Nature’s Silent Killer: The Dangers of Fructose
Many of you reading have read about the dangers of high sugar diets, with words like “insulin resistance” and “glycemic index” thrown around commonly to try to convince us not to eat these foods. On this very blog, we have had articles stressing the need to stick to the Paleo game plan, eschewing grains and sugars for good fats, clean animals, and a daily vegetable intake surpassing most people’s monthly amount.
But, one element often forgotten in the big dietary picture is a sugar many of us know of but know little about: fructose. We tend to lump fructose into the same group as other sugars, thinking of things like high fructose corn syrup (of processed food fame) as just another way to say “sugar” without saying it. In reality, fructose by itself presents a significant danger to the body beyond simply caloric value and should be avoided in all but minute, sporadic doses.
Before we launch into the discussion of its dangers, it is prudent that we explore fructose metabolism. Fructose, like glucose, is a 6 carbon sugar. However, it is arranged in a 5 carbon ring instead of a 6 carbon ring; simply, fructose chemically very different than glucose and thus is utilized differently by the body.
Fructose is most notably found in fruit, however its presence there is attenuated by fiber, vitamins, minerals, and other beneficial elements that makes normal fruit consumption acceptable and biologically manageable (though even this can go overboard). It is also present in sucrose, which until recently was a relatively expensive luxury product until cheaper sources could be obtained. Sucrose, or ordinary sugar, is made by linking one glucose and one fructose together into one molecule. When metabolized by the body, this bond is broken, releasing one fructose for every glucose. Thus 50% of the sugar consumed is by definition fructose.
But, we really run into trouble when fructose alone is extracted/synthesized and concentrated into a sweetener. Fructose is nearly twice as sweet as glucose and sweeter alone than when in sucrose. This makes it a much more attractive sweetener for use in artificially sweetened products. Only in the last few decades has fructose become a major part of our diet, and we have our ballooning waistlines and declining overall health to show for it.
Under normal circumstances, dietary fructose is converted to glucose by the small intestine. But, this capacity is small and can be easily overrun, allowing fructose to enter the blood stream unconverted. When in the blood, fructose is immediately captured by the hepatocytes (liver cells), which are some of the only cells in the body that contain the fructose specific transport protein GLUT2 (note: GLUT5 is also a fructose transporter used in the small intestine and kidneys, however they have much less activity than GLUT 2). GLUT2 allows the liver cells to capture fructose quickly and remove it from the blood stream. In comparison, when glucose enters the body, it is immediately taken up by the small intestine into the blood stream and distributed to various tissues for direct use.
When the fructose is taken into the liver cells, it enters an alternate pathway from glucose that creates the same intermediaries, allowing it also to be used in energy generation. But, this all occurs within a cell that does not require them for energy beyond a certain small amount. Because of this, an ever increasing amount of intermediates remain, unable to be utilized for cellular metabolism. Even more distressing, fructose is metabolized without any negative feedback, meaning that all fructose will be metabolized as soon as possible. This differs from glucose, which will not be broken down unless it is metabolically necessary. Over time, this issue can lead to a depletion of metabolic materials, such phosphate from ATP, as well as a major alteration in enzyme activity, such as decreased glucokinase activity leading to less glycogen storage.
Importantly, the fructose intermediates glyceraldehyde and dihydroxyacetone phosphate (DHAP) are easily converted into glycerol 3-phosphate, which forms the backbone for a triglyceride. Given that triglycerides are the main long term energy storage molecule and the building blocks of body fat, the problem becomes apparent very quickly. As the liver cells are forced to deal with ever increasing amounts of fructose, the amount of fructose intermediates converted to triglycerides far surpasses the amount used for energy.
So what then becomes of those excess triglycerides? The simple answer is they are stored. Unfortunately, given the location of processing, the liver receives a disproportionate share along with the body’s normal adipose (fat) tissue. As such, one of the major issues facing those with long term high fructose intake is a disease called “non-alcoholic fatty liver disease.” While the symptoms themselves are relatively benign, those with this condition are at much higher risk for metabolic diseases (insulin resistance, diabetes, high cholesterol, high blood pressure, obesity) as well as progression to a much more dangerous disease called NASH (non-alcoholic steatohepatitis). NASH often progresses into cirrhosis and ultimately liver failure.
Beyond the liver, fructose overconsumption has been linked to everything from metabolic syndrome to kidney disease to cancer. While this may seem like a wide scope, it is logical that if fructose can damage the liver it is capable of causing negative effects on any fructose capable tissue. Most especially, its obvious role in the alteration of metabolic pathways can and does have serious long term consequences. The mechanisms behind these issues are outside the scope of this article, though for reference the articles by Douard and Ferraris and Tappy and Le list them very clearly.
Bottom line, it is clear that fructose presents a clear and present danger to our health on many different levels. The dangers of regular fructose overconsumption cannot be understated and should be addressed immediately. I suggest diving into the provided sources to get a much more in depth idea of this silent public health disaster.
Justin Seltzer is a CrossFit Level 1 instructor, graduate of USC, and author of the science and medicine blog The Weekly Paper. He currently conducts medical clinical research and will be attending medical school in the fall.
Bezerra RM, Ueno M, Silva MS, Tavares DQ, Carvalho CR, Saad MJ. “A high fructose diet affects the early steps of insulin action in muscle and liver of rats.” J Nutr, 2000 Jun; 130(6): 1531-1535.
Douard V and Ferraris RP. “The role of fructose transporters in diseases linked to excessive fructose intake.” J Physiol, 2013 Jan; 591 (Pt 2): 401-414.
Joesten MD, Hogg JL, Castellion ME. “Sweeteness Relative to Sucrose (table)”. The World of Chemistry: Essentials (4th ed.): 359.
Lee O, Bruce WR, Dong Q, Bruce J, Mehta R, O’Brien PJ. “Fructose and carbonyl metabolites as endogenous toxins.” Chem Biol Interact, 2009 Mar; 178(1-3): 332-339.
Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, Johnson RJ, Abdelmalek MF. “Fructose consumption as a risk factor for non-alcoholic fatty liver disease.” J Hepatol, 2008 Jun; 48 (6): 993–999.
Sillero MAG, Sillero A, Sols A. “Enzymes Involved in Fructose Metabolism in Liver and the Glyceraldehyde Metabolic Crossroad.” Eur J Biochem, 1969 Jun; 10: 345-350.
Tappy L, Le KA. Metabolic effects of fructose and the worldwide increase in obesity.” Physiol Rev, 2010 Jan; 90(1): 23-46.
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