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J J Strain

Publications and source records attributed to J J Strain.

At least 19 recordsLinked to original sources

Determination of an acute no-observed-adverse-effect level (NOAEL) for copper in water.

A prospective, double-blind controlled study was designed to determine the acute no-observed-adverse-effect level (NOAEL) of nausea in an apparently healthy population of 179 individuals who drank copper-containing water as the sulfate salt. Subjects were recruited at three different international sites and given a blind, randomly selected dose (0, 2, 4, 6, or 8 mg Cu/L) in a bolus of 200 ml (final total copper dose was equivalent to 0, 0.4, 0.8, 1.2, and 1.6 mg) once weekly over a consecutive 5-week period. Gastrointestinal (GI) symptoms of nausea, abdominal pain, vomiting, or diarrhea were screened for a period of up to 24 h. Nausea was the most frequently reported effect and was reported within the first 15 min of ingestion. For the combined trisite population (n=179), 8, 9, 14, 25, and 44 subjects responded positively to one or more GI symptoms at 0, 2, 4, 6, and 8 mg Cu/L, respectively. Analysis of the data demonstrated a clear dose response to the combined positive GI effects and to nausea alone. Statistically significant greater reporting of effects occurred at 6 and 8 mg Cu/L. Therefore, an acute NOAEL and lowest-observed-adverse-effect level of 4 and 6 mg Cu/L (0.8 and 1.2 mg Cu), respectively, were determined in drinking water for a combined international human population.

Adult↗

Effect of supplemental methionine on plasma homocysteine concentrations in healthy men: a preliminary study.

Hyperhomocysteinaemia is an established risk factor for vascular disease. The only source of homocysteine in humans is the amino acid methionine found in dietary protein. In an 8-week study, fasting plasma homocysteine concentrations were examined in a group of healthy male subjects (n = 6) under usual dietary conditions (weeks 1-4) and in response to weekly graded (25, 50 and 75 mg/kg/d) supplementary methionine (weeks 5, 6, 7). Nutrient intakes, including methionine, were calculated from 4 x 3 day food records. Under usual dietary conditions (mean methionine intake; 0.95 +/- 0.51 mg/d) weekly mean plasma homocysteine concentrations for the group were not significantly different (ANOVA) from each other ranging from 6.82 +/- 1.77 to 9.42 +/- 2.73 mumol/l. Doubling (supplementing with 25 mg/kg/d; + 2.04 g/d) or quadrupling (50 mg/kg/d; + 4.08 g/d) methionine intakes did not result in a significant increase in plasma homocysteine (8.56 +/- 3.68 mumol/l and 13.37 +/- 5.09 mumol/l respectively). A significant increase, however, was achieved when diets were supplemented with methionine at the highest level of 75 mg/kg/d (+6.14 g/d) resulting in a mean plasma homocysteine concentration of 18.05 +/- 11.8 mumol/l. Mean plasma homocysteine concentration returned to baseline (8.76 +/- 3.42 mumol/l), 10 days post-supplementation. The results of this study indicate that an increased dietary methionine will only cause elevated fasting homocysteine concentrations if ingested at intakes equivalent to five times usual intake. Because it is very unlikely that such levels could be achieved through dietary means alone we conclude that plasma homocysteine is unlikely to be affected by longer-term changes in food methionine intake.

Adult↗

No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status.

OBJECTIVE: To investigate the effects of increasing Cu intakes, above the usual dietary intake, on biomarkers of bone metabolism in healthy young adult females (aged 21-28 y) over a 4 week period. DESIGN: A double-blind, placebo-controlled randomised repeat crossover Cu supplementation trial. SETTING: The study was conducted at the Royal Veterinary and Agricultural University (RVAU), Copenhagen, Denmark. SUBJECTS: Sixteen healthy young adult females aged 20-28 y were recruited from among students at the RVAU. INTERVENTION: During the 4 week intervention periods in this randomised, crossover trial (3x4 weeks with a minimum 3 week wash-out period), each subject received, in addition to their usual diet, either 3 or 6 mg elemental Cu/day as CuSO4 or a matching placebo. On the last 3 days of each dietary period 24 h urines were collected. In addition, blood was collected on the last day of each dietary period. RESULTS: Serum Cu and erythrocyte superoxide dismutase (but not caeruloplasmin protein concentration or activity (putative indices of Cu status)) were significantly increased (P<0.05) after daily Cu supplementation with 3 and 6 mg/day for 4 weeks. Serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline (Pyr)/Cr or deoxypyridinoline (Dpyr)/Cr excretion, or daily urinary Pyr or Dpyr excretion (biomarkers of bone resorption) were unaffected by Cu supplementation. CONCLUSION: Copper supplementation of the usual diet in healthy young adult females, while apparently improving Cu status, had no effect on biochemical markers of bone formation or bone resorption over 4 week periods. SPONSORSHIP: Funding from the European Commission.

Adult↗

Genetic aspects of nutrition and toxicology: report of a workshop.

The health and resilience of humans and animals is, in large part, determined by the quality and quantity of the diet. This, in turn, may influence an individual's capability to deal with stress including toxic insult. In addition, there may be specific components of the diet that modulate the toxicity of specific toxicants whether the latter are ingested as food or absorbed via other routes. Many examples attest to the importance of interactions between dietary components and toxicants after absorption in the body. Such interactions occur at every level of biological organization from the molecular to the whole organism. Some may be synergistic, others antagonistic. Some may involve direct chemical reaction between the nutrient molecule and the toxicant, others may occur by indirect action at the cellular or organ levels. All examples point to the importance of considering diet when measuring the response to toxic agents whether in animals or humans. In order to foster interaction between the sciences of nutrition and toxicology, The Heinz Institute of Nutritional Sciences as sponsoring a series of workshops. The first of these was held in June, 1999 at the University of Ulster to address evolutionary aspects of nutrition--toxicology (for report see Eur. J. Nutr, 39, 49-52, 2000). In June, 2000, a second workshop was held at the University of Toronto to address genetic aspects, and this is a brief summary of the proceedings. We are beginning to understand the molecular basis of the regulation of gene expression by dietary factors and how genetic changes can affect response to toxicants. Recent advances in technology and a detailed understanding of disease etiology has led to the ability to study molecular determinants of disease risk. The workshop provided a forum for nutritionists, toxicologists, molecular biologists, epidemiologists and others to discuss common interests and to merge their efforts towards an integrated approach to nutrition--toxicology via genetics and genomics. The first session dealt with the mechanism by which nutrients such as fatty acids (Clarke), amino acids (Jefferson) and metal ions (Cousins) can regulate gene expression. In the second session, there were presentations on the effects of nutritional factors on genes of toxicological significance such as phase I and phase II enzymes of drug metabolism (Guengerich, Goodfellow and Grant) as well as on oxidative DNA damage and its repair (Collins, Weindruch). Session three dealt with gene-nutrient interactions in the development of chronic diseases such as diabetes (Hegele, Berdanier) and cancer (Kim, Ambrosone et al.). New developments such as DNA microarrays (McGlynn) and the use of transgenic and knockout models (Sehayek) were presented in the final session.

Aging↗

Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete.

BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. CONCLUSIONS: Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation.

Aged↗

Socio-economic position and coronary heart disease risk factors in youth. Findings from the Young Hearts Project in Northern Ireland.

BACKGROUND: This study investigates the existence of socioeconomic differentials in behavioural and biological risk factors for coronary heart disease in young people from Northern Ireland, taking into account differences in biological maturation. METHODS: A school-based prospective study, with measurements in 1989/1990 and 1992/1993. Socio-economic position was based on occupational level of the main family breadwinner. Behavioural risk factors included were physical inactivity, the intake of total energy, dietary fat and a number of micronutrients. Biological risk factors included were blood pressure, body fatness, lipoproteins and cardio-pulmonary fitness. Biological maturation was based on Tanner's stages. PARTICIPANTS: 251 boys and 258 girls who were measured at the age of 12 years and re-examined at the age of 15 years. RESULTS: Cross-sectional analyses showed that socio-economic differences in cholesterol intake (in boys) and physical inactivity and total energy intake (in girls) were present at 12 and 15 years of age, while differences in fat and fruit intake and smoking behaviour (in boys and girls) became established at the age of 15 years, with unfavourable levels in subjects in the manual group. Longitudinal analyses confirmed that differences in behavioural risk factors exist or develop during adolescence. No clear pattern of differences in biological risk factors was found by socio-economic position. Adjustment for biological maturation did not materially alter the results. CONCLUSION: Differences in lifestyle by socio-economic position seem to become established in adolescence. These differences however, are not (yet) reflected in differences in biological risk factors by socio-economic position.

Adolescent↗

Fitness, fatness, and coronary heart disease risk in adolescents: the Northern Ireland Young Hearts Project.

PURPOSE: The purpose of this study was to examine the independence and relative strengths of association between coronary heart disease (CHD) risk status and both body fatness and cardiorespiratory (C-R) fitness in 12- and 15-yr-old adolescents. METHODS: The study cohort consisted of 1015 schoolchildren aged 12 and 15 yr (251 12-yr-old boys, 258 12-yr-old girls, 252 15-yr-old boys, and 254 15-yr-old girls), representing a 2% random sample of each population group. For each child, height, weight, sexual maturity (pubertal status), skin-fold thicknesses (4 sites), blood pressure (random zero sphygmomanometer), nonfasting serum total, and high density lipoprotein (HDL)-cholesterol and C-R fitness (20-m shuttle run; 20-MST) were determined under standardized conditions. Socioeconomic status and habitual physical activity were also determined from questionnaire information. Multiple regression analyses were carried out to examine relationships between five CHD risk factors, and fitness and fatness and to examine the relative strengths of fitness and fatness on CHD risk status, correcting for potential confounding variables. RESULTS: Our main findings were: 1) Relationships between fatness and CHD risk factors are invariably stronger than between fitness and the same risk factors. For example, partially adjusted standardized regression coefficients for 12-yr-old boys revealed significant relationships between all five CHD risk factors and fatness, compared with three of five for fitness. The corresponding figures for 12-yr-old girls were three of five (fatness) and one of five (fitness). Broadly similar results were apparent for 15-yr-olds. 2) Although relationships between fitness and CHD risk factors do not survive further adjustment for fatness, the relationships between fatness and CHD risk are more robust and are unaffected by further adjustment for fitness. CONCLUSION: Our results indicate that the observed relationships between C-R fitness and CHD risk status in adolescents are mediated by fatness, whereas the observed relationships with fatness are independent of fitness. Primary prevention of CHD during childhood should therefore concentrate upon preventing or reversing undue weight gain.

Adipose Tissue↗

Plasma homocysteine is not subject to seasonal variation.

BACKGROUND: Studies investigating the relationship between plasma total homocysteine (tHcy) and vascular disease usually rely on a single measurement. Little information is available, however, on the seasonal variability of plasma tHcy. The aim of this study was to investigate the seasonal variation in fasting plasma tHcy and related B-vitamin intake and status in a group of people who did not consume fortified foods or take B-vitamin supplements. METHODS: In this longitudinal study, a group of 22 healthy people were followed for 1 year. A fasting blood sample and dietary information were collected from each individual every 3 months, i.e., at the end of each season. RESULTS: There was no significant seasonal variation in plasma tHcy or in B-vitamin intake or status with the exception of red cell folate (significantly lower in spring compared with autumn or winter) and serum folate (significantly lower in spring compared with the other seasons). Although the between-person variation in plasma tHcy was high (47%), the within-person variation was low (11%). This low variation, combined with the low methodologic imprecision of 3.8%, yielded a high reliability coefficient for plasma tHcy (0.97). CONCLUSIONS: Although there was a small seasonal variation in folate status, there was no corresponding seasonal variation in plasma tHcy. The high reliability coefficient for plasma tHcy suggests that a single measurement is reflective of an individual's average plasma tHcy concentration, thus indicating its usefulness as a potential predictor of disease. This, however, needs to be confirmed in different subgroups of the population.

Adolescent↗

The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers.

A multicenter European study (FoodCue) was undertaken to provide data on the significance of increased dietary copper as a pro-oxidant or antioxidant in vivo. The present work describes the effect of Cu supplementation on (2,2'-azo-bis(2-amidinopropane) hydrochloride (AAPH)-induced red blood cell oxidation in middle-aged people. Double-blinded copper supplementation was achieved in 26 healthy volunteers (50-70 years) with pills containing 3 mg CuSO(4), 3 mg Cu glycine chelate (CuG) and 6 mg CuG. Each 6 week supplementation period was preceded and followed by 6 weeks of washout (WO) on placebo. The results show significant increases in time necessary to achieve 50% hemolysis (LT(50)) after 3CuSO(4) and 6CuG compared with values after WO periods. Cu supplementation did not increase the levels of (Cu,Zn)SOD activity in red blood cells. Resistance to hemolysis was significantly and positively correlated (r =.30, p <.01) with alpha- and beta-carotene content in the plasma. Together, these data suggest that intake of copper as high as 7 mg/d has no pro-oxidant activity and may rather result in protection of red blood cells against oxidation. The decreased oxidizability of red blood cells did not result from increased (Cu,Zn)SOD activity and may occur through other mechanisms such as changes in membrane antioxidant content.

Aged↗

Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project).

The oxidative modification of low-density lipoprotein cholesterol (LDL) has been implicated in the pathogenesis of atherosclerosis. Copper (Cu) is essential for antioxidant enzymes in vivo and animal studies show that Cu deficiency is accompanied by increased atherogenesis and LDL susceptibility to oxidation. Nevertheless, Cu has been proposed as a pro-oxidant in vivo and is routinely used to induce lipid peroxidation in vitro. Given the dual role of Cu as an in vivo antioxidant and an in vitro pro-oxidant, a multicenter European study (FOODCUE) was instigated to provide data on the biological effects of increased dietary Cu. Four centers, Northern Ireland (coordinator), England, Denmark, and France, using different experimental protocols, examined the effect of Cu supplementation (3 or 6 mg/d) on top of normal Cu dietary intakes or Cu-controlled diets (0.7/1.6/6.0 mg/d), on Cu-mediated and peroxynitrite-initiated LDL oxidation in apparently healthy volunteers. Each center coordinated its own supplementation regimen and all samples were subsequently transported to Northern Ireland where lipid peroxidation analysis was completed. The results from all centers showed that dietary Cu supplementation had no effect on Cu- or peroxynitrite-induced LDL susceptibility to oxidation. These data show that high intakes (up to 6 mg Cu) for extended periods do not promote LDL susceptibility to in vitro-induced oxidation.

Adult↗

Interactions between vitamins C and E in human subjects.

Despite convincing in vitro evidence, a vitamin C-E interaction has not been confirmed in vivo. This study was designed to examine the effects of supplementation with either vitamin C or E on their respective plasma concentrations, other antioxidants, lipids and some haemostatic variables. Fasting blood was collected before and after intervention from thirty healthy adults in a double-blinded crossover study. Baselines for measured variables were established after 2 weeks of placebo supplementation, followed by daily supplementation with 73.5 mg RRR-alpha-tocopherol acetate or 500 mg ascorbic acid, and placebo, for 6 weeks. A 2 month washout preceded supplement crossover. Mean values showed that plasma lipid standardised alpha-tocopherol increased with ascorbic acid supplementation: from 4.09 (sem 0.51) to 4.53 (sem 0.66) micromol/mmol total cholesterol plus triacylglycerol (P < 0.05), and plasma ascorbic acid increased from 62.8 (sem 14.9) to 101.3 (sem 22. 2) micromol/l (P < 0.005). Supplementation with (RRR)-alpha-tocopherol acetate increased plasma alpha-tocopherol from 26.8 (sem 3.9) to 32.2 (sem 3.8) micromol/l (P < 0.05), and lipid-standardised alpha-tocopherol from 4.12 (sem 0.48) to 5.38 (sem 0.52) micromol/mmol (P < 0.001). Mean plasma ascorbic acid also increased with vitamin E supplementation, from 64.4 (sem 13.3) to 76. 4 (sem 18.4) micromol/l (P < 0.05). Plasma ferric reducing (antioxidant) power and glutathione peroxidase (U/g haemoglobin) increased in both groups, while urate, total cholesterol and triacylglycerol levels decreased (P < 0.05 throughout). Results are supportive of an in vivo interaction between vitamins C and E.

Adult↗

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans.

OBJECTIVE: To examine the effect of low-dose fish oil supplementation on specific growth factors, purported to play a central role in lesion formation, and also on the total growth factor activity of serum, as assessed by the induction of DNA synthesis in cultured human arterial smooth muscle cells. DESIGN: Randomized placebo-controlled double-blind intervention study. SETTING: Free-living population. SUBJECTS: Sixty-three healthy volunteers, 37 males and 26 females. INTERVENTIONS: Four treatment regimes with subjects receiving 0, 0.3,0.6 or 0.9 g/day of n-3 PUFA for an 8 week period. Blood samples were taken at baseline and following the 8 week intervention. All samples were analysed in batch following completion of the study. RESULTS: Consumption of fish oil had no effect on serum platelet-derived growth factor (PDGF), or transforming growth factor beta (TGFbeta) concentration. Furthermore, fish oil supplementation did not alter the total growth factor activity of serum. CONCLUSIONS: Results indicate that low-dose fish oil supplementation, equivalent to about two portions of fatty fish per week and providing less than 1 g n-3 PUFA/day, does not alter the levels of the major serum growth factors and does not modify total serum growth factor activity in healthy human volunteers. SPONSORSHIP: European Union shared cost project (FAIR-CT-95-0085).

Adult↗

Frequency of fruit and vegetable consumption and blood antioxidants in the Caerphilly cohort of older men.

OBJECTIVE: To assess the number of portions of fruit and vegetables consumed daily by a large representative sample of older men, and to determine how blood antioxidant (vitamins E, A and carotenoids) concentrations vary with fruit and vegetable consumption. DESIGN: Cross-sectional study of free-living men. SUBJECTS: Men aged 55-69 y (dietary data, n=1957; blood data, n=1874) participating in Phase III (1989-1993) of the Caerphilly and Speedwell Collaborative Heart Disease Studies. METHODS: Dietary data were obtained by semi-quantitative food-frequency questionnaire and blood samples were analysed for antioxidant vitamins. Men were subdivided into groups on the basis of portions per day of fruit and vegetables. Within these sub-groups, mean and 95% ranges of intakes and of blood antioxidant levels were obtained. Log transformations were performed where appropriate. RESULTS: Only 4.3% of the men met the recommended target of five portions, while 33.3% of the men consumed one or fewer portions of fruit and vegetables per day. Those men who consumed the poorest diets with respect to fruit and vegetable intakes were more likely to be from lower socio-economic classes, drink more alcohol and be current smokers. Fruit and vegetable intake reflected plasma concentrations of antioxidants, which showed a dose-response relationship to frequency of consumption. CONCLUSIONS: Older men in the UK consume much less fruit and vegetables than current recommendations. Major difficulties are likely to be encountered in trying to meet a dietary target that is clearly much higher than the fruit and vegetable consumption of large sections of the older population in the UK. SPONSORSHIP: This work was supported by the Medical Research Council.

Aged↗

Plasma diamine oxidase activity is greater in copper-adequate than copper-marginal or copper-deficient rats.

The object of this study was to determine whether serum diamine oxidase activity could distinguish among adequate, marginal and deficient copper status in rats. Male weanling Sprague-Dawley rats (n = 21) were randomly assigned to one of three dietary regimens, with copper concentrations of 0.52, 1.73 and 6.7 mg/kg diet. On completion of the study, body weights were significantly different among dietary groups, with copper-marginal rats displaying the highest mean weight and copper-deficient rats the lowest. Copper-deficient rats ate significantly less food than the other two groups. Rats fed the three diets had significantly different liver copper concentrations. Liver and heart superoxide dismutase and cytochrome c oxidase activities, and plasma ceruloplasmin and erythrocyte superoxide dismutase activities were significantly lower in the copper-deficient rats than in the other two groups. Plasma diamine oxidase activity was lower in both copper-deficient (0.18 +/- 0.11 U/L) and marginal (0.21 +/- 0.11 U/L) rats compared with copper-adequate rats (3.35 +/- 0.28 U/L). Of the biochemical indices measured, only liver copper concentration (-20%) and plasma diamine oxidase activity (-94%) differed between rats fed copper-marginal and copper-adequate diets. Plasma diamine oxidase activity, therefore, may be a sensitive functional biomarker of suboptimal copper status.

Amine Oxidase (Copper-Containing)↗

Fluctuations in dietary methionine intake do not alter plasma homocysteine concentration in healthy men.

A moderate elevation in plasma total homocysteine (tHcy) has been established as an independent risk factor for vascular disease. An important exogenous source of homocysteine is methionine found in foods rich in animal protein. We investigated the response of tHcy to fluctuations in methionine intake in a cross-over intervention trial (two arms). Healthy men (n = 52; 19-29 y) were screened for habitual methionine intake using a food-frequency questionnaire. Subjects in the top quartile for methionine intake (n = 13), with a baseline fasting tHcy of 7.01 +/- 1.84 micromol/L (mean +/- SD), were randomly assigned to receive either a low-methionine intervention diet for 1 wk followed by a control diet for 1 wk or vice-versa. Simultaneously, those in the bottom quartile for methionine intake (n = 11), with a fasting plasma tHcy of 9.79 +/- 7. 20 micromol/L (mean +/- SD), received either a high methionine intervention diet for 1 wk followed by a control diet or vice-versa. All subjects had serum folate, red-cell folate, serum vitamin B-12 and plasma pyridoxal phosphate (PLP) concentrations within normal ranges. During the intervention, subjects in the top quartile for methionine intake reduced their daily methionine intake 79%, from 1969 +/- 639 to 407 +/- 83 mg/d (P: </= 0.001), and those in the bottom quartile almost doubled their methionine intake, from 1155 +/- 401 to 2112 +/- 379 mg/d (P: </= 0.001). Despite these changes in methionine intake, no corresponding changes in plasma tHcy were observed. These results suggest that in the absence of an obvious deficiency of relevant B-vitamins, fasting plasma tHcy is unaffected by intermediate-term fluctuations (up to 100% of usual intake) in dietary methionine.

Adult↗