Minimal Carb Reduction, Maximal Results? Study Compares 60% vs. 40% CHO Diets + 6-Week 25% Energy Reduction

Does "moderate low carb" work? And if so how much of the usual triglyceride and glucose lowering benefits of walking the whole nine yard are you going to miss?

I know that 40% carbs is not what you consider "moderate", but for most of our fellow countrymen and women, cutting back on at least one serving of their beloved pasta and bread is already more than you can ask for if you want a compliance that's beyond 1%. Against that background it is all the more important to know whether even small changes in the overall carbohydrate intake have to offer obviously less pronounced, but still significantly beneficial health benefits to overweight and obese individuals -- small changes like the 20% reduction in carbohydrate intake in the "moderately-restricted carbohydrate diet" (MRCD) arm of the most recent study from the Isfahan University of Medical Sciences in Teheran, Iran (Rajaie. 2014), for example.

1/2 low carb = 100% adherence, but at which costs?

The experiment was conducted by Somayeh Rajaie and colleagues. The results will be published in the January 2014 edition of the peer-reviewed scientific journal Nutrition. Results of which the authors say that they are particularly relevant, because...

"[...e]arlier studies on the management of metabolic syndrome (MetS) have mostly focused on very low carbohydrate diets" whereas long-term adherence to such diets is difficult for apparently healthy people."(Rajaie. 2014)

I can already hear the first people arguing that this was bullshit. What is bullshit, though, is to close your eyes and ignore the real world problems people encounter, when they go from years of sugar, sugar, sugar, sugar and fat to diet that have almost no sugar in them. I mean, come on low carb boys and girls, ask your non-fitness-infected friends about going without pasta and pizza for the rest of their lives. What are these people going to answer? ... You see: long-term adherence to very-low-carb diets is difficult for the average "apparently healthy people", the Iranian scientists are talking about, here ;-)

Figure 1: Number of servings from different food groups (left) and macronutrient composition (right) of the basleine diet of the 39 overweight study participants (Rajaie. 2014)

While it may not be as straight forward as it is with rodent studies, we still have to take into account that the baseline diet could render the significance of the data from a human study similarly questionable as that from rodent studies. Figure 1 does yet tell you that these aforementioned "average apparently healthy" man or woman in Iran eats pretty much the same sh*t as his / her American or European counterparts: a diet that's a "perfect" mixture of fats and sugar that will blow you up much more effectively than a really high carbohydrate + low fat, or a really low carbohydrate + high fat diet.

Apropos "high carbohydrate": The basline carbohydrate intake is actually so "low", that the subjects in the high carbohydrate group of the study at hand had to increase their carbohydrate intake to get it up to the recommended 60% of their total energy intake. By implication, this means that the subjects in the "moderately restricted carbohydrate" group didn't reduce their carbohydrate intake by 20% (as the abstract appears to imply), but only by 10% vs. baseline.

Adding or subtracting 10% carbs - what's better when you're dieting?

Ok, enough of the number games. Basically what I am trying to say was that the effective reduction in carbohydrate intake during the 6-week intervention period is only 10% - not 20%, as the difference between the high carbohydrate and the "moderately restricted" carbohydrate group (MRC) would suggest.

Figure 2: Macronutrient composition of the diets during the 6-week intervention (left) and changes in macrontrient composition (right) expressed relative to baseline (Rajaie. 2014)

As I already pointed out, this implies that the high carbohydrate group effectively increased their relative carbohydrate intake (see Figure 2, right). In contrast to what the increasing number of carbophobs out there would probably have expected, this outrageous increase in carbohydrate intake did not result in weight or fat gain.

Small changes make a difference! But that's small changes in energy, not carbohydrate intake

As the data in Figure 3 goes to show you, both groups lost almost exactly the same amount of body weight (1.72kg HC vs. 1.70kg MRC), they also gained the same ~800g of lean mass and lost 1.3kg of body fat.

Figure 3: Changes in body weight, BMI and body composition after 6 weeks (Rajiae. 2014)

In other words: From a body composition perspective the 20% difference in carbohydrate intake obviously didn't make a difference - and the "trend toward greater reduction in waist" in the MRC group, the authors highlight in their abstract could be mediated by the baseline difference (1 cm larger waists in the MRC group).

A very similar image emerges for the often advertised beneficial effects "real" low carb diets have on the serum triglyceride (TG) levels. In the "moderately restricted carbohydrate" group, they were simply not there. With a p-value of p = 0.07 for the inter-group difference, these changes were even more "random" than the previously cited effects on the waist line. And if the "greater reduction of systolic blood pressure (−8.93 versus −2.97 mm Hg; P = 0.06) and diastolic blood pressure (−12.7 versus −1.77 mm Hg; P = 0.001)" in the MRC group was not simply a result of a (in the long term) not necessarily beneficial reduction in the sympathetic tone is similarly difficult to tell.

Read: " Two Days A Week High Protein, Low Carb Fast Cuts >10% of Body Fat in 4 Months" | more

Bottom line: Hovering around in the "comfort zone" is not going to help you make huge changes. When you run a 25% energy restriction you will lose body weight. As the study at hand shows, even without sacrificing muscle tissue. Whether you do that with a 40% or 60% carbohydrate does not appear to matter for the average overweight individual.

Long story short, if you don't go to the extremes and adhere to a sane energy deficit (>20%, but <35%), it really doesn't matter whether you eat some more carbs or some more fats. And let's be honest, brutally honest: For an increasing part of the ever more obese inhabitants of the Western obesity belt, it would already be a remarkable achievement not to get fatter every day. If these people managed to lose ~1.3kg of pure fat while increasing their lean mass by almost 1kg that would be a major success.

Reference:

• Rajaie, S., Azadbakht, L., Khazaei, M., Sherbafchi, M., & Esmaillzadeh, A. (2014). Moderate replacement of carbohydrates by dietary fats affects features of metabolic syndrome: A randomized crossover clinical trial. Nutrition, 30(1), 61-68.

Sucralose, Hazardous or Innocent? Part II: Appetite, Gut Health & Food Reward | Sucralose, Gluttony & Adiposity?

Plain mineral water is still the best thing to quench your thirst.

Today we are going to continue our thorough, educated reading of the recently published overview over the biological issues with sucrolase, a "popular" artificial sweetener most of you will probably know by its brand name Splenda. The focus of part I of this series was on the potential pro-diabetic effects of this agent that belongs to a class of molecules that has originally been hailed as a solution to the diabetes problem (it goes without saying that I am talking about artificial sweeteners here, right?). In a way we are thus only continuing the discussion, when we are trying to verify Schiffman's & Rother's argument that the consumption of sucralose is associated with an increase in obesity risk... or, put more simply that using sucralose is going to make you fat, not lean.

The good old "energy in" vs. "energy out" argument

As SuppVersity readers you are well aware that the oversimplified concept of an "energy balance" is fundamentally flawed. My recent post "Anorexia study suggests: Your body can easily reduce its resting metabolic rate by 10%" in the SuppVersity Facebook News is only one out of thousands of scientific papers you could quote to point out that replacing 420kcal of energy from pure sugar, i.e. three cans of regular coke, with its diet variety is not going to produce a net weight, let alone fat loss of 420g per week (suggested read: "Busting the 3,500kcal = 1lbs Weight Loss Myth!" | learn more).

This is part II of a multi-part series:

Sucralose, insulin, glucose, GLP-1

Appetite, Obesity & Gut Health

Cancer, Drug & Hormone Interact.

I know that Mark Sisson likes to says this, but this website is not written by a machine, but by a man who has the same "short" 24h days you have... basically, what I am trying to say is that I had to split this review of the review into a "trilogy" - and be honest, you wouldn't want an article thrice as long as this one, would you?

Thus being "in the know", you can only shake your head, when you read how Schiffman and Rother (ab-)use a recent study by Ruyter et al. (2012) to support the non-significant, not sufficiently differentiated data from epidemiological studies which inform us that obese people are more likely to consume artificial sweetened products than lean ones, to subliminally imply that artificial sweeteners would not help, in some cases even hinder weight loss.

"In an 18-mo trial with children, participants were randomly assigned to receive an 8-oz can per day of either a noncalorically sweetened or a sugarsweetened beverage that provided 104 kcal (de Ruyter et al., 2012). [...] The calorie consumption from these beverages was 46,627 kcal greater for children in the sugar-sweetened group than in the sucralose-sweetened group (5.8 × 77.3 × 104). In spite of this highly significant difference in calories consumed from the beverages, the total weight gain over this 18-mo study was only 1 kg greater for children in the sugar-sweetened group compared to sucralose group. No explanation was provided to account for the small difference in weight gain given the large difference in caloric consumption from the beverages." (Schiffman. 2013)

Despite the fact that Schiffman & Rother acknowledge that the scientists would not have been able to detect, if the children who consumed the sugar-sweetened beverages compensated by reducing their food intake, the reviewers fail to point out that neither this, nor the second "evidence" they cite, a 2-year study by Ebbeling et al. (2012), where Schiffman & Rother simply ignore the fact that the mere provision of diet sodas to the families of the adolescent subjects did reduce the weight gain in the active intervention period (1st year, see Figure 1, below), would confirm a negative real-world effect on body weight.

Figure 1: Change in body fat percentage (vs. basleline) of adolescents during the intervention & follow up period in the Ebbeling study (2012), of which the reviewers only cite the results of the follow up.

Let's be honest: If you actually take a look at the results from the Ebbeling study (Figure 1), you will have to concede that this study refutes the claim that artificial sweeteners make you fat. During the active treatment period, in the course of which the adolescent participants were...

• 

  "What Really Happens, When Nutrition Science Meets Real Life" | more

  ... supplied with noncaloric beverages (e.g., bottled water and “diet” beverages for the whole family) every 2 weeks, getting monthly motivational telephone calls with parents (30 minutes per call), 
• ... having three check-in visits with participants (20 minutes per visit), and 
• ... receiving written intervention messages with instructions to drink the delivered beverages and not to buy or drink sugar-sweetened beverages, were mailed to participants

...they do exactly what we originally expected them to do: They ameliorate the body fat gain in the adolescent subjects. In other words: As long as respective products are available, and dietary adherence is encourages, replacing regular sugar sweetened with artificial sweetened or unsweetened beverages can have a significant ameliorative effect on the body fat gains of adolescents - irrespective of the fact that they were obviously free to compensate with chocolate, cookies, etc..

Contemporary evidence from RCTs suggest either no, or beneficial effects

If you follow Schiffman's and Rother's lead and discard potential differences between sucrose and other sweeteners, acknowledge the fact that the results from previous rodent experiments have repeatedly failed to translate to human beings and take into account that this data is "inconsistent and conflicting" (Schiffman. 2013), anyways, you will be hard pressed to find arguments to support the claim that artificial sweeteners could hinder weight loss.

"No-Carb Foods, Artificial Sweeteners & The Cravings" | more

Potential mechanisms for the obesogenic effects: In a very detailed review Mattes & Popkin list a whole host of hypothesis ranging from the disproven stimulation of insulin and differences in the GLP-1 response, over osmotic effects and increase food palatability, up to the "Zero sugar, great, I'll have 10 instead of one of those cookies!" effect and the development of an extremely sweet tooth. What's important, though, is that none of this mechanisms is "supported by the available evidence, although some warrant further consideration" (Mattes. 2009).

In fact, the vast majority of RCTs clearly supports the assumption that non-nutritive sweeteners (NNS), artificial or not, promote weight loss and blunt weight (re-)gain (De la Hunty. 2006; Bellisle. 2007). The argument that these effects do satisfy the calories in vs. calories out hypothesis is pathetic, to say the least. Even a 100% controlled diet won't comply to an equation that is about as accurate as "1+2=343". We can thus register that:

1. There is ample evidence to support the beneficial effects of artificial sweeteners (including sucralose) as a tool during controlled dietary interventions.
2. There is insufficient evidence to support the claim that their regular consumption has a negative effect on body weight.

With respect to (2) we would even have to say that the limited amount of useful* evidence we have would rather suggest beneficial than detrimental effects (*a 'useful' study is not a study that tells me that obese individuals are more likely to consume artificially sweetened products than lean ones like the often cited epidemiological data). This is particularly true, for controlled interventions where sugar-sweetened beverages were replaced by their artificially sweetened counterparts.

The great unknown: Hunger, appetite and food reward

If data on the real-world effects of sucralose consumption on body weight gain is "scarce", consistent, experimentally verified hypotheses that would explain the potential underlying mechanism are quasi non-existent... or, I should clarify: They are still in their infancy. Against that background it's quite astonishing that more and more people appear to take it for granted that the consumption of artificially sweetened foods will mess with both, (a) your ability to control your energy intake and (b) the hedonistic response you derive from foods.

Table 1: Sweetness, dose to stimulate the sweet taste receptor (EC50; based on Matsuda. 2011) and correlation of sweetness and EC-50 value.

It goes without saying that there is no sucralose-specifc data out there, but the decrease in hypothalamic sweet taste receptor density I mentioned in the first installment of this series is something I'd expect to see in response to all artificial sweeteners that make it across the blood brain barrier (Note: Even Schiffman & Rother acknowledge that we do not know if they even do that!) - probably "sweetness" dependent,  by the way.  This would imply that sucralose would be the worst, cyclamate the least offender among the common artificial sweeteners in Table 1. With a sweetness that's 300x higher than that of sucrose, stevia would end up being the "(un?)happy medium".

Despite the fact that Schiffman & Rother don't really address this issue in their paper, I still want want to address the practical and thus relevant aspect of the various proposed theories for potential sweetener-induced increases in energy consumption.

Figure 2: Mean effective change in energy intake (%) in RCTs investigating the degree of energy compensation in response to the provision of artificial sweetened products (De la Hunty. 2006)

As the data from De La Hunty's 2006 meta-analysis of 32 study outcomes in Figure 2 clearly demonstrates, there is a statistically highly significant (p < 0.001) trend towards reduced energy consumption in the RCT [randomized controlled trial]. In that, the degree of compensation for the sudden energy reduction due to ingestion of calorically less dense, since artificially sweetened product ranged from statistically non-significant 18% to statistically highly significant 86% in trials such as Porikos et al. (1982), where 6 men lost and gained 0.8kg of body weight within 2x12 days in a metabolic ward on artificially sweetened and sucrose sweetened ad-libitum diets, respectively.

Non-nutritive sweetener (NNS) intake 1965-2004 (Mattes. 2009)

So, sweeteners can't ever make you hungry? I would not necessary subscribe to this idea. While the consumption of artificial sweetened foods as part of your regular diet, e.g. diet coke with your dinner, does not seem to be a problem, Mattes & Popkin (2009) rightly point out that "non-energy-yielding products may heighten appetite", when they are not "ingested in conjunction with other energy sources". So, if you are guzzling diet coke all day, this may very well trigger binge eating. With an ever increasing consumption of sweeteners from partially / totally artificially sweetened beverages (see table to the left), this could thus well be part of our obesity problem.

Just like the previously discussed (relatively short term) effects on insulin, GLP-1 and co, the #2 on the list of most frequently heard objections against the use of artificial sweeteners, i.e. dietary overcompensation, does thus appear to have little basis in fact. What we do not know, though, is whether the results will be identical for all types of sweeteners, or whether sucralose may be the toxic (this aspect will be covered in the next installment) or gut microbiome disrupting exception to the rule.

Sucralose induces changes in the gut microbiome

The last issue I want to address in this second installment of the "Sucralose, Hazardous or Innocent Trilogy" will thus revolve around the question, whether a modulatory effect of sucralose on the microbial composition of your gut could induce potential negative long-term effects that would not show up in the hitherto discussed RCTs.

Under the headline "Effect of Sucralose on the Number and Relative Proportions of Different Intestinal Bacterial Types", Schiffman & Rother argue that it has long been known that bacteria from the oral cavity and soil cannot use sucralose as a growth substrate. If the same was true for the bacteria in our guts the replacement of regular sugar with sucralose would thus starve our (beneficial) subtenants.

Table 2: Differences (%) in bacterial counts in feces of rodents on diets containing what in human terms would be ~14mg, 43mg, 71mg and 156mg of sucralose per day after 12 weeks treatment and 12 weeks into "recovery" (Abou-Donia. 2008)

Based on the fecal bacterial count of rodents on diets that would be equivalent to 14mg, 43mg, 71mg and 156mg of sucralose per day in human beings (see Table 2), Schiffman & Rother argue that chronic (12-week) ingestion of relatively low amounts of sucralose (a single can of Diet Crush Cream Soda, for example, has 42mg of sucralose) lead to highly significant reductions in the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria.

In view of the fact that Abou-Donia et al. (2008) observed the most significant losses in bifido- and lactobacillus strains, i.e. those strains that have repeatedly been implicated as the driving forces of the beneficial health effects of probiotic supplementation, this and not the previously discussed pro-diabesity effects should be the point where people start to freak out.

Table 4: Other sweeteners are preferred food for certain bacteria and may also alter the gut microbiome (Payne. 2012).

This is particularly true if you take into account that at least part of the beneficial effects of lactobacilli may be related to their ability to keep the number of enterobacteria, a large family of Gram-negative bacteria that includes both harmless symbionts, as well as a whole host of familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella, Proteus, Enterobacter, Serratia, and Citrobacter in check (Liévin-Le Moal. 2006) - exactly those bacteria, which produce the nasty lipo polysaccharides (LPS) that have been associated with inflammation and its downstream metabolic effects, such as obesity, diabetes, heart disease, gastrointestinal cancer etc. and, as the data in Table 2 tells you. Now, unfortunately, the these villains are all part only type of bacteria that was not significantly decimated by the sucralose challenge.

As Schiffman et al. point out these reductions are not, as Brusick et al. (2009) suggest simply a result of "normal variation". In fact, the probability to see a similar random reduction in bifidobacterial count occur "naturally"within 12 weeks would be 1/5000. It is thus more than just unlikely that the71.9%, 76%, and 77.7% reductions in bifidobacteria counts Abou-Donia et al. observed at dosages of 3.3, 5.5, and 11 mg/kg/d were coincidental.

Prebiotics, anyone? In view of the alleged neg. effects on your gut microbiome, you may feel inclined to increase your prebiotic intake. If that's the case, this top 10 list of food items with prebiotic fiber contents of up to 65% of total weight may help:

1. Chicory root - 65%
2. Jerusalem artichoke - 32%
3. Dandelion greens - 24%
4. Garlic - 18%
5. Leek - 12%
6. Onion - 9% 
7. Cooked Onion - 5% 
8. Asparagus - 5% 
9. Wheat bran - 5% 
10. Banana - 1% 

Remember: These are the "richest" not necessary the "best" sources ;-)

If there is reason to be concerned it's about your gut health and its downstream metabolic effects: In view of the important role of bacteroides for the health of the intestinal eco-system (Lee. 2013) and their persistent reduction even after the 12-week recovery period, the selective antibiotic activity of sucralose is as of now the by far most disconcerting negative health effect discussed in this series.

If the changes Abou-Donia et al. observed in their rodent studies were to be confirmed in human studies, where the subjects consumed a balanced whole foods diet with a high prebiotic content. The profound changes the researchers from the Duke University Medical Center report in their paper from September 2008 would be reason enough to revise my previous conclusions about a potential contribution of sucrose to the diabesity (=obesity + diabetes) epidemic.

In fact, a revision of the potential long(er) term downstream effects of sucralose on your metabolic health could be all the more indicated, if it turns out that the alleged toxic and endocrine-disrupting effects I will discuss in the next installment of this series turn out to be substantiated, as well.

Reference:

• Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health, Part A, 71(21), 1415-1429.
• Bellisle, F., & Drewnowski, A. (2007). Intense sweeteners, energy intake and the control of body weight. European Journal of Clinical Nutrition, 61(6), 691-700.
• De la Hunty, A., Gibson, S., & Ashwell, M. (2006). A review of the effectiveness of aspartame in helping with weight control. Nutrition Bulletin, 31(2), 115-128.
• de Ruyter, J. C., Olthof, M. R., Seidell, J. C., & Katan, M. B. (2012). A trial of sugar-free or sugar-sweetened beverages and body weight in children. New England Journal of Medicine, 367(15), 1397-1406.
• Ebbeling, C. B., Feldman, H. A., Chomitz, V. R., Antonelli, T. A., Gortmaker, S. L., Osganian, S. K., & Ludwig, D. S. (2012). A randomized trial of sugar-sweetened beverages and adolescent body weight. New England Journal of Medicine, 367(15), 1407-1416.
• Liévin-Le Moal, V., & Servin, A. L. (2006). The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota. Clinical Microbiology Reviews, 19(2), 315-337.
• Mattes, R. D. (1996). Dietary compensation by humans for supplemental energy provided as ethanol or carbohydrate in fluids. Physiology & Behavior, 59(1), 179-187.
• Mattes, R. D., & Popkin, B. M. (2009). Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. The American journal of clinical nutrition, 89(1), 1-14.
• Payne, A. N., Chassard, C., & Lacroix, C. (2012). Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity. Obesity Reviews, 13(9), 799-809.
• Porikos, K. P., Hesser, M. F., & Van Itallie, T. B. (1982). Caloric regulation in normal-weight men maintained on a palatable diet of concentional foods. Physiology & behavior, 29(2), 293-300.
• Schiffman, S. S., & Rother, K. I. (2013). Sucralose, A Synthetic Organochlorine Sweetener: Overview Of Biological Issues. Journal of Toxicology and Environmental Health, Part B, 16(7), 399-451. 

Warding Off Holiday Weight Gain 2.0: The Anti-Diabesity Effect of Coffee Goes Beyond its Caffeine Content.

Image 1: If they are not laden with pesticides and anti-fungals, the small brown beans from the coffee pant can easily compete with green, black oolong and pu-erh teas, when it comes to countering the unwanted side-effects of the "holiday diet"

Back in the days, both, tea and coffee were luxury goods and people felt privileged if they could have any of them. Today, they have become another of the endless commodities of our convenience society, where coffee, the former drink of the kings (and popes), has gotten a bad rep lately as being the underlying cause of the "adrenal burnout" that has befallen 90% of the visitors of pertinent Internet bulletin boards. I was thusly not surprised that SuppVersity student Fat Free commented yesterday's blogpost on the anti-obesity effects of tea rather sheepishly. As if his wish for "a coffee" on the list of the anti-holiday-weight-gain items was some atrocious act in the sense that "a coffee" could never be as healthy as a hip green tea. I mean wasn't it bad enough that the "holy" green tea was outperformed by its primitive black brother?

Well, guess what, dear green tea connoisseurs, it may well be that (organic) coffee beans are in no way inferior to the unquestionably healthy, yet recently slightly over-hyped unoxidized camellia sinensis leaves. At least this is what a soon to be published study by Yuji Matsuda and his colleagues from the Nagoja University in Japan would suggest (Matsuda. 2011).

Tea or coffee during the holiday season - only a matter taste?

Matsuda et al. put a group of 8-week old mice on a pro-diabetic high-fat diet (this is the type of "high fat diet" that is high both in fat and in carbs and thusly is a perfect image of what 75% of the people are "eating" in the holiday season ;-). In the course of the 17-week study period the mice received either regular drinking water, or 2.5x diluted coffee, or water that was laced with 200mg of caffeine per liter (with a water intake of 13-14g/100g BW this would translate to a daily dose of 2.8mg/100mg and a human equivalent of 2.3mg/kg, or 182mg of caffeine per day for an 80kg human being). The intention was to investigate whether the results of epidemiological studies by van Dam (2002; 2005), Huxley (2009) and Goto (2011), which suggest that regular coffee consumption is associated with a profoundly reduced risk of developing metabolic syndrome or type II diabetes, could be replicated in a laboratory setting.

Figure 1: Body weight at the beginning and end of the study period in the control group and the mice receiving 2.5x dilluted coffee or 200mg/L caffeine in their drinking water; food intake in g per 100g of  body weight (data adapted from Matsuda. 2011).

If you look at the weight changes of the animals in figure 1, it becomes evident that despite a (non significantly) greater food intake esp. in the "real coffee" group, the mice on the coffee or caffeine supplemented high-fat diets gained approx. 8% less body weight than their water guzzling peers.

Figure 2: Fat weight in mice after 17 weeks on high fat diet with either water, 2.5x diluted coffee or water + 200mg caffeine per L (data adapted from Matsuda. 2011).

Now while the intrinsically flawed concept of a "body mass index" that is still propagated by mainstream media would suggest that there is something like an "ideal body weight", the numbers on your scale, alone, have no predictive value in terms of future health risk. The reductions in visceral (epididymal fat) and subcatenous fat accumulation in the mice of the coffee and caffeine arm is thusly a considerably more important finding of this study than the slightly reduced weight gain. After all, the amount of visceral (=inter-organ) fat you are carrying around is one of the few relatively reliable indicators of whether you are going to see your grand-children graduate, or not.

Time and again: Whole foods, or drinks, outperform extracts

If you take a closer look you will notice that despite a general tendency towards lower body fat levels in the coffee and caffeine group, the "whole food", or I should say, "whole beverage" has a much more pronounced effect on the "bad" visceral (epididymal) fat depots. So, just in case you still like your pills, caps and powders: This is only the latest in a long line of foods (this is the stuff that is not sold in caps or powder form) with verified health benefits, where one isolated compound, of which we believe that it is the "active ingredient" turns less potent than the whole food - so, could it possibly be that Nature knows best?

Figure 3: Reductions in inflammatory cytokine (MCP-1, TNF-alpha, IL-6) and adipokine expression in the epididymal fat pads of mice receiving 2.5x diluted coffee or water laced with 200mg/L caffeine in addition to their high fat diet (data calculated based on Matsuda. 2011).

The "whole foods" vs. "extract" difference is also evident in the differential effects coffee and caffeine had the expression of the inflammatory cytokines MCP-1, TNF-Alpha and IL-6 and the adipokines adiponectin and leptin. With a more pronounced expression of the latter (leptin) and an almost identical expression of the former (adiponectin) indicating an improved visceral fat metabolism in the epididymal fat pads of the "coffee-drinking" mice.

Figure 4: Insulin response (area under the curve in mg * min / dl) during glucose tolerance at different time-points during the 17-week study period (data calculated based on Matsuda. 2011).

As the areas under the insulin response curve in the glucose tolerance test go to show. Coffee (=whole food!) consumption does also reduce the transient caffeine induced decrease in insulin sensitivity that has been touted as one of the reasons why coffee would be "bad" for you. As the data from the study goes to show, this effect is only temporary, even for plain caffeine and should not be an issue for the habitual coffee drinker. Moreover, the long term benefits totally outweigh any short term increases in fasting blood glucose (approx. +8% in the first weeks of the study) - or, getting back to the initial research hypothesis: Coffee consumption is a possible way to reduce the risk of developing type II diabetes (at least  for mice ;-)

Coffee or tea? The choice is up to thee!

Since a direct comparison of the data from yesterday's tea study on teas would not be valid, anyways, and because I do not want to disturb the pre-Chrismas harmony and provoke a war between coffee and tea drinkers in the comment area of this blogpost, I would just advice everyone to just decline the soda your relatives may be offering you over the holidays and stick to either tea or coffee... whatever you like better - and by the way, dehydration is neither an issue for the habitual tea nor the habitual coffee drinker (Grandjean. 2000)!

Is Hypoglycemia Obesogenic? Is the GI Totally Worthless? Is Mild, But Chronic Stress Behind the Diabesity Pandemic? Is Leptin Obesogenic? And How Do You Calculate the Energy Requirements of Diabetics?

One of the mistakes researchers and dieters make time and again, using the scale as their only guide

Since I had a couple of interesting, but not earth-shatteringly exciting studies on obesity, body weight gain, the GI, leptin and a couple of other things lying around, I thought I'd compile a brief potpourri for you to get you on par with the helplessness with which researchers are still facing the diabesity pandemic. So don't expect any of the one-size-fits-it-all solutions the scientists still appear to be looking for from any of the following items. What you may find, however, is some inspiration when you read between the lines or follow up on the suggested reads, I mention. And if that's not the case, you can still browse previous articles on fat loss or simply go to the gym and try the fat loss example routine from the SuppVersity "Step By Step Guide for Your Own Workout Routine" or simply go to be early to preserve your circadian rhythm.

• Going "Hypo" time and again will make you fat (McNay. 2012) -- Usually you think of hyogylcemia as a sign of a lack of energy, yet despite the fact that this may well be the case this very lack in energy has recently been shown to exert obesogenic effects in a rodent model.
  
  

  

  Often a picture says more than 1000 words: Normal (left) and repeatedly hypoglycemic rodents after 8 months of weekly insulin injections (McNay. 2012)

  The weekly injections Ewan C McNay and his colleagues administered to their rodents and the subsequent episodes of hypoglycemia lead to profound weight gain in the absence of diabetes, hyperphagia, changes in hypothalamic NPY or POMC mRNA expression and  the other usual suspects that could explain this phenomenon. The one thing that's left is therefore what the researchers call a "multi-faceted deficit in metabolic regulation" (McNay. 2012) - interestingly enough the 69.5% higher body weight at 12 months went hand in hand with the usual laziness (-25% activity) of people whose brains are starving in abundance (e.g. type II diabetics).
  
  What remains to be seen, though, is whether similar effects would occur in response to "regular" non-insulin induced hypoglycemia. In view of the easy with which crash dieters and people with roller-coaster blood glucose levels gain weight, it is yet not unlikely that it is actually the avoidance of (reactive) hypoglycemia and not so so much the prevention of hyperglycemia that makes low GI diets successful for weight maintenance (for weight loss the picture is more complicated, since this will require a energy deficit and that's a game changer).

• Dietary glycemic index and load are not associated with type II diabetes risk in 12,403 Europeans (Sluijs. 2012) -- Apropos GI, scientists from the University Medical Center in Utrecht did not find statistical significant correlations dietary glycemic index and/or glycemic load and the risk to develop type II diabetes in in a subcohort of the European Prospective Investigation into Cancer and Nutrition Study (n = 12,403 participants).
  
  Even when they compared participants in the highest and lowest quantiles, the increase in risk was only 5% and 7% for GI and GL respectively. Since this is by no means the first study that suggests that the still propagated concept of the beneficial health effects "low GI diets" is faulty, I would suggest you rather watch the actual food items, than their respective glycemic indexes if you intend to ward off obesity and diabetes. Potatoes for example may have a high GI (including sweet potatoes, by the way), but their high potassium and overall mineral content, as well as the mere fact that you can hardly eat the same amount of total carbohydrates you can easily annihilate, when you are eating pasta still makes them one of the best sources of starchy carbs you have (learn more in the Potato Manifesto, Part I & II).

• 

  Figure 1: There were no statistically significant difference in terms of weight gain or loss, but the 2-week re-feed had a greater impact on blood glucose and insulin levels in the high GI group (Lagerpusch. 2012)

  There is use for the GI on a bulk or after a diet, but only if you are concerned about insulin sensitivity (Lagerpusch. 2012) -- While the general value of the GI as a means to distinguish good from bad carbohydrate sources is certainly questionable, the recently published results from a study that was conducted at the Institute of Human Nutrition and Food Science, of the -Albrechts University in Kiel, Germany, does suggest that monitoring the GI of your diet and adding additional fiber to reduce the insulin response to your meals can come quite handy, in phases, where you are particularly prone to store body fat. On a bulk, for example, or even more so when you have been dieting and are trying to return to a normal caloric intake.
  
  According to the results Lagerpusch et al. present in the November issue of the British Journal of Nutrition even healthy young men who were subjected to a 3-week diet phase (-50% in caloric intake) and subsequent overfeeding (+50% in caloric intake) the subjects in the high GI study arm had a 135% higher increase in fasting insulin levels during the refeed than those in the low GI group. In view of the fact that the glucose clearance (measured in an oral glucose tolerance test) was identical, it is not only no wonder that the weight gain did not differ either (see figure 1), but also unlikely that we would see significant differences as far as the fat gains are concerned (the latter were unfortunately not measured in the study at hand). At the same time, longer hyper-caloric high GI diets are certainly a risk factor for both insulin resistance and obesity, so that you are probably still at lower risk with 65g instead of 27g of fibre per day and a mean GI of 40 vs. 74.
  
  If you are interested in the influence of different diets on weight gain and health during overfeeding, I suggest you check out the following two SuppVersity posts: "194 Bananas in Three Weeks" and "A Tale of Macro- and Micronutrient Modifications".

• 

  Figure 2: Chronic mild stress leads to an overactivation of the HTPA and subsequen metabolic dysregulations (Takahashi. 2012)

  Further evidence that chronic mild stress is to blame for the obesity pandemic (Takahashi. 2012) -- As researchers from the Tohoku University Graduate School of Medicine in Japan report in the latest issue of the  American Journal of Physiology - Endocrinology & Metabolism, the localized re-setting of the clock genes in the liver, yet not the hypothalamic suprachiasmatic nuculeus (SCN), of BALB/c mice in response to chronic mild stress exposure elevated and phase-shifted serum corticosterone levels (see figure 2).
  
  Takahashi et al. argue that the observed changes are indicative of an overactivation of the HPA axis, which induced disturbances in the rhythmic expressions of core clock genes, e.g. Clock, Npas2, Bmal1, Per1 and Cry1 in the liver and subsequently circadian patterns of glucose and lipid metabolism-related genes such as the proliferator activated receptor (PPAR) family which favor the storage and hamper the oxidation of fatty acids.
  
  If you want to learn more about clock genes and how you can modify them, (re-)read the SuppVersity Circadian Rhythm Series!

• Scientists develop improved formula to calculate the resting energy expenditure of diabetics (Ikeda. 2012) -- While I would hope that you don't belong to the group who would have to use the new and improved formula scientists from the Department of Diabetes and Clinical Nutrition at the Kyoto University in Japan have now proposed, you may have clients or relatives who could benefit from its high predictive validity (78% +/- 103kcal vs. 50% for Harris-Benedict; 38% for Oxford, 42% for Liuand 63% for Ganpule):
  
  
  What you should keep in mind though, is that this equation was tested on Japanese individuals. Since we know from other studies that there are certain metabolic differences between people with different ethnic backgrounds I would remain a "healthy skeptic" as far as the outcomes of this equation are concerned - the same obviously goes for any other equation, e.g. the ones for athletes I provided in part III of the Female Athlete Triad series.

• 

  If you are interested in ways to modulate your leptin levels that may facilitate weight gain, I suggest you take a look at my second "Carbs Past 6PM Won't Make You Fat" post.

  Leptin induced weight gain? 13% more body fat in 2 weeks, when it hits the wrong part of the brain (Harris. 2012) -- With the mixed results from intervention trials, the enthusiasm around leptin has abated over the past months, the general consensus is yet still that leptin and leptin resistance loom large in the metabolic dysregulation that's at the heart of the diabesity pandemic. Against that background, the results Ruth B.S: Harris presents in her latest paper in the American Journal of Physiology - Endocrinology & Metabolism are unquestionably surprising.
  
  When Harris injected twice the amount of leptin (0.6 µg leptin/day) that had previously been shown to decreased 24 food intake, body fat and lean tissue, when it was injected into the third ventricle of the hindbrain, into the fourth ventricle of her lab rats, the rodents gained an almost incredible amount of 13% body fat within only 2 weeks! And that in the absence of statistically significant change in daily food intake, suggests an "increase in efficiency of energy utilization" (Harris. 2012). Fortunately, further experiments showed that the pro-obesogenic effects of leptin in the 4th ventricle was antagonized when both the 3rd and the 4th ventricle were exposed to leptin. In this scenario the leptin exposure of the 4th ventricle did even protect the lean mass of the rodents from the negative effects the exclusive exposure of the 3rd ventricle had. Overall, the study is yet somewhat chaotic and a clearcut message aside from "look people things are even more complex than we already thought", is probably not going to contribute to a solution of the obesity dilemma in the near future. 

There are, as usual more news on Facebook, some of them, such as the relation between hypothyroidism during pregnancy and the diabetes risk of the offspring later in life, are even related to the topic at hand. And if that's nothing you are interested, you may want to read about ...

• the non-existent effects of coffee consumption before bed on the sleep quality of habitual coffee drinkers (read more),
• the problem with inaccurate vitamin D tests and the absence of a reliable and scientifically sound definition of "vitamin D deficiency" (read more), or
• the strength promoting in-vitro effects of sodium bicarbonate, or in other words, a rather alkaline milieu on muscular force production (read more)

... and if neither of those can satisfy your thirst for more information from the realms of exercise and nutrition sciences, you can still wait for the next serving of facebook news or tomorrow's SuppVersity article :-)


References:

• Harris RB. Leptin-induced increase in body fat content of rats. Am J Physiol Endocrinol Metab. 2012 Dec 4.
• Ikeda K, et al. A new equation to estimate basal energy expenditure of patients with diabetes. Clinical Nutrition. 2012 [article in press] 
• Lagerpusch M, Enderle J, Later W, Eggeling B, Pape D, Müller MJ, Bosy-Westphal A. Impact of glycaemic index and dietary fibre on insulin sensitivity during the refeeding phase of a weight cycle in young healthy men. Br J Nutr. 2012 Nov 28:1-11.
• McNay EC, Teske JA, Kotz CM, Dunn-Meynell A, Levin BE, McCrimmon RJ, Sherwin RS. Long-term, intermittent, insulin-induced hypoglycemia produces obesity without hyperphagia or insulin resistance: a model for weight gain with insulin therapy. Am J Physiol Endocrinol Metab. 2012 Nov 20.
• Sluijs I, Beulens JW, van der Schouw YT, van der A DL, Buckland G, Kuijsten A, Schulze MB, Amiano P, Ardanaz E, Balkau B, Boeing H, Gavrila D, Grote VA, Key TJ, Li K, Nilsson P, Overvad K, Palli D, Panico S, Quirós JR, Rolandsson O, Roswall N, Sacerdote C, Sánchez MJ, Sieri S, Slimani N, Spijkerman AM, Tjønneland A, Tumino R, Sharp SJ, Langenberg C, Feskens EJ, Forouhi NG, Riboli E, Wareham NJ; on behalf of the InterAct consortium. Dietary Glycemic Index, Glycemic Load, and Digestible Carbohydrate Intake Are Not Associated with Risk of Type 2 Diabetes in Eight European Countries. J Nutr. 2012 Nov 28.
• Takahashi K, Yamada T, Tsukita S, Kaneko K, Shirai Y, Munakata Y, Ishigaki Y, Imai J, Uno K, Hasegawa Y, Sawada S, Oka Y, Katagiri H. Chronic mild stress alters circadian expressions of molecular clock genes in the liver. Am J Physiol Endocrinol Metab. 2012 Dec 4.

Dairy - The Good, the Bad or The Ugly? Latest Studies On Heart Disease, Diabetes, Cancer, Obesity and Co. Plus: What Dairy Peptides Do For Your Heart, Gut, Brain, etc.

Do you take Liz Hurley's word and set all warnings about the "non-paleo-ness" of dairy in general and milk in particular at naught? Or do you put faith into the "got milk?" campaign? Personally, I'd suggest not to do one or the other. I'd rather suggest you join me and take a look at a selection of recent studies.

If you've been following the SuppVersity Facebook News and / or have read previous SuppVersity articles on milk and dairy, you will be aware that I am not exactly convinced that the mere existence of allergic reactions and the "fact" that "our ancestors did not drink milk before ..." *put your favorite guesstimate here* allows for the conclusion that we are "not meant" to consume cow's milk. I am nevertheless open to scientific arguments that would convince me that dairy is bad for me - it's just that I don't see this evidence outside of "western diet + dairy makes you fat and that makes you sick" contexts.

What I do see, though, are papers such as the one Sandra Abreu or the recent review by Flávia Galvão Cândido et al. - studies that tell us that the intake of milk is negatively associated with the clustering of cardiometabolic risk factors in adolescents (Abreu. 2013), and reviews which conclude that "the consumption of low-fat dairy products may be an important strategy to prevent and control T2DM [type 2 diabetes]" (Cândido. 2013).

The evidence that dairy is bad for us all is simply not there

But hey, ... let's tackle the evidence one by one. I mean, there is plenty of news-worthy material here and we don't want the fun to be over prematurely, do we? So, let's start with a brief sketch of what Sandra Abreu and her colleagues from the University of Porto base their assessment that the intake of milk, but not total dairy, yogurt, or cheese, is negatively associated with the clustering of cardiometabolic risk factors in Spanish adolescents - shall we?

No! Full-fat dairy is not bad for you: While most of the epidemiological studies with their hilariously unreliable food questionnaires appear to suggest that only low fat dairy was good for your heart, a recent study from the Harvard School of Public Health found a clever way to test the association more objectively. Instead of questioning their subjects, 2837 US adults aged 45 to 84 years, they tested the amount of certain phospholipids in their blood and found that "plasma phospholipid 15:0, a biomarker of dairy fat, was inversely associated with incident CVD [-19%] and CHD [-26%]." (de Oliveira Otto. 2013) The fact that other dairy related phospholipids were not associated (neither positive nor negative) with cardiovascular and coronary heart disease risk does yet, as the scientists rightly point out, warrant further investigation.

"To test th[e] hypothesis [that a higher dairy product intake is associated with lower cardiometabolic risk factor clustering in adolescents], a cross-sectional study was conducted with 494 adolescents aged 15 to 18 years from the Azorean Archipelago, Portugal. We measured fasting glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body fat, and cardiorespiratory fitness. We also calculated homeostatic model assessment and total cholesterol/high-density lipoprotein cholesterol ratio. For each one of these variables, a z score was computed using age and sex. A cardiometabolic risk score (CMRS) was constructed by summing up the z scores of all individual risk factors. High risk was considered to exist when an individual had at least 1 SD from this score. Diet was evaluated using a food frequency questionnaire, and the intake of total dairy (included milk, yogurt, and cheese), milk, yogurt, and cheese was categorized as low (equal to or below the median of the total sample) or “appropriate” (above the median of the total sample). The association between dairy product intake and CMRS was evaluated using separate logistic regression, and the results were adjusted for confounders." (Abreu. 2013)

I know that sounds really sophisticated, but in the end, it's just standard procedure for cross-sectional studies like this - studies with one unfortunate downside: It's impossible to detect causal relationships. 

Figure 1: Dietary intake in the low and "adequate" dairy-, milk-, yogurt-intake groups (Abreu. 2013)

Keep that in mind, when you take a closer look at the data in Figure 2 which indicates that the average adolescent milk connoisseur of whom you can see in Figure 1 that he / she consumes significantly more energy on a daily basis has a significantly reduced cardiometabolic risk (predicted by cardiometabolic risk score; CMRS):

Figure 2: Cardiometabolic risk in "adequate" vs. low dairy, milk, yogurt and cheese consuming adolescents; adjusted for parental education , pubertal stage, low-energy reporter, energy intake, total fat , protein , and dietary fiber intake.

I personally was surprised to see a statistically significant protective effect only with milk - it's not that I had expected to see that for all forms of dairy, but based on previous studies I would have expected the fermented yogurt products to outperform conventional milk.

The negative effects of cheese on the other hand are by no means surprising. Food logs do after all include all types of "cheese" including the fake yellow vegetable oil based cheese analogues the kids shovel down with their pizzas, burgers and the rest of the fast food dirt. A high cheese intake has thus (unfortunately) become an indicator of low diet quality and the results of the study at hand hardly a credible marker that cheese is bad for you.

If 95% of your "dairy intake" comes from pizza, you are unlikely to see...

... any of the following benefits of dairy peptides, Blanca Hernández-Ledesma, María José García-Nebot, Samuel Fernández-Tomé, Lourdes Amigo, and Isidra Recio summarized in a soon-to-be-published review in the peer-reviewed scientific journal International Dairy Science:

• 

  Figure 3: Reduction of systolic blood pressure in mmHg per mg/kg of the said peptide you consume - mind the logarithmic scale(!); data calculated based on rodent studies summarized in Hernández-Ledesma (2014)

  Cardiovascular health effects due to the antihypertensive, anti-inflammatory, general antioxidant and hypocholesterolaemic properties of various dairy peptides
• Intestinal health effects due to the ability of dairy peptides to modulate and regenerate the gut mucosa, increase mineral absorption, exert local anti-inflammatory effects at the gastrointestinal level
• Antidiabesity effects that are related to both direct pro-insulinogenic effects of dairy peptides ant their ability to increase satiety. 
• Central nervous system relaxant and antinociceptive (pain-killing) effects
• Immune health which is promoted by antimicrobial and immunomodulatory peptides that are either already present in dairy or arise during the digestion process
• Anticancer effects that are mediated by the overall anti-inflammatory properties of certain dairy peptides, as well as direct anti-proliferative effects of dairy

Now, it goes without saying that you won't see the same effect from eating some goat kefir as Miguel et al. (2010) observed it, when they administered fraction 58-68 of goat casein to their lab rodents, but the data in Figure 3 can explain the well-established blood pressure lowering effects of dairy in general and the whey and casein induced BP reduction Figueroa et al. observed only recently in a study with obese women (Figueroa. 2013; see SuppVersity Facebook News).

Bottom line: You can't expect dairy to fully protect you against diabesity, cancer and a leaky, you can't expect it to lean you out in days, and you can't expect it to build muscle overnight, but you can expect general health benefits not detriments from incorporating a variety of fermented and unfermented dairy products into your diet - as long as you ain't lactose intolerant.

"Are Camels the Better Cows? Cancer, CVD, Allergies,Infections & More - Camel Milk Prevents or Fixes All These Ailments" | more

One thing you should keep in mind, though, is the unfortunate fact that the amount of "non-dairy" cheese, cream and other products is increasing by the day. Especially the former, the fake yellow vegetable oil based cheese analogues is something you want to avoid. The same goes for many of low fat products. While much of the "magic" is in the peptides, most of the commercially available "diet" products contain tons of sugar and all sorts of questionable additive to make up for the loss of color, taste and texture that's brought about by the removal of the fat. And lastly all products that extend the shelf-life to "eternity" by adding questionable preservatives.

References

• Abreu, S., Moreira, P., Moreira, C., Mota, J., Moreira-Silva, I., Santos, P. C., & Santos, R. (2013). Intake of milk, but not total dairy, yogurt, or cheese, is negatively associated with the clustering of cardiometabolic risk factors in adolescents. Nutrition Research.
• Cândido, F.G., Ton, T. S., & Alfenas, R. D. C. G. (2013). Dairy products consumption versus type 2 diabetes prevention and treatment; a review of recent findings from human studies. Nutr Hosp, 28(5), 1384-1395.
• de Oliveira Otto, M. C., Nettleton, J. A., Lemaitre, R. N., Steffen, L. M., Kromhout, D., Rich, S. S., ... & Mozaffarian, D. (2013). Biomarkers of dairy fatty acids and risk of cardiovascular disease in the multi‐ethnic study of atherosclerosis. Journal of the American Heart Association, 2(4), e000092.
• Figueroa, A., Wong, A., Kinsey, A., Kalfon, R., Eddy, W., & Ormsbee, M. J. (2013). Effects of Milk Proteins and Combined Exercise Training on Aortic Hemodynamics and Arterial Stiffness in Young Obese Women With High Blood Pressure. American Journal of Hypertension, hpt224. 
• Freedman, B. J. (1980). Sulphur dioxide in foods and beverages: its use as a preservative and its effect on asthma. British Journal of Diseases of the Chest, 74, 128-134.
• Hernández-Ledesma, B., García-Nebot, M.J., Fernández-Tomé, S., Amigo, L.,
  Recio, I., Dairy protein hydrolysates: Peptides for health benefits, International Dairy Journal(2014), ahead of print
• Iammarino, M., Di Taranto, A., Palermo, C., & Muscarella, M. (2011). Survey of benzoic acid in cheeses: contribution to the estimation of an admissible maximum limit. Food Additives and Contaminants: Part B, 4(4), 231-237.

Chromium Picolinate Worsens Insulin Sensitivity in Healthy, Non-Diabetic, Non-Obese Individuals by Up to 25%

The more supplements you take the more likely you are to get way more than the 200mcg of chromium of which previous studies have shown that they are useless for healthy people, but at least not detrimental (cf. Lukaski 1996 & 2007; Vincent. 2007). Especially people who like the  'poly-supplementary' approach are yet at risk of getting so much of a this trace mineral that it will hamper not improve their insulin sensitivity.

I don't have to tell you that you would already be dead if you were following all the bro-scientific advice that's out there on the Internet and still I usually recognize a certain reluctance to give up on what X suggests and Y has tried an what has worked so well for Z. One of the instances, where I have hitherto been missing a 100% convincing argument to argue that this is just another instance where common wisdom would in fact be better called "common stupidity" is the "insulin mimetic" or "insulin sensitizer" (or whatever your favorite bro-expert may call it) chromium picolinate. With the recent publication of the result of a study on the effects of chromium supplementation in healthy individuals there is now finally a human study that confirms that chromium, which has never been an "insulin sensitizer", but rather an "insulin release amplifier" that reduced blood glucose in diabetics by simply having them produce even more insulin is not a supplement any healthy man or woman, let alone athlete should consider a staple of his or her regimen.

The long and short: Chromium hampers insulin sensitivity in normoglycemic individuals

For their experiment lead author Umesh Masharani and his colleagues from the UCSA recruited a group of 27 non-obese, non-diabetic, healthy subjects between the ages of 20 and 50 with a body mass index of less than 27 kg/m² and <24 kg/m² for subjects with Asian heritage (the cut-off limits were set so that they would be below a BMI that has not yet been shown to be an independent risk factor for insulin resistance; cf. Clausen. 1996; Newell-Morris. 1998).

To evaluate whether chromium picolinate (ChrPic) supplements, which contributed with $150,000,000 to the revenue of the supplement industry in 1996 (Nielsen. 1996), could come up to the claims that they would exert beneficial effects on glucose tolerance and insulin sensitivity, the study participants were randomized to take either a placebo or a high dose 500µg CrPic supplement twice daily for 4 months (the dosage was selected in view of previews studies reporting greater benefits of 1,000 vs. 200mcg of CrPic in - you already guessed it - diabetic subjects; cf. Morris. 2000).

Figure 1: Insulin sensitivity measured by euglycemic clamp before and after the 16 week intervention (left); change in insulin sensitivity of the individual subjects plotted against serum chromium levels at the end of the study (Masharani. 2012)

As the data in figure 1 goes to show, the results of the CrPic intervention were more or less the exact opposite of what the ~10 million US consumers of respective supplements probably expect from the pills many of them are taking almost religiously. Despite the fact that all subjects had very low chromium levels at the beginning of the study, the previously non-significant minimally benificial relation between both serum and urinary chromium, on the one hand, and insulin sensitivity (r = 0.24, p=0.1; r=0.08, p=0.79 respectively), on the other hand, had turned into a very significant negative correlation between high(er) urinary and serum chromium concentrations and lower insulin sensitivity at the end of the 16 week intervention period (figure 1, right).

"Due to the apparent variation in the degree of chromium absorption between subjects, we examined the relationship between serum chromium and change in insulin resistance. After controlling for baseline patient characteristics, results of a multiple regression analysis showed a strong association between serum chromium and worsening of insulin–mediated glucose disposal (β= -0.83, p<0.01), where subjects with the highest serum chromium had a decline in their insulin sensitivity. To further explore the association between chromium absorption and insulin resistance, patients within the chromium group were divided (based on  a medial split at 3.10 µg/L) into a high (n=6) and low (n=8) serum chromium group [...] There were no group differences at baseline; however, at post-assessment participants in the high serum chromium group (> 3.1  µg/L) were more insulin resistant than participants in the low serum chromium group (≤3.1  µg/L) or the placebo group (p=0.02, p=0.05 respectively) (Figure 3)." (my emphases in Masharani. 2012)

Due to the fact that the scientists did not observe any differences between the placebo and low serum  chromium groups (on a side note, contrary to many other studies insulin Masharani et al. measured the insulin sensitivity in a very reliable way with an euglycemic hyperinsulinemic clamp; cf. Defronzo. 1979), the scientists also conducted a post-hoc analysis to identify potential confounding factors that may have influenced the outcome of the trial. Neither changes in triglycerides levels LDL, BMI, or truncal fat were yet associated with the differences they observed between the supplemented and non-supplemented participants. Interactions that would reduce the significance of the observed correlations were likewise absent:

"Furthermore, when changes in triglycerides, LDL, BMI, and truncal fat were individually added to the model, none were independent significant predictors of change in insulin sensitivity, and chromium absorption remained a significant predictor of reduced insulin sensitivity in each model." (Masharani. 2012)

Against that background the scientists conclude that there must be a "direct effect of chromium on changes in insulin action". A mechanism, by the way, which is totally independent of classic markers of insulin resistance such as high serum lipids and abdominal / truncal adiposity .

Being healthy is a good predictor of increased chromium absorption and more pronounced negative effects, so if you are healthy and want to stay this way don't even think of taking high dose chromium supplements.

Despite the fact that the changes in insulin resistance did not depend on changes in serum lipids and other markers of metabolic health, Masharani and his colleagues were able to show that the increase in chromium levels in response to supplementation did. With the already mentioned statistically significant correlation between increases in serum chromium levels (higher response to supplementation = higher increase), on the one hand, and the worsening of insulin sensitivity, on the other hand, this means that the healthiest subjects, namely ...

"[...] subjects with lower triglycerides, and those with lower levels of homocysteine [who had] a greater likelihood of being in the high absorption group" (Masharani. 2012)

... were at the same time those who were at the greatest risk of the ill side-effects high dose chromium supplements exert on the insulin tolerance of healthy, non-diabetic, normal-weight individuals.

No matter if it may have helped you produce insulin back in your obese days, once you have accomplished this you better avoid high dose or multiple (hidden) sources of supplemental chromium like a plague - unless you can't afford new jeans, of course ;-)

Bottom line: Unless you are not a type II diabetic or feel the urgent desire to become one, you better steer clear of exuberant amounts of supplemental chromium the RDA is enough. This is particularly true, if you are already taking a multi (which is almost guaranteed to have 200mcg in it), or any BB-style supplements. After all, "broscience" wants it that chromium is in everything that's even remotely related to insulin / nutrient uptake or whatever. With the use of only one of these products and 200mcg of supplemental dietary chromium per day, you may still argue that it probably won't do much harm. When you add another 200mcg from your "nutrient partitioner" on top of the 200mcg you get from your multi and the 200mcg of which you probably did not even realize yet that they are part of your pre-workout supplement, however, you can hardly complain about simply not being able to tolerate carbohydrates - I mean, what's your body supposed to do if you are dumb enough to believe in the promises of fat loss and lean mass increases that have been debunked in the late 1990s, already (cf. Lukaski 1996 & 2007; Vincent. 2007), and simply chose to ignore the latest scientific evidence that chromium picolinate supplements are not just useless, but actually detrimental to your health?


References:

• Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K, Pedersen O. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of  the impact of gender, body fat, physical fitness, and life-style factors.  J Clin Invest. 1996;  98(5):1195– 1209.
• Defronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237:E214–E223. 
• Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr. 1996 Jun;63(6):954-65.
• Lukaski HC, Siders WA, Penland JG.  Chromium picolinate supplementation in women: effects on body weight, composition, and iron status. Nutrition. 2007; 23(3):187– 195.
• Masharani U, Gjerde C, McCoy S, Maddux BA, Hessler D, Goldfine ID, Youngren JF. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2012 Nov 30;12(1):31.
• Morris BW, Kouta S, Robinson R, MacNeil S, Heller S. Chromium supplementation improves insulin resistance in patients with Type 2 diabetes mellitus.  DiabetMed. 2000; 17(9):684–685.
• Newell-Morris LL, Treder RP, Shuman WP, Fujimoto WY. Fatness, fat distribution, and glucose tolerance in second-generation Japanese-American (Nisei) men. Am J Clin Nutr. 1989; 50(1):9–18.
• Nielsen FH. Controversial Chromium: Does the superstar minearal of the mountebanks receive appropriate attention from clinicians and nutritionists?  Nutr Today. 1996; 31(6):226–233.
• Vincent JB: The nutritional biochemistry of chromium (III). Amsterdam, Boston: Elsevier. 2007.