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This article is excerpted from Diet and Cardiovascular Disease: An Overview from Dr. James J. Kenney, PhD, RD, FACN from 21st Century Heart - A Master Kit for You and Your Patients. For more information, click here

Fructose Raises Cholesterol

The NCEP and the AHA have focused most of their dietary guidelines for reducing LDL-C on the amount and type of dietary lipids (mainly fats and cholesterol). However, there are other dietary factors that can affect blood lipids or the development of atherosclerosis and/or CVD. Just as the amount and type of dietary fat affects serum cholesterol, so does the amount and type of dietary carbohydrate. For example, fructose appears to have a modest LDL-C-raising effect. This may be important because dietary fructose and high fructose corn syrup and total sugar have all increased in the average American diet in the last 30 years. This increase has partially offset the LDL-C-lowering effects due to a moderate drop in the consumption of both saturated fat (18 to 13% en) and cholesterol (from about 550 to 350 mg/d).

There is considerable scientific evidence that shows that various sugars have disparate effects on blood lipids, specifically serum LDL-C. In baboons, dietary fructose has been shown to promote atherosclerosis compared to other carbohydrates.[114] Another study found that fructose glycosylated hemoglobin 7 times faster than glucose.[115] This may be important because glycosylation (as well as oxidation) of other proteins, including LDL & HDL particles, may increase the growth rate of atheroma.[116]

Serum LDL-cholesterol is the most important risk factor for the development of CVD. The more likely it is that a given sugar would elevate LDL-C, the less desirable the use of that sugar would be. Unfortunately, while evidence continues to mount for the hypocholesterolemic-effect of fructose relative to other sugars, its use as a sweetener in the average American diet has been increasing. This is due largely to the displacement of sucrose (50% fructose) and corn syrup (0% fructose) with high fructose corn syrup (up to 90% fructose) and crystalline fructose. There has also been an increase in total per capita sugar intake.

Researchers have found that fructose appears to increase TC primarily by elevating LDL-C.[117] Increasing dietary fructose from 3% to 20% of calories at the expense of starch increased TC by 9% and LDL-C by 11%. It appears that a 2% increase in dietary fructose raises LDL-C more than 1%. There is now reason to believe that dietary fructose will increase the risk of atherosclerosis. It seems prudent at this time to limit the use of sweeteners containing fructose in order to reduce CVD.

Both fructose and sucrose have a tendency to increase blood lipids, especially in those with elevated serum TG (many of whom exhibit insulin resistant, Type IV hyperlipoproteinemia, and/or Type-2 DM). [118],[119],[120],[121] There is also some evidence showing that both fructose and sucrose impair glucose tolerance.[122],[123],[124]

The mechanism by which dietary fructose increases LDL-C is still a matter of debate. However, because fructose metabolism in the liver bypasses the rate-limiting step catalyzed by phosphofructokinase (PFK), it is more readily converted to acetate and fatty acids than glucose. In the short term, the addition of either sucrose or fructose to a fat load is known to greatly exaggerate the postprandial rise in serum TG levels.[125]

It is possible that some or most of the adverse impact of dietary fructose and sucrose compared with starch on blood lipids may be to enhance the hyperlipidemic effects
of a diet with a high ratio of SFA to PUFA. An increase in dietary cholesterol and SFA may exaggerate the TG-raising effects of sucrose and fructose.[126] By
contrast, an increase in dietary fiber appears to blunt the TG-raising impact of sucrose and fructose.[127]

Sucrose has been shown to increase BP in spontaneously hypertensive rats when it replaces starch[128] and in normotensive young men.[129] There is some evidence
in rats that a diet high in sucrose and fat can impair endothelial cell function and raise blood pressure. Switching the animals to low-fat, high-CHO diet reverses this

Others have reported that much of the adverse effects of high-CHO diets on blood lipids appear to be due to a higher intake of sucrose.[131] Since both fructose and
sucrose appear to increase IR, they may contribute to the development of IRS or Syndrome X and Type-2 DM, both of which increase the risk of CVD. These
presumably adverse metabolic effects of consuming fructose or sucrose appear to warrant a position of limiting the use of refined fructose-rich sweeteners in diabetic or
obese subjects, as well as individuals with elevated blood lipids. Nevertheless, the American Dietetic Association adopted a position paper on the use of nutritive and
nonnutritive sweeteners that stated, "At this time there is no evidence that current levels of fructose intake contribute to hyperlipidemia."[132] Obviously there is some
evidence but none of the research referenced above was discussed in the current ADA position paper on sweeteners.

While dietary fructose and sucrose appear to have some adverse effects on blood lipids, it should be noted that these effects are fairly modest compared to SFA. A 2%
increase in fructose raises LDL-C a little more than 1% on average. By contrast, a 2% increase in SFA raises LDL-C about 4%. This suggests that the isocaloric
exchange of fructose for either MUFA or starch would raise LDL-C about one-fourth as much as the isocaloric exchange of SFA for either MUFA or starch. This also
means that the isocaloric exchange of fructose for SFA would lower LDL-C, even though fructose itself raises LDL-C. This means it is more important to focus more
on dietary SFA than dietary fructose in order to lower LDL-C. Nevertheless, there is scientific evidence that clearly indicates that dietary fructose and sucrose can
increase serum LDL-C and TG levels, at the very least, under some circumstances and in some patients. It seems reasonable in patients at risk for CVD because of
elevated LDL-C or TG levels that they should be encouraged to reduce their intake of both sucrose and fructose.

The amount of the sugars in fruits and some vegetables is not a problem. However in patients with dyslipidemia the use of refined sugars containing fructose should be
discouraged as much as possible.

[114]. Kritchevisky D, Davidson LM, Kim HK, et al. Influence of type of carbohydrate on atherosclerosis in baboons fed semipurified diets plus 0.1% cholesterol. Am J Clin Nutr 1980;33:1869-87.
[115]. Bunn HF, Higgins PJ. Reaction of monosaccharides with proteins: possible evolutionary significance. Science 1981;213:222-9.
[116]. Bierman EL. Arteriosclerosis and Thrombosis 1992;12:647-646.
[117]. Swanson JE, Laine DC, Thomas W, Bantle JP. Metabolic effects of dietary fructose in healthy subjects. Am J Clin Nutr 1992;55:851-6.
[118]. Hallfrisch J,Reiser S, Prather ES, et al. Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Am J Clin Nutr 1983;37:740-748.
[119]. Reiser S, Hallfrisch J, Michaelis OE, et al. Isocaloric exchange of dietary starch and sucrose in humans: effects on levels of fasting blood lipids. Am J Clin Nutr 1978;32:1659-69.
[120]. Reiser S, Bickland MC, Hallfrisch J, et al. Blood lipids and their distribution in lipoproteins in hyperinsulinemic men consuming three different levels of sucrose. J Nutr
[121]. Groen JJ, Balogh M, Yaron E, Cohen AM. Effect of interchanging bread and sucrose as the main source of carbohydrate in a low fat diet on the serum cholesterol levels of healthy volunteer subjects. Am J Clin Nutr 1966;19:46-58.
[122]. Reiser S, Hallfrisch J, Fields M, et al. Effects of sugars on indices of glucose tolerance in humans. Am J Clin Nutr 1986;43:151-159
[123]. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988;37:1595-160.
[124]. Beck-Nielson H,Pedersen O.Lindskov HO, et al. Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Am J Clin Nutr 1980;33:273-278.
[125]. Cohen JC, Schall R. Reassessing the effects of simple carbohydrates on the serum triglyceride responses to fat meals. Am J Clin Nutr 1988;48;1031-4.
[126]. Birchwood BL, Little JA, Antar MA, et al. Interrelationship between the kinds of dietary carbohydrate and fat in hyperlipoproteinemic patients. Part 2. Sucrose and starch with mixed saturated and polyunsaturated fat. Atherosclerosis 1970;11:183-90.
[127]. Albrink JM, Ullrich IH. Interaction of dietary sucrose and fiber on serum lipids in healthy young men fed high carbohydrate diets. Am J Clin Nutr 1986;43:419-28.
[128]. Young JB, Landsberg L. Effect of oral sucrose on blood pressure in spontaneously hypertensive rats. Metabol 1981;30:421-7.
[129]. Rebello T, Hodges RE, Smith JL. Short-term effects of various sugars on antinaturesis and blood pressure changes in normotensive young men. Am J Clin Nutr 1983;38:84-90.
[130]. Reil TD, Barnard RJ, Kashyap VS, et al. Diet-induced changes in endothelial-dependent relaxation of the rat aorta. J Surg Res 1999;85:96-100.
[131]. Liu G, Coulston A, Hollenbeck C, Reaven G. The effect of sucrose content in high and low carbohydrate diets on plasma glucose, insulin, and lipid responses in hypertriglyceridemic humans. J Clin Endocrinol Metab 1984;59:636-42.
[132]. Position of the American Dietetic Association: Use of nutritive and nonnutritive sweeteners. J Am Diet Assoc 1998;98:580-7.

This article is excerpted from Diet and Cardiovascular Disease: An Overview from Dr. James J. Kenney, PhD, RD, FACN from 21st Century Heart - A Master Kit for You and Your Patients. For more information, click here