Minimal Amounts of Fish Peptide Hydrolysate Double Fat Loss Compared to Whey Isolate on Energy Restricted Diet

Minimal Amounts of Fish Peptide Hydrolysate Double Fat Loss Compared to Whey Isolate on Energy Restricted Diet

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I certainly recommend eating fish. Whether I will be recommending fish hydrolysate supplements in the future, however, will have to be determined when additional studies with different baseline diets will have been published.

You may remember that I've written about fish protein hydrolysates / peptides before. Unlike today's article, however, previous articles dealt with the effects of fish protein in rodents. Intrigued by in vitro and animal studies showing that fish-derived peptides demonstrated antihypertensive (Hatanaka. 2009; Kim. 2012; Li. 2012; Ngo. 2011), antioxidant (Nazeer. 2012; Najafian. 2012), immunomodulating effects (Duarte. 2006), reparative properties in the intestine (Fitzgerald. 2005; Marchbank. 2008), and effects in reducing plasma cholesterol and triglycerides levels (Möller. 2008), a group of Italian researchers decided to investigated the effect of Slimpro(R), a supplement containing commercially available fish protein hydrolysate from blue whiting (Micromesistius poutassou), on body composition and on stimulating cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) secretion in 120, overweight, non-obese (25 kg/m² < BMI < 30 kg/m²), male (25%) and female (75%) subjects aged 18 - 55 year.

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Unlike the product that was used may suggest, the study was not sponsored by the supplement company. The authors received neither funding nor other external support and they also declare that they don't have a conflict of interest that may be related to patents or direct involvements in the industry. I guess it's important to point that out, even though fact that the scientists chose whey, i.e. an actually relevant control, instead of carbohydrates or just plain water, may have given away the lack of sponsorship, anyways.

Two weeks before the study started, subjects were asked to fill in an alimentary diary reporting their food preferences. A mild hypocaloric ( 300 kcal/day) diet was elaborated for each subject by a dietitian based on subject’s food preferences and habits as reported in the alimentary diary.

Figure 1: The low protein content of the diet is - as highlighted in the annotations to this graphical illustration of the macronutrient composition of the test diets - problematic, to say the least.

Approximately, 55% of energy intake was from carbohydrates, 25% from lipids, and the remaining 20% from proteins. Part of these 20% of protein were either 1.4g and 2.8g of fish protein or 1.4g of whey protein isolate as a control (I just assume that the dosage was 1.4g, because there was only one whey group), which were consumed in form of a flavored shake according to the following protocol:

"Both the active (one dose treatment arm) and the placebo products were taken as follows: ‘dilute the content of one sachet in a large glass of cool water (200 ml). Shake or stir with a spoon. Consume within 10 30 min before the main meal’. In the case of two-dose treatment arm, one sachet of the active product was taken 30 min before lunch and one sachet 30 min before dinner" (Nobile. 2016).

To be able to tell what could be responsible for advantages or disadvantages of the two treatments, the scientists assessed more than just body weight, fat mass (DXA scans), and safety of use as well as the secondary efficacy endpoints, extracellular water, and the circumference of waist, hips, and thighs. They also checked the CCK and GLP-1 levels in their subjects' blood. This is relevant, because this is how the fish hydrolysate is advertised on the manufacturers website:

"Taken daily before meals, Slimpro® increases the production of CCK and GLP-1 in the body, thus amplifying messages associated with a decrease of food intake. Promising results were reported from in vivo et in vitro trials of these molecules that may control food intake. Scientists have described this ingredient as a direct action on the hunger process" (Nobile. 2015).

As it is usually the case in studies like this, some patients were "lost". In this case, we're talking about a total count of eleven subjects who did not reappear for the follow-up check (One subject in the one-dose treatment arm, four subjects in the twodose treatment arm, and six subjects in the placebo treatment arm discontinued intervention because they were no longer interested to participate in the study). The results of the other subjects are plotted in Figure 2:

Figure 2: Changes in body composition after 45 and 90 days of dieting w/ the specific supplements (Nobile. 2016).

As you can see, double-dosing had astonishingly little effect on the subjects' ability to lose body fat. That's in contrast to switching from fish protein hydrolysate to whey protein isolate, which produced measurably, but not statistically reduced rates of fat loss and waist reductions.

Figure 3: Blood biomarker levels. (a) CCK blood levels and (b) GLP-1 blood levels. Intragroup (vs. D0) statistical analysis is reported upon the bars of the histogram. The lines report the intergroup (vs. placebo) statistical analysis. Statistical analysis is reported as follows: *p < 0.05, **p < 0.01, and ***p < 0.001. Data are mean +/- SE (Nobile. 2016).

And guess what: Even though the bars don't look like it, the asterisks over the bars tell you that these differences may be caused by the same differential expression of the satiety hormones CCK and GLP-1 in the fish hydrolysate vs. whey protein group that has been observed with other control protein in previous studies and is boldly advertised on the producer's website.

Great! Let's eat more fish... It stands out of question that the former is actually a very good idea (assuming you make the right fish choices). I have to warn you, though: Firstly, the fish protein consumed in the study at hand came from fish, but just like whey protein and milk, fish and fish protein hydrolysates will also have different effects.

Is Wild Caught Fish Always the Better Choice? With Sign. More N3 and Less Pollutants?  Learn more!

What is probably way more important, however, is the relative protein deficiency of the subjects. With only 20% of the diet being protein, the study participants hovered around at the meager level of the RDA. Since the effects of 1.4g of fish protein hydrolysate you throw on top of a low protein diet are probably very different from those of the same amount of fish protein consumed alongside 2g/kg of dietary and supplemental protein, I wouldn't guarantee and in fact even doubt that you would see a similar almost 100% increase in fat loss while dieting - and still,  the CCK and GLP-1 boosting effects of fish protein hydrolysates are intriguing | Comment on Facebook!

References:

• Duarte, Jairo, et al. "Immunomodulating capacity of commercial fish protein hydrolysate for diet supplementation." Immunobiology 211.5 (2006): 341-350.
• Hatanaka, Akimasa, et al. "Isolation and identification of antihypertensive peptides from antarctic krill tail meat hydrolysate." Journal of food science 74.4 (2009): H116-H120.
• Kim, Se-Kwon, Dai-Hung Ngo, and Thanh-Sang Vo. "Marine fish-derived bioactive peptides as potential antihypertensive agents." Adv Food Nutr Res 65 (2012): 249-260.
• Li, Ying, et al. "Purification of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide with an antihypertensive effect from loach (Misgurnus anguillicaudatus)." Journal of agricultural and food chemistry 60.5 (2012): 1320-1325.
• Marchbank, T., et al. "Clinical trial: protective effect of a commercial fish protein hydrolysate against indomethacin (NSAID)‐induced small intestinal injury." Alimentary pharmacology & therapeutics 28.6 (2008): 799-804.
• Möller, Niels Peter, et al. "Bioactive peptides and proteins from foods: indication for health effects." European journal of nutrition 47.4 (2008): 171-182.
• Nazeer, R. A., NS Sampath Kumar, and R. Jai Ganesh. "In vitro and in vivo studies on the antioxidant activity of fish peptide isolated from the croaker (Otolithes ruber) muscle protein hydrolysate." Peptides 35.2 (2012): 261-268.
• Najafian, L., and Abd Salam Babji. "A review of fish-derived antioxidant and antimicrobial peptides: their production, assessment, and applications." Peptides 33.1 (2012): 178-185.
• Ngo, Dai-Hung, et al. "Free radical scavenging and angiotensin-I converting enzyme inhibitory peptides from Pacific cod (Gadus macrocephalus) skin gelatin." International journal of biological macromolecules 49.5 (2011): 1110-1116.

Overeating = Natural Response to Strict Dieting That Occurs Despite Increased Satiety Hormone Response to XXL-Meal

Overeating = Natural Response to Strict Dieting That Occurs Despite Increased Satiety Hormone Response to XXL-Meal

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This is not a photo from the full-text of the study, but it could be. After all the energy deficient diet was >90% below the maintenance intakes of the subjects. That's unfortunately much more severe than the average dieter's approach, but some of the things the scientists observed still have very general applications.

If you've ever dieted to make the cut in a sports with weight classes, you will know this insatiable hunger which climaxes on the last two days when you are down to a handful of  calories per day. It's a hunger that won't be satisfied even if you eat an extra 1000 kcal above maintenance.

Athletes competing in sports with weight classes may need to accept the post-dieting binge, but what about average Joes and Janes? Will a fasting day ruin the average dieters dieting efforts by making them eat more extra-calories on day 2 than they've economized the day before? A recent study from the US Army Research Institute of Environmental Medicine, in which scientists have attempted to stimulate and simulate this insatiable hunger in a tightly controlled experimental environment, may hold the answer.

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As Kristie L O'Connor et al. point out an altered secretion of appetite-mediating hormones is the #1 candidate to explain the common tendency for weight regain (Sumithran. 2013 | see Figure 1). This hypothesis is supported by several studies that have reported decreases in circulating leptin and insulin concentrations in response to weight loss that are disproportionately greater than contemporaneous reductions in fat mass (Mars. 2005; Blom. 2006; MacLean. 2006; Pasiakos. 2011; Sumithran. 2011). Other studies have documented blunted postprandial gastroenteropancreatic hormone responses after weight loss (Chan. 2004).

Figure 1: Selected pathways involved in body weight regulation (left) and tabular overview of physiological changes after diet-induced weight loss and their effect on energy intake and storage (right | Sumithran. 2013).

Scientists have speculated that these ill effects may be countered by eating diets with a low energy density and thus putting equivalent stress on the gastric mechanoreceptors in our guts. Unfortunately, this alone has turned out to be as ineffective as other attempts to minimize the adaptive response to energy restriction. On the other hand, the existing effects the volume of what we have will have on our satiety is something that has been overlooked in previous studies.

Figure 2: Study design. EB, energy balance; ED, energy deprivation; EE, energy expenditure; EI, energy intake; RMR, resting metabolic rate; TDEE, total daily energy expenditure; VAS, visual analogue scale (O'Connor. 2016).

Overall, our understanding of the complex relationship between what and how much we eat and how this affects our subjective satiety and corresponding hormone response is still very limited. To address this knowledge gap O'Conner et al. created 2 isovolumetric diets that differed in energy density but were otherwise comparable in taste, texture, and appearance that were fed to healthy young adults during a period of energy balance (EB) and a period of 90% energy deprivation (ED), in oder to "examine the physiologic effects of short-term ED on appetite-mediating hormones and appetite independent from reductions in diet volume" (O'Connor. 2016 | see Figure 2).

It is a common misunderstanding that you "must" lose your weight slowly: While most mainstream diet advise involves the recommendation that you shouldn't reduce your energy intake too significantly and that you must lose your weight slowly, the existing peer-reviewed experimental and observational evidence does not support the notion that (a) slow eight gain would support greater lean mass retention or (b) prevent weight regain. Learn why that's the case.

Figure 3: Overview of energy intake, deficits and macronutrient composition in the two study groups (O'Connor. 2016).

As the scientists had expected the energy deficit that was induced over two seperate 48-h periods during which the energy intake was matched to energy expenditure to maintain energy balance (EB) (-44 +/- 92 kcal/d) or yield less than 10% of the energy the subjects required (ED).

In conjunction with the low-to-medium intensity exercise regimen (0–65% VO2peak for 187 6 +/- 21 min/d) that burned an extra 1683 +/- 329 kcal/d, the ED group did thus end up having a whopping -3696 +/- 742-kcal/d deficit on each of the two days (!).

It is thus no wonder that the scientists observed a whole host of significant differences in the hormonal response to the "diet" (diet vs. fasting). One difference you probably know much better however, is depicted in Figure 4, which shows that the subjects in the ED group consumed not simply the amount of energy they needed on the subsequent ad-libitum meal condition, but an extra 811 kcal - and they still felt a significantly greater desire to eat right after and 180 minutes after the meal.

Figure 4: Energy intake on an ad-libitum (eat as much as you want) meal before and after the intervention (left)
and the corresponding desire to eat before and after the meal (right); the dotted line at 20 min in the right graph
indicates the time at which the ad-libitum meal was served (O'Connor. 2016).

Unfortunately, the complexity of the hormonal changes does not allow us to identify this one parameter we could target to counter this effect. With significantly reduced fasting insulin (256% 6 42%) and acyl ghrelin (260% 6 17%) concentrations, as well as leptin concentrations that decreased more during ED compared with EB (-47% 6 +/- 27% compared with -20% +/- 27%; P-interaction = 0.05), we have two three (expected) candidates that could explain the increased hunger and desire to eat before the ad-libitum meal. The increased postprandial insulin (57% +/- 63%; P < 0.001), GLP-1 (14% 6 28%; P = 0.04), and PP (54% +/- 52%; P < 0.001) areas under the curve (AUCs), as well as the reduced acyl ghrelin increase (-56% +/- 13%; P < 0.001) after ED compared with after EB, on the other hand, appear to contradict the lack of satiating effect of the 1834 kcal lunch in the 18–39 year-old healthy men and nonpregnant women who participated in the study at hand.

Intermittent Fasting Works, But is It Better Than "Regular" Dieting? What Do the Latest Reviews / Meta-Analyses Say? Find out in this SuppVersity Classic!

So what can be done? Well, the increase in appetite and desire to eat is probably a generally unavoidable effect of "starvation diets" and since this is what the study at hand focuses on, it is difficult to predict how pronounced the effect would have been if the ~3500kcal energy deficit, the subjects in the study at hand reached within just one day, would have been induced over the course of 3-5 days. A dieting approach like that would after all been much closer to what the average dieter does over the course of 3-5 days only to then overeat and fall off the wagon on the weekend. In addition, a lower calorie deficit may have (a) made it easier to identify what exactly it is that causes the rebound effect and may (b) have been insufficient to compensate for the binge.

This leads us directly to the most important result of the study at hand: As suboptimal as the diet may be, one significant and probably mostly underappreciated result of the study at hand is that - once again - the energy deficit you accumulate during a quasi-fast was not fully compensated for over the 36h follow up period. A fact that adds to the existing evidence in favor of cyclic diets as every-other-day fasting, where you cycle hunger and ad-libitum diet days | Comment!

References:

• Blom, Wendy AM, et al. "Fasting Ghrelin Does Not Predict Food Intake after Short‐term Energy Restriction." Obesity 14.5 (2006): 838-846.
• Chan, Jean L., et al. "Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects." The Journal of Clinical Endocrinology & Metabolism 89.1 (2004): 335-343.
• Egecioglu, Emil, et al. "PRECLINICAL STUDY: FULL ARTICLE: Ghrelin increases intake of rewarding food in rodents." Addiction biology 15.3 (2010): 304-311.
• MacLean, Paul S., et al. "Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 290.6 (2006): R1577-R1588.
• Mars, Monica, et al. "Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake." The American journal of clinical nutrition 81.3 (2005): 570-577.
• O'Connor, et al. "Altered Appetite-Mediating Hormone Concentrations Precede Compensatory Overeating After Severe, Short-Term Energy Deprivation in Healthy Adults." Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions (2016).
• Pasiakos, Stefan M., et al. "Appetite and Endocrine Regulators of Energy Balance After 2 Days of Energy Restriction: Insulin, Leptin, Ghrelin, and DHEA‐S." Obesity 19.6 (2011): 1124-1130.
• Sumithran, Priya, et al. "Long-term persistence of hormonal adaptations to weight loss." New England Journal of Medicine 365.17 (2011): 1597-1604.
• Sumithran, Priya, and Joseph Proietto. "The defence of body weight: a physiological basis for weight regain after weight loss." Clinical Science 124.4 (2013): 231-241.