The Role of Whole-Grain Foods in Chronic Disease
By Nicola M. McKeown, MD
Recent observational studies have found that diets rich in whole-grain foods appear to protect against several chronic diseases, including cardiovascular disease,1,2 stroke,3 Type 2 diabetes mellitus,4,5 and certain cancers.6,7 Whole-grain breads and breakfast cereals often are the major food contributors to whole-grain intake; however, other sources of whole grains include popcorn, cooked oatmeal, wheat germ, brown rice, whole-wheat pasta, and crackers.2,4,8,9 Yet despite dietary recommendations to "choose a variety of grains daily, especially whole grains,"10 current intakes remain low in the United States, with less than 8% of women consuming more than three servings of whole grains per day.11
Whole grains contain most of the intact or cracked kernel, which consists of the fiber-rich bran and germ layer. During the grain-refining process, the bran and germ layer are removed, leaving behind the starchy endosperm, which is ground into flour.12,13 Refined grain foods contain lower amounts of vitamin E, fiber, and magnesium than whole-grain foods, but enrichment of refined flour with thiamin, riboflavin, niacin, iron, and folic acid has improved the nutritional value of refined grains.13,14 Despite enrichment, however, there appears to be no evidence of a protective association between refined grain intake and risk of heart disease1 or Type 2 diabetes.4,5
The exact mechanism by which whole grains may play a causal role in health remains unknown. It may depend on the presence or interaction of several biologically active nutrients found in whole grains, such as dietary fiber, folate, potassium, magnesium, and vitamin E, among other measured and unmeasured nutrients.15 Current evidence suggests that the health benefits of whole grains are not attributed solely to a single nutrient, but rather to the synergistic effect of several constituents found in whole grains. In this review, emphasis will be placed on the observational data linking whole-grain intake to risk of chronic diseases among women, although similar health benefits have been observed in men.16-18
The first prospective study to comprehensively examine the relationship between whole-grain intake and heart disease was conducted among 34,492 postmenopausal women in the Iowa Women’s Health Study.1 After controlling for age and dietary and cardiovascular risk factors, the relative risk (RR) of ischemic heart disease mortality was approximately one-third lower (RR 0.70, 95% confidence interval [CI] 0.5-0.98; P = 0.02 for trend) among those women eating three or more servings of whole-grain foods per day, compared to those women who rarely ate whole-grain foods.
Liu and colleagues also found that whole-grain intake was protective against coronary heart disease (CHD) in the Nurses Health Study.8 In this cohort of 75,521 middle-aged women, 761 cases of CHD occurred over the period of 10 years. After adjustment for potential confounding factors, the multivariate adjusted RR of CHD was 0.75 (95% CI 0.59-0.95; P = 0.01 for trend) when the highest category was compared with the lowest category of whole-grain intake. In both prospective cohorts, the Iowa Women’s Health Study and the Nurses Health Study, refined grain intake was not associated with coronary disease risk.
Liu and colleagues also examined the effects of reported whole-grain intake and risk of ischemic stroke among middle-aged women in the Nurses Health Study.3 After adjustment for factors known or suspected to increase the risk of ischemic stroke, the authors found a strong inverse association between whole-grain intake, but not refined grain intake, and risk of ischemic stroke. The RR for ischemic stroke in the highest category of whole-grain intake (with a median intake of 2.7 servings/d) in comparison to the lowest category (median intake of 0.13 servings/d) was 0.69 (95% CI 0.50-0.98; P = 0.04 for trend).
Type 2 Diabetes
Whole-grain foods also may protect against the development of Type 2 diabetes, a disease that affects approximately 600,000 Americans each year.19 In the Iowa Women’s Health Study, women consuming an average of three servings of whole grains per day had a 21% lower risk (RR 0.79, 95% CI 0.65-0.96) of developing diabetes than those with the lowest intake of whole grains.4 Similarly, daily consumption of whole grains was associated with a lower risk of Type 2 diabetes in the Nurses Health Study.5 In this study, the multivariate adjusted RR of Type 2 diabetes among women with the lowest (< 1 serving/d) to the highest (2.7 servings/d) intake of whole grains were 1.0, 0.84, 0.82, 0.72, 0.75 (P = 0.005 for trend).
Metabolic Risk Factors
The influence of whole grains on Type 2 diabetes and cardiovascular disease risk may be mediated through multiple pathways such as reducing blood lipids20,21 and blood pressure,22 enhancing insulin sensitivity, and improving blood glucose control.23 Randomized clinical trials20 and metabolic studies21 have shown that oats and oat bran reduce total blood cholesterol. Jacobs et al found that serum total cholesterol and systolic blood pressure were reduced slightly among Norwegian women who consumed approximately three slices of whole-grain bread per day.17 In the Framingham Offspring Study of 2,941 men and women, total cholesterol and LDL concentrations were significantly lower in the highest quintile category of whole-grain intake.9
Insulin sensitivity, as measured by a hyperinsulinemic euglycemic clamp, improved in overweight adults after six weeks on a whole-grain diet compared to a refined grain diet, independent of body weight.24 In the Coronary Artery Risk Development in Young Adults Study (CARDIA) there was a mean difference of 1.0 uU/mL (7.18 pmol/L) in concentrations of fasting insulin between the least (< 2 servings/wk) vs. the most frequent consumers (> 9 servings/wk) of whole grains.25 In the Framingham Offspring Cohort, fasting insulin concentrations were lower in those with a higher intake of whole-grain foods, comparing the lowest with the highest quintile of intake, (207 and 198 pmol/L, P = 0.002 for trend) after controlling for body mass index and other risk factors.9
To date, there are few prospective studies examining the association between whole-grain intake and cancer risk. One prospective study found no significant association between whole-grain intake and risk of endometrial cancer among middle-aged women overall, although a moderate association was found among women who had never used hormone replacement therapy.26 Among this subgroup, the RR of endometrial cancer was lower among women with the lowest (mean 1.8 servings/wk) to the highest (mean 25 servings/wk) intake of whole grains; RR were 1.0, 0.77, 0.70, 0.66, and 0.63 (P = 0.05 for trend). These findings need to be confirmed in future prospective studies.
In a review of 40 case-control studies,6 dietary exposures associated with whole-grain intake (such as whole-grain bread or pasta, whole-meal bread, brown bread, or high-fiber cereal products) appeared to be protective against various cancers, particularly colon, stomach, and endometrial cancer.
Potential Mediating Nutrients in Whole Grain
Several nutrients found in whole grains may contribute to the lower risk of cardiovascular disease and Type 2 diabetes. Dietary fiber has been shown to reduce blood lipids and improve postprandial glycemic response and circulating insulin concentrations both in normal subjects and those with Type 2 diabetes.27-30 Chandalia et al demonstrated that Type 2 diabetics consuming a high-fiber diet, compared with a low-fiber diet, had significantly lower fasting glucose and insulin concentrations at the end of the study.31 Furthermore, epidemiological evidence suggests that fiber intake is associated inversely with fasting insulin32 and that insoluble and cereal fiber intake significantly reduces the risk of Type 2 diabetes.4,16,33
Magnesium, a nutrient found in the outer bran of whole grains, has been linked to Type 2 diabetes. Clinical studies have reported that low plasma concentrations of magnesium are associated with insulin resistance and that supplementation with magnesium improves insulin sensitivity.34,35 Furthermore, observational studies have found that high intakes of magnesium are associated with lower risk of Type 2 diabetes.16,33
Vitamin E, manganese, antioxidants, and lignans, among other measured and unmeasured nutrients, are integral factors of whole grains that may independently or synergistically contribute to disease prevention. Notably, the inverse association between whole-grain intake and coronary risk could not be attributed solely to nutrients found in whole grains.1,8
Due to their physical form, whole-grain foods are less easily digested and absorbed compared to refined grain products.36 This elicits a much smaller postprandial response and consequently exerts less insulin demand on the pancreatic b-cells. The glycemic index (GI) was proposed to measure a carbohydrate’s ability to raise blood glucose concentrations.37 A low GI is characteristic of most whole-grain foods such as whole-grain breakfast cereals, brown rice, and oat-bran products.38 Evidence is accumulating to suggest that dietary glycemic load (the product of the GI value of a food and its carbohydrate content) is associated with risk factors for cardiovascular disease39,40 and increased risk of coronary heart disease among women.41
Lack of consumer knowledge of the health benefits of whole grains and the difficulty encountered by consumers in identifying whole-grain products may explain, in part, the low whole-grain intake in the United States.42 The current dietary guidelines for Americans include a table that specifies key ingredients to help identify whole-grain foods.10 Given that whole-grain intake is one modifiable dietary risk factor that may lead to substantial health benefits, greater emphasis should be placed on increasing consumption of whole-grain foods. This could be achieved easily simply by substituting refined grain foods for whole-grain alternatives. For example, brown rice could be substituted for white rice, whole grain for white bread, wheat for white pasta, and popcorn for potato chips or other refined grain snacks. From a public health point of view, the current recommendation to increase whole-grain consumption is warranted and, based on the findings of several prospective studies, may lead to a reduction in the risk of several chronic diseases.
Dr. McKeown is a Research Associate at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
1. Jacobs DR, Jr., et al. Whole-grain intake may reduce the risk of ischemic heart disease death in postmenopausal women: The Iowa Women’s Health Study. Am J Clin Nutr 1998;68:248-257.
2. Jacobs DR, Jr., et al. Is whole grain intake associated with reduced total and cause-specific death rates in older women? The Iowa Women’s Health Study. Am J Public Health 1999;89:322-329.
3. Liu S, et al. Whole grain consumption and risk of ischemic stroke in women: A prospective study. JAMA 2000;284:1534-1540.
4. Meyer KA, et al. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 2000;71:921-930.
5. Liu S, et al. A prospective study of whole-grain intake and risk of type 2 diabetes mellitus in U.S. women. Am J Public Health 2000;90:1409-1415.
6. Jacobs DR, Jr., et al. Whole-grain intake and cancer: An expanded review and meta-analysis. Nutr Cancer 1998;30:85-96.
7. Levi F, et al. Refined and whole grain cereals and the risk of oral, oesophageal and laryngeal cancer. Eur J Clin Nutr 2000;54:487-489.
8. Liu S, et al. Whole-grain consumption and risk of coronary heart disease: Results from the Nurses’ Health Study. Am J Clin Nutr 1999;70:412-419.
9. McKeown NM, et al. Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study. Am J Clin Nutr 2002;76:390-398.
10. U.S. Departments of Agriculture and Health and Human Services. Nutrition and your health: Dietary guidelines for Americans. Washington, DC: U.S. Government Printing Office; 2000.
11. Cleveland LE, et al. Dietary intake of whole grains. J Am Coll Nutr 2000;19:331S-338S.
12. Pedersen B, et al. Nutritive value of cereal products with emphasis on the effect of milling. World Rev Nutr Diet 1989;60:1-91.
13. Slavin JL, et al. Grain processing and nutrition. Crit Rev Food Sci Nutr 2000;40:309-326.
14. Food Standards: Amendment of the standards of indentity for enriched grain products to require addition of folic acid. Final Rule. Fed Regist 1996;61: 8781-8797.
15. Slavin JL, et al. Plausible mechanisms for the protectiveness of whole grains. Am J Clin Nutr 1999;70: 459S-463S.
16. Salmeron J, et al. Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care 1997;20: 545-550.
17. Jacobs DR, Jr., et al. Reduced mortality among whole grain bread eaters in men and women in the Norwegian County Study. Eur J Clin Nutr 2001;55:137-143.
18. Fung TT, et al. Whole-grain intake and the risk of type 2 diabetes: A prospective study in men. Am J Clin Nutr 2002;76:535-540.
19. Harris M. Diabetes in America: Diabetes data compiled 1995. Bethesda, MD: U.S. Department of Health and Human Services publication (PHS) 95-1468. National Institutes of Health 1995;VI 1-31.32:1-13.
20. Ripsin CM, et al. Oat products and lipid lowering. A meta-analysis [published erratum appears in JAMA 1992;268:3074]. JAMA 1992;267:3317-3325.
21. Johnston L, et al. Cholesterol-lowering benefits of a whole grain oat ready-to-eat cereal. Nutr Clin Care 1998;1:6-12.
22. Sacks FM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med 2001;344:3-10.
23. Jenkins DJ, et al. Dietary fibre, lente carbohydrates and the insulin-resistant diseases. Br J Nutr 2000;83 (Suppl 1):S157-S163.
24. Pereira MA, et al. The effect of whole grains on insulin sensitivity in overweight adults. FASEB J 2000;A:203.
25. Pereira MA, et al. The association of whole grain intake and fasting insulin in a biracial cohort of young adults: The CARDIA Study. CVD Prevention 1998;1: 231-242.
26. Kasum CM, et al. Whole grain intake and incident endometrial cancer: The Iowa Women’s Health Study. Nutr Cancer 2001;39:180-186.
27. Anderson JW, et al. Dietary fiber and diabetes: A comprehensive review and practical application. J Am Diet Assoc 1987;87:1189-1197.
28. Fukagawa NK, et al. High-carbohydrate, high- fiber diets increase peripheral insulin sensitivity in healthy young and old adults. Am J Clin Nutr 1990; 52:524-528.
29. Anderson JW, et al. Metabolic effects of high-carbohydrate, high-fiber diets for insulin-dependent diabetic individuals. Am J Clin Nutr 1991;54:936-943.
30. Hallfrisch J, et al. Diets containing soluble oat extracts improve glucose and insulin responses of moderately hypercholesterolemic men and women. Am J Clin Nutr 1995;61:379-384.
31. Chandalia M, et al. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. N Engl J Med 2000;342:1392-1398.
32. Ludwig DS, et al. Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults. JAMA 1999;282:1539-1546.
33. Salmeron J, et al. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA 1997;277:472-477.
34. Paolisso G, et al. Improved insulin response and action by chronic magnesium administration in aged NIDDM subjects. Diabetes Care 1989;12:265-269.
35. Paolisso G, et al. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr 1992;55:1161-1167.
36. Jenkins DJ, et al. Low glycemic response to traditionally processed wheat and rye products: Bulgur and pumpernickel bread. Am J Clin Nutr 1986;43:516-520.
37. Jenkins DJ, et al. Glycemic index of foods: A physiological basis for carbohydrate exchange. Am J Clin Nutr 1981;34:362-366.
38. Foster-Powell K, Miller JB. International tables of glycemic index. Am J Clin Nutr 1995;62:871S-890S.
39. Ford ES, Liu S. Glycemic index and serum high-density lipoprotein cholesterol concentration among U.S. adults. Arch Intern Med 2001;161:572-576.
40. Liu S, 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;73:560-566.
41. Liu S, et al. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in U.S. women. Am J Clin Nutr 2000;71: 1455-1461.
42. Kantor LS, et al. Choose a variety of grains daily, especially whole grains: A challenge for consumers. J Nutr 2001;131:473S-486S.