Another example of biased scientific reporting - does fructose consumption lead to weight gain?

As I have promised in my previous article: Misreporting in the scientific literature, I am going to show you another example of biased scientific reporting. 

In the previous article you could see how the American Heart Association Scientific Statement (AHA Statement) misreported the actual findings of two particular studies which in fact did not suggest at all that the sugary soft drinks led to increased food intake as a direct result of the drinks consumption. 

In this article I am going to distinguish between the effect of fructose and sugar sweetened beverages (SSB) on people's metabolism and body weight and to bring more light into reporting of the metabolic studies. 

Again, I have cropped the relevant pieces of the AHA Statement text and I am going to write my comments on it. 

Cross-sectional studies

The first sentence of the text above reports that people consuming energy dense beverages have a higher energy intake. I have already discussed this in my previous article as a logic consequence and why people ate more of anything that was put in front of them. I am not going to elaborate more on this.

That people in the Western world, habitually consuming processed foods, have poor nutrition is no news to me and most other people having a genuine interest in nutrition and health. 

It is the 'suggestions' made that related only the excessive FRUCTOSE consumption with various metabolic issues in humans which I have found intriguing. These suggestions seem to conclude that the excess of anything else is not a problem at all, despite this anything comes together with fructose at once. There were studies listed as reference. You can find these at the end of this article. 

Let's just repeat the obvious facts I have mentioned numerous times in my articles:

The USDA and NHANES data suggest that the trends in sugars intake almost copied the trends in fats intake, up to year 2000. In addition, it was the processed starch based carbohydrates the consumption of which had increased more prior year 2000 than the consumption of sugars or fat. Therefore the Americans have been eating more of EVERYTHING, not only of sugar or fructose. That is one fact. The another fact is that since 2000 it was mostly the processed cheap vegetable oils that shot up in consumption trends, while the carbohydrates remained stable and overall sugar (mainly the HFCS) consumption went down. So how could the cross-sectional studies suggest that it was only the excess fructose that played a role in the obesity, dyslipidemia, hypertension, insulin resistance and type 2 diabetes??? If they said it was sugar (the combination of glucose and fructose) I would partly agree, but at this point I cannot. This is because the population does not normally consume fructose alone. It is the combination of fructose and glucose and the two first references (25 and 26) listed the soft drinks as such (one comparing HFCS to aspartame), not fructose only sweetened drinks.

Metabolic studies

Then, in the text, there is a small metabolic study mentioned. This study was of Stanhope et al (2009). I have reviewed the results of this study (among other 28 studies of various designs) and this is what the authors reported:  

• The participants were fed in various settings, during which they received glucose or fructose sweetened drinks after each main meal.
• The participants were aged 40-72 years, just to give you an idea. They were not very young and fit, only having their body weight stable in terms not gaining or attempting to lose, or doing so for several months prior the study. 
• They were sedentary, i.e. not exercising more than 3.5 hours per week and at no higher intensity than fast walking. 
• The participants were either overweight or obese. I have written a separate paragraph below to address my concerns about this detail. 
• Both sugar groups had increased body weight at the end of the study: fructose fed by 1.4% from the baseline and glucose fed by 1.8%. Therefore this study produced results which were is in contrary with the past beliefs that fructose was responsible for the population weight gain while glucose was OK. I have also elaborated more on this later in this article.
• Fructose group had increased visceral (in the abdomen, risky) adiposity while the glucose group had increased subcutaneous (under the skin, 'healthy') adiposity, also around the waist.
• Blood pressure did not change among any of the two groups - in contrary to many who believe that fructose leads to hypertension. 
• Fructose group had (surprisingly?) increased HDL - the good (Happy) cholesterol. 
• The team reported increased DNL in fructose group. This also needs more discussion, see below this bullet points paragraph.
• Fructose group had increased lipoproteins and 23-h curve triglycerides, fasting glucose and fasting insulin while having reduced insulin sensitivity index (data for the glucose homeostasis metabolism). 
• However, the glucose group had increased fasting triglycerides and mean 24-h free fatty acids concentrations in blood plasma while fructose had not. It was commonly reported that fructose feeding led to drop in FFA and increase of triglycerides, on the synthesis of which those FFAs were used.
• Interestingly, men were more affected in their blood lipids (increased) whereas women were more affected in their insulin sensitivity (reduced).

Regarding the DNL levels mentioned above, these were differed between glucose and fructose settings, depending on whether they were postprandial (after eating a meal) or fasting. Have a look: 

In a fasted state the glucose group had continued producing new lipids, while the fructose group reduced their production in comparison to the baseline levels, but after eating and drinking the sugary drink straight after, the liver was overwhelmed so it produced more new lipids than those consuming glucose. In addition, I have already challenged the different methodologies of DNL measurement and how these can vastly differ as a result of different methodology used.

Interestingly, the fasting HDL in glucose group was decreased (-2.4%) and I have already mentioned that in the fructose group it increased (+3.5%) from the baseline. Fasting HDL is one of the five metabolic syndrome features for the clinical settings assessment. Fasting triglycerides (TG) are another one in the assessment of dyslipidemia. The increase of fasting TG was more than twice as high in the glucose group (+9.7%) than in the fructose group (+3.9%), in comparison to the baseline. However, some scientists suggest that postprandial TG are more relevant to the cardiovascular disease risk than the fasting TG. It was the postprandial TG levels that shot up and kept the overall 24-h levels of TG markedly increased in the fructose group when compared to the glucose group. This was also partly due to the reduced clearance of the lipids to the adipose tissue (mediated by lower insulin excursions after fructose intake) - which actually aids in the control of the body weight. So, although in contrast with the current definition of metabolic syndrome, the lipids metabolism results of this study were used as a proof of dyslipidemia caused by excess fructose consumption.

Have you found the information above overwhelming? And that was just an overview of the most relevant details. And, by the way: 

1. Glucose or fructose sweetened drink were given at 25% of total energy intake (TEI) - that is beyond the usual intake by the average American population. Can you imagine a quarter of your daily calories coming from sugar? Sure, there are some individuals who can manage that and they do. However, when stratified the population into the levels of sugar consumption, those consuming combined sugar at > 25% TEI formed only 13% of the population (as per data between NHANES 2003-2006, sugar consumption continued to decrease after that) and the majority of these were adolescents, especially male, not people in middle age or elderly. On top of that, fructose contributes less than half to this amount of added sugar. Doubling the fructose intake so much beyond the usual or habitual intake as it was in this particular study is considered toxic. You would have to consume over half of your daily calories in sugar to cover this amount of fructose intake - which is ridiculous. Such high doses of fructose are often given in the metabolism challenge studies. These are designed to study the mechanism of action and they should not be interpreted as an every-day situation typical for the general population.
2. The fructose or glucose drinks were tested for 8 weeks in ad libitum free-living settings and then for 2 weeks of energy balanced settings. The ad libitum means that people could eat anything and any amount of food they normally consume, plus consuming these drinks at each of three main daily meals. Positive energy balance was reported and this variable has constantly been a confounding the outcomes of similar studies. Blood samples were taken at 0, 2, 8 and 10 weeks of the study duration. 

This 2009 study was a parallel-arm study to another similar one of Stanhope et al (2011). In the 2011 study the fasting insulin in the fructose group was NOT increased in comparison to glucose group, which was in contrast with the results of 2009 study. The participants were the same and they consumed the same amounts of sugars over the same weeks pattern. Also the plasma glycated albumin was lower in fructose than in glucose group which is in contrast with Dr Lustig's claims that fructose is 7-times faster in browning reactions in the body, hence causing irreversible damage to the arteries. On top of that, the fructosamine levels did not differ between fructose and glucose groups.

Although this 2011 study was not included in the AHA Statement from 2009 (obviously), I would like to elaborate a little on the difference between these two parallel studies. 

Below is an overview of some variables assessed by the 2011 study:

From the table you can see that the differences were small, albeit statistically significant. However, were they clinically relevant? That is the question. 

The scientists have found slightly increased fasting glucose, but the fasting insulin levels were not significantly different between fructose and glucose groups. Although the fasting insulin levels were initially higher at the 2 weeks of ad libitum settings, at the end of 8 weeks it was lower in fructose than in glucose group. This may have been due to the metabolic adaptation or an effect of different diets of the free-living participants. I have seen conflicting results on glucose homeostasis among similar studies many times and it is not easy to come to a final conclusion whether fructose does lead to insulin resistance or not. Therefore, if the insulin sensitivity was slightly reduced in the fructose group at the end of the study that is true for this study only and others have produced different results. On top of that, this was after the final 2 weeks of energy balanced settings, nothing was reported after the first 2 weeks and at the the 8 weeks of ad libitum settings. All other variables had the parameters reported for both time points during the ad libitum settings. I wonder why this parameter was missing here. 

It is also worth to mention that the female participants were post-menopausal which could also contribute to the adverse metabolic outcomes. It is well established that women after the menopause start to catch up with men in several metabolic variables, mainly the lipid metabolism. 

It is also important to note that it is the teenage boys that consume most sugar from the whole population and as the population ages, the consumption of sugar decreases. Therefore, if we wanted to assess the effect of some dietary compounds on the population, it should be studied in amounts relevant to that population instead of feeding toxic amounts of an individual sugar (fructose) to middle-aged and elderly sedentary participants. To match the composition of the sugar to the real life situation, the population would need to consume over 50% of their daily calories in sugar or HFCS, which is a non-sense. 

Meanwhile, do you recall that it was conducted on overweight and obese people? I have already debunked one particular claim of Dr Lustig based on one such study. And you may recall my other article The matter of relativity and relevance, which outlined that 80% of obese people have metabolic issues in comparison to 40% of those with BMI below 30. Yet, just because 20% of obese appear as metabolically normal at a given time and the scientists put the overweight, normal weight and underweight into the other category (those 40%), this led some researchers and other individuals to the conclusion that excess body fatness is not a problem. 

Now you see what everything has to be taken into consideration before you interpret and use the results in the argumentation. It is not as simple as the articles often print. 

Discrepancies in the reporting

Moving to the last part of the selected content: the reduced SSB led to decreased body weight among children. That takes us back to the beginning: when removing some sugar calories from the diet would you not expect the weight go down in case you have not replaced the sugar calories with some other?

However, what I wanted to point at, and that is very important, is that in the selected text  from the AHA Statement, the sugar (HFCS) was used interchangeably with the sole effect of fructose as if the glucose was without the effect. You could see in the discussion of the metabolic studies above that glucose also has some metabolic effect and it led to a higher weight gain than fructose. On top of that, the text I have placed here was published under a subheading FRUCTOSE. Now you might appreciate the level of misreporting in the AHA Statement. They really believed (or wanted us to believe) that fructose makes people obese.

Back in 2009 and even before that, as per Elliott et al. 2002 listed as a reference for the AHA Statement at the end of this chapter, it was common among the scientific community to present fructose as THE sugar that promotes weight gain. The mechanism was explained this way: because it does not lead to the insulin release typical for glucose, it does not sufficiently stimulate the hypothalamus which should otherwise responds with the satiety signals and make us stop eating. One of the listed references, Havel (2005) said:

"Fructose does not increase insulin and leptin or suppress ghrelin, which suggests an endocrine mechanism by which it induces a positive energy balance."

This mechanism, as a leading factor to hyperphagia (increased feeding) due to sugar (HFCS) consumption, is no longer true. However, people still believe this mechanism is the main contributing factor in the weight gain of people consuming added sugars. I have written a short article about why I think the children ate more food in a restaurant after they consumed a soft drink. It was just my idea as the studies uniformly pointed at fructose or discussed sugar as such, without taking into account the possible effects of glucose in it. As I mentioned previously, about half of the usually consumed sugars consist of glucose. Would you not expect this glucose to do some job on the hypothalamus, making it stop requiring more food when sugar or HFCS sweetened drinks and food items were consumed? Yet the 'professionals' tried to convince us that the brain or even pancreas perhaps do not see that glucose either, like if there was no insulin release when glucose was consumed along fructose in the sodas. In fact, the hypothalamus also responds to glucose as such by reducing the appetite. So it is both: glucose and insulin that trigger satiety signals and even if the half fructose in the sugar did not have such effect, the other half of the sugar comprised of glucose should do something. And it certainly does. 

In addition, you are probably familiar with the glycaemic and insulinaemic effect of dietary glucose (also in white bread or other processed starch products) and how it promotes lipid storage and blunts the lipid oxidation - leading to easier weight gain when lots of fats are consumed along starch or sugar. It is glucose and its effect on insulin that promotes weight gain more than fructose and the modern low-carb enthusiasts bet exactly on that. This fructose caused weight gain myth was also disproved by other study of Swarbrick et al (2008). 

This study was published before the AHA Statement was published in 2009. In this study, the post-menopausal women reduced their body weight after 10 weeks of energy balanced diet by 1.5% on average (representative of 1 kg for 70 kg heavy lady). They also consumed 25% of their energy in fructose but they did not over-eat. This is nearly a proof that it is rather due to overeating that people gain weight, not because of fructose. Those consuming fructose in this study, similarly to those in Stanhope et al 2009, did not consume glucose along as the normal population does. Yet the fructose led to reduced body weight in energy balanced settings (proving Havel 2005 wrong) and in lower weight gain in comparison to the same amounts of added glucose consumed in the Stanhope et al (2009). Yet in 2009 the AHA 'Scientific' Statement announced that fructose plays a role in obesity. How big role and in what context?

Conclusion

Fructose is a known lipogenic agent, whether by enhanced DNL when consumed in high amounts or as a re-esterifying agent which brings together the glycerol and FFAs for the formation of triglycerides or the lipoproteins (the blood 'cholesterol'). And, although fructose has been repeatedly presented as contributing to the very low density lipoproteins (VLDL), now you know that it has been found to increase HDL as well and producing lower levels of glycated proteins in the blood plasma - in comparison to glucose. To my understanding, it is the increased oxidation of various blood components and other tissues that is responsible for the atherosclerosis more than the presence of lipids and lipoproteins. And, because fructose occurs in blood in much smaller concentrations than glucose, it is unlikely that fructose would be a leading factor in the atherosclerosis development, leading to the biggest killer in the world: cardiovascular diseases. However, it does contribute to oxidized VLDL - released from the liver, which metabolises majority of the ingested fructose. Regarding the insulin sensitivity or resistance, I have seen during the research for my dissertation that the scientific papers produced conflicting results for the risk factors of type 2 diabetes. Hypertension as a result of excess fructose feeding was also not confirmed here.
Things are rarely only black or white and a deep knowledge is needed to see through the flaws even of the peer-reviewed scientific papers. Therefore, I would rather think about the combined effect of glucose and fructose in the sugar as we consume it, along the positive energy balance (over-eating and under-exercising) and perhaps other components of the diet (processed vegetable fats), than blaming fructose alone for most of current metabolic issues.

Indeed, as Stanhope et al (2011) wrote:

"a limitation of the current study was that it did not address the possibility that there is a synergistic relation between increased glucose and insulin excursions and unregulated hepatic fructose metabolism, which occurs when fructose and glucose are consumed in combination."

And, regarding the obesity due to fructose consumption, I think it does not need any further comment except that the opposite was found to be true. 

Below are the references I mentioned earlier and I am looking forward to read your comments.