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  • Published: 12 September 2019

The effects of plant-based diets on the body and the brain: a systematic review

  • Evelyn Medawar   ORCID: orcid.org/0000-0001-5011-8275 1 , 2 , 3 ,
  • Sebastian Huhn 4 ,
  • Arno Villringer 1 , 2 , 3 &
  • A. Veronica Witte 1  

Translational Psychiatry volume  9 , Article number:  226 ( 2019 ) Cite this article

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  • Human behaviour
  • Molecular neuroscience
  • Psychiatric disorders

Western societies notice an increasing interest in plant-based eating patterns such as vegetarian and vegan, yet potential effects on the body and brain are a matter of debate. Therefore, we systematically reviewed existing human interventional studies on putative effects of a plant-based diet on the metabolism and cognition, and what is known about the underlying mechanisms. Using the search terms “plant-based OR vegan OR vegetarian AND diet AND intervention” in PubMed filtered for clinical trials in humans retrieved 205 studies out of which 27, plus an additional search extending the selection to another five studies, were eligible for inclusion based on three independent ratings. We found robust evidence for short- to moderate-term beneficial effects of plant-based diets versus conventional diets (duration ≤ 24 months) on weight status, energy metabolism and systemic inflammation in healthy participants, obese and type-2 diabetes patients. Initial experimental studies proposed novel microbiome-related pathways, by which plant-based diets modulate the gut microbiome towards a favorable diversity of bacteria species, yet a functional “bottom up” signaling of plant-based diet-induced microbial changes remains highly speculative. In addition, little is known, based on interventional studies about cognitive effects linked to plant-based diets. Thus, a causal impact of plant-based diets on cognitive functions, mental and neurological health and respective underlying mechanisms has yet to be demonstrated. In sum, the increasing interest for plant-based diets raises the opportunity for developing novel preventive and therapeutic strategies against obesity, eating disorders and related comorbidities. Still, putative effects of plant-based diets on brain health and cognitive functions as well as the underlying mechanisms remain largely unexplored and new studies need to address these questions.

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Introduction.

Western societies notice an increasing interest in plant-based eating patterns such as avoiding meat or fish or fully excluding animal products (vegetarian or vegan, see Fig.  1 ). In 2015, around 0.4−3.4% US adults, 1−2% British adults, and 5−10% of German adults were reported to eat largely plant-based diets 1 , 2 , 3 , 4 , due to various reasons (reviewed in ref. 5 ). Likewise, the number of scientific publications on PubMed (Fig.  2 ) and the public popularity as depicted by Google Trends (Fig.  3 ) underscore the increased interest in plant-based diets. This increasing awareness calls for a better scientific understanding of how plant-based diets affect human health, in particular with regard to potentially relevant effects on mental health and cognitive functions.

figure 1

From left to right: including all food items (omnivore), including all except for meat (pesco-vegetarian) or meat and fish (ovo-lacto-vegetarian) to including only plant-based items (vegan)

figure 2

Frequency of publications on PubMed including the search terms “vegan” (in light green), vegetarian (in orange) and plant-based (dark green)—accessed on 19 April 2019

figure 3

Note indicates technical improvements implemented by Google Trends. Data source: Google Trends . Search performed on 18 April 2019

A potential effect of plant-based diets on mortality rate remains controversial: large epidemiological studies like the Adventist studies ( n  = 22,000−96,000) show a link between plant-based diets, lower all-cause mortality and cardiovascular diseases 6 , 7 , while other studies like the EPIC-Oxford study and the “45 and Up Study” ( n  = 64,000−267,000) show none 8 , 9 . Yet, many, but not all, epidemiological and interventional human studies in the last decades have suggested that plant-based diets exert beneficial health effects with regard to obesity-related metabolic dysfunction, type 2 diabetes mellitus (T2DM) and chronic low-grade inflammation (e.g. refs. 6 , 7 , 10 , 11 , for reviews, see refs. 12 , 13 , 14 , 15 , 16 , 17 , 18 ). However, while a putative link between such metabolic alterations and brain health through pathways which might include diet-related neurotransmitter precursors, inflammatory pathways and the gut microbiome 19 becomes increasingly recognized, the notion that plant-based diets exert influence on mental health and cognitive functions appears less documented and controversial 20 , 21 , 22 , 23 , 24 . We therefore systematically reviewed the current evidence based on available controlled interventional trials, regarded as the gold standard to assess causality, on potential effects of plant-based diets on (a) metabolic factors including the microbiome and (b) neurological or psychiatric health and brain functions. In addition, we aimed to evaluate potential underlying mechanisms and related implications for cognition.

We performed a systematic PubMed search with the following search terms “plant-based OR vegan OR vegetarian AND diet AND intervention” with the filter “clinical trial” and “humans”, preregistered at PROSPERO (CRD42018111856; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=111856 ) (Suppl. Fig.  1 ). PubMed was used as search engine because it was esteemed to yield the majority of relevant human clinical trials from a medical perspective. Exclusion criteria were insufficient design quality (such as lack of a control group), interventions without a plant-based or vegetarian or vegan diet condition, intervention with multiple factors (such as exercise and diet), and the exclusive report of main outcomes of no interest, such as dietary compliance, nutrient intake (such as vitamins or fiber intake), or nonmetabolic (i.e., not concerning glucose metabolism, lipid profile, gastrointestinal hormones or inflammatory markers) or non-neurological/psychiatric disease outcomes (e.g. cancer, caries).

Studies were independently rated for eligibility into the systematic review by three authors based on reading the abstract and, if needed, methods or other parts of the publication. If opinions differed, a consensus was reached through discussion of the individual study. This yielded 27 eligible out of 205 publications; see Table  1 for details. To increase the search radius for studies dealing with microbial and neurological/psychiatric outcomes, we deleted the search term “intervention”, which increased the number of studies by around one third, and checked for studies with “microbiome/microbiota”, “mental”, “cognitive/cognition” or “psychological/psychology” in the resulting records. Through this, we retrieved another five studies included in Table  1 . Further related studies were reviewed based on additional nonsystematic literature search.

Section I: Effects of plant-based diets on body and brain outcomes

Results based on interventional studies on metabolism, microbiota and brain function.

Overall, the vast majority of studies included in this systematic review reported a short-term beneficial effect of plant-based dietary interventions (study duration 3−24 months) on weight status, glucose, insulin and/or plasma lipids and inflammatory markers, whereas studies investigating whether plant-based diets affect microbial or neurological/psychiatric disease status and other brain functions were scarce and rather inconclusive (Table  1 ).

More specifically, 19 out of 32 studies dealing with T2DM and/or obese subjects and seven out of 32 dealing with healthy subjects observed a more pronounced weight loss and metabolic improvements, such as lowering of glycated hemoglobin (HbA1c)—a long-term marker for glucose levels—decreased serum levels of low-density (LDL) and high-density lipoproteins (HDL) and total cholesterol (TC), after a plant-based diet compared to an omnivore diet. This is largely in line with recent meta-analyses indicating beneficial metabolic changes after a plant-based diet 25 , 26 , 27 .

For example, Lee et al. found a significantly larger reduction of HbA1c and lower waist circumference after vegan compared to conventional dieting 28 . Jenkins et al. found a disease-attenuating effect in hyperlipidemic patients after 6 months adopting a low-carbohydrate plant-based diet compared to a high-carbohydrate lacto-ovo-vegetarian diet 29 , 30 . However, lower energy intake in the vegan dieters might have contributed to these effects. Yet, while a plant-based diet per se might lead to lower caloric intake, other studies observed nonsignificant trends toward higher effect sizes on metabolic parameters after a vegan diet, even when caloric intake was comparable: two studies in T2DM patients 31 , 32 compared calorie-unrestricted vegan or vegetarian to calorie-restricted conventional diets over periods of 6 months and 1.5 years, respectively, in moderate sample sizes ( n  ~ 75−99) with similar caloric intake achieved in both diet groups. Both studies indicated stronger effects of plant-based diets on disease status, such as reduced medication, improved weight status and increased glucose/insulin sensitivity, proposing a diabetes-preventive potential of plant-based diets. Further, a five-arm study comparing four types of plant-based diets (vegan, vegetarian, pesco-vegetarian, semi-vegetarian) to an omnivore diet (total n  = 63) in obese participants found the most pronounced effect on weight loss for a vegan diet (−7.5 ± 4.5% of total body weight) 33 . Here, inflammation markers conceptualized as the dietary inflammatory index were also found to be lower in vegan, vegetarian and pesco-vegetarian compared to semi-vegetarian overweight to obese dieters 33 .

Intriguingly, these results 28 , 29 , 30 , 31 , 32 , 33 cohesively suggest that although caloric intake was similar across groups, participants who had followed a vegan diet showed higher weight loss and improved metabolic status.

As a limitation, all of the reviewed intervention studies were carried out in moderate sample sizes and over a period of less than 2 years, disregarding that long-term success of dietary interventions stabilizes after 2−5 years only 34 . Future studies with larger sample sizes and tight control of dietary intake need to confirm these results.

Through our systematic review we retrieved only one study that added the gut microbiome as novel outcome for clinical trials investigating the effects of animal-based diets compared to plant-based diets. While the sample size was relatively low ( n  = 10, cross-over within subject design), it showed that changing animal- to plant based diet changed gut microbial activity towards a trade-off between carbohydrate and protein fermentation processes within only 5 days 35 . This is in line with another controlled-feeding study where microbial composition changes already occurred 24 h after changing diet (not exclusively plant-based) 36 . However, future studies incorporating larger sample sizes and a uniform analysis approach of microbial features need to further confirm the hypothesis that a plant-based diet ameliorates microbial diversity and health-related bacteria species.

Considering neurological or psychiatric diseases and brain functions, the systematic review yielded in six clinical trials of diverse clinical groups, i.e. migraine, multiple sclerosis, fibromyalgia and rheumatoid arthritis. Here, mild to moderate improvement, e.g. measured by antibody levels, symptom improvement or pain frequency, was reported in five out of six studies, sometimes accompanied by weight loss 37 , 38 , 39 , 40 (Table  1 ). However, given the pilot character of these studies, indicated by small sample sizes ( n  = 32−66), lack of randomization 37 , or that the plant-based diet was additionally free of gluten 40 , the evidence is largely anecdotal. One study in moderately obese women showed no effects on psychological outcomes 41 , two studies with obese and nonobese healthy adults indicated improvements in anxiety, stress and depressive symptom scores 23 , 24 . Taken together, the current evidence based on interventional trials regarding improvements of cognitive and emotional markers and in disease treatment for central nervous system disorders such as multiple sclerosis or fibromyalgia remains considerably fragmentary for plant-based diets.

Among observational studies, a recent large cross-sectional study showed a higher occurrence of depressive symptoms for vegetarian dieters compared to nonvegetarians 20 . Conversely, another observational study with a sample of about 80% women found a beneficial association between a vegan diet and mood disturbance 24 .

Overall, the relationship between mental health (i.e. depression) and restrictive eating patterns has been the focus of recent research 20 , 21 , 22 , 24 , 42 ; however, causal relationships remain uninvestigated due to the observational design.

Underlying mechanisms linking macronutrient intake to metabolic processes

On the one hand, nutrient sources as well as their intake ratios considerably differ between plant-based and omnivore diets (Suppl. Table  1 ), and on the other hand, dietary micro- and macromolecules as well as their metabolic substrates affect a diversity of physiological functions, pointing to complex interdependencies. Thus, it seems difficult to nail down the proposed beneficial effects of a plant-based diet on metabolic status to one specific component or characteristic, and it seems unlikely that the usually low amount of calories in plant-based diets could explain all observed effects. Rather, plant-based diets might act through multiple pathways, including better glycemic control 43 , lower inflammatory activity 44 and altered neurotransmitter metabolism via dietary intake 45 or intestinal activity 46 (Fig.  4 ).

figure 4

BMI body-mass-index, HbA1c hemoglobin A1c, LDL-cholesterol low-density lipoprotein cholesterol, Trp tryptophan, Tyr tyrosine. Images from commons.wikimedia.org , “Brain human sagittal section” by Lynch 2006 and “Complete GI tract” by Häggström 2008, “Anatomy Figure Vector Clipart” by http://moziru.com

On the macronutrient level, plant-based diets feature different types of fatty acids (mono- and poly-unsaturated versus saturated and trans) and sugars (complex and unrefined versus simple and refined), which might both be important players for mediating beneficial health effects 18 . On the micronutrient level, the EPIC-Oxford study provided the largest sample of vegan dieters worldwide ( n (vegan) = 2396, n (total) = 65,429) and showed on the one hand lower intake of saturated fatty acids (SFA), retinol, vitamin B12 and D, calcium, zinc and protein, and on the other hand higher intake of fiber, magnesium, iron, folic acid, vitamin B1, C and E in vegan compared to omnivore dieters 47 . Other studies confirmed the variance of nutrient intake across dietary groups, i.e. omnivores, vegetarians and vegans, showing the occurrence of critical nutrients for each group 48 , 49 . Not only the amount of SFA but also its source and profile might be important factors regulating metabolic control (reviewed in ref. 14 ), for example through contributing to systemic hyperlipidemia and subsequent cardiovascular risk. Recently, it has been shown in a 4-week intervention trial that short-term dietary changes favoring a diet high in animal-based protein may lead to an increased risk for cardiovascular derangements mediated by higher levels of trimethylamine N-oxide (TMAO), which is a metabolite of gut bacteria-driven metabolic pathways 50 .

Secondly, high fiber intake from legumes, grains, vegetables and fruits is a prominent feature of plant-based diets (Table  1 ), which could induce beneficial metabolic processes like upregulated carbohydrate fermentation and downregulated protein fermentation 35 , improved gut hormonal-driven appetite regulation 51 , 52 , 53 , 54 , 55 , and might prevent chronic diseases such as obesity and T2DM by slowing down digestion and improving lipid control 56 . A comprehensive review including evidence from 185 prospective studies and 58 clinical trials concluded that risk reduction for a myriad of diseases (incl. CVD, T2DM, stroke incidence) was greatest for daily fiber intake between 25 and 29 g 57 . Precise evidence for underlying mechanisms is missing; however, more recently it has been suggested that high fiber intake induces changes on the microbial level leading to lower long-term weight gain 58 , a mechanism discussed below.

The reason for lower systemic inflammation in plant-based dieters could be due to the abundance of antiinflammatory molecule intake and/or avoidance of proinflammatory animal-derived molecules. Assessing systemic inflammation is particularly relevant for medical conditions such as obesity, where it has been proposed to increase the risk for cardiovascular disease 59 , 60 . In addition, higher C-reactive protein (CRP) and interleukin-6 (IL-6) levels have been linked with measures of brain microstructure, such as microstructural integrity and white matter lesions 61 , 62 , 63 and higher risk of dementia 64 , and recent studies point out that a diet-related low inflammatory index might also directly affect healthy brain ageing 65 , 66 .

Interventional studies that focus on plant- versus meat-based proteins or micronutrients and potential effects on the body and brain are lacking. A meta-analysis including seven RCTs and one cross-sectional studies on physical performance and dietary habits concluded that a vegetarian diet did not adversely influence physical performance compared to an omnivore diet 67 . An epidemiological study by Song et al. 11 estimated that statistically replacing 3% of animal protein, especially from red meat or eggs, with plant protein would significantly improve mortality rates. This beneficial effect might however not be explained by the protein source itself, but possibly by detrimental components found in meat (e.g. heme-iron or nitrosamines, antibiotics, see below).

Some studies further hypothesized that health benefits observed in a plant-based diet stem from higher levels of fruits and vegetables providing phytochemicals or vitamin C that might boost immune function and eventually prevent certain types of cancer 68 , 69 , 70 . A meta-analysis on the effect of phytochemical intake concluded a beneficial effect on CVD, cancer, overweight, body composition, glucose tolerance, digestion and mental health 71 . Looking further on the impact of micronutrients and single dietary compounds, there is room for speculation that molecules, that are commonly avoided in plant-based diets, might affect metabolic status and overall health, such as opioid-peptides derived from casein 72 , pre- and probiotics 73 , 74 , carry-over antibiotics found in animal products 75 , 76 or food-related carcinogenic toxins, such as dioxin found in eggs or nitrosamines found in red and processed meat 77 , 78 . Although conclusive evidence is missing, these findings propose indirect beneficial effects on health deriving from plant-based compared to animal-based foods, with a potential role for nonprotein substances in mediating those effects 18 . While data regarding chemical contaminant levels (such as crop pesticides, herbicides or heavy metals) in different food items are fragmentary only, certain potentially harmful compounds may be more (or less) frequently consumed in plant-based diets compared to more animal-based diets 79 . Whether these differences lead to systematic health effects need to be explored.

Taken together, the reviewed studies indicating effects of plant-based diets through macro- and micronutrient intake reveal both the potential of single ingredients or food groups (low SFA, high fiber) and the immense complexity of diet-related mechanisms for metabolic health. As proposed by several authors, benefits on health related to diet can probably not be viewed in isolation for the intake (or nonintake) of specific foods, but rather by additive or even synergistic effects between them (reviewed in refs. 12 , 80 ). Even if it remains a challenging task to design long-term RCTs that control macro- and micronutrient levels across dietary intervention groups, technological advancements such as more fine-tuned diagnostic measurements and automated self-monitoring tools, e.g. automatic food recognition systems 81 and urine-related measures of dietary intake 82 , could help to push the field forward.

Nutrients of particular interest in plant-based diets

As described above, plant-based diets have been shown to convey nutritional benefits 48 , 49 , in particular increased fiber, beta carotene, vitamin K and C, folate, magnesium, and potassium intake and an improved dietary health index 83 . However, a major criticism of plant-based diets is the risk of nutrient deficiencies for specific micronutrients, especially vitamin B12, a mainly animal-derived nutrient, which is missing entirely in vegan diets unless supplemented or provided in B12-fortified products, and which seems detrimental for neurological and cognitive health when intake is low. In the EPIC-Oxford study about 50% of the vegan dieters showed serum levels indicating vitamin B12 deficiency 84 . Along other risk factors such as age 85 , diet, and plant-based diets in particular, seem to be the main risk factor for vitamin B12 deficiency (reviewed in ref. 86 ), and therefore supplementing vitamin B12 for these risk groups is highly recommended 87 . Vitamin B12 is a crucial component involved in early brain development, in maintaining normal central nervous system function 88 and suggested to be neuroprotective, particularly for memory performance and hippocampal microstructure 89 . One hypothesis is that high levels of homocysteine, that is associated with vitamin B12 deficiency, might be harmful to the body. Vitamin B12 is the essential cofactor required for the conversion of homocysteine into nonharmful components and serves as a cofactor in different enzymatic reactions. A person suffering from vitamin B12 insufficiency accumulates homocysteine, lastly promoting the formation of plaques in arteries and thereby increasing atherothrombotic risk 90 , possibly facilitating symptoms in patients of Alzheimer’s disease 91 . A meta-analysis found that vitamin B12 deficiency was associated with stroke, Alzheimer’s disease, vascular dementia, Parkinson’s disease and in even lower concentrations with cognitive impairment 92 , supporting the claim of its high potential for disease prevention when avoided or treated 93 . Further investigations and longitudinal studies are needed, possibly measuring holotranscobalamin (the active form of vitamin B12) as a more specific and sensitive marker for vitamin B12 status 94 , to examine in how far nonsupplementing vegan dieters could be at risk for cardiovascular and cognitive impairment.

Similar health dangers can stem from iron deficiency, another commonly assumed risk for plant-based dieters and other risk groups such as young women. A meta-analysis on 24 studies proposes that although serum ferritin levels were lower in vegetarians on average, it is recommended to sustain an optimal ferritin level (neither too low nor too high), calling for well-monitored supplementation strategies 95 . Iron deficiency is not only dependent on iron intake as such but also on complimentary dietary factors influencing its bioavailability (discussed in ref. 95 ). The picture remains complex: on the one hand iron deficiency may lead to detrimental health effects, such as impairments in early brain development and cognitive functions in adults and in children carried by iron-deficient mothers 96 and a possible role for iron overload in the brain on cognitive impairment on the other hand 97 . One study showed that attention, memory and learning were impaired in iron-deficient compared to iron-sufficient women, which could be restored after a 4-month oral iron supplementation ( n  = 118) 98 . Iron deficiency-related impairments could be attributed to anemia as an underlying cause, possibly leading to fatigue, or an undersupply of blood to the brain or alterations in neurobiological and neuronal systems 99 provoking impaired cognitive functioning.

This leads to the general recommendation to monitor health status by frequent blood tests, to consult a dietician to live healthily on a plant-based diet and to consider supplements to avoid nutrient deficiencies or nutrient-overdose-related toxicity. All in all, organizations such as the Academy of Nutrition and Dietetics 100 and the German Nutrition Society do not judge iron as a major risk factor for plant-based dieters 101 .

Section II: Effects of diet on the gut microbiome

The link between diet and microbial diversity.

Another putative mechanistic pathway of how plant-based diets can affect health may involve the gut microbiome which has increasingly received scientific and popular interest, lastly not only through initiatives such as the Human Microbiome Project 102 . A common measure for characterizing the gut community is enterotyping, which is a way to stratify individuals according to their gut bacterial diversity, by calculating the ratio between bacterial genera, such as Prevotella and Bacteroides 103 . While interventional controlled trials are still scarce, this ratio has been shown to be conclusive for differentiating plant-based from animal-based microbial profiles 36 . Specifically, in a sample of 98 individuals, Wu et al. 36 found that a diet high in protein and animal fats was related to more Bacteroides, whereas a diet high in carbohydrates, representing a plant-based one, was associated with more Prevotella. Moreover, the authors showed that a change in diet to high-fat/low-fiber or to low-fat/high-fiber in ten individuals elicited a change in gut microbial enterotype with a time delay of 24 h only and remained stable over 10 days, however not being able to switch completely to another enterotype 36 . Another strictly controlled 30-day cross-over interventional study showed that a change in diet to either an exclusively animal-based or plant-based diet promoted gut microbiota diversity and genetic expression to change within 5 days 35 . Particularly, in response to adopting an animal-based diet, microbial diversity increased rapidly, even overshadowing individual microbial gene expression. Beyond large shifts in overall diet, already modest dietary modifications such as the daily consumption of 43 g of walnuts, were able to promote probiotic- and butyric acid-producing bacterial species in two RCTs, after 3 and 8 weeks respectively 104 , 105 , highlighting the high adaptability of the gut microbiome to dietary components. The Prevotella to Bacteroides ratio (P/B) has been shown to be involved in the success of dietary interventions targeting weight loss, with larger weight loss in high P/B compared to low P/B in a 6-month whole-grain diet compared to a conventional diet 106 . Only recently, other microbial communities, such as the salivary microbiome, have been shown to be different between omnivores and vegan dieters 107 , opening new avenues for research on adaptable mechanisms related to dietary intake.

A continuum in microbial diversity dependent on diet

Plant-based diets are supposed to be linked to a specific microbial profile, with a vegan profile being most different from an omnivore, but not always different from a vegetarian profile (reviewed in ref. 15 ). Some specifically vegan gut microbial characteristics have also been found in a small sample of six obese subjects after 1 month following a vegetarian diet, namely less pathobionts, more protective bacterial species improving lipid metabolism and a reduced level of intestinal inflammation 108 . Investigating long-term dietary patterns a study found a dose-dependent effect for altered gut microbiota in vegetarians and vegans compared to omnivores depending on the quantity of animal products 109 . The authors showed that gut microbial profiles of plant-based diets feature the same total number but lower counts of Bacteroides, Bifidobacterium, E. coli and Enterobacteriaceae compared to omnivores, with the biggest difference to vegans. Still today it remains unclear, what this shift in bacterial composition means in functional terms, prompting the field to develop more functional analyses.

In a 30-day intervention study, David et al. found that fermentation processes linked to fat and carbohydrate decomposition were related to the abundance of certain microbial species 35 . They found a strong correlation between fiber intake and Prevotella abundance in the microbial gut. More recently, Prevotella has been associated with plant-based diets 110 that are comparable to low-fat/high-fiber diets 111 and might be linked to the increased synthesis of short-chain fatty acids (SCFA) 112 . SCFAs are discussed as putative signaling molecules between the gut microbiome and the receptors, i.e. free fatty acid receptor 2 (FFA2) 51 , found in host cells across different tissues 113 and could therefore be one potential mechanism of microbiome−host communication.

The underlying mechanisms of nutrient decomposition by Prevotella and whether abundant Prevotella populations in the gut are beneficial for overall health remain unknown. Yet it seems possible that an increased fiber intake and therefore higher Prevotella abundance such as associated with plant-based diets is beneficial for regulating glycemic control and keeping inflammatory processes within normal levels, possibly due to reduced appetite and lower energy intake mediated by a higher fiber content 114 . Moreover, it has been brought forward that the microbiome might influence bodily homeostatic control, suggesting a role for the gut microbiota in whole-body control mechanisms on the systemic level. Novel strategies aim to develop gut-microbiota-based therapies to improve bodily states, e.g. glycemic control 115 , based on inducing microbial changes and thereby eliciting higher-level changes in homeostasis. While highly speculative, such strategies could in theory also exert changes on the brain level, which will be discussed next in the light of a bi-directional feedback between the gut and the brain.

Effects on cognition and behavior linking diet and cognition via the microbiome−gut−brain axis

While the number of interventional studies focusing on cognitive and mental health outcomes after adopting plant-based diets overall is very limited (see Section I above), one underlying mechanism of how plant-based diets may affect mood could involve signaling pathways on the microbiome−gut−brain axis 116 , 117 , 118 , 119 . A recent 4-week intervention RCT showed that probiotic administration compared to placebo and no intervention modulated brain activity during emotional decision-making and emotional recognition tasks 117 . In chronic depression it has been proposed that immunoglobulin A and M antibodies are synthesized by the host in response to gut commensals and are linked to depressive symptoms 120 . Whether the identified gram-negative bacteria might also play a role in plant-based diets remains to be explored. A meta-analysis on five studies concluded that probiotics may mediate an alleviating effect on depression symptomatic 121 —however, sample sizes remained rather small ( n  < 100) and no long-term effects were tested (up to 8 weeks).

Currently, several studies aim to identify microbial profiles in relation to disease and how microbial data can be used on a multimodal way to improve functional resolution, e.g. characterizing microbial profiles of individuals suffering from type-1 diabetes 122 . Yet, evidence for specific effects of diet on cognitive functions and behavior through changes in the microbiome remains scarce. A recent study indicated the possibility that our food choices determine the quantity and quality of neurotransmitter-precursor levels that we ingest, which in turn might influence behavior, as shown by lower fairness during a money-redistribution task, called the ultimatum game, after a high-carbohydrate/protein ratio breakfast than after a low-ratio breakfast 123 . Strang et al. found that precursor forms of serotonin and dopamine, measured in blood serum, predicted behavior in this task, and precursor concentrations were dependent on the nutrient profile of the consumed meal before the task. Also on a cross-sectional level tryptophan metabolites from fecal samples have been associated with amygdala-reward network functional connectivity 124 . On top of the dietary composition per se, the microbiota largely contributes to neurotransmitter precursor concentrations; thus, in addition to measuring neurotransmitter precursors in the serum, metabolomics on fecal samples would be helpful to further understand the functional role of the gut microbiota in neurotransmitter biosynthesis and regulation 125 .

Indicating the relevance of gut microbiota for cognition, a first human study assessing cognitive tests and brain imaging could distinguish obese from nonobese individuals using a microbial profile 126 . The authors found a specific microbiotic profile, particularly defined by Actinobacteria phylum abundance, that was associated with microstructural properties in the hypothalamus and in the caudate nucleus. Further, a preclinical study tested whether probiotics could enhance cognitive function in healthy subjects, showing small effects on improved memory performance and reduced stress levels 127 .

A recent study could show that microbial composition influences cerebral amyloidogenesis in a mouse model for Alzheimer’s disease 128 . Health status of the donor mouse seemingly mattered: fecal transplants from transgenic mice had a larger impact on amyloid beta proliferation in the brain compared to wild-type feces. Translational interpretations to humans should be done with caution if at all—yet the results remain elucidative for showing a link between the gut microbiome and brain metabolism.

The evidence for effects of strictly plant-based diets on cognition is very limited. For other plant-based diets such as the Mediterranean diet or DASH diet, there are more available studies that indicate protective effects on cardiovascular and brain health in the aging population (reviewed in refs. 129 , 130 ). Several attempts have been made to clarify potential underlying mechanisms, for example using supplementary plant polyphenols, fish/fish-oil consumption or whole dietary pattern change in RCTs 131 , 132 , 133 , 134 , 135 , 136 , 137 , yet results are not always equivocal and large-scale intervention studies have yet to be completed.

The overall findings of this paragraph add to the evidence that microbial diversity may be associated with brain health, although underlying mechanisms and candidate signaling molecules remain unknown.

Based on this systematic review of randomized clinical trials, there is an overall robust support for beneficial effects of a plant-based diet on metabolic measures in health and disease. However, the evidence for cognitive and mental effects of a plant-based diet is still inconclusive. Also, it is not clear whether putative effects are due to the diet per se, certain nutrients of the diet (or the avoidance of certain animal-based nutrients) or other factors associated with vegetarian/vegan diets. Evolving concepts argue that emotional distress and mental illnesses are linked to the role of microbiota in neurological function and can be potentially treated via microbial intervention strategies 19 . Moreover, it has been claimed that certain diseases, such as obesity, are caused by a specific microbial composition 138 , and that a balanced gut microbiome is related to healthy ageing 111 . In this light, it seems possible that a plant-based diet is able to influence brain function by still unclear underlying mechanisms of an altered microbial status and systemic metabolic alterations. However, to our knowledge there are no studies linking plant-based diets and cognitive abilities on a neural level, which are urgently needed, due to the hidden potential as a dietary therapeutic tool. Also, further studies are needed to disentangle motivational beliefs on a psychological level that lead to a change in diet from causal effects on the body and the brain mediated e.g., by metabolic alterations or a change in the gut microbiome.

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Acknowledgements

This work was supported by a scholarship (E.M.) by the German Federal Environmental Foundation and by the grants of the German Research Foundation contract grant number CRC 1052 “Obesity mechanisms” Project A1 (AV) and WI 3342/3-1 (A.V.W.).

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Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Evelyn Medawar, Arno Villringer & A. Veronica Witte

Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany

Evelyn Medawar & Arno Villringer

Charité—Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany

Helmholtz Centre for Environmental Research GmbH—UFZ, Leipzig, Germany

Sebastian Huhn

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E.M., A.V. and A.V.W. designed research; E.M. conducted research; E.M., S.H. and A.V.W. analyzed data; E.M. and A.V.W. wrote the paper; E.M., A.V. and A.V.W. had primary responsibility for final content. All authors read and approved the final manuscript.

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Medawar, E., Huhn, S., Villringer, A. et al. The effects of plant-based diets on the body and the brain: a systematic review. Transl Psychiatry 9 , 226 (2019). https://doi.org/10.1038/s41398-019-0552-0

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Introduction, evidence acquisition, metabolic and molecular mechanisms associated with vegetarian diets, evidence from prospective studies, evidence from randomized clinical trials, potential health risks of vegan and vegetarian diets, the importance of consuming healthy vegetarian diets, conclusions, supplementary data, declarations, data availability.

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Vegetarian and vegan diets: benefits and drawbacks

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Tian Wang, Andrius Masedunskas, Walter C Willett, Luigi Fontana, Vegetarian and vegan diets: benefits and drawbacks, European Heart Journal , Volume 44, Issue 36, 21 September 2023, Pages 3423–3439, https://doi.org/10.1093/eurheartj/ehad436

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Plant-based diets have become increasingly popular thanks to their purported health benefits and more recently for their positive environmental impact. Prospective studies suggest that consuming vegetarian diets is associated with a reduced risk of developing cardiovascular disease (CVD), diabetes, hypertension, dementia, and cancer. Data from randomized clinical trials have confirmed a protective effect of vegetarian diets for the prevention of diabetes and reductions in weight, blood pressure, glycosylated haemoglobin and low-density lipoprotein cholesterol, but to date, no data are available for cardiovascular event rates and cognitive impairment, and there are very limited data for cancer. Moreover, not all plant-based foods are equally healthy. Unhealthy vegetarian diets poor in specific nutrients (vitamin B12, iron, zinc, and calcium) and/or rich in highly processed and refined foods increase morbidity and mortality. Further mechanistic studies are desirable to understand whether the advantages of healthy, minimally processed vegetarian diets represent an all-or-nothing phenomenon and whether consuming primarily plant-based diets containing small quantities of animal products (e.g. pesco-vegetarian or Mediterranean diets) has beneficial, detrimental, or neutral effects on cardiometabolic health outcomes. Further, mechanistic studies are warranted to enhance our understanding about healthy plant-based food patterns and the biological mechanisms linking dietary factors, CVD, and other metabolic diseases.

A comparison of healthy vegetarian diets vs. unhealthy vegetarian diets. HbA1c, glycosylated haemoglobin; LDL-C, low-density lipoprotein cholesterol.

A comparison of healthy vegetarian diets vs. unhealthy vegetarian diets. HbA1c, glycosylated haemoglobin; LDL-C, low-density lipoprotein cholesterol.

Plant-based diets have become increasingly popular thanks to their purported health benefits and more recently for their positive environmental impact. 1 There are different types of plant-based diets, but in this review, we will focus our attention primarily on vegan (100% plant-based), lacto-ovo vegetarian (i.e. plant-based except for dairy products and/or eggs), and pesco-vegetarian or pescatarian (i.e. plant-based except for fish and seafood with or without eggs and dairy) diets. All vegetarian diets exclude meat (e.g. beef, pork, lamb, venison, chicken, and other fowl) and related meat products.

According to the American and Canadian Dietetic Associations, appropriately planned and supplemented vegan and lacto-ovo vegetarian diets are nutritionally adequate and suitable for individuals in all stages of the life cycle and may provide health benefits in disease prevention and treatment. 2 , 3 These statements are supported mainly by cross-sectional and prospective studies with accumulating data from a limited number of clinical randomized trials. Moreover, not all plant-based foods are equally healthy. Vegetarian diets rich in refined flours, hydrogenated oils, high-fructose corn syrup (HFCS), sucrose, artificial sweeteners, salt, and preservatives have been shown to increase morbidity and mortality ( Figure 1 ). 4–6 The purpose of this article is to review succinctly the current knowledge on the effects of vegetarian diets on the risk of developing some of the most common and costly chronic diseases, including cardiovascular disease (CVD), obesity, type 2 diabetes mellitus (T2DM), hypertension, dementia, and cancer, and to discuss what is known about its metabolic and molecular adaptations and effects.

Metabolic effects of healthy and unhealthy vegetarian diets. MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides.

Metabolic effects of healthy and unhealthy vegetarian diets. MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides.

We searched EMBASE, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed, from inception until 20 September 2022. Hand searches of reference lists of reviews, protocols, and clinical trial registries (ClinicalTrials.gov) were performed to supplement searches. Search terms included diet , plant-based , vegetarian , vegan , cardiovascular , cardiovascular diseases , diabetes , T2DM , hypertension , cancer , dementia , and cognitive function . The authors of the ongoing trials were contacted to retrieve preliminary findings and full manuscripts. Both basic science and clinical research studies were reviewed. The published clinical reports that we reviewed included epidemiologic studies, case-control studies, and randomized controlled trials. Quality of data was assessed by taking into account publication in a peer-reviewed journal, number of individuals studied, objectivity of measurements, and techniques used to minimize bias.

The precise mechanisms by which well-designed and balanced vegetarian or vegan diets may exert their beneficial effects in lowering the risk of coronary heart disease (CHD) and possibly cancer and dementia are under scrutiny. Many factors have been hypothesized to play a role, including (i) lipid-lowering effect; (ii) glucose-lowering, insulin sensitizing, and hormonal effects; (iii) protection against oxidative stress, inflammation, and hypertension, and (iv) production of intestinal microbial metabolites influencing metabolic and immune health ( Figure 2 ).

Cardioprotective mechanisms of healthy vegetarian diets. Multiple nutritional effectors of a healthy vegetarian diet modulate important metabolic, hormonal, and immune factors associated with the development of cardio- and cerebrovascular diseases. K, potassium; Mg, magnesium; Se, selenium; NaCl, sodium chloride; SCFA, short-chain fatty acids; LDL-C, low-density lipoprotein cholesterol; VLDL, very-low-density lipoprotein; GI, glycaemic index; BCAA, branched-chain amino acid; TMAO, trimethylamine N-oxide.

Cardioprotective mechanisms of healthy vegetarian diets. Multiple nutritional effectors of a healthy vegetarian diet modulate important metabolic, hormonal, and immune factors associated with the development of cardio- and cerebrovascular diseases. K, potassium; Mg, magnesium; Se, selenium; NaCl, sodium chloride; SCFA, short-chain fatty acids; LDL-C, low-density lipoprotein cholesterol; VLDL, very-low-density lipoprotein; GI, glycaemic index; BCAA, branched-chain amino acid; TMAO, trimethylamine N -oxide.

Lipid-lowering effect

Several factors can explain why vegetarians have significantly lower levels of plasma cholesterol, especially when they consume minimally processed plant foods. Vegetarians do not consume meat, and vegans also avoid milk, butter, and dairy. Beef, lamb, and pork contain high levels of saturated fat and cholesterol and minimal amounts of polyunsaturated fats; even lean cuts of beef may contain up to 4.5 g of saturated fat per 100 g serving. One-cup serving of whole milk contains 4.5 g of saturated fat, and one tablespoon of butter contains 102 kcal and 7 g of saturated fat. In contrast, one tablespoon of olive oil contains 119 kcal and only 1.9 g of saturated fatty acids. Epidemiological studies have shown a strong linear relationship between saturated fat intake, plasma cholesterol levels, and CHD. 7 , 8 Substituting 5% of energy intake from saturated fatty acids with a similar quantity of energy from polyunsaturated fats, monounsaturated fats, or carbohydrates from whole grains is associated with a 25%, 15%, and 9% lower risk of CHD, respectively. However, when saturated fats are replaced with carbohydrates from refined carbohydrates, the risk of developing CHD increases substantially. 9 Data from randomized clinical trials have demonstrated a cause–effect relationship; 10–12 replacing saturated fat with vegetable polyunsaturated fats decreases CHD by 30% that is similar to the reduction induced by statin therapy. 13 Seeds and nuts are excellent sources of polyunsaturated fatty acids and contain soluble and insoluble fibres and sterols that are known to lower cholesterol. 14 Epidemiological studies suggest that frequent nut consumption can reduce the risk of CHD by 40%–60%. 15 Data from randomized clinical trials confirm that consuming a diet rich in nuts, viscous fibres from oats, barley, psyllium, and plant sterol ester–enriched margarine can reduce plasma low-density lipoprotein (LDL) cholesterol by 13%. 16 Moreover, vegetarian diets rich in whole grains, legumes, nuts, and dried fruits can provide ∼15 g of dietary fibre per 1000 kcal. In a 4 month weight loss double-blind, placebo-controlled clinical trial, overweight or obese men and women who received a daily supplement of soluble fibre (3 g Plantago ovata husk and 1 g glucomannan) experienced a significant greater drop in LDL cholesterol than those in the placebo group. 17 Dietary fibres and phytosterols reduce the (re)absorption of cholesterol and bile acids in the small intestine, thus resulting in an increased LDL uptake by the liver. 18 , 19 Moreover, foods rich in dietary fibre and with low glycaemic index can lower insulin production and increase the levels of short-chain fatty acids produced by fibre fermentation, which have both been shown to inhibit cholesterol synthesis. 19

Glucose-lowering, insulin sensitizing, and hormonal effects

Vegetarians, and especially vegans, tend to have lower body weights than omnivores. In a survey of the American Adventists population, average body mass index (BMI) in omnivores, semi-vegetarians, lacto-ovo vegetarians, and vegans was 28.3, 27.3, 26.1, and 24.1 kg/m 2 , respectively. 20 Although consuming a vegetarian diet does not require counting calories, results from clinical trials demonstrate that people randomized to a vegetarian diet tend to lose more weight than those consuming Western diets. 21 , 22 Preclinical, epidemiological, and clinical studies suggest that distinct dietary interventions may promote atherogenic and metabolic fat depot mobilization differently. 23 The high-fibre and water content and lower energy density of vegetables, legumes, and whole grains may in part explain this effect. Consumption of diets rich in dietary fibre induces gastric distention, delays gastric emptying, and prevents large fluctuations in postprandial blood glucose. 24 Short-chain fatty acids produced by the intestinal microbial metabolism of resistant starch and oligosaccharides of minimally refined plant foods induce satiety by inhibiting gastric emptying through incretins such as peptide-YY and glucagon like peptide-1 that markedly reduce blood glucose and body weight in randomized clinical trials. 25–27 Moreover, whole-food vegan and vegetarian diets may result in fewer bioavailable calories, and it is well known that calorie restriction with adequate nutrition in humans exert a powerful effect in improving glucose tolerance, insulin sensitivity, and many other cardiometabolic, inflammatory, and hormonal factors implicated in the pathogenesis of CVD and cancer. 28–30 As reviewed elsewhere, 28 , 31 excessive (central) adiposity causes insulin resistance, dysregulation of sex hormones and insulin-like growth factor-1 (IGF-1) signalling, low-grade chronic inflammation, and immune dysregulation of natural killer cells and stromal tumour-infiltrating lymphocytes, limiting antitumour responses. Compensatory hyperinsulinaemia together with increased bioavailability of oestradiol, testosterone, and IGF-1 promotes cell proliferation and genomic instability through activation of the PI3K/AKT and p66 shc pathways, which have been associated with increased risk of multiple cancers, including breast, endometrial, prostate, and colon cancer. 28 , 31

Additional mechanisms mediating the insulin sensitizing and glucose-lowering effects of healthful minimally processed vegetarian diets are the low glycaemic index/load and the lower intake of protein, especially of sulphur and branched-chain amino acids. Estimated daily protein intake for omnivores in Western societies is ∼90–100 g of which ∼70%–85% is animal proteins rich in methionine, valine, leucine, and isoleucine. Results from both population and randomized experimental diet interventions show that high protein intake, especially of branched-chain amino acids, is associated with an increased prevalence and risk of developing pre-diabetes and T2DM. 32 Diabetes risk increases by 20%–40% for every 10 g of protein consumed in excess of 64 g per day. 33 , 34 Interestingly, in some studies, high intake of animal protein, but not of plant protein, was associated with the higher risk of developing T2DM. 32 , 34 , 35 In weight loss trials of obese women, high protein intake (1.3 g kg −1 per day including two servings of a whey protein isolate) completely prevented the markedly improved insulin sensitivity observed in women consuming a normal protein diet (0.8 g kg −1 per day) who lost the same amount of body weight and visceral and liver fat. 36 Furthermore, dietary branched-chain amino acid (BCAA) restriction in mice recapitulates many of the beneficial effects of protein restriction observed in rodents and humans, including reduced adiposity, increased glucose tolerance, and increased energy expenditure, but not increased FGF21 levels. 37 In contrast, high dietary intake of BCAA increases platelet activation and arterial thrombosis risk by enhancing tropomodulin-3 propionylation. 38 Consistently, data from two trials demonstrated that consuming high-protein diets (comprising dairy and meat products and whey protein supplements) cause a reduction in insulin sensitivity and an associated increase in blood insulin levels. 39 , 40 In an another trial of patients with T2DM, high consumption of chicken, fish, eggs, low-fat milk, and cheeses prevented the expected improvements in glucose metabolism and insulin sensitivity induced by a 2 month weight loss intervention. 41 High-protein diets, particularly those rich in leucine, can also play a role in promoting atherosclerosis and plaque instability in mice by exacerbating macrophage apoptosis induced by atherogenic lipids, via mTORC1-dependent inhibition of mitophagy and accumulation of dysfunctional mitochondria. 42

Protection against oxidative stress, inflammation, and hypertension

Well-designed vegetarian diets rich in vegetables, whole grains, legumes, nuts, seeds, and fruits provide a wide range of vitamins (vitamin C, vitamin E, and beta-carotene), minerals (selenium), and phytochemicals (tannins, phenols, alkaloids, and flavonoids) with xenohormetic effects. 43 Numerous large observational studies suggest that an inverse relationship exists between antioxidant and polyphenol intake and the risk of developing diabetes, CVDs, cancer, and possibly dementia. 44 High intake of dietary antioxidants and phytochemicals may reduce the risk of developing atherosclerotic plaques because it triggers adaptive modulations of stress-response enzymes and receptors that prevent lipoprotein oxidation, endothelial dysfunction, and immune activation. 45 , 46 Findings from large prospective studies suggest that dietary patterns with higher inflammatory potential are significantly associated with higher level of systemic and vascular inflammation, an unfavourable lipid profile, and ultimately with a higher incidence of CHD and stroke. 47 Dietary patterns with lower inflammatory potential are those that favour foods rich in dietary antioxidants and vegetable fibre (e.g. green leafy and dark yellow vegetables, whole grains, fruit, tea, and coffee) and avoid red and processed meat and refined liquid and solid carbohydrates. 48–52

Diets rich in vegetable fibre, potassium, and magnesium and low in sodium, especially when associated with a healthy body weight and regular endurance exercise training, markedly lower systolic and diastolic blood pressure, 53–56 which is a powerful risk factor for the development of CHD, heart failure, stroke (both ischaemic and haemorrhagic), and dementia. Indeed, data from epidemiological and genetic causal inference studies show that elevated systolic blood pressure, insulin resistance, and excess adiposity at midlife are important risk factors for developing cognitive impairment and Alzheimer’s disease because they cause endothelial dysfunction and vascular damage to the brain, particularly at the level of perforating cerebral arteries and neurovascular units. 57 , 58 In contrast, reduction of systolic blood pressure prevents and/or slows progression of cognitive impairment to dementia. 59

Modulation of gut microbiome function and effect on human metabolic state

Diet composition has a pervasive effect in modulating systemic microbiome biology. Metagenomic data show that specific nutrients, especially insoluble fibre, and protein intake deeply influence gut microbiota structure and function and the production of a growing list of metabolically active molecules. 60 , 61 For instance, unlike vegetarians diets, Western diets rich in red meat, eggs, and cheese contain higher concentrations of nutrients such as choline and L-carnitine that increase the microbial production of trimethylamine N -oxide (TMAO). 62 , 63 Animal and human studies have shown that higher levels of circulating TMAO increase the risk of developing CVD, independent of traditional cardiometabolic risk factors, by inducing vascular inflammation and platelet activation. 64 , 65 In contrast, healthful plant-based diets rich in whole grains, legumes, and nuts can markedly increase the intake of dietary fibres, key fermentable substrates for the proliferation of Bacteroidetes and the production of short-chain fatty acids such as acetate, propionate, and butyrate. 66 , 67 Experimental animal data indicate that these microbial metabolites exert powerful blood pressure–lowering and immune-modulating effects, via activation of specific G-protein–coupled receptors expressed on enteroendocrine and intestinal immune cells. 61 , 68 Long-term consumption of vegetarian diets has also been associated with more phylogenetic biodiversity of stool microbiota; in contrast, multigenerational exposure to Western diets poor in ‘microbiota-accessible carbohydrates’ causes an extinction of specific bacterial lineages, which impairs immune function and maturation, and increases the risk of developing a range of metabolic, inflammatory, allergic, and autoimmune diseases. 69 , 70 Interestingly, data from the DIRECT-PLUS trial show that a calorie-restricted and (almost) red-meat-free version of the Mediterranean diet enriched in plant-based proteins (Green-MED diet) is superior to the classical Mediterranean diet in improving the 10-year Framingham risk score and in lowering waist circumference, intrahepatic fat, LDL cholesterol, diastolic blood pressure, C-reactive protein, and HOMA insulin resistance. 71 These cardiometabolic beneficial effects were partially mediated by a major shift in the composition and function of the gut microbiome, including enrichments in the genus Prevotella and reductions in the genus Bifidobacterium with associated inhibition in BCAA biosynthesis and up-regulation of BCAA degradation enzymatic pathways. 72 This is crucial because a growing body of evidence show that reprogramming microbial functions through long-term adherence to healthier plant-rich diets has profound effects in shaping physiologic response to specific nutrients, to calorie restriction, and to other features of host biology that are instrumental in promoting health and longevity. 73 , 74

Prospective epidemiological studies have suggested that consuming vegetarian diets might have protective effects against the development of obesity, diabetes, hypertension, CHD, several type of cancers, and, most recently, cognitive decline. Whether these associations are causal deserves careful consideration of all available evidence, including data from other types of studies.

Hypertension

Findings from observational studies suggest that people consuming vegetarian and vegan diets have lower blood pressure than people eating Western diets, even after adjusting for age, sex, and BMI. 75 Compared with Seventh-day Adventist who are omnivores, those who follow a vegetarian diet have lower blood pressure and a reduced incidence of hypertension, independent of body weight and sodium intake. 76 Data from multiple observational studies including three large prospective American cohort studies suggest that consuming red meat and poultry is associated with an increased risk of hypertension, independent of vegetable, whole grain, and fruit intake. 77

Type 2 diabetes mellitus

Several studies suggest protective effects of vegetarian diets in the prevention of T2DM. Findings from the Adventist Health Study-2 (41 387 participants free of diabetes followed for 2 years) found that, even after controlling for multiple confounding factors, vegetarians had a significantly lower risk of T2DM than omnivores. 78 The most apparent protective effect was for vegan diets with a 62% risk reduction, followed by semi-vegetarian (51% reduction) and lacto-ovo vegetarian (38% reduction) diets. The Adventist Mortality Study and Adventist Health Study followed a cohort of 8401 individuals for more than 17 years. 79 After controlling for weight and weight change, long-term adherence to a diet incorporating weekly meat intake was associated with a 38% higher risk of T2DM compared with a vegetarian diet with no meat intake. This finding are supported by data from a joint analysis of three large cohort studies (the Health Professionals Follow-up Study, n = 26,357; the Nurses’ Health Study, n = 48,709; and the Nurses’ Health Study II, n = 74,077) confirming a statistically significant association between red meat consumption and an increased risk of T2DM ( P < .001 for all studies). 80 After adjusting for initial BMI and concurrent weight gain, a daily increase of > 0.5 servings of red meat was linked with a 30% higher risk of T2DM. In contrast, reducing red meat intake by > 0.5 servings/day was associated with a 14% lower risk of T2DM.

Cardiovascular disease

A joint analysis of five prospective studies including 76 172 individuals has shown a lower CHD mortality in vegetarians than in omnivores: 34% less in lacto-ovo vegetarians and pesco-vegetarians and 26% lower in vegans. 81 Another meta-analysis of 7 studies (124 706 participants) report a 29% decreased mortality from CHD in vegetarians than omnivores. 82 The EPIC-Oxford cohort study (44 561 participants) showed a 32% risk reduction of CHD in vegetarians than non-vegetarians. 83 However, subsequent studies suggest that the protective effect against CHD of vegetarian diets seems to be almost exclusively limited to the Seventh-day Adventists, who don’t smoke, don’t drink alcohol, do regular physical activity, and are very religious and socially connected. 84 Indeed, data from epidemiological studies of English and German vegetarians show only a modest protective effect against cardiovascular and overall mortality. 85–87 A German prospective study of 1225 vegetarians and 679 health-conscious non-vegetarians has shown that there is no difference in mortality among vegetarians and this control group of health-conscious individuals consuming meat three to four times per month. 88 Cigarette smoking, obesity, alcohol intake, and exercise patterns seem to explain most of the differences in cardiovascular mortality among these different groups. Another potential problem is diet quality, which can vary greatly among both vegetarian and non-vegetarians. 4 , 5 , 89

The effects of vegetarian diets on major cardiometabolic risk factors (i.e. hypercholesterolaemia, dyslipidaemia, hypertension, T2DM, and obesity) are more consistent. Well-educated vegetarians who consume balanced diets tend to have a lower body weight than non-vegetarians 21 together with lower levels of cholesterol, glucose, and blood pressure. 90 A recent umbrella review integrated evidence from 20 meta-analyses and found that people following vegetarian diets had significantly lower total cholesterol and LDL cholesterol than people consuming Western diets. 91 On average, total and HDL cholesterol are ∼0.36 and 0.10 mmol/L, respectively, lower in vegetarians than in omnivores. 92

A meta-analysis of 7 epidemiological studies (124 706 participants) found an 18% lower cancer incidence in vegetarians than omnivores {relative risk [RR]: 0.82 [95% confidence interval (CI): 0.67, 0.97]}. 82 Results from the EPIC-Oxford study on a cohort of 65 000 men and women found that the overall cancer risk was 10% lower in vegetarians and 18% lower in vegans than in meat-eaters. 93 However, after correcting for multiple confounding factors, only stomach and haematological cancers were significantly lower, while cervical cancer was 90% higher in vegetarians. Recent data from the UK Biobank prospective study on 409 110 participants show that compared with omnivores, vegetarians had a 13% and pescatarians a 7% lower overall cancer risk, respectively. In this study, vegetarians had a lower risk of colorectal and prostate cancer, and pescatarians had a lower risk of melanoma. However, when these data were pooled with eight previously published studies in a meta-analysis, only the association with colorectal cancer persisted. 94 These findings suggest that other factors beyond vegetarian diets may explain these associations. The incidence of lung cancer, for example, is lower in vegetarians than in people consuming typical Western diets, but this seems due primarily to the reduced smoking habit of vegetarians. No difference has been reported for lung cancer risk for vegetarians in maximally adjusted models. 95–97 The incidence of colon cancer is reduced by 22% among Seventh-day Adventist vegetarians, but not in British vegetarians. In the latter group, for example, it seems that vegans have an even higher risk of colon cancer, while in pesco-vegetarians, there is a 33% reduction, even after correcting for body weight. 95 The quality of diet probably plays a major role. Indeed, unhealthy plant-based diets rich in refined and processed carbohydrates and unhealthy fats are associated with higher risk of colon cancer, but healthy plant-based diets enriched in whole grains, legumes, and vegetables are associated with lower incidence of colorectal cancer, especially KRAS-wildtype subtype. 6 The risk of developing breast cancer is no different between vegetarian and non-vegetarian women in most studies, and some epidemiological data in Adventist and British women suggest vegans, but not lacto-ovo vegetarians, may have an increased risk. 98 The same is true for prostate cancer, with the risk no different among lacto-ovo vegetarians and omnivores but 34% lower in the Adventists vegans. 99 A lower intake of dairy products may explain this association because milk consumption increases serum IGF-1 levels, a risk factor for prostate cancer, breast, and colon cancer. 100

Very little is known about the effects of vegetarian diets on cognitive function and dementia risk. A recent systematic review and meta-analysis suggests that vegetarian diets are not associated with any significant improvement in memory when compared with omnivorous diets, but heterogeneity among studies was very high. 101 Findings from a small prospective study (5710 participants with 121 incident cases) conducted in Taiwan suggest that vegetarians might have a lower risk of dementia than non-vegetarians. 102

Data from a meta-analysis of 7 clinical trials including 311 participants show that consuming a vegetarian diet is associated with a reduction of mean systolic [−4.8 mmHg (−6.6 to −3.1)] and diastolic [−2.2 mmHg (−3.5 to −1.0)] blood pressure compared with non-vegetarian diets. 103 A meta-analysis of 11 trials and 983 participants showed that strict plant-based (vegan) diets seem less effective than less restrictive diets and reduced systolic [−4.10 mmHg (−8.14 to −0.06)] and diastolic [−4.01 mmHg (−5.97 to −2.05)] blood pressure only in patients with a baseline systolic blood pressure (SBP) ≥130 mmHg. 104 A recent meta-analysis of randomized trials show that the lacto-ovo vegetarian diet is as effective as other healthy diets containing some animal products [Dietary Approaches to Stop Hypertension (DASH) and healthy Nordic diet] at reducing blood pressure. In contrast, vegan diets did not significantly reduce blood pressure unless caloric restrictions was also prescribed, 105 suggesting that complete elimination of animal food is not required for lowering blood pressure and might even increase haemorrhagic stroke risk, possibly due to very low intake of saturated fat. 93 Other factors such as calorie restriction and weight loss, 30 , 54 , 106 lower dietary sodium and high potassium and magnesium intake, 53 , 55 and regular endurance exercise training 56 are important factors beyond fibre-rich plant food consumption. Moreover, findings from a meta-analysis of 15 randomized trials show that reduced alcohol consumption dose-dependently lowers systolic and blood pressure in both in non-hypertensive and hypertensive individuals. 107

The results of a recent meta-analysis of nine randomized clinical trials provide evidence that vegetarian diets can significantly reduce fasting glucose (range 0.1–1.0 mmol/L) and glycosylated haemoglobin (HbA1c) (range 0.12%–0.45%) together with LDL cholesterol (range 0.04–0.2 mmol/L) and body weight (range 1.3–3.0 kg) in T2DM patients. 108 Interestingly, one randomized clinical trial comparing a low-fat vegan diet with the American Diabetes Association (ADA) diet demonstrated that both diets caused significant improvements in HbA1c, body weight, plasma lipid concentrations, and urinary albumin excretion in individuals with T2DM. 109 Forty-three percent of patients randomized to the vegan group and 26% of those allocated to the ADA group reduced the use of glucose-lowering drugs. Moreover, among medication-stable patients, the effects of the low-fat vegan diet on HbA1c, weight, waist circumference, and LDL cholesterol were significantly greater than in the control group. Similar improvements in HbA1c levels have been found in a population of Korean men and women affected by T2DM. 110 Thus, these trials suggest that low-fat vegan diets might be more effective than conventional diabetic diets in glycaemic control, but more studies with long-term follow-up are needed to confirm these findings. Table 1 summarizes the ongoing clinical trials with vegetarian diet interventions in people with T2DM.

Study characteristics of completed and ongoing clinical trials in people with type 2 diabetes mellitus

ADA, American Diabetes Association; CI, confidence interval; F & V, fruits and vegetables; HbA1c, haemoglobin A1c; LDL-C, low-density lipoprotein cholesterol; LF, low-fat; LOV, lacto-ovo vegetarian diet; MD, mean differences; SBP, systolic blood pressure; DNSG, Diabetes and Nutrition Study Group; EASD, European Association for the Study of Diabetes; NA, not applicable; RR, relative risk; F, females; M, males; NI, no information; OR, odds ratio; RCT, randomized controlled trial; IQR, interquartile range; M, males; WFPB, whole foods plant-based.

Randomized clinical trials are usually considered gold standard studies for evaluating the cause–effect relationship of health interventions, although misleading conclusions can easily occur due to low adherence to the intervention or inadequate follow-up time. To the best of our knowledge, there are no randomized clinical trials that have tested the effects of vegetarian diets alone on CHD event rates. The Lifestyle Heart Trial was designed to investigate the effects of an intensive lifestyle programme comprising a 10% fat whole foods vegetarian diet together with aerobic exercise, stress management training, smoking cessation, and group psychosocial support in 48 patients with moderate to severe CHD. 119 Only 20 of the 28 patients randomized to the experimental group completed the 5-year follow-up and experienced a small but significant regression of coronary atherosclerosis (a 7.9% relative improvement) and a decrease in symptomatic and scintigraphic myocardial ischaemia. 119 , 120 In contrast, patients randomized to the usual care control group who completed the study ( n = 15) experienced a 27.7% relative worsening of the average percent diameter stenosis. However, this was a very small, under-powered study that does not allow to differentiate the effects of the vegetarian regimen from those induced by the very low-fat diet, regular aerobic exercise, smoking cessation, and stress reduction programme.

Many randomized clinical trials have tested the effects of different forms of vegetarian diets on cardiometabolic risk factors. Recent meta-analyses reported that vegetarian diets significantly improve several risk factors, including body weight (1.2–2.8 kg reduction), 121 SBP (3.3–7.6 mmHg reduction), 103 , 105 total cholesterol (0.32–0.76 mmol/L reduction), LDL cholesterol (0.32–0.59 mmol/L reduction), high-density lipoprotein (HDL) cholesterol (0.088–0.093 mmol/L reduction), 122 and HbA1c (0.15%–0.65% reduction). 123 A crossover randomized trial showed that a vegetarian diet was as effective as the Mediterranean diet in reducing body weight and fat mass, but the former resulted in significantly lower LDL cholesterol levels in middle-aged men and women. 22 However, many of these meta-analyses were focused on relatively healthy populations or did not stratify patients for gender and disease status. Evidence of the metabolic effects of plant-based diets in people with CVD is limited. Table 2 summarizes the ongoing clinical trials with vegetarian diet interventions in people with CVD.

Study characteristics of completed and ongoing clinical trials in people with cardiovascular diseases

CI, confidence interval; CHD, coronary heart disease; CR, calorie-restricted; F & V, fruits and vegetables; LDL-C, low-density lipoprotein cholesterol; LF, low-fat; LOV, lacto-ovo vegetarian diet; MD, mean differences; RCT, randomized controlled trial; SBP, systolic blood pressure; AHA, American Heart Association; HbA1c, haemoglobin A1c; IQR, interquartile range; NA, not applicable.

To our knowledge, only one randomized clinical trial to date has investigated the effects of a vegan diet on cancer outcomes, and preliminary data show a significant reduction in body weight and cholesterol at 8 weeks. 130   Table 3 summarizes the ongoing interventional clinical trials on the effects of vegetarian diets in people with cancer.

Study characteristics of clinical trials in people with cancer

LDL-C, low-density lipoprotein cholesterol; MD, mean differences; NA, not applicable; SBP, systolic blood pressure; WFPBD, whole-food plant-based diet; CR, calorie-restricted; MGUS, monoclonal gammopathy of undetermined significance; N-111, nutraceutical supplement, ingredients unspecified.

To the best of our knowledge, no randomized clinical trials to date have investigated the effects of vegetarian or vegan diets on cognitive impairment or dementia outcomes. Our search of ongoing randomized clinical trials identified only one study testing the effects of a low-fat vegan diet on dementia (NCT04606420).

Accumulating evidence indicate that some vegetarians, especially vegans who are consuming restrictive diets, are at greater risk of developing haemorrhagic stroke, bone fractures, and a range of vitamin and mineral deficiencies that are particularly dangerous for growing children and pregnant and breastfeeding women. 136 , 137 Vitamin B12, for example, is an essential vitamin produced by specific strains of soil bacteria that animals ingest when grazing grass. During digestion, large amounts of vitamin B12 are formed and incorporated in the animal’s meat, milk, and eggs. Fish and shellfish also contain considerable amount of vitamin B12; for instance, 100 g of clams contain up to 49 µg of vitamin B12. People following strict vegan diets must take a vitamin B12 supplement and/or consume foods supplemented with vitamin B12, including vitamin B12–fortified nutritional yeast, to avoid developing megaloblastic anaemia, a potentially irreversible form of neuropathy, and impaired bone formation. Vitamin B12 in spirulina or other algae is not bioavailable and may even inhibit vitamin B12 metabolism, 136 but vitamin B12 in duckweed is bioavailable. 138 Other potential deficiencies that vegetarians may develop are those from iron and zinc and occasionally riboflavin. 139 These deficiencies are especially important in vegan children, pregnant/breastfeeding women, and those with menorrhagia. Many plant foods contain iron and zinc, but their bioavailability is limited due plant anti-nutrients, such as phytates, tannins, lectins, and oxalates. Cooking, sprouting, fermenting, and processing plant foods with vitamin C rich foods can increase iron and zinc absorption. 140 Dietary calcium deficiency especially when coupled with protein restriction and excessive sodium intake can increase the risk of bone fractures in ethical vegans who do not consume healthy diets rich in calcium- and protein-rich plant foods. 93 , 137 , 141–143 Many plants contain calcium, and in some of these, its bioavailability is very high. For instance, 40%–60% of the calcium contained in cabbage, broccoli, or broccoli sprouts is absorbed because of their low oxalate content, against only 31%–32% of the calcium in cow’s milk. 144 Legumes, soy products (especially tofu made with calcium sulphate), and figs are also excellent sources of dietary calcium and protein. Regular exercise training, adequate sun exposure, and vitamin D supplementation are also important to promote bone health and prevent fractures 145 and may play a key role in the protection against certain autoimmune diseases and advanced (metastatic) cancers. 146 , 147

Vegetarians should pay close attention to the quality and composition of their diets. Data from epidemiological studies suggest that men and women consuming plant-based diets rich in healthier plant foods (fresh vegetables, legumes, minimally processed whole grains, fruits, nuts, monounsaturated-rich vegetable oils, tea, and coffee) have lower risks of CHD and overall mortality with regular fish intake providing additionally health benefits. 4 , 87 , 148–150 In contrast, people eating ‘unhealthy’ plant-based diets that emphasize refined grains, potatoes, high-sodium preserved vegetables, fried goods, sweets, juices, and sweetened beverages experienced higher risk of CHD and mortality. 4 , 5 Similar results have been found for T2DM. 5 Plant-based food products marketed as vegetarian and/or vegan can be rich in refined starch, added sugar, HFCS, salt, partially hydrogenated ( trans ) fat, and saturated fatty acids from tropical oils (e.g. one tablespoon of coconut oil contains 12 grams of saturated fat). Consumption of ultra-processed foods rich in sucrose and in HFCS, even if labelled as ‘vegetarian’ or ‘vegan’, promotes the development of insulin resistance, cardiometabolic syndrome, fatty liver disease, CVD, and cancer. 151 , 152 High salt intake not only increases the risk of developing hypertension, CHD, and stroke, 55 , 153 but it also triggers inflammation by increasing monocyte CCR2 expression. 154   Trans -fatty acids from partially hydrogenated oils have markedly adverse effects on serum lipids, systemic inflammation, endothelial function, and ultimately on the risk of developing T2DM and CVD. 155 However, naturally occurring trans -fatty acids found in milk and meat of ruminant animals have also similar adverse effects on LDL cholesterol, total cholesterol to HDL cholesterol ratio, and apolipoprotein B levels as do industrially produced trans -fatty acids. 156 Finally, people consuming unhealthy vegetarian diets rich in refined carbohydrates might also be at risk of protein malnutrition. Plant foods contain all the nine essential amino acids but in different proportions. Legumes, for instance, are high in lysine, but low in tryptophan and methionine. In contrast, whole grains are low in lysine but high in tryptophan and methionine. Therefore, it is essential to consume every day a mixture of whole grains, beans and nuts, and/or protein-rich plant foods (e.g. tofu and mankai, a cultivated strain of the Wolffia globosa aquatic plant) to provide adequate amounts of all the essential and non-essential amino acids.

Consuming vegetarian diets rich in minimally processed plant foods has been associated with a reduced risk of developing multiple chronic diseases including CVD, diabetes, hypertension, cancer, and dementia. Data from randomized clinic trials have confirmed a protective effect of vegetarian diets for the prevention of diabetes, hypercholesterolaemia, hypertension, and overweight, but to date, no data are available for acute coronary syndrome, heart failure, stroke, cognitive impairment, and dementia, and there are very limited data for cancer. However, since many individuals commonly and increasingly adopt vegetarian diets worldwide for ideological, cultural, environmental, and personal factors, it is of paramount importance to define which vegetarian dietary compositions provide better health outcomes and which components are detrimental to human health ( Graphical Abstract ).

New randomized trials are needed to understand whether the advantages of healthy plant-based diets represent an all-or-nothing phenomenon and if consuming less strict plant-based diets containing small quantities of animal products (e.g. pescatarian or traditional Mediterranean diets) has beneficial or detrimental effect on specific health outcomes, including the prevention of haemorrhagic stroke and bone fracture. Further, mechanistic studies are warranted to enhance our understanding about healthy plant-based food patterns and the biological mechanisms linking dietary factors and chronic diseases.

Recommendations for clinicians and allied health practitioners

For overweight men and women seeking weight loss and cardiometabolic improvement as means of primary and secondary prevention of T2DM, hypertension, and CVD, well-balanced and supplemented vegetarian diets rich in minimally processed plant foods may be an option, especially when coupled with calorie restriction and regular exercise training as recommended in the 2018 Physical Activity Guidelines Advisory Committee Scientific Report. 28 , 157 Regular fish intake can provide additional cardiovascular health benefits. 158 Additional trials are warranted to determine whether patients with CVD will ultimately benefit from consuming vegetarian and vegan diets and, if so, in what ways. As with any potential therapeutic strategy, the risks and benefits of vegetarian diets must be discussed with patients. There is evidence to suggest that some vegetarians, particularly those who follow restrictive diets such as vegans, may be at greater risk of haemorrhagic stroke and bone fractures if they do not carefully plan their diets and consume fortified plant-based foods or supplements. In addition, vegans and some vegetarians may be at risk of deficiencies in vitamins and minerals such as vitamin B12, riboflavin, iron, zinc, calcium, and omega-3 fatty acids. This can be particularly dangerous for pregnant and breastfeeding women and growing children, as these nutrients are crucial for foetal and child development. It is recommended that anyone considering a vegetarian or vegan diet consult with a registered dietitian or healthcare provider to ensure that their diet is nutritionally adequate. Consuming vegetarian diets rich in refined grains, potatoes, high-sodium preserved vegetables, fried goods, sweets, juices, and sweetened beverages can increase the risk of developing T2DM and CVD morbidity and mortality. Finally, in the case of vegetarian diets and cancer, the benefits and risks are not well defined. As a weight loss strategy, this may be an option for some cancer patients, but there are currently no data to suggest that vegetarian or vegan diets in the absence of weight loss and/or changes in physical activity patterns will have a positive impact on cancer outcomes, including either recurrence or the development of metastatic cancers.

Supplementary data are not available at European Heart Journal online.

Disclosure of Interest

All authors declare no conflict of interest for this contribution.

Most extracted data and study materials are available from previously published research. Additional data extracted from the corresponding author of included studies will be shared upon reasonable request.

L.F. is supported by grants from the Australian National Health and Medical Research Council’s Investigator Grant (APP1177797), Australian Youth and Health Foundation, and Philip Bushell Foundation. W.W. is supported by grants from the National Institutes of Health on the epidemiology of cancer.

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  • Published: 23 November 2020

Vegetarian and vegan diets and risks of total and site-specific fractures: results from the prospective EPIC-Oxford study

  • Tammy Y. N. Tong   ORCID: orcid.org/0000-0002-0284-8959 1 ,
  • Paul N. Appleby 1 ,
  • Miranda E. G. Armstrong 2 ,
  • Georgina K. Fensom 1 ,
  • Anika Knuppel 1 ,
  • Keren Papier 1 ,
  • Aurora Perez-Cornago 1 ,
  • Ruth C. Travis 1 &
  • Timothy J. Key 1  

BMC Medicine volume  18 , Article number:  353 ( 2020 ) Cite this article

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There is limited prospective evidence on possible differences in fracture risks between vegetarians, vegans, and non-vegetarians. We aimed to study this in a prospective cohort with a large proportion of non-meat eaters.

In EPIC-Oxford, dietary information was collected at baseline (1993–2001) and at follow-up (≈ 2010). Participants were categorised into four diet groups at both time points (with 29,380 meat eaters, 8037 fish eaters, 15,499 vegetarians, and 1982 vegans at baseline in analyses of total fractures). Outcomes were identified through linkage to hospital records or death certificates until mid-2016. Using multivariable Cox regression, we estimated the risks of total ( n  = 3941) and site-specific fractures (arm, n  = 566; wrist, n  = 889; hip, n  = 945; leg, n  = 366; ankle, n  = 520; other main sites, i.e. clavicle, rib, and vertebra, n  = 467) by diet group over an average of 17.6 years of follow-up.

Compared with meat eaters and after adjustment for socio-economic factors, lifestyle confounders, and body mass index (BMI), the risks of hip fracture were higher in fish eaters (hazard ratio 1.26; 95% CI 1.02–1.54), vegetarians (1.25; 1.04–1.50), and vegans (2.31; 1.66–3.22), equivalent to rate differences of 2.9 (0.6–5.7), 2.9 (0.9–5.2), and 14.9 (7.9–24.5) more cases for every 1000 people over 10 years, respectively. The vegans also had higher risks of total (1.43; 1.20–1.70), leg (2.05; 1.23–3.41), and other main site fractures (1.59; 1.02–2.50) than meat eaters. Overall, the significant associations appeared to be stronger without adjustment for BMI and were slightly attenuated but remained significant with additional adjustment for dietary calcium and/or total protein. No significant differences were observed in risks of wrist or ankle fractures by diet group with or without BMI adjustment, nor for arm fractures after BMI adjustment.

Conclusions

Non-meat eaters, especially vegans, had higher risks of either total or some site-specific fractures, particularly hip fractures. This is the first prospective study of diet group with both total and multiple specific fracture sites in vegetarians and vegans, and the findings suggest that bone health in vegans requires further research.

Peer Review reports

Fractures in adulthood and older ages are a common occurrence which pose a significant burden to health systems worldwide [ 1 ]. Previous epidemiological studies have shown that vegetarians had lower bone mineral density (BMD) than non-vegetarians [ 2 , 3 ], but the associations of vegetarian diets with fracture risks are unclear. Potential risk differences are plausible however, owing to differences in several dietary factors, such as the substantially lower intakes of calcium in vegans [ 4 , 5 ], lower intakes of dietary protein in both vegetarians and vegans [ 6 , 7 ], and the lower body mass index (BMI) of non-meat eaters [ 2 , 8 ].

Prior studies have linked both calcium and protein intakes to bone health, but their relationships with fracture risks are nuanced. For calcium, although previous meta-analyses have found that calcium supplements are effective in producing small increases in BMD [ 9 ], it is less clear whether this degree of improvement would be sufficient to reduce fracture risks [ 10 ]. However, a recent meta-analysis of randomised trials showed that combined vitamin D and calcium supplementation, but not vitamin D supplementation alone, was effective in fracture prevention, therefore supporting the importance of calcium [ 11 ]. For protein, while older studies suggested that high protein intake might lead to higher calcium excretion and therefore weaker bones [ 12 ], more recent evidence has suggested a positive association between protein and bone health, although this might not translate to differences in fracture risk [ 13 ]. In addition, BMI is also an important factor for fracture risk [ 14 ], and a recent study suggested that the lower BMD observed in US vegetarians might be largely explained by their lower BMI and waist circumference [ 15 ]. However, the directions of association between BMI and fracture risk differ across fracture sites, and low BMI has been associated with a higher risk of hip fracture but lower risk of ankle fracture [ 14 ].

The largest study to date on vegetarian diet group and fracture risks came from previous analyses in EPIC-Oxford on around 30,000 participants, and reported that vegans, but not vegetarians, had higher risks of total fractures, although this analysis had a short follow-up (5 years) and relied on self-reported outcome data [ 16 ]. The only two other studies on the topic included a small number of participants and did not report on site-specific fractures [ 17 , 18 ]. Hence, the possible differences in fracture risks by vegetarian diet groups are still unclear, and it is not known whether the risks might differ by fracture sites.

Therefore, the aim of this study was to examine the risks of total and site-specific fractures in a prospective cohort with close to 18 years of average follow-up, including a large proportion of non-meat eaters, and with outcome data based on record linkage.

Study population

EPIC-Oxford is a prospective cohort study which recruited approximately 65,000 men and women across the UK between 1993 and 2001, via either general practices or by postal questionnaire. Details of the recruitment process and eligibility criteria for inclusion in the analyses can be found in Additional File  1 : Supplementary methods [ 4 , 19 ] and in the participant flow chart (Additional File 1 : Fig. S1). The study has approval by a Multicentre Research Ethics Committee (Scotland A Research Ethics Committee). All participants provided written informed consent.

Classification of diet group

At recruitment, participants completed a questionnaire which asked about diet, socio-demographic characteristics, lifestyle, and medical history. A follow-up questionnaire which asked similar questions was sent to participants in 2010. Based on the responses to both questionnaires (if the participant completed the follow-up questionnaire), the participants were categorised into meat eaters, fish eaters (did not eat meat but ate fish), vegetarians (did not eat meat or fish, but ate one or both of dairy or eggs), and vegans (participants who did not eat meat, fish, dairy, and eggs) at both time points. Further details on the questionnaires, classification of diet group including agreement of diet group at baseline and follow-up, and data collection of other baseline characteristics can be found in Additional File 1 : Supplementary methods [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].

Outcome assessment

Participants were followed up for health outcomes via record linkage to National Health Service records until 31 March 2016 in England, 31 May 2016 in Wales, and 31 October 2016 in Scotland. The outcomes of interest were the first recorded hospital admission (inpatient admissions in England, inpatient admissions and day cases in Wales and Scotland) or death from total and site-specific fractures, including fractures of the arm (i.e. humerus, radius, and ulna), wrist, hip, leg (i.e. femur [excluding neck of femur], patella, tibia, and fibula), ankle, and other main sites (i.e. clavicle, rib, or vertebra), identified by the relevant 9th or 10th revisions of the World Health Organization’s International Classification of Diseases (ICD-9/ICD-10) codes (Additional File 1 : Table S1). For total fractures, incidence was defined as the first recorded occurrence of any diagnosis of any fracture; for site-specific fractures, incidence was defined as the first recorded occurrence of any fracture at that particular site, without censoring for previous fractures at other sites. Fractures at the clavicle, rib, and vertebra were examined as one composite outcome due to the small number of cases at these sites, but the three sites were examined separately in secondary analyses.

Statistical analyses

Baseline characteristics and food and nutrient intakes of the EPIC-Oxford participants were summarised by diet group. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between the four diet groups (meat eaters, fish eaters, vegetarians, vegans) and total and each site-specific fracture of interest, using meat eaters as the reference group. The underlying time variable was the age at recruitment to the age at diagnosis, death, or administrative censoring, whichever occurred first. For participants who completed both the baseline and follow-up questionnaires, diet group and relevant time-varying covariates (smoking and alcohol consumption, BMI, dietary calcium or protein) were updated at follow-up; otherwise, the baseline dietary or covariate information was carried forward.

All analyses were stratified by sex, method of recruitment, and region of residence, and adjusted for year of recruitment, ethnicity, Townsend deprivation index [ 25 ], education level, physical activity [ 26 ], smoking, alcohol consumption, dietary supplement use, height, and in women menopausal status, hormone replacement therapy use, and parity. We tested models with and without adjustment for BMI. Details on the categorisation of covariates can be found in the Supplementary methods. The proportional hazards assumption was assessed on the basis of Schoenfeld residuals and was not violated for the variables of interest in the adjusted model for any of the outcomes. Subsequently, we estimated absolute rate differences based on the BMI adjusted model, using a previously reported method [ 28 ].

To evaluate the influence of dietary calcium and protein on the associations, we included models further adjusting for either dietary calcium or dietary protein intake, and simultaneously adjusting for both variables. Additional analyses were also performed limited to people with sufficient dietary calcium (≥ 700 mg/day) or dietary protein intake (≥ 0.75 g of protein per day/kg body weight) in accordance with UK dietary guidelines [ 29 , 30 ].

As sensitivity analyses, we repeated the analyses (with adjustment for BMI) further adjusting for energy intake, excluding the first 5 years of follow-up, excluding participants with prior diseases (baseline history of diabetes, heart disease, stroke, or cancer), excluding participants who were receiving long-term treatment for any illness, and with multiple imputation for missing covariates [ 31 ]. Heterogeneity of results by age at recruitment (below and above age 50), sex, menopausal status, physical activity level (inactive/low and moderate/high activity), and BMI (below and above 22.5 kg/m 2 ) was assessed for total and hip fractures, which had the largest numbers of cases. Cut-offs of age and BMI were chosen to ensure a reasonable distribution of number of cases in categories across all diet groups, based on analyses of total fractures.

All analyses were performed using Stata version 15.1 (StataCorp, TX, USA), and 2-sided p values < 0.05 were considered significant. The forest plot was generated using R (R Foundation for Statistical Computing, Vienna, Austria).

The study population included a minimum of 54,898 participants (in analyses for total fractures), of whom 30,391 had repeated measures of diet 14 years later (details in Additional File 1 : Fig. S1). Baseline characteristics in the overall cohort are tabulated by the four diet groups in Table  1 , and separately for men and women in Additional File 1 : Table S2. Other dietary and nutrient intakes are tabulated by the four diet groups, separately for men and women in Additional File 1 : Table S3. A summary description of the baseline and dietary characteristics can be found in Additional File 1 : Supplementary results.

Over an average of 17.6 years of follow-up, we observed 3941 cases of total fractures (including 12 first reported at death; 943,934 person-years), 566 arm fractures (1 at death; 967,829 person-years), 889 wrist fractures (965,127 person-years), 945 hip fractures (1 at death; 967,599 person-years), 366 leg fractures (1 at death; 968,985 person-years), 520 ankle fractures (967,399 person-years), and 467 other main site fractures (968,921 person-years). The results of longitudinal associations between diet group and total and site-specific fractures are shown in Fig.  1 and Table  2 . Absolute rate differences (AD) in the outcomes by diet group based on the BMI adjusted model are shown in Table  3 .

figure 1

Risks of total and site-specific fractures by diet group in EPIC-Oxford. Estimates also shown in Table  2 as model 2. All analyses were stratified by sex, method of recruitment (general practice or postal), and region (7 categories), and adjusted for year of recruitment (per year from ≤ 1994 to ≥ 1999), ethnicity (white, other, unknown), Townsend deprivation index (quartiles, unknown), education level (no qualifications, basic secondary (e.g. O level), higher secondary (e.g. A level), degree, unknown), physical activity (inactive, low activity, moderately active, very active, unknown), smoking (never, former, light, heavy, unknown), alcohol consumption (< 1 g, 1–7 g, 8–15 g, 16+ g/day), dietary supplement use (no, yes, unknown), height (5 cm categories from < 155 to ≥ 185 cm, unknown), body mass index (< 18.5, 18.5–19.9, 20–22.4, 22.5–24.9, 25–27.4, 27.5–29.9, 30–32.4, ≥ 32.5 kg/m 2 , unknown), and in women menopausal status (premenopausal, perimenopausal, postmenopausal, unknown), hormone replacement therapy use (never, ever, unknown), and parity (none, 1–2, ≥ 3, unknown). Other main site fractures are defined as fractures of the clavicle, rib, or vertebra

Compared with meat eaters, vegetarians (HR 1.11; 95% CI 1.02, 1.21) and vegans (1.50; 1.26, 1.78) had higher risks of total fractures after adjustment for confounders (Table  2 model 1). The associations attenuated with additional adjustment of BMI (vegetarians—1.09; 1.00, 1.19; vegans—1.43; 1.20, 1.70), but remained clearly significant in vegans (Table  2 model 2, Fig.  1 ). The equivalent rate differences were 4.1 (0.8, 7.6) more cases in vegetarians and 19.4 (9.6, 30.9) more cases in vegans for every 1000 people over 10 years. The associations were attenuated further but remained significant in vegans with additional adjustment for dietary calcium (1.31; 1.10, 1.57, Table  2 model 3), total dietary protein (1.39; 1.16, 1.67, Table  2 model 4), or both dietary factors simultaneously (1.30; 1.08, 1.56, Table  2 model 5).

For site-specific fractures (Fig.  1 and Table  2 ), the largest magnitudes in risk difference by diet group were observed for hip fractures. After adjustment for BMI, the risks were higher in fish eaters (HR 1.26; 1.02, 1.54, or AD 2.9; 0.6, 5.7), vegetarians (HR 1.25; 1.04, 1.50, or AD 2.9; 0.9, 5.2), and vegans (HR 2.31; 1.66, 3.22, or AD 14.9; 7.9, 24.5) than meat eaters. Similar to the findings for total fractures, the associations appeared stronger before BMI adjustment and attenuated but remained strongly significant in vegans after further adjustment for both calcium and protein.

For the other sites, after adjustment for BMI, the vegans had a higher risk of leg fractures (2.05; 1.23, 3.41) and other main site fractures (clavicle, rib, vertebra, 1.59; 1.02, 2.50) than the meat eaters (Fig.  1 and Table  2 ). When the other main site fractures were examined separately, a significantly higher risk was observed in the vegans for vertebral fracture (2.42; 2.31, 4.48), but not for the other two sites (Additional File 1 : Table S4). No significant differences in risks between diet groups were observed for arm, wrist, or ankle fracture, after adjustment for BMI (Fig.  1 and Table  2 ), although a higher risk of arm fractures was observed in both vegetarians (1.28; 1.03, 1.60) and vegans (1.67; 1.07, 2.61) in the multivariable model before BMI adjustment (Table  2 model 1).

Results from secondary analyses are reported in more detail in the Supplementary results. Overall, results were consistent when the analyses were restricted to participants with sufficient intakes of calcium and protein (Table  4 ), and also in other secondary analyses, including with further adjustment for energy intake, excluding the first 5 years of follow-up, excluding participants with prior diseases or receiving long-term treatment for any illness, or with multiple imputation for missing covariates (Additional File 1 : Table S5).

In stratified analyses of total (Table  5 ) and hip fractures (Additional File 1 : Table S6), a significantly higher risk of both total and hip fractures was only observed in vegetarians over age 50 at recruitment, although vegans had higher risks in both age groups, and a significant p for interaction was only observed for total fractures. For both types of fractures, the significant associations in vegans appeared stronger in women, particularly those who were postmenopausal, and participants with low physical activity and lower BMI, possibly partly due to the larger number of participants in most of these subgroups, but a higher risk of hip fracture was only observed in the fish eaters and vegetarians in the higher BMI category. Because the numbers of cases in these subgroup analyses were often very small, it is likely that we did not have sufficient power to identify possible differences.

Summary of findings

Overall, vegans in this study had higher risks of total and some site-specific fractures (hip, leg, vertebra) than meat eaters. The strongest associations were observed for hip fractures, for which fish eaters, vegetarians, and vegans all had higher risks. These risk differences might be partially explained by the lower average BMI, and lower average intakes of calcium and protein in the non-meat eaters. However, because the differences remained, especially in vegans, after accounting for these factors, other unaccounted for factors may be important.

Comparison with previous studies

Few previous studies have examined the associations of vegetarian diets with fracture risk. In previous EPIC-Oxford analyses of self-reported fractures with short follow-up, vegans, but not fish eaters or vegetarians, were reported to have 30% (HR 1.30; 1.02, 1.66) higher risks of total fractures, but in contrast to the current findings, the association attenuated completely when restricted to participants who reported consuming at least 525 mg/day of calcium [ 16 ]. This apparent inconsistency might be explained by several differences between the current and previous analysis; while the current analysis included close to 4000 hospital-admitted cases over more than 17 years of average follow-up on around 55,000 participants, the previous study included under 2000 self-reported fracture cases over 5 years of follow-up on around 35,000 participants. Given the difference in case ascertainment method, the current analysis is less prone to reporting error and is not susceptible to selective drop-out. It is also possible that there was insufficient power to detect a difference after stratifying by calcium intake status in the previous analysis, which also did not examine site-specific fractures.

The only other studies which reported on risks of fractures by diet groups were one small prospective study in Vietnam of 210 women (105 vegans) which found no significant difference in fracture incidence (10 cases in total) between vegans and omnivores over 2 years [ 17 ], and one prospective study in India which reported a higher crude rate of stress fractures (604 cases in total) among 2131 vegetarian than 6439 non-vegetarian army recruits [ 18 ]. Separately, previous findings from the Adventist Health Study 2, which has a large proportion of vegetarians, showed that participants who ate meat more than three times a week had lower risks of hip fractures (HR 0.60; 0.41, 0.87) than participants who ate meat less than once a week [ 32 ], while combined analyses of peri- and postmenopausal women from Adventist Health Study 1 and 2 found that participants who ate meat more than four times a week had lower risks of wrist fractures (HR 0.44; 0.23, 0.84) than participants who never ate meat [ 33 ], but these results cannot be used to infer risks in fish eaters, vegetarians, or vegans as separate diet groups.

Interpretation of results and implications

The higher observed risks of fractures in non-meat eaters were usually stronger before BMI adjustment, which suggests that the risk differences were likely partially due to differences in BMI. Vegetarians and vegans generally have lower BMI than meat eaters [ 2 , 8 ], and previous studies have reported an inverse association between BMI and some fractures, particularly hip fractures, possibly due to reasons including the cushioning against impact force during a fall, enhanced oestrogen production with increased adiposity, or stronger bones from increased weight-bearing [ 14 , 34 ]. However, a positive association between BMI and fracture risk has been observed for some other sites, including ankle fractures, possibly as a result of higher torques from twisting of the ankle in people with higher BMI [ 14 ]. No significant differences in the risks of ankle fractures by diet group were observed in our study, but the point estimates were directionally consistent with a lower risk in all non-meat eaters before BMI adjustment, and the results might reflect a counterbalance between a protective effect from lower BMI but higher risk due to lower intakes of nutrients related to bone health in the non-meat eaters.

In our stratified analyses, there is limited evidence of heterogeneity in fracture risk by BMI categories. Although a statistically significant higher risk of total and hip fractures was only observed in vegans in the lower BMI category (< 22.5 kg/m 2 ), our interpretation is limited by the small numbers of cases in each stratum in these analyses, especially because of the strong correlation between diet group and BMI, which results in very few vegans in the higher BMI category, and vice versa comparatively small numbers of meat eaters with a low BMI. In addition to BMI, previous studies have reported that muscle strength is an important risk factor which is protective against fall risk and subsequently fractures in older adults [ 35 ]. A previous study in the UK found lower lean mass and grip strength in vegetarians and vegans compared to meat eaters [ 2 ]; therefore, the possible influences of muscle strength and fall risk in addition to bone health on fracture risk in vegetarian and vegan populations should be further investigated. Fractures at some sites, especially at the hip, may also be more related to osteoporosis than fractures at some other sites, which might be more likely to be the result of violent impacts in accidents [ 36 , 37 ]. We were unable to differentiate fragility and traumatic fractures in this study, since data were not available on the causes of the fractures.

In this study and previous studies, vegans had substantially lower intakes of calcium than other diet groups since they do not consume dairy, a major source of dietary calcium [ 4 , 5 ], while both vegetarians and vegans had lower protein intakes on average [ 6 , 7 ]. In the human body, 99% of calcium is present in bones and teeth in the form of hydroxyapatite, which in cases of calcium deficiency gets resorbed to maintain the metabolic calcium balance, and thus, osteoporosis could occur if the calcium was not restored [ 38 , 39 , 40 ]. A recent meta-analysis reported that increasing calcium intake from either dietary sources or supplements resulted in small increases in BMD [ 9 ], but the evidence on fracture risk has been less consistent. Previous analyses in EPIC-Oxford found a higher risk of self-reported fractures in women, but not men, with calcium intakes below 525 mg/day compared with over 1200 mg/day [ 41 ]. A recent meta-analysis of both randomised trials and prospective studies concluded that there was no evidence of an association between calcium intake from diet and fracture risk, but a possible weak protective association between calcium supplement use and some fractures [ 10 ]. More recently however, a separate meta-analysis showed a protective effect against fractures of combined vitamin D and calcium supplements, but not vitamin D supplements alone [ 11 ].

For protein, some older studies suggested that excessive protein intake would lead to an increased metabolic acid load, subsequently buffered by bone resorption and calciuria, and thus poorer bone health [ 12 , 42 ]. However, more recent experimental evidence has shown that high protein intake also increases intestinal calcium absorption [ 43 ], and stimulates the production of insulin-like growth factor (IGF)-I [ 44 ], which in turn is associated with better bone health [ 45 , 46 ]. Two meta-analyses, which included different studies, both reported a possible protective effect of higher protein intake on lumbar spine BMD [ 13 , 47 ]; several epidemiological studies have reported inverse associations between protein intake and fracture risks [ 48 , 49 , 50 ], though a recent meta-analysis found no significant association between protein intake and osteoporotic fractures [ 51 ].

The higher risks of fractures especially in the vegans remained significant after adjustment for dietary calcium and protein, which suggests that these factors may at most only partly explain the differences in fracture risks by diet group, and other factors may also contribute. However, estimation of intakes of these nutrients by questionnaires has substantial error, and we were only able to account for differences in dietary calcium but not differences in calcium supplement use, since data on the latter were not available. A detailed analysis of the associations of specific foods, such as meat or dairy, with fracture risk is beyond the scope of the current study, but should be explored in further studies. Future research should also focus on possible effects of other nutrients or biological markers on fracture risks, for example circulating vitamin D, vitamin B 12 , or IGF-I, which may vary by degree of animal-sourced food intake [ 52 , 53 , 54 ]. The value of incorporating habitual dietary habits in addition to established parameters for predicting fracture risks in clinical settings should also be further explored.

Strengths and limitations

The strengths of this study were that it included a large number of non-meat eaters with a long follow-up, and studied both total and site-specific fractures, after accounting for a range of confounders. We updated diet group and relevant confounders where possible, to account for changes over the period of follow-up. There was little evidence of reverse causality, as results were similar after excluding the first 5 years of follow-up. The outcome data were ascertained based on hospital records, which reduced misreporting and selective loss to follow-up, although a possible limitation of this approach was that less serious fractures that did not require hospitalisation would not have been captured.

Of other limitations, while we excluded known cases of fractures before baseline based on hospital records, this may not be a complete exclusion, since no questions on previous diagnosis of fractures (prior to the earliest available hospital data) or osteoporosis were asked at baseline, and no data on the use of anti-osteoporosis medication were available. Repeat measures of diet were not available in all participants, and the exact date of dietary change during follow-up was also not recorded, but considering the good agreement of diet group in participants who did provide a repeat measure, and the fact that a dietary change may only influence fracture risk after a period of time, we do not expect substantial misclassification. As with all observational studies, residual confounding from both dietary and non-dietary factors may be present; for example, the role of calcium might have been underestimated due to measurement error. As the study predominantly includes white European participants, generalisability to other populations or ethnicities may be limited, which could be important considering previously observed differences in BMD [ 2 , 55 ] and fracture risks [ 56 ] by ethnicity. We also observed only a small number of cases in many subgroup analyses, and thus, it is likely we had insufficient power to reliably assess whether there might be any heterogeneity by these subgroups including age, sex, menopausal status, or BMI; additional data are therefore needed to confirm or refute possible differences. In particular, because the EPIC-Oxford cohort consists predominantly of women (77%), further work should be conducted in cohorts with a larger proportion of men to explore heterogeneity by sex and to derive reliable sex-specific estimates.

Overall, we found that compared with meat eaters, vegans had higher risks of total, hip, leg, and vertebral fractures, while fish eaters and vegetarians had higher risk of hip fractures. These risk differences were likely partly due to their lower BMI, and possibly to lower intakes of calcium and protein. More studies are needed especially from non-European and contemporary populations to examine the generalisability of our findings and to explore possible heterogeneity by factors including age, sex, menopausal status, and BMI. Future work might benefit from examining possible biological pathways by investigating serum levels of vitamin D, vitamin B 12 , or IGF-1, or in assessing the possible roles of other nutrients that are abundant in animal-sourced foods.

Availability of data and materials

The data access policy for the EPIC-Oxford study is available via the study website ( www.epic-oxford.org/data-access-sharing-and-collaboration/ ).

Abbreviations

Bone mineral density

  • Body mass index

European Prospective Investigation into Cancer and Nutrition

International Classification of Diseases

Insulin-like growth factor-1

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Acknowledgements

We thank all participants in the EPIC-Oxford cohort for their invaluable contribution.

The work is supported by the UK Medical Research Council MR/M012190/1 and Wellcome Trust Our Planet Our Health (Livestock, Environment, and People, LEAP 205212/Z/16/Z). The funders had no role on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford, OX3 7LF, UK

Tammy Y. N. Tong, Paul N. Appleby, Georgina K. Fensom, Anika Knuppel, Keren Papier, Aurora Perez-Cornago, Ruth C. Travis & Timothy J. Key

Centre for Exercise, Nutrition and Health Sciences, School for Policy Studies, University of Bristol, Bristol, UK

Miranda E. G. Armstrong

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TYNT and TJK conceived and designed the research question. TYNT analysed the data and wrote the first draft of the manuscript. All authors provided input on data analysis and interpretation of results. All authors revised the manuscript critically for important intellectual content, and read and approved the final manuscript. TYNT is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

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The study has approval by a Multicentre Research Ethics Committee (Scotland A Research Ethics Committee). All participants provided written informed consent.

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The authors declare that they have no competing interests.

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Supplementary information

Additional file 1:.

Supplementary results. Fig. S1. Participant flow chart. Table S1. ICD codes for incident fractures. Table S2. Baseline characteristics by diet group and sex. Table S3. Food and nutrient intake by diet group and sex. Table S4. Risks of subtypes of main site fractures. Table S5-Sensitivity analyses. Table S6. Risks of hip fractures by age, sex, menopausal status, physical activity and BMI.

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Tong, T.Y.N., Appleby, P.N., Armstrong, M.E.G. et al. Vegetarian and vegan diets and risks of total and site-specific fractures: results from the prospective EPIC-Oxford study. BMC Med 18 , 353 (2020). https://doi.org/10.1186/s12916-020-01815-3

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Association between vegetarian and vegan diets and depression: A systematic review

Affiliations.

  • 1 Department of Nutrition and Dietetics, School of Life Course and Population Sciences, King's College London, London, UK.
  • 2 Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus.
  • PMID: 36045075
  • DOI: 10.1111/nbu.12540

Recent evidence suggests that vegetarian and vegan diets may increase the risk and symptoms of depression, a mental health condition affecting 350 million people globally. We aimed to systematically review the literature on the associations between vegetarian and/or vegan diets and the risk or symptoms of depression using evidence from both observational and intervention studies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with pre-specification of all methods. A systematic search for relevant papers was performed on Medline and Embase, Web of Science and the Cochrane Library for cohort, case-control, cross-sectional studies or randomised controlled trials examining associations between a vegetarian or vegan diet and depression in adults. Three independent reviewers extracted data and assessed risk of bias using the National Heart, Lung, and Blood Institute of the National Institutes of Health for Quality Assessment of Observational Cohort and Cross-Sectional Studies and Controlled Studies. Evidence was tabulated according to the type of diet analysed as vegetarian, vegan or both and narratively synthesised. A total of 23 studies (18 cross-sectional, three prospective cohort and two randomised controlled trials) with 25 study outcomes were eligible for inclusion in this review. Conflicting evidence was found on the association between vegetarian or vegan diets and depression. Eleven (44%) of the outcomes indicated that vegetarian and vegan diets were associated with higher rates of depression, while seven (28%) outcomes revealed beneficial effects of the diets on depression. Seven (28%) outcomes found no association between vegetarian and vegan diets and depression, although two of these studies found a higher risk of depression in some groups. The quality of evidence was rated as good for four of the studies with the remaining 19 studies rated as fair. The evidence on the effect of vegetarian and vegan diets on depression is contradictory, possibly due to the heterogeneity of the studies analysed. Further research, including longitudinal and intervention studies, is required to resolve this observation.

Keywords: adults; depression; systematic review; vegan diet; vegetarian diet.

© 2022 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.

Publication types

  • Systematic Review
  • Cross-Sectional Studies
  • Depression / epidemiology
  • Diet, Vegan*
  • Diet, Vegetarian* / adverse effects
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • United States
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J.D. Biersdorfer has been writing about consumer technology for The Times since 1998. She also creates the weekly interactive literary quiz for the Book Review and occasionally contributes reviews. More about J. D. Biersdorfer

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Colombia’s Fernando Trujillo named Nat Geo’s 2024 Explorer of the Year

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In honor of his immense dedication to working with local communities in South America to co-create conservation solutions that protect endangered aquatic wildlife and ecosystems, the National Geographic Society announced that Fernando Trujillo is the 2024 recipient of the Rolex National Geographic Explorer of the Year Award.

The award given from Washington D.C., will be presented at the National Geographic Society’s annual Explorers Festival, and hosted in collaboration with Rolex, a leading corporate partner of the Society.

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Trujillo has had a long history with the Society, receiving his first grant in 2008 to study the abundance of the Amazonian river dolphins in Brazil and Peru. He is currently a lead Explorer on the National Geographic and Rolex Perpetual Planet Amazon Expedition , a comprehensive, multi-year, scientific and storytelling exploration of the Amazon River basin from the Andes to the Atlantic. He serves as a mentor to National Geographic Young Explorers and has hosted the Society’s live streamed Spanish language Explorer Classroom sessions.

The biologist has spent decades studying aquatic wildlife with special attention to the Amazonian pink river dolphin in South America. His deep connection with the species earned him the nickname “omacha.” In Tikuna Indigenous culture, omacha can transform into a man to protect the other dolphins from harm.

“Trujillo embodies this spirit in his tireless efforts to build a deeper understanding, and appreciation for river dolphins among the local community,” highlighted the National Geographic Society. “He works with community leaders, veterinarians and local scientists to track the dolphins’ migratory patterns and conduct health assessments of this iconic species as a barometer for river health,” noted the prestigious conservation entity.

“As Amazonia experiences some of the most extreme climate phenomena in decades, it is critical to shine a spotlight on this issue, conduct deeper research and generate solutions to protect this magnificent region,” believes Trujillo. “Through this award, the Society is providing a megaphone for me to reach a global audience and encourage them to learn more and to care about the changes impacting our planet,” he said.

research paper about vegetarian

Over his career, Trujillo has worked with local and national governments to increase fishery agreements, enhance protection of wetlands, and led tree planting initiatives to revitalize ecosystems deeply impacted by climate and environmental change.

The environmental crusader has facilitated groundbreaking regional and international collaborations to protect dolphins and their rivers, including a river dolphin Conservation Management Plan signed by the governments of Brazil, Colombia, Ecuador, Peru, Bolivia and Venezuela during the International Whaling Commission – IWC – convening.

In October 2023, along with fellow National Geographic Explorers Maria Jimena Valderrama and Mariana Frias, Trujillo spearheaded the signing of the first-of-its-kind global declaration for the protection of river dolphins.

Trujillo is a founding member of the Fundación Omacha , reflecting his nickname, the South American based nonprofit creates sustainable conservation strategies that enhance protection of surrounding forests, rivers, lakes, and wildlife while still sustaining the livelihood of the local communities.

Fernando Trujillo made the front page of The City Paper’s edition No.56.

Fernando Trujillo’s campaign to the save Colombia’s pink river dolphin

The City Paper was founded in 2008 as Colombia’s first free English language newspaper. A decade later, it was awarded the country’s Manuel Murillo Toro medal in communications for contributing to informed and objective coverage of Colombia.

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    Quality of life relates to a subjective perception of well-being and functionality, and encompasses four main life domains: physical, psychological, social, and environmental. The adoption of a vegetarian diet, despite being a dietary pattern, could potentially influence and be influenced by all of these domains, either positively or negatively.

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    Results. Regarding macronutrients, vegan diets are lower in protein intake compared with all other diet types. Veganism is also associated with low intake of vitamins B 2, Niacin (B 3), B 12, D, iodine, zinc, calcium, potassium, selenium.Vitamin B 12 intake among vegans is significantly lower (0.24-0.49 μg, recommendations are 2.4 μg) and calcium intake in the majority of vegans was below ...

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    Recent evidence suggests that vegetarian and vegan diets may increase the risk and symptoms of depression, a mental health condition affecting 350 million people globally. ... with pre-specification of all methods. A systematic search for relevant papers was performed on Medline and Embase, Web of Science and the Cochrane Library for cohort ...

  14. Vegetarian diet and mental health: Cross-sectional and longitudinal

    Much research in western countries has shown that altruistic and ethical concerns are primary reasons for becoming vegetarian, but this research on motives has yet to be extended to eastern cultures (Timko et al., 2012; Jabs et al., 1998; Fox and Ward, 2008; Lea and Worsley, 2003). It could be that differences in motivation explain the ...

  15. Artificially Intelligent Help for Planning Your Summer Vacation

    Travel-focused A.I. bots and more eco-friendly transportation options in online maps and search tools can help you quickly organize your seasonal getaway. By J. D. Biersdorfer J.D. Biersdorfer has ...

  16. Colombia's Fernando Trujillo named Nat Geo's 2024 Explorer of the Year

    The Society is extraordinarily proud to name Fernando the 2024 Rolex National Geographic Explorer of the Year as a testament to the positive, profound difference he continues to make for our planet and those who call it home," she said. Trujillo has had a long history with the Society, receiving his first grant in 2008 to study the abundance ...

  17. Beyond Meatless, the Health Effects of Vegan Diets: Findings from the

    1. Introduction. A recent Gallup Poll conducted in July 2012 reported that 5% of the American adult population is vegetarian. Only 2% reported adopting a vegan diet, in that they abstain from meat, fish, dairy, and eggs [].The attitudes towards vegetarianism have gained better acceptance; however, the percentage of Americans who consider themselves to be vegetarians is largely unchanged since ...

  18. Impact of vegetarian versus non-vegetarian diet on health outcomes in

    In the present study, the vegetarian group showed increased mindful eating scores which can be a reason for reduced weight in the vegetarian group. Research has found that individuals practicing mindful eating also have lower problematic eating behaviors and consume smaller serving sizes of energy-dense foods [43]. Also in the present study ...