journal of Neurology.

[43]  M. Jägerstad,et al.  Nutrient intake and health status of lactovegetarians: chemical analyses of diets using the duplicate portion sampling technique. , 1981, The American journal of clinical nutrition.

[44]  J. Beattie,et al.  Holmium as a faecal marker for copper absorption studies in adults , 2002 .

[45]  J. Turnlund,et al.  Dietary copper intake influences skin lysyl oxidase in young men , 1997 .

[46]  R. Gambino,et al.  Associations of dietary and serum copper with inflammation, oxidative stress, and metabolic variables in adults. , 2008, The Journal of nutrition.

[47]  J. Hunt,et al.  Apparent copper absorption from a vegetarian diet. , 2001, The American journal of clinical nutrition.

[48]  G. Ferns,et al.  Determinants of serum copper, zinc and selenium in healthy subjects , 2005, Annals of clinical biochemistry.

[49]  G. Barbati,et al.  Is cognitive function linked to serum free copper levels? A cohort study in a normal population , 2010, Clinical Neurophysiology.

[50]  J. Karl,et al.  Nutrient deficiencies after gastric bypass surgery. , 2013, Annual review of nutrition.

[51]  J. Schneider,et al.  Dietary copper and high saturated and trans fat intakes associated with cognitive decline. , 2006, Archives of neurology.

[52]  J. Prohaska,et al.  Role of copper transporters in copper homeostasis. , 2008, The American journal of clinical nutrition.

[53]  A. Khalique,et al.  A Comparative Study Based on Gender and Age Dependence of Selected Metals in Scalp Hair , 2005, Environmental monitoring and assessment.

[54]  T. Starks,et al.  65Copper absorption by women fed intrinsically and extrinsically labeled goose meat, goose liver, peanut butter and sunflower butter. , 1988, The Journal of nutrition.

[55]  S. Sadhra,et al.  Dietary exposure to copper in the European Union and its assessment for EU regulatory risk assessment. , 2007, The Science of the total environment.

[56]  V. McKelvey-Martin,et al.  Copper Supplementation Has No Effect on Markers of DNA Damage and Liver Function in Healthy Adults (FOODCUE Project) , 2003, Annals of Nutrition and Metabolism.

[57]  B. Zietz,et al.  Copper concentrations in tap water and possible effects on infant's health--results of a study in Lower Saxony, Germany. , 2003, Environmental research.

[58]  I. Davies,et al.  Use of mathematical modeling to study copper metabolism in humans. , 2005, The American journal of clinical nutrition.

[59]  J. Turnlund,et al.  Copper absorption and retention in young men at three levels of dietary copper by use of the stable isotope 65Cu. , 1989, The American journal of clinical nutrition.

[60]  P. van’t Veer,et al.  Projected Prevalence of Inadequate Nutrient Intakes in Europe , 2011, Annals of Nutrition and Metabolism.

[61]  J. Suliburska,et al.  A Comparison of Levels of Select Minerals in Scalp Hair Samples with Estimated Dietary Intakes of These Minerals in Women of Reproductive Age , 2011, Biological Trace Element Research.

[62]  H. Adlercreutz,et al.  Simultaneous Investigation of Dietary and Plasma Copper, Zinc, Iron and Selenium in Pre- and Post-menopausal Omnivores, Vegetarians and Patients with Early Breast Cancer , 1994 .

[63]  D. Thiele,et al.  How reliable and robust are current biomarkers for copper status , 2007 .

[64]  M. Olivares,et al.  Gastrointestinal symptoms and blood indicators of copper load in apparently healthy adults undergoing controlled copper exposure. , 2003, The American journal of clinical nutrition.

[65]  A. Schatzkin,et al.  Mineral Intake and Lung Cancer Risk in the NIH-American Association of Retired Persons Diet and Health Study , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[66]  J. Turnlund,et al.  Copper absorption, excretion, and retention by young men consuming low dietary copper determined by using the stable isotope 65Cu. , 1998, The American journal of clinical nutrition.

[67]  J. Turnlund Human whole-body copper metabolism. , 1998, The American journal of clinical nutrition.

[68]  J. Turnlund,et al.  Long-term high copper intake: effects on copper absorption, retention, and homeostasis in men. , 2005, The American journal of clinical nutrition.

[69]  A. Hofman,et al.  Serum copper and zinc and the risk of death from cancer and cardiovascular disease. , 1988, American journal of epidemiology.

[70]  I. Hosen,et al.  Oxidative stress and human health , 2012 .

[71]  I. Voskoboinik,et al.  Signals regulating trafficking of Menkes (MNK; ATP7A) copper-translocating P-type ATPase in polarized MDCK cells. , 2004, American journal of physiology. Cell physiology.

[72]  J. Salonen,et al.  Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland. , 1991, American journal of epidemiology.

[73]  M. Georgieff Nutrition and the developing brain: nutrient priorities and measurement. , 2007, The American journal of clinical nutrition.

[74]  J. Dwyer,et al.  Do dietary supplements improve micronutrient sufficiency in children and adolescents? , 2012, The Journal of pediatrics.

[75]  M. Bonham,et al.  Response of putative indices of copper status to copper supplementation in human subjects , 2000, British Journal of Nutrition.

[76]  J. King,et al.  A stable isotope study of copper absorption in young men: effect of phytate and alpha-cellulose. , 1985, The American journal of clinical nutrition.

[77]  K. Cashman,et al.  Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males , 1999, European Journal of Clinical Nutrition.

[78]  J. M. Munoz,et al.  Whole body surface loss of trace metals in normal males. , 1981, The American journal of clinical nutrition.

[79]  M. Bonham,et al.  The immune system as a physiological indicator of marginal copper status? , 2002, The British journal of nutrition.

[80]  E. Barrett-Connor,et al.  Plasma trace elements and cognitive function in older men and women: The Rancho Bernardo study , 2008, The journal of nutrition, health & aging.

[81]  F. Nielsen,et al.  Effects of a diet low in copper on copper-status indicators in postmenopausal women. , 1996, The American journal of clinical nutrition.

[82]  H. Lukaski,et al.  Increased cholesterol in plasma in a young man during experimental copper depletion. , 1984, Metabolism: clinical and experimental.

[83]  B. Cozzi,et al.  Accumulation of copper and other metal ions, and metallothionein I/II expression in the bovine brain as a function of aging , 2008, Journal of Chemical Neuroanatomy.