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

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.

Do not underestimate fish as a protein source - fish is more than just omega-3!

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Cod protein for recovery

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5x More Than FDA Allows

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.

3.8 vs. 2.3 g/kg Protein + Exercise to Improve Body Comp. | Digestive Enzymes to Pimp Vegan Proteins | High Protein vs. MUFA Meals for GLP1 | ISSN Research Review '15 #3

"If some is good, more is better!" Unfortunately, this simple maxime does rarely apply when it comes to the physiological response to certain foods and/or supplements. For protein, however, it appears as if the relation holds - at least as long as protein does not become the only energy source in your diet.

I guess by now I can simply skip the lengthy introduction telling you about how I didn't want to cherry pick only three out of more than twenty newsworthy studies that were presented at the Twelfth International Society of Sports Nutrition (ISSN) Conference and Expo in 2015, when I started writing this series right (click here if you have missed the previous articles)?

Well, that's good because it leaves more room for a brief preview of the studies I am about to discuss in today's third serving of the SuppVersity ISSN Research Review 2015 - studies that are all related (in one way or another) to increased protein intake. Either in overweight or obese people, for whom higher protein meals increase the post-prandial increase of the "satiety hormone" GLP-1, or in vegans, vegetarians and everyone else who wants to make the most of his vegetable protein sources (pea and rice protein, to be precise) by adding digestive enzymes to the mix, or - last but not least - gymrats who ramp up their protein intake from 2.3 to 3.8 g/kg body weight to see even more pronounced improvements in body composition.

Read more about ISSN and other studies at the SuppVersity

Vitargo, Red Bull, Creatine & More | ISSN'15 #1

Pump Supps & Synephrine & X | ISSN'15 #2

High Protein, Body Comp & X | ISSN'15 #3

Keto Diet Re- search Update | ISSN'15 #4

The Misquantified Self & More | ISSN'15 #5

BCAA, Cholos-trum, Probiotics & Co | ISSN'15 #6

• High protein, high GLP-1, ... highly beneficial? As a SuppVersity reader you are aware of the far-reaching metabolic effects of GLP-1 on appetite (suppression | Näslund. 1999), glucose and fat metabolism, as well as thermogenesis (Lejeune. 2006). Against that background, you will know that the small, but statistically significant increase in GLP-1 Franklin et al. (2015) observed in their latest study which compared the effects of a high protein and high mono-unsaturated fat meal on the well-known incretin hormone may have significant long-term effects even though the blood glucose levels of the study's twenty-four overweight or obese participants (male/female: 12/12; age: 38.7 ± 15.3 (mean ± standard deviation) years; BMI: 31.6 ± 4.0kg/m²), who consumed isocaloric meals containing either 35.2% energy from fat and 20.7% from monounsaturated fat (HMF meal) or 31.9% energy from protein (HP meal), did not trigger differences in post-prandial glucose levels at 30, 60, 120, and 180 min.
  
  

  

  Figure 1: Levels of active GLP-1 in response to high protein (HP) or high MUFA (HMF) meals (Franklin. 2015).

  To believe that "simply eating more protein" is going to solve all your weight problems, though, would be short-sighted - especially for the overweight obese for whom the study at hand as well as previous studies investigating the effects of GLP-1 on glucose metabolism suggest that they may benefit to a lesser extent from protein induced increases in GLP-1 than lean individuals, in whom the "satiety hormone" will trigger much more pronounced β-cell responses that in in patients with sign. insulin resistance and pre- or full-blown type 2 diabetes (Kjems. 2003).
  
  If that sounds like you, using the high(er) protein meals in conjunction with an energy restricted diet to lose weight and thus to improve your insulin sensitivity can obviously still be beneficial. Without a planned, reasonable caloric deficit, however, high(er) protein intakes alone are probably not going to "cut it" (all puns intended).

Even if weight loss is the goal, training fasted and thus hungry does not appear to provide significant benefits. Learn more about this longstanding myth and the reality in my write-up of Schoenfeld et al's seminal paper on fasted cardio and fat loss. A paper that finally had a long-standing and die-hard fat loss myth tumble.

Are you hungry before your workouts? In this case you may be interested in the results of a paper by Nystrom et al.' who suggest that athletes have to use "more proactive strategies [...] to optimize training adaptations". Why's that? Well, of the 481 (240 women, 241 men) NCAA Division I athletes representing eleven intercollegiate sports from three universities in three athletic conferences (i.e., Atlantic 10, Atlantic Coast Conference, Conference USA) who participated in the researchers investigation into the nutrient timing habits of Division I NCAA athletes, 79% reported feeling hungry prior to training, practice or competition - and that despite the fact that most of them had breakfast. It is thus well possible that the amount and types of foods athletes eat before their workouts do still receive (too) little by athletes and their athletic departments which often provide post-workout meals, but fail to do so pre-workout.

• Pimp my plant protein - digestive enzymes can do the trick! Despite the fact that pea and other protein powders have become widely (and cheaply) available over the past years, vegan and vegetarian athletes and gymrats are still having a harder time satisfying their protein requirements than their omnivore competition or gym-buddies. Against that background and in view of the fact that more and more athletes are "going vegan" or at least vegetarian, the latest study by Julie Minevich (2015) and colleagues from the University of Tampa and the formulators, manufacturers and vendors of digestive enzymes and respective supplements from Chemi-Source and Increnovo LLC, was in fact published quite timely. A study that was designed...

  "to investigate if co-ingestion of a plant protein specific digestive enzyme blend (Digest-All® VP, a proprietary enzyme blend consisting of protease 6.0, protease 4.5, peptidase, bromelain and alpha-galactosidase, Chemi-Source, Inc., Oceanside, CA) can reduce the significant differences in amino acid appearance in the blood between plant and animal proteins" (Minevich. 2015).

  To this ends, 11 resistance-trained male subjects (age: 21.4 ± 1.5 years, body weight: 82.5 ± 3.9kg, height: 177.3cm ± 6.1cm | average training status of 2.3 years ± 1.9 years) were randomly assigned to receive either 60 g of whey protein concentrate, or the same amount of protein in form of a 70:30 blend of pea and rice protein concentrates (Veg), either alone or alonside the enzyme blend Digest-All® VP in a double-blind, crossover study. All supplements were provided on an empty stomach after a 12 hour overnight fast. The three testing sessions, in which blood was drawn immediately prior to, and at 30 minutes, 1, 2, 3, and 4 hours following consumption of the supplements, were separated by a washout period of 7 days.
  

  

  Figure 2: Time to achieve peak amino acid levels and total amount of amino acids that made it to the blood stream with whey protein, the pea + rice mix and the pea + rice mix w/ digestive enzymes (Minevich. 2015).

  Ok, I have to admit that the differences are not exactly staggering and the standard deviations (see error bars) are large, but still. One potentially important determinant of skeletal muscle metabolism, the time it takes for the serum levels of essential amino acids - including leucine - to peak, i.e. T_max in Figure 2, was visibly improved by the addition of digestive enzymes to the otherwise comparatively slow digested rice + pea protein mix (if you look at the error bars, you will see that this was just a "trend", though).
  
  If you also take into account that the digestive enzyme blend brought the area under the EAA curve (see Figure 2) and the peak amino acid levels (not shown in Figure 2) of the vegetable protein blend up to the same level as it was observed with whey protein, it would seem as if the study would provide the missing evidence of the usefulness of proteases and co. for people who want to make the absolute most of their vegetable protein supplements - what is missing, obviously, is data that would allow us to quantify the downstream effects on muscle gains and other practically relevant study outcomes.
• High protein + training = WIN?! You will certainly remember the impressive results of Antonio et al.'s 2014 study on the effects of a 4.4g/kg protein diet on the body composition healthy resistance-trained men and women (learn more). Right after said study had been published the authors promised a follow up that would combine a similarly high protein intake with a controlled exercise intervention and... voila! The first results of this study were presented at this year's ISSN meeting.
  
  For the corresponding experiment, Ellerbroek et al. recruited forty-eight healthy resistance-trained men and women in their early twenties. who consumed either 2.3g/kg body weight per day (NP) or 3.4g/kg body weight per day (HP) of dietary protein during the treatment period. Moreover, all subjects participated in a split-routine, body part heavy resistance-training program. Training and diet (everyday) logs were kept by each subject.

Learn everything about the previous study.

Don't worry! I am going to write a full review of this study as soon as it will be published. In theory I would have had to skip it just like the other studies, but since I would have been mad at me if for doing that if I were you, I decided to give summarize the little information you can find in the abstract. Against that background I hope you will understand that I will refrain from making any definite conclusions until I've read the full-text. The abstract does after all lack a lot of potentially relevant information, such as the type of workouts, the way the subjects achieved the increase in protein intake (dietary or supplemental protein), the adherence, actual protein, carb & fat intakes, etc.

• As the scientists point out in the results section of the abstract, their two-time point (Pre, Post) by two-group (NP, HP) repeated-measures analysis of variance (ANOVA) showed (a) significant time by group (p ≤ 0.05) changes in body weight with weight gains and loss in the normal and high protein groups, respectively (1.3 ± 1.3 kg NP, -0.7 ± 4.0 HP), as well as reductions in total and relative body fat in both groups (-0.3 ± 2.2 kg NP, -1.7 ± 2.3 HP), and % BF (-0.7 ± 2.8 NP, -2.4 ± 2.9 HP) - both as you can see in Figure 3 with significant advantages for the HP group.
  

  

  Figure 3: Changes in body weight, fat and fat free mass in the normal and high protein groups during the diet + training intervention; mind the error bars = high inter-individual differences (Ellerbroek. 2015).

  In the absence of any form of ill health effects due to the high protein intake (both groups consumed significantly more than the recommended daily allowance of 0.8g/kg), Ellerbroek et al. also found a significant time effect for the increase in fat-free mass  (1.5 ± 1.8 NP, 1.5 ± 2.2 HP), 1-RM on the bench and squats and vertical jump and pull-up performance - albeit without significant diet-induced inter-group differences.

So what's not in this issue? Poster presentations I decided not to discuss "at length" in this issue are the allegedly interesting presentation by Galvan et al. on the "[e]ffects of 28 days of two creatine nitrate based dietary supplements on bench press power in recreationally active males." Just as it was the case for the previously referenced studies on BCAAs, I'd rather wait for the full-text to be published before I make up my mind on whether creatine nitrate is the first form of "advanced creatines" that's actually worth it's money (unlike the rest of the pack | Jäger. 2011).

Blocking Inflammation is Like Cho- king the Fire: Long Term Weight-, Visceral- and Android-Fat Gain in Human Study Emphasizes Essential Role of TNF-α in Metabolic Control!

The same must be said of a study by Detzel, et al. (2015) in which the researchers compared the effects of functional animal proteins on mTOR and endotoxins like , pro-inflammatory compounds, that arise as a consequence of intense training. There's no debating: The way serum the derived protein supplements (BioBeef, SerumPro, and SuperSerum) were capable of neutralizing endotoxin is is interesting, but to comment on the practical usefulness of blending of high-quality protein sources with functional serum protein supplements (SuperSerum and SerumPro) the abstract that does not provide numbers to assess the relevance of the reductions in IL-8 cytokine production by THP-1 monocytes is simply not sufficient | Comment!

References:

• Detzel, Christopher J., et al. "Functional animal proteins activate mTOR and bind pro-inflammatory compounds." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P35.
• Ellerbroek, Anya, et al. "The effects of heavy resistance training and a high protein diet (3.4 g/kg/d) on body composition, exercise performance and indices of health in resistance-trained individuals-a follow-up investigation." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P37.
• Franklin, Brian, et al. "The effect of meal composition on postprandial glucagon-like peptide-1 response in overweight/obese participants." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P12.
• Galvan, E., et al. "Effects of 28 days of two creatine nitrate based dietary supplements on bench press power in recreationally active males." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P17.
• Jäger, Ralf, et al. "Analysis of the efficacy, safety, and regulatory status of novel forms of creatine." Amino Acids 40.5 (2011): 1369-1383.
• Lejeune, Manuela PGM, et al. "Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber." The American journal of clinical nutrition 83.1 (2006): 89-94.
• Näslund, E., et al. "Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men." International journal of obesity 23.3 (1999): 304-311.
• Nystrom, M. G., et al. "Nutrient timing habits of Division I NCAA athletes." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P33.
• Minevich, Julie, et al. "Digestive enzymes reduce quality differences between plant and animal proteins: a double-blind crossover study." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P26.

Food Matrices: Protein & Fat Ameliorate Glucose Spikes After Standardized Glucose Load | Plus: Timing Matters if You Want to Turn Regular into Resistant Starch

This is what it's all about. Real food does not come in form of "macros". It comes in form of complex food matrices that determine its effect on one's health - including one's glycemic health.

You will probably remember that I have touched on a specific aspect of the effects of and interactions between different macronutrients in what scientists often refer to as "food matrices" on the glycemic response to standardized glucose loads in previous articles like the famous "True or False?" article that dealt with the question: "Will Adding Fat to A Carby Meal Lower the Insulin Response?" (read it).

You don't remember this or any of the other articles? Well, in that case, I probably have to tell you again that the mere fact that the postprandial glucose are lower does not mean that a certain food or combination of certain macronutrients would increase your insulin sensitivity (adding fat to a high carbohydrate meal certainly doesn't do that, believe me).

You can learn more about resistance starch and probiotics at the SuppVersity

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While this is possible for certain supplements like berberine and other AMPK activators, it is mandatory that we differentiate the following three cases:

1. Reduced postprandial blood glucose levels in response to an increase in insulin sensitivity as it is triggered by exercise or AMPK activators,
2. Reduced postprandial blood glucose levels in response to increased insulin levels as they occur with the co-ingestion with whey protein and
3. Reduced postprandial blood glucose levels in response to increased insulin levels and a decreased rate of absorption of glucose as it is the case if you add fat to carbohydrates.

That was too fast? Too complicated? Or both? Never mind. The discussion of two recent articles from the Lund University and the Yong Loo Lin School of Medicine (see blue box) will hopefully help you understand the difference - I promise ;-)

Let's take a look at study design, results and implications

In their study, Wathik Alsalim and his colleagues from the Lund University in Sweden and the Consiglio Nazionale delle Ricerche in Italy investigated the integrative impact of macronutrients on postprandial glycemia, β-cell function, glucagon and incretin hormones in man. The subjects were male and female Caucasian subjects, aged 30-70 years and BMI 20-35 kg/m², without diabetes (normal fasting glucose and normal HbA1c) or with T2D without any pharmacological glucose-lowering therapy and HbA1c <60 mmol/mol (<7.8%).

"Exclusion criteria were liver disease, diabetic nephropathy, proliferative diabetic retinopathy, pregnancy or breast feeding, treatment with oral antidiabetic or insulin, previous myocardial infarction, coronary heart disease or angina pectoris, previous surgery on the gastrointestinal tract, larger surgical intervention the last 12 weeks or treatment with oral steroids or thiazide diuretics" (Alsalim. 2015).

Participants were studied at the Lund University's Clinical Research Center on four occasions in a randomized cross-over design, separated by at least four and maximally eight weeks. After overnight-fast (no food after 10pm), subjects were provided with antecubital vein catheter. After two baseline samples at 5, and 2 mins, they ingested in randomized order either one of the macronutrients alone

• glucose - 330kcal = 83g; Skåne University Hospital Pharmacy, Lund, Sweden,
• protein mixture - 110kcal = 30g; ISO WHEY protein consisting of milk and egg protein
• fat emulsion - 110kcal = 24ml; 50% long-chain triglycerides and 50% water;

The response to the individual macros was then compared to the ingestion of a 550kcal meal containing 330kcal (60%) from glucose, 110kcal (20%) from protein and 110kcal (20%) fat - a proportion of which the scientists say that it "was selected to represent a common meal with 60% carbohydrate, 20% protein and 20% fat" (Alsalim. 2015).

Figure 1: To allow for maximal control, the "meal" (macro composition on the right) was a shake (Alsalim. 2015).

Water was ingested at the same time of each load to standardize the ingested volume to 400ml; all ingestions were consumed within 5 min. Blood samples were taken throughout a 300min period after each challenge test.

Both vegetable oils and ghee had identical (beneficial) effects on the starch composition, but they have to be added  during boiling or before frying and boiling (Kaur. 2015).

Modifying the glycemic potential and starch content of foods with fats - In the initially cited article, Collier & O'Dea restricted their study to potatoes, only. In a more recent study, Kaur et al. investigated the effects of adding fat to white bread and rice, as well and what's even more important they did so during, not after the cooking process. In other words, instead of "buttering" potatoes, as Collier et al. did it, Karr et al. conducted a study in which they assessed the starch digestibility of white and red rice prepared with 2 oil types: vegetable oil (unsaturated fat) and ghee (clarified butter, saturated fat) added at 3 different time points during the cooking process (“before”: frying raw rice in oil before boiling, “during”: adding oil during boiling, and “after”: stir-frying cooked rice in oil | details).

Unfortunately, the results are less "unique" than the design of the study. (A) Red rice produced a slower digestion rate than white rice. (B) The digestibility of white rice was not affected by oil type, but was affected by addition time of oil, in general. (C) Adding oil “after” (stir-frying) to white or red rice resulted in higher slowly digestible starch. In that, (D) adding the fat before or during cooking and frying respectively had the most significant effect on the subject's postprandial glycemic response and the resistant starch content of the food.

Now, guess what? Yes, yes, and no ... the glucose meal was not the most insulinogenic one. Accordingly, we have to be careful not to mistake the scientists' conclusion that "[a]dding protein and fat macronutrients to glucose in a mixed meal diminishes glucose" (Alsalim. 2015) as evidence that fat and protein will reduce the potential obesogenic effect of carbohydrates. After all, the data in Figure 2 leaves no doubt that we are not talking about effect (a) from our list at the beginning of the article, i.e. a reduction in glucose excursions in response to "an increase in insulin sensitivity as it is triggered by exercise" (see introduction).

Figure 2: Glucose and insulin response as well as corresponding insulinogenic index and insulin clearance of the individual macros and the mixed meal - all data expressed relative to the values of 110kcal of glucose (Alsalim. 2015).

Rather than that, the reduced glucose AUC was a result of (c), i.e. an increase in insulin levels due to increased insulin production, as well as a decreased clearance of insulin and a decreased rate of absorption of glucose (-16%, -52%, -59% and -70% reduced glucose influx through the portal vein at 30, 45, 60 and 90 min after the meal) - and with the increased insulin levels you will also run an increased "risk" of fat storage (whether you gain weight will still depend on your overall energy intake not your insulin levels, though).

Figure 3: Insulin is not always the bad guy. A 2004 study by Hallschmid, et al. shows that it's centrally mediated effects in the brain can actually help men (but not women) lose weight effortlessly, when they administer it cyclically (only chronically elevated insulin levels are truly problematic) intranasally.

At this point, it may be necessary to point out that the increase in insulin in response to the co-ingestion of protein and fat does not imply that guzzling glucose on its own would be healthier than eating a mixed meal. In conjunction with the increases in the important (fat burning) satiety hormone GLP1, which were observed only in the diabetic subjects, though, these changes are yet far more beneficial for the average type II diabetic than they are for the lean athlete, who doesn't need the extra-insulin to maintain normal blood glucose levels and may even consider them an obstacle on his / her way to single-digit body fat levels.

So what? Just as the previously discussed study on butter + potatoes, the study at hand does not confirm that you just have to add fat (and protein) to a meal to stay lean and healthy forever. The GLP-1 increase, which occured only in the diabetics, and the significant increase in insulin production, which occurred in both diabetic and healthy subjects, fully explain the reduced glucose spikes and can be considered "beneficial" only for type II diabetics, who can thus compensate their insulin resistance w/ even more insulin. For lean / healthy individuals who get the questionable benefit of increased GIP and insulin levels, but don't benefit from the increase in GLP-1, the benefits - if there are any - are less obvious.

Are You Afraid that the Fructose Boogieman Clogs Up Your Liver? Citrulline or Alanine, Glycine, Proline, Histidine and Aspartate Mix Will Protect You + Maybe Lean You Out

If there's an advantage of adding protein and fat to carbs in order to reduce the postprandial glucose excursions in lean individuals, that's probably not the often heard of "stay lean" effect, but rather a long(er) term health advantage. Elevated postprandial glucose levels have after all been linked to type II (as a consequence of the ill effects of elevated glucose on your pancreas | Robertson. 2003) and type III diabetes (type III = all sorts of downstream effects of constantly elevated glucose levels like Alzheimer's | Steen. 2005), increased inflammation and cardiovascular disease risk and a lot of other ailments you certainly want to avoid even more urgently than being pot-bellied or "chubby" | Comment on Facebook!

References:

• Alsalim et al. "Mixed meal diminishes glucose excursion compared to glucose by several adaptive mechanisms in man." Diabetes, Obesity and Metabolism (2015): Accepted article.
• Collier G, O'Dea K. The effect of coingestion of fat on the glucose, insulin, and gastric inhibitory polypeptide responses to carbohydrate and protein. Am J Clin Nutr. 1983 Jun;37(6):941-4.
• Hallschmid, Manfred, et al. "Intranasal insulin reduces body fat in men but not in women." Diabetes 53.11 (2004): 3024-3029.
• Kaur B, Ranawana V, Teh AL, Henry CJ. "The Glycemic Potential of White and Red Rice Affected by Oil Type and Time of Addition." J Food Sci. (2015).
• Robertson, R. Paul, et al. "Glucose toxicity in β-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection." Diabetes 52.3 (2003): 581-587.
• Steen, Eric, et al. "Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease-is this type 3 diabetes?." Journal of Alzheimer's disease 7.1 (2005): 63-80.

Polydextrose and Resistant Maltodextrin as Dieting Aids W/ GLP-1 Boosting & Appetite Reducing Effects: 7% Reduced Energy Intake per 10g/day of Polydextrose in Clinical Trials

Many of them look like powder sugar, but they are much more. Novel food ingredients like polydextrose or resistant maltodextrin may help us to slow the progression of obesity, but they won't solve the global obesity problems.

Whenever we are talking about resistant starches, we are not actually interested in the starches themselves, but rather in what happens after they are digested by the bacteria in our guts. The result of this process are short-chain fatty acids. These specific fatty acids interact with receptors in the digestive tract which in turn trigger the release of GLP-1, of which you as a SuppVersity reader have long known that it is of paramount importance for glucose and weight control (learn more).

Next to naturally occuring resistant starches in foods like cooled potatoes or green bananas and relative expensive high molecular weight designer starches, polydextrose and resistant maltodextrose constitute two promising food ingredients of which researchers believe that they may help us to keep the obesity epidemic at bay.

You can learn more about the gut & your health at the SuppVersity

Bugs Dictate What You Crave

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet

Resistant maltodextrin (RMD) is a water-soluble, non-viscous and non-digestible saccharide. Like polydextrose, resistant maltodextrin has previously been reported to improve the glycaemic response (12,13) and postprandial TAG elevation (14), and also promotes mineral absorption (15). The mechanisms involved in the improvement of glucose tolerance, however, are poorly understood.

Accordingly, the goal of Tohru Hira et al.'s latest study was to examine whether these effects that have been observed in both human and rodent studies, previously, could be mediated by changes in plasma GLP-1 levels and GLP-1 production in the small and large intestines.

Figure 1: Glucose levels after glucose load (A), changes in glucose (B) and total GLP-1 and active GLP-1 levels (C, D) with different amounts of resistant maltodextrin or fructo-oligosaccharides in the diet of the rodents (Hira. 2015).

If you've read the introductory paragraph of this article, you will not be surprised to see that the data from the Hokkaido University in Japan shows that the ingestion of resistant maltodextrin lead to dose-dependent (more = better) increases in GLP-1 in the blood (Figure 1, C-D) and the intestine (not shown), as well as corresponding improvements in glucose control (Figure 1, A-B).

Do not make the fatal mistake to believe that increasing your resistant starch intake alone will help you lose weight. Unless the increases in GLP-1 make you eat less food, you will -just like the rodents in the study at hand- not lose a single pound of body fat. In addition, polydextrose and probably also resistant maltodextrin - like many of the sugar replacements - has the nasty side effect of giving you the run if you consume high doses in isolation (Flood. 2004). So, if you want to use them, use them wisely.

In that, it is particularly important that the benefits the healthy rodents derived from the ingestion of resistant maltodextrin was significantly more pronounced than the benefits of fructo-oligosaccharides which have likewise been hailed as potential obesity preventers (Arora. 2013).

Speaking of obesity preventers,...

you are probably already wondering about the other "obesity preventer" I mentioned in the headline: Polydextrose, a a glucose polymer that is completely soluble in water and is used asa food additive to give foods the texture of sucrose at 75% lower calories in over 60 countries.

The effects and potential benefits this agent which is usually labeled as "fiber" on the label of commercially produced foods have recently been reviewed by scientists from the St Luke’s Roosevelt Hospital Center in New York (Ibarra. 2015). As of now, we know from several individual studies that polydextrose has the ability to reduce energy intake, but until now, no one had systematically reviewed the disparate evidence on this topic.

Figure 2: Calculated slopes of the effects of adding polydextrose to the diets of men and women on their food intake at lunch (left) and over 24h (right) - individual study results are represented as dots (Ibarra. 2015).

With the study by Ibarra et al. (2015) this review is now available and it shows significant effects on food intake at lunch (Figure 2, left) and total 24h food intake (Figure 2, right). Only the food intake at dinner was not significantly influenced in the few hitherto existing amply controlled clinical human trials (not shown in Figure 2).

A closer look at the data in Figure 2 does also show that there was - just like it was the case for the GLP-1 response to resistant maltodextrin ingestion in the Hira study - a dose-dependent increase in satiety with the ingestion of only 25g of polydextrose per day being able to reduce the total 24h food intake by more than 12%! Based on linear regression analysis the Ibarra et al. calculated the average decrease in food intake over 24h to be 3.8% and 2.3% per 10 gram of polydextrose consumed in men and women respectively. Significantly more pronounced effects were observed in studies investigating the effects of polydextrose ingestion at breakfast on food intake during an ad-libitum lunch which was reduced 7% and 5.7% per 10g in men and women.

According to the first meta-analysis of the existing human clinical trials consuming 10g of polydextrose per day leads will significantly decrease the food intake. The data does yet also show: Women benefit to a lesser degree than men.

Bottom line: There is little doubt that the consumption of increased amounts of resistant starches and more specifically GLP-1 boosting and appetite reducing resistant maltodextrin and polydextrose may help you to lose / control the amount of body fat you are carrying.

It is unrealistic, however, to assume that adding 20g of either of the agents to your diet would be sufficient to trigger significant fat loss in the absence of other lifestyle changes. It is furthermore interesting to observe that - once more - women appear to benefit less from the appetite reducing effects of these agent and that despite the fact that the relative contribution of 20g of these agents to the total food intake of a woman is lower than it would be for a man who obviously consumes more food | Comment on Facebook!

References:

• Arora, Tulika, Satvinder Singh, and Raj Kumar Sharma. "Probiotics: Interaction with gut microbiome and antiobesity potential." Nutrition 29.4 (2013): 591-596.
• Flood, M. T., M. H. Auerbach, and S. A. S. Craig. "A review of the clinical toleration studies of polydextrose in food." Food and chemical toxicology 42.9 (2004): 1531-1542.
• Hira, Tohru, et al. "Resistant maltodextrin promotes fasting glucagon-like peptide-1 secretion and production together with glucose tolerance in rats." British Journal of Nutrition (2015): 1-9.
• Ibarra, Alvin, et al. "Effects of polydextrose on different levels of energy intake. A systematic review and meta-analysis." Appetite 87 (2015): 30-37.

If Insulin Sensitivity is Key, What's the Key to Insulin Sensi- tivity? Artemisia Dracunculus, Lixisenatide, Calcium & Bi- carbonated Water - True Promoters of Insulin Sensitivity?

Insulin sensitivity is a necessary pre- requisite for much more than a profane set of sixpack abs.

You will probably have realized that the number of short-news like articles on the SuppVersity has been increasing as of late. The reasons for that are twofold: For one, it's the fact that it pisses me off (sorry, but that's how it is) that all the interesting stuff I post on the SuppVersity Facebook Page disappears into an oblivion of which I can only hope that it is not Mark Zuckerberg's *** Secondly, I am currently working my regular job, doing some additional University stuff and working on another nutrition and exercise science related project and don't have the time to do the extensive research that's necessary to produce articles like part II of the "perfect frying oil" article, you may (rightly) already be waiting for.

In other words: If you don't want me to switch to a twice or thrice (max) a week schedule, you will have to live with less in-depth articles like this - sorry! If you would prefer a new schedule, on the other hand, let me know.

Artemisia dracunculus and Lixisenatide, two names to remember?

Actually the first of these names, namely Artemesia dracunculus is a herb you should be vaguely familiar with, if you remember an old SuppVersity article with the title "SuppVersity Supplement Scrutiny: Athletic Edge Nutrition Creatine RT - More Than Yet Another Marketing Gag?" (refresh your memories). In said article I acknowledged the insulin-sensitizing prowess of Tarragon extract, but doubted that its purported effects on the uptake of creatine into the muscle had any real-world relevance.

I guess, some of you will probably say the same of the observation that the tarragon bioactives "improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines" in a recent in vitro study by scientists from the Louisiana State University. Before you do so, I would yet like to remind you of the existing evidence that supports the insulin-sensitizing (Wang. 2011), muscle-preserving (Kirk-Ballard. 2013), anti-diabetic (Watcho. 2010; Eisenman. 2011;  Scherp. 2012),  as well as anti-NAFLD (Wang. 2013) and eye (Watcho. 2011) and nervous system protecting (Singh. 2014) effects of this herb.

If you still don't trust a supplement that failed you once,...

there is obviously still BigPharma's answer to herbal supplements: Lixisenatide, a synthetic GLP-1 analogon that has just demonstrated that it could be the future of (type II) diabetes treatment.

Lixisenatide comes in a fool-proof pen - what else?

In a study that was conducted by no one else than the inventors over at Sanofi-Aventis in Frankfurt, Germany, injecting the drug subcutaneously 2 hours before an intravenous glucose challenge accelerated the disposal of glucose to "nearly physiological intensity" (Becker. 2014) - in other words: The mere injection of the GLP-1 analog reduced the insulin requirements of the diabetics to zero and helped push the glucose into the cells at a rate that's identical to the one of non-diabetics.

In view of the fact that it did not impair the counter-regulation to low glucose levels by glucagon, it's probably just feasibility question (can you time it properly), if and when at least some diabetics will have Lixisenatide pens (see image to the right), instead of insulin syringes in the neat "I want that piece of cake now, so I have to inject tons of insulin"-bags they are carrying wherever they go.

And if you don't do drugs, ...

... a very simple and, as a recent study appears to confirm, effective way to improve your glucose management would be to increase your intake of calcium containing foods and/or "hard" (=high calcium) water around meals.

Don't forget your bicarbonated mineral water folks! It's not calcium, but it works wonders: Sodium bicarbonate - In a 2007 paper, researchers from the Spanish Council for Scientific Research report that the consumption of 0.5l of sodium-rich bicarbonated mineral water with a standard fat-rich meal lead to significantly reductions in postprandial insulinemia in postmenopausal women compared to the same meal with regular water (Schoppen. 2007).

Why? Well, as a SuppVersity veteran you should actually remember that rumors had it for years that a high calcium intake would help with weight loss, but the observations in corresponding experiments were mixed and the contemporary scare about the connection between calcium supplements, on the one hand, and cardiovascular heart disease (CHD) and/or prostate cancer, on the other hand, put another question-mark, this time one that corresponds to safety issues, behind the "calcium for weight loss" paradigm.

Figure 1: Relative serum / blood levels of GIP, GLP-1, insulin, glucose, lactate and NEFA after meals with high calcium content compared to isocaloric meal w/ identical macronutrients w/ low calcium (Gonzalez. 2013).

Now, the results of a recent study from the Northumbria University in the UK won't make this question.mark disappear. What they definitely do, though, is clarify the underlying mechanism of action, which is - and this should be obvious, when you look at the data in Figure 1 - mediated by the calcium-induced 47 % and 22 % increases in GIP1–42 and GLP-1 respectively (Gonzalez. 2013).

Figure 2: Overview of the purported anti-obesity + anti-diabetic effects of calcium + vitamin D (Soares. 2014)

In conjunction with the 19 % increase in insulin areas under the curve for the 120 min following consumption of the macronutrient-matched meals these hormonal changes induced a 12 % reduction in appetite in the 10 healthy male subjects.

The combination of increased insulin levels and improved blood glucose clearance, on the one, and an increased production of the fat-burning satiety hormone GLP1, on the other hand, renders these observations interesting for both: The overweight, insulin resistant couch potato and the normal-weight individual on his / her way to a physique model body.

Figure 2: The increased bioavailability of citrate-bound calcium Sakhaee et al. calculated based on a meta- analysis of 15 studies (184 subjects) suggests that calcium citrate would be your preferential calcium source - and that irrespective of whether you're takin' it with meals or on empty  (Sakhaee. 1999).

Bottom Line: After my recent post about the beneficial effects of sufficient and the questionable benefits of additional calcium intake in Part IV of the"There is More To Glucose Control Than Carbohydrates"-Series (read all installments), I am very hesitant to suggest adding another calcium carbonate or citrate tablet on top of the 200mg of calcium you got from the whey protein you have had after your workout today and the 400mg of calcium that's in the micellar casein you are about to sip before you collapse into your bed, later today.

In case you are missing out on these high protein calcium, sources, don't guzzle calcium containing mineral (in German tap water) and have a low intake of green leafy veggies and other high calcium food, there may however be room for additional 400mg calcium citrate (you can buy that for a few pennies as powder in an animal food store, if you don't have the bucks for the expensive tablets) in your supplement regimen. And yes, I think that's more useful than artemisia or GLP-1 analogues.

Reference:

• Becker, et al. "Lixisenatide Resensitizes The Insulin-Secretory Response To Intravenous Glucose Challenge In People With Type 2 Diabetes – A Study In Both People With Type 2 Diabetes And Healthy Subjects." Diabetes, Obesity and Metabolism (2014) - Accepted Article.
• Eisenman, Sasha W., et al. "Qualitative variation of anti-diabetic compounds in different tarragon (Artemisia dracunculus L.) cytotypes." Fitoterapia 82.7 (2011): 1062-1074. 
• Gonzalez, Javier T., and Emma J. Stevenson. "Calcium co-ingestion augments postprandial glucose-dependent insulinotropic peptide1–42, glucagon-like peptide-1 and insulin concentrations in humans." European journal of nutrition (2013): 1-11.
• Kirk-Ballard, Heather, et al. "An extract of Artemisia dracunculus L. inhibits ubiquitin-proteasome activity and preserves skeletal muscle mass in a murine model of diabetes." PloS one 8.2 (2013): e57112.
• Scherp, Peter, et al. "Proteomic analysis reveals cellular pathways regulating carbohydrate metabolism that are modulated in primary human skeletal muscle culture due to treatment with bioactives from< i> Artemisia dracunculus</i> L." Journal of proteomics 75.11 (2012): 3199-3210.
• Sakhaee, Khashayar, et al. "Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate." American journal of therapeutics 6.6 (1999): 313-322.
• Singh, Randhir, Lalit Kishore, and Navpreet Kaur. "Diabetic peripheral neuropathy: Current perspective and future directions." Pharmacological Research 80 (2014): 21-35. 
• Soares, Mario J., Kaveri Pathak, and Emily K. Calton. "Calcium and Vitamin D in the Regulation of Energy Balance: Where Do We Stand?." International Journal of Molecular Sciences 15.3 (2014): 4938-4945.
• Vandanmagsa, B. et al. "Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture." Diabetes, Obesity and Metabolism (2014) - Accepted Article.
• Wang, Zhong Q., et al. "An extract of Artemisia dracunculus L. enhances insulin receptor signaling and modulates gene expression in skeletal muscle in KK-A y mice." The Journal of nutritional biochemistry 22.1 (2011): 71-78.
• Watcho, Pierre, et al. "High-fat diet-induced neuropathy of prediabetes and obesity: effect of PMI-5011, an ethanolic extract of Artemisia dracunculus L." Mediators of inflammation 2010 (2010).
• Wang, Zhong Q., et al. "< i> Artemisia scoparia</i> extract attenuates non-alcoholic fatty liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway." Metabolism 62.9 (2013): 1239-1249.
• Watcho, Pierre, et al. "Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus L., on peripheral neuropathy in streptozotocin-diabetic mice." International journal of molecular medicine 27.3 (2011): 299-307.