Tuesday, August 5, 2014

What's Worse for Your Body Composition & Liver Health? 10g of Sugar from Coke or the Same 10g From Cookies? Plus: Liquid Sucrose is Harder on the Liver Than Fructose

Hard do believe, but the 10g from coke may actually do more harm than the same amount from cookies.
If you want to scare me away from a discussion about the "fat problems" the US and large parts of Europe are struggling with, you just have to repeat Taubs'ian statements such as "if we had not eaten carbohydrates all the mess wouldn't have happened."

It's certainly true that the exorbitant and mislead carbohydrate intake and the psyochological consequences ("Fat is bad, isn't it?") of the "low fat" decades from the 1970-1990s is part of the problem, but when we look closer, it's not as simple as to say "we don't eat enough fat".

As Yvonne Ritze and her colleagues from the University of Hohenheim, the Technische Universit√§t M√ľnchen, and the Interdisciplinary Obesity Center in Rorschach (Switzerland) write in their latest paper in PLoS One, it's rather the unhealthy conglomerate of "changes in dietary and eating behavior such as preferring sugar-sweetened beverages and sugar-rich processed food, in addition to a sedentary life style", which is to blame form the "sharp rise in obesity" (Ritze. 2014).
Learn more about alternatives to sugar sweetened beverages at the SuppVersity

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Artif. Sweetened Foods Good, Not Bad for Fat Loss.
In said paper, Ritze and her colleagues present data from rodent and human experiments they conducted which highlight the fact the "form of sugar intake (liquid versus solid) is presumably more important than the type of sugar" (Ritze. 2014), when it comes to its ability to disturb our appetite regulation, increase the fat accumulation in the liver and promote the development of type II diabetes.

In mice, Ritze et al. observe a liquid high-sucrose diet caused an enhancement of total caloric intake which was not comparable to the effects the solid variety of the high sucrose diet had.
Figure 1: Diet (left) and energy (right) intake in the five diet groups (Ritze. 2014)
Over the course of the experiment (8 weeks), the female C57BL/6 mice (Janvier, Saint Berthevin Cedex, France) had been feed on one out of the following five ad-libitum (=eat as much as you want to) diets:
  • Group 1 (controls, C) received water and mouse breeding (MZ)-diet (standard diet from Sniff, Soest, Germany) containing 10% (g/g) sugars. 
  • Groups 2 (fructose liquid, Fl) and 3 (sucrose liquid, Sl) received water supplemented with fructose or sucrose at 30% (vol/vol), respectively, and enriched MZ-diet to compensate for reduced food uptake. 
  • Groups 4 (fructose solid, Fs) and 5 (sucrose solid, Ss) received water and the high-fructose or -sucrose diet containing 65% (g/g) sugars, which equals the sugar amount per day that mice ingested when offered sugar water at 30%. 
Every two weeks the mice were placed in metabolic cages for 24 h, to which they had been acclimatized before. The mice were weighed, their food intake and feces analyzed and their body composition quantified; and what the scientists found was:
  1. The sugar intake in groups 2-4 was significantly higher than in group 1 - obviously a simple and necessary consequence of the composition of the diet
  2. The mice on the liquid diets consumed significantly more energy, sugar, liquid and food - distinct evidence that the rodent equivalent of sugar-sweetened beverages leads to overeating
  3. The fructose diets were not by any means worse than the sucrose diets - an observation that confirms what I have been preaching to the choir: The fructose bashing as "lustig" (engl. "funny") as some experts believe it was, is based on a shortsighted prejudice
  4. The weight increase in the solid high-sucrose groups was small compared to that of the mice in groups 2 & 3 who were fed sucrose or fructose in their water - this is the logical consequence of the increased energy intake
  5. When the scientists compared the obesogenic effects (weight gain per food intake) of the diets, they found a significant difference between the liquid and solid sugars but not the sugar types - more evidence we cannot simply blame everything on fructose
  6. Interestingly, all four high sugar-diets caused an increase in blood glucose and in tendency some increase in liver weight, which was more pronounced if the sugars were administered in solid form.
In addition, Ritze et al. found a strong increase in GLUT2 mRNA expression (Fl = about 90 fold;  P < 0.001; Sl = about 160 fold; P < 0.001) when sugars were dissolved in drinking water compared to the control mice - again more pronounced in the sucrose vs. fructose group. Compared to the 90x & 160x increase in the liquid groups, the likewise significan increase of ileal GLUT2 mRNA expression (P < 0.05) in the solid high sugar groups 4 & 5 was almost negligible.
"Similar results were obtained for GLUT5 mRNA expression. Comparing sugar form and type we showed a significant difference between liquid and solid sugar form for GLUT2 and GLUT5 (P < 0.001) as well as a significant difference of sugar type (fructose versus sucrose) for GLUT5 (P < 0.05) within the different dietetic groups." (Ritze. 2014)
Whether these difference in glucose transporter activity are actually relevant (they would simply speed up the uptake of glucose / fructose) is questionable.

Is absorption speed all that matters?

Figure 2: Suspiciously similar changes in glut-2 & 5 expression in the two groups fed liquid diets (top) and obese vs. lean human (bottom)
The fact that Ritze et al. observed them when they compared the GLUT2 and GLUT5 expression in obese and lean human subjects, as well, is yet quite telling. In the end, it may thus in fact all be about "speed" and the question "How fast is the sugar trickling into your body?"

Whether the speed of the sugar influx is also responsible for the slightly up-regulated ghrelin mRNA levels in mice who were fed the liquid diet compared to the solid diet (P < 0.05) is something, I cannot tell. What I can tell you though is that (a) elevated or rather not appropriately reduced ghrelin levels after a meal are characteristic of obese vs. lean humans, too (Le Roux. 2005) and that (b) there was once again no difference between fructose and sucrose diet.
Did you ever notice that none of the "fructose is bad studies" was conducted with a solid diet? The fructose was always provided on top of a solid diet with the liquid, just like the the surcose and fructose in the diet at hand. And if we are honest, it does not look like fructose was by any means significantly worse than simple sugar (which obviously is a 1:1 glucose : fructose mixture).
Figure 3: Effect of high-sugar diets on hepatic lipid accumulation. Concentrations of triglycerides in the liver (A), and liver to body ratio (B) were detected. Portal endotoxin (C), and Oil Red O staining showing fat accumulation in the liver (D) are shown
Now, what certainly comes as a surprise is the fact that it's not the liquid fructose group which had the highest liver fat concentrations, but rather the group that received the equivalent of sugar (=sucrose) sweetened beverages in their diets (see Figure 3, A). Accordingly, the Oil Red O staining in Figure 3, D is most significant in the Sl (=sucrose liquid) diet group.

The endotoxin concentration in the portal vein (see Figure 3, C), on the other hand, are the highest (yet not significantly elevated!) in the fructose groups. In conjunction with the relatively low triglyceride levels in the liver this goes against a theory by Bergheim et al. which revolves around the idea that fructose induced changes in the gut microbiome would lead to an increased endotoximia (this is true) and consequent fatty liver disease (this is at least less severe that with sucrose in the study at hand).
Bottom line: Let's get away from the "fructose vs. the rest of the world" discussion and focus on those "foods" that contain significant amounts of fructose. If you click on "foods highest in fructose" on nutritiondata.com, you will obviously find "pops, sodas, and soft drinks" on the first three ranks. And while they do have a high fructose concentration (29.8g per 200ml serving), the study at hand should remind you of another thing they have in common... ha? Yeah! Right, they are liquid fast absorbing and a real stressor for your liver.

Figure 4: Replacing SSBs or juices with water or artificially sweetened beverages has identical beneficial effects on the weight trajectory of adults (Pan. 2013) - Even low fat milk would have you gain less body weight!
I am far from suggesting that after blaming fructose for everything, we should now start blaming liquid foods for everything, but the results Ritze et al. present in their latest paper do in fact "provide evidence that liquid versus solid high-sugar diets differentially modulate feeding behavior, distinct intestinal sugar transporters and weight regulating hormones" and may thus be "a critical component for the development of obesity and fatty liver disease", not just in mice, but also in humans, where Ritze et al. found "similar enhanced sugar transporter regulation within the small intestine as in liquid high-sugar diet fed mice" and previous studies suggest that simply replacing energy containing drinks with water will inhibit or at least slow down long-term weight gain (Pan. 2013)
  • Bergheim, Ina, et al. "Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin." Journal of hepatology 48.6 (2008): 983-992. 
  • Le Roux, C. W., et al. "Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects." The Journal of Clinical Endocrinology & Metabolism 90.2 (2005): 1068-1071. 
  • Pan, An, et al. "Changes in water and beverage intake and long-term weight changes: results from three prospective cohort studies." International journal of obesity 37.10 (2013): 1378-1385. 
  • Ritze, Yvonne, et al. "Effect of High Sugar Intake on Glucose Transporter and Weight Regulating Hormones in Mice and Humans." PloS one 9.7 (2014): e101702.