Whole grain intake, compared to refined grain, improves postprandial glycemia and insulinemia: a systematic review and meta-analysis of randomized controlled trials

Figures & data

Figure 1. Flow diagram of literature search process for the effect of whole grain, compared to refined grain, on short-term and long-term measures of glycemia and insulinemia.

Table 1. Effect of WG intake, compared to RG intake, on postprandial glycemia in adults.

		95% CI
Reference	SMD	Lower limit	Upper limit	P − value
Belobrajdic et al. (2019)	0.16	−0.29	0.62	0.480
RamyaBai et al. (2019) (pilaf)	−0.52	−1.08	0.04	0.068
RamyaBai et al. (2019) (brown rice)	0.51	−0.04	1.07	0.070
RamyaBai et al. (2019) (ugali)	−0.13	−0.65	0.40	0.639
Wolever et al. (2019a) (instant oatmeal)	0.15	−0.21	0.51	0.415
Wolever et al. (2019a) (old − fashioned oatmeal)	−0.02	−0.38	0.34	0.925
Wolever et al. (2019a) (steel cut oatmeal)	−0.71	−1.11	−0.31	0.001
Wolever et al. (2019b) (overnight oatmeal)	−0.75	−1.10	−0.40	0.000
Zhu et al. (2019) (black waxy rice)	0.68	−0.01	1.36	0.053
Zhu et al. (2019) (adlay)	0.37	−0.27	1.01	0.254
Zhu et al. (2019) (foxtail millet)	0.51	−0.15	1.17	0.129
Costabile et al. (2018)	0.08	−0.45	0.60	0.768
Hamad, Zafar, and Sidhu (2018) (healthy)	−0.15	−0.59	0.29	0.502
Hamad, Zafar, and Sidhu (2018) (T2D)	−0.13	−0.63	0.38	0.626
L. Li et al. (2018)	−0.25	−0.63	0.12	0.186
Wolever et al. (2018)	−0.14	−0.45	0.18	0.393
Kondo et al. (2017)	−0.80	−1.57	−0.03	0.042
Lee et al. (2017) (40 g rye porridge)	−0.07	−0.49	0.36	0.764
Lee et al. (2017) (55 g rye porridge)	0.36	−0.08	0.81	0.107
Osman, Mohd-Yusof, and Ismail (2017)	−0.69	−1.35	−0.04	0.039
Shobana et al. (2017)	−1.13	−1.86	−0.41	0.002
Cioffi et al. (2016)	0.69	−0.20	1.59	0.127
Gabrial, Shakib, and Gabrial (2016) (healthy, quinoa)	−0.91	−1.58	−0.23	0.008
Gabrial, Shakib, and Gabrial (2016) (healthy, buckwheat)	−13.98	−19.61	−8.36	0.000
Gabrial, Shakib, and Gabrial (2016) (T2D, quinoa)	−8.12	−11.42	−4.82	0.000
Gabrial, Shakib, and Gabrial (2016) (T2D, buckwheat)	−16.31	−22.85	−9.76	0.000
Nordlund et al. (2016) (sourdough rye)	−0.33	−0.91	0.25	0.266
Nordlund et al. (2016) (yeast rye)	0.11	−0.46	0.68	0.705
Nordlund et al. (2016) (yeast wheat)	−0.04	−0.60	0.53	0.903
Se et al. (2016) (red rice variety #9)	−1.21	−1.96	−0.47	0.001
Se et al. (2016) (red rice variety #10)	−0.31	−0.89	0.27	0.298
Se et al. (2016) (red rice variety #11)	−0.59	−1.20	0.03	0.060
Se et al. (2016) (Thai red rice)	−0.84	−1.49	−0.18	0.013
Wolever et al. (2016) (30 g quick oats)	−0.83	−1.19	−0.46	0.000
Wolever et al. (2016) (40 g quick oats)	−0.42	−0.75	−0.09	0.014
Wolever et al. (2016) (60 g quick oats)	−0.99	−1.38	−0.60	0.000
Geliebter et al. (2015) (healthy)	0.52	0.02	1.01	0.040
Geliebter et al. (2015) (overweight)	0.22	−0.25	0.69	0.357
Gonzalez-Anton et al. (2015)	−0.14	−0.56	0.28	0.507
Johansson et al. (2015)	0.19	−0.22	0.60	0.366
Soong, Quek, and Henry (2015) (WG corn vs. rice)	−0.17	−0.74	0.40	0.551
Soong, Quek, and Henry (2015) (WG corn vs wheat)	0.15	−0.42	0.71	0.616
Soong, Quek, and Henry (2015) (WG oat vs rice)	−1.84	−2.77	−0.91	0.000
Soong, Quek, and Henry (2015) (WG oat vs wheat)	−1.23	−1.97	−0.48	0.001
Soong, Quek, and Henry (2015) (WG barley vs rice)	−1.86	−2.79	−0.92	0.000
Soong, Quek, and Henry (2015) (WG barley vs wheat)	−1.16	−1.89	−0.43	0.002
Zafar et al. (2015)	−1.08	−1.77	−0.40	0.002
Hartvigsen et al. (2014a)	−0.35	−0.89	0.19	0.202
Hartvigsen et al. (2014b)	−0.44	−0.97	0.09	0.105
Luhovyy et al. (2014) (50 g HA maize)	−0.66	−1.05	−0.26	0.001
Luhovyy et al. (2014) (25 g HA maize)	−0.22	−0.58	0.14	0.232
Breen et al. (2013) (buttermilk wheat bread)	−0.10	−0.72	0.52	0.759
Breen et al. (2013) (pumpernickel rye bread)	−0.64	−1.32	0.04	0.065
Stringer et al. (2013) (healthy)	0.02	−0.55	0.58	0.952
Stringer et al. (2013) (T2D)	0.05	−0.51	0.62	0.858
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Celebrity WG vs RG porridge)	−0.30	−0.94	0.33	0.350
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Parkhill WG vs RG porridge)	−0.38	−1.02	0.26	0.248
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Fibar WG vs RG porridge)	−0.38	−1.02	0.26	0.247
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Celebrity vs RG wheat)	−−2.78	−4.15	−1.41	0.000
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Chief vs RG wheat)	−2.30	−3.49	−1.12	0.000
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Rattan vs RG wheat)	−2.42	−3.64	−1.19	0.000
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Klinck vs RG wheat)	−2.12	−3.23	−1.00	0.000
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Kawartha vs RG wheat)	−2.44	−3.67	−1.20	0.000
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Alberta vs RG wheat)	−2.24	−3.40	−1.08	0.000
Aldughpassi, Abdel-Aal el, and Wolever (2012) (GB vs RG wheat)	−2.65	−3.97	−1.34	0.000
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Celebrity WG vs RG pasta)	0.41	−0.24	1.05	0.214
Aldughpassi, Abdel-Aal el, and Wolever (2012) (Parkhill WG vs RG pasta)	0.29	−0.34	0.93	0.365
Hallstrom et al. (2011) (WG HA wheat bread)	−0.36	−0.91	0.18	0.186
Hallstrom et al. (2011) (WG wheat bread)	−0.30	−0.84	0.23	0.265
Rosen, Ostman, and Bjorck (2011b) (Commercial WG rye)	0.04	−0.40	0.48	0.864
Rosen, Ostman, and Bjorck (2011b) (Amilo rye)	−0.04	−0.47	0.40	0.870
Rosen, Ostman, and Bjorck (2011b) (Evolo rye)	−0.25	−0.69	0.20	0.276
Rosen, Ostman, and Bjorck (2011b) (Picasso rye)	−0.24	−0.68	0.21	0.297
Rosen, Ostman, and Bjorck (2011b) (Vicello rye)	−0.24	−0.68	0.21	0.295
Rosen, Ostman, and Bjorck (2011b) (Kaskelott rye)	−0.12	−0.56	0.32	0.580
Rosen, Ostman, and Bjorck (2011a) (rye bread)	0.06	−0.56	0.68	0.855
Rosen, Ostman, and Bjorck (2011a) (rye kernels)	0.12	−0.50	0.74	0.699
Rosen, Ostman, and Bjorck (2011a) (wheat kernels)	−0.36	−1.00	0.28	0.265
Rosen et al. (2011c) (D. Zlote rye)	−0.05	−0.57	0.48	0.855
Rosen et al. (2011c) (H. Loire rye)	−0.13	−0.65	0.40	0.641
Rosen et al. (2011c) (Nikita rye)	−0.18	−0.71	0.35	0.509
Rosen et al. (2011c) (Rekrut rye)	−0.41	−0.96	0.13	0.137
Rosen et al. (2011c) (Amilo rye)	−0.38	−0.92	0.17	0.175
Zafar, Kabir, and Ghazaii (2011)	−0.38	−0.97	0.20	0.198
Anderson et al. (2010)	−0.99	−1.58	−0.39	0.001
Kristensen et al. (2010) (ctrl: RG wheat bread)	−0.42	−0.93	0.09	0.110
Kristensen et al. (2010) (ctrl: RG wheat pasta)	0.28	−0.22	0.78	0.276
Marinangeli, Kassis, and Jones (2009)	−0.34	−0.80	0.12	0.149
Najjar et al. (2009) (WG wheat)	0.45	−0.20	1.10	0.178
Najjar et al. (2009) (WG wheat/barley)	0.10	−0.53	0.72	0.764
Ranawana et al. (2009) (brown rice, lg portion)	0.38	−0.26	1.03	0.242
Ranawana et al. (2009) (brown rice, sm portion)	−0.03	−0.65	0.59	0.916
Ranawana et al. (2009) (wild rice)	−0.49	−1.14	0.17	0.146
Ranawana et al. (2009) (Thai red rice)	−0.76	−1.47	−0.06	0.033
Rosen et al. (2009) (WG rye bread vs RG rye)	0.23	−0.37	0.83	0.451
Rosen et al. (2009) (WG rye bread vs RG wheat)	−0.73	−1.39	−0.06	0.032
Rosen et al. (2009) (WG rye porridge vs RG rye)	0.17	−0.42	0.77	0.565
Rosen et al. (2009) (WG rye porridge vs RG wheat)	−0.20	−0.80	0.39	0.506
Nilsson et al. (2008c) (barley flour)	−0.14	−0.71	0.42	0.618
Nilsson et al. (2008c) (oat)	−0.59	−1.20	0.02	0.059
Nilsson et al. (2008c) (wheat)	−0.64	−1.26	−0.02	0.044
Nilsson et al. (2008c) (rye)	−0.96	−1.65	−0.28	0.006
Nilsson et al. (2008c) (barley kernels)	−1.15	−1.88	−0.42	0.002
Hlebowicz et al. (2007)	−0.27	−0.84	0.31	0.364
Juntunen et al. (2003)	−0.35	−0.81	0.12	0.143
Granfeldt, Hagander, and Bjorck (1995) (boiled oat kernels)	−1.14	−1.98	−0.30	0.008
Granfeldt, Hagander, and Bjorck (1995) (boiled wheat kernels)	−1.23	−2.10	−0.37	0.005
Granfeldt, Hagander, and Bjorck (1995) (raw rolled oats)	−0.31	−0.98	0.36	0.364
Granfeldt, Hagander, and Bjorck (1995) (boiled rolled oats)	−0.18	−0.84	0.48	0.596
Granfeldt et al. (1994) (hull − less barley)	−3.27	−4.83	−1.71	0.000
Granfeldt et al. (1994) (hulled barley)	−3.00	−4.45	−1.55	0.000
Granfeldt et al. (1994) (HA hull − less barley)	−3.31	−4.89	−1.73	0.000
Granfeldt et al. (1994) (HA hulled barley)	−2.73	−4.08	−1.38	0.000
Granfeldt et al. (1994) (barley flour)	−1.52	−2.43	−0.61	0.001
Granfeldt et al. (1994) (HA barley flour)	−1.89	−2.93	−0.86	0.000
Lia and Andersson (1994)	−0.13	−0.79	0.52	0.692
Liljeberg and Bjorck (1994) (barley flour)	−0.23	−0.93	0.47	0.526
Liljeberg and Bjorck (1994) (scalded barley flour)	−0.05	−0.74	0.64	0.884
Holm and Bjorck (1992)	−0.35	−0.99	0.28	0.277
Hagander et al. (1987) (rye bread)	−1.09	−2.02	−0.15	0.023
Hagander et al. (1987) (rye flakes)	−0.08	−0.83	0.66	0.824
Hagander et al. (1985) (soft wheat bread)	−0.47	−1.16	0.22	0.178
Hagander et al. (1985) (crisp wheat bread)	0.00	−0.65	0.65	1.000
Jenkins et al. (1981) (pasta)	−0.61	−1.48	0.26	0.172
Jenkins et al. (1981) (rice)	−0.25	−1.01	0.50	0.509
O’Dea, Nestel, and Antonoff (1980) (unground rice)	−0.49	−1.34	0.36	0.258
O’Dea, Nestel, and Antonoff (1980) (ground rice)	0.07	−0.73	0.87	0.864
Total (random effects)^1	−0.30	−0.43	−0.18	<0.001
Heterogeneity: Q = 183, I^2 = 68.8, P < 0.001

1 A pooled effect size and variance was used for studies with multiple comparisons when either active or control groups comprised data from the same subjects.

Abbreviations: CI = confidence interval, HA = high amylose, lg = large, ON = after overnight fast, RG = refined grain, sm = small, SMD = standardized mean difference, T2D = type 2 diabetes, WG = whole grain

Table 2. Subgroup analysis for the effect of WG, compared to RG, on postprandial glycemia in adults.

Outcome and subgroups	Comparisons/ Studies	Effect estimate SMD^1	95% CI^1	I^2 (%)	P-value
Type of WG (test)
Barley	24/5	−0.88	−1.53, −0.22	85.5	0.009
Buckwheat	4/2	−3.27	−5.62, −0.91	93.7	0.007
Corn	6/4	−0.37	−0.74, −0.004	56.7	0.047
Oat	19/11	−0.35	−0.60, −0.09	73.6	0.009
Quinoa	3/2	−1.77	−3.41, −0.13	91.5	0.035
Rice	18/10	−0.27	−0.56, 0.03	62.5	0.073
Rye	29/13	−0.20	−0.36, −0.04	26.4	0.017
Wheat	20/17	−0.21	−0.40, −0.03	42.3	0.024
Between subgroup heterogeneity (Q = 14.5, P = 0.043)
Feeding approach
Matched available  CHO	113/41	−0.35	−0.48, −0.21	67.2	<0.001
Other	14/11	−0.14	−0.41, 0.13	72.1	0.310
Between subgroup heterogeneity (Q = 1.7, P = 0.189)
Same grain (test & ctrl)
Barley	5/1	−0.01	−0.65, 0.34	69.1	0.983
Rice	16/8	−0.32	−0.61, −0.02	54.2	0.035
Rye	6/4	−0.10	−0.38, 0.18	14.4	0.489
Wheat	19/16	−0.18	−0.35, −0.003	32.0	0.046
Between subgroup heterogeneity (Q = 1.4, P = 0.698)
Flours only
Barley	7/4	−0.78	−1.53, −0.02	79.8	0.043
Corn	6/4	−0.37	−0.74, −0.004	56.7	0.047
Rye	22/9	−0.17	−0.35, 0.01	17.6	0.067
Wheat	13/12	−0.05	−0.27, 0.18	43.3	0.685
Between subgroup heterogeneity (Q = 4.9, P = 0.183)
Amount of WG (median split)
≤ 79.1 g	64/31	−0.37	−0.54, −0.19	72.8	<0.001
> 79.1 g	63/25	−0.31	−0.50, −0.12	71.3	0.002
Between subgroup heterogeneity (Q = 0.19, P = 0.661)
Health status
Healthy	110/44	−0.33	−0.46, −0.19	69.4	<0.001
Overweight/Obese	4/3	0.03	−0.31, 0.38	41.1	0.852
Type 2 diabetes	11/7	−0.38	−0.92, 0.17	78.3	0.179
Between subgroup heterogeneity (Q = 3.98, P = 0.264)
Sex
Male	12/6	−0.36	−0.66, −0.07	52.4	0.016
Female	9/5	−0.27	−0.70, 0.16	68.7	0.223
Between subgroup heterogeneity (Q = 0.12, P = 0.723)

1 A pooled effect size and variance was used for studies with multiple comparisons when either active or control groups comprised data from the same subjects.

Significance of bold values is p ≤ 0.05.Abbreviations: CHO = carbohydrate, SMD = standardized mean difference, RG = refined grain, WG = whole grain

Table 3. Effect of WG intake, compared to RG intake, on postprandial insulinemia in adults.

		95% CI
Reference	SMD	Lower limit	Upper limit	P-value
Belobrajdic et al. (2019)	−0.44	−0.91	0.03	0.067
Wolever et al. (2019a) (instant oatmeal)	0.13	−0.22	0.49	0.463
Wolever et al. (2019a) (old-fashioned oatmeal)	−0.02	−0.38	0.34	0.916
Wolever et al. (2019a) (steel cut oatmeal)	−0.21	−0.58	0.15	0.246
Wolever et al. (2019b) (overnight oatmeal)	−0.48	−0.81	−0.15	0.004
Costabile et al. (2018)	−0.30	−0.84	0.23	0.265
Kondo et al. (2017)	−0.48	−1.23	0.28	0.214
Cioffi et al. (2016)	−0.75	−1.65	0.16	0.105
Nordlund et al. (2016) (sourdough rye)	0.17	−0.40	0.73	0.570
Nordlund et al. (2016) (yeast rye)	0.11	−0.45	0.68	0.696
Nordlund et al. (2016) (yeast wheat)	0.45	−0.14	1.04	0.137
Sandberg, Bjorck, and Nilsson (2016)	−0.99	−1.68	−0.30	0.005
Se et al. (2016) (red rice variety #9)	−0.45	−1.04	0.14	0.137
Se et al. (2016) (red rice variety #10)	−0.11	−0.67	0.46	0.711
Se et al. (2016) (red rice variety #11)	−0.64	−1.26	−0.02	0.044
Se et al. (2016) (Thai red rice)	0.06	−0.40	0.52	0.804
Geliebter et al. (2015) (healthy)	0.15	−0.31	0.62	0.518
Geliebter et al. (2015) (overweight)	0.15	−0.27	0.57	0.494
Gonzalez-Anton et al. (2015)	0.17	−0.24	0.58	0.422
Johansson et al. (2015)	−0.61	−1.19	−0.04	0.035
Hartvigsen et al. (2014a)	−1.22	−1.89	−0.56	0.000
Hartvigsen et al. (2014b)	−1.37	−2.23	−0.51	0.002
Breen et al. (2013) (buttermilk wheat bread)	−1.95	−3.00	−0.89	0.000
Breen et al. (2013) (pumpernickel rye bread)	−0.16	−0.76	0.43	0.587
Johansson et al. (2013)	−0.34	−0.93	0.24	0.247
Stringer et al. (2013) (healthy)	0.50	−0.06	1.05	0.080
Stringer et al. (2013) (T2D)	−0.10	−0.62	0.43	0.712
Hallstrom et al. (2011) (WG HA wheat bread)	−0.11	−0.55	0.33	0.634
Hallstrom et al. (2011) (WG wheat bread)	−0.38	−0.84	0.07	0.097
Rosen, Ostman, and Bjorck (2011b) (Commercial WG rye)	−0.36	−0.82	0.09	0.115
Rosen, Ostman, and Bjorck (2011b) (Amilo rye)	−0.41	−0.87	0.04	0.076
Rosen, Ostman, and Bjorck (2011b) (Evolo rye)	−0.52	−0.98	−0.05	0.030
Rosen, Ostman, and Bjorck (2011b) (Picasso rye)	−0.43	−0.89	0.04	0.076
Rosen, Ostman, and Bjorck (2011b) (Vicello rye)	−0.13	−0.79	0.52	0.690
Rosen, Ostman, and Bjorck (2011b) Rosen et al. (Kaskelott rye)	−0.09	−0.71	0.53	0.785
Rosen, Ostman, and Bjorck (2011a) (rye bread)	−0.68	−1.37	0.01	0.052
Rosen, Ostman, and Bjorck (2011a) (rye kernels)	−0.26	−0.80	0.27	0.331
Rosen, Ostman, and Bjorck (2011a) (wheat kernels)	0.08	−0.44	0.61	0.761
Rosen et al. (2011c) (D. Zlote rye)	−0.11	−0.63	0.42	0.691
Rosen et al. (2011c) (H. Loire rye)	−0.41	−0.96	0.13	0.137
Rosen et al. (2011c) (Nikita rye)	−0.53	−1.09	0.03	0.063
Rosen et al. (2011c) (Rekrut rye)	−0.01	−0.63	0.61	0.979
Rosen et al. (2011c) (Amilo rye)	−0.13	−0.75	0.49	0.686
Najjar et al. (2009) (WG wheat)	0.53	−0.07	1.14	0.084
Najjar et al. (2009) (WG wheat/barley)	−1.20	−1.94	−0.46	0.002
Rosen et al. (2009) (WG rye bread vs RG rye)	0.73	0.06	1.39	0.032
Rosen et al. (2009) (WG rye bread vs RG wheat)	0.05	−0.54	0.64	0.862
Rosen et al. (2009) (WG rye porridge vs RG rye)	0.10	−0.35	0.55	0.675
Rosen et al. (2009) (WG rye porridge vs RG wheat)	−0.65	−1.36	0.07	0.078
Juntunen et al. (2003)	−0.67	−1.40	0.05	0.068
Granfeldt, Hagander, and Bjorck (1995) (boiled oat kernels)	−0.10	−0.76	0.55	0.763
Granfeldt, Hagander, and Bjorck (1995) (boiled wheat kernels)	−0.18	−0.84	0.48	0.586
Granfeldt, Hagander, and Bjorck (1995) (raw rolled oats)	−1.11	−1.89	−0.32	0.006
Granfeldt, Hagander, and Bjorck (1995) (boiled rolled oats)	−1.07	−1.85	−0.29	0.007
Granfeldt et al. (1994) (hull − less barley)	−1.25	−2.08	−0.43	0.003
Granfeldt et al. (1994) (hulled barley)	−1.17	−1.97	−0.36	0.004
Granfeldt et al. (1994) (HA hull − less barley)	−0.62	−1.33	0.09	0.088
Granfeldt et al. (1994) (HA hulled barley)	−0.69	−1.42	0.04	0.062
Granfeldt et al. (1994) (barley flour)	0.00	−0.65	0.65	1.000
Granfeldt et al. (1994) (HA barley flour)	−0.37	−1.08	0.35	0.316
Lia and Andersson (1994)	−0.43	−1.15	0.30	0.248
Liljeberg and Bjorck (1994) (barley flour)	−0.21	−0.84	0.41	0.505
Liljeberg and Bjorck (1994) (scalded barley flour)	−0.04	−0.78	0.70	0.916
Holm and Bjorck (1992)	0.00	−0.74	0.74	1.000
Hagander et al. (1987) (rye bread)	−0.23	−0.90	0.43	0.487
Hagander et al. (1987) (rye flakes)	0.15	−0.50	0.81	0.647
Hagander et al. (1985) (soft wheat bread)	−0.37	−1.20	0.46	0.379
Hagander et al. (1985) (crisp wheat bread)	−0.08	−0.88	0.72	0.842
O’Dea, Nestel, and Antonoff (1980) (unground rice)	−0.44	−0.91	0.03	0.067
O’Dea, Nestel, and Antonoff (1980) (ground rice)	0.13	−0.22	0.49	0.463
Total (random effects)^1	−0.23	−0.35	−0.10	<0.001
Heterogeneity: Q = 54.5, I^2 = 43.1, P = 0.006

1 A pooled effect size and variance was used for studies with multiple comparisons when either active or control groups comprised data from the same subjects.

Abbreviations: CI = confidence interval, HA = high amylose, lg = large, ON = after overnight fast, RG = refined grain, sm = small, SMD = standardized mean difference, T2D = type 2 diabetes, WG = whole grain.

Table 4. Subgroup analysis for the effect of WG, compared to RG on postprandial insulinemia in adults.

Outcome and subgroups	Comparisons/ Studies	Effect estimate SMD1	95% CI	I2 (%)	P-value
Type of WG (test)
Barley	8/2	−0.63	−1.17, −0.10	31.0	0.020
Oat	10/5	−0.12	−0.33, 0.10	29.1	0.285
Rice	7/3	−0.40	−0.76, −0.05	0.0	0.025
Rye	25/11	−0.27	−0.54, 0.006	66.5	0.055
Wheat	15/12	−0.23	−0.48, 0.02	53.2	0.069
Between subgroup heterogeneity (Q = 4.3, P = 0.513)
Feeding approach
Matched available  CHO	62/25	−0.25	−0.39, −0.11	38.4	<0.001
Other	6/5	−0.11	−0.39, 0.16	44.2	0.422
Between subgroup heterogeneity (Q = 0.75, P = 0.388)
Same grain (test & ctrl)
Rice	7/3	−0.40	−0.76, −0.05	0.0	0.025
Rye	6/4	0.18	−0.10, 0.45	6.1	0.202
Wheat	13/11	−0.20	−0.46, 0.06	53.7	0.130
Between subgroup heterogeneity (Q = 7.4, P = 0.025)
Flours only
Barley	4/2	−0.49	−0.93, −0.05	0.0	0.030
Rye	22/9	−0.13	−0.39, 0.12	53.5	0.310
Wheat	10/9	−0.14	−0.45, 0.16	59.0	0.359
Between subgroup heterogeneity (Q = 2.0, P = 0.364)
Amount of WG (median split)
≤ 82.4 g	34/18	−0.19	−0.33, −0.04	37.5	0.011
> 82.4 g	34/17	−0.34	−0.56, −0.13	58.6	0.002
Between subgroup heterogeneity (Q = 1.4, P = 0.233)
Health status
Healthy	55/23	−0.19	−0.30, −0.07	25.6	0.002
Overweight/Obese	3/2	0.06	−0.29, 0.42	0.0	0.734
Type 2 diabetes	8/5	−0.33	−0.81, 0.14	63.9	0.168
Between subgroup heterogeneity (Q = 7.7, P = 0.054)
Sex
Male	8/3	−0.21	−0.54, 0.13	0.0	0.224
Female	4/2	0.15	−0.17, 0.47	0.0	0.347
Between subgroup heterogeneity (Q = 2.3 P = 0.126)

1 A pooled effect size and variance was used for studies with multiple comparisons when either active or control groups comprised data from the same subjects.

Abbreviations: CHO = carbohydrate, SMD = standardized mean difference, RG = refined grain, WG = whole grain.

Figure 2. Forest plot of the meta-analyses on the effect of whole grain, compared to refined grain, on fasting glucose in adults.

Figure 3. Forest plot of the meta-analyses on the effect of whole grain, compared to refined grain, on fasting insulin in adults.

Table 5. Subgroup analysis for the effect of WG, compared to RG, on fasting glucose and insulin in adults.

Outcome and subgroups	Comparisons/ Studies	Effect estimate SMD^1	95% CI	I^2(%)	P-value^1
Fasting glucose
Type of WG
Wheat	4/4	0.34	−0.09, 0.76	62.5	0.121
Mixed	12/11	−0.15	−0.28, −0.03	0.0	0.013
Between subgroup heterogeneity (Q = 4.7, P = 0.031)
Amount of WG (median split)
≤ 100 g	12/12	−0.07	−0.28, 0.15	63.1	0.552
> 100 g	11/11	−0.14	−0.28, 0.01	25.3	0.060
Between subgroup heterogeneity (Q = 0.30, P = 0.586)
Study design
Parallel	14/13	−0.05	−0.27, 0.16	62.5	0.633
Crossover	9/9	−0.17	−0.31, −0.04	0.0	0.010
Between subgroup heterogeneity (Q = 0.90, P = 0.344)
Study duration (median split)
≤ 8 wks	14/14	−0.12	−0.29, 0.06	51.4	0.185
> 8 wks	9/8	−0.08	−0.30, 0.14	50.9	0.461
Between subgroup heterogeneity (Q = 0.07, P = 0.792)
Health status
Healthy	6/6	−0.23	−0.42, −0.03	0.0	0.027
Overweight/Obese	9/8	−0.01	−0.27, 0.26	67.7	0.959
Metabolic dysfunction^2	8/8	−0.11	−0.33, 0.12	55.4	0.363
Between subgroup heterogeneity (Q = 1.7, P = 0.420)
Fasting insulin
Type of WG
Wheat	4/4	−0.60	−0.31, 0.20	0.0	0.646
Mixed	11/10	−0.02	−0.14, 0.10	0.0	0.728
Between subgroup heterogeneity (Q = 0.07, P = 0.791)
Amount of WG (median split)
≤ 100 g	10/10	−0.04	−0.02, 0.09	0.0	0.513
> 100 g	9/9	−0.00	−0.13, 0.13	0.0	0.998
Between subgroup heterogeneity (Q = 0.21, P = 0.649)
Study design
Parallel	12/11	−0.03	−0.16, 0.10	0.0	0.684
Crossover	7/7	−0.03	−0.20, 0.13	21.9	0.705
Between subgroup heterogeneity (Q = 0.001, P = 0.970)
Study duration (median split)
≤ 8 wks	11/11	−0.05	−0.18, 0.08	0.0	0.455
> 8 wks	8/7	0.00	−0.15, 0.15	0.0	0.998
Between subgroup heterogeneity (Q = 0.23, P = 0.628)
Health status
Healthy	3/3	−0.31	−0.58, −0.04	11.8	0.027
Overweight/Obese	9/8	0.02	−0.13, 0.16	0.0	0.831
Metabolic dysfunction^2	7/7	0.02	−0.13, 0.18	0.0	0.770
Between subgroup heterogeneity (Q = 4.8, P = 0.090)

1 A pooled effect size and variance was used for studies with multiple comparisons when either active or control groups comprised data from the same subjects.

2 Subjects had one or more risk factors for metabolic syndrome, hypertension or slightly elevated total cholesterol.

Abbreviations: CHO = carbohydrate, RG = refined grain, WG = whole grain, wks = weeks.

Figure 4. Forest plot of the meta-analysis on the effect of whole grain, compared to refined grain, on HbA1c in adults.

Table 6. Quality of evidence included in the systematic review and meta-analysis of WG on measures of glycemia and insulinemia, based on GRADE approach.

Outcome	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication Bias	Decision
Postprandial glycemia	Some concerns	Serious	No serious indirectness	Moderate imprecision	Possible	⊕⊕∅∅ Low
Postprandial insulin	Some concerns	Consistent	No serious indirectness	Moderate imprecision	Likely	⊕⊕⊕∅ Moderate
2^nd meal glycemia	Low	Serious	No serious indirectness	Moderate imprecision	Possible	⊕⊕∅∅ Low
2^nd meal insulin	Low	Consistent	No serious indirectness	Moderate imprecision	Undetected	⊕⊕⊕∅ Moderate
Fasting glucose	Low	Moderate	No serious indirectness	Moderate imprecision	Undetected	⊕⊕⊕∅ Moderate
Fasting insulin	Low	Consistent	No serious indirectness	Moderate imprecision	Undetected	⊕⊕⊕∅ Moderate
HbA1c	Some concerns	Consistent	No serious indirectness	Moderate imprecision	Undetected	⊕⊕⊕∅ Moderate
HOMA-IR	Low	Consistent	No serious indirectness	Moderate imprecision	Undetected	⊕⊕⊕∅ Moderate
OGTT glucose	Some concerns	Consistent	No serious indirectness	Serious imprecision	Undetected	⊕⊕∅∅ Low
OGTT insulin	Some concerns	Moderate	No serious indirectness	Serious imprecision	Undetected	⊕⊕∅∅ Low

Abbreviations: GRADE = Grading of Recommendations Assessment, Development and Evaluation, HbA1c = glycated hemoglobin, HOMA-IR = homeostatic model assessment of insulin resistance, OGTT = oral glucose tolerance test.

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