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Over the past few months, there has been a lot of baseless claims trying to link high fructose corn syrup (HFCS) and a variety of diseases, especially Type 2 diabetes. Like many of these medical myths, there is, at its core, some tiny bit of evidence that is generally misinterpreted or misused. But let’s take a close look at Type 2 diabetes, HFCS and the evidence that either supports or refutes the hypothesis that drinking HFCS is any more responsible for the disease than other sugars.
Just for background, the claimed link is between HFCS and Diabetes mellitus Type 2 (or Type 2 diabetes, T2DM), a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In general, someone with T2DM produces low (or maybe even adequate) levels of insulin, but various cells and organs become resistant to insulin, so cells don’t remove or store blood glucose. Although the cause of Type 2 diabetes is not completely understood, it results from a complex interaction between diet, obesity, genetics, age and gender. Some of the causes of T2DM are under a person’s own control, like diet and obesity, but many of the factors aren’t.
Because they are often confused, it’s important to note that T2DM has a completely different cause and pathophysiology than Diabetes mellitus Type 1 (T1DM, and once called juvenile diabetes). Type 1 diabetes results from the inability of the beta cells of the pancreas to produce insulin, mostly as a result of an autoimmune disease. Typically, T1DM begins in children, though there are forms of the disease that begin in 30-40’s that had been confused with the type 2 version in the past, but blood tests can determine if it is Type 1 or Type 2. As far as we currently know, T1DM is neither preventable nor curable, and there is only some conflicting evidence about what actually causes T1DM. Diet, including consumption of sugars, won’t cause T1DM. Furthermore, although there are numerous treatments and lifestyle changes that can change the course of T2DM, and there are several medical treatment regimens, Type 1 is a death sentence without regular daily insulin injections. However, over 90-95% of diabetes is the Type 2 form.
The consequences of both types of diabetes are almost the same. Complications of poorly managed diabetes mellitus may include cardiovascular disease, diabetic neuropathy, and diabetic retinopathy, among many other chronic conditions. I was intending to make this a quick explanation of diabetes, but I thought it would be beneficial to understanding the hype behind high fructose corn syrup.
After giving you a background discussion of diabetes, it’s time for a similar focus on the basics of sugar biochemistry.
There are two broad types of sugars, aldose and ketose, along with over twenty individual, naturally-found sugars, called monosaccharides. Of all of those sugars, only four play any significant role in human nutrition: glucose, fructose, galactose, and ribose (which has a very minor nutritional role, though a major one as the backbone of DNA and RNA). Got that? Four sugars. Whatever you eat, however you consume it, you can only absorb 4 sugars. And no matter the source, fructose, glucose, or galactose, whether from a chemical factory, or sugar cane, or from organic honey lovingly taken from the wild honeybees of Switzerland who were gently allowed to fly amongst the organic clover fields of the high alps, are, individually, the same chemical. “Natural” or synthesized fructose is always the same chemical structure. The same with glucose or galactose. So, if you buy some sugar from an organic food store, or your local chemical factory, the structure, based on carbon, hydrogen and oxygen, will be exactly alike for each different sugar.
Of course, it does get a bit more complicated. Many sugars form disaccharides that are compounds made of two monosaccharide sugars covalently bound together. Table sugar, the white stuff in our sugar bowls, is called sucrose which is one molecule of glucose bound to one molecule of fructose. Sucrose is also the main sugar in most commercially purchased sugars that you find including brown sugar, molasses, beet sugar, and maple sugar (and syrup). Milk sugar is lactose, which is a glucose and galactose disaccharide, maltose is two glucose molecules, and there are a few dozen less common ones. Each disaccharide has a slightly different taste and sweetness, and different combinations of disaccharides provide unique tastes to certain fruits and vegetables.
There are more complex sugars, called polysaccharides, that are long chains of sugars which are are the constituent biochemical in a lot of plant and animal cellular-level and gross-anatomy structures. For example, chitin, the exoskeleton of insects and crustaceans, is essentially a long chain of glucose molecules that’s extremely hard (and completely indigestible by humans).
Before we can continue onto our discussion about HFCS you need to know one important thing. Humans can only absorb monosaccharides, specifically glucose, fructose, galactose and ribose. In other words, all of those disaccharides and polysaccharides must be broken down into the constituent monosaccharides before it has any usefulness for a human. The gut has a variety of different enzymes that break down these starches and disaccharides–so sucrose is not absorbed by the small intestine, but it is instead broken down by the sucrase enzyme into glucose and fructose, and only at that point, it is absorbed into the bloodstream to be used for energy. By the way, any disaccharide or polysaccharide that are not broken down remain in the gut, providing food for our gut bacteria, thereby maintaining a healthy digestive system. Moreover, some individuals lack certain enzymes to digest some disaccharides; lactose intolerance results from the lack of of lactase, which breaks down lactose into glucose and galactose. Thus, in these individuals, lactose cannot be absorbed, and it passes to the bacterial flora, the result of which causes significant intestinal distress to the lactose intolerant individual.
It is important to note that fructose is 1.73 times more sweet than sucrose despite having the same exact caloric content. So technically, you could use about 58% less fructose than sucrose to get the same sweetness. And any food that has more fructose (like honey, pears and grapes) will taste sweeter, even though it has no additional calories.
HFCS consists of 24% water, and the rest fructose and glucose. There are two main types of HFCS, HFCS 55 (used mostly in soft drinks) which is approximately 55% fructose and 42% glucose; and HFCS 42 (used in other types of beverages and processed foods), which is approximately 42% fructose and 53% glucose. There is another type, HFCS-90, approximately 90% fructose and 10% glucose, which is used in small quantities for specialty applications (interestingly, low calorie drinks, because, for the same sweetness as sucrose based drinks, about 33% less calories are added), but it is primarily blended with HFCS 42 to make HFCS 55.
And despite the fact that HFCS is produced from corn, it is contains the same fructose and glucose that is found in table sugar, or any other plant in the world. Fructose and glucose do not chemically differ in any way from fructose and glucose found anywhere else, it is a fixed chemical structure. Admittedly, HFCS is used in some foods because of cost. For the equivalent sweetness as sucrose (cane sugar for example), the manufacturer can use less with fewer calories. Given that HFCS contains both natural fructose and natural glucose, and it is just as sweet with fewer calories, you’d think that people would be all over that.
I hope that’s clear. HFCS is nothing more than a syrup that contains a higher ratio of “natural” fructose to “natural” glucose than table sugar.
The story now becomes complicated, and it is the basis of some of the speculation about HFCS and diabetes, because galactose, fructose and glucose are treated differently by human metabolism. Glucose passes through the liver unchanged, and can be used by all cells for energy. The level of glucose is controlled by insulin, which causes it to be stored if the blood levels get high, and glucagon, another hormone which causes the release of glucose from storage. This control system is highly complicated, and in non-diabetics, is a finely tuned system. Fructose and galactose don’t signal insulin, but are captured by the liver, eventually processed into a couple of different biochemicals, one of which is glucose. So, because fructose is treated in a different manner by the body, speculation has been that fructose might be implicated in T2DM. How the body controls blood sugar levels, and how fructose and galactose are involved in that control, is incredibly complex and would take at least a year of graduate level classwork to even begin to understand the physiology (I know this, because I took those classes, and even today I scratch my head about how complex it is).
Except, there are some problems with this speculation about fructose and T2DM. For example, fructose has a very low glycemic index of 19 ± 2, compared with 100 for glucose and 68 ± 5 for sucrose. Because fructose is 1.73X sweeter than sucrose, diabetics can consume significantly less fructose (than other forms of sugars) for an equivalent level of sweetness. Studies show that fructose consumed before a meal may even lessen the glycemic response of the meal. In other words, specifically because of the sweetness and lower insulin reactivity, fructose may actually be preferred for those who are attempting a low glycemic index diet.
A lot of the current “mania” about HFCS and T2DM results from a recent article in an open source journal, Global Public Health which has an impact factor of 0.92, about as low as you can get on the impact factor scale. The authors tried to establish a correlation between availability of HFCS foods and the incidence of Type 2 diabetes. This type of study is at the population level, which may seem like it would give you great numbers, but the problem is that it allows in so many confounding factors, and ignores all sorts of other information that might provide us with better information. In other words, it is simply not a way to establish correlation, let alone causation.
The problems with this study are numerous:
- They assume that availability of HFCS foods is the major cause of obesity. It simply isn’t. It is possible that high amounts of HFCS means accessibility to various others foods that might cause obesity.
- Obesity itself is not a causal factor in T2DM, it is one of number of causes of the disease.
- Even though the researchers attempted to control for other factors, there are just too many factors that may skew the results at a country level. The best type of epidemiological study would a prospective study, which would allow for controlling of different factors along with getting more detailed data about each patient. A prospective study takes time, is expensive, but gives some of the best results upon which to confirm or refute a hypothesis about HFCS being causal to T2DM. The authors of this study took the easiest and simplest route to write a paper: they obtained country-level data for T2DM, Gross domestic product, HFCS production in foodstuffs, and calories consumed. This type of work takes a few days, and would require you just to leave the computer for sustenance. I could look up the sales of Xbox and Playstations in each country and compare it to T2DM, get it published in a bad journal, and make a name for myself that video gaming is correlated to Type 2 diabetes. And even if I could show some correlation between video gaming and diabetes, it wouldn’t be worth anything, though I’d make a big name for myself.
In a review article examining the health implications of HFCS, the author, James Rippe, MD, states that “most of the studies being cited to support the proposed linkages between fructose consumption and obesity and other metabolic conditions employ epidemiologic data that establishes associations rather than cause and effect.” The study I critiqued above is a perfect example of the type of study dismissed by Dr. Rippe. He goes on to conclude that:
While the fructose hypothesis is an interesting one, it poses the danger of distracting us from further exploration and amelioration of the known causes of obesity and related metabolic conditions. It is important to remember that many of the metabolic abnormalities currently being postulated as attributable to fructose consumption may also be ascribed to obesity itself.
The epidemiologic evidence being cited to support metabolic abnormalities related to fructose consumption leaves many questions unanswered. There are compelling data to support excessive caloric consumption as the major dietary driver of obesity. The fructose hypothesis is based largely on epidemiologic data that do not establish cause and effect. All too often, we have been led astray by confusing associations with cause and effect. With the fructose argument, we are in danger of repeating mistakes frequently made in the past by basing judgments on insufficient evidence.
It’s clear that there are individuals want to “prove” that HFCS is unsafe and causes all sorts of problems to humans. But HFCS is a sugar syrup, close to honey in ratio of fructose to glucose. Just because it has this scary chemical name, high fructose corn syrup, people must think that it’s made up of some evil fructose chemical. But all fructose molecules are exactly the same, whether it’s in honey, a fruit, maple syrup, cane sugar, or HFCS.
High quality reviews of the research around HFCS and T2DM have consistently stated that the data does not show any causality between the sugar and the disease. We could cherry pick a few poorly designed epidemiological studies or force-feeding rats to induce diabetes studies, but neither of those types of studies provide us with solid or even intriguing evidence that HFCS has some responsibility for T2DM. Until we have two pieces of information, one, a high powered prospective epidemiological study, and two, a definitive explanation of how fructose could disrupt the metabolism leading to T2DM, we completely lack any reliable evidence to think that HFCS itself causes T2DM rather than simply any sugar. Because the hypothesis that is well understood, and well supported by evidence, is the one that says any sugar can lead to obesity, thus leading to a higher risk of T2DM.
If I were raising children, and frankly, I have, I would keep them from HFCS. And sucrose. And honey. And fruit juices. And cotton candy. And chocolate bars. And fatty foods. And potato chips. Picking on HFCS just seems crazy.
- Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ. Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr. 2002 Nov;76(5):911-22. Review. PubMed PMID: 12399260.
- Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr. 2002 Jul;76(1):5-56. PubMed PMID: 12081815.
- Goran MI, Ulijaszek SJ, Ventura EE. High fructose corn syrup and diabetes prevalence: a global perspective. Glob Public Health. 2013;8(1):55-64. doi: 10.1080/17441692.2012.736257. Epub 2012 Nov 27. PubMed PMID: 23181629. Impact factor=0.920.
- Heacock PM, Hertzler SR, Wolf BW. Fructose prefeeding reduces the glycemic response to a high-glycemic index, starchy food in humans. J Nutr. 2002 Sep;132(9):2601-4. PubMed PMID: 12221216.
- Rippe JM. The health implications of sucrose, high-fructose corn syrup, and fructose: what do we really know? J Diabetes Sci Technol. 2010 Jul 1;4(4):1008-11. PubMed PMID: 20663468; PubMed Central PMCID: PMC2909536.
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