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Damage Control: Glucose Metabolite and HDL Cholesterol

By Christopher Clark
September 24, 2014
Damage Control: Glucose Metabolite and HDL Cholesterol image

Earlier this month, researchers from the University of Warwick published a study in Nutrition & Diabetes regarding the interaction of methylglyoxal (MG), a reactive glucose metabolite, and HDL cholesterol. HDL is universally known as "good cholesterol" and low HDL is an independent risk factor for cardiovascular disease.1 The study’s lead author, Dr. Naila Rabbani, claims "MG damage to HDL is a new and likely important cause of low and dysfunctional HDL, and could count for up to a 10% risk of heart disease."2

Blood MG levels increase with short-term and persistent increases in blood glucose levels.3, 4 MG is particularly reactive, up to 40,000 times the reactivity of glucose, but is kept in check by an enzyme called glyoxalase 1 (Glo1).5 To address the problems of decreased HDL by way of decreased Glo1 and elevated MG, Rabbani suggests the creation of new food supplements and drugs: "By understanding how MG damages HDL we can now focus on developing drugs that reduce the concentration of MG in the blood."6

While this recent study is an important contribution to scientific literature on "good" and "bad" cholesterol, it begs the question, can't proper nutrition negate, or at least diminish, the need for proposed new supplements and drugs? According to a 2003 USDA publication, the average American eats an estimated 32 teaspoons of sugar daily.7

Sugar sweetened beverages may be uniquely dangerous with respect to decreased HDL levels. A 2012 study found that each additional teaspoon of added sugar per day consumed in beverage form results in a 0.12 mg/dL decrease in HDL.8 Since elevated blood glucose levels are associated with elevated MG levels, cutting drastically back on sugar is a logical first step toward establishing healthier MG levels.

The Paleo Diet®, of course, eschews sugar, delivering only small amounts of glucose (and fructose) via fruits and vegetables, thereby promoting optimal MG and HDL levels. Other aspects of the Paleo Diet also promote increased HDL. For example, phenolic compounds in olive oil have been shown to increase HDL.9 DHA, a particular variety of omega-3 abundant in seafood, increases HDL.10Saturated fat, which is embraced by the Paleo Diet, increases HDL.11

An unfortunate trajectory of medical research is the emphasis on developing products designed to address disease symptoms rather than addressing their underlying causes. If we are serious about getting healthy, we must make meaningful lifestyle changes. The diseases of modernity, including cancer, heart disease, and diabetes, are often referred to as lifestyle diseases because they are primarily caused by improper diet, smoking, and sedentary lifestyles.

Supplements and drugs are of little worth absent meaningful lifestyle changes. With respect to cholesterol, this means forgoing added sugar while eating a diet rich in animal foods and vegetables, with modest amounts of fruits, seeds, and nuts. In other words, the Paleo Diet promotes balanced cholesterol levels, making cholesterol-modifying supplements and drugs largely unnecessary.


1. Mahdy, AK, et al. (November 2012). Cardiovascular disease risk reduction by raising HDL cholesterol--current therapies and future opportunities. British Journal of Pharmacology, 167(6). Retrieved September 18, 2014.

2. University of Warwick. (September 1, 2014). Sugar substance 'kills' good HDL cholesterol. Retrieved September 18, 2014.

3. Beisswenger, PJ, et al. (April 2001). α-Dicarbonyls Increase in the Postprandial Period and Reflect the Degree of Hyperglycemia. Diabetes Care, 24(4). Retreived September 18, 2014.

4. McLellan, AC, et al. (July 1994). Glyoxalase system in clinical diabetes mellitus and correlation with diabetic .omplications. Clinical Science (London), 87(1). Retrieved September 18, 2014.

5. Thornalley, PJ. (December 2003). Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation. Biochemical Society Transactions, 31(6). Retrieved September 18, 2014.

6. Ibid, University of Warwick.

7. United States Department of Agriculture, Agriculture Fact Book 2001–2002, March 2003, Office of Communications. Retrieved September 18, 2014.

8. Welsh, JA, et al., (April 2012). The association between sugar intake and HDL levels varies by sugar type and source. The FASEB Journal, 26(Supplement). Retrieved September 18, 2014.

9. Covas, MI, et al., (September 2006). The Effect of Polyphenols in Olive Oil on Heart Disease Risk Factors. Annals of Internal Medicine, 145(5). Retrieved September 18, 2014.

10. Bernstein, AM, et al. (January 2012). A meta-analysis shows that docosahexaenoic acid from algal oil reduces serum triglycerides and increases HDL-cholesterol and LDL-cholesterol in persons without coronary heart disease. Journal of Nutrition, 142(1). Retrieved September 18, 2014.

11. Hayek, T, et al., (April 1993). Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice. Journal of Clinical Investigation, 91(4). Retrieved September 18, 2014.

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