Whole grain, fiber, and health

David Jacobs, PhD Professor of Epidemiology, School of Public Health, University of Minnesota Guest Professor, Department of Nutrition, University of Oslo University of Class lecture September 23, 2005 University of Oslo, Norway

What is a whole cereal grain?

Go to Fulcher slide show

Fiber amounts in different whole cereal grains

Fiber per 100 g of grain wheat oats rye corn brown rice refined wheat white rice 12 g 10.6 g 14.6 g 7.3 g 3.5 g <2 g <2 g

How can we tell whether whole grain consumption is good for health?

1.

Epidemiology 1. Cross-section 2. Case-control 3. Prospective 2.

4. Long term clinical trial Feeding study

Overview of Study Design, 1

• Cross-section – Everyone sampled at one time – Can’t define whether exposure or disease comes first (temporality) – Any disease has already happened, so disease can cause changes in exposure – Effect measures: risk difference, relative prevalence

Overview of Study Design, 2

• Case-control – Sample separately from cases and from controls – Can’t define whether exposure or disease comes first (temporality) – Any disease has already happened, so disease can cause changes in exposure – Effect measures: prevalence odds ratio (approximately relative risk if disease is rare)

Overview of Study Design, 3

• Prospective – Cross-sectional sample excluding prevalent disease – Exposure stated before disease is known (temporality well-defined) – Disease has not happened, so it can not cause changes in exposure – As in cross-section and case-control, level of nutritional exposure is naturally occurring and correlated with demographics and other behaviors – Effect measures: risk difference or relative risk or relative hazard (if time to event is considered)

Overview of Study Design, 4

• Long term clinical trial – Cross-sectional sample excluding prevalent disease, randomly assigned to different nutritional exposures – Temporality well-defined – Assigned nutrition exposure uncorrelated with other factors, but other nutrition exposures are naturally occurring and correlated with demographics and other behaviors – Effect measures: risk difference or relative risk or relative hazard (if time to event is considered)

Overview of Study Design, 5

• Long term clinical trial (continued) – Very difficult to carry out over years – Successful examples include Lyon Diet Heart Study and PREDIMED (in recruitment phase)

Overview of Study Design, 6

• Feeding study – Short term (hours, days or weeks) – Exposure assigned randomly – All food provided or supplemental food only provided – Excellent for study short term effects such as changes in body weight or plasma insulin (disease intermediaries)

How do we know what people are eating?

• • Epidemiology – Ask questions about diet • Short term recall (detailed, not representative of long term) • Long term frequency (intuitive, less detailed, representative, guess work) • Study what people actually eat Feeding – Provide all or some food – Study what the researcher is interested in

Common epidemiologic representations of whole grain

• • • • • • • Dark bread Brown bread Whole wheat bread Brown rice Usual breakfast cereal Hot cereal Must ask about food in terms the participant understands, so if whole grain is not understood, the participant can’t tell you about it

Norwegian example using bread

(1) how many slices of bread do you usually eat per day? (<2 slices per day; 2 ± 4; 5 ± 6; 7 ± 8; 9 ± 12; 13+) (2) what kind of bread do you eat most often? (store bought; home-baked) (3) If you buy, what type most often? (white bread, fine or light bread, whole grain or dark bread) (4) If you bake at home, what proportion of the flour is whole grain (dark)? (don't use whole grain flour; <1/4 whole grain flour; 1/4- 1/2 whole grain flour; more than 1/2 whole grain flour). Based on a 24 hour recall, store bought whole grain bread was overestimated and used a recipe with less whole grain Whole grain bread score: the number of slices of bread eaten per day times the proportion of whole grain flour.

American example using breakfast cereal

Ask usual breakfast cereal Refer to coding list for whole grain content of several hundred brand name products Does not account for people eating multiple products

American example using bread

The term whole grain bread is not well known and is confused with organic (which is irrelevant) and multigrain (which be all refined) Dark bread in US and brown bread in UK identify most whole grain breads, but misclassifies breads containing dark color, such as molasses

Whole grain and cancer: case control experience

Chatenoud L, Tavani A, La Vecchia C, Jacobs DR Jr, Negri E, Levi F, Franceschi S.

Whole grain food intake and cancer risk. Int J Cancer. 1998 Jul 3;77(1):24-8. Jacobs DR Jr, Marquart L, Slavin J, Kushi LH.

Whole-grain intake and cancer: an expanded review and meta-analysis. Nutr Cancer. 1998;30(2):85-96. Review.

Meta-analysis of case-control studies of whole grain food intake and cancer, 1998 Ratio Cancer Site Studies Reduced Risk? Pooled Odds Gonadotrophic hormone-related Prostate Breast, endometrium, ovary Aerodigestive Upper aerodigestive Colon, rectum, and polyps Pancreas Other Brain 1 6 15 13 4 1 6 14 10 4 0.9

0.85

0.6

0.8

0.7

Lymphoma Soft tissue sarcoma Bladder 3 3 2 1 2 3 2 1 0.7

0.5

0.3

0.5

Myeloma Liver Thyroid 1 1 1 1 1 1 0.5

0.6

0.6

Whole grain and heart disease/type 2 diabetes: prospective study experience

Jacobs DR Jr, Gallaher DD.

Whole grain intake and cardiovascular disease: a review. Curr Atheroscler Rep. 2004 Nov;6(6):415-23. Review.

Whole grain confounding with other behaviors

Iowa Women’s Health Study

34,492 postmenopausal Iowa women, 1986; levels adjusted for age and energy intake

Health Behaviors Current smoker, % Vitamin supplement use, % Physical activity % engaging in regular activity Hormone replacement therapy % ever Whole grain intake Quintile Quintile 1 5 24.7

53.7

12.1

68.7

30.3

34.0

45.5

42.6

Refined grain intake Quintile Quintile 1 5 16.0

70.9

17.1

54.4

49.5

40.4

30.0

34.7

34,492 postmenopausal Iowa women, 1986; levels adjusted for age and energy intake

Whole Grain Quintile Quintile 1 5 Refined Grain Quintile Quintile 1 5 Other Aspects of Diet Fruits and vegetables, no juice mean, servings/week 34.1

39.9 45.5 28.6

Red meat , mean, servings/week 6.6 5.1 6.0

5.4

Keys score , mean, mg/dl 45.7

Sucrose , mean, g/day 42.2

38.9

42.8 41.0

38.8 37.6 47.3

Constituent Nutrients Dietary fiber , mean, g/day 16.3 22.3 21.7

17.1

Vitamin E , mean, IU/day 8.9 10.1 10.2 9.0

Folate , mean, µg/day 270.7

332.3 342.1

264.7

Whole grain and cancer – Norwegian and Iowa prospective studies

Unpublished talk give in Montreal, American Association of Cereal Chemists, 2002 Findings much less clear than in case-control studies Same questions and design as for heart disease and diabetes

Iowa Women’s Health Study: Fiber in 2 groups with similar total grain fiber

71% grain fiber from whole 77% grain fiber from refined Sample size Whole grain fiber grain 3.6 - 6 g / 2000 kcal whole fiber grain <3.6 g / 2000 kcal whole fiber <3.6 g / 2000 kcal refined fiber 7481



3.6 g / 2000 kcal refined fiber 3559 4.7 ± 0.7 1.3 ± 1.0 1.9 ± 0.8 4.5 ± 0.9 Refined grain fiber Total grain fiber Total dietary fiber 6.6 ± 1.0 23.3 ± 5.3 5.8 ± 1.2 19.2 ± 4.5

Jacobs DR, Pereira MA, Meyer KA, Kushi LH. J Amer Col Nutr 2000

Iowa Women’s Health Study: 11-year relative risk of mortality in 11040 women: cereal fiber in itself does not predict death

Total mortality Coronary heart disease Hazard Rate Ratio (95% CI) in 71% whole grain fiber eaters relative to 77% refined grain fiber eaters 0.83 (0.73, 0.94) 0.89 (0.66,1.20) All cancer All other mortality 0.92 (0.75,1.12) 0.83 (0.71, 0.97)

Which direction from here? Problems with whole grain theory, 1

• • • • • • Supported by selected feeding and supplement studies Reliability Validity Residual confounding A synergy model is consistent with the complexity of biology In vitro studies also suggest synergy

Which direction from here? Problems with whole grain theory, 2

• • • • • • Fiber not the whole answer Myriad phytochemicals coexist with fiber in all plant foods These include enzymes, pesticides, antioxidant defense, signal transducers Though the nutrient model has some value, it seems more helpful to think of foods and food combinations than of nutrients.

Other plant foods are broadly similar – fruit, vegetables, nut, legumes, spices Plant-based food patterns are more reliably ascertained epidemiologically and less prone to dietary confounding, inverse to many chronic diseases

Nutrients vs Foods

Fiber is probably not as active as its accompanying phytochemicals The value of carbohydrate depends on whether it is fiber rich (with accompanying phytochemicals) or fiber poor The value of fat depends on saturation and location of the double bond if unsaturated

Some single nutrient conditions

• A single nutrient deficiency disease would be alleviated by introduction of an isolated nutrient in the form of a supplement – Scurvy and vitamin C – Pellagra, beri-beri and B-vitamins – Rickets and vitamin D – Neural tube defects and folate – Trans fatty acids, increased cholesterol and coronary heart disease – Hypertension and salt

Nutrition in the etiology of disease

• Focus on food and the synergy of its components may be a method for better understanding nutrition and disease etiology – Reductionism looks for simple, biochemically-based associations – Some diseases are the result of deficiency or excess of single nutrients – Food synergy is defined as additive or more than additive influences of foods and food constituents on health – Chronic diseases such as atherosclerosis, ischemic heart disease, and cancers, are complex with multiple etiologies and not simple deficiencies

The food synergy approach

A hierarchical structure of dietary patterns, foods, and nutrients for study of food synergy. “Top down” research begins with the higher levels, searching for combinations of foods and their constituents that influence health “Bottom up” research begins at the lowest level, searching for individual constituents that influence health.

Examples of dietary component at each synergy level Food synergy level Level 5: Dietary pattern ‘Prudent diet’, ‘Western diet’, other combinations of food groups Whole grain, dairy, fruit, vegetables, meat Level 4: Food groups Level 3: Whole grain Level 2: Whole wheat Level 1: Bran or a single phytochemical Whole wheat, brown rice, rolled oats Bran, germ, endosperm; extract of fat soluble portion Specific nutrients or phytochemicals

Maximize nutritional value per bite

• We are increasingly inactive – We are getting fat from positive energy balance – Even so, energy intake is less than it used to be – We cannot afford to waste bites eaten food with low nutritional value, such as nutrient-poor carbohydrate – Eat a varied diet rich in plant foods