Faster Muscle Hypertrophy, Lower Visceral & Liver Fat, Trig & Glucose Levels W/ Fish vs. Casein | Plus: Shift From Slow to Fast Twitch Muscle Interesting for Strength Athletes

If casein protein is good for slow and fish protein is good for fast twitch muscle, "fish and cheese" would be the perfect muscle food, no? Read the whole article and find out if that's the case.

As a SuppVersity reader you've read about the "wonders" of fish protein before. If I am not completely mistaken, though, the study at hand which is about to be published in the peer-reviewed journal Bioscience, Biotechnology, and Biochemistry very soon, is the "fish protein study" with the most impressive results.

So impressive, in fact, that I am willing to write about it, although the study was conducted with "hairy" athletes aka rodents. So, let's not make it too exciting and start with the main results, right away: Fuminori Kawabata and his Japanese colleagues found that fish protein intake increases fast-twitch muscle weight, reduces liver triglycerides and serum glucose levels in rats, compared with a casein diet.

You can learn more about protein intake at the SuppVersity

Are You Protein Wheysting?

Cod protein for recovery

Salmon Hydro. > Whey?

High EAA protein for fat loss

Fast vs. slow protein

Phys. response to Cod protein

As you can see in Figure 1, the improvements in lipid management were significant specifically for the triglycerides in the blood and liver of the rodents who were fed iso-caloric diets containing either casein or fish protein for 8 weeks.

Figure 1: Changes in serum and liver lipids; * indicates statistical significance (Kawabata. 2014)

In view of the close relationship between triglyceride and glucose management (remember the TRIG has a carbohydrate backbone), it's not really surprising that there was a small, but statistically significant improved (=lower) glucose response to the oral glucose tolerance test, as well (see Figure 2).

Figure 2: Improved glucose clearance during oral glucose tolerance test at the end of the 8 week study period in the fish vs. casein protein groups (Kawabata. 2014)

If we look at the underlying mechanisms, we'd have to name the following findings as potential mechanistic causes of these effects:

• an increase in muscle mass in the fish vs. casein fed rodents (9.5% soleus muscle, 9.7% gastrocnemius, 10% extensor digitorum longus muscle)
• reductions in white fat (-3% total; -11% visceral) and non significant increases in brown fat (+1%)
• increases in muscle GLUT-4 expression (+39%)

With the latter, i.e. the upregulation of genes involved in the fast-twitch muscle and glucose uptake, probably being the most significant change in terms of blood glucose management.

Will you see the same results with eating fish? I doubt they will be identical to the consumption of faster-absorbing fish protein powders (which taste like crap, by the way), but the study at hand should certainly be an incentive to up your fish intake... you won't regret it, although it's not going to make you big and ripped instantaneously. Even if you're planning to have a baby, scientists from the University of Washington have calculated that the benefits in terms of reduced myocardial infarction risk outweigh any potential issues with increased mercury intake from fish (Ponce. 2000) | Learn more about the healthiest fish and "Make the Right Fish Choices"!

In addition, Kawabata et al. found that the consumption of fish vs. casein protein led to a small but significant relative increase of type II (fast twitch; resistance training; see Figure 3 at the bottom) vs. type I (slow twitch; endurance training) fibers:

"Since there were no reported protein sources that affect musclefiber-type changes, and overall, very few foods change muscle fiber type from slow to fast, the possibility of switch to fast-twitch muscle caused by fish protein observed in the present study is thought to be a significant phenomenon in thefield of skeletal muscle physiology." (Kawabata. 2014)

Now, the obvious question is: "We see changes, but what's so different about fish vs. sodium caseinate - is it the amino acid composition?

Table 1: Amino acid component and nutritional analysis of protein sources (Kawabata. 2014).

Table 1 shows the amino acid composition of the fish and casein protein that was added the rodent diets. Among the things that could maybe explain the differences are taurine (no taurine in casein, ~0.5% in fish protein), glycine (+2.4%), cystine (+0.7%), and arginine (+2.58%).

All of the aforementioned amino acids have previously been linked to improvement in blood glucose and / or blood lipid management, but it's hard to believe that the small inter-protein differences could explain the significant differences.

Furthermore, casein protein contains a higher amount of BCAAs which would stand in contrast to its inferior muscle building effects in the non-exercised Sprague Dawley rats in the study at hand.

Figure 3: The effect offish protein on myosin heavy chain gene expressions in the soleus and extensor digitorum longus muscles

Bottom line: I am afraid, I cannot tell you why fish protein favors type II muscle growth. What I can tell you, though, is that this is not the first study to observe that fish vs. casein protein leads to increased muscle gains in type II muscle fibers. The fact that the inter-group differences in this study compared to a previous 4 weeks study by Mizushige et al. were significantly more pronounced do also suggest that the beneficial effects of fish protein on skeletal muscle weight are enhanced by extending the fish protein feeding period (Mizushige. 2010).

A possible explanation for the general increase in fiber size would be a reduction in atrophy-related ubiquitin ligases the scientists observed in the study at hand.

The general change from fat utilization (lipoprotein lipase, an enzyme that breaks down triglycerides, was sign. reduced in the fish oil group) to carbohydrate utilization (GLUT-4 & co were increasd), on the other hand, could explain the improvements in glucose management and reductions in triglycerides. Still, "[f]urther investigations are needed to elucidate whether fish protein intake shifts muscle fiber type from slow to fast." Comment on Facebook!

References:

• Kawabata, Fuminori, et al. "Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats." Bioscience, biotechnology, and biochemistry ahead-of-print (2014): 1-8. 
• Mizushige, Takafumi, et al. "Fast-twitch muscle hypertrophy partly induces lipid accumulation inhibition with Alaska pollack protein intake in rats." Biomedical Research 31.6 (2010): 347-352.
• Ponce, Rafael A., et al. "Use of Quality‐Adjusted Life Year Weights with Dose‐Response Models for Public Health Decisions: A Case Study of the Risks and Benefits of Fish Consumption." Risk Analysis 20.4 (2000): 529-542.

Whey Protein Hydrolysates Were Yesterday! Study Shows Salmon Protein Hydrolysate Can Deliver Protein Even Faster, But Does This Also Mean They Are More "Anabolic"?

That's salmon, yes, but it's not processed enough to compete with any hydrolysate. Well, unless you decide to eat and regurgitate it - after some time, obviously, 'cause "hydrolyzed" proteins are in the end only pre-digested proteins.

As a SuppVersity reader you know that the amount of protein is not the only determinant of the potential muscle building effects of a given protein source. The digestion time and thus the amount of protein that is released into the bloodstream on a "per minute"-basis, as well as the amino acid profile (preferably all essential amino acids (EAAs) and a high amount of leucine) are also important determinants of the "anabolic" qualities of a given protein source.

Using a quite unique multi-compartmental dynamic model that closely simulates in vivo gastrointestinal tract digestion in humans scientists from the Institute of Nutrition and Functional Foods (INAF) at the Université Laval in Quebec, did now determine that salmon not whey protein hydrolysates are the "numero uno", when it comes to digestion speed.

You can learn more about protein intake at the SuppVersity

Are You Protein Wheysting?

Cod protein for recovery

Protein requ. of athletes

High EAA protein for fat loss

Fast vs. slow protein

5x More Than FDA Allows

If you take a closer look at the data in Figure 2 at the bottom of the article, you will notice that salmon and whey hydrolysates were not the only products the scientists tested (I would love to help you along with the amino acid compositions, but unfortunately the full text does not provide any details and Hofseth  Biocare the producer of the salmon protein hydrolysate does not disclose if it's made from fish heads or salmon filets... I am not kidding, scientists have been investigating methods to produce salmon protein hydrolysates from the waste material for years; cf. Gbogour. 2004).

In view of the fact that we don't really know if salmon has similar real-world pro-anabolic effects, it may thus be at least as interesting to compare the digestion speed of whey hydrolysates and isolates.

Figure 1: Nitrogen distribution throughout the TIM-1 compartments at the end of the 2 hour digestion. SHP, salmon protein hydrolysate; WPH-High, whey protein hydrolysate extensively hydrolysed; WPH-Low, whey protein hydrolysate weakly hydrolysed; WPI, whey protein isolate (Framroze. 2014)

The latter is, as you can see in Figure 1, only significant if the hydro-whey is "extensively hydrolyzed". The difference between regular hydro-whey and the two whey isolates, on the other hand, is too to assume that it may - by any means - be relevant.

Figure 2: Data shows how much of the protein content is released in the course of a 120min digestion period (Framoze. 2014).

Let's not jump tp conclusions, here: In spite of the fact that the nitrogen digestibility data in Figure 2 supports the notion that salmon is not just the faster digesting, but also the more bioaccessible protein source. The currently available evidence on the effects of salmon protein hydrolysates on skeletal muscle hypertrophy, fat loss, blood pressure and inflammation - all things where we have plenty of evidence for beneficial effects of whey protein - is non-existent. Considering the fact that salmon protein hydrolysates are probably even more disgusting than their whey counterparts, I would thus not go and buy the next best product you can possibly find on the Internet.

Reference: 

• Framroze, Bomi, et al. "Comparison of Nitrogen Bioaccessibility from Salmon and Whey Protein Hydrolysates using a Human Gastrointestinal Model (TIM-1)." Functional Foods in Health and Disease 2014; 4(5):222-231  
• Gbogouri, G. A., et al. "Influence of hydrolysis degree on the functional properties of salmon byproducts hydrolysates." Journal of food science 69.8 (2004): C615-C622.

Fishing for Better Wheys to Improve Your Physique and Overall Health? 6g/d Cod Protein Could Help You Cut Body Fat & Build Muscle Without Having to Change Your Diet

Image 1: This can of tuna (140g) would contains exactly 7 servings of muscle building fat burning fish protein... well, sort of. At least it contains as much protein as the subjects in the Vikøren study consumed in the form of capped cod protein isolate in the 2nd half, the "high-dose" phase of the 8-week intervention (Vikøren. 2012)

Protein days at the SuppVersity! Well, sort of... after yesterday's news on the pro-insulinogenic effects of whey protein and its not so significant negative impacts on your body composition in the absence of profoundly increased energy consumption (i.e. whey, ah... I mean "way" beyond the ~20% max. increase I suggest for a clean bulk). We will take a look at another, hitherto largely overlooked protein source: Fish! Yeah, I know, you all eat your serving of fish once or twice a week - fatty fish to be precise to derive the alleged health benefits of the latter, but did you ever remotely consider supplementing with fish protein? As a regular you may in fact have done that after reading about the superiority of cod over casein and pea as far as muscle repair are concerned, here at the SuppVersity, and if you have not the data from a recently published study from the Institute of Medicine and the Department of Heart Disease at the University of Bergen in Norway (Vikøren. 2012) could not just be an incentive for you to do so, it could in fact promote the production of fish protein isolates, which has not really kicked off before the 2011 when a Peruvian company hit the market with fat-free, membrane-refined fish protein and fish peptide products at prices of $5/kg and thus at least 38% cheaper than whey or egg protein isolates (Daniells. 2011).

Fish protein supplementation: A little goes a long way

What is so particularly stunning about the data from the 8-week double-blinded cod protein supplementation trial Linn A. Vikøren and her colleagues conducted were not so much the results,

• a decrease in postprandial blood glucose AUC,
• more pronounced, yet less sustained insulin responses (sign of increases insulin sensitivity),
• a decrease in C-reactive peptide (CRP) levels, and
• reduced LDL cholesterol, as well as
• increases in lean muscle mass, and
• decreases in fat mass,

but rather the amount of supplemental fish protein which elicited those changes: 3g/day for the first 4 weeks and 6g/day for the last 4 weeks - not much, if you relate that to the average protein intake (70-90g) of the overweight, yet healthy middle-aged study participants, right?

The whole is mostly way more than just the sum of its parts

If we go simply by the protein content that previous studies, such as , even the large dose, i.e. the 6g of cod protein isolate per day, the subjects received in the 2nd month of the intervention period, equals no more than

*Please keep in mind that Pilon et al. observed differences with respect to the physiological effects of fish proteins from different sources. In their rodent study, only salmon, yet not bonito, herring or mackerel protein had ameliorative effects on body weight and visceral body fat gain in rodents on a high-fat diet (Pilon. 2011)

• 20g of tuna
• 21g anchovies
• 22g salmon or halibut
• 23g snapper or tilapia

Now, feeding them fish, was however not a viable option. After all, it is pretty easy to distinguish a can of tuna such as the one in image 1 from a similar can with chicken, let alone "fillers and sweeteners", the sole ingredients of the placebo tablets. So in as much as you may decry the use of supplemental, instead of real fish protein, it is hardly debatable that the use of 500mg fish protein (cod) caps was necessary to effectively double-blind the study.

Figure 1: Comparison of amino acid concentration  (g/kg) of fish and whey protein (data for fish and whey from Vikøren. 2012 and Engelen. 2012, respectively)

If we take a look at the actual amino acid content (which is yet, as you should know, only one of the potential reasons we would see differences to other protein sources), it is evident that cod has a similarly high essential amino acids content as whey, but contains significantly less proline, much more arginine, glutamine and taurine.

Reminder: Just in case you have forgotten about the SuppVersity news from Friday, May 4th, 2012, I suggest you briefly go back and read up on how "Cod Protein Promotes Muscle Repair After Injury More than Casein or Peanut Protein"

What is it about fish protein that makes it so potent - arginine, taurine, or synergistic effects?

As a regular, here at the SuppVersity, you will also know that there exists a fairly decent amount of research on potential and scientifically established health effects of arginine and taurine. Whether those two individual amino acids or rather synergistic effects due to the specific protein / peptide structure of cod proteins are able to explain any of the observed health benefits (see bullet points 1-4) or the changes in body composition (see bullet points 5-6 and figure 2, below) remains yet to be elucidated.

Figure 2: Macronutrient composition of the diets at baseline, after 4 weeks and 8 weeks and changes in body composition compared to baseline (Vikøre. 2012)

Whatever the exact reasons may be, the -1.6% drop in body fat percentage (this is different from body fat mass!) is certainly astonishing given the fact that it occurred in the absence of significant changes in either the macronutrient composition or total energy content of the subjects' diets.

So what? Are fish protein isolates, the better whey?

Now without knowing the exact physiological mechanism behind the the observed effects on glucose and lipid metabolism and body composition of the 16 male and 19 female study participants, which could, as Vikoren et al. rightly point be a result of either the

• specific amino acid profile,
• the presence or formation of specific peptides (protein bonds), or 
• as of yet unknown bioactive components of fish/cod protein,

it would certainly be premature for most of you to make a switch from whey to cod, before scientific data from human trials confirms not just the efficacy, but also the supremacy of high(er) dose cod supplements over whey and other dairy proteins as the go-to muscle builders for physical culturists.

In view of the results of previous studies by by Zhang etl al. (1993), Shukla et al. (2006), and specifically van Post-Skagagard et al. (2006) on the health effects of supplemental cod protein, it may yet be prudent to make another switch in your dietary / supplement regimen, namely one from fish oils to whole fish, which has already been shown to produce superior weight-loss and health effects than supplemental fish oil (e.g. Gunnarsdotti. 2008) - results of which we know by know that they well be mediated by the synergistic effects of oil and protein from whole fish.

References

1. Daniells S. Low-cost, fat-free fish protein facility gets go ahead. Nutraingredients-usa.com. May, 27 2011. < http://www.nutraingredients-usa.com/Industry/Low-cost-fat-free-fish-protein-facility-gets-go-ahead >
2. Engelen MP, Rutten EP, De Castro CL, Wouters EF, Schols AM, Deutz NE. Casein protein results in higher prandial and exercise induced whole body protein anabolism than whey protein in Chronic Obstructive Pulmonary Disease. Metabolism. 2012 Apr 16.  
3. Gunnarsdottir I, Tomasson H, Kiely M, Martinéz JA, Bandarra NM, Morais MG, Thorsdottir I. Inclusion of fish or fish oil in weight-loss diets for young adults: effects on blood lipids. Int J Obes (Lond). 2008 Jul;32(7):1105-12. Epub 2008 May 20.
4. Lavigne C, Tremblay F, Asselin G, Jacques H, Marette A. Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats. Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E62-71.
5. Pilon G, Ruzzin J, Rioux LE, Lavigne C, White PJ, Frøyland L, Jacques H, Bryl P, Beaulieu L, Marette A. Differential effects of various fish proteins in altering body weight, adiposity, inflammatory status, and insulin sensitivity in high-fat-fed rats. Metabolism. 2011 Aug;60(8):1122-30.
6. von Post-Skagegård M, Vessby B, Karlström B. Glucose and insulin responses in healthy women after intake of composite meals containing cod-, milk-, and soy protein. Eur J Clin Nutr. 2006 Aug;60(8):949-54.
7. Shukla A, Bettzieche A, Hirche F, Brandsch C, Stangl GI, Eder K. Dietary fish  protein alters blood lipid concentrations and hepatic genes involved in cholesterol homeostasis in the rat model. Br J Nutr. 2006 Oct;96(4):674-82.
8. Vikøren LA, Nygård OK, Lied E, Rostrup E, Gudbrandsen OA. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults. Br J Nutr. 2012 May 31:1-10.

Fishing for Muscle: Cod Protein Promotes Muscle Repair After Injury More than Casein or Peanut Protein

Image 1: There are obviously more nutritionally valuable parts to cod than just its liver.

On Wednesday, you have learned that diet-deoptimization with rice instead of casein protein is a possible way to gain less weight. Today, we are going to tackle what appears to be a way more promising alternative to the dairy-based top-dogs among the protein supplements: Cod protein! Within the health and fitness community, the cold(er) water fish is hitherto, above all, known for its vitamin-laden liver and the oil humans have been producing from it and consuming for centuries, now. That the arginine-, glycine- and taurine-rich protein of its tasty white flesh could soon replace - or at least complement - dairy proteins (casein, whey) as the physical culturists' go-to protein for muscle building and regeneration will yet probably be news to most of you, right?

COD - Canned or dried? Probably doesn't matter as long as you eat it.

In a recently published paper on yet another rodent protein feeding trial (Dort. 2012), Junio Dort and his colleagues from the Laval University and the Research Center of CHUQ, CHUL in Quebec, Canada, report that the artificially injured tibialis muscle of rodents that were kept on cod-protein based diets for 21-days healed significantly faster than the skeletal muscle of the peanut or casein protein control groups.

Figure 1: Amino acid profile of casein, peanut and cod protein source on which the otherwise identical rodent diets were based (based on Dort. 2012)

For the smart SuppVersity student you are, it should not take more than just a brief glance at the amino acid profiles of the three protein sources to identify cod protein and casein as superior and peanut (as it was to be expected) inferior protein source. With -24% and -30% less branched-chain (BCAA) and total essential amino acids (EAA), peanut protein would certainly not be the first choice of any non-vegan physical culturist, let alone bodybuilder, who is interested in opti- and not deoptimizing his his/her diet (on an unrelated not: Don't you Americans never refer to the ladies, first? I always read "his/her" - that would not exactly be gentleman-like here, in Germany!).

118 neutrophils and still counting: Cod protein (not oil, in this case) tames the inflammation

In order to assess how peanut, casein and cod-based diets would modulate the rodents' response to muscular injury the animals were treated with bupivacaine, a substance that is myotoxic ("kills" muscle cells, but - and this is a specialty of bupicacaine - not satellite cells) at higher doses (here 100µL). The drug was injected into one of the animals' tibialis muscles, while the contra-lateral side was sham-injected (saline injection) to serve as a control. At days 3, 14, and 24 post-injury, both the injured and sham-injected tibialis muscles were "collected" (8 animals per dietary group) and the neutrophil count, and macrophage infiltration - both measures of ongoing inflammation and thusly incomplete healing subsequent to prior muscle damage - were assessed.

Figure 2: Neutrophil count and EDI+ macrophage count in bupivacaine injected tibialis muscle 3 and 14 days and 14 and 24 days after the injection; data expressed relative to sham control (data calculated based on Dort. 2012)

As the data in figure 2 goes to show, the cod protein group showed a markedly faster reduction in neutrophil and EDI+ macrophage count than the casein group, which - in a separate experiment - had already been found to sustain the healing process better than the nutritionally inferior peanut proteins, which also exhibited a -19% lower feeding efficacy (meaning that similar to the rice protein in Wednesday's newspost, it lead reduced weight gain; again, not necessarily desirable, specifically in injured rats) and, "in results previously published, [...] lower skeletal muscle mass than those fed casein [even] before injury" (Dort. 2012).

The anti-inflammatory effects of cod protein reach beyond skeletal muscle

Though muscle is, as my friend Carl Lanore likes to say, "metabolic currency" and it's protection and repair should be on everyone's, man and women top list of health priorities, the benefits of cod protein extend beyond skeletal muscle. A brief review of the literature revealed among others ...

• increases in HDL, decreasse in VLDL with cod over casein and soy (Jacques. 1995)
• restoration of GLUT-4 activity in skeletal muscle of HFD obese rodents (Trembley. 2003)
• lower hepatic triglyceride production vs. beef or casein (Demonti. 2003)
• lowest insulin / glucose ratio (vs. soy or casein), when given as part of complex test meal (Post-Skagegard. 2006)
• improvements in insulin sensitivity and reductions in C-reactive protein vs. diet containing beef, pork, veil, eggs and dairy in insulin resistant men and women (Ouellet. 2007; Ouellet. 2008)

Just as the improved healing of the muscoskeletal injury in the rodent study at hand, most of the aforementioned effects are probably attributable to the modulatory the homemade cod protein (the scientists simply used frozen cod fillets to prepare their protein powder) exerts on the immune system. In this context, it is particularly important to mention that

[...] an impairment of insulin-stimulated glucose uptake and a reduction of protein synthesis, combined with an increase of muscle protein degradation, are the main adverse metabolic changes induced by injuries in skeletal muscle.

In previous studies, the researchers were also able to show that the profound impairment of the AKT /PKB pathway, which is one of the key mechanisms behind the nutrient induced increase of protein synthesis, is protected from the impairments of "high fat diets" (the researcher variety, which is more akin to the standard American than to "low carb" diet), if the latter contains cod, instead of soy- or casein-protein (Tremblay. 2003).

Arginine for repair, EAA for growth: It may be of interest that Dort et al. attribute the muscle building and muscle repairing effects of cod protein to different amino acid in the cod protein. While they believe that its high arginine content suffices as NO precursor to drive and accelerate the repair process, they hold the high essential amino acid (EAA) content responsible for its pro-anabolic effects which are comparable to those of casein (and probably even whey) proteins.

Image 2: Fish is not for you? Maybe you just don't know how to prepare it properly? It's not really difficult to grill a fillet, trust me - even I can do that.

It stands to reason, that both the restoration and / or maintenance of skeletal muscle mass and insulin sensitivity, as well as the general anti-inflammatory properties of cod protein (remember: the protein in the study was derived directly from frozen fillets and contained almost no fat!) come handy for everyone who wants to live a healthy and active live into the old age. In this regard the study result do not only underline the importance and multifaceted benefits of regular fish consumption (fatty or not) as part of a healthy diet, they also support my repeatedly proffered believe that the latter should not be defined by macronutrient ratios, let alone calories, but must be build around concrete meal and food suggestions, as well as general and flexible recommendations regarding the frequency and combinations in which these can be consumed.

New Insights Into the Difference Between Whey, Casein, Cod & Wheat Proteins: Increased Dopamine, Decreased Gastric Emptying, Unknown Hydroxy-Fatty Acids & More

This is not your average protein shoot-out - the amount of leucine and the mTOR and protein synthetic response were not even measured.

It's actually rare to read the phrease "in contrast to previous studies" in a study about whey protein. There have been dozens,... ah, what do I see, hundreds of studies that have investigated almost all aspects of the biochemical, digestive, and health properties of whey proteins and still, there it is: The sentence-starter "in contrast to previous studies" in a paper that's about to be published in one of the upcoming issues of the Journal of Proteome Research.

The proteome, by the way, is the entire set of proteins expressed by a genome, cell, tissue or organism at a certain time and a study that compares the acute differential effects between whey isolate, cod and gluten (=wheat) protein on postprandial amino acid, and lipid levels, as well as other metabolites is not what I would be looking for in this journal.

You can learn more about protein intake at the SuppVersity

Are You Protein Wheysting?

Cod protein for recovery

Protein requ. of athletes

High EAA protein for fat loss

Fast vs. slow protein

Too much ado about protein?

But alas! I am happy that the research by Jan Stanstrup, Simon Stubbe Schou, Jens Holmer-Jensen, Kjeld Hermansen, and Lars O. Dragsted got published at all; I mean "in contrast to previous studies" - that certainly sounds promising, doesn't it?

So what was in contrast to previous studies, then?

Quite a good question, well... ok, I am not going to keep you on the tenderhooks any longer. The surprise finding the researchers made, when they conducted this randomized, single-blinded, crossover meal study with 11 obese non-diabetics, aged 40 – 68 years with BMI 30.3 – 42.0, is after all mentioned in the title of the paper, as well:

"Whey protein delays gastric emptying and suppresses plasma fatty acids and their metabolites compared to casein, gluten and fish protein." (Stanstrup. 2014).

As a regular at the SuppVersity it should be easy for you to identify what is odd here: The digestion speed of the isocaloric test meals which consisted of an energy-free soup with 100 g of good Danish butter, 25 g of raw leek and 45 g of either whey isolate (WI), casein (CAS), cod protein isolate (COD), or a wheat protein (GLUT) and was served with white bread (total carbohydrate content 45 g) was different from what it should have been.

Figure 1: Amino acid composition of the 4 protein sources used in the study (Stanstrup. 2014)

As a well-versed student of the SuppVersity you do of course know that one of the characteristic qualities of whey isolate is that it passes through the gut at lightning speed - so fast, in fact, that some people develop diarrhea, but that's a topic for a different SuppVersity article. Accordingly, it's not surprising that Stanstrup et al. state that the delayed gastric emptying for whey isolate was

"[...] surprising since β-lactoglobulin (the major whey protein) was found to be highly soluble in the gastric juices and rapidly emptied from the stomach when compared to other protein sources such as casein, which coagulates in acidic environments and is therefore retained in the stomach." (Stanstrup. 2014)

On the other hand, others have reported similar rates of gastric emptying for whey and casein (Calbet. 2005), before - albeit in a scenario, where they were administered alone and not in combination with a meal.

"When Whey & Casein Unite in the Spirit of True Physique Improvements, BCAAs & Glutamine Better Shut the F*** Up" | learn more

Delayed gastric emptying w/ whey? In contrast to previous studies, we are dealing with the time it takes to evacuate a whole meal, not a shake. In view of the well-known amino acid kinetics (=fast appearance w/ whey vs. slow appearance w/ casein) which were confirmed in the study at hand, there is no reason to question the established benefits of whey protein.

In other words: It still makes sense to combine whey + casein to create the perferct "anabolic" as I outlined it in "When Whey & Casein Unite in the Spirit of True Physique Improvements, BCAAs & Glutamine Better Shut the F*** Up" | learn more.

Figure 2: The digestion process (Stanstrup. 2014)

If you take a closer look at the graphical illustration in Figure 2 you will see that what appears to be counter-intuitive at first, is eventually only logical. The slow(er) transit of the whey protein through the gastrointestinal tract does after all leave more time for the complete assimilation of the amino acid content, which - and this is something you knew already - is particularly fast, because whey is easier to disassemble than casein for example.

You also know that the increased influx of amino acids goes hand in hand with an insulin spike that's more pronounced than it would be for white bread (learn more).

Many of you will probably also know (some by experience) that this spike in insulin leads to an increase in glucose uptake that leaves many low carbers notoriously hypoglycemic and makes them feel tired, shaky and miserable. What you probably didn't know, though, is that the increased glucose clearance goes hand in hand with a decrease in the amount of various fatty acids in the blood, while the cheap (see Table 1) wheat gluten meal caused elevated levels of a number of unidentified hydroxy fatty acids and dicarboxylic fatty acids, which is somewhat scary, since increases in linolic acid derived hydroxy fatty acids in human low density lipoproteins have also been observed in atherosclerotic patients (Jira. 1998; note: it's not clear whether the HCFs Stanstrup et al. observed were identical to the ones Jira et al. associated with atherosclerosis).

You can tell me whatever you want: Wheat gluten is not "kosher"

In the results section of their paper, the researchers from the University of Copenhagen and the University Hospital in Aarhus, also point out that dopamine-3-O-sulfate (the predominant form of dopamine in plasma) levels increase above baseline at 2 h for the GLU meal. In spite of the fact that the plasma levels returned to baseline again at 4 h, this appears to be in contrast to previous findings that a gluten-free diet increased major serotonin and dopamine metabolite concentrations in brain (Hallert. 1983). What Stanstrup et al. forget to mention, though, is that Hallert et al. observed this effect in patients with celiac disease; and unlike the average Internet guru tries to make you believe, we don't all suffer from gluten intolerance, let alone full-blown celiac disease.

Table 1: Wheat gluten is the cheapest form of protein - no wonder it's so popular among food manufacturers (Day. 2006)

It's still not impossible that "these findings suggest that gluten causesdecreased uptake of dopamine into the brain with concomitant increase in plasma dopamine" (Stanstrup. 2014), on the other hand there are a dozen of other possible mechanisms to explain the appearance of increased levels of dopamine-3-O-sulfate in response to the ingestion of the wheat protein isolate. This, as well as the effects of the Dicarboxylic and hydroxy fatty acids elevation after the wheat (=gluten) protein meal certainly need further investigation, though.

Bottom line: Irrespective of the initially counter-intuitive increase in gastric emptying time in response to the whey protein-laden meal, the study at hand provides additional evidence for the various metabolic benefits of whey protein (increased glucose clearance, reduced fatty acid levels, superior amino acid delivery, etc.).

Seitan looks like meat, but is actually "bread" - Due to its incredibly cheap price and its convenient processing properties gluten has become extremely popular among "food" manufacturers.

As far as wheat proteins are concerned, the effects the systemic levels of dopamine, as well as the sudden increase in certain Dicarboxylic and hydroxy fatty acids in response to the wheat protein meal require immediate follow-up studies. After all gluten proteins are "finding increasing use as a food ingredient to provide a range of functional properties at a more modest price than competitors such as milk and soy proteins" (Day. 2006) - if it turned out that this stuff has negative side effects that go way beyond the contemporary gluten scare (i.e. the tummy), the ever-increasing number of vegetarians and vegans who resort to seitan products as their main protein sources may be paying for the industry's decision to use cheap, convenient wheat protein instead of expensive soy or dairy proteins dearly in the years to come.

References:

• Calbet, Jose AL, and Jens J. Holst. "Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans." European journal of nutrition 43.3 (2004): 127-139.
• Day, Li, et al. "Wheat-gluten uses and industry needs." Trends in Food Science & Technology 17.2 (2006): 82-90.
• Hallert, Claes, and Göran Sedvall. "Improvement in central monoamine metabolism in adult coeliac patients starting a gluten-free diet." Psychol Med 13.2 (1983): 267-71.
• Jira, Wolfgang, et al. "Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients." Chemistry and physics of lipids 91.1 (1998): 1-11.
• Stanstrup, Jan, et al. "Whey protein delays gastric emptying and suppresses plasma fatty acids and their metabolites compared to casein, gluten and fish protein." Journal of Proteome Research (2014).

Science Round-Up Seconds: DHA, Algae Oil, Fish Protein, Insulin Sensitivity, Fat Loss & Muscle Gain. Plus: Night Shifts & BPA = Pro-Carcinogenic From Breast to Prostate

It's somewhat ironic that Nurse's are one of the three high risk groups for breast cancer, because they work night shifts to help others. Who the other two groups are? Female military personnel and flight attendants on international flights.

If you did already listen to yesterday's installment of the Science Round-Up, you should actually be able to connect the dots between both, the first and second course of today's installment of the Science Round-Up Seconds, and the studies on the effects of DHA on fatty acid metabolism, as well as the fallacies of insufficient, interrupted, or irregular sleep Carl and I have been addressing, yesterday.

If all that does not ring a bell, I suspect you missed the show and have not had a chance to listen to the podcast (as usual the Science Round-Up starts in the 2nd hour of the show), yet. In this unfortunate case, I'd suggest you do at least start downloading the file while you take the first bite of today's two course menu ;-)

More things fishy from proteins with funky names to DHA and fish protein

Pollachius virens (Photo: Tino Strauss) is king, when it comes to the n:3/n:6 ratio, but with <1% of fat you will still be hard pressed to get tons of omega-3s from eating pollock... but is more really better, let alone necessary? Learn how to make the right fish choices here.

(Lane. 2013; Vikøren. 2013) -- Actually I wanted to title this one "Some Things Fishy", but then I remembered that there is already a SuppVersity post with this title, one I am still not able to make head or fin... ah, pardon tail of, by the way, because it clearly suggest that the consumption of oxidized fish oil is not a problem. Be that as it may, these are the SuppVersity Science Round Up Seconds, so the "more" does not refer to the said SuppVersity post on oxidized fish oil, but rather to the 70x* increase in the expression of a protein called Angiopoietin-like 4, which controls the availability of fatty acids for fuel I mentioned during the podcast (*the differential response for DHA was elucidated in a separate study on isolated rat hepatic cells, the general effect was however observed in a human trial, where all tested fatty acids, not just DHA, produced 11-12x ANGPTL-4 increases).

In view of the more of less undisputed benefits of having reasonable amounts of DHA (400mg) in your diet, it would obviously be nice if we could increase our intake of this relatively scarce omega-3 fatty acid in our diet, without having to resort  to fish and fish oil caps. A recently published overview of vegetarian dietary sources of omega-3 fatty acids by Katie Lane and her colleagues does however confirm what you've heard both Carl and me say on previous episodes of the SuppVersity Science Round Up, already.

The conversion of alpha linolic acid (ALA, the short-chain version of omega-3) from nuts (walnut) and seeds (flaxseed, echium) to DHA is literally zero. 

According to he researchers' review of the literature, only the ingestion of oils that were derived from micro-algae provide some, albeit preliminary evidence to support their usefulness as dietary source of DHA. The number of studies is yet relatively limited and "further research is necessary to evaluate optimal doses" (Lane. 2013) of respective supplements and/or food additives for "functional foods" (how I hate this word)

Micro-algae oils are not fish, though, and thus you would once more be missing out on the unique synergy only real foods have to offer: The fish proteins!

If you are not one of the many new visitors who have found their way to the SuppVersity only recently, the keyword "fish protein" should actually ring a bell... exactly! That's the stuff that has previously been shown to have astonishingly pronounced effects on glucose metabolism. Effect that have initially been observed in rodent studies and are not being replicated in human trials. Trials such as the one by Vikøren and his colleagues from the University of Bergen who report in their latest paper that was February issue of the British Journal of Nutrition that the provision of 3 g/d of a cabbed fish protein supplements for the first 4 weeks and 6 g/d for the last 4 weeks of a 2 months placebo controlled intervention study effectively and significantly

• 

  Table 1: Amino acid composition of fish, whey and casein protein (Hall. 2003; Vikøren. 2013)

  lowered the values of fasting glucose
• 2 h postprandial glucose and glucose-area under the curve,

• increased the important early insulin and 
• decreased the detrimental late insulin response to glucose ingestion 

• reduced the amount of  LDL-cholesterol (P< 0·05) and

• led to increases in lean (+0.8%) and decreases in fat mass  (-1.6%)

compared to the calorie-free placebo. Pretty impressive results, right? That's particularly true in view of the fact that neither the food intake nor the physical activity levels changed in the course of the 8-week intervention period.

What's that: Fish protein + fish oil? (Almost) whole fish, right!

Fish happens to be a way better source of taurine than the sperm of this Belgian Blue. There is in fact so little taurine bull sperm that it is "supplemented" with this amino acid in order to keep it fresh and stable and have it survive refrigeration. Apropos, you do remember that taurine can boost testosterone levels up to 250% - at least in rodents?

The obvious question therefore is: How does that work? The scientists don't provide a satisfactory explanation and to be honest, I have nothing more than a couple of half-assed hypotheses either. My best bet, and I am suggesting that despite the fact that a recent post of mine was entitled "Don't Judge a Protein By Its Amino Acid Content", would in fact be the amino acid content. If you take a look at table 1 it is obvious that the cod protein the scientists used in the study contained one amino acid you as a SuppVersity reader should by now be familiar with and neither whey, nor casein or any of the other standard proteins has to offer: Taurine!

Yet despite the fact that taurine has the potential to boost testosterone levels, increases insulin sensitivity and has in fact been shown to actively reduce body weight in a 2003 human study by Zhang et al. (Zhang. 2003), I am not sold on the idea that the relatively minor total quantity of taurine in the already low amount of fish protein (I mean 8g?) is the only reason for the non-negligible health benefits the scientists observed in their 10 male and 10 female participants (BMI 31-37kg/m²). Maybe it's another of those funky di-peptides you've read about in the context of the nutrient repartitioning effect of whey protein hydrolysate, only lately.

Regardless of what exactly it may be that facilitated the improvements in blood glucose management and the minor, but significant improvements in body composition, the health benefits you can derive from the consumption of cod protein make the notion of fish oil, let alone micro-algae oil supplementation appear even more retarded, when eating fish once or twice a week offers a way more natural and unquestionably more tasty solution to satisfy your DHA requirement.

Night shifts and breast, BPA and prostate cancer

There are two clockworks operating parallel in your body. The one in the brain has to be hacked by light exposure (learn more about "Sunlight a la Carte"), the one in your liver and other peripheral organs, on the other hand, can be (re-)set by specific feeding strategies, like Intermittent Fasting (learn more)

I simply assume that you have by now downloaded and listened to the podcast and are thus aware of what I said about the importance of rythmicity (if you did not really get the notion, I suggest you read up on the posts in the SuppVersity Circadian Rhythm Series to get a better grasp of the different clocks that are ticking in your body ;-) Exactly this kind of rhythmicity is continuously disturbed when you are either switching back and forth from day- to night-shifts or work the night-shift continuously and dare having a social life that's simply not compatible with sleeping all day and waking all night.

That the life of a nurse, for example takes it's toll on your health and precipitates not just the development of breast cancer (+36% after 30 years of rotating night shifts; Schernhammer. 2001), but colorectal cacers (+35% after 15 years of rotating night shifts; Schernhammer. 2003) and endometrial cancer (+47% after 20+ years and even +109% in obese women; Viswanathan. 2007), as well, has been debated ever since the early years of the 21st century.

With the recent publication of two meta-analyses the debate probably will not be over; and that despite the fact that even the less unsettling analysis by Kamdar et al. reports increases in breast cancer risk of +21% for women "with ever night-shift work exposure" (Kamdar. 2013).

"Subgroup analyses suggested that flight attendants with international or overnight work exposure and nurses working night-shifts long-term were at increased risk of breast cancer." (my emphases in Kamdar. 2013)

While the Kamdar study also included observational data, this 2nd meta-analysis, which was likewise published less than a week ago, included only case-control and cohort-studies yielding risk increases of +32% and +8%, respectively (Jia. 2013). Somethin else thatg may be worth mentioning is the fact that both, the studies the scientists ranked as "high quality" research, as well as the only existing study involving female military personnel observed even higher risk increases of +40%.

Despite methodological differences and slightly different outcomes of the two meta-analyses, both research groups do reach very similar conclusions stating that the evidence is still "weak", but does "support previous reports that night-shift work is associated with increased breast cancer risk" (Kamar. 2013) and that "large-scale epidemiological studies are needed" (Jia. 2013).

From breasts to prostates ;-)

Figure 1: Effects of 4-days of BPA injections at different dosages on systemic hormone levels (Castro. 2013)

I know the subheading sounds somewhat gross, but there are certain parallels. For one, there is the same need for large-scale epidemiological studies on the connection between BPA exposure and the development and malignancy of prostate cancer as it is the case with breast cancer and night shifts. On the other hand, BPS of which a recent study was now able to show that it messes with the aromatase and 5-alpha reductase activity in the prostate and can thus precipitate prostate cancer even in adulthood (Castro. 2013), is unquestionably relevant for the development of breast cancer, as well.

What's more, the reductions in 5α-R1 and 5α-R2 Castro et al. observed in their previously healthy, adult rodents after only 4-days of BPA injections at doses of 25, 50, 300, or 600 µg/kg per day and the concommitant increase in the expression of the third isoform of 5-α reductase (5α-R3) does not only precipitate cancerous growth, it's also a recently proposed as a biomarker of cancer malignancy. In conjunction with the quasi-reversal of hormones (see figure 1), the results of this study, which happens to be the first one to demonstrate such profound detrimental effects on mature mammals, should remind us of the fact gestation and early childhood are not the only time-points in our lives, we have to beware of endocrine disruptors.

---

That's it for the Seconds and in case you are missing the information about fruits and vegetables, I will serve those tomorrow as part of the as of in fact short, but way more numerous "Short News". In case you are still hungry for more, I suggest you make take a slight detour to the SuppVersity Facebook Wall before you you sally into the weekend. There are a couple of appetizers waiting for you there:

• 

  "Does the Usefulness of Vitamin E Supplementation Depend on Your Activity Level?" While the marathon runners in the facebook study took only 50IU, 400IU is what most supplements have to offer as a minimum. Is that too much, for you? Do athletes need more? What about the hormetic response to exercise - it it even hormetic? (learn more)

  EGCG is an "anti-folate" - You still don't have to worry, nature has made sure that those who value the synergy of whole foods, or in this case drinks, won't be harmed (read more)
• LOW(!) doses of vitamin C & E (125mg & 50IU) don't diminish the benefits of exercise - On the contrary, in marathon runners that's enough to blunt the neutrophil damage (read more)
• Smart Kids = Lean Adults  - General intelligence as assessed in childhood has a significant and direct effect on adult obesity risk (read more)
• Valine, vanadium and oxygenated water - All useless for athletes. That's at least what the latest installment of the "A–Z of nutritional supplements" says (read more)

When you are done with those, it's about to start news fasting, for a couple of hours until tomorrow's morning news (for you probably today's late evening news) will be published on Facebook. Have a great "Post-Valentine's Day", everyone - I just  hope your spouses were happy with their presents ;-)


References:

• Castro B, Sánchez P, Torres JM, Preda O, Del Moral RG, Ortega E. Bisphenol A Exposure during Adulthood Alters Expression of Aromatase and 5α-Reductase Isozymes in Rat Prostate. PLoS One. 2013;8(2):e55905.
• Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr. 2003 Feb;89(2):239-48.
• Jia Y, Lu Y, Wu K, Lin Q, Shen W, Zhu M, Huang S, Chen J. Does night work increase the risk of breast cancer? A systematic review and meta-analysis of epidemiological studies. Cancer Epidemiol. 2013 Feb 8.
• Kamdar BB, Tergas AI, Mateen FJ, Bhayani NH, Oh J. Night-shift work and risk of breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013 Feb 12. 
• Lane K et al. Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature. Critical Reviews in Food and Science Nutrition. February 2013 [Epub ahead of print].
• Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8. 
• Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Fuchs CS, Colditz GA. Night-shift work and risk of colorectal cancer in the nurses' health study. J Natl Cancer Inst. 2003 Jun 4;95(11):825-8. 
• Vikøren LA, Nygård OK, Lied E, Rostrup E. Gudbrandsen OA. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults. British Journal of Nutrition. 2013; 109:648-657.
• Viswanathan AN, Hankinson SE, Schernhammer ES. Night shift work and the risk of endometrial cancer. Cancer Res. 2007 Nov 1;67(21):10618-22.
• Zhang M, Bi LF, Fang JH, Su XL, Da GL, Kuwamori T, Kagamimori S. Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids. 2004 Jun;26(3):267-71. Epub 2003 Dec 15.