Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study.

We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored. Haemodynamics were examined in a laboratory using radial pulse wave analysis and whole-body impedance cardiography in the supine position and during orthostatic challenge. There were no differences between the effects of the two treatments and placebo on the measurements of BP at home or on BP, systemic vascular resistance index and cardiac index in the laboratory, neither in the supine nor in the upright position. The changes in plasma LDL-cholesterol concentration were - 0.1 (95% CI - 0.3, 0.1 and - 0.3, 0.0) mmol/l in the 5 and 25 mg/d LTP groups, respectively, and +0.1 (95% CI - 0.1, 0.3) mmol/l during placebo (P= 0.024). Both at baseline and at week 12, the increase in systemic vascular resistance during head-up tilt was lower in the 25 mg/d LTP group than in the 5 mg/d LTP group (P< 0.01), showing persistent differences in cardiovascular regulation between these groups. In subjects with the MetS, intake of LTP and Pse in fermented milk product showed a lipid-lowering effect of borderline significance, while no antihypertensive effect was observed at home or in the laboratory.

Effect of Milk Fat Globule Membrane- and Protein-Containing Snack Product on Physical Performance of Older Women-A Randomized Controlled Trial.

INTRODUCTION: Sarcopenia is common in people 70+ years of age, and its prevalence increases with further aging. Insufficient energy and protein intake accelerates muscle loss, whereas sufficient protein intake and milk fat globule membrane (MFGM) may suppress age-associated deterioration of muscle mass and strength. Our objective was to test whether a snack product high in MFGM and protein would improve physical performance in older women. METHODS: In this 12-week randomized controlled trial, women ≥ 70 years, with protein intake < 1.2 g/body weight (BW) kg/day (d), were randomized into intervention (n = 51) and control (n = 50) groups. The intervention group received a daily snack product containing ≥ 23 g of milk protein and 3.6-3.9 g of MFGM. Both groups were advised to perform a five-movement exercise routine. The primary outcome was the change in the five-time-sit-to-stand test between the groups. Secondary outcomes included changes in physical performance, cognition, hand grip strength, and health-related quality of life. RESULTS: The change in the five-time-sit-to-stand test did not differ between the intervention and the control groups. The change in the total Short Physical Performance Battery score differed significantly, favoring the intervention group (p = 0.020), and the balance test showed the largest difference. Protein intake increased significantly in the intervention group (+14 g) compared to the control group (+2 g). No other significant changes were observed. CONCLUSIONS: Our results indicate that the combination of MFGM and protein may improve the physical performance-related balance of older women.

High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension.

Milk casein-derived angiotensin-converting enzyme (ACE)-inhibitory tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) have been shown to have antihypertensive effects in human subjects and to attenuate the development of hypertension in experimental models. The aim of the present study was to investigate the effect of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols on already established hypertension, endothelial dysfunction and aortic gene expression. Male spontaneously hypertensive rats (SHR) with baseline systolic blood pressure (SBP) of 195 mmHg were given either active milk (tripeptides and plant sterols), milk or water ad libitum for 6 weeks. SBP was measured weekly by the tail-cuff method. The endothelial function of mesenteric arteries was investigated at the end of the study. Aortas were collected for DNA microarray study (Affymetrix Rat Gene 1.0 ST Array). The main finding was that active milk decreased SBP by 16 mmHg compared with water (178 (SEM 3) v. 195 (SEM 3) mmHg; P < 0.001). Milk also had an antihypertensive effect. Active milk improved mesenteric artery endothelial dysfunction by NO-dependent and endothelium-derived hyperpolarising factor-dependent mechanisms. Treatment with active milk caused mild changes in aortic gene expression; twenty-seven genes were up-regulated and eighty-two down-regulated. Using the criteria for fold change (fc) < 0.833 or > 1.2 and P < 0.05, the most affected (down-regulated) signalling pathways were hedgehog, chemokine and leucocyte transendothelial migration pathways. ACE expression was also slightly decreased (fc 0.86; P = 0.047). In conclusion, long-term treatment with fermented milk enriched with tripeptides and plant sterols decreases SBP, improves endothelial dysfunction and affects signalling pathways related to inflammatory responses in SHR.

Ile-Pro-Pro and Val-Pro-Pro tripeptide-containing milk product has acute blood pressure lowering effects in mildly hypertensive subjects.

Casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) lower blood pressure (BP) in long-term clinical studies. Their acute effects on BP and vascular function, important for daily dosing scheme, were studied in a placebo-controlled double-blind crossover study using a single oral dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro as well as plant sterols. Twenty-five subjects with untreated mild hypertension received in random order 250 g of study product (25 mg peptides and 2 g plant sterols) or placebo. Ambulatory BP was monitored for 8 h post-dose and arterial stiffness measured by pulse wave analysis at 2, 4, and 8 h. Blood and urine samples were analyzed for markers of the renin-angiotensin system (RAS) and endothelial function. Baseline adjusted treatment effect for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial BP was -2.1 mmHg (95% CI: -4.1 to -0.1, p = 0.045), -1.6 mmHg (95% CI: -3.1 to -0.1, p = 0.03), and -1,9 mmHg (95% CI: -3-3 to -0.4, p = 0.0093), respectively, in favor of the active treatment for 8 h post- dose. No significant differences between the treatments were seen in brachial or aortic augmentation index, pulse wave velocity, or markers of RAS. Urinary excretion of cGMP, the second messenger of endothelial nitric oxide, was higher in the active group vs. placebo (p = 0.01). The results indicate that a single dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols acutely lowers brachial SBP and DBP in mildly hypertensive subjects.

Protein Supplements and Their Relation with Nutrition, Microbiota Composition and Health: Is More Protein Always Better for Sportspeople?

Sports nutrition products are developed and targeted mainly for athletes to improve their nutrient intake, performance, and muscle growth. The fastest growing consumer groups for these products are recreational sportspeople and lifestyle users. Although athletes may have elevated physiological protein requirements and they may benefit from dietary supplements, the evidence regarding the role of dietary protein and supplements in the nutrition of recreational sportspeople and sedentary populations is somewhat complex and contradictory. In high-protein diets, more undigested protein-derived constituents end up in the large intestine compared to moderate or low-protein diets, and hence, more bacterial amino acid metabolism takes place in the colon, having both positive and negative systemic and metabolic effects on the host. The aim of the present review is to summarize the impact of the high-protein products and diets on nutrition and health, in sportspeople and in sedentary consumers. We are opening the debate about the current protein intake recommendations, with an emphasis on evidence-based effects on intestinal microbiota and personalized guidelines regarding protein and amino acid supplementation in sportspeople and lifestyle consumers.

Immunological and metabolic effects of cis-9, trans-11-conjugated linoleic acid in subjects with birch pollen allergy.

Animal studies suggest that conjugated linoleic acid (CLA) may modulate the immune response, while studies in healthy human subjects have shown little effect and results are controversial. However, the effects of CLA may be more prominent in situations of immune imbalance, such as allergy. We studied the effects of the natural CLA isomer, cis-9, trans-11-CLA, on allergy symptoms and immunological parameters in subjects with birch pollen allergy. In a randomised, placebo-controlled study, forty subjects (20-46 years) with diagnosed birch pollen allergy received 2 g CLA/d in capsules, which contained 65.3 % cis-9, trans-11-CLA and 8.5 % trans-10, cis-12-CLA (n 20), or placebo (high-oleic acid sunflower-seed oil) (n 20) for 12 weeks. The supplementation began 8 weeks before the birch pollen season and continued throughout the season. Allergy symptoms and use of medication were recorded daily. Lymphocyte subsets, cytokine production, immunoglobulins, C-reactive protein, lipid and glucose metabolism and lipid peroxidation were assessed before and after supplementation. The CLA group reported a better overall feeling of wellbeing (P < 0.05) and less sneezing (P < 0.05) during the pollen season. CLA supplementation decreased the in vitro production of TNF-alpha (P < 0.01), interferon-gamma (P < 0.05) and IL-5 (P < 0.05). Total plasma IgE and birch-specific IgE concentrations did not differ between groups, whereas plasma IgA (P < 0.05), granulocyte macrophage colony-stimulating factor (P < 0.05) and eosinophil-derived neurotoxin (P < 0.05) concentrations were lower after CLA supplementation. Urinary excretion of 8-iso-PGF2alpha, a major F2-isoprostane (P < 0.01), and 15-keto-dihydro-PGF2alpha, a primary PGF2alpha metabolite (P < 0.05), increased in the CLA group. The results suggest that cis-9, trans-11-CLA has modest anti-inflammatory effects in allergic subjects.

Bioconversion of vaccenic acid to conjugated linoleic acid in humans.

BACKGROUND: Vaccenic acid (11-trans octadecenoic acid; VA), a major trans fatty acid in the fat of ruminants, is produced in the rumen and converted in tissues to rumenic acid (9-cis, 11-trans octadecenoic acid; RA), an isomer of conjugated linoleic acid, by Delta(9)-desaturase. There are indications that this conversion also occurs in humans. OBJECTIVE: The aim of this controlled intervention was to study the conversion of VA to RA in humans after consumption of diets with increasing amounts of VA. DESIGN: Thirty healthy subjects consumed a baseline diet rich in oleic acid for 2 wk. The subjects were then divided into 3 groups (n = 10 per group) and provided a diet containing 1.5, 3.0, or 4.5 g VA/d for 9 d. All diets contained equal amounts of macronutrients and differed only in their fatty acid compositions. The fats were mixed into conventional foods, and nearly all food was provided during the study. RESULTS: The proportion of VA in serum total fatty acids increased 94%, 307%, and 620% above baseline with the 1.5-, 3.0-, and 4.5-g diets, respectively. This was associated with a linear increase in the proportion of RA. The conversion rate was 19% on average, with significant interindividual differences with all 3 intakes of VA. The urinary excretion of 8-iso-prostaglandin F(2alpha) increased in all groups (P < 0.001). CONCLUSIONS: The results quantify the desaturation of VA to RA in humans. Conversion is likely to contribute significantly to the amount of RA available to the body, and dietary intakes of VA should thus be taken into account when predicting RA status.

Antihypertensive effects of bioactive tripeptides-a random effects meta-analysis.

A meta-analysis of possible antihypertensive effects of small doses of bioactive tripeptides isoleucine-proline-proline and valine-proline-proline in commercial milk products or tablets was carried out. A random effects model was used on 19 randomized, placebo-controlled clinical intervention trials (published 1996-October 2010) consisting of about 1500 prehypertensive or mildly hypertensive subjects.The overall blood pressure lowering for systolic blood pressure was -4.0 mmHg (95% CI -5.9 to -2.1 mmHg, P < 0.001) and for diastolic blood pressure -1.9 mmHg (95% CI -3.1 to -0.8 mmHg, P < 0.001). However, a positive effect was not reported in all the studies. The results suggest that rather small daily doses of the lactotripeptides in different functional food products may offer a valuable option as a non-pharmacological treatment of prehypertension or mild hypertension as part of life-style advice.

A spread containing bioactive milk peptides Ile-Pro-Pro and Val-Pro-Pro, and plant sterols has antihypertensive and cholesterol-lowering effects.

Lifestyle intervention is recommended as the primary treatment for mild hypertension and hypercholesterolemia. We studied the effects of a spread containing bioactive milk peptides IPP and VPP, as well as plant sterols, on cardiovascular risk factors in 104 hypertensive, hypercholesterolemic subjects in a randomised, placebo-controlled double-blind intervention. Middle-aged subjects consumed 20 g day⁻¹ of a spread containing 4.2 mg of IPP and VPP as well as 2 g of plant sterols for 10 weeks after a 2 week run-in period. Blood pressure was measured at home 3 times a week. Office blood pressure and 24 h ambulatory blood pressure measurements were performed at the end of the run-in and intervention periods. Blood samples were analysed for serum lipids, plasma glucose and inflammation markers. A significant decrease (-4.1 mmHg vs. -0.5 mmHg, p = 0.007) in systolic blood pressure was seen in the active group, compared to placebo at home measurements. Office blood pressure and 24 h nighttime or daytime ambulatory systolic or diastolic pressure did not differ between the groups. Total (-0.16 vs. 0.25 mmol l⁻¹, p = 0.005) and LDL cholesterol (-0.16 vs. 0.18 mmol l⁻¹, p = 0.006) decreased significantly in the active group compared to the placebo. No significant differences between groups were seen for plasma glucose or inflammation markers. The results thus suggest that milk peptides IPP and VPP and plant sterols, in a low-fat spread matrix, produce a clinically significant reduction in systolic blood pressure as well as serum total and LDL cholesterol without adverse effects. Functional foods that affect 2 major risk factors offer a safe and convenient way to reduce the risk of cardiovascular disease by supporting lifestyle intervention.

Plant sterols and casein-derived tripeptides attenuate blood pressure increase in spontaneously hypertensive rats.

In this study, we investigated the synergistic effects of plant sterols (PS) and casein-derived tripeptides on arterial tone and blood pressure in experimental hypertension. We hypothesized that PS and tripeptides could have positive, synergistic effects on the development of hypertension and endothelial dysfunction in young spontaneously hypertensive rats (SHR). Six-week-old male SHR were divided into 3 groups to receive milk products containing PS, or PS with tripeptides, or a control containing no active components for 8 weeks. Systolic blood pressure (SBP) was measured weekly, and vascular reactivity measurements with isolated mesenteric arteries were performed at the end of the study. Biochemical measurements for several parameters were performed by enzyme-linked immunosorbent assay using plasma samples. Levels of angiotensin-converting enzyme 1, cyclooxygenase-2, endothelial nitric oxide synthase, and P-selectin messenger RNA expressions were determined from aortic tissue by real-time polymerase chain reaction. The study showed that long-term treatment with PS + tripeptides attenuated the development of hypertension in SHR (SBP, 187 ± 5 mm Hg vs 169 ± 4 mm Hg in control group; P < .01). Plant sterols alone did not affect SBP significantly. Endothelial dysfunction was observed in all SHR; however, treatment with PS resulted in poorer endothelium-dependent and nitric oxide-mediated relaxation compared with other groups. Aortic cyclooxygenase-2 and P-selectin were significantly down-regulated in PS and PS + tripeptides groups when compared with the control group. The expression of endothelial nitric oxide synthase was significantly lower in PS than in PS + tripeptides group. In conclusion, long-term treatment with PS has a slight but not significant antihypertensive effect. Plant sterols do not provide any beneficial effects on endothelial function in hypertensive rats; however, treatment with both PS and tripeptides showed mild anti-inflammatory effects.

Casein-derived tripeptide Ile-Pro-Pro improves angiotensin-(1-7)- and bradykinin-induced rat mesenteric artery relaxation.

AIMS: Milk casein-derived bioactive tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) lower blood pressure in animal models of hypertension and humans. In some studies, their angiotensin-converting enzyme (ACE)-inhibitory effect has been demonstrated. Besides classical ACE-angiotensin II-AT(1)-receptor pathway (ACE-Ang II- AT(1)), the significance of ACE2-angiotensin-(1-7)-Mas-receptor (ACE2-Ang-(1-7)-Mas) axis in the blood pressure regulation has now been acknowledged. The present study was aimed to further evaluate the renin-angiotensin system (RAS)-related vascular effects of Ile-Pro-Pro in vitro using rat mesenteric arteries. MAIN METHODS: Superior mesenteric arteries of spontaneously hypertensive rat (SHR) were isolated, cut into rings and mounted in standard organ bath chambers. Endothelium-intact arterial rings were incubated in Krebs solution either with Ile-Pro-Pro, proline-proline (Pro-Pro), isoleucine (Ile), proline (Pro) or captopril for 6h at +37°C and vascular reactivity was measured. KEY FINDINGS: In the presence of AT(1)-antagonist valsartan, Ang II induced vasodilatation, which was more pronounced in the arteries incubated with Ile-Pro-Pro (P<0.05) compared to the other compounds. Ang-(1-7)-induced vasodilatation was augmented by Ile-Pro-Pro or Pro (P<0.001 vs. control). Mas-receptor antagonist A-779 did not alter the responses. Ile-Pro-Pro and Pro augmented also bradykinin-induced relaxations (P<0.001 vs. control). Control arteries and arteries incubated with captopril showed only slight relaxations at higher bradykinin concentrations. SIGNIFICANCE: Casein-derived tripeptide Ile-Pro-Pro and amino acid Pro enhance the vasodilatory effect of Ang-(1-7) and bradykinin. The role of ACE2-Ang-(1-7)-Mas axis in the modulation of vascular tone by these compounds seems probable.

Dairy products and metabolic effects in overweight men and women: results from a 6-mo intervention study.

BACKGROUND: Some epidemiologic studies have suggested inverse relations between intake of dairy products and components of the metabolic syndrome. OBJECTIVE: The objective was to investigate the effects of an increased intake of dairy products in persons with a habitually low intake on body composition and factors related to the metabolic syndrome. DESIGN: Middle-aged overweight subjects (n = 121) with traits of the metabolic syndrome were recruited in Finland, Norway, and Sweden and randomly assigned into milk or control groups. The milk group was instructed to consume 3-5 portions of dairy products daily. The control group maintained their habitual diet. Clinical investigations were conducted on admission and after 6 mo. RESULTS: There were no significant differences between changes in body weight or body composition, blood pressure, markers of inflammation, endothelial function, adiponectin, or oxidative stress in the milk and the control groups. There was a modest unfavorable increase in serum cholesterol concentrations in the milk group (P = 0.043). Among participants with a low calcium intake at baseline (<700 mg/d), there was a significant treatment effect for waist circumference (P = 0.003) and sagittal abdominal diameter (P = 0.034). When the sexes were analyzed separately, leptin increased (P = 0.045) and vascular cell adhesion molecule-1 decreased (P = 0.001) in women in the milk group. CONCLUSIONS: This study gives no clear support to the hypothesis that a moderately increased intake of dairy products beneficially affects aspects of the metabolic syndrome. The apparently positive effects on waist circumference and sagittal abdominal diameter in subjects with a low calcium intake suggest a possible threshold in relation to effects on body composition.

Effects of conjugated linoleic acid on linoleic and linolenic acid metabolism in man.

Evidence from animal studies suggests that conjugated linoleic acid (CLA) modulates plasma and tissue appearance of newly synthesized PUFA. The effects of a 1.2g (0.5 % energy) daily intake of the cis-9,trans-11 (c9,t11) isomer of CLA, trans-10,cis-12 (t10,c12) isomer of CLA or olive oil (placebo) on linoleic acid (LA) and linolenic acid (LNA) metabolism in healthy human volunteers was investigated. Fifteen subjects were fed an experimental diet and supplemented with c9,t11-CLA, t10,c12-CLA or placebo for 7 d before consuming a tracer dose of U-[(13)C]LA (50 mg) and U-[(13)C]LNA (50 mg). Blood samples were taken at 0, 2, 4, 6, 8, 24, 48, 72 and 168 h and analysed using high-precision MS. No differences between the groups in peak plasma [(13)C]LA (10.3-11.6 % of dose), [(13)C]LNA (2.5-2.9 % of dose), [(13)C]arachidonic acid (0.09-0.12 % of dose), [(13)C]EPA (0.04-0.06 % of dose) or [(13)C]DHA (0.06-0.10 % of dose) were detected. Concentration v. time curves (area under the curve) also showed no significant differences between groups. This suggests that, in healthy human subjects consuming a diet with adequate intake of essential fatty acids, CLA does not affect metabolism of LA or LNA.

No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects.

BACKGROUND: High intake of vegetables and fruits is associated with decreased risk of coronary heart disease. Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits, such as flavonoids. AIM OF THE STUDY: To study the effects of high and low intake of vegetables, berries and apple on platelet function and inflammatory markers. METHODS: The study was a randomised, controlled parallel human dietary intervention with healthy female and male volunteers (n = 77, 19-52 y). Nineteen healthy volunteers served as controls. The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables, berries and apple and rich either in linoleic acid (11% of energy, en%) or oleic acid (12 en%). Blood and three 24-hour urine samples were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation. RESULTS: No differences between the treatment groups were seen in platelet count or volume, markers of platelet activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide, protein kinase C activity, urinary 2,3-dinor-thromboxane B2 excretion, plasma P-selectin), plasma intercellular adhesion molecule-1, sensitive C-reactive protein, or antiphospholipid antibodies. CONCLUSIONS: The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables, berries and apple do not differ in their effects on platelets or inflammation.