ArticlePDF AvailableLiterature Review

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


Abstract and Figures

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.
Content may be subject to copyright.
Medawar et al. Translational Psychiatry (2019) 9:226
ranslational Psychiatry
The effects of plant-based diets on the body
and the brain: a systematic review
Evelyn Medawar
, Sebastian Huhn
, Arno Villringer
and A. Veronica Witte
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
interventionin PubMed ltered for clinical trials in humans retrieved 205 studies out of which 27, plus an additional
search extending the selection to another ve studies, were eligible for inclusion based on three independent ratings.
We found robust evidence for short- to moderate-term benecial effects of plant-based diets versus conventional diets
(duration 24 months) on weight status, energy metabolism and systemic inammation 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 upsignaling 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.
Western societies notice an increasing interest in plant-
based eating patterns such as avoiding meat or sh or fully
excluding animal products (vegetarian or vegan, see
Fig. 1). In 2015, around 0.43.4% US adults, 12% British
adults, and 510% of German adults were reported to eat
largely plant-based diets
, due to various reasons
(reviewed in ref.
). Likewise, the number of scientic
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 scientic understanding of
how plant-based diets affect human health, in particular
with regard to potentially relevant effects on mental
health and cognitive functions.
Study aims
A potential effect of plant-based diets on mortality rate
remains controversial: large epidemiological studies like
the Adventist studies (n=22,00096,000) show a link
between plant-based diets, lower all-cause mortality and
cardiovascular diseases
, while other studies like the
EPIC-Oxford study and the 45 and Up Study(n=
64,000267,000) show none
. Yet, many, but not all,
epidemiological and interventional human studies in the
last decades have suggested that plant-based diets exert
benecial health effects with regard to obesity-related
© The Author(s) 2019
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, whi ch permits use, sharing, adaptation, distribution and reproduction
in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a linktotheCreativeCommons license, and indicate if
changes were made. The images or other third party material in this article are included in the articles Creative Commons license, unless indicated other wise in a credit line to the material. If
material is not included in the articles Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this license, visit
Correspondence: Evelyn Medawar (
Department of Neurology, Max Planck Institute for Human Cognitive and
Brain Sciences, Leipzig, Germany
Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin,
Full list of author information is available at the end of the article.
metabolic dysfunction, type 2 diabetes mellitus (T2DM)
and chronic low-grade inammation (e.g. refs.
, for
reviews, see refs.
). However, while a putative link
between such metabolic alterations and brain health
through pathways which might include diet-related neu-
rotransmitter precursors, inammatory pathways and the
gut microbiome
becomes increasingly recognized, the
notion that plant-based diets exert inuence on mental
health and cognitive functions appears less documented
and controversial
. 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 interventionwith the lter
clinical trialand humans, preregistered at
PROSPERO (CRD42018111856;
(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. Exclu-
sion criteria were insufcient 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
ber intake), or nonmetabolic (i.e., not concerning glu-
cose metabolism, lipid prole, gastrointestinal hormones
or inammatory markers) or non-neurological/psychia-
tric 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
Fig. 1 The spectrum of diets including all or only certain types of
animal-based products. From left to right: including all food items
(omnivore), including all except for meat (pesco-vegetarian) or meat
and sh (ovo-lacto-vegetarian) to including only plant-based items
Fig. 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
Medawar et al. Translational Psychiatry (2019) 9:226 Page 2 of 17
through discussion of the individual study. This yielded 27
eligible out of 205 publications; see Table 1for 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/cognitionor psychological/psychologyin the
resulting records. Through this, we retrieved another ve
studies included in Table 1. Further related studies were
reviewed based on additional nonsystematic literature
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 benecial effect
of plant-based dietary interventions (study duration 3
24 months) on weight status, glucose, insulin and/or
plasma lipids and inammatory 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 specically, 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 levelsdecreased 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 benecial metabolic changes after a
plant-based diet
For example, Lee et al. found a signicantly larger
reduction of HbA1c and lower waist circumference after
vegan compared to conventional dieting
. 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
. 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 nonsignicant
trends toward higher effect sizes on metabolic parameters
after a vegan diet, even when caloric intake was com-
parable: two studies in T2DM patients
calorie-unrestricted vegan or vegetarian to calorie-
Fig. 3 Google Trends Search for search term hits for vegan,vegetarianand meatin Germany (adapted to vegetarisch,veganand
eisch), the USA and the UK from 2004 to present. Note indicates technical improvements implemented by Google Trends. Data source:
Google Trends. Search performed on 18 April 2019
Medawar et al. Translational Psychiatry (2019) 9:226 Page 3 of 17
Table 1 Intervention studies on the effect of plant-based diets
Author Year Study design npatients nhealthy Nature of intervention, and
if calorie-restricted
Duration of
Measures Effect of intervention Favoring
vegan diet
Weight loss, blood-based metabolic markers
et al. (2007)
RCT; overweight postmenopausal
women: low-fat vegan vs. National
Cholesterol Education Program diet
two replications
62; rst run 28 (14
vs. 14), second
run 34 (17 vs. 17)
Low-fat vegan diet
fruits, vegetables,
legumes, grains
animal products proscribed
limit high-fat plant foods
vs. National Cholesterol
Education Program diet
see guidelines
14 weeks
(24 months
Body weight weight loss higher in vegan
group at year 1 and year 2
Burke et al. (2008)
RCT; obese subjects; four groups:
freely chosen vegetarian vs. freely
chosen conventional vs. assigned
vegetarian vs. assigned conventional
178 (48 vs. 35 vs.
48 vs. 45)
Vegetarian (restricted):
no meat, poultry, sh
vs. Standard behavioral
therapy, group sessions led by
behavioral scientist
monitoring of physical
activity and calorie/fat content
of foods
cooking magazines
18 months Body weight weight loss higher in both
groups that were assigned to a
certain diet
trend to higher weight loss in
both vegetarian groups
all groups showed signicant
weight loss
Barnard et al.
RCT; T2DM patients;
two groups:
Vegan vs. conventional restrictive diet
99 (49
vs. 50)
Vegan (unrestricted):
10% fat, 15% protein, 75%
daily cholesterol intake <
50 mg
vegetables, fruit, grains,
no animal products, fatty
foods and high-glycaemic
index foods
vs. Conventional:
<7% fat, 1520% protein, 60
70% carbohydrates
meal plan with dietician, 3-
day dietary record
74 weeks Body weight, blood
signicant weight loss in both
groups (trend towards stronger
effect in vegan group)
lower HbA1C, total-/LDL-/ and
non-HDL-cholesterol after
intervention in both groups, trend
towards lower HbA1C in
vegan group
controlling for medication
changes led to signicantly
greater reductions in HbA1C,
total- and LDL-cholesterol in
vegan group
Elkan et al. (2008)
Rheumatoid arthritis patients 66 (38
vs. 28)
Gluten-free vegan diet
(protein energy level was 10%
of the total energy intake, the
carbohydrates 60%, and fat
30%; contained vegetables,
root vegetables, nuts, fruits)
vs. well-balanced non-vegan
(contained 10 to 15% protein,
55 to 60% carbohydrate, no
more than 30% fat)
12 months Body weight, blood
lower BMI, LDL, TC and higher
anti-PC IgM in the vegan
diet group
Marniemi et al.
Moderately obese subjects 110 in total (31 vs.
37 vs. 42)
Lactoovo (1200 kcal/day)
vs. mixed diet (1200 kcal/day)
vs. control (no intervention)
12 months Body weight, blood
Weight-reduction, improved
lipid metabolism in both
intervention groups, stronger
effects in mixed diet compared to
lactovegetarian diet
Acharya et al.
Pilot study for RCT; overweight and
obese subject
143 in total (79
vs. 64)
Standard calorie- and fat-
restricted diet vs. calorie- and
6 months Body weight no signicant effect on weight
dependent on diet
Medawar et al. Translational Psychiatry (2019) 9:226 Page 4 of 17
Table 1 continued
Author Year Study design npatients nhealthy Nature of intervention, and
if calorie-restricted
Duration of
Measures Effect of intervention Favoring
vegan diet
fat-restricted lacto-ovo-
vegetarian diet
Wright et al. (2017)
RCT; mid-age to old T2DM and
overweight patients;
whole food plant-based unrestricted
vs. usual care
65 (32
vs. 33)
Low-fat plant-based:
715% fat
whole grains, legumes,
vegetables, fruits
avoid animal products and
rened oils, high-fat plant
foods, sugar, salt, caffeine
50 μg/day vitamin B12
6 months Body weight, blood
reduced BMI and mean
cholesterol in plant-based group
Jenkins et al. (2014)
RCT; overweight hyperlipidemic
patients; low-carb vegan vs. high-carb
39 (19
vs. 20)
caloric restriction to 60% of
estimated caloric
low-carb vegan:
26% carbohydrates, 31%
plant protein, 43% fat
vs. high-carb lacto-ovo-
58% carbohydrates, 16%
protein, 25% fat
6 months Body weight, blood
higher weight loss and lower
LDL and TG for low-carb
vegan group
after 1 month
weight loss reduced in both
groups (about 4.0 kg) (n.s.
difference across groups)
more reduced LDL, TC,
apolipoproteins for plant-
based group
et al. (2015)
RCT; healthy overweight subjects 25-
49.9 kg/m
; calorie-unrestricted
50 (12 vs. 13 vs.
13 vs. 12)
avoid fast foods and
processed foods; self-
based diets
all groups received weekly
dietary sessions except for the
omnivore group (kept
following their usual diet)
no animal products, focus
on plant-based foods
vs. vegetarian:
no meat, sh, poultry, but
eggs and dairy
vs. pesco-vegetarian:
no meat, poultry, but sh,
shellsh, eggs, dairy
vs. semi-vegetarian:
all foods, red meat limited
to 1/week and poultry limited
to <5/week
6 months Body weight, blood
higher weight loss in vegan
group (particularly decreased fat
and saturated fat)
et al. (2014)
RCT; overweight subjects with
polycystic syndrome:
vegan vs. low-calorie diet
18 (9 vs. 9) Vegan:
exclude all animal products,
limit high glycaemic-
index foods
vs. Low-calorie:
restricted to 1200
1500 kcal/day depending on
body weight
assessed by weekly
24 h recall
6 months Body weight,
polycystic syndrome
higher weight loss at 3 months
for vegan group (not after
6 months)
lower energy intake after
6 months for vegan group (lower
fat, lower protein)
no changes for polycystic
Kahleova et al.
RCT; T2DM patients;
two groups:
vegetarian vs. conventional
diabetic diet
74 (37
vs. 37)
Vegetarian (restricted)
vs. Conventional (restricted)
all meals provided
6 months Body weight,
polycystic syndrome
reduced medication, higher
weight loss, increased insulin
sensitivity, reduced visceral and
subcutaneous fat, increase in
Medawar et al. Translational Psychiatry (2019) 9:226 Page 5 of 17
Table 1 continued
Author Year Study design npatients nhealthy Nature of intervention, and
if calorie-restricted
Duration of
Measures Effect of intervention Favoring
vegan diet
after 12 weeks physical
exercise added
plasma adiponectin, decrease in
leptin in the vegan group
Ferdowsian et al.
RCT; overweight and/or T2DM
patients: low-fat vegan diet vs.
control; onsite
113 Low-fat vegan:
no meat, poultry, sh, dairy,
eggs, <5% saturated fat, <25%
total fat, < 50 mg
cholesterol daily
multivitamin supplement
(incl. B12)
vs. control:
usual diet
5,5 months Body weight reduced body weight and waist
circumference in
intervention group
Mishra et al. (2013)
(same sample as
Agarwal et al. (2015)
and partly overlapping
with Ferdowsian et al.
RCT; overweight and/or T2DM
patients; multicomponent worksite
intervention; low-fat vegan vs.
usual diet
291 at
4 sites; (142
vs. 149)
low-fat vegan (unrestricted):
avoid all animal products,
minimize added oils, favor
whole grains
vitamin B12 and
multivitamin supplements
vs. Control:
usual diet; no instruction
18 weeks Blood measures lower total cholesterol in
vegan group
Kahleova et al.
RCT; T2DM patients 74 (37
vs. 37)
vegetarian diet (500 kcal/
vs. control isocaloric
conventional anti-diabetic diet
(500 kcal/day)
16 weeks Anthropo-metric
greater reduction in total leg
area for thigh adipose tissue
distribution after vegetarian diet
Lee et al. (2016)
RCT; healthy Korean subjects;
two groups:
Vegan vs. conventional restrictive diet
106 (46 vs. 47) Vegan (unrestricted):
(1) ingest unpolished rice
(brown rice); (2) avoid
polished rice (white rice); (3)
avoid processed food made of
rice our or wheat our; (4)
avoid all animal food products
(i.e., meat, poultry, sh, daily
goods, and eggs); and (5) favor
low-glycemic index foods (e.g.,
legumes, legumes-based
foods, green vegetables, and
vs. Conventional (restricted)
(1) restrict their individualized
daily energy intake based on
body weight, physical activity,
need for weight control, and
compliance; (2) total calorie
intake comprised 5060%
carbohydrate, 1520% protein
(if renal function is normal),
<25% fat, <7% saturated fat,
minimal trans-fat intake, and
200 mg/day cholesterol
12 weeks Body weight, blood
signicantly larger reduction of
HbA1C levels, trends towards
lower BMI and lower waist
circumference in the vegan
intervention group
Barnard et al.
RCT; premenopausal women 51 (35) low-fat vegetarian (10% fat)
vs. normal diet incl. a
placebo pill
3 months Blood measures decreased LDL, HDL, TC after
10% fat-vegetarian diet
Rauma et al.
Rheumatoid arthritis patients 43 (22
vs. 21)
vegan vs. control (usual diet) 3 months Body weight, urine
9% reduction of body weight in
the vegan group
Medawar et al. Translational Psychiatry (2019) 9:226 Page 6 of 17
Table 1 continued
Author Year Study design npatients nhealthy Nature of intervention, and
if calorie-restricted
Duration of
Measures Effect of intervention Favoring
vegan diet
Gardner et al.
RCT; hypercholesterolemic
outpatients 3065 years
120 (59
vs. 61)
low-fat diet (incl. animal
vs. low-fat plus diet (more
veggie, legumes, whole
1 month Blood measures lower TC, LDL for low-fat plus
(plant-based) diet
Macknin et al.
Randomized; obese
hypercholesterolemic children and
their parents
30 (16
vs. 14)
plant-based no added fat
diet (PB)
vs. American Heart Association
Diet (AHA)
1 month Body weight, blood
lower BMI and hsCRP levels as
well as higher waist
circumference in the plant-based
and no-added fat diet condition
in children,
lower cholesterol, LDL and
HbA1c in the plant-based and no-
added fat diet condition in
Sciarrone et al.
Parallel randomized trial, healthy men 20 (10 vs. 10) lacto-ovo-vegetarian diet
vs. omnivorous diet
initial 2 weeks under caloric
restriction, afterwards
6 weeks Body weight, blood
no signicant differences in
body weight, glucose, insulin or
catecholamines between groups
Alleman et al.
Interventional study, healthy subjects 29 (16 vs. 13) traditional (vegan)
vs. modied Daniel Fast diet
(incl. daily meat and dairy)
3 weeks Body weight, blood
no signicant weight changes
after dietary intervention for
neither condition
both diets show improvement
of blood lipids, inammation
Neacsu et al.
Within-subject cross-over design;
obese men
20 in total meat-based high-protein diet
vs. vegetarian soy high-protein
diet (both diets: 30% protein,
30% fat, 40% carbohydrate)
2 weeks Body weight, blood
n. s. differences between
weight loss and gut hormone
Koebnick et al.
RCT; healthy subjects; site-based study 32 in total low-fat plant-based (20% fat)
vs. control
1 week Blood measures reduced TC, LDL, TG in
vegan diet
David et al. (2014)
Within-subject cross-over design,
healthy, young volunteers
10 exclusively plant-based diet
vs. nearly exclusively animal-
based diet (unrestricted)
5 days 16S rRNA gene
sequencing (stool
Higher abundance of bile-tolerant
microorganisms (Alistipes,
Bilophila, Bacteroides)
and decreased levels of Firmicutes
Eubacterium rectale,
Ruminococcus bromii).
Neurological/psychiatric disease outcomes and brain functions
Karlsson et al.
RCT; moderately obese women 60 1300 kcal lacto-vegetarian diet
vs. 1300 kcal conventional
weight-reducing diet
3, 8, 24 months Psychological
measures incl. mental
well-being, functional
status; body weight
no signicant differences
between groups on psychological
measures and BMI
Kjeldsen-Kragh et al.
RCT; rheumatoid arthritis patients,
vegetarian vs. omnivorous diet
53 (27
vs. 26)
vegetarian diet (fasting 7
10 days, gluten free vegan
diets for 3.5 months,
afterwards lacto-
vegetarian diet
vs. - normal omnivorous diet
13 months General Health
improvements in psychological
distress including depression and
anxiety subscores in the
vegetarian group
Yadav et al. (2016)
RCT; multiple sclerosis patients 61 (32
vs. 29)
very low-fat plant-based diet:
starchy plant foods, 10% fat,
12 months Brain MRI,
no clear effect on brain MRI
outcomes; improvement of
Medawar et al. Translational Psychiatry (2019) 9:226 Page 7 of 17
Table 1 continued
Author Year Study design npatients nhealthy Nature of intervention, and
if calorie-restricted
Duration of
Measures Effect of intervention Favoring
vegan diet
14% protein, 76%
(no meat, sh, eggs, dairy
products or vegetable oils)
vs. control:
usual diet
assessed by FFQ and
meetings with dietician
body weight,
blood sample
fatigue, weight status and
metabolic markers in the
vegan group
Bunner et al.
RCT; cross-over trial
migraine patients;
Low-fat vegan vs. placebo
42 in total Vegan diet:
Favored intake of whole
grains, lentils, certain
vegetables; avoidance of all
animal products, nuts and
seeds, alcohol, coffee
vs. Placebo:
10 mcg alpha-linolenic acid
and 10 mcg vitamin E/day
9 months Headache pain
measured with The
Patients Global
Impression of Change
improvement of migraine
during last 2 weeks in the
vegan group
Kahleova et al.
Randomized, open, parallel design,
T2DM patients, vegetarian vs.
control group
74 (37
vs. 37)
vegetarian diet (500 kcal/
vs. control isocaloric
conventional anti-diabetic diet
(500 kcal/day)
24 weeks Quality of life,
depressive symptoms,
eating behavior
improved quality of life, dietary
restraint and disinhibition and
lower depression scores in the
vegetarian group
Agarwal et al.
RCT; overweight and/or T2DM
patients; multicomponent worksite
intervention; low-fat vegan vs.
usual diet
291 at
4 sites; (142
vs. 149)
low-fat vegan (unrestricted):
avoid all animal products,
minimize added oils, favor
whole grains
vitamin B12 and
multivitamin supplements
vs. Control:
usual diet; no instruction
18 weeks Depression, anxiety,
fatigue, emotional
all measures signicantly
improved in the vegan group
Kaartinen et al.
Non-randomized; bromyalgia
32 (18
vs. 15)
low-salt, raw vegan diet
vs. omnivorous diet
3 months Disease improvement,
urine and blood
less pain, improved joint
stiffness and quality of sleep,
decreased weight, TC, and urine
sodium in the vegan diet group
Beezhold et al.
Healthy subjects; omnivorous 39 (in locks at 3,
i.e. 13 in
each group)
control group consuming
meat, sh, and poultry
daily (OMN)
vs. a group consuming sh 3
4 times weekly but avoiding
meat and poultry (FISH)
vs. a vegetarian group
avoiding meat, sh, and
poultry (VEG)
2 weeks Stress, depression,
mood, anxiety,
blood levels
decrease in stress, anxiety and
improved mood in vegan group
decreased fatty acids, increased
n6ton3 ratio and decrease in
alpha-linoleic acid in the VEG
compared to OMN group
Medawar et al. Translational Psychiatry (2019) 9:226 Page 8 of 17
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 ve-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)
. Here, inammation markers con-
ceptualized as the dietary inammatory index were also
found to be lower in vegan, vegetarian and pesco-
vegetarian compared to semi-vegetarian overweight to
obese dieters
Intriguingly, these results
cohesively suggest that
although caloric intake was similar across groups, parti-
cipants 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 25 years
. Future studies with larger sample sizes and tight
control of dietary intake need to conrm 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
. This is in line with another
controlled-feeding study where microbial composition
changes already occurred 24 h after changing diet (not
exclusively plant-based)
. However, future studies
incorporating larger sample sizes and a uniform analysis
approach of microbial features need to further conrm
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, bromyalgia and rheumatoid arthritis.
Here, mild to moderate improvement, e.g. measured by
antibody levels, symptom improvement or pain frequency,
was reported in ve out of six studies, sometimes
accompanied by weight loss
(Table 1). However,
given the pilot character of these studies, indicated by
small sample sizes (n=3266), lack of randomization
or that the plant-based diet was additionally free of
, the evidence is largely anecdotal. One study in
moderately obese women showed no effects on psycho-
logical outcomes
, two studies with obese and nonobese
healthy adults indicated improvements in anxiety, stress
and depressive symptom scores
. 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 bromyalgia remains con-
siderably 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 non-
. Conversely, another observational study
with a sample of about 80% women found a benecial
association between a vegan diet and mood disturbance
Overall, the relationship between mental health (i.e.
depression) and restrictive eating patterns has been the
focus of recent research
; however, causal rela-
tionships remain uninvestigated due to the observational
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 difcult to nail down the proposed benecial
effects of a plant-based diet on metabolic status to one
specic 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
, lower inammatory
and altered neurotransmitter metabolism via
dietary intake
or intestinal activity
(Fig. 4).
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
unrened versus simple and rened), which might both be
important players for mediating benecial health effects
On the micronutrient level, the EPIC-Oxford study pro-
vided 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 ber, magnesium, iron, folic
acid, vitamin B1, C and E in vegan compared to omnivore
. Other studies conrmed the variance of nutrient
intake across dietary groups, i.e. omnivores, vegetarians
and vegans, showing the occurrence of critical nutrients
Medawar et al. Translational Psychiatry (2019) 9:226 Page 9 of 17
for each group
. Not only the amount of SFA but also
its source and prole might be important factors reg-
ulating metabolic control (reviewed in ref.
), 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 trimethyla-
mine N-oxide (TMAO), which is a metabolite of gut
bacteria-driven metabolic pathways
Secondly, high ber intake from legumes, grains, vege-
tables and fruits is a prominent feature of plant-based
diets (Table 1), which could induce benecial metabolic
processes like upregulated carbohydrate fermentation and
downregulated protein fermentation
, improved gut
hormonal-driven appetite regulation
, and might
prevent chronic diseases such as obesity and T2DM by
slowing down digestion and improving lipid control
comprehensive review including evidence from 185 pro-
spective studies and 58 clinical trials concluded that risk
reduction for a myriad of diseases (incl. CVD, T2DM,
stroke incidence) was greatest for daily ber intake
between 25 and 29 g
. Precise evidence for underlying
mechanisms is missing; however, more recently it has
been suggested that high ber intake induces changes on
the microbial level leading to lower long-term weight
, a mechanism discussed below.
The reason for lower systemic inammation in plant-
based dieters could be due to the abundance of antiin-
ammatory molecule intake and/or avoidance of proin-
ammatory animal-derived molecules. Assessing systemic
inammation is particularly relevant for medical condi-
tions such as obesity, where it has been proposed to
increase the risk for cardiovascular disease
. In addi-
tion, 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
and higher risk of dementia
and recent studies point out that a diet-related low
inammatory index might also directly affect healthy
brain ageing
Fig. 4 The effects of a plant-based diet on the microbiomegutbrain axis including the here reviewed effects on overall health,
microbial composition and activity, behavior and cognition. BMI body-mass-index, HbA1c hemoglobin A1c, LDL-cholesterol low-density
lipoprotein cholesterol, Trp tryptophan, Tyr tyrosine. Images from,Brain human sagittal sectionby Lynch 2006 and
Complete GI tractby Häggström 2008, Anatomy Figure Vector Clipartby
Medawar et al. Translational Psychiatry (2019) 9:226 Page 10 of 17
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 vege-
tarian diet did not adversely inuence physical perfor-
mance compared to an omnivore diet
epidemiological study by Song et al.
estimated that
statistically replacing 3% of animal protein, especially
from red meat or eggs, with plant protein would sig-
nicantly improve mortality rates. This benecial 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
Some studies further hypothesized that health benets
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
. A meta-analysis on
the effect of phytochemical intake concluded a benecial
effect on CVD, cancer, overweight, body composition,
glucose tolerance, digestion and mental health
. 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
, pre- and probiotics
carry-over antibiotics found in animal products
food-related carcinogenic toxins, such as dioxin found in
eggs or nitrosamines found in red and processed
. Although conclusive evidence is missing, these
ndings propose indirect benecial effects on health
deriving from plant-based compared to animal-based
foods, with a potential role for nonprotein substances in
mediating those effects
. 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 com-
pared to more animal-based diets
. Whether these dif-
ferences lead to systematic health effects need to be
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 ber) and the immense
complexity of diet-related mechanisms for metabolic
health. As proposed by several authors, benets on health
related to diet can probably not be viewed in isolation for
the intake (or nonintake) of specic foods, but rather by
additive or even synergistic effects between them
(reviewed in refs.
). 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 ne-tuned
diagnostic measurements and automated self-monitoring
tools, e.g. automatic food recognition systems
urine-related measures of dietary intake
, could help to
push the eld forward.
Nutrients of particular interest in plant-based diets
As described above, plant-based diets have been shown
to convey nutritional benets
, in particular increased
ber, beta carotene, vitamin K and C, folate, magnesium,
and potassium intake and an improved dietary health
. However, a major criticism of plant-based diets is
the risk of nutrient deciencies for specic micro-
nutrients, especially vitamin B12, a mainly animal-derived
nutrient, which is missing entirely in vegan diets unless
supplemented or provided in B12-fortied 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 deciency
. Along other risk
factors such as age
, diet, and plant-based diets in par-
ticular, seem to be the main risk factor for vitamin B12
deciency (reviewed in ref.
), and therefore supple-
menting vitamin B12 for these risk groups is highly
. Vitamin B12 is a crucial component
involved in early brain development, in maintaining nor-
mal central nervous system function
and suggested to
be neuroprotective, particularly for memory performance
and hippocampal microstructure
. One hypothesis is that
high levels of homocysteine, that is associated with vita-
min B12 deciency, might be harmful to the body. Vita-
min 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 insufciency accu-
mulates homocysteine, lastly promoting the formation of
plaques in arteries and thereby increasing athero-
thrombotic risk
, possibly facilitating symptoms in
patients of Alzheimers disease
. A meta-analysis found
that vitamin B12 deciency was associated with stroke,
Alzheimers disease, vascular dementia, Parkinsons dis-
ease and in even lower concentrations with cognitive
, supporting the claim of its high potential
for disease prevention when avoided or treated
. Further
investigations and longitudinal studies are needed, possi-
bly measuring holotranscobalamin (the active form of
vitamin B12) as a more specic and sensitive marker for
vitamin B12 status
, to examine in how far non-
supplementing vegan dieters could be at risk for cardio-
vascular and cognitive impairment.
Similar health dangers can stem from iron deciency,
another commonly assumed risk for plant-based dieters
and other risk groups such as young women. A meta-
Medawar et al. Translational Psychiatry (2019) 9:226 Page 11 of 17
analysis on 24 studies proposes that although serum fer-
ritin 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 sup-
plementation strategies
. Iron deciency is not only
dependent on iron intake as such but also on compli-
mentary dietary factors inuencing its bioavailability
(discussed in ref.
). The picture remains complex: on the
one hand iron deciency may lead to detrimental health
effects, such as impairments in early brain development
and cognitive functions in adults and in children carried
by iron-decient mothers
and a possible role for iron
overload in the brain on cognitive impairment on the
other hand
. One study showed that attention, memory
and learning were impaired in iron-decient compared to
iron-sufcient women, which could be restored after a 4-
month oral iron supplementation (n=118)
. Iron
deciency-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
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 deciencies or nutrient-
overdose-related toxicity. All in all, organizations such as
the Academy of Nutrition and Dietetics
and the Ger-
man Nutrition Society do not judge iron as a major risk
factor for plant-based dieters
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 micro-
biome which has increasingly received scientic and
popular interest, lastly not only through initiatives such as
the Human Microbiome Project
. 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 bac-
terial genera, such as Prevotella and Bacteroides
. While
interventional controlled trials are still scarce, this ratio
has been shown to be conclusive for differentiating plant-
based from animal-based microbial proles
. Specically,
in a sample of 98 individuals, Wu et al.
found that a diet
high in protein and animal fats was related to more
Bacteroides, whereas a diet high in carbohydrates, repre-
senting a plant-based one, was associated with more
Prevotella. Moreover, the authors showed that a change in
diet to high-fat/low-ber or to low-fat/high-ber 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
. 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
. 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 modications such as the
daily consumption of 43 g of walnuts, were able to pro-
mote probiotic- and butyric acid-producing bacterial
species in two RCTs, after 3 and 8 weeks respec-
, 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 conven-
tional diet
. Only recently, other microbial commu-
nities, such as the salivary microbiome, have been shown
to be different between omnivores and vegan dieters
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 specic
microbial prole, with a vegan prole being most different
from an omnivore, but not always different from a vege-
tarian prole (reviewed in ref.
). Some specically 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 protec-
tive bacterial species improving lipid metabolism and a
reduced level of intestinal inammation
. Investigating
long-term dietary patterns a study found a dose-
dependent effect for altered gut microbiota in vegetar-
ians and vegans compared to omnivores depending on the
quantity of animal products
. The authors showed that
gut microbial proles of plant-based diets feature the
same total number but lower counts of Bacteroides,
Bidobacterium, 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
eld 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
. They found a strong correlation
between ber intake and Prevotella abundance in the
microbial gut. More recently, Prevotella has been asso-
ciated with plant-based diets
that are comparable to
low-fat/high-ber diets
and might be linked to the
increased synthesis of short-chain fatty acids (SCFA)
Medawar et al. Translational Psychiatry (2019) 9:226 Page 12 of 17
SCFAs are discussed as putative signaling molecules
between the gut microbiome and the receptors, i.e. free
fatty acid receptor 2 (FFA2)
, found in host cells across
different tissues
and could therefore be one potential
mechanism of microbiomehost communication.
The underlying mechanisms of nutrient decomposition
by Prevotella and whether abundant Prevotella popula-
tions in the gut are benecial for overall health remain
unknown. Yet it seems possible that an increased ber
intake and therefore higher Prevotella abundance such as
associated with plant-based diets is benecial for reg-
ulating glycemic control and keeping inammatory pro-
cesses within normal levels, possibly due to reduced
appetite and lower energy intake mediated by a higher
ber content
. Moreover, it has been brought forward
that the microbiome might inuence 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
, 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 microbiomegutbrain 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 microbiomegutbrain axis
. A recent 4-
week intervention RCT showed that probiotic adminis-
tration compared to placebo and no intervention modu-
lated brain activity during emotional decision-making and
emotional recognition tasks
. In chronic depression it
has been proposed that immunoglobulin A and M anti-
bodies are synthesized by the host in response to gut
commensals and are linked to depressive symptoms
Whether the identied gram-negative bacteria might also
play a role in plant-based diets remains to be explored. A
meta-analysis on ve studies concluded that probiotics
may mediate an alleviating effect on depression sympto-
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
proles in relation to disease and how microbial data can
be used on a multimodal way to improve functional
resolution, e.g. characterizing microbial proles of indi-
viduals suffering from type-1 diabetes
. Yet, evidence for
specic 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
inuence 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
. Strang et al. found that
precursor forms of serotonin and dopamine, measured in
blood serum, predicted behavior in this task, and pre-
cursor concentrations were dependent on the nutrient
prole 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
. On top of the diet-
ary 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
Indicating the relevance of gut microbiota for cogni-
tion, a rst human study assessing cognitive tests and
brain imaging could distinguish obese from nonobese
individuals using a microbial prole
found a specic microbiotic prole, particularly dened
by Actinobacteria phylum abundance, that was asso-
ciated with microstructural properties in the hypotha-
lamus 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
A recent study could show that microbial composition
inuences cerebral amyloidogenesis in a mouse model for
Alzheimers disease
. 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 allyet 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 cardi-
ovascular and brain health in the aging population
(reviewed in refs.
). Several attempts have been
made to clarify potential underlying mechanisms, for
example using supplementary plant polyphenols, sh/
sh-oil consumption or whole dietary pattern change in
, yet results are not always equivocal and
large-scale intervention studies have yet to be completed.
Medawar et al. Translational Psychiatry (2019) 9:226 Page 13 of 17
The overall ndings of this paragraph add to the evi-
dence that microbial diversity may be associated with
brain health, although underlying mechanisms and can-
didate signaling molecules remain unknown.
Based on this systematic review of randomized clinical
trials, there is an overall robust support for benecial
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 incon-
clusive. 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 ill-
nesses are linked to the role of microbiota in neurological
function and can be potentially treated via microbial
intervention strategies
. Moreover, it has been claimed
that certain diseases, such as obesity, are caused by a
specic microbial composition
, and that a balanced gut
microbiome is related to healthy ageing
. In this light, it
seems possible that a plant-based diet is able to inuence
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, fur-
ther 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.
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 mechanismsProject A1
(AV) and WI 3342/3-1 (A.V.W.).
Author details
Department of Neurology, Max Planck Institute for Human Cognitive and
Brain Sciences, Leipzig, Germany.
Berlin School of Mind and Brain, Humboldt-
Universität zu Berlin, Berlin, Germany.
CharitéUniversitätsmedizin Berlin,
Humboldt-Universität zu Berlin, Berlin, Germany.
Helmholtz Centre for
Environmental Research GmbHUFZ, Leipzig, Germany
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 nal content. All authors read and approved the nal
Conict of interest
The authors declare that they have no conict of interest.
Publishers note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional afliations.
Supplementary Information accompanies this paper at (
Received: 20 February 2019 Revised: 22 June 2019 Accepted: 17 July 2019
1. GOV.UK. National Diet and Nutrition Survey: headline results from years 1, 2
and 3 (combined) of the rolling programme 2008/092010/11. https://www.
201011 (2012).
2. V. E. B. U. Deutschland & Joy, S. Anzahl der Veganer und Vegetarier in
Deutschland. Stand 31, 2016 (2015).
3. Mensink,G.,Barbosa,C.L.&Brettschneider,A.-K.Verbreitungdervegetar-
ischen Ernährungsweise in Deutschland 1, (2016).
4. The Vegetarian Resource Group. How many adults in the U.S. are
vegetarian and vegan?
2016_adults_veg.htm (2016).
5. Rosenfeld, D. L. & Burrow, A. L. Vegetarian on purpose: understanding the
motivations of plant-based dieters. Appetite 116,456463 (2017).
6. Orlich, M. J. et al. Vegetarian dietary patterns and mortality in Adventist
Health Study 2. JAMA Intern. Med. 173,12301238 (2013).
7. Le,L.T.&Sabaté,J.Beyondmeatless,thehealtheffectsofvegandiets:
ndings from the Adventist cohorts. Nutrients 6, 21312147 (2014).
8. Mihrshahi, S. et al. Vegetarian diet and all-cause mortality: evidence from a
large population-based Australian cohort-the 45 and up study. Prev. Med. 97,
17 (2017).
9. Key, T. J. et al. Mortality in British vegetarians: results from the European
Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). Am. J. Clin.
Nutr. 89, 1613S1619S (2009).
10. Fung, T. T. et al. Low-carbohydrate diets and all-cause and cause-specic
mortalitytwo cohort studies. Ann. Intern. Med. 153,289298 (2010).
11. Song, M. et al. Association of animal and plant protein intake with all-cause
and cause-specic mortality. JAMA Intern. Med. 176,14531463 (2016).
12. Hu, F. B. Plant-based foods and prevention of cardiovascular disease: an
overview. Am. J. Clin. Nutr. 78, 544S551S (2003).
13. Tonstad,S.,Butler,T.,Yan,R.&Fraser,G.E.Typeofvegetariandiet,
body weight, and prevalence of type 2 diabetes. Diabetes Care 32,
791796 (2009).
14. McEvoy, C. T., Temple, N. & Woodside, J. V. Vegetarian diets, low-meat diets
and health: a review. Public Health Nutr. 15,22872294 (2012).
15. Glick-Bauer, M. & Yeh, M.-C. The health advantage of a vegan diet: exploring
the gut microbiota connection. Nutrients 6,48224838 (2014).
16. Appleby, P. N. & Key, T. J. The long-term health of vegetarians and vegans.
Proc. Nutr. Soc. 75,287293 (2016).
17. Eichelmann, F., Schwingshackl, L., Fedirko, V. & Aleksandrova, K. Effect of
plantbased diets on obesityrelated inammatory proles: a systematic
review and metaanalysis of intervention trials. Obes. Rev. 17,10671079
18. McMacken, M. & Shah, S. A plant-based diet for the prevention and treat-
ment of type 2 diabetes. J. Geriatr. Cardiol. 14, 342 (2017).
19. Rogers, G. B. et al. From gut dysbiosis to altered brain function and mental
illness: mechanisms and pathways. Mol. Psychiatry 21,738748 (2016).
20. Hibbeln, J. R., Northstone, K., Evans, J. & Golding, J. Vegetarian diets and
depressive symptoms among men. J. Affect Disord. 225,1317 (2018).
21. Forestell, C. A. & Nezlek, J. B. Vegetarianism, depression, and the ve factor
model of personality. Ecol. Food Nutr. 57,246259 (2018).
22. Matta, J. et al. Depressive symptoms and vegetarian diets: results from the
constances cohort. Nutrients 10,1695(2018).
23. Agarwal, U. et al. A multicenter randomized controlled trial of a nutrition
intervention program in a multiethnic adult population in the corporate
setting reduces depression and anxiety and improves quality of life: the
GEICO study. Am.J.HealthPromot.29,245254 (2015).
24. Beezhold, B., Radnitz, C., Rinne, A. & DiMatteo, J. Vegans report less stress and
anxiety than omnivores. Nutr. Neurosci. 18,289296 (2015).
25. Barnard, N. D., Levin, S. M. & Yokoyama, Y. A systematic review and meta-
analysis of changes in body weight in clinical trials of vegetarian diets. J.
Acad. Nutr. Diet. 115,954969 (2015).
Medawar et al. Translational Psychiatry (2019) 9:226 Page 14 of 17
26. Huang,R.-Y.,Huang,C.-C.,Hu,F.B.&Chavarro,J.E.Vegetariandietsand
weight reduction: a meta-analysis of randomized controlled trials. J. Gen.
Intern. Med. 31,109116 (2016).
27. Benatar, J. R. & Stewart, R. A. H. Cardiometabolic risk factors in vegans: a meta-
analysis of observational studies. PLoS ONE 13, e0209086 (2018).
28. Lee, Y.-M. et al. Effect of a brown rice based vegan diet and conventional
diabetic diet on glycemic control of patients with type 2 diabetes: a 12-week
randomized clinical trial. PLoS ONE 11, e0155918 (2016).
29. Jenkins, D. J. A. et al. Effect of a 6-month vegan low-carbohydrate (Eco-
Atkins) diet on cardiovascular risk factors and body weight in hyperlipi-
daemic adults: a randomised controlled trial. BMJ Open 4, e003505 (2014).
30. Jenkins,D.J.A.etal.Theeffectofaplant-basedlow-carbohydrate(Eco-
Atkins) diet on body weight and blood lipid concentrations in hyperlipi-
demic subjects. Arch. Intern. Med. 169, 10461054 (2009).
31. Barnard, N. D. et al. A low-fat vegan diet and a conventional diabetes diet in
the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical
trial. Am.J.Clin.Nutr. (2009).
32. Kahleova, H., Hill M. & Pelikánova, T. Vegetarian vs. conventional diabetic diet
a 1-year follow-up. Cor Vasa 56.
crvasa.2013.12.004 (2016).
33. Turner-McGrievy, G. M., Davidson, C. R., Wingard, E. E., Wilcox, S. & Frongillo, E.
A. Comparative effectiveness of plant-based diets for weight loss: a rando-
mized controlled trial of ve different diets. Nutrition 31,350358 (2015).
34. Wing, R. R. & Phelan, S. Long-term weight loss maintenance. Am.J.Clin.Nutr.
82,222S225S (2005).
35. David, L. A. et al. Diet rapidly and reproducibly alters the human gut
microbiome. Nature 505,559563 (2014).
36. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial
enterotypes. Science (80-) 334,105108 (2011).
37. Kaartinen, K. et al. Vegan diet alleviates bromyalgia symptoms. Scand. J.
Rheumatol. 29,308313 (2000).
38. Yadav, V. et al. Low-fat, plant-based diet in multiple sclerosis: a randomized
controlled trial. Mult. Scler. Relat. Disord. 9,8090 (2016).
39. Rauma, A. L., Nenonen, M., Helve, T. & Hänninen, O. Effect of a strict vegan
diet on energy and nutrient intakes by Finnish rheumatoid patients. Eur. J.
Clin. Nutr. 47,747749 (1993).
40. Elkan, A.-C. et al. Gluten-free vegan diet induces decreased LDL and oxidized
LDL levels and raised atheroprotective natural antibodies against phos-
phorylcholine in patients with rheumatoid arthritis: a randomized study.
Arthritis Res. Ther. 10, R34 (2008).
41. Karlsson, J. et al. Predictors and effects of long-term dieting on mental well-
being and weight loss in obese women. Appetite 23,1526 (1994).
42. Beezhold, B. L. & Johnston, C. S. Restriction of meat, sh, and poultry in
omnivores improves mood: a pilot randomized controlled trial. Nutr. J. 11,9
43. Yokoyama, Y., Barnard, N. D., Levin, S. M. & Watanabe, M. Vegetarian diets and
glycemic control in diabetes: a systematic review and meta-analysis. Cardi-
ovasc. Diagn. Ther. 4,373382 (2014).
44. Sutliffe,J.T.,Wilson,L.D.,deHeer,H.D.,Foster,R.L.&Carnot,M.J.C-reactive
protein response to a vegan lifestyle intervention. Complement Ther. Med. 23,
3237 (2015).
45. Strasser, B., Gostner, J. M. & Fuchs, D. Mood, food, and cognition: role of
tryptophan and serotonin. Curr. Opin. Clin. Nutr. Metab. Care 19,5561 (2016).
46. OMahony,S.M.,Clarke,G.,Borre,Y.E.,Dinan,T.G.&Cryan,J.F.Serotonin,
tryptophan metabolism and the brain-gut-microbiome axis. Behav. Brain Res.
277,3248 (2015).
47. Davey,G.K.etal.EPICOxford: lifestyle characteristics and nutrient intakes in
a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK. Public
Health Nutr. 6,259268 (2003).
48. Schüpbach,R.,Wegmüller,R.,Berguerand,C.,Bui,M.&Herter-Aeberli,I.
Micronutrient status and intake in omnivores, vegetarians and vegans in
Switzerland. Eur. J. Nutr. 56,283293 (2017).
49. Clarys, P. et al. Comparison of nutritional quality of the vegan, vegetarian,
semi-vegetarian, pesco-vegetarian and omnivorous diet. Nutrients 6,
13181332 (2014).
50. Park, J. E., Miller, M., Rhyne, J., Wang, Z. & Hazen, S. L. Differential effect of
short-term popular diets on TMAO and other cardio-metabolic risk markers.
Nutr. Metab. Cardiovasc. Dis. 29, 513517 (2019).
51. Psichas, A. et al. The short chain fatty acid propionate stimulates GLP-1 and
PYY secretion via free fatty acid receptor 2 in rodents. Int J. Obes. 39,424
52. Lin,H.V.etal.Butyrateandpropionate protect against diet-induced obesity
and regulate gut hormones via free fatty acid receptor 3-independent
mechanisms. PLoS ONE 7, e35240 (2012).
53. Canfora,E.E.,Jocken,J.W.&Blaak,E.E.Short-chainfattyacidsincontrolof
body weight and insulin sensitivity. Nat. Rev. Endocrinol. 11, 577 (2015).
54. Guo, Y. et al. Physiological evidence for the involvement of peptide YY in the
regulation of energy homeostasis in humans. Obesity 14,15621570 (2006).
55. Holzer, P., Reichmann, F. & Farzi, A. Neuropeptide Y, peptide YY and pan-
creatic polypeptide in the gutbrain axis. Neuropeptides 46,261274 (2012).
56. Kendall, C. W. C., Esfahani, A. & Jenkins,D.J.A.Thelinkbetweendietarybre
and human health. Food Hydrocoll. 24,4248 (2010).
57. Reynolds, A. et al. Carbohydrate quality and human health: a series of sys-
tematic reviews and meta-analyses. Lancet.
6736(18)31809-9 (2019).
58. Menni, C. et al. Gut microbiome diversity and high-breintakearerelatedto
lower long-term weight gain. Int. J. Obes. 41, 1099 (2017).
59. Van Gaal, L. F., Mertens, I. L. & Christophe, E. Mechanisms linking obesity with
cardiovascular disease. Nature 444, 875 (2006).
60. Ferreira, C. M. et al. The central role of the gut microbiota in chronic
inammatory diseases. J. Immunol. Res. 2014,
689492 (2014).
61. Wersching,H.etal.SerumC-reactive protein is linked to cerebral micro-
structural integrity and cognitive function. Neurology 74,10221029 (2010).
62. Gu, Y. et al. Circulating inammatory biomarkers in relation to brain structural
measurements in a non-demented elderly population. Brain Behav. Immun.
65,150160 (2017).
63. Lampe,L.etal.Visceralobesityrelates to deep white matter hyperintensities
via inammation. Ann. Neurol. 85,194203 (2018).
64. Schmidt,R.etal.Earlyinammation and dementia: a 25year followup of the
HonoluluAsia Aging Study. Ann. Neurol. 52,168174 (2002).
65. Rosano, C., Marsland, A. L. & Gianaros, P. J. Maintaining brain health by
monitoring inammatory processes: a mechanism to promote successful
aging. Aging Dis. 3,16(2012).
66. Tangney,C.C.etal.RelationofDASH-and Mediterranean-like dietary patterns
to cognitive decline in older persons. Neurology 83,14101416 (2014).
67. Craddock, J. C., Probst, Y. & Peoples, G. Vegetarian nutritioncomparing
physical performance of omnivorous and vegetarian athletes. J. Nutr.
Intermed. Metab. 4, 19 (2016).
68. Liu,R.H.Healthbenets of fruit and vegetables are from additive and
synergistic combinations of phytochemicals. Am.J.Clin.Nutr.78, 517S520S
69. Boffetta, P. et al. Fruit and vegetable intake and overall cancer risk in the
European Prospective Investigation into Cancer and Nutrition (EPIC). J. Natl.
Cancer Inst. 102,529537 (2010).
70. Reczek, C. R. & Chandel, N. S. Revisiting vitamin C and cancer. Science (80-)
350, 13171318 (2015).
71. Probst, Y. C., Guan, V. X. & Kent, K. Dietary phytochemical intake from foods
and health outcomes: a systematic review protocol and preliminary scoping.
BMJ Open 7, e013337 (2017).
72. Hartmann, R. & Meisel, H. Food-derived peptides with biological activity: from
research to food applications. Curr. Opin. Biotechnol. 18, 163169 (2007).
73. Tillisch, K. et al. Consumption of fermented milk product with probiotic
modulates brain activity. Gastroenterology 144,13941401 (2013).
74. Gibson, G. R. et al. Expert consensus document: The International Scientic
Association for Probiotics and Prebiotics (ISAPP) consensus statement on
thedenition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14,491
75. Nisha,A.R.Antibioticresidues-a global health hazard. Vet. World 1,375377
76. Wang, H. et al. Antibiotic residues in meat, milk and aquatic products in
Shanghai and human exposure assessment. Food Control 80,217225
77. Bertazzi,P.A.etal.Healtheffectsof dioxin exposure: a 20-year mortality
study. Am. J. Epidemiol. 153,10311044 (2001).
78. Bouvard, V. et al. Carcinogenicity of consumption of red and processed meat.
Lancet Oncol. 16,15991600 (2015).
79. VanAudenhaege,M.etal.Impactof food consumption habits on the
pesticide dietary intake: comparisonbetweenaFrenchvegetarianandthe
general population. Food Addit. Contam.26,13721388 (2009).
80. Jacobs, D. R. & Tapsell, L. C. Food synergy: the key to a healthy diet. Proc. Nutr.
Soc. 72, 200206 (2013).
Medawar et al. Translational Psychiatry (2019) 9:226 Page 15 of 17
81. Kawano, Y. & Yanai, K. Foodcam: a real-time food recognition system on a
smartphone. Multimed. Tools Appl. 74,52635287 (2015).
82. Garcia-Perez, I. et al. Objective assessment of dietary patterns by use of
metabolic phenotyping: a randomised, controlled, crossover trial. Lancet
Diabetes Endocrinol. 5,184195 (2017).
83. Turner-McGrievy, G. M. et al. Changes in nutrient intake and dietary quality
among participants with type 2 diabetes following a low-fat vegan diet or a
conventional diabetes diet for 22 weeks. J. Am. Diet. Assoc. 108,16361645
84. Gilsing, A. M. J. et al. Serum concentrations of vitamin B12 and folate in British
male omnivores, vegetarians and vegans: results from a cross-sectional
analysis of the EPIC-Oxford cohort study. Eur. J. Clin. Nutr. 64,933939 (2010).
85. Allen, L. H. How common is vitamin B-12 deciency? Am.J.Clin.Nutr.89,
693S696S (2008).
86. Pawlak,R.,Parrott,S.J.,Raj,S.,Cullum-Dugan,D.&Lucus,D.Howprevalentis
vitamin B12 deciency among vegetarians? Nutr. Rev. 71,110117 (2013).
87. Rizzo, G. et al. Vitamin B12 among vegetarians: status, assessment and
supplementation. Nutrients 8, 767 (2016).
88. Stabler,S.P.VitaminB12deciency. N. Engl. J. Med.368, 149160 (2013).
89. Köbe, T. et al. Vitamin B-12 concentration, memory performance, and hip-
pocampal structure in patients with mild cognitive impairment, 2. Am.J.Clin.
Nutr. 103, 10451054 (2016).
90. Ganguly,P.&Alam,S.F.Roleofhomocysteineinthedevelopmentof
cardiovascular disease. Nutr. J. 14, 6 (2015).
91. McCaddon,A.,Regland,B.,Hudson,P.&Davies,G.FunctionalvitaminB12
deciency and Alzheimer disease. Neurology 58,13951399 (2002).
92. Moore, E. et al. Cognitive impairment and vitamin B12: a review. Int. Psy-
chogeriatr. 24,541556 (2012).
93. Spence, J. D. Metabolic vitamin B12 deciency: a missed opportunity to
prevent dementia and stroke. Nutr. Res. 36,109
116 (2016).
94. Nexo, E. & Hoffmann-Lücke, E. Holotranscobalamin, a marker of vitamin B-12
status: analytical aspects and clinical utility. Am.J.Clin.Nutr.94, 359S365S
95. Haider,L.M.,Schwingshackl,L.,Hoffmann,G.&Ekmekcioglu,C.Theeffectof
analysis. Crit. Rev. Food Sci. Nutr. 58,13591374 (2018).
96. Lozoff,B.&Georgieff,M.K.etal.Irondeciency and brain development.
Semin. Pediatr. Neurol. 13,158165 (2006).
97. Ayton, S. et al. Brain iron is associated with accelerated cognitive decline in
people with Alzheimer pathology. Mol. Psychiatry 1,
s41380-019-0375-7 (2019).
98. Murray-Kolb,L.E.&Beard,J.L.Irontreatment normalizes cognitive func-
tioning in young women. Am.J.Clin.Nutr.85, 778787 (2007).
99. Beard, J. Iron deciency alters brain development and functioning. J. Nutr.
133, 1468S1472S (2003).
100. Melina, V., Craig, W. & Levin, S. Position of the Academy of Nutrition and
Dietetics: vegetarian diets. J. Acad. Nutr. Diet. 116,19701980 (2016).
101. Richter, M. et al. For the German Nutrition Society (DGE)(2016) Vegan diet.
Position of the German Nutrition Society (DGE). Ernaehrungsumschau 63,
92102 (2016).
102. Peterson, J. et al. The NIH human microbiome project. Genome Res. 19,
23172323 (2009).
103. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473,
174180 (2013).
104. Bamberger, C. et al. A walnut-enriched diet affects gut microbiome in
healthy Caucasian subjects: a randomized, controlled trial. Nutrients 10,244
105. Holscher, H. D. et al. Walnut consumption alters the gastrointestinal micro-
biota, microbially derived secondary bile acids, and health markers in healthy
adults: a randomized controlled trial. J. Nutr. 148,861867 (2018).
106. Hjorth, M. F. et al. Pre-treatment microbial Prevotella-to-Bacteroides ratio,
determines body fat loss success during a 6-month randomized controlled
diet intervention. Int J. Obes. 42, 580 (2018).
107. Hansen,T.H.etal.Impactofavegandiet on the human salivary microbiota.
Sci. Rep. 8, 5847 (2018).
108. Kim,M.,Hwang,S.,Park,E.&Bae,J.Strictvegetariandietimprovestherisk
factors associated with metabolic diseases by modulating gut microbiota
andreducingintestinalinammation. Environ. Microbiol. Rep. 5,765775
109. Zimmer, J. et al. A vegan or vegetarian diet substantially alters the human
colonic faecal microbiota. Eur. J. Clin. Nutr. 66,5360 (2012).
110. De Filippis, F., Pellegrini, N., Laghi, L., Gobbetti, M. & Ercolini, D. Unusual sub-
genus associations of faecal Prevotella and Bacteroides with specicdietary
patterns. Microbiome 4,57(2016).
111. Kumar, M., Babaei, P., Ji, B. & Nielsen,J.Humangutmicrobiotaandhealthy
aging: Recent developments and future prospective. Nutr. Health Aging 4,
316 (2016).
112. Wu, G. D. et al. Comparative metabolomics in vegans and omnivores reveal
constraints on diet-dependent gut microbiota metabolite production. Gut
65,6372 (2014).
113. Morrison, D. J. & Preston, T. Formation of short chain fatty acids by the gut
microbiota and their impact on human metabolism. Gut Microbes 7,189200
114. Wanders, A. J. et al. Effects of dietary breonsubjectiveappetite,energy
intake and body weight: a systematic review of randomized controlled trials.
Obes. Rev. 12,724739 (2011).
115. Brunkwall, L. & Orho-Melander, M. The gut microbiome as a target for pre-
vention and treatment of hyperglycaemia in type 2 diabetes: from current
human evidence to future possibilities. Diabetologia 60,943951 (2017).
116. Lach,G.,Schellekens,H.,Dinan,T.G.&Cryan,J.F.Anxiety,depression,andthe
microbiome: a role for gut peptides. Neurotherapeutics 15,3659 (2018).
117. Bagga, D. et al. Inuence of 4-week multi-strain probiotic administration on
resting-state functional connectivity in healthy volunteers. Eur. J. Nutr. 58,
18211827 (2018).
118. Foster,J.A.&Neufeld,K.-A.M.Gutbrain axis: how the microbiome inu-
ences anxiety and depression. Trends Neurosci. 36,305312 (2013).
119. Saulnier, D. M. et al. The intestinal microbiome, probiotics and prebiotics in
neurogastroenterology. Gut Microbes 4,1727 (2013).
120. Maes, M., Kubera, M., Leunis, J.-C. & Berk, M. Increased IgA and IgM responses
against gut commensals in chronic depression: further evidence for
increased bacterial translocation or leaky gut. J. Affect Disord. 141,5562
121. Huang, R., Wang, K. & Hu, J. Effect of probiotics on depression: a systematic
review and meta-analysis of randomized controlled trials. Nutrients 8,483
122. Heintz-Buschart, A. et al. Integrated multi-omics of the human gut micro-
biome in a case study of familial type 1 diabetes. Nat. Microbiol. 2, 16180
123. Strang, S. et al. Impact of nutrition on social decision making. Proc. Natl Acad.
Sci. 114, 65106514 (2017).
124. Osadchiy, V. et al. Correlation of tryptophan metabolites with connectivity of
extended central reward network in healthy subjects. PLoS ONE 13, e0201772
125. Franzosa, E. A. et al. Sequencing and beyond: integrating molecularomicsfor
microbial community proling. Nat. Rev. Microbiol. 13,360372 (2015).
126. Fernandez-Real, J.-M. et al. Gut microbiota interacts with brain microstructure
and function. J. Clin. Endocrinol. Metab. 100,45054513 (2015).
127. Allen, A. P. et al. Bidobacterium longum 1714 as a translational psychobiotic:
modulation of stress, electrophysiology and neurocognition in healthy
volunteers. Transl. Psychiatry 6, e939 (2016).
128. Harach, T. et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic
mice in the absence of gut microbiota. Sci. Rep. 7, 41802 (2017).
129. Huhn, S., Masouleh, S. K., Stumvoll, M., Villringer, A. & Witte, A. V. Components
of a Mediterranean diet and their impact on cognitive functions in aging.
Front Aging Neurosci 7, 132 (2015).
130. Larsson, S. C., Wallin, A. & Wolk, A. Dietary approaches to stop hypertension
diet and incidence of stroke: results from 2 prospective cohorts. Stroke 47,
986990 (2016).
131. van de Rest, O. et al. Effect of sh oil on cognitive performance in older
subjects: a randomized, controlled trial. Neurology 71,430438 (2008).
132. Witte, A. V. et al. Long-chain omega-3 fatty acids improve brain function and
structure in older adults. Cereb. Cortex 24, 30593068 (2013).
133. Witte, A. V., Kerti, L., Margulies, D. S. & Flöel, A. Effects of resveratrol on
memory performance, hippocampal functional connectivity, and glucose
metabolism in healthy older adults. J. Neurosci. 34,78627870 (2014).
134. Brickman,A.M.etal.Enhancingdentategyrusfunctionwithdietaryavanols
improves cognition in older adults. Nat. Neurosci. 17, 1798 (2014).
135. Martínez-González,M.A.etal.Benets of the Mediterranean diet: insights
from the PREDIMED study. Prog. Cardiovasc. Dis. 58,5060 (2015).
136. Huhn, S. et al. Effects of resveratrol on memory performance, hippocampus
connectivity and microstructure in older adultsa randomized controlled
trial. Neuroimage (2018).
Medawar et al. Translational Psychiatry (2019) 9:226 Page 16 of 17
137. Rosenberg, A. et al. Multidomain lifestyle intervention benets a large
elderly population at risk for cognitive decline and dementia
regardless of baseline characteristics: The FINGER trial. Alzheimers.
Dement. 14, 263270 (2018).
138. Turnbaugh, P. J. Microbes and diet-induced obesity: fast, cheap, and out of
control. Cell Host Microbe 21,278281 (2017).
139. Turner-Mc Grievy, G. M., Barnard, N. D. & Scialli, A. R. A two-year randomized
weight loss trial comparing a vegan diet to a more moderate low-fat diet*.
Obesity 15, 22762281 (2007).
140. Burke, L. E. et al. A randomized clinical trial of a standard versus vegetarian
diet for weight loss: the impact of treatment preference. Int. J. Obes. 32,
166176 (2008).
141. Barnard, N. D. et al. A low-fat vegan diet and a conventional diabetes diet in
the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical
trial. Am. J. Clin. Nutr. 89,1588S1596S (2009).
142. Marniemi, J., Seppänen, A. & Hakala, P. Long-term effects on lipid metabolism
of weight reduction on lactovegetarian and mixed diet. Int. J. Obes. 14,
113125 (1990).
143. Acharya,S.D.,Brooks,M.M.,Evans,R.W.,Linkov,F.&Burke,L.E.Weightlossis
more important than the diet type in improving adiponectin levels among
overweight/obese adults. J. Am. Coll. Nutr. 32,264271 (2013).
144. Wright, N., Wilson, L., Smith, M., Duncan, B. & McHugh, P. The BROAD study: A
randomised controlled trial using a whole food plant-based diet in the
community for obesity, ischaemic heart disease or diabetes. Nutr. Diabetes 7,
e256 (2017).
145. Turner-McGrievy, G. M., Davidson, C. R., Wingard, E. E. & Billings, D. L. Low
glycemic index vegan or low-calorie weight loss diets for women with
polycystic ovary syndrome: a randomized controlled feasibility study. Nutr.
Res. 34, 552558 (2014).
146. Kahleova, H. et al. Vegetarian diet improves insulin resistance and oxidative
stress markers more than conventional diet in subjects with Type 2 diabetes.
Diabet. Med 28,549559 (2011).
147. Ferdowsian, H. R. et al. A multicomponent intervention reduces body weight
and cardiovascular risk at a GEICO corporate site. Am.J.Heal.Promot24,
384387 (2010).
148. Mishra, S. et al. A multicenter randomized controlled trial of a plant-
based nutrition program to reduce body weight and cardiovascular
risk in the corporate setting: the GEICO study. Eur. J. Clin. Nutr. 67, 718
149. Agarwal, U. et al. A multicenter randomized controlled trial of a nutrition
intervention program in a multiethnic adult population in the corporate
setting reduces depression and anxiety and improves quality of life: the
GEICO study. Am.J.Heal.Promot29,245254 (2015).
150. Kahleova,H.,Dort,S.,Holubkov,R.&Barnard,N.Aplant-basedhigh-carbo-
hydrate,low-fatdietinoverweightindividuals in a 16-week randomized
clinical trial: the role of carbohydrates. Nutrients 10, 1302 (2018).
151. Barnard, N., Scialli, A. R., Bertron, P., Hurlock, D. & Edmonds, K. Acceptability of
a therapeutic low-fat, vegan diet in premenopausal women. J. Nutr. Educ. 32,
314319 (2000).
152. Gardner, C. D. et al. The effect of a plant-based diet on plasma lipids in
hypercholesterolemic adults: a randomized trial. Ann. Intern. Med. 142,733
153. Macknin, M. et al. Plant-based, no-added-fat or American Heart Association
diets: impact on cardiovascular risk in obese children with hypercholester-
olemia and their parents. J. Pediatr. 166,953959 (2015).
154. Sciarrone, S. E. et al. Biochemical and neurohormonal responses to the
introduction of a lacto-ovovegetarian diet. J. Hypertens. 11, 849860 (1993).
155. Alleman, R. J., Harvey, I. C., Farney, T. M. & Bloomer, R. J. Both a traditional and
modied Daniel Fast improve the cardio-metabolic prole in men and
women. Lipids Health Dis. 12, 114 (2013).
156. Neacsu,M.,Fyfe,C.,Horgan,G.&Johnstone,A.M.Appetitecontroland
biomarkers of satiety with vegetarian (soy) and meat-based high-protein
diets for weight loss in obese men: a randomized crossover trial.Am.J.Clin.
Nutr. 100,548558 (2014).
157. Koebnick, C. et al. Double-blind, randomized feedback control fails to
improve the hypocholesterolemic effect of a plant-based low-fat diet in
patients with moderately elevated total cholesterol levels. Eur. J. Clin. Nutr. 58,
1402 (2004).
158. Kjeldsen-Kragh,J.,Haugen,M.,Førre.,Laache,H.&Malt,U.F.Vegetarian
diet for patients with rheumatoid arthritis: can the clinical effects be
explained by the psychological characteristics of the patients? Rheumatology
33,569575 (1994).
159. Bunner,A.E.,Agarwal,U.,Gonzales,J.F.,Valente,F.&Barnard,N.D.Nutrition
intervention for migraine: a randomized crossover trial. J. Headache Pain. 15,
69 (2014).
160. Kahleova, H., Hrachovinova, T., Hill, M. & Pelikanova, T. Vegetarian diet in type
2diabetesimprovement in quality of life, mood and eating behaviour.
Diabet. Med 30,127129 (2013).
161. Turner-McGrievy, G. M. et al. Randomization to plant-based dietary approa-
ches leads to larger short-term improvements in Dietary Inammatory Index
scores and macronutrient intake compared with diets that contain meat.
Nutr. Res. 35,97106 (2015).
Medawar et al. Translational Psychiatry (2019) 9:226 Page 17 of 17
... According to an article from 2019, women suffering from iron deficiency (n = 118) had their cognitive functions hampered and weakened. However more study is required to address this statement (Medawar, Huhn, Villringer, and Witte, 2019). ...
... According to EPIC-Oxford study, approximately 50% of patients suffered from B 12 deficiency (Medawar et al., 2019). In the cross-sectional study entitled "Threats and benefits of a vegan diet", two groups of people were subjected to the study; 36 participants followed a vegan diet and other 36 followed a traditional diet. ...
Full-text available
A plant-based diet is a type of diet gaining more and more popularity. It is a elimination diet excluding all animal products and by-products. There are many reasons for switching from a traditional diet to a plant-based diet. This paper focuses on the four most prevalent reasons for switching diet: economical, health-related, ethical and ecological. The potential benefits and threats of a plant-based diet are also presented.
... vegetable consumption were not associated with better cognitive function (51,70,74,77,78). The effects of a plant-based diet reviewed by Medawar et al. (79) reported the impact on cognition/cognitive processes, brain activity for language and empathy-related tasks, emotional health, and personality traits. Rajaram et al. (62) also reported that consumption of citrus fruits, grapes, berries, nuts, green tea, cocoa and coffee improved specific cognitive domains, especially the executive functions. ...
Full-text available
Multiple factors affect cognitive health, such as age-related changes in the brain, injuries, mood disorders, substance abuse, and diseases. While some cannot be changed, evidence exists of many potentially possibly modifiable lifestyle factors: diet, physical activity, cognitive and social engagement, smoking and alcohol consumption which may stabilize or improve declining cognitive function. In nutrition, the focus has been mainly on its role in brain development in the early years. There is a strong emerging need to identify the role of diet and nutrition factors on age-related cognitive decline, which will open up the use of new approaches for prevention, treatment or management of age-related disorders and maintaining a good quality of life among older adults. While data on effect of high protein diets is not consistent, low-fat diets are protective against cognitive decline. Several micronutrients like B group vitamins and iron, as well as many polyphenols play a crucial role in cognitive health. Mediterranean, Nordic, DASH, and MIND diets are linked to a lower risk of cognitive decline and dementia. The relationship between the gut microbiome and brain function through the gut-brain axis has led to the emergence of data on the beneficial effects of dietary fibers and probiotics through the management of gut microbes. A “whole diet” approach as well as macro- and micro-nutrient intake levels that have protective effects against cardiovascular diseases are most likely to be effective against neurodegenerative disorders too. Young adulthood and middle age are crucial periods for determining cognitive health in old age. The importance of cardio metabolic risk factors such as obesity and hypertension, smoking and physical inactivity that develop in middle age suggest that preventive approaches are required for target populations in their 40s and 50s, much before they develop dementia. The commonality of dementia risk with cardiovascular and diabetes risk suggests that dementia could be added to present non-communicable disease management programs in primary healthcare and broader public health programs.
... Trends observed here for equol aligned with those of the other phytoestrogens investigated in this study, with elevated consumption at the beginning of the year and a subsequent decline after March. Statistical analysis revealed a strong positive correlation between daidzein and equol (ρ = 0.84), with a precursor-to-metabolite ratio of 0.2 (Fig. 2), relatively in line Naturally occurring, plant-derived chemicals known as phytoestrogens can serve as biomarkers indicative of a plant-based diet as they are consumed through a wide variety of foods, including cruciferous vegetables, berries, nuts, flaxseed, soybeans, oat and wheat [6][7][8][9] . Two major classes of phytoestrogens commonly consumed in the United States include isoflavones (soy-based foods and food products), as well as lignans, which are much more ubiquitous. ...
Full-text available
Population-level nutritional assessments often rely on self-reported data, which increases the risk of recall bias. Here, we demonstrate that wastewater-based epidemiology can be used for near real-time population dietary assessments. Neighbourhood-level, untreated wastewater samples were collected monthly from within an urban population in the south-western United States from August 2017 to July 2019. Using liquid chromatography–tandem mass spectrometry, we identify recurring seasonal dynamics in phytoestrogen consumption, including dietary changes linked to the winter holiday season. Using 16S ribosomal RNA gene amplicon sequencing, we demonstrated the feasibility of detecting sewage-derived human gut bacterial taxa involved in phytoestrogen metabolism, including Bifidobacterium, Blautia and Romboutsia. Combined metabolomic and genomic wastewater analysis can inform nutritional assessments at population scale, indicating wastewater-based epidemiology as a promising tool for actionable and cost-effective data collection to support public health nutrition.
... Plant-based diets have gained popularity, in industrialized nations and the western societies 15 . These diets emphasize plant-derived foods and reduce or eliminate animal-derived products 16 . ...
Objective: This systematic review aimed to evaluate the influence of the nature of diet (vegan, vegetarian, and omnivore) on the oral health status in adults. Methods: This systematic review and meta-analysis was performed using the PRISMA guidelines. Electronic databases [PubMed, Embase, CENTRAL], online search engines (Google Scholar), research portals, and hand searches were performed systematically to identify studies. The last literature search was performed February 1st, 2021. Studies were included if they reported on the influence of the nature of diet on the oral health status (oral hygiene, periodontal health, dental status, and salivary function) in adults, by two investigators. Inter-investigator reliability was evaluated using Kappa (κ) statistics. PROSPERO registration number: CRD42020211567. Results: Twenty-two studies were included for data extraction and final analysis. The meta-analysis revealed that the bleeding on probing measure was higher in omnivores (Z = -4.057, p < 0.0001; 95% CI: -0.684, -0.238; I2 = 0.0%) and the overall periodontal health was significantly better in vegan/vegetarians than omnivores (Z = -2.632, p = 0.008; 95% CI: -0.274, -0.073; I2 = 29.7%). Vegan/vegetarians demonstrated more dental erosion (Z = 3.325, p = 0.001; 95% CI: 0.170, 0.659; I2 = 0.0%). In adults over 60 years old, the prevalence of caries was higher in omnivores (Z = 3.244, p = 0.001; 95% CI: 0.092, 0.371; I2 = 0.0%), while complete edentulism was more prevalent in vegetarians (Z = -4.147, p < 0.0001; 95% CI: -0.550, -0.197; I2 = 0.0%). Conclusions: This review reveals that adults on an omnivore diet may be associated with a higher risk for periodontal problems and dental caries, while vegetarians/vegans may be associated with a higher risk for dental erosion.
... Numerous studies show that a plant-based diet, especially vegan, is characterized by an insufficient supply of ingredients such as protein, ω-3 fatty acids, vitamin B12, iron, vitamin D, and calcium [9][10][11]. Less numerous studies also indicate deficiencies in zinc and iodine [12,13]. ...
Full-text available
The aim of this research was to estimate the effect of a vegan diet on the Recommended Dietary Allowance (RDA) coverage for iodine in people from Poland. It was hypothesized that the problem of iodine deficiency is a concern, especially among vegans. The survey study was conducted in the years 2021–2022 on 2200 people aged 18–80 with omnivore and vegan diets. The exclusion criteria in the study were pregnancy and lactation. The study found that the coverage of RDA for iodine among people with a vegan diet was lower than among people with an omnivore diet (p < 0.05); 90% of the participants with a vegan diet had an iodine intake below 150 µg/day. Plant-based dairy and meat analogs were consumed by vegans frequently and in large portions, but none were fortified with iodine. It was found that iodized salt was each group’s primary source of iodine. However, it was observed that the iodine supply from this source was limited among vegans, especially in female subjects, who consumed less salt and smaller portions of meals. That is why consideration should be given to the iodine fortification of plant-based foods commonly consumed by vegans.
... The anti-inflammatory effects of plant-based diets have been well proven [72][73][74]. Into the bargain, it has been shown that many natural plant-derived nutrients can positively affect mitochondria by modulating their metabolism, biogenesis, and redox status. Protecting mitochondrial function with these compounds may be important in explaining their beneficial effects on male reproductive performance [15]. ...
Full-text available
Infertility is a disease globally affecting 20-30% of the reproductive age female population. However, in up to 50% on recorded cases, problems with infertility are ascribed to men; therefore, it is important to popularize healthy eating also in this group. During the last decade, it has been observed that society's lifestyle changed drastically: reduced energy expenditure in physical activity per day, increased consumption of hypercaloric and high-glycemic-index foods with high content of trans fats, and reduced consumption of dietary fiber, which negatively affects fertility. Increasing evidence points to a link between diet and fertility. It is becoming clear that well-planned nutrition can also contribute to the effectiveness of ART. The low-GI plant-based diet appears to have a positive effect, especially when it is based on Mediterranean dietary patterns: rich in antioxidants, vegetable protein, fiber, MUFA fatty acids, omega-3, vitamins, and minerals. Importantly, this diet has been shown to protect against chronic diseases associated with oxidative stress, which also translates into pregnancy success. As lifestyle and nutrition seem to be important factors affecting fertility, it is worth expanding knowledge in this regard among couples trying to conceive a child.
... Additionally, some health-related values of vegans such as blood pressure, cholesterol levels, and body weight are usually in a normal range [19]. Similarly, since the body weight and body mass index (BMI) of vegans are lower than omnivores [11,20,21], vegans have a slightly reduced risk of being overweight or obese [22]. Besides, some studies suggest that vegans might be more conscious of health-related issues and adopt this lifestyle by not developing harmful habits like smoking [19]. ...
Full-text available
Vegetarian diets have become prominent in recent years since the benefits that they provide to overall health and the body are brought to light. When their advantages are taken into consideration, the question of whether it might also be beneficial for athletes to keep themselves healthy and improve their performances.
... Plant-based (PB) diet, vegetarian, or vegan diets [34][35][36][37][38] Plant-based diets focus predominately on eating whole foods from plants, and most exclude meat, poultry, and seafood (or products containing these foods). Energy ranges of 50-78% (TE) from CHO per day, 10-35% fat per day. ...
Full-text available
Some specific dietary patterns improve glycaemic levels and cardiovascular risk factors better than others. We aimed to identify the most effective dietary patterns using a food-focused approach to improve blood glucose management (primary outcome) and cardiovascular risk factors (secondary outcome) in people with type 2 diabetes. An umbrella review was conducted comparing dietary patterns for the management of these outcomes. Studies published between 2012 and 2022 were identified using PubMed Central, ProQuest, Web of Science, and the Cochrane Database of Systematic Reviews. Thirty systematic reviews met the inclusion criteria. Twenty-two of thirty reviews quantitated (via meta-analyses of over 212 randomised control trials) the effect size of different dietary patterns. Twelve reviews found Low-carbohydrate (LC), Mediterranean (M), Plant-based (PB), and/or Low-glycaemic Index (LGI) diets reduced HbA1c moderately more than control diets (typically a high-carbohydrate, low-fat diet) (i.e., LC: −0.1 to −0.5%; M: −0.3 to −5%; PB: −0.2 to −0.4%; LGI −0.2 to −0.5%; all p-value < 0.01). We conclude that Low-carbohydrate, Mediterranean, Plant-based, and Low-glycaemic Index dietary patterns are all clinically effective for people with type 2 diabetes as alternatives to high-carbohydrate, low-fat diets typically used for managing glycaemic levels and CVD risk. However, quality evidence about the sustainability of effects and safety remains limited, warranting future research.
... This value comes from polyphenols that are found only in the plant kingdom. A number of substances contained in plants have proven effects on mental and physical conditions [10][11][12]. The most widespread way of administration is in the form of infusions [13]. ...
Full-text available
The aim of this study was to determine antioxidant activity (DPPH and phosphomolyb-denum method), polyphenols content (total polyphenols, flavonoids, and phenolic acids), mineral compounds composition (Cu, Zn, Mn, Fe, Cr, Ni, Co, Pb and Cd) and antimicrobial activity (with disc diffusion method) of medicinal herbs traditionally used in the Slovak republic. The tested plants belonged to the Primulaceae, Urticaceae, Grossulariaceae, Rosaceae, Lamiaceae, Asteraceae, Equisetaceae, Tropaeolaceae, and Plantaginaceae families. The highest antioxidant activities were found in samples of Rosa canina L. (DPPH-29.43 ± 0.11 mg TE/g; TE-Trolox equivalent) and Fragaria vesca L. (phosphomolybdenum method-679.56 ± 3.06 mg TE/g), both from the Rosaceae family. Total polyphenols (determined using the Folin-Ciocâlteu-reagent) were most abundant in a sample of Fragaria vesca L.-124.51 ± 5.05 mg GAE/g (GAE-gallic acid equivalent), total flavonoids (determined using the aluminum chloride method)-in a sample of Primula veris L.-48.35 ± 3.77 mg QE/g (QE-quercetin equivalent), and total phenolic acids (determined using Arnova reagent)-in a sample of Thymus serpyllum L.-102.31 ± 2.89 mg CAE/g (CAE-caffeic acid equivalent). Regarding mineral compounds composition, samples of Fragaria vesca L. and Thymus serpyllum L. showed the highest levels of iron. In samples of Calendula officinalis L. and Trapaeolum majus L., the highest amounts of zinc were determined, while copper was the most abundant in samples of Urtica dioica L. and Melissa officinalis L. The amounts of heavy metals were within legally acceptable limits. The extract of Equisetum arvense L. showed the strongest inhibitory activity towards Clostridium perfrin-gens CCM 4991 (6 mm), while the one from Mentha piperita L.-towards Candida glabrata CCM 8270 (4.83 mm) and Candida tropicalis CCM 8223 (4.33 mm).
This article contributes to the literature theorizing military social order, embodiment, and resistance in IR. The military institution is known to resist change, and much research have been devoted to challenges to the gendered order of the military. One area that has received little attention, however, is the reluctance of many militaries in the West to facilitate veganism during service in spite of the increasing demand for vegan food options, diversity, and sustainability. Drawing on research on the military social order and gender theory, I conduct an unpacking of conflicting elements and representations of military and vegan bodies, and theorize this reluctance as institutional resistance. Typically, the military does not offer motivations for its stance – which makes it difficult to detect and counter. As a consequence, vegans are silenced and excluded, not facilitated to enter the military. This is a challenge to increasing attempts at governing sustainability and diversity in the military.
Full-text available
Background: Dietary nutrient intake and its metabolism by the gut microbiome have recently been implicated in cardiovascular disease (CVD) risk. In particular, trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, has been shown to be a predictor of incident CVD events. Elevated levels of branched-chain amino acids (BCAA) have also been associated with an increased propensity for insulin resistance. Methods: To study the association of dietary intake with systemic TMAO, its nutrient precursors, and BCAA levels on fasting plasma levels of TMAO and its nutrient precursors and BCAA, we conducted an exploratory post-hoc analysis of 3 popular diets - high fat (Atkins), Mediterranean (South Beach), and very low fat (Ornish) - using plasma samples from a prior randomized, crossover study, with each isocaloric dietary phase lasting 4 weeks. Metabolites were quantified using stable isotope dilution HPLC with on-line tandem mass spectrometry. Results: Compared to the low fat Ornish phase, the high fat Atkins dietary phase was characterized by increased levels of TMAO (3.3 vs. 1.8 μM, p = 0.01), and the BCAA valine (272.8 vs. 235.8 μM, p = 0.005) and leucine (105.9 vs. 96.4 μM, p = 0.01). The high fat Atkins dietary phase was also associated with higher levels of TMAO (3.3 vs 1.6 μM, p = 0.04), valine (272.8 vs. 240.7 μM, p = 0.004), and leucine (105.9 vs. 96.4 μM, p = 0.01) compared to baseline. Conclusions: These data suggest that over a 4-week interval, a saturated fat diet that is predominantly animal-based, compared to an isocaloric, low fat, predominantly plant-based diet, is associated with heightened risk for cardiometabolic derangements, as monitored by a higher plasma levels of both TMAO and BCAA.
Full-text available
Cortical iron has been shown to be elevated in Alzheimer’s disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (β [SE] = 9.7 [2.6]; P = 3.0 × 10−4) in the inferior temporal cortex only in subjects who were diagnosed with clinical AD during life and had a diagnosis of AD confirmed post-mortem by standardized criteria. Although iron was weakly associated with the extent of proteinopathy in tissue with AD neuropathology, it was strongly associated with the rate of cognitive decline (e.g., global cognition: β [SE] = -0.040 [0.005], P = 1.6 × 10−14). Thus, cortical iron might act to propel cognitive deterioration upon the underlying proteinopathy of AD, possibly by inducing oxidative stress or ferroptotic cell death, or may be related to an inflammatory response.
Full-text available
Background There is increasing evidence that plant based diets are associated with lower cardiovascular risk. Objective To evaluate effects of a vegan compared to an omnivorous diet on cardio-metabolic risk factors. Methods Meta-analysis of observational studies published between 1960 and June 2018 that reported one or more cardio-metabolic risk factors in vegans and controls eating an omnivorous diet were undertaken. Macro-nutrient intake and cardio-metabolic risk factors were compared by dietary pattern. The Newcastle Ottawa Scale (NOS) was used to assess the quality of each study. The inverse-variance method was used to pool mean differences. Statistical analyses were performed using RevMan software version 5•2 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen. Results 40 studies with 12 619 vegans and 179 630 omnivores were included. From food frequency questionnaires in 28 studies, vegans compared to omnivores consumed less energy (-11%, 95% confidence interval -14 to -8) and less saturated fat (- 51%, CI -57 to -45). Compared to controls vegans had a lower body mass index (-1.72 kg/m², CI -2.30 to -1.16), waist circumference (-2.35 cm, CI -3.93 to -0.76), low density lipoprotein cholesterol (-0.49 mmol/L CI -0.62 to -0.36), triglycerides (-0.14 mmol/L, CI -0.24 to -0.05), fasting blood glucose (-0.23 mmol/, CI -0.35 to -0.10), and systolic (-2.56 mmHg, CI -4.66 to -0.45) and diastolic blood pressure (-1.33 mmHg, CI -2.67 to -0.02), p<0.0001 for all. Results were consistent for studies with < and ≥ 50 vegans, and published before and after 2010. However in several large studies from Taiwan a vegan diet was not associated with favourable cardio-metabolic risk factors compared to the control diets. Conclusion In most countries a vegan diet is associated with a more favourable cardio- metabolic profile compared to an omnivorous diet.
Full-text available
Objective: White matter hyperintensities (WMH) are linked to vascular risk factors and increase the risk of cognitive decline, dementia and stroke. We here aimed to determine if obesity contributes to regional WMH using a whole‐brain approach in a well‐characterized population‐based cohort. Methods: Waist‐to‐hip ratio (WHR), body mass index (BMI), systolic/diastolic blood pressure, hypertension, diabetes and smoking status, blood glucose and inflammatory markers as well as distribution of WMH were assessed in 1825 participants of the LIFE‐adult study (age 20‐82 years; BMI 18.4 ‐ 55.4 kg/m²) using high‐resolution 3‐Tesla MRI. Voxel‐wise analyses tested if obesity predicts regional probability of WMH. Additionally, mediation effects of high‐sensitive C‐reactive protein (CRP) and interleukin‐6 (IL6) measured in blood were related to obesity and WMH using linear regression and structural equation models. Results: WHR related to higher WMH probability predominantly in the deep white matter, even after adjusting for effects of age, sex, and systolic blood pressure (mean ß=0.0043 (0.0008 SE), 95%CI [0.00427, 0.0043], TFCE/FWE‐corrected p<0.05). Conversely, higher systolic blood pressure was associated with WMH in periventricular white matter regions. Mediation analyses indicated that both higher WHR and higher BMI contributed to increased deep‐to‐periventricular WMH‐ratio through elevated IL6. Interpretation: Our results indicate an increased WMH burden selectively in the deep white matter in obese subjects with high visceral fat accumulation, independent of common obesity co‐morbidities such as hypertension. Mediation analyses proposed hat visceral obesity contributed to deep white matter lesions through increases in pro‐inflammatory cytokines, suggesting a pathomechanistic link. Longitudinal studies need to confirm this hypothesis. This article is protected by copyright. All rights reserved.
Full-text available
The association between depressive symptoms and vegetarian diets is controversial. This study examines the cross-sectional association between depressive symptoms and vegetarian diets while controlling for potential confounders. Among 90,380 subjects from the population-based Constances cohort, depressive symptoms were defined by a score ≥19 on the Centre of Epidemiologic Studies-Depression (CES-D) scale and diet types (omnivorous, pesco-vegetarian, lacto-ovo-vegetarian and vegan) were determined with a food frequency questionnaire. Associations between depressive symptoms and diet were estimated through logistic regressions adjusting for socio-demographics, other foods, alcohol and tobacco consumption, physical activity and health-related concerns; specificity analyses considered the exclusion of any other food group. Depressive symptoms were associated with pesco-vegetarian and lacto-ovo-vegetarian diets in multivariable analyses (Odds-Ratio [95% confidence interval]: 1.43 [1.19–1.72] and 1.36 [1.09–1.70], respectively), especially in case of low legumes intake (p for interaction < 0.0001), as well as with the exclusion of any food group (e.g., 1.37 [1.24–1.52], 1.40 [1.31–1.50], 1.71 [1.49–1.97] for meat, fish and vegetables exclusion, respectively). Regardless of food type, the Odds-Ratio of depressive symptoms gradually increased with the number of excluded food groups (p for trend < 0.0001). Depressive symptoms are associated with the exclusion of any food group from the diet, including but not restricted to animal products.
Full-text available
The effects of carbohydrates on body weight and insulin sensitivity are controversial. In this 16-week randomized clinical trial, we tested the role of a low-fat, plant-based diet on body weight, body composition and insulin resistance. As a part of this trial, we investigated the role of changes in carbohydrate intake on body composition and insulin resistance. Participants (n = 75) were randomized to follow a plant-based high-carbohydrate, low-fat (vegan) diet (n = 38) or to maintain their current diet (n = 37). Dual-energy X-ray absorptiometry was used to measure body composition. Insulin resistance was assessed with the Homeostasis Model Assessment (HOMA-IR) index. A repeated measure ANOVA model was used to test the between-group differences from baseline to 16 weeks. A linear regression model was used to test the relationship between carbohydrate intake, and body composition and insulin resistance. Weight decreased significantly in the vegan group (treatment effect −6.5 [95% CI −8.9 to −4.1] kg; Gxt, p < 0.001). Fat mass was reduced in the vegan group (treatment effect −4.3 [95% CI −5.4 to −3.2] kg; Gxt, p < 0.001). HOMA-IR was reduced significantly in the vegan group (treatment effect −1.0 [95% CI −1.2 to −0.8]; Gxt, p = 0.004). Changes in consumption of carbohydrate, as a percentage of energy, correlated negatively with changes in BMI (r = −0.53, p < 0.001), fat mass (r = −0.55, p < 0.001), volume of visceral fat (r = −0.35, p = 0.006), and HOMA (r = −0.27, p = 0.04). These associations remained significant after adjustment for energy intake. Changes in consumption of total and insoluble fiber correlated negatively with changes in BMI (r = −0.43, p < 0.001; and r = −0.46, p < 0.001, respectively), fat mass (r = −0.42, p < 0.001; and r = −0.46, p < 0.001, respectively), and volume of visceral fat (r = −0.29, p = 0.03; and r = −0.32, p = 0.01, respectively). The associations between total and insoluble fiber and changes in BMI and fat mass remained significant even after adjustment for energy intake. Increased carbohydrate and fiber intake, as part of a plant-based high-carbohydrate, low-fat diet, are associated with beneficial effects on weight, body composition, and insulin resistance.
Full-text available
Objective A growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions play an important role in human health and disease, including hedonic food intake and obesity. We performed a tripartite network analysis based on graph theory to test the hypothesis that microbiota-derived fecal metabolites are associated with connectivity of key regions of the brain’s extended reward network and clinical measures related to obesity. Methods DTI and resting state fMRI imaging was obtained from 63 healthy subjects with and without elevated body mass index (BMI) (29 males and 34 females). Subjects submitted fecal samples, completed questionnaires to assess anxiety and food addiction, and BMI was recorded. Results The study results demonstrate associations between fecal microbiota-derived indole metabolites (indole, indoleacetic acid, and skatole) with measures of functional and anatomical connectivity of the amygdala, nucleus accumbens, and anterior insula, in addition to BMI, food addiction scores (YFAS) and anxiety symptom scores (HAD Anxiety). Conclusions The findings support the hypothesis that gut microbiota-derived indole metabolites may influence hedonic food intake and obesity by acting on the extended reward network, specifically the amygdala-nucleus accumbens circuit and the amygdala-anterior insula circuit. These cross sectional, data-driven results provide valuable information for future mechanistic studies.
Full-text available
Background: Epidemiologic data suggest that diets rich in nuts have beneficial health effects, including reducing total and cause-specific mortality from cancer and heart disease. Although there is accumulating preclinical evidence that walnuts beneficially affect the gastrointestinal microbiota and gut and metabolic health, these relations have not been investigated in humans. Objective: We aimed to assess the impact of walnut consumption on the human gastrointestinal microbiota and metabolic markers of health. Methods: A controlled-feeding, randomized crossover study was undertaken in healthy men and women [n = 18; mean age = 53.1 y; body mass index (kg/m2): 28.8]. Study participants received isocaloric diets containing 0 or 42 g walnuts/d for two 3-wk periods, with a 1-wk washout between diet periods. Fecal and blood samples were collected at baseline and at the end of each period to assess secondary outcomes of the study, including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health. Results: Compared with after the control period, walnut consumption resulted in a 49-160% higher relative abundance of Faecalibacterium, Clostridium, Dialister, and Roseburia and 16-38% lower relative abundances of Ruminococcus, Dorea, Oscillospira, and Bifidobacterium (P < 0.05). Fecal secondary bile acids, deoxycholic acid and lithocholic acid, were 25% and 45% lower, respectively, after the walnut treatment compared with the control treatment (P < 0.05). Serum LDL cholesterol and the noncholesterol sterol campesterol concentrations were 7% and 6% lower, respectively, after walnut consumption compared with after the control treatment (P < 0.01). Conclusion: Walnut consumption affected the composition and function of the human gastrointestinal microbiota, increasing the relative abundances of Firmicutes species in butyrate-producing Clostridium clusters XIVa and IV, including Faecalibacterium and Roseburia, and reducing microbially derived, proinflammatory secondary bile acids and LDL cholesterol. These results suggest that the gastrointestinal microbiota may contribute to the underlying mechanisms of the beneficial health effects of walnut consumption. This trial was registered at as NCT01832909.