Table 1.

Characteristics of studies included in meta-analysis.

Author publication year, location, reference number,	Sample age in years	Duration period	Exposure	Dietary assessment	Whole grain item†	Cause of death: number	Risk estimate	Death confirmation/ death code	Covariates
Fraser 1992, US, (17)	26,473 Adventists ≥25 years	6 years 1977–1982	Whole grain food	Baseline FFQ	Whole grain bread 100% whole-wheat bread used most often vs. white bread used most often.	CVD: 463	CVD: reference 0.77(0.54–1.08) 0.74(0.56–0.99)	death certificates, registry and records ICD	Age, sex, smoking, exercise, relative weight, high blood pressure, nuts, beef, cheese, fish, coffee, legumes, and fruits.
Key 1996, UK, (24)	10,771 vegetarians 16–79 years	17 years 1973–1995	Whole grain food	Baseline FFQ	Whole grain bread Having whole grain daily vs. not having whole grain daily.	All-cause: 2562 CHD: 350 stroke: 147 Cancer: 451	Whole grain bread: All-cause: 0.88(0.78, 0.98) CHD: 0.85(0.68, 1.06); Stroke: 1.08(0.75, 1.54) Cancer: 0.91(0.75, 1.11)	death certificates, ICD8, ICD9	Age, sex, and smoking
Jacobs 2001, Norway, (18)	33,848 35–56 years	14 years 1977–1994	Whole grain from bread Self-developed	Baseline FFQ	Whole grain bread Women (median bread score): 0.38/0.83/1.13/1.65/2.7 Men (median bread score): 0.45/0.83/0.90/1.65/3.30	All-cause: 2058 CVD: 758 Cancer: 870	All-cause: reference 0.87(0.75–1.01) 0.8(0.71–0.92) 0.85(0.74–0.98) 0.75(0.65–0.88) CVD: reference 0.93(0.73–1.18) 0.84(0.68–1.05) 0.84(0.66–1.05) 0.77(0.6–0.98) Cancer: reference 0.96(0.76–1.2) 0.89(0.73–1.08) 0.9(0.73–1.11) 0.79(0.62–1.02)	Registry ICD8, ICD9	Age, energy intake, sex, current smoking, past smoking, physical activity during leisure, physical activity during work, customary use of cod liver oil, customary use of multivitamins, saturated fat intake, systolic blood pressure, serum total cholesterol, and body mass index
Steffen 2003,US,(26)	11,940 45–64 years	11 years 1987–1999	Whole grain food	Repeated FFQ	Dark bread and Whole grain cold breakfast cereal. Whole grain cold cereals contained ≥ 25% whole grain or bran by weight	All-cause: 867	All-cause: reference 0.96(0.79–1.17) 0.8(0.65–0.99) 0.87(0.7–1.08) 0.77(0.61–0.97)	Family report, death record, registry N.A.	Age, race, sex, time-dependent energy intake, smoking status, pack-years of smoking, physical activity, alcohol intake, and hormone replacement in women
Sahyoun 2006, US, (19)	535 60–98 years	12–15 years 1981–1995	Whole grain MPED	3-day food record	All Whole grain foods from 3-day food records. Whole grain (serving/day): 0.31/0.86/1.49/2.9	CVD:89	CVD: reference 0.76(0.41–1.43) 0.76(0.41–1.41) 0.48(0.25–0.96)	Registry ICD9	Age, sex, race, educational attainment, marital status, smoking status, BMI, waist-to-hip ratio, systolic blood pressure, exercise, calories, percentage calories from saturated fatty acids, use of antihypertensive medication, and use of lipid-lowering medication
Jacobs 2007, US, (20)	27,312 women 55–69 years	17 years 1986–2001	Whole grain food	Baseline FFQ	Dark bread, cold breakfast cereal, brown rice, popcorn, wheat germ, bran, cooked oatmeal, other grains (e.g., bulgur, kasha, and couscous). Breakfast cereals containing ≥25% whole grain or bran were considered whole grains. Whole grain range (serving/week): 0–3.5(median 1.75) 4–7(median: 5.5) 7.5–10.5(median: 9) 11–18.5(median: 14.75) ≥19(median: 22.75)	All-cause: 5552 CVD: 1,900 Cancer: 2,099	All-cause: reference 0.88(0.81–0.96) 0.88(0.81–0.96) 0.8(0.73–0.87) 0.79(0.72–0.87) CVD: reference 0.96(0.84–1.1) 0.83(0.72–0.96) 0.83(0.71–0.96) 0.73(0.62–0.86) Cancer: reference 0.86(0.75–0.99) 0.95(0.83–1.09) 0.83(0.72–0.96) 0.89(0.77–1.04)	death record ICD9, ICD10	Age, energy intake, BMI, waist-hip ratio, smoking, education, physical activity, estrogen use, multivitamin supplement use, and intakes of alcohol, refined grain, coffee, red meat, fish and seafood, and total fruit and vegetables
Tognon 2011, Sweden, (27)	1,037 70 years	N.A. 1971–2009	Whole grain food	Dietary history questionnaire	Whole grain cereal Above vs. below medians. Medians were 74.2g in women and 92.8g in men.	All-cause: 630	All-cause: 0.85(0.73–1)	Registry N.A.	Sex, baseline body mass index (BMI), waist circumference, smoking status, physical activity level, marital status, education, and birth cohort.
Huang 2015, US, (21)	367,442 50–71 years	14 years 1995–2009	Whole grain MPED	Baseline FFQ	Ready-to-eat cereals, high-fiber cereals, other fiber cereals, Whole grain bread or dinner rolls, cooked cereal, popcorn, pancakes, waffles, French toast or crepes, rice or other cooked grains, bagels, English muffins, tortillas, pasta, crackers, chips, cookies/brownies, sweet pastries, and pies Median (serving/day): 0.13/0.3/0.47/0.69/1.2	All-cause: 46,067 CVD: 11283 Cancer: 19,043	All-cause: reference 0.93(0.9–0.95) 0.89(0.87–0.92) 0.85(0.82–0.87) 0.83(0.81–0.86) CVD: reference 0.93(0.88–0.98) 0.88(0.83–0.93) 0.81(0.77–0.86) 0.83(0.78–0.88) Cancer: reference 0.94(0.9–0.98) 0.91(0.87–0.95) 0.88(0.84–0.92) 0.85(0.81–0.89)	Registry ICD9, ICD10	Age, gender, number of cigarettes smoked per day, time of smoking cessation, race or ethnicity group, alcohol intake, education level, marital status, health status, obesity, physical activity, consumption of red meat, total fruit and total vegetables, total energy intake, and hormone usage
Roswall 2015, US, (28)	44,961 women 29–49 years	21 years 1992–2013	Whole grain food	Baseline FFQ	Whole grain bread, oatmeal Whole grain consumers vs. non-consumers	All-cause: 1,855 CVD: 270 Cancer: 1,113	Bread All-cause: reference 0.83(0.76–0.92) Oatmeal All-cause: reference 0.99(0.9–1.09)	Registry ICD9, ICD10	Age, smoking status, duration, current tobacco consumption, time since smoking cessation, school education, BMI, alcohol intake, red meat intake, processed meat intake, and energy intake
Johnsen 2015, Scandinavian, (22)	119,518 30–64 years	12.1 years 1992–2009	Whole grain Self-developed	Baseline FFQ	Breakfast cereals, non-white bread, crisp bread Median (g/d): Men, all-cause mortality: 21/37/54/80 Women, all-cause mortality: 20/33/49/74/ Men, CHD mortality: 21/36/54/82 Women, CHD mortality: 21/33/51/70 Men, stroke mortality: 20/37/50/79 Women, stroke mortality: 20/31/53/76 Men, cancer mortality: 21/37/54/80 Women, cancer mortality: 21/33/49/76	All-cause: 7,839 CHD: 1,156 stroke: 280 Cancer: 3,150	Men All-cause: reference 0.82(0.75–0.9) 0.72(0.66–0.78) 0.75(0.68–0.82) CHD: reference 0.79(0.65–0.96) 0.8(0.66–0.97) 0.74(0.61–0.91) Stroke: reference 0.7(0.44–1.1) 0.69(0.43–1.11) 0.71(0.44–1.15) Cancer: reference 0.85(0.73–0.99) 0.68(0.58–0.79) 0.74(0.63–0.87) Women All-cause: reference 0.8(0.73–0.87) 0.74(0.67–0.81) 0.74(0.67–0.81) CHD: reference 0.83(0.6–1.14) 0.59(0.42–0.82) 0.65(0.46–0.91) Stroke: reference 0.55(0.34–0.88) 0.5(0.31–0.82) 0.8(0.48–1.33) Cancer: reference 0.99(0.87–1.13) 0.94(0.82–1.07) 0.88(0.77–1.02)	Registry N.A.	Age, follow-up time, education, smoking intensity, alcohol, BMI, total energy intake and alcohol intake, with Whole grain products and Whole grain types mutually adjusted
Wu 2015, US, (23)	74,341 female nurses 38–63 years	26 years 1984–2010	Whole grain Self-developed	Repeated FFQ	Whole wheat and whole-wheat flour, whole oats and whole-oat flour, whole cornmeal and whole-corn flour, whole rye and whole-rye flour, whole barley, bulgur, buckwheat, brown rice and brown rice flour, popcorn, amaranth, and psyllium Whole grain (g/d): 4.2/9.7/14.7/21.1/33.0	All-cause: 15106 CVD: 2,989 Cancer: 5,964	All-cause: reference 0.98(0.93–1.03) 1.0001(0.95–1.05) 0.94(0.89–0.99) 0.88(0.84–0.93) CVD: reference 0.97(0.87–1.08) 0.96(0.86–1.08) 0.82(0.73–0.92) 0.86(0.76–0.96) Cancer: reference 1.02(0.94–1.1) 1.1(1.02–1.19) 1.06(0.98–1.15) 0.99(0.91–1.07)	family report or registry ICD8	Age, ethnicity; body mass index; smoking status; alcohol intake; physical activity; family history of diabetes mellitus, cancer, and heart disease; multivitamin use; aspirin use at least once per week; history of hypertension; high cholesterol level or diabetes at baseline; and total energy, postmenopausal status and postmenopausal hormone use (women), and alternative healthy eating index).
Wu 2015, US, (23)	43,744 male health professionals 32–87 years	24 years 1986–2010	Whole grain Self-developed	Repeated FFQ	Whole wheat and whole-wheat flour, whole oats and whole-oat flour, whole cornmeal and whole-corn flour, whole rye and whole-rye flour, whole barley, bulgur, buckwheat, brown rice and brown rice flour, popcorn, amaranth, and psyllium Whole grain (g/day): 5.9/14.4/22.1/31.3/47.8	All-cause: 11,814 CVD: 3,621 Cancer: 3,921	All-cause: 1(1, 1); 1.00(0.94, 1.05) 0.97(0.91, 1.02) 1.01(0.95, 1.07) 0.95(0.89, 1.00) CVD:1(1, 1) 0.92(0.84, 1.02) 0.92(0.83, 1.02) 0.91(0.82, 1.01) 0.84(0.75, 0.93) Cancer: (1, 1) 1.01(0.92, 1.11) 0.98(0.88, 1.08) 1.01(0.91, 1.12) 0.95(0.86, 1.05)	family report or registry ICD8	Age, ethnicity; body mass index; smoking status; alcohol intake; physical activity; family history of diabetes mellitus, cancer, and heart disease; multivitamin use; aspirin use at least once per week; history of hypertension; high cholesterol level or diabetes at baseline; and total energy, and alternative healthy eating index.
NHANES III unpublished, US	11,666 >20 years	20 years 1988–2010	Whole grain MPED	24-hour dietary recall	All foods containing whole grains in 24-hour dietary recall	All-cause: 2,545 CVD: 702 Cancer: 636	All-cause: reference 0.98(0.86, 1.12) 0.88(0.77, 1.02) CVD: reference 1.11(0.86, 1.44) 0.99(0.71, 1.39) Cancer: reference 1.08(0.82, 1.42) 0.84(0.66, 1.07)	Registry ICD9, ICD10	Age, ethnicity, education, physical activity, smoking status, alcohol consumption, BMI, energy intake, and HEI score.
NHANES 1999–2004 unpublished, US	12,488 >20 years	20 years 1999–2010	Whole grain MPED	24-hour dietary recall	All foods containing whole grains in 24-hour dietary recall	All-cause: 972 CVD: 229 Cancer: 245	All-cause: reference 0.90(0.73, 1.11) 0.83(0.65, 1.07) CVD: reference 0.98(0.53, 1.80) 0.74(0.41, 1.32) Cancer: reference 0.72(0.48, 1.07) 0.63(0.37, 1.09)	Registry ICD9, ICD10	Age, ethnicity, education, physical activity, smoking status, alcohol consumption, BMI, fruit, vegetable, meat, energy intake, and added sugar

^*Abbreviations: N.A., Not available; MPED, MyPyramid Equivalents Database; FFQ, food frequency questionnaire; CVD, Cardiovascular disease; ICD, International Statistical Classification of Diseases and Related Health Problems; BMI, body mass index; NHANES, National Health and Nutrition Examination Survey; HEI, health eating index.

^†Details of whole grain calculation are provided in Supplemental Methods