High Dose Caffeine Restores Insulin Sensitivity and Limits Total as Well as Visceral Fat Gain Due to High Sugar Diets

High Dose Caffeine Restores Insulin Sensitivity and Limits Total as Well as Visceral Fat Gain Due to High Sugar Diets

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Yes, the study at hand is on caffeine, but the results are relevant for coffee, too.

A decade ago, the medical community though coffee would dehydrate you, would make you insulin resistant and would increase your risk of heart disease. Recent studies show that coffee does not negatively affect your hydration status (Killer. 2014), that higher coffee consumption is associated with reduced diabetes risk and increasing your coffee consumption can reduce your risk of T2DM (Akash. 2014) and that a "daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects" on coronary heart disease, congestive heart failure, arrhythmias, and stroke (O'Keefe. 2013).

Against that background it may not be as surprising as it would have been 10 years ago that Joana C. Coelho, et al. (2016) found caffeine to be able to restores insulin sensitivity and glucose tolerance in high-sucrose diet rats. And yet, I personally believe that it is still worth pointing out the results of this study as the high sucrose diet the mice were fed is the same "high sugar diet" about which you will read all over the news that it is to blame for the obesity and diabetes epidemic.

You can learn more about coffee and caffeine at the SuppVersity

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Against that background, it is particularly interesting to take a closer look at the data from Coelho's study, because it is the first to actually provide a valid explanation for the observed improvements in glucose sensitivity in response to the ingestion of caffeine.

Figure 1: 16-wk food intake, weight gain, fat gain and visceral fat gain according to caffeine intake (Coelho. 2016).

Now, the bad news is that significant effects were only observed for the highest dose of caffeine, ie..e 1g/L drinking water. That appears to be ridiculously high, but is in fact only "very high". If you do take into consideration that a wistar rat consumes only 100 ml/kg body weight per day, that's a dosage equivalent of 100 mg/kg for a rodent and thus ~16 mg/kg for a human being or ~6-7 cups of coffee (over a 24h period).

University of Memphis: Caffeine can help control the increase in blood lipids and oxidation after inhaling (10 minutes) a high calorie + high fat milk shake, controlled trial involving twelve healthy men shows (Crone. 2016).

Yes, the dosage is high, but actually less may have more benefits, and...  the most relevant benefits (reduced fat gain) were seen at a dosage that would be equivalent to only 4-5 cups of coffee, which happens to be roughly what epidemiological studies show to be in the zone of maximal benefits. Don't mistake this as a recommendation to guzzle liters of coffee, though... and that even if another recent study shows that 400mg of caffeine will lower the fatty acid onslaught and oxidation 12 men experience after consuming a large high fat milk-shake (Crone. 2016)... and speaking of coffee: you may also want to make sure to get a dark roast, because the latter has just been found to improve glucose metabolism and redox balance even if it is low in caffeine (Di Girolamo. 2016). 

While I am not sure how healthy the chronic consumption of these amounts of caffeine actually is. I am aware of several people who get their 6-7 cups of regular coffee per day and are in perfect health. With that being said, the latter may be at least partly due to the the highly beneficial effects of caffeine on the expression of glucose transporter 4 (GLUT4) and insulin receptor expression and phosphorylation (not shown in Figure 2) in the visceral fat depots of coffee connaisseurs.

Figure 2: Effects of different doses of caffeine on GLUT4 and insulin receptor expression in rats (Coelho. 2016).

The above elevations were accompanied by profound increases in protein kinase B (Akt) expression and activity, as well - an observation the scientists regard as being evidence of the fact that "[c]hronic caffeine administration improved whole-body glucose homeostasis and insulin signaling pathways in adipose tissue" (Coelho. 2016).

This conclusion cannot be questioned. What can be questioned, though, is the scientists assumption that this would occur only with high doses of caffeine and in response to increases in GLUT4 and insulin receptor expression in the visceral fat. Why's that? Well take a look at the figure in the bottom line: it shows that significant improvements in glycemia were improved at all dosages. The latter wouldn't have been possible if the lower dosages wouldn't have had an effect on glucose uptake, as well. Whether that's an effect in muscle cells (which would be great), needs further investigation. The previously discussed effects of caffeine on muscle glycogen storage (learn more), on the other hand, would suggest just that: an effect on skeletal muscle, and or a reduction in gluconeogenesis which could, among other things, be triggered by coffee's / caffeine's ability to inhibit the reactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1" (Atanasov. 2006).

As you can see sign. improvements in glycemia occured even with the lowest amount of caffeine in the drinking water. And that in spite of the fact that the GLUT4 and insulin receptor levels in the visceral fat did not increase significantly... well, maybe those in the rodents' muscle did?

Bottom line: I am not suggesting that the rodent study at hand would provide enough evidence to suggest that everyone should drink at least 4 cups of high caffeine coffee per day. What I do suggest, however, is that the study at hand provides more evidence on potential mechanisms that explain why coffee drinkers are plagued less often by metabolic disease.

With that being said, I would like to remind you that the abuse of caffeine to combat a lack of sleep and/or overtraining may make you dig a deep black hole out of which you will be able to crawl only within weeks of abstinence... and I am talking about abstinence from caffeine and exercise, assuming that it was the combination of both that got your into trouble | Comment on Facebook!

References:

• Akash, Muhammad Sajid Hamid, Kanwal Rehman, and Shuqing Chen. "Effects of coffee on type 2 diabetes mellitus." Nutrition 30.7 (2014): 755-763.
• Atanasov, Atanas G., et al. "Coffee inhibits the reactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1: A glucocorticoid connection in the anti-diabetic action of coffee?." FEBS letters 580.17 (2006): 4081-4085.
• Coelho, Joana C., et al. "Caffeine Restores Insulin Sensitivity and Glucose tolerance in High-sucrose Diet Rats: Effects on Adipose Tissue."
• Crone, et al. "Impact of Meal Ingestion Rate and Caffeine Coingestion on Postprandial Lipemia and Oxidative Stress Following High-Fat Meal Consumption." Journal of Caffeine Research (2016): Ahead of print. DOI: 10.1089/jcr.2016.0004.
• Di Girolamo, Filippo Giorgio, et al. "Roasting intensity of naturally low-caffeine Laurina coffee modulates glucose metabolism and redox balance in humans." Nutrition (2016).
• Killer, Sophie C., Andrew K. Blannin, and Asker E. Jeukendrup. "No evidence of dehydration with moderate daily coffee intake: a counterbalanced cross-over study in a free-living population." PloS one 9.1 (2014): e84154.
• O'Keefe, James H., et al. "Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality." Journal of the American College of Cardiology 62.12 (2013): 1043-1051.

Path to Fat-Induced Obesity is Sprinkled With Salt - Sodium Boosts Food & Energy Intake & Reduces Fat's Satiety Effect

Path to Fat-Induced Obesity is Sprinkled With Salt - Sodium Boosts Food & Energy Intake & Reduces Fat's Satiety Effect

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Think you cannot eat the whole pizza? Add salt - this should "help" with the hardest all-you-can-eat challenges.

I am not telling you something new if I tell you that excess fat consumption has been linked to the development of obesity. I hope that it's also not news to you that the consistent association between high(er) fat intakes and weight gain in epidemiological studies cannot be reproduced in human studies where the diet is just high in fat and doesn't have the perfect "potato chips"-combination of fat and carbohydrate that has not just been proven to increase food intake, but also to have pro-addictive effects on the brain (Hoch. 2015).

The fat to carbohydrate ratio Hoch et al. identified as a crucial determinant of snack food intake and brain reward responses in their 2015 study is yet not the only characteristic feature of potato chips.

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Another similarly striking feature chips share with a couple of other highly addictive foods is their salt content. The same salt content of which Bolhuis et al. write in their soon-to-be-published paper in The Journal of Nutrition that we don't know yet how it interacts with the appetitive effects of fat. Apropos fat, whether fat will increase or decrease your appetite is actually highly individual question. Some studies even suggest that a high fat content has appetite reducing effects - at least in those individuals with a high fat taste sensitivity.

Unfortunately, the results of pertinent studies are inconclusive; and that even in people with intact fat taste sensitivity. In view of previous research showing similar associations between the salt content of snack foods and their appetizing effects as they were observed for high carbohydrate + high fat foosds, Bolhuis et al. speculated that our fat taste sensitivity may be influenced by the co-ingestion of salt. To test this hypothesis, the researchers recruited forty-eight healthy adults [16 men and 32 women, aged 18–54 y, body mass index (kg/m2): 17.8–34.4]. After an initial assessment of their individual fat taste sensitivity, the subjects participated in a randomized 2 x 2 crossover design trial, in which each participant attended 4 lunchtime sessions after a standardized breakfast.

Figure 1: The high salt meals were generally rated as more pleasant, while fat had no effect on the perceived pleasantness of the meal (Bolhuis. 2016).

The meals seemed to be identical elbow macaroni (56%) with sauce (44%); the sauces, however, were manipulated to be

• low-fat (0.02% fat, wt:wt)/low-salt (0.06% NaCl, wt:wt),
• low-fat/high-salt (0.5% NaCl, wt:wt), 
• high-fat (34% fat, wt:/wt)/low-salt, or 
• high-fat/high-salt.  

Ad libitum intake (primary outcome) and eating rate, pleasantness, and subjective ratings of hunger and fullness (secondary outcomes) were measured.

The results indicate that salt increased food (= food weight) intakes by 11%, independent of fat concentration (P = 0.022), while increasing the fat intake had no independent effect of fat on food intake (P = 0.6 for the amount of food, not its energy content).

Figure 2: This is what really counts, the effects of modfiying fat and salt content of the meals on total energy intake during the meals; data in kcal per meal (Bolhuis. 2016).

A slightly different picture emerges for the total energy intake, though. Here, the salt intake still mattered (significant with high vs. low salt meals), the main determinant of the total energy intake, however, was the fat content of the meal, with the high-fat meals triggering a whopping +60% (P < 0.001) increase in energy intake in the average subject.

Figure 3: When the diet was high in salt, the mediating effect of fat taste sensitivity on food intake (in g) is lost (Bolhuis. 2016)

Unlike the amount of fat in the meals, the sex of the participants had an effect on the food intake (P = 0.006), with women consuming 15% less by weight of the high-fat meals than the low-fat meals.

More importantly, however, the fat taste sensitivity appeared to decrease signifi-cantly with increasing amounts of salt in the high-fat meals (fat taste x salt interaction on delta intake of high-fat - low-fat meals; P = 0.012), which tended to trigger a satiety effect in the fat sensitive subjects only if they were also low in salt (see Figure 3).

The Overfeeding Overview: High Fat, Carb, Protein, MCTs, Leptin, Testosterone, T3 & Reverse T3 - Get an Overview of the Consequences of Short- & Long-Term Overfeeding - Yes, the existing research shows that high fat intakes (in the presence of carbo-hydrates) are the most fattening.

Bottom line: As the authors of this intriguing study rightly point out, their results "suggest that salt promotes passive overconsumption of energy in adults" (Bolhuis. 2016) and as if that was not bad enough, even those who are sensitive to a higher fat content of food will be fooled into overeating when the high salt content of said foods overrides the fat-mediated satiation.

Ah,... before you rejoice and start eating tons of unsaltet potato chips - there's one thing I should remind you of: even though an excessive increase in dietary fat (from 0.6 to 15.5 g/100g) did not have a main effect on food intake by weight, it led to a 60% higher energy intake, irrespective of the salt content of the meal - an observation that should remind you of the "volume hypothesis" of satiety | Comment!

References:

• Bolhuis, Dieuwerke P. et al. "Salt Promotes Passive Overconsumption of Dietary Fat in Humans." The Journal of Nutrition (2016): Ahead of print.
• Hoch, Tobias, et al. "Fat/carbohydrate ratio but not energy density determines snack food intake and activates brain reward areas." Scientific reports 5 (2015).

Artificial Sweetener Saccharin Increases Weight Gain in Rodent Study Without Increasing Food Intake | Plus: Meta-Analysis of Human Studies Says: "No Reason to Worry!"

Artificial Sweetener Saccharin Increases Weight Gain in Rodent Study Without Increasing Food Intake | Plus: Meta-Analysis of Human Studies Says: "No Reason to Worry!"

artificial sweetener artificial sweeteners diabesity fat gain glucose health insulin leptin lose fat saccharin sweeteners weight gain

Should you freak out about a small increase in body weight in a small-scale rodent study that is attributed to the consumption of saccharin in yogurt?

While epidemiological studies show that the consumption of products containing non-nutritive sweeteners (NNS) is associated with increased adiposity (Colditz. 1990; Fowler. 2008), type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular disease (Dhingra. 2007; Lutsey, Steffen. 2008). A mechanistic link between aspartame, sucralose, stevia & co and weight gain as well as its ill metabolic and cardiovascular consequences in humans is non-existent (learn more).

Rather than weight increases controlled human studies show that the consumption of artificially sweetened foods promote, not hinder the loss of body fat (Sørensen. 2014).

You can learn more about sweeteners at the SuppVersity

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In animal models, though, the results have been more conflicting. While many studies show no effect of artificial sweetener consumption, the latest stud by Kelly Carraro Foletto and colleagues is not the first rodent study to suggest that non-nutritive sweeteners may also interfere in the regulation of compensatory appetite promoting weight gain (Davidson. 2011; Polyák. 2010; Rogers. 1988). This does yet not refute the findings of one of the latest meta-analysis of the effects of low-energy sweetener consumption on energy intake and body weight in man - a meta-analysis published in Nature's prestigious International Journal of Obesity that says...

Figure 1: The forest plots of the practically most relevant data of individual and combined effect sizes for sustained intervention studies comparing the effects on body weight of sweeteners versus sugar (upper panel) and versus water (lower panel) shows that not a single long(er) term study found negative effects - the exact opposite is the case. Even compared to water the use of low-energy sweeteners (artificial or not) lead to measurable, yet not always significant decreases in body weight in human trials (Rogers. 2015).

"that the balance of evidence indicates that use of LES [low or no energy sweeteners] in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water" (Rogers. 2015 | my emphasis).

And with respect to the often-cited "evidence" from animal and observational studies, the autors of the meta-analysis submit that...

"[...] the present review of a large and systematically identified body of evidence from human intervention studies, with varying designs, settings and populations (including children and adults, males and females, and lean, overweight and obese groups), provide no support for that view. The question then is whether those hypotheses should be rejected or whether, as seems unlikely, the relevant human intervention studies are consistently flawed in a way that leads, in most cases, to exactly the opposite outcome" (Rogers. 2015)

I do thus want to warn you: Do not overrate the already relatively small amount of extra-weight the rodents in saccharin group of Foletto's recent study gained (see Figure 2, left).

Figure 2: Cumulative weight gain and total cumulative energy intake of (only) 16 male Wistar reds fed diets that were supplemented with either saccharin-sweetened or non-sweetened yogurt added (Foletto. 2015)

In a previous study, Folleto et al. had already observed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. In their latest study they did not try to prove that this effect is independent of the rodents' energy intake and mediated by insulin-resistance and / or modified levels of leptin and PYY in the fasting state.

Was it fat they gained or lean tissue mass? Well, I would like to answer these important questions, but Foletto did not disclose (or not even measure?) this important parameter. The practical relevance and reliability of their results is further reduced due to the small cages (44x34x16 cm individual cages) into which the rodents were confined to reduce their voluntary physical activity during the 14 weeks of the experiment, as well as the exclusion of rats who didn't consume the aspired 70% of the planned 75 kcal in form of yogurt per week (the number of rats who fell into this category is also not disclosed).

To this ends, the researchers randomly assigned 16 male Wistar rats to receive ~78kcal per week from either saccharin-sweetened (0.3% saccharin) yogurt or non- sweetened yogurt (0.5 kcal/g) in addition to chow (2.93 kcal/g) and water ad lib. For 14 weeks, Foletto, et al. measured the total food intake (from yogurt and chow) daily and the weight gain on a weekly basis (the results are plotted in Figure 2). Fasting leptin, glucose, insulin, PYY and HOMA-IR levels were measured only at the end of the 14-week study period, though.

Table 1: In view of the fact that any existing negative effects of dietary sweeteners may well be compound-specific. It is certainly worth noting that saccharin is no longer used in modern sweetener formulations of sodas (Wikipedia. 2015)

In spite of the already reported ~5% increase in cumulative weight gain over 14 weeks (p=0.027), the researchers found no differences in HOMA-IR (=insulin resistance), fasting leptin or PYY levels between groups that could mechanistically explain why the rodents who received saccharin sweetened yogurt gained more weight than their peers who received non-sweetened yogurts.

Measurable weight increases are a common pattern in rodent studies particularly for the (today rarely used) artificial sweetener saccharin. It is thus well possible that any existing negative effects are compound-specific. For aspartame, for example, similar evidence is rare to non-existent.

Bottom line: In the absence of a proven theory about the mechanism that may trigger the increased weight gain and in view of the lack of health-relevant data (no information about the body composition of the rodents) and health-relevant side-effects you would usually see in response to pathologic weight gain (changes in insulin resistance, leptin or PYY), I can only refer you back to the quote from the latest meta-analysis of the effects of low- to no-energy-sweetener intake on food intake and weight gain in humans, which say that "the balance of evidence indicates that use of LES [low or no energy sweeteners] in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water" (Rogers. 2015).

Furthermore, more relevant evidence from human clinical trials supports the use of artificially sweetened foods as dieting aids (Sørensen. 2014 | learn more).

Whether that's enough to convince you that the unproven negative effects of saccharin on caloric expenditure or increases in the glucose transport mediated by gut sweet-receptors, of which Foletto et al. speculate that they may explain the results of their study, are relevant enough to avoid non-nutritive sweeteners altogether is now up to you. For me it's not enough... | Comment on Facebook!

References:

• Foletto, Kelly Carraro, et al. "Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats." Appetite (2015).
• Rogers, P. J., et al. "Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies." International Journal of Obesity (2015).
• Sørensen, Lone B., et al. "Sucrose compared with artificial sweeteners: a clinical intervention study of effects on energy intake, appetite, and energy expenditure after 10 wk of supplementation in overweight subjects." The American journal of clinical nutrition (2014): ajcn-081554.