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Biomedical subjects

J J Strain

Publications and source records attributed to J J Strain.

At least 19 recordsLinked to original sources

Effect of high-dose iron supplements on fractional zinc absorption and status in pregnant women.

BACKGROUND: Women have an increased risk of iron deficiency during pregnancy because of the demands of the developing fetus. Iron supplements are commonly advocated as a prophylactic treatment and are generally taken with meals to reduce side effects, but iron can interfere with the absorption of zinc. OBJECTIVE: The aim was to determine the effect of consuming an iron supplement (100 mg Fe/d as ferrous gluconate) with meals from 16 wk gestation to term on zinc status and absorption. DESIGN: Stable-isotope techniques were used to measure zinc status (exchangeable zinc pool, EZP) and fractional zinc absorption (FZA) in early and late pregnancy from a meal consumed at a different time from that of iron supplement or placebo consumption in 6 women given iron supplements and 7 given a placebo. RESULTS: FZA increased during pregnancy, independent of iron supplementation. FZA was significantly higher (P < 0.001) at week 34 than at weeks 16 and 24, and urinary zinc excretion was higher at week 34 than at week 16 (P = 0.02). The size of the EZP remained unchanged throughout pregnancy and was unaffected by iron supplementation. The iron status of iron-supplemented women was higher than that of the placebo group. CONCLUSIONS: In iron-replete pregnant women who consumed a Western diet, no detectable adverse effects on zinc metabolism were observed after ingestion of 100 mg Fe/d. An increase in the efficiency of zinc absorption was observed during late pregnancy.

Administration, Oral↗

The relationship between whole-blood serotonin and subjective mood in apparently healthy postmenopausal women.

The aim of this research has been to determine the degree to which biochemical indices of mood reflect subjective mood. Potential relationships between whole-blood (WB) serotonin (5-hydroxytryptamine, 5-HT) levels as determined by the positive and negative affect schedule (PANAS) have been explored in apparently healthy postmenopausal women (n=39). Partial correlations indicated that WB 5-HT was positively associated with positive affect (p=0.03). No association was apparent for negative affect. These findings indicate that WB 5-HT and positive affect are related in postmenopausal women.

Affect↗

Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults.

OBJECTIVE: To assess the vitamin D status of healthy young people living in Northern Ireland and the effect of vitamin D supplementation on vitamin D status and bone turnover. DESIGN: Double-blinded randomised controlled intervention study. SETTING: University of Ulster, Coleraine, Northern Ireland. SUBJECTS: In total, 30 apparently healthy students (15 male and 15 female subjects), aged 18-27 years, were recruited from the university, with 27 completing the intervention. INTERVENTIONS: Subjects were randomly assigned, to receive either 15 microg (600 IU) vitamin D(3) and 1,500 mg calcium/day (vitamin D group), or 1,500 mg calcium/day (control group) for 8 weeks between January and March. Vitamin D status, bone turnover markers, serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention. RESULTS: At baseline, vitamin D status was low in both the vitamin D group (47.9 (s.d. 16.0)) and the control group (55.5 (s.d. 18.6) nmol/l 25(OH)D). Post intervention vitamin D status was significantly higher in the vitamin D-treated group (86.5 (s.d. 24.5)) compared to the control group (48.3 (s.d. 16.8) nmol/l) (P<0.0001). There was no significant effect of supplementation on bone turnover markers or PTH concentrations. CONCLUSIONS: This study suggests that young adults in Northern Ireland do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime. A daily supplement of 15 microg vitamin D(3) significantly increased vitamin D status in these individuals to levels of sufficiency. Achievement of an optimum vitamin D status among young adults may have future positive health implications.

Adolescent↗

Tracking of energy and nutrient intakes from adolescence to young adulthood: the experiences of the Young Hearts Project, Northern Ireland.

OBJECTIVE: To assess tracking of energy and nutrient intakes between adolescence and young adulthood. DESIGN: Longitudinal study of a random sample of adolescents (aged 15 years at baseline). The extent of tracking of dietary intakes (assessed by diet history) was investigated using weighted kappa statistics (kappa). SETTING: Northern Ireland population survey. SUBJECTS: Adolescents who participated in the Young Hearts Project, Northern Ireland at age 15 years, and subsequently at young adulthood aged between 20 and 25 years (n=245 males, n=231 females). RESULTS: Despite overall increases in height and weight (both P<0.001), increases in body mass index in males (P<0.001) and body fatness in females (P<0.001), median reported intakes of energy (kJ kg(-1) day(-1)), carbohydrate (g day(-1)) and fat (g day(-1)) decreased (all P<0.001) over time. Expressed as nutrient densities (per MJ), diets at young adulthood were overall richer in thiamin, vitamin B6, total folate (all P<0.001), vitamin C (P<0.01) and vitamin D (P<0.05). Whereas the nutrient density of the males' diets decreased over time for calcium (P<0.05) and vitamin A (P<0.001), iron and riboflavin densities increased in the females' diet (P<0.001). Tracking of energy (MJ day(-1)) and nutrient intakes (expressed per MJ day(-1)) at the individual level was only poor to fair (all kappa<0.25), indicating substantial drift of subjects between the low, medium and high classes of intake with increasing age. CONCLUSIONS: These data suggest that individual dietary patterns exhibited at 15 years of age are unlikely to be predictive of dietary intakes at young adulthood.

Adolescent↗

The rate of intestinal absorption of natural food folates is not related to the extent of folate conjugation.

BACKGROUND: Evidence is conflicting as to whether the bioavailability of food folates is influenced by the extent of their conjugation. OBJECTIVE: The objective was to compare the bioavailability of 3 representative food folate sources with various degrees of glutamylation-ie, egg yolk, spinach, and yeast, whose polyglutamyl folate content measured 0%, 50%, and 100%, respectively. DESIGN: In a randomized crossover trial, 13 male subjects, after a prestudy folate saturation procedure, received in random order either placebo or 500 mug total folate, which was provided as concentrated freeze-dried extract removed from the normal food matrix of egg yolk, spinach, or yeast. Blood samples (n = 10) were collected before and up to 10 h after treatments, which were administered at weekly intervals. RESULTS: A significant increase from baseline plasma folate concentrations was observed by 0.5 h after treatment with egg yolk folate or spinach folate and by 1 h after treatment with yeast folate, and the concentrations remained significantly elevated for 3-5 h; no plasma folate response was observed after placebo treatment. The overall responses, calculated as plasma folate area under the curve (AUC) for egg yolk, spinach, and yeast folate, were 122.6 +/- 23.6, 136.2 +/- 21.4, and 102.5 +/- 21.1 nmol . h/L, respectively. No significant differences in AUC were seen between monoglutamyl (egg yolk) folate and either of the polyglutamate-containing folates examined. CONCLUSION: These results suggest that the ratio of monoglutamate to polyglutamate in natural folates is not a factor that limits the extent of intestinal absorption of food folate.

Administration, Oral↗

Whole blood analysis of phagocytosis, apoptosis, cytokine production, and leukocyte subsets in healthy older men and women: the ZENITH study.

Few studies to date have examined age-related changes in markers of immune status in healthy older individuals. The immune status of 93 healthy individuals aged 55-70 years was assessed by two- and three-color flow cytometry and biochemical analysis. There were significant age effects (p <or=.05) on monocyte phagocytic activity and cluster of differentiation (CD) 3/human leukocyte antigen-D-related (HLA-DR) late-activated T lymphocytes (% expression). There was a significant (p <or= 0.1) Age x Sex interaction in absolute counts (x 10(9)/L) of CD3/CD8 total cytotoxic T lymphocytes (CTL), the CD4 T- helper to CD8 CTL ratio, the CD3/CD4/CD45RA naïve T helper to CD3/CD4/CD45RO memory T helper lymphocyte ratio, and interleukin (IL)-1beta (% expression) by activated monocytes. The study shows that alterations in markers of immune status occur between 55 and 70 years, and provides reference values for the lymphocyte measures in healthy men and postmenopausal women in this age group. The study further highlights the need for sex-specific reference ranges for such markers.

Aged↗

Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation.

There is increasing evidence to suggest that reduced folate status may be a causative factor in carcinogenesis, particularly colorectal carcinogenesis. Folate is essential for the synthesis of S-adenosylmethionine, the methyl donor required for all methylation reactions in the cell, including the methylation of DNA. Global DNA hypomethylation appears to be an early, and consistent, molecular event in carcinogenesis. We have examined the effects of folate depletion on human-derived cultured colon carcinoma cells using 2 novel modifications to the Comet (single cell gel electrophoresis) assay to detect global DNA hypomethylation and gene region-specific DNA hypomethylation. Colon cells cultured in folate-free medium for 14 d showed a significant increase in global DNA hypomethylation compared with cells grown in medium containing 3 micromol/L folic acid. This was also true at a gene level, with folate-deprived cells showing significantly more DNA hypomethylation in the region of the p53 gene. In both cases, the effects of folate depletion were completely reversed by the reintroduction of folic acid to the cells. These results confirm that decreased folate levels are capable of inducing DNA hypomethylation in colon cells and particularly in the region of the p53 gene, suggesting that a more optimal folate status in vivo may normalize any DNA hypomethylation, offering potential protective effects against carcinogenesis. This study also introduces 2 novel functional biomarkers of DNA hypomethylation and demonstrates their suitability to detect folate depletion-induced molecular changes.

Azacitidine↗

Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism.

BACKGROUND: Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status. METHODS AND RESULTS: From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C-->T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, n=26) or wild-type (CC, n=28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in erythrocyte glutathione reductase activation coefficient; P<0.01 in each case). However, homocysteine responded only in the TT group, with levels decreasing by as much as 22% overall (from 16.1+/-1.5 to 12.5+/-0.8 micromol/L; P=0.003; n=32) and markedly so (by 40%) in those with lower riboflavin status at baseline (from 22.0+/-2.9 and 13.2+/-1.0 micromol/L; P=0.010; n=16). No homocysteine response was observed in the CC or CT groups despite being preselected for suboptimal riboflavin status. CONCLUSIONS: Although previously overlooked, homocysteine is highly responsive to riboflavin, specifically in individuals with the MTHFR 677 TT genotype. Our findings might explain why this common polymorphism carries an increased risk of coronary heart disease in Europe but not in North America, where riboflavin fortification has existed for >50 years.

Adolescent↗

A common insertion/deletion polymorphism of the thymidylate synthase (TYMS) gene is a determinant of red blood cell folate and homocysteine concentrations.

Substantial evidence suggests that a low folate/high homocysteine phenotype is pathogenic. We analyzed the impact of the thymidylate synthase (TYMS) 3'UTR ins/del polymorphism on folate and homocysteine levels and assessed the relationship between the TYMS 3'UTR ins/del polymorphism and key genetic and lifestyle variables. Among non-smokers only, the TYMS 3'UTR ins/del polymorphism was significantly associated with red blood cell folate (RBC folate; P=0.002) and homocysteine (P=0.03) concentrations. Median RBC folate concentration was much higher for TYMS 3'UTR del/del subjects (434 microg/l) compared with either ins/ins (282 microg/l) or ins/del (298 microg/l) subjects. The median homocysteine concentration for del/del homozygotes was considerably lower compared with either ins/ins homozygotes or ins/del heterozygotes. A possible additive effect for the impact of the TYMS 3'UTR del/del and MTHFR 677CC genotypes on RBC folate concentration was also observed. Our findings suggest that the TYMS 3'UTR del/del genotype is a significant determinant of elevated RBC folate concentration in a non-smoking population of northwestern European adults and that this genotype confers protection against diseases for which a low folate/high homocysteine phenotype appears to be an etiologic component.

3' Untranslated Regions↗

Zinc status and taste acuity in older Europeans: the ZENITH study.

BACKGROUND: Age-related decline in taste acuity may be both a cause and an effect of depleted zinc and/or increased zinc requirement. OBJECTIVE: The aim of this study was to explore associations between zinc status and taste acuity in healthy older European adults aged 55-90 y. SAMPLE: Volunteers were recruited within Italy (n = 108 aged 70-90 y), the United Kingdom (UK) (n = 93 aged 55-70) and two regions of France (n = 186), Grenoble (aged 70-90 y) and Clermont-Ferrand (aged 55-70 y). METHODS: A signal detection theory approach was adopted, employing a three-alternative, forced-choice procedure. The data were converted to R-indices and bivariate correlations were computed to explore relationships between serum zinc, erythrocyte zinc and taste acuity. ANOVA was undertaken to determine regional differences in zinc status. RESULTS: Higher erythrocyte zinc status was associated with better acuity for salt (sodium chloride) taste in the sample as a whole (P = 0.012) (n = 385). Higher serum zinc levels were associated with greater sensitivity to sour taste (citric acid) (P = 0.015) only in the older groups (aged 70-90 y). There were no apparent associations between serum or erythrocyte zinc status and acuity for bitter (quinine) or sweet (sucrose) tastes irrespective of age. CONCLUSION: These results agree with those previously suggesting that age-related detriment in sensitivity for salt taste may be associated with depleted zinc.

Age Factors↗

Zinc status and age-related changes in peripheral blood leukocyte subpopulations in healthy men and women aged 55-70 y: the ZENITH study.

OBJECTIVE: To determine zinc status and age-related changes in the immune function of healthy late-middle-aged men and women (aged 55-70 y). DESIGN: Observational study. SETTING: Population of Northern Ireland. SUBJECTS: Apparently healthy, free-living individuals (45 men, 48 women) aged 55-70 y. INTERVENTION: Zinc status markers were analysed by flame atomic absorption spectrometry and commercially available kits. Immune function was assessed by flow cytometry. RESULTS: Serum and erythrocyte zinc concentrations were 13.0 (s.d. 1.40) micromol/l and 222 (s.d. 48.2) micromol/l, respectively. Serum alkaline phosphatase (ALP) concentrations were 76.8 (s.d. 16.1) U/l; women showed significantly higher concentrations of ALP (P = 0.011). Women demonstrated (1) a significant inverse correlation in naive T lymphocytes, specifically naive T-helper lymphocytes (% expression, r = -0.364, P = 0.007 and absolute count, r = -0.275, P = 0.036) with age and (2) a significant positive correlation between late activation of T lymphocytes (% expression, r = 0.299, P = 0.019 and absolute count, r = 0.260, P = 0.039) with advancing age. Men demonstrated a significant positive correlation in the % expression of (CD3-/CD16+/CD56+) natural killer (NK) cells with age (r = 0.316, P = 0.017). CONCLUSIONS: Between the ages of 55 and 70 y, healthy individuals experience significant alterations in immune function; however, such changes appear largely sex specific. Given the reported importance of adequate zinc status in maintaining optimal immune function, further studies are required to explore the effect of enhanced zinc status on emerging immune deficiencies in cell-mediated immunity in healthy 55-70 y olds.

Age Factors↗

Effect of copper supplementation on indices of copper status and certain CVD risk markers in young healthy women.

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 randomised 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 samples 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.

Adult↗

Inter-relationships between DNA damage, ascorbic acid and glycaemic control in Type 2 diabetes mellitus.

AIMS: The onset of complications in Type 2 diabetes mellitus (DM) patients cannot be predicted in individuals. Evidence suggests a link between complications and hyperglycaemia, oxidative stress and antioxidants, but causality is unclear. This study investigated baseline (entry) fasting plasma ascorbic acid, lymphocytic DNA damage and glycaemic control in Type 2 DM as part of a long-term study, the aim of which is to explore a biomarker profiling approach to identify and improve outcome in high-risk subjects. METHODS: A cross-sectional study, in which DNA damage, glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and ascorbic acid (AA) were measured on fasting blood samples collected from 427 Type 2 DM subjects. RESULTS: DNA damage was significantly (P < 0.0001) and directly correlated to both FPG (r = 0.540) and HbA(1c) (r = 0.282), and was significantly (P < 0.0001), independently and inversely correlated to plasma AA (r = -0.449). In those subjects with both poor glycaemic control and low AA (< 48 microm, the overall mean value for the study group), DNA damage was significantly (P < 0.005) higher compared with those subjects with a similar degree of hyperglycaemia but with AA above the mean. CONCLUSIONS: The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer-term follow-up is underway.

Ascorbic Acid↗

Milk consumption, stroke, and heart attack risk: evidence from the Caerphilly cohort of older men.

OBJECTIVE: To examine associations between milk consumption and incident heart disease and stroke. DESIGN: A representative population sample of men was asked to weigh and record their food intake for seven days. The total consumption of milk was obtained from these records. Details of all deaths and vascular events were collected during the following 20 years. Incident ischaemic strokes and heart disease events were diagnosed by standard criteria. SETTING: The Caerphilly cohort, a representative population sample of men in South Wales, aged 45-59 when first seen in 1979-83. PARTICIPANTS: A representative 3:10 subsample of the men in the cohort. MAIN RESULTS: 665 men (87% of those approached) returned satisfactory seven day diet diaries. After adjustment, the relative odds of an event in the men whose milk consumption was the median or higher, relative to those with lower intakes of milk, were 0.52 (0.27 to 0.99) for an ischaemic stroke and 0.88 (0.56 to 1.40) for an ischaemic heart disease event. Deaths from all causes were similar in the two milk consumption groups (relative odds 1.08; 0.74 to 1.58). CONCLUSIONS: These results give no convincing evidence of an increased risk of vascular disease from milk drinking. Rather, the subjects who drank more than the median amount of milk had a reduced risk of an ischaemic stroke, and possibly a reduced risk of an ischaemic heart disease event. These conclusions are in agreement with the results of a previously reported overview of 10 large, long term cohort studies based on food frequency intake records.

Animals↗

Vitamins C and E: acute interactive effects on biomarkers of antioxidant defence and oxidative stress.

Oxidative stress is implicated in the aetiology of many diseases; however, most supplementation trials with antioxidant micronutrients have not shown expected beneficial effects. This randomized, double-blinded, placebo-controlled study evaluated acute effects (at 90, 180min and 24h [fasting] post-ingestion) of single doses of Vitamins C (500mg) and E (400IU), alone and in combination, on biomarkers of plasma antioxidant status, lipid peroxidation and lymphocyte DNA damage in 12 healthy, consenting volunteers. Plasma ascorbic acid increased significantly (P < 0.01) within 2h of ingestion of Vitamin C, and alpha-tocopherol was significantly (P < 0.01) higher at 24h post-ingestion Vitamin E. The pattern of response was not significantly different whether Vitamin C (or Vitamin E) was taken alone or in combination, indicating no augmentation of response to one by co-ingestion of the other vitamin. No significant changes were seen in plasma FRAP in the group overall (although increases (P < 0.05) were seen at 90 and 180min post-ingestion in women after Vitamin C ingestion) or in MDA across treatments, and no evidence of increased DNA damage, or of DNA protection, was seen at any time point after Vitamin C and/or E ingestion. In conclusion, the data from this first controlled study of acute effects of single doses of Vitamin C and/or E show no evidence of either a protective or deleterious effect on DNA damage, resistance of DNA to oxidant challenge, or lipid peroxidation. No evidence of a synergistic or cooperative interaction between Vitamins C and E was seen, but further study is needed to determine possible interactive effects in a staggered supplementation cycle, and study of subjects under increased oxidative stress or with marginal antioxidant status would be useful. It would be of interest also to study the effects of these vitamins ingested with, or in, whole food, to determine if they are directly protective at doses above the minimum required to prevent deficiency, if combinations with other food components are needed for effective protection, or if Vitamins C and E are largely surrogate biomarkers of a 'healthy' diet, but are not the key protective agents.

Adult↗

The 5,10-methylenetetrahydrofolate reductase C677T polymorphism interacts with smoking to increase homocysteine.

Elevated homocysteine is a risk marker for several human pathologies. Risk factors for elevated homocysteine include low folate and homozygosity for the T allele of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Because nitric oxide may inhibit folate catabolism and endothelial nitric oxide synthase activity is reduced in smokers, we postulated that smoking status might modify the impact of the MTHFR C677T polymorphism on homocysteine (tHcy) concentrations. We tested this hypothesis in a healthy young adult population for which MTHFR C677T genotypes and tHcy concentrations were previously reported. The MTHFR 677TT genotype was significantly associated with elevated tHcy concentrations in smokers (P = 0.001) but not in non-smokers (P = 0.36). Among smokers, the MTHFR 677TT genotype was significantly associated with high tHcy in heavy smokers (P = 0.003) but not light smokers (P = 0.09), in men (P = 0.003) but not women (P = 0.11), and in subjects from the lowest serum folate quartile (P = 0.49) but not from folate quartiles 2-4 (P = 0.49). After adjustment for nutritional variables, interactions between MTHFR C677T genotype and NOS3 G894T genotype, and between MTHFR genotype, smoking status and gender were statistically significant. We propose that hyperhomocysteinemia in MTHFR 677TT homozygote smokers is the consequence of mild intracellular folate deficiency caused by a smoking-related reduction of NOS3 activity that is exacerbated when serum folate is low.

Adult↗