Substitution of animal-based with plant-based foods on cardiometabolic health and all-cause mortality: a systematic review and meta-analysis of prospective studies

The current food system has been shown to be detrimental to planetary health by depleting Earth’s resources and contributing to climate change, thus decreasing the quality and sufficiency of food [1, 2]. Furthermore, non-communicable diseases related to dietary choices such as cardiovascular diseases (CVD) and type 2 diabetes (T2D) highly contribute to deaths worldwide [3]. Therefore, the food system and current dietary habits negatively impact both planetary and human health [2]. Consequently, one of the approaches to address these problems is to change dietary habits [2, 4]. Plant-based diets are the focus of recent studies suggesting that increased intake of plant-based foods is not only beneficial for planetary health [2, 4], but also reduces the risk of T2D, CVD, and premature death [5, 6]. In contrast, the production and consumption of animal-based foods, especially red and processed meat, pose a high burden on the environment [2] and have been linked to increased risk for CVD, T2D, and mortality [7‐9]. Such findings contribute to recommendations to reduce the intake of red and processed meat. However, to keep energy intake constant, other foods need to be consumed instead and the association with disease risks may depend on this substitution [10]. A promising option is the replacement of animal-based with plant-based foods. In this context, epidemiological studies investigated the substitution of animal-based foods with other protein sources and indicated that such a replacement is associated with reduced risk of CVD, T2D, and mortality [11‐14]. A recent systematic review and meta-analysis found a lower risk for coronary heart disease (CHD) when replacing red meat with poultry, dairy, eggs, nuts, or legumes and a lower risk of all-cause mortality when substituting red meat with fish/seafood, poultry, eggs, or nuts [15]. However, the authors did not investigate further cardiometabolic endpoints, including CVD or T2D. Furthermore, the substitution of any animal based-foods with only plant-based foods has yet to be investigated in a systematic review and meta-analysis. Therefore, to clarify the strength and certainty of the overall evidence on this topic, there is an urgent need for a systematic review and meta-analysis examining the association between substituting animal-based with purely plant-based foods and cardiometabolic health outcomes, including CVD, stroke, myocardial infarction (MI), T2D, and mortality. Thus, it was our aim to summarize and evaluate the meta-evidence on the substitution of animal-based with plant-based foods regarding cardiometabolic health outcomes and all-cause mortality.

Our protocol was pre-registered at PROSPERO (https://​www.​crd.​york.​ac.​uk/​prospero/​display_​record.​php?​ID=​CRD42022302982). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 2020 [16]. All steps were conducted by at least two investigators, independently. Disagreements were solved by consensus.

Of the 1216 studies identified in our search after the removal of duplicates, 158 fulltext articles were considered for inclusion. Out of these, 126 publications were excluded, leaving 32 studies to be included in our analyses. A list of the excluded studies with reasons is provided in Additional file 2: Table S4 [12, 34‐157]. Additionally, five relevant studies were identified via hand search. Thus, 37 studies were included in our final meta-analyses (Fig. 1). All identified publications were prospective cohort studies. No randomized controlled trials (RCTs) analyzed as observational studies were included.

Twenty-two publications including 12 cohorts were conducted in the USA [11, 13, 14, 24‐29, 138, 154, 158‐168], ten publications including seven cohorts in Europe [30, 156, 157, 169‐175], and four studies including three cohorts in Asia [155, 176‐178]. One publication included one US and one European cohort [179]. In all cohorts except for three (using consecutive 24-h recalls [173, 177, 178]), diet was assessed using validated food frequency questionnaires. The mean follow-up duration was 19 years. All cohorts except for five included both men and women. One cohort (Health Professionals’ Follow-up Study (HPFS)) only included men [11, 13, 24‐29, 138, 154, 162, 163, 166] and four cohorts (Nurses’ Health Study (NHS), NHS II, Women’s Health Initiative (WHI), and Black Women’s Health Study (BWHS)) only women [11, 24‐29, 138, 154, 158, 159, 161‐166, 179] (Additional file 2: Table S2).

All publications were judged as moderate risk of bias, except for one [169] (Additional file 3: Fig. S1), which was judged as serious risk of bias due to insufficient adjustment of confounders (Additional file 3: Fig. S2). No study was judged as low risk of bias due to the possibility of residual confounding in observational studies and the possibility of measurement error in the dietary assessment.

This is the first systematic review and meta-analysis that summarized the associations between the substitution of animal-based with plant-based foods with a wide range of cardiometabolic outcomes, such as CVD mortality; incidence of CVD, CHD, and T2D; diabetes mortality, and all-cause mortality, and evaluated the risk of bias and certainty of evidence of the meta-findings. Our results indicate that replacing animal-based with plant-based foods is beneficially associated with cardiometabolic health. The substitution of red and processed meat with nuts, legumes, and whole grains reduced the risk of total CVD, CHD, and T2D and all-cause mortality with moderate certainty of evidence. We also observed moderate certainty of evidence for the association between the replacement of eggs with nuts and a lower incidence of total CVD and all-cause mortality. Additionally, replacing butter with olive oil lowered the incidence of total CVD, CVD mortality, total diabetes, and all-cause mortality with moderate certainty of evidence.

Furthermore, we found moderate certainty of evidence for an inverse association between the substitution of poultry with whole grains and T2D incidence and for the replacement of dairy products with nuts and legumes regarding all-cause mortality. For the other associations regarding the replacement of dairy products, poultry, or fish/seafood with plant-based foods, the certainty of evidence was low. However, our results indicated an inverse association for the substitution of poultry with nuts or legumes in relation to T2D incidence but no clear association for replacing dairy products, fish/seafood, or poultry with nuts or legumes regarding total CVD. In addition, no association was observed for the substitution of fish/seafood or poultry with nuts or legumes regarding all-cause mortality.

Our results are in agreement with a previous systematic review and meta-analysis investigating the replacement of red meat with other protein sources on CHD and all-cause mortality [15]. The authors observed a lower risk of CHD, when replacing red meat, processed red meat, and unprocessed red meat with nuts or legumes, and a lower risk of all-cause mortality when substituting red meat with nuts and processed red meat with nuts or legumes [15]. The certainty of evidence was assessed using NutriGrade [180] and was also rated as moderate for these associations [15]. However, they did not investigate further cardiometabolic endpoints, such as CVD mortality, CVD incidence, or T2D. Previous meta-analyses also support our findings that higher meat intake was associated with a risk of T2D [8], CHD, and stroke [7], as well as all-cause mortality [9]. This also applies to the associations between olive oil and CVD, T2D, and all-cause mortality [181, 182]. In contrast, a higher intake of eggs and butter was not associated with these outcomes in previous studies [7‐9]. However, these studies included no substitution analyses. This suggests that not only the amount of these foods consumed is important but that it also plays a role what foods they are replaced with. Furthermore, our results indicate that the replacement of dairy products with nuts and legumes is associated with a lower risk of CVD or all-cause mortality. However, dairy includes a wide range of different products (e.g., milk, yogurt, cheese) with different associations with cardiometabolic outcomes. For example, contrary to our results, a higher intake of yogurt was inversely associated with risk for all-cause and CVD mortality [183]. Thus, associations for the replacement of different subtypes of dairy products with plant-based foods might differ, and more research is needed on this aspect. A network meta-analysis of randomized controlled trials comparing different food groups and their effect on intermediate diseases markers, such as blood lipids, blood pressure, and glycaemic control parameters, also found that plant-based foods, such as nuts, legumes, and whole grains, were most beneficial for all outcomes combined [184]. Given these results, stronger associations for the replacement of animal-based foods with legumes might have been expected. However, the network meta-analysis focussed on intermediate endpoints and rather reflects short-term effects due to the inclusion of RCTs with shorter follow-up times (mainly around 8–12 weeks). Therefore, long-term effects on hard endpoints might differ. However, the certainty of evidence for the majority of the findings on legumes was low or very low, limiting our confidence in the results. Thus, future studies might provide more insight into these associations. Moreover, in line with our results, a network meta-analysis comparing different types of oils and solid fats on blood lipids confirmed a more beneficial effect of olive oil compared to butter [185].

There are different mechanisms that might explain the observed associations. First, it is likely that persons favoring plant-based foods follow a more health-conscious lifestyle in general. However, the included studies all adjusted for important lifestyle confounders such as total energy intake, physical activity, alcohol intake, and smoking, and the associations persisted. Nevertheless, residual confounding cannot be ruled out.

Furthermore, processed meat contains saturated fatty acids, such as stearic and palmitic acid, which potentially increase the risk of CVD and T2D [108, 116]. Moreover, red and processed meats contain compounds promoting oxidative stress and chronic low-grade inflammation, such as heme iron, sodium, nitrates, and nitrites that might be associated with increased risk of CVD, T2D, and mortality [54, 186]. In contrast, plant-based foods such as nuts, legumes, and whole grains, as well as olive oil, contain high amounts of anti-oxidant and anti-inflammatory compounds, including fiber, phytochemicals, vitamins and minerals, and polyphenols that show beneficial associations with cardiovascular health and, in relation to cardiovascular health, obesity [187, 188]. Thus, both the reduction of animal-based foods, especially meat, and the increase of plant-based foods simultaneously contribute to the observed beneficial associations regarding cardiometabolic health.

Our findings also highlight the need for future research. First, some of the results still show some inconsistencies. For example, both the substitution of processed and unprocessed red meat with legumes were associated with a lower risk of total CVD, while the association for the replacement of red meat with legumes was less clear. This was mainly due to an imprecise estimate of the latter association also resulting in a very low level of the certainty of evidence. Therefore, more studies on this association are needed in order to provide further insights into the consistency of these associations and to improve our confidence in the findings. In general, to increase the certainty of evidence, well-conducted prospective observational studies on the associations with low and very low certainty of evidence and on the associations only investigated in single studies are needed. This includes for example the substitution of dairy products, especially subtypes of dairy products, poultry, or fish/seafood with plant-based products, or the replacement of animal-based foods with further plant-based foods, such as fruit and vegetables. These studies should minimize the risk of bias, e.g., by using models with a sufficient level of adjustment, and use standardized portion sizes (e.g., 50 g for meat/poultry/fish/seafood, 30 g for whole grains/legumes, 5 g for butter/olive oil) for both the substituted food and the replacement in order to improve the comparability between the results and to decrease heterogeneity between the studies. Furthermore, the majority of the studies investigated a theoretical substitution. Future studies should focus more on an observed change in food intake, as was done in three recent studies [11, 29, 30]. Moreover, more research is needed on the substitution of animal-based products with meat and dairy replacement foods, which strongly gained popularity in recent years.

Our findings suggest that a shift in diet from a high consumption of animal-based foods, especially red and processed meat, to plant-based foods (e.g., nuts, legumes, and whole grains) is associated with a lower risk of all-cause mortality, CVD, and T2D. Thus, a change in dietary habits towards an increment of plant-based products appears to be important for cardiometabolic health. However, more research is needed in order to strengthen the existing evidence and to investigate new associations, especially with a focus on meat and dairy replacement products.