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)!

Stevia - So Much More Than Just a Natural Sweetener: Combination "Therapy" With Stevia and Fenugreek as Effective as Common Diabetes Drug!

Image 1: Nature vs. Pharma. Leavs and seeds vs. chemicals - guess who will win!

I have been wondering for quite some time now, why I, as a resident of the European Union, do still have to use my hair-care products to sweeten my tea, my yogurt, or whatever else, if I do want to avoid artificial sweeteners or the good, or I should say, "bad" old table sugar... for those of you who are now wondering how hair-care products relate to my sweet tooth - here in Europe, Stevia rebaudiana Bertoni has still not been approved as a food additive, so that the myriad of health-food shops carrying respective products simply relabel them as "hair-care" or "cosmetic products, not intended for internal application"... and as a obedient citizen I would, of course, never even remotely consider ingesting a product such as stevia that is so utterly natural and genetically unmodified that it must be harmful ;-)

A pros pos harmful: As it turns out, stevia could in fact be pretty harmful - yet not for my or your physiological health, but certainly for the financial health of the big pharma companies. After all, scientists from the Departments of Pharmacology at the Bangladesh Agricultural University and the Faculty of Medicine at the Kagawa University in Japan have recently been able to show that Stevia rebaudiana Bertoni, in combination with Fenugreek aka Methi (Trigonella foenum-graecum), exhibits similarly potent hypoglycemic effects in Streptozotocin treated rats (the reference model for type II diabetes) as Amaryl(R), a commonly used diabetes drug based on the active ingredient Glimepiride (Rafiq. 2011). It thusly stands to reason that big pharma has a vested interest in delaying or even preventing the admission of stevia as an allowable food additive. Think about it: Who would buy all the Amaryls, Metformins & Co if Coca Cola decided to put stevia instead of aspartame into their soft-drinks and - all of a sudden - all those pre-diabetic soft-drink junkies would not develop full-blown type II diabetes, anymore? Ah... I am digressing again. Let's get back to the facts.

For their study Kazi Rafiq and his (I hope that "Kazi" is a male first name ;-) colleagues had collected fresh stevia and methi (=fenugreek) leaves and seeds and prepared them according to the following procedure:

Fresh Stevia leaves that were collected from the garden were oven dried first and then dried leaves were grinded with Grinder machine. Then 1g dried leaves samples were mixed with 10ml distilled water and were allowed to stay for whole night. Everyday fresh extract were prepared by using these techniques. Water extract of methi was made from 100g fresh seed sample by grinding with Grinder machine, and mixed with 2000 ml distilled water. Then the water extract was lyophilized in Central Laboratory, BAU. Finally the herbal drug was collected as powder form by Freeze drying in Central Laboratory, BAU.

The scientists then injected their 30 of their 36 Long Evans rats with Streptozotocin (STZ) to induce insulin resistance (again, STZ-treaded rodents are the most commonly used model of type II diabetes). After two weeks of STZ injection the (then) diabetic rats were divided into 5 groups:

• Group-B: diabetic control (STZ).
• Group-C: STZ + aqueous extract of stevia leaves @ 100 mg/kg,
• Group-D: STZ + aqueous extract of methi leaves @ 500 mg/kg,
• Group-E: STZ + combination of aqueous extract of stevia and methi leaves @ 500 mg/kg
• Group-F: Amaryl @ 800µg/kg

The plant extracts and the drug were administered orally once daily for 60 days. Blood glucose levels were monitored during the treatment period and an oral glucose tolerance test was conducted at the end of the 60-day experiment (results cf. figure 1).

Figure 1: Blood glucose levels (in mg/dl) in response to oral glucose tolerance test in normal and diabetic (STZ) rats after 6 weeks on a combination of stevia and fengreek extracts or the anti-diabetes drug Amaryl - left; change in area under the respective curve (AUC) relative to normal control - right (data adapted from Rafiq. 2011)

As you can see Amaryl and the combination therapy with stevia and fenugreek extracts at 500mg/kg per day (equivalent to 81mg/kg for a human being; or ~6.5g of each for someone weighing about 80kg) were equally effective in ameliorating the blood glucose response (within the statistical margin the AUC was identical).

Figure 2: Elevations in blood sugar levels (compared to healthy control) after STZ treatment and consecutive administration of stevia, fenugreek, a combination of both or Amaryl (data calculated based on Rafiq. 2011)

Moreover, the combination of stevia and fenugreek ameliorated the negative effect the Streptozotocin treatment had on blood glucose concentrations to a similar extend as Amaryl (cf. figure 2), which led the scientists to conclude that...

these findingslend pharmacological support to the suggested folkloric and ethnomedical user of these plants in managing and /or controlling of diabetes mellitus in rural communities of Bangladesh.

While the use of small amounts of stevia to sweeten your beverages and / or food will probably not have the same profound effects on your blood glucose levels as the combination of what would amount to a ~6g equivalent of leaf and seed extracts from stevia and fenugreek used in this study, I would assume that those dubious"hair-care products" still constitutes the most healthy sugar-alternative on the European market - so do your pancreas, ahh.. I mean hair, a favor and get yourself some stevia ;-)

Melato Cola™ or What? Fructose for Improved Glucose Metabolism and Melatonin to Counter Fructose Overload

There was a time, when Coke still contained "coke"... so why not add some melatonin for health benefits? I am obviously just kidding here, but a combination of fructose + melatonin may actually make sense.

The title of today's SuppVersity article is confusing, I know. Firstly, it contains the almost heretical notion that fructose could actually improve instead of impair your glucose metabolism and secondly it does not appear to make sense that you would have to use melatonin to counter the pro-diabetic effects of fructose, if the latter is in fact so good for you.

Before you are getting totally confused, let me clarify how the improvements in glucose metabolism and the melatonin-powered diabesity protection go together: Both have been observed in a recent study from the Pontificia Universidad Católica Argentina in Buenos Aires, Argentina (Cardinali. 2013), in the course of which the improved glucose metabolism was nothing but a side-finding of a study Cardinali et al. conducted to  examine the effect of melatonin when it is administered to rodents simultaneously with fructose in the drinking water.

This is the Coke + sufficient sleep study ;-)

Obviously this is not as the subheading would suggest the "coke + sufficient sleep study", but in light of the fact melatonin is after all the "sleep" hormone and in view of the results of a recent study by Senador et al. who observed that fructose had a negative effect on glucose management only, when it was available during the light phase (which is the inactive phase for a rodent; cf. Senador. 2012), it comes close; and that despite the fact that fructose timing was yet not an issue in the study at hand. Instead of modifying the timing, Cardinali et al. used different amounts of fructose with half of the rodents in the experimental arm of the study having a 5% and the other half having a 10% fructose solution as their main water supply.

Figure 1: Glycemia (mg/dL) 0-140min after 2g/kg body weight  glucose tolerance test (Cardinali. 2013)

If we trust the nutritiondata.com information about the average fructose content of a "carbonated beverage, cola, with higher caffeine" ...

• the rodents in the 10% fructose group were consuming the total carbohydrate equivalent of coke, but with a 100% instead of ~50% fructose content, while
• the rodents in the 5% fructose group were consuming less total carbohydrates, but roughly the same amount of fructose someone would ingest if he drank nothing but coke.

A direct comparison of either of the groups to the "coke only"-drinking human being is thus not warranted.

It is nevertheless intriguing that the 5% fructose group showed a significantly higher glucose tolerance - not just compared to the 10% fructose group, but also compared to the control group that was fed with water, only (see figure 1).

"Meta-Analysis: Lower Glucose, Insulin and HbA1c Levels From 'Catalytic' Dose of 36g Fructose" | read more

"But isn't fructose the reason you develop diabetes?" Before we get on to the effects of melatonin, I want to emphasize that this is by no means an outlier, in fact, I have written about the catalytic effects of 36g of fructose in a previous post "6x Bananas a Day!? Meta-Analysis: Lower Glucose, Insulin and HbA1c Levels From 'Catalytic' Dose of 36g Fructose" (learn more).

Previous studies have also shown that a 2:1 mixture of glucose + fructose is at least up to the regular glucose only drinks in terms of post-workout glycogen repletion (learn more) - partly because the fructose will keep the liver occupied, while the muscles suck up the glucose.

As previously mentioned the main research interest of the Argentinian scientists was not the effect of fructose on the glucose sensitivity of their rodents, but rather if the administration of 25 μg/mL of melatonin in the tapwater the rodents received would lead to significant changes in the study outcomes.

Figure 2: Effects of melatonin in drinking water with or without 5% [left] and 10% [right] fructose on body weight, systolic blood pressure and glucose response to glucose tolerance test (Cardinali. 2013)

As you can see in figure 1 it did: Melatonin did ameliorate the weight gain, and the increase in blood pressure that was observed even with only 5% fructose in the drinking water. It did not improve the glycemic response of the rats in the 5% fructose group even more, though, but it bulnted the negative effects of the 10% fructose solution had on the glycemic response in the glucose tolerance (figure 2, right).

SuppVersity Suggested Read: "Circadian Rhythmicity - Sunlight, Bluelight, Backlight & Co Mess Learn How THey W/ Your Internal Clock. Plus: Tips & Tricks to Prevent Negative Side-Effects" | read more

Is a melatonin solution the solution? If we also consider the negative effects of 10% fructose feeding on LDL (the rodents on 10% + Mel had even lower LDL than the control), the normalization of triglycerides and the potential therapeutic reduction in uric acid (-30% even vs. control), of which Cardinali et al. point out that it could have therapeutic effects in people with gout and other uric acid related metabolic disorders, it would appear smart that do dissolve the human equivalent dose of 21-35mg melatonin in your drinking water in the morning and keep guzzling it all day long.

Well, as I said, it "would appear to be" smart, but is it really smart? I wouldn't be too sure about that. Despite the fact that that you probably won't die, the chronically increased systemic melatonin levels could have long-term negative consequences on your circadian rhythm that could undo all potential benefits.

Restricting your fructose intake to fructose from fruit, only, getting enough sleep and using melatonin timely, i.e. 20min before bed would thus appear to be a more prudent approach to improve / maintain optimal blood glucose levels and insulin sensitivity. And if you are more into hard facts than "erring on the side of caution", you may consider the acute decrease in glucose tolerance, Cagnacci et al. observed in postmenopausal women, when they participated in a blood glucose test after the administration of 1 mg melatonin more convincing (Cagnacci. 2001).

References:

• Cagnacci A, Arangino S, Renzi A, Paoletti AM, Melis GB, Cagnacci P, Volpe A. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf). 2001 Mar;54(3):339-46. 
• Cardinali DP, Bernasconi PA, Reynoso R, Toso CF, Scacchi P. Melatonin may curtail the metabolic syndrome: studies on initial and fully established fructose-induced metabolic syndrome in rats. Int J Mol Sci. 2013 Jan 25;14(2):2502-14.
• Senador D, Shewale S, Irigoyen MC, Elased KM, Morris M. Effects of restricted fructose access on body weight and blood pressure circadian rhythms. Exp Diabetes Res. 2012;2012:459087.

Is Low Blood Sugar Obesogenic? Hypoglycemic Episodes Characteristic of Weight Loss Plateaus & Weight Regain - What to Do? Diet, Sleep, Exercise & Mental Work Matter

Tip: Restore your muscle and liver glycogen after workouts and before long fasts to ensure a smooth transition from glucose to fat utilization.

In view of the diabetes pandemic it sounds stupid, when J-P Chaput and A Tremblay write that low blood sugar levels could contribute to the ever-increasing obesity rates in the US and other Western countries.

Their reasoning, however, is sound: An increase in blood glucose concentrations results in increased feelings of satiety whereas a drop in blood glucose concentrations has the opposite effect.

Chronically low levels of glucose, as well as the glucose excursions we see in the few (still) healthy people after shoveling down packages of twinkies and dingdongs, would thus precipitate overeating and eventually obesity and diabetes.

Use alternatives to sugar sweetened beverages if you want to stabilize your blood glucose!

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Sweeteners & the Gut Microbiome Each is Diff.

Sweeter Than Your Tongue Allows!

Stevia, Much More Than Sweet?

Artif. Sweetened Foods Good, Not Bad for Fat Loss.

Compared to the way the hypothesis was originally formulated by Jean Mayer in the 1950s, the theory Chaput & Tremblay present in a 2009 review of the literature is significantly more complex (Mayer. 1953 & 1955. Chaput. 2009) and more of a glucose homeastasis hypothesis of obesity.

In contrast to the mainstream version of the "bad blood sugar spikes", Mayer and later Chaput and Tremblay focus on the role of the blood sugar troughs, we rarely think about. It all goes back to the classic glucostatic theory of food intake which postulates that

"that reduced glucose utilization in critical brain regions leads to perception and expression of hunger, and increased glucose utilization in these same glucosensitive sites leads to decreased hunger and cessation of eating." (Chaput. 2009)

In a state of decreased glucose utilization aka "metabolic hypoglycemia" (Mayer. 1955), there is a point at which the peripheral arteriovenous difference in blood glucose becomes negligible and glucose is no longer entering ‘metabolizing cells’ - this, according to Mayer, is the the signal for meal
initiation.

Does this mean that fasting is counter-indicated? For most of you probably not. If your liver gylcogen levels are well-stocked at the onset of the fast and assuming that you have a decent degree of metabolic flexibility, the transition into the fast will not put you at risk of metabolic (temporary glucose shortage at the cellular level) and / or full-blown hypoglycemia (really low blood glucose levels). So, fasting is ok, if you don't turn it into "starving" by extending the fast indefinitely and/or not restocking your glycogen levels in the feeding windows.

Interestingly, Mayer argued in his previously cited 1955 paper, already that the glucostatic theory would explain the short-term control of hunger and food intake, whereas a lipostatic mechanism would control the long-term regulation of body weight and energy balance.

There is nothing static about the glucostatic theory

Today, the role of glucose in the control of food intake is thought to be dynamic: it is a satiety factor and an initiation signal that has been associated with body fat by Chaput and Tremblay in two studies, which examined the effects of low glucose concentrations on long-term energy balance and weight gain in (Boulé. 2008)

Figure 1: Surprisingly linear increase in weight and body fat regain in prospective study and experimantal trial with lower blood glucose levels after OGGT (Boulé. 2008)

• 259 participants between 20 and 67 years of age involved in the Quebec Family Study - A study which revealed a closeassociation between glucose concentrations at the end of anoral glucose challenge and changes in body mass over the course of a 6-year follow up (Boulé . 2008).

• 44 obese participants on a 15-week weight-loss programme in either a drug therapy group or a placebo group coupled with energy intake restriction - A study which showed a higher propensity for weight regain over a follow up period of 83 weeks in those who had glucose levels below fasting values at the end of the oral glucose tolerance test during the weight loss intervention (Boulé. 2008)

In view of the fact that it would be easy to over-read the significance of these results: The researchers found that (1) lower glucose concentrations at the end of an OGTT were correlated with weight gain over time, that (2) large amounts of weight loss were associated with low glycemia at the end of an OGTT, and that (3) these low glucose concentrations were strong predictors of the amount of weight regained after weight loss.

The GI does matter - but only before and after you try to lose weight

Of these findings (2) is particularly interesting as it would support the notion that low glycemia can do both: It supports weight loss, when the energy intake is restricted and it increases the risk and extend of weight (re-)gain, when there is no energy restriction.

Figure 2: When the dietary energy intake is tightly controlled, there is hardly a difference in weight loss and body fat loss with high GI, low GI and high fat dieting in obese men & women (Raatz. 2005)

These observations would support previous evidence that a high glycemic index of foods, which would obviously be connected to higher glucose excursions after meals, figures large on ad-libitum (Alfenas. 2005), but only marginally on tightly controlled diets (Raatz. 2005).

It is thus no wonder that Chaput & Tremblay write in their latest review that their results are relevant only in phases without deliberate (significant) energy restriction. In these phases, the present research clearly suggests that weight-reduced obese individuals are at particular risk of weigh (re-)gain; an observation of which the scientists say that it is brought about by a destabilization of the "body homeostasis" that occurs, whenever the weight loss exceeds 10% of the initial body weight. And indeed: Tremblay et al. have observed in 1999, already that the mean glycemia of participants who had reached the point where their weight loss stagnated had reached an all-time low of 3.3 mmol/ l, of which studies by LeBlanc show that that it is significant enough to evoke a significant counter-regulatory hormonal response (LeBlanc. 1982; Tremblay. 1999).

Hypoglycemia and depression? The reduced glycemia could also be the underlying cause of diet induced increases in symptoms of depression as they were observed by Chaput et al. in a previous trial (2005), in the course of which their male volunteers became increasingly depressed, when they had surpassed the 10% weight loss margin (Chaput. 2007a). A direct association between low glycemia and depression in weight loss was confirmed in a follow up that used a low calorie diet (700kcal/day) + aerobic exercise. (Chaput. 2007b). Intriguingly, depression peaked, when the subjects finally hit a weight loss plateau in both studies.

These "significant counter-regulatory hormonal responses", which manifest in form of blunted growth hormone and epinephrine responses and appear to be controllable by regular exercise, are of particularly interest for those of you whose weight loss efforts have plateaued. A better glucose control with a focus on avoiding low glucose levels and regular physical activity could thus help you solve this problem... switching to a ketogenic diet which guarantees 100% glucose stability since the glucose is no longer used as a substrate, would be a another option.

Exercise to the rescue!

Another and eventually probably the most promising way of increasing glucose stability, facilitating further weight loss and forestalling future weight (re-)gain would be regular workouts.

"Physical exercise can be described as a stimulus contributing to optimal body functioning. This is discretely expressed at many levels of regulatory processes, be it by stimulating the effect of key enzymes, by increasing the sensitivity to hormones, by facilitating substrate transport through the membranes, by influencing cell receptors in a tissue-specific manner and probably many others.  The participation in regular physical activity has also been shown to prevent both hyperglycemia and hypoglycemia, which is concordant with the idea that exercise enhances the accuracy of substrate balance regulation." (Chaput. 2008)

It's thus not best to sit around all day to avoid your blood glucose levels from plummeting. On the contrary, individuals who are physically engaged in their daily schedule may expect a better control of both high and low glucose levels and better overall glucose homeostasis. And in fact, previous research also suggests that physically fit individuals are less likely to experience feelings of hunger associated with declines in blood glucose (Chaput. 2008).

The unbeatable benefits of exercise include both improved glucose control in the traditional sense of avoiding hyperglycemia and improved glucose control in the more comprehensive sense of avoiding both high and low glucose levels.

Chaput and Tremblay do yet add another factor to the discussion: Mental exercise! The glucose demands of our brain during cognitive activity are a commonly overlooked factor, when it comes to both glucose and energy control and that in spite of the fact that we all know that (with the exception of full ketosis) carbohydrate represents a critical energy substrate for the brain. Against that background,...

"the low capacity of the body to store carbohydrate might be perceived as a paradox of nature, particularly when cognitive activities are dominant in the daily activity schedule. This limitation is exacerbated by the inability of the body to synthesize glucose from free fatty acids." (Chaput. 2009)

It is thus not surprising that Cognitively and thus energetically demanding tasks will influence the ad-libitum meal intake, even if the measured energy expenditure during sitting at the desk doing nothing and performing a reading–writing task for 45 min is practically the same (13kj difference in Chaput. 2007c).

The brain may be your hungriest muscle

Figure 3: In contrast to both high (HIE) and low intensity exercise (LIE) 45 minutes of knowledge-based work will increase energy intake at a subsequent buffet (McCann. 1990)

In that the results presented in Figure 3 are not a statistical artifact. They agree with the results with the results of a study involving scientists from the University of Washington who increased their energy and fat intake at the time of the preparation of NIH grant applications (the additional influence of stress should be considered, here, as well | McCann. 1990)

In conjunction with the increase in the variability of glycemia, Chaput et al. observed in a 2008 follow up (Chaput. 2008), this may well explain the increased food intake the researchers observed in response to "cognitive work" in the broadest sense in all three studies.

Unquestionably, Chaput & Tremblay are right, when they warn that these observations raise the question as to whether other sedentary leisure activities (for example, video game playing, television viewing, chatting on internet) are also hyperphagic stimuli. In other words, whether they will make you overeat similar toknowledge-based work; and whether associations with glucose instability, as they were observed by Chaput et al. in 2008 exist for "texting", as well.  And even if that wasn't the case, the mere fact that knowledgebased work represents the main working modality in the current way of living, alone, would warrant further research in this direction.

Apropos "modern lifestyle", sleep or rather a lack thereof figures, as well

If you take a look at the data in Figure 4, you will realize that another feature of the modern way of living, i.e. a lack of sleep quantity and quality is associated with glucose excursions into hypoglycemia as well.

Figure 4: Mean glucose area below fasting glucose concentrations (GABF | higher values increase more severe / longer episodes of hypoglycemia) in men and women according to their habitual sleep duration (Chaput. 2007d)

The mean glucose area below fasting glucose concentrations (GABF) Chaput et al. measured in a yet another study they conducted in 2007 (Chaput. 2007d) clearly indicate that border line hypoglycemia is much less pronounced in long vs. short sleepers.

In that, it is interesting to see that the differences in mean glucose area below fasting glucose concentrations reflect the contemporary evidence of associations between sleep duration, obesity and type II diabetes - both sleeping too short (Xi. 2013) and too long is associated with increased risk of metabolic syndrome and/or type II diabetes (Ohkuma. 2014).

Bottom line: I doubt that hypoglycemia is the ultimate weight loss tool, but I hope you will agree that the previously presented evidence is significant enough to argue that you better keep an eye on both overtly high and overtly low glucose levels.

Table 1: Overview of factors that are believed to directly influence glucose homeostasis (Chaput. 2009)

As I've pointed out before, the latter damaging effects of low glucose levels are particularly pronounced, when you're not dieting. Yet even if you're calorically restricted, it's certainly a wise advise to keep the number and duration of episodes with borderline low glucose levels to a minimum to (a) reduce cravings, specifically for sweets, (b) minimize the negative long(er) term effects on the production of catecholamine and thyroid hormone (Leung. 1975), testosterone (Oltmanns. 2001) and the rest of the hormones the production of which depends on an intact hypothalamic signalling that is disrupted as a consequence of low glucose availability in the brain | Comment on Facebook!

References:

• Alfenas, Rita CG, and Richard D. Mattes. "Influence of glycemic index/load on glycemic response, appetite, and food intake in healthy humans." Diabetes Care 28.9 (2005): 2123-2129.
• Boulé NG, Chaput JP, Doucet E, Richard D, Despre´s JP, Bouchard Cet al. Glucose homeostasis predicts weight gain: prospective and clinical evidence.Diabetes Metab Res Rev 2008;24: 123–129. 
• Chaput, Jean-Philippe, et al. "Psychobiological impact of a progressive weight loss program in obese men." Physiology & behavior 86.1 (2005): 224-232.
• Chaput, Jean‐Philippe, et al. "Psychobiological effects observed in obese men experiencing body weight loss plateau." Depression and anxiety 24.7 (2007a): 518-521.
• Chaput, Jean-Philippe, et al. "Increase in depression symptoms with weight loss: association with glucose homeostasis and thyroid function." Applied Physiology, Nutrition, and Metabolism 33.1 (2007b): 86-92.
• Chaput, Jean-Philippe, and Angelo Tremblay. "Acute effects of knowledge-based work on feeding behavior and energy intake." Physiology & behavior 90.1 (2007c): 66-72. 
• Chaput, J-P., et al. "Association of sleep duration with type 2 diabetes and impaired glucose tolerance." Diabetologia 50.11 (2007d): 2298-2304.
• Chaput, Jean-Philippe, et al. "Glycemic instability and spontaneous energy intake: association with knowledge-based work." Psychosomatic medicine 70.7 (2008): 797-804. 
• Chaput, J. P., and A. Tremblay. "The glucostatic theory of appetite control and the risk of obesity and diabetes." International journal of obesity 33.1 (2008): 46-53.
• LeBlanc, J., et al. "Variations in plasma glucose, insulin, growth hormone and catecholamines in response to insulin in trained and non-trained subjects." Metabolism 31.5 (1982): 453-456.
• Leung, Yan, et al. "The effect of hypoglycemia on hypothalamic thyrotropin-releasing hormone (TRH) in the rat." Endocrinology 97.2 (1975): 380-384.
• Mayer J. Glucostatic mechanism of regulation of food intake. N Engl J Med1953;249: 13–16.
• Mayer J. Regulation of energy intake and the body weight, the glucostatic theory and the lipostatic hypothesis.Ann NY Acad Sci 1955;63: 15–43.
• McCann, Barbara S., G. Russell Warnick, and Robert H. Knopp. "Changes in plasma lipids and dietary intake accompanying shifts in perceived workload and stress." Psychosomatic medicine 52.1 (1990): 97-108. 
• Ohkuma, Toshiaki, et al. "U-shaped association of sleep duration with metabolic syndrome and insulin resistance in patients with type 2 diabetes: The Fukuoka Diabetes Registry." Metabolism 63.4 (2014): 484-491.
• Oltmanns, Kerstin M., et al. "Hypoglycemia, but not insulin, acutely decreases LH and T secretion in men." The Journal of Clinical Endocrinology & Metabolism 86.10 (2001): 4913-4919.
• Raatz, Susan K., et al. "Reduced glycemic index and glycemic load diets do not increase the effects of energy restriction on weight loss and insulin sensitivity in obese men and women." The Journal of nutrition 135.10 (2005): 2387-2391. 
• Tremblay, Angelo, et al. "Metabolic Fitness in Active Reduced‐Obese Individuals." Obesity research 7.6 (1999): 556-563. 
• Xi, Bo, et al. "Short sleep duration predicts risk of metabolic syndrome: A systematic review and meta-analysis." Sleep medicine reviews (2013).

Stevia - Natural Sweetener With Anti-Diabetes + Anti-Obesity Effects? A Brief Research Update: GLP-1, Insulin, Glucose Transport and Uptake, Inflammation, Bitterness & Safety

Stevia is certainly one of the best choices to use as a sweetening agent. It is yet important to point out that this has nothing to do with the fact that it is "natural" - as "natural" as the white stevioside powder ism anyway.

You may remember from the Facebook News that Ripken et al. reported in a recent paper in the  Journal of Agricultural and Food Chemistry (2014) that Stevia will stimulate the release of the satiety (and pro-metabolic) hormones GLP-1 and PYY in the stomach of our (digestion- & nutrition-wise) next relatives, the pigs.

The results Ripken et al. presented about 3 weeks ago are yet only the tip of a whole heap of studies of which Nabilatul Hani Mohd-Radzman and colleagues believe that it is sufficient to postulate that the Stevia rebaudiana Bertoni plant "could benefit the community medicinally through several different pathways, all eventually leading to its antihyperglycemic qualities." (Mohd-Radzman. 2014)

You can learn more about sweeteners at the SuppVersity

Unsatiating Truth About Sweeteners?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Sweeter Than Your Tongue Allows!

Stevia, Much More Than Sweet?

Artif. Sweetened Foods Help Weight Loss!

But is there really convincing  evidence that the beneficial effects of the consumption / use of stevia and its main sweetening agent stevioside go beyond the mere reduction in sugar consumption? Yes, there is; and here is a brief overview of what we've learned so far:

• Anti-inflammatory effects -- Some scientists believe that Stevia’s utility in diabetes protection is due to its antioxidant properties; a hypothesis that is supported by analysis of the phenols that may be extracted from the plant.
  
  Stevia has a large overall proportion of phenols, up to 91 mg/g; it is proposed that these constituents extracted from the leaves are the major agents contributing towards the anti- hyperglycemic activities exerted by the plant (Shivanna. 2013). This is further supported by the fact that the leaves have a greater ability to scavenge free radicals and prevent lipid peroxidation than controls such as butylated hydroxytoluene, butylated hydroxyanisole, and tertiary butyl hydroxyquinone.
  

  

  Figure 1: Effect of Stevia on lipid peroxidation in liver in STZ treated rats (n = 8; Shivanna. 2013).

  The mere presence of anti-oxidants does not ensure anti-diabetic effects, though. Against that background it's important that corresponding experimental evidence from streptozotocin-induced diabetic rats, in which phenolic compounds prevented several diabetic complications is already available. In addition, Shivanna et al. (2013) observed a significant decrease (about 30%) in peroxidation in the livers of Stevia-pre-fed rats, compared to those of their control groups. In view of the previously discussed involvement of the liver in the etiology of the metabolic syndrome, this is a good indicator of reduction in the progression of diabetic complications.
  
  The same goes for the levels of the pro-inflammatory cytokine NF-kappaB and TNF-alpha of which researchers from the Shanghai Institute of Endocrine and Metabolic Diseases report that it was significantly downregulated in a study on a C57BL6J mouse model of insulin-resistance, when the rodents received stevioside supplemented chow (Wang. 2012).
• Direct beneficial effects on blood glucose levels --  Whether the beneficial effects of stevia on blood glucose management are mediated solely via its anti-inflammatory effects is not yet certain. The initially mentioned effects on GLP-1, for example, could (and probably will) also contribute to the significant decrease in blood-glucose levels Susuki et al. observed in a study from 1977 that was published in the Japanese science journal Nippon Nogei Kagaku Kaishi (Susuki. 1977).  The Japanese researchers fed rats a stevia enriched high carbohydrate + high fat diet and observed "a significant reduction in glycemia" after four weeks on the otherwise highly prodiabetic rodent equivalent of the Western diet. 

You cannot stand the bitter taste of stevia? Unlucky you! You've simply got the wrong genes. As scientists from the Laboratory of Molecular Anthropology and Centre for Genome Biology at the University of Bologna observed in a very recent study, men and women with the TAS2R4 gene polymorphism rs2234001 and /or the TAS2R14 (TAS = taste receptor) gene polymorphism rs3741843 will never understand how the rest of us can ignore the obnoxious bitterness of steviosides - I know, that's bitter ;-)

• That these benefits are not rodent specific and don't arise in response to an interaction with certain components in the rodent chow was demonstrated 27 years later by Gregersen, et al.  (2004). In their paper in the January issue of Metabolism, the scientists report that they observed a similar, highly significant reduction (an average of 18%) in postprandial glucose levels in Type II diabetic patients given test meals supplemented with stevioside..
  
  A 2010 study by Anton et al. confirmed this (Anton. 2010) this; postprandial glucose levels were significantly lowered in patients supplemented with Stevia, compared to those
  given aspartame (a type of synthetic sweetener) or sucrose (normal table sugar). In that, the slightly increased insulin levels in the stevia vs. aspartame group provides further support for the involvement of GLP-1, which is likewise involved in health insulin function (Kjems. 2003)
  

  

  Figure 2: Total energy intake of type II diabetics in kcal/day on days with aspartame, setvia or sucrose sweetened foods (left); corresponding plasma insulin levels (Anton. 2010)

  In addition, patient satiety as an aftereffect of the different sweeteners was also tested; it was found that subjects given lower-calorie sweeteners (Stevia or aspartame) did not compensate by eating more than those given sucrose. Any potential increase in insulin did thus have the proven, but largely ignored satiety effect insulin is supposed to have (Vanderweele. 1994). 
• Possible interactions with the gut & its microbiome -- The research on the interactions of stevia with the microbes in our gut is still in its infancy.
  

  

  Table 1: Effects of non-nutritive sweeteners on gut hormones and glucose absorption:in vivo effects on animals (Brown. 2014)

  Nevertheless, the repeatedly mentioned effects on GLP-1, as well as evidence from animal studies which show a decrease in glucose uptake, when carbohydrates are fed in the presence of stevia (Brown. 2012) clearly indicate that there is more to the anti-diabetic & -obesity effects of stevia (and maybe other non-nutritive sweeteners) than direct antioxidant effects (Payne,. 2012).

Is stevia even safe? At "sane" intake levels toxic effects appear unlikely (Aze. 1990); studies show no detrimental effects on female reproduction, when consumed in amounts equivalent to those you would use in food products (Yodyingyuad. 1991; Saenphetet. 2006); there are minimal negative effects on seminal vesicle weight in high dose study with male rodents (Oliveira-Filho. 1989); studies show no genotoxic effects or DNA interactions (Brusick. 2008); stevia even appears to have a limited anti-viral activity (Takahashi 2000 & 2001)

"Natural and good", not "good since natural": As the previous elaborations have shown stevia really appears to be one of the best sugar replacements to chose. This is yet not due to the "naturalness" of stevia, but due to the specific molecular structure of the the glycosides the food industry extracts from the leaves of a plant.

Accordingly, the white substance we wrongfully call "stevia", when it's eventually only an extract of the sweet(est) tasting steviosides wouldn't be less effective or unhealtier if it was synthesized in the laboratories of Monsanto or extracted from the poop of genetically modified bacteria. And you know what? I guess, when the market keeps growing the way it does, this is soon going to be the white-washed sterile environment of a laboratory is probably soon going to be where 90% of the stevia is going to come from.

Reference:

• Anton, Stephen D., et al. "Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels." Appetite 55.1 (2010): 37-43. 
• Aze, Y., et al. "Subchronic oral toxicity study of stevioside in F344 rats." Eisei Shikenjo hokoku. Bulletin of National Institute of Hygienic Sciences 109 (1990): 48-54.
• Brown, Rebecca J., and Kristina I. Rother. "Non-nutritive sweeteners and their role in the gastrointestinal tract." The Journal of Clinical Endocrinology & Metabolism 97.8 (2012): 2597-2605. 
• Brusick, D. J. "A critical review of the genetic toxicity of steviol and steviol glycosides." Food and Chemical Toxicology 46.7 (2008): S83-S91.
• Gregersen, Søren, et al. "Antihyperglycemic effects of stevioside in type 2 diabetic subjects." Metabolism 53.1 (2004): 73-76.
• Kjems, Lise L., et al. "The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion Effects on β-Cell Sensitivity in Type 2 and Nondiabetic Subjects." Diabetes 52.2 (2003): 380-386.
• Oliveira-Filho, Ricardo M., et al. "Chronic administration of aqueous extract of< i> Stevia rebaudiana</i>(Bert.) Bertoni in rats: Endocrine effects." General Pharmacology: The Vascular System 20.2 (1989): 187-191.
• Payne, A. N., C. Chassard, and C. Lacroix. "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 (2012): 799-809.
• Ripken, Dina, et al. "Stevia Glycoside Rebaudioside A Induces GLP-1 and PYY Release in a Porcine Ex Vivo Intestinal Model." Journal of agricultural and food chemistry (2014).
• Shivanna, Naveen, et al. "Antioxidant, anti-diabetic and renal protective properties of  Stevia rebaudiana." Journal of Diabetes and its Complications 27.2 (2013): 103-113.
• Suzuki, H., et al. "Influence of oral administration of stevioside on levels of blood glucose and liver glycogen of intact rats." Journal of the Agricultural Chemical Society of Japan (1977).
• Takahashi, K., et al. "Extracts from Stevia rebaudiana is a potent anti-rotavirus inhibitor in vitro and in vivo." Antiviral Research. Vol. 46. No. 1. PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS: ELSEVIER SCIENCE BV, 2000.
• Takahashi, Kazuo, et al. "Analysis of anti-rotavirus activity of extract from< i> Stevia rebaudiana</i>." Antiviral research 49.1 (2001): 15-24.
• Vanderweele, Dennis A. "Insulin is a prandial satiety hormone." Physiology & behavior 56.3 (1994): 619-622.
• Wang, Zhiquan, et al. "Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-kappaB pathway." Biochemical and biophysical research communications 417.4 (2012): 1280-1285.
• Yodyingyuad, Vithaya, and Supranee Bunyawong. "Effect of stevioside on growth and reproduction." Human Reproduction 6.1 (1991): 158-165.

No More Excuses! It's not Your Parents' Fault: Type II Diabetes is Reversible by Diet & Life-Style Changes Alone.

Image 1: Symptoms of Diabetes

Have you ever met one of these poor fat guys or girls, who "have done everything" to shed some weight, always "eat healthy" and exercise "whenever they can", but are "held back by their genetics"? Well, I mean those, whose parents and grandparents already had type II diabetes; those poor critters who are condemned.... I don't know about you, but I cannot tolerate the whimpering anymore. A recent study (Lim. 2011) published in the May issue of the international Journal Diabetologia clearly shows: Type 2 diabetes is reversible!

Within 8 weeks on what certainly was a brutal diet (@ 600kcal per day it was rather a fast, supported by a commercial diet drink, Optifast, and sustained by three portions of non-starchy vegetables per day) the eleven type 2 diabetic subjects (49.5± 2.5 years, BMI 33.6±1.2 kg/m2 , nine male and two female) who participated in the study by Lim et al. achieved normalisation of both beta cell function and hepatic insulin sensitivity.

Figure 1: Anthropometric data before and during the 8 weeks
of dietary intervention (data adapted from Lim. 2011)

After only one week of severe calorie restriction, the fasting plasma glucose had already dropped from 9.2 to 5.9 mmol/l (from high to normal)...

Insulin suppression of hepatic glucose output improved from 43±4% to 74±5% (p=0.003 vs baseline; controls 68±5%). Hepatic triacylglycerol content fell from 12.8±2.4% in the diabetic group to 2.9±0.2% by week 8 (p=0.003).

In the course of study the first-phase insulin response increased by 70% (from 0.19±0.02 to 0.46± 0.07 nmol min−1m−2; p<0.001) and approached control values (0.62±0.15 nmol min−1 m−2 ; p=0.42). 

At the end of the trial the maximal insulin response [had become] supranormal (1.37± 0.27 vs controls 1.15±0.18 nmol min−1m−2) [and] pancreatic triacylglycerol [had] decreased from 8.0±1.6% to 6.2±1.1% (p=0.03).

So don't you tell me its not your fault! Not for the aesthetically pleasing improvements in body composition (cf. figure 1), but for the sake of your health, get your ass up, your caloric intake down and rid of your diabetes.

On a side note: This study the hypothesis that the primary weapon in the war against the metabolic syndrome with all its ugly facets is weight loss, not medication or supplementation. Yet, fasts like the one used in this study may get your weight faster, your success, however, will probably be more difficult to sustain. If you do not get away from the sedentary fast-food lifestyle that has gotten you where you were, the ~15kg will be back on your hips within no time and your health condition may turn out to be worse than ever before. We take it for granted, but in fact our health is something we have to work for 24/7, and that not just for 8 weeks, but for the rest of our lives.

SuppVersity World Cup Special: What Football Can Do For Your Health & Performance Now & As You Age - It's Better for Heart & Bones (!) Than Lifting

Soccer! For Young & Old, Heart & Bones, Blood Sugar & Body Fat Now & Beyond World Cup 2012

Ok, I have to admit, in spite of the fact that the World Cup starts today, I wouldn't have produced this article, if the editor(s) of the Scandinavian Journal of Medicine & Science in Sports didn't have a similar idea and I wouldn't have "early view" access to a bunch of soon-to-be-published on the beneficial and not so beneficial effects of what I call "football" and most of you call "soccer".

But enough of the prelude, let's take a look at what I have to report, here: Schmidt et al. present the amazing cardiovascular adaptations they observed in response to 4 and 12 months of football or strength training in 65- to 75-year-old untrained men.

If you want to get fit fast, try HIIT | learn more at the SuppVersity

Never Train To Burn Calories!

Tabata = 14.2kcal /min ≠ Fat Loss

30s Intervals + 2:1 Work/Rec.

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Making HIIT a Hit Part II/II

Triple Your Energy Exp.

The study was conducted at the Copenhagen Centre for Team Sport and Health of the University of Copenhagen and involved, as you would have guessed, 26 untrained men (age: 68.2 ± 3.2 years). The guys were randomized to football training (FTG; n = 9), strength training (STG; n = 9), or control (CG; n = 8).

Football (soccer), older hearts will love it!

Maximum oxygen consumption (VO2max; L/min) and resting heart rate (RHR; bpm) in elderly healthy 65- to 75-yearold men at baseline, after 4 & 12 months of football training (FTG), strength training (STG), and control (CG) - Schmidt. 2014

Aside from the impressive improvements in VO2max (vs. no improvement in either the strength training or the control group; see Figure 1), the researchers observed the following beneficial structural changes of the heart:

• increases in left ventricular diastolic diameter +8%
• increases in end-diastolic volume +21%
• increases in ventricular mass index +18%

Unlike the improvements in ejection fraction (+8% in FTG vs. +5% in STG), these changes were "football"-exclusive.The systolic longitudinal two-dimensional strain increased by 8% (FTG) and 6% (STG), whereas the right ventricular systolic function improved (P < 0.05) by 22% in FTG, but not in STG and CG.

In conjunction with the football-exclusive increases in diastolic mitral inflow (E/A) ratio and peak early diastolic velocity (E') improved (25% and 12%, respectively), your 3x1h of training may thus be better spend on football than on resistance training if your main goal is to improve your VO2max and kick heart disease's ass.

If we look at the benefits the older guys in the Schmidt study derived from their soccer training it can hardly be surprising that Anderson et al. (2014a) report similarly "hearty" benefits in 31 untrained males with mild-to-moderate hypertension who were randomized 2:1 to a football training group (n = 20) and a control group receiving traditional recommendations on healthy lifestyle (n = 11).

While the football group exhibited significant (P < 0.05) changes in cardiac dimensions and function after just 3 months similar to those in the Schmidt study, as well as significant reduction in arterial blood pressure, the results in the "traditional take this *bs* advice" group were mediocre tat best. Consequently, the researchers conclude that even in the short term (3-6 months)...

"football training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension [and] improve longitudinal systolic function of both ventricles." (Anderson. 2014a)

 Now, SuppVersity readers are not generally hypertensive, and I am gathering that the few highly appreciated "best agers" in my readership are also in the minority. Against that background it's worth mentioning that the heart is not the only part of your body that will benefit from soccer practices - your bones will, too. Ok, I see you laughin' cause you're hittin' the weights, regularly, but what would you say if I told you that ...

"4 months of recreational football for elderly men had an osteogenic effect, which was further developed after 12 months, whereas resistance training had no effect."  (Helge. 2014)

I see, I've got your attention, now! Well, the authors, again researchers from the Copenhagen Centre for Team Sport and Health speculate that the anabolic response may be due to increased bone turnover, especially improved bone formation which was obviously promoted to a greater extent in those 9 of the initially 26 healthy sedentary men (age 68.2 ± 3.2 years) who had been randomized to the  football (F; n = 9) and not the resistance training (R; n = 9) group - and that despite the fact that both trained two to three times weekly for a total of 45–60 min training.

Playing soccer is good for your health, watching it... well, watching it can increase your risk of being hospitalized for acute myocardial infarction minimally (+1%; cf. Barone-Adesi. 2010), unless, of course, your team wins! During the 1998 World Cup, which was won by France, the myocardial infarction risk of French men was actually reduced by 35% (Berthier. 2003)

When it comes to improving the functional ability and physiological response to submaximal exercise, in older men, however, it's difficult to pinpoint a difference between three football and three resistance training sessions per week. Unsurprisingly, study #4 in today's review did yet report that only football trainign "additionally elevates maximal aerobic fitness and exhaustive exercise performance." (Anderson. 2014b).

What's left to discuss, oh yes! Anderson. 2014c and the effects on glucose management!

Yeah, with 21 middle-aged men (49.8 ± 1.7 years ± SEM) with T2DM as subjects, this study will certainly appeal to all the Average Joes out who unfortunately don't get their daily dose of SuppVersity wisdom, yet (Anderson. 2014c).

The said middle-aged subjects were divided into a football training group (FG; n = 12) and an inactive control group (CG; n = 9) - the absence of a strength training "control" is a pity... but alas, after the 24-week intervention period, in the course of which the sick guys covered only During 4.7 ± 0.2 km at a mean heart reate of 83 ± 2% of HRmax per 1h soccer training, they experienced a 11% increase in VO2peak and lost 1.7 kg and 12.8% of their total fat and android fat, respectively.

Against that background it's not that surprising that Anderson et al. report concomitant improvements in plasma glucose and an increased expression of the glucose transporters (GLUT-4). Most importantly, however, the Danish researchers did also observe an overall time effect for glycosylated hemoglobin (HbA1) and thus significant and continuous improvements in glucose management in the soccer group.

Bottom line: "There you have it" ... that's actually something my good friend Carl Lanore from www.superhumanradio.com like to say. There you have the benefits of playing soccer. Improved heart health, fat loss and reductions in blood glucose in type II diabetes are probably nothing, you wouldn't have expected, anyways, right?

 "The 100 Squats A Day Challenge: Body Weight Squats Get You in Shape in Less Than 3 Minutes." | read more

Well, what about the benefits on bone health, then? I personally was surprised that the impact of soccer training was more pronounced than the one of strength training. In the end, I would yet expect equal results if the latter, i.e. the strength training had included free-weight squats and/or deadlifts. Those and not sissy curls and lat pulldowns are true bone builders, but honestly - when I see some of the 60+ agers at my gym do them I think to myself: You better leave that to true physical culturists, like my previously mentioned friend Carl Lanore (www.superhumanradio.com) and head over to the soccer training, folks ;-)

References:

• Andersen, L. J., Randers, M. B., Hansen, P. R., Hornstrup, T., Schmidt, J. F., Dvorak, J., Søgaard, P., Krustrup, P. and Bangsbo, J. (2014a), Structural and functional cardiac adaptations to 6 months of football training in untrained hypertensive men. Scandinavian Journal of Medicine & Science in Sports. doi: 10.1111/sms.12237 
• Andersen, T. R., Schmidt, J. F., Nielsen, J. J., Randers, M. B., Sundstrup, E., Jakobsen, M. D., Andersen, L. L., Suetta, C., Aagaard, P., Bangsbo, J. and Krustrup, P. (2014b), Effect of football or strength training on functional ability and physical performance in untrained old men. Scandinavian Journal of Medicine & Science in Sports. doi: 10.1111/sms.12245
• Andersen, T. R., Schmidt, J. F., Thomassen, M., Hornstrup, T., Frandsen, U., Randers, M. B., Hansen, P. R., Krustrup, P. and Bangsbo, J. (2014b), A preliminary study: Effects of football training on glucose control, body composition, and performance in men with type 2 diabetes. Scandinavian Journal of Medicine & Science in Sports. doi: 10.1111/sms.12259
• Barene, Svein, et al. "Soccer and Zumba as health-promoting activities among female hospital employees: a 40-weeks cluster randomised intervention study." Journal of sports sciences ahead-of-print (2014): 1-11. 
• Barone-Adesi, Francesco, et al. "It is just a game: lack of association between watching football matches and the risk of acute cardiovascular events." International journal of epidemiology 39.4 (2010): 1006-1013.
• Berthier, Fabrice, and Frédéric Boulay. "Lower myocardial infarction mortality in French men the day France won the 1998 World Cup of football." Heart 89.5 (2003): 555-556.
• Helge, E. W., Andersen, T. R., Schmidt, J. F., Jørgensen, N. R., Hornstrup, T., Krustrup, P. and Bangsbo, J. (2014), Recreational football improves bone mineral density and bone turnover marker profile in elderly men. Scandinavian Journal of Medicine & Science in Sports. doi: 10.1111/sms.12239.
• Ramírez-Campillo, Rodrigo, et al. "Effects of In-Season Low-Volume High-Intensity Plyometric Training on Explosive Actions and Endurance of Young Soccer Players." The Journal of Strength & Conditioning Research 28.5 (2014): 1335-1342.
• Schmidt, J. F., Hansen, P. R., Andersen, T. R., Andersen, L. J., Hornstrup, T., Krustrup, P. and Bangsbo, J. (2014), Cardiovascular adaptations to 4 and 12 months of football or strength training in 65- to 75-year-old untrained men. Scandinavian Journal of Medicine & Science in Sports. doi: 10.1111/sms.12217

The Unsatiating Truth About Aspartame, Acesulfam K, Sucralose & Co: They Don't Induce Glucose or Insulin Spikes, But Do They Make You Hungry?

Image 1: If you plan to eat the stuff on the plate behind the coffee cup, I guess it does not really matter if you use sugar, fructose, Aspartame, Acesulfam K, Sucralose or everybody's  new darling, stevia to sweeten the coffee ;-)

If there was a yearly top 10 list of the furiously and most passionately debated topics, in the health & fitness community, the issue of "artificial sweeteners" (personally I would include high fructose corn syrup as "artificial", but I guess the FDA or rather their financiers think otherwise) would probably make it to the TOP 5 every year. All concerns about toxicity issues aside, the two main concerns people are worrying about are a direct negative effect on glucose metabolism and an indirect intake on subsequent / concurrent food intake. Both would obviously predispose consumers who buy respective products because they trust in the industry's promise that they would help the lose weight and/or ward off diabetes to the exact ailments they are intended to prevent.

Sweet taste receptors are all over the place!

My personal interest in this topic has always revolved around the issue of "sweet taste receptors" (i.e. cells that will recognize certain molecules as being sweet), the existence of which in / on all sorts of organs / tissues scientists had been overlooked for decades. I mean, isn't it revealing that the same "sensors" that are responsible for the sweet sensation you experience when you spooning your delicious full-chocolate ice cream are also present in your gut and even on your pancreas, where their activation sets the stage for the release of insulin into the bloodstream (Nakagawa. 2009)? This rather recent revelation could after all finally explain the early results of Blundell et al. who observed an increase in calorie consumption in subjects after consumption of foods containing the artificial sweeteners Aspartame and Saccharin (Coke light & Co), back in the fat-phobic 1980s (Blundell. 1986; 1989). Subsequent more sophisticated studies were yet unable to reproduce those early results (at least in humans).

Artificial sweeteners are obesogenic! Bitter truth or just another myth?

With the advent of a more sophisticated understanding of the complex physiological processes and integrated signaling systems which regulate appetite and satiety in mammals and humans in particular (I doubt we will ever be able to understand all the psychological factors that come into play with the latter), Robert E. Steinert and his colleagues from the Clinical Research Center at the University Hospital in Basel (Steinert. 2012), Switzerland, took another, more closer look at what actually happens, when we consume beverage which taste as if they contained tons of sugar, but are totally devoid of nutrients.

Figure 1: Intensity of sweetness, total amount per 250ml solution and energy equivalent of the five sweet test solutions (the sixth beverage was plain water); mind the logarithmic scale! (data adapted from Steinert. 2012)

To this ends, the Swiss scientists recruited 12 healthy, non-smoking volunteers (6 men, 6 women; mean age 23.3y; normalweight, BMI 23kg/m², min. 3 months of stable weight) to perform a randomised, placebo-controlled, double-blind, six-way cross-over trial. In each of the 6 trials, which were seperated by 3-5d the subjects reported to the lab at 8:00am after an 10h overnight fast (no alcohol, no exercise, no supplements or medication), where they received one (on each occasion) out of six 250ml test solutions containing either tap water (no problem to drink that, in Switzerland ;-), or freshly prepared solutions with concentrations of the different sweeteners, of which the scientists state that they "were comparable with the amounts found in commercially available beverages and soft drinks" (Steinert. 2012; cf. figure 1).

Note: I guess I should mention that the test beverages were administered via an intranasal feeding tube. I honestly have no clue, why the scientists chose this method over the natural route through the mouth. After all, this reduces the real world significance of their results. If, for example the sweet taste receptors in the oral cavity (which were obviously bypassed by the intranasal feeding tube) are hard-wired to the brain, while those in the gut are not, this would not only influence the "psychological" aspect of satiety, but could also induce hormonal, i.e. physiological effects... but hey, who am I to criticize the professionals? After all I am only a stray physicist in the realms of nutrition and exercise science ;-)

The intranasal feeding tube was removed immediately after the administration of the respective test beverages. Blood was drawn at regular time intervals at 5, 10, 15, 20, 30, 45, 60, 75, 90 and 120 min and the subjects were asked to rate their hunger, satiety and fullness on a visual analogue scale.

No insulin response, no glucose response to any artificial sweetener

Before we get to the significant findings, I want to address the often touted insulinogenic effect some of the artificial sweeteners are supposed to have... let me make it short and concise, so that everyone can understand it: There was NO insulin response to ANY of the ARTIFICIAL SWEETENERS!

Figure 2: Glucose and insulin response to glucose and fructose sweetened beverages; there were NO changes in either glucose or insulin in response to the artificially sweetened beverages (adapted from Steinert. 2012)

If you scrutinize figure 2 you will notice that I did not even bother to plot the "straight" lines for either Aspartam, Acesulfam K, or Succralose. The reasons for me to include the glucose and insulin responses, at all, were that...

1. there was a minimal yet statistically non-significant increase in both blood glucose as well as insulin levels in response to the fructose sweetened beverage, and
    
2. there was a huge +/- 20µU/ml (=20%!) standard deviation for the insulin response to glucose at the 20min mark.

While the former, i.e. the fructose induced increase in both blood glucose and insulin is probably a result of gluconeogensis in the liver, the latter, i.e. the huge inter-individual variation with respect to the amount of insulin that was released to a standardized beverage, which contained 50g of glucose, goes to show you how large the discrepancies wrt "insulin tolerance / resistance" actually are, even in otherwise healthy young individuals.

Sweetness alone is not satiating - neither "hormonally", ...

Apposite to the previously established non-insulinogenic effects of the three artificial sweeteners in the study, neither Aspartame, nor Acesulfam K or Sucralose led to increases in the glucagon-like peptide-1 (GLP-1, cf. figure 3), which is involved in the so-called "incretin effect". The latter is responsible for the more pronounced insulin response to an oral vs. an intravenous glucose load and is ascribed to the presence / release of GLP and GIP in the gut.

Figure 3: Area under the curve (AUC) and maximal value (Cmax) of GLP-1, PYY and Ghrelin in response to the administration of the six test beverages; values expressed relative to water = control (data calculated based on Steinert. 2012)

In a similar vein, the administration of the artificially sweetened beverages increased neither the "satiety hormone" peptide tyrosine tyrosine (PYY) nor the "hunger hormone" ghrelin over the levels the scientists observed for the control beverage which contained plain water, relative to which the values in figure3 are expressed. Glucose and fructose, on the other hand, led to large and small increases both the area under the curve (AUC, figure 3, left) and the maximal expression (Cmax, figure 3, right) of GLP-1 and PYY, as well as corresponding decreases in ghrelin. Accordingly, Steinert et al. conclude:

We infer from these obser- vations that sweetness per se is not sufficient to stimulate the secretion of these peptides in humans. Additional chemosensory mechanisms directed towards the structural integrity of the glucose molecule (as one of the major fuels for the body) must exist including active transport systems. Finally, potential energy-sensing mechanisms or energy thresholds might exist for the secretion of GLP-1 and PYY, although it is unlikely that the release is directly related to the energetic load in a dose–response manner.

And if we were all nothing but hormonally controlled machines, I guess this would be the end of today's blogpost, but since we are not, it is probably prudent to look at the subjective hunger, satiety and fullness ratings of the study participants before we settle this case.

... nor "psychologically", and in fact, it could even make some people hungrier!

If we had to make prediction based on the hormonal data Steiner et al. collected, what would you say, which group will feel the most satiated and the least hungry? What? The glucose group? Why? Because they consumed the largest amount of calories? But what about the insulin spike? Well, I guess, it is pointless to continue this feigned dialog... so, let's just take a look at the actual results:

Figure 3: Time (in min) until hunger, satiety and fullness after ingestion of the six test beverages returned to baseline; statistical averages, left; median, right (data adapted from Steinert. 2012)

I guess, the results won't please everyone out there, after all fructose, which has as of late been deemed responsible for whatever ailment our obesity ridden society is suffering from, induced the most profound (=long lasting) satiety effect. Fructose reduced the hunger longer than any other sweetener and the subjects felt full for a longer time period after the ingestion of the fructose-sweetened beverage than after any other sample.

A brief note: Maybe I can calm the followers of Dr. Lustig down, if I remind them of the way fructose is metabolized? Remember? Fructose is largely being processed into triglycerides by the liver. Now, the latter obviously are fats and I guess nobody will challenge the satiating effects of fat, these days, right?.

With the glucose beverage taking a close second and only non-significant (you know "statistically" ;-) differences to the artificial sweeteners, Steinert et al. thusly summarize their results as follows:

The appetite profile revealed that the (energy-containing) carbohydrate sugar loads induced the longest-lasting increase in fullness ratings above baseline, which was prolonged for fructose 108·4 (SEM 6·1) min and for glucose 90·5 (SEM 11·2) min. In contrast, water (74·0 ( SEM 13·4) min) and the AS [artificial sweeteners] acesulfame K (65·6 (SEM 15·8) min), aspartame (83·1 (SEM 15·9) min) and sucralose (65·3 ( SEM 14·1) min) induced shorter augmented fullness above initial ratings. However, due to the large data variability, these differences did not reach statistical significance. Satiety and hunger ratings showed similar trends, however, with generally smaller differences. Overall, the AS increased satiety and fullness and reduced hunger ratings to an amount that was intermediate between the carbohydrate sugars and the water control.

Now, the SuppVersity would not be the place to go to read about the latest studies, if I would content myself with someone else's analysis of data that has already undergone a selection process, in the process of which the individual responses got lost. If we do yet take a look at the difference in mean (i.e. the statistical average; figure 3, left) and median (which is the median value in an ordered list; figure 3, right) time it took for the hunger, satiety and fullness ratings to return to baseline, we have - yet again - enough evidence for the presence of a huge interpersonal variability.

Figure 4: Ratio of the statistical averages and the respective median time until the hunger, satiety and fullness ratings returned to baseline after ingestion of the six test beverages.

If we take the ratio of the average to the median as an obviously very unreliable marker of this inter-personal variability (I plotted the respective values for you in figure 4). It becomes obvious that Acesulfame K, which is the sweetener most companies who pride themselves of not using Aspartame put into their products, could in fact be a wolf in sheep's clothing. While the low median satiety scores in figure 3 (right) already suggested that it must have been significantly less satiating than plain water, let alone the other sweetened beverages, for some of the subjects, at least, the alternative representation of the data as the ratio of the average to the median in figure 4 reveals how pronounced this effect actually is.

"So, tell me: What's the unsatiating truth now?"

In spite of the fact, that I do believe that the concerns about potential insulin spikes from foods / beverages which are sweetened with artificial sweeteners only is unwarranted, the large intra-individual variation of the satiety effects of the Acesulfam K should raise your awareness of your individual response to artificial sweeteners, in general, and anything that contains Acesulfam K, in particular. If you feel that respective foods make it difficult for you to stick to your diet, just don't eat / drink them! If, on the other hand, the 1l of Coke light you consume during your fast (just an example ;-) does not make you hungrier than the same amount of water and you are not worried about the fact that rats develop cancer when you feed them with amounts of Aspartame that would equal the consumption of several truckloads of diet coke per day (and that over weeks or months), don't bother and stick to what works for you...

If you do however have trouble sticking to your diet, cannot lose weight or have existing blood sugar issues, don't use the results of this study as an excuse for your unwillingness to (at least try to) go without your beloved diet Coke for at least a month to see whether or not the latter is not part of the underlying physiological (and psychological) causes of your misery!