Eating Vegetables Does Not Protect Against Heart Disease; BBC headline is 'Vegetables alone not enough to reduce heart risk, study finds'

Raw and Cooked Vegetable Consumption and Risk of Cardiovascular Disease: A Study of 400,000 Adults in UK Biobank. Qi Feng. Frontiers in Nutrition, Feb 21 2022. https://doi.org/10.3389/fnut.2022.831470

Objectives: Higher levels of vegetable consumption have been associated with a lower risk of cardiovascular disease (CVD), but the independent effect of raw and cooked vegetable consumption remains unclear.

Methods: From the UK Biobank cohort, 399,586 participants without prior CVD were included in the analysis. Raw and cooked vegetable intakes were measured with a validated dietary questionnaire at baseline. Multivariable Cox regression was used to estimate the associations between vegetable intake and CVD incidence and mortality, adjusted for socioeconomic status, health status, and lifestyle factors. The potential effect of residual confounding was assessed by calculating the percentage reduction in the likelihood ratio (LR) statistics after adjustment for the confounders.

Results: The mean age was 56 years and 55% were women. Mean intakes of raw and cooked vegetables were 2.3 and 2.8 tablespoons/day, respectively. During 12 years of follow-up, 18,052 major CVD events and 4,406 CVD deaths occurred. Raw vegetable intake was inversely associated with both CVD incidence (adjusted hazard ratio (HR) [95% CI] for the highest vs. lowest intake: 0.89 [0.83–0.95]) and CVD mortality (0.85 [0.74–0.97]), while cooked vegetable intake was not (1.00 [0.91–1.09] and 0.96 [0.80–1.13], respectively). Adjustment for potential confounders reduced the LR statistics for the associations of raw vegetables with CVD incidence and mortality by 82 and 87%, respectively.

Conclusions: Higher intakes of raw, but not cooked, vegetables were associated with lower CVD 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.

Press release: Eating Vegetables Does NOT Protect Against Heart Disease (scitechdaily.com)

Discussion

In this large prospective cohort study, total vegetable intake was associated with reduced risks of CVD incidence, CVD mortality, and all-cause mortality. When assessing the independent effect of raw and cooked vegetable intake, only raw vegetable intake showed inverse associations with CVD outcomes, whereas cooked vegetables showed no association. However, given the large reductions in the predictive values of total and raw vegetable intake after adjustment for socioeconomic and lifestyle factors, residual confounding is likely to account for much, if not all, of the remaining associations.

The modest inverse associations of total vegetable intake with CVD outcomes and all-cause mortality in our analyses are consistent with previous large-scale observational evidence. For example, a meta-analysis of 24 cohort studies estimated that high vegetable intake reduced all-cause mortality by about 13% (relative risk 0.87 [0.82–0.92]) (15). Previous systematic reviews showed total vegetable consumption was associated with a risk reduction in CVD incidence by 11 (15) to 18% (16), similar to the ~10% lower risk in this study. Our findings of the inverse association with MI are also in line with published meta-analyses with effect sizes ranging from 9 to 15% (15–17). Although previous studies have also demonstrated an association with a reduced risk of stroke (15–17), we did not find sufficient evidence for such an association.

In contrast to a large number of studies on total vegetable intake, there is limited evidence on the independent effect of raw and cooked vegetables on all-cause mortality. Aune et al. (15) conducted a meta-analysis that found cooked vegetable was associated with 13% (relative risk 0.87 [0.80–0.94]) lower risk of all-cause mortality, and raw vegetable was associated with 12% (relative risk 0.88 [0.79–0.98]) lower risk of mortality, although the analyses of raw and cooked vegetables were not mutually adjusted. Studies that have attempted to assess the independent effects of raw and cooked vegetable intakes on all-cause mortality have reported conflicting results. Our results are broadly consistent with the EPIC study (7), in which both raw vegetable intake and cooked vegetable intake were associated with reduced risk of all-cause mortality. By contrast, the PURE study (8) reported an inverse association with all-cause mortality for raw vegetable intake, but not for cooked vegetable intake, while an Australian cohort study (9) reported that only cooked vegetable intake was associated with lower overall mortality. The characteristics and main findings of these studies are summarized in Supplementary Table 10.

In this study, cooked vegetable intake and raw vegetable intake showed different associations with cardiovascular outcomes. We found inverse associations of raw vegetables with CVD incidence and mortality, but null associations with cooked vegetables. This is consistent with the MORGEN study, a Dutch cohort (18), in which raw, but not processed, vegetables were associated with a reduced risk of ischemic stroke. In the EPIC cohort (7), there was a stronger inverse association of CVD mortality with raw than cooked vegetables. Whereas the PURE study (8) found no evidence of an association of CVD and raw vegetable intake, and high intakes levels of cooked vegetable was positively associated with CVD incidence.

Previous studies that reported associations of higher levels of vegetable intake with lower risk of CVD have proposed various mechanisms by which these associations might be mediated. For example, it has been suggested that diets high in vegetables have, on average, fewer calories and replace foods that are high in fat, sodium, and glycemic load (15, 19). It has also been hypothesized that the lower risk might be mediated by micronutrients, namely, higher intake of vitamins, polyphenols, and antioxidant compounds (2, 5), which are required for regulating various biological processes, including anti-oxidation, anti-inflammation, lipid metabolism, and endothelial function (20). As for the different associations of raw and cooked vegetables observed in this and other studies, several possible mechanisms have been proposed in previous studies. First, it has been proposed that the kinds of vegetables that are usually consumed cooked (e.g., beans, peas, eggplant) may differ from those typically consumed raw (e.g., lettuce). Second, cooking processes can alter the digestibility of food as well as the bioavailability of nutrients (21). For example, Lee et al. found that vitamin C retention after cooking ranged from 0 to 91% for various combinations of cooking methods and vegetable, with higher retention after microwaving and lower retention after boiling (22). Third, the seasoning and oils used in cooking vegetables often increase intake of sodium and fat, which are known risk factors for CVD incidence and mortality (23, 24).

Despite these proposed mechanisms, this study indicates that observed associations of vegetable intakes with CVD risk and all-cause mortality are likely to be mostly accounted for by residual confounding. Studies using Mendelian randomization (which are less susceptible to confounding, and other biases of observational studies) might be particularly useful in reliably assessing the associations of diet on disease risk. For example, a recent Mendelian randomization study that used genetic determinants of plasma vitamin C concentration as a surrogate for vegetable intake reported a null association with ischemic heart disease (odds ratio 0.90 [0.75–1.08]) and all-cause mortality (odds ratio 0.88 [0.72–1.08]), despite strong inverse associations between vitamin C and these outcomes in observational analyses (25).

This study found the observed associations were mainly accounted for by socioeconomic status and lifestyle factors (26). Both the low socioeconomic status and major lifestyle factors, such as smoking and alcohol intake, are established risk factors for CVD, and there is strong evidence that the effect of socioeconomic status is partially mediated by the known lifestyle factors (27). For example, one study reported that an unhealthy lifestyle (including smoking, drinking, obesity, physical inactivity, and others) mediated 34–38% of the association between socioeconomic status and all-cause death (28). Therefore, given the complicated inter-relationship between socioeconomic status, lifestyle, and health outcomes, adjustment of measures of both socioeconomic status and lifestyle factors is likely to be important.

This study has some limitations. First, we did not measure intake of specific types of raw or cooked vegetables, nor were we able to account for differences in cooking methods. Second, vegetable intakes are self-reported in the baseline dietary questionnaire, although the validity and repeatability of the UK Biobank baseline dietary questionnaire have been evaluated and confirmed in previous studies (12). Third, we did not adjust for total calorie intake because such information was not available from the baseline dietary questionnaire, but we did adjusted for physical activity level and BMI, which has been shown as a valid method for isocaloric adjustment (29). Future studies should seek to address these limitations. However, such studies should also be aware of the importance of assessing reliably for residual confounding using similar methods to this report, or other approaches, such as Mendelian randomization.

Although this report does not find strong evidence of an association between higher vegetable intake and reduced risk of major CVD, the wider literature suggests that increasing vegetable intake is likely to reduce the risk of some other common diseases (4). As such, the public health recommendations on the benefits to health and the environment of a diet that is high in vegetable intake remain.