Scientists tested how much whole grain makes a difference. The answer was not simply “more”

by · News-Medical

Across 87 randomized trials, researchers examined how different amounts of whole grains affected cholesterol, blood pressure, blood glucose, body weight and inflammation, revealing a complex dose-response pattern.

Study: Whole-grain consumption and cardiometabolic risk: a meta-analysis of randomized trials. Image Credit: Ulada / Shutterstock

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A recent meta-analysis of randomized controlled trials published in the European Heart Journal found that higher whole-grain intake was associated with improvements in several cardiometabolic risk factors in adults, though many individual changes were small and clinically irrelevant. Dose-response analyses identified clinically relevant effects for some outcomes at specific intake levels.

Background

Cardiometabolic diseases include disorders like type 2 diabetes and cardiovascular disease (CVD), the latter being the leading cause of premature death worldwide. A healthy diet helps prevent cardiometabolic disease.

Whole grains are a key component of healthy diets. They contain the bran, germ, and endosperm of the grain, and are rich in cardioprotective compounds. Low whole-grain intake remains among the major factors associated with higher mortality and disease burden.

Their consumption has been associated with better cardiometabolic health in observational studies, but these studies cannot establish causality. Randomized controlled trials have not provided consistent evidence of improvements in body weight or blood lipid levels with increased whole-grain intake.

The current study sought to provide clearer information on this question.

Study characteristics

The researchers conducted a systematic review and meta-analysis of randomized controlled trials investigating the effects of whole-grain consumption on cardiometabolic risk factors. In particular, they aimed to assess the dose-response relationship between whole-grain consumption and cardiometabolic risk factors.

Eligible trials lasted at least two weeks and compared a diet containing whole grains with a low-whole-grain diet, usual or routine care, or a diet containing refined grains. Whole-grain interventions generally provided between about 12 and 213 g per day of whole grains, measured as dry weight.

The review included 101 publications representing 87 randomized trials. The primary outcomes were body weight, LDL cholesterol, fasting plasma glucose, and adverse events. Multiple secondary outcomes were also evaluated, including waist circumference, body fat, blood pressure, HbA1c, fasting insulin, and lipoprotein profiles. Health-related quality of life and inflammatory markers were also measured.

Effects on weight, blood glucose and LDL cholesterol

Whole-grain consumption was associated with a small reduction in body weight. Across 60 trials involving 4,390 participants, whole-grain interventions reduced body weight by an average of 0.51 kg compared with control diets. Although the evidence was considered high certainty, the magnitude of the reduction was clinically irrelevant.

Fasting plasma glucose was also slightly lower with whole-grain consumption. The average reduction was 0.07 mmol/L, though results varied substantially between studies. The researchers rated this as moderate-certainty evidence, but considered the reduction too small to be clinically important.

Among the primary outcomes, the clinically relevant finding in the pairwise analysis was a reduction in LDL cholesterol of 0.13 mmol/L with increased whole-grain consumption. The evidence was rated as moderate certainty, and the reduction exceeded the predefined threshold for a clinically relevant difference.

Other cardiometabolic outcomes

Whole-grain consumption was associated with small reductions in several additional measures. Waist circumference decreased by 0.60 cm, while HbA1c decreased by 0.05 percentage points. Both changes were considered clinically irrelevant.

Triglycerides decreased by 0.05 mmol/L and total cholesterol by 0.17 mmol/L. Though the reductions were statistically significant, neither was considered clinically important according to the researchers' predefined thresholds.

The intervention also produced small reductions in blood pressure. Systolic blood pressure decreased by an average of 1.50 mmHg, while diastolic blood pressure decreased by 0.82 mmHg. Both effects were considered clinically irrelevant.

Whole-grain consumption was also associated with a small reduction in interleukin-6 (IL-6), an inflammatory marker, but this reduction was considered clinically irrelevant. Several of these associations, such as with diastolic blood pressure, body fat percentage, HbA1c, and IL-6, were sensitive to the removal of individual studies. Other parameters did not show clear effects or were supported by lower-certainty evidence.

Whole-grain intake was not associated with an increase in mild-to-moderate adverse events, but these events were inconsistently reported, and the evidence was of low certainty.

Dose-response relationship

The dose-response analysis found that an increase of 48 g per day of whole grains, equivalent to about 90 g of fresh weight or three servings, was linearly associated with reductions in LDL cholesterol, body weight, fasting glucose, waist circumference, HOMA-IR, a measure of insulin resistance, triglycerides, total cholesterol, systolic blood pressure, C-reactive protein and interleukin-6.

Nonlinear analyses suggested that some outcomes showed their greatest reductions at moderate intake levels rather than in strictly progressive fashion.

For total cholesterol, LDL cholesterol and triglycerides, the largest estimated reductions were associated with an intake of about 80 g of whole grain per day. At this intake, the reductions were approximately 0.21, 0.16 and 0.08 mmol/L, respectively. The LDL cholesterol reduction exceeded its predefined threshold for clinical importance. The authors also interpreted the reduction in triglycerides as clinically relevant, while the total cholesterol estimate remained below its listed threshold.

HDL cholesterol initially decreased slightly with increasing whole-grain intake up to about 60 g per day and then increased at higher intakes. Relatively few data points were available at these higher intake levels.

The largest estimated increase was at approximately 220 g per day, corresponding to 0.19 mmol/L, exceeding the predefined minimally important difference. This high-intake estimate is less certain because few trials tested such doses.

The pattern for systolic blood pressure was also nonlinear. The greatest estimated reductions occurred at approximately 60 and 80 g per day, with reductions of 2.44 and 2.35 mmHg, respectively, exceeding the predefined minimally important difference.

C-reactive protein showed another nonlinear pattern, with the greatest reduction (0.58 mg/L) at around 60 g per day, but the estimated reduction decreased at higher intakes.

Clinical relevance

The current analysis included more trials and evaluated more outcomes using both linear and nonlinear dose-response analyses. The researchers also accounted for differences in whole-grain dose ranges and subtypes.

These differences may have contributed to the ability to identify some associations more clearly than with previous studies. The reductions in LDL-C and triglycerides at 80 g/day, compared with the greatest estimated increase in HDL-C at 220 g/day, could contribute to lower coronary heart disease risk, according to the authors. The difference in pattern suggests a stronger contribution from reductions in LDL-C and triglycerides than from increases in HDL-C.

Limitations

Because the analysis was based on randomized trials, it provides stronger evidence on the effects of whole-grain interventions than an analysis based solely on observational associations.

The median follow-up was eight weeks, which might not have allowed for the observation of larger or cumulative effects, possibly contributing to the fact that observational analyses show stronger inverse associations of whole-grain intake with CVD risk. The authors also note that whole grains may have additive effects across multiple cardiovascular risk factors, resulting in a greater reduction in cardiovascular risk than would be inferred from the effects on individual risk factors.

There was substantial variation across studies in the type of whole grain consumed, outcomes, follow-up duration, study populations, and sample sizes. Participants and staff delivering the interventions were generally not blinded. Many studies also handled missing data by analyzing only participants who adhered to the trial protocol rather than using intention-to-treat analyses.

Background whole-grain intake was not typically reported, though habitual dietary patterns are important contributors to overall cardiometabolic risk and might blur the distinction between intervention and control diets. The apparent effects may also depend on what whole grains replaced in participants' diets, with comparisons against refined grains providing the clearest evidence of substitution effects. Data were sparse above about 140 g/day, which widened confidence intervals and limited certainty about very high intakes. The sensitivity analyses found that some results, including those for diastolic blood pressure, HbA1c, interleukin-6 and body fat percentage, changed markedly after individual studies were removed.

Conclusion

This meta-analysis of randomized trials found that increasing whole-grain consumption was associated with modest improvements in several cardiometabolic measures. The authors suggest that intakes of around 60 to 100 g/day dry weight may be associated with improvements in multiple cardiovascular risk factors and caution that “these targets should be interpreted as evidence-based benchmarks rather than universal prescriptions.”

The dose-response analyses suggested that some cardiometabolic effects may be greatest at moderate rather than continuously rising levels of whole-grain consumption.

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