The American journal of clinical nutrition
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Surrogate biomarkers for clinical outcomes afford scientific and economic efficiencies when investigating nutritional interventions in chronic diseases. However, valid scientific results are dependent on the qualification of these disease markers that are intended to be substitutes for a clinical outcome and to accurately predict benefit or harm. In this article, we examine the challenges of evaluating surrogate markers and describe the framework proposed in a 2010 Institute of Medicine report. ⋯ We present case studies of 2 well-accepted surrogate markers [blood pressure within sodium intake and cardiovascular disease (CVD) context and low density lipoprotein-cholesterol concentrations within a saturated fat and CVD context]. We also describe additional cases in which the evidence is insufficient to validate their surrogate status. Guidance is offered for future research that evaluates or uses surrogate markers.
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Randomized Controlled Trial Multicenter Study
Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy.
Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber. Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy. ⋯ Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal toxicity both acutely and at 1 y compared with habitual-fiber intake. Restrictive, non-evidence-based advice to reduce fiber intake in this setting should be abandoned. This trial was registered at clinicaltrials.gov as NCT 01170299.
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Background: The benefits of the use of folic acid supplements (FASs) during the periconception period to prevent neural tube defects and to ensure normal brain development in offspring are well known. There is concern, however, about the long-term effects of the maternal use of high dosages of FASs that exceed the Tolerable Upper Intake Level (UL) (≥1000 μg/d) on child neurocognitive outcomes. Objective: The objective of the study was to examine the association between the use of high dosages of FASs during pregnancy and child neuropsychological development at ages 4-5 y. ⋯ The use of FAS dosages ≥1000 μg/d in this period was negatively associated with several neuropsychological outcomes scores in children: global verbal (β = -2.49; 95% CI: -4.71, -0.27), verbal memory (β = -3.59; 95% CI: -6.95, -0.23), cognitive function of posterior cortex (β = -2.31; 95% CI: -4.45, -0.18), and cognitive function of left posterior cortex (β = -3.26; 95% CI: -5.51, -1.01). Conclusions: The use of FAS dosages exceeding the UL (≥1000 μg/d) during the periconception period was associated with lower levels of cognitive development in children aged 4-5 y. The use of FAS dosages ≥1000 μg/d during pregnancy should be monitored and prevented as much as possible, unless medically prescribed.
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Randomized Controlled Trial Comparative Study
Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial.
Background: There are conflicting views in the literature as to whether vitamin D2 and vitamin D3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D2 or vitamin D3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y (n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D2, biscuit supplemented with 15 μg vitamin D2, juice supplemented with 15 μg vitamin D3, or biscuit supplemented with 15 μg vitamin D3 daily for 12 wk. ⋯ Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D3 was more effective than vitamin D2 in increasing serum 25(OH)D in the wintertime. Vitamin D3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591.
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Randomized Controlled Trial Comparative Study
Increased vitamin D intake differentiated according to skin color is needed to meet requirements in young Swedish children during winter: a double-blind randomized clinical trial.
Background: Dark skin and low exposure to sunlight increase the risk of vitamin D insufficiency in children. Objective: The aim of the study was to evaluate the amount of vitamin D needed to ascertain that most children >4 y of age attain sufficient serum 25-hydroxyvitamin D [S-25(OH)D; i.e., ≥50 nmol/L] during winter regardless of latitude and skin color. Design: In a longitudinal, double-blind, randomized, food-based intervention study, 5- to 7-y-old children from northern (63°N) and southern (55°N) Sweden with fair (n = 108) and dark (n = 98) skin were included. ⋯ By using 95% prediction intervals for 30 and 50 nmol S-25(OH)D/L, intakes of 6 and 20 μg/d are required in fair-skinned children, whereas 14 and 28 μg/d are required in children with dark skin. Conclusion: Children with fair and dark skin require vitamin D intakes of 20 and 28 μg/d, respectively, to maintain S-25(OH)D ≥50 nmol/L, whereas intakes of 6 and 14 μg/d, respectively, are required to maintain concentrations ≥30 nmol/L during winter. This trial was registered at clinicaltrials.gov as NCT01741324.