Table 2. Grading of evidence for etiologic effects of specific dietary factors on cardiometabolic outcomes1.
| Dietary Factor | Cardiometabolic Outcome | Strength | Consistency | Temporality | Coherence | Specificity | Analogy | Plausibility | Biological Gradient | Experiment |
|---|---|---|---|---|---|---|---|---|---|---|
| Foods | ||||||||||
| Fruits | CHD | + | ++ | +++ | +++ | ++ | +++5 | +++ | +++ | ++23 |
| Ischemic stroke | ++ | +++ | +++ | +++ | ++ | +++5 | +++ | +++ | ++23 | |
| Hemorrhagic stroke | +++ | +++ | +++ | +++ | ++ | +++5 | +++ | +++ | ++23 | |
| Vegetables | CHD | + | ++ | +++ | +++ | ++ | +++5 | +++ | +++ | ++23 |
| Ischemic stroke | ++ | ++ | +++ | +++ | ++ | +++5 | +++ | +++ | ++23 | |
| Hemorrhagic stroke | ++ | ++ | +++ | +++ | ++ | +++5 | +++ | +++ | ++23 | |
| Beans/legumes | CHD | +++ | +++ | +++ | +++ | +++ | +++5 | +++ | +++ | ++ |
| Nuts/seeds | CHD (fatal) | +++ | +++ | +++ | +++ | ++ | +++5 | +++ | +++ | +++ |
| CHD (non-fatal) | +++ | +++ | ++ | +++ | ++ | +++5 | +++ | +++ | +++ | |
| Diabetes | ++ | +++ | +++ | +++ | ++ | +++5 | +++ | +++ | ++ | |
| Whole grains | CVD | + | +++ | +++ | +++ | ++ | +++6 | +++ | +++ | +++24 |
| CHD | + | +++ | +++ | +++ | ++ | +++6 | +++ | +++ | +++24 | |
| Diabetes | ++ | +++ | +++ | +++ | ++ | +++6 | +++ | +++ | +++24 | |
| Red meats, unprocessed | Diabetes | ++ | +++ | +++ | +++ | +++ | +++7 | ++ | +++ | ++ |
| Processed meats | CHD | +++ | +++ | +++ | +++ | ++ | +++8 | +++ | +++ | +++ |
| Diabetes | +++ | +++ | +++ | +++ | ++ | +++7 | ++ | +++ | ++ | |
| Yogurt | Diabetes | ++ | ++ | +++ | +++ | +++ | ++9 | ++ | +++ | ++25 |
| Sugar-sweetened beverages | Body mass index | +++4 | +++ | +++ | +++ | +++ | +++10, 11 | +++ | +++ | +++ |
| CHD | ++ | +++ | ++ | +++ | ++ | ++10 | ++ | +++ | ++ | |
| Diabetes | +++ | +++ | +++ | +++ | +++ | +++11 | +++ | +++ | +++ | |
| Nutrients | ||||||||||
| PUFAs | CHD | + | ++ | +++ | +++ | +++ | +12 | +++ | +++ | +++ |
| Seafood ω-3s (fish/seafood)2 | CHD (fatal) | ++ | +++ | +++ | +++ | +++ | +++13 | +++ | +++22 | +++ |
| Trans-fats | CHD | +++ | +++ | +++ | +++ | +++ | ++14 | +++ | +++ | +++ |
| Dietary fiber | CVD | +++ | +++ | +++ | +++ | ++ | +++15 | +++ | +++ | +++ |
| CHD | +++ | +++ | +++ | +++ | ++ | +++15 | +++ | +++ | +++ | |
| Stroke | ++ | +++ | +++ | +++ | ++ | +++15 | +++ | +++ | ++ | |
| Diabetes | ++ | +++ | +++ | +++ | ++ | +++16 | +++ | +++ | +++ | |
| Glycemic load | CHD | +++3 | +++3 | +++ | +++ | ++ | ++10 | ++ | ++21 | ++ |
| Stroke | ++ | +++ | +++ | +++ | ++ | +17 | ++20 | ++21 | ++ | |
| Diabetes | + | ++ | +++ | +++ | ++ | +++11 | +++ | ++21 | +++ | |
| Sodium | Systolic BP | ++4 | +++ | +++ | +++ | +++ | +19 | +++ | +++ | +++ |
| CVD (fatal) | ++ | ++ | +++ | +++ | ++ | +++18 | +++ | + | +++ | |
| Potassium | Stroke | ++ | +++ | +++ | +++ | +++ | +++18 | +++ | +++ | +++ |
1 To score each Bradford-Hill criterion, the following general principles were utilized, focusing on evidence from meta-analyses of prospective cohort studies and/or randomized controlled trials: +++ Consistent evidence from several well-designed studies with relatively few limitations; ++ Consistent evidence from several studies but with some important limitations; + Emerging evidence from a few studies or conflicting results from several studies;—criterion not met. Definitions for each of the nine criteria and adaptations to the general scoring system were as follows: Strength: magnitude of association, including RRs for protective factors of >0.9 (+), 0.8–0.89 (++), or <0.8 (+++); and for harmful factors, of <1.11 (+), 1.25 (++), and >1.25 (+++). Since magnitude is directly dependent on both the selected serving size and frequency of consumption, we utilized serving sizes most similar to standard dietary guidelines and frequencies of consumption representing modest, standardized differences in intake (e.g., 1 serving/d of fruit) that are easily communicated and could be feasibly achieved by an intervention. Consistency: association is repeatedly observed in different populations and circumstances, including ≥80% of included study-specific estimates being in the expected direction (+++); ≥60 - <80% (++); ≥40 - <60% (+); and <40% (not meeting criteria). Temporality: exposure precedes outcome. Because all evidence was based on longitudinal studies, this was a necessary criterion (+++); when relatively few overall studies were available (<5), we graded this criterion conservatively as ++. Coherence: interpretation of association does not conflict with known natural history and biology of the disease, for example based on pathways of disease occurrence and laboratory findings on the dietary factor. Specificity: exposure linked to a specific outcome. Because many nutritional factors can plausibly have diverse effects and influence multiple outcomes, scoring was based on three principles: 1) dietary factor influences a mechanism/pathways known to cause the outcome; 2) dietary factor not associated with multiple other, unrelated non-communicable diseases (e.g., multiple cancers, chronic obstructive pulmonary disease (COPD)); 3) dietary association has additional specificity within the set of cardiometabolic outcomes (coronary heart disease (CHD), stroke, diabetes mellitus). Analogy: based on the effects of similar factors on the disease outcome; see detailed footnotes below. Plausibility: association supported by one or more credible biological mechanisms. Biological gradient: exposure and outcome are related by a monotonic dose-response curve. Experiment: association is also supported by evidence from randomized controlled trials on intermediate risk factors (or, less commonly, disease outcomes) plus supportive laboratory studies.
2 Given their common sources, these factors were evaluated together based on studies of fish/seafood, dietary long-chain omega-3 fats, and fish oil supplements.
3 In secondary stratified analyses, +++ for women, and—for men (main effect: null).
4 Effect size does not correspond to relative risk, but comparison with effect sizes on body mass index or blood pressure (BP) for other lifestyle-based interventions. For BP, the overall scored strength reflects the average of +++ for older adults, blacks, and hypertensives; and + for healthy, white, younger adults.
5 Based on analogies with other minimally processed, higher fiber, phytochemical rich foods.
6 Based on analogies with other less-processed foods, dietary fiber, and glycemic load.
7 Based on analogies to processed meats (or unprocessed red meats), blood ferritin levels, and hemochromatosis.
8 Based on analogies to sodium.
9 Based on analogies to probiotics in relation to weight gain.
10 Based on analogies to other poor-quality carbohydrates in relation to both CHD and weight gain.
11 Based on analogies to other poor-quality carbohydrates in relation to both diabetes mellitus and weight gain.
12 Based on analogies to vegetable oils in relation to CHD and cardiovascular risk factors.
13 Based on analogies to fish.
14 Based on analogies to other dietary fats.
15 Based on analogies to other higher-quality carbohydrates and other fiber-rich foods such as nuts, fruits, and vegetables.
16 Based on analogies to other higher-quality carbohydrates in relation to both diabetes mellitus and weight gain.
17 Based on analogies to other poor-quality carbohydrates in relation to diabetes mellitus, and diabetes as a risk factor for stroke.
18 Based on analogies to other lifestyle-related and nonlifestyle-related blood pressure interventions and to foods high in sodium (e.g., processed meats).
19 Based on analogies to potassium.
20 Based on insulin resistance/diabetes mellitus pathways.
21 Several individual studies show dose response; no published dose-response meta-analyses.
22 Between 0 and 250 mg/d; meta-analyses suggest no major additional benefits for fatal CHD above 250 mg/d.
23 Because while strong and consistent evidence from trials of dietary patterns rich in fruits and vegetables, few trials separately evaluated only fruits or vegetables.
24 Based on overall effects of carbohydrate quality, including studies of dietary fiber and glycemic load; much less evidence for benefits of whole grains independent of dietary fiber and glycemic load.
25 Based on findings for yogurt and weight gain (animal studies, human cohorts) and for probiotics and weight gain (animal and human experiments).