Does fructose make you fat?

Here we go again. I have watched the first lecture of Dr Lustig about the bitter truth about sugar from 2009 maybe 5 times. As I said elsewhere, this lecture gave me an idea for the topic for my final year project at the university: Fructose and Metabolic Syndrome. I have read a lot about this topic and while I studied for my degree I have also gained a great insight into the complexity of factors contributing to obesity of the population. Because I would like to complete my 'mission' to debunk some claims about the sole role of fructose in obesity and some other metabolic issues, and to offer my own view about the mechanisms, I have returned to the very beginning of my journey. By doing so I would like to focus on several other points from the 2009 lecture of Dr Lustig, which were not covered in much detail or not covered at all in my previous almost 60 articles of this blog.

Here is the summary of the 2009 lecture of Dr Lustig: 

I have discussed some parts of it in my previous articles so I will not elaborate too much on each of these summary points. In this article I will focus on the supposed weight gain promoting properties of fructose which were presented to you by a qualified clinician and professor, expert in endocrinology, admired and praised by perhaps millions of people today. Before proceeding I would like to say that I have no idea where Dr Lustig got it from that fructose interferes with obesity intervention. I have a different information based on a scientific data and I have decided to share it with you. 

Energy balance - does fructose promote weight gain?

There are several aspects to this question and I will try to cover them in separate paragraphs, reflecting on the content of Dr Lustig's presentation from 2009.

You could see this simple scales diagram showing the traditional view of the causes of obesity: eating more energy that can be burned leads to weight gain - just to learn from Dr Lustig that this scheme is flawed. He explained to you that it is not the amount of food you eat - it is the composition of the food you eat. He aimed at a specific compound in the processed food that makes you storing energy instead of burning it, disrupting the healthy energy balance.  

You could that things which make you spend energy make you feel good, such as coffee or exercise. In contrast, things that make you gain weight make you feel less energetic and sluggish, whether it is overeating or starving. I can agree with that. Eat too much and you feel like having a nap. Do not cover your energy needs and the body will make you slow down, conserving the energy for its survival. It was suggested that the compound disrupting healthy energy balance was sugar. But we eat combined sugar named sucrose. This sucrose is a molecule consisting of glucose and fructose which are metabolized differently to some extent.

Which sugar makes you storing energy rather than burning it?

Then you could hear an impressive story about how insulin promotes weight gain. This mechanism was explained as working by promoting storage of the food energy instead of burning it. When you eat too much sugar, the insulin rises and clears up the sugar and fat from the blood stream, because the blood sugar has to be controlled and kept within narrow limits. And then, when the energy (here: sugar) is stored, the sugar concentration in the blood drops fast, which leads to fatigue, hunger and further eating. So, as Dr Lustig presented it on an example, even if you require 2000 kcal per day and you have eaten 2000 kcal, you end up with 1500 kcal available for metabolism because those 500 kcal were stored (presumably as fat, but that is not that simple). Then you end up eating further 500 kcal to feel balanced, but by then you have overeaten those 500 kcal and you are gaining weight. Here, it was not made clear to you, that it is mainly the glucose part in sugar that is responsible for this. But read further, it is getting interesting.

How does FRUCTOSE variable come into the equation?

Just a reminder: Dr Lustig announced at several occasions that 'glucose is a good guy' while fructose is the bad guy. He demonstrated it on comparison of Atkins and Japanese diet and blaming fructose for the increased prevalence of obesity and gastric surgeries in Japan today. Or China, or Australia, after they adopted the westernized diet and lifestyle. Remember?

Do you think the countries suffering from an obesity boom today adopted only fructose consumption and nothing else??? 

Is it fructose that dominates the processed food industry and fast food???

I tell you something. That diagram above is an outstanding example of flawed logic and perhaps of a direct manipulation of the minds of people who do not have a deeper insight into the topic. This concept of the fructose as a common factor is just fundamentally wrong. We should not ask what the Atkins and Japanese diet have in common. We have to ask why they work?! 

The fact is that Atkins diet eliminates ALL CARBOHYDRATES, while traditional Japanese diet was LOW IN FAT (read more). They are quite an opposite of each other and fructose had little to do with that. It is the merging of the two factors these diets lack that leads to obesity: consuming excess of the insulin promoting carbohydrate with the excess of fat. Remember, that insulin also helps storing fat, not just glucose. One without the other result in a trim body like in case of Japanese or Atkins dieters. 

Back to basics: A recap what promotes energy storage in the body.

Now you know it is the glucose part in sugar that makes pancreas producing insulin significantly more than the little portion of fructose you can find in the blood stream. While in the past Dr Lustig said that fructose does not lead to insulin secretion, in a more recent lecture he said that even the tiny concentrations of fructose in the blood can make pancreas producing insulin. He basically contradicts himself. I cannot help myself but seeing it this way: blaming fructose for increased insulin then sounds like not seeing the forest because a single tree is obscuring our vision.

You could have heard the doctor saying in other videos that although sucrose or HFCS contain about the equal amount of glucose and fructose, most of fructose (claimed 100%) is directly metabolized by the liver and only a tiny fraction is released into the blood stream. He presented calculations about how many calories from glucose and fructose are metabolized in the liver and how fructose is the alcohol without the buzz. Hence, the actual amount of fructose in the circulation can be lower by the magnitude of thousand of that of glucose. We measure glucose concentration in blood in milligrams, but fructose can be found there in micrograms concentrations. Even if such small concentration of fructose in the bloodstream was able to stimulate pancreas producing some more insulin, this effect would be dwarfed by the capacity of glucose doing the same. After all, that property of glucose is the basis of the modern low-carb or Atkins dieting, is it not? They do not cut down on sugar or fruits only, they exclude most sources of carbohydrates, including starches which are polymers of glucose. Got it?

Because fructose does not lead to noticeable insulin secretion, it does not cause drops in blood sugar levels, therefore it cannot contribute to the disrupted energy balance as you were made to believe (read more).

It was claimed that fructose is not a sugar, it is a fat (as it ends up as fat after all). You may remember the claim of sugar being the only compound being a carbohydrate and fat at once. However, that is not quite true. Only a small fraction of fructose is converted to fatty acids in humans. We are not rodents who have a significantly higher potential to convert sugars into fat in the process called de-novo-lipogenesis (DNL). Regardless, even when a small portion of fructose is converted into fat, how does this little amount compare to the amount of ever increasing fats and oils consumption by the Americans and other nations worldwide, so that one could say that fructose is the sole responsible factor for obesity epidemics? This just does not make sense. You might have already learned about the trends in macronutrients consumption among the Americans, where it is apparent that the sugar consumption was decreasing since year 2000 (and fructose within) while the fat and oils intake continued rising, along constantly rising obesity levels in the country. Put it together and see another fundamentally wrong argument. Or, just read more here.

Could it be due to different appetite inhibitory mechanisms?

It was not a long time ago when the scientific papers (one, two), and Dr Lustig himself, kept explaining to you that fructose leads to a higher food consumption because it does not function in the body like glucose does. The scientists explained this mechanism by appetite inhibiting action of glucose and insulin on the brain receptors, which was not observed with the fructose. Then there was ghrelin added to the equation with that the fructose did not reduce the production of this hunger hormone, but glucose did. Some leptin resistance in the brain was mentioned and for this fructose was blamed again.

What fructose, I am asking. That fructose which was mostly held by the liver and metabolized there?

1. The scientists supported this mechanism with the short term studies of which most lasted no longer than 24-48 hours. 
2. In addition to that, their participants were already overweight or obese with a disrupted metabolism (for whatever reason). That is not exactly what is discussed here: whether fructose can lead to overweight or obesity, is it?
3. The scientists compared mechanisms of overfeeding with fructose versus overfeeding with glucose in metabolically already affected people for the duration of one or two days. How this relates to the fact that people normally consume glucose and fructose combined??? Can you see the flaws?
4. With every gram of increased fructose intake, there is about the same increase of glucose intake. So, if glucose reduced appetite or hunger, it should do so and the fructose has nothing to do with that!

What really happens in free living conditions.

When I did my research on this topic, I came across one particular study which reported an opposite effect to what you have been told previously. People were recruited and asked to consume either glucose or fructose sweetened drinks in free living conditions and lead a normal life without any dietary restrictions. We call it ad libitum, or 'as much as they want'. Their diet was described as balanced (50% carbohydrates, 15% proteins and 35% fat), but that was before adding the drinks. The amount of either sugar they had to consume each day was 150 g (600 kcal), which is quite a lot. They did this for four weeks and they were assessed for the compliance. From the results of body weight changes it was apparent that it was the fructose group that reduced their calorie intake more because their body weight increased only slightly: by 0.2 kg over 4 weeks in comparison to 1.7 kg in glucose group on average. Both groups had reduced insulin sensitivity and it was in glucose group that expressed increased fasting insulin with the statistical significance. Just saying.
A note: the abstract in the link for this study did not mention changes in participants' body weight, which were not the core focus of the study. I have had the chance to read the full copy and there I found these details. If you are interested, I can scan the copy and post it to you so you can see yourself.

Although this study had some limitations, it still provides a great hint what this all is about and supports the current knowledge that glucose promotes weight gain more via its insulin action than fructose. I am very confident that if such a similar study was conducted again and it was designed to the standards, the body weight results would be the same. My belief is based on the fact that our food consumption fluctuates from day to day and it is the energy balance over a longer period of time that is responsible for weight gain or weight loss and the associated metabolic effects.

Some other effect of fructose on food intake.

Could it be its sweetness?

I remember Dr Lustig saying how fructose is the sweetest natural sugar we know and how sweet taste makes us to enjoy food and perhaps eating more than if the food was bland.

That is true.

Then he continued that glucose is not sweet enough to make us desire more.

That is not true.

The sweetness of glucose is lower than of fructose but it is sweet enough for us to sense it and to enjoy it. In fact, the standard oral glucose tolerance test (OGTT), containing 75 g of glucose in Rapilose drink (300ml) is still perceived by most people as unpleasantly sweet. That is half the concentration I was told they used to get before Rapilose was used in our Epidemiology Unit. That time some people had adverse reactions to the doubled concentration of glucose in the manually prepared drink for the OGTT test. They felt nauseous and generally unwell. I did the test myself with the Rapilose twice and I can tell you that it really tastes very sweet. So if we only fed people with glucose as a sweetener in their drinks and other confectionery, they would certainly experience a pleasure comparable to the combined sugars widely consumed today. The reason why the market is not using only glucose is perhaps the price and practicability. The natural sugar is a combination of glucose and fructose, and since fructose is sweeter than glucose, less sweetener is needed in the product to achieve a desirable sweetness, reducing the manufacturing cost.

Could it be epigenetics?

You could hear at some point how Dr Lustig announced that new research shows that the more sugar the mother consumes, more gets through the placenta and the child is developmentally programmed to like sweet taste – which was supposed to explain the obesity epidemics of 6 months old or even the increased body weight of a child at birth. 

Well, how does this preference to sweet taste relate to the already overweight embryo or a toothless infant still entirely milk fed or just being weaned? That sweet tooth refers more to its lager age. Even then, the individual can stay away from sugar but become obese just by eating processed carbohydrates and fats, like in pastry (starch and fat), for example. How can fructose be the villain here? 

Some metabolic outcomes you may not have been aware of

Here is a scientific paper from 1999 making it clear how human body adjusts its carbohydrate metabolism to the amount of carbohydrates consumed, rather sparing the consumed fat and storing it. It basically says that we have a very limited capacity for converting carbohydrates to fat. And that applies to fructose as well!

Other study confirmed that fructose consumption led to a higher metabolic rate than glucose, based on the recovered labelled carbon isotope in the exhaled carbon dioxide. That carbon isotopes were previously in either glucose or fructose the study volunteers consumed. 

These isotope labelled studies are an excellent way of how to distinguish between variable metabolic pathways of different sugars. Even more importantly, these studies allow us to see the level of contribution of glucose or fructose to their shared metabolic pathways, because it is known that they do share many metabolic pathways. Fructose is even converted to glucose and glycogen, did you know that? In fact, more fructose can be converted to liver glycogen than glucose! 

That brings me to the end of this particle with a conclusion that regardless of how I look at it, I cannot support the sole effect of fructose on the disrupted appetite control in people, especially when they are initially metabolic normal, which is the point of this article: Does fructose make you fat?

I welcome your comments and suggestions.

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. 

Is it in the liver or pancreas after all?

I am getting confused now. Where does the fructose cause diabetes then? 

Dr Lustig explained the mechanism of oxidation stress and how this affects the binding of proteins inside the liver cell compartments at 55:20 of the video. It was illustrated with a picture: 

I agree with what he said, but then what caught my attention, was that he suddenly talked not about the liver cells but about the pancreatic cells instead. This pointed at how bad fructose is for pancreas. Well, did he not say some while ago, that fructose can, after consumption of excess sugar, occur in the blood in 5 micromoles concentration, which is 1000 times lower than of normal glucose concentration? He said that this was enough to trigger insulin response, too... 

My question is: if little fructose is good for the liver (certainly at higher concentration than 5 micromoles), but this small concentration in the systemic circulation can damage pancreas to such extend it can lead to diabetes and insulin resistance, where glucose comes into this picture? Pancreas responds primarily to glucose levels in blood... glucose, albeit 7-times slower in browning reaction (in vitro), has more capacity for this damage because it appears in blood in 1000 times higher concentrations than fructose. And diabetics with a poorly managed blood glucose levels are known to have increased concentrations of glycosylated haemoglobin. It is not the fructose that causes it. 

My other question is: how much insulin can fructose make the pancreas producing so that the insulin concentration raises to the level classified as hyperinsulinemia? Dr Lustig suggested this as well but he did not explain it further.  

DEBUNKING DR LUSTIG

I have typed this title in capitals, because I think it deserves it. I have written about 45 articles in this blog so far as a response to some points in his lectures he delivered worldwide and many of them contain my disbelief that obesity is not a problem as Dr Lustig claims. Before that he used to say that fructose consumption causes obesity, but he stopped saying this because the body of evidence disproved his claims from 2009 and suddenly sugar is not THE cause of obesity anymore:

Dr Lustig has changed his focus and says that the obesity actually does not matter.

Instead it is only the metabolic syndrome that is the problem, plus the type 2 diabetes and other metabolic disorders:

He kept supporting his argument by one diagram, saying that 20% of obese people are metabolically healthy and that the people of 'normal weight' contribute to the pool of metabolic diseases by 40 percents: 

He had even put it in numbers: 

I have highlighted several times throughout this blog that this group of 'normal weight' did not distinguish between slim and overweight people and I suspected that most of these 40% would apply to the overweight subgroup. Therefore, in my opinion, the prevalence of metabolic diseases closely relates to the prevalence of excess adiposity among the population, where the overweight and obese people form a distinct group from people of truly normal weight. My suspicion was proven correct, as the linked article shows at its end, based on earlier published content of Dr Lustig himself. In the light of this information, now his sudden turn looks suspicious. 

Dr Lustig has been saying again and again that anybody can get metabolic syndrome and that the obesity is irrelevant. Well, I have different information, which contradict this thesis. One of such information can be easily found online if one puts a little effort in it. Just type key words 'healthy obese' and see what comes up.

One of several studies I have found, published in 2012, concluded:  

"...metabolically healthy obese individuals are at higher risk to develop hypertension, type 2 diabetes and the metabolic syndrome than their non-obese counterparts. Our data provide further evidence that opposes the notion of metabolically healthy obese as harmless conditions."

The study also stated: 

" ...there is no evidence that these subjects are permanently protected from the risk of obesity-related co-morbidities."

This was a prospective cohort study on Taiwanese population and they applied the cut-off points typical for Asians: BMI 23 for overweight and BMI 25 for obese Class I, and for Class II the BMI cut-off point was 27. All participants with any feature of metabolic syndrome were excluded, except the waist circumference, which is larger in obese people anyway. 

Here you have another article which summarizes the current research on what is the truth about the healthy obese people. Here you can also read, that: 

"We have an enormous challenge at a public health and individual level in dealing with obesity-related disorders. Being obese doesn't just affect the heart. Being obese means you're more likely to have joint disease, psychiatric disorders and cancers," Puri said.

He added that, over the next couple of decades, obesity and its consequences will be driving health care costs."

So, where does the money go, Dr Lustig? And what do people actually die from? I have discussed my concerns, before I actually looked at these data, in another article here. 

I think this was enough to make you see that Dr Lustig is ready to ignore objective facts, announcing that he does not believe in common sense, because he believes in data - selectively picked by him and presented so it fits his agenda, I add.

In fact, as I have realized some time ago, Dr Lustig even negates his own work from 2005, where he published together with E. Isganaitis that obesity is central to the development of insulin resistance - which was in opposite to his newer claims that liver is the primary target to insulin (which it is not as you will read later) and that people get obese because they firstly develop a hepatic insulin resistance, as another article of mine discusses. Below you see the snapshot of the 2005 work of Dr Lustig which, despite it was emerging from the new evidence back then, does not seem to be true anymore - according to the new information presented by Dr Lustig. 

The 2005 article further discusses the role of increased concentration of free fatty acids in the peripheral insulin resistance and I will come to this point later as well. The scientific community is accepting this mechanism, but Dr Lustig seems to go against the flow with his fructose induced hepatic insulin resistance as a primary cause of the peripheral insulin resistance in 'normal weight' people and that the insulin resistance causes obesity, not vice versa.  

In addition, at the end of the snapshot you can read how the evidence shows that reducing of body weight leads to improvement of insulin sensitivity. Yet Dr Lustig claimed quite recently that reducing obesity does not lead to improved metabolic health. Come on! All this twist just to rise the argument about how excess fructose causes all the metabolic issues in people indulging on fast food rich in both sugars and processed fats, being of high glycemic index, consuming larger portions of highly palatable food and not exercising enough, as he published in the 2005 article as well???

Obesity does not cause metabolic syndrome; insulin resistance causes obesity. True?

I have already discussed my concerns about whether obesity is a disease or not and here we have another attempt of Dr Lustig to make the obesity irrelevant, pronouncing it as only an associated factor with the metabolic syndrome (MetS). He believes that not obesity causes insulin resistance but that insulin resistance causes obesity. He also believes that it is only the abdominal fat (inside the abdomen) that is a factor for the insulin resistance development whereas the subcutaneous fat is not the cause of anything.  

I agree that fat deposits in different body parts represent a different risk of metabolic diseases. However, does that make the excess subcutaneous fat irrelevant, so that we could ignore the obesity and focus only on the MetS features? I doubt so. 

Just a recap: 80% of obese people still suffer metabolic diseases (that is 4 out of 5) and as Dr Lustig said, so does the 40% of those having a 'normal weight'. However, about 50% of these 'normal weight' are actually overweight. So, is the obesity and excess adiposity under the skin really irrelevant? What percentage of these overweight would actually suffer metabolic issues in contrast to those really of a normal weight? 

Dr Lustig insists that firstly there is an insulin resistance, leading to leptin resistance, which leads to obesity and when this insulin issue is fixed, then the leptin issue is fixed, and then the obesity will be fixed as well: 

Because:

You know what? I AGREE with that. Partly. People tend to develop metabolic issues as they are becoming overweight and obese. In this mechanism it is really difficult to distinguish to what extent it is a marker (due to wrong diet and lifestyle) and to what extent it is a cause. Meanwhile, it is individual for each person WHEN and at what level of excess adiposity they will qualify for the diagnosis of MetS.

Just think: if people were not constantly in a positive energy balance for weeks and months - would they develop metabolic disturbances? Would they get high cholesterol, high blood pressure, would they become insulin resistant, because the muscles cannot take any more energy molecules in? I bet that most of them would not and as you may be aware, in many people, who reduce their body weight, their metabolic markers also improve. Slim people do not tend to suffer metabolic syndrome at such a large scale as obese and overweight people do. 

Should we therefore dismiss the link between obesity and metabolic diseases just because some thin people become ill and 1 in 5 obese does not?

Dr Lustig made it clear: people develop metabolic diseases irrespectively of the excess of subcutaneous body fat and he did it via this slide: 

He said that insulin resistance is what the obesity and lipodystropy have in common. However, you might have already read my objections against using this lipodystrophy case. It was because these people are genetically predisposed for insulin resistance which makes them too different from the rest of us. In addition, these familial partial dystrophy cases are rare. In the nutshell, the lipodystrophy means abnormal distribution of body fatness and represents a group of various diagnoses that are characteristic with lipodystropny. People are either genetically predisposed or they acquire this condition as a consequence of other condition such as being HIV positive and treated with various medication of having a history of autoimmune disease. 

The lipodystrophy is a specific condition and is rather rare in comparison to the prevalent overweight and obesity cases which mostly occur due to simply overeating and having low levels of physical activity. People suffering from lipodystrophy are often overeating due to leptin deficiency, while overweight and obese people become leptin resistant due to constantly positive energy balance, often leading to insulin resistance, too. What they have in common is that both cases: lipodystrophic and obese people have disturbed metabolism of energy. However, there is difference: 

• lipodystrophic people are unable to store fat in some body parts (under the skin in limbs), but  they can store it in other body parts (neck, face, around the organs), which makes them to look slim, but in fact they are metabolically ill and obese inside. The inability to store fat under the skin and excess adiposity in other places affects the whole endocrine system, sometimes also leading to overeating, which further worsens the condition. This is what Dr Lustig has been describing. Nonetheless, the whole condition is caused by some other condition, as mentioned above. Overeating is a consequence of reduced subcutaneous fat tissue and low leptin levels and the insulin resistance develops as a consequence of this.
• obese people, on the other hand, usually develop metabolic disturbances as a consequence of simply consuming too much energy, (or unhealthy diet as such, this is a broader topic) while they were initially healthy and metabolically normal. They become insulin resistant and as such, because the elevated insulin interferes with leptin receptors of hypothalamus, they also become leptin resistant as a consequence. And so they continue eating like they did from the time when they were slim, because they love food, it is cheap, plenty of it and unaware of its energy content. And the leptin resistance does not make them stop even if they have increased leptin concentrations in blood. Therefore the mechanism is the opposite than in people suffering various forms of lipodystrophy. 

Therefore, in my opinion, this example of lipodystrophy should not have been used to disprove the link between the body fatness and metabolic diseases in the population not affected by the lipodystrophy.

The Reframing the debate slide ended with this: 

Does this disprove the close link between excess body weight (or the process of gaining weight) and various features of metabolic syndrome? I do not think so. I see this initiative as messing around because at the end, there will again be FRUCTOSE. 

Going back to The Reality image, I have already highlighted that the metabolic dysfunction cannot be the cause of obesity for people who are metabolically normal and start to gain weight because of the obesogenic environment. And you could see that I gained weight without the symptoms of the metabolic disturbances just because I enjoyed the palatable and fattening foods too much and did not bother to move to burn the extra energy. I halted this trend when I reached BMI 27+ but if I did not do so I would most likely follow the fate of my close family who suffer a whole spectrum of metabolic dysfunctions, including obesity, hypertension, high cholesterol, cardiovascular diseases, fatty liver, type 2 diabetes, etc. I currently suffer none of these as a result of my lifestyle, I never did and I hope I will successfully avoid such conditions in the future. 

What Dr Lustig was talking about were his obese patients who struggled to lose weight because of having their biochemistry already affected for various reasons: hypothalamic trauma, specific genetic condition, being obese for some time already, unhealthy lifestyle, etc.

What I am saying is that although for many people the insulin resistance makes them to fail losing weight, but for them to gain weight firstly the insulin resistance is not a necessary factor. It tends to work the other way around: as people are gaining weight, they become insulin resistant in the process of gaining weight or when they finally become obese, because having this extra amount of fat in the body is not healthy at all. 

What happened to the food dollars and what it means?

At the minute 55:39 of the video you could hear Dr Lustig summarizing how the spending for different food items has changed over the past 30 years. There you could see and hear that the spending for meat has decreased (-9.8%) as did for dairy products (-2.6%). All remaining categories saw increased spending of dollar on them, although the diagram below suggests otherwise. The spending on fruits and vegetables increased by +0.1%, grains and baked products + 1.2%, beverages +0.1% and the processed foods and sweets by +11.4%. The data came from Bureau of Labor Statistics, just in case somebody was interested. 

This graph followed a short speech about how the processed food has been spiked with sugar, that sugar is in everything and it makes people to buy more of these products. I do not object against this argument but there is more into the picture you could see. Have you noticed almost no change in beverages? Large portion of these on the market are occupied by sugar sweetened beverages (SSB) which contribute to the sugar intake the most, sweets are the negligible part of sugar intake on the population level and it was rather the SSBs that were studied the most in relation to obesity and metabolic diseases. 

In light of what you have just read, how it match the diagram, Dr Lustig repeatedly presented to you all the time?

I have already discussed the true trend of sugar sweetened beverages over a longer term period than is in this second diagram and how flawed were the argument of Dr Lustig in this respect:

"... between NHANES 1999-2000 and 2007-2008, the total consumption of added sugars decreased by mean 23.4 grams per day, representing a decrease 3.5% by which added sugars contributed to the total energy intake... two thirds of the decreased added sugar consumption was due to the decrease in soda intake, corresponding to net mean reduction by 14.6 g/d." 

Moreover, the first diagram says nothing about the increased consumption of sugar as such, which, as we know now, has been decreasing since 2000 in the U.S. This graph simply illustrates how the spending of the population has changed over 30 years, dollar per dollar, not capturing the changes of prices for different commodities and the dietary changes of the population - the lower expenditure on meat does not necessarily mean that people purchase less meat. It may as well mean that the cost of meat has declined due to the rise of intensive livestock farming. Or it also could mean that there are more vegetarians nowadays so that the sale of meat has plummeted - also due to the increase of food processing, offering meat substitute alternatives such as soy mycoprotein based, my favorite Quorn. However, the category Meats most likely only referred to the meat bought as such whereas the Processed Foods category may also contained processed meats and meat products. This was not said. 

All Dr Lustig actually presented was that people pay more for the processed food and some sweets within, but nothing about the actual consumption of sugar and fructose. And I do not quite understand why sweets have been put together into one category with processed foods, but the beverages were listed differently. The sweets are more related to the beverages (mostly sugar sweetened) than to processed foods, are they not?

It is true that the processed food market has seen its boom over the past decades but this category is too large for us to be able to draw a final conclusion which nutrient in this category has increased the most, whether in terms of consumption or increased spending. Processed foods refer to anything from those sweets (a minor contributor to sugar intake), through pastries for the microwaves to ready-made pizzas or peanut butter. My peanut butter contains only about 2g of sugar per over 200g of product. Can we say that this extra two grams of sugar and about one gram of fructose within can contribute significantly to the consumers health issues if the consumer drunk a tin of coke afterwards? Meanwhile, we do not consume the whole pack of peanut butter at once... I taste it more salty than sweet, anyway. How about added salt in most of the processed food products and hypertension in salt sensitive part of the population? People love salt as much as they love sugar. And the most fattening foods, those chips and crisps are rather salty than sweet... Sugar came as third, remember?

At 56:04 you could hear Dr Lustig saying, in relation to the category of Grains and Baked goods that carbohydrates went up but not much (1%). 

Excuse me? 

Was it only this category that contained carbohydrates? There is a lot of carbohydrates in the category of Processed foods, too! 

The analysis of how much the non-sugar carbohydrates has increased over about 30 years can be found here. What the graph actually means, is, that the dollar spent for this particular food group has grown only by 1%, not that the consumption of the particular commodity has increased that little. It has increased much more over the 30 years. 

And, please, Dr Lustig, how come you had no idea that the sweet BBQ sauce had added sugar in there, until you were told or checked the ingredients list? Tomato sauce often contains sugar, not only because it appeals on the taste buds of the consumers, but also because it is a processed food that aims to survive a long shelf-life without being prematurely spoiled. And: how much sugar is in there actually and what the natural sugar found in tomatoes anyway? 

I have grown my own tomatoes and they were exceptionally sweet - unlike those in the shop. Mine grew in a compost rich soil, too, with all the nutrients available that the plants scrappings had in them, not just a few artificial minerals in the fertilizers which are used to grow beautiful but tasteless and of lower nutrition value tomatoes available in the supermarket. Were these sweet and full of flavor and nutrients rich home grown tomatoes harmful to my health just because some laboratory would be able to extract the extra sugars (also fructose, tomatoes are botanically a fruit) from my tomatoes and put the same sugar back? I doubt so. 

And the final point: Sugar not only makes food palatable so people tend to buy more. The increased purchase of processed foods simply reflects on the busier than ever population that likes quick fixes and convenience. And within these there you can find the occasional candy or chocolate bar, but also potato crisps and other savory snacks, in which you also can find a a tiny gram of sugar for flavoring or moisture. 

I hope you now have an idea about the complexity of the issue with the changed purchases for various food items. Adding sweets to the processed food is a very unfortunate move and only misleads the audience, again. It is for sure that the sugar consumption has decreased but the purchase of processed food, mainly fast food and ready-made meals and snacks has increased, as did their portion size. This increased portion size is also a reason for increased spending because people want a value and buy a double portion of a ready meal. But instead of sharing it with a partner they often manage to shovel it in alone, usually in front of the TV or a computer.   

Take it that it is the increased purchase and the consumption of processed food that has been behind the increased obesity and metabolic issues trends because even the increased addition of sugar into these foods has not managed to reverse the sugar consumption trends in the available data.