Multiple Micronutrients, Including Zinc, Selenium and Iron, Are Positively Associated with Anemia in New Zealand Aged Care Residents.

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.

Qualitative and quantitative vibrational spectroscopic analysis of macronutrients in breast milk.

Raman and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to analyze 208 breast milk samples as part of a larger research study. Comprehensive qualitative and quantitative analysis was carried out using chemometric methods: principal component analysis (PCA) and partial least squares (PLS) regression. The obtained information on the main macronutrients (protein, fat and carbohydrate) were primarily evaluated in relation to the available metadata of the samples, where study location and respective primary food sources revealed a stronger differentiation in fat composition than its absolute content. The limitations and challenges of using both spectroscopic techniques for the type of analysis are also highlighted.

Multiple micronutrient status and predictors of anemia in young children aged 12-23 months living in New Delhi, India.

Anemia has been identified as a severe public health concern among young children in India, however, information on the prevalence of anemia attributed to micronutrient deficiencies is lacking. We aimed to assess multiple micronutrient status (iron, zinc, selenium, vitamin A, vitamin D, folate and vitamin B12) in young Indian children and to investigate the role of these seven micronutrients and other non-nutritional factors on hemoglobin concentrations and anemia. One-hundred and twenty children aged 12 to 23 months were included in a cross-sectional nutritional assessment survey, of which 77 children provided a blood sample. Hemoglobin (Hb), serum ferritin, soluble transferrin receptor (sTfR), total body iron, zinc, selenium, retinol binding protein (RBP), folate, vitamin B12 and 25-hydroxyvitamin D (25(OH)D) were measured, and adjusted for inflammation using C-reactive protein (CRP) and α-1-acid glycoprotein (AGP), where appropriate. Predictors for hemoglobin and anemia were identified in multiple regression models. Most of the children were classified as anemic, of which 86 to 93% was associated with iron deficiency depending on the indicator applied. Deficiencies of folate (37%), and notably vitamin D (74%) were also common; fewer children were classified with deficiencies of vitamin B12 (29%), zinc (25%), and vitamin A (17%) and selenium deficiency was nearly absent. Multiple micronutrient deficiencies were common with over half (57%) deficient in three or more micronutrients, and less than 10% of children were classified with adequate status for all the micronutrients measured. Iron status was found to be the only nutritional factor statistically significantly inversely associated with anemia (P = 0.003) in multivariate analysis after controlling for sex. A coordinated multi-micronutrient program is urgently needed to combat the co-existing micronutrient deficiencies in these young children to improve micronutrient status and reduce the high burden of childhood anemia.

Effect of vitamin D supplementation on depressive symptoms and psychological wellbeing in healthy adult women: a double-blind randomised controlled clinical trial.

Epidemiological evidence has linked low vitamin D status to a range of mood disorders. However, studies examining whether vitamin D supplementation can improve mood-related outcomes in healthy populations are limited. We investigated whether vitamin D supplementation over winter is beneficial for improving mood-related outcomes in healthy women. A total of 152 healthy women (18-40 years) in Dunedin, New Zealand were randomly assigned to receive 50 000 IU (1·25 mg) of oral vitamin D3 or placebo once per month for 6 months. They completed the Center for Epidemiologic Studies Depression Scale, the anxiety subscale of the Hospital Anxiety and Depression Scale and the Flourishing Scale every month. Additionally, they reported their positive and negative mood each day for three consecutive days every 2 months. Participants provided a blood sample at the beginning and at the end of the study for 25-hydroxyvitamin D3 analysis. ANCOVA was used to compare the outcome measures between the groups, controlling for baseline. We found no evidence of lower depression (P = 0·339), lower anxiety (P = 0·862), higher flourishing (P = 0·453), higher positive moods (P = 0·518) or lower negative moods (P = 0·538) in the treatment group compared with the control group at follow-up. Mood outcomes over the study period were similar for the two groups. We found no evidence of any beneficial effect of monthly vitamin D3 supplementation on mood-related outcomes in healthy premenopausal women over the winter period, so recommendations for supplementations are not warranted in this population for mood-related outcomes.

A comparison of methods for adjusting biomarkers of iron, zinc, and selenium status for the effect of inflammation in an older population: a case for interleukin 6.

Background: Older people are at risk of micronutrient deficiencies, which can be under- or overestimated in the presence of inflammation. Several methods have been proposed to adjust for the effect of inflammation; however, to our knowledge, none have been investigated in older adults in whom chronic inflammation is common. Objective: We investigated the influence of various inflammation-adjustment methods on micronutrient biomarkers associated with anemia in older people living in aged-care facilities in New Zealand. Design: Blood samples were collected from 289 New Zealand aged-care residents aged >65 y. Serum ferritin, soluble transferrin receptor (sTfR), total body iron (TBI), plasma zinc, and selenium as well as the inflammatory markers high-sensitivity C-reactive protein (CRP), α1-acid glycoprotein (AGP), and interleukin 6 (IL-6) were measured. Four adjustment methods were applied to micronutrient concentrations: 1) internal correction factors based on stages of inflammation defined by CRP and AGP, 2) external correction factors derived from the literature, 3) a regression correction model in which reference CRP and AGP were set to the maximum of the lowest decile, and 4) a regression correction model in which reference IL-6 was set to the maximum of the lowest decile. Results: Forty percent of participants had elevated concentrations of CRP, AGP, or both, and 37% of participants had higher than normal concentrations of IL-6. Adjusted geometric mean values for serum ferritin, sTfR, and TBI were significantly lower (P < 0.001), and plasma zinc and selenium were significantly higher (P < 0.001), than the unadjusted values regardless of the method applied. The greatest inflammation adjustment was observed with the regression correction that used IL-6. Subsequently, the prevalence of zinc and selenium deficiency decreased (-13% and -14%, respectively; P < 0.001), whereas iron deficiency remained unaffected. Conclusions: Adjustment for inflammation should be considered when evaluating micronutrient status in this aging population group; however, the approaches used require further investigation, particularly the influence of adjustment for IL-6.

A Longitudinal Study of 25-Hydroxy Vitamin D and Parathyroid Hormone Status throughout Pregnancy and Exclusive Lactation in New Zealand Mothers and Their Infants at 45° S.

Vitamin D status and associated metabolism during pregnancy and lactation have been assessed in only a limited number of longitudinal studies, all from the northern hemisphere, with no infant data concurrently reported. Therefore, we aimed to describe longitudinal maternal and infant 25-hydroxy vitamin D (25OHD) and parathyroid hormone (PTH) status during pregnancy and up to 5 months postnatal age, in New Zealand women and their infants living at 45° S latitude. Between September 2011 and June 2013, 126 pregnant women intending to exclusively breastfeed for at least 20 weeks were recruited. Longitudinal data were collected at three time-points spanning pregnancy, and following birth and at 20 weeks postpartum. Vitamin D deficiency (25OHD < 50 nmol/L) was common, found at one or more time-points in 65% and 76% of mothers and their infants, respectively. Mean cord 25OHD was 41 nmol/L, and three infants exhibited secondary hyperparathyroidism by postnatal week 20. Maternal late pregnancy 25OHD (gestation 32-38 weeks) was closely correlated with infant cord 25OHD, r² = 0.87 (95% CI (Confidence interval) 0.8-0.91), while no correlation was seen between early pregnancy (<20 weeks gestation) maternal and cord 25OHD, r² = 0.06 (95% CI -0.16-0.28). Among other variables, pregnancy 25OHD status, and therefore infant status at birth, were influenced by season of conception. In conclusion, vitamin D deficiency in women and their infants is very common during pregnancy and lactation in New Zealand at 45° S. These data raise questions regarding the applicability of current pregnancy and lactation policy at this latitude, particularly recommendations relating to first trimester maternal vitamin D screening and targeted supplementation for those "at risk".

Acute Supplementation with High Dose Vitamin D3 Increases Serum Anti-Müllerian Hormone in Young Women.

Anti-Müllerian hormone (AMH) is a paracrine regulator of ovarian follicles. Vitamin D (Vit D) regulates AMH production in vitro, but its role as a regulator of ovarian AMH production is contentious. If Vit D influences ovarian AMH production, then an acute rise in Vit D level should lead to an acute rise in circulating AMH levels. This hypothesis was tested with a randomized double-blind design, with 18-25-year-old women recruited from the community. The study was conducted in early spring, when the marker of Vit D level (25-hydroxyvitamin D, 25(OH)D) tends to be at its nadir. The women consumed either an oral dose of 50,000 IU of Vit D3 (n = 27) or placebo (n = 22). The initial 25(OH)D ± SD value was 53.6 ± 23.3 nmol/L, with 42 of the 49 women having a value below 75 nmol/L, consistent with seasonal nadir. All women receiving Vit D3 treatment exhibited a robust increase in serum 25(OH)D within 1 day (15.8 ± 1.1 nmol/L (n = 27), p < 0.0001), with the increase sustained over the study week. Circulating levels of AMH in the women receiving Vit D3 progressively rose during the following week, with a mean increase of 12.9 ± 3.7% (n = 24, p = 0.001). The study supports the hypothesis that Vit D's positive effects on the fertility of woman may involve the regulation of ovarian AMH levels.

High-Dose Monthly Maternal Cholecalciferol Supplementation during Breastfeeding Affects Maternal and Infant Vitamin D Status at 5 Months Postpartum: A Randomized Controlled Trial.

BACKGROUND: Many countries recommend daily infant vitamin D supplementation during breastfeeding, but compliance is often poor. A monthly, high-dose maternal regimen may offer an alternative strategy, but its efficacy is unknown. OBJECTIVE: The objective of the study was to determine the effect of 2 different monthly maternal doses of cholecalciferol on maternal and infant 25-hydroxyvitamin D [25(OH)D] status during the first 5 mo of breastfeeding. METHODS: With the use of a randomized, double-blind, placebo-controlled design, women who were planning to exclusively breastfeed for 6 mo (n = 90; mean age: 32.1 y; 71% exclusively breastfeeding at week 20) were randomly assigned to receive either cholecalciferol (50,000 or 100,000 IU) or a placebo monthly from week 4 to week 20 postpartum. The treatment effects relative to placebo were estimated as changes in maternal and infant serum 25(OH)D from baseline to week 20 postpartum by using a linear fixed-effects regression model. Additional secondary analyses, adjusted for potential confounders such as season of birth, vitamin D-fortified formula intake, and infant or maternal skin color, were also conducted. RESULTS: After 16 wk of supplementation, changes in maternal serum 25(OH)D were significantly higher in the 50,000-IU/mo (12.8 nmol/L; 95% CI: 0.4, 25.2 nmol/L) and 100,000-IU/mo (21.5 nmol/L; 95% CI: 9.2, 33.8 nmol/L) groups than in the placebo group (P = 0.43 and P < 0.001, respectively). For infants, the unadjusted mean changes in serum 25(OH)D were 4.5 nmol/L (95% CI: -16.2, 25.0 nmol/L) for the 50,000-IU/mo group and 15.8 nmol/L (95% CI: -4.7, 36.4 nmol/L) for the 100,000-IU/mo group, but the changes did not differ from the placebo reference group. However, after adjustment for season of birth, vitamin D-fortified formula intake, and infant skin color, the mean change effect size for the 100,000-IU/mo group was 19.1 nmol/L (95% CI: 2.5, 35.6 nmol/L; P = 0.025) higher than that in the placebo group. CONCLUSIONS: Maternal cholecalciferol supplementation at a dose of 100,000 IU/mo during the first 5 mo of breastfeeding potentially benefits infant vitamin D status. Further studies are required to determine optimum dose and dosing frequency. This trial was registered at www.anzctr.org.au as ACTRN12611000108910.

Vitamin D status and its predictors in New Zealand aged-care residents eligible for a government-funded universal vitamin D supplementation programme.

OBJECTIVE: The provision of prescribed vitamin D to all aged-care residents has been implemented in New Zealand as part of a government-led falls prevention programme. To our knowledge, there has been no evaluation of this universal programme on vitamin D status and functional and health outcomes. Thus, we aimed to determine 25-hydroxyvitamin D (25(OH)D) concentrations and their predictors in aged-care residents across the country and to investigate whether the government-funded programme was associated with adequate vitamin D status. DESIGN: Cross-sectional survey of sociodemographic, biochemical, anthropometric, dietary and health characteristics. Blood samples were analysed for serum 25(OH)D and other biochemical measures. Multiple regression was used to examine predictors of vitamin D status. SETTING: Sixteen residential aged-care facilities throughout New Zealand. SUBJECTS: Residents aged ≥60 years with residency duration >12 weeks (n 309). RESULTS: Mean serum 25(OH)D was 89·9 (95 % CI 85·2, 94·5) nmol/l and monthly supplements (1250 µg (50 000 IU)) were taken by 75 % of all residents. Of those not taking a funded supplement, 65·3 % had serum 25(OH)D 125 nmol/l. CONCLUSIONS: Residents taking supplemental vitamin D had adequate vitamin D status; however monitoring of long-term supplementation should be considered, due to the high proportion of participants with high serum 25(OH)D levels.

Serum 25-hydroxyvitamin D concentrations and depressive symptoms among young adult men and women.

There has been an increased interest in the role of vitamin D in depression; however, there have been few studies conducted in younger population groups. Our aim was to investigate the association between vitamin D status and depressive symptoms in a non-clinical young adult sample living in Dunedin, New Zealand. A cross-sectional sample of 615 young adults completed a questionnaire including demographics and the Centre for Epidemiological Studies Depression Scale (CES-D). Height, weight and a blood sample for 25-hydroxyvitamin D [25(OH)D] was obtained. Serum 25(OH)D was used to predict depression scores, adjusting for potential confounders including time spent outdoors for 13 consecutive days, BMI, age, sex and ethnicity. Prevalence of low vitamin D was high even in this age group, and serum 25(OH)D was negatively associated with depression symptoms before and after adjustment. When investigating the relationship between the presence versus absence of depressive symptoms and quartiles of 25(OH)D, participants in the lowest quartile were more likely to report depressive symptoms compared with those in the highest quartile. Although our findings suggest that vitamin D is a predictor of depression symptomatology, even when controlling for time spent outdoors, a randomised controlled trial in this young adult target group is needed to confirm the association.

Vitamin D status among Thai school children and the association with 1,25-Dihydroxyvitamin D and parathyroid hormone levels.

In several low latitude countries, vitamin D deficiency is emerging as a public health issue. Adequate vitamin D is essential for bone health in rapidly growing children. In the Thai population, little is known about serum 25-hydroxyvitamin D [25(OH)D] status of infants and children. Moreover, the association between 25(OH)D and the biological active form of 1,25-dihydroxyvitamin D [1,25(OH)]2D is not clear. The specific aims of this study were to characterize circulating serum 25(OH)D, 1,25(OH)2D and their determinants including parathyroid hormone (PTH), age, sex, height and body mass index (BMI) in 529 school-aged Thai children aged 6-14 y. Adjusted linear regression analysis was performed to examine the impact of age and BMI, and its interaction with sex, on serum 25(OH)D concentrations and 1,25(OH)2D concentrations. Serum 25(OH)D, 1,25(OH)2D and PTH concentrations (geometric mean ± geometric SD) were 72.7±1.2 nmol/L, 199.1±1.3 pmol/L and 35.0±1.5 ng/L, respectively. Only 4% (21 of 529) participants had a serum 25(OH)D level below 50 nmol/L. There was statistically significant evidence for an interaction between sex and age with regard to 25(OH)D concentrations. Specifically, 25(OH)D concentrations were 19% higher in males. Moreover, females experienced a statistically significant 4% decline in serum 25(OH)D levels for each increasing year of age (P = 0.001); no decline was seen in male participants with increasing age (P = 0.93). When BMI, age, sex, height and serum 25(OH)D were individually regressed on 1,25(OH)2D, height and sex were associated with 1,25(OH)2D with females exhibiting statistically significantly higher serum 1,25(OH)2D levels compared with males (P<0.001). Serum 1,25(OH)2D among our sample of children exhibiting fairly sufficient vitamin D status were higher than previous reports suggesting an adaptive mechanism to maximize calcium absorption.

Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months.

Public health recommendations do not distinguish between vitamin D2 and vitamin D3, yet disagreement exists on whether these two forms should be considered equivalent. The objective of the present study was to evaluate the effect of a daily physiological dose of vitamin D2 or vitamin D3 on 25-hydroxyvitamin D (25(OH)D) status over the winter months in healthy adults living in Dunedin, New Zealand (latitude 46°S). Participants aged 18-50 years were randomly assigned to 25 µg (1000 IU) vitamin D3 (n 32), 25 µg (1000 IU) vitamin D2 (n 31) or placebo (n 32) daily for 25 weeks beginning at the end of summer. A per-protocol approach, which included ≥ 90 % supplement compliance, was used for all analyses. Serum 25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2) and parathyroid hormone (PTH) were measured at baseline and at 4, 8, 13 and 25 weeks. Geometric mean total serum 25(OH)D concentrations (sum of 25(OH)D2 and 25(OH)D3) at baseline was 80 nmol/l. After 25 weeks, participants randomised to D2 and placebo had a significant reduction in serum 25(OH)D3 concentrations over the winter months compared with vitamin D3-supplemented participants (both P< 0.001). Supplementation with vitamin D2 increased serum 25(OH)D2 but produced a 9 (95 % CI 1, 17) nmol/l greater decline in the 25(OH)D3 metabolite compared with placebo (P< 0.036). Overall, total serum 25(OH)D concentrations were 21 (95 % CI 14, 30) nmol/l lower in participants receiving vitamin D2 compared with those receiving D3 (P< 0.001), among whom total serum 25(OH)D concentrations remained unchanged. No intervention-related changes in PTH were observed. Daily supplementation of vitamin D3 was more effective than D2; however, the functional consequence of the differing metabolic response warrants further investigation.

Quantitation of whole-blood total folate within defined MTHFR C677T genotype groups by isotope dilution-liquid chromatography-tandem mass spectrometry differs from microbiologic assay.

Standardization of folate measurement is needed for accurate assessment of folate status. We compared the measurement of whole-blood folate by isotope dilution-liquid chromatography-tandem MS (ID-LC-MS/MS) with the historical gold standard microbiological assay (MA) using 3 common calibrators within the frame of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Seventy-three whole-blood samples with an even distribution of MTHFR C677T genotypes (24 CC, 24 CT, 24 TT) were prepared, and total folate was determined by ID-LC-MS/MS and MA using the following calibrators: 5-methyltetrahydrofolate (5-methylTHF) (Merck), folic acid (FA) (Merck), and FA (Sigma). To compare the methods, 5-formyltetrahydrofolate (5-formylTHF) was excluded in the ID-LC-MS/MS summation of total folate, because it is likely that the majority of 5-formylTHF detected is a pyrazino-s-triazine oxidation product of 5-methylTHF. MA whole-blood folate measured by using the FA calibrators was consistently higher than with the 5-methylTHF calibrator. Differences between dilutions and analysis of spiked whole-blood samples showed a nonlinear response, with overrecovery of 5-methylTHF by ~23% toward the higher end of the MA calibration range. Significant proportional biases between ID-LC-MS/MS and MA were found in all comparisons except when the MA was calibrated with 5-methylTHF and a higher sample dilution of 1:1600 (regression slope: 1.05; P = 0.31; intercept-21, P = 0.16). Calibration bias and matrix effects in the MA underscore the need for a formally accepted whole-blood folate reference method. ID-LC-MS/MS procedures have the potential to offer a high degree of accuracy; however, further work is needed to determine the origin of the pyrazino-s-triazine derivative.

Body mass index status is effective in identifying metabolic syndrome components and insulin resistance in Pacific Island teenagers living in New Zealand.

Although adults of Pacific ethnicity living in New Zealand have more than double the prevalence of diabetes and cardiovascular disease than the general population, little is known regarding the presence of risk factors for these disorders among young Pacific Islanders. The study aim was to examine relationships between body composition, glucose and lipid metabolism, and components of the metabolic syndrome (MS) in a community sample of Pacific Island (PI) teenagers living in Dunedin. Anthropometry, body composition (dual-energy x-ray absorptiometry), glucose and lipid metabolism, insulin resistance (homeostasis model assessment [HOMA2], McAuley index), and components of MS were assessed in 80 PI teenagers (aged 15-18 years). Results showed that 6 participants had full MS, 2 had high fasting blood glucose values (>7.0 mmol/L), 55 had high adiposity, and 21 had insulin resistance. Assessment of the components of MS by body mass index (BMI) status showed that obese participants (n = 29) had a high prevalence (86.2% had one or more component), whereas only 10.5% of those with healthy BMI status (n = 19) had any MS component. Elevated fat mass had substantial effects on fasting insulin values, HOMA2, and the McAuley index because in data adjusted for age, sex, and lean mass, a 10% greater fat mass was associated with a 4.7% increase in fasting insulin, a 5.3% rise in HOMA2, and a 2.3% decrease in the McAuley index. Our results suggest that the antecedents of cardiovascular disease and type 2 diabetes mellitus occur frequently in young Pacific Islanders having high adiposity. We conclude that community studies of PI adolescents should focus on assessing risk factors whenever BMI values are high.

Variation in the cholesteryl ester transfer protein (CETP) gene does not influence individual plasma cholesterol response to changes in the nature of dietary fat.

BACKGROUND AND AIMS: Some individuals respond to a greater extent than others to changes in dietary fat and cholesterol even when dietary intake is consistent. A prospective study has been undertaken in which two groups of individuals according to cholesteryl ester transfer protein (CETP) genotype were compared in terms of plasma lipid response to altering the nature of dietary fat in a free-living situation. METHODS AND RESULTS: Following genotyping, 35 individuals with the CETP Taq1 B1B1 genotype were paired with age and sex-matched individuals with one or two CETP B2 alleles, to undertake a single crossover trial with a diet high in saturated fat and a diet high in polyunsaturated fat. There was no washout period between the two 4-week phases. Plasma lipoproteins were measured at the beginning and end of each phase. The difference (95% CI) in plasma LDL-cholesterol concentration at the end of the PUFA and SAFA diets was 0.95 (0.71, 1.19) mmol/l in the CETP B1B1 group and 0.80 (0.57, 1.04) mmol/l in the group with at least one CETP B2 allele. The dietary induced changes in the two genotype groups were not significantly different (p=0.38) from each other. Comparable results were observed for plasma total cholesterol. The high PUFA and SAFA diets did not significantly alter plasma HDL concentration in either of the CETP genotype groups. Response was also similar according to apolipoprotein E genotype (E3E3 vs E4+) and lipoprotein lipase genotype (S447X). CONCLUSIONS: The results of this study do not support previous studies in which CETP genotype predicted plasma LDL-cholesterol response to diet. CETP genotype does not significantly affect the change in plasma total and LDL-cholesterol concentrations that occur when altering the nature of dietary fat. These data suggest that the influence of genetic factors on total and LDL-cholesterol may be relatively small in comparison with the effect of dietary manipulation.

Dietary counseling to increase natural folate intake: a randomized, placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine.

BACKGROUND: The association between vascular disease and elevated plasma total homocysteine (tHcy) concentrations is caused, in part, by inadequate intakes of dietary folate. Increasing folate intake either through supplements or foods naturally rich in folates has been shown to decrease tHcy concentrations. OBJECTIVE: The aim of this study was to determine whether a similar reduction in tHcy was possible in free-living persons receiving dietary counseling. DESIGN: The study included a 4-wk placebo-controlled dietary intervention trial in which participants consumed either unfortified breakfast cereal (control group) or an extra 350 micro g folate derived from food/d (dietary group). Serum folate and tHcy concentrations in both groups were measured before and after the intervention period, and the concentrations in the dietary group were also measured 17 wk after the intervention period. RESULTS: During the 4-wk intervention, mean dietary folate intake in the dietary group increased from 263 (95% CI: 225, 307) to 618 micro g/d (535, 714), resulting in a mean increase in serum folate of 37% (15%, 63%) and a decrease in tHcy from 12.0 (10.9, 13.3) to 11.3 micro mol/L (10.2, 12.5). A further decrease in tHcy occurred in the dietary group during follow-up, with a final tHcy concentration of 9.7 micro mol/L (8.8, 10.8). CONCLUSIONS: Increasing natural folate intake improved folate status and decreased tHcy concentrations to an extent that may significantly reduce the risk of vascular disease. Dietary modification may have advantages over folic acid fortification because the altered food-consumption patterns lead to increased intakes of several vitamins and minerals and decreased intakes of saturated fatty acids.

Intensive lifestyle changes are necessary to improve insulin sensitivity: a randomized controlled trial.

OBJECTIVE: The extent to which lifestyle must be altered to improve insulin sensitivity has not been established. This study compares the effect on insulin sensitivity of current dietary and exercise recommendations with a more intensive intervention in normoglycemic insulin-resistant individuals. RESEARCH DESIGN AND METHODS: Seventy-nine normoglycemic insulin-resistant (determined by the euglycemic insulin clamp) men and women were randomized to either a control group or one of two combined dietary and exercise programs. One group (modest level) was based on current recommendations and the other on a more intensive dietary and exercise program. Insulin sensitivity was measured using a euglycemic insulin clamp, body composition was measured using dual-energy X-ray absorptiometry, and anthropometry and aerobic fitness were assessed before and after a 4-month intervention period. Four-day dietary intakes were recorded, and fasting glucose, insulin, and lipids were measured. RESULTS: Only the intensive group showed a significant improvement in insulin sensitivity (23% increase, P=0.006 vs. 9% in the modest group, P=0.23). This was associated with a significant improvement in aerobic fitness (11% increase in the intensive group, P=0.02 vs. 1% in the modest group, P=0.94) and a greater fiber intake, but no difference in reported total or saturated dietary fat. CONCLUSIONS: Current clinical dietary and exercise recommendations, even when vigorously implemented, did not significantly improve insulin sensitivity; however, a more intensive program did. Improved aerobic fitness appeared to be the major difference between the two intervention groups, although weight loss and diet composition may have also played an important role in determining insulin sensitivity.