Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This systematic review and dose–response meta-analysis examined whole grains, refined grains cardiovascular risk across prospective cohorts to quantify how incremental intakes relate to incident cardiovascular disease (CVD) events and all-cause mortality, while grading the certainty of evidence using NutriGrade. The authors pooled 68 studies (46 on whole grains; 22 on refined grains) and modeled both linear and non-linear relationships with restricted cubic splines. Forest plots on page 4 summarize high-vs-low contrasts, while the dose–response curves on page 5 show nonlinearity for CVD and mortality with whole grains; refined-grain splines appear on page 8. Random-effects meta-analyses harmonized exposures to grams/day, typically assuming 30 g per serving.
Who was reviewed?
Eligible evidence comprised 1,624,407 adults followed 5.4–26 years from America, Europe, Asia, and multicountry cohorts, with diet mainly assessed by validated food-frequency questionnaires; disease-specific cohorts were excluded. For whole grains, 1,507,041 participants contributed to stroke, coronary heart disease (CHD), heart failure (HF), composite CVD, and all-cause mortality analyses; for refined grains, 443,965 participants contributed across the same endpoints. NutriGrade ratings were high for whole-grain associations with CVD and all-cause mortality, moderate for stroke and CHD, and low for HF; all refined-grain evidence was low.
Most important findings
| Critical point | Details |
|---|---|
| Whole grains reduce composite CVD risk | Per 30 g/day higher whole-grain intake, CVD risk fell 8% (RR 0.92, 95% CI 0.88–0.96). The dose–response was nonlinear: benefits accrued from 0 to ~125 g/day with a flattening slope thereafter (Figure 2C, page 5). Evidence quality: high. |
| Whole grains lower CHD risk linearly | Each 30 g/day increase associated with 6% lower CHD risk (RR 0.94, 0.92–0.97), with linear trend (Figure 2B, page 5). High-vs-low contrast showed 18% lower risk. Evidence quality: moderate; publication-bias sensitivity did not alter the effect. |
| Whole grains and all-cause mortality | Each 30 g/day higher intake linked to 6% lower all-cause mortality (RR 0.94, 0.92–0.97). The curve was nonlinear with diminishing returns up to ~220 g/day (Figure 2D, page 5). Evidence quality: high. |
| Whole grains and stroke | Pooled stroke reduction per 30 g/day was borderline (RR 0.98, 0.96–1.00); significance appeared in sensitivity analyses excluding two studies. Stroke subtype differences (ischemic vs hemorrhagic) may explain heterogeneity (page 7). Evidence quality: moderate. |
| Whole grains and HF | No significant association for HF overall (RR 0.97, 0.89–1.07 per 30 g/day), with low evidence quality due to few studies and heterogeneity |
| Refined grains and CVD, CHD, stroke | No significant linear associations per 30 g/day for CVD (RR 1.01), CHD (RR 1.02), or stroke (RR 0.98); heterogeneity substantial and evidence low. High-vs-low contrasts were likewise nonsignificant |
| Refined grains and mortality | High-vs-low refined-grain intake showed higher all-cause mortality (RR 1.12, 0.95–1.31) with a positive spline trend (Figure 5D, page 8); linear dose–response per 30 g/day was null overall (RR 1.00), but became inverse after excluding PURE, highlighting definitional differences (e.g., exclusion of white rice from refined grains in PURE). Evidence low. |
| Evidence certainty | NutriGrade rated whole-grain evidence high for CVD and mortality, supporting causal plausibility via fiber, lipid, glucose, blood-pressure, inflammatory, and antioxidant pathways discussed on page 8. Refined-grain evidence uniformly low. |
Key implications
For regulators, whole-grain grains refined-grain cardiovascular risk evidence justifies endorsing whole-grain intake targets and discouraging high refined-grain patterns in HTMC-aligned standards. Certification should require grain-type disclosure, serving-size quantification per 30 g, and verification that “whole grain” includes bran and germ. Industry can reformulate staples toward higher whole-grain content. Research gaps include stroke subtypes, grain-type specificity, and consistent refined-grain definitions. Practically, set tiered HTMC benchmarks at ≥60–90 g/day whole grains while restricting refined-grain servings.
Citation
Hu H, Zhao Y, Feng Y, Yang X, Li Y, Wu Y, Yuan L, Zhang J, Li T, Huang H, Li X, Zhang M, Sun L, Hu D. Consumption of whole grains and refined grains and associated risk of cardiovascular disease events and all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies. The American Journal of Clinical Nutrition. 2023;117(1):149-159. doi:10.1016/j.ajcnut.2022.10.010
