Dietary Intervention with Whey Protein Concentrate Does Not Affect Toll-like Receptor Responses and Gene Expression Patterns in Peripheral Blood Mononuclear Cells of Healthy Volunteers.

Bovine milk contains bioactive proteins, carbohydrates, and phospholipids with immunomodulatory properties impacting human immunity, potentially contributing to resistance to infections and allergies through diverse mechanisms. One such mechanism is the enhancing of the innate immune response to secondary pathogen-related stimuli, termed innate immune training. Although in vitro studies demonstrate that milk immunoglobulin G (IgG) can train human monocytes, evidence for in vivo immune training is limited. To explore the potential of bovine IgG for inducing innate immune training in vivo, this human study utilized an IgG-rich whey protein concentrate (WPC). Healthy male volunteers were assigned to a high dose WPC, low dose WPC, or placebo group. Blood was collected pre- and post-two weeks of WPC consumption. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with TLR ligands, evaluating IL-6 and TNF-α production by monocytes, myeloid DCs, and plasmacytoid DCs. Additionally, RNA was isolated for differential gene expression (DGE) analysis. Results indicated that the two-week WPC intervention did not influence the ex vivo response of studied cells to TLR agonists. Furthermore, PBMC gene expression patterns showed no significant differences between the placebo and high dose WPC groups. The data suggests that oral WPC ingestion did not enhance immune responses in young, healthy male participants.

A Double-Blind, Randomized Intervention Study on the Effect of a Whey Protein Concentrate on E. coli-Induced Diarrhea in a Human Infection Model.

Infectious diseases are a major cause of morbidity and mortality worldwide. Nutritional interventions may enhance resistance to infectious diseases or help to reduce clinical symptoms. Here, we investigated whether a whey protein concentrate (WPC) could decrease diarrheagenic Escherichia coli-induced changes in reported stool frequency and gastrointestinal complaints in a double-blind, parallel 4-week intervention study. Subjects were randomly assigned to a whey hydrolysate placebo group, a low-dose WPC group or a high-dose WPC group. After 2 weeks of consumption, subjects (n = 121) were orally infected with a high dose of live but attenuated diarrheagenic E. coli (strain E1392/75-2A; 1E10 colony-forming units). Subjects recorded information on stool consistency and the frequency and severity of symptoms in an online diary. The primary outcome parameters were a change in stool frequency (stools per day) and a change in Gastrointestinal Symptom Rating Scale (GSRS) diarrhea score between the first and second days after infection. Neither dose of the whey protein concentrate in the dietary treatment affected the E. coli-induced increase in stool frequency or GSRS diarrhea score compared to placebo treatment. The composition of the microbiota shifted between the start of the study and after two weeks of consumption of the products, but no differences between the intervention groups were observed, possibly due to dietary guidelines that subjects had to adhere to during the study. In conclusion, consumption of the whey protein concentrate by healthy adults did not reduce diarrhea scores in an E. coli infection model compared to a whey hydrolysate placebo control.

Whey protein supplementation does not accelerate recovery from a single bout of eccentric exercise.

The current double blind, randomized, placebo-controlled trial with two parallel groups aimed to assess the impact of whey protein supplementation on recovery of muscle function and muscle soreness following eccentric exercise. During a 9-day period, forty recreationally active males received twice daily supplementation with either whey protein (PRO; 60 g/day) or an iso-energetic amount of carbohydrate (CON). Muscle function and soreness were assessed before, and 0, 3, 24, 48, and 72 h after performing 100 drop jumps. Recovery of isometric maximal voluntary contraction (MVC) did not significantly differ between groups (timextreatment, P = 0.56). In contrast, the recovery of isokinetic MVC at 90°·s-1 was faster in CON as opposed to PRO (timextreatment interaction, P = 0.044). Recovery of isokinetic MVC at 180°·s-1 was also faster in CON as opposed to PRO (timextreatment interaction, P = 0.011). Recovery of countermovement jump performance did not differ between groups (timextreatment interaction, P = 0.52). Muscle soreness, CK and CRP showed a transient increase over time (P < 0.001), with no differences between groups. In conclusion, whey protein supplementation does not accelerate recovery of muscle function or attenuate muscle soreness and inflammation during 3 days of recovery from a single bout of eccentric exercise.

Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health.

Metabolism maintains homeostasis at chronic hypercaloric conditions, activating postprandial response mechanisms, which come at the cost of adaptation processes such as energy storage, eventually with negative health consequences. This study quantified the metabolic adaptation capacity by studying challenge response curves. After a high-fat challenge, the 8 h response curves of 61 biomarkers related to adipose tissue mass and function, systemic stress, metabolic flexibility, vascular health, and glucose metabolism was compared between 3 metabolic health stages: 10 healthy men, before and after 4 wk of high-fat, high-calorie diet (1300 kcal/d extra), and 9 men with metabolic syndrome (MetS). The MetS subjects had increased fasting concentrations of biomarkers representing the 3 core processes, glucose, TG, and inflammation control, and the challenge response curves of most biomarkers were altered. After the 4 wk hypercaloric dietary intervention, these 3 processes were not changed, as compared with the preintervention state in the healthy subjects, whereas the challenge response curves of almost all endocrine, metabolic, and inflammatory processes regulating these core processes were altered, demonstrating major molecular physiologic efforts to maintain homeostasis. This study thus demonstrates that change in challenge response is a more sensitive biomarker of metabolic resilience than are changes in fasting concentrations.

Dietary supplementation of different doses of NUTRIOSE FB, a fermentable dextrin, alters the activity of faecal enzymes in healthy men.

BACKGROUND: It is well documented that fermentation of carbohydrates that escape digestion exert several effects supposed to be beneficial for (colonic) health, including an increase in stool volume, a shorter intestinal transit time, production of short chain fatty acids and a decrease of colonic pH (Kritchevsky 1988). NUTRIOSE FB is a dextrin that is not completely hydrolysed and absorbed in the small intestine, due to many alpha-1.6 linkages and the presence of non-digestible glucoside linkages (e. g. alpha-1.2 and alpha-1.3). To be beneficial for 'colonic' health effective NUTRIOSE FB must reach the cecum in some form. AIM OF THE STUDY: To estimate how much non digested NUTRIOSE FB is fermented and to determine the fibre-like effect of the wheat dextrin NUTRIOSE((R))FB by analysing enzymatic activity in faeces. METHODS: In a randomized, double-blind,multiple dose, placebo-controlled, combined cross-over and parallel trial, 20 healthy men (age 31.7 +/- 9.1 yrs; BMI 24.5 +/- 2.9 kg.m(-2) received different treatments. One group of ten subjects consumed on top of their diet 10, 30 and 60 g daily of NUTRIOSE FB or maltodextrin (placebo). The other group of 10 subjects consumed 15, 45 and 80 g daily. Each dose was consumed for 7 days. On the last two days of each of the 7-day period, faeces were collected in which the enzymatic activity and NUTRIOSE FB residue were analysed. RESULTS: As expected, the faecal residue of NUTRIOSE FB non-linearly increased with the dose of NUTRIOSE FB to approximately 13% of 80 g/d. Compared with the placebo, 30, 45, 60 and 80 g/d of NUTRIOSE FB increased the concentration of alpha-glucosidase significantly. All daily doses of NUTRIOSE FB (10 g/d to 80 g/d) led to significant changes in concentration of beta-glucosidase. CONCLUSIONS: The small amount of the residue of NUTRIOSE FB in the faeces suggests that approximately 87% or more of NUTRIOSE FB is digested or fermented in the gastrointestinal tract. Fermentation of NUTRIOSE FB led to an increased faecal concentration of alpha- and beta-glucosidase.

Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation.

BACKGROUND: Endothelial cell dysfunction may be related to an increase in cellular oxidative stress. Carotenoids and vitamins could have an antioxidant-mediated tempering influence on endothelial function and inflammation, thereby reducing the risk of atherosclerosis. METHODS: We measured serum carotenoids, alpha-tocopherol and Vitamin C concentrations in 379 subjects sampled from the general population. High-sensitive C-reactive protein (CRP), fibrinogen (Fbg) and leukocytes were measured as markers of inflammation. Furthermore, soluble intercellular adhesion molecule-1 (sICAM-1) and flow-mediated vasodilation (FMD; n= 165) were measured as markers of endothelial function. Relationships between serum carotenoids and vitamins and markers of endothelial function and inflammation were analysed after adjustment for confounding. RESULTS: In the total study group, lutein and lycopene were inversely related to sICAM-1 with regression-coefficients of -0.38+/-0.19 (p = 0.04) and -0.16+/-0.08 (p = 0.04) per 1 micromol/l, respectively. beta-Carotene was inverse related to leukocytes (-0.23+/-0.07; p = 0.007) and CRP (-1.09+/-0.30; p = 0.0003) per 1 micromol/l. Vitamin C was inverse related to CRP (-0.01+/-0.005; p = 0.04) per 1 micromol/l, whereas alpha-tocopherol was positively related to CRP (0.03+/-0.01; p = 0.02) per 1 micro/l. Zeaxanthin was inversely related to FMD (31.2+/-15.3; p = 0.04) per 1 micromol/l. CONCLUSION: The inverse relations between carotenoids, Vitamin C and sICAM-1, CRP and leukocytes may help to explain the possible protective effect of carotenoids and Vitamin C on atherosclerosis through an influence on inflammatory processes and endothelial function.

Decreased carotenoid concentrations due to dietary sucrose polyesters do not affect possible markers of disease risk in humans.

Excessive consumption of energy and fat increases the risk for obesity. Snacks containing sucrose polyesters (SPE) as a dietary fat replacer are on the market in the United States. SPE products have been shown to lower concentrations of serum carotenoids in short-term studies. Experimental studies on the longer-term effects on health of decreased carotenoid concentrations are lacking. A 1-y randomized, double-blind, placebo-controlled parallel trial was performed. Subjects (n = 380) with a habitual low or high fruit and vegetable intake were assigned to the treatments (0, 7, 10 or 17 g/d SPE). SPE was given in the form of spreads, chips or both. The groups were compared for serum carotenoids, vitamins and markers of oxidative damage, eye health, cardiovascular health and immune status. After 1 y, serum lipid-adjusted carotenoids showed the largest decrease in the SPE chips and spread group (17 g/d) compared with the control group [alpha-carotene 33%; beta-carotene 31%, lycopene 24%, beta-cryptoxanthin 18%, lutein 18% (all P < 0.001) and zeaxanthin 13% (P < 0.05)]. Consumption of SPE spread (10 g/d SPE) decreased carotenoid concentrations by 11-29% (all P < 0.05). SPE chips (7 g/d SPE) decreased zeaxanthin (11%), beta-carotene (12%) and alpha-carotene (21%; all P < 0.05). Serum lipid adjusted alpha-tocopherol decreased significantly by 6-8% (all P < 0.001) in all SPE groups. No negative effects were observed on markers of oxidation, eye health, cardiovascular health or immune status. This study shows that decreases in serum carotenoid concentrations do not affect possible markers of disease risk.

Lens aging in relation to nutritional determinants and possible risk factors for age-related cataract.

OBJECTIVE: To investigate whether nutritional factors and possible risk factors for cataract influence the lens optical density (LOD). DESIGN: Three hundred seventy-six subjects, aged 18 to 75 years, were recruited. In a cross-sectional design, serum was analyzed for lutein, zeaxanthin, vitamin C, alpha-tocopherol, and cholesterol levels. Adipose tissue (n = 187) was analyzed for lutein level. The LOD and the macular pigment optical density (MPOD) were measured by spectral fundus reflectance. RESULTS: The mean +/- SD LOD at 420 nm was 0.52 +/- 0.17. It showed a significant association with age (beta =.008, P<001) and MPOD (beta = -.096, P =.02). For subjects 50 years and younger (mean +/- SD LOD, 0.45 +/- 0.11), we found only a single significant beta coefficient, for age (beta =.006, P<.001). For subjects older than 50 years (mean +/- SD LOD, 0.68 +/- 0.16), we found significant beta coefficients for age (beta =.011, P<.001) and MPOD (beta = -.240, P =.005). Controlling for age, we found no associations between LOD and other possible risk factors for age-related cataract or serum or adipose tissue concentrations of carotenoids, vitamin C, and alpha-tocopherol. CONCLUSIONS: Macular pigment is composed of lutein and zeaxanthin, the only carotenoids found in human lenses. The inverse relationship between LOD and MPOD suggests that lutein and zeaxanthin may retard aging of the lens.

Intake of conjugated linoleic acid, fat, and other fatty acids in relation to postmenopausal breast cancer: the Netherlands Cohort Study on Diet and Cancer.

BACKGROUND: Conjugated linoleic acid (CLA), which is present in milk products and meat from ruminants, appears to have anticarcinogenic activity against breast cancer in animal and in vitro experiments. To date, few epidemiologic data are available in humans. OBJECTIVE: This study evaluated the relation between intakes of CLA and other fatty acids and breast cancer incidence in the Netherlands Cohort Study. DESIGN: Intake data derived from a validated 150-item food-frequency questionnaire were linked to an existing database with analytic data on specific fatty acids in European foods (the TRANSFAIR study). With 6.3 y of follow-up and 941 incident cases of breast cancer, multivariate rate ratios and 95% CIs were calculated for energy-adjusted intakes of fatty acids and CLA-containing food groups (eg, butter, cheese, milk, other milk products, and meat). RESULTS: CLA intake showed a weak, positive relation with breast cancer incidence (rate ratio for highest compared with lowest quintile: 1.24, 95% CI: 0.91, 1.69; P for trend = 0.02). Statistically significant positive associations were found with total trans fatty acids and (borderline) with saturated fatty acids. Significant inverse associations were found with monounsaturated and cis unsaturated fatty acids, whereas total fat and energy intake of CLA-containing food groups were not related to breast cancer incidence. CONCLUSION: The suggested anticarcinogenic property of CLA in animal and tissue culture models could not be confirmed in this epidemiologic study in humans.

Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin.

BACKGROUND: Macular pigment (MP), concentrated in the central area of the retina, contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk factor for age-related macular degeneration. Little information is available regarding MP density in relation to serum lutein and zeaxanthin and adipose lutein concentrations in a general population. OBJECTIVE: The objective was to investigate the associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein, taking into account potential confounders in a population. DESIGN: Volunteers (n = 376) aged 18-75 y were recruited. In a cross-sectional design, serum (n = 376) and adipose tissue (n = 187) were analyzed for carotenoids, and MP density was measured by spectral fundus reflectance. RESULTS: Mean MP density in the total study group was 0.33 +/- 0.15. MP density was 13% higher in men than in women (P < 0.05). Serum and blood concentrations of alpha-tocopherol, vitamin C, and all carotenoids except lycopene were significantly higher in women. Adipose lutein concentrations were also significantly higher in women than in men. Regression models showed a positive significant association between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations in men after adjustment for age, but no relation in women. In men, serum lutein remained significantly associated with MP density after adjustment for age, total cholesterol, body mass index, and smoking. CONCLUSION: The associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations are stronger in men than in women.

Association between toenail scandium levels and risk of acute myocardial infarction in European men: the EURAMIC and Heavy Metals Study.

The association between scandium status and risk of acute myocardial infarction (MI) was examined in a multicentre case control study in 10 centres from Europe and Israel. Scandium in toenails was assessed in 684 cases and 724 controls less than 70 years of age. Mean concentrations of toenail scandium were 6.74 micro/kg in cases and 7.75 microg/kg in controls. Scandium among controls, adjusted for age and centre was positively associated with concentrations of lycopene and oleic acid in adipose tissue (P = 0.002 for both nutrients). Pearson correlations adjusted for age and centre were significant (P < 0.05) between scandium and lycopene (r = 0.08), zinc (r = 0.08), mercury (r = 0.18) and oleic acid (r = 0.21). Overall, cases had lower levels of scandium than controls after adjustment for age and centre (case control ratio, 0.87; 95% CI 0.79-0.96). This association persisted after adjustment for other cardiovascular risk factors (case-control ratio 0.88; 95% CI, 0.79-0.98). The risk of MI at high scandium levels was reduced after adjustment for age and centre (P-trend = 0.04). Further adjustments for BMI, history of hypertension, smoking, alcohol intake, diabetes, family history of CHD, alpha-tocopherol, beta-carotene, lycopene, selenium and mercury slightly attenuated this trend (P = 0.055). Our results suggest that toenail scandium level is associated with a reduced risk of acute MI, but we are uncertain whether this element can really play a protective role in the development of CHD. Without an identified plausible mechanism, these results should be regarded as preliminary and should be tested in future studies.