Coffee - 3 Cups Per Day Keep Insulin at Bay: You Better Start Today if You Want to Retain Your Insulin Sensitivity, and Stay Cancer & CVD Free Beyond Your Own Centennial!

I am not entirely sure how often I have used the sentence "consistency is key", here at the SuppVersity, but there is no way I don't reiterate it in the context of the never-ending debate over the pros and cons of habitual coffee drinking, once again. While much of the experimental evidence would suggest that coffee, or to be precise, caffeine the major methylxanthine in the brown brew is a bad sympathetic nervous system activator that stresses your body and will deteriorate your glucose and fat metabolism, the majority of the epidemiological evidence points into the exact opposite direction.

A paper that's going to be published in the next issue of AGE the Journal of the American Aging Association could however help not just to bridge the widening gap between the ever-increasing number of epidemiological studies showing between moderate caffeine consumption and metabolic, cardiovascular, neurological, and cellular health (see list at the end of this post) and the conflicting evidence from experiments that investigate the acute response to caffeine ingestion in both caffeine-naive individuals and habitual caffeine consumers.

Consistent caffeine consumption is the key to "chronic health" ;-)

I am pretty sure this study won't close the lit on the never-ending debate about the pros and cons of caffeine consumption - mostly because it's a rodent study, but also in view of the fact that there is no definite border between "habitual consumption" and "chronic abuse", when it comes to a substance the stimulating side-effects of which can keep you functioning (and training!), when your body would otherwise long have called a halt.

Against that background it is important to realize that the rodents in the study at hand were leading a happy, more or less stress-free life. They consumed what you would consider a "healthy" diet for a rodent and had free access to a wheel, the average male and female Wistar who has neither television, nor Internet or a PlayStation in his or her cage, will actually make good use of.

Figure 1: Body weight (in g), visceral fat weight (in g/kg body weight) and skeletal muscle glucose transporter 4 expression (GLUT4 activity relative to glucose breakdown) over the course of 24 months with or without the provision of the human equivalent of caffeine of roughly 3 cups of coffee in the drinking water (data based on Guarino. 2012)

Accordingly, you should not wonder, let alone be disappointed that there is no magical "fat destruction" such as the one we've seen about a months ago in the CLA-study (see "CLA Destroys Body Fat: Effect Borders Pathological Lipodystrophy!"). Remember: Consistency is key! And some of the benefits of today's coffee may not show before you are in your late 70s... but let's get back to the results data from figure 1 and their implications for your current and future health:

Additional observations:

• the decrease in visceral fat mass was not due exclusively to increased lipolysis
• the increase in insulin sensitivity induced by caffeine was not attributable to weight loss, increased NO production, caffeine-mediated antioxidant effects, decreased cortisol levels, or decreased SNS activity
• caffeine intake did not modify blood pressure, endogenous NO production, or antioxidant capacity in aged animals 
• caffeine administration restored Glut4 expression in the elderly group, but it was not able to increase Glut4 expression above amaximal level in the 12Mgroup

• the rodents were kept on a normal diet, a healthy body weight is thus only a sign of overall metabolic health (remember: skinnier does not equal healthier!),
• the 42% lower visceral fat levels in what would be middle aged rodents (12 months) is one of the most significant predictors of healthy aging (optimal brain and metabolic health + no cancer), and
• the maintenance of skeletal muscle GLUT4 expression is of fundamental importance to ward of those increasingly common "age-related" diseases of which we already know that they are at least precipitated by insulin resistance and high glucose levels, such as Alzheimer's and "regular" dementia (e.g. Rönnemaa. 2008; Accardi. 2012; Williamson. 2012)

Against the background of the previously mentioned conflict between experimental (caffeine induces stress and thwarts glucose and fatty acid metabolism) and epidemiological (caffeine correlates with metabolic health) evidence it is also important to mention that these beneficial effects were not negated by the dreaded stress-induced increases in non-esterified fatty acids (NEFA), which is the most commonly heard argument of the opponents of caffeine / coffee consumption. On the contrary, the ...

"[...] increase in insulin sensitivity induced by caffeine was not attributable to weight loss, increased NO production, caffeine-mediated antioxidant effects, decreased cortisol levels, or decreased SNS activity [so that caffeine effectively] restored [otherwise elevated] circulating NEFA in aged animals to values observed in young 3 M control rats." (Guarino. 2012)

In the absence of increased NEFA levels, an increased sympathetic tone (=higher catecholamine and cortisol levels) and in the presence of optimal GLUT-4 expression and low visceral fat levels in the young and middle aged rodents, there is actually no reason why we would see any of the putative negative effects on glucose metabolism of about which you will probably have read and heard numerous times in the laypress.

Figure 2: Glucose clearance during ITT (in % glucose/min), basal plasma and insulin levels (in mM) over the course of 24 months (basically one rodent lifespan) with or without the provision of the human equivalent of caffeine of roughly 3 cups of coffee in the drinking water (data based on Guarino. 2012)

And, as a matter of fact, the data in figure 2 does confirm just that: The chronic administration of caffeine at a dosage of which the researchers state, that it will generate plasma caffeine levels "comparable to those in moderate to low consumers of caffeinated beverages" (Guarino. 2012), i.e. people who drink about 3 cups of the delicious brew per day (300-500mg caffeine; Gasio. 2002), is probably one of the most delicious and convenient ways to ward off age-related declines in glucose tolerance... this does yet not mean that drinking coffee (let alone Coke or energy drinks) could make up for a sedentary lifestyle and (ab-)using caffeine pills and stims to keep functioning will probably even have the opposite effects.

Glucose management figures everywhere and so does coffee!

Did you know that the data from a recently published trial suggests that "14-day caffeine supplementation [at 5mg/kg body weight] can probably decrease exercise-induced inflammatory response (CRP elevation and Leukocytosis) following 30 min downhill running in male non-athletes" (Jafari. 2012)? That's actually pretty intruiging, as it shows that the already mentioned differences between the chronic and acute effects of trimethylxanthie aka caffeine are not restricted to its effect on overall and metabolic health, especially as, caffeine has hitherto not exactly been known as a an ergogenic the effects of which build up over time... in fact, rather the opposite is usually assumed, although the evidence for the decline of the ergogenic (not the stimulant!) effects of caffeine are still inconclusive.

In view of the major role of glucose management in all sorts of the metabolic, endocrine and neurcrine diseases, it is thus no wonder that study after study finds beneficial effects of moderate caffeine consumption on...

• risk of heart failure (Mostofsky. 2012)
• perceptibility to arrhythmia (Klatsky. 2011)
• venous thromboembolism (Enga. 2011)
• general cardiovascular disease (Bøhn. 2012)
• dementia & Parkison's (Cao. 2012; Campdelacreu. 2012)
• diabesity (Hjellvik. 2011; Matsuura. 2012)
• pancreatic cancer (Dong. 2011), as well as 
• bladder, breast, buccal and pharyngeal cancer (Yu. 2011) 
• colorectal, endometrial, esophageal cancer (Yu. 2011) 
• hepatocellular, leukemic, and prostate cancers (Yu. 2011)

And though, I could certainly extend this list by a dozen or so references for each item and half a dozen additional items, I guess I'd rather end today's blogpost on the note that coffee (and tea) contain way more than just caffeine. I would therefore suggest you don't rely on caffeine alone, but rather grab yourself an old-fashioned black cup of coffee (ad some creme if you can't stand it black, or coconut oil, if you like that better) and the time it takes to savor the aroma and taste of it... I can guarantee: That will exponentiation its health effects and will allow you to catch up on the 5 minutes you may have lost in no time.

References:

• Accardi G, Caruso C, Colonna-Romano G, Camarda C, Monastero R, Candore G. Can Alzheimer disease be a form of type 3 diabetes? Rejuvenation Res. 2012 Apr;15(2):217-21.
• Bøhn SK, Ward NC, Hodgson JM, Croft KD. Effects of tea and coffee on cardiovascular disease risk. Food Funct. 2012 Jun;3(6):575-91.
• Campdelacreu J. Parkinson disease and Alzheimer disease: environmental risk factors. Neurologia. 2012 Jun 13.
• Cao C, Loewenstein DA, Lin X, Zhang C, Wang L, Duara R, Wu Y, Giannini A, Bai G, Cai J, Greig M, Schofield E, Ashok R, Small B, Potter H, Arendash GW. High Blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimers Dis. 2012;30(3):559-72.
• Dong J, Zou J, Yu XF. Coffee drinking and pancreatic cancer risk: a meta-analysis of cohort studies. World J Gastroenterol. 2011 Mar 7;17(9):1204-10.
• Enga KF, Braekkan SK, Hansen-Krone IJ, Wilsgaard T, Hansen JB. Coffee consumption and the risk of venous thromboembolism: the Tromsø study. J Thromb Haemost. 2011 Jul;9(7):1334-9.
• Gasior M, Jaszyna M,Munzar P,Witkin JM, Goldberg SR. Caffeine potentiates the discriminative-stimulus effects of nicotine in rats. Psychopharmacology (Berl). 2002; 162:385–395 
• Guarino MP, Ribeiro MJ, Sacramento JF, Conde SV. Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity. Age (Dordr). 2012 Sep 14.
• Hjellvik V, Tverdal A, Strøm H. Boiled coffee intake and subsequent risk for type 2 diabetes. Epidemiology. 2011 May;22(3):418-21.
• Jafari A, Kherad N, Melekirad AA. Effect of short-term caffeine supplementation on downhill running induced inflammatory response in non-athletes. Journal of Cell. Winter 2012; 2(4):377-385
• Klatsky AL, Hasan AS, Armstrong MA, Udaltsova N, Morton C. Coffee, caffeine, and risk of hospitalization for arrhythmias. Perm J. 2011 Summer;15(3):19-25.
• Matsuura H, Mure K, Nishio N, Kitano N, Nagai N, Takeshita T. Relationship between coffee consumption and prevalence of metabolic syndrome among Japanese civil servants. J Epidemiol. 2012;22(2):160-6.
• Mostofsky E, Rice MS, Levitan EB, Mittleman MA. Habitual coffee consumption and risk of heart failure: a dose-response meta-analysis. Circ Heart Fail. 2012 Jul 1;5(4):401-5. Epub 2012 Jun 26.
• Nature.com Reviews. Heart failure: Moderate coffee consumption linked with reduced risk of HF. Nat Rev Cardiol. 2012 Jul 17;9(9):492.
• Rönnemaa E, Zethelius B, Sundelöf J, Sundström J, Degerman-Gunnarsson M, Berne C, Lannfelt L, Kilander L. Impaired insulin secretion increases the risk of Alzheimer disease. Neurology. 2008 Sep 30;71(14):1065-71.
• Williamson R, McNeilly A, Sutherland C. Insulin resistance in the brain: An old-age or new-age problem? Biochem Pharmacol. 2012 Sep 15;84(6):737-45.
• Yu X, Bao Z, Zou J, Dong J. Coffee consumption and risk of cancers: a meta-analysis of cohort studies. BMC Cancer. 2011 Mar 15;11:96.

Cold Thermogenesis - A Safe Ephedra Alternative? 70kcal Increase in 24h Energy Expenditure is Negligible, 50% Lower Than Ephedrine, Not Likely to Occur Obese or Older People

Image 1 (odditycentral): Jin Songhao, one of China’s most seasoned icemen and not exactly as lean as you may expect based on what you currently read around the blogosphere, managed to beat the previous world record for the longest ice bath - 120min! Congrats, Jin!

Ephedrine for years the go-to OTC fat burner for physique athletes and average Joe's and Jane's alike is no longer (officially) available: No matter how bold the label claims about X mg of "ephedra extract" may be - NONE(!) of the currently available "ephedra based" over-the-counter (OTC) fat-burners contains significant amounts of the active alkaloids, which made the old Mua huang based herbal ephedra products so effective. Against that background, dieters are constantly on the look-out for novel "gimmicks" to help them finally get rid of those annoying love-handles. One of those gimmicks, which has caught quite some attention as of late, is called "cold thermogenesis" and revolves around the idea that our bodies should consume more energy to keep a normal body temperature in a cold, compared to a normal temperature environment.

How is that different from a "thermogenic fat burner"

The most obvious difference between cold thermogenesis and "thermogenic fat burners" is actually so straight forward that I hardly dare stating that the former is induced by exposing yourself to low(er than normal) temperatures, while the promise of the latter is that the various ingredients of currently or formerly available OTC "fat burners" will induce a thermogenic response, irrespective of the current ambient temperature.

Figure 1: Antropomorphic data of the study participants (Cypess. 2012)

The results of a recently published study from the the Boston Harvard Medical School does yet provide somewhat more sophisticated insights into the differences between cold exposure and a sympathomimetic (i.e. an activator of the sympathetic nervous system), such as ephedrine. On three separate, independent study visits that took place in random order the ten healthy volunteers (age 27.1 years) who participated in the study (see figure 1 for DEXA based anthropometric data) and had been fasting since 12am the day before were exposed to one of the following "stimuli":

• ephedrine - a single intramuscular dose of 1mg/kg ephedrine
• saline control - an equal volume of saline
• cold exposure - in a surgeon’s cooling vest (Polar Products) w/ water temperature 14 °C

60min after the injection of ephedrine, saline, or the initiation of cold exposure, the change in metabolic rate was measured and blood was drawn to determine several metabolic and endocrine markers. Another 60min later, PET-CT scanner images (cf. figure 2, right) to quantify BAT mass and activity were taken. Since the participants obviously had to get rid of their cooling vests for this procedure, the total cold exposure time was limited to 120min, so that it is questionable how valid the 24h energy expenditure calculation (cf. figure 3) actually is. After all, it is not very likely that the norepinephrine levels would constantly stay at 200% over baseline (cf. figure 2).

Figure 2: Metabolic and endocrine effects (expressed relative to saline) of ephedrine injection and cold exposure (main image); CT scans with green arrows in the combined scans indicating  the principal cervical, supraclavicular,
and thoracic depots of BAT (Cypess. 2012)

As far as the acute phase is concerned, it is yet quite obvious that both cold exposure and ephedrine elicited statistically significant effects on various metabolic and endocrine parameters. The exact nature and the purported mechanism that is responsible for these metabolic and endocrine effects are however very different for both treatments:

• while ephedrine lead to an increase in blood glucose (probably subsequent to increased glyconeogenesis), cold exposure did not 
• while ephedrine lead to significant increases in lactic acid levels (corresponding to increases in glucose + glucose oxidation), cold exposure did not
• while ephedrine lead to profound increases in β-hydroxybutyrate (increased ketone productions from fat), cold exposure did not
• while ephedrine increased serum non-esterified fatty acid (NEFA) concentrations (due to increased lipolysis), cold exposure did not
• while ephedrine elevated insulin production (probably due to stress induced insulin resistance), cold exposure did not (p = 0.29)
• while ephedrine lead to highly significant (p < 0.001) increases in C-reactive peptide, cold exposure elicited "only" significant elevations (p = 0.005)
• while ephedrine produced already highly significant increases in noripenephrine levels, those were even more pronounced upon cold exposure
• while ephedrine lead to statistical significant increases in thyroid hormone Total T3 (+14%, p = 0.026) and Free T4 (+19%, p = 0.014), cold exposure did not
• while ephedrine lead to a profound (-22%) and statistical significant (p = 0.007) drop in ghrelin ("hunger hormone" and metabolic regulator), cold exposure did not

In conjunction with the combined CT scans from figure 2 these differences clearly indicate that contrary to ephedrine, which is a mere sympathomimetic (put simply a potent "stim" ;-) without depot-specific (here brown adipose tissue) thermogenic effects, mild cold exposure (remember: those were no ice-baths!) has the ability to stimulate brown adipose tissue (BAT) energy expenditure without significant systemic effects on heart rate or thyroid hormone metabolism.

What does that mean? Is GNC soon going to carry cooling vests instead of fat burner pills?

If you read the scientists' rave conclusion that "[i]n contrast to ephedrine [...] mild cold exposure stimulates a specific response by the SNS [sympathetic nervous system] to activate BAT and increase energy expenditure with few other metabolic effects" and their subsequent reference to the "obesity and diabetes pandemics" and the demand for "safe and novel treatments" of the latter, it is quite understandable that people who are referred by their gurus to "scientific evidence" like this are willing to believe that "cold thermogenesis" would help them to finally get rid of their beer-, burger- and burrito-bellies.

Figure 3: Increase in 24h energy expenditure (kcal/day, left) and detectable BAT volume (right; Cypess. 2012)

If you do yet take a look at the actual metabolic effects (cf. figure 3) the 2x more pronounced effect of ephedrine on 24h energy expenditure (+140kcal/day vs. 70kcal) confirms what my previous overview of the metabolic and endocrine effects of ephedrine and cold exposure already suggested: Ephedrine does not simply have more "side effects" it is also more effective.

Figure 4: Activity of BAT activity in relation to body fat levels (van Marken Lichtenbelt. 2009)

Important:  One thing the scientists wink at in both the abstract as well as the conclusion are the profound inter-individual differences in terms of detectable BAT volume and activity. While the median volume of detectable brown adipose tissue in men and women was 22mL and 20mL, respectively, there was one female subject with a BAT mass of 190mL (85x over median!), one with 7ml and one woman without any detectable brown adipose tissue. Similarly, the BAT mass in the men ranged from 46mL to 12mL. Both the existence of individuals without any significant amounts of metabolically active body fat, as well as the observation of high inter-personal variability in the study at hand stand in line with previous results of Saito et al. who found a ratio of 15/32 (45%) non-responders in young (23-35y) and 22/24 (92%!) in older (38-65y) subjects (Saito. 2009). And as if that alone would not render the practical value of cold exposure as a means to battle the "obesity and diabetes pandemic" questionably enough, van Marken Lichtenbelt et al. report that exactly those people for whom ephedrine and other sympathomimetics such as sibutramine would actually pose a non-negligible health risk, i.e. obese and metabolically deranged people, don't just have 40% less brown adipose tissue, but also a -76% reduced BAT activity (van Marken Lichtenbelt. 2009; cf. figure 4). The implications of these findings should be obvious: It is a) by no means certain that sitting in a non-heated room, let alone an ice-bath, is not just going to give you a cold, but even if it works it is b) probably not going to make a difference for those people who need it most - I mean, let's do the math: "70kcal/day minus 76% of the former equals 16.8kcal per day"!

That being said, even the profoundly greater total increase in energy expenditure in the ephedrine group is of a "magnitude" (I would write "minitude" if such a word existed) that would be completely negligible if it were not for the bad and "dangerous" sympathostimulating side effects (Andraws. 2005), which will allow you to train longer, to diet harder (Astrup et al. ascribe 75% of the weight loss effect due to the ingestion of the infamous ECA stack to anorexia, i.e. loss of appetite; cf. Astrup. 1992) than any ice-filled bathtub in the world will ever do.

Skip on ice-baths, stop winning about the ephedra ban. Get your diet & workouts in check!

Image 2: I don't think Francine Sablan, IFBB Figure Pro and like Adelfo one of Myotropics' sponsored athletes, uses the air-conditioning, let alone a funky cooling vest or ice-baths to propel her fat loss. And why would she? She loves working out and she has her diet in check ;-)

I know this is not going to be a popular conclusion, but believe me, the additional +70kcal/day you could expend in the cold, if you are one of the lucky non-obese "responders" (see red box above), won't make you lose a single pound. Even the "good old" ECA stack (remember: the Cypess study used intravenously administered ephedrine; hence, the effect sizes are directly comparable with pertinent studies from the late 1980s and 1990s using orally administered herbals) worked its fat burning magic only, when it was combined with a comprehensive diet and exercise protocol - and in those scenarios it was mostly the influence of its sympathostimulating activity on your ability to adhere to your diet and to endure the hardships of strenuous workouts and not its often-touted and largely overestimated "thermogenic" effects (cf. Astrup. 1985; Astrup. 1992) that were mostly responsible for the larger-than-life results, people are still raving about.

References:

1. Andraws R, Chawla P, Brown DL. Cardiovascular effects of ephedra alkaloids: a comprehensive review. Prog Cardiovasc Dis. 2005 Jan-Feb;47(4):217-25. 
2. Astrup A, Bülow J, Madsen J, Christensen NJ. Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol. 1985 May;248(5 Pt 1):E507-15.
3. Astrup A, Toubro S, Christensen NJ, Quaade F. Pharmacology of thermogenic drugs. Am J Clin Nutr. 1992 Jan;55(1 Suppl):246S-248S.
4. Cypess AM, Chen YC, Sze C, Wang K, English J, Chan O, Holman AR, Tal I, Palmer MR, Kolodny GM, Kahn CR. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci U S A. 2012 Jun 4. 
5. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009 Apr 9;360(15):1500-8. Erratum in: N Engl J Med. 2009 Apr 30;360(18):1917.
6. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009 Jul;58(7):1526-31. Epub 2009 Apr 28.

L-Arginine - 6g/Day Boost Cholesterol- & Non-Esterified Fatty Acid Lowering Effects of Resistance Training. Are Classic Pre-Workouts Actually "Health Supplements"?

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

In the spirit of Tuesday's post on the potential negative effects of nitrate supplements on weight loss (learn more + see box below for some important clarifications), I would like to invite you to take a look at the effects of "short-term  L-arginine  supplementation  on  lipid  profile  and  inflammatory proteins after acute resistance exercise in overweight men" as they are about to be reported in one of the future issues of e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism by Nascimento et al. (Nascimento. 2014) - it's not essentially new, but actually quite a nice reminder of the fat that what I said about l-arginine in the nitrate article was not all made up.

An addendum to the nitrate study: Even a persistent 5% reduction in RMR would not necessarily inhibit weight loss + you can argue that your body needs less energy / oxygen, because it works more effectively and contrary to common believe that's what a true ergogenic should do!

In the introduction to the said article, I already hinted at and linked to the potential weight loss benefits of l-arginine. In spite of the fact that it is literally useless as an NO-booster (remember without increase in NOS, the enzyme that produces NO from arginine, simply piling up more arginine in your blood will only lead to increases in uric acid), previous studies have already shown that L-arg improves the metabolic profile of people with suboptimal health status.

• 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)

Other studies report beneficial effects on blood pressure and - as discussed in the anti-diabetes series - an ameliorating effect on the blood glucose levels of diabetic and/or insulin resistant individuals (McKnight. 2010; Dong. 2011).

So, the results of this most recent study don't really come as a surprise

In view of what we already knew about l-arginine, the results of the Nascimento study, i.e. reductions in  LDL cholesterol and NEFA levels, in response to the ingestion of 3x2g of pure l-arginine per day in this double blind, randomized crossover study don't come as a surprise.

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)

What's "news", though, is the interaction with exercise that sheds a whole new light the good old NO-Xplode (learn more, but keep in mind that one characteristic feature of this products is and was being totally underdosed) and its identical clones! I mean, who would have expected that he was buying a health supplement that potentiates the beneficial effects of exercise, in this case...

• 

  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

...on the potentially artherogenic low-density lipoprotein (LPL) and the amount of pro-diabetic non-esterified fatty acids in his bloodstream? You did? Well... I should have anticipated that, Mr & Mr Smar Alec ;-)

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.

References:

• 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.