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2.  ASSOCIATIONS BETWEEN UNCOUPLING PROTEIN 2, BODY COMPOSITION, AND RESTING ENERGY EXPENDITURE IN LEAN AND OBESE AFRICAN AMERICAN, CAUCASIAN, AND ASIAN CHILDREN 
Background
Little is known about genes affecting childhood body weight.
Objective
To examine alleles of the mitochondrial uncoupling protein-2 (UCP2) gene for association with obesity, since UCP2 may influence energy expenditure.
Design
We related UCP2 genotype to body composition, and to resting energy expenditure, in 105 children aged 6–10y. Overweight children and non-overweight children of overweight parents were genotyped for a 45 bp deletion/insertion (del/ins) in 3’ UTR of exon 8 and for an exon 4 C to T transition.
Results
89 children were genotyped for the exon 8 allele: 50 children had del/del, 33 del/ins, and 6 ins/ins. Body mass index (BMI) was greater for del/ins (24.1 ± 5.9 kg/m2) than for del/del (20.4 ± 4.8 kg/m2, p<0.001). BMI of ins/ins (23.7 ± 7.8 kg/m2) was not different from del/ins. This effect was independent of race and gender (ANOVAs, p< 0.05). Body composition was also different according to UCP2 genotype. All body circumferences and skin fold thicknesses examined were significantly greater in del/ins than in del/del. DXA body fat mass (p<0.005) was also greater in del/ins than del/del. For 104 children genotyped at exon 4, no significant differences in BMI or body composition were found among the three exon 4 genotypes. Neither resting energy expenditure nor respiratory quotient were different according to UCP2 exon 4 or exon 8 genotype.
Conclusion
The exon 8 ins/del polymorphism of UCP2 appears to be associated with childhood-onset obesity. The UCP2/UCP3 genetic locus may play a role in childhood body weight.
PMCID: PMC4495659  PMID: 10837279
Body Mass Index; Weight; Obesity; Polymorphism; Genetics
3.  A food pattern that is predictive of flavonol intake and risk of pancreatic cancer2 
Background
In the Multiethnic Cohort (MEC) study, we showed inverse associations between flavonols and pancreatic cancer risk.
Objective
We aimed to define a food pattern associated with intakes of quercetin, kaempferol, and myricetin; to examine the association of that pattern with pancreatic cancer risk; and to investigate the associations in an independent study.
Design
Reduced rank regression was applied to dietary data for 183 513 participants in the MEC. A food group pattern was extracted and simplified and applied to dietary data of 424 978 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intake in both studies was assessed by using specially developed questionnaires. Multivariate Cox proportional hazards models were used to estimate relative risks for pancreatic cancer in the MEC (610 cases) and the EPIC (517 cases) studies.
Results
The food group pattern consisted mainly of tea, fruit, cabbage, and wine. In the MEC, inverse associations with pancreatic cancer in smokers were observed for the food group pattern [relative risk: 0.59 (95% CI: 0.31, 1.12) when extreme quintiles were compared; P for trend = 0.03]. In the EPIC study, the simplified pattern was not associated with pancreatic cancer risk (P for trend = 0.78).
Conclusions
A food pattern associated with the intake of quercetin, kaempferol, and myricetin was associated with lower pancreatic cancer risk in smokers in a US-based population. However, failure to replicate the associations in an independent study weakens the conclusions and raises questions about the utility of food patterns for flavonols across populations.
doi:10.3945/ajcn.2008.26398
PMCID: PMC4484860  PMID: 19064528
4.  The association of glycemic load and carbohydrate intake with colorectal cancer risk in the Multiethnic Cohort Study1–3 
Background
High-glycemic-load diets may increase colorectal cancer risk through hyperinsulinemic effects.
Objective
We analyzed data for 191 004 participants in the Multiethnic Cohort Study to determine the risk of colorectal cancer associated with glycemic load (GL), carbohydrate, and sucrose and to ascertain whether this risk was modified by sex and ethnicity.
Design
During 8 y of follow-up, 2379 incident cases of colorectal adenocarcinoma occurred. We used baseline quantitative food-frequency questionnaire data to assess usual dietary intake over the preceding year. Using Cox regression, we calculated adjusted relative risks (RRs) and 95% CIs for colorectal cancer associated with quintiles of GL, carbohydrate, and sucrose.
Results
For both men and women in this cohort, white rice was the major contributor to GL. In multivariate models, RRs for colorectal cancer decreased significantly with increasing GL in women (RR for the highest quintile versus the lowest: 0.75; 95% CI: 0.57, 0.97; P for trend = 0.02) but not in men (RR: 1.15; 95% CI: 0.89, 1.48; P for trend = 0.19). Results for carbohydrate and sucrose were similar. The inverse association with GL was found in women of all ethnic groups (P for interaction = 0.58). In men, an interaction was found between ethnicity and GL (P < 0.01): white men had a positive association with increasing GL (RR: 1.69; 95% CI: 0.98, 2.92; P for trend < 0.01), but men of other ethnic groups did not.
Conclusion
GL and carbohydrate intake appear to protect against colorectal cancer in women in the Multiethnic Cohort, perhaps because a major source of GL is white rice.
PMCID: PMC4482108  PMID: 18842796
5.  Association of vegetable, fruit, and grain intakes with colorectal cancer: the Multiethnic Cohort Study123 
Background
It is uncertain whether or not vegetables, fruit, or grains protect against colorectal cancer.
Objective
In a large prospective study, we investigated the association of vegetable, fruit, and grain intakes with colorectal cancer risk.
Design
Between 1993 and 1996, 85 903 men and 105 108 women completed a quantitative food-frequency questionnaire that included ≈180 foods and beverages in the Multiethnic Cohort Study. A diagnosis of colorectal cancer was made in 1138 men and 972 women after an average follow-up of 7.3 y. Cox proportional hazards models were used to calculate multivariate-adjusted relative risks and 95% CIs for colorectal cancer.
Results
In men, multivariate adjustment for energy intake, dietary, and nondietary variables resulted in relative risks in the highest quintile group of 0.74 (95% CI: 0.59, 0.93; P for trend = 0.02) for vegetables and fruit combined, 0.80 (95% CI: 0.64, 0.99; P for trend = 0.09) for fruit alone, and 0.85 (95% CI: 0.69, 1.05; P for trend = 0.05) for vegetables alone. When colon and rectal cases were separated among men, the inverse associations were stronger for colon than for rectal cancer. In women, none of the associations with vegetables, fruit, or vegetables and fruit combined were significant. Grain intake was not associated with colorectal cancer for either men or women.
Conclusion
The intake of vegetables and fruit was inversely related to colorectal cancer risk among men but not among women. The association appears stronger for colon than for rectal cancer.
PMCID: PMC4482464  PMID: 18779290
6.  Phylloquinone intake, insulin sensitivity, and glycemic status in adult men and women 
Background
Limited evidence suggests that vitamin K may have a beneficial role in glucose homeostasis. No observational data exist on the associations between vitamin K intake and insulin sensitivity.
Objective
The aim was to examine associations between vitamin K intake and measures of insulin sensitivity and glycemic status in men and women, aged 26-81 y.
Design
We assessed the cross-sectional associations between self-reported phylloquinone (vitamin K1) intake and insulin sensitivity, and with glycemic status in the Framingham Offspring Cohort. Dietary and supplemental phylloquinone intakes were assessed by food-frequency questionnaire. Insulin sensitivity was measured by fasting and 2-h post oral glucose tolerance test (OGTT) insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI0,120). Glycemic status was assessed by fasting and 2-h post OGTT glucose and hemoglobin A1c (HbA1c).
Results
Higher phylloquinone intake was associated with greater insulin sensitivity and glycemic status, as measured by 2-h post OGTT insulin and glucose, and ISI0,120, after adjustment for age, sex, waist circumference, lifestyle characteristics and diet quality (2-h post OGTT insulin: lowest vs. highest quintile, 81.0 vs. 72.7 μU/mL, P for trend = 0.003; ISI0,120: 26.3 vs. 27.3 mg·L2/mmol·mU·min, P for trend = 0.01; 2-h post OGTT glucose: 106.3 vs. 101.9 mg/dL, P for trend = 0.01). Phylloquinone intake was not associated with fasting insulin and glucose concentrations, HOMA-IR and HbA1c.
Conclusions
Our findings support a potential beneficial role for phylloquinone in glucose homeostasis in adult men and women.
PMCID: PMC4457282  PMID: 18614743
Insulin sensitivity; glycemic status; vitamin K; phylloquinone; Framingham Offspring Cohort
8.  Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age1–3 
Background
Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown.
Objective
We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of recurrent wheeze in children at 3 y of age.
Design
The participants were 1194 mother-child pairs in Project Viva—a prospective prebirth cohort study in Massachusetts. We assessed the maternal intake of vitamin D during pregnancy from a validated food-frequency questionnaire. The primary outcome was recurrent wheeze, ie, a positive asthma predictive index (≥2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma).
Results
The mean (±SD) total vitamin D intake during pregnancy was 548 ± 167 IU/d. By age 3 y, 186 children (16%) had recurrent wheeze. Compared with mothers in the lowest quartile of daily intake (median: 356 IU), those in the highest quartile (724 IU) had a lower risk of having a child with recurrent wheeze [odds ratio (OR): 0.39; 95% CI: 0.25, 0.62; P for trend <0.001]. A 100-IU increase in vitamin D intake was associated with lower risk (OR: 0.81; 95% CI: 0.74, 0.89), regardless of whether vitamin D was from the diet (OR: 0.81; 95% CI: 0.69, 0.96) or supplements (OR: 0.82; 95% CI: 0.73, 0.92). Adjustment for 12 potential confounders, including maternal intake of other dietary factors, did not change the results.
Conclusion
In the northeastern United States, a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood.
PMCID: PMC4406411  PMID: 17344501
Vitamin D; pregnancy; dietary intake; childhood wheeze; asthma
9.  Adherence to healthy eating patterns is associated with increased circulating total and high molecular weight adiponectin and decreased resistin concentrations in women from the Nurses’ Health Study 
Background
Adherence to a healthy dietary pattern, such as the Alternate Healthy Eating Index (AHEI), is associated with a lower risk of diabetes and atherosclerosis. Whether these benefits are mediated by changes in plasma adipokine concentrations remains to be elucidated.
Objective
To determine whether adherence to the AHEI is associated with higher plasma total and high molecular weight (HMW) adiponectin concentrations and lower concentrations of resistin, as well as biomarkers of inflammation, endothelial dysfunction, and insulin resistance.
Design
Evaluation of 1922 women from the Nurses’ Health Study, 62% of whom were overweight, with no history of diabetes or cardiovascular disease, plasma biomarker concentrations measured in 1990 and data on dietary intake from SFFQs administered in 1984, 1986, and 1990, averaged to account for long-term dietary exposure and reduce within subject variability.
Results
After adjustment for age and energy intake, women with the highest average adherence to the AHEI had 24% higher median total adiponectin and 32% higher median HMW adiponectin concentrations, as well as 16% lower resistin, 41% lower CRP, 19% lower sE-selectin, 24% lower ferritin concentrations (P<0.01 for all). These associations remained significant after adjustment for BMI, physical activity, and smoking status. Inverse associations between the AHEI and sTNF-αRII, IL-6, sICAM-1, sVCAM-1, c-peptide, insulin, and HbA1c were evident, but were not significant after adjustment for BMI.
Conclusions
The preventive effects of healthier dietary patterns on risk for diabetes and atherosclerosis may be mediated by improvements in plasma concentrations of adipokines or other biomarkers of risk for diabetes and CVD.
PMCID: PMC4370425  PMID: 18996855
10.  Dietary glycemic index, dietary glycemic load, and cardiovascular disease in middle-aged and older Swedish men1–3 
Background
In women, dietary glycemic index (GI) and dietary glycemic load (GL) have been associated with cardiovascular disease; in men, however, the evidence for an association is weaker.
Objective
We tested the hypothesis that men consuming diets high in GI or GL have a greater risk of cardiovascular disease.
Design
At baseline, we assessed dietary GI and dietary GL by using food-frequency questionnaires in 36 246 Swedish men aged 45–79 y without diabetes or prior cardiovascular disease. Participants were followed through inpatient, cause-of-death, and death registries from 1 January 1998 until 31 December 2003 for myocardial infarction, ischemic stroke, hemorrhagic stroke, and cardiovascular mortality and until 31 December 2005 for all-cause mortality. We used Cox models with age as the time scale to estimate relative risks adjusted for cigarette smoking, body mass index, physical activity, demographic characteristics, and nutritional factors.
Results
Dietary GI and dietary GL were not associated with myocardial infarction (n = 1324), ischemic stroke (n = 692), cardiovascular mortality (n = 785), or all-cause mortality (n = 2959). Dietary GL was associated with hemorrhagic stroke [n = 165; relative risk = 1.44 comparing extreme quartiles (95% CI: 0.91, 2.27); P for trend = 0.047].
Conclusions
Dietary GI and dietary GL were not associated with ischemic cardiovascular disease or mortality, but dietary GL was associated with a greater risk of hemorrhagic stroke. Discrepancies between these findings and those of previous studies may be due to variations in the associations by sex or to differences in dietary contributions to GI and GL.
PMCID: PMC4355937  PMID: 17556687
Carbohydrate; glycemic index; glycemic load; myocardial infarction; stroke
11.  Oral Glutamine Increases Circulating GLP-1, Glucagon and Insulin Levels in Lean, Obese and Type 2 Diabetic Subjects 
Background
Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in meal-related insulin secretion. We previously demonstrated that glutamine is a potent stimulus of GLP-1 secretion in vitro.
Objective
To determine whether glutamine increases circulating GLP-1 and GIP levels in vivo and, if so, whether this is associated with an increase in plasma insulin.
Design
We recruited 8 healthy, normal-weight volunteers (LEAN), 8 obese individuals with type 2 diabetes or impaired glucose tolerance (OB-DIAB) and 8 obese non-diabetic controls (OB-CON). Oral glucose (75g), glutamine (30g) and water were administered on three separate days in random order and plasma concentrations of GLP-1, GIP, insulin, glucagon and glucose were measured over 120 minutes.
Results
Oral glucose led to increases in circulating GLP-1 levels, peaking at 30 min in LEAN (31.9±5.7 pmol/L) and OB-CON (24.3±2.1 pmol/L) subjects and at 45 min in OB-DIAB subjects (19.5±1.8 pmol/L). Circulating GLP-1 levels increased in all study groups following glutamine ingestion, with peak levels at 30 min of 22.5±3.4 pmol/L, 17.9±1.1 pmol/L and 17.3±3.4 pmol/L in LEAN, OB-CON and OB-DIAB subjects, respectively. Glutamine also increased plasma GIP levels, but less effectively than glucose. Consistent with the increases in GLP-1 and GIP, glutamine significantly increased circulating plasma insulin levels. Glutamine stimulated glucagon secretion in all three study groups.
Conclusion
Glutamine effectively increases circulating GLP-1, GIP and insulin levels in vivo and may represent a novel therapeutic approach to stimulating insulin secretion in obesity and type 2 diabetes.
doi:10.3945/ajcn.2008.26362
PMCID: PMC4340573  PMID: 19056578
GLP-1; GIP; glucagon; insulin secretion; glutamine; diabetes
12.  Overweight children find food more reinforcing and consume more energy than do nonoverweight children1–3 
Background
The reinforcing value of food is a reliable index of motivation to eat and energy intake. Obese adults find food more reinforcing than do nonobese adults.
Objective
The present study was designed to assess whether the relative reinforcing value of food differs as a function of weight status in 8–12-y-old children and whether the relative reinforcing value of food differs depending on the types of available nonfood alternatives.
Design
The reinforcing value of pizza (experiment 1) or snack foods (experiment 2) was measured on progressive ratio schedules of reinforcement in nonoverweight and overweight children. Experiment 2 also compared the relative reinforcing value of food and 2 nonfood alternatives: time to spend playing a hand-held video game or time to spend reading magazines or completing word searches or mazes.
Results
In both experiments, overweight children found food more reinforcing and consumed more energy than did their leaner peers. In experiment 2, the relative reinforcing value of food versus sedentary activity was higher in overweight children, but lower in nonover-weight children, regardless of the type of alternative activity available.
Conclusions
These results show that overweight children find food more reinforcing than do nonoverweight children. This individual difference was replicated in different experiments using different types of foods and food alternatives. These studies provide support for studying food reinforcement as a factor associated with overweight and obesity.
PMCID: PMC4185183  PMID: 18469229
13.  Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis 
Background
Data on the relations of different types of fish meals and long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) with measures of atherosclerosis are sparse.
Objective
We examined intakes of long-chain n-3 PUFAs and fish in relation to clinical measures of subclinical atherosclerosis.
Design
A cross-sectional study was conducted in 5,488 multiethnic adults aged 45–84 years and free of clinical cardiovascular disease. Diet was assessed using self-administered food frequency questionnaires. Subclinical atherosclerosis was determined by common carotid intima-media thickness (cCIMT, >80th percentile), internal CIMT (iCIMT, >80th percentile), coronary artery calcium score (CAC, >0) or ankle-brachial index (ABI, <0.90), respectively.
Results
After adjustment for potential confounders, intakes of long-chain n-3 PUFAs and non-fried (broiled, steamed, baked or raw) fish were inversely related to subclinical atherosclerosis determined by cCIMT but not iCIMT, CAC or ABI. The multivariable odds ratio comparing the highest to the lowest quartile of dietary exposures in relation to subclinical atherosclerosis determined by cCIMT was 0.69 (95% CI: 0.55, 0.86; p for trend<0.01) for n-3 PUFA intake, 0.80 (95% CI: 0.64, 1.01; p=0.054) for non-fried fish and 0.90 (95% CI: 0.73, 1.10; p=0.33) for fried fish consumption.
Conclusions
This study indicates that dietary intake of long-chain n-3 PUFAs or non-fried fish is associated with lower prevalence of subclinical atherosclerosis classified by cCIMT although significant changes in iCIMT, CAC and ABI were not observed. Our findings also suggest that the association of fish and atherosclerosis may vary depending on the type of fish meal consumed and the measures of atherosclerosis.
PMCID: PMC4151325  PMID: 18842801
long-chain n-3 polyunsaturated fatty acids; fish; fish oil; biomarker; subclinical atherosclerosis; multi-ethnicities
14.  Symposium introduction: metabolic syndrome and the onset of cancer1, 2, 3, 4 
Diabetes, obesity, and related metabolic disorders are among the most pressing of today’s health care concerns. Recent evidence from epidemiologic and basic research studies, as well as translational, clinical, and intervention studies, supports the emerging hypothesis that metabolic syndrome may be an important etiologic factor for the onset of cancer. On March 15–16, 2006, The Harvard Medical School Division of Nutrition hosted the symposium “Metabolic Syndrome and the Onset of Cancer” as a platform to systematically evaluate the evidence in support of this hypothesis. This symposium, which gathered leaders in the fields of metabolism, nutrition, and cancer, will stimulate further research investigating the etiologic role of metabolic syndrome in cancer. Furthermore, it will help to guide the development of effective cancer prevention strategies via nutritional and lifestyle modifications to alleviate metabolic syndrome.
PMCID: PMC4144325  PMID: 18265474
Metabolic syndrome; cancer; obesity; nutrition; epidemiology; symposium
15.  Vitamin D insufficiency in southern Arizona1, 2, 3 
Background
Vitamin D deficiency or insufficiency has been observed among populations in the northern United States. However, data on the prevalence of vitamin D deficiency in areas of high sun exposure, such as Arizona, are limited.
Objective
The purpose of this study was to analyze serum 25-hydroxyvitamin D [25(OH)D] concentrations in residents of southern Arizona and to evaluate predictors of 25(OH)D in this population.
Design
Cross-sectional analyses of serum from participants in a colorectal adenoma prevention study were conducted to determine rates of vitamin D deficiency. Participants were categorized into 4 groups on the basis of serum 25(OH)D concentrations: <10.0 ng/ mL, ≥10.0 ng/mL and <20.0 ng/mL, ≥20.0 ng/mL and <30.0 ng/mL, and ≥30.0 ng/mL.
Results
The mean serum 25(OH)D concentration for the total population was 26.1 ± 9.1 ng/mL. Of 637 participants, 22.3% had 25(OH)D concentrations =30 ng/mL, 25.4% had concentrations <20 ng/mL, and 2.0% had concentrations <10 ng/mL. Blacks (55.5%) and Hispanics (37.6%) were more likely to have deficient 25(OH)D concentrations (<20 ng/mL) than were non-Hispanic whites (22.7%). Sun exposure had a greater effect on 25(OH)D in whites than in blacks and Hispanics, whereas BMI appeared to be more important in the latter groups.
Conclusion
Despite residing in a region with high chronic sun exposure, adults in southern Arizona are commonly deficient in vitamin D deficiency, particularly blacks and Hispanics.
PMCID: PMC4113473  PMID: 18326598
Vitamin D deficiency; race-ethnicity; 25-hydroxyvitamin D; 25(OH)D; Arizona
16.  Effects of diet, physical activity and performance, and body weight on incident gout in ostensibly healthy, vigorously active men 
Background
Physical activity and cardiorespiratory fitness are not currently recognized as factors related to preventing gout, nor are risk factors for gout in physically active men well understood.
Objective
The objective was to identify risk factors for gout in ostensibly healthy, vigorously active men.
Design
Incident self-reported gout was compared with baseline diet, body mass index (BMI; in kg/m2), physical activity (in km/d run), and cardiorespiratory fitness (in m/s during 10-km footrace) prospectively in 28 990 male runners.
Results
Men (N=228; 0.79%) self-reported incident gout during 7.74 y of follow-up. The risk of gout increased with higher alcohol intake [per 10 g/d; relative risk (RR): 1.19; 95% CI: 1.12 to 1.26; P<0.0001], meat consumption (per servings/d; RR: 1.45; 95% CI: 1.06 to 1.92; P=0.002), and BMI (RR: 1.19; 95% CI: 1.15 to 1.23; P<0.0001) and declined with greater fruit intake (per pieces/d; RR: 0.73; 95% CI: 0.62 to 0.84; P<0.0001), running distance (per km/d; RR: 0.92; 95% CI: 0.88 to 0.97; P<0.001), and fitness (per m/s; RR: 0.55; 95% CI: 0.41 to 0.75; P<0.0001). The RR per 10 g alcohol/d consumed as wine (1.27; P=0.002), beer (1.19; P<0.0001), and mixed drinks (1.13; P=0.18) was not significantly different from each other. Men who consumed >15 g alcohol/d had 93% greater risk than abstainers, and men who averaged >2 pieces fruit/d had 50% less risk than those who ate <0.5 fruit/d. Risk of gout was 16-fold greater for BMI>27.5 than <20. Compared with the least active or fit men, those who ran ≥8 km/d or >4.0 m/s had 50% and 65% lower risk of gout, respectively. Lower BMI contributed to the risk reductions associated with distance run and fitness.
Conclusion
These findings, based on male runners, suggest that the risk of gout is lower in men who are more physically active, maintain ideal body weight, and consume diets enriched in fruit and limited in meat and alcohol.
PMCID: PMC4090353  PMID: 18469274
17.  Weight loss and calcium intake influence calcium absorption in overweight postmenopausal women12–3 
Background
Weight loss (WL) reduces bone mass and increases fracture risk. Mechanisms regulating calcium metabolism during WL are unclear.
Objective
The objective was to assess the effect of 6 wk of WL at 2 different amounts of calcium intake [normal (NlCa): 1 g/d; high (HiCa): 1.8 g/d] on true fractional calcium absorption (TFCA), bone turnover, and bone-regulating hormones in overweight postmenopausal women.
Design
Seventy-three women (body mass index, 26.9 ± 1.9 kg/m2) were recruited either to consume a moderately energy-restricted diet (WL group) or to maintain their body weight [weight-maintenance (WM) group] and were randomly assigned to either the HiCa or the NlCa group in a double-blind manner. Subjects underwent weekly diet counseling, and measurements were taken at baseline and after 6 wk.
Results
Fifty-seven women completed the study and had a baseline TFCA of 24.9 ± 7.4%. Energy restriction significantly decreased the total calcium absorbed (P < 0.05) in the WL group (n = 32) compared with the WM group (n = 25; analysis of covariance). Regression analysis showed that a greater rate of weight loss suppressed TFCA and the total calcium absorbed (P < 0.05) in the HiCa group. The women in the NlCa WL group absorbed inadequate amounts of calcium (195 ± 49 mg/d), whereas the women in the HiCa WL group absorbed adequate amounts (348 ± 118 mg/d). Parathyroid hormone explained 22% of the variance in calcium absorbed in the NlCa group only.
Conclusions
We suggest that WL is associated with elevated calcium requirements that, if not met, could activate the calcium-parathyroid hormone axis to absorb more calcium. Normal intakes of calcium during energy restriction result in inadequate total calcium absorption and could ultimately compromise calcium balance and bone mass.
PMCID: PMC4016237  PMID: 15213038
Calcium absorption; bone turnover; diet; postmenopausal status; weight loss
18.  Premenopausal overweight women do not lose bone during moderate weight loss with adequate or higher calcium intake123 
Background
Weight loss is associated with bone loss, but this has not been examined in overweight premenopausal women.
Objective
The aim of this study was to assess whether overweight premenopausal women lose bone with moderate weight loss at recommended or higher than recommended calcium intakes.
Design
Overweight premenopausal women [n = 44; x‒ (±SD) age: 38 ± 6.4 y; body mass index (BMI): 27.7 ± 2.1 kg/m2] were randomly assigned to either a normal (1 g/d) or high (1.8 g/d) calcium intake during 6 mo of energy restriction [weight loss (WL) groups] or were recruited for weight maintenance at 1 g Ca/d intake. Regional bone mineral density and content were measured by dual-energy X-ray absorptiometry, and markers of bone turnover were measured before and after weight loss. True fractional calcium absorption (TFCA) was measured at baseline and during caloric restriction by using a dual-stable calcium isotope method.
Results
The WL groups lost 7.2±3.3% of initial body weight. No significant decrease in BMD or rise in bone turnover was observed with weight loss at normal or high calcium intake. The group that consumed high calcium showed a strong relation (r = 0.71) between increased femoral neck bone mineral density and increased serum 25-hydroxyvitamin D. No significant effect of weight loss on TFCA was observed, and the total calcium absorbed was adequate at 238±81 and 310±91 mg/d for the normal- and high-calcium WL groups, respectively.
Conclusion
Overweight premenopausal women do not lose bone during weight loss at the recommended calcium intake, which may be explained by sufficient amounts of absorbed calcium.
PMCID: PMC4008879  PMID: 17413095
Bone; calcium absorption; hormones; premenopausal women; weight loss
19.  A PROSPECTIVE STUDY OF DIETARY ENERGY DENSITY AND WEIGHT GAIN IN WOMEN 
Background
Little is known about the long-term effects of dietary energy density (ED) on weight gain.
Methods
We conducted a prospective study of 50,026 women (mean age: 36.5; SD: 4.6) in the Nurses' Health Study II followed from 1991 to 1999. Dietary ED and body weight were ascertained in 1991, 1995, and 1999. Total dietary ED was calculated by dividing each subject's daily energy intake (kcal) by the reported weight (g) of all foods consumed.
Results
Dietary ED was positively correlated with saturated fat (r=0.16), trans fat (r=0.15), and the glycemic index (r=0.16), but inversely correlated with vegetable protein (r=−0.30), vegetables (r=−0.27), and fruits (r=−0.17). ED was not significantly correlated with total fat intake (r=0.08). Women who increased their dietary ED during follow-up the most (5th quintile) had a statistical significant greater multivariate-adjusted weight gain as compared with those who decreased their dietary ED most (1st quintile) (in the 8-y time period: 6.42 kg versus 4.57 kg; p for trend < 0.001). However, the amount of weight change over time varied considerably according to the ED of individual foods and beverages.
Conclusion
Increases in total dietary ED were associated with long-term weight gain among younger and middle-aged women. However, public health recommendations cannot be made simply based on ED values of individual foods and beverages only. Reducing consumption of foods high in saturated and trans fats and refined carbohydrates and increasing consumption of fruits and vegetables may help to reduce dietary ED and prevent weight gain.
PMCID: PMC3977032  PMID: 18779295
20.  Dietary flavonoid intake and non-Hodgkin lymphoma risk 
Background
The role of dietary factors in non-Hodgkin lymphoma (NHL) risk is not yet well understood. Dietary flavonoids are polyphenolic compounds proposed to be anticarcinogenic. Flavonoids are well-characterized antioxidants and metal chelators, and certain flavonoids exhibit antiproliferative and antiestrogenic effects.
Objective
We aimed to evaluate the hypothesis that higher flavonoid intake is associated with lower NHL risk.
Design
During 1998–2000, we identified incident NHL cases aged 20–74 y from 4 US Surveillance, Epidemiology, and End Results cancer registries. Controls without history of NHL were selected by random-digit dialing or from Medicare files and frequency-matched to cases by age, center, race, and sex. Using 3 recently developed US Department of Agriculture nutrient-specific databases, flavonoid intake was estimated from participant responses to a 117-item food-frequency questionnaire (n = 466 cases and 390 controls). NHL risk in relation to flavonoid intake in quartiles was evaluated after adjustment for age, sex, registry, education, NHL family history, and energy intake.
Results
Higher total flavonoid intake was significantly associated with lower risk of NHL (P for trend < 0.01): a 47% lower risk in the highest quartile of intake than in the lowest (95% CI: 31%, 73%). Higher intakes of flavonols, epicatechins, anthocyanidins, and proanthocyanidins were each significantly associated with decreased NHL risk. Similar patterns of risk were observed for the major NHL subtypes—diffuse large B-cell lymphoma (n = 167) and follicular lymphoma (n = 146).
Conclusion
A higher intake of flavonoids, dietary components with several putative anticarcinogenic activities, may be associated with lower NHL risk.
PMCID: PMC3971470  PMID: 18469269
21.  Abdominal obesity and hyperglycemia mask the effect of a common APOC3 haplotype on the risk of myocardial infarction123 
Background
Plasma apolipoprotein (apo) C-III strongly predicts myocardial infarction (MI) and directly activates atherogenic processes invascularcells.Geneticvariationintheinsulinresponseelementofthe APOC3 promoter is associated with an increased risk of MI.
Objective
The objective was to determine whether the APOC3 promoter variation affects plasma apo C-III concentrations and MI only when insulin sensitivity is normal.
Design
TheAPOC3*222haplotype,definedbytheminorallelesofthe single nucleotide polymorphisms 3238C→G, –455T→C, and –482C→T, was studied in 1703 matched nonfatal case-control pairs with MI in the Central Valley of Costa Rica. We used fasting hyper-glycemia and abdominal obesity as surrogates for insulin sensitivity.
Results
The APOC3*222 haplotype was associated with higher apo C-III concentrations only in those with the lowest waist circumference or fasting glucose concentration. The association between the APOC3*222 haplotype and nonfatal MI, previously reported in this population, was strongly influenced by fasting hyperglycemia and abdominal obesity. The odds ratios for MI for the APOC3*222 haplotype were 1.72 (95% CI: 1.16, 2.54) and 1.84 (1.31, 2.59) in subjects in the lowest quintiles of abdominal obesity and fasting hyperglycemia, respectively, and were 0.75 (0.54, 1.05) and 1.16 (0.85, 1.59) in subjects in the highest quintiles, respectively (P for interaction <0.05).
Conclusion
The results support the concept that mutations in the APOC3 promoter inhibit the down-regulation of APOC3 expression by insulin. This cardioprotective system becomes dysfunctional in abdominal obesity and hyperglycemia.
PMCID: PMC3861874  PMID: 18541587
22.  Neighborhood socioeconomic status and fruit and vegetable intake among Whites, Blacks, and Mexican-Americans in the United States 
Background
Socioeconomic and racial/ethnic disparities in health status across the United States are large and persistent. Obesity rates are rising faster in Black and Hispanic populations than in Whites and foreshadow even greater disparities in chronic diseases such as diabetes and cardiovascular disease in years to come. Factors that influence dietary intake of fruits and vegetables in these populations are only partly understood.
Objective
We examined associations between fruit and vegetable intake and neighborhood socioeconomic status (NSES), analyzed whether NSES explains racial differences in intake, and explored the extent to which NSES has differential effects by race/ethnicity of United States (U.S.) adults.
Design
Using geocoded residential addresses from the Third National Health and Nutrition Examination Survey (NHANES III), we merged individual-level data with county and census-tract level U.S. Census data. We estimated three-level hierarchical models predicting fruit and vegetable intake with individual characteristics and an index of neighborhood SES as explanatory variables.
Results
Neighborhood SES was positively associated with fruit and vegetable intake: a one standard deviation increase in the neighborhood SES index was associated with consumption of nearly 2 additional servings of fruit and vegetables per week. Neighborhood SES explained some of the Black-White disparity in fruit and vegetable intake and was differentially associated with fruit and vegetable intake among Whites, Blacks, and Mexican-Americans.
Conclusions
The positive association of neighborhood SES with fruit and vegetable intake is one important pathway through which the social environment of neighborhoods affects population health and nutrition for Whites, Blacks and Hispanics in the United States.
PMCID: PMC3829689  PMID: 18541581
Neighborhood Socioeconomic Status; Race/Ethnicity; Fruit and Vegetable Consumption
23.  Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults2 
The American journal of clinical nutrition  2009;89(6):10.3945/ajcn.2009.27465.
Background
Rodent studies show that oligofructose promotes weight loss, stimulates satiety hormone secretion, reduces energy intake, and improves lipid profiles.
Objective
Our objective was to examine the effects of oligofructose supplementation on body weight and satiety hormone concentrations in overweight and obese adults.
Design
This study was a randomized, double-blind, placebo-controlled trial. Forty-eight otherwise healthy adults with a body mass index (in kg/m2) > 25 were randomly assigned to receive 21 g oligo-fructose/d or a placebo (maltodextrin) for 12 wk. Body composition (by dual-energy X-ray absorptiometry); meal tolerance tests, including satiety hormone response; food intake; and subjective appetite ratings were determined.
Results
There was a reduction in body weight of 1.03 ±0.43 kg with oligofructose supplementation, whereas the control group experienced an increase in body weight of 0.45 ± 0.31 kg over 12 wk (P = 0.01). A lower area under the curve (AUC) for ghrelin (P = 0.004) and a higher AUC for peptide YY (PYY) with oligofructose (P = 0.03) coincided with a reduction in self-reported caloric intake (P ≤ 0.05). Glucose decreased in the oligofructose group and increased in the control group between initial and final tests (P ≤ 0.05). Insulin concentrations mirrored this pattern (P ≤ 0.05). Oligofructose supplementation did not affect plasma active glucagon-like peptide 1 secretion. According to a visual analog scale designed to assess side effects, oligofructose was well tolerated.
Conclusions
Independent of other lifestyle changes, oligofructose supplementation has the potential to promote weight loss and improve glucose regulation in overweight adults. Suppressed ghrelin and enhanced PYY may contribute in part to the reduction in energy intake. The trial was registered at clinicaltrials.gov as NCT00522353.
doi:10.3945/ajcn.2009.27465
PMCID: PMC3827013  PMID: 19386741 CAMSID: cams3657
24.  Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib1,2,3 
Background
Type I glycogen storage disease (GSD) is caused by a deficiency of glucose-6-phosphatase resulting in severe fasting hypoglycemia.
Objective
We compared the efficacy of a new modified starch with the currently used cornstarch therapy in patients with type Ia and Ib GSD.
Design
This was a randomized, 2-d, double-blinded, crossover pilot study comparing the commonly used uncooked cornstarch with the experimental starch in 12 subjects (6 GSDIa, 6 GSDIb) aged ≥13 y. At 2200, the subjects were given 100 g of digestible starch, and glucose and lactate were measured hourly until the subject's plasma glucose concentration reached 60 mg/dL or until the subject had fasted for 10 h. The order in which the products were tested was randomized in a blinded fashion.
Results
The matched-pair Gehan rank test for censored survival was used to compare the therapies. The experimental starch maintained blood glucose concentrations significantly longer than did the traditional therapy (P = 0.013) in the 2-sided analysis. Most of the benefit was found to be after glucose concentrations fell below 70 mg/dL. The currently used cornstarch resulted in higher peak glucose concentrations and a more rapid rate of fall than did the new starch.
Conclusions
The experimental starch was superior to standard therapy in preventing hypoglycemia (≤60 mg/dL). This therapy may allow patients with GSD to sleep through the night without awakening for therapy while enhancing safety. Additional studies are warranted to determine whether alternative dosing will further improve control in the therapeutic blood glucose range.
PMCID: PMC3808112  PMID: 18996862
25.  How can the Developmental Origins of Health and Disease (DOHaD) hypothesis contribute to improving health in developing countries?23 
The American journal of clinical nutrition  2011;94(6 0):10.3945/ajcn.110.000562.
The relevance of nutrition during pregnancy and early infancy in defining short-term health and survival has been well established. However, the Developmental Origins of Health and Disease (DOHaD) paradigm provides a framework to assess the effect of early nutrition and growth on long-term health. This body of literature shows that early nutrition has significant consequences on later health and well-being. In this article, we briefly present the main consequences of malnutrition that affect human growth and development and consider how the DOHaD paradigm, with its evolutionary implications, might contribute to better addressing the challenge of improving nutrition. We examine how this paradigm is particularly appropriate in understanding the health and nutrition transition in countries that face the double burden of nutrition-related diseases (acute malnutrition coexisting with obesity and other chronic diseases). We focus on stunting (low height-for-age) to examine the short- as well as long-term consequences of early malnutrition with a life-course, transgenerational, and multidisciplinary perspective. We present current global and regional prevalence of stunting and discuss the need to reposition maternal and infant nutrition not only in health and nutrition intervention programs but also in consideration of the emerging research questions that should be resolved to better orient program and policy decisions.
doi:10.3945/ajcn.110.000562
PMCID: PMC3808270  PMID: 21543534

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