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Identifying a need for developing a conceptual framework for the future development of Food-Based Dietary Guidelines (FBDG) in Europe, The Federation of European Nutrition Sciences established a Task Force for this purpose. A workshop was held with the specific objective to discuss the various dimensions considered as particularly relevant. Existing frameworks for FBDG were discussed, and presentations from various countries illustrated not only several commonalities but also a high degree of heterogeneity in the guidelines from different countries. Environmental aspects were considered in several countries, and dimensions like food safety, dietary habits and preparation were included in others. The workshop provided an overview of the use of FBDG – both in developing front-of-pack nutrition labels and for reformulation and innovation. The European FBDG dimensions were described with examples from the close connection between FBDG and European Union (EU) policies and activities and from the compilation of a database of national FBDG. Also, the challenges with communication of FBDG were discussed. Considering the current scientific basis and the experiences from several countries, the Task Force discussed the various dimensions of developing FBDG and concluded that environmental aspects should be included in the future conceptual framework for FBDG. A change in terminology to sustainable FDBG (SFBDG) could reflect this. The Task Force concluded that further work needs to be done exploring current practice, existing methodologies and the future prospects for incorporating other relevant dimensions into a future Federation of European Nutrition Societies conceptual framework for SFBDG in Europe and working groups were formed to address that.

Objective:To derive healthy and sustainable food-based dietary guidelines (FBDG) for different target groups in the Netherlands and describe the process.Design:Optimised dietary patterns for children, adolescents, adults and the elderly were calculated using an optimisation model. Foods high in saturated and trans-fatty acids, salt and sugar, and low in dietary fibre, were excluded. The dietary patterns resembled the current food consumption as closely as possible, while simultaneously meeting recommendations for food groups, nutrients, maximum limits for foods with a high environmental impact, and within 85 % of the energy requirement. Recommended daily amounts of food groups were based on the optimised dietary patterns and expert judgement.Setting:The Netherlands.Participants:FBDG were derived for Dutch people with different ages, genders, activity levels and food preferences.Results:For most target groups the optimisation model provided dietary patterns that complied with all requirements. For some food groups, the optimised amounts varied largely between target groups. For consistent messages to consumers, the optimised dietary patterns were adjusted to uniform recommendations per target group. Recommendations were visualised in the Wheel of Five. The advice is to eat the recommended amounts of foods according to the Wheel of Five and limit consumption of other foods.Conclusions:Based on an optimisation model, scientific evidence, information on dietary patterns and expert knowledge, we derived FBDG for different target groups. The Wheel of Five is a key food-counselling model that can help Dutch consumers to make their diets healthier and more environmentally sustainable.

Endothelial dysfunction (ED) and low-grade inflammation (LGI) have a role in the development of CVD. The two studies reported here explored the effects of dietary proteins and carbohydrates on markers of ED and LGI in overweight/obese individuals with untreated elevated blood pressure. In the first study, fifty-two participants consumed a protein mix or maltodextrin (3×20 g/d) for 4 weeks. Fasting levels and 12 h postprandial responses of markers of ED (soluble intercellular adhesion molecule 1 (sICAM), soluble vascular cell adhesion molecule 1 (sVCAM), soluble endothelial selectin and von Willebrand factor) and markers of LGI (serum amyloid A, C-reactive protein and sICAM) were evaluated before and after intervention. Biomarkers were also combined into mean Z-scores of ED and LGI. The second study compared 4 h postprandial responses of ED and LGI markers in forty-eight participants after ingestion of 0·6 g/kg pea protein, milk protein and egg-white protein. In addition, postprandial responses after maltodextrin intake were compared with a protein mix and sucrose. The first study showed significantly lower fasting ED Z-scores and sICAM after 4 weeks on the high-protein diet (P≤0·02). The postprandial studies found no clear differences of ED and LGI between test meals. However, postprandial sVCAM decreased more after the protein mix compared with maltodextrin in both studies (P≤0·04). In conclusion, dietary protein is beneficial for fasting ED, but not for fasting LGI, after 4 weeks of supplementation. On the basis of Z-scores, postprandial ED and LGI were not differentially affected by protein sources or carbohydrates.

Diet composition may affect blood pressure (BP), but the mechanisms are unclear. The aim of the present study was to compare postprandial BP-related responses to the ingestion of pea protein, milk protein and egg-white protein. In addition, postprandial BP-related responses to the ingestion of maltodextrin were compared with those to the ingestion of sucrose and a protein mix. We hypothesised that lower postprandial total peripheral resistance (TPR) and BP levels would be accompanied by higher plasma concentrations of nitric oxide, insulin, glucagon-like peptide 1 (GLP-1) and glucagon. On separate occasions, six meals were tested in a randomised order in forty-eight overweight or obese adults with untreated elevated BP. Postprandial responses of TPR, BP and plasma concentrations of insulin, glucagon, GLP-1 and nitrite, nitroso compounds (RXNO) and S-nitrosothiols (NOx) were measured for 4 h. No differences were observed in TPR responses. Postprandial BP levels were higher after the ingestion of the egg-white-protein meal than after that of meals containing the other two proteins (P≤ 0·01). The ingestion of the pea-protein meal induced the highest NOxresponse (P≤ 0·006). Insulin and glucagon concentrations were lowest after the ingestion of the egg-white-protein meal (P≤ 0·009). Postprandial BP levels were lower after the ingestion of the maltodextrin meal than after that of the protein mix and sucrose meals (P≤ 0·004), while postprandial insulin concentrations were higher after the ingestion of the maltodextrin meal than after that of the sucrose and protein mix meals after 1–2 h (P≤ 0·0001). Postprandial NOx, GLP-1 and glucagon concentrations were lower after the ingestion of the maltodextrin meal than after that of the protein mix meal (P≤ 0·008). In conclusion, different protein and carbohydrate sources induce different postprandial BP-related responses, which may be important for BP management. Lower postprandial BP levels are not necessarily accompanied by higher NOx, insulin, glucagon or GLP-1 responses.

In post-transplant conditions, sulfur may be protective by intermediate conversion to hydrogen sulfide and thiosulfate. However, sulfate, the end product of sulfur-containing amino acids (SAAs), contributes to metabolic acid load and may adversely influence acid-base homeostasis. We investigated the association of urinary sulfur metabolites with cardiometabolic parameters in renal transplant recipients (RTRs) and analyzed their predictive capacity for mortality. We studied urinary sulfate and thiosulfate excretion in 24-hour urine samples from 707 RTRs at a median 5.4 years (interquartile range, 1.9 to 12.2) after transplantation as well as from 110 controls. Diet was assessed for SAA content and various risk factors were measured. Urinary sulfate was similar, whereas thiosulfate was higher in RTRs versus controls. SAA intake was lower in RTRs compared with controls and correlated with sulfate but not thiosulfate excretion. Sulfate beneficially associated with eGFR, net acid excretion, systolic BP, high-sensitivity C-reactive protein, N-terminal probrain natriuretic peptide, and proteinuria (all P≤0.01). Thiosulfate beneficially associated with eGFR, serum acidity, high-sensitivity C-reactive protein, and N-terminal probrain natriuretic peptide (all P≤0.001). During a median 27 months (interquartile range, 22-36) of follow-up, 47 RTRs died. After adjustment for age, sex, and eGFR, hazard ratios for mortality were 0.87 (95% confidence interval, 0.82 to 0.92; P

Hypertension is highly prevalent among renal transplant recipients (RTR) and a risk factor for graft failure and cardiovascular events. Protein intake has been claimed to affect blood pressure (BP) in the general population and may affect renal function. We examined the association of dietary protein with BP and renal function in RTR. We included 625 RTR (age 53 (sd13) years; 57 % male). Protein intake was assessed with a FFQ, differentiating between animal and plant protein. BP was measured according to a strict protocol. Creatinine clearance and albuminuria were measured as renal parameters. Protein intake was 83 (sd12) g/d, of which 63 % derived from animal sources. BP was 136 (sd17) mmHg systolic (SBP) and 83 (sd11) mmHg diastolic (DBP). Creatinine clearance was 66 (sd26) ml/min; albuminuria 41 (10–178) mg/24 h. An inverse, though statistically insignificant, association was found between the total protein intake and both SBP (β = − 2·22 mmHg persd,P= 0·07) and DBP (β = − 0·48 mmHg persd,P= 0·5). Protein intake was not associated with creatinine clearance. Although albuminuria was slightly higher in the highest tertile of animal protein intake compared with the lowest tertile (66v. 33 mg/d, respectively,P= 0·03), linear regression analyses did not reveal significant associations between dietary protein and albuminuria. Protein intake exceeded the current recommendations. Nevertheless, within the range of protein intake in our RTR population, we found no evidence for an association of dietary protein with BP and renal function. Intervention studies focusing on different protein types are warranted to clarify their effect on BP and renal function in RTR.

OBJECTIVES: It is not yet clear whether dietary protein could help maintaining a healthy blood pressure (BP). We investigated the association between total protein intake, estimated from 24-h urinary urea excretion, and incident hypertension in Dutch men and women. METHODS: We analyzed data of 3997 men and women (aged 28-75 years) who participated in the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, a prospective cohort study. Urea excretion was assessed in two consecutive 24-h urine collections at baseline and approximately 4 years later, from which total protein intake was estimated using the Maroni method. Participants were followed for 9 years for hypertension incidence, defined as BP at least 140/90mmHg or initiation of antihypertensive medication. Hazard ratios (HR) were obtained in sex-specific quintiles of protein intake using time-dependent Cox regression, adjusted for age, sex, BMI, smoking, alcohol use, and 24-h urinary excretions of sodium and potassium. RESULTS: Baseline BP was on average 119/70mmHg and 976 participants developed hypertension during follow-up. Mean protein intake (in g/kg ideal body weight) was 1.18±0.26 for men and 1.12±0.25 for women. Estimated protein intake was nonlinearly inversely associated with incident hypertension in the fully adjusted model, with nonsignificant HR of 0.77, 0.75, 0.82, and 0.83 in consecutive quintiles compared with the lowest quintile (P-trend: 0.52). CONCLUSION: Protein intake, as assessed by urinary urea excretion, was not significantly associated with 9-year hypertension incidence in Dutch men and women. © 2013 Wolters Kluwer Health / Lippincott Williams & Wilkins.

Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function.

BACKGROUND AND OBJECTIVES: Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. This study examined the association of metabolic acid load with acidosis and with cardiovascular risk factors in RTRs and aimed to identify dietary factors associated with acidosis. DESIGN, PARTICIPANTS, SETTING, MEASUREMENTS: 707 RTRs were included. Metabolic acid load was assessed by measuring 24-hour urinary net acid excretion (NAE; i.e., titratable acid + ammonium - bicarbonate). Acidosis was defined as serum [HCO(3)(-)] < 24 mmol/L. BP and insulin resistance, reflected by hemoglobin A1c, were among cardiovascular risk factors. Diet was assessed with food-frequency questionnaires. Linear regression analysis was applied to investigate association between NAE and acidosis and between dietary factors and acidosis. RESULTS: Mean age +/- SD was 53+/-13 years; 57% of patients were male. Acidosis was present in 31% of RTRs. NAE was associated with acidosis (serum HCO(3)(-): beta=-0.61; serum pH: beta=-0.010; both P

The general feeling of wellness after food consumption may play an important role in regulating food intake. This exploratory study aimed at identifying and evaluating measures of such postprandial wellness, tentatively defined as subjective appreciation of life after food intake. The study had a randomized cross-over, double blind design. Twenty-one healthy men with mean age of 33 ± 14 years received two liquid breakfasts with either high protein/low carbohydrate (HP/LC) or low protein/high carbohydrate (LP/HC) ratio on separate days with a washout period of one week in between. Subjective reports on satiety and postprandial wellness (pleasantness, satisfaction, relaxation, sleepiness, physical energy and mental alertness) were established using visual analogue scales at regular time points after consumption of the breakfasts up to 240. min. Blood concentrations of CCK, ghrelin, glucose, and insulin were determined at the same time points. The HP/LC breakfast induced higher levels of satiety and specific parameters of postprandial wellness (satisfaction, pleasantness and the pleasantness of these feelings) than the LP/HC breakfast at 3 or 4. h after consumption. The corresponding higher CCK and lower ghrelin concentrations at these time points supported these subject reported changes. These results indicate that meal composition influences some parameters of postprandial wellness in line with physiological responses. Further research is warranted to confirm the observed relationships. Also the relevance for food intake behaviour remains to be established. © 2010 Elsevier Ltd.

Randomized trials have shown significant blood pressure (BP) reductions after increased protein compared with carbohydrate intake, but the effect on BP maintenance after initial weight loss is unclear. We examined the effect of a high-protein diet on the maintenance of reduced BP after weight loss in 420 overweight adults from the Diet, Obesity and Genes study. After an 8-week weight-loss period (>8% BW), subjects (42+/-6 years) were randomized to either a high-protein diet (23-28 en% protein) or a lower-protein control diet (10-15 en% protein) for 26 weeks. BMI after weight loss was 30.3+/-4.3 kg m-2, BP was 118/73 mm Hg and 28 subjects (6.5%) used antihypertensive agents. Systolic BP during 26 weeks of weight maintenance dietary intervention increased in both treatment groups, but it was 2.2 mm Hg less (95% CI: -4.6 to 0.2 mm Hg, P=0.08) in the high-protein group than in the lower-protein control group. In 191 (pre)hypertensive subjects (baseline systolic BP120 mm Hg), a larger difference was observed (-4.2 mm Hg (-7.7, -0.7), P=0.02). The effect was attenuated after adjustment for initial BP (-3.4 mm Hg (-6.9, -0.03), P=0.048), and after additional adjustment for weight change (-2.7 mm Hg (-6.1, 0.4), P=0.11). Adjustment for 24-h urinary excretion of sodium and potassium did not change the results. Diastolic BP yielded similar results. These findings suggest that a BP reduction after weight loss is better maintained when the intake of protein is increased at the expense of carbohydrates. This effect is partly mediated by body weight.Journal of Human Hypertension advance online publication, 24 April 2014; doi:10.1038/jhh.2014.30.

Vitamin E is the major lipid-soluble antioxidant in human subjects and is crucial in protecting polyunsaturated fatty acids (PUFA) against lipid peroxidation. Dietary PUFA have been suggested to inhibit the absorption of vitamin E. The present study in young male rats was designed to investigate the effect of increasing concentrations of dietary linoleic acid on the faecal excretion of vitamin E. The rats were fed on semi-synthetic diets containing two concentrations of fat (59 g/kg diet, 15 energy % (en%) or 131 g/kg, 30 en%) for 3 weeks. Triacylglycerol rich in linoleic acid was added at the expense of triacylglycerol rich in saturated fatty acids to obtain dietary concentrations of 13,39 or 66 g linoleic acid/kg diet for the high-fat diet (131 g fat/kg) and 12, 24 or 36 g linoleic acid/kg diet for the reduced-fat diet (59 g fat/kg). The results from the present study demonstrate that the faecal excretion of vitamin E was significantly lower in rats fed on diets with high levels of linoleic acid compared with rats fed on lower levels of linoleic acid irrespective of the dietary fat content. The concentration of vitamin E in liver and plasma was significantly lower in animals fed on the highest concentration of linoleic acid compared with those fed on the lowest level. Results from the present study also demonstrate that at the same concentration of linoleic acid, the faecal excretion of vitamin E in rats fed on reduced-fat diets was significantly lower than in rats fed on high-fat diets. Our findings indicate that the apparent absorption of vitamin E is not inhibited by dietary PUFA. Results from the present study also demonstrate that a reduction of dietary fat content from 30 en% to 15 en% does not lower the apparent absorption of vitamin E

Background: Dietary protein may beneficially influence blood pressure (BP), but evidence is not conclusive. Objective: To quantify the association of total protein, plant protein, and animal protein intake with BP and incident hypertension by means of meta-analysis. Methods: A systematic literature search for eligible studies was conducted until January 2012, using MEDLINE and manual search. Of >3,000 titles evaluated, 29 met the inclusion criteria. Dose-response meta-analyses were performed using STATA 11.0. We included 8 cross-sectional studies (total of 48,985 participants), 4 prospective studies (11,761 participants), and 17 randomized controlled trials (1,449 subjects). Results: Total protein intake was significantly inversely associated with systolic BP ([[Unable to Display Character: ‑]]0.20 mmHg per SD, 95%-CI: [[Unable to Display Character: ‑]]0.39 to [[Unable to Display Character: ‑]]0.01) in cross-sectional studies, but no relation was found with incident hypertension in prospective studies (HR of 0.99 per SD, 95%-CI: 0.96 to 1.02). Trials showed an overall reduction of [[Unable to Display Character: ‑]]2.1 mmHg in systolic BP (95%-CI:[[Unable to Display Character: ‑]]2.9 to [[Unable to Display Character: ‑]]1.4) for a weighed difference in protein intake of 41 g/d, compared to carbohydrates. Plant protein, but not animal protein, was weakly inversely associated with BP in cross-sectional studies. Plant protein and animal protein showed similar associations in prospective studies (non-significant HR of 0.96 and 0.98 per SD, respectively) and randomized trials (-2.0 vs -2.2 mmHg, P Conclusion: Dietary protein may have a beneficial effect on BP if consumed instead of carbohydrates. No clear difference was observed between plant and animal protein, but data on protein from different sources and BP is scarce and more research is needed to draw conclusions.

Background: Mild metabolic acidosis may result in elevated blood pressure (BP). Several formulas to estimate dietary acid load have been developed. However, studies in which these formulas have been validated are limited. Objectives: To validate and/or improve existing formulas for dietary acid load and to examine the association between dietary protein, acid load and BP. Methods: We performed a randomized 14d crossover dietary intervention involving 37 healthy subjects (age: 21±2 y) who consumed individualized, isocaloric diets that were either low or high in protein (0.5 versus 2.0 g protein/kg BW/d). Duplicate portions of the provided diets were collected and analysed for energy and nutrients. We used two measures to characterize dietary acid load (i.e. PRAL and NEAP). Urinary Net Acid Excretion (NAE; i.e. titratable acid + ammonium - bicarbonate) was analysed. BP was measured according to standardized procedures. Results: Mean dietary intakes significantly differed between the low and high protein diet, resulting in significantly different acid load values (Table 1, all p Conclusion: PRAL predicts NAE reasonably well in healthy adults for normal to high protein intake. PRAL can be influenced by diet, but this cannot be clearly attributed to protein intake alone. PRAL does not seem to influence short-term BP in healthy adults with normal BP.

The influence of high CaCO3, intake on the bioavailability of Fe from FeSO4, was assessed during Fe repletion of rats with Fe-deficiency-induced anaemia. Fe-deficient rats with a mean blood haemoglobin concentration of 4. 1 mmol/l were fed on purified Fe-adequate diets containing either 6.2 or 25.0g CaCO,/kg (ten rats per group). Haemoglobin repletion after 14 d was significantly depressed by high CaCO, intake (9.5 v. 9.8 mmol/l for high and low CaCO, intake respectively; P = 0·03), as was apparent Fe retention (367 v. 552 µg/d during days 5–7, P59Fe and Cr as a non-absorbable marker. Mucosal transfer was significantly diminished by CaCO, loading (90 v. 100% of mucosal uptake; P = 0·04), whereas mucosal uptake was not.59Fe retention values at 14 d after administration were not significantly different (57.6 v. 51.9%; P = 0·14). Fe contents of liver and spleen were significantly decreased by high compared with low CaCO, intake (879 v. 590 pg Fe in liver, P < 0·001; 92 v. 63pg Fe in spleen, P

In the present controlled, randomised, multiple cross-over dietary intervention study, we aimed to identify potential biomarkers for dietary protein from dairy products, meat and grain, which could be useful to estimate intake of these protein types in epidemiological studies. After 9 d run-in, thirty men and seventeen women (22 (sd4) years) received three high-protein diets (aimed at approximately 18 % of energy (en%)) in random order for 1 week each, with approximately 14 en% originating from either meat, dairy products or grain. We used a two-step approach to identify biomarkers in urine and plasma. With principal component discriminant analysis, we identified amino acids (AA) from the plasma or urinary AA profile that were distinctive between diets. Subsequently, after pooling total study data, we applied mixed models to estimate the predictive value of those AA for intake of protein types. A very good prediction could be made for the intake of meat protein by a regression model that included urinary carnosine, 1-methylhistidine and 3-methylhistidine (98 % of variation in intake explained). Furthermore, for dietary grain protein, a model that included seven AA (plasma lysine, valine, threonine, α-aminobutyric acid, proline, ornithine and arginine) made a good prediction (75 % of variation explained). We could not identify biomarkers for dairy protein intake. In conclusion, specific combinations of urinary and plasma AA may be potentially useful biomarkers for meat and grain protein intake, respectively. These findings need to be cross-validated in other dietary intervention studies.

Background. Hypertension is common among renal transplant recipients (RTR) and a risk factor for graft failure and mortality. Sodium intake is a well-established determinant of blood pressure (BP) in the general population. However, data in RTR are limited. International guidelines recommend a maximum daily sodium intake of 70 mmol. We investigated sodium intake in RTR as compared to healthy controls and its association with BP. Methods. We included 660 RTR (age 53 ± 13 years, 58 male) and 201 healthy controls (age 54 ± 11 years, 46 male). Sodium intake was assessed from 24-h urine collections. The morning after completion of urine collection, BP was measured according to a strict protocol. Results. Urinary sodium excretion was 156 ± 62 mmol/24 h in RTR and 195 ± 75 in controls (difference: P < 0.001), and 95 of RTR had a urinary sodium excretion >70 mmol/24 h. Systolic BP (SBP) and diastolic BP (DBP) were 136 ± 18 and 82 ± 11 mmHg, respectively. Sodium intake was positively associated with SBP (β 0.042 mmHg/mmol/24 h, P 0.002) and DBP (β 0.023 mmHg/mmol/24 h, P 0.007), independent of potential confounders. Conclusion. sAlthough RTR had a lower sodium intake than healthy controls, their intake still exceeded current guidelines. Reduction of sodium intake to recommended amounts could reduce SBP by 45 mmHg. Better control of sodium intake may help to prevent graft failure and mortality due to hypertension among RTR. © The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background: Dietary protein intake may help to manage blood pressure (BP) and prevent complications associated with elevated BP. Objective: The objective of this study was to determine whether 4 wk of increased protein intake (∼25% compared with ;15% of energy intake that isoenergetically replaces carbohydrate intake) lowers office and daytime BP compared with increased carbohydrate intake. Design: A randomized, double-blind, parallel study compared consumption of 3 x 20 g protein/d (20% pea, 20% soy, 30% egg, and 30% milk-protein isolate) with 3 x 20 g maltodextrin/d. Protein or maltodextrin were isoenergetically substituted for a sugar-sweetened drink. Primary outcomes were office and daytime BP. A total of 99 men and women [age range: 20-70 y; BMI (in kg/m2): 25-35] with untreated elevated BP (BP ≥130/85 and

Background: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP).Objective: The objective was to examine whether dietary acid load was associated with incident hypertension in a cohort of older Dutch adults from the Rotterdam Study.Design: The analyses included 2241 participants aged >= 55 y who were free of hypertension at baseline (1990-1993) and who had complete dietary and BP data. Dietary data were obtained from a 170-item food-frequency questionnaire. We used 2 measures to characterize dietary acid load: 1) potential renal acid load (PRAL) by using an algorithm including protein, phosphorus, potassium, calcium, and magnesium, and 2) estimated net endogenous acid production (NEAP) based on protein and potassium. HRs for 6-y incidence of hypertension were obtained in tertiles of PRAL and NEAP with adjustment for age, sex, BMI, smoking, education, and intakes of alcohol, fiber, and total energy.Results: We identified 1113 incident cases of hypertension during 8707 person-years of follow-up. The median dietary acid load ranged from -14.6 to 19.9 mEq/d across categories of PRAL. Hypertension risk was not significantly associated with dietary acid load. The multivariate HRs (95% CIs) in consecutive tertiles of PRAL were 1.00 (reference), 1.01 (0.87, 1.17), and 1.02 (0.88, 1.18) (P trend = 0.83). The median dietary acid loads were 30.4, 36.7, and 43.7 mEq/d, respectively, in consecutive tertiles of NEAP. Corresponding HRs for NEAP were 1.00 (reference), 0.92 (0.80. 1.07), and 0.94 (0.81, 1.10) (P-trend = 0.46).Conclusion: The findings from this prospective cohort study provided no evidence of an association between dietary acid load and risk of hypertension in older adults. Am J Clin Nutr 2012;95: 1438-44.

Background: Elevated blood pressure (BP), which is a major risk factor for cardiovascular disease, is highly prevalent worldwide. Recently, interest has grown in the role of dietary protein in human BP. We performed a systematic review of all published scientific literature on dietary protein, including protein from various sources, in relation to human BP.Methodology/Principal Findings: We performed a MEDLINE search and a manual search to identify English language studies on the association between protein and blood pressure, published before June 2010. A total of 46 papers met the inclusion criteria. Most observational studies showed no association or an inverse association between total dietary protein and BP or incident hypertension. Results of biomarker studies and randomized controlled trials indicated a beneficial effect of protein on BP. This beneficial effect may be mainly driven by plant protein, according to results in observational studies. Data on protein from specific sources (e.g. from fish, dairy, grain, soy, and nut) were scarce. There was some evidence that BP in people with elevated BP and/or older age could be more sensitive to dietary protein.Conclusions/Significance: In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. A blood pressure lowering effect of protein may have important public health implications. However, this warrants further investigation in randomized controlled trials. Furthermore, more data are needed on protein from specific sources in relation to BP, and on the protein-BP relation in population subgroups.

Apparent magnesium absorption is depressed in rats fed diets containing soybean protein or enriched with sodium phytate or phosphate in comparison with casein, whereas it is raised in rats fed lactose. However, the possibility that changes in apparent absorption are caused by changes in fecal excretion of endogenous magnesium cannot be excluded. We studied the effects of casein, soybean protein, sodium phytate, lactose and phosphate on apparent and true absorption of magnesium. True magnesium absorption was measured with the use of oral and intraperitoneal administration of tracer doses of 28Mg. Fecal excretion of endogenous magnesium was calculated from apparent and true absorption. True magnesium absorption was not affected by either substitution of soybean protein for casein or by the addition of sodium phytate to a diet containing casein. Endogenous magnesium excretion in feces was significantly increased by soybean protein and sodium phytate. Thus the observed impairment of apparent magnesium absorption in rats fed soybean protein or sodium phytate is due to enhanced fecal excretion of endogenous magnesium. With the other dietary treatments, enhanced fecal excretion of endogenous magnesium was not associated with a discrepancy in the effects on apparent and true magnesium absorption. Dietary lactose vs. dextrose and supplemental phosphate both stimulated fecal excretion of endogenous magnesium, but lactose raised both true and apparent magnesium absorption, and phosphate depressed both true and apparent magnesium absorption.

The effects of casein and soybean protein on magnesium absorption and magnesium concentration in the femur were investigated in rats. Purified diets containing either casein or soybean protein and three concentrations of added magnesium (0.82, 1.64 or 2.46 mmol/100 g diet) were used. The isonitrogenous diets were carefully balanced for the different mineral concentrations in the protein preparations. Absolute and percent magnesium absorption and urinary magnesium excretion were significantly decreased in rats fed soybean protein when compared with casein, irrespective of the dietary concentration of added magnesium. The magnesium content of femur was significantly lower in rats fed soybean protein, but this effect was seen only when the diet contained 0.82 mmol magnesium/100 g diet. The addition of sodium phytate to the casein diets, to a concentration identical to that in the diets containing soybean protein as provided by the soybean protein preparation, produced similar effects on magnesium absorption as the diets containing soybean protein. These results indicate that soybean protein, when compared with casein, decreases magnesium absorption through its phytate component.

A number of studies have shown that tea catechins can inhibit intestinal iron absorption, mostly iron in the nonhaem form. This randomized, double-blind, placebo-controlled, 3-periods cross-over study examined the degree of inhibition of nonhaem iron absorption by pure crystalline epigallocatechin gallate (EGCG). The study was designed to show the maximum inhibitory action of EGCG by selecting 30 healthy women with low iron stores. Treatments were 150 mg, 300 mg EGCG and placebo each for 8 consecutive study days with a wash-out period of 14 days between treatments. Iron incorporation was assessed by supplying 57Fe orally and 58Fe intravenously. Differences in fractional nonhaem iron absorption between the treatments were evaluated by using two-sided ANOVA. Results showed a relative nonhaem iron absorption reduction of 14% with 150 mg EGCG and 27% for 300 mg EGCG treatment compared to placebo. Differences were statistically significant (p≤0.05) between the placebo and the 300 mg EGCG treatments and between the 150 and 300 mg EGCG treatments. The inverse relation between EGCG dose and fractional nonhaem iron absorption was linear (p=0.0002). In this study the magnitude of the inhibitory action of EGCG on nonhaem iron absorption was found to be much lower than that reported in the literature for black tea and similar compounds. The doses of EGCG in supplements, which will be lower than those used in this study, are not expected to have any health relevant effects on iron absorption in subjects with normal iron stores. © 2005 Elsevier GmbH. All rights reserved.

D-Tagatose is partly absorbed in the stomach and small intestine. Most of it is fermented by the large intestinal microbiota. The effect of D-tagatose on the composition of the microbiota and production of short chain fatty acids (SCFAs) was studied in vivo and in vitro. Gastrointestinal (GI) complaints were also studied. The in vivo study was performed according to a randomized, placebo-controlled, double-blind, five-way cross-over design in healthy subjects (12 men and 18 women). All subjects consumed 30 g raspberry jam containing 7.5 or 12.5 g D-tagatose, 7.8 g fructo-oligosaccharides (positive reference), 7.6 g D-tagatose plus 7.5 g fructo-oligosaccharides, or 15.1 g sucrose (negative reference) at breakfast for 2 weeks in different orders. At the end of each treatment period lipids and safety parameters in blood and GI complaints were evaluated by questionnaires, and faecal microbiota and SCFAs were measured. Furthermore, test-tube incubations of faecal slurries with D-tagatose, fructo-oligosaccharides and sucrose were performed. An in vitro model simulating the large intestine was used to assess the mechanistic effect of D-tagatose on microbiota composition and SCFA production. The high-tagatose treatment resulted in increased numbers of faecal lactobacilli in men, but not in women. Also in vitro , lactobacilli increased. Both the test-tube incubations of fresh faeces from the in vivo study with D-tagatose and the study in the in vitro model showed increased butyrate production after all treatments with D-tagatose. High-tagatose, but not lowtagatose, resulted in a slightly increased defecation frequency and stools of thinner consistency. Only a few GI complaints were reported. The data indicate that daily consumption of 7.5 or 12.5 g D-tagatose may lead to increased production of butyrate and to an increase of lactobacilli, without serious GI complaints. In view of the health-promoting effects of butyrate and lactobacilli, D-tagatose may be considered a prebiotic substrate.Key words: D-tagatose, butyrate, microbiota, colon, healthy subjects, gastrointestinal health

Background: A high homocysteine concentration is a potential risk factor for cardiovascular disease that can be reduced through betaine supplementation. Choline is the precursor for betaine, but the effects of choline supplementation on plasma total homocysteine (tHcy) concentrations in healthy humans are unknown. Objective: The objective was to investigate whether supplementation with phosphatidylcholine, the form in which choline occurs in foods, reduces fasting and postmethionine-loading concentrations of plasma tHcy in healthy men with mildly elevated plasma tHcy concentrations. Design: In a crossover study, 26 men ingested ≈2.6 g choline/d (as phosphatidylcholine) or a placebo oil mixture for 2 wk in random order. Fatty acid composition and fat content were similar for both treatments. A methionine-loading test was performed on the first and last days of each supplementation period. Results: Phosphatidylcholine supplementation for 2 wk decreased mean fasting plasma tHcy by 18% (-3.0 μmol/L; 95% CI: -3.9, -2.1 μmol/L). On the first day of supplementation, a single dose of phosphatidylcholine containing 1.5 g choline reduced the postmethionine-loading increase in tHcy by 15% (-4.8 μmol/L; 95% CI: -6.8, -2.8 μmol/L). Phosphatidylcholine supplementation for 2 wk reduced the postmethionine-loading increase in tHcy by 29% (-9.2 μmol/L; 95% CI: -11.3, -7.2 μmol/L). All changes were relative to placebo. Conclusions: A high daily dose of choline, supplemented as phosphatidylcholine, lowers fasting as well as postmethionine-loading plasma tHcy concentrations in healthy men with mildly elevated tHcy concentrations. If high homocysteine concentrations indeed cause cardiovascular disease, choline intake may reduce cardiovascular disease risk in humans. © 2005 American Society for Clinical Nutrition.

Objective: To evaluate both efficacy and safety in humans of long-term consumption of spreads containing plant sterol esters. Design: Randomized double-blind placebo-controlled parallel trial. Subjects: Hundred and eighty-five healthy volunteers (35-64y). Intervention: Volunteers daily consumed 20g spread enriched with 1.6g plant sterols as fatty acid esters or a control spread for 1 y. They continued their habitual diet and lifestyle. Outcome measures included efficacy markers such as total and LDL-cholesterol, a large range of safety parameters, and reporting of adverse events. Results: Consumption of the plant sterol ester-enriched spread consistently lowered total and LDL cholesterol during the 1 y period on average by 4 and 6%, respectively (0.01 < P < 0.05). Plant sterols intake did on average not result in a lower carotenoid concentration (when expressed per LDL-cholesterol) after 52 weeks (P > 0.05). However, carotenoid concentrations changed over time. Plant sterols intake reduced lipid adjusted α- and β-carotene-concentrations by only 15-25% after 1 y, relative to control. Lipid-adjusted fat-soluble vitamin concentrations remained unchanged. Plant sterol concentrations in serum were increased from 2.76 to 5.31 (μmol/mmol total cholesterol) for campesterol (P < 0.0001) and from 1.86 to 2.47 (μmol/mmol total cholesterol) for β-sitosterol (P < 0.0001). The increase in total plant sterol concentration in red blood cells (5.29-9.62 μg/g) did not affect red blood cell deformability. Hormone levels in males (free and total testosterone) and females (luteinizing hormone, follicle stimulating hormone, β-estradiol and progesterone) as well as all clinical chemical and hematological parameters measured were unaffected. Adverse events reported were not different between subjects consuming control spread and subjects consuming plant sterol esters-enriched spread. Conclusion: Consumption of a plant sterol esters-enriched spread is an effective way to consistently lower blood cholesterol concentrations and is safe to use over a long period of time.

Objective: Several intervention trials have shown that diet composition affects blood pressure (BP). In this study we focused on postprandial hemodynamic changes on a high carbohydrate versus a high protein diet. Design and Method: In this randomized double-blind parallel group study, 53 adult untreated overweight subjects with mildly elevated BP (BMI 25-35 kg/m2, BP > 130/85 and

Vegetable fats and oils are major sources of dietary vitamin E. Consequently the current trend to reduce fat consumption is accompanied by a reduction of the intake of vitamin E. In addition, the absorption of vitamin E is thought to be dependent on the hydroiysis of dietary lipids in the small intestine. It is therefore conceivable that a lower dietary fat intake also diminishes the intestinal absorption of vitamin E. The present 3-week feeding study in young male rats was designed to investigate whether different concentrations of vitamin E added to a very-low-fat product (0, 330 or 1350mgdl-α-tocopheryl acetate/kg product) were absorbed. We therefore incorporated these products into a very-low-fat meal (final fat concentration: 7 g/kg) or a low-fat meal containing 52 g fat/kg. The magnitude of vitamin E absorption from these meals was compared with that from meals containing similar amounts of vitamin E, but a high fat concentration of 190 g/kg. Apparent vitamin E absorption was defined as intake of α- tocopherol equivalents (αTE) minus faecal αTE excretion over 4 d during week 3 of the experimental period. The results of this study showed that apparent absorption of vitamin E from a very-low-fat meal varied, depending on the vitamin E concentration, from 73 to 83%. The magnitude of this vitamin E absorption was not significantly different from that from meals containing a high amount of fat. Liver vitamin E status was equal in rats fed on the very-low-fat meals compared with those fed on the high- fat meals. We conclude that, when very-low-fat or low-fat products are used as a replacement for full- fat products, addition of vitamin E to these products, asdl-α-tocopheryl acetate, might be useful in meeting the vitamin E requirements.

In this study the effect of the positional distribution of stearic acid (18 :0) and oleic acid (18 :1) in a triacylglycerol on absorption of fat, energy and nutrients was investigated in young rats. In addition the effect of dietary calcium on these variables was studied. Forty rats were fed purified diets containing either a fat blend high in 2-oleoyl-distearate or a fat blend high in 1-oleoyl-distearate. Both diets were given at low (0.3 g/100 g) and high (1.0 g/100 g) dietary calcium concentrations. Total fat absorption, expressed as the percentage of fat intake, was significantly lower in rats fed 2-oleoyl-distearate compared with 1-oleoyl-distearate at both dietary calcium concentrations. When expressed as absolute figures, the lower fat absorption in rats fed 2-oleoyl-distearate compared with 1-oleoyl-distearate only reached statistical significance at the high dietary calcium concentration. The reduced absorption of total fat was mainly caused by the lower absorption of stearic acid. The percentage of, but not absolute, absorption of oleic acid and energy were lower in rats fed 2-oleoyl-distearate. Absolute and percentage of calcium absorption were lower in rats fed 2-oleoyl-distearate compared with 1-oleoyl-distearate. Absolute and percentage of magnesium absorption were not significantly affected by the positional distribution of stearic acid and oleic acid in the triacylglycerol, but were decreased at a high dietary calcium concentration. We concluded that the lowered stearic acid absorption from 2-oleoyl-distearate compared with 1-oleoyl-distearate might have been due to the greater formation of insoluble calcium and magnesium soaps in the intestine. J. Nutr. 125 : 2379-2387, 1995.

The effect of lactose on the urinary excretion of Mg and Ca, as an index of absorption, was studied in a double-blind, crossover study during three 1-week periods. Twenty-four healthy, lactose-tolerant, adult volunteers maintained their habitual diets with the exception that all lactose-containing dairy products in the diet were replaced by 600 g/d of three specially prepared dairy products. These products were based on either lactose-enriched cow's milk or lactose-enriched, lactase (EC3.2.1.23)-treated cow's milk, with or without added Mg, and were given in turn during 1 week. Lactose intake was increased by 127 mmol/d (46 g/d) while taking the lactose-enriched products. While taking the Mg-enriched products, Mg intake was increased by 2.8 mmol/d (69 mg/d) which was equivalent to 17% of the habitual Mg intake. Apart from the lactose and Mg intake, nutrient intake was comparable during the three dietary periods. Urinary excretions of Mg and Ca were used as indicators for their absorption. Mg supplementation significantly increased urinary Mg excretion by 0.97 mmol/d (equivalent to an increase of 18%,P< 0.001), indicating that urinary Mg excretion is a valid indicator for intestinal Mg absorption. Hydrolysis of lactose did not affect urinary excretion of Mg and Ca, which implies that lactose intake does not affect the absorption of Mg and Ca in healthy adults.

The hypothesis was tested that dietary lactosev. glucose stimulates Mg absorption in rats because lactose lowers pH of the ileal lumen, which improves Mg solubility which in turn enhances Mg availability for transport across the ileal epithelium. For comparison, the effects of lactulose were studied because it shares with lactose the characteristic of being poorly digestible. Replacement of glucose by lactose (100 g/Kg) significantly stimulated apparent absorption of Mg. Apart from Mg absorption, lactulose also significantly enhanced absorption of Ca and phosphate. Lactosev. glucose lowered the pH of the ileal lumen from 7·5 to 7·2, whereas lactulose significantly reduced it to 7·0. Inin vitroincubations a decrease in pH within the range of fluctuationin vivowas found to cause an improved solubility of Mg, and to a lesser extent also of Ca and phosphate. The smaller fall of ileal pH induced by feeding lactose instead of lactulose may explain why lactose improved Mg absorption only. For all individual rats combined there were negative relationships between ileal pH and apparent absorption of minerals, the relationship being strongest for Mg. Neither lactose nor lactulose was found to raise ileal solubility of minerals, which could relate to the possibility that the time of sampling was not appropriate. It is suggested that lactose-induced stimulation of Mg absorption in rats is caused by a lowering of ileal pH.

We tested the hypothesis that increased intakes of calcium and phosphate lower magnesium solubility in the intestinal lumen, causing a decreased magnesium absorption. In in vitro experiments at a constant magnesium concentration, increasing calcium concentrations reduced magnesium solubility. This effect did not occur in the absence of phosphate. Increasing phosphate concentrations decreased the solubility of magnesium in the presence, but not in the absence, of calcium. These results suggest that the formation of an insoluble calcium-magnesium-phosphate complex determines magnesium solubility. To extend this concept to in vivo conditions, rats were fed purified diets containing a constant concentration of magnesium (16.4 mumol/g) but different concentrations of calcium (25, 100 or 175 mumol/g) and phosphate (58, 103 or 161 mumol/g). Increased intakes of calcium decreased magnesium solubility in the ileal lumen and lowered magnesium absorption. The latter result occurred only if the dietary phosphate concentration was at least 103 mumol/g. Increasing dietary phosphate concentrations reduced both magnesium solubility in the ileum and magnesium absorption, but only if the dietary calcium concentration was at least 100 mumol/g. These results support those obtained in vitro. We conclude that increased intakes of calcium and phosphate decrease magnesium absorption by the formation of an insoluble calcium-magnesium-phosphate complex in the intestinal lumen.

The milk components lactose and casein enhance the apparent absorption of magnesium and possibly also of calcium, whereas phytate, which occurs in soya-bean products, has an inhibitory effect. This implies that soya-bean beveragev.cow's milk could lower bioavailability of Mg and Ca. This hypothesis was tested in two experiments with growing rats. Feeding soya-bean beveragev.cow's milk consistently lowered body-weight gain, enhanced bone turnover, as measured by increased plasma alkaline phosphatase (EC3.1.3.1) activity and increased urinary hydroxyproline excretion, and decreased Mg and Ca concentrations in the femur. Because the mineral compositions of the soya-bean beverage and the cow's milk were different, the intake of Mg was higher in rats fed on soya-bean beverage, whereas that of Ca was higher in rats fed on cow's milk. Supplementation of the soya-bean beverage either with phosphorus and Ca or with P, Ca and methionine, to concentrations identical to those in milk, restored growth and bone mineralization. When using diets carefully balanced for Mg, Ca, P, sodium, potassium and methionine, soya-bean beveragev.cow's milk in the diets decreased apparent absorption and urinary excretion of Mg and Ca. Hydrolysis of lactose in milk decreased absorption and urinary excretion of Mg; it did not significantly affect Ca absorption but lowered urinary Ca excretion. The present study shows that soya-bean beveragev.milk depresses Mg and Ca bioavailability, as would be predicted on the basis of reported effects of their purified components.

There is growing evidence from epidemiological studies that dietary protein may beneficially influence blood pressure (BP), but findings are inconclusive. We performed a meta-analysis of 29 observational studies and randomized controlled trials (RCTs) of dietary protein and types of protein in relation to BP or incident hypertension, published until January 2012. The analysis included eight cross-sectional studies (n = 48 985), four prospective studies (n = 11 761) and 17 RCTs (n = 1449). A modest inverse association between total protein intake and BP ( 0.20 mm Hg systolic (95% CI: 0.39, 0.01) per 25 g (similar to 1 s.d.)) was found in cross-sectional studies, but not in prospective studies (relative risk of 0.99 (95% CI: 0.96, 1.02)). For RCTs that used carbohydrate as a control treatment, the pooled BP effect was -2.11 mm Hg systolic (95% CI: -2.86, -1.37) for a weighed mean contrast in protein intake of 41 g per day. A non-significant inverse association of -0.52 mm Hg systolic (95% CI: -1.10, +0.05) per 11 g (similar to 1 s.d.) was found for plant protein in cross-sectional studies, whereas animal protein was not associated with BP. In prospective studies and RCTs, however, the associations of plant protein and animal protein with BP were broadly similar. These findings suggest that increasing the intake of protein at the expense of carbohydrates may have a beneficial effect on BP. The BP effect of specific types of protein remains to be established.