Search PubMed⌕ Search

Biomedical subjects

Mary Ward

Publications and source records attributed to Mary Ward.

9 recordsLinked to original sources

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↗

Homocysteine is lower in the third trimester of pregnancy in women with enhanced folate status from continued folic acid supplementation.

BACKGROUND: In many countries, current recommendations are that women take a daily 400-mug folic acid supplement from before conception until the end of the 12th week of gestation for the prevention of neural tube defects. Low folate status is associated with an increased concentration of plasma total homocysteine (tHcy), a risk factor associated with pregnancy complications such as preeclampsia. METHODS: In a longitudinal study, we determined tHcy and corresponding folate status in 101 pregnant women at 12, 20, and 35 weeks of gestation, in 35 nonpregnant controls sampled concurrently, and in a subgroup (n = 21 pregnant women and 19 nonpregnant controls) at 3 days postpartum. RESULTS: Plasma tHcy was significantly lower throughout pregnancy compared with nonpregnant controls, with values lowest in the second trimester before increasing toward nonpregnant values in the third trimester. Importantly, mean tHcy concentrations were lower in pregnant women taking folic acid supplements than in those not, an effect that reached significance in the third trimester (5.45 vs 7.40 micromol/L; P <0.05). During the third trimester, tHcy concentrations were significantly higher in pregnant women with a history of miscarriage than in women with no previous history (8.15 vs 6.38 micromol/L; P <0.01). CONCLUSIONS: This is the first longitudinal study to show that homocysteine concentrations increase in late pregnancy toward nonpregnant values; an increase that can be limited by enhancing folate status through continued folic acid supplementation. These results indicate a potential role for continued folic acid supplementation in reducing pregnancy complications associated with hyperhomocysteinemia.

Adolescent↗

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↗

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↗

The views of people with a physical disability on day activity centres in the Eastern Region of Ireland.

PURPOSE: The overall aim of this study was to evaluate the effectiveness of day activity centres in providing a service to physically disabled clients in the Eastern Region of Ireland. METHOD: Qualitative and quantitative methodologies were used. Four focus groups with clients were undertaken. This informed questionnaire content and design for subsequent quantitative work. Interviewer administered questionnaires were distributed to 156 randomly selected clients. Areas covered in the questionnaire included: demographic characteristics, income, living circumstances, medical information, access to day centre, activities at the centre, staff, outcome of attendance and satisfaction with the centre. RESULTS: There was a very positive response to the survey, all clients selected agreed to participate. The majority of clients were unmarried, unemployed and disabled due to a neurological disorder. While most lived in owner-occupied occupation, they were dependent on state benefits for their principal source of income. The majority of clients attended the centres for social and recreational reasons. Although there was a high level of satisfaction with the service overall, some aspects, such as availability of therapy and lack of continuity of staff are areas identified that need improvement. CONCLUSION: This study highlighted aspects of day activity services that clients value. The results of this evaluation should guide the proposed future development and expansion of this service.

Adolescent↗

Sampling private wells at past homes to estimate arsenic exposure: a methodologic study in New England.

We are conducting a collaborative, population-based case-control study in Maine, New Hampshire, and Vermont to investigate the reasons for the elevated bladder cancer mortality in northern New England. Arsenic in drinking water is one of the primary exposures under investigation. To estimate subjects' lifetime exposure to waterborne arsenic, it will be necessary to obtain water samples from private wells that subjects used in the past. We conducted a methodologic study to assess the feasibility of locating and sampling from private wells at subjects' past residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a questionnaire requesting the complete address, dates of occupancy, and drinking water sources for each home lived in since birth. An interviewer then asked subjects for more detailed information about each home to assist in a field search of past homes in the three-state study area of Maine, New Hampshire, and Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of 103 private wells in 95 previous homes located in these three states. We conducted a field search to locate these 95 homes, visited town offices to find the properties on tax maps and obtain the current owners' names and addresses, attempted to obtain permission from the current owners to sample the wells, and collected water samples. In all, 48 (47%) of the 103 past wells in the study area were sampled successfully. The remaining wells were not sampled because the homes were not located (22%) or had been demolished (2%), permission to sample the wells was not obtained (17%), the wells had been destroyed (7%) or could not be found on the grounds of the residence (3%), or for other reasons (2%). Various approaches for improving the success rates for sampling water from private wells are discussed, as is the use of predictive modeling to impute exposures when sampling is not feasible.

Adult↗