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Metabolic Danger of High-Fructose Corn Syrup

December 2008

By Dana Flavin, MS, MD, PHD

Atherogenic Lipid Profiles and Coronary Artery Disease

Atherogenic Lipid Profiles and Coronary Artery Disease

Unlike glucose, fructose is readily converted to fat by the liver, leading to an excessive concentration of fats and lipoproteins in the body.9 High and prolonged fructose ingestion increases unfavorable lipid profiles in the body. By increasing triglyceride levels12,27—an independent risk factor for coronary heart disease—fructose promotes potentially dangerous lipoprotein changes that increase atherogenic risk. For example, fructose increases apoB100—the primary lipoprotein responsible for carrying cholesterol to the tissues—which leads to the formation of fatty deposits. Conversely, high-density lipoprotein (HDL), which is responsible for carrying cholesterol particles back to the liver to be eliminated, is decreased by fructose.28 Fructose ingestion therefore contributes to fat deposits in the liver (fatty liver)7 and increases the amount of dangerous lipoproteins that enhance cholesterol deposits in blood vessels walls.29 This can lead to plaque buildup and narrowing of the blood vessels—a ticking time bomb for the development of both stroke and heart attack.

Potential Consequences of Excess Dietary Fructose Consumption
  • Accelerated aging

  • Insulin resistance

  • Type 2 diabetes

  • Diabetic complications

Retinopathy (may lead to blindness)

Nephropathy (may lead to severe kidney disease, requiring chronic dialysis)

Neuropathy (may involve numbness, pain, impotence, speech impairment, loss of bladder control, etc.)

  • Non-alcoholic fatty liver disease

  • Abnormally high blood uric acid levels (hyperuricemia; may result in the development of gout; implicated in the development of diabetes and the metabolic syndrome)

  • Abnormally high triglyceride levels (hypertriglyceridemia; implicated in the development of atherosclerosis and cardiovascular disease).5,7,15

Non-Alcoholic Fatty Liver Disease

Once a relatively rare clinical oddity, non-alcoholic fatty liver disease is now estimated to affect 20-30% of adult populations in developed countries.19 Like obesity and diabetes, the rise in non-alcoholic fatty liver disease cases has paralleled the rise in consumption of dietary fructose.4 For example, a recent study by scientists at the University of Florida, Gainesville, determined that fructose consumption in patients with established non-alcoholic fatty liver disease was about two to three-fold higher than among normal control subjects.4

As its name suggests, non-alcoholic fatty liver disease is a constellation of conditions affecting the liver, characterized by excessive accumulation of fat in the organ, and unrelated to alcoholism. It is associated with higher rates of death from liver diseases, such as cirrhosis and liver cancer, and with cardiovascular disease.30-32 It is intimately linked to insulin resistance and the metabolic syndrome, and often progresses to an inflammatory condition known as non-alcoholic steatohepatitis.33

The AGE Connection

The adverse effects of excess dietary fructose are not limited to detrimental effects on blood sugar meta-bolism, lipid profiles, or liver health. Excess fructose also encourages the formation of toxic advanced glycation end products (AGEs). These are aberrant hybrid proteins, formed when sugars and lipids react with these molecules, altering their structures and damaging their functionality. As AGEs accumulate they encourage inflammation and oxidative stress. They have also been linked to accelerated aging. Advanced glycation end products are believed to play a key role in the development of hypertension as well as complications associated with type 2 diabetes like neuropathy and retinopathy.5,7,34-37 Neuropathy afflicts the nerves and can cause tingling, prickling sensations, numbness, and pain, while retinopathy damages the eye’s retina and may lead to blindness.

In terms of the reactions that lead to the development of AGEs, fructose is far more reactive than glucose, so even a small amount of fructose circulating in the bloodstream is potentially damaging. In the laboratory, it has been shown that the rate of fructose/protein cross-linking is 10 times greater than the linkage rate associated with glucose.38 This suggests that excess dietary fructose is intimately linked to accelerated aging, as this type of protein cross-linking is a common manifestation of aging.7,39-41

These aging-accelerating effects of dietary sugars were investigated in lab rats fed diets featuring sucrose, glucose, or fructose. Three measures of aging, including the cross-linking of collagen (a protein that provides structure and support for the skin and other tissues), were each significantly greater in rats that were fed fructose than rats that consumed glucose or sucrose. “The data suggest that long-term fructose consumption induces adverse effects on aging,” concluded researchers.42

Advanced glycation end products are also known to induce acute endothelial dysfunction.43 Endothelial dysfunction is implicated in the development of atherosclerosis, and thus cardiovascular disease.44 Scientists also believe that AGEs may contribute to the development and progression of chronic heart failure by inducing vascular and myocardial stiffening.45

Supplements that May Protect Against Fructose-Induced Damage

Excessive intake of dietary fructose from sources such as high-fructose corn syrup (HFCS) may contribute to myriad adverse health effects ranging from metabolic syndrome to kidney stones to the complications of diabetes. In addition to limiting exposure to dietary fructose, nutritional supplements may offer important protection against these harmful effects.

Protect against Advanced Glycation End Products.

Fructose promotes the formation of advanced glycation end products (AGEs), which are clearly linked to some of the worst side effects of diabetes.5,50 Advanced glycation end products are also linked to accelerated aging, even among the healthy.7,39,40

  • Benfotiamine: This highly bioavailable vitamin B1 analog has been shown to prevent some of the damage associated with diabetes-related high blood sugar levels. Benfotiamine blocks three of the “major molecular pathways” by which hyperglycemia damages cells.51 A recent study of patients with type 1 diabetes confirmed that benfotiamine, in combination with supplemental alpha-lipoic acid, “…completely normalized increased AGE formation…” associated with diabetic complications. Benfotiamine also corrected endothelial cell deficits associated with high blood glucose levels.52 Benfotiamine similarly shows promise against the adverse effects of type 2 diabetes.5

  • Benfotiamine also acts as an antioxidant.
    According to new research published by German scientists, “benfotiamine shows a direct antioxidant action. This effect of benfotiamine may be involved in the improvement of diabetic late complications, including peripheral neuropathy.”54

  • Alpha-lipoic acid: Recommended to preventglycation and reduce the accumulation of AGEs as well as enhance glucose utilization.55 Alpha-lipoic acid may decrease the development or improve the symptoms of neuropathy in diabetic patients.56 Alpha-lipoic acid offers powerful antioxidant effects in both aqueous and lipid environments. Only lipid-soluble antioxidants readily enter cells’ organellesto prevent damage from free radicals. Alpha-lipoic acid is a mitochondrial metabolite; it is particularly effective at protecting these vulnerable cellular “powerhouses” from oxidative damage.57-61

  • Carnosine: This dipeptide acts as an anti-glycating agent that inhibits AGE formation as well as protein glycation, oxidation, and cross-linking associated with aging and its associated pathologies. Animal studies suggest that carnosine suppresses the complications of diabetes.62-65 Late research suggests that carnosine may prevent diabetes-associated atherosclerosis.66

  • Pyridoxamine: Harvard-based researchers recently showed that pyridoxamine, an advanced formulation of vitamin B6, acts as a “broad inhibitor” of advanced glycation to benefit patients with diabetic nephropathy (kidney disease).67,68

Fight the Metabolic Syndrome. Excessive fructose intake is intimately linked with metabolic syndrome and its components such as elevated triglycerides, high blood pressure, and increased cardiovascular risk.

  • Supplement regularly with omega-3 fatty acids (fish oil). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are omega-3 fatty acids, found primarily in fish oil, which have been shown to decrease inflammation, improve the lipid profile, reduce insulin resistance, and improve cardiovascular health.69-73

  • Alpha-lipoic acid: Ameliorates several components of the metabolic syndrome in animal studies, including insulin resistance, atherogenic lipid profiles, and high blood pressure.74

  • Acetyl-L-carnitine: In combination with alpha-lipoic acid (also a mitochondrial antioxidant), acetyl-L-carnitine has been shown to improve blood pressure in patients with coronary artery disease.75

Reduce the Risk of Elevated Uric Acid Blood Level. High dietary intake of fructose—particularly in the form of HFCS—is associated with elevated blood levels of uric acid, which are linked with gout.
  • Supplemental vitamin C: A recent study of more than 1,300 men showed that a greater intake of vitamin C decreases the risk of abnormally high blood levels of uric acid (hyperuricemia).76 Hyperuricemia is strongly linked to the risk of developing gout. Intakes of 500 mg vitamin C per day or more were associated with correspondingly low levels of uric acid in the bloodstream.76

Uric Acid Elevation, Gout, and Kidney Stones

A recent study by Canadian researchers clearly shows that drinking high-fructose sugar-sweetened beverages is associated with elevated blood levels of uric acid. Known as hyperuricemia, this condition is incontrovertibly linked to elevated risk of suffering from the painful joint disease, gout. Researchers drew their conclusions based on data gathered from nearly 15,000 adult Americans who participated in the Third National Health and Nutrition Examination Survey (1988-1994). “Serum uric acid levels increased with increasing sugar-sweetened soft drink intake,” wrote the scientists. Tellingly, drinking diet soft drinks, which do not contain HFCS, was not associated with elevated uric acid levels.15

Uric Acid Elevation, Gout, and Kidney Stones

“Fructose-induced hyperuricemia might have a causal role in metabolic syndrome, hypertension, and other chronic disease,” noted Harvard-based scientists in 2007.46 In 2008, Canadian researchers narrowed the focus of their previous inquiries, examining the relationship between soft drinks, fructose consumption, and the risk of gout in men. In this study, more than 46,000 men with no history of gout were followed for a dozen years. Writing in the influential British Medical Journal, they concluded: “Prospective data suggest that consumption of sugar-sweetened soft drinks and fructose is strongly associated with an increased risk of gout in men.”17

In a recent study, researchers at Harvard Medical School analyzed data gathered from literally hundreds of thousands of subjects, comparing fructose intake with risk of developing kidney stones. While “non-fructose carbohydrates” were not associated with increased risk, the relative risks of kidney stones “significantly increased” for subjects with the highest intake of dietary fructose, compared with subjects who had the lowest intake. It should be noted that sucrose (table sugar) acts as a source of dietary fructose, as it comprises fructose and glucose. “Our study suggests that fructose intake is independently associated with an increased risk of incident kidney stones,” researchers concluded.13 This information is so new few scientists have had time to even attempt to replicate it. But the enormous sample size of the study, and the prestige of its authors, lends credence to the results.

Abnormally elevated levels of blood uric acid have been cited as one potential mechanism by which HFCS precipitates the undesirable metabolic changes leading to conditions such as the metabolic syndrome.47,48 It is likely that this fructose-driven increase in serum uric acid also plays a role in the increased risk of kidney stones. The ability of fructose to induce an increase in uric acid may be a major mechanism by which fructose can cause cardiorenal (heart and kidney) disease.


High-fructose corn syrup (HFCS) quietly and grimly entered the food supply decades ago. Today HFCS is ubiquitous in a wide variety of foods, including pasta sauces and salad dressings.

High-fructose corn syrup has been linked to an increased risk of a broad range of metabolic diseases and conditions. Fructose is preferentially stored in the liver as fat, and is associated with abnormal spikes in blood levels of uric acid.

Non-Alcoholic Fatty Liver Disease

High levels of fructose consumption are also associated with the development of AGEs, which, in turn, are linked to accelerated aging and some of the worst side effects associated with type 2 diabetes. Despite assurances of safety by the corn sweetener industry, prudent health-conscious consumers would do well to decrease their intake of sweeteners containing HFCS. The nutritional content of HFCS offers “empty calories” - calorie-dense, with no micronutrient (e.g. vitamins, minerals, phytonutrients) value. Because sucrose (table sugar) is half fructose, intake of this sweetener should also be limited whenever possible. The best way to reduce your intake of high-fructose corn syrup (HFCS) is to read the label of food products before you purchase them. One can slash their dietary intake of HFCS by avoiding foods that contain it and other added sugars such as sucrose.

Dana Flavin, MS, MD, PhD is former science assistant to the associate bureau director for toxicology at the FDA.

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370


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