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It doesnt matter if you want to turn fat into fit, fit into fitter or strong into stronger. Todays SuppVersity science potpourri has something to offer for every physical culturist who is looking for ways to improve his health, performance and physique and for trainers and coaches who work with this challenging clientele.

In view of the fact that the last news-potpourri on appetite related scientific studies was a major success, I thought it may be worth writing another of these long-neglected short-news items. This time about exercise and supplementation, though.

You may already have seen the link to Stuart Philipps latest "Review of Higher Dietary Protein Diets in Weight Loss" with a "A Focus on Athletes" on Facebook. For those of you who have been following the SuppVersity News theres probably little new information in the document, though. When I read the paragraph about optimal protein intakes for maximal muscle retention, I still thought that it may be worth to remind you of the results of the Pasiokos study which clearly suggest that eating more protein is not always going to increase the net protein retention when you are dieting.
A fact that brings me back to Philipps review in which he points out that dieters commonly overlook that any increase in protein intake will go at the expense of either fat or carbohydrate. A "side effect" that could be particularly problematic for athletes, for whom Philipps recommends (just like I do) "to balance the increase in protein consumption with what macronutrient is reduced" (Phillips. 2014). In particular, athletes should "focus on reducing intakes of lipids to allow carbohydrate intakes to achieve performance" (Phillips. 2014).

After this brief introductory interlude, I would like to get to the actual topic at hand, a brief overview of a couple of interesting, but not exactly "full-article worthy" papers from the realms of exercise, nutrition and supplementation:

• Low volume, high intensity the exercise key to perfect health? A recent paper in the latest edition of Sports Medicine reviewed the health benefits of two different low volume exercise regimen: The classic sprint interval training (black spikes in Figure 1) and a HIIT protocol (grey bars in Figure 1).
  
  The researchers from the McMaster University in Hamilton, Ontario, highlight that the currently available evidence is largely based on short-term interventions. And while long(er)-term interventions would be needed to " to advance our basic understanding of how manipulating the exercise stimulus translates into physiological remodeling" (Gibala. 2014), it can already be said that...

  Figure 1: Comparison of the power output (% of VO2peak) during sprint interval training (SIT, black peaks), high intensity interval training (HIIT, grey bars) and moderate intenstity continuous training (MICT, striped box)

  "[f]rom an applied perspective, there is value in trying to establish the minimum ‘dose’ of HIIT or SIT needed to stimulate meaningful improvements in clinical markers that are associated with disease risk.
  
  This is particularly germane given that ‘lack of time’ remains the most commonly cited barrier to regular exercise participation, and considering evidence that suggests that low-volume interval training is perceived to be more enjoyable than MICT." (Gibala. 2014)

  As Gibala et al. point out, there is also evidence that nutritional interventions can influence both acute and chronic adaptations to interval training - with one of my personal favorites, i.e. sodium bicarbonate being the #1 candidate to among the "interval-specific" ergogenics that are currently available on the market (learn why).

  Figure 2: Everything works, as long as you pick the right type of exercise for your type.

  Moreover, as suggested by van Loon and Tipton (van Loon. 2013), the significantly greater adaptation efficiency compared to "regular" steady state cardio training has clinical relevance, especially for individuals with severe exercise intolerance.
• Low dose caffeine (200mg) not effective for everyone - A recent study from the University of Guelph found that low doses of caffeine (<3 mg/kg body mass, ~200 mg) can be ergogenic in some exercise and sport situations, but for most athletes they will not alter the peripheral wholebody responses to exercise, or improve vigilance, alertness, and mood and cognitive processes during and after exercise.
  
  

  Figure 3: Effects of ingesting no caffeine (0) or 3, 6 or 9 mg/kg body mass of caffeine (dose) on running time to exhaustion at ~85 % of VO2max (Graham. 1995).

  In view of the fact that low dose caffeine regimen are also "associated with few, if any, side effects" (Spriet. 2014), and generally depend on an athletes individual response to caffeine, Lawrence L. Spriet still suggests that athletes should "determine whether the ingestion of ~200 mg of caffeine before and/or during training and competition is ergogenic on an individual basis" (Spriet. 2014); and, assuming that it is, make use of the lowest effective dose, of which the data in Figure 3 clearly indicates that it is not necessarily the one with the lowest performance benefits.
• Science-Based Recommendations for Training to Maximize Concurrent Training - Right from the desk of Keith Baar comes a set of recommendations to maximize the benefits of concomitant training, i.e. combined / sequential endurance and strength training that consists of a set of four tips:
  
  • Do HIIT in the AM: Any high-intensity endurance training sessions should be performed early in the day. Then, a period of recovery of at least 3 h should be given, so that AMPK and SIRT1 activity can return to baseline levels, before resistance exercise is performed. This suggestion is based on the fact that AMPK activity increases rapidly and then returns to baseline levels within the first 3 h after high-intensity exercise (Wojtaszewski. 2000), whereas mTORC1 activity can be maintained for at least 18 h after resistance exercise (Baar. 1999; MacKenzie. 2009).

  • Build 3.2kg of lean mass overnight w/ 40g of casein pre-bed | learn more.

    Drink your whey protein shake right after your strength workout: Resistance exercise should be supported by readily digestible, leucine-rich protein as soon as possible after training to maximize leucine uptake, mTOR recruitment to the lysosome, and protein synthesis.
    
    In view of the fact that Baar recommends to do your RT sessions later in the day, it is also advisable to consume another protein shake right before bed to maximize the synthetic response overnight (learn more).
  • Fully refuel between the morning high-intensity endurance training session and the afternoon strength session: Its not going to reduce the exercise induced increase in AMPK and SIRT1 activation, but will allow you to perform at maximal intensity during your resistance training session later in the day.
    
    As Baar points, out athletes who have to diet during certain phases of their training cycle should make sure to "reserve a portion of the offseason (and short periods in season) exclusively for increasing muscle size and strength and then use higher dietary protein intakes to maintain that muscle mass as the aerobic load increases through the season" (Baar. 2014).
  • If you do low-intensity cardio, do your resistance training right after cardio: To improve the endurance response to lower-intensity endurance training sessions and provide a strong strength stimulus, Baar recommends performing strength training immediately after low-intensity, non-depleting, endurance sessions.
    
    Performing a strength session immediately after a low-intensity endurance session results in a greater stimulus for endurance adaptation than the low-intensity endurance session alone (Wang. 2011) and the low-intensity session will not affect signaling pathways regulating strength gains (Coffey. 2009; Lundberg. 2012; Apró. 2013).
  At first, these rrecommendations may sound somewhat random. If you take a closer look at the long paper, you will yet have to concede that the simple recommendations are based on our current understanding of the molecular response to exercise. In that, they should allow for the maximal adaptive response to both endurance and strength exercise.
  

References:

• Apró, William, et al. "Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle." American Journal of Physiology-Endocrinology and Metabolism 305.1 (2013): E22-E32.
• Baar, Keith, and Karyn Esser. "Phosphorylation of p70S6kcorrelates with increased skeletal muscle mass following resistance exercise." American Journal of Physiology-Cell Physiology 276.1 (1999): C120-C127. 
• Coffey, Vernon G., et al. "Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle." Journal of applied physiology 106.4 (2009): 1187-1197.
• Graham, T. E., and L. L. Spriet. "Metabolic, catecholamine, and exercise performance responses to various doses of caffeine." Journal of Applied Physiology 78.3 (1995): 867-874. 
• Lundberg, Tommy R., et al. "Aerobic exercise alters skeletal muscle molecular responses to resistance exercise." Medicine and science in sports and exercise 44.9 (2012): 1680-1688.
• Pasiakos, Stefan M., et al. "Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial." The FASEB Journal 27.9 (2013): 3837-3847.
• van Loon, Luc JC, and Kevin D. Tipton. "Concluding Remarks: Nutritional Strategies to Support the Adaptive Response to Prolonged Exercise Training." (2013): 135-141. 
• Wall, et al. "Dietary Protein Considerations to Support Active Aging." Sports Med (2014) 44 (Suppl 2):S185–S194.
• Wang, Li, et al. "Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle." Journal of applied physiology 111.5 (2011): 1335-1344.
• Wojtaszewski, Jørgen FP, et al. "Isoform-specific and exercise intensity-dependent activation of 5?-AMP-activated protein kinase in human skeletal muscle." The Journal of physiology 528.1 (2000): 221-226.

Does a (very) high fish oil diet entail the risk of going rancid - in spite of all its short-term health benefits?

Dont worry, I am not addressing the prostate cancer issue, again. In a way, I am still going to resume a discussion, you should be familiar with from my article "Sesame Powered High Omega-6 Diet Boosts Endurance Performance in Rodents - High Omega-3 Diet Sucks" | read more. Its the notion that the extensive incorporation of easily oxidizable (or already rancid) omega-3 fatty acids into metabolically highly active tissues, such as our musculature, will only be beneficial until a certain optimal threshold level is reached. Beyond this point, any further increase of the long-chain PUFA content becomes as problematic as the overabundance of other fatty acids.

This article is about balance!

By now, you should have realized that this post is all about balance, the critical balance of stable saturated and unstable (poly-)unsaturated fatty acids - not in your diet, but in cells & tissue.
Recent evidence of the importance of these numbers comes from a study that was conducted by researchers from the INRA UMR in Montpelier, France (Feillet-Coudray. 2013). It is, as you may have suspected, a rodent study. With a study duration of 12 weeks and the aspiration to investigate the long-term effects of diets containing 50 or 300 g lipid/kg  in the form of either lard or fish oil, this was yet more than a concession to financial constraints.

In the life of a rodent, three months are equivalent to several human years (some sources would say 5 years, but I would not bet on that). A similar study in man would thus take several years - years in the course of which all study participants would have to be locked away in a metabolic ward to ensure that they eat nothing but what the scientists serve them.

Figure 1: Total fatty acid (FA) composition of the LIVER and MUSCLE (mg FA/g tissue; Feillet-Coudray. 2013)

Against that background it is unlikely, but not impossible that we will see similar changes (see Figure 1) in the muscle and liver lipid levels of a human subject within only 3 months, even if he or she would reduce his or her overall fat intake to almost zero while upping the amount of fish oil in the diet into the 50g+ range. For 99% of the existing human studies this means that they are 100% irrelevant in view of the long (and if I write "long", I mean "long" like in years!) term high dose fish oil intakes and the corresponding changes in the fatty acid content and ratios of muscle, liver and other tissue.

No changes in muscle fatty acid make-up. How Come?

Apropos changes! If you look a the data in Figure 1 you will realize that the fatty acid make-up of the musculature in the study by Feillet-Coudray et al. did not change at all. In view of the significant changes in the fatty acid composition of the liver, this appears to be counter-intuitive and if we recall the study design and results of the previously cited study by Ayre et al. (1997) probably a result of the comparatively high omega-6:omega-3 ratio of the purported "fish oil" diet, which contained only 15g of omega-3 fatty acids per kg, and a whopping 21.7g of omega-6s. With an additional 25g of monounsaturated and 27.4g of saturated fats it is thus by no means an "omega-3", let alone "fish oil" diet as the one in the Airy study, which lead to major performance impairments in muscular endurance (and probably strength, which was yet not measured in the Ayre study | learn more).

Figure 2: Fatty acid composition of the test diets (Feillet-Coudray. 2013)

If you take a closer look at Figure 2 you will realize that - compared to the allegedly unhealthy lard diet" - the major difference is not, as people who still believe lard contained almost exclusively saturated fats could believe, the saturated-to-polyunsaturated fatty acid ratio, but simply the absence of significant amounts of omega-3 fatty acids in the mixed control and lard diets (one good reason to supplement a lard only diet with reasonable amounts of fish oil; e.g. 1g per day or 4g twice a week).

Not exactly representative of the contemporary diets, but still meaningful

From a scientific point of view the significant, but still small differences may be a limitation. From a practical point of view, the omega-3 : omega-6 ratios are however more realistic than those of a real fish oil only diet:

• CONTROL & LARD ~ 7:1 vs.  FISH ~ 3:2 
• SAD ~ 15:1 vs. HIGH N3 ~ 1:1 - 3:1

What they are not, however, is representative of the difference between the SAD (standard American) and a high omega-3 diet (HIGH N3).
As close as the FISH diet may be to the often hailed "optimal 1:1" ratio, the CONTROL and LARD diets both contain much more omega-3s / less omega-6s than the SAD diet. Against that background its actually quite astonishing that

Meta-Analysis Says: Fish Oil Does Not Help You Lean Out! Plus: Its Still Worth Having Fatty Fish 1-2x/Week | more

• all rats developed liver steatosis associated with moderate liver injury when fed the 30 % lipid diets
• the rats in both the CONTROL and FISH group did so without getting obese (only the rats "on" the 30% LARD diet became obese; 11% higher body weight, 32% more body fat)
• both FISH (+30%) and LARD (+103%) had elevated insulin levels compared to the rodents on the 30% CONTROL diet; despite higher insulin levels, the effective glucose uptake in the FISH group was normal, while it was already compromised in the LARD group

Its yet not all surprising and unexpected. The FISH diet did produce the expected improvements in total cholesterol and the HDL:LDL ratio. In spite of the -35% (vs. CONTROL; -47% vs. LARD) lower triglyceride levels, "[t]he fish-oil 30 % lipid diet failed to prevent the development of hepatic steatosis" (Feillet-Coudray. 2013) - an effect which may be mediated by concomitant increases in liver lipid oxidation, of which the researchers write that it

Additional Read: "Fish Oil Compromises, Fish Improves Adiponectin Levels in "Overweight, But Healthy" Individuals. Neither Promotes Weight or Fat Loss Within a 4-Week Study Period" | more.

"[...] was increased with the fish-oil diet in comparison with the mixed and the lard diets. Within the 5 % lipid diets, the liver TBARS level was increased by 22 % with the fish-oil diet compared with the mixed diet, whereas within the 30 % lipid diets, the liver TBARS level was increased by 104 % with the fish-oil diet compared with the mixed diet." (Feillet-Coudray. 2013)

It turned out that there was a direct correlation of pathological lipid oxidation and the amount of omega-3 fatty acids in the liver (p < 0·001; r = 0·319). Accordingly, the...

"glutathione peroxidase activity was decreased with the fish-oil 30 % lipid diet in comparison with the lard 30 % lipid diet" (Feillet-Coudray. 2013)

The answer to the the question I raised in the caption of the image in the title of this article, i.e. "Does a (very) high fish oil diet entail the risk of going rancid - in spite of all its short-term benefits?" is "Yes, it does!".
References:

• Ayre KJ, Hulbert AJ. Dietary fatty acid profile affects endurance in rats. Lipids. 1997 Dec;32(12):1265-70 (learn more) 
• Browning, Lucy M., et al. "Compared with Daily, Weekly n–3 PUFA Intake Affects the Incorporation of Eicosapentaenoic Acid and Docosahexaenoic Acid into Platelets and Mononuclear Cells in Humans." The Journal of nutrition (2014): jn-113.
• Feillet-Coudray C, Aoun M, Fouret G, Bonafos B, Ramos J, Casas F, Cristol JP, Coudray C. Effects of long-term administration of saturated and n-3 fatty acid-rich diets on lipid utilisation and oxidative stress in rat liver and muscle tissues. Br J Nutr. 2013 Nov;110(10):1789-802.

Blueberries and other foods w/ tons of polyphenols are GSH boosters (Moskaug. 2005) and make supplements obsolete.

If you have been interested in dietary supplements for some time, I am pretty sure that you will have heard about oral glutathione ob(GSH) supplements in one of the "snake oil warnings" on various websites. The "master antioxidant" as it is called is after all believed by many to be not bioavailable - at least not orally. Studies in animal models, however, have already shown that oral GSH, administered either in the diet or by gavage, has the ability to increase plasma and tissue GSH levels ( Loven. 1986; Aw. 1991; Favilli. 1997; Kariya. 2007). It would thus be more appropriate to say that the efficacy of oral glutathione in humans has not yet been tested in peer-reviewed studies.
Now, the absence of human studies should definitely ring an alarm bell in the head of every healthily skeptic supplement user, what it should not do, though is mislead you to believe that GSH supplements dont work in human beings.

Now this is where John P. Richie Jr. and his colleagues from the Penn State Cancer Institute, the Department of Microbiology and Immunology at the Penn State University College of Medicine and the Orentreich Foundation for the Advancement of Science, come into play. As the scientist state, their "objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults." (Richie. 2014)
To this end, they conducted a 6-month randomized, double-blinded,placebo-controlled trial in the course of which the subjects, 41 women and 13 men (6 dropouts not included) with a normal BMI and no known health issues, consumed either ...

• an oral GSH supplement dosed at 250mg/day,
• an oral GSH supplement dosed at 1,000mg/day, or
• an identically looking placebo.

The main study outcomes were obviously analyses of the GSH levels in (a) blood, (b) erythrocytes, (c) plasma, (d) lymphocytes and (e) exfoliated buccal mucosal cells (the effects on a battery of immune markers was tested only in a handful of subjects).

Figure 1: Effects of 6 months GSH supplementation on ratio of oxidized to reduced GSH and natural killer cell cytotoxicity in healthy men and women aged 28-72y (Richie. 2014)

As the data in Figure 1 already suggests, there was a dose-dependent increase in GSH levels. With the high dose (1,000mg/day) producing GSH increases of 30–35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells (P<0.05) and increases of 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P<0.05 - data not shown in Figure 1).

These improvements had beneficial downstream effects on the overall status of the subjects antioxidant defense system. A fact you can conclude based on the decreased ratio of oxidized (used) to reduced (fresh) glutathione in whole blood the scientists observed in their subjects after 6 months. These benefits came hand in hand with an increase in natural killer cytotoxicity (+100%), another potentially highly desirable health benefit.

References:

• Aw, Tak Yee, Grazyna Wierzbicka, and Dean P. Jones. "Oral glutathione increases tissue glutathione in vivo." Chemico-biological interactions 80.1 (1991): 89-97.
• Favilli, Fabio, et al. "Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters." British journal of nutrition 78.02 (1997): 293-300.
• Kariya, Chirag, et al. "A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration." American Journal of Physiology-Lung Cellular and Molecular Physiology 37.6 (2007): L1590.
• Loven, Dean, et al. "Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozocin-induced diabetes." Diabetes 35.5 (1986): 503-507.
• Moskaug, Jan Ø., et al. "Polyphenols and glutathione synthesis regulation." The American journal of clinical nutrition 81.1 (2005): 277S-283S.
• Richie Jr, John P., et al. "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione." European journal of nutrition (2014): 1-13.