Zinc Absorption from Milk Is Affected by Dilution but Not by Thermal Processing, and Milk Enhances Absorption of Zinc from High-Phytate Rice in Young Dutch Women.

Background: Milk has been suggested to increase zinc absorption. The effect of processing and the ability of milk to enhance zinc absorption from other foods has not been measured directly in humans.Objective: We aimed to assess zinc absorption from 1) milk undergoing various processing and preparatory steps and 2) from intrinsically labeled high-phytate rice consumed with milk or water.Methods: Two randomized crossover studies were conducted in healthy young women [age:18-25 y; body mass index (in kg/m2): 20-25]: 1) a milk study (n = 19) comparing the consumption of 800 mL full-fat ultra-high temperature (UHT) milk [heat-treated milk (HTM)], full-fat UHT milk diluted 1:1 with water [heat-treated milk and water (MW)], water, or unprocessed (raw) milk (UM), each extrinsically labeled with 67Zn, and 2) a rice study (n = 18) comparing the consumption of 90 g intrinsically 67Zn-labeled rice with 600 mL of water [rice and water (RW)] or full-fat UHT milk [rice and milk (RM)]. The fractional absorption of zinc (FAZ) was measured with the double-isotope tracer ratio method. In vitro, we assessed zinc extraction from rice blended into water, UM, or HTM with or without phytate.Results: FAZ from HTM was 25.5% (95% CI: 21.6%, 29.4%) and was not different from UM (27.8%; 95% CI: 24.2%, 31.4%). FAZ from water was higher (72.3%; 95% CI: 68.7%, 75.9%), whereas FAZ from MW was lower (19.7%; 95% CI: 17.5%, 21.9%) than HTM and UM (both P < 0.01). FAZ from RM (20.7%; 95% CI: 18.8%, 22.7%) was significantly higher than from RW (12.8%; 95% CI: 10.8%, 14.6%; P < 0.01). In vitro, HTM and UM showed several orders of magnitude higher extraction of zinc from rice with HTM than from rice with water at various phytate concentrations.Conclusions: Milk enhanced human FAZ from high-phytate rice by 62% compared with water. Diluting milk with water decreases its absorption-enhancing proprieties, whereas UHT processing does not. This trial was registered at the Dutch trial registry as NTR4267 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4267).

Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial.

An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18-70 years of age, with a body mass index >25 kg/m(2), elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure.

Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges.

BACKGROUND: Resilience or the ability of our body to cope with daily-life challenges has been proposed as a new definition of health, with restoration of homeostasis as target resultant of various physiological stress responses. Challenge models may thus be a sensitive measure to study the body's health. The objective of this study was to select a dietary challenge model for the assessment of inflammatory resilience. Meals are a challenge to metabolic homeostasis and are suggested to affect inflammatory pathways, yet data in literature are limited and inconsistent. METHOD: The kinetic responses of three different dietary challenges and a water control challenge were assessed on various metabolic and inflammatory markers in 14 healthy males and females using a full cross-over study design. The dietary challenges included glucose (75 g glucose in 300 ml water), lipids (200 ml whipping cream) and a mix of glucose and lipids (same amounts as above), respectively. Blood samples were collected at baseline and at 0.5, 1, 2, 4, 6, 8 and 10 h after consumption of the treatment products. Inflammation (IFNγ, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-α CRP, ICAM-1, VCAM-1, SAA, E-selectin, P-selectin, thrombomodulin, leukocytes, neutrophils, lymphocytes) and clinical (e.g. glucose, insulin, triglycerides) markers as well as gene expression in blood cells and plasma oxylipin profiles were measured. RESULTS: All three dietary challenges induced changes related to metabolic control such as increases in glucose and insulin after the glucose challenge and increases in triglycerides after the lipid challenge. In addition, differences between the challenges were observed for precursor oxylipins and some downstream metabolites including DiHETrE's and HODE's. However, none of the dietary challenges induced an acute inflammatory response, except for a modest increase in circulating leukocyte numbers after the glucose and mix challenges. Furthermore, subtle, yet statistically significant increases in vascular inflammatory markers (sICAM-1 and sVCAM-1) were found after the mix challenge, when compared to the water control challenge. CONCLUSIONS: This study shows that dietary glucose and lipid challenges did not induce a strong acute inflammatory response in healthy subjects, as quantified by an accurate and broad panel of parameters.

IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial.

BACKGROUND: Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH) on reducing blood pressure (BP) as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II. METHODS: We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP), MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP), or placebo (containing cellulose) for 4 weeks. RESULTS: In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080) and diastolic BP by 2.3 mm Hg (P = 0.0065) compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II. CONCLUSIONS: MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP. TRIAL REGISTRATION: ClinicalTrials.gov NCT00471263.

Measures of postprandial wellness after single intake of two protein-carbohydrate meals.

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 + or - 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 4h 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.

Lactotripeptides and antihypertensive effects: a critical review.

Hypertension or high blood pressure is a significant health problem worldwide. Typically, lifestyle changes, including adopting a healthy diet, are recommended for people with an elevated blood pressure. Lactotripeptides are bioactive milk peptides with potential antihypertensive properties in man. These peptides, as part of a food product or as nutraceutical, may contribute to the prevention and treatment of hypertension. This paper reviews the current evidence of the blood pressure control properties of lactotripeptides in man. Blood pressure-lowering effects of lactotripeptides are typically measured after 4-6 weeks of treatment. However, in some cases, a blood pressure response has been observed after 1-2 weeks. Maximum blood pressure reductions approximate 13 mmHg (systolic blood pressure) and 8 mmHg (diastolic blood pressure) after active treatment compared with placebo, and are likely reached after 8-12 weeks of treatment. Effective dosages of lactotripeptides range from 3.07 to 52.5 mg/d. Evidence indicates that lactotripeptides are only effective at elevated blood pressure; no further lowering of normal blood pressure has been observed. Concomitant intake of antihypertensive medication does not seem to influence the potency of lactotripeptides to lower blood pressure. Similarly, ethnicity has not been found to influence the extent of lactotripeptide-induced blood pressure lowering. Based on the currently available data, lactotripeptides appear to be safe and effective. Thus, they can be part of a healthy diet and lifestyle to prevent or reduce high blood pressure.

Evidence of the regulatory effect of Ginkgo biloba extract on skin blood flow and study of its effects on urinary metabolites in healthy humans.

Ginkgo biloba extract has been advocated for the improvement of blood circulation in circulatory disorders. This study investigated the effect of the Gingko biloba extract EGb 761 on skin blood flow in healthy volunteers and accompanying changes in urinary metabolites. Twenty-seven healthy middle-aged subjects participated in a randomized, double-blind, placebo-controlled, crossover study. Subjects received 240 mg/d EGb 761 or placebo for periods of 3 weeks. Skin blood flow was measured on the forefoot using laser Doppler flowmetry and changes in urinary metabolites were identified by a combination of nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis (MVDA). These measurements were performed on 24-h urine samples collected at the end of the intervention periods. Following EGb 761 treatment, overall mean skin blood flow was significantly reduced as compared with placebo. Remarkably, the change of skin blood flow after EGb 761 intervention was proportionally related to blood flow after placebo treatment: subjects showed either an increased, decreased or unaltered skin blood flow. NMR/MDVA analyses showed that urinary metabolic patterns differed depending on the change in baseline blood flow after treatment with EGb 761. The present findings substantiate that EGb 761 has a multi-directional modulating action on blood flow in healthy subjects and support findings of a vasoregulatory role of this extract. Moreover, the results indicate that metabolic fingerprinting provides a powerful means to identify biochemical markers that are associated with functional changes.

Dietary serine and cystine attenuate the homocysteine-raising effect of dietary methionine: a randomized crossover trial in humans.

BACKGROUND: A high plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease. The increase in tHcy induced by methionine, the sole dietary precursor of homocysteine, might be modulated by other amino acids present in dietary proteins. OBJECTIVES: Our objectives were to compare the postprandial effect of free and dietary methionine on plasma tHcy concentrations and to investigate whether serine and cystine modify the effect of free methionine on tHcy. DESIGN: We conducted a randomized crossover trial in 24 healthy men. Each subject ingested 4 meals on separate days, which were separated by 1 wk. tHcy concentrations were measured in the fasting state and at 2, 4, 6, 8, 10, and 24 h after meal ingestion. The meals were 1) a low-protein meal fortified with 30 mg methionine/kg body wt (reference, denoted by "Met"), 2) meal 1 additionally fortified with 60.6 mg serine/kg body wt (MetSer), 3) meal 1 additionally fortified with 12.3 mg cystine/kg body wt (MetCys), and 4) a protein-rich meal containing 30 mg methionine, 60.6 mg serine, and 12.3 mg cystine per kg body wt (Protein). RESULTS: The mean (+/-SD) fasting tHcy concentration was 9.1 +/- 2.7 micromol/L. Mean peak tHcy concentrations were 17.9 +/- 4.5, 14.3 +/- 3.3, 14.8 +/- 3.9, and 11.2 +/- 3.1 micromol/L after Met, MetSer, MetCys, and Protein, respectively. Compared with the mean 24-h area under the tHcy-by-time curve after Met, the mean curves after MetSer, MetCys, and Protein were 37%, 32%, and 77% smaller, respectively (all P < 0.0005). CONCLUSIONS: Dietary methionine increases tHcy much less than does free methionine. Serine and cystine attenuate the tHcy-raising effect of free methionine. Thus, dietary proteins with a high content of serine or cystine relative to methionine may lead to lower postprandial tHcy responses.

Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women.

High plasma homocysteine is a risk for cardiovascular disease and can be lowered through supplementation with 6 g/d of betaine. However, dietary intake of betaine is approximately 0.5-2 g/d. Therefore, we investigated whether betaine supplementation in the range of dietary intake lowers plasma homocysteine concentrations in healthy adults. Four groups of 19 healthy subjects ingested three doses of betaine or placebo daily for 6 wk. A methionine loading test was performed during run in, on d 1 of betaine supplementation, and after 2 and 6 wk of betaine supplementation. Fasting plasma homocysteine after 6-wk daily intakes of 1.5, 3 and 6 g of betaine was 12% (P < 0.01), 15% (P < 0.002) and 20% (P < 0.0001) less than in the placebo group, respectively. Furthermore, the increase in plasma homocysteine after methionine loading on the 1st d of betaine supplementation was 16% (P < 0.06), 23% (P < 0.008) and 35% (P < 0.0002) less than in the placebo group, respectively, and after 6 wk of supplementation was 23% (P < 0.02), 30% (P < 0.003) and 40% (P < 0.0002) less, respectively. Thus, doses of betaine in the range of dietary intake reduce fasting and postmethionine loading plasma homocysteine concentrations. A betaine-rich diet might therefore lower cardiovascular disease risk.

Human skin condition and its associations with nutrient concentrations in serum and diet.

BACKGROUND: Nutritional factors exert promising actions on the skin, but only scant information is available on the modulating effects of physiologic concentrations of nutrients on the skin condition of humans. OBJECTIVE: The objective was to evaluate whether nutrient concentrations in serum and diet are associated with the skin condition of humans. DESIGN: A cross-sectional study was conducted in which data on serum concentrations of nutrients, dietary intake of nutrients, and the hydration, sebum content, and surface pH of skin were obtained from 302 healthy men and women. Skin condition was measured with the use of noninvasive techniques. Dietary intake was assessed with 2 complementary food-frequency questionnaires. Multiple regression analysis was used to evaluate associations of serum vitamins and carotenoids and of dietary micro- and macronutrients with skin condition. RESULTS: After adjustment for potential confounders, including sex, age, and smoking, statistically significant associations were shown in the total population between serum vitamin A and skin sebum content and surface pH and between the dietary intake of total fat, saturated fat, monounsaturated fat, and skin hydration. Monounsaturated fat intake was also associated with surface pH. Associations between serum beta-cryptoxanthin and skin hydration and between surface pH and fluid and calcium intakes were observed in men only. CONCLUSION: Several associations between nutrients in serum and diet and skin condition were observed, indicating that changes in baseline nutritional status may affect skin condition.

Characterization of reconstructed skin models.

The aim of the present study was to evaluate tissue architecture and lipid composition of commercially available reconstructed human skin models; EpiDerm, SkinEthic and Episkin in comparison to in-house reconstructed epidermis on a de-epidermized dermis (RE-DED) model and native tissue. For this purpose, the tissue architecture was examined using light microscopy, electron microscopy and immunohistochemistry; epidermal lipid composition was analyzed by HPTLC. Histological examination showed a completely stratified epithelium in all skin models closely resembling normal human epidermis. Low intra-batch variation in tissue architecture was observed in all skin models, but moderate to considerable inter-batch variation was noticed. In the stratum corneum extracellular space, lipid lamellae consisting of multiple alternating electron-dense and electron-lucent bands were present. Lipid analyses revealed the presence of all major epidermal lipid classes. Compared with native epidermis and RE-DED in EpiDerm, SkinEthic and Episkin models, the content of polar ceramides 5 and 6 was lower, ceramide 7 was absent, and the content of free fatty acids was very low. Evaluation of the expression and localization of a number of differentiation-specific protein markers revealed that all skin models showed an aberrant expression of keratin 6, skin-derived antileukoproteinase, small-proline-rich proteins, involucrin and transglutaminase. Although variation within batches was low, in particular keratin 6, involucrin and skin-derived antileukoproteinase expression demonstrated some inter-batch variation. In conclusion, all skin models provide a promising means for studying the effects of topically applied chemicals, although the observed deviations in tissue homeostasis and barrier properties need to be diminished. All skin models tested reproduced many of the characteristics of normal human epidermis and therefore provide a morphologically relevant in vitro means to assess skin irritation and perform other skin-related studies.