In the past, carbohydrates were classified as simple or complex, based on the number of simple sugars in the molecule. Carbohydrates composed of one or two simple sugars like fructose or sucrose (table sugar; a disaccharide composed of one molecule of glucose and one molecule of fructose) were labeled simple, while starchy foods were labeled complex because starch is composed of long chains of the simple sugar, glucose. Advice to eat fewer simple and more complex carbohydrates (i.e., polysaccharides) was based on the assumption that consuming starchy foods would lead to smaller increases in blood glucose than results from consuming sugary foods.1 This assumption turned out to be too simplistic, since the blood glucose (glycemic) response to “complex” carbohydrates has been found to vary considerably. A more accurate indicator of the relative glycemic response to dietary carbohydrates should be glycemic load, which incorporates the relative quality and quantity of carbohydrates in the diet.
To determine the glycemic index of a food, volunteers are typically given a test food that provides 50 g of carbohydrate and a control food (white bread or pure glucose) that provides the same amount of carbohydrate on different days.2 Blood samples for the determination of glucose are taken prior to eating and at regular intervals after eating over the next several hours. The changes in blood glucose over time are plotted as a curve. The glycemic index is calculated as the area under the glucose curve after the test food is eaten, divided by the corresponding area after the control food is eaten. The value is multiplied by 100 to represent a percentage of the control food. For example, a baked potato has a glycemic index of 76 relative to glucose (Table A1.1) and 108 relative to white bread, which means that the blood glucose response to the carbohydrate in a baked potato is 76% of the blood glucose response to the same amount of carbohydrate in pure glucose and 108% of the blood glucose response to the same amount of carbohydrate in white bread.3 In contrast, cooked brown rice has a glycemic index of 55 relative to glucose and 79 relative to white bread.4 In the traditional system of classifying carbohydrates, both brown rice and potato would be classified as complex carbohydrates, despite the difference in their effects on blood glucose levels.
By definition, the consumption of high-glycemic-index foods results in higher and more rapid increases in blood glucose levels than the consumption of low-glycemic-index foods. Rapid increases in blood glucose are potent signals to the β-cells of the pancreas to increase insulin secretion.2 Over the next few hours, the high insulin levels induced by consumption of high-glycemic-index foods may cause a sharp decrease in blood glucose levels (hypoglycemia). In contrast, the consumption of low-glycemic-index foods results in lower but more sustained increases in blood glucose and lower insulin demands on pancreatic β-cells.5
The glycemic index compares the potential of foods containing the same amount of carbohydrate to raise blood glucose. However, the amount of carbohydrate consumed also affects blood glucose levels and insulin responses. The glycemic load of a food is calculated by multiplying the glycemic index by the amount of carbohydrate in grams provided by a food and dividing the total by 100 (Table A1.1).1 Dietary glycemic load is the sum of the glycemic loads for all foods consumed in the diet. The concept of glycemic load was developed by scientists to simultaneously describe the quality (glycemic index) and quantity of carbohydrate in a meal or diet.
After a meal with a high glycemic load, blood glucose levels rise more rapidly and insulin demand is greater than after a meal with a low glycemic load. High blood glucose levels and excessive insulin secretion are thought to contribute to the loss of the insulin-secreting function of the pancreatic β-cells that leads to irreversible diabetes.6 In several large prospective studies, high dietary glycemic loads have been associated with an increased risk of developing type 2 diabetes mellitus (DM). In the Nurses’ Health Study (NHS), women with the highest dietary glycemic loads were 37% more likely to develop type 2 DM over a 6-year period than women with the lowest dietary glycemic loads.7 Additionally, women with high-glycemic-load diets that were low in cereal fiber were more than twice as likely to develop type 2 DM than women with low-glycemic-load diets that were high in cereal fiber. The results of the Health Professionals’ Follow-up Study (HPFS), which followed male health professionals over 6 years, were similar.8 In the NHS II study, a prospective study of younger and middle-aged women, those who consumed foods with the highest glycemic-index values and the least cereal fiber were also at significantly higher risk of developing type 2 DM over the next 8 years.9 The foods that were most consistently associated with increased risk of type 2 DM in the NHS and HPFS cohorts were potatoes (cooked or French-fried), white rice, white bread, and carbonated beverages.6 The Black Women's Health study, a prospective study in a cohort of 59 000 black women in the United States, found that women who consumed foods with the highest glycemic-index values had a 23% greater risk of developing type 2 DM over 8 years of follow-up compared with those who consumed foods with the lowest glycemic-index values.10 In the American Cancer Society Cancer Prevention Study II, which followed 124 907 men and women for 9 years, high glycemic load was associated with a 15% increased risk of type 2 DM.11 Further, in a cohort of over 64 000 Chinese women participating in the Shanghai Women's Health Study, high glycemic load was associated with a 34% increase in risk of type 2 DM; this positive association was much stronger among overweight women.12
A US ecological study of national data from 1909 to 1997 found that increased consumption of refined carbohydrates in the form of corn syrup, coupled with declining intake of dietary fiber, has paralleled the increase in prevalence of type 2 DM.13 Today, high-fructose corn syrup (HFCS) is used as a sweetener and preservative in many commercial products sold in the United States, including soft drinks and other processed foods. To make HFCS, the fructose content of corn syrup (100% glucose) has been artificially increased; common formulations of HFCS now include 42%, 55%, or 90% fructose.13 When consumed in large quantities on a long-term basis, HFCS is unhealthful and may contribute to other chronic diseases besides type 2 DM, including obesity and cardiovascular disease.
Impaired glucose tolerance and insulin resistance are known to be risk factors for cardiovascular disease and type 2 DM. In addition to increased blood glucose and insulin concentrations, high dietary glycemic loads are associated with increased serum triglyceride concentrations and decreased high-density lipoprotein (HDL) cholesterol concentrations; both are risk factors for cardiovascular disease.14,15 High dietary glycemic loads have also been associated with increased serum levels of C-reactive protein, a marker of systemic inflammation that is also a sensitive predictor of cardiovascular disease risk.16 In the NHS cohort, women with the highest dietary glycemic loads had a risk of developing coronary heart disease (CHD) over the next 10 years that was almost twice as high as that of those with the lowest dietary glycemic loads.17 The relationship between dietary glycemic load and CHD risk was more pronounced in overweight women, suggesting that people who are insulin resistant may be most susceptible to the adverse cardiovascular effects of high dietary glycemic loads.1 A similar finding was reported in a cohort of middle-aged Dutch women followed for 9 years.18 More recently, a prospective study in an Italian cohort of 47 749 men and women, who were followed for almost 8 years, found that a high glycemic load was associated with an increased risk of CHD in women but not in men.19 Yet, studies to date have reported mixed results, and more research is needed to determine if diets with a low glycemic index decrease the risk for CHD.20
In the first 2 hours after a meal, blood glucose and insulin levels rise higher after a meal with a high glycemic load than they do after a meal with a low glycemic load containing an equal number of calories. However, in response to the excess insulin secretion, blood glucose levels drop lower over the next few hours after a high-glycemic-load meal than they do after a low-glycemic-load meal. This may explain why 15 out of 16 published studies found that the consumption of low-glycemic-index foods delayed the return of hunger, decreased subsequent food intake, and increased satiety (feeling full) when compared with high-glycemic-index foods.21 The results of several small, short-term trials (1–4 months) suggest that low-glycemic-load diets result in significantly more weight or fat loss than high-glycemic-load diets.22–24 Although long-term randomized controlled trials of low-glycemic-load diets in the treatment of obesity are lacking, the results of short-term studies on appetite regulation and weight loss suggest that low-glycemic-load diets may be useful in promoting long-term weight loss and decreasing the prevalence of obesity. A recent review of six randomized controlled trials concluded that overweight or obese individuals who followed a low-glycemic-index/load diet experienced greater weight loss than individuals on a comparison diet that either had a high glycemic index or was energy restricted and low fat.25 The length of the dietary interventions in these trials ranged from 5 weeks to 6 months.
Evidence that high overall dietary glycemic index or high dietary glycemic loads are related to cancer risk is inconsistent. Prospective cohort studies in the United States, Denmark, France, and Australia have found no association between overall dietary glycemic index or dietary glycemic load and risk of breast cancer.26–29 In contrast, a prospective cohort study in Italy reported a positive association between breast cancer risk and high-glycemic-index diets as well as high dietary glycemic loads.30 A prospective study in Canada found that postmenopausal but not premenopausal women with high overall dietary glycemic-index values were at increased risk of breast cancer, particularly those who reported no vigorous physical activity,31 while a prospective study in the United States found that premenopausal but not postmenopausal women with high overall dietary glycemic-index values and low levels of physical activity were at increased risk of breast cancer.32 In a French study of postmenopausal women, both glycemic index and glycemic load were positively associated with risk of breast cancer but only in a subgroup of women who had the highest waist circumference (median of 84 cm [33 in]).29 Higher dietary glycemic loads were associated with moderately increased risk of colorectal cancer in a prospective study of US men, but no clear associations between dietary glycemic load and colorectal cancer risk were observed in prospective studies of US men,33 US women,33–36 Swedish women,37 and Dutch men and women.38 However, one prospective cohort study of US women found that higher dietary glycemic loads were associated with increased risk of colorectal cancer.39 A meta-analysis of case–control and cohort studies suggested that glycemic index and glycemic load were positively associated with colorectal cancer,40 but a more recently published meta-analysis did not find glycemic index or load to be significantly associated with colorectal cancer.41 Two separate meta-analyses reported that high dietary glycemic loads were associated with increased risk of endometrial cancer.40,42 Although there is some evidence that hyperinsulinemia (elevated serum insulin levels) may promote the growth of some types of cancer,43 more research is needed to determine the effects of dietary glycemic load and/or glycemic index on cancer risk.
Results of two studies indicate that dietary glycemic index and glycemic load may be positively related to risk of gallbladder disease. Higher dietary glycemic loads were associated with significantly increased risks of developing gallstones in a cohort of men participating in the HPFS44 and in a cohort of women participating in the NHS.45 Likewise, higher glycemic index diets were associated with increased risks of gallstone disease in both studies.44,45 However, more epidemiological and clinical research is needed to determine an association between dietary glycemic index/load and gallbladder disease.
Low-glycemic-index diets appear to improve the overall blood glucose control in people with type 1 and type 2 DM. A meta-analysis of 14 randomized controlled trials that included 356 patients with diabetes found that low-glycemic-index diets improved short-term and long-term control of blood glucose levels, reflected by clinically significant decreases in fructosamine and hemoglobin A1C levels.46 Episodes of serious hypoglycemia are a significant problem in people with type 1 DM. In a study of 63 men and women with type 1 DM, those randomized to a high-fiber, low-glycemic-index diet had significantly fewer episodes of hypoglycemia than those on a low-fiber, high-glycemic-index diet.47
Some strategies for lowering dietary glycemic load include:
• Increasing the consumption of whole grains, nuts, legumes, fruits, and nonstarchy vegetables
• Decreasing the consumption of starchy high-glycemic-index foods like potatoes, white rice, and white bread
• Decreasing the consumption of sugary foods like cookies, cakes, candy, and soft drinks
1. Liu S, Willett WC. Dietary glycemic load and atherothrombotic risk. Curr Atheroscler Rep 2002;4(6):454–461
2. Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287(18):2414–2423
3. Fernandes G, Velangi A, Wolever TM. Glycemic index of potatoes commonly consumed in North America. J Am Diet Assoc 2005;105(4):557–562
4. Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr 2002;76(1):5–56
5. Willett WC. Eat, Drink, and be Healthy: The Harvard Medical School Guide to Healthy Eating. New York: Simon & Schuster; 2001
6. Willett W, Manson J, Liu S. Glycemic index, glycemic load, and risk of type 2 diabetes. Am J Clin Nutr 2002;76(1):274S–280S
7. Salmerón J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA 1997;277(6):472–477
8. Salmerón J, Ascherio A, Rimm EB, et al. Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care 1997;20(4):545–550
9. Schulze MB, Liu S, Rimm EB, Manson JE, Willett WC, Hu FB. Glycemic index, glycemic load, and dietary fiber intake and incidence of type 2 diabetes in younger and middle-aged women. Am J Clin Nutr 2004; 80(2):348–356
10. Krishnan S, Rosenberg L, Singer M, et al. Glycemic index, glycemic load, and cereal fiber intake and risk of type 2 diabetes in US black women. Arch Intern Med 2007;167(21):2304–2309
11. Patel AV, McCullough ML, Pavluck AL, Jacobs EJ, Thun MJ, Calle EE. Glycemic load, glycemic index, and carbohydrate intake in relation to pancreatic cancer risk in a large US cohort. Cancer Causes Control 2007; 18(3):287–294
12. Villegas R, Liu S, Gao YT, et al. Prospective study of dietary carbohydrates, glycemic index, glycemic load, and incidence of type 2 diabetes mellitus in middle-aged Chinese women. Arch Intern Med 2007; 167(21):2310–2316
13. Gross LS, Li L, Ford ES, Liu S. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am J Clin Nutr 2004;79(5):774–779
14. Ford ES, Liu S. Glycemic index and serum high-density lipoprotein cholesterol concentration among US adults. Arch Intern Med 2001;161(4):572–576
15. Liu S, Manson JE, Stampfer MJ, et al. Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women. Am J Clin Nutr 2001;73(3):560–566
16. Liu S, Manson JE, Buring JE, Stampfer MJ, Willett WC, Ridker PM. Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Am J Clin Nutr 2002;75(3):492–498
17. Liu S, Willett WC, Stampfer MJ, et al. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr 2000;71(6):1455–1461
18. Beulens JW, de Bruijne LM, Stolk RP, et al. High dietary glycemic load and glycemic index increase risk of cardiovascular disease among middle-aged women: a population-based follow-up study. J Am Coll Cardiol 2007;50(1):14–21
19. Sieri S, Krogh V, Berrino F, et al. Dietary glycemic load and index and risk of coronary heart disease in a large italian cohort: the EPICOR study. Arch Intern Med 2010;170(7):640–647
20. Franz MJ. Is there a role for the glycemic index in coronary heart disease prevention or treatment? Curr Atheroscler Rep 2008;10(6):497–502
21. Ludwig DS. Dietary glycemic index and the regulation of body weight. Lipids 2003;38(2):117–121
22. Slabber M, Barnard HC, Kuyl JM, Dannhauser A, Schall R. Effects of a low-insulin-response, energy-restricted diet on weight loss and plasma insulin concentrations in hyperinsulinemic obese females. Am J Clin Nutr 1994;60(1):48–53
23. Bouché C, Rizkalla SW, Luo J, et al. Five-week, lowglycemic index diet decreases total fat mass and improves plasma lipid profile in moderately overweight nondiabetic men. Diabetes Care 2002;25(5):822–828
24. Spieth LE, Harnish JD, Lenders CM, et al. A low-glycemic index diet in the treatment of pediatric obesity. Arch Pediatr Adolesc Med 2000;154(9):947–951
25. Thomas DE, Elliott EJ, Baur L. Low glycaemic index or low glycaemic load diets for overweight and obesity. Cochrane Database Syst Rev 2007; (3):CD005105
26. Jonas CR, McCullough ML, Teras LR, Walker-Thurmond KA, Thun MJ, Calle EE. Dietary glycemic index, glycemic load, and risk of incident breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2003;12(6):573–577
27. Nielsen TG, Olsen A, Christensen J, Overvad K, Tjønneland A. Dietary carbohydrate intake is not associated with the breast cancer incidence rate ratio in postmenopausal Danish women. J Nutr 2005; 135(1):124–128
28. Giles GG, Simpson JA, English DR, et al. Dietary carbohydrate, fibre, glycaemic index, glycaemic load and the risk of postmenopausal breast cancer. Int J Cancer 2006;118(7):1843–1847
29. Lajous M, Boutron-Ruault MC, Fabre A, Clavel Chapelon F, Romieu I. Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women. Am J Clin Nutr 2008;87(5):1384–1391
30. Sieri S, Pala V, Brighenti F, et al. Dietary glycemic index, glycemic load, and the risk of breast cancer in an Italian prospective cohort study. Am J Clin Nutr 2007;86(4):1160–1166
31. Silvera SA, Jain M, Howe GR, Miller AB, Rohan TE. Dietary carbohydrates and breast cancer risk: a prospective study of the roles of overall glycemic index and glycemic load. Int J Cancer 2005;114(4):653–658
32. Higginbotham S, Zhang ZF, Lee IM, Cook NR, Buring JE, Liu S. Dietary glycemic load and breast cancer risk in the Women's Health Study. Cancer Epidemiol Biomarkers Prev 2004;13(1):65–70
33. Michaud DS, Fuchs CS, Liu S, Willett WC, Colditz GA, Giovannucci E. Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 2005;14(1):138–147
34. Michaud DS, Liu S, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. J Natl Cancer Inst 2002;94(17):1293–1300
35. McCarl M, Harnack L, Limburg PJ, Anderson KE, Folsom AR. Incidence of colorectal cancer in relation to glycemic index and load in a cohort of women. Cancer Epidemiol Biomarkers Prev 2006;15(5):892–896
36. Strayer L, Jacobs DR Jr, Schairer C, Schatzkin A, Flood A. Dietary carbohydrate, glycemic index, and glycemic load and the risk of colorectal cancer in the BCDDP cohort. Cancer Causes Control 2007;18(8):853–863
37. Larsson SC, Giovannucci E, Wolk A. Dietary carbohydrate, glycemic index, and glycemic load in relation to risk of colorectal cancer in women. Am J Epidemiol 2007;165(3):256–261
38. Weijenberg MP, Mullie PF, Brants HA, Heinen MM, Goldbohm RA, van den Brandt PA. Dietary glycemic load, glycemic index and colorectal cancer risk: results from the Netherlands Cohort Study. Int J Cancer 2008;122(3):620–629
39. Higginbotham S, Zhang ZF, Lee IM, et al; Women's Health Study. Dietary glycemic load and risk of colorectal cancer in the Women's Health Study. J Natl Cancer Inst 2004;96(3):229–233
40. Gnagnarella P, Gandini S, La Vecchia C, Maisonneuve P. Glycemic index, glycemic load, and cancer risk: a meta-analysis. Am J Clin Nutr 2008;87(6):1793–1801
41. Mulholland HG, Murray LJ, Cardwell CR, Cantwell MM. Glycemic index, glycemic load, and risk of digestive tract neoplasms: a systematic review and meta-analysis. Am J Clin Nutr 2009;89(2):568–576
42. Mulholland HG, Murray LJ, Cardwell CR, Cantwell MM. Dietary glycaemic index, glycaemic load and endometrial and ovarian cancer risk: a systematic review and meta-analysis. Br J Cancer 2008;99(3):434–441
43. Boyd DB. Insulin and cancer. Integr Cancer Ther 2003;2(4):315–329
44. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Dietary carbohydrates and glycaemic load and the incidence of symptomatic gall stone disease in men. Gut 2005;54(6):823–828
45. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Glycemic load, glycemic index, and carbohydrate in-take in relation to risk of cholecystectomy in women. Gastroenterology 2005;129(1):105–112
46. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Lowglycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. Diabetes Care 2003;26(8):2261–2267
47. Giacco R, Parillo M, Rivellese AA, et al. Long-term dietary treatment with increased amounts of fiber-rich low-glycemic index natural foods improves blood glucose control and reduces the number of hypoglycemic events in type 1 diabetic patients. Diabetes Care 2000;23(10):1461–1466