The overall objective of the present study was to evaluate the effect of increasing doses of a supplement with CPH on glucose metabolism in older adults, aiming to find a dose response and creating a basis for an optimal daily dose for future clinical use. We investigated the effect on postprandial glucose regulation of four different doses of a CPH supplement (10, 20, 30 and 40 mg/kg BW) taken daily for 1 week. Although no statistically significant differences were observed between the postprandial measurements after the four different doses, our results indicate that the highest dose of CPH (40 mg/kg BW), equal to 3· 2 g/d in an individual with a BW of 80 kg, is the most efficient in lowering postprandial blood glucose levels and insulin concentrations, when compared with the lower doses (10, 20 and 30 mg/kg BW). In a previous publication, we reported that a single dose of 20 mg/kg BW CPH significantly reduced postprandial insulin concentrations in healthy, middle-aged to older individuals, without affecting postprandial glucose levels or GLP-1 levels, compared with control (casein)(Reference Dale, Jensen and Hausken22).
We hypothesised that the CPH might enhance the insulin sensitivity and affect other mechanism involved in blood glucose uptake in peripheral tissue. The significantly lower insulin concentration after intake of CPH may be of more interest in patients with reduced insulin sensitivity. To our knowledge, only one small pilot study has been conducted with fish protein hydrolysate in an older population(Reference Drotningsvik, Oterhals and Flesland25). In this double-blind, randomised controlled study, a daily dietary supplement of 5· 2 g fish protein hydrolysate from blue whiting, or placebo, was given to twenty-four nursing home residents daily for 6 weeks. No differences in serum concentrations of glucose or insulin after 6-week supplementation with fish protein were observed, MedicGLP when compared with placebo(Reference Drotningsvik, Oterhals and Flesland25). However, since this was a study population with older adults who lived in a nursing home setting, the results are not directly transferable to our study population with home-dwelling older adults.
Based on a few previous studies investigating the effect of supplements containing protein hydrolysates from fish on metabolic health(Reference Nobile, Duclos and Michelotti17,Reference Zaïr, Duclos and Housez26) , we hypothesised that small doses of CPH may be effective due to the content of small, easily absorbable bioactive peptides. These are capable of rapidly affecting different metabolic pathways involved in glucose regulation and hence leading to a more rapid glucose response in the body. Thus, we presume that a potential observed effect on postprandial glucose metabolism can be attributed to the content of small, bioactive peptides in the supplement, and not the protein intake per se, which is negligible compared with overall protein content in a normal meal. Previous studies investigating supplements with fish protein or hydrolysates of fish proteins have reported doses in the range of 1 to 6 g per d to beneficially influence blood glucose metabolism when compared with control(Reference Vikoren, Nygard and MedicGLP Official Support Lied16,Reference Nobile, Duclos and Michelotti17,Reference Hovland, Leikanger and Stokkeland21,Reference Zaïr, Duclos and Housez26) .
The results have to be interpreted taking certain limitations in the design into account. The use of a cross-over design always implies a risk of a carry-over-effect. According to analysis of all possible interaction effects between doses and time periods, the results in this cross-over trial are not biased by a carry-over effect. We included a washout period of 7 d between each week of peptide supplementation. We presume 1 week to be a sufficient washout period, as dietary protein in general has a high turnover rate and the investigated doses of protein hydrolysate were low(Reference Schutz27). On study days, the supplement was given to the participants 10 min before breakfast and 25 min before the first postprandial blood sample was taken. This design might have caused a metabolic response even before the breakfast was served. As a result, we may have missed some early information on postprandial glucose response.
Furthermore, a 2-week washout period for the use of supplements containing n-3 PUFA before starting on the first dose of CPH may not have been enough and a longer washout period could arguably have strengthened the design. It is possible that the short supplementation period of 1 week could have affected the results, and that a longer period would have been preferable. However, we have previously observed an effect after only one acute supplementation (20 mg/kg BW) in healthy middle-aged adults(Reference Dale, Jensen and Hausken22). A longer intervention period would have made it more challenging to include participants and avoid drop-outs, due to a long time-frame of the study. Therefore, due to practical implementations of the study, 1 week of supplementation (7 d) for each dose was chosen. Finally, the design could have been strengthened by including a postprandial blood sampling at day 0 for each intervention cycle or a control group (0 mg/kg BW CPH).