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.

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.

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.