Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D.

CONTEXT AND PURPOSE: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. METHODS: IPD analysis using data from 1429 participants (ages 2-89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. RESULTS: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). CONCLUSIONS: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.

Duckweed for Human Nutrition: No Cytotoxic and No Anti-Proliferative Effects on Human Cell Lines.

Duckweeds (Lemnaceae) possess good qualitative and quantitative profiles of nutritional components for its use as human food. However, no studies have been conducted on the probable presence or absence of any adverse effects. The extracts from seven duckweed species (Spirodela polyrhiza, Landoltia punctata, Lemna gibba, Lemna minor, Wolffiella hyalina, Wolffia globosa, and Wolffia microscopica) covering all five genera of the plant family were herewith tested for cytotoxic effects on the human cell lines HUVEC, K-562, and HeLa and for anti-proliferative activity on HUVEC and K-562 cell lines. From these assays, it is evident that duckweeds do not possess any detectable anti-proliferative or cytotoxic effects, thus, the high nutritional value is not diminished by such detrimental factors. The present result is a first step to exclude any harmful effects of highly nutritious duckweed for human.

High phosphorus intake and gut-related parameters - results of a randomized placebo-controlled human intervention study.

BACKGROUND: In recent years, high phosphate intakes were discussed critically. In the small intestine, a part of the ingested phosphate and calcium precipitates to amorphous calcium phosphate (ACP), which in turn can precipitate other intestinal substances, thus leading to a beneficial modulation of the intestinal environment. Therefore, we analysed faecal samples obtained from a human intervention study regarding gut-related parameters. METHODS: Sixty-two healthy subjects (men, n = 30; women, n = 32) completed the double-blind, placebo-controlled and parallel designed study (mean age: 29 ± 7 years; mean BMI: 24 ± 3 kg/m2). Supplements were monosodium phosphate and calcium carbonate. During the first 2 weeks, all groups consumed a placebo sherbet powder, and afterwards a sherbet powder for 8 weeks according to the intervention group: P1000/Ca0 (1000 mg/d phosphorus), P1000/Ca500 (1000 mg/d phosphorus and 500 mg/d calcium) and P1000/Ca1000 (1000 mg/d phosphorus and 1000 mg/d calcium). After the placebo period and after 8 weeks of intervention faecal collections took place. We determined in faeces: short-chain fatty acids (SCFA) and fat as well as the composition of the microbiome (subgroup) and cyto- and genotoxicity of faecal water (FW). By questionnaire evaluation we examined tolerability of the used phosphorus supplement. RESULTS: Faecal fat concentrations did not change significantly due to the interventions. Concentrations of faecal total SCFA and acetate were significantly higher after 8 weeks of P1000/Ca500 supplementation compared to the P1000/Ca0 supplementation. In men, faecal total SCFA and acetate concentrations were significantly higher after 8 weeks in the P1000/Ca1000 group compared to the P1000/Ca0 one. None of the interventions markedly affected cyto- and genotoxic activity of FW. Men of the P1000/Ca1000 intervention had a significantly different gut microbial community compared to the men of the P1000/Ca0 and P1000/Ca500 ones. The genus Clostridium XVIII was significantly more abundant in men of the P1000/Ca1000 intervention group compared to the other groups. Supplementations did not cause increased intestinal distress. CONCLUSIONS: The used high phosphorus diet did not influence cyto- and genotoxicity of FW and the concentrations of faecal fat independent of calcium intake. Our study provides first hints for a potential phosphorus-induced modulation of the gut community and the faecal total SCFA content. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov as NCT02095392 .

ANGPTL8 (Betatrophin) is Expressed in Visceral Adipose Tissue and Relates to Human Hepatic Steatosis in Two Independent Clinical Collectives.

Angiopoietin-like protein 8 (ANGPTL8)/betatrophin expression in visceral adipose tissue and associations with circulating fatty acid profile have not yet been investigated.Forty subjects were included in a cross-sectional study, 57 in a dietary weight reduction intervention. Circulating Angiopoietin-like protein 8/betatrophin was measured in all subjects. Liver and adipose tissue were sampled and plasma fatty acids and tissue Angiopoietin-like protein 8/betatrophin expression were evaluated in the cross-sectional study. In the intervention study oral glucose testing and liver magnetic resonance scanning at baseline and after 6 months were performed. Angiopoietin-like protein 8/betatrophin mRNA was increased in visceral compared to subcutaneous adipose tissue (p<0.001). Circulating ANGPTL8/betatrophin correlated with liver steatosis (r=0.42, p=0.047), triacylglycerols (r=0.34, p=0.046), saturated (r=0.43, p=0.022), monounsaturated (r=0.51, p=0.007), and polyunsaturated fatty acids (r=-0.53, p=0.004). In the intervention study, baseline Angiopoietin-like protein 8/betatrophin correlated with age (r=0.32, p=0.010) and triacylglycerols (r=0.30, p=0.02) and was increased with hepatic steatosis (p=0.033). Weight loss reduced liver fat by 45% and circulating Angiopoietin-like protein 8/betatrophin by 11% (288±17 vs. 258±17 pg/ml; p=0.015). Angiopoietin-like protein 8/betatrophin is related to liver steatosis, while visceral adipose tissue represents an additional site of expression in humans.

Increased lipogenesis in spite of upregulated hepatic 5'AMP-activated protein kinase in human non-alcoholic fatty liver.

AIMS: Molecular adaptations in human non-alcoholic fatty liver disease (NAFLD) are incompletely understood. This study investigated the main gene categories related to hepatic de novo lipogenesis and lipid oxidation capacity. METHODS: Liver specimens of 48 subjects were histologically classified according to steatosis severity. In-depth analyses were undertaken using real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. Lipid profiles were analyzed by gas chromatography/flame ionization detection, and effects of key fatty acids were studied in primary human hepatocytes. RESULTS: Real-time polymerase chain reaction, immunoblotting, and immunohistochemistry indicated 5'AMP-activated protein kinase (AMPK) to be increased with steatosis score ≥ 2 (all P < 0.05), including various markers of de novo lipogenesis and lipid degradation (all P < 0.05). Regarding endoplasmic reticulum stress, X-Box binding protein-1 (XBP1) was upregulated in steatosis score ≥ 2 (P = 0.029) and correlated with plasma palmitate (r = 0.34; P = 0.035). Palmitate incubation of primary human hepatocytes increased XBP1 and downstream stearoyl CoA desaturase-1 mRNA expression (both P < 0.05). Moreover, plasma and liver tissue exposed a NAFLD-related lipid profile with reduced polyunsaturated/saturated fatty acid ratio, increased palmitate and palmitoleate, and elevated lipogenesis and desaturation indices with steatosis score ≥ 2 (all P < 0.05). CONCLUSION: In humans with advanced fatty liver disease, hepatic AMPK protein is upregulated, potentially in a compensatory manner. Moreover, pathways of lipid synthesis and degradation are co-activated in subjects with advanced steatosis. Palmitate may drive lipogenesis by activating XBP1-mediated endoplasmic reticulum stress and represent a target for future dietary or pharmacological intervention.

Evaluation of the Impact of Ruminant Trans Fatty Acids on Human Health: Important Aspects to Consider.

The definition and evaluation of trans fatty acids (TFA) with regard to foodstuffs and health hazard are not consistent. Based on the current situation, the term should be restricted only to TFA with isolated double bonds in trans-configuration. Conjugated linoleic acids (CLA) should be separately assessed. Ideally, the origin of the consumed fat should be declared, i.e., ruminant TFA (R-TFA) and industrial TFA (non-ruminant; I-TFA). In ruminant fat, more than 50% of R-TFA consists of vaccenic acid (C18:1 t11). In addition, natural CLA, i.e., c9,t11 CLA is also present. Both are elevated in products from organic farming. In contrast to elaidic acid (t9) and t10, which occur mainly in partially hydrogenated industrial fat, t11 is partially metabolized into c9,t11 CLA via Δ9-desaturation. This is the major metabolic criterion used to differentiate between t11 and other trans C18:1. t11 indicates health beneficial effects in several studies. Moreover, CLA in milk fat is associated with the prevention of allergy and asthma. An analysis of the few studies relating to R-TFA alone makes clear that no convincing adverse physiological effect can be attributed to R-TFA. Only extremely high R-TFA intakes cause negative change in blood lipids. In conclusion, in most European countries, the intake of R-TFA is assessed as being low to moderate. Restriction of R-TFA would unjustifiably represent a disadvantage for organic farming of milk.

Consequences of a high phosphorus intake on mineral metabolism and bone remodeling in dependence of calcium intake in healthy subjects - a randomized placebo-controlled human intervention study.

BACKGROUND: Epidemiological studies reported an association between plasma phosphate concentrations and a higher risk for death and cardiovascular events in subjects free of chronic kidney diseases. The main aims of the present study were to determine the influence of a high phosphorus intake in combination with different calcium supplies on phosphorus, calcium, magnesium and iron metabolism as well as fibroblast growth factor 23 (FGF23) concentrations within eight weeks of supplementation. METHODS: Sixty-two healthy subjects completed the double-blind, placebo-controlled parallel designed study. Supplements were monosodium phosphate and calcium carbonate. During the first two weeks, all groups consumed a placebo sherbet powder, and afterwards, for eight weeks, a sherbet powder according to the intervention group: P1000/Ca0 (1 g/d phosphorus), P1000/Ca500 (1 g/d phosphorus and 0.5 g/d calcium) and P1000/Ca1000 (1 g/d phosphorus and 1 g/d calcium). Dietary records, fasting blood samplings, urine and fecal collections took place. RESULTS: Fasting plasma phosphate concentrations did not change after any intervention. After all interventions, renal excretions and fecal concentrations of phosphorus increased significantly after eight weeks. Renal calcium and magnesium excretion decreased significantly after eight weeks of P1000/Ca0 intervention compared to placebo. Plasma FGF23 concentrations were significantly higher after four weeks compared to eight weeks of all interventions. CONCLUSIONS: The long-term study showed in healthy adults no influence of high phosphorus intakes on fasting plasma phosphate concentrations. A high phosphorus intake without adequate calcium intake seems to have negative impact on calcium metabolism. Plasma FGF23 concentrations increased four weeks after high phosphorus intake and normalized after eight weeks. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov as NCT02095392 .

Consumption of echium oil increases EPA and DPA in blood fractions more efficiently compared to linseed oil in humans.

BACKGROUND: A plant-based strategy to improve long-chain (LC) omega (n)-3 PUFA supply in humans involves dietary supplementation with oils containing α-linolenic acid (ALA) alone or in combination with stearidonic acid (SDA). The study aimed to compare the effects of echium oil (EO) and linseed oil (LO) on LC n-3 PUFA accumulation in blood and on clinical markers. METHODS: In two double-blind, parallel-arm, randomized controlled studies, all volunteers started with 17 g/d run-in oil (2 weeks). Thereafter, subjects received diets enriched in study 1 with EO (5 g ALA + 2 g SDA; n = 59) or in study 2 with LO (5 g ALA; n = 9) daily for 8 weeks. The smaller control groups received fish oil (FO; n = 19) or olive oil (OO; n = 18). Participants were instructed to restrict their dietary n-3 PUFA intake throughout the studies (e.g., no fish). To investigate the influence of age and BMI on the conversion of ALA and SDA as well as clinical markers, the subjects recruited for EO and LO treatment were divided into three subgroups (two age groups 20-35 y; 49-69 y with BMI 18-25 kg/m(2) and one group with older, overweight subjects (age 49-69 y; BMI >25 kg/m(2)). RESULTS: In plasma, red blood cells (RBC), and peripheral blood mononuclear cells (PBMC), EPA and docosapentaenoic acid (DPA) were ~25 % higher following EO compared to LO. Comparing all treatments, the effectiveness of increasing EPA and DPA in plasma, RBC, and PBMC was on average 100:25:10:0 and 100:50:25:0 for FO:EO:LO:OO, respectively. EO led to a lower arachidonic acid/EPA-ratio compared to LO in plasma, RBC, and PBMC. Following EO, final DHA was not greater compared to LO. Higher BMI correlated negatively with increases in plasma EPA and DPA after EO supplementation, but not after LO supplementation. Decreasing effect on plasma LDL-C and serum insulin was greater with EO than with LO. CONCLUSIONS: Daily intake of SDA-containing EO is a better supplement than LO for increasing EPA and DPA in blood. However, neither EO nor LO maintained blood DHA status in the absence of fish/seafood consumption. TRIAL REGISTRATION: ClinicalTrials.gov Reg No. NCT01856179; ClinicalTrials.gov Reg No. NCT01317290.

Effects of a dietary intervention with conjugated linoleic acid on immunological and metabolic parameters in children and adolescents with allergic asthma--a placebo-controlled pilot trial.

BACKGROUND: Circumstantial evidence suggests that conjugated linoleic acid (CLA) beneficially modulates immune function in allergic subjects. C9,t11-CLA, naturally occurring in ruminant fats, is suggested to be the effective isomer. In contrast, for the t10,c12-CLA isomer, which is naturally found only in traces but usually constitutes a relevant part in commercial CLA mixtures, adverse effects have been reported. Aim of this study was to assess putative immunomodulatory effects of highly enriched c9,t11-CLA in allergic subjects. To our best knowledge, our study is the first in that a CLA preparation was used for such purpose which was free of t10,c12-CLA. DESIGN: Twenty-nine asthmatic children and adolescents (age 6-18 y) with diagnosed allergic sensitization against grass pollen, house dust mite, or cat hair/epithelia consumed daily a portion of yoghurt containing either 3 g CLA (75 % c9,t11-CLA, 87 % purity) or placebo (safflower oil) over a period of 12 weeks. At study start and end, lung function parameters, specific IgE, in vitro allergen-induced cytokine production in peripheral blood mononuclear cells (PBMC), plasma ECP, urinary 8-oxodG as marker of oxidation, fatty acid profiles of erythrocytes, and routine haematological parameters were determined. Prior to blood samplings, 3-days dietary records were requested. Throughout the study, the participants documented daily their peak expiratory flow and kept protocol about their allergy symptoms and usage of demand medication. RESULTS: In contrast to the CLA group, PBMC-produced IFN-γ and IL-4 increased significantly and by trend, respectively, in the placebo group. Moreover, plasma ECP tended to increase in the placebo group. In the pollen subgroup, FEV1 improved upon both CLA and placebo oil supplementation. In both intervention groups, the n-6/n-3 PUFA ratio in red blood cells decreased, mainly due to an increase in n-3 PUFA. Moreover, 8-oxodG excretion increased in both groups. No changes occurred regarding specific IgE concentrations, allergy symptoms, and volume parameters. CONCLUSION: Our results indicate that CLA modestly dampens the inflammatory response on the cellular level. A clinically relevant amelioration of the symptoms could not be proved in atopic manifest patients. TRIAL REGISTRATION: NCT01026506.

Quantitative assessment of the degree of lipid unsaturation in intact Mortierella by Raman microspectroscopy.

Fungi of the genus Mortierella can accumulate large amounts of unusual lipids depending on species, strain, and growth conditions. Fast and easy determination of key parameters of lipid quality for these samples is required. In this contribution, we apply Raman microspectroscopy to determine the degree of unsaturation for fungal lipids directly inside intact hyphae without elaborate sample handling. Six Mortierella species were grown under varying conditions, and Raman spectra of single lipid vesicles were acquired. From the spectra, we calculate a peak intensity ratio I(1270 cm(-1))/I(1445 cm(-1)) from the signals of =CH and -CH2/-CH3 groups, respectively. This ratio is linked to the iodine value (IV) using spectra of reference compounds with known IV. IVs of fungal samples are compared to gas chromatography results. Values from both methods are in good accordance. Lipid composition is found to vary between the investigated species, with Mortierella alpina having the most unsaturated lipid (IV up to 280) and Mortierella exigua the least unsaturated (IV as low as 70). We find Raman microspectroscopy a suitable tool to determine the IV reliably, fast, and easily inside intact hyphae without extensive sample handling or treatment. The method can also be transferred to other microscopic samples.

Benefits of foods supplemented with vegetable oils rich in α-linolenic, stearidonic or docosahexaenoic acid in hypertriglyceridemic subjects: a double-blind, randomized, controlled trail.

PURPOSE: The aim of the study was to investigate the influence of foods enriched with vegetable oils varying in their n-3 polyunsaturated fatty acids profile on cardiovascular risk factors for hypertriglyceridemic subjects. METHODS: Fifty-nine hypertriglyceridemic subjects (triglycerides ≥ 1.5 mmol/L) were included in the randomized, double-blind, placebo-controlled, crossover study. The placebo group received sunflower oil [linoleic acid (LA) group; 10 g LA/day]. The intervention groups received linseed oil [α-linolenic acid (ALA) group; 7 g ALA/day], echium oil [stearidonic acid (SDA) group; 2 g SDA/day] or microalgae oil [docosahexaenoic acid (DHA) group; 2 g DHA/day] over 10 weeks. Blood samples were collected at baseline and at the end of each period. RESULTS: Total cholesterol (TC) and low-density-lipoprotein cholesterol decreased significantly in the LA and ALA groups (LA: P ≤ 0.01, ALA: P ≤ 0.05). No changes in blood lipids were observed in the SDA group. Significant increases in TC and high-density-lipoprotein cholesterol occurred in the DHA group (P ≤ 0.05). In the ALA and SDA groups, the content of eicosapentaenoic acid in erythrocyte lipids increased significantly (P ≤ 0.05) after 10 weeks (ALA group: 38 ± 37 %, SDA group: 73  ± 59 %). CONCLUSION: Foods enriched with different vegetable oils rich in ALA or SDA are able to increase the n-3 long-chain polyunsaturated fatty acids content in erythrocyte lipids; echium oil is more potent in comparison with linseed oil. Blood lipids were beneficially modified through the consumption of food products enriched with sunflower, linseed and microalgae oils, whereas echium oil did not affect blood lipids. ClinicalTrials.gov: NCT01437930.

Effects of long-term dietary supplementation with conjugated linoleic acid on bovine oocyte lipid profile.

Nutritional and environmental conditions around conception and during early embryonic development may have significant effects on health and well-being in adult life. Here, a bovine heifer model was used to investigate the effects of rumen-protected fat supplementation on oocyte quality and embryo development. Holstein-Friesian heifers (n=84) received a dietary supplement consisting of rumen-protected conjugated linoleic acid (CLA) or stearic acid (SA), each on top of an isocaloric basic diet. Oocytes were collected via ultrasound-guided follicular aspiration and subjected to in vitro maturation followed by either desorption electrospray ionisation mass spectrometry (DESI-MS) for lipid profiling of individual oocytes or in vitro fertilisation and embryo culture. The type of supplement significantly affected lipid profiles of in vitro-matured oocytes. Palmitic acid and plasmalogen species were more abundant in the mass spectra of in vitro-matured oocytes after rumen-protected SA supplementation when compared with those collected from animals supplemented with CLA. Lipid concentrations in blood and follicular fluid were significantly affected by both supplements. Results show that rumen-protected fatty-acid supplementation affects oocyte lipid content and may pave the way for the establishment of a large-animal model for studies towards a better understanding of reproductive disorders associated with nutritional impairments.

Fatty acid profiles and antioxidants of organic and conventional milk from low- and high-input systems during outdoor period.

BACKGROUND: Intensification of organic dairy production leads to the question of whether the implementation of intensive feeding incorporating maize silage and concentrates is altering milk quality. Therefore the fatty acid (FA) and antioxidant (AO) profiles of milk on 24 farms divided into four system groups in three replications (n = 71) during the outdoor period were analyzed. In this system comparison, a differentiation of the system groups and the effects of the main system factors 'intensification level' (high-input versus low-input) and 'origin' (organic versus conventional) were evaluated in a multivariate statistical approach. RESULTS: Consistent differentiation of milk from the system groups due to feeding-related impacts was possible in general and on the basis of 15 markers. The prediction of the main system factors was based on four or five markers. The prediction of 'intensification level' was based mainly on CLA c9,t11 and C18:1 t11, whereas that of 'origin' was based on n-3 PUFA. CONCLUSION: It was possible to demonstrate consistent differences in the FA and AO profiles of organic and standard conventional milk samples. Highest concentrations of nutritionally beneficial compounds were found in the low-input organic system. Adapted grass-based feeding strategies including pasture offer the potential to produce a distinguishable organic milk product quality.

Cis-9,trans-11-conjugated linoleic acid affects lipid raft composition and sensitizes human colorectal adenocarcinoma HT-29 cells to X-radiation.

BACKGROUND: Investigations concerned the mechanism of HT-29 cells radiosensitization by cis-9,trans-11-conjugated linoleic acid (c9,t11-CLA), a natural component of human diet with proven antitumor activity. METHODS: The cells were incubated for 24h with 70µM c9,t11-CLA and then X-irradiated. The following methods were used: gas chromatography (incorporation of the CLA isomer), flow cytometry (cell cycle), cloning (survival), Western blotting (protein distribution in membrane fractions), and pulse-field gel electrophoresis (rejoining of DNA double-strand breaks). In parallel, DNA-PK activity, γ-H2AX foci numbers and chromatid fragmentation were estimated. Gene expression was analysed by RT-PCR and chromosomal aberrations by the mFISH method. Nuclear accumulation of the EGF receptor (EGFR) was monitored by ELISA. RESULTS AND CONCLUSIONS: C9,t11-CLA sensitized HT-29 cells to X-radiation. This effect was not due to changes in cell cycle progression or DNA-repair-related gene expression. Post-irradiation DSB rejoining was delayed, corresponding with the insufficient DNA-PK activation, although chromosomal aberration frequencies did not increase. Distributions of cholesterol and caveolin-1 in cellular membrane fractions changed. The nuclear EGFR translocation, necessary to increase the DNA-PK activity in response to oxidative stress, was blocked. We suppose that c9,t11-CLA modified the membrane structure, thus disturbing the intracellular EGFR transport and the EGFR-dependent pro-survival signalling, both functionally associated with lipid raft properties. GENERAL SIGNIFICANCE: The results point to the importance of the cell membrane interactions with the nucleus after injury inflicted by X -rays. Compounds like c9,t11-CLA, that specifically alter membrane properties, could be used to develop new anticancer strategies.

The formation of short-chain fatty acids is positively associated with the blood lipid-lowering effect of lupin kernel fiber in moderately hypercholesterolemic adults.

Lupin kernel fiber beneficially modifies blood lipids because of its bile acid-binding capacity. The aim of this study was to evaluate the preventive effects of a lupin kernel fiber preparation on cardiovascular diseases and to clarify possible mechanisms. In a randomized, double-blind, controlled crossover trial, 60 moderately hypercholesterolemic adults (plasma total cholesterol: >5.2 mmol/L) passed 3 intervention periods in different orders with a 2-wk washout phase between each. Participants consumed either a high-fiber diet containing 25-g/d lupin kernel fiber (LF) or citrus fiber (CF), or a low-fiber control diet (CD) for 4 wk each. Anthropometric, plasma, and fecal variables were assessed at baseline and after the interventions. Contrary to the CF period, total (9%) and LDL (12%) cholesterol as well as triacylglycerols (10%) were lower after the LF period when compared with the CD period [P ≤ 0.02, adjusted for baseline, age, gender, and body mass index (BMI)]. HDL cholesterol remained unchanged. Moreover, the LF period reduced high-sensitivity C-reactive protein (P = 0.02) and systolic blood pressure (P = 0.01) when compared with baseline. Bile acid binding could not be shown because the excretion of total bile acids remained constant after the high-fiber diets. However, the LF period resulted in an enhanced formation of the main short-chain fatty acids in comparison with the CD period. During the CF period, only acetate increased significantly. Both high-fiber diets led to higher satiety and modified nutritional behavior, resulting in significantly lower body weight, BMI, and waist circumference compared with the CD period. The blood lipid-lowering effects of LF are apparently not a result of bile acid binding. Rather, we hypothesize for the first time, to our knowledge, that the blood lipid-lowering effects of LF may be mainly attributed to the formation of short-chain fatty acids, specifically propionate and acetate. This trial was registered at clinicaltrials.gov as NCT01035086.

Dietary echium oil increases long-chain n-3 PUFAs, including docosapentaenoic acid, in blood fractions and alters biochemical markers for cardiovascular disease independently of age, sex, and metabolic syndrome.

Dietary supplementation with echium oil (EO) containing stearidonic acid (SDA) is a plant-based strategy to improve long-chain (LC) n-3 (ω-3) polyunsaturated fatty acid (PUFA) status in humans. We investigated the effect of EO on LC n-3 PUFA accumulation in blood and biochemical markers with respect to age, sex, and metabolic syndrome. This double-blind, parallel-arm, randomized controlled study started with a 2-wk run-in period, during which participants (n = 80) were administered 17 g/d run-in oil. Normal-weight individuals from 2 age groups (20-35 and 49-69 y) were allotted to EO or fish oil (FO; control) groups. During the 8-wk intervention, participants were administered either 17 g/d EO (2 g SDA; n = 59) or FO [1.9 g eicosapentaenoic acid (EPA); n = 19]. Overweight individuals with metabolic syndrome (n = 19) were recruited for EO treatment only. During the 10-wk study, the participants followed a dietary n-3 PUFA restriction, e.g., no fish. After the 8-wk EO treatment, increases in the LC n-3 metabolites EPA (168% and 79%) and docosapentaenoic acid [DPA (68% and 39%)] were observed, whereas docosahexaenoic acid (DHA) decreased (-5% and -23%) in plasma and peripheral blood mononuclear cells, respectively. Compared with FO, the efficacy of EO to increase EPA and DPA in blood was significantly lower (∼25% and ∼50%, respectively). A higher body mass index (BMI) was associated with lower relative and net increases in EPA and DPA. Compared with baseline, EO significantly reduced serum cholesterol, LDL cholesterol, oxidized LDL, and triglyceride (TG), but also HDL cholesterol, regardless of age and BMI. In the FO group, only TG decreased. Overall, daily intake of 15-20 g EO increased EPA and DPA in blood but had no influence on DHA. EO lowered cardiovascular risk markers, e.g., serum TG, which is particularly relevant for individuals with metabolic syndrome. Natural EO could be a noteworthy source of n-3 PUFA in human nutrition.

Effect of supplementary calcium phosphate on plasma gastrointestinal hormones in a double-blind, placebo-controlled, cross-over human study.

Gastrointestinal hormones and Ca are associated with bone metabolism. The objective of the present human study was to determine the effect of calcium phosphate on the postprandial circulation of gastrointestinal hormones. A total of ten men participated in the present double-blind, placebo-controlled, cross-over study. The participants were divided into two groups. Of these, one group consumed bread enriched with 1 g Ca (pentacalcium hydroxy-triphosphate, CaP) daily for 3 weeks. The other group consumed placebo bread. After 2 weeks of washout, the intervention was changed between the groups for another 3 weeks. The subjects consumed a defined diet at the beginning (single administration) and at the end (repeated administration) of the intervention periods, and blood samples were drawn at 0, 30, 60, 120, 180 and 240 min. Between 0 and 30 min, the participants consumed a test meal, with or without CaP. The concentrations of gastrointestinal hormones (glucose-dependent insulinotropic polypeptide, glucagon-like peptide (GLP) 1 and GLP2), insulin and glucose were determined. The AUC of GLP1 (total and active) and GLP2 increased significantly after the repeated CaP administrations compared with that after placebo administration. The AUC of insulin and glucose showed no differences between the CaP and placebo administrations. CaP affects the postprandial plasma concentrations of gastrointestinal hormones through the modulation of the intestinal environment, e.g. bile acids and microbiota.

Effect of calcium phosphate and vitamin D3 supplementation on bone remodelling and metabolism of calcium, phosphorus, magnesium and iron.

BACKGROUND: The aim of the present study was to determine the effect of calcium phosphate and/or vitamin D3 on bone and mineral metabolism. METHODS: Sixty omnivorous healthy subjects participated in the double-blind, placebo-controlled parallel designed study. Supplements were tricalcium phosphate (CaP) and cholecalciferol (vitamin D3). At the beginning of the study (baseline), all subjects documented their normal nutritional habits in a dietary record for three successive days. After baseline, subjects were allocated to three intervention groups: CaP (additional 1 g calcium/d), vitamin D3 (additional 10 µg/d) and CaP + vitamin D3. In the first two weeks, all groups consumed placebo bread, and afterwards, for eight weeks, the test bread according to the intervention group. In the last week of each study period (baseline, placebo, after four and eight weeks of intervention), a faecal (three days) and a urine (24 h) collection and a fasting blood sampling took place. Calcium, phosphorus, magnesium and iron were determined in faeces, urine and blood. Bone formation and resorption markers were analysed in blood and urine. RESULTS: After four and eight weeks, CaP and CaP + vitamin D3 supplementations increased faecal excretion of calcium and phosphorus significantly compared to placebo. Due to the vitamin D3 supplementations (vitamin D3, CaP + vitamin D3), the plasma 25-(OH)D concentration significantly increased after eight weeks compared to placebo. The additional application of CaP led to a significant increase of the 25-(OH)D concentration already after four weeks. Bone resorption and bone formation markers were not influenced by any intervention. CONCLUSIONS: Supplementation with daily 10 µg vitamin D3 significantly increases plasma 25-(OH)D concentration. The combination with daily 1 g calcium (as CaP) has a further increasing effect on the 25-(OH)D concentration. Both CaP alone and in combination with vitamin D3 have no beneficial effect on bone remodelling markers and on the metabolism of calcium, phosphorus, magnesium and iron. TRIAL REGISTRATION: NCT01297023.

Balancing virtual land imports by a shift in the diet. Using a land balance approach to assess the sustainability of food consumption. Germany as an example.

Nutrition is considered as one of the main drivers of global environmental change. Dietary patterns in particular, embedded in the international trade of foods and other biomass based commodities, determine the dimension of beneficial or harmful environmental impacts of the agri-food sector - both domestically and abroad. In this study we analysed different dietary scenarios from a virtual land flow perspective, based on representative consumption data for Germany in the years 2006 and 1985-89. Further we identified the consumer groups that would have to adapt most to balance Germany's virtual land import and analysed the impact reduced food wastage. For the study, official data sets concerning production, trade and consumption were used. We derived land use data from environmentally extended input-output data sets and FAO statistics. The conversion of agricultural raw products to consumed commodities is based on official processing and composition data. Subgroup-specific intake data from the last representative National Nutrition Survey in Germany were used. We analysed 42 commodities, aggregated into 23 product groups, seven land use types and six nutrition scenarios. The results show that in the baseline scenario the average nutrition in the year 2006 leads to a virtual land import of 707m(2)p(-1)a(-1), which represents 30% of the total nutrition-induced land demand of 2365m(2)p(-1)a(-1). On the other hand, the German agri-food sector exports virtual land, in the form of commodities, equivalent to 262m(2)p(-1)a(-1). In this paper we calculate that the resulting net import of virtual land could be balanced by way of a shift to an officially recommended diet and a reduction in the consumption of stimulants (cocoa, coffee, green/black tea, wine). A shift to an ovo-lacto-vegetarian or vegan diet would even lead to a positive virtual land balance (even with maintained consumption of stimulants). Moreover, we demonstrate that a shift in the average diet profile could lead to maintained or even expanded export competitiveness and simultaneously enable environmental benefits. Since such a diet shift complies with official dietary recommendations, it follows that public health benefits may well result. We show further that a reduction of avoidable food losses/wastage would not be sufficient to level out the virtual land balance of the average nutrition in Germany. Regarding the dietary developments in the last 20years, we argue that a dietary shift resulting in a zero land balance is within reach. The population groups that would have to be addressed most are younger and middle-aged men. Nevertheless, women's land saving potentials should not be ignored neither. Due to the fact that a western-style diet prevails in Germany, we argue that our basic findings are applicable to other industrialised and densely populated countries.

Inactivation of hepatitis C virus infectivity by human breast milk.

BACKGROUND: Hepatitis C virus (HCV) is spread through direct contact with blood, although alternative routes of transmission may contribute to the global burden. Perinatal infection occurs in up to 5% of HCV-infected mothers, and presence of HCV RNA in breast milk has been reported. We investigated the influence of breast milk on HCV infectiousness. METHODS/RESULTS: Human breast milk reduced HCV infectivity in a dose-dependent manner. This effect was species-specific because milk from various animals did not inhibit HCV infection. Treatment of HCV with human breast milk did not compromise integrity of viral RNA or capsids but destroyed the lipid envelope. Fractionation of breast milk revealed that the antiviral activity is present in the cream fraction containing the fat. Proteolytic digestion of milk proteins had no influence on its antiviral activity, whereas prolonged storage at 4°C increased antiviral activity. Notably, pretreatment with a lipase inhibitor ablated the antiviral activity and specific free fatty acids of breast milk were antiviral. CONCLUSIONS: The antiviral activity of breast milk is linked to endogenous lipase-dependent generation of free fatty acids, which destroy the viral lipid envelope. Therefore, nursing by HCV-positive mothers is unlikely to play a major role in vertical transmission.