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.

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.  

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.  

Thinking outside the box and seeing the whole picture

When watching the video of Dr Lustig against sugar/fructose I was amazed by his attempts to manipulate the game towards his agenda. 

At 10:27 minute he shows a slide:

What he says was already picked up by others and made fun of it because at other time Dr Lustig even said:

"There is no foodstuff on the planet that has both fat and carbohydrate at the same time. It is one or the other..."

He used a few examples, such as coconut, avocado or olives that have fat but no carbohydrate. Well, a quick check on Wikipedia and you can see that 100g of avocado contains 14.7 g of fat and 8.5 g of carbohydrate (of which sugars are 0.7 g). Similarly for olives: 15.3 g of fat in 100 g of fruit, and some 3.8 g of carbohydrates. Sugars again form only mere 0.5 g. The rest of the carbohydrate is listed as fiber, but this does not mean that it is THE fiber, which we cannot digest. This includes all sorts of carbohydrates, including resistant starches. So the nature DOES put carbohydrate and fat together, although in different ratio and one of them usually dominates over the other. In most of fruits there is little fat but mostly carbohydrates. But saying that no food stuff on the planet has them both at the same time is a pure nonsense. 

Besides that, Dr Lustig further talks that it is the sugar that has fat and carbohydrate at the same time - now it becomes clearer - he considers a glucose as carbohydrate and fructose as fat. I am not surprised after what I have heard from him over the past five years. And this alleged properties of sugar should make it so dangerous for people. 

Only the blue sentence at the bottom of the screenshot suggests that Dr Lustig knows and admits that fructose is converted to fat under certain conditions and until these conditions are met, fructose is not converted into fat - I suppose. Or not at such a large scale to be considered dangerous. And that is exactly the real mechanism.

However, humans do not have such capacity for the de-novo lipogenesis (DNL) as some scientists promote. The lipogenic properties of fructose are much lower in humans, especially in healthy humans. So saying that fructose is fat while glucose is a carbohydrate is wrong, because glucose also can be converted to fat when consumed in large amounts, i.e. beyond the capacity of the cells to convert it to energy directly. 

Here I would like to point out at a wider picture instead of focusing on one dietary compound. That larger picture is the DIET rich in both: carbohydrates and fats as it is typical for the Western diet. You could have seen elsewhere what were the trends in the intake of sugars, fats and non-sugar carbohydrates among the U.S. population. You could also see that the sugar consumption decreased since 2000 and the consumption of fat has increased while the consumption of flours and starches leveled off. Here you have a perfect example of the both: non-sugar (glucose based) carbohydrates and fats dominating the general American diet since 2000 while the sugar consumption went down. This was all in kcal per capita, no need to convert the grams into energy. People have been consuming more energy while the technological advancements made them less and less physically active over time - in general. I know there are many people who exercise regularly. 

In my previous articles you could see that even Dr Lustig admitted that the foods causing obesity were french fries and potato crisps. Other times you could hear him saying a word DONUT, although by this example he meant something different than it actually was (sugar and fat vs. fat and starch plus some sugar). And in another article of mine you could see how the U.S. not only has a high consumption of sugars but also the fats. Dr Lustig kept showing the sugar map, I have found the fat map for you to see the whole reality, not just the cherry-picked information on which this agenda was based. 

I always prefer to see the problem in its complexity instead of fiddling with one dietary compound in the corner and trying to push the single macronutrient agenda across the whole room, ignoring the complexity of the problem. 

Discrepancies and distortions of the reality - have we been screwed?

At 40:45 minute of the 2012 video of Dr Lustig you could hear that high glycaemic foods are not the same as insulin resistance. Based on the information I could hear from him so far I suggest that the insulin resistance develops due to fructose and its lipogenic properties, whereas glucose is good for us and as such the insulin secretion should not worry us. 

However, at 42:22 minute Dr Lustig said: 

"I am for getting insulin down, any way you can."

This was initiated with the question of the audience about the reduced glycaemic index by accompanied fat in the meal saying that insulin is the problem and they have to get the insulin down. He further said that insulin is the bad guy because it makes fat cells to store fat and it also causes the cell proliferation - typical for cancers. 

He then continues saying that there are two main approaches to bring the insulin down: to eat a low-carbohydrate diet, because glucose drives insulin up, or to reduce sugar intake to cut down the insulin resistance. I guess that this second part was again meant to be due to fructose moiety of the sugar. Nothing about fat, nothing about positive energy balance, nothing about the energy saturated muscle cells due to overeating and low physical activity which prevents the muscles to take in any more glucose - making the pancreas producing more insulin to get rid of the blood plasma glucose for any cost... 

So, is the insulin good or bad? Is glucose good or bad? Sometimes you hear Dr Lustig saying that it is a good guy, other times less so. It is always about how it fits his momentary picture he wants to draw. 

Another example. 

Going back to whether obesity is a problem or not, in another video at 5:20 he said that because 20% of obese people are metabolically normal, the obesity is associated with metabolic diseases but it is not a cause of them. This was supported by the diagram of 'normal' people who also get these problems such as hypertension, hyperinsulinemia, dementia, etc.

Pardon me? 

You could have read my objections against this picture and that the overweight category was left out. Now I would like to know, where the statistics of Dr Lustig stands when he tried to convince the audience that if 25 or 29% of diabetes was statistically found to be CAUSED by sugar availability, how about those remaining 75 or 79%? That was not explained and he stated that also. They had no idea, they did not examine it. They were just happy with that little picture of the whole complex mosaic and they presented it proudly like something the world has been waiting for and it will stay as a fact til the end of the days.  

On these two simple examples you can see that whatever fits the agenda, it is used the way it supports it, even if it is completely out of context and the facts are being skewed. 

I am not happy with that.

Thinking inside the box again

I remember Dr Lustig elaborating in 2009 about how fructose leads to obesity because brain does not read it as a source of energy. The mechanism was explained and supported by some studies, that fructose is not a glucose and it does not rise insulin levels to the same level as glucose. According to this scenario the hypothalamus does not see the calories and therefore it does not stop the person eating more. We now know that is not true, but Dr Lustig had put a lot of effort in his presentation to convince you that he was right. I have not heard him saying that anymore. Instead of obesity he now focuses on fructose effect on metabolic diseases and again exacerbates things quite often. 

You could hear him elaborating with a similar passion in the video at 13:23 where he was explaining the mechanism of insulin and leptin resistance in obese people like if there were only these two hormones regulating appetite or hunger and the energy metabolism. He talked about how every attempt to cut down the energy intake for losing weight leads to decreased leptin concentration down to only 25% within 12 hours so now the poor obese folks not only are leptin resistant, but they no longer have enough leptin to stimulate those few responsive receptors in their brains and this is supposed to drive the hyperphagia (excessive eating) or yo-yo dieting further. The body supposedly thinks it is starving. 

Except one thing: the levels of released hormones in the body are not always constant and the leptin is rather a hormone of a long-term energy regulation than acting in a short-term manner. Our endocrine system is very complex and inter-dependent. Leptin levels can decrease even when the fat cells have not been significantly affected in the acute settings. Of course they could not, who loses fat within 12 hours? There are other functions for leptin in the body, not all are fully known and its levels are affected by other factors, too. 

I remember my professor of endocrinology saying that we have more anorexigenic hormones (make us to stop eating) but those orexigenic (the opposite) are more powerful.Take ghrelin which acts in a short-term manner in response to the actual food consumption, or rather not-consumption. Do not eat for several hours and you will get hungry, regardless of the leptin and insulin concentrations in blood. This study provides more information about other hormones which participate in appetite regulation and how the palatability of food affects the satiety signals. 

Switch your brain on and put it together in your head. And learn more about leptin before you will be fooled again. 

This is just a very unfortunate practice by many who are seeking sensations: taking things out of context and elaborating on them so much that it will become a topic of the week. People then do not understand or see the whole context and are disappointed that the media publish one thing one day and the complete opposite the next day. Does that sound familiar to you? 

I am not saying that Dr Lustig is completely wrong. I am saying that he again focused too much on one mechanism, which is not as important in isolation because our endocrine system is too complicated for that. After all, he is the endocrinologist, not me. 

The mechanism of insulin resistance development - which one is correct?

In one of my previous articles you could read my discussion on the possible causes of hyperinsulinemia in people. This condition is closely related to insulin resistance, whether as a cause or a consequence and it also is connected with metabolic syndrome on which I did my research for dissertation. People with elevated glucose concentration in blood, when having pancreas functioning, secrete more insulin and this helps to keep blood glucose under control. But after time, as this condition persists, especially when being overweight or even obese, insulin resistance can develop in muscles or elsewhere in the body. And, as the animal studies suggest, high fat diet can promote insulin resistance in the hypothalamus and this could eventually lead to overeating and overweight. This requires more research. Nonetheless, Dr Lustig proudly presented to the audience how he managed to fix obesity in otherwise healthy patient just by simply lowering the high insulin levels by using a drug. 

What I would like to discuss in this lengthy article (make yourself comfortable, a cup of tea or coffee might be useful, too), is the alleged origin of insulin resistance promoted by Dr Lustig. When discussing the causes or origin of metabolic syndrome, he highlighted few points: 

Then he asks a question WHERE this insulin resistance happens?

He again presented quite an amount of biochemistry and recent advancements in research.

Firstly he refused the traditional adipocentric view of the metabolic syndrome development. This traditional view operates with a gradual accumulation of the excess adipose tissue leading to insulin resistance, which metabolically affects other organs and body systems: 

The background of this Dr Lustig's refusal was that the obesity is not an issue, because 1 in 5 obese people are metabolically normal. Read more on my comments about this here.

Here he provides a different scenario: 

In order to go deeper into this problem he firstly presented how the scientists bred animals lacking insulin receptors in eight various tissues and examining how their metabolism was affected: 

Dr Lustig pointed ad the PODIRKO mouse, which was insulin resistant in its kidneys, although the blood glucose were normal. In this breed the insulin caused severe damage to the animal kidneys, similar to those of poorly managed diabetics. Dr Lustig concluded that it was not the glucose causing the tissue damage, it was insulin. Of course it was insulin, because their blood glucose was NORMAL, I add. In diabetic patients the blood glucose is elevated, often together with insulin - can we say that in these it is again only the insulin that causes kidney (and other organs) damage? Dr Lustig said nothing about that but you could repeatedly hear how fructose is a browning agent and damages the cells and tissues. Except the fact that the fructose concentrations in blood are 10-1000 times lower than the concentrations of glucose. In one video Dr Lustig announced that 6 micromoles of fructose concentrations can occur in blood, which is 1000 times less than a physiological concentration of glucose measured in millimoles. 

Now please look at the MIRKO mouse, which is of interest for me. These animals were insulin resistant in their muscles, but protected from obesity. I am fine with that, except the fact, as I have mentioned elsewhere, a lack of physical activity while overeating can result in the signs of prediabetes within 1 or 2 days. So, does the focus on the liver and brain insulin resistance, when associated with obesity, matter that much? What is more: does not the insulin resistance induced by non-exercising muscles affect the brain, which then fails to read the leptin? I guess it does. Although the study reports that MIRKO mice were not sufficiently affected in terms of glucose homeostasis (which drives insulin higher for some time), it also stated that: 

" muscle...communicates with and regulates insulin sensitivity in other tissues."

The study also mentioned in their conclusion, that: "...primary insulin resistance in muscle may lead to increased adiposity and development  of obesity." This seems to be in contrast with the content mentioned by Dr Lustig in the slide. Moreover, the group of 6 traits was only presented as immune against obesity, but nothing was indicated how prone they were to the metabolic syndrome. 

Overall, the slide above  does not disprove my point that a person can become insulin resistant when overeating and not being physically active; and this can emerge from the diet lacking fructose. Please bear this in mind as you will read further, because Dr Lustig will try to convince you that it is the fructose that is the absolute villain in the development of hepatic insulin resistance and as such it drives the metabolic syndrome development, insulin resistance in the whole body or even type 2 diabetes. 

Secondly, you could see a brief overview of how the body functions under different conditions in relation to insulin sensitivity or resistance:

When the liver is functional and insulin sensitive, in the presence of insulin it stops producing glucose and at the same time it produces fat (triglycerides) which are released into the blood. This happens primarily after glucose consumption, no fructose was mentioned here. Fructose has very little insulin stimulating activity because it almost does not occur in the blood. This fat stimulating effect can easily happen in fructose-free diet, based on processed starches of a high glycaemic index. 

Dr Lustig also said at 17:55 minute that the produced VLDL from the hepatic DNL can "CAUSE atherogenesis as a direct effect". The fact is that the presence of VLDL is only a risk factor, not a direct cause of atherosclerosis. Other factors must be present, such as hypertension, damaging the delicate epithelium of the arteries, being oxidized by elevated glucose concentrations and other processes such as inflammation. The circulating lipoproteins on their own are not as bad, it is what acts upon them that makes them a time bomb. 

A similar diagram, illustrating the LIRCO (liver insulin resistant mouse), shows how the liver is blind to the insulin stimulated triglycerides production and the inhibition of gluconeogenesis is not stimulated either, so the animal has a high blood glucose, but allegedly not the metabolic syndrome. 

Well, since for the metabolic syndrome at least the three of five main features of the clinical definition must be present, while this scenario does not support it, I must agree. But is the elevated glucose harmless? Hardly so. 

Then Dr Lustig moves to a third scenario. where there is a selective insulin resistance because although the glucose is high, also the triglycerides are high. 

In this case a metabolic syndrome, along obesity, were the result while in the previous case there was only the obesity without the metabolic syndrome (albeit the hepatic insulin resistance was present), on which Dr Lustig has probably built his own new theory: obesity is not enough and insulin resistance is also not enough, as you could see in the first slide in this article. 

Well, for me and also for the diabetics it is enough to have a high blood glucose to go blind, having kidney failure or have a leg amputated. But Dr Lustig apparently pushes the boat towards the more complex condition - metabolic syndrome so that he can make fructose the captain.

One thing I would like to highlight here: these mechanisms were studied on mice which were bred to lack the insulin receptors at specific tissues while other insulin receptors remained functional. Is this representative for the general population? I do not think so. Moreover, as several genes normally affect one metabolic pathway, one gene can influence several metabolic processes, too. This is how our biology is complicated. 

Let's continue. I have already outlined my concerns about how the inactive muscles are not able to take in any more glucose or fats for energy and this can lead to prediabetic condition within a couple of days in humans. These people have elevated glucose and also can have elevated lipids, upon which the glucose will act and make them atherogenic. 

Do you think that the insulin resistance due to a positive energy balance develops in isolation on specific organs in normal free-living humans? I mean those without a genetic predisposition, because those with some genetic trait would be similar to the selectively bred mice in their risks. The study I mentioned earlier suggested that the metabolism in normal organisms is interconnected and the insulin resistance of one organ (adipose tissue, muscles) can affect the metabolism of other organs (liver) and the whole glucose homeostasis. 

According to Dr Lustig, the scenario is the opposite: excess dietary fructose makes liver to store fat and AFTER THAT it becomes insulin resistant while still producing extra triglycerides - leading to metabolic syndrome and affecting the rest of the body as a consequence - just because 20% of obese people are metabolically healthy and there are non-obese (albeit half of them overweight) who also express metabolic syndrome... Think.  

Before I end this post I would like you to look at the adipocentric picture at the beginning of the post again. There you can see that it was published in 2005. In my other article you could also read, that in the same year a scientific paper supported the peripheral insulin resistance as a more likely reason for developing fatty liver condition than the insulin resistance of the liver itself, which Dr Lustig advocates. They basically said that the NAFLD was a consequence of the peripheral insulin resistance and not the other way round, according to the available evidence. But Dr Lustig does not seem to accept this in 2014 and focuses on hepatic insulin resistance only, supporting his theory by the research on the genetically manipulated animals and persistently blaming the fructose in the diet as an ubiquitous factor that explains all the following aspects: 

What followed after this slide I have discussed in another article. 

To conclude and answer the question in the title: I do not have the answer. You could see how complicated the issue is, but from my point of view I tend to contradict Dr Lustig, at least in part, because the metabolism is really complicated and things do not tend to happen on isolated tissues or organs at once unless there is a genetic condition that makes it happen on a single tissue or organ. Maybe both of these opinions are partly true and the mechanism of insulin resistance can have different scenario in different people, depending on their genetic traits, lifestyle, exposure to different factors, etc. 

Obesity and dementia

You may have heard it a few times already by now: obese people are more likely to develop dementia earlier than thin people. 

You could also hear Dr Lustig asking whether sugar causes dementia and seeing him presenting this slide in his lecture at 52:27:

He spent some time referring to the statements you can see on the left side of the slide. Let me just summarize these points: 

We have proven association between obesity and dementia in humans and animals but only for animals there was some data for causative relationship between the consumption of sugar and declined cognitive skills, which were not affected by the obesity of the animals. 

Since you have learned in the previous article, that sugar is not the main cause of obesity (it was fried potato products) and the sugar consumption has been declining over the past 14 years while the dementia cases continue to rise, can we still say that it can be predicted that sugar causes cognitive decline independently of the consumption of other fast food items and possibly other environmental factors? Remember that the consumption of fast-food continued to rise when the sugar consumption started to decline in 2000. You could also hear Dr Lustig saying that the western diet as whole has been associated with dementia in humans and that we do not know which aspect of it can be attributed to the dementia cases. 

It is also a fact that rodents, which the rats are, have much higher de-novo lipogenesis (DNL) capacity in their bodies than humans have. Could we hypothesize that this factor could have contributed to the decline of the cognitive function of rats while it would be less straightforward in humans if we managed to assess it a similar way? The scientists already made this mistake in the past when predicting the same DNL in humans after finding the extend of DNL in rodents. Now we know that in humans it is different. 

What is more, while it was obesity that was correlated with dementia in both animals and humans, regardless of whether it was sugar or fat as a proximate cause, can we hypothesize that obesity is an absolute cause of dementia? That point that it was sugar, not fat, which leads to the declined cognitive function in animals does not dismiss the link between obesity and dementia as such. Dr Lustig also said that the omega-3 fats produced increased cognitive function in rats. How about omega-6 which is prevalent in our diet? How about the fats, if consumed at high amounts, leading to obesity even without the sugar? It is enough to consume fats with processed carbohydrates such as white bread or the chips as such. 

For now, as Dr Lustig said it openly, we do not have the causative data for dementia in humans in relation to sugar or any other dietary component. We only know that omega-3 fatty acids help reduce the risk. And I would like to keep it at this point, instead of drawing suggestive conclusions, until we have the data.

What I remember though is that even brain can be insulin resistant. But can this be due to fructose content in our diet? Fructose concentrations in the blood appears at 10 - 1000 lower amounts than of glucose. People can become obese even at relatively low amount of refined sugar or HFCS, by simply overeating on processed foods, when muscles do not take much energy in and the increased glucose and insulin concentrations in blood can lead to inflammation of the cells sensitive to insulin and finally down-regulation of insulin receptors. I have heard about patients who improved their cognitive function by consuming coconut oil. A portion of this energy source is converted into ketone bodies by the liver and these serve as an alternative fuel for the insulin resistant brain. Interesting, is it not?