The idea that fruits and vegetables are beneficial seems indisputable. We have all had it drilled into our heads that we should eat multiple servings per day.
The American Heart Association, for example, recommends eating "plenty of fruits and vegetables" (1).
Despite these recommendations, the evidence in support of fruits and vegetables is surprisingly weak. The bulk of the "evidence" comes from the epidemiological observational study — a design with major limitations.
Even worse, epidemiological studies themselves have started doubting the alleged benefits of fruits and vegetables, as the following quotations show (2-6):
In this large prospective study, we found some small inverse associations between plant foods and IHD [ischemic heart disease] risk. . . . As with other observational studies, the associations reported may be subject to residual confounding, and whether these small associations are causal remains unclear [2].
Higher intakes of raw, but not cooked, vegetables were associated with lower CVD [cardiovascular disease] risk. Residual confounding is likely to account for much, if not all, of the observed associations. This study suggests the need to reappraise the evidence on the burden of CVD disease attributable to low vegetable intake in the high-income populations [3].
Cooked and raw vegetable intake was not associated with CHD [coronary heart disease], AF [atrial fibrillation] or HF [heart failure]. Raw vegetable intake is likely to reduce risk of stroke, but warrants more research. Solely increasing vegetable intake may have limited protection, if any, on cardiovascular health [4].
With vegetables, we did not see a protective effect [6].
Thus, fruits and vegetables may indeed associate with cardiovascular disease in many epidemiological cohorts, but these associations may simply reflect biases, not cause and effect.
What About Biomarkers?
For biomarkers (lipids, blood pressure, blood glucose, etc.), high-quality long-term evidence is lacking.
Rees and colleagues (2021) observed "considerable uncertainty about the effects of a vegan diet [exclusively plant-based] on CVD clinical endpoints and CVD risk factors for both primary and secondary prevention" (7). This review, however, could not isolate the potential effects of fruits and vegetables.
Perhaps more surprising is the inconsistent evidence on oxidative damage. Part of the alleged benefit of fruits and vegetables is supposedly from their antioxidant content, but there is no consistent evidence that antioxidant-rich foods will prevent oxidative damage:
While some studies have shown that antioxidant-rich foods or beverages can lower oxidative damage levels in vivo, many have not, or have given mixed messages [8].
And even if fruits and vegetables did have clear effects on biomarkers, the clinical relevance of these changes would remain unclear. We know that biomarkers are generally poor predictors of health outcomes (see here).
Therefore, neither the observational nor the biomarker data could provide convincing evidence in favor of fruits and vegetables.
To quote a 2022 paper by Dr. Qi Feng:
So far, most of the evidences are observational or generated from small randomized trials with short follow-up periods. The observational associations are very likely to be limited by residual confounding, whereas the small trails with short follow-up periods provide restricted evidence for the long-term effects. . . . Previous evidence on the effects of vegetable intake on metabolic risk factors are mainly from observational studies or small randomized controlled trials, and showed substantial inconsistency [9].
Randomized Trials on Hard Outcomes
There are two main randomized trials on fruit/vegetable intake: The Women’s Healthy Eating and Living (WHEL) Study published in 2007 (10), and The Men’s Eating and Living (MEAL) Study published in 2020 (11).
The WHEL trial tested a diet “very high in vegetables, fruit, and fiber and low in fat” on breast cancer events and total mortality. Throughout the 7.3-year follow-up, fruit and vegetable intake (including vegetable juice) remained higher in the intervention group than in the control group (supported by plasma biomarkers).
So, what were the results?
For breast cancer, the researchers did not find evidence of benefit:
During the study, 518 participants had a breast cancer event, representing 256 participants (16.7%) in the intervention group and 262 participants (16.9%) in the comparison group. The disease-free survival curves were virtually identical across groups [HR, 0.99; 95% CI, 0.83-1.17; P = .87].
Similarly, there was no evidence that the intervention affected the risk of death (overall mortality):
There were 315 deaths reported within the study period, with 155 (10.1%) in the intervention group and 160 (10.3%) [HR, 0.97; 95% CI, 0.78-1.22; P = .82].
Thus, they concluded:
Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.
The MEAL trial, on the other hand, asked the following question:
Does a behavioral intervention promoting vegetable consumption decrease cancer progression in men with early-stage prostate cancer on active surveillance?
The MEAL investigators randomized participants to an intervention with increased vegetable consumption or a control group. At 12 months, the intervention participants reported "significant increases" in daily total vegetable servings, cruciferous servings, and total carotenoids, which persisted throughout the study (supported by plasma biomarkers).
Just as in the WHEL study, the researchers did not find evidence of benefit, stating:
The behavioral intervention in this study produced robust, sustained increases in carotenoid, cruciferous-rich, and leafy green vegetable intake for 2 years, but did not significantly reduce the risk of clinical progression compared with control in patients with early-stage prostate cancer on active surveillance. These data fail to support prevailing assertions in evidence-based clinical guidelines and the popular media that diets high in micronutrient-enriched vegetables improve cancer-specific outcomes among prostate cancer survivors.
They also noted the limitations of epidemiology and the need for more trials:
Enthusiasm for diet-based cancer interventions remains high, driven by assumptions of causality made from epidemiological data. Inherent limitations in these data include small effect sizes and substantial confounding. The overdependence of prostate cancer nutrition guidelines on observational studies with uncertain clinical validity suggests a need to shift nutritional research toward definitive RCTs.
A few other points:
First, the intervention in both WHEL and MEAL led to a slight decrease in saturated fat intake (a 15% to 19% reduction). This is consistent with larger analyses suggesting little to no benefit for modifying fat consumption on cancer mortality or overall mortality.
Second, some researchers hypothesize that those with lower intakes of fruits and vegetables at baseline would benefit. But this was not supported by analyses from WHEL and MEAL. It remains to be seen whether those with zero consumption of fruits and vegetables would benefit from eating some.
Third, there are other (multiple-interventional) trials involving increased intakes of fruits and vegetables, but these did not indicate a potential benefit (12-15).
Conclusion
In 2009, Dauchet, Amouyel, and Dallongeville published a review on fruit and vegetables with the following key points (16):
Thirteen years later, these points still largely hold. If anything, there is less support now for vegetable intake than ever before.
References
1) Lichtenstein, A. H., Appel, L. J., Vadiveloo, M., Hu, F. B., Kris-Etherton, P. M., Rebholz, C. M., ... & American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; and Stroke Council. (2021). 2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association. Circulation, 144(23), e472-e487.
2) Perez-Cornago, A., Crowe, F. L., Appleby, P. N., Bradbury, K. E., Wood, A. M., Jakobsen, M. U., ... & Key, T. J. (2021). Plant foods, dietary fibre and risk of ischaemic heart disease in the European prospective investigation into cancer and nutrition (EPIC) cohort. International journal of epidemiology, 50(1), 212-222.
3) Feng, Q., Kim, J. H., Omiyale, W., Bešević, J., Conroy, M., May, M., ... & Lacey, B. (2022). Raw and cooked vegetable consumption and risk of cardiovascular disease: a study of 400,000 adults in UK Biobank. Frontiers in nutrition, 77.
4) Feng, Q., Grant, A. J., Yang, Q., Burgess, S., Besevic, J., Conroy, M., ... & Lacey, B. (2022). Vegetable intake and cardiovascular risk: genetic evidence from Mendelian randomization. medRxiv.
5) Weston, L. J., Kim, H., Talegawkar, S. A., Tucker, K. L., Correa, A., & Rebholz, C. M. (2022). Plant-based diets and incident cardiovascular disease and all-cause mortality in African Americans: A cohort study. PLoS medicine, 19(1), e1003863.
7) Rees, K., Al-Khudairy, L., Takeda, A., & Stranges, S. (2021). Vegan dietary pattern for the primary and secondary prevention of cardiovascular diseases. Cochrane Database of Systematic Reviews, (2).
8) Halliwell, B., & Gutteridge, J. M. (2015). Free radicals in biology and medicine. Oxford university press, USA.
9) Feng, Q., & Besevic, J. (2022). Vegetable intake and metabolic risk factors: A Mendelian randomization study. medRxiv.
10) Pierce, J. P., Natarajan, L., Caan, B. J., Parker, B. A., Greenberg, E. R., Flatt, S. W., ... & Stefanick, M. L. (2007). Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial. Jama, 298(3), 289-298.
11) Parsons, J. K., Zahrieh, D., Mohler, J. L., Paskett, E., Hansel, D. E., Kibel, A. S., ... & Marshall, J. (2020). Effect of a behavioral intervention to increase vegetable consumption on cancer progression among men with early-stage prostate cancer: the MEAL randomized clinical trial. JAMA, 323(2), 140-148.
12) Schatzkin, A., Lanza, E., Corle, D., Lance, P., Iber, F., Caan, B., ... & Polyp Prevention Trial Study Group. (2000). Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. New England Journal of Medicine, 342(16), 1149-1155.
13) Howard, B. V., Van Horn, L., Hsia, J., Manson, J. E., Stefanick, M. L., Wassertheil-Smoller, S., ... & Kotchen, J. M. (2006). Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. Jama, 295(6), 655-666.
14) Burr, M. L., Gilbert, J. F., Holliday, R. A., Elwood, P. C., Fehily, A. M., Rogers, S., ... & Deadman, N. M. (1989). Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). The Lancet, 334(8666), 757-761.
15) Fehily, A. M., Vaughan‐Williams, E., Shiels, K., Williams, A. H., Horner, M., Bingham, G., ... & Holliday, R. M. (1989). The effect of dietary advice on nutrient intakes: evidence from the diet and reinfarction trial (DART). Journal of Human Nutrition and Dietetics, 2(4), 225-235.
16) Dauchet, L., Amouyel, P., & Dallongeville, J. (2009). Fruits, vegetables and coronary heart disease. Nature Reviews Cardiology, 6(9), 599-608.