Showing papers in "Journal of Nutrition in 2012"
TL;DR: The findings suggest that closer adherence to the 2005 Dietary Guidelines may lower risk of major chronic disease, however, the AHEI-2010, which included additional dietary information, was more strongly associated with chronic disease risk, particularly CHD and diabetes.
Abstract: The Healthy Eating Index-2005 (HEI-2005) measures adherence to the 2005 Dietary Guidelines for Americans, but the association between the HEI-2005 and risk of chronic disease is not known. The Alternative Healthy Eating Index (AHEI), which is based on foods and nutrients predictive of chronic disease risk, was associated inversely with chronic disease risk previously. We updated the AHEI, including additional dietary factors involved in the development of chronic disease, and assessed the associations between the AHEI-2010 and the HEI-2005 and risk of major chronic disease prospectively among 71,495 women from the Nurses' Health Study and 41,029 men from the Health Professionals Follow-Up Study who were free of chronic disease at baseline. During ≥24 y of follow-up, we documented 26,759 and 15,558 incident chronic diseases (cardiovascular disease, diabetes, cancer, or nontrauma death) among women and men, respectively. The RR (95% CI) of chronic disease comparing the highest with the lowest quintile was 0.84 (0.81, 0.87) for the HEI-2005 and 0.81 (0.77, 0.85) for the AHEI-2010. The AHEI-2010 and HEI-2005 were most strongly associated with coronary heart disease (CHD) and diabetes, and for both outcomes the AHEI-2010 was more strongly associated with risk than the HEI-2005 (P-difference = 0.002 and <0.001, respectively). The 2 indices were similarly associated with risk of stroke and cancer. These findings suggest that closer adherence to the 2005 Dietary Guidelines may lower risk of major chronic disease. However, the AHEI-2010, which included additional dietary information, was more strongly associated with chronic disease risk, particularly CHD and diabetes.
1,364 citations
TL;DR: The very long-chain (n-3) PUFA have a range of physiological roles that relate to optimal cell membrane structure and optimal cell function and responses, and play a key role in preventing, and perhaps treating, many conditions of poor health and well-being.
Abstract: (n-3) PUFA are a family of biologically active fatty acids. The simplest member of this family, α-linolenic acid, can be converted to the more biologically active very long-chain (n-3) PUFA EPA and DHA; this process occurs by a series of desaturation and elongation reactions, with stearidonic acid being an intermediate in the pathway. Biological activity of α-linolenic and stearidonic acids most likely relates to their conversion to EPA. The very long-chain (n-3) PUFA have a range of physiological roles that relate to optimal cell membrane structure and optimal cell function and responses. Thus, (n-3) PUFA play a key role in preventing, and perhaps treating, many conditions of poor health and well-being. The multiple actions of (n-3) PUFA appear to involve multiple mechanisms that connect the cell membrane, the cytosol, and the nucleus. For some actions, (n-3) PUFA appear to act via receptors or sensors, so regulating signaling processes that influence patterns of gene expression. Some effects of (n-3) PUFA seem to involve changes in cell membrane fatty acid composition. Changing membrane composition can in turn affect membrane order, formation of lipid rafts, intracellular signaling processes, gene expression, and the production of both lipid and peptide mediators. Under typical Western dietary conditions, human cells tend to have a fairly high content of the (n-6) fatty acid arachidonic acid. Increased oral intake of EPA and DHA modifies the content of arachidonic acid as well as of EPA and DHA. Arachidonic acid is the substrate for eicosanoids involved in physiology and pathophysiology. The eicosanoids produced from EPA frequently have properties that are different from those that are produced from arachidonic acid. EPA and DHA are also substrates for production of resolvins and protectins, which seem to be biologically extremely potent. Increasing the contents of EPA and DHA in membranes modifies the pattern of production of these different lipid mediators.
717 citations
TL;DR: Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention and potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials.
Abstract: Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48-80 g whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in post-intervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose: -0.93 mmol/L (95% CI: -1.65, -0.21), total cholesterol: -0.83 mmol/L (-1.23, -0.42); and LDL-cholesterol: -0.82 mmol/L (-1.31, -0.33)]. [corrected] Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials.
629 citations
TL;DR: Although iodine nutrition has been improving since 2003, global progress may be slowing and intervention programs need to be extended to reach the nearly one-third of the global population that still has inadequate iodine intakes.
Abstract: Salt iodization has been introduced in many countries to control iodine deficiency. Our aim was to assess global and regional iodine status as of 2011 and compare it to previous WHO estimates from 2003 and 2007. Using the network of national focal points of the International Council for the Control of Iodine Deficiency Disorders as well as a literature search, we compiled new national data on urinary iodine concentration (UIC) to add to the existing data in the WHO Vitamin and Mineral Nutrition Information System Micronutrients Database. The most recent data on UIC, primarily national data in school-age children (SAC), were analyzed. The median UIC was used to classify national iodine status and the UIC distribution to estimate the number of individuals with low iodine intakes by severity categories. Survey data on UIC cover 96.1% of the world’s population of SAC, and since 2007, new national data are available for 58 countries,including Canada, Pakistan, the UK, and the US. At the national level, there has been major progress: from 2003 to 2011, the number of iodine-deficient countries decreased from 54 to 32 and the number of countries with adequate iodine intake increased from 67 to 105. However, globally, 29.8% (95% CI = 29.4, 30.1) of SAC (241 million) are estimated to have insufficient iodine intakes. Sharp regional differences persist; southeast Asia has the largest number of SAC with low iodine intakes (76 million) and there has been little progress in Africa, where 39% (58 million) have inadequate iodine intakes. In summary, although iodine nutrition has been improving since 2003, global progress may be slowing. Intervention programs need to be extended to reach the nearly one-third of the global population that still has inadequate iodine intakes. J. Nutr. doi: 10.3945/jn.111.149393.
574 citations
TL;DR: In this paper, a randomized controlled trial aimed to investigate the effects of fermentable carbohydrate restriction on luminal microbiota, SCFA, and GI symptoms in patients with irritable bowel syndrome (IBS).
Abstract: Preliminary studies indicate that dietary restriction of fermentable short-chain carbohydrates improves symptoms in irritable bowel syndrome (IBS). Prebiotic fructo-oligosaccharides and galacto-oligosaccharides stimulate colonic bifidobacteria. However, the effect of restricting fermentable short-chain carbohydrates on the gastrointestinal (GI) microbiota has never been examined. This randomized controlled trial aimed to investigate the effects of fermentable carbohydrate restriction on luminal microbiota, SCFA, and GI symptoms in patients with IBS. Patients with IBS were randomized to the intervention diet or habitual diet for 4 wk. The incidence and severity of symptoms and stool output were recorded for 7 d at baseline and follow-up. A stool sample was collected and analyzed for bacterial groups using fluorescent in situ hybridization. Of 41 patients randomized, 6 were withdrawn. At follow-up, there was lower intake of total short-chain fermentable carbohydrates in the intervention group compared with controls (P = 0.001). The total luminal bacteria at follow-up did not differ between groups; however, there were lower concentrations (P < 0.001) and proportions (P < 0.001) of bifidobacteria in the intervention group compared with controls when adjusted for baseline. In the intention-to-treat analysis, more patients in the intervention group reported adequate control of symptoms (13/19, 68%) compared with controls (5/22, 23%; P = 0.005). This randomized controlled trial demonstrated a reduction in concentration and proportion of luminal bifidobacteria after 4 wk of fermentable carbohydrate restriction. Although the intervention was effective in managing IBS symptoms, the implications of its effect on the GI microbiota are still to be determined.
473 citations
TL;DR: The present evidence suggests that EPA and DHA have both shared and complementary benefits and increasing consumption of either would be advantageous compared to little or no consumption.
Abstract: Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially for DPA. Nonetheless, the present evidence suggests that EPA and DHA have both shared and complementary benefits. Based on current evidence, increasing consumption of either would be advantageous compared to little or no consumption. Focusing on their combined consumption remains most prudent given the potential for complementary effects and the existing more robust literature on cardiovascular benefits of their combined consumption as fish or fish oil for cardiovascular benefits.
337 citations
TL;DR: Introduction of OSP to Ugandan farming households increased vitamin A intakes among children and women and was associated with improved vitamin A status among children.
Abstract: Vitamin A deficiency (VAD) persists in Uganda and the consumption of β-carotene-rich orange sweet potato (OSP) may help to alleviate it. Two large-scale, 2-y intervention programs were implemented among Ugandan farmer households to promote the production and consumption of OSP. The programs differed in their inputs during year 2, with one being more intensive (IP) and the other being reduced (RP). A randomized, controlled effectiveness study compared the impact of the IP and RP with a control on OSP and vitamin A intakes among children aged 6-35 mo (n = 265) and 3-5 y (n = 578), and women (n = 573), and IP compared with control on vitamin A status of 3- to 5-y-old children (n = 891) and women (n = 939) with serum retinol 30 percentage points) and women (>25 percentage points) (P < 0.01), with no differences between the IP and RP groups of children (P = 0.75) or women (P = 0.17). There was a 9.5 percentage point reduction in prevalence of serum retinol <1.05 μmol/L for children with complete data on confounding factors (n = 396; P < 0.05). At follow-up, vitamin A intake from OSP was positively associated with vitamin A status (P < 0.05). Introduction of OSP to Ugandan farming households increased vitamin A intakes among children and women and was associated with improved vitamin A status among children.
253 citations
TL;DR: The data demonstrate a beneficial shift in the gut microbiome of adults consuming PDX and SCF, with potential application as prebiotics, and a distinct clustering of individuals consuming supplemental fibers.
Abstract: The relative contribution of novel fibers such as polydextrose and soluble corn fiber (SCF) to the human gut microbiome and its association with host physiology has not been well studied. This study was conducted to test the impact of polydextrose and SCF on the composition of the human gut microbiota using 454 pyrosequencing and to identify associations among fecal microbiota and fermentative end-products. Healthy adult men (n = 20) with a mean dietary fiber (DF) intake of 14 g/d were enrolled in a randomized, double-blind, placebo-controlled crossover study. Participants consumed 3 treatment snack bars/d during each 21-d period that contained no supplemental fiber (NFC), polydextrose (PDX; 21 g/d), or SCF (21 g/d) for 21 d. There were no washout periods. Fecal samples were collected on d 16-21 of each period; DNA was extracted, followed by amplification of the V4-V6 region of the 16S rRNA gene using barcoded primers. PDX and SCF significantly affected the relative abundance of bacteria at the class, genus, and species level. The consumption of PDX and SCF led to greater fecal Clostridiaceae and Veillonellaceae and lower Eubacteriaceae compared with a NFC. The abundance of Faecalibacterium, Phascolarctobacterium, and Dialister was greater (P < 0.05) in response to PDX and SCF intake, whereas Lactobacillus was greater (P < 0.05) only after SCF intake. Faecalibacterium prausnitzii, well known for its antiinflammatory properties, was greater (P < 0.05) after fiber consumption. Principal component analysis clearly indicated a distinct clustering of individuals consuming supplemental fibers. Our data demonstrate a beneficial shift in the gut microbiome of adults consuming PDX and SCF, with potential application as prebiotics.
230 citations
TL;DR: Results indicate that fish oil supplementation is associated with inhibition of TLR4 and NOD2 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.
Abstract: Long-chain (n-3) PUFA exert beneficial effects on inflammatory bowel diseases in animal models and clinical trials. In addition, pattern recognition receptors such as toll-like receptors (TLR) and nucleotide-binding oligomerization domain proteins (NOD) play a critical role in intestinal inflammation. We hypothesized that fish oil could alleviate Escherichia coli LPS-induced intestinal injury via modulation of TLR4 and NOD signaling pathways. Twenty-four weaned piglets were used in a 2 × 2 factorial design and the main factors included a dietary treatment (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline). After feeding fish oil or corn oil diets for 21 d, pigs were injected with LPS or saline. At 4 h postinjection, blood samples were collected and pigs were killed. EPA, DHA, and total (n-3) PUFA were enriched in intestinal mucosa through fish supplementation. Fish oil improved intestinal morphology, indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, indicated by decreased plasma diamine oxidase (DAO) activity and increased mucosal DAO activity as well as enhanced protein expression of intestinal tight junction proteins including occludin and claudin-1. Moreover, fish oil decreased intestinal TNFα and PGE(2) concentrations and caspase-3 and heat shock protein 70 protein expression. Finally, fish oil downregulated the mRNA expression of intestinal TLR4 and its downstream signals myeloid differentiation factor 88, IL-1 receptor-associated kinase 1, TNFα receptor-associated factor 6, and NOD2, and its adaptor molecule, receptor-interacting serine/threonine-protein kinase 2. Fish oil decreased the protein expression of intestinal NFκB p65. These results indicate that fish oil supplementation is associated with inhibition of TLR4 and NOD2 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.
224 citations
TL;DR: Quercetin treatment attenuated most of the symptoms of metabolic syndrome, including abdominal obesity, cardiovascular remodeling, and NAFLD, with the most likely mechanisms being decreases in oxidative stress and inflammation.
Abstract: Metabolic syndrome is a risk factor for cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). We investigated the responses to the flavonol, quercetin, in male Wistar rats (8-9 wk old) divided into 4 groups. Two groups were given either a corn starch-rich (C) or high-carbohydrate, high-fat (H) diet for 16 wk; the remaining 2 groups were given either a C or H diet for 8 wk followed by supplementation with 0.8 g/kg quercetin in the food for the following 8 wk (CQ and HQ, respectively). The H diet contained ~68% carbohydrates, mainly as fructose and sucrose, and ~24% fat from beef tallow; the C diet contained ~68% carbohydrates as polysaccharides and ~0.7% fat. Compared with the C rats, the H rats had greater body weight and abdominal obesity, dyslipidemia, higher systolic blood pressure, impaired glucose tolerance, cardiovascular remodeling, and NAFLD. The H rats had lower protein expressions of nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and carnitine palmitoyltransferase 1 (CPT1) with greater expression of NF-κB in both the heart and the liver and less expression of caspase-3 in the liver than in C rats. HQ rats had higher expression of Nrf2, HO-1, and CPT1 and lower expression of NF-κB than H rats in both the heart and the liver. HQ rats had less abdominal fat and lower systolic blood pressure along with attenuation of changes in structure and function of the heart and the liver compared with H rats, although body weight and dyslipidemia did not differ between the H and HQ rats. Thus, quercetin treatment attenuated most of the symptoms of metabolic syndrome, including abdominal obesity, cardiovascular remodeling, and NAFLD, with the most likely mechanisms being decreases in oxidative stress and inflammation.
216 citations
TL;DR: In conclusion, degraded mood, increased perception of task difficulty, lower concentration, and headache symptoms resulted from 1.36% dehydration in females, and increased emphasis on optimal hydration is warranted, especially during and after moderate exercise.
Abstract: Limited information is available regarding the effects of mild dehydration on cognitive function. Therefore, mild dehydration was produced by intermittentmoderate exercise without hyperthermia and its effects on cognitive function of women were investigated. Twenty-five females (age 23.0 6 0.6 y) participated in three 8-h, placebo-controlled experiments involving a different hydration state each day: exercise-induced dehydration with no diuretic (DN), exerciseinduced dehydration plus diuretic (DD; furosemide, 40 mg), and euhydration (EU). Cognitive performance, mood, and symptoms of dehydration were assessed during each experiment, 3 times at rest and during each of 3 exercise sessions. The DN and DD trials in which a volunteer attained a $1% level of dehydration were pooled and compared to that volunteer’s equivalent EU trials. Mean dehydration achieved during these DN and DD trials was 21.36 6 0.16% of body mass. Significant adverse effects of dehydration were present at rest and during exercise for vigor-activity, fatigue-inertia, and total mood disturbance scores of the Profile of Mood States and for task difficulty, concentration, and headache as assessed by questionnaire. Most aspects of cognitive performance were not affected by dehydration. Serum osmolality, a marker of hydration, was greater in the mean of the dehydrated trials in which a $1% level of dehydration was achieved (P = 0.006) compared to EU. In conclusion, degraded mood, increased perception of task difficulty, lower concentration, and headache symptoms resulted from 1.36% dehydration in females. Increased emphasis on optimal hydration is warranted, especially during and after moderate exercise. J. Nutr. doi: 10.3945/jn.111.142000.
TL;DR: In community-dwelling older adults, higher adherence to a Mediterranean-style diet was inversely associated with the development of frailty, and lower adherence after a 6-y follow-up was associated with lower odds of developing frailty.
Abstract: Adherence to a Mediterranean-style diet is associated with a lower risk for mortality, cognitive decline, and dementia. Whether adherence to a Mediterranean-style diet protects against age-related frailty is unclear. Therefore, our objective was to examine the association between a Mediterranean-style diet with the risk of frailty in community-dwelling older persons. We conducted longitudinal analyses using data from 690 community-living persons (≥65 y) who were randomly selected from a population registry in Tuscany, Italy. Participants of the Invecchiare in Chianti study of aging completed the baseline examination in 1998-2000 and were re-examined at least once over 6 y. Adherence to a Mediterranean-style diet (scored 0-9, modeled categorically as ≤3, 4-5, and ≥6) was computed from the European Prospective Investigation into Cancer and nutrition FFQ previously validated in this cohort. Frailty was defined as having at least 2 of the following criteria: poor muscle strength, feeling of exhaustion, low walking speed, and low physical activity. After a 6-y follow-up, higher adherence (score ≥6) to a Mediterranean-style diet was associated with lower odds of developing frailty [OR = 0.30 (95% CI: 0.14, 0.66)] compared with those with lower adherence (score ≤3). A higher adherence to a Mediterranean-style diet at baseline was also associated with a lower risk of low physical activity (OR = 0.62; 95% CI: 0.40, 0.96) and low walking speed [OR = 0.48 (95% CI: 0.27, 0.86)] but not with feelings of exhaustion and poor muscle strength. In community-dwelling older adults, higher adherence to a Mediterranean-style diet was inversely associated with the development of frailty.
TL;DR: It is demonstrated that the rumen microbial ecosystem is directly linked to theRumen fermentation pattern and, to some extent, to the efficiency of diet utilization by dairy cattle.
Abstract: Belanche Gracia, A., Doreau, M., Edwards, J. E., Moorby, J. M., Pinloche, E., Newbold, C. J. (2012). Shifts in the rumen microbiota due to the type of carbohydrate and level of protein ingested by dairy cattle are associated with changes in rumen fermentation. The Journal of Nutrition, 142 (9), 1684-1692.
TL;DR: Concerns that dissociating sweetness from energy may disrupt the balance between taste response, appetite, and consumption patterns, especially during development mean further studies are needed to clarify the developmental trajectory of taste responses to low-calorie sweeteners and their potential impact on the diet quality of children and youth.
Abstract: Human desire for sweet taste spans all ages, races, and cultures. Throughout evolution, sweetness has had a role in human nutrition, helping to orient feeding behavior toward foods providing both energy and essential nutrients. Infants and young children in particular base many of their food choices on familiarity and sweet taste. The low cost and ready availability of energy-containing sweeteners in the food supply has led to concerns that the rising consumption of added sugars is the driving force behind the obesity epidemic. Low-calorie sweeteners are one option for maintaining sweet taste while reducing the energy content of children’s diets. However, their use has led to further concerns that dissociating sweetness from energy may disrupt the balance between taste response, appetite, and consumption patterns, especially during development. Further studies, preferably based on longitudinal cohorts, are needed to clarify the developmental trajectory of taste responses to low-calorie sweeteners and their potential impact on the diet quality of children and youth.
TL;DR: Safe and effective food-based strategies could increase 25(OH)D across the population distribution and prevent vitamin D deficiency with potential benefit for public health.
Abstract: Food fortification is a potentially effective public health strategy to increase vitamin D intakes and circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We updated a previous systematic review to evaluate current evidence from randomized controlled intervention studies in community-dwelling adults of the effect of fortified foods on 25(OH)D concentrations. Ovid MEDLINE, PubMed, CINAHL, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled intervention studies with vitamin D-fortified foods in free-living adults and data on circulating 25(OH)D. Two reviewers independently screened 441 papers for eligibility and extracted the relevant data. A meta-analysis of the absolute mean change in circulating 25(OH)D concentrations was conducted using a random effects model. Sixteen studies from 15 publications were included, of which 14 showed a significant effect of fortified foods on 25(OH)D concentrations. Heterogeneity was high (P = <0.0001, I(2) = 89%) and was partly explained by dose, latitude (range, 3-60°), and baseline 25(OH)D (range, 24.0-83.6 nmol/L). When combined in a random effects analysis (n = 1513; 767 treated, 746 controls), a mean individual intake of ~11 μg/d (440 IU/d) from fortified foods (range, 3-25 μg/d) increased 25(OH)D by 19.4 nmol/L (95% CI: 13.9, 24.9), corresponding to a 1.2 nmol/L (95% CI: 0.72, 1.68) increase in 25(OH)D for each 1 μg ingested. Vitamin D food fortification increases circulating 25(OH)D concentrations in community-dwelling adults. Safe and effective food-based strategies could increase 25(OH)D across the population distribution and prevent vitamin D deficiency with potential benefit for public health.
TL;DR: Food insecurity prevalence is high in Inuit communities, with implications for diet quality that over the long-term would be anticipated to exacerbate the risk of diet-related chronic diseases.
Abstract: Indigenous peoples experience a disproportionate burden of food insecurity and the Arctic is no exception. We therefore evaluated the prevalence, socio-demographic, and dietary correlates of food insecurity in the most comprehensive assessment of food insecurity in Arctic Canada. A cross-sectional survey of 1901 Inuit households was conducted in 2007–2008. Measurements included food insecurity, 24-h dietary recalls, socio-demographics, and anthropometry. Food insecurity was identified in 62.6% of households (95% CI = 60.3–64.9%) with 27.2% (95% CI = 25.1–29.3%) of households severely food insecure. The percent with an elevated BMI, waist circumference, and percent body fat was lower among individuals from food insecure households compared to food secure households (P # 0.001). Adults from food insecure households had a significantly lower Healthy Eating Index score and consumed fewer vegetables and fruit, grains, and dairy products, and consumed a greater percent of energy from high-sugar foods than adults from food secure households (P # 0.05). Food insecurity was associated with household crowding, income support, public housing, single adult households, and having a home in need of major repairs (P # 0.05). The prevalence of having an active hunter in the home was lower in food insecure compared to food secure households (P # 0.05). Food insecurity prevalence is high in Inuit communities, with implications for diet quality that over the long-term would be anticipated to exacerbate the risk of diet-related chronic diseases. Actions are required to improve food security that incorporate the traditional food system and healthy market food choices. J. Nutr. doi: 10.3945/jn.111.149278.
TL;DR: A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome.
Abstract: First defined in the mid-1990s, prebiotics, which alter the composition and activity of gastrointestinal (GI) microbiota to improve health and well-being, have generated scientific and consumer interest and regulatory debate. The Life Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess the current state of the science and the international regulatory environment for prebiotics, identify research gaps, and create a strategy for future research. A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome. Prebiotics also increase the bioavailability and uptake of minerals and data suggest that they reduce the risk of obesity by promoting satiety and weight loss. Additional research is needed to define the relationship between the consumption of different prebiotics and improvement of human health. New information derived from the characterization of the composition and function of different prebiotics as well as the interactions among and between gut microbiota and the human host would improve our understanding of the effects of prebiotics on health and disease and could assist in surmounting regulatory issues related to prebiotic use.
TL;DR: These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants, but hypercaloric fructose consumption may, however, increase uric Acid concentrations.
Abstract: Hyperuricemia is linked to gout and features of metabolic syndrome. There is concern that dietary fructose may increase uric acid concentrations. To assess the effects of fructose on serum uric acid concentrations in people with and without diabetes, we conducted a systematic review and meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials (through August 19, 2011). Analyses included all controlled feeding trials ≥ 7 d investigating the effect of fructose feeding on uric acid under isocaloric conditions, where fructose was isocalorically exchanged with other carbohydrate, or hypercaloric conditions, and where a control diet was supplemented with excess energy from fructose. Data were aggregated by the generic inverse variance method using random effects models and expressed as mean difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and quantified by I(2). A total of 21 trials in 425 participants met the eligibility criteria. Isocaloric exchange of fructose for other carbohydrate did not affect serum uric acid in diabetic and nondiabetic participants [MD = 0.56 μmol/L (95% CI: -6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric supplementation of control diets with fructose (+35% excess energy) at extreme doses (213-219 g/d) significantly increased serum uric acid compared with the control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4, 46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot be ruled out in the hypercaloric trials. These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants. Hypercaloric fructose intake may, however, increase uric acid concentrations. The effect of the interaction of energy and fructose remains unclear. Larger, well-designed trials of fructose feeding at "real world" doses are needed.
TL;DR: It is suggested that consumption of 15–30 g/d of HAM-RS2 improves SI in men, and additional research is needed to understand the mechanisms that might account for the treatment × sex interaction observed.
Abstract: This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (SI) in participants with waist circumference $89 (women) or $102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model SI was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean 6 SEM) age 49.5 6 1.6 y, with a BMI of 30.6 6 0.5 kg/m 2 and waist circumference 105.3 6 1.3 cm. A treatment main effect (P = 0.018) and a treatment 3 sex interaction (P = 0.033) were present. In men, least squares geometric mean analysis for SI did not differ after intake of 15 g/d HAM-RS2 (6.90 3 10 25 pmol 21 × L 21 3 min 21 ) and 30 g/d HAM-RS2 (7.13 3 10 25 pmol 21 × L 21 3 min 21 ), but both were higher than after the control treatment (4.66 3 10 25 pmol 21 × L 21 3 min 21 )( P , 0.05). In women, there was no difference among the treatments (overall least squares ln-transformed mean 6 pooled SEM = 1.80 6 0.08; geometric mean = 6.05 3 10 25 pmol 21 × L 21 3 min 21 ). These results suggest that consumption of 15‐30 g/d of HAM-RS2 improves SI in men. Additional research is needed to understand the mechanisms that might account for the treatment 3 sex interaction
TL;DR: Previous NHANES reports overestimated the increase in prevalence of hypovitaminosis D and the recent decline in vitamin D status in the U.S. is more likely due to increased prevalence of obesity and other lifestyle changes but not to changes in milk consumption.
Abstract: Prevalence of hypovitaminosis D from previous NHANES reports did not account for assay changes and drifts over time. Thus, published NHANES reports on vitamin D status for the U.S. population were likely either over- or underestimated. We investigated changes in vitamin D status in the U.S. using assay-adjusted serum 25-hydroxyvitamin D [25(OH)D] data from NHANES, 1988-1994 (n = 18,641) and three cycles of NHANES, 2001-2006 (n = 23,424). Changes in geometric mean serum 25(OH)D and prevalence estimates for various serum 25(OH)D cut points ( 80th percentile (P 80th percentile (P < 0.001). Previous NHANES reports overestimated the increase in prevalence of hypovitaminosis D. The recent decline in vitamin D status in the U.S. is more likely due to increased prevalence of obesity and other lifestyle changes but not to changes in milk consumption.
TL;DR: In this article, the authors compared the Bio-Rad radioassay (BR) and the microbiologic assay (MBA) for measuring folate status of the U.S. population from pre-1994 to post-2010 by measuring serum and RBC folate concentrations.
Abstract: The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999-2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was ≤ 1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups. The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and postfortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact.
TL;DR: Because of the inefficient conversion of ALA, the appearance of SDA in enriched soy oil offers a biologically effective and cost effective approach to providing a sustainable plant source for (n-3) FA in the future.
Abstract: Dietary fatty acids (FA) are increasingly recognized as major biologic regulators and have properties that relate to health outcomes and disease. The longer chain, more bioactive (n-6) (or omega-6) FA and (n-3) (or omega-3) FA share similar elongation and desaturation enzymes in their conversion from the essential (n-6) FA, linoleic acid, and (n-3) FA, α-linolenic acid (ALA). Conversion from these essential FA is very inefficient. However, now for the (n-3) FA series, soy oil can be enriched with (n-3) stearidonic acid (SDA) to allow for much more efficient conversion to longer chain EPA. EPA and the longer chain DHA possess distinct physical and biological properties that generally impart properties to cells and tissue, which underlie their ability to promote health and prevent disease. Although active in a number of areas of human biology, mechanisms of action of EPA and DHA are perhaps best defined in cardiovascular disease. There is concern that to reach the intake recommendations of EPA and DHA, their supply from cold water fish will be insufficient. Gaps in understanding mechanisms of action of (n-3) FA in a number of health and disease areas as well as optimal sources and intake levels for each need to be defined by further research. Because of the inefficient conversion of ALA, the appearance of SDA in enriched soy oil offers a biologically effective and cost effective approach to providing a sustainable plant source for (n-3) FA in the future.
TL;DR: Examination of the effects of individual essential AA on cellular signaling and fractional protein synthesis rates in bovine mammary cells found regulation of protein synthesis will result in variable efficiency of transfer of absorbed EAA to milk protein and is incompatible with the assumption that a single nutrient limits protein synthesis.
Abstract: Understanding the regulatory effects of individual amino acids (AA) on milk protein synthesis rates is important for improving protein and AA requirement models for lactation. The objective of this study was to examine the effects of individual essential AA (EAA) on cellular signaling and fractional protein synthesis rates (FSR) in bovine mammary cells. Omission of L-arginine, L-isoleucine, L-leucine, or all EAA reduced (P < 0.05) mammalian target of rapamycin (mTOR; Ser2448) and ribosomal protein S6 (rpS6; Ser235/236) phosphorylation in MAC-T cells. Phosphorylation of mTOR and rpS6 kinase 1 (S6K1; Thr389) decreased (P < 0.05) in the absence of L-isoleucine, L-leucine, or all EAA in lactogenic mammary tissue slices. Omission of L-tryptophan also reduced S6K1 phosphorylation (P = 0.01). Supplementation of L-leucine to media depleted of EAA increased mTOR and rpS6 and decreased eukaryotic elongation factor 2 (Thr56) phosphorylation (P < 0.05) in MAC-T cells. Supplementation of L-isoleucine increased mTOR, S6K1, and rpS6 phosphorylation (P < 0.05). No single EAA considerably affected eukaryotic initiation factor 2-α (eIF2α; Ser51) phosphorylation, but phosphorylation was reduced in response to provision of all EAA (P < 0.04). FSR declined when L-isoleucine (P = 0.01), L-leucine (P = 0.01), L-methionine (P = 0.02), or L-threonine (P = 0.07) was depleted in media and was positively correlated (R = 0.64, P < 0.01) with phosphorylation of mTOR and negatively correlated (R = -0.42, P = 0.01) with phosphorylation of eIF2α. Such regulation of protein synthesis will result in variable efficiency of transfer of absorbed EAA to milk protein and is incompatible with the assumption that a single nutrient limits protein synthesis that is encoded in current diet formulation strategies.
TL;DR: Consumption of whole-grain products resulted in a greater reduction in the percentage fat mass, whereas body weight changes did not differ between the RW and WW groups, which may suggest a cardioprotective role for whole grain.
Abstract: Observational studies show inverse associations between intake of whole grain and adiposity and cardiovascular risk; however, only a few dietary intervention trials have investigated the effect of whole-grain consumption on health outcomes. We studied the effect of replacing refined wheat (RW) with whole-grain wheat (WW) for 12 wk on body weight and composition after a 2-wk run-in period of consumption of RW-containing food intake. In this open-label randomized trial, 79 overweight or obese postmenopausal women were randomized to an energy-restricted diet (deficit of ~1250 kJ/d) with RW or WW foods providing 2 MJ/d. Body weight and composition, blood pressure, and concentration of circulating risk markers were measured at wk 0, 6, and 12. Fecal output and energy excretion were assessed during run-in and wk 12. Plasma alkylresorcinol analysis indicated good compliance with the intervention diets. Body weight decreased significantly from baseline in both the RW (-2.7 ± 1.9 kg) and WW (-3.6 ± 3.2 kg) groups, but the decreases did not differ between the groups (P = 0.11). The reduction in body fat percentage was greater in the WW group (-3.0%) than in the RW group (-2.1%) (P = 0.04). Serum total and LDL cholesterol increased by ~5% (P < 0.01) in the RW group but did not change in the WW group; hence, the changes differed between the groups (P = 0.02). In conclusion, consumption of whole-grain products resulted in a greater reduction in the percentage fat mass, whereas body weight changes did not differ between the RW and WW groups. Serum total and LDL cholesterol, two important risk factors of cardiovascular disease, increased with RW but not WW consumption, which may suggest a cardioprotective role for whole grain.
TL;DR: The Spanish population is drifting away from the MD to adopt a less healthy diet, typical of Western countries, which mostly affects the socially disadvantaged and clusters with other unhealthy lifestyles, which may have synergistic undesirable effects on health.
Abstract: This work examined the Spanish populations degree of accordance with the Mediterranean diet (MD). This was a crosssectional study conducted in 2008–2010 among 11,742 individuals representative of the Spanish population aged $18 y. Habitual food consumption was assessed with a computerized diet history. Accordance of food consumption with the MD was assessed with the MD Adherence Screener (MEDAS) score using the cutoffs $9 to define strict accordance and $7 (mid-range value) for modest accordance. Accordance of nutrient intake with the MD was defined as $4.5 points (midrange value) on the high-unsaturated fat OmniHeart diet score. The diet of 12% (95% CI: 11.3–12.7%) of the Spanish population reached MEDAS-based strict accordance with the MD and 46% (95% CI: 44.7–47.7) attained modest accordance. Moreover, 39.0% (95%: 37.8–40.1%) of the population achieved OnmiHeart-based MD accordance. Factor analysis identified 2 main dietary patterns. The first one was called ‘‘Westernized’’ and was rich in red and processed meat, French fries, refined cereals, and sweetened beverages and poor in fresh fruit; the second pattern was named ‘‘Mediterranean’’ and was rich in olive oil and plant-based foods. Regardless of how it was defined, MD accordance was less frequent and the Westernized pattern was more frequent among the younger, the less educated, current smokers, and those less physically active and more sedentary. In conclusion, the Spanish population is drifting away from the MD to adopt a less healthy diet, typical of Western countries. The departure from the MD mostly affects the socially disadvantaged and clusters with other unhealthy lifestyles, which may have synergistic undesirable effects on health. J. Nutr. doi: 10.3945/jn.112.164616.
TL;DR: The effects of Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota and ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe.
Abstract: Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies Fe is essential not only for the human host but also for nearly all gut bacteria We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats Weanling rats were fed an Fe-deficient diet for 24 d and then repleted for 13 d with FeSO4 (n = 15) or electrolytic Fe (n = 14) at 10 and 20 mg Fe · kg diet−1 In addition, one group of rats (n = 8) received the Fe-deficient diet and one group (n = 3) received a Fe-sufficient control diet for all 37 d Fecal samples were collected at baseline and after the depletion and repletion periods, and colonic tissues were examined histologically Microbial metabolite composition in cecal water was measured and fecal samples were analyzed for microbial composition with temporal temperature gradient gel electrophoresis and qPCR Compared to Fe-sufficient rats, Fe-deficient rats had significantly lower concentrations of cecal butyrate (−87%) and propionate (−72%) and the abundance of dominant species was strongly modified, including greater numbers of lactobacilli and Enterobacteriaceae and a large significant decrease of the Roseburia spp/E rectale group, a major butyrate producer Repletion with 20 mg FeSO4 · kg diet−1 significantly increased cecal butyrate concentrations and partially restored bacterial populations compared to Fe-deficient rats at endpoint The effects on the gut microbiota were stronger in rats repleted with FeSO4 than in rats repleted with electrolytic Fe, suggesting ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe Repletion with FeSO4 significantly increased neutrophilic infiltration of the colonic mucosa compared to Fe-deficient rats In conclusion, Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota
TL;DR: The findings of significant associations of high SSB intake with frequent fast-food restaurant use and sedentary behaviors may be used to tailor intervention efforts to reduceSSB intake among high-risk populations.
Abstract: This cross-sectional study examined associations of demographic characteristics, weight status, availability of school vending machines, and behavioral factors with sugar-sweetened beverage (SSB) intake, both overall and by type of SSB, among a nationally representative sample of high school students. The 2010 National Youth Physical Activity and Nutrition Study data for 11,209 students (grades 9–12) were used. SSB intake was based on intake of 4 nondiet beverages [soda, other (i.e., fruit-flavored drinks, sweetened coffee/tea drinks, orflavored milk), sports drinks, and energy drinks]. Nationwide, 64.9% of high school students drank SSB $1 time/d, 35.6% drank SSB $2 times/d, and 22.2% drank SSB $ 3t imes/d. The most commonly consumed SSB was regular soda. Factors associated with a greater odds for high SSB intake ($3 times/d) were male gender [OR = 1.66 (95% CI = 1.41,1.95); P , 0.05], being non-Hispanic black [OR = 1.87 (95% CI = 1.52, 2.29); P , 0.05], eating at fast-food restaurants 1–2 d/wk or eating there $3 d/wk [OR = 1.25 (95% CI = 1.05, 1.50); P , 0.05 and OR = 2.94 (95% CI = 2.31, 3.75); P , 0.05, respectively] and watching television .2 h/d [OR = 1.70 (95% CI = 1.44, 2.01); P , 0.05]. Non-Hispanic other/multiracial [OR = 0.67 (95% CI = 0.47, 0.95); P , 0.05] and being physically active $60 min/d on ,5 d/wk were associated with a lower odds for high SSB intake [OR = 0.85 (95% CI = 0.76, 0.95); P , 0.05]. Weight status was not associated with SSB intake. Differences in predictors by type of SSB were small. Our findings of significant associations of high SSB intake with frequent fast-food restaurant use and sedentary behaviors may be used to tailor intervention efforts to reduce SSB intake among high-risk populations. J. Nutr. doi: 10.3945/jn.111.148536.
TL;DR: It is found that following starch ingestion, HA individuals had significantly lower postprandial blood glucose concentrations at 45, 60, and 75 min, as well as significantly lower AUC and peakBlood glucose concentrations than the LA individuals, which is interpreted to suggest that HA individuals may be better adapted to ingest starches, whereas LA Individuals may be at greater risk for insulin resistance and diabetes if chronically ingesting starch-rich diets.
Abstract: In the current study, we determined whether increased digestion of starch by high salivary amylase concentrations predicted postprandial blood glucose following starch ingestion. Healthy, nonobese individuals were prescreened for salivary amylase activity and classified as high (HA) or low amylase (LA) if their activity levels per minute fell 1 SD higher or lower than the group mean, respectively. Fasting HA (n = 7) and LA (n = 7) individuals participated in 2 sessions during which they ingested either a starch (experimental) or glucose solution (control) on separate days. Blood samples were collected before, during, and after the participants drank each solution. The samples were analyzed for plasma glucose and insulin concentrations as well as diploid AMY1 gene copy number. HA individuals had significantly more AMY1 gene copies within their genomes than did the LA individuals. We found that following starch ingestion, HA individuals had significantly lower postprandial blood glucose concentrations at 45, 60, and 75 min, as well as significantly lower AUC and peak blood glucose concentrations than the LA individuals. Plasma insulin concentrations in the HA group were significantly higher than baseline early in the testing session, whereas insulin concentrations in the LA group did not increase at this time. Following ingestion of the glucose solution, however, blood glucose and insulin concentrations did not differ between the groups. These observations are interpreted to suggest that HA individuals may be better adapted to ingest starches, whereas LA individuals may be at greater risk for insulin resistance and diabetes if chronically ingesting starch-rich diets.
TL;DR: The results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce BP and circulating cell adhesion molecules, resulting in improvements in vascular function.
Abstract: We evaluated the effects of grape polyphenols in individuals classified with metabolic syndrome (MetS). Men (n = 24) aged 30-70 y were randomly assigned to consume either a freeze-dried grape polyphenol powder (GRAPE) or a placebo for 30 d in a double-blind, crossover design, separated by a 3-wk washout period. Participants were asked to maintain their usual diet and physical activity during the study and abstain from consuming polyphenol-rich foods. MetS criteria including blood pressure (BP) and markers of vascular endothelial function including brachial artery flow-mediated vasodilation (FMD), plasma total nitrite + nitrate (NOx) to estimate NO production, plasma soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured at the end of each dietary period. Systolic BP (P < 0.0025) and plasma sICAM-1 concentrations (P < 0.025) were lower, whereas the FMD response was higher (P < 0.0001), during the GRAPE compared with the placebo period. In addition, changes in sVCAM-1 concentrations between periods were positively correlated with changes in systolic BP (r = 0.45; P < 0.05). Although NOx concentrations did not differ between periods, changes in systolic BP were negatively correlated with changes in NOx concentrations (r = -0.44; P < 0.05), indicating the vasodilating properties of NO. Other MetS variables did not differ between the GRAPE and placebo periods. These results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce BP and circulating cell adhesion molecules, resulting in improvements in vascular function.
TL;DR: Despite widespread maternal ID, however, iron nutrition seemed to meet fetal needs except when mothers were very iron deficient, which confirmed that ID anemia remains common during pregnancy in rural southeastern China.
Abstract: Iron deficiency (ID) is common in pregnant women and infants, particularly in developing countries. The relation between maternal and neonatal iron status remains unclear. This study considered the issue in a large sample of mother-newborn pairs in rural southeastern China. Hemoglobin (Hb) and serum ferritin (SF) were measured in 3702 pregnant women at ≥37 wk gestation and in cord blood of their infants born at term (37-42 wk gestation). Maternal anemia (Hb 370 μg/L, n = 208 and/or C-reactive protein (CRP) >5 mg/L, n = 233]. Piecewise linear regression analyses identified a threshold for maternal SF at which cord-blood SF was affected. For maternal SF below the threshold of 13.6 μg/L (β = 2.4; P = 0.001), cord SF was 0.17 SD lower than in neonates whose mothers had SF above the threshold (167 ± 75 vs. 179 ± 80 μg/L). The study confirmed that ID anemia remains common during pregnancy in rural southeastern China. Despite widespread maternal ID, however, iron nutrition seemed to meet fetal needs except when mothers were very iron deficient. The impact of somewhat lower cord SF on iron status later in infancy warrants further study.