Fat Loss Principles That Work: 10g+ of EAAs W/ Every Meal. Do Energetic Costs of Protein Synthesis Trigger This Effect?

EAAs beyond whey: It may not necessarily look like this, but this salad (repicecorner) is an EAA power horse with cheddar cheese (25% protein, 0.49 EAA / P ratio), tuna (in oil, 29%,  0.45) and kidney beans (9%, 0.45). You see, it does not always have to be chicken breasts or whey to get beyond the 10g+ EAA threshold, I have repeatedly suggested as one of the fundamental rules of dieting for weight loss, maintenance and muscle gain.

Many people take it for granted that you become fat, when you get old. If you look at the statistics, you could even make a point that obesity has some protective effects with esp. with respect to CVD mortality. Scientists call this the "obesity paradox" (Kastorini. 2013). What's particularly paradox, at least in my humble opinion, is yet not the phenomenon itself, but rather the fact that it gets smart scientists derailed from working on useful dietary and exercise interventions to prevent the development of heart disease, cancer, metabolic syndrome etc. in early years. Instead, they argue ex-post, i.e. when the baby has already been thrown out with the bathtub by comparing sick lean (in parts even cachectic) and sick "obese" people, why their statistical shenanigan that's based on the useless BMI produces paradoxical results. And that, when studies such as the one Jacobs et al. did in 2010 clearly show that 50+ year old men and women with waist circumference >120cm and >110cm, respectively, have 2x higher all-cause mortality risk than their lean peers - irrespective of BMI (Jacobs. 2010)!

To get lean and stay lean, yet not thin and skinny fat is therefore a challenge everyone...

... from the child in the Kindergarten to the obese granny in the nursing home is facing. Against that background a previous study by Loenneke et al. comes to mind. The results of their analysis, which were published in Nutrition and Metabolism in January 2013 clearly show that the amount of times people eat meals with a 10g+ EAA content per day was inversely related to percent central abdominal fat (Loenneke. 2013). In previous studies EAAs have also been shown to improve glucose clearance without increases in insulin and in the absence of effects on the fat burnin and health promoting expresion of AMPK-alpha2 in skeletal muscle tissue (see "EAAs Stimulate Muscle Glucose Uptake by Exponentiating Insulin's Effect on GLUT4 Expression"). With the advanced publication of a study by Coker, Miller, Schutzler, Deutz and Wolfe in the online verison of the Nutrition Journal a couple of days ago, the notion that EAAs have a particularly beneficial effect on fat loss - in this case in obese elderly individuals - gets further support from a well-controlled randomized trial (Cooker. 2013).

EAA-rich protein increases fat loss to a greater extent than low EAA protein

The researchers from the Center for Translational Research in Aging and Longevity and the University of Arkansas for Medical Sciences in Little Rock, AR, USA randomized 12 elderly individuals (mean age 69 years) to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (~850 kcal/day; the exact nutrient composition can be found in figure 1) + ~400kcal from solid foods (total intake: ~1,250kcal/day; the subjects were free to chose their solid meals but were provided with a list of examples the should pick from, if possible).

Figure 1: Macronutrient composition of the meal replacements used in the study (Cooker. 2013)

The diet was designed to induce a 7% weight loss in two months. And while both,  the rate of weight loss (~1.6lbs per week), as well as the relatively high caloric deficit are certainly appropriate for someone with a 30+ BMI and ~40% body fat, leaner people will fare better with a less pronounced kcal deficit or (alternatively) have to add some strategically planned refeeds to the equation in order to minimize the loss of lean mass and, more importantly, avoid the ensuing reduction in energy expenditure (for the obese, the latter is actually less of the problem, because the downsides of being calorically deprived are at least partly counglucose tolerance and leptin sensitivity with every gram of body can actually help the body recognize that there is still plenty of energy that has just not been available (glucose) or "visible" (fat) before).

Figure 2: Changes in lean and fat mass (kg, left) and fractional protein synthesis rates (FSR) in participants receiving iso-caloric meal replacements with identical macronutrient compositions (see figure 1), but different amounts of essential amino acids (EAAs) content (Coker. 2013)

As the data in figure 2 goes to show you even the obese individuals in the study at hand lost a non-negligible amount of lean mass - unfortunately the body composition was measure with a sophisticated, but still body impedance based device, the trends are still accurate, but it is questionable in how much we are actually talking about ~2 and 2.5kg of muscle mass (figure 2, left), because somebody's "lean body mass" does obviously include more than just skeletal muscle.

When it comes to supplements, we are often like children on Christmas eve. About all the new stuff we get we tend to forget our former favorite and often way more fun to play with toys. Don't make this mistake and ditch your PWO whey (personally, I like a ~1.5:1 whey + micellar casein mixture) for EAAs, they don't come close... read more

Be that as it may - since the before and after values were taken with the same device the changes should be correct, so that both the slightly yet not statistically significantly ameliorated loss of lean body mass and, more importantly, the significantly higher degree of body fat loss in the EAA meal replacement (EAAMR) group speak in favor of the 5 servings of a the 170 kcal, 6g EAA per day. Moreover, "the sparing influence of muscle loss might have been demonstrated with a larger sample size", so that you can take it for granted that the preservation of precious muscle mass is an advantage of being choosy with your protein sources and preferring those with higher over those with lower essential amino acid contents.

On a related note: I don't know if you noticed, but with a total energy content of 850kcal and 30g EAA these 5 meal replacements did in fact have exactly those 10g+ of essential amino acids, I have repeatedly recommended to have with each of the 3 meals most people consume in the course of the day.

In all fairness, it should also be mentioned that despite not being significantly different at baseline, the body fat percentage of the subjects in the EAA meal replacement group was ~3% higher to begin with.This may seem irrelevant, since figure 2 compares lean mass and fat mass as absolute changes and not their percentages, but in the end, the amount of fat you you can drop within a given time-frame decreases with lower body fat percentages.

Do the energetic costs of protein synthesis drive fat loss?

Another interesting observation Coker et al. made is the close association between fat loss, on the one hand, and increased protein synthesis (55%), on the other hand. The researchers take this as an incentive to do one of the of the much loved calories in vs. calories out calculation and come up with the following hypothesis:

"Acute administration of EAAMR did promote a significant increase in skeletal muscle protein FSR compared to CMR. Assuming that the energy cost of protein synthesis is 3.6 kJ/g and the baseline GAIA-derived lean tissue mass was 56.4 kg for EAAMR and 54.4 kg for the CMR, we can extrapolate that the overall energy discrepancy between the two groups was roughly equivalent to 27,170 kcal or 3.5 kg of weight loss across the entire caloric restriction-based weight loss paradigm. Based on the amount of total lean mass in each group, this value takes into account a consistent intervention structure of five servings/day across an eight week period. In short, these calculations suggest that differences in the source of intact protein/formulation of EAA may have a significant influence on diet-induced energy expenditure that coincides closely with the greater reduction of adipose tissue in EAAMR compared to CMR." (my emphasis in Coker. 2013)

I usually discard fallacious calculations like this one if they are not highlight the stupidity of trying to eat exactly as much as some funky formula + the figure on your treadmill, pedometer, heart rate monitor or whatever fancy tool you may use to "measure" your energy expenditure suggest you would have burned in the last 24h. In this case, however, I made an exception, because I feel that the notion that protein quality is one of the myriad of parameters that are missing from this foolish calculation is important, for lean and obese people from all age groups who are trying to shed body fat.

Bottom line: The take away message of the study is in the end identical to the previously mentioned study by Loenneke et al.: Make sure you hit the 10g EAA threshold with each and every of your meals, if being lean and muscular not skinny yet fat is your goal.

References:

• Coker RH, Miller S, Schutlzer S, Deutz N, Wolfe RR. Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals. Nutr J. 2013 Dec 11;11(1):105. [Epub ahead of print]
• Jacobs EJ, Newton CC, Wang Y, Patel AV, McCullough ML, Campbell PT, Thun MJ, Gapstur SM. Waist circumference and all-cause mortality in a large US cohort. Arch Intern Med. 2010 Aug 9;170(15):1293-301.
• Kastorini CM, Panagiotakos DB. The obesity paradox: methodological considerations based on epidemiological and clinical evidence--new insights. Maturitas. 2013 Jul;72(3):220-4.
• Loenneke JP, Wilson JM, Manninen AH, Wray ME, Barnes JT, Pujol TJ. Quality protein intake is inversely related with abdominal fat. Nutr Metab (Lond). 2013 Jan 27;9(1):5.

A Higher Intake of CLA and Vaccenic Acid from Dairy, Beef, Veal and Lamp Could Prevent Subtle Weight Gain in Healthy Middle-Aged Individuals. Is 1.5g/day the Magic Number?

A dairy cow: Does her stomach hold the key to a leaner, healthier life or are CLA and vaccenic acid, the ruminant trans-fatty acids just as bad as their grainy cousins?

There are supplements that work and supplements that don't work and then there are those supplements, where nobody can actually tell, whether they belong to the former or the latter category. Conjugated linoleic acid, the ruminant omega-6 trans-fat you will find at particularly high concentrations in milk and meat products from grassfed dairy, unquestionably belongs to the latter category. While we do actually have plenty of in parts almost unsettlingly impressive rodent data (e.g. "CLA Destroys Body Fat & Increases Endurance! But at Which Costs?"), the outcomes of independent  controlled human studies are equivocal; with results ranging from "total failure", to "promising, but not half as impressive as we have expected based on previous rodent studies".

That being said, I was quite intrigued, when I hit onto a recently published study that takes a novel angle on the whole CLA for weight loss issue. One I usually don't like, as it involves a lot of statistical shenanigan, but still appears appropriate in this particular case, where the controlled small scale trials are failing us.

The Nordic Men (and women) love their full-fat dairy - rightly so?

If you are a loyal reader of the SuppVersity, who does not just read the detailed elaborations here on www.suppversity.com, but is also following the latest short news on the SuppVersity Facebook Wall, it probably won't surprise you that the study which is going to be published in the October issue of the European Journal of Clinical Nutrition has been conducted in Northern Europe. After all, you will have noticed that many of the interesting short news items relating to (larger scale) studies on the effects of one or another of the "bad fats" are conducted at universities and research centers in Sweden, Finland, Norway and, as in this case, Denmark - at the Aarhus University, to be precise, where Hansen and his colleagues datasets from the Diet, Cancer and Health study from December 1993 to May 1997. The participants, 160,725 men and women, aged 50–64 years, who were all born in Denmark and had been living in the greater Aarhus or Copenhagen areas, had all completed detailed food frequency questionnaire (FFQ) and a self-administered lifestyle questionnaire, before they underwent a physical examination and a follow up 5-6 years later.

How did the scientists know how much CLA and vaccinic acid the individual food items contained? unfortunately, they didn't. The way by which they calculated / estimated it,  i.e, by combining the content of r-TFAs in milk fat (data based on another Danish study) with the content of milk fat in dairy products given by the Danish food composition tables and using the values of r-TFA content in ruminant meat products representative of the supply in Denmark, does however make sense to me. The resulting averages should therefore be relatively reliable.

Based on the 77 food items of the food frequency questionnaires which contained ruminant trans-fatty acids R-TFA (this includes both CLA, as well as vaccinic acid which can be converted to CLA in the human body; cf. Turpeinen. 2002), i.e.

• dairy products (n=63), 
• ruminant meat products (beef, veal or lamb) (n=2), and
• composite recipes containing both dairy and ruminant meat (n=12) 

Hansen et al. calculated the average r-TFA intake of each of the 57053 subjects with complete datasets and correlated them with the participants changes in body weight and waist circumference (WC) over the 5-year period to the follow-up.

A massive amount of data suggest minimal amounts of r-TFA are necessary

As the subheading to this paragraph already reveals, the result of the all this statistical shenanigan suggest that the ruminant trans-fatty acid intake from foods, not supplements, does have a beneficial effect on the change in total body weight (an ameliorating effect on weight gain, to be precise).

Figure 1: Absolute intake of ruminant R-TFA (in g/day) and changes in weight; adjustment for sex, age, height, baseline weight, smoking, alcohol intake, education, weighted intake of foods containing high amounts of I-TFA (g/day) and in women, menopausal status and hormone replacement therapy (Hansen. 2013).

A brief glance at the graphs in figure 1 will yet also tell you that their effect on body fatness (as indicated by changes in visceral adipose tissue), is negligible, not to say non-existent. In a way you may say that this is a good thing, because the turning point at a daily r-TFA intake of >1.5g/day, where the restricted cubic spline (that's a statistical fit into the data; figure 1, solid lines) seems to indicate that r-TFA intakes of more than 1.5g/day would precipitate weight gain, is thus absent as well.

Figure 2: Relative intake of R-TFA (in % of total energy intake) and changes in waist circumference. Solid lines: restricted cubic spline with five knots; Dashed lines: 95% confidence interval; same adjustments as in figure 1(Hansen. 2013)

In addition, if we do also consider total energy consumption and the contribution of r-TFAs to the latter (see figure 2), it becomes obvious that we cannot neglect the profound widening of the 95% confidence interval in figure 1 (dashed lines), which tells us that some of the high r-TFA consumers did get even leaner, while others did gain a significant amount of weight. Adjusted for caloric intake and the other confounding variables this effect vanishes and a trend towards lower / even no body weight gain in high r-TFA consumers becomes visible (even within the higher intakes, where the confidence interval widens, due to the lower number of participants, but does not change the general trend). The beneficial effect on waist circumference, however, remains negligible.

So what, if anything, can we learn from these results?

At first sight, the results of the study at hand seem to stand in line with what you have read in "Fat Advantage: 61% Lower Rates of Metabolic Syndrome in High Fat Dairy Lovers", here at the SuppVersity exactly one week ago. It even appears to provide a mechanism by which the high fat dairy products could exert their highly desirable anti-obesity effects, if the high CLA + vaccenic acid (r-TFAs) consumers in the Hansen study were not just the subjects who gained the least weight (measured against their nutrient intake and adjusted for all sort of other confounding factors), but also those with the lowest increase in visceral adipose tissue.  

If that were the case, however, the graph on the right hand side of figure 2 should have at least some kind of slope. Since it hasn't, we must assume that the beneficial health effects of r-TFAs are either (a) not brought about by changes in visceral obesity, (b) the latter are not appropriately quantified by simply measuring the waist circumference or (c) in view of the fact that we are not talking about "weight loss", but rather a prevention of the (partly probably age induced) increase in weight gain a stable waist circumference has to be considered a "success", already.

The scale is an unreliable tool to judge visceral obesity. And even a measuring tape can be misleading, if you are really "skinny fat".

Personally, I tend towards a combination of all three. First of all even moderate weight gain has been shown to increase the risk of impeding metabolic syndrome. The weight stability over >5years in the high r-TFA consumers must therefore be considered to be prognostic of a lower risk of metabolic syndrome. Secondly, visceral does not necessarily equal abdominal fat. Especially in older individuals the gynoid fat areas contribute to visceral obesity, as well. Moreover, we all know the skinny fats, men and women with a relatively large amount of highly inflammatory visceral fat and normal or even low waist circumferences also known as "normal weight obese"; cf. Romero-Corral. 2010).

And thirdly and most importantly: Weight loss is mainly an issue for people who are already overweight or obese. For best-agers who are still in form (and in Denmark there are such people ;-), success is better defined by maintaining the muscle mass you have, not accumulating additional (visceral) body fat and leading an overall healthy lifestyle. That ruminant trans-fatty acids can, maybe even should be a part of the dietary side of this healthy life-style is therefore the main take home message of this study.

What should not be forgotten, however, is the fact that this study was at least in parts supported by the Danish Dairy Research Foundation, certainly not an organization with a particular interest in "bad news" on vaccenic acid, conjugated linoleic acid and dairy products in general, right?


References:

• Hansen CP, Berentzen TL, Halkjær J, Tjønneland A, Sørensen TI, Overvad K, Jakobsen MU. Intake of ruminant trans fatty acids and changes in body weight and waist circumference. Eur J Clin Nutr. 2013 Oct;66(10):1104-9. doi: 10.1038/ejcn.2013.87.
• Romero-Corral A, Somers VK, Sierra-Johnson J, Korenfeld Y, Boarin S, Korinek J, Jensen MD, Parati G, Lopez-Jimenez F. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010 Mar;31(6):737-46.
• Turpeinen AM, Mutanen M, Aro A, Salminen I, Basu S, Palmquist DL et al. Bioconversion of vaccenic acid to conjugated linoleic acid in humans.Am J Clin Nutr2002;76: 504–510.

Fat Advantage: 61% Lower Rates of Metabolic Syndrome in High Fat, 101% Higher Rates in Low Fat Dairy Lovers

"Got milk" is not the question health conscious supermen and -women should pose. "Got full fat milk, fermented dairy and cheese" is the line to remember (the original image was part of the "Got Milk Campaign")

While diet fads come and go, the advice the wise (not seldom obese or otherwise sick) experts on the boards and panels of our well-meaning governments is calling "dietary recommendations" is about as resistant to reform as the dreaded MSRA strains are to the antibiotics doctors are throwing at you whenever you sneeze. Against that background the recent trend we are seeing with respect to an increase in the recommended amount of dietary protein does almost amount to a quantum leap; a leap with a significant caveat, however. A fat caveat, so to say:

"A healthy diet includes [...] lean meats, poultry, fish, beans and fat-free or low-fat dairy products" (NIH. 2013).

Luckily, you as a SuppVersity reader do not have to rely on the NHI's thwarted interpretations of the latest research they claim to use, when they are "turning discovery into health" (no joke, this is a literal citation from the footer of the NHI website!), but can compare it to my thwarted interpretations of the latest research and cherry picked data ;-)

Cherry pick of the day: Longitudinal large scale study on dairy intake and metabolic health

 For Today, this means that you get to enjoy the latest results of a large scale observational study from the University of Sydney that's based on datasets from the Blue Mountains Eye Study (BMES) a population-based cohort study of common eye diseases and other health conditions in residents aged 49 years and over in the Blue Mountains area, west of Sydney. A longitudinal study the baseline information was obtained in 1992/1994 from  and complemented by follow-up ten years later.

The data sets included food frequency questionnaires, as well as anthropometric and biochemical assessments all of which were included in the present analysis of the association betweenn dairy consumption with the ten-year incidence of Metabolic syndrome (MetSyn) and type 2 diabetes. What's so special about this dataset, is that the food questionnaires were actually detailed enough to assess the effects of full- and low-fat dairy, separately - a very important advantage, as a cursory glance at the data in figure 1 reveals.

Figure 1: Odds ratios (95% confidence intervals) of incident metabolic syndrome according to quartiles of reduced/low fat,
regular fat and total dairy product intake (data based on Louie. 2013; adjustments for age and sex (basic model), smoking status, physical activity (metabolic equivalents), dietary glycemic load, fibre from vegetables, total energy intake and family history of type 2 diabetes (model 1) and calcium (model 2))

While the standard analysis for total dairy consumption (figure 1, left) yielded neither conclusive, nor statistically significant results (the p-values for the different models can be found in the upper right corner of the respective graphs). The categorization into low- and high fat dairy and the adjustments for age and sex (basic model), smoking status, physical activity (metabolic equivalents), dietary glycemic load, fibre from vegetables, total energy intake and family history of type 2 diabetes (model 1) and calcium (model 2) yields very clear and, after adjustment for calcium intake, pretty unflattering result the formulators of the afore mentioned "dietary recommendations" will probably file in their already bristling "statistical outliers"-folder:

• after adjustment for calcium intake subject in quartiles 2 / 3 / 4 of low-fat dairy are 50% / 145% / 101% more likely to be struck by metabolic syndrome, than those in the lowest quartile of low fat dairy intake (p = 0.043), while
• subjects in the highest quartile of full-fat dairy intake are - depending on the adjustments made -  48% / 59% / 61% less likely (base model / model 1 / model 2) to suffer frommetabolic syndrome, than those in the lowest quartile of high fat dairy intake (p-values:  0.018 / 0.004 / 0.004)

Yet while the scientists are well aware, that these results stand in stark contrast to the initially cited dietary recommendations, is it not this contrast that surprises them, but rather the fact that a similar significant benefit was not observed for type II diabetes, which is, after all, one of the hallmark features of the rather loosely defined triad of obesity, insulin resistance and cardiovascular disease(s), we usually refer to as 'metabaolic syndrome':

"Due to its higher saturated fat content, regular fat/high fat dairy products were previously believed to increase the risk of type 2 diabetes as a high saturated fat intake is associated with insulin resistance . However, cohort studies and a meta-analysis now suggest otherwise, with higher regular fat/high fat dairy consumption being considered mostly neutral or protective for type 2 diabetes. The results of the present study are consistent with these findings that higher regular fat dairy consumption may be protective of MetSyn and type 2 diabetes. The potential harmful effects of higher saturated fat from regular fat dairy products may have been offset by the protective components of regular fat dairy such as trans-palmitoleate, a fatty acid nearly unique to ruminant foods. Circulating level of trans-palmitoleate was shown to be significantly associated with reduced risk of type 2 diabetes (Q5 vs Q1: 62% reduced risk, p-trend < 0.001). Moreover, the protective effect of trans-palmitoleate may be exerted via the suppression of hepatic fat synthesis, where the latter was strongly associated with insulin resistance." (Louie. 2013; my emphases)

In view of these mechanism, it is all the more surprising that the study at hand and many previous studies didn't find any significant correlations between (regular fat) dairy intake and type II diabetes.

Reduction in metabolic risk, but no effect on type diabetes? Hold on...

Wolverine could be the only face of the "Got Milk" campaign who does not have to care about potential negative health effects of homogenized milk.

And upon a cursory read of the latest literature it does in fact seem as if "null findings" like this, were nothing special. Only recently by Sluijs et al. who had analyzed datasets from a nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) includind a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403; cf. Slujis. 2013):

"This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study." (Sluijs. 2013)

If we do yet take a closer look at the actual results the actually not so surprising truth is that there was a statistically significant inverse association with diabetes for cheese (p = 0.01) and fermented dairy (p = 0.02).

An association that suggests a 12% reduction in diabetes risk in those study participants who consumed the most cheese and fermented dairy (cheese, yogurt, and thick fermented milk)

And since you all know your real foods, I guess I don't have to tell you that despite the fact that there are low fat varieties of cheese yogurts and other fermented milk products, 90% of them contain way more than the 1.5% let alone 0.1% fat the allegedly healthy low fat "milk" is boasting of. Mere coincidence? I don't think so. Reason to assume that low-fat milk will make you sick? No, but certainly not an argument to avoid the full-fat variety simply because it contains fat (which is the only argument the average dietitian has to favor low- over full-fat dairy products).

Mutant Milk!? New Research Fuels the Flames on Hushed Up Concerns About Ill Health Effects of Homogenized Milk 

Ask Dr. Andro: Are Colostrum and Milk Products in General Healthy Muscle Builders, a Waste of Money or Toxic Waste?

All about milk: Browse past news and articles at the SuppVersity

^ Suggested reads

Additional recent dairy science:Similar beneficial findings for all-cause mortality and fermented dairy (yet inconclusive results for CVD and diabetes) come from the recently published Whitehall II study (4526 subjects,72 % men, mean age 56 years; Soedamah-Muthu. 2013) and for dairy intake during adolescents and diabetes (-38% risk reduction for 2 servings per day or more) from a reanalysis of somewhat questionable data (who remembers exactly how much dairy he had during his adolescence?) from the Nurses' Health Study II cohort that comprises 37,038 women who completed a food-frequency questionnaire about their diet during high school were followed from the time of return of the questionnaire in 1998-2005 (Malik. 2013).


References:

• Louie JC, Flood VM, Rangan AM, Burlutsky G, Gill TP, Gopinath B, Mitchell P. Higher regular fat dairy consumption is associated with lower incidence of metabolic syndrome but not type 2 diabetes. Nutr Metab Cardiovasc Dis. 2013 Sep 26. pii: S0939-4753(12)00193-7. 
• Malik VS, Sun Q, van Dam RM, Rimm EB, Willett WC, Rosner B, Hu FB. Adolescent dairy product consumption and risk of type 2 diabetes in middle-aged women. Am J Clin Nutr. 2011 Sep;94(3):854-61.
• NIH. Health in the News: Love Your Heart. February 2013. < http://newsinhealth.nih.gov/issue/feb2013/feature1 > retreived Oct 02, 2013.
• Soedamah-Muthu SS, Masset G, Verberne L, Geleijnse JM, Brunner EJ. Consumption of dairy products and associations with incident diabetes, CHD and mortality in the Whitehall II study. Br J Nutr. 2013 Jun 7:1-9.
• Sluijs I, Forouhi NG, Beulens JW, van der Schouw YT, Agnoli C, Arriola L, Balkau B, Barricarte A, Boeing H, Bueno-de-Mesquita HB, Clavel-Chapelon F, Crowe FL, de Lauzon-Guillain B, Drogan D, Franks PW, Gavrila D, Gonzalez C, Halkjaer J, Kaaks R, Moskal A, Nilsson P, Overvad K, Palli D, Panico S, Quirós JR, Ricceri F, Rinaldi S, Rolandsson O, Sacerdote C, Sánchez MJ, Slimani N, Spijkerman AM, Teucher B, Tjonneland A, Tormo MJ, Tumino R, van der A DL, Sharp SJ, Langenberg C, Feskens EJ, Riboli E, Wareham NJ; InterAct Consortium. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study. Am J Clin Nutr. 2013 Aug;96(2):382-90.

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. 2013)

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. 2013; Williamson. 2013)

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. 2013)

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. 2013)

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. 2013), 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. 2013)? 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. 2013)
• perceptibility to arrhythmia (Klatsky. 2011)
• venous thromboembolism (Enga. 2011)
• general cardiovascular disease (Bøhn. 2013)
• dementia & Parkison's (Cao. 2013; Campdelacreu. 2013)
• diabesity (Hjellvik. 2011; Matsuura. 2013)
• 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. 2013 Apr;15(2):217-21.
• Bøhn SK, Ward NC, Hodgson JM, Croft KD. Effects of tea and coffee on cardiovascular disease risk. Food Funct. 2013 Jun;3(6):575-91.
• Campdelacreu J. Parkinson disease and Alzheimer disease: environmental risk factors. Neurologia. 2013 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. 2013;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). 2013 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 2013; 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. 2013;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. 2013 Jul 1;5(4):401-5. Epub 2013 Jun 26.
• Nature.com Reviews. Heart failure: Moderate coffee consumption linked with reduced risk of HF. Nat Rev Cardiol. 2013 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. 2013 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.

Leucine + Resveratrol - Synergistic Sirtuin Boosters: +118% Fatty Acid Oxidation, 60% Increase In Muscular Glucose Uptake, -30% Visceral Fat & More - To Good to be True?

Image 1: Can you really team up leucine (or HMB) and resveratrol to make tired mitochondria get a move on? NuSirt Sciences says "YES!" And in the dish and rodents it's actually already working.

What happens if you marry a well-known AMPK promoter and exercise mimetic, with an even more prominent exercise adjuvant and nutritional mTOR booster? Will they neutralize each other? Think about it.... ok, now gimme your answer: What happens if you put resveratrol and leucine together? At first it does not really make sense, does it? Right, it doesn't, at least not unless you follow the same train of thought, the researchers from NuSirt Sciences. NuSirt? That rings a bell, hah? Yeah those were the guys who did a study on their 250mg leucine + 30mg vitamin B6 proprietary blend NuFit (see "Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize & More") and actually, the leucine + resveratrol combination is sort of a spin-off of this initial research.

If you put Sirt1 & Sirt1 together, it suddenly makes sense!

In their latest study (and you bet a future product!) Bruckbauer et al. build on their previous research on the agonistic effects HMB, alpha-KIC or leucine have on skeletal muscle Sirt-1 activity (Bruckbauer. 2011) and rationalize that it seems legit to combine one Sirtuin portein promoter with another one in order to achieve an even more pronounced effect - makes sense, right? Resveratrol the proven AMPK-promoter and igniter of the longevity, gene transcription, cell survival and apoptosis regulating Sir2 proteins (=sirtuins) and leucine the mTOR promoting and, as of late, proven Sirt1 agonist, they could actually form a synergistic duo for fat oxidation, glucose management, the reduction of oxidative stress and inflammation and even longevity!

Figure 1: Effects on sirtuin & AMPK expression in muscle and fat cells upon incubation with leucine, HMB and resveratrol and the respective combinations (left) and effects fatty acid oxidation in isolated rat skeletal muscle upon incubation in low and high glucose conditions (data based on Bruckbauer. 2013)

Now, aside from Sirt1, which is mainly expressed in the nucleus of a cell, another one of the Sir2 proteins, Sirt3, which is expressed predominantly in the mitochondria has as of late gathered quite some attention, as mitochondrial dys- or malfunction is one, if not the common denominator of many of the pathological features of the metabolic and neuro-endocrine ailments the Western diabesity society is suffering from: insulin resistance, type II diabetes, Alzheimer's , you name them! No wonder the NuSirt guys (and girls) are striving to find a marketable way to set them both in full gear and if you take a closer look at the data in figure 1 their initially counter-intuitive approach to bath muscle and fat cells in resveratrol  + HMB / leucine solutions yields impressive results:

• resveratrol, leucine and HMB, alone, exerted only weak independent effects on Sirt1, Sirt 3 and AMPK
• resveratrol and leucine or HMB, combined, yielded Sirt1 and Sirt3 activity increases in the ~50% range (p < 0.05) and AMPK increases of +42% and +55% (p < 0.03); particularly noteworthy are the ~125-175% increases (p < 0.02) muscle cells (remember: Sirt3 is expressed in the mitochondria!)
• the ensuing increases in fatty acid oxidation in incubated muscle cells reached statistical significance in the presence of low (5 mM) glucose levels, only, when and 5 µM HMB or  0.5 mM leucine were co-incubated with 200 nM (~18%; p < 0.05), in the high glucose condition, however, all treatments broad about significant increases in fatty acid oxidation, of which those in the leucine- and HMB-resveratrol combination treatments were the most pronounced (118% and 91% stimulation, respectively; p < 0.005)

Especially the last finding, i.e. the increase in fatty acid oxidation in an in-vitro condition that resembles the hyperglycemic state the average type II diabetic who is not popping tons of metformin and/or injecting insulin is constantly in, makes these results particularly interesting, as it appears as if a "non-pharmacological" (what by the way is "pharmacological" and what isn't?) solution to the diabesity problem could already be hidden on the shelves of your GNC right next door (I assume they carry leucine and resveratrol products ;-)!

Outside of the box... ahh, I mean, ... the petri dish!

In view of the fact that 75% of the in-vitro high performers suck in the rodent model already and of those another 75% don't work in human trials you will be pleased to hear that NuScirt Sciences' resveratrol + leucine / HMB combination has already overcome the first of these hurdles: At least in DIO (diet-induced-obese) rodents who on a 6-week high fat diet regimen, the combination works.

Figure 2: Weight gain, visceral adipose volume, PET measured palmitate uptake, respiratory rate (lower levels = higher relative fat oxidation), heat production relative to body weight, food intake; all value expressed relative to DIO mice who were maintained on an unsupplemented control diet (data based on Bruckbauer. 2013)

Now, it's not as if the rodents would have made it to the Mr Olympia stage, but if you take a closer look at the pattern that's emerging here, it's quite clear that the sirtuin booster does its job in this rodent model. Aside from its ameliorative effect on weight gain, the combination of resveratrol and leucine, led to statistically significant improvements in glucose management and improvements in inflammatory markers (including the anti-inflammatory adipokine adiponectin, see figure 2).

Figure 2: Glucose, insulin and HOMA IR levels, muscular glucose uptake (left), C-reactive protein , IL-6, MCP-1 and adiponectin (right) ; all value expressed relative to DIO mice who were maintained on an unsupplemented control diet (data based on Bruckbauer. 2013)

Most importantly, however it effectively cut through the exuberant amount of visceral adipose tissue (>30% reduction), ramped up the palmitate (fatty acid) uptake, oxidation and heat production (=thermogenesis). Despite all these metabolic improvements which took place in the absence of a simple reduction in food intake, there are still a couple of things left to be desired:

What are the human equivalent doses, here? Since I know you would be asking I did the math for you and you will be pleasantly surprised (HED for 80kg humans)

• 12.5mg resv. = 9mg
• 225mg resv. = 136mg
• 2g HMB = 1.1-1.4g
• 10g HMB = 7.2g
• 24g leucine = 14.3g

I am well aware that it must look as if I had the typical poor arithmetic abilities of the average physicist who has totally forgotten how to calculate using figures instead of letters, but the reason for the discrepancies is that I calculated the exact HEDs based on body weight and food intake for each of the groups.

1. Supplementation with the respective human equivalent doses should yield the same astonishing results in humans as it did in the diet-induced obese mice.
2. The protocol should have effects not just in morbidly obese diabetic human beings, but also in overweight and ideally even lean individuals.
3. The supp must work if you don't put it into the chow, but pop it in separate doses (e.g. 3x/day) as a capsule or tablet.

The good news however is that if 1-3 apply, you could start benefiting from this "super supplement" right now! After all, the resveratrol dose of 12.5mg per kilogram of chow (the mice in the study did not consume more than max. 4g(!) per day) is so low that the 10g package I just saw for 20$ over at the webshop of a major bulk supplier would last you literally forever ...

Unfortunately, this is exactly why I don't believe that LeuResSirt, or whatever other stupid name the final product will be given, is going to work - I mean, come on, you can't tell me that there are not already people out there who get 15-20g of leucine everyday and pop resveratrol in 100x the necessary dose of 8-9mg everyday!? And did they turn into a beast, become fast-food resistant or lose fat magically? What? Yeah... that must be Phil Heath secret, right... how come I did not realize that before? ;-)

Bottom line: Regardless of the probably justified skepticism, I will still keep you posted on whether or not NuSirt knocks out another incredible (in the literal sense) human study like the one on NuFit (see "Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize & More"). So stay tuned, you all know that no supplement will ever more ergogenic than your daily dose of SuppVersity news!

References:

• Bruckbauer A, Zemel MB. Effects of dairy consumption on SIRT1 and mitochondrial biogenesis in adipocytes and muscle cells. Nutr Metab (Lond). 2011 Dec 20;8:91.
• Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab (Lond). 2013 Aug 22;9(1):77.

Are Elevated Iron and Uric Acid Levels Too Much of a Price to Pay for a Creatine-Induced 11% Performance Increase?

Video 1 (GSSI): Notre Dame's Michael Floyd goes all out on the Wingate test (click to watch)

I guess you could say that these are the "classic days", here at the SuppVersity, contrary to my previous post on choline, which is - judged by the few people who still use it today, an "old school supplement" (cf. "Choline: Stronger, Faster, Leaner & More Muscular, or Just Another Dumb-and-Barbell Story?") - yesterday's post on caffeine highlighted the efficacy of a potent ergogenic aid and metabolic activator, with the effects of which most of us are so familiar that we are alway tempted to turn to useless crap like raspberry ketones, when what we are already doing is not only tried and proven, but based on respectable scientific data even more effective than the latest "innovation" from the snake oil industry. And let's be honest, haven't we all been tempted by one or another "new creatine", as well?

+11% peak performance in one week, solely from 5x4g of creatine per day!

A a matter of fact, creatine monhydrate does in fact share the same fate of being proven, but "boring" staple supplement and although that alone should be incentive enough to address the unquestionably outstanding +11% in anaerobic peak performance, +5% in continuous anaerobic performance and a +6% increase in total workload in a classic wingate anaerobic performance test speak, Barros et al. observed in a group of trained male subjects in response to a 7-day creatine loading protocol (20g creatine monohydrate, in 5 doses spread across the day, not glucose / sugar added; cf. Barros. 2013) After all, my gut tells me that the contemporary changes in the concentration of iron in the blood of the subjects in the the creatine arm of the study could revoke the mainstream-media fearmongerish hoopla over the purported dangers of the #1 natural ergogenic.

Figure 1: Basal iron, FRAP, malondialdehyde (MDA) and uric acid levels before and after 7-day supplementation with 5x4g of creatine monohydrate per day (based on Barros. 2013)

I mean, there is no debating, the level of iron in the blood of the creatine supplemented undergraduate students (age, 23.1 ± 5.8 years; height, 175.4 ± 2.3 cm; weight, 81.1 ± 9.3 kg) all of whom had been avid trainees for at least 6 months did increase by no less than 94.3%, while the subjects in the placebo group experienced a -21% reduction of these highly reactive molecules (Just as an aside, the decline in serum iron in the placebo group and the significant difference in baseline levels between the random groups, alone, render any implications at least questionable; I mean, wouldn't you expect the serum parameters to stay the same, when you do nothing extraordinary, aside from popping some sugar pills?).

Figure 2: Changes in wingate anaerobic performance (left) and exercise induced changes iron, FRAP, malondialdehyde (MDA) levels during the wingate test at the end of the supplementation period (based on Barros. 2013)

In conjunction with the likewise highly significant increase in uric acid levels, conventional (blogosphere-)wisdom, which constantly ignores the antioxidative nature of uric acid, which acts as efficient antioxidant and chelating agent for iron ions (Karlsson. 1997), limits the oxidation of polyunsaturated fatty acid in the erythrocyte membrane and prevents hemolysis (= the rupture of red blood cells) in vitro (Einsele. 1987), would suggest that taking creatine takes a close second to fructose on the list of the villains of the bad, bad "neolithic" century.

How dangerous is the creatine induced increase in iron?

Image 1 (Paramount Pictures): I guess, it must have been creatine monohydrate, then, that turned Robert Downey Jr. into Ironman ;-)

Now, despite the as of late publicly propagated concerns about increased iron levels and their potential causative role in the etiology of insulin resistance and diabesity (obesity + diabetes), recent scientific evidence suggests that "high iron", such as all previous scapegoats people like to hold liable, just to make sure not to admit that it is the sickening combination of laziness, convenience and unsound dietary advice that is at the heart of the current obesity epidemic.

Huang et al., for example, did observe a direct effect of iron overload on diabetes risk - the latter was however a result of hereditary hemochromatosis (a genetic defect in iron metabolism) in their 2011 rodent trial (Huang. 2011). Results from two more recent studies by Silva et al. also indicate that the metabolic disturbances lead to differential expressions of the proteins involved in the metabolism of iron and thus substantiate the associative (and not causative) nature of the relation between high iron / ferritin and the metabolic syndrome (Silva. 2011; Silva. 2013).

Iron not causative? So why does phlebotomy help, then? If you read my post on the recently published data from the first controlled human trial that investigated the effects of phlebotomy on markers of blood glucose management, you will be aware that the measures they took, e.g. the HOMA-IR, are not really appropriate to assess the effects of this particular treatment (cf. "Phlebotomy: Can You Bleed Yourself Healthy and Lean?"). Furthermore, it is only logical that the removal of some of this "highly inflammable stuff" from an inflamed body will provide health benefits, even if the latter was totally benign for someone who has a lot less inflammation going on.

What is even more important, though, is that the difference between exercise-induced increases in serum iron and diet and diabesity-related increases in the storage form of iron, ferritin, in the liver. This is particularly true in view of the fact that our understanding of the former, i.e. the exercise induced release of iron into the blood stream is more than limited (Roberts. 1989; Smith. 1994). What we do see in the Barros study, however, is that the overall effect of creatine is rather anti- than pro-oxidative, since the increase in overall antioxidative capacity (as indicated by the changes in the iron-specific FRAP essay; cf. figure 1) did not just...

• negate the potential negative effects of increased basal iron levels (see lowered baseline MDA levels post supplementation in figure 1), it also 
• countered the exercise-induced lipid oxidation during the 2nd wingate test (as indicated by lower MDA levels; cf. figure 2). 

Eventually, the scientists say, the increase in antioxidant activity that is brought about by the ingestion of 20g/day creatine irrespective of whether you exercise or not could actually yield "general health benefits" (Barrios. 2013); and I would like to add that evidence for Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, recovery from ischemia and, guess what, diabetes already exists (Tarnopolsky. 2000;"Creatine Ameliorates Type II Diabetes")! Certainly not bad for one of those bodybuilding supplements, "anabolics" or "gateway drugs", as creatine is often mislabeled , when a 100% clueless "journalist" tries to get the attention of his editor-in-chief, wouldn't you agree?

Suggested readings (some also mentioned in the text):

• The Pharmacology of Creatine (Part 1 and Part 2) 
• Supercharging Creatine With Baking Soda (click here to read)
• 5g/day Creatine for Type II Diabetics? (click here to read)
• All posts tagged with "creatine" (click here to read)
• Phlebotomy: Can You Bleed Yourself Healthy and Lean? (click here to read)

References:

1. Barros MP, Ganini D, Lorenço-Lima L, Soares CO, Pereira B, Bechara EJ, Silveira LR, Curi R, Souza-Junior TP. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test. J Int Soc Sports Nutr. 2013 Jun 12;9(1):25. 
2. Huang J, Jones D, Luo B, Sanderson M, Soto J, Abel ED, Cooksey RC, McClain DA. Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes. 2011 Jan;60(1):80-7.
3. Orozco MN, Solomons NW, Schümann K, Friel JK. Response of urinary biomarkers of systemic oxidation to oral iron supplementation in healthy men. Food Nutr Bull. 2013 Mar;33(1):53-62. 
4. Roberts D, Smith DJ. Effects of high-intensity exercise on serum iron and α1-antitrypsin in trained and untrained men. Clin Sports Med 1989, 1:63–71.
5. Silva M, Bonomo Lde F, Oliveira Rde P, Geraldo de Lima W, Silva ME, Pedrosa ML. Effects of the interaction of diabetes and iron supplementation on hepatic and pancreatic tissues, oxidative stress markers, and liver peroxisome proliferator-activated receptor-α expression. J Clin Biochem Nutr. 2011 Sep;49(2):102-8.
6. Silva M, de Brito Magalhães CL, de Paula Oliveira R, Silva ME, Pedrosa ML. Differential expression of iron metabolism proteins in diabetic and diabetic iron-supplemented rat liver. J Biochem Mol Toxicol. 2013 Mar;26(3):123-9. 
7. Smith DJ, Roberts D. Effects of high volume and/or intense exercise on selected blood chemistry parameters. Clin Biochem 1994, 27:435–440.
8. Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Curr Opin Clin Nutr Metab Care. 2000 Nov;3(6):497-502.

Zinc: 15mg Are Plenty - After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome

Image 1 (scipop): Physicists and battery specialists know that copper and zinc make a galvanizing couple. If you put too much copper into your "battery" it will however stop working.

A recently published study from the Panjab University in India clearly suggests that doubling or quadrupling your zinc intake, a common practice in the health and fitness community, could do more harm than good. After only 4 months on a low phytate, high zinc diet (2x or 4x more zinc than in the standard chow), the rodents in the medium and high zinc intake goups showed a couple of unsettling metabolic changes (Taneja. 2013):

• 20-40% increase in food intake
• 20% increased body weight
• 2x or 2.7x elevated blood sugar
• 3.75x or 6x elevated insulin levels
• 100% increase in cortisol
• 2x or 2.5x elevated leptin levels

In short, while the Wistar rats that consumed the basal diet with the "rodent RDA" of 20mg zing per kg diet (0.53mg/day, 1mg/kg; HED ~0.17mg/kg or 8014mg/day) those with a two (human equivalent: 30mg) or four times (HED: 60mg/per) higher intakes developed all the classic symptoms of the metabolic syndrome

• insatiable hunger despite overabundant energy intake
• uncontrolled weight-gain => obesity
• high blood sugar, insulin resistance => type II diabetes
• constantly elevated cortisol levels
• leptin resistance

Interestingly, these highly undesirable effects of long-term were precipitated by profound morphological changes in the structure of the mucosal epithelial cell layer of the intestine:

Figure 1: Mean microvillus height and number/unit surface area of mucosal epithelial cell of intestine in normal zinc (control) or high zinc groups (Taneja. 2013)

The TEM studies of intestinal segment revealed a significant increase in the absorption surface area of the absorptive mucosal epithelial cells. It was reflected as increase in mean height and number/ unit surface area of the microvillus (figure 1). Their mean height (nm) was calculated as 506.1 ± 2.30 in control group-I, 749 ± 1.22 in group-II and 942 ± 1.30 in group-III. Their  number/unit surface area (µm) was found to be 10.4 ± 0.51 in group-I, 13.2 ± 0.33 in group-II and 15.4 ± 0.36 in group-III (figure 1).

The increases in height and number/unit surface area were suggestive of increased capability of the intestine to absorb the nutrients per unit area than the control group-I.

Now what is interesting about these observations is not just that it is 100% logical (at least for a physicist like me) that an increase in epithelial surface area will increase the nutrient absorption, but also that scientists knew about them and their beneficial side-effects in people with Crohn's disease, a damaged  or "leaky" gut all along (Sturniolo. 2001) and still nobody ever even thought about the downsides of subsequently increased nutrient assimilation. Instead, it was once again simply concluded that what helps the sick, obese and pre-diabetic cannot hurt normal people - and that despite the absence of ample evidence for consistent beneficial effects of  zinc supplementation as a protective, let alone curative means in sick people (Beletate. 2007), or zinc (+ magnesium) supplementation in athletes (Wilborn. 2004)

Double or quadruple your zinc intake, avoid phytates and turn from athletic to diabetic!?

Figure 2: After only 120 days the rodent in the high zinc groups exhibited all the typical symptoms of the metabolic syndrome (Taneja. 2013)

In view of the fact that still way too many gymrats adhere to the false belief that a zinc supplement (just like a "high performance" multivitamin) was an absolute staple supplement everybody striving to build a better physique should consume, it is no wonder that supplement vendors like to put copious amounts of this cheap ingredient into their products. Even if you are cheap (or smart) and avoid buying one of the "performance" multis, the 15mg of zinc every standard multi has plus the 30-50mg of your "nightly" ZMA, would take you right into the danger zone and even beyond and assuming that you follow another currently often proffered advice, which is to avoid phytate containing foods like a plague, your additional dietary zinc intake would probably get you right into the 60mg/day zone, which was so detrimental to the metabolic health of the rodents in the Tenja study.

In the defense of zinc supplements it should yet be mentioned that the chow the rodents were fed in the course of the experiment was not exactly what you, as an educated SuppVersity students would consider healthy, let alone "optimal". After all the diet was deliberately composed of "semi-synthetic" ingredients such as refined sucrose instead of the regular "grainy" pallets you would find in standard rodent chow, "to rule out the possibility of Zn-interaction with fibres and phytates" (Taneja. 2013), so that it would not take so long for the effects of the exuberant zinc intake to manifest.

"But my ZMA works! I feel so much better on it and if I drop my multi I get sick!"

"Artificial diet, rodent study, no real world implications", I hear ya! A 2004 study by Xiang et al. is yet only one out of many examples which suggest that you should not be so sure that will get away with taking your zinc-laden "staple supplements" (and in the case of the "multi" not just because of the zinc) for years: Increased lipid oxidation after 2 weeks, and increases in total cholesterol, triglycerides, LDL-C, ApoB100 and decreased in HDL and ApoA1 after 8 weeks of 50mg zinc per day in formerly healthy men are likewise clear indices of developing metabolic syndrome (Xiang. 2004). A result, by the way, that does not stand in contrast to studies on the effects of dietary zinc intake on glucose management such as Kanoni et al. (2011), where the highest dietary zinc intake of all subjects was 12.4mg (!) and thus still below the RDA and right on par with what the "average" American gets from his junkfood diet and supplements (see figure 3)!

Figure 3: I would not hope that you are eating like the "average American", are pre-diabetic and / or obese, but the data from the NHANES study is another puzzle to the picture that explains why Mr./Mrs. Average's health may benefit, while yours may suffer from supplemental zinc - they just don't get enough in their diet (Briefel. 2000)

If you are not constantly wreaking havoc on your gut lining and want it to regrow, are obese or diabetic (we do have some studies that suggest that at least in certain subgroups supplemental zinc can ameliorate this condition, yet mostly at the expense of higher insulin levels), you may want to reconsider if those staples of yours are really necessary, at least beneficial or maybe detrimental to the way you look feel and perform. And in the, as the guy at your local supp store would probably say, "totally improbable" case that despite taking all the staples he recommended, your blood glucose levels are getting out of whack, your cortisol is skyrocketing and your HDL is plummeting towards zero, you better not take his advice that all that will resolve once you introduced the latest (R-)ALA based nutrient partitioner into your supplement regimen (cf. "Lean & Muscular With Alpha Lipoic Acid?" ;-)

References:

1. Briefel RR, Bialostosky K, Kennedy-Stephenson J, McDowell MA, Ervin RB, Wright JD. Zinc intake of the U.S. population: findings from the third National Health and Nutrition Examination Survey, 1988-1994. J Nutr. 2000 May;130(5S Suppl):1367S-73S.
2. Beletate V, El Dib RP, Atallah AN. Zinc supplementation for the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005525. Review. 
3. Kanoni S, et al. Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis. Diabetes. 2011 Sep;60(9):2407-16.
4. Taneja SK, Jain M, Mandal R, Megha K. Excessive zinc in diet induces leptin resistance in Wistar rat through increased uptake of nutrients at intestinal level. J Trace Elem Med Biol. 2013 Jun 8.
5. Sturniolo GC, Di Leo V, Ferronato A, D'Odorico A, D'Incà R. Zinc supplementation tightens "leaky gut" in Crohn's disease. Inflamm Bowel Dis. 2001 May;7(2):94-8.
6. Wilborn CD, Kerksick CM, Campbell BI, Taylor LW, Marcello BM, Rasmussen CJ, Greenwood MC, Almada A, Kreider RB. Effects of Zinc Magnesium Aspartate (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism. J Int Soc Sports Nutr. 2004 Dec 31;1(2):12-20. 
7. Xiang Y, Yang X, Bian J, Wang L. [Effects of high level Zn intake on metabolism in man]. Wei Sheng Yan Jiu. 2004 Nov;33(6):727-31.

Epigallocatechin Gallate (EGCG), Capsaicins, Piperine & Carnitine: Rather a Health Than a Fat Loss Stack?

That's not what the ultimate weight loss diet looks like. The pill remains a supplement, i.e. something to supplement (and support) your dietary and exercise efforts, nothing more, but - as long as you pick the right one for your type and goal - also nothing less (photo ehow.com)

Let me first remind you of the fact that something that works in your obese neighbor does not necessarily work as effectively in someone like yourself, a devoted physical culturist who is only a couple of steps away from the six pack he has always been dreaming of. Let me also emphasize the fact that taking the supplement alone, i.e without the -600kcal reduction in energy intake all of the 86 overweight subjects (healthy males and females aged 25–45 years, with a body mass index greater than 25 kg/m² less than 35 kg/m²) had to stick to, there probably wouldn't have been any weight loss at all. And lastly, let me also formulate the hypothesis that the various health benefits, such as the increases in insulin sensitivity, the improvements in the leptin/adiponectin ratio or the decreasing LDL levels would probably have been less pronounced without the game-changing reduction in energy intake.

Simple Truth: The right diet, not the right supplements is the key factor in losing body fat

Apropos reduction in energy intake, one of the most underrated but practically highly relevant beneficial effects the administration of the epigallocatechin gallate (EGCG from green tea), capsaicins, piperine, L-carnitine and a few minor ingredients (see figure 1, left) probably brought about certainly were the psychological benefits, such as the 3.3 pts decrease on the Beck depression inventory (BDI-II), since the ability and will to adhere to a diet - whether this may be for 8 weeks as in the study at hand or (preferably) for life - obviously hinges on the question: "Can you stick to it?"

Figure 1: Energy content (primary axis in kcal) and macronutrient composition (secondary axis in g) and ingredients of the of the weight loss supplement (Rondanelli. 2013)

That said, the diet composition in figure 1 (left) certainly raises another question: "Would it even be wise to adhere to this diet for longer than 8 weeks?" I mean it stands out of question that living on a caloric deficit for the rest of your life is not an option. If you look a the macronutrient composition of the diet, on the other hand, my personal  prognosis is that this program will not yield long-term success. Not because it's high in carbs, but because it is too low in protein and lacks an exercise component - typical mainstream dieting = typical mainstream failure - with or without "bioactive food ingredients" (Rondanelli. 2013).

Fat loss or anti-diabesity stack? That is the question!

The combination of a lack of exercise stimuli and a relatively low dietary protein intake (certainly below the threshold limit of 10g+ of EAA per meal) is probably also the main reason for the slight loss in lean muscle tissue, a phenomenon  - and that's interesting, although the difference did not reach statistical significance - occured only in the supplemented  group.

Figure 2: Changes in body composition (left) and selected markers of glucose management and fatty acid metabolism, adipokine expression and inflammation (Rondelli. 2013)

Now, there are obviously dozens of potential reasons for the minimal muscle loss in the supplement group. In my humble opinion the most likely explanation does yet relate to the very same increase in resting energy expenditure (+120.6kcal/day) that's (alongside the metabolic improvements, cf. figure 2, left) behind the additional 600g of body fat, the subjects in the supplement group shed in the course of the 8-week dietary intervention.

"600g in 8 weeks? Are you kiddin' me?"

Yep, you read me right, 600grams is all the supplement yielded as far as additional fat loss is concerned. That, plus the fact that neither this, nor any of the differences in between the changes in anthropometric data reached significance does tell you something about the actual weight loss effects even obese and insulin resistant subjects can expect from taking an epigallocatechin gallate (EGCG from green tea), capsaicins, piperine and L-carnitine based dietary supplement.

What? That's pathetic? Well, it would be if these changes were not accompanied by way more important and statistically significant different effects on the insulin sensitivity of the 41 overweight subjects in the supplement group who completed the study.

As far as the inhibition of diet induced weight gain and insulin resistance are concerned, there is no synergism of green tea and the L. plantarum, a probiotic. Green tea does the job, the bacteria stand by and watch in awe (read more)

Bottom line: As I've pointed out numerous times before. There are a different types of weight loss adjuvants, with one of the most general, if you will "fundamental" distinctions between (a) those weight loss supplements that have a more or less pronounced direct effect on the energy balance (=carb/fat blocker, beta-agonists, thyroid mimetics, appetite suppressants etc.) and (b) their healthier cousins that promote your weight loss efforts by ironing out acquired metabolic obstacles, such as leptin and insulin resistance. And though you could certainly make a point that green tea exhibits some features of both categories, the overall stack used in this study belongs to the second category and it's efficacy is therefore going to drop the healthier (=less inflamed, insulin & leptin sensitive) you are, when you start dieting.

You may want to keep that, as well as the (un-)fortunate truth that there simply is no "fat burner pill" on the market that will do the allegedly hard dieting and exercising for you, in mind, whenever you pass by the storeboard with the virtual or real shelves of a supplement store and are tempted to invest 50$ or so into yet another "next generation fat burner"... without having a diet and workout plan and the will to stick to it, you can just as well save the 50$.

References:

• Rondanelli M, Opizzi A, Perna S, Faliva M, Solerte SB, Fioravanti M, Klersy C, Edda C, Maddalena P, Luciano S, Paola C, Emanuela C, Claudia S, Donini LM. Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months' consumption of a combination of bioactive food ingredients in overweight subjects. Endocrine. 2013 Dec 28. [Epub ahead of print]