Thursday, April 01, 2010

Eating high fructose corn syrup makes Yogi bear.......

.......fatter than the average bear.

Apologies for that awful title that I couldn't resist.
If you are fond of sweets, chocolates, candy, cookies and ice cream, and have ever read the label for the ingredients, you must have noticed one of them, called high fructose corn syrup (HFCS). You might have wondered about it a little, or just thought that fructose is sweet like glucose, and gone on with your indulgence. HFCS has now largely replaced table sugar (or sucrose) as the main sweetener in most confectioneries sold in most stores. A huge reason for this has been the easy availability of the vast quantities of corn grown in the US, from which high fructose corn syrup is extracted, making it cheaper than sucrose. While there has been speculation for a while (and increasing correlative data) suggesting that HFCS may increase obesity or other health problems related to sugar, much of this has been decried by the food industry.

However, the data is slowly shifting towards the adverse health effects of HFCS. A recent paper in Pharmacology Biochemistry and behavior (Bocarsly et al, now suggests that HFCS causes the characteristics of obesity, from increases in body weight to increased triglycerides in the blood.

Let's take a look at what this study shows.

The researchers studied the effects of HFCS in captive rats. Their experiments were simple. They fed groups male or female rats, either normal rat chow, or rat food mixed with sucrose (sugar), or rat food mixed with equal amounts (and calories) of HFCS (and each sample size was ten rats). They varied their experiment so that the rats could eat HFCS with every meal, or HFCS was provided only for 12 hours during the day. They carried out these studies over a short time frame (two months) as well as a longer time frame (6 months). Here is the rationale behind this experiment. The experiment not only tested if HFCS could cause increase in weight, but compared it directly with consuming table sugar, sucrose. Now sucrose is a compound that is made of one molecule of glucose and one molecule of fructose. So when sucrose is broken down, it breaks down to fructose and glucose. Secondly, the process by which glucose and fructose are broken down are similar, and the amount of energy they each can release is the same. HFCS has around 55% fructose and 45% glucose. So the food industry has always claimed that using sucrose, or using an equivalent amount of fructose would be biologically very similar. However, when rats were fed either regular food, or food + sucrose, or food + HFCS, the results were quite different.

Here is what the experiment unambiguously revealed.

The male rats fed HCFS gained more weight than mice fed with regular chow or chow supplemented with sugar even over a two month period. Over a six month period, this weight gain in male rats was very significant when compared with rats eating regular chow. In male rats, after 6 months of these diets, the rats on HFCS weighed on average a 100g more than rats fed on regular food. Female rats also gained weight eating HFCS, but at a lower rate than males. After a 7 month duration on these diets, the rats fed with normal food weighed 177% over baseline. However, the rats with continuous access to HFCS were ~200% heavier than baseline. There were a few other interesting observations, indicative of the effects of HFCS on obesity. In both male and female rats, the increase in body weight was accompanied by an increase in actual abdominal body fat, as well as increased triglycerides. So if the same effects hold for humans, the weight gain would primarily be around the abdominal region.

There remain some limitations in this study. The dramatic increases in body weight as well as abdominal fat was observed in rats that had food + HFCS available continuously. In female rats that had access to HFCS only for 12 hours during the day (for a long duration) did not show those dramatic weight increases. However, male rats even with controlled access to HFCS showed this increase in abdominal fat accumulation. Since we care about human consumption of HFCS, does human consumption of HFCS reflect tightly controlled access to it, or a constant availability of HFCS with any meal? Secondly, there will be some differences in the rates of metabolism of glucose and fructose between humans and rats. However, the broad processes of absorption and breakdown of these nutrients are very similar in us and in rats, so it is quite likely that this general phenomenon will hold true in humans. But doing these experiments in humans (where a long term study could be five or ten years) would be extremely difficult to control. Secondly, the experiments were done in rats kept in cages in a laboratory. One could argue that there is clearly nothing in common between laboratory rats and humans. These rats exercise very little and are largely sedentary. They don't run around as much as they should, are already somewhat obese even before feeding on HFCS, and have fairly unlimited access to food and can eat whenever they want to, and as much as they want to in one sitting. Surely that can't be the way humans live. Oh but wait a minute!

The authors in their discussion speculate on why HFCS might cause increased body weight gain when compared to regular food or even food supplemented with an equivalent amount of sucrose, but their discussion only briefly touches on aspects of sugar metabolism that could explain this. So I'll elaborate a little more, and add some of my own speculation based on how these sugars are metabolized. In short, it all comes down to the body's way to regulate sugar levels, sense how much is there, and feedback to control the effects of these sugars.

Firstly, glucose and fructose are absorbed very differently. Glucose is absorbed early in the small intestine, while fructose is absorbed later. But the big difference comes in how and where the two sugars, as well as sucrose itself are metabolized. Sucrose has to be broken down in the stomach into glucose and fructose before it can be used. Glucose can be used by just about every cell in the body through a process called glycolysis, to break it down into usable energy. The process of glucose breakdown is a very tightly regulated process called glycolysis. In this process, a key regulatory step happens when glucose is converted to another sugar called fructose-6-phosphate, and then to another sugar called fructose-1,6-bisphosphate, which is then broken down into triglycerides and then energy. Now, the enzyme that does this conversion to fructose-1,6-bisphosphate is called phosphofructokinase and it is highly and exquisitely regulated by multiple inputs, including other co-factors as well as other modifications. This allows the cell to tightly and precisely control how much glucose is broken down. Fructose however is broken down not in all cells but largely only in the liver through a process called fructolysis. Here, instead of fructose being converted to fructose-6-phosphate, and then being tighly regulated in its conversion to 1,6-bisphosphate and later triglycerides, it is converted into a similar (but biologically very different) sugar called fructose-1-phosphate. This small change in the position of that single phosphate group makes a huge difference biologically, since the breakdown of this sugar into triglycerides happens very quickly and easily, and is not tightly controlled by many inputs. The result of this is that fructose is very rapidly and easily broken down into triglycerides which can then be used for energy, or be converted into glycogen or fats for storage. While the eventual outcome of glucose and fructose is similar, the way the two are regulated and controlled is very different. In other words, the body has much more control over how fast glucose is broken down, but far less control over fructose breaking down.

So this phenomenon, combined with the fact that HFCS has over 55% fructose, and 45% glucose means that the body is dealing with a much higher ratio of fructose to glucose when compared with just plain old table sugar (sucrose). The difference is small over a few meals, but over a long period of time, this adds up to quite a lot. Also, what this difference in circulating glucose (that is regulated and not tightly broken down) does is change the way the body responds to feeding. Glucose controls insulin release, which in turn controls a hormone called leptin, which controls apetite and satiety in the brain. Now, this small but continuous difference in fructose/glucose ratios (comparing HFCS to sucrose) alters how much circulating glucose remains in the blood, which can alter leptin levels as well as leptin sensitivity, and this finally alters the brain's ability to be satiated after a meal. Over time, HFCS could change the satiety achieved by eating, and also finally alter eating patterns. All this put together could cause the increase in body weight seen over time.

Of course, there will be people unsatisfied with these data. But the data is suggestive, and this idea is compelling.

Miriam E. Bocarslya, Elyse S. Powella, , Nicole M. Avenaa, and Bartley G. Hoebel (2010).
High-fructose corn syrup causes characteristics of obesity in rats: Increased body weight, body fat and triglyceride levels Pharmacology Biochemistry and Behavior


Mr. Gunn said...

I don't have an issue with the argument that fructose is metabolized different by the body, but I do have an issue with the argument that HFCS is an chemical that evil food manufacturers are poisoning America with. Unfortunately, the latter is the message that people who write about this seem to want to communicate.

If it's true that fructose makes you fat, wouldn't you expect the same negative effects from a diet higher in fruit?

Sunil said...

Mr. Gunn...thanks for your comment. I don't really think HFCS is a chemical made by the "evil" food manufacturers. I don't think food manufacturers are evil. But I do think the biochemistry here makes solid sense. Unfortunately, as far as HFCS goes, it is more a quantity issue than anything else. Most Americans consume massive amounts of HFCS...and only few people watch what they eat carefully. As far as your comment on fruit actually won't have the same negative effects with fruit because it is again a matter of quantity, and how much fructose you can consume with fruit. Fruit like strawberries, oranges and grapefruit are low on fructose. Some others (grapes, apples, bananas) have higher amounts, but even there, fructose is at best about 5-7% of the total weight of a fruit. So you'll need to eat a pound of fruit to get 5 teaspoons of fructose. Compare that to the average cookie or ice cream, and you'll see what I mean.

Sunil said...

Thanks for your comment Mr. Gunn. Actually I don't think the food industry is evil or anything. As far as HFCS goes, the big issue is quantity of consumption, and most Americans get "too much" of it. With fruit, you actually won't get those side effects unless you are consuming a massive amount of fruit. Many fruit (like strawberries, oranges or grapefruit) are fairly low fructose, while others like apples, bananas and grapes have more. But even there, the most fructose you have is around 5-7% by weight. So, you'll need to eat a whole pound of fruit to get 5 teaspoons of fructose. Almost no one continuously eats that much fruit (typical healthy diets will have one or two cups of fruit, thats it). Compare that to the average cookies or ice cream, and you'll see what i mean.