Biomedical subjects

J J Strain

Publications and source records attributed to J J Strain.

At least 37 records · Page 2Linked to original sources

PubMed2004

Total homocysteine is not a determinant of arterial pulse wave velocity in young healthy adults.

AIMS: Hyperhomocysteinaemia has been associated with reduced pulse wave velocity (PWV) in patients with end-stage renal disease and in those with hypertension. The aim of this study was to examine the association between total homocysteine (tHcy) concentrations, the biochemical and genetic determinants of tHcy and PWV in healthy young adults. METHODS AND RESULTS: A total of 489 subjects aged 20-25 years participated. A fasting blood sample was taken and PWV measured using a non-invasive optical method. tHcy did not correlate with PWV, whether assessed at the aorto-iliac segment (P = 0.18), the aorto-radial segment (P = 0.39) or the aorto-dorsalis-pedis segment (P = 0.22). When tHcy was classified into normal (<15) and high (> or =15micromol/l), PWV did not differ between the two groups at any segment. PWV did not differ by MTHFR C677T or NOS3 G894T genotype, even when smoking and folate sub-groups were considered. Considering aortic PWV as a dependent variable, stepwise regression analysis showed that the only parameter entering the model for all segments was systolic blood pressure (aorto-iliac, P < 0.001; aorto-radial, P = 0.01; aorto-dorsalis-pedis, P = 0.001). Age, sex, COL1A1 genotype and triglycerides entered the model significantly for two of three segments. CONCLUSION: This study shows that arterial PWV is not associated with tHcy in a healthy young population.

Adult↗

PubMed2004

Insulin-like growth factor-I (IGF-I) and its association with lymphocyte homeostasis in the ageing cat.

Ageing affects feline lymphocyte homeostasis in a similar pattern to that observed in other long-lived mammalian species, contributing to increased levels of morbidity and mortality in the ageing cat. Insulin-like growth factor-I (IGF-I) is now recognised as an important endocrine regulator of immunity and has been shown to decline with age in humans and rodent species. Analysis of plasma IGF-I in adult and senior cats confirmed that the older cats had significantly lower circulating levels of IGF-I. In order to determine whether an association existed between lymphocyte subpopulations and IGF-I levels in the cat, each parameter was measured and subjected to regression analysis. A highly significant association was found in vivo between plasma IGF-I and CD4(+) T-cell values in the senior group, but no such association was observed in the adult group. In order that this relationship could be examined further, in vitro studies were undertaken to investigate the effects of physiologically relevant concentrations of recombinant human IGF-I (rhIGF-l) on peripheral blood lymphocyte (PBL) cultures from adult and senior cats. While rhlGF-I induced low-level thymidine incorporation in the lymphocytes isolated from the senior group, it did not enhance the proliferative response to T-cell mitogens, Con A and PHA in either group, nor did it rescue cells from oxidatively induced apoptosis. Furthermore, the proliferative response of PBL from seniors did not attain the magnitude of that from the adults at any concentration of rhIGF-l. We propose that the observed association is not a direct effect of IGF-I on PBL, but may be mediated through an effect of IGF-I on the thymus.

Aging↗

PubMed2004

Age-related differences in parameters of feline immune status.

In order to assess age-related differences in feline immune status, 101 domestic short haired cats were assigned to two groups, adult (2-5 years, n=50) and senior (10-14 years, n=51). Analyses of leucocyte populations, lymphocyte subsets, complement activity, serum immunoglobulins and acute-phase proteins were undertaken and revealed significant differences between the two groups. The senior group had significantly lower WBC, lymphocyte and eosinophil counts than the adult group. Neutrophil, monocyte and basophil counts did not differ between the groups. Flow cytometry analysis, in combination with differential WBC data, revealed that the absolute values (cells/l) of T-cells, B-cells and natural killer (NK) cells were significantly lower in the older animals. While serum immunoglobulins IgA and IgM were higher in the senior group when compared with the adult group, no significant differences were observed in complement activity or in serum acute-phase proteins. Our findings suggest that age-related changes to parameters of immune status in the feline model are likely to follow a similar pattern to those observed in other long-lived mammalian species.

Age Factors↗

PubMed2004

B-vitamins, homocysteine metabolism and CVD.

The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6 and riboflavin, that are involved in homocysteine metabolism. Homocysteine is a S-containing amino acid and its plasma concentrations can be raised by various constitutive, genetic and lifestyle factors, by inadequate nutrient status and as a result of systemic disease and various drugs. Hyperhomocysteinaemia is a modest independent predictor of CVD and stroke, but causality and the precise pathophysiological mechanism(s) of homocysteine action remain unproven. The predominant nutritional cause of raised plasma homocysteine in most healthy populations is folate insufficiency. Vitamin B12 and, to a lesser extent, vitamin B6 are also effective at lowering plasma homocysteine, especially after homocysteine lowering by folic acid in those individuals presenting with raised plasma homocysteine. However, riboflavin supplementation appears to be effective at lowering plasma homocysteine only in those individuals homozygous for the T allele of the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. This gene codes for the MTHFR enzyme that produces methyltetrahydrofolate, which, in turn, is a substrate for the remethylation of homocysteine by the vitamin B12-dependent enzyme methionine synthase. Individuals with the MTHFR 677TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.

Carbon-Nitrogen Ligases↗

PubMed2004

Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men.

BACKGROUND: Short-term high copper intake does not appear to affect indexes of copper status or functions related to copper status, but the effects of long-term high copper intake are unknown. OBJECTIVE: A study was conducted in men to determine the effect of long-term high copper intake on indexes of copper status, oxidant damage, and immune function. DESIGN: Nine men were confined to a metabolic research unit (MRU) for 18 d and were fed a 3-d rotating menu providing an average of 1.6 mg Cu/d. The men continued the study under free-living conditions for 129 d and supplemented their usual diets with 7 mg Cu/d. The men then returned to the MRU for 18 d of the same diet as during the first period, except that copper intake was 7.8 mg/d. Plasma copper, ceruloplasmin activity, ceruloplasmin protein, plasma malondialdehyde, benzylamine oxidase activity, erythrocyte superoxide dismutase, hair copper, urinary copper, and urinary thiobarbituric acid-reactive substances were measured during each MRU period. RESULTS: Ceruloplasmin activity, benzylamine oxidase, and superoxide dismutase were significantly higher at the end of the second MRU period than at the end of the first. Urinary copper excretion, hair copper concentrations, and urinary thiobarbituric acid-reactive substances were significantly higher during the second MRU period than during the first. Polymorphonuclear cell count, the percentage of white blood cells, lymphocyte count, and interleukin 2R were affected by copper supplementation. Antibody titer for the Beijing strain of influenza virus was significantly lower in supplemented subjects after immunization than in unsupplemented control subjects. CONCLUSIONS: Under highly controlled conditions, long-term high copper intake results in increases in some indexes of copper status, alters an index of oxidant stress, and affects several indexes of immune function. The physiologic implications of these changes are unknown.

Adult↗

PubMed2004

Determining bioavailability of food folates in a controlled intervention study.

BACKGROUND: The concept of dietary folate equivalents (DFEs) in the United States recognizes the differences in bioavailability between natural food folates and the synthetic vitamin, folic acid. However, many published reports on folate bioavailability are problematic because of several confounding factors. OBJECTIVE: We compared the bioavailability of food folates with that of folic acid under controlled conditions. To broadly represent the extent to which natural folates are conjugated in foods, we used 2 natural sources of folate, spinach (50% polyglutamyl folate) and yeast (100% polyglutamyl folate). DESIGN: Ninety-six men were randomly assigned according to their screening plasma homocysteine (tHcy) concentration to 1 of 4 treatment groups for an intervention period of 30 d. Each subject received (daily under supervision) either a folate-depleted "carrier" meal or a drink plus 1) placebo tablet, 2) 200 microg folic acid in a tablet, 3) 200 microg natural folate provided as spinach, or 4) 200 microg natural folate provided as yeast. RESULTS: Among the subjects who completed the intervention, responses (increase in serum folate, lowering of tHcy) relative to those in the placebo group (n = 18) were significant in the folic acid group (n = 18) but not in the yeast folate (n = 19) or the spinach folate (n = 18) groups. Both natural sources of folate were significantly less bioavailable than was folic acid. Overall estimations of folate bioavailability relative to that of folic acid were found to be between 30% (spinach) and 59% (yeast). CONCLUSION: Relative bioavailability estimates were consistent with the estimates from the metabolic study that were used as a basis to derive the US DFE value.

Administration, Oral↗

PubMed2004

The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men.

The natural folate derivative, 5-methyltetrahydrofolate ([6S]-5-MTHF), could be an option for supplementation and fortification but its bioavailability remains unclear. This study compared the bioavailability of [6S]-5-MTHF with that of folic acid (FA) by measuring plasma folate responses after a single ingestion of equivalent doses of the two folate forms. In a double-blind, crossover study, 13 men (presaturated with FA) received in random order each of the following treatments administered orally at 1-wk intervals: 1) placebo capsule; 2) 500 micro g FA capsule; and 3) 500 micro g [6S]-5-MTHF capsule. Plasma total folate concentrations were measured before and up to 10 h after each treatment (n = 10 samples per treatment). Plasma folate concentrations increased significantly (compared with baseline) from 0.5 to 5 h after both folate treatments. The maximum plasma folate response did not differ between the two treatments (mean +/- SEM, 33.4 +/- 3.9 vs. 31.8 +/- 3.9 nmol/L, P = 0.7, for FA and [6S]-5-MTHF, respectively) and typically occurred in individuals between 0.5 and 3 h postprandially. The area under the plasma folate response curve was significantly greater after both folate treatments compared with placebo, and the response did not differ between the treatments. These results indicate that the short-term bioavailabilities of [6S]-5-MTHF and FA are equivalent. Supplementation with the natural folate derivative could have all the beneficial effects associated with FA, but without the potential disadvantage of masking the anemia of vitamin B-12 deficiency.

Adult↗

PubMed2004

Whistleblowing in academic medicine.

Although medical centres have established boards, special committees, and offices for the review and redress of breaches in ethical behaviour, these mechanisms repeatedly prove themselves ineffective in addressing research misconduct within the institutions of academic medicine. As the authors see it, institutional design: (1) systematically ignores serious ethical problems, (2) makes whistleblowers into institutional enemies and punishes them, and (3) thereby fails to provide an ethical environment. The authors present and discuss cases of academic medicine failing to address unethical behaviour in academic science and, thereby, illustrate the scope and seriousness of the problem. The Olivieri/Apotex affair is just another instance of academic medicine's dereliction in a case of scientific fraud and misconduct. Instead of vigorously supporting their faculty member in her efforts to honestly communicate her findings and to protect patients from the risks associated with the use of the study drug, the University of Toronto collaborated with the Apotex company's "stalling tactics," closed down Dr Olivieri's laboratory, harassed her, and ultimately dismissed her. The authors argue that the incentives for addressing problematic behaviour have to be revised in order to effect a change in the current pattern of response that occurs in academic medicine. An externally imposed realignment of incentives could convert the perception of the whistleblower, from their present caste as the enemy within, into a new position, as valued friend of the institution. The authors explain how such a correction could encourage appropriate reactions to scientific misconduct from academic medicine.

Clinical Trials as Topic↗

PubMed2003

The thymidylate synthase tandem repeat polymorphism is not associated with homocysteine concentrations in healthy young subjects.

Thymidylate synthase (TYMS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) may compete for their common cofactor 5,10-methylenetetrahyhdrofolate (5,10-meTHF). Limiting 5,10-meTHF results in elevated homocysteine, especially in individuals homozygous for the T allele of the MTHFR C677T polymorphism. The TYMS gene has a tandem repeat polymorphism (two repeats or three repeats, designated 2R or 3R, respectively), which may also affect homocysteine concentrations. The 3R allele is subject to increased translational efficiency in vitro and the 3R3R genotype is associated with both decreased serum folate and elevated plasma homocysteine (tHcy) in a population of Singapore Chinese. We assessed the relationship between TYMS genotype and key biochemical and genetic variables in a random sample of 392 healthy young Northwestern European men and women. The tHcy concentrations for 3R3R homozygotes (median 8.5 micromol/l) did not differ significantly from those for 2R2R homozygotes (median 8.7 micromol/l) or 2R3R heterozygotes (median 9.3 micromol/l) in the population as a whole (P=0.43), or in subsets of subjects with low serum folate (P=0.60) or the MTHFR 677TT genotype (P=0.90). Furthermore, there was no trend toward elevated tHcy in 3R3R homozygotes. Similarly, the TYMS tandem repeat polymorphism was not associated with serum folate concentrations. Our findings indicate that the TYMS 3R3R genotype is not a determinant of homocysteine in this sample of healthy young Caucasian adults from Northern Ireland.

Adult↗

PubMed2003

Protocol for the production of concentrated extracts of food folate for use in human bioavailability studies.

To provide a tool to study folate bioavailability under controlled conditions, a methodology was developed to produce extracts representative of natural food folates but removed from their matrix and sufficiently concentrated so as to elicit a response in biomarkers of folate status without distorting usual dietary intake patterns. Egg, spinach, and yeast were selected to represent the wide range in extent of folate conjugation found in foods (0, 60, and 100% polyglutamyl folate, respectively). The protocol, which was based on extracting food folates using only reagents safe for human consumption, was optimized in the laboratory (thermal extraction for 10 min in a 2% ascorbate solution at pH 5) and then adapted for industrial scale production in a food-processing facility. Results showed that the extracts were 2.3-12 times more concentrated in folate compared with their corresponding food sources. Neither the mono- to polyglutamate ratio nor the distribution of the main folate derivatives was altered during processing, making these extracts suitable for use in human bioavailability studies.

Biological Availability↗

PubMed2003

Genetic evidence that nitric oxide modulates homocysteine: the NOS3 894TT genotype is a risk factor for hyperhomocystenemia.

OBJECTIVE: Mild hyperhomocystenemia is an independent, graded risk factor for cardiovascular disease. Genetic determinants of hyperhomocystenemia include functional polymorphisms in several folate/homocysteine metabolic enzymes. Nitric oxide may also modulate plasma homocysteine (tHcy) concentrations, either by direct inhibition of methionine synthase or via an indirect effect on folate catabolism. METHODS AND RESULTS: The hypothesis that the endothelial nitric oxide synthase (NOS3) G894T polymorphism is a genetic determinant of tHcy concentrations was tested in 2 independent healthy adult populations. In both populations, NOS3 genotype was significantly associated with tHcy concentrations in nonsmokers with low folate (P=0.03 for each). Models were constructed to adjust for known determinants of tHcy concentrations and test for interactions between NOS3 genotype and these determinants in nonsmokers from each population. NOS3 genotype remained a significant determinant of tHcy concentrations after adjustment. Interactions between NOS3 genotype and serum folate were significant in both populations, and the interaction between NOS3 genotype and MTHFR C677T genotype was significant in the larger population. CONCLUSIONS: These data indicate that the NOS3 894TT genotype is a risk factor for elevated tHcy in healthy nonsmoking adults with low serum folate and supports the hypothesis that nitric oxide modulates homocysteine through an effect on folate catabolism.

Adult↗

PubMed2003

Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults.

A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine beta-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B(12), and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between the MTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B(12). Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2003

Detection of replicative integrity in small colonic biopsies using the BrdUrd comet assay.

The alkaline single-cell gel electrophoresis or comet assay is a relatively simple method of measuring DNA single-strand breaks and alkali-labile sites in individual cells. Previously, we have used a combination of this with bromodeoxyuridine labelling of DNA and immunolocalisation of the BrdUrd to show that DNA replicative integrity can be assessed in single cultured cells. This study demonstrates the application of the technique to single cells derived from small human colonic biopsies isolated at routine endoscopy. A high level of reproducibility within replicate comet slides and between comet slides prepared from various colonic sites within a single patient is shown. Preliminary results demonstrate that defects in replication can be detected in tumour and premalignant colonic tissue adjacent to the tumour, suggesting that alterations in replicative integrity are an early event in neoplasia, appearing in premalignant mucosal cells. This development deems the BrdUrd comet assay suitable as an ex vivo molecular end point that can be measured easily in tissue collected by biopsy at routine colonic endoscopy. Thus, the BrdUrd comet assay has the potential to facilitate trial investigations of diet- or environment-related factors that may affect replicative integrity in the colon and provides a novel biomarker for colon carcinogenesis.

Aged↗

PubMed2003

Confirmation of an acute no-observed-adverse-effect and low-observed-adverse-effect level for copper in bottled drinking water in a multi-site international study.

In a double blind, 3x3 factorial (volumexdose) study, 70 adult females (18-60 years of age) at four different international sites (total pooled n=269) were given 100, 150, or 200ml of bottled drinking water with 0.4, 0.8, or 1.2mg of copper (Cu) as the sulfate salt once each week. Two additional doses (0 and 1.6mg Cu) were added at the 200ml volume to determine a dose-response relationship and corroborate previously reported results. All subjects completed a questionnaire at 0, 0.25, and 1h post-dosing that screened for positive gastrointestinal (GI) effects (nausea, vomiting, abdominal pain, and diarrhea). Nausea was the most prevalent symptom reported and was generally reported within the first 15min (water volume, p<0.032; copper dose, p<0.0001; and water volumexcopper interaction, p<0.97). As volume increased, the effect of Cu-induced nausea decreased; as Cu dose increased, the incidence of nausea increased. At 200ml, a significant increase in reported incidence of nausea at 0.25h occurred at 1.2 mg Cu (6mg Cu/L), indicating a NOAEL of 0.8mg Cu (4mg Cu/L) for adult females. These data confirm a previously determined human acute NOAEL for Cu added to distilled water, and provide additional, controlled human data for determining safe concentrations of Cu in drinking water.

Administration, Oral↗

PubMed2003

An evaluation of the sensitivity and specificity of energy expenditure measured by heart rate and the Goldberg cut-off for energy intake: basal metabolic rate for identifying mis-reporting of energy intake by adults and children: a retrospective analysis.

OBJECTIVE: To identify adults and children as under- (UR), acceptable (AR), or over-reporters (OR) of energy intake (EI) using energy expenditure measured by doubly labelled water (DLW) (EE(DLW)), and to use this as a reference to determine the sensitivity and specificity of (i) EE measured by heart rate (EE(HR)), and (ii) the Goldberg cut-off technique for classifying subjects into the same categories. DESIGN: Retrospective analysis of a dataset comprising concurrent measurements of EE(DLW), EE(HR), basal metabolic rate (BMR), and EI by weighed record (EI(WR)) on 14 adults and 36 children. EI by diet history (EI(DH)) was also measured in the children only. EI(WR):EE(DLW) provided the reference definition of subjects as UR, AR or OR. Three strategies for classifying mis-reporters based on EE(HR) and Goldberg cut-offs were then explored. Sensitivity and specificity were calculated respectively as the proportion of UR and non-UR correctly identified. RESULTS: Approximately 80% of all subjects were AR. For EI(WR) and EI(DH) respectively, the sensitivity of EE(HR) was 0.50 and 1.00, and specificity was 0.98 and 1.00. Although designating subjects as having low, medium or high activity levels (EE(HR):BMR(meas)) and calculating cut-offs based on appropriate WHO physical activity level PALs did not change sensitivity, specificity dropped to 0.98 (EI(WR)) and 0.97 (EI(DH)). Cut-offs based on a PAL of 1.55 reduced sensitivity to 0.33 (EI(WR)) and 0.00 (EI(DH)), but specificity remained unchanged. The sensitivity of all cut-offs based on physical activity level (PALs) for EI(WR) was 0.50 (adults) and 0.25 (children). CONCLUSIONS: If the precision of EE(HR) was improved, it may be useful for identifying mis-reporters of EI.

Adolescent↗

PubMed2003

Zinc supplementation has no effect on circulating levels of peripheral blood leucocytes and lymphocyte subsets in healthy adult men.

As a result of evidence documenting harmful effects of Zn supplementation on immune function and Cu status, thirty-eight men were recruited onto a Zn supplementation trial. The aim was to examine the effects of chronic Zn supplementation on circulating levels of peripheral blood leucocytes and lymphocyte subsets. Subjects (n 19) took 30 mg Zn/d for 14 weeks followed by 3 mg Cu/d for 8 weeks to counteract adverse effects, if any, of Zn supplementation on immune status resulting from lowered Cu status. A control group (n 19) took placebo supplements for the duration of the trial. Dietary intakes of Zn approximated 10 mg/d. Blood samples, taken throughout the trial, were assessed for full blood profiles and flow cytometric analyses of lymphocyte subsets. Putative indices of Cu status were also examined. Results indicate that there was no effect of Zn supplementation on circulating levels of peripheral blood leucocytes or on lymphocyte subsets. Cu status was also unaltered. Independent of supplement, there appeared to be seasonal variations in selected lymphocyte subsets in both placebo and supplemented groups. Alterations in circulating levels of B cells (cluster of differentiation (CD) 19), memory T cells (CD45RO) and expression of the intracellular adhesion molecule-1 (CD54) on T cells were observed. Findings indicated no adverse effects of Zn supplementation on immune status or Cu status and support the US upper level of Zn tolerance of 40 mg/d. The seasonal variations observed in lymphocyte subsets in the group as a whole could have implications for seasonal variability in the incidence of infectious diseases.

Adult↗

PubMed2003

Nutritional factors may modify the toxic action of methyl mercury in fish-eating populations.

The historical record of clinical cases of methyl mercury poisoning dates back to the 19th century when the first chemical synthesis occurred. The potent fungicidal properties of both methyl and the closely related ethyl mercury compound were subsequently discovered, which led to widespread agricultural application for prevention of fungal infection in seed grain. Several catastrophic outbreaks of poisoning occurred in the mid-20th century when the treated seed grain was mistakenly used to prepare homemade bread. The largest outbreak took place in rural Iraq in the early 1970s. Human poisonings also occurred in Japan due to the release of methyl mercury into bodies of fresh and ocean water. The most infamous outbreak occurred in the area of Minamata Bay: methyl mercury, which was unwittingly discharged into the ocean water, avidly accumulated in the aquatic food chain to such an extent that people who consumed fish were severely poisoned. Today, human exposure to methyl mercury occurs from consumption of fish and sea mammals. Inorganic mercury that is present in aquatic sediments is methylated by microorganisms and accumulates in the aquatic food chain. Although no cases of clinical poisoning have been reported, a number of epidemiological studies have been carried out that raise the possibility of prenatal damage. Previous studies (especially the Iraq outbreak) indicate that the prenatal stage of the life cycle is the most vulnerable. However, ongoing epidemiological studies of heavy fish consumers of the Seychelles Islands in the Indian Ocean do not reveal adverse effects. To the contrary, the results of some developmental tests that were conducted on prenatally exposed children indicate beneficial outcomes that correlate with mercury levels during pregnancy. This article discusses the potential role of micronutrients in fish as a plausible explanation for these findings.

Animals↗

PubMed2003

Copper supplementation has no effect on markers of DNA damage and liver function in healthy adults (FOODCUE project).

BACKGROUND/AIMS: Copper is routinely used in the laboratory to promote oxidation in vitro. However, copper concentrations are million-fold higher than physiological concentrations and, in contrast, accumulating evidence suggests that copper may have an antioxidant role in vivo. The aim of this study was to provide data on how increased intake of copper affected mononuclear leukocyte DNA damage and liver function in healthy young free-living men and women. METHODS: The study design was a double-blind repeated crossover trial with treatment and intervening placebo periods, each of 6 weeks' duration. The following supplementations were given orally in sequence: CuSO(4) at a dose of 3 mg copper/day and copper amino acid chelates at doses of 3 and 6 mg copper/day. Oxidative DNA damage was assessed using a modification of the alkaline Comet assay incorporating an endonuclease III digestion step. The assessment of liver function was by measurement of the liver enzymes, alanine aminotransferase and L-gamma-glutamyltransferase. RESULTS: There was no significant alteration in mononuclear leukocyte DNA damage or on liver function after 6 weeks of copper supplementation at two doses (3 and 6 mg/day). CONCLUSIONS: Copper supplementation (giving total copper intake at the highest level of 7 mg/day) did not induce DNA damage or adversely affect liver function in healthy adults.

Adult↗