TABLE 1.
The effect of whole-grain intake on inflammatory biomarkers in adults aged ≥18 y1
| Diet type | Outcome2 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author, year (ref) | Participants, n | Age,3 y | Health condition | Feeding status | Design | Intervention | Control | Duration, wk | Intervention (mean ± SD) | Control (mean ± SD) | Adjust/matching4 | Risk of bias5 |
| Giacco et al. 2010 (6) | F: 12, M: 3 | 54.5 ± 7.6 | Overweight and obesity | Feeding | RCT, crossver | Whole-wheat products | Refined wheat products | 3 | CRP; post: 1.8 ± 2.3 | CRP; post: 2.9 ± 4.1 | — | L/U/L/U |
| Kristensen et al. 2012 (8) | F: 72 WG: 38, RG: 34 | WG: 59.1 ± 5.6; RG: 60.3 ± 5.3 | Overweight and obesity | Feeding | RCT, parallel | Whole-wheat; WG = 105 g/d, hypocaloric diet | Refined wheat; WG = 0, hypocaloric diet | 12 | CRP; pre: 0.95 ± 0.30, post: 0.85 ± 0.30 | CRP; pre: 1.00 ± 0.29, post: 1.07 ± 0.29 | — | L/U/H/L |
| IL-6: pre: 2.45 ± 0.16, post: 2.65 ± 1.57 | IL-6; pre: 1.70 ± 0.17, post: 1.83 ± 0.16 | |||||||||||
| Vitaglione et al. 2015 (9) | F: 68 WG: 36, RG: 32 | WG: 40 ± 2.0; RG: 37 ± 2.0 | Overweight and obesity | Feeding | RCT, parallel | 100% WG wheat product; WG = 70 g/d | Refined wheat products | 8 | IL-6; pre: 57.50 ± 7.50, post: 46.9 ± 4.00 | IL-6; pre: 65.50 ± 7.50, post: 60.20 ± 7.20 | — | L/L/L/L |
| TNF-α; pre: 341.90 ± 25.50, post: 243.0 ± 26.0 | TNF-α; pre: 321.90 ± 52.10, post: 329.80 ± 50.60 | |||||||||||
| Katcher et al. 2008 (10) | F: 25, M: 25 WG: 25, CON: 25 | WG: 45.4 ± 8; CON: 46.6 ± 9.7 | Obesity with metabolic syndrome | Nonfeeding | RCT, parallel | Different WGs; WGs = 4, 5, 6, or 7 servings/d; hypocaloric diet | Nonconsumption of WG foods based on a list of WG foods; hypocaloric diet | 12 | CRP; change: −2.4 ± 5.10 | CRP; change: 0.2 ± 2.9 | 2,3 | L/U/L/L |
| TNF-α; change: −0.04 ± 0.30 | TNF-α; change: 0.10 ± 0.20 | |||||||||||
| IL-6; change: −0.90 ± 3.60 | IL-6; change: −0.1 ± 0.4 | |||||||||||
| Harris Jackson et al. 2014 (11) | F: 25, M: 25 WG: 25, RG: 25 | WG: 46.4 ± 5.9; RG: 45.8 ± 6 | Overweight and obesity with metabolic syndrome | Feeding | RCT, parallel | Different WG foods; isocaloric diet for the first 6 wk, followed by a hypocaloric diet for the second 6 wk; WG = 187 g/d | RG foods; isocaloric diet for the first 6 wk, followed by a hypocaloric diet for the second 6 wk; WG = 0 g/d | 12 | CRP; pre: 3.0 ± 1.93, post: 0.60 ± 0.50 | CRP; pre: 2.10 ± 1.26, post: 0.60 ± 0.40 | 1,2,3 | L/U/L/U |
| IL-6; pre: 1.70 ± 1.26, post: 0.10 ± 0.20 | IL-6; pre: 1.70 ± 0.74, post: 0.10 ± 0.20 | |||||||||||
| TNF-α; pre: 1.20 ± 0.22, post: 0.00 ± 0.10 | TNF-α; pre: 1.40 ± 0.37, post: −0.10 ± 0.10 | |||||||||||
| Roager et al. 2019 (12) | F: 32, M: 18 WG: 50, RG: 50 | 20–65 | At risk of metabolic syndrome | Feeding | RCT, crossover | WG products; WG = 157.9 ± 35.0 | RG products; WG = 6.0 ± 4.8 | 8 | CRP; pre: 6.30 ± 14, post: 4.20 ± 6.80 | CRP; pre: 3.10 ± 2.60, post: 5.0 ± 5.80 | 1,2,4 | L/L/L/L |
| TNF-α; pre: 1.70 ± 0.90, post: 1.70 ± 0.90IL-6; pre: 1.60 ± 1.02, post: 1.40 ± 1.10 | TNF-α; pre: 1.70 ± 0.80, post: 1.70 ± 0.08 | |||||||||||
| IL-6; pre: 1.20 ± 0.70, post: 2.0 ± 2.0 | ||||||||||||
| Ross et al. 2011 (13) | F: 11, M: 6 WG: 17, RG: 17 | WG: 36.5 ± 4.2; CON: 36.5 ± 4.2 | Healthy | Feeding | RCT, crossover | Different WG foods; WG = 151 g/d | Different RG foods | 2 | CRP; pre, females: 3.0 ± 1.0, males: 2.20 ± 0.90 | CRP; pre, females: 5.60 ± 2.0, males: 1.70 ± 0.20 | 1,2,3,5,7 | L/L/L/L |
| Post: both sexes: 3.38 ± 0.92 | Post: both sexes: 3.01 ± 0.90 | |||||||||||
| Tighe et al. 2010 (14) | F: 102, M: 104 WG: 73, RG: 63 | WG: 52.1 ± 0.9; RG: 51.8 ± 0.8 | Healthy | Feeding | RCT, parallel | Group 1: 3 servings of whole-wheat foods (70–80 g WG bread + 30–40 g WG cereals) | Refined cereals and white bread | 12 | Group 1: CRP; pre: 3.30 ± 1.03, post: 0.90 ± 0.88Group 1: IL-6; pre: 1.20 ± 1.03, post: 1.40 ± 1.07 | CRP; pre: 1.40 ± 1.25, post: 1.10 ± 1.33IL-6; pre: 1.30 ± 1.14, post: 1.40 ± 1.25 | 1,2,3,5 | L/L/L/L |
| Group 2: 1 serving of whole-wheat foods and 2 servings of oats | ||||||||||||
| Group 2: CRP; pre: 1.0 ± 0.74, post: 1.0 ± 1.07 | ||||||||||||
| Group 2: IL-6; pre: 1.10 ± 0.92, post: 1.10 ± 0.88 | ||||||||||||
| Vetrani et al. 2016 (15) | F: 24, M: 16 WG: 21, RG: 19 | WG: 57.2 ± 1.9; RG: 58.4 ± 1.6 | Metabolic syndrome | Feeding | RCT, parallel | WG products plus a small portion of endosperm rye bread | Commercial products based on refined cereals | 12 | CRP; pre: 2.52 ± 0.50, post: 2.44 ± 0.50 | CRP; pre: 2.27 ± 0.40, post: 2.39 ± 0.40 | — | L/U/H/L |
| TNF-α; pre: 1.71 ± 0.60, post: 1.50 ± 0.60 | TNF-α; pre: 1.07 ± 0.40, post: 1.31 ± 0.50 | |||||||||||
| IL-6: pre: 1.84 ± 0.20, post: 2.23 ± 0.30 | IL-6; pre: 1.69 ± 0.30, post: 1.70 ± 0.30 | |||||||||||
| Meydani et al. 2016 (16) | F: 49, M: 32 WG: 41, RG: 40 | 40–65 | Healthy | Feeding | RCT, parallel | Different WGs: WG = 207 ± 39 | Different RGs: WG = 0 | 6 | CRP | CRP | — | — |
| de Mello et al. 2011 (17) | F: 34, M: 34 WG: 34, RG: 34 | WG: 58 ± 8; RG: 59 ± 7 | Overweight and obesity | Nonfeeding | RCT, parallel | Consumption of usual cereal products with ≥50% of their composition from a WG source plus WG oat snack bars once per day | Were asked to replace the breads with refined wheat breads, and other cereal products with low-fiber products | 12 | CRP; pre: 1.50 ± 1.70, post: 1.20 ± 0.92 | CRP; pre: 2.86 ± 2.96, post: 2.34 ± 1.57 | 1,2,3,6,5 | L/L/H/L |
| TNF-α; pre: 0.70 ± 0.51, post: 0.60 ± 0.48 | TNF-α; pre: 0.6.0 ± 0.40, post: 0.50 ± 0.44 | |||||||||||
| IL-6; pre: 1.40 ± 1.22, post: 1.50 ± 1.11 | IL-6; pre: 1.30 ± 1.03, post: 1.40 ± 1.07 | |||||||||||
| Kondo et al. 2017 (18) | F: 10, M: 18 WG: 14, RG: 14 | 40–80 | Type 2 diabetes | Feeding | RCT, parallel | Brown rice; 10 of 21 meals/wk | White rice; 10 of 21 meals/wk | 8 | CRP; pre: 0.09 ± 0.12, post: 0.05 ± 0.05 | CRP; pre: 0.04 ± 0.03, post: 0.05 ± 0.06 | 1,2,3,5 | L/L/L/U |
| Ampatzoglou et al. 2016 (19) | F: 21, M: 12 WG: 33, CON: 33 | 48.8 ± 1.1 | Healthy | Feeding | RCT, crossover | Diet high in WG (>80 g/d) | Diet low in WG (<16 g/d, RG diet) | 6 | CRP; pre: 2.20 ± 0.50, post: 1.60 ± 0.40 | CRP; pre: 1.70 ± 0.30, post: 1.80 ± 0.30 | — | L/U/L/U |
| TNF-α; pre: 10.80 ± 0.40, post: 10.80 ± 0.60 | TNF-α; pre: 10.50 ± 0.50, post: 10.70 ± 0.50 | |||||||||||
| IL-6; pre: 1.20 ± 0.20, post: 1.20 ± 0.10 | IL-6; pre: 1.30 ± 0.20, post: 1.40 ± 0.20 | |||||||||||
| Andersson et al. 2007 (20) | F: 22, M: 8 WG: 30, RG: 30 | 59 ± 5 | Overweight | Feeding | RCT, crossover | Different WGs; WG = 112 g/d | Different RGs; RG = 111 g | 6 | CRP; pre: 2.03 ± 1.62, post: 2.38 ± 2.29 | CRP; pre: 2.86 ± 2.96, post: 2.34 ± 1.57 | — | L/L/L/L |
| IL-6; pre: 14.80 ± 32.20, post: 15.20 ± 33.20 | IL-6; pre: 15.90 ± 32.40, post: 15.80 ± 30.90 | |||||||||||
| Brownlee et al.2010 (21) | F: 133, M: 133 Group 1: 85, Group 2: 81, CON: 100 | Int 1: 45.9 ± 10.1; Int 2: 45.7 ± 9.9; CON: 45.6 ± 1.0 | Overweight | Feeding | RCT, parallel | Group 1: 60 g WG/d for 16 wk, Group 2: 60 g WG/d for 8 wk followed by 120 g WG/d for 8 wk | No dietary changes; habitual diet (WG ≤30 g/d) | 16 | Group 1; CRP; pre: 2.40 ± 9.90, 16 wk: 3.10 ± 4.30 | CRP; pre: 2.40 ± 2.30, 8 wk: 2.70 ± 2.80, 16 wk: 2.90 ± 3.50 | 1,2,3 | L/U/L/U |
| Group 2; CRP; pre: 3.20 ± 4.60, 8 wk: 3.50 ± 7.20, 16 wk: 3.2 ± 5.90 | ||||||||||||
| Kirwan et al. 2016 (26) | F: 27, M: 6, WG: 33, RG: 33 | 39 ± 7.0 | Overweight and obesity | Feeding | RCT, crossover | WG diet; WG = 93 ± 19 | RG diet, WG = 0 | 8 | CRP; change: 0.80 ± 2.74 | CRP; change: −2.30 ± 3.56 | 1,2,4,5,9 | L/L/L/H |
| TNF-α; pre: 71.0 ± 36.0, post: 55.0 ± 24.0 | TNF-α; pre: 62.0 ± 38.0, post: 51.0 ± 19.0 | |||||||||||
1
CON, control; CRP, C-reactive protein; F, female; H, high risk; Int, intervention; L, low risk; RCT, randomized controlled trial; ref, reference; RG, refined grain; U, unclear risk; WG, whole grain.
2
CRP reported as mg/L, IL-6 as pg/mL, TNF-α as pg/mL.
3
Mean ± SD (all such values).
4
Age (1), sex (2), BMI (3), body weight (4), baseline measurements (5), fasting plasma glucose (6), treatment order (7), change in body fat (8), fiber intake (9).
5
Risk of bias was assessed as: 1) Sequence generation and allocation concealed? 2) All subjects received the same attention? 3) Was analysis in an intent-to-treat population? and 4) Was the article selective in outcome reporting? Studies were considered as “high risk” if they contained methodological flaws that could have affected the results, “low risk” if the flaw was deemed inconsequential, and “unclear risk” if information was insufficient to determine. In the current meta-analysis, studies that were “low risk” for all domains were considered as high quality or having low risk of bias.