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EDITORIAL |
1 From the Department of Internal Medicine, University of Kentucky, Lexington
2 Address reprint requests to JW Anderson, 1030 South Broadway, Suite 5, Lexington, KY 40504-2681. E-mail: jwandersmd{at}aol.com.
See corresponding article on page 1492.
More than 30 y ago, Trowell (1) surmised that a diet rich in whole grains protected against coronary heart disease (CHD). Trowell believed that the protective effect of grains was in the whole grain and was disappointed that his hypothesis was interpreted as a "fiber hypothesis" rather than as a "high-fiber food hypothesis" (2). Morris et al (3) provided nutrition information suggesting that cereal fiber intake was associated with significantly lower rates of CHD among British men. Since then, many prospective epidemiologic studies (4, 5) have shown that the consumption of whole grain is associated with a significantly lower risk of CHD. The current report of Jensen et al (6) extends these findings and suggests that wheat bran may contribute importantly to this protective effect. This is of further interest given that the consumption of whole grain is linked to protection against ischemic stroke (7), diabetes (8), insulin resistance (9), obesity (10), and premature death (7).
Most whole-grain wheat kernels are composed of 
80% endosperm (the predominant component of refined flour, which is rich in starch and protein but poor in most micronutrients), 15% bran (a major source of fiber, micronutrients, antioxidants, and phytochemicals), and 5% germ (plant embryo) (5, 11). The relative contribution of the hundreds of bioactive constituents of whole grains to health-protective effects has not been delineated. However, refined-grain products and their fiber do not appear to confer health-protective effects; this suggests that these health benefits do not lie in the endosperm (7, 10). Results of the study by Jensen et al (6) suggest that germ, likewise, may not be an important source of protective constituents. Furthermore, this same study strongly suggests that bran components may contain the most important bioactive constituents. The multivariate model indicates that whole-grain intake in the highest quintile is associated with a hazard ratio for CHD of 0.82 (P = 0.01 for trend) and is not significantly altered after adjustment for dietary fiber (hazard ratio: 0.85; P = 0.06); this comparison indicates that the effects of whole grain are robust and are not greatly affected by adjustments for dietary fiber. The effects of added bran appear even stronger than those of whole grain, and the highest bran intake group had a hazard ratio of 0.70 (P < 0.0001 for trend). Thus, persons with the highest intake of added bran may have a 30% lower risk of CHD than do persons who do not consume bran. In our meta-analysis of 7 studies including >150 000 persons, those with the highest dietary fiber intake had a 29% lower risk of CHD than did those with the lowest intake (4).
Wheat bran is rich in dietary fiber, minerals, antioxidants, lignans, and other phytochemicals (11). Starting with the report of Morris et al (3), the evidence that cereal fiber consumption is associated with a lower risk of CHD (4) was puzzling because the apparent protection associated with cereal fiber intake did not correlate with serum cholesterol concentrations in some studies (5). Although wheat bran does not have hypocholesterolemic effects in humans (5) or in carefully controlled animal studies (12), it may decrease serum triacylglycerol concentrations (12, 13). Furthermore, increased intakes of whole grains increase soluble fiber intakes adequately enough to lower serum cholesterol concentrations to a small but significant degree (14). Van Dam et al (15) noted that Dutch men whose diets did not include whole grains had higher serum cholesterol concentrations than did those who consumed whole grains. In addition to dietary fibers, the whole-grain arsenal includes a wide variety of nutrients and phytochemicals that reduce the risk of CHD. The compounds that have hypocholesterolemic effects include polyunsaturated fatty acids, oligosaccharides, plant sterols and stanols, and saponins (11). Thus, whole grains probably have a favorable effect on serum lipoprotein concentrations that may not be discerned in some epidemiologic observations.
Whole grains are also important dietary sources of water-soluble, fat-soluble, and insoluble antioxidants. The long list of cereal antioxidants includes vitamin E, tocotrieonols, selenium, phenolic acids, and phytic acid. These multifunctional antioxidants come in immediate-release to slow-release forms and thus are available throughout the gastrointestinal tract over a long period after being consumed (5, 11). The high antioxidant capacity of wheat bran is 20-fold that of refined wheat flour (endosperm) (16). Although the role of antioxidant supplementation in protecting against CHD has been questioned (17), prospective epidemiologic studies suggest that antioxidant intakes from dietary sources are associated with significant protection against CHD (18). Because lipoprotein oxidation appears to contribute significantly to the pathogenesis of atherosclerotic cardiovascular disease, the broad range of antioxidant activities from these whole-grain phytochemicals is thought to play a strong role in these cardiovascular-protective effects.
As are soybeans, whole grains are sources of phytoestrogens, which may affect serum lipoprotein concentrations, vascular reactivity, bone metabolism, and many other cellular metabolic processes (11, 19). Whole grains are rich sources of lignans that are converted by the human gut to enterolactone and enterodiole (11). Serum enterolactone concentrations had an inverse relation to CHD-related and all-cause deaths among Finnish men, which suggests that the higher dietary intakes of plant lignans may contribute to the protective effects of whole grains (20).
In many persons, the risks of atherosclerotic cardiovascular disease, diabetes, and obesity are linked to insulin resistance (21). Higher intakes of whole grains are associated with increased sensitivity to insulin in epidemiologic observations (22–24) and clinical trials (9, 25). Lower plasma insulin concentrations (22, 23) and decreased features of the metabolic syndrome (26) may contribute to the protective effects of whole grain consumption. Proposed mechanisms contributing to the improved insulin sensitivity that is attributed to whole-grain intake include a lower glycemic index (22), higher fiber intake (22), higher magnesium intake (22), and higher vitamin E intake (22).
Health-promoting eating patterns are usually accompanied by other health-promoting fellow travelers. In the Nurses' Health Study, women in the lowest-risk lifestyle category had a CHD risk that was only 18% that of women in the high-risk category (27). One limitation of even prospective observational studies, such as Jensen et al's (6), relates to the difficulty of isolating the food group of interest, eg, whole grains, from other healthy eating patterns. It may be very difficult to discern the effect of small intakes of soyfoods, fish, or nuts. Nevertheless, the take-home message is that consumption of generous amounts of whole grains, cereal fiber, total fiber, fruit, or vegetables decreases the risk of CHD by 
30%, irrespective of other lifestyle behaviors. These observations encourage us to recommend that 3 servings of whole grains be consumed daily.
ACKNOWLEDGMENTS
I appreciate the help of Tyler Lamkin.
Supported by the NIH, Veterans Administration, HCF Nutrition Foundation, Amylin, Astra-Zenica, Aventis, Bristol-Myers Squibb, GlaxoSmithKline, Health Management Resources, Johnson & Johnson, Kellogg, Merck, Novartis, Orexigen, Novo Nordisk, Nutrinova, NutriPharma, Regeneron, Roche, Sanofi, Solae, and Slim Fast. Consultant: Cargill, Herbalife, NutriPharma, Sanitarium, and Wacker. Honoraria: Coca Cola, General Mills, Johnson & Johnson, Monsanto, and Solae.
REFERENCES
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 J. A. Nettleton, L. J. Harnack, C. G. Scrafford, P. J. Mink, L. M. Barraj, and D. R. Jacobs Jr. Dietary Flavonoids and Flavonoid-Rich Foods Are Not Associated with Risk of Type 2 Diabetes in Postmenopausal Women J. Nutr., December 1, 2006; 136(12): 3039 - 3045. [Abstract] [Full Text] [PDF]
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N. R Sahyoun, P. F Jacques, X. L Zhang, W. Juan, and N. M McKeown Whole-grain intake is inversely associated with the metabolic syndrome and mortality in older adults Am. J. Clinical Nutrition, January 1, 2006; 83(1): 124 - 131. [Abstract] [Full Text] [PDF]
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