Amino Acid Plasma Profiles from a Prolonged-Release Protein Substitute for Phenylketonuria: A Randomized, Single-Dose, Four-Way Crossover Trial in Healthy Volunteers.

Several disorders of amino acid (AA) metabolism are treated with a protein-restricted diet supplemented with specific AA mixtures. Delivery kinetics impacts AA absorption and plasma concentration profiles. We assessed plasma profiles after ingestion of an AA mixture engineered to prolong AA absorption with Physiomimic TechnologyTM (Test) in a randomized, single-dose, four-way crossover trial in healthy volunteers (Trial Registration: ISRCTN11016729). In a two-step hypothesis, the primary endpoints were (i) significant reduction in peak plasma concentrations (Cmax) of essential amino acids (EAAs) while (ii) maintaining EAA bioavailability (AUC0-300 min) compared to a free AA mixture (Reference). Secondary endpoints included effects on plasma profiles of other AA groups and effects on several metabolic markers. Thirty subjects completed the study. Both co-primary endpoints were met: Cmax for EAAs was 27% lower with the Test product compared to the Reference product (ratio, 0.726, p < 0.0001); overall plasma EAA levels from the two AA mixtures was within the pre-specified bioequivalence range (AUC0-300min ratio, 0.890 (95% CI: 0.865, 0.915)). These findings were supported by the results of secondary endpoints. Prolongation of AA absorption was associated with modulation of several metabolic markers. It will be important to understand whether this can improve the long-term management of disorders of AA metabolism.

Prospective, randomized, double-blinded, placebo-controlled study on safety and tolerability of the krill powder product in overweight subjects with moderately elevated blood pressure.

BACKGROUND: Krill powder is rich in bioactive ingredients such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), phospholipids, protein and astaxanthin. Containing dominantly EPA, it is considered to be effective in lowering lipids, foremost serum triglycerides and LDL cholesterol. Krill-derived protein hydrolysates/peptides may have positive effect on blood pressure and astaxanthin has anti-oxidative and anti-inflammatory properties. Thus, krill powder has a lot of potential in improving lipid and metabolic profile and reinforcing the activity of the antioxidant system. However, randomized clinical trials on krill powder are scarce and systematic data of krill meal on human safety is limited. Some of the earlier studies have reported several, non-serious adverse events, mostly related to gastrointestinal tract, but systematic sufficiently powered study on safety is lacking. The aim of this study was to collect data on safety and tolerability of krill powder in humans and simultaneously gain efficacy data by measuring the risk factors for cardiovascular disease. METHODS: The study was a randomised, double-blinded, placebo-controlled intervention study with 35 overweight subjects with mildly or moderately elevated blood pressure, who took 4 g krill oil powder or 4 g of placebo during an 8-week follow-up period. The study consisted of a pre-screening, screening, day 0 baseline (randomization visit) and three follow-up visits on days 14, 28 and 56. The reported adverse events in the groups were compared as primary endpoint and haematological safety parameters and changes in systolic and diastolic pressure and blood total and lipoprotein lipids were measured as secondary end points. RESULTS: There were in total 80 reported adverse events during the follow-up; 50 in placebo and 30 in krill powder group. Gastrointestinal symptoms (flatulence, heartburn and diarrhea) were the most commonly reported among those probably related to the test products. No serious adverse events were reported. The mean value of all measured hematology variables remained within the reference values in all study subject and no significant changes were observed in blood pressure or lipid values. CONCLUSIONS: The results seem to indicate that using krill powder as a source for EPA and DHA is safe in therapeutic dose and the risk of adverse events, let alone serious ones, is low. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03112083 , retrospectively registered.

Cereal-Based Snack Bar with Added Plant Stanol Ester (Benecol®) Consumed between Meals Lowers Serum Total and LDL Cholesterol Effectively in Mildly to Moderately Hypercholesterolemic Subjects.

The cholesterol-lowering effect of foods with added plant sterols or stanols consumed as snacks might be compromised. The purpose of this study was to confirm the cholesterol-lowering efficacy of a specially formulated cereal-based snack bar with added plant stanol ester (1.6 g plant stanols/day) when consumed between meals twice a day. In a double-blind, placebo-controlled, 4-week parallel-design study, 71 mildly to moderately hypercholesterolemic subjects were randomized into one of two groups, stanol or placebo group. Subjects were advised to replace their ordinary snacks with test products in an isocaloric manner and otherwise keep their habitual diet unchanged. The study showed that a snack bar product with added plant stanol ester lowered LDL and non-HDL cholesterol by 8.6% and 9.2% (mean%-change), respectively, as compared to the placebo product. The change in LDL cholesterol was statistically significantly different (P = 0.001) between the groups while the change in HDL cholesterol or triglycerides did not differ between the groups. In conclusion, the cereal-based snack bar with added plant stanol ester ingested without a meal reduced LDL cholesterol significantly without affecting HDL cholesterol or triglyceride concentrations in mildly hypercholesterolemic men and women. The study is registered as NCT03284918.

Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects--a randomized, single-dose, cross-over trial.

BACKGROUND: Krill contains two marine omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly bound in phospholipids. Typical products from krill are krill oil and krill meal. Fish oils contain EPA and DHA predominantly bound in triglycerides. The difference in the chemical binding of EPA and DHA has been suggested to affect their bioavailability, but little is known on bioavailability of EPA and DHA in krill meal. This study was undertaken to compare the acute bioavailability of two krill products, krill oil and krill meal, with fish oil in healthy subjects. METHODS: A randomized, single-dose, single-blind, cross-over, active-reference trial was conducted in 15 subjects, who ingested krill oil, krill meal and fish oil, each containing approx. 1 700 mg EPA and DHA. Fatty acid compositions of plasma triglycerides and phospholipids were measured repeatedly for 72 hours. The primary efficacy analysis was based on the 72 hour incremental area under the curve (iAUC) of EPA and DHA in plasma phospholipid fatty acids. RESULTS: A larger iAUC for EPA and DHA in plasma phospholipid fatty acids was detected after krill oil (mean 89.08±33.36%×h) than after krill meal (mean 44.97±18.07%xh, p<0.001) or after fish oil (mean 59.15±22.22%×h, p=0.003). Mean iAUC's after krill meal and after fish oil were not different. A large inter-individual variability in response was observed. CONCLUSION: EPA and DHA in krill oil had a higher 72-hour bioavailability than in krill meal or fish oil. Our finding that bioavailabilities of EPA and DHA in krill meal and fish oil were not different argues against the interpretation that phospholipids are better absorbed than triglycerides. Longer-term studies using a parameter reflecting tissue fatty acid composition, like erythrocyte EPA plus DHA are needed. TRIAL REGISTRATION: NCT02089165.

Berries reduce postprandial insulin responses to wheat and rye breads in healthy women.

Starch in white wheat bread (WB) induces high postprandial glucose and insulin responses. For rye bread (RB), the glucose response is similar, whereas the insulin response is lower. In vitro studies suggest that polyphenol-rich berries may reduce digestion and absorption of starch and thereby suppress postprandial glycemia, but the evidence in humans is limited. We investigated the effects of berries consumed with WB or RB on postprandial glucose and insulin responses. Healthy females (n = 13-20) participated in 3 randomized, controlled, crossover, 2-h meal studies. They consumed WB or RB, both equal to 50 g available starch, with 150 g whole-berry purée or the same amount of bread without berries as reference. In study 1, WB was served with strawberries, bilberries, or lingonberries and in study 2 with raspberries, cloudberries, or chokeberries. In study 3, WB or RB was served with a mixture of berries consisting of equal amounts of strawberries, bilberries, cranberries, and blackcurrants. Strawberries, bilberries, lingonberries, and chokeberries consumed with WB and the berry mixture consumed with WB or RB significantly reduced the postprandial insulin response. Only strawberries (36%) and the berry mixture (with WB, 38%; with RB, 19%) significantly improved the glycemic profile of the breads. These results suggest than when WB is consumed with berries, less insulin is needed for maintenance of normal or slightly improved postprandial glucose metabolism. The lower insulin response to RB compared with WB can also be further reduced by berries.

Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women.

BACKGROUND: Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE: We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN: Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS: Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.

Postprandial glucose, insulin and glucagon-like peptide 1 responses to sucrose ingested with berries in healthy subjects.

Berries are often consumed with sucrose. They are also rich sources of polyphenols which may modulate glycaemia after carbohydrate ingestion. The present study investigated the postprandial glucose, insulin and glucagon-like peptide 1 (GLP-1) responses to sucrose ingested with berries, in comparison with a similar sucrose load without berries. A total of twelve healthy subjects were recruited to a randomised, single-blind, placebo-controlled crossover study. They participated in two meal tests on separate days. The berry meal was a purée (150 g) made of bilberries, blackcurrants, cranberries and strawberries with 35 g sucrose. The control meal included the same amount of sucrose and available carbohydrates in water. Fingertip capillary and venous blood samples were taken at baseline and at 15, 30, 45, 60, 90 and 120 min after starting to eat the meal. Glucose, insulin and GLP-1 concentrations were determined from the venous samples, and glucose also from the capillary samples. Compared to the control meal, ingestion of the berry meal resulted in lower capillary and venous plasma glucose and serum insulin concentrations at 15 min (P = 0·021, P < 0·007 and P = 0·028, respectively), in higher concentrations at 90 min (P = 0·028, P = 0·021 and P = 0·042, respectively), and in a modest effect on the GLP-1 response (P = 0·05). It also reduced the maximum increases of capillary and venous glucose and insulin concentrations (P = 0·009, P = 0·011 and P = 0·005, respectively), and improved the glycaemic profile (P < 0·001 and P = 0·003 for capillary and venous samples, respectively). These results suggest that the glycaemic control after ingestion of sucrose can be improved by simultaneous consumption of berries.

Feasibility and antihypertensive effect of replacing regular salt with mineral salt -rich in magnesium and potassium- in subjects with mildly elevated blood pressure.

BACKGROUND: High salt intake is linked to hypertension whereas a restriction of dietary salt lowers blood pressure (BP). Substituting potassium and/or magnesium salts for sodium chloride (NaCl) may enhance the feasibility of salt restriction and lower blood pressure beyond the sodium reduction alone. The aim of this study was to determine the feasibility and effect on blood pressure of replacing NaCl (Regular salt) with a novel mineral salt [50% sodium chloride and rich in potassium chloride (25%), magnesium ammonium potassium chloride, hydrate (25%)] (Smart Salt). METHODS: A randomized, double-blind, placebo-controlled study was conducted with an intervention period of 8-weeks in subjects (n = 45) with systolic (S)BP 130-159 mmHg and/or diastolic (D)BP 85-99 mmHg. During the intervention period, subjects consumed processed foods salted with either NaCl or Smart Salt. The primary endpoint was the change in SBP. Secondary endpoints were changes in DBP, daily urine excretion of sodium (24-h dU-Na), potassium (dU-K) and magnesium (dU-Mg). RESULTS: 24-h dU-Na decreased significantly in the Smart Salt group (-29.8 mmol; p = 0.012) and remained unchanged in the control group: resulting in a 3.3 g difference in NaCl intake between the groups. Replacement of NaCl with Smart Salt resulted in a significant reduction in SBP over 8 weeks (-7.5 mmHg; p = 0.016). SBP increased (+3.8 mmHg, p = 0.072) slightly in the Regular salt group. The difference in the change of SBP between study groups was significant (p < 0.002). CONCLUSIONS: The substitution of Smart Salt for Regular salt in subjects with high normal or mildly elevated BP resulted in a significant reduction in their daily sodium intake as well as a reduction in SBP.

Berries modify the postprandial plasma glucose response to sucrose in healthy subjects.

Sucrose increases postprandial blood glucose concentrations, and diets with a high glycaemic response may be associated with increased risk of obesity, type 2 diabetes and CVD. Previous studies have suggested that polyphenols may influence carbohydrate digestion and absorption and thereby postprandial glycaemia. Berries are rich sources of various polyphenols and berry products are typically consumed with sucrose. We investigated the glycaemic effect of a berry purée made of bilberries, blackcurrants, cranberries and strawberries, and sweetened with sucrose, in comparison to sucrose with adjustment of available carbohydrates. A total of twelve healthy subjects (eleven women and one man, aged 25-69 years) with normal fasting plasma glucose ingested 150 g of the berry purée with 35 g sucrose or a control sucrose load in a randomised, controlled cross-over design. After consumption of the berry meal, the plasma glucose concentrations were significantly lower at 15 and 30 min (P < 0.05, P < 0.01, respectively) and significantly higher at 150 min (P < 0.05) compared with the control meal. The peak glucose concentration was reached at 45 min after the berry meal and at 30 min after the control meal. The peak increase from the baseline was 1.0 mmol/l smaller (P = 0.002) after ingestion of the berry meal. There was no statistically significant difference in the 3 h area under the glucose response curve. These results show that berries rich in polyphenols decrease the postprandial glucose response of sucrose in healthy subjects. The delayed and attenuated glycaemic response indicates reduced digestion and/or absorption of sucrose from the berry meal.

Safety of barley starch syrup in patients with allergy to cereals.

It is not known whether trace amounts of proteins that may remain in cereal-starch-derived food ingredients even after food processing can trigger allergic symptoms in cereal-allergic individuals. The aim of this study was to find out if barley starch syrup causes allergic reactions in patients with allergy to wheat, barley, rye or oats. Fifteen children with allergy to these cereals, confirmed by double-blind placebo-controlled food challenge (DBPCFC), were selected for the study. When exposed to cereals, seven of the children (47%) showed immediate type reactions, such as urticaria, rash or anaphylaxis. Eight of the children (53%) showed delayed type reactions, such as deterioration of atopic dermatitis or diarrhoea. The fifteen children with allergy to cereals were exposed to barley starch syrup in DBPCFC and none of them showed any objective signs of allergy. On skin-prick tests (SPT), five of the children (33.3%) showed a positive (>or= 3 mm) reaction to at least one of the cereals but none of them to barley starch syrup. This study confirmed with 98% confidence that at least 90% of the patients with verified allergy to cereals will not react with allergic symptoms to barley starch syrup.

Safety aspects and cholesterol-lowering efficacy of chitosan tablets.

OBJECTIVE: The purpose of this study was to determine the effect of two different doses of chitosan on serum fat-soluble vitamin concentrations, cholesterol concentrations, and other safety parameters. METHODS: A total of 65 men and women consumed 0, 4.5, 6.75 g per day of chitosan or 6.75 g per day glucomannan for eight weeks in a parallel, placebo-controlled, single-blind study. Altogether, 56 participants completed the study. RESULTS: No differences were detected among the treatments in serum vitamins (vitamin A, vitamin E, 25-hydroxyvitamin D), carotenes (alpha- and beta-carotene), clinical chemistry or hematology measurements. The changes in the total and LDL-cholesterol concentrations among the study groups were not statistically significant. CONCLUSION: In the present study, the consumption of chitosan tablets was found to be safe, but there was no significant effect on cholesterol concentration.

Measuring the glycemic index of foods: interlaboratory study.

BACKGROUND: Many laboratories offer glycemic index (GI) services. OBJECTIVE: We assessed the performance of the method used to measure GI. DESIGN: The GI of cheese-puffs and fruit-leather (centrally provided) was measured in 28 laboratories (n=311 subjects) by using the FAO/WHO method. The laboratories reported the results of their calculations and sent the raw data for recalculation centrally. RESULTS: Values for the incremental area under the curve (AUC) reported by 54% of the laboratories differed from central calculations. Because of this and other differences in data analysis, 19% of reported food GI values differed by >5 units from those calculated centrally. GI values in individual subjects were unrelated to age, sex, ethnicity, body mass index, or AUC but were negatively related to within-individual variation (P=0.033) expressed as the CV of the AUC for repeated reference food tests (refCV). The between-laboratory GI values (mean+/-SD) for cheese-puffs and fruit-leather were 74.3+/-10.5 and 33.2+/-7.2, respectively. The mean laboratory GI was related to refCV (P=0.003) and the type of restrictions on alcohol consumption before the test (P=0.006, r2=0.509 for model). The within-laboratory SD of GI was related to refCV (P<0.001), the glucose analysis method (P=0.010), whether glucose measures were duplicated (P=0.008), and restrictions on dinner the night before (P=0.013, r2=0.810 for model). CONCLUSIONS: The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.

The effect of meat products enriched with plant sterols and minerals on serum lipids and blood pressure.

The purpose of the study was to investigate the effect of non-esterified plant sterol-enriched and mineral-enriched low-fat and low-salted meat products compared with control meat products, on serum total and lipoprotein lipids and blood pressure in subjects with mildly to moderately elevated serum cholesterol concentration. A randomised, placebo-controlled, single-blind, repeated measure design was used. Altogether 21 volunteers completed the study. The study began with a pre-trial period of 1-2 weeks, which was followed by three different test periods in the following order: meat products enriched with plant sterols (1.2 g/day), potassium, calcium and magnesium (MP1); meat products with no added plant sterols and minerals (control); and meat products with plant sterols (2.1 g/day), potassium, calcium and magnesium (MP2). Each test period lasted for 3 weeks. During the MP2 period, the serum total and low-density lipoprotein cholesterol concentration decreased 4.9+/-7.5% (P<0.05) and 4.6+/-11.3% (not significant), respectively, compared with the control period. No differences in the high-density lipoprotein cholesterol and total triglyceride concentrations or in systolic blood pressure and diastolic blood pressure were found among the test periods. In conclusion, the present study showed that frankfurters and cold cuts enriched with plant sterols from tall oil, potassium, calcium and magnesium, as part of habitual Finnish diet reduced the serum total cholesterol concentration in hypercholesterolemic subjects when the intake of sitosterols was 2.1 g/day, but not with the lower dose.

Effect of alpha-linolenic acid-rich Camelina sativa oil on serum fatty acid composition and serum lipids in hypercholesterolemic subjects.

Camelina sativa-derived oil (camelina oil) is a good source of alpha-linolenic acid. The proportion of alpha-linolenic acid in serum fatty acids is associated with the risk of cardiovascular diseases. We studied the effects of camelina oil on serum lipids and on the fatty acid composition of total lipids in comparison to rapeseed and olive oils in a parallel, double-blind setting. Sixty-eight hypercholesterolemic subjects aged 28 to 65 years were randomly assigned after a 2-week pretrial period to 1 of 3 oil groups: camelina oil, olive oil, and rapeseed oil. Subjects consumed daily 30 g (actual intake, approximately 33 mL) of test oils for 6 weeks. In the camelina group, the proportion of alpha-linolenic acid in fatty acids of serum lipids was significantly higher (P <.001) compared to the 2 other oil groups at the end of the study: 2.5 times higher compared to the rapeseed oil group and 4 times higher compared to the olive oil group. Respectively the proportions of 2 metabolites of alpha-linolenic acid (eicosapentaenoic and docosapentaenoic acids) increased and differed significantly in the camelina group from those in other groups. During the intervention, the serum low-density lipoprotein (LDL) cholesterol concentration decreased significantly by 12.2% in the camelina oil group, 5.4% in the rapeseed oil group, and 7.7% in the olive oil group. In conclusion, camelina oil significantly elevated the proportions of alpha-linolenic acid and its metabolites in serum of mildly or moderately hypercholesterolemic subjects. Camelina oil's serum cholesterol-lowering effect was comparable to that of rapeseed and olive oils.

Short-term LDL cholesterol-lowering efficacy of plant stanol esters.

BACKGROUND: The short-term cholesterol-lowering efficacy of plant stanol esters has been open to debate, and the data from different clinical studies with hypercholesterolemic subjects are variable, partly due to lack of systematic studies. Therefore, we investigated the time in days needed to obtain the full cholesterol-lowering effect of stanol esters in hypercholesterolemic subjects. METHODS: Eleven mildly to moderately hypercholesterolemic subjects consumed stanol ester margarine (2.0 g/day of stanols) as a part of their habitual diet for 14 days and the changes in serum lipid values were measured three times at 4, 8 and 15 days after the initiation of test margarine consumption (0 day). The returning of serum lipid concentrations to baseline was measured two times after 2 or 3 days and after 7 days of the end of the test margarine consumption. RESULTS: Serum LDL cholesterol concentrations were reduced from 0 day (4.51 +/- 0.66 mmol/l) by 3.5% (P = ns), 9.9% (p < 0.05) and 10.2% (P < 0.05) at 4, 8 and 15 days, respectively. Serum campesterol/total cholesterol ratio, an indirect marker of intestinal cholesterol absorption, was significantly reduced on day 4 already. After ending the stanol ester use serum cholesterol concentrations began to return rapidly and after 7 days serum LDL cholesterol was 5.3% less than the initial value (P = ns). CONCLUSION: The specific effect of plant stanol esters on serum LDL cholesterol can fully be obtained within 1-2 weeks of the use of plant stanol ester-enriched margarine.

Association of the fatty acid profile of serum lipids with glucose and insulin metabolism during 2 fat-modified diets in subjects with impaired glucose tolerance.

BACKGROUND: Both the amount and quality of dietary fat can modify glucose and insulin metabolism. OBJECTIVE: The objective was to examine the relation between serum lipid fatty acids and glucose metabolism before and after the consumption of a diet enriched in either monounsaturated (Mono diet) or polyunsaturated (Poly diet) fatty acids. DESIGN: After consuming a high-saturated-fat run-in diet for 3 wk, 31 subjects with impaired glucose tolerance were randomly counseled to consume the Mono [40% fat; 11%, 19%, and 8% of energy as saturated, monounsaturated, and polyunsaturated fatty acids (S:M:P), respectively] or the Poly (34% fat; S:M:P of 11%:10%:10%) diet for 8 wk. Serum lipid fatty acids were measured, and an intravenous-glucose-tolerance test was performed at baseline and at 8 wk. RESULTS: At baseline, a higher glucose effectiveness (S(G)) was associated with higher proportions of oleic (r = 0.57, P = 0.04) and alpha-linolenic (r = 0.64, P = 0.01) acids in phospholipids. An increase in the proportions of oleic and alpha-linolenic acids in phospholipids was associated with a decrease in fasting plasma glucose [r = -0.53 (P = 0.002) and r = -0.47 (P = 0.009), respectively]. An increase in the S(G) was associated with an increase in the proportion of oleic acid (r = 0.55, P = 0.004) and with a decrease in that of arachidonic acid (r = -0.40, P = 0.04) in phospholipids. CONCLUSIONS: The beneficial changes in fasting plasma glucose and in the S(G) during the Mono diet were associated with alterations in the proportions of oleic, alpha-linolenic, and arachidonic acids in phospholipids.