Table 1.
Intervention trials exploring the effects of fish-derived protein hydrolysates on health, exercise performance, and ageing in healthy humans.
| Reference | Participants | Research Design | FPH Source Species | Dosage | Exercise Protocol | Main Outcomes | Key Findings |
|---|---|---|---|---|---|---|---|
| Alvares et al. [59] | Healthy adults (6 males, 3 females; mean age not reported) | Randomised, double-blind, placebo-controlled, crossover trial | Nile tilapia—Oreochromis niloticus | 5 g FPH or PLA (sucralose) dissolved in 100 mL water | N/A | Primary outcomes: Flow-mediated dilation (FMD), tissue oxygen saturation (StO2) Secondary outcome: total antioxidant capacity (TAC) of each beverage | FMD and StO2 parameters did not significantly change between FPH and PLA supplementation. TAC was significantly greater in the FPH supplement compared with the PLA. |
| Cordeiro et al. [68] | Physically active subjects (6 males, 3 females; age 27 ± 2 years) | Randomised, double-blind, placebo-controlled, crossover trial | Nile tilapia—Oreochromis niloticus | 0.25 g·kg−1·body mass−1 WPH, FPH or PLA immediately following RE | 3 sets × 10–12 RM leg press and leg extension | Primary outcomes: Plasma TAAs, EAAs, BCAAs, leucine (0, 30, 60, 90, 120, 180 min post-supplement) | Rapid and pronounced aminoacidaemia was observed following FPH and WPH, with no significant differences between protein sources at any time point. |
| Dale et al. [69] | Healthy, active individuals (15 males, 26 females; age 51 ± 6 years) | Randomised, double-blind, crossover trial | Atlantic cod—Gadus morhua | 20 mg FPH or casein (control) per kg body weight before standardised breakfast | N/A | Primary outcomes: Serum glucose and insulin at 20 min intervals from 0 to 180 min postprandial Secondary outcomes: Plasma GLP-1 at the same time points | Postprandial serum insulin secretion was significantly lower following FPH, with no difference observed between FPH and control for serum glucose or plasma GLP-1. |
| Dale et al. [70] | Healthy individuals (15 males, 26 females; age 51 ± 6 years) | Randomised, double-blind, crossover trial | Atlantic cod—Gadus morhua | 20 mg FPH or casein (control) per kg body weight before standardised breakfast | N/A | Primary outcomes: Plasma acylated ghrelin at 0, 20, 40, 80, 180 min postprandial Secondary outcomes: Subjective appetite sensations at the same time points | No effect of single-dose FPH on plasma acylated ghrelin, subjective satiety, or fullness sensations. |
| Dale et al. [71] | Irritable bowel syndrome (IBS) patients: FPH (n = 13, age 42.7 ± 11.9 years) or PLA (n = 15, age 45.1 ± 14.8 years) | Randomised, double-blind, placebo-controlled, parallel-intervention trial | Atlantic cod—Gadus morhua. | 2.5 g FPH or PLA (maltodextrin) consumed daily for six weeks | N/A | Primary outcomes: IBS-SSS and QoL scores Secondary outcomes: Serum pro-inflammatory cytokines and gut integrity markers, faecal SCFAs and calprotectin | Total IBS-SSS scores reduced in both groups and did not differ at the end of the six weeks. No significant changes in serum pro-inflammatory cytokines, gut integrity markers or faecal measures. |
| Drotningsvik et al. [72] | Nursing home residents (intervention group: n = 12, age 84 ± 8 years; control group: n = 9, age 87 ± 5 years) | Randomised, double-blind, placebo-controlled pilot trial | Blue whiting—Micromesistius poutassou | 5.2 g FPH or PLA daily for six weeks | N/A | Primary outcome: Feasibility of FPH intervention in older nursing home residents (participant compliance). Secondary outcomes: Serum markers of glucose metabolism and inflammation (MCP-1, CRP) | FPH intervention was feasible (completion rate = 88%). No significant between-group differences in baseline parameters. Serum MCP-1 was reduced and CRP increased from baseline to endpoint in the intervention group compared with the control group. Glucose, insulin, and fructosamine were unaffected by the intervention. |
| Jensen et al. [73] | Healthy older adults (13 male, 18 female; age 67.8 ± 4.9 years) | Randomised, double-blind, dose range crossover trial | Atlantic cod—Gadus morhua | 10, 20, 30, or 40 mg·kg−1·body weight daily for one week with washout periods (one week) in between | N/A | Primary outcomes: Serum glucose and insulin at 20 min intervals for 2 h following FPH consumption and standardised breakfast on day 7 of each cycle. Secondary outcomes: Plasma GLP-1 at the same time points | No differences in estimated maximum value of insulin, glucose, or GLP-1 were found when comparing the lowest dose to higher doses. No significant differences in total AUC for any variable irrespective of dose. |
| Marchbank et al. [74] | Healthy volunteers (age 25–40 years; 5 males, 5 females) | Randomised, double-blind, placebo-controlled crossover trial | Pacific whiting | 1 g FPH or placebo capsule three times daily for seven days followed by a two-week washout period, then the corresponding arm. Indomethacin (50 mg three times daily) was added for the final five days. | N/A | Primary outcomes: Gut permeability measured using 5 h urinary lactulose:rhamnose ratios. Secondary outcome: Dyspepsia incidence | Gut permeability increased approximately five-fold in placebo and indomethacin, but this effect was mitigated in the FPH arm. Dyspepsia was present in 50% of participants in the placebo arm but 0% in the FPH arm. |
| Mjøs et al. [75] | Healthy, trained, male cyclists (age 45.6 ± 5.3 years) | Randomised, double-blind, placebo-controlled trial | Atlantic cod—Gadus morhua | CHO-WP (PLA) or CHO-WP-FPH (20 mg FPH; isonitrogenous and isoenergetic beverages) following a cycling session, then 4 h recovery before an identical cycling session | 20 min moderate intensity cycling at 60% VO2max; 90% VO2max for 5 min, then TTE at 95% VO2max | Primary outcome: TTE. Secondary outcomes: HR, RER, blood lactate, and glucose | No significant difference between supplementations measured by TTE, HR, RER, blood glucose, or lactate. |
| Nobile et al. [76] | Healthy, slightly overweight (25 kg/m2 ≤ BMI ≤ 30 kg/m2) male (25%) and female (75%) subjects (age approximately 40 years) | Randomised, double-blind, placebo-controlled, parallel trial | Blue whiting—Micromesistius poutassou | Either 1.4 g FPH, 2.8 g FPH, or whey protein isolate (PLA) daily for 90 consecutive days | N/A | Primary outcomes: Body composition (weight, fat mass, extracellular water, circumference of the waist, hips, and thighs) Secondary outcomes: Fasting plasma concentrations of total CCK and GLP-1 | Treated subjects had improved body composition after 90 days. Measured end points did not differ significantly between 1.4 g and 2.8 g FPH. Increased fasting concentrations of CCK and GLP-1 were observed after 90 days in all conditions. |
| Oliveira et al. [60] | Healthy young (6 males, 3 females; age 22.5 ± 3.3 years), physically active adults | Randomised, double-blind, placebo-controlled, crossover trial | Nile tilapia—Oreochromis niloticus | 20 g single dose of FPH, WPH dissolved in 100 mL water or 5 g PLA (sucralose; six capsules) taken with 100 mL water | N/A | Primary outcome: FMD at 10, 30, 60, and 120 min postprandial. Secondary outcome: Total antioxidant capacity (TAC) of each condition. | Endothelium-dependent dilation increased at 30 min following WPH but not FPH. TAC was greater in the FPH compared with the WPH and PLA. |
| Siegler et al. [77] | Healthy (median (IQR): age 23 (6) years), aerobically trained males (mean ± SD: VO2max 52.5 ± 5.2 mL·kg−1·min−1) | Randomised, double-blind, crossover design | Salmon | 180 mL of the following beverages every 15 min during exercise (CHO only: 67 g·h−1 maltodextrin; CHO-PRO: 53.1 g·h−1 maltodextrin and 13.6 g·h−1 WPC; CHO-PRO-PEP: 53.1 g·h−1 maltodextrin, 13.6 g·h−1 WPC, and 2.4 g·h−1 FPH) | 90 min bout of cycling at 50% Wmax followed by a 5-km time trial | Primary outcome: 5-km TT time to completion, power output. Secondary outcomes: RER, HR | Mean 5-km TT time to completion and power output did not differ between trials. RER in CHO-PRO was higher than CHO and CHO-PRO-PEP. |
| Vegge, Rønnestad and Ellefsen [78] | Well-trained male cyclists (age 22 ± 2 years; VO2max 65 ± 4 mL·kg−1·min−1) | Randomised, double-blind, crossover trial | NutripeptinTM (Np; codfish-based) | Either a CHO beverage containing 8.3% maltodextrin (60 g·h−1), PROCHO (maltodextrin and 2.1% intact whey protein, 12.4 g·h−1), or NpPROCHO (maltodextrin and whey plus 0.4% Np (2.7 g·h−1). | Prolonged cycling (120 min) at 50% Wmax followed by 5 min mean-power test | Primary outcome: 5-min mean-power performance. Secondary outcomes: HR, VO2, RER, RPE, blood glucose and lactate, blood urea nitrogen | 5-min mean-power did not differ between beverages. There were no differences between beverages for HR, RER, VO2, glucose, lactate, or RPE. Blood urea nitrogen significantly increased from baseline to 120 min in NpPROCHO and PROCHO only. |
| Zaïr et al. [79] | Healthy, overweight (BMI: 25–30 kg/m2) women (age 18–50 years) | Randomised, double-blind, placebo-controlled crossover trial | Blue whiting | 1 g FPH or placebo (microcrystalline cellulose) twice daily for two weeks, followed by a two-week washout period. Testing sessions lasted 420 min, with products consumed at 0 min and 240 min, followed by an ad libitum lunch at 270 min | N/A | Primary outcome: Subjective appetite sensations. Secondary outcomes: Plasma glucose, insulin, CCK, and GLP-1. Ad libitum energy intake | No differences in hunger AUC between FPH and placebo. Lower plasma glucose at 270 min in FPH compared with PLA. No differences in plasma insulin, CCK and GLP-1 or ad libitum energy intake |
Abbreviations: AUC, area under the curve; BCAA, branched-chain amino acid; BMI, body mass index; CCK, cholecystokinin; CHO, carbohydrate; CRP, C-reactive protein; EAA, essential amino acid; FMD, flow-mediated dilation; FPH/PEP, fish protein hydrolysate; GLP-1, glucagon-like peptide 1; HR, heart rate; IBS-SSS, Irritable Bowel Syndrome Severity Scoring System; IQR, interquartile range; MCP-1, monocyte chemoattractant protein 1; N/A, not applicable; PLA, placebo; PRO, protein; QoL, quality of life; RER, respiratory exchange ratio; RPE, rating of perceived exertion; SCFA, short-chain fatty acid; SD, standard deviation; StO2, skeletal muscle oxygen saturation; TAA, total amino acid; TAC, total antioxidant capacity; TT, time trial; TTE, time to exhaustion; WPC, whey protein concentrate; WPH, whey protein hydrolysate; VO2, volume of oxygen; VO2max, maximal oxygen uptake.