Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial.

BACKGROUND & AIMS: In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk. METHODS: Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 µg) and vitamin-B12 (500 µg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease. RESULTS: A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51-58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 µmol/l). No age-dependent effects were present. CONCLUSIONS: This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.

Calcium intake, levels and supplementation and effect modification by genetic variation of calcium homeostasis on the risk of colorectal cancer: the Rotterdam study.

OBJECTIVES: Previous studies showed that high calcium intake may be associated with the reduced colorectal cancer (CRC) risk, but results were inconclusive. In this study, we evaluated whether calcium intake from diet and supplements, as well as the calcium levels itself, were associated with the CRC risk in middle-aged and older individuals. Also, we evaluated whether these associations were modified by genetic variation of calcium homeostasis. DESIGN: This study was embedded in the Rotterdam study, a prospective cohort study among adults aged 55 years and older without CRC at baseline, from the Ommoord district of Rotterdam, The Netherlands (N = 10 941). Effect modification by a predefined polygenetic risk score (PRS) from seven loci known to be associated with calcium concentrations, was evaluated. RESULTS: The incidence rate of CRC in the study population was 2.9 per 1000 person-years. Relative to the recommended dietary calcium intake, only higher than the recommended dietary calcium intake (≥1485 mg/day) was associated with a reduced risk of CRC [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.44-1.00]. No significant associations were found for calcium supplementation and only in the subgroup analysis, albumin-adjusted calcium levels were associated with an increased risk of CRC (HR = 1.11; 95% CI, 1.00-1.23). PRS showed effect modification in the association between calcium intake and CRC (P for interaction = 0.08). After stratification of PRS into low, intermediate and high, we found a lower CRC risk for low-weighted PRS per increase in calcium intake. CONCLUSION: There is no consistent association between calcium indices on CRC. However, the association between calcium intake and CRC may be modified by genetic variation associated with serum calcium concentrations that deserves further replication in other studies with different population.

B-vitamins and body composition: integrating observational and experimental evidence from the B-PROOF study.

PURPOSE: Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals. METHODS: A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA). RESULTS: Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per µgmol/L) was associated with a 1.108 kg/m2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention. CONCLUSIONS: Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.

Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial.

BACKGROUND: Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. METHODS: Long-term follow-up of B-PROOF trial participants (N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 µg) and vitamin B12 (500 µg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for colorectal cancer. RESULTS: Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08-2.90, P = 0.02]. CONCLUSIONS: Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer. IMPACT: Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency.

Potential Mechanisms Underlying the Role of Coffee in Liver Health.

Coffee, the most consumed hot beverage worldwide, is composed of many substances, of which polyphenols, caffeine, and diterpenoids are well studied. Evidence on potential effects of coffee on human health has been accumulating over the past decades. Specifically, coffee has been postulated to be hepatoprotective in several epidemiological and clinical studies. Several underlying molecular mechanisms as to why coffee influences liver health have been proposed. In this review, the authors summarized the evidence on potential mechanisms by which coffee affects liver steatosis, fibrosis, and hepatic carcinogenesis. The experimental models reviewed almost unanimously supported the theorem that coffee indeed may benefit the liver. Either whole coffee or its specific compounds appeared to decrease fatty acid synthesis (involved in steatogenesis), hepatic stellate activation (involved in fibrogenesis), and hepatic inflammation. Moreover, coffee was found to induce apoptosis and increased hepatic antioxidant capacity, which are involved in carcinogenesis.

Dietary patterns in an elderly population and their relation with bone mineral density: the Rotterdam Study.

PURPOSE: Our aim was to identify dietary patterns that are associated with bone mineral density (BMD) against a background of relatively high dairy intake in elderly Dutch subjects. METHODS: Participants were 55 years of age and older (n = 5144) who were enrolled in The Rotterdam Study, a population-based prospective cohort study. Baseline intake of 28 pre-defined food groups was determined using a validated food frequency questionnaire. Dietary patterns were identified using principal component analysis. BMD was measured using dual-energy X-ray absorptiometry at baseline and at three subsequent visits (between 1993 and 2004). Linear mixed modelling was used to longitudinally analyse associations of adherence to each pattern with repeatedly measured BMD (both in Z scores). RESULTS: After adjustment for confounders, two dietary patterns were associated with high BMD: a "Traditional" pattern, characterized by high intake of potatoes, meat and fat (ß = 0.06; 95 % CI 0.03, 0.09) and a "Health conscious" pattern, characterized by high intake of fruits, vegetables, poultry and fish (ß = 0.06; 95 % CI 0.04, 0.08). The "Processed" pattern, characterized by high intake of processed meat and alcohol, was associated with low BMD (ß = -0.03; 95 % CI -0.06, -0.01). Associations of adherence to the "Health conscious" and "Processed" pattern with BMD were independent of body weight and height, whereas the association between adherence to the "Traditional" pattern with BMD was not. CONCLUSIONS: Against a background of high dairy intake and independent of anthropometrics, a "Health conscious" dietary pattern may have benefits for BMD, whereas a "Processed" dietary pattern may pose a risk for low BMD.

A priori and a posteriori derived dietary patterns in infancy and cardiometabolic health in childhood: The role of body composition.

BACKGROUND & AIMS: Cardiometabolic risk has its origins in early life. However, it is unclear whether diet during early childhood is associated with cardiometabolic health, and what the role is of obesity. We aimed to study whether overall diet during early childhood is associated with cardiometabolic health and to examine if difference in body composition explain this association. METHODS: We examined associations of different types of dietary patterns in infancy with cardiometabolic health at school age among 2026 Dutch children participating in a population-based cohort in the Netherlands. Food intake at the age of 1 year was assessed with a food-frequency questionnaire. Three dietary pattern approaches were used: 1) An a priori-defined diet quality score; 2) dietary patterns based on variation in food intake, derived from principal component analysis (PCA); and 3) dietary patterns based on variations in fat and fat-free mass index, derived with reduced-rank regression (RRR). At the children's age of 6 years, we measured their body composition, systolic and diastolic blood pressure, and serum concentrations of insulin, triglycerides, and HDL-cholesterol, which we combined in a cardiometabolic risk-factor score. RESULTS: We observed that, after adjustment for confounders, children with higher adherence to a 'Health-conscious' PCA-derived pattern had a lower cardiometabolic risk-factor score (-0.07 SD (95%CI -0.12; -0.02) per SD). This association did not change after adjustment for fat and fat-free mass index. The RRR-derived dietary patterns based on variations in body composition were not associated with the cardiometabolic risk-factor score. CONCLUSIONS: Our results suggest that diet in early childhood may affect cardiometabolic health independent of differences in body composition.

Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: The Rotterdam study.

BACKGROUND & AIMS: Coffee and tea have been proposed to limit the progression of liver fibrosis in established liver disease, but it is unknown if this is also true for subclinical fibrosis. We therefore aimed to evaluate whether coffee and tea consumption are associated with liver stiffness in the general population. METHODS: The Rotterdam Study is an ongoing prospective population-based cohort. We included participants who underwent transient elastography, ultrasound and completed a food frequency questionnaire. Coffee and tea consumption were categorized into no, moderate (>0-3), or frequent (⩾3) intake (cups/day), and tea further into green, black and herbal tea (no/any). Significant fibrosis was defined as liver stiffness measurements (LSM) ⩾8.0kPa. We performed regression analyses relating coffee and tea intake with fibrosis, steatosis and log-transformed LSM and adjusted for energy, sugar and creamer intake, age, gender, BMI, steatosis/LSM, HOMA-IR, ALT, alcohol, smoking, soda, healthy diet index and physical activity. RESULTS: We included 2,424 participants (age 66.5±7.4; 43% male) of whom 5.2% had LSM ⩾8.0kPa and 34.6% steatosis. Proportion of LSM ⩾8.0kPa decreased with higher coffee consumption (7.8%, 6.9% and 4.1% for no, moderate and frequent respectively; Ptrend=0.006). This inverse association was confirmed in multivariable regression (ORmod 0.75, 95% CI 0.33-1.67; ORfreq 0.39, 95% CI 0.18-0.86; p=0.005). Amongst tea consumers, only herbal tea consumers (36.3%) had lower log-transformed LSM after adjustment (Beta-0.05, 95% CI-0.08;-0.02, p=0.001). Subtypes of tea were associated with steatosis in univariate but not multivariable analysis. CONCLUSIONS: In the general population, frequent coffee and herbal tea consumption were inversely related with liver stiffness but not steatosis. Longitudinal analyses, as well as studies validating and unravelling underlying mechanisms are needed. LAY SUMMARY: The Rotterdam Study is a large ongoing population study of suburban inhabitants of Rotterdam in whom data on liver stiffness, as proxy for liver fibrosis, presence of fatty liver on ultrasound and detailed information on coffee and tea consumption were obtained in 2,424 participants. The consumption of herbal tea and daily consumption of three or more cups of coffee was related to the presence of lower liver stiffness, independent of a great number of other lifestyle and environmental factors. Previous studies have found a protective effect of coffee on established liver disease and we now show for the first time that this effect is already measurable in the general population.

Dietary mineral intake and lung cancer risk: the Rotterdam Study.

OBJECTIVE: Limited data are available on the role of mineral intake in the development of lung cancer (LC). We investigated whether dietary calcium, copper, iron, magnesium, selenium and zinc intake were associated with LC risk. METHODS: We analyzed data from 5435 participants of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years and older. At baseline (1990-1993), diet was measured by a validated food frequency questionnaire. LC events were diagnosed on the basis of pathology data and medical records. Hazard ratios (HRs) on LC for energy-adjusted mineral intake were calculated using Cox regression models while adjusting for potential confounders. RESULTS: During a follow-up period of 22 years, we identified 211 incident cases of LC. A higher zinc intake was associated with 42 % reduction in risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.35; 0.94, P-for trend = 0.039). Similarly, high intake of iron was associated with reduced risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.37; 0.92, P-for trend = 0.021). There was no association between dietary intake of calcium, copper, magnesium and selenium and LC risk. CONCLUSIONS: Our results suggest that dietary zinc and iron intake are associated with reduced risk of LC. No evidence was found for an association between calcium, copper, magnesium and selenium intake and LC risk.

Risk factors for resistance to ciprofloxacin in community-acquired urinary tract infections due to Escherichia coli in an elderly population.

BACKGROUND: Antimicrobial resistance to ciprofloxacin is rising worldwide, especially in bacteria causing urinary tract infections (UTIs). Prudent use of current antibiotic drugs is therefore necessary. OBJECTIVES: We analysed (modifiable) risk factors for ciprofloxacin-resistant Escherichia coli. METHODS: Urinary cultures of UTIs caused by E. coli were collected from participants in the Rotterdam Study, a prospective cohort study in an elderly population, and analysed for susceptibility to ciprofloxacin. Multivariate logistic regression was performed to investigate several possible risk factors for resistance. RESULTS: Ciprofloxacin resistance in 1080 E. coli isolates was 10.2%. Multivariate analysis showed that higher age (OR 1.03; 95% CI 1.00-1.05) and use of two (OR 5.89; 95% CI 3.45-10.03) and three or more (OR 3.38; 95% CI 1.92-5.97) prescriptions of fluoroquinolones were associated with ciprofloxacin resistance, while no association between fluoroquinolone use more than 1 year before culture and ciprofloxacin resistance could be demonstrated. Furthermore, a high intake of pork (OR 3.68; 95% CI 1.36-9.99) and chicken (OR 2.72; 95% CI 1.08-6.85) and concomitant prescription of calcium supplements (OR 2.51; 95% CI 1.20-5.22) and proton pump inhibitors (OR 2.04; 95% CI 1.18-3.51) were associated with ciprofloxacin resistance. CONCLUSIONS: Ciprofloxacin resistance in community-acquired UTI was associated with a high intake of pork and chicken and with concomitant prescription of calcium supplements and proton pump inhibitors. Modification of antibiotic use in animals as well as temporarily stopping the prescription of concomitant calcium and proton pump inhibitors need further evaluation as strategies to prevent ciprofloxacin resistance.

Dietary polyunsaturated fatty acids intake modifies the positive association between serum total cholesterol and colorectal cancer risk: the Rotterdam Study.

BACKGROUND: It remains unclear whether serum total cholesterol is associated with colorectal cancer (CRC) risk. Interplay between dietary fatty acids and serum total cholesterol on CRC risk may be present as well. We aimed to investigate the association between serum total cholesterol with CRC. Furthermore, we investigated whether this association was modified by intake of dietary polyunsaturated fatty acids (PUFAs). METHODS: We analysed data from 6628 participants of the Rotterdam Study, a prospective population-based follow-up study among patients aged 55 years and older. Serum total cholesterol was measured at baseline. During a mean follow-up time of 12.9 years, we identified 248 new CRC cases based on pathology data and medical records. Multivariable HRs were calculated using Cox regression models. RESULTS: After adjustment, serum total cholesterol levels were associated with a higher risk of CRC (HR 1.49; 95% CI 1.08 to 2.06 for highest vs lowest tertile). Statistically significant effect modification was present for PUFAs intake (P-interaction=0.04). After stratification by median PUFAs intake, an increased risk with increasing tertiles of serum total cholesterol was observed among patients with low PUFAs intake (3rd tertile vs 1st tertile: HR 2.43; 95% CI 1.41 to 4.18), whereas no association was observed among patients with high PUFAs intake (3rd tertile vs 1st tertile: HR 0.93; 95% CI 0.55 to 1.58). CONCLUSIONS: Taken together, these findings suggest that high levels of serum total cholesterol increase CRC risk, but this risk may be reduced by high dietary PUFAs intake.

The effects of lutein on cardiometabolic health across the life course: a systematic review and meta-analysis.

BACKGROUND: The antioxidant lutein is suggested as being beneficial to cardiometabolic health because of its protective effect against oxidative stress, but evidence has not systematically been evaluated. OBJECTIVE: We aimed to evaluate systematically the effects of lutein (intake or concentrations) on cardiometabolic outcomes in different life stages. DESIGN: This is a systematic review with meta-analysis of literature published in MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar up to August 2014. Included were trials and cohort, case-control, and cross-sectional studies in which the association between lutein concentrations, dietary intake, or supplements and cardiometabolic outcomes was reported. Two independent investigators reviewed the articles. RESULTS: Seventy-one relevant articles were identified that included a total of 387,569 participants. Only 1 article investigated the effects of lutein during pregnancy, and 3 studied lutein in children. Furthermore, 31 longitudinal, 33 cross-sectional, and 3 intervention studies were conducted in adults. Meta-analysis showed a lower risk of coronary heart disease (pooled RR: 0.88; 95% CI: 0.80, 0.98) and stroke (pooled RR: 0.82; 95% CI: 0.72, 0.93) for the highest compared with the lowest tertile of lutein blood concentration or intake. There was no significant association with type 2 diabetes mellitus (pooled RR: 0.97; 95% CI: 0.77, 1.22), but higher lutein was associated with a lower risk of metabolic syndrome (pooled RR: 0.75; 95% CI: 0.60, 0.92) for the highest compared with the lowest tertile. The literature on risk factors for cardiometabolic diseases showed that lutein might be beneficial for atherosclerosis and inflammatory markers, but there were inconsistent associations with blood pressure, adiposity, insulin resistance, and blood lipids. CONCLUSIONS: Our findings suggest that higher dietary intake and higher blood concentrations of lutein are generally associated with better cardiometabolic health. However, evidence mainly comes from observational studies in adults, whereas large-scale intervention studies and studies of lutein during pregnancy and childhood are scarce.

The effects of lutein on respiratory health across the life course: A systematic review.

BACKGROUND: Lutein, a fat-soluble carotenoid present in green leafy vegetables and eggs, has strong antioxidant properties and could therefore be important for respiratory health. DESIGN: We systematically reviewed the literature for articles that evaluated associations of lutein (intake, supplements or blood levels) with respiratory outcomes, published in Medline, Embase, Cochrane Central, PubMed, Web of Science and Google Scholar, up to August 2014. RESULTS: We identified one Randomized Control Trial (RCT), two longitudinal, four prospective and six cross-sectional studies. The individual studies obtained a Quality Score ranging between 3 and 9. Six studies were performed in children, which examined bronchopulmonary dysplasia (BPD), asthma and wheezing. In adults, 7 studies investigated asthma, respiratory function and respiratory mortality. The RCT found a borderline significant effect of lutein/zeaxanthin supplementation in neonates on the risk of BPD (OR 0.43 (95% CI 0.15; 1.17). No association was found between lutein intake or levels and respiratory outcomes in children. A case-control study in adults showed lower lutein levels in asthma cases. Three studies, with a prospective or longitudinal study design, in adults found a small but a significant positive association between lutein intake or levels and respiratory function. No association was found in the other two studies. In relation to respiratory mortality, one longitudinal study showed that higher lutein blood levels were associated with a decreased mortality (HR 0.77 (95% CI 0.60; 0.99), per SD increase in lutein). CONCLUSION: The published literature suggests a possible positive association between lutein and respiratory health. However, the literature is scarce and most studies are of observational nature.

Baseline dietary glutamic acid intake and the risk of colorectal cancer: The Rotterdam study.

BACKGROUND: Animal studies have shown that glutamine supplementation may decrease colon carcinogenesis, but any relation with glutamine or its precursors has not been studied in humans. The primary aim of this study was to assess whether dietary glutamic acid intake was associated with colorectal cancer (CRC) risk in community-dwelling adults. A secondary aim was to evaluate whether the association could be modified by the body mass index (BMI). METHODS: This study was embedded in the Rotterdam study, which included a prospective cohort from 1990 onward that consisted of 5362 subjects who were 55 years old or older and were free of CRC at the baseline. Glutamic acid was calculated as a percentage of the total protein intake with a validated food frequency questionnaire at the baseline. Incident cases of CRC were pathology-based. RESULTS: During follow-up, 242 subjects developed CRC. Baseline dietary glutamic acid intake was significantly associated with a lower risk of developing CRC (hazard ratio [HR] per percent increase in glutamic acid of protein, 0.78; 95% confidence interval [CI], 0.62-0.99). After stratification for BMI, the risk reduction for CRC by dietary glutamic acid was 42% for participants with a BMI ≤ 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.58; 95% CI, 0.40-0.85), whereas no association was found in participants with a BMI > 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.97; 95% CI, 0.73-1.31). CONCLUSIONS: Our data suggest that baseline dietary glutamic acid intake is associated with a lower risk of developing CRC, but this association may be mainly present in nonoverweight subjects.

Lutein intake at the age of 1 year and cardiometabolic health at the age of 6 years: the Generation R Study.

Lutein is a carotenoid with strong antioxidant properties. Previous studies in adults suggest a beneficial role of lutein on cardiometabolic health. However, it is unknown whether this relation also exists in children; therefore, we aimed to assess the relation between lutein intake at 13 months of age and cardiometabolic outcomes at the age of 6 years. We included 2044 Dutch children participating in a population-based prospective cohort study. Diet was measured at 13 months of age with an FFQ. Lutein intake was standardised for energy and ß-carotene intake. Blood pressure, anthropometrics, serum lipids and insulin were measured at the age of 6 years. Dual-energy X-ray absorptiometry was performed to measure total and regional fat and lean mass. A continuous cardiometabolic risk factor score was created, including the components body fat percentage, blood pressure, insulin, HDL-cholesterol and TAG. Age- and sex-specific standard deviation scores were created for all outcomes. Multivariable linear regression was performed, including socio-demographic and lifestyle variables. Median (energy-standardised) lutein intake was 1317 mcg/d (95% range 87, 6069 mcg/d). There were no consistent associations between lutein intake at 13 months and anthropometrics and body composition measures at 6 years of age. In addition, lutein intake was not associated with a continuous cardiometabolic risk factor score, nor was it associated with any of the individual components of the cardiometabolic risk factor score. Results from this large population-based prospective cohort study do not support the hypothesis that lutein intake early in life has a beneficial role for later cardiometabolic health.

Dietary Fiber Intake Modifies the Positive Association between n-3 PUFA Intake and Colorectal Cancer Risk in a Caucasian Population.

BACKGROUND: The association between dietary fat intake and the risk of colorectal cancer (CRC) is still unclear. OBJECTIVES: We analyzed whether intakes of dietary polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs) were associated with CRC risk and whether these associations were modified by dietary fiber (DF) intake. METHODS: This study was embedded in the Rotterdam Study, a prospective cohort study among subjects aged ≥55 y (n = 4967). At baseline, diet was measured by a food-frequency questionnaire. CRC events were diagnosed on the basis of pathology data and medical records. Multivariable adjusted HRs were calculated using Cox regression models. RESULTS: During a mean follow-up period of 14.6 y, we identified 222 incident cases of CRC. There was no association between total PUFA, n-6 (ω-6) PUFA, or SFA intake and CRC risk. n-3 PUFA intake was associated with an increased risk of CRC [tertile 3 vs. tertile 1: HR = 1.44 (95% CI: 1.02, 2.04), P-trend = 0.04]. When data were analyzed by food sources, only n-3 PUFAs from nonmarine sources were associated with an increased risk of CRC. A significant interaction between n-3 PUFA and DF intakes was found (P-interaction = 0.02). After stratification by median DF intake, an increased risk of CRC caused by n-3 PUFA intake was observed in participants with a DF intake less than the median [tertile 3 vs. tertile 1: HR = 1.96 (95% CI: 1.20, 3.19), P-trend = 0.01]. No association was observed in subjects with DF intake equal to or higher than the median. CONCLUSIONS: This study suggests that intake of n-3 PUFAs by adults is associated with an increased risk of CRC, which may be driven mainly by sources other than fish. Moreover, a complex interaction with DF intake may be present.

Effects of choline on health across the life course: a systematic review.

CONTEXT: Choline is a precursor of both betaine and acetylcholine and might, therefore, influence cardiovascular and cognitive outcomes. There has been concern, however, that it may influence blood lipid levels because it is an essential component of very-low-density lipoproteins. OBJECTIVE: The aim was to systematically review, using PRISMA guidelines, the literature pertaining to the effects of choline on body composition and on metabolic, cardiovascular, respiratory, and neurological outcomes in different life stages. DATA SOURCES: The MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar databases were searched up to July 2014. DATA EXTRACTION: Fifty relevant articles were identified. These comprised trials and cohort, case-control, and cross-sectional studies that assessed blood levels of choline, dietary intake of choline, and supplementation with choline in a population free of diseases at baseline. DATA SYNTHESIS: There is some observational evidence that choline during pregnancy may be beneficial for the neurological health of the child. In adults, choline may have beneficial effects on cognition, but high-quality (intervention) studies are lacking. Results on the effects of choline on body composition, blood lipids, and cardiovascular health were inconsistent. CONCLUSIONS: Evidence to confirm the suggested effects of choline on health in different stages of life is scarce. Potential effects of choline need to be confirmed by intervention studies. Possible harmful effects on cardiometabolic health need careful evaluation.

Polyunsaturated fatty acids and serum C-reactive protein: the Rotterdam study.

We aimed to investigate whether dietary intake of total or individual (n-3, n-6, and n-3:n-6 ratio) polyunsaturated fatty acids (PUFAs) was prospectively associated with serum levels of C-reactive protein (CRP), a marker of inflammation. We analyzed 4,707 participants (1,943 men and 2,764 women) from the Rotterdam Study, a prospective follow-up study of subjects aged 55 years or older in the Netherlands. At baseline (1989-1993), dietary intake of PUFAs was assessed by validated food frequency questionnaire. CRP was measured at baseline and at the third study visit (1997-1999). Regression coefficients (ß) and 95% confidence intervals were obtained using linear generalized estimating equations. Dietary intake of butter and margarine explained most of the variance in PUFA intake. After adjustment for possible confounding factors, higher intake of total PUFAs was associated with lower CRP levels (fourth quartile vs. first quartile: ß = -0.08, 95% confidence interval: -0.15, -0.01). Similarly, intake of n-6 PUFAs was inversely related to CRP (fourth quartile vs. first: ß = -0.09, 95% confidence interval: -0.16, -0.01). No consistent trends were observed regarding n-3 PUFAs or n-3:n-6 PUFA ratio and CRP. These findings suggest that high intakes of total PUFAs are associated with lower levels of CRP, reflecting diminished chronic systemic inflammation, which in our study was mainly driven by n-6 PUFAs.

The development of a diet quality score for preschool children and its validation and determinants in the Generation R Study.

BACKGROUND: Although many studies have examined health effects of infant feeding, studies on diet quality shortly after the weaning and lactation period are scarce. OBJECTIVES: Our aims were to develop and evaluate a diet score that measures overall diet quality in preschool children and to examine the sociodemographic and lifestyle determinants of this score. METHODS: On the basis of national and international dietary guidelines for young children, we developed a diet score containing 10 components: intake of vegetables; fruit; bread and cereals; rice, pasta, potatoes, and legumes; dairy; meat and eggs; fish; oils and fats; candy and snacks; and sugar-sweetened beverages. The total score ranged from 0 to 10 on a continuous scale and was standardized to an energy intake of 1200 kcal/d with the residual method. The score was evaluated in 3629 children participating in the Generation R Study, a population-based prospective cohort study. Food consumption was assessed with a food-frequency questionnaire (FFQ) at a median age of 13 mo. RESULTS: The mean ± SD diet score was 4.1 ± 1.3. The food-based diet score was positively associated with intakes of many nutrients, including n-3 (ω-3) fatty acids [FAs; 0.25 SD increase (95% CI: 0.22, 0.27) per 1 point increase in the diet score], dietary fiber [0.32 (95% CI: 0.30, 0.34)], and calcium [0.13 (95% CI: 0.11, 0.16)], and was inversely associated with intakes of sugars [-0.28 (95% CI: -0.31, -0.26)] and saturated fat [-0.03 (95% CI: -0.05, -0.01)]. A higher diet score was associated with several health-conscious behaviors, such as maternal folic acid supplement use during pregnancy, no smoking during pregnancy, and children watching less television. CONCLUSION: We developed a novel food-based diet score for preschool children that could be applied in future studies to compare diet quality in early childhood and to investigate associations between diet in early childhood and growth, health, and development.