It's one thing to make strength and mass gains, it's a whole different story to make them last - if possible, for the rest of your life! Study suggests: Training intense, may help.

Don't forget to feed your muscles and learn more about protein intake at the SuppVersity

Are You Protein Wheysting?

Spread or waste your protein?

Protein requ. of athletes

High EAA intra-workout fat loss

Fast vs. slow protein

Too much ado about protein?

"determine the influences of short term detraining after two kinds of resistance training on strength performance and body composition in trained athletes."  (Tadibi. 2013)

• group (I) who performed resistance training with low intensity and high volume (GRI: n=15), weight 73.7±10.3 kg, height 174.5±7.5 m and age 24.7±1.4 years old and 
• group (II) who performed low volume and high intensity (GRII: n=25), weight 63.2±6.2, height 175.8±5.5 and age 25.4±1 (years old). 

• warm up, specific or related training and cool down. 

Learn more about the effects of circuit training: When you build a circuit training routine, don't forget: There are lot's of metabolically demanding kettle- bell exercises to spice things up. There are probably a dozen of reasons why people train. Many of them are really good: Wanting to stay healthy, to live longer, or to excel in your sports. Of others, however, I am not so sure whether they are actually worth pursuing, or do you think" - suggested read: "Circuit vs. Classic Strength Training, Which System is More Metabolically Demanding? What are the Energetic Costs and Where Does the Energy Come From, Fat or Glucose?" | read more.

• Figure 1: Graphical overview of the two training regimen

  bench press, 
• squat, 
• biceps curls, 
• triceps extensions, 
• shoulder press

"[s]ubjects performed 12– 15 maximal repetitions/set (55–60% 1RM) in group I, low intensity and high volume (LIHV protocol), and 5 maximal repetitions/set (85–90% 1RM) in the group II, low volume and high intensity (HILV protocol)" (Tadibi. 2013)

Figure 1: Relative changes in max strength (left) and body comp (right) from pre- to post-detraining (Tadibi. 2013)

• Contrary to what common wisdom would predict, the low intensity, high volume (LIHV) and the high intensity, low volume (HILV) regimen produce statistically identical strength gains over the course of the six-weeks training phased (not shown in Figure 1)
• The gains on the high intensity, low volume (HILV) regimen were - albeit not significantly - but visibly more persistent than those that were brought about by the high volume low intensity regimen.
• The high volume training turned out to have significant fat burning effects of the initially significant relative reduction in body fat % of 18% (from  12.15% to 9.73 in LIHV vs.   11.91% to 10.59% in the HILV group), there were yet only 7% left after 2 weeks of detraining (the BF% went back up from 9.73±3.12% to 11.27±3.37%).

• Häkkinen, K. "Neuromuscular adaptation during strength training, aging, detraining, and immobilization." Critical Reviews in Physical and Rehabilitation Medicine 6 (1994): 161-161.
• Tadibi, Vahid, et al. "Effect of acute detraining following two types of resistance training on strength performance and body composition in trained athletes." (2013).

They "take" spermine everyday!

• Double Your IGF-1 & Reduce Your Body Fat By 19% W/ Betaine!? I have to admit, the evidence I have to support this hilarious claim is not conclusive, but it's interesting. That's for sure.

• The data was published in a not exactly totally recent paper from the Department of Veterinary Medicine at the Faculty of Veterinary Science of the Chulalongkorn University in Thailand. The subjects were pigs and the objective of the present study was, therefore, to evaluate the effect of betaine supplementation (at 0.125% of the total diet) on carcass quality, growth performance and changes in serum IGF-1 and TG concentrations of finishing pigs.
  

  Figure 1: Relative IGF-1 & triglyceride levels, as well as thickness of back fat (Lothong. 2013)

  Aside from the previously mentioned improvements in body fat and IGF-1, the pigs on the "high" betaine diet (my calculation would suggest that we are talking about a human equivalent of only 2-3g per day) did also lead to significant reductions in serum triglyceride and could thus also help people with high blood lipids. 
• The Unknown Fat Loss Power of Spermine - You don't even know what spermine is? That's funny, 'cause you all have plenty of it in your body. It's after all a polyamine that's involved in cellular metabolism found in all eukaryotic cells.

• On the other hand, if you google it, you will soon realize that not just you, but also we (as in we as humans) know relatively little about Aethylenimin, as Spermin has previously been called. Thus, it took me a brief excursion into the archives the scientific journals of the world to come up with some information about its distribution in the mammalian body (see Figure 2) and following information (Tabor. 1976).

  Figure 2: Spermidine content of various tissues (left; Tabor. 1976); effects of 4 weeks of spermidine supplementation on body weight (g) of pre-fattened (high fat group) mice (Sadasivan. 2014)

  With respect to its functions, Anthony E. Pegg, a researcher from the Pennsylvania State University writes in his latest review published in January 2014:
  

  Table 1: Spermine-rich foods (data in mg/100g calc. based on Nishimura et al. 2006)

  "Polyamines play important roles in cell physiology including effects on the structure of cellular macromolecules, gene expression, protein function, nucleic acid and protein synthesis, regulation of ion channels, and providing protection from oxidative damage.
  
  Vertebrates contain two polyamines, spermidine and spermine, as well as their precursor, the diamine putrescine. Although spermidine has an essential and unique role as the precursor of hypusine a post-translational modification of the elongation factor eIF5A, which is necessary for this protein to function in protein synthesis, no unique role for spermine has been identified unequivocally. The existence of a discrete spermine synthase enzyme that converts spermidine to spermine suggest that spermine must be needed and this is confirmed by studies with Gy mice and human patients with Snyder-Robinson syndrome in which spermine synthase is absent or greatly reduced. In both cases, this leads to a severe phenotype with multiple effects among which are intellectual disability, other neurological changes, hypotonia, and reduced growth of muscle and bone." (my emphasis in Pegg. 2014)

  In other words, we know that we know... well, very little ;-) What we do know from a very recent study that was conducted (red alert!) by scientists working for Connexios Life Sciences Private Limited and is about to be published in one of the future issues of European Journal of Pharmacology is that spermine has the ability to bring diet-induced obese rodents back to a normal weight within four weeks! At least if it's dosed at a human equivalent of ~60-75mg per day.
  
  Aside from the profound reduction in body weight (-24%), the Connexios researchers observed in their fattened up mice, the spermine treatment did also reduce the fasting blood glucose levels by -18%. The corresponding improvements in glucose metabolism came hand in hand with the increases in fatty acid oxidation that were responsible for the rapid loss of white adipose tissue mass. 

As SuppVersity reader you know that betaine's IGF boosting effects occur in humans as well | learn more

Bottom line: Contrary to the use of spermidine supplements, which is still pie in the sky, betaine aka TMG (trimethylglicine) is a readily available amino acid of which you, as an avid SuppVersity reader know that it has also been shown to increase size and strength gains in athletes (learn more), to sooth the negative inflammation in your adipose organs (learn more), to set the anabolic stage for muscle growth by increasing IGF-1 and decreasing cortisol (evidence, more evidence) and to have a mild yet possibly overblown effect on the purported cardiovascular disease (CVD) marker homocysteine (learn more).

If you asked me, my money would thus be on betaine, not spermine on the moment, if I had to bet which of those could make a valuable addition to your supplement routine. Why? That's a question you shouldn't be asking if this ain't your first visit to the SuppVersity. With one sponsored rodent study supporting its efficiacy, spermine may qualify as the "new go to supplement" for the supplement industry, but for you as a critical thinker, it will obviously take independent human trials before you throw your money at Connexios and possible copycats.

• Jafarnejad, A., et al. "Effect of spermine on lipid profile and HDL functionality in the streptozotocin-induced diabetic rat model." Life sciences 82.5 (2008): 301-307.
• Lothong, Muttarin, Pornchalit Assavacheep, and Kittipong Tachampa. "Effects of Dietary Betaine Supplementation on Growth Performance, Carcass Quality and Serum IGF-1 and Triglyceride of Finishing Pigs." (2013). 
• Nishimura, Kazuhiro, et al. "Decrease in polyamines with aging and their ingestion from food and drink." Journal of biochemistry 139.1 (2006): 81-90.
• Pegg, Anthony E. "The function of spermine." IUBMB life (2014). 
• Soda, Kuniyasu. "Polyamine intake, dietary pattern, and cardiovascular disease." Medical hypotheses 75.3 (2010): 299-301. 
• Sadasivan, SK et al. "Exogenous administration of Q2 spermine results in improved glucose utilization and decrease in bodyweight of mice." European Journal of Pharmacology (2014). Accepted article.
• Tabor, Celia White, and Herbert Tabor. "1, 4-Diaminobutane (putrescine), spermidine, and spermine." Annual review of biochemistry 45.1 (1976): 285-306.

No pain... ah no creatine, no gain ;-)

You can learn more about creatine at the SuppVersity

Pharmacokinetics of Creatine PI & PII

Supercharge Creatine W/ Baking Soda

Creatine & the Brain

Creatine + ALA = Better Uptake?

Creatine Before or After Workouts?

Creatine, DHT & Hairloss?

"After two weeks of conditioning, the groups were begun performing resistance training (both weight bearing and weight free exercises). Weight exercises include deadlift, barbell squat, bench press, etc. Push up, curl up and brisk walking were some of the weight free exercises which were performed by both groups.

The duration of exercise was 45 minutes with the frequency of 3 days per week. Efforts were put to control the subjects. They were advised, not to participate in any other physical activity." (Kebrit. 2013)

Figure 1: Strength gains after 6 (left) and 12 weeks of resistance training with and without the provision of 5g of creatine monohydrate per day (Kebrit. 2013)

Figure 2: comparison of the relative increase in bench press strength in response to creatine supplementation (Kebrit. 2013) and testosterone enanthate (Bhasin. 1996) both in conjunction w/ exercise.

I am not kiddin't this is steroid like! I know it sounds hilarious, but if you look at the results of the often cited study Bhasin et al.  published in the New England Journal of Medicine on the 4th of July in 1996, you will see that the even a supra-physiological dose of injectable testosterone enanthate did not double the gains of the young, healthy study participants in the said study.

It's an apples vs. oranges comparison, I know, but it's still impressive, right? Well, I thought so and that's why I did include this study in the SuppVersity news, although each of you should know that creatine and protein are the only two "must have supplements" for strength trainees.

• Bhasin, Shalender, et al. "The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men." New England Journal of Medicine 335.1 (1996): 1-7.
• Kebrit, Daniel, and Sangeeta Rani. "Muscle strength and muscle endurance: with and without creatine supplementation." Turkish Journal of Sport and Exercise (2013).

Melt the belly, keep the muscle - a decent amount of protein is key, but more ain't more and as a recent study shows: This has nothing to do with hormones.

The data from the Pasiokos study shows: 1.6g/kg and not 2.4g/kg allows for the optimal balance of fat loss and lean mass retention (Pasiakos. 2013)

I guess, I have to warn you again! More protein is not a solution - even if some gurus want to make you believe it was. While the study at hand will only confirm that it does not help, a previous study by Pasiakos et al. (2013) revealed that eating too much protein (in this case 3x the RDA, i.e. 2.4g/kg) and thus necessarily too few carbohydrates and fats (learn more in " Evidence From the Metabolic Ward: 1.6-2.4g/kg Protein Turn Short Term Weight Loss Intervention into a Fat Loss Diet" | go back)

• 0.8g/kg protein per day (RDA),
• 1.6g/kg protein per day (2X-RDA), and
• 2.4g/kg protein per day (3X-RDA)

Figure 1:  Relative pre vs. post changes in testosterone and IGF-1 & its binding proteins (Henning. 2014)

It takes some profound changes in T-levels to see real-world effects on lean and/or fat mass | learn more

Bottom line: Protein helps, but it's effect are non-hormonal and mediated via the activation of the p-AKT/mTOR protein synthetic cascade. Put simply: A higher protein intake can help you keep the protein synthetic machinery running. In conjunction with exercise (s. red box), the unquestionably the most powerful anti-catabolic, a higher protein intake helps to preserve lean mass on a diet. What (additional) protein cannot do, though is to ameliorate the diet-induced reductions in testosterone and IGF-1 that occur, whenever you consume significantly less energy than you need.

Whether you consider it surprising or even unbelievable or simply natural that this doesn't mean that you will "fall apart", is probably a matter of how deeply rooted your (from a science perspective) unwarranted believe in the effects of reductions / increases in testosterone within the normal range is (with 420ng/dL even the men in the 3xRDA group who had the lowest T-levels were still "in range"). If you've read my previous dissertations in "Quantifiying the Big T" (read more), you shouldn't be all too surprised, though (suggested read: "IGF-1 and its Splice Variants MGF, IGF-IEa & Co - Master Regulators or a Bunch of Cogs in the Wheel of Muscle Hypertrophy?" | more).

• Henning, et al. "High protein diets do not attenuate decrements in testosterone and IGF-I
  during energy deficit." Metabolism (2014). Accepted Paper - 14. February 2014
• Pasiakos SM, Cao JJ, Margolis LM, Sauter ER, Whigham LD, McClung JP, Rood JC, Carbone JW, Combs GF Jr, Young AJ. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 2013 Jun 5. [previous SuppVersity article]
• Rossow LM, Fukuda DH, Fahs CA, Loenneke JP, Stout JR. Natural Bodybuilding Competition Preparation and Recovery: A 12-Month Case Study. Int J Sports Physiol Perform. 2013 Feb 14 [previous SuppVersity article]

This is part I of a multipart series, you will be able to navigate by clicking on the pictures in the box below.

You can learn more about this topic at the SuppVersity

Amino Acids, Proteins, Peptides

Read these ➲ while waiting

Are You Protein Wheysting?

Spread or waste your protein?

Protein requ. of athletes

High EAA intra-workout fat loss

It does not even take whole proteins. Single amino acids and dipeptides (=2-amino acids) can have glucose repoartitioning trick, too | learn more

Figure 1: Effects of 12 week of WPC vs. ISP supplementation on fasting blood glucose (Tahavorgar. 2014)

• systolic and diastolic blood pressure
  ⤷ improved heart health, 
• apo lipoprotein A-I and apo B
  ⤷ improved cholesterol metabolism, 
• malondialdehyde
  ⤷ reduced lipid oxidation,
• HDL, LDL and triglycerides
  ⤷ improved lipid metabolism,
• high sensitive C- reactive protein
  ⤷ reduced inflammation

Figure 2: Glucose and insulin release levels after 50g glucose load w/ 30g whey or 30g canola oil (Lan-Pidhainy. 2010)

Figure 3: Relative GLP-1 production in intestinal cell culture exposed to BCAAs, skim milk or casein (Chen. 2009)

"Although the mechanism is not well understood, some in vitro studies show how the insulinotropic effect might be induced (Dunne, 1990; Brennan. 2005; Cunningham. 2005). In cell experiments with the application of L-alanine, the increase in insulin secretion might be caused by an increased intracellular oxidation of amino acids, which raises the ATP content of the cell. Increase in intracellular ATP content leads to closure of the ATP-sensitive potassium channels, and this channel closure leads to depolarization of the cell membrane and activation of the calcium channels. Activation of the calcium channels then causes an exocytosis of insulin from the cells (Brennan. 2005; Cunningham. 2005)." (Heer. 2014)

While 200mcg of chromium are essential, consuming way more can have pro-diabetic effects | learn more.

You can learn more about the other nutrients in the next installment(s): I know that this is not exactly fair, but let's be honest - Aren't there better ways to spend a Sunday afternoon than writing SuppVersity articles? I personally feel the answer is "YES!" The discussion of the effects of dietary fat, in general, (one of the things that's going to be mentioned may already be inferred from Figure 2) and individual fatty acids in particular, as well as the influence of vitamin D, vitamin K, calcium, magnesium, chromium, zinc, sodium, and a couple of other nutrients will thus have to wait until next week (some even longer ;-).

• Astrup, Arne, et al. "Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide." International journal of obesity 36.6 (2012): 843-854. 
• Bendtsen, Line Q., et al. "Effect of dairy proteins on appetite, energy expenditure, body weight, and composition: A review of the evidence from controlled clinical trials." Advances in Nutrition: An International Review Journal 4.4 (2013): 418-438.
• Brennan, Lorraine, et al. "A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic β-cell line metabolism of L-alanine is important to the regulation of insulin secretion." Diabetes 51.6 (2002): 1714-1721.
• Chen, Qixuan, and Raylene A. Reimer. "Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro." Nutrition 25.3 (2009): 340-349. 
• Cunningham, GA, et al. "L-Alanine induces changes in metabolic and signal transduction gene expression in a clonal rat pancreatic β-cell line and protects from pro-inflammatory cytokine-induced apoptosis." Clinical science 109 (2005): 447-455.
• Dunne, M. J., et al. "Effects of alanine on insulin-secreting cells: Patch-clamp and single cell intracellular Ca ²⁺ measurements." Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1055.2 (1990): 157-164.
• Heer, Martina, et al. "High Protein Intake Improves Insulin Sensitivity but Exacerbates Bone Resorption in Immobility (WISE Study)." (2012).
• Lan-Pidhainy, Xiaomiao, and Thomas MS Wolever. "The hypoglycemic effect of fat and protein is not attenuated by insulin resistance." The American journal of clinical nutrition 91.1 (2010): 98-105.
• Meier, Juris J. "GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus." Nature Reviews Endocrinology 8.12 (2012): 728-742.
• Tahavorgar, Atefeh, et al. "Effects of whey protein concentrate consumption compared with isolated soy protein on metabolic indices, inflammatory and oxidative stress factors in healthy overweight and obese men." Razi Journal of Medical Sciences 20.115 (2014): 17-30.

If you want to know how to get of pubertal acne, you got to ask professional pubescents ;-)

Figure 1: Changes in inflammatory acne lesion counts with time (left, top), noninflammatory acne lesion counts with time (left, bottom), and changes in patients' subjective assessment (VAS) with time (right; Jung. 2014)

Figure 2: Before (top) and after (bottom) photos (Jung. 2014)

"Mean non-inflammatory acne lesion counts were also reduced by omega-3 and GLA supplementation (23.5 ± 9.2 to 18.9 ± 8.3, p < 0.05, and 22.8 ± 8.4 to 19.2 ± 7.2, p < 0.05, respectively) at final visits, whereas mean lesion count in the control group was unchanged (from 21.8 ± 9.7 to 22.0 ± 8.6). Significant differences were evident between the treatment groups and the control group after 10 weeks (p < 0.05)." (Jung. 2014)

GLA, EPA & Co play an important role in thyroid disorders, as well | learn more

"Where Bro- and Pro-Science Unite in the Spirit of True Wisdom": The study at hand exemplifies this simple principle almost perfectly. DHA + EPA and GLA have been used to manage acne vulgaris for years.

It was thus high time for the "pro-science" to catch up with what "bro-scientists" all around the world knew all along. Fish oil and borage oil help with acne vulgaris.

Why? Well, in both cases it's probably the reduction of the production of arachidonic acid-derived pro-inflammatory eicosanoids.

• Cordain, Loren, et al. "Acne vulgaris: a disease of Western civilization." Archives of Dermatology 138.12 (2002): 1584-1590.
• Jung, Jae Yoon, et al. "Effect of Dietary Supplementation with Omega-3 Fatty Acid and gamma-linolenic Acid on Acne Vulgaris: A Randomised, Double-blind, Controlled Trial." (2014).
• Wolf, Ronni, Hagit Matz, and Edith Orion. "Acne and diet." Clinics in dermatology 22.5 (2004): 387-393.

I have to admit: Whether a conclusion as general at this is warranted based on the data from a recent study is questionable.

"[...] overeating SFA promotes hepatic and visceral fat storage whereas excess energy from PUFA may instead promote lean tissue in healthy humans." (Rosqvist. 2014)

"[...]liver fat accumulation during moderate weight gain could be counteracted if the excess energy originate mainly from PUFA rather than from SFA." (Rosquist. 2014)

Don't interpret this article as incentive to follow all dietary recommendations to the "T" before you've read my 2012 article on the effects of an allegedly heart healthy low fat diet on the LDL particle profile of healthy volunteers | read more

• Figure 1: Rel. changes in liver, visceral and subcutaneous fat in subjects over-consuming a high vs. low (white) saturated fat diet.

  the subjects were randomly allocated to the two intervention groups
• the scientists made sure that the subjects gained weight at identical rates (3%) (the amount of muffins consumed per day was individually adjusted weekly, i.e. altered by +/- 1 muffin/day depending on the rate of weight gain of the individual)
• the dietary intervention was based on highly standardized food items 
• muffins containing sunflower oil (high in the major dietary PUFA, linoleic acid, 18:2 n-6) or 
• muffins containing palm oil (high in the major SFA, palmitic acid, 16:0). 
• the muffing were baked in large batches under standardized conditions in a metabolic
  kitchen at Uppsala University
• except  for  the type of fat, the  muffins  were  identical  with  regard  to  energy,  fat (51%),  protein (5%), carbohydrate (44%; sugar to starch ratio 55:45), and cholesterol content, as well as taste and structure.

Figure 2: Relative contribution of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids to the total energy intake of the subject before and after the study (Rosquist. 2014)

Figure 3: There is a distinct correlation between the relative amount of omega-6 fatty acids in the blood and the change in lean mass - a beneficial one!

More or less flawless, but still questionable: Whether that's enough for you to accept that the Rosquist et al. used their results to make a general statements about the effects of saturated vs. unsaturated fat intake is up to you. The same goes for the real-world significance of the different body and liver fat trajectories in Figure 1.

In view of non-negligible increases in total, liver and visceral body fat and the absence of the often-touted pro-anabolic effects of saturated fats (mind the proportionality of an increase in the allegedly bad omega-6 concentration in the blood and the lean mass increases / decreases in Figure 3), it's difficult to keep nibbling on a chunk of bacon without at least taking into consideration that the "bad PUFAs" may not be as bad after all.

"Whut?" Calm down, I am not suggesting that you have to go back to the "saturated fat is bad for you" mantra, but I would like to invite you to take a parting look at Figure 2 (right) and note that the main characteristic of the "PUFA" diet is not its high PUFA content, but it's balanced fat content. Maybe the sentence "The optimal diet is characterized by a balanced intake of all three main types of dietary fat" would thus be a conclusion we can agree on - ha?

• Bjermo, Helena, et al. "Effects of n− 6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial." The American journal of clinical nutrition 95.5 (2012): 1003-1012.
• Rosqvist, Fredrik, et al. "Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans." Diabetes (2014): DB_131622.

YoYo flywheel device similar to the one used in the study from the Karolinska Institute in Stockholm.

• The EPO-Effect of Oxygen Shortage : A study from the University of Western Australia shows athletes who train in a low-oxygen environment (simulated high altitude training) have significantly higher hepcidin (a protein that inhibits iron transport from the gut into the portal vein)and erythropoietin (EPO) levels in the early hours after the workout.

  Figure 1: Changes in serum IL-6 (pre vs. post), hepcidin and EPO levels (pre vs. 3h post; Badenhorst. 2014)

  As Claire E. Badenhorst and her colleagues point out, this would lead to an immediate increase in dietary iron absorption and formation of red blood cells that may be partly responsible for the well-known ergogenic effects of altitude training.
  
  Whether the decreased IL-6 levels immediately after the 8 × 3 min interval running sessions at 85 % of the subject's maximal aerobic capacity are likewise something to celebrate is yet questionable in view of the most recent research on the involvement of this allegedly "bad" inflammatory cytokine (Knudsen. 2014) - I mean, if, as Knudsen et al. argue, the IL-6 increase is responsible for the increase oxidation of fat after a workout you would not necessarily want to decrease it... correct?! The improvements in maximal strength and power, researchers from the Karolinska Institute in Sweden have observed in their latest experiments have been "slightly greater" in the male vs. female subjects. In view of the overall effect size, it is obvious, though that eccentric-overload resistance training is a training technique, both men and women should not forget about prematurely (Fernandez‑Gonzalo. 2014).
• Eccentric Overload Training for Him and Her - While you are looking at the data in Figure 2 you do have to keep in mind, thought, that doing 6 weeks (15 sessions) of flywheel supine squat RE training is probably not what you had in mind, when you read about "eccentric overload training for him and her" - right?
  

  Figure 2: Pre vs. post changes after 6-weeks of eccentric flyhweel training (Fernandez‑Gonzalo. 2014)

  Well, in view of the fact that the subjects in the study at hand were not obese couch-potatoes, but science undergraduate students (16 men;  and 16 women) who engaged in 4–6 h of recreational exercise per week, it may be worth to convince the owner of your gym to head over to "yoyotechnology.com" and buy one of these funky devices ;-)
• A Little Less TV, a Little More Sports! I must say, I was not surprised when I hit on a recent study by Sjaan R. Gomersall, Kevin Norton, Carol Maher, Coralie English, and Tim S.
  

  "In search of lost time: When people undertake a new exercise program, where does the time come from? A randomised controlled trial." (Gomersall. 2014)

  That's the title of the paper that was published in the Journal of Science and Medicine in Sport. And if we are honest it's also a paper with unsurprising results. It does after all tell us, what most of you will probably already have expected: Reducing their screen time (=TV watching) is the #1 setscrew that will allow previously sedentary individuals to make room for exercise in their lives.

  Figure 3: Changes Physical Activity Level (PAL, in METs) and time (min/day) in front of the computer, for active transport, self-care, quite time and work and study activities (Gomersall. 2014).

  Likewise on the list of reduced activities are the time spent in front of the computer and the time that's wasted on video games (not shown) - wasted unless it's Tetris, of which you've learned only recently that it will help you lose weight; see "An Effective Appetite Suppressant From the 90s" (learn more).
  
  What's interesting and actually in line with previous research is the fact that the increased activity levels did not reduce the time spent with friends (socio-cultural) or at work. In other words: Working out will not turn you into a lonely jobless person ;-)

Figure 4: Relative risk of obesity according to sedentary behaviours (in h); adj. for Relative risk of obesity according to sedentary behaviours and physical activity (Banks. 2011)

Bottom line: Whether you manage to exercise in a hypoxic environment or on a flyhweel machine is unquestionably negligible, as long as you decide to exercise instead of sitting in front of computer and television for a couple of hours, everyday.

Why you would possible want to do that? Well, what about the 23% increase in obesity risk that comes with 2h of additional screen time per day of which Banks et al. observed in the 91 266 participants of the 45 and Up Study that it cannot be compensated by extra physical activity (see Figure 4; Banks. 2011)?

• Badenhorst, C.E. et al. "Influence of post‑exercise hypoxic exposure on hepcidin response
  in athletes."  European Journal of Applied Physiology (2014). 
• Banks, Emily, et al. "Screen-time, obesity, ageing and disability: findings from 91 266 participants in the 45 and Up Study." Public health nutrition 14.01 (2011): 34-43.
• Fernandez‑Gonzalo, R et al. "Muscle damage responses and adaptations to eccentric-overload resistance exercise in men and women." European Journal of Applied Physiology (2014).
• Knudsen, Jakob G., et al. "Role of IL-6 in Exercise Training-and Cold-Induced UCP1 Expression in Subcutaneous White Adipose Tissue." PloS one 9.1 (2014): e84910.
• Gomersall, Sjaan R., et al. "In search of lost time: When people start an exercise program, where does the time come from? A randomised controlled trial." Journal of Science and Medicine in Sport (2014).

FSR ≠ more muscle = no news for ya!

Suggested read: "Protein Intake & Muscle Catabolism: Fasting Gnaws on Your Muscle Tissue and Abundance Causes Wastefulness " | more

"Briefly, participants trained four times weekly with two upper and two lower body workouts. Lower body exercises are described above in the acute exercise session. Upper body exercises consisted of chest press, shoulder press, seated row, lat pulldown, bicep curl and tricep extension. The program was progressive in linear manner moving from 3 sets of 12 repetitions to 4 sets of 6  repetitions. At the end of the training period, MRI, DXA scans and strength testing were repeated." (Mitchell. 2014)

Figure 1: Myofibrillar fractional protein synthesis rate (left) measured acutely after a single workout and changes in muscle volume (%) over the whole 16-week study period as a function of the 1-6h post-workout FSR (Mitchell. 2014).

Figure 2: Changes in muscle volume (%) expressed relative to acute increases in 4E-BP (Mitchell. 2014).

SuppVersity Suggested Read: "Protein Wheysting?! No Significant Increase in PWO Protein Synthesis W/ 40g vs. 20g Whey, But 100% Higher Insulin, 340% More Urea & 52x Higher Oxidative Amino Acid "Loss" | more

"Though shalt not make quantitative predictions about long(er) term muscle gains based on acute FSR measurements!"- This statement is unquestionably correct. It's something I have written about before and it's a statement that is supported (if not confirmed) by the data of the study at hand.

The statement "though shalt not make qualitative predictions about long(er) term muscle gains based on acute FSR measurements", on the other hand, would yet be unwarranted and is probably incorrect. We do after all have more than enough evidence that increases in post-workout protein synthesis will (sooner or later) result increases in muscle size. The fact that we cannot predict the extent of long(er) term hypertophy effects based on measuring acute changes in FSR does not imply that these changes would not matter at all. It does only mean that we have to be careful about overestimating the real-world effects of differences in protein synthesis between training modalities and supplements, even if they are statistically significant in the hours after a workout.

• Burd, Nicholas A., et al. "Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men." British Journal of Nutrition 108.06 (2012): 958-962.

It's often cited as the source of all nutritional (and environmental) evil and still: The experimental evidence informs us that the epidemiologically instigated politically subsidized meat hating is unreasonable.

Table 1: Energy & Nutrient intake at baseline and during the meaty intervention period (Murphy. 2014)

"All participants were seen fortnightly to monitor body weight, discuss any issues arising in the intervention and collect a selection of frozen meat products including lean beef or pork steak or chicken breast, stir fry, diced and mince. All participants kept a weekly log of study meat consumption" (Murphy. 2014)

Figure 1: Changes in body composition during the 6 months pork, chicken, beef phase (Murphy. 2014)

• Figure 2: Lean mas at baseline and after the meaty intervention (Murphy. 2014)

  ... the weight loss occured in the absence of prescribed energy reduction and / or increase in activity level or the total protein intake (see Table 1) of  the 50 ± 2 year-old overweight male and female participants , 
• ... there was an extremely health-relevant 7% increase in lean mass (that's +3.5 ± 0.1kg (!); see Figure 2) in and all women
• ... the researchers did not observe any negative side effects in either of the groups.

Bottom line: The significance of the decrease in fat and increase in lean mass, the researcher observed in the study at hand can hardly be overestimated. Unfortunately, there are still way too many men and even more women who consider the "weight loss" their main "health goal" - a goal, of which Allison et al. (1999) have been able to show that it increases all-cause mortality, which a loss of body fat, as it occured in the study at hand, lowers all-cause mortality!

Suggested read: "Reduced Weight Gain, Improved Insulin Sensitivity and No Adverse Side Effects from 'Red Meat Supplementation' Even in Rodents!" | read more.

In that, it should not be surprising for you as a SuppVersity reader that an increased intake of (mostly) lean + unprocessed red meat can be the driving force of corresponding changes in body composition. I have, after all, written about the unwarranted over-generalized assault on meats repeatedly (" The Meaty Gritty on the Red Meat Debate: A Comprehensive Rebuttal of the Constant Assault On My Beloved Steaks " | read more); and in view of the data German researchers presented in a 2011 paper (Petzke. 2011), it should be clear that similar benefits of meat in general and lean pork in particular will occur in lean women, as well (see "Additional(!) 200g Pork/Day Build Lean Mass + Improve Blood Lipids & Glucose Levels" | read more)

• Allison, D. B., et al. "Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies." International Journal of Obesity & Related Metabolic Disorders 23.6 (1999).
• Murphy, Karen J., et al. "A Comparison of Regular Consumption of Fresh Lean Pork, Beef and Chicken on Body Composition: A Randomized Cross-Over Trial." Nutrients 6.2 (2014): 682-696.
• Petzke, Klaus J., Susen Lemke, and Susanne Klaus. "Increased fat-free body mass and no adverse effects on blood lipid concentrations 4 weeks after additional meat consumption in comparison with an exclusion of meat in the diet of young healthy women." Journal of nutrition and metabolism 2011 (2011).

Weight loss is easy, but doing it fast and without losing muscle is - as of now - more of an art than a science.

Little has previously been known about metabolic effects of changes in the composition of either FM or FFM with weight loss and gain." (Pourhassan. 2014)

Figure 1: Changes in glucose and insulin response during oral glucose tolerance test after diet and/or exercise induced weight loss (Dengel. 1996)

"Metabolic adaptations are a result of changes in body composition and variations in the metabolism of individual body components. Weight loss had a strong effect on improving insulin resistance in overweight and obese individuals (Dengel. 1996; Niskanen. 1996).

[...] determination of whether metabolic effects of weight loss result from the reduction of specific fat depots (eg, in VAT) or a generalized decline of adipose tissue" (Pourhassan. 2014).

• body composition by using the 4-component model and whole-body MRI
• resting energy expenditure (REE),
• plasma thyroid hormone concentrations, and
• insulin resistance

Figure 1: Changes in body composition, and thyroid hormones (left) corresponding before calculated (unadjusted) and measured REE levels in weight gainers, losers and stable subjects (Pourhassan. 2014).

Figure 3: Resting energy expenditure (x-axes) expressed as function of total body mass (left), and lean body mass of weight losers (middle) and gainers (right), respectively (Pourhassan. 2014).

"In a first analysis, we included changes in FFM and FM as independent variables.
Changes in FM explained 22.8% of the variance in changes in REE(measured), and changes in FFM explained an additional 7.4% of the variance. In a second analysis, we added changes in individual components of FFM (ie, changes in skeletal muscle, bone mass, adipose tissue, heart mass, kidney mass, liver mass, and brain mass) and changes in FM as independent variables. Changes in skeletal muscle explained 29.8% of the variance in changes in REE(measured), and changes in FM explained additional 4.2%."

"[...i]t is likely that the magnitude of these adaptations are proportional to the size of the energy deficit, so it is recommended to utilize the smallest possible deficit that yields appreciable weight loss." (Trexler. 2014)

• stick to stepwise reductions of total energy intake - start with 15% and increase in 5-10% steps, whenever you hit a plateau
• if not absolutely necessary limit your energy deficit to max. 40% - if you hit a plateau, take two weeks off and begin dieting again, instead of running yourself into the ground 
• keep lifting heavy while you're dieting to minimize muscle loss - you can use bot inter- (e.g. 1x powerlifting, 2x higher rep bodybuilding or circuit training routines per week) as well as intra-workout periodization (eg. a heavy compound lift for 5x5 and auxiliary exercises for 3x10 reps and 4x15 reps)

• Never work out to burn calories | learn why

  use your diet, and only your diet to generate an energy deficit - there is room for both high intensity interval and classic low intensity steady state (walking on an inclined treadmill) exercise, but it must not be done to "burn calories" (learn why) - unless, obviously, you actually want to feel miserable and accelerate the fal loss stalling adaptive reduction in energy expenditure
• increase in protein intake to >25% of total energy - as long as you stick to the "-40% max"-rule this should leave enough room for the "magic" 2x RDA (1.6g/kg) value of which a study by Pasiakos showed that it produces a better lean-to-fat mass loss ratio than a diet with 2.4g/kg protein (learn more)
• consume at least 30g of EAA-rich protein per meal - this will bring you up to the magic 10g of EAAs which have been shown to be associated with improved body composition in epidemiological studies (don't use isolated amino acids, instead - they are non-satiating and have inferior metabolic and protein anabolic effects)
• implement regular refeeds, whenever your total energy deficit is >25% - the refeeds will consist of a single day of 10-15% above maintenance energy intake with a focus on carbohydrates, and should be implemented once or twice a week; they are are believed "to temporarily increase circulating leptin and stimulate the metabolic rate" (Trexler. 2014) and will thus postpone the occurrence of weight loss plateaus 

• The beneficial metabolic effects of veggies are mediated in parts by stretch receptor <> vagus nerve interactions in your gut (Rolls. 2002; de Graaf. 2011). These are reduced / absent if you juice or powder your veggies.

  fill yourself up with vegetables - except from a few "high energy" exceptions you can and should eat as many veggies as possible; aside from the tons of healthy vitamins and phytonutrients, the mere increase in food volume is going to have a major metabolic impact that goes way beyond an increase in satiety and cannot be achieved with powdered and is significantly reduced with juiced vegetables (you can still "juice", if you insist even waste money on greens supplements, but their benefits will never be up to fresh produce)
• avoid post-starvation obesity by working your way up to your habitual energy intake progressively - this is particularly important to avoid the formation of new fat cells (=adipocyte hyperplasia), which are currently believed to stick "forever" (=the cells whole life-cycle of ~10 years); neither the pizza and McDonald's diet, nor - and this is something most people tend to overlook - returning to the dietary habits that brought you into a situation, where dietary restriction became obligatory to get (back) in shape are feasible ways of eating after a diet; increase your energy intake in <5% steps every three days and watch the scale and your image in the mirror carefully to minimize fat gains (it's impossible not to gain a minimal amount of fat)

• Bosy-Westphal, A., et al. "Effect of weight loss and regain on adipose tissue distribution, composition of lean mass and resting energy expenditure in young overweight and obese adults." International Journal of Obesity 37.10 (2013): 1371-1377.
• de Graaf, Cees. "Why liquid energy results in overconsumption." Proceedings of the Nutrition Society 70.02 (2011): 162-170.
• Dengel, Donalald R., et al. "Distinct effects of aerobic exercise training and weight loss on glucose homeostasis in obese sedentary men." Journal of Applied Physiology 81.1 (1996): 318-325.
• Niskanen, L., et al. "The effects of weight loss on insulin sensitivity, skeletal muscle composition and capillary density in obese non-diabetic subjects." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 20.2 (1996): 154-160.
• Pourhassan, Maryam, et al. "Impact of body composition during weight change on resting energy expenditure and homeostasis model assessment index in overweight nonsmoking adults." The American journal of clinical nutrition (2014): ajcn-071829. 
• Rolls, Barbara J., and Liane S. Roe. "Effect of the volume of liquid food infused intragastrically on satiety in women." Physiology & behavior 76.4 (2002): 623-631.
• Trexler et al. Metabolic adaptation to weight loss: implications for the athlete." Journal of the International Society of Sports Nutrition 11 (2014):7.

Yeah! I am in the active arm of the study! Now I Can Eat All The Crap in The World and Still Lose Weight!

You can learn more about fat burners at the SuppVersity

Capsaicin as a Thermogenic

Piperine vs. Silbutramine

New Ephedra Sources?

Inflammation = True Fat Burner

Fat Oxidation ￪￪ w/ Caffeine

High Calcium Diets = Fat Burner?

• "the test pill will help you to attain weight loss" - active arm of the study

• "the test pill is a placebo that will be used in a future study" - placebo arm

"The food in this buffet, which remained consistent over the course of the experiment, consisted of six healthy items (e.g., fruit, salad with Japanese dressing, vegetable pizza, steamed bean cu steamed fish, and sugar-free green tea) and six less healthy items (e.g., chocolate cookies, French fries, fried chicken, cheeseburgers, soda, and custard). Healthy and less healthy items were identified by two nutritionists blind to the purposes of the experiment." (Chang. 2014)

Figure 1: Relative differences in total, unhealthy and healthy food intake in subjects who believed that they consumed the weight loss pill; data expressed relative to control group (Chang. 2014)

Suggested Read: "Forgotten Dieting Aids: Choline, Carnitine, Caffeine and the Anti-Weight-Loss Plateau Effects of Sugar and Phosphates" | more

Bottom line: I am not telling you not to support your weight loss efforts by using a stim-based fat burner. These products can keep you going, suppress appetite and will help you function in your everyday life, when your calorie intake drops and the lack of energy takes it's toll.

NONE of the currently available OTC fat burners will actually "burn" the fat you are to lazy to lose. If you are taking these products to have the occasional slice of pizza every other day, you are doomed to fail. Sales of indulgences like this may work in the confession box, but they don't work on the (body fat) scale.

• Chang, Yevvon Y., and Wen-Bin Chiou. "The Liberating Effect of Weight-Loss Supplements on Dietary Control: A Field Experiment." Nutrition (2014).

Some say "fat is a mistake" others say "it was our fattest mistake to believe just that" - who is right? Or are things eventually more complicated than that?

You can learn more about this topic at the SuppVersity

Proteins, Peptides & Blood Glucose

SFA, MUFA, PUFA & Blood Glucose

Read these ➲ while waiting

Low Fat Advantage on IF

16 Weeks High Fat Diet

Fat to Blunt Insulin?

• the general effect of dietary fat on the absorption, appearance and clearance of glucose from the bloodstream, and
• the different effects of saturated, monounsaturated, and polyunsaturated short- and long-chain fatty acids on glucose homeostasis

• 27nmol/L LDL Per 1% Reduction in Trans Fat Intake | learn more

  A high intake of trans-fats for example will lead to an accumulation of trans-isomers of linoleic acid in the heart and a highly significant 50% risk increase for cardiac arrest (Lemaitre. 2002).
• A high concentration of linoleic acid (n-6) in the erythrocyte membrane has been shown to be negatively, a high palmitic acid content positively associated with incident type 2 diabetes in 1346 Finnish men aged 45–73y researchers from the University of Eastern Finland followed for 5-years in recently conducted a population-based study (note: The researchers detected no protective effect of omega-3 fats; cf. Mahendran. 2014).

Fatty acid ⇆ PPAR interaction (Kota. 2005)

"More recent experimental data also point toward other mechanisms which involve direct regulatory effects on gene expression and enzyme activity.

For example, in vitro studies and studies in animal models suggest that fatty acids could act directly on insulin-sensitive tissues (Risérus. 2008)." (Heer. 2014)

"Substituting saturated fat with unsaturated fat seems to have beneficial effects on insulin sensitivity, although the clinical significance of modifying fat quality alone is still unclear." (Risérus. 2008)

• MUFAs boost resting energy expenditure: Next to its beneficial effects on blood glucose and lipid management, a high intake of monounsaturated fatty acids can also increase the resting energy expenditure in humans by 3% in the fed and 4% in the fasted state, respectively (Kien. 2013).
  Monounsaturated fats - MUFAs -- Gadgil et al. report that 2 weeks on high MUFA diets lead to prompt improvements in insulin sensitivity in 64 individuals with prehypertension or stage 1 hypertension without diabetes (Gadgil. 2013). Two years before Gillinghan et al. wrote in a review of the effect of high mono-unsatuarated fatty acid intakes that the "[c]onsumption of dietary MUFA promotes healthy blood lipid profiles, mediates blood pressure, improves insulin sensitivity and regulates glucose levels" (Gillingham. 2011).
• Polyunsaturated fats = PUFAs -- Similar beneficial effect on heart health have been reported for the replacement of saturated fat with polyunsaturated fatty acids (both, omega-3 and omega-6; see Flock. 2014). Evidence for the beneficial effects of omega-3 fatty acids, in particular, dates back to the late 1980s, when Popp-Snijders et al. observed that 8 weeks of daily supplementation of 3 g of the omega 3 fatty acids eicosapentaenoic and docosahexaenoic acid improves the insulin sensitivity of subjects with non-insulin-dependent diabetes (Popp-Snijders. 1987).
  
  Unfortunately, studies like this have triggered an unwarranted euphoria even among healthy individuals, whose hope for further improvements in insulin sensitivity are not just unwarranted (Risérus. 2008), but could actually mislead them to mimic the high-dose fish oil supplementation regimen of the diabetic subjects in a 2006 study by Mostad et al. (1.8 g 20:5n−3, 3.0 g 22:6n−3, and 5.9 g total n−3 fatty acids from fish oil) to end up with a similar negative effect on blood glucose levels and glucose utilization (see Figure 1).

  Figure 1: Blood glucose levels (left), glucose utilization and C-peptide levels (right) of 26 diabetic subjects after 8 weeks of high dose fish oil vs. corn oil supplementation (Mostad. 2006)

  It must be said, though, that the Mostad study is an exception. Most fish oil supplementation studies used lower amounts of fish oil and showed improvements in lipid metabolism, but no effect on insulin sensitivity, similar to those Kabir et al. observed in 2007. Accordingly, reviewers agree fish oil supplementation in moderate dosages (equivalent to 1-2 g/day n-3 LCPUFA) has no significant adverse effects on fasting glucose, HbA1c, fasting insulin, or insulin sensitivity (McManus. 1996; Friedberg. 1998; Montori. 2000; Lombardo. 2006; Akinkuolie. 2011; Lee. 2013) - unfortunately, it does not improve these parameters, either.

• "unnatural" cis- and trans monounsaturated fatty acids as they occur in partially hydrogenated fats, but also
• "natural" ones such as vaccenic acid and the conjugated isomers of linoleic acid (CLA) in dairy

Contrary to the benefits of supplemental CLA, the beneficial effects of vaccenic acid and other ruminant transfats in dairy are beyond doubt | more

If you wanted to destroy your body fat, you'd have to consume exclusively the prodiabetic, inflammatory tans-10, cis-12 isomer | learn more

Stay away from mixed CLA supplements: Contrary to the health-benefits of their food-borne brethren, the usefulness of the transfats you will find in gel-caps at each and every supplement store are still "controversial" it is clear that "more research is needed before the widely available CLA supplements (racemic mixtures of both isomers with prodiabetic effects; cf. Risérus. 2002) should be advocated as an adjunct to control body weight" (Heer. 2014) - and this is specifically true in view of the opposing effect of cis-9,trans-11 (anti-inflammatory, anti-diabetic | Moloney. 2007)  and trans-10,cis-12 (inflammatory | Poirier. 2006) conjugated linoleic acid on blood lipids and glucose metabolism (Halade. 2010)

Figure 2: Blood glucose (mmol/L, left), GIP (pmol/L, top-right), and insulin (mU/L, bottom-right) response to a standardized mashed potato meal 30min after the ingestion of water, olive oil, or both (Gentilcore. 2006)

Figure 3: Pro-inflammatory dietary fats are only one of the components that drive the contribution of the postprandial inflammatory response to the self-intensifying circle of metabolic inflammation (Margioris. 2009)

• the commonly cited negative effects of dietary fat on insulin sensitivity are real - even a high fat, low carb diets will lead to acute reductions in glucose tolerance (Hales. 1963),
• the negative effects on insulin sensitivity are partially mediated by increases in free fatty acids (Roden. 1996),
• the ill health effects of the high fat-induced reduction in glucose tolerance depends on the presence and amount of carbohydrates, as well as the total energy intake and -expenditure and other non-nutrient dependent parameters (Margois. 2009),
• in the postprandial phase, the impaired / slowed influx of glucose and the prolongation of the postprandial hyperinsulinemia may provide an acute relief for people with already elevated blood glucose levels (Gentilcore. 2006), eventually, they will yet promote the development and progression of insulin resistance (Marangou. 1986)

• Figure 4: Insulin secretion rates in response to isocaloric meals based water (CONT), palm oil (SFA), olive oil (MUFA) and safflower oil (PUFA) in overweight and obese but otherwise health non-diabetic men (Xiao. 2006)

  the postprandial inflammation that occurs after the ingestion of a high fat meal is problematic for individuals with an already high baseline inflammation (Peairs. 2011),
• based on epidemiological evidence it would appear that the replacement of saturated with mono-unsaturated fats will result in long-term improvements in blood glucose management (Gillingham. 2011),
• compared to saturated fat, an increase in polyunsaturated fats improves the acute insulin response to an otherwise isocaloric meal (see Figure 4; safflower vs. olive vs. palm oil in Xiao. 2006),
• the anti-inflammatory effect of omega-3 fatty acids do not produce consistent improvements in blood glucose management (Akinkuolie. 2011),

• Figure 5: Paleo-lovers listen up! Aside from a higher protein and a sign. lower N6/N3 ratio, the alleged "paleo diet" or rather the diet, Cordain, Eaton & co tell you our ancestors ate had a 50% lower SFA:PUFA ratio (Simopoulos. 2002)

  there are concerns that very high intakes of omega-3 fatty acids (>6g of LCPUFA for months) could lead to reductions in insulin sensitivity similar to those we are seeing with the imbalanced omega-6 intake of the Western diet (Simopoulos. 2002; Mostad. 2006),
• the anti-diabetes effects of high(er) PUFA intakes come hand in hand with a pro-obesogenic increase in PPAR-gamma activity similar to, but less pronounced than those of thiazolidinedione-based anti-diabetes drugs like pioglitazone - keyword: "obese, but healthy"
• the existence and even more so the extent of the often-claimed negative effects of transfats on glucose metabolism are dubious (Aronis. 2012); if anything, they occur as long(er) term down-stream effects of more general pro-inflammatory and hyperlipidemic effects of non-ruminate trans fatty acids and the foods that contain them (Remig. 2010), and lastly
• there is accumulating evidence that the natural blend of ruminant transfats in high fat dairy exerts beneficial effects on glucose metabolims (Mensink. 2005; Lim. 2014)

The superior lean mass and significantly reduced fat gains, Mendes-Netto et al. observed in 2011 with an extreme high carb + low fat diet are a perfect example of the fact you better stay away from fat, when you feel the need to overeat on carbs on a bulk or whenever else | more.

When it's all said and done, the central message of this extensive analysis is probably that it is simply impossible to look at the effect of dietary fat on glucose homeostasis in man in isolation. In combination with high amounts of 'preferably' fast-digesting carbs dietary fats - specifically saturated ones - are pro-diabetic villains and their sixfold unsaturated cousins are not a tad better.

In concert with a balanced whole-foods diet, regular physical activity and quality sleep, however, your health and insulin sensitivity are not going to be threatened by the consumption of reasonable amounts of saturated fats and their potentially pro-inflammatory omega-6 cousins whose overabundance and not their inclusion in the modern Western is a highly obesogenic problem (see Figure 5).

• Akinkuolie, Akintunde O., et al. "Omega-3 polyunsaturated fatty acid and insulin sensitivity: a meta-analysis of randomized controlled trials." Clinical Nutrition 30.6 (2011): 702-707.
• Aranceta, Javier, and Carmen Pérez-Rodrigo. "Recommended dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids: a systematic review." British Journal of Nutrition 107.S2 (2012): S8-S22. 
• Astrup, Arne, et al. "The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010?." The American journal of clinical nutrition 93.4 (2011): 684-688. 
• Benoit, Stephen C., et al. "Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents." The Journal of clinical investigation 121.1 (2011): 456.
• Carlson, Susan E., Jane D. Carver, and Stephen G. House. "High fat diets varying in ratios of polyunsaturated to saturated fatty acid and linoleic to linolenic acid: a comparison of rat neural and red cell membrane phospholipids." The Journal of nutrition 116.5 (1986): 718-725. 
• den Besten, Gijs, et al. "The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism." Journal of lipid research 54.9 (2013): 2325-2340.
• Flock, Michael R., Jennifer A. Fleming, and Penny M. Kris-Etherton. "Macronutrient replacement options for saturated fat: effects on cardiovascular health." Current opinion in lipidology 25.1 (2014): 67-74. 
• Friedberg, Cylla E., et al. "Fish oil and glycemic control in diabetes: a meta-analysis." Diabetes Care 21.4 (1998): 494-500.
• Gadgil, Meghana D., et al. "The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity Results from the OmniHeart Trial." Diabetes care 36.5 (2013): 1132-1137. 
• Gentilcore, Diana, et al. "Effects of fat on gastric emptying of and the glycemic, insulin, and incretin responses to a carbohydrate meal in type 2 diabetes." Journal of Clinical Endocrinology & Metabolism 91.6 (2006): 2062-2067.
• Gillingham, Leah G., Sydney Harris-Janz, and Peter JH Jones. "Dietary monounsaturated fatty acids are protective against metabolic syndrome and cardiovascular disease risk factors." Lipids 46.3 (2011): 209-228.
• Grygiel-Górniak, Bogna. "Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review." Nutrition journal 13.1 (2014): 17. 
• Halade, Ganesh V., Md M. Rahman, and Gabriel Fernandes. "Differential effects of conjugated linoleic acid isomers in insulin-resistant female C57Bl/6J mice." The Journal of nutritional biochemistry 21.4 (2010): 332-337. 
• Hales, C. N., and P. J. Randle. "Effects of low-carbohydrate diet and diabetes mellitus on plasma concentrations of glucose, non-esterified fatty acid, and insulin during oral glucose-tolerance tests." The Lancet 281.7285 (1963): 790-794.
• Harvey, Kevin A., et al. "Long-chain saturated fatty acids induce pro-inflammatory responses and impact endothelial cell growth." Clinical Nutrition 29.4 (2010): 492-500.
• Herieka, Mohammed, and Clett Erridge. "High‐fat meal induced postprandial inflammation." Molecular nutrition & food research 58.1 (2014): 136-146.
• Kennedy, Arion, et al. "Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications." The Journal of nutrition 139.1 (2009): 1-4.
• Khan, Mehmood A., John V. St Peter, and Jay L. Xue. "A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone." Diabetes Care 25.4 (2002): 708-711.
• Kien, C. Lawrence, et al. "Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood." The American journal of clinical nutrition 97.4 (2013): 689-697.
• Kimura, Ikuo, et al. "The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43." Nature communications 4 (2013): 1829.
• Kota, Bhavani Prasad, Tom Hsun-Wei Huang, and Basil D. Roufogalis. "An overview on biological mechanisms of PPARs." Pharmacological Research 51.2 (2005): 85-94. 
• Lombardo, Yolanda B., and Adriana G. Chicco. "Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review." The Journal of nutritional biochemistry 17.1 (2006): 1-13.
• Lemaitre, Rozenn N., et al. "Cell membrane trans-fatty acids and the risk of primary cardiac arrest." Circulation 105.6 (2002): 697-701.
• Lovejoy, Jennifer C., et al. "Effects of diets enriched in saturated (palmitic), monounsaturated (oleic), or trans (elaidic) fatty acids on insulin sensitivity and substrate oxidation in healthy adults." Diabetes care 25.8 (2002): 1283-1288. 
• Marangou, A. G., et al. "Metabolic consequences of prolonged hyperinsulinemia in humans: evidence for induction of insulin insensitivity." Diabetes 35.12 (1986): 1383-1389.
• Margioris, Andrew N. "Fatty acids and postprandial inflammation." Current Opinion in Clinical Nutrition & Metabolic Care 12.2 (2009): 129-137.
• McManus, Ruth M., et al. "A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes." Diabetes Care 19.5 (1996): 463-467. 
• Mendes-Netto, R. S., et al. "Effect of the dietary glycid/lipid calorie ratio on the nitrogen balance and body composition of bodybuilders." Nutrire-Revista da Sociedade Brasileira de Alimentação e Nutrição 36.1 (2011): 137-150.
• Mensink, Ronald P. "Metabolic and health effects of isomeric fatty acids." Current opinion in lipidology 16.1 (2005): 27-30.
• Kabir, Morvarid, et al. "Treatment for 2 mo with n− 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study." The American journal of clinical nutrition 86.6 (2007): 1670-1679. 
• Lee, C., et al. "Fish consumption, insulin sensitivity and beta-cell function in the Insulin Resistance Atherosclerosis Study (IRAS)." Nutrition, Metabolism and Cardiovascular Diseases 23.9 (2013): 829-835.
• Lim, Ji-Na, et al. "trans-11 18: 1 Vaccenic Acid (TVA) Has a Direct Anti-Carcinogenic Effect on MCF-7 Human Mammary Adenocarcinoma Cells." Nutrients 6.2 (2014): 627-636.
• Mahendran, Yuvaraj, et al. "Association of erythrocyte membrane fatty acids with changes in glycemia and risk of type 2 diabetes." The American journal of clinical nutrition 99.1 (2014): 79-85.
• Montori, Victor M., et al. "Fish oil supplementation in type 2 diabetes: a quantitative systematic review." Diabetes Care 23.9 (2000): 1407-1415.
• Mostad, Ingrid L., et al. "Effects of n− 3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation." The American journal of clinical nutrition 84.3 (2006): 540-550. 
• Peairs, Abigail D., Janet W. Rankin, and Yong Woo Lee. "Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults." Nutr J 10.1 (2011): 122.
• Poirier, Hélène, et al. "Nutritional supplementation with trans-10, cis-12–conjugated linoleic acid induces inflammation of white adipose tissue." Diabetes 55.6 (2006): 1634-1641.
• Popp-Snijders, C., et al. "Dietary supplementation of omega-3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin-dependent diabetes." Diabetes Research (Edinburgh, Scotland) 4.3 (1987): 141-147. 
• Remig, Valentina, et al. "Trans Fats in America: A Review of Their Use, Consumption, Health Implications, and Regulation." Journal of the American Dietetic Association 110.4 (2010): 585-592.
• Risérus, Ulf, et al. "Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome." Diabetes care 25.9 (2002): 1516-1521.
• Risérus, Ulf. "Fatty acids and insulin sensitivity." Current Opinion in Clinical Nutrition & Metabolic Care 11.2 (2008): 100-105.
• Roden, Michael, et al. "Mechanism of free fatty acid-induced insulin resistance in humans." Journal of Clinical Investigation 97.12 (1996): 2859.
• Sawada, Keisuke, et al. "Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells." Lipids Health Dis 11.1 (2012): 36-44. 
• Simopoulos, Artemis P. "The importance of the ratio of omega-6/omega-3 essential fatty acids." Biomedicine & pharmacotherapy 56.8 (2002): 365-379.
• Schwingshackl, L., B. Strasser, and G. Hoffmann. "Effects of monounsaturated fatty acids on glycaemic control in patients with abnormal glucose metabolism: a systematic review and meta-analysis." Annals of Nutrition and Metabolism 58.4 (2011): 290-296. 
• Vessby, Bengt, et al. "Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study." Diabetologia 44.3 (2001): 312-319.
• Williams, Michael JA, et al. "Impaired endothelial function following a meal rich in used cooking fat." Journal of the American College of Cardiology 33.4 (1999): 1050-1055. 
• Xiao, C., et al. "Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans." Diabetologia 49.6 (2006): 1371-1379.

If you want other to see your pump, you got to be ripped. If not, why care about reductions in BMR?

Figure 1: The Arginine- and the Nitrate-Nitrite - NO pathway are the yin and yan of nitric oxide production (Lundberg. 2008).

Figure 2: VO2 consumption (marker of fatty acid oxidation) and basal metabolic rate (BMR) relative to means (left), thyroid hormone (T3, T4) levels after 3-d dietary intervention with sodium nitrate (Larsen. 2014)

Suppversity Suggested Read: " The Beat Your Personal Bests W/ Beets 101: How Much? 8.4 mmol Nitrate ~400-1300g Beets! When? 2.5h Pre Workout!" | read more

Bottom line: If the 0.1mmol/kg were not equivalent to only 200–300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate, I would probably say: Here you have it! Another supplement that's not just useless, but actually detrimental to your goals.

The way things are, I will refrain from ranting and rather suggest you simply skip the supps and consume the spinach, beetroot, lettuce and other high nitrate veggies right away. Most of the human studies which support the ergogenic potential of nitrates have been conducted with beetroot juice instead of capped sodium-nitrate.

And let's be honest, the weight loss advantage of having green and not so green nitrate containing vegetables in your is eventually beyond doubt. So, if there was a similar reduction in RMR from your daily serving of spinach, you can be more or less certain that it was compensated by the beneficial weight loss effects of the whole spectrum of nutrients that's present in this edible flowering plant in the family of Amaranthacea.

• Bailey, Stephen J., et al. "Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans." Journal of Applied Physiology 107.4 (2009): 1144-1155.
• Hotta, Yuji, et al. "Oral l‐citrulline supplementation improves erectile function and penile structure in castrated rats." International Journal of Urology (2014).
• Larsen, Filip J., et al. "Dietary inorganic nitrate improves mitochondrial efficiency in humans." Cell metabolism 13.2 (2011): 149-159.
• Lundberg, Jon O., Eddie Weitzberg, and Mark T. Gladwin. "The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics." Nature Reviews Drug Discovery 7.2 (2008): 156-167.
• Neuzillet, Y., et al. "A randomized, double‐blind, crossover, placebo‐controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction." Andrology 1.2 (2013): 223-228.

Eggs or Flakes? Not 30% vs. 25% protein! A brief reminder of the fact that the stuff you eat is still food.

• One-and-a-half cup of Special K® RTE cereal, 200 ml Silk® original soymilk, one slice of Natural Grain “Wheat n’ Fiber”® bread, 13 g of butter, and 10 g of sugar-free strawberry jam (CG)

• Two scrambled eggs, 120 mL skim milk, two slices of Holsum® thin white  bread, 5 g of butter, and 18 g of Smuckers® strawberry jam

Figure 1: Level(s) of "satiety hormones" after the different breakfasts (Bayham. 2014)

• On an individual basis, i.e. on just one of the two eating occasions, the higher levels of acetylated ghrelin and PYY did not suppress the 20 healthy overweight or obese subjects energy intake during the subsequent lunch
• For day 1 and day 7, together, on the other hand, the 64kcal the egg eaters consumed less than the cereal eaters did reach statistical significance.

Increased lipid oxidation in athletes w/ low dose fish oil (Filaire. 2010)

The health benefits of omega-3s: The often-cited evidence of the benefits of high omega-3 levels in the cells is by far not so conclusive as the laypress and supplement producers would have it. Danthi et al. have shown only recently that fish consumption, but not the omega-3 content of your cells is a reliable predictor of cognitive performance in the elderly. Associations between heart health, mortality, etc. and cellular omega-3 levels could thus be mediated by the whole food source of those omega-3s, i.e. fish consumption, and not by their mere presence in the cells, as well.

Figure 2: Body composition analysis at the end of the study (Patterson. 2014)

Figure 3: Changes (%) in relevant metabolic markers in response to the different diets (Patterson. 2014)

"[...] Ingestion of the HF-flaxseed/fish oil diet for 16 weeks led to significantly increased tissue concentrations of EPA, docosapentaenoic acid and DHA compared with ingestion of all the other diets (P< 0·05); furthermore, the diet significantly increased the intestinal population of Bifidobacterium at the genus level compared with the LF-high-maize starch diet (P< 0·05). These data indicate that both the quantity and quality of fat have an impact on host physiology with further downstream alterations to the intestinal microbiota population, with a HF diet supplemented with flaxseed/fish oil positively shaping the host microbial ecosystem." (Petterson. 2014).

Fat = Diabetes - A FAT Mistake?

• Bayham, Brooke E., et al. "A Randomized Trial to Manipulate the Quality Instead of Quantity of Dietary Proteins to Influence the Markers of Satiety." Journal of Diabetes and its Complications (2014).
• Filaire, Edith, et al. "Effect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletes." International journal of sport nutrition 20.6 (2010): 496.
• Danthiir, Vanessa, et al. "Cognitive Performance in Older Adults Is Inversely Associated with Fish Consumption but Not Erythrocyte Membrane n–3 Fatty Acids." The Journal of nutrition (2014): jn-113.
• Patterson, E., et al. "Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice." The British journal of nutrition (2014): 1-13.

Grazing not allowed!

"Even if subjective and physiological data suggest a beneficial effect of frequent eating on appetite in obese men, no effect was demonstrated on energy intake. Moreover, the decrease in diet induced thermogenesis and lipolysis, reflected by NEFA profiles, could be deleterious on energy balance in the long run."

"[A]fter being included, the subjects had a first visit for a lunch at the experimental restaurant of Institut Paul Bocuse Research Centre (IPB). The aim of this first visit was to familiarize the subjects with the environment and the foods which would be used during the study.

During this visit, subjects were invited to the experimental restaurant at 12:00 and were asked to taste all of the food items offered at an individual buffet-type meal. A choice of classical hot and cold French food items with varied macronutrient compositions was offered. [...] Subjects were instructed to eat ad libitum. The mean rating of food items, measured on a 100 mm electronic visual analog scale (VAS), varied from 4.4 ± 0.4 (for grated carrots), to 7.5 ± 0.4." (Allriot. 2014)

• Subjects were requested to avoid vigorous activities and to abstain from alcohol consumption the day before each session. 
• Subjects were also asked to select a dinner they consume regularly and to eat this same meal the evening before each session. 
• Subjects were also instructed tofinish eating this dinner by 9:00 pm and to eat nothing else after this time. 

• 20 min in  T0 (8:00 am) (F1 condition) or 
• 4x10 min long (168.7 kcal each) every hour at T0, T60, T120 and T180 min (F4 condition). 

Figure 1: Subjective satiety and hunger scores in the obese subjects during the 2x2 testing conditions (Allriot. 2014)

Figure 2: Insulin (left) and NEFA (right) levels after the test-meals (Allriot. 2014)

Bottom line: You want it really short? Don't fu**** graze / eat 10x a day! Despite the beneficial impact on appetite sensations and on ghrelin and GLP-1 concentrations, this study provides evidence that an isocaloric increase of the number of eating episodes does not have a short term positive effect on energy intake in obese men.

Suggested Read: ""Breakfast Keeps You Lean" Myth or Mystically True? Bias + Unwarranted Causal Implications" | read more

Contrary to what the authors write in their conclusion, this does eventually stand in line with findings in lean individuals, where a similar reduction in dietary thermogenesis and inhibited lipolysis was observed (Allirot. 2013). This is obviously of paramount importance for us, because it confirms that "the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data" are not worth the anti-weight loss effects due to the reduced thermogenecis and decreases in lipolysis "that could be deleterious on energy balance in the long run." (Allriot. 2013) - for once, I have nothing to add, here ;-)

• Allirot, Xavier, et al. "An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men." Physiology & behavior 110 (2013): 169-178.
•  Allirot, Xavier, et al. "Effects of a breakfast spread out over time on the food intake at lunch and the hormonal responses in obese men." Physiology & behavior (2014).

HMB-FA could be for ladies, too - or don't you want to look good naked, girls?

• 12 weeks is the study length we are looking at -- plenty of time for muscle growth, you would say, but if you want to use trained athletes, this is probably as short as it may be to make sure that you get measureable results 

• Table 1: Overview of Phase 1-3 (Wilson. 2014)

  three training phases -- with Phase 1 (Table 1, top) consisting of a daily undulating periodized
  resistance-training program 3 days per week during,  Phase 2 (Table 1, middle) 2-week
  overreaching cycle during weeks 9 and 10, and Phase 3 (Table 1, bottom) tapering (volume) for weeks 11 and 12 - needless to say that this is an intense protocol which will, even without HMB, produce serious gains
• 20 is the number of resistance trained men who participated in the study -- with 9 guys in the placebo and 11 guys in the HMB group enough to detect statistically significant differences, if those are actually physiologically relevant (in other words: a single outlier, maybe a "non-responder" - if there was such a thing - won't ruin the whole data set)
• standardized baseline tests for strength & body comp, as well as blood draws and analyses -- this is so basic that I actually thought about even mentioning it
• 3g of per day that's the dosage of HMB in a free acid form (HMB-FA) -- the free form of HMB has been shown by Fuller et al. in 2011, already, to have a superior bioavailability

• 30g of whey protein isolate (Dymatize ISO100, chocolate) that's the dosage of additional whey protein all subjects received -- this information is unfortunately missing from the original paper - a mishap that had me question the value of the data, initially; and if I had not been able to acquire it from Jacob directly, I would probably have torn the study apart, pointing to the possibility that HMB (FA or not) would produce similar non-existent results as the 3g+ of leucine people add to their whey protein shakes, falsely hoping this would increase the protein synthesis "beyond 100%"

Figure 1: Changes in strength and body composition over the course of the 12-week study (Wilson. 2014))

"HMB-FA resulted in increased total strength (bench press, squat, and deadlift combined) over the 12-week training (77.1  ±  18.4 vs. 25.3  ±  22.0  kg, p  <  0.001); a greater increase in vertical jump power (991 ± 168 vs. 630 ± 167 W, p < 0.001); and increased lean body mass gain (7.4  ±  4.2 vs. 2.1  ±  6.1  kg, p < 0.001) in HMB-FA- and placebo-supplemented groups, respectively." (Wilson. 2014)

• Fuller Jr, John C., et al. "Subchronic toxicity study of β-hydroxy-β-methylbutyric free acid in Sprague-Dawley rats." Food and Chemical Toxicology (2014).
• Rathemacher, John, et al. "Improved method of administering beta-hydroxy-beta-methylbutyrate (hmb)" WO 2011075741 A1. 2011
• Wilson, Gabriel J., Jacob M. Wilson, and Anssi H. Manninen. "Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review." Nutr Metab (Lond) 5 (2008): 1.
• Wilson, Gabrial J., et al. "The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study." European Journal of Applied Physiology (2014)

Lifting will improve your blood lipids, l-arginine will boost the effect.

• Schulze et al.. for example, observed that l-arginine speed up the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides (Schulze. 2009)

• El-Kirsh et al. found that both, L‐arginine and L‐citrulline supplementation ameliorated the biochemical parameters and blunted arthesclerotic lesions in high‐fat and high‐cholesterol‐fed rats (El-Kirsh. 2011)

Figure 1: Changes in triglycerides, total & LDL cholesterol and NEFA levels in response to exercise, only (control) and exercise + arginine (arginine) supplementation; figures in boxes ind. inter-group diff. (Nascrimento. 2014)

• The official SuppVersity Supplement Shoot-Out! The longstanding veteran, NOXplode AVPT, is challenged by a clone of its own,  NOXplode 2.0 Advanced Strength - which will be the last pre-workout standing?

  four acute, machine-based resistance training sessions
• stretching + general warm-up and cool down before / after sessions
• three sets of 12 repetitions; 60% of the 1RM; 60s rest between sets
• starting with large, ending with small muscle groups
• large muscle groups: Chest press, leg press, pull down, leg extensions
• small muscle groups: Deltoid machine, leg curl, biceps curl, triceps pulley

There is one question left to answer: What exactly is the mechanism here? I know that some of you won't care - as long as it works - but let's be honest, wouldn't it be nice to know? Well, acute and chronic exercise increase have already been shown to increase the activity of lecithin-cholesterol aciltransferase (L- CAT), the enzyme responsible for the cholesterol ester transfer to HDL, which will then evacuate the cholestrol from the circulation. If this effect is either increased or the transport facilitated by l-arginine, this would explain the reduction in LDL the researchers observed in the study at hand.

Figure 2: The short-term improvements in adiponectin Nascrimento et al. observed stand in line with the well-known long-term improvements in blood glucose management.

Moreover, studies by Tan et al. (2011) suggest that L-arginine will have direct effects on the expression of fat-metabolic genes in skeletal muscle and white adipose tissue, which favor lipogenesis in the muscle (not a problem if those lipids are subsequently burned as fuel during workouts) and a reduced storage of fat in the adipose organ. In conjunction with its proven ability to stimulate mitochondrial biogenesis and brown adipose tissue development (McKnight. 2010) and the previously discussed effects on WAT,  hyperphagia,  improved insulin sensitivity and - much contrary to nitrate (learn more) - increased energy expenditure (albeit only on low protein diets; Clemmensen. 2012). In sum these effects would appear to be profound enough to explain the observations in the study at hand, and those I reported in previous SuppVersity articles on l-arginine - specifically those discussing the potential fat burning (more) and anti-diabetic / glucose lowering effects (more).

Whether that's reason enough for you to begin supplementing again, is yet probably a question of your current metabolic state... if you are by no means like the seven overweight, hypertensive men, non-smoking and sedentary with a mean age of 46±5 yrs and a body weight of 93.1±12.0 kg, ain't insulin resistance, or have high cholesterol levels, it's pretty unlikely that you will see huge benefits.

• Clemmensen, Christoffer, et al. "L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances." Amino acids 43.3 (2012): 1265-1275.
• Dong, Jia-Yi, et al. "Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials." American heart journal 162.6 (2011): 959-965.
• El‐Kirsh, Amal Ashmawy Ahmed, et al. "The effect of L‐arginine or L‐citrulline supplementation on biochemical parameters and the vascular aortic wall in high‐fat and high‐cholesterol‐fed rats." Cell biochemistry and function 29.5 (2011): 414-428.
• McKnight, Jason R., et al. "Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health." Amino acids 39.2 (2010): 349-357.
• Schulze, Friedrich, et al. "L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides." Nutrition research 29.5 (2009): 291-297.
• Tan, Bie, et al. "Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle." The Journal of nutritional biochemistry 22.5 (2011): 441-445.

Is the vitamin D you produce at the beach you're visiting only rarely the secret to perfect glucose control?

You can learn more about this topic at the SuppVersity

Proteins, Peptides & Blood Glucose

SFA, MUFA, PUFA & Blood Glucose

Vitamin D & Diabetes

Read these ➲ while waiting

16 Weeks High Fat Diet

Fat to Blunt Insulin?

• Vitamin D is an acute phase reactant - but what are the impli- cations? Firstly, this would imply that serum 25-hydroxy- vitamin D is an unreliable biomarker of vitamin D status after an acute inflammatory insult (for the obese, even a meal is an acute inflammatory result; Blackburn. 2006). Secondly, hypovitaminosis D may be the consequence rather than the widely purported cause of a myriad of chronic diseases (Gama. 2012).
  "Low vitamin D causes / triggers insulin resistance." -- An excellent example of someone confusing correlation and causation. What is often accepted as a scientific fact, is possible. In view of the fact that vitamin D has recently been shown to act as an acute phase reactant in inflammatory conditions, it is yet rather unlikely. In fact, it appears more likely that what we are seeing here is a correllative reduction of vitamin D, whenever someone - like a type II diabetic, for example - is chronically inflamed (Waldron. 2013)
• "Vitamin D supplements can be used to ameliorate insulin sensitivity." -- In an assertion like this, the authors go even one step further. After making the unwarranted conclusions that vitamin D triggers the onset of insulin resistance, they assume that supplemental vitamin D (usually D3), of which the current evidence shows that it does not elevate the levels of 1,25-hydroxy vitamin D, i.e. calcitriol, the only form of vitamin D, of which we actually have some rodent data that it's exogenous administration produces the anti-diabetic + weight loss effects everyone appears to expect from "regular" D3. An immediate effect of calcitriol on glucose uptake does yet not appear to exist - at least not in healthy individuals (Fliser. 1997).

Figure 1: If we compare the fat "loss effects" of vitamin D supplementation in the studies by Zitterman (2009) and Salehpour (2012) in Figure 1 (left), and invoke the results of the latest meta-analysis by Pathak, et al. (2014) in Figure 1 (right), it is hard to argue Pathak's conclusion that the divergent results from previous trials would suggest that "Vitamin D supplementation did not decrease measures of adiposity in the absence of caloric restriction" (Pathak. 2014).

• Inomata (1986) - 1-alpha (OH)D3 (active vitamin D) administration improves glucose tolerance in diabetic subjects
• Nilas (1983) - No effect of vitamin D or its analogues on body weight or glucose management in post-menopausal women
• Orwoll (1994) - No effect of calcitriol (active vitamin D) on glucose homeostasis in non-insulin-dependent diabetes mellitus

Figure 2: The latest meta-analysis says: No long-term improvement in blood glucose management w/ vitamin D supplements (George. 2012).

Figure 3: No improvement in insulin sensitivity in people w/ normal, min. effects in those with compromised insulin sensitivity w/ vitamin D supplements, says meta-analysis (George. 2012).

Figure 4: Increase in vitamin D levels in response to supplementation w/ different amounts of vitamin D3 in caucasian (!) women according to BMI categories (Gallagher. 2013)

• Belenchia, Anthony M., et al. "Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial." The American journal of clinical nutrition 97.4 (2013): 774-781.
• Blackburn, Patricia, et al. "Postprandial variations of plasma inflammatory markers in abdominally obese men." Obesity 14.10 (2006): 1747-1754. 
• Close, Graeme L., et al. "The effects of vitamin D3 supplementation on serum total 25 [OH] D concentration and physical performance: a randomised dose–response study." British journal of sports medicine 47.11 (2013): 692-696.
• Fliser, D., et al. "No effect of calcitriol on insulin‐mediated glucose uptake in healthy subjects." European journal of clinical investigation 27.7 (1997): 629-633.  
• Forouhi, Nita G., et al. "Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance the medical research council ely prospective study 1990–2000." Diabetes 57.10 (2008): 2619-2625.
• Gama, Rousseau, et al. "Hypovitaminosis D and disease: consequence rather than cause." BMJ 345 (2012): e5706-e5706.
• Gallagher, J. Christopher, Vinod Yalamanchili, and Lynette M. Smith. "The effect of vitamin D supplementation on serum 25OHD in thin and obese women." The Journal of steroid biochemistry and molecular biology 136 (2013): 195-200. 
• George, P. S., E. R. Pearson, and M. D. Witham. "Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta‐analysis." Diabetic Medicine 29.8 (2012): e142-e150. 
• Johnson, Andrew MF, and Jerrold M. Olefsky. "The origins and drivers of insulin resistance." Cell 152.4 (2013): 673-684.
• Inomata, S., et al. "Effect of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes mellitus." Bone and mineral 1.3 (1986): 187-192. 
• Nagpal, J., J. N. Pande, and A. Bhartia. "A double‐blind, randomized, placebo‐controlled trial of the short‐term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle‐aged, centrally obese men." Diabetic Medicine 26.1 (2009): 19-27.
• Need, Allan G., et al. "Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women." Clinical endocrinology 62.6 (2005): 738-741.
• Ng, Kimmie, et al. "Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial." The American journal of clinical nutrition (2014): ajcn-067777.
• Nilas, L., and C. Christiansen. "Treatment with vitamin D or its analogues does not change body weight or blood glucose level in postmenopausal women." International journal of obesity 8.5 (1983): 407-411.
• Orwoll, Eric, Matthew Riddle, and Melvin Prince. "Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus." The American journal of clinical nutrition 59.5 (1994): 1083-1087.
• Pathak, K., et al. "Vitamin D supplementation and body weight status: a systematic review and meta‐analysis of randomized controlled trials." Obesity Reviews (2014).
• Salehpour, Amin, et al. "A 12-week double-blind randomized clinical trial of vitamin D3 supplementation on body fat mass in healthy overweight and obese women." Nutr J 11.1 (2012): 78.
• Tai, Kamilia, et al. "Glucose tolerance and vitamin D: effects of treating vitamin D deficiency." Nutrition 24.10 (2008): 950-956.
• Waldron, Jenna Louise, et al. "Vitamin D: a negative acute phase reactant." Journal of clinical pathology 66.7 (2013): 620-622.
• Zittermann, Armin, et al. "Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers." The American journal of clinical nutrition 89.5 (2009): 1321-1327.

Actually, even cherry tomatoes were not allowed in the first 4 days ;-)

Figure 1: Schematic overview of the different phases of the diet + exercise intervention (Calbet. 2014)

Figure 2: Lean mass (left) and fat mass (right) development during the four phases of the intervention (Calbet. 2014)

Suggested Read: "Cell Swelling Keeps Muscles "Pumped" For More Than 52h - Could It Even Help You Build Muscle?" | read more

Lean mass can be tissue, water and glycogen: Early "muscle loss" is mostly water + glycogen (esp. on low carb diets; Kreitzman. 1992). In view of older studies on the muscle-building mechanisms of creatine (Persky. 2001) and the latest research on the involvement of muscular (hyper-)hydration in skeletal muscle hypertrophy Ribero et al. (2014), the loss of water and glycogen - as benign and as far as the glycogen goes, even metabolically beneficial (leaves room to store glucose ➲ improves insulin sensitiviy) as it may be - could hamper your gains.

Figure 3: Progressive changes in body fat and lean mass (in kg) over the course of the study period (Calbet. 2014)

That's quite astonishing: Would you have expected that this "4-days of madness" diet would generate a total fat loss of -3.8kg (2.8kg of those from the potentially life-threatening trunk fat) and thus produce an outcome of which the researchers rightly say that it "is better than several interventions combining low-calorie diets and exercise lasting from 12 weeks to 1 year (Garrow. 1995; Shaw. 2009)" and bet the largest randomized control trial for the response to 8-month resistance training, aerobic training, or combined aerobic and resistance training (Willis et al., 2012)? Certainly not, right?

Figure 4: Weight loss (not fat loss!) maintenance in Calbet et al. and the average US dieter according to a meta-analysis by Anderson et al. (2001)

Well, considering the fat that the mean fat loss here is greater than that achieved by the latest pharmacological intervention, i.e. the administration of glucagon-like peptide-1 (GLP-1) agonists for 20 weeks (which gave a weighted mean loss of 2.9 kg in 21 trials involving 6411 participants; Vilsboll. 2012), I am actually happy that there was a one year follow up to show that a short-term intervention can never replace permanent life-style changes... although, when you look at the whey protein group, who regained a meager 1.09kg in Phase V and thus significantly less than the 50-80% the average subject on a medically supervised weight loss diets (Anderson. 2001; see Figure 4), I do have to admit this is not just surprising.

This is damn impressive, even if the comparison is unfair, due to longer follow ups in the average study in Anderson's meta-analysis. Still, there is one thing I would like to see before I'd recommend this type of diet to anyone who doesn't have to lose another 2kg of fat before a physique show or photoshoot at the end of the week: A comparison of the health benefits of successful whey-based(!) crash dieting.

• Anderson, James W., et al. "Long-term weight-loss maintenance: a meta-analysis of US studies." The American journal of clinical nutrition 74.5 (2001): 579-584.
• Calbet, J. A. L., et al. "A time-efficient reduction of fat mass in 4 days with exercise and caloric restriction." Scandinavian Journal of Medicine & Science in Sports. (2014). Accepted Manuscript. doi: 10.1111/sms.12194 
• Garrow, J. S., and C. D. Summerbell. "Meta-analysis: effect of exercise, with or without dieting, on the body composition of overweight subjects." European journal of clinical nutrition 49.1 (1995): 1-10.
• Kaleta, Christoph, Luís F. de Figueiredo, and Stefan Schuster. "Against the stream: relevance of gluconeogenesis from fatty acids for natives of the arctic regions." International journal of circumpolar health 71 (2012).
• Kreitzman, Stephen N., Ann Y. Coxon, and Kalman F. Szaz. "Glycogen storage: illusions of easy weight loss, excessive weight regain, and distortions in estimates of body composition." The American journal of clinical nutrition 56.1 (1992): 292S-293S.
• Persky, Adam M., and Gayle A. Brazeau. "Clinical pharmacology of the dietary supplement creatine monohydrate." Pharmacological Reviews 53.2 (2001): 161-176.
• Ribeiro, Alex S., et al. "Resistance training promotes increase in intracellular hydration in men and women." European journal of sport science ahead-of-print (2014): 1-8. 
• Shaw, K., et al. "Exercise for overweight or obesity." Cochrane Database Syst Rev 4 (2006).
• Vilsbøll, Tina, et al. "Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials." BMJ: British Medical Journal 344 (2012).
• Willis, Leslie H., et al. "Effects of aerobic and/or resistance training on body mass and fat mass in overweight or obese adults." Journal of Applied Physiology 113.12 (2012): 1831-1837.