nutrients

Review
Nuts and Cardiovascular Disease Outcomes: A Review of the
Evidence and Future Directions
Andrea J. Glenn 1,2,3 , Dagfinn Aune 4,5,6 , Heinz Freisling 7 , Noushin Mohammadifard 8 ,
Cyril W. C. Kendall 2,3,9 , Jordi Salas-Salvadó 10,11 , David J. A. Jenkins 2,3,12,13,14 , Frank B. Hu 1,15,16
and John L. Sievenpiper 2,3,12,13,14, *

1 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
2 Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto,
Toronto, ON M5S 1A8, Canada
3 Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification
Centre, St. Michael’s Hospital, Toronto, ON M5C 2T2, Canada
4 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London,
London SW7 2AZ, UK
5 Department of Nutrition, Oslo New University College, 0372 Oslo, Norway
6 Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital,
0586 Oslo, Norway
7 Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO),
69366 Lyon, France
8 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical
Sciences, Isfahan JMXM+4VX, Iran
9 College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
10 Department of Biochemistry & Biotechnology, School of Medicine, Institut d’Investigacions Sanitàries Pere i
Virgili, Rovira i Virgili University, 43204 Reus, Spain
11 CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III,
28029 Madrid, Spain
12 Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON M5B 1T8, Canada
13 Division of Endocrinology and Metabolism, Department of Medicine, St. Michael’s Hospital,
Toronto, ON M5C 2T2, Canada
14 Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Citation: Glenn, A.J.; Aune, D.;
15 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and
Freisling, H.; Mohammadifard, N.;
Harvard Medical School, Boston, MA 02115, USA
Kendall, C.W.C.; Salas-Salvadó, J.; 16 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Jenkins, D.J.A.; Hu, F.B.; Sievenpiper, * Correspondence: [email protected]
J.L. Nuts and Cardiovascular Disease
Outcomes: A Review of the Evidence
Abstract: Nuts are nutrient-rich foods that contain many bioactive compounds that are beneficial
and Future Directions. Nutrients 2023,
for cardiovascular health. Higher consumption of nuts has been associated with a reduced risk of
15, 911. https://doi.org/10.3390/
several cardiovascular diseases (CVD) in prospective cohort studies, including a 19% and 25% lower
nu15040911
risk of CVD incidence and mortality, respectively, and a 24% and 27% lower risk of coronary heart
Academic Editor: Kalliopi Karatzi disease incidence and mortality, respectively. An 18% lower risk of stroke mortality, a 15% lower
Received: 20 January 2023 risk of atrial fibrillation, and a 19% lower risk of total mortality have also been observed. The role
Revised: 1 February 2023 of nuts in stroke incidence, stroke subtypes, peripheral arterial disease and heart failure has been
Accepted: 6 February 2023 less consistent. This narrative review summarizes recommendations for nuts by clinical practice
Published: 11 February 2023 guidelines and governmental organizations, epidemiological evidence for nuts and CVD outcomes,
nut-containing dietary patterns, potential mechanisms of nuts and CVD risk reduction, and future
research directions, such as the use of biomarkers to help better assess nut intake. Although there
are still some uncertainties around nuts and CVD prevention which require further research, as
Copyright: © 2023 by the authors.
summarized in this review, there is a substantial amount of evidence that supports that consuming
Licensee MDPI, Basel, Switzerland.
nuts will have a positive impact on primary and secondary prevention of CVD.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Keywords: tree nuts; peanuts; nutrition; cardiovascular diseases; review
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

Nutrients 2023, 15, 911. https://doi.org/10.3390/nu15040911 https://www.mdpi.com/journal/nutrients

Nutrients 2023, 15, 911 2 of 16

1. Introduction
Cardiovascular diseases (CVD) are the leading cause of death worldwide and a major
cause of premature mortality, causing an estimated 31% of all deaths globally [1]. Major
modifiable risk factors for CVD include smoking, harmful alcohol use, physical inactivity,
unhealthy diets, abdominal obesity, hypertension, dyslipidemia, high fasting glucose
and diabetes, and kidney dysfunction [2]. Furthermore, there are many downstream
complications of CVD that can significantly impact quality of life and cause disability and
death, including dementia, peripheral arterial disease (PAD), heart failure (HF), kidney
disease, frailty and poor aging, among others [3].
Despite a decline in CVD in several regions around the globe, it remains a major threat
to public health as the absolute numbers continue to increase, with prevalent cases of total
CVD nearly doubling from 1990 to 2019 [4]. These numbers are expected to increase even
further in upcoming years due to population growth and aging. For example, a recent
analysis in the United States projects large future increases in CVD risk factors and CVD
prevalence (e.g., 31% increase in ischemic heart disease and 34% increase in stroke) by
2060 [5]. According to the Global Burden of Diseases (GBD) Study, unhealthy diets are
the greatest contributor to premature morbidity and mortality worldwide, including CVD
mortality [6]. The main dietary risk factors attributable to the global burden of diseases
include diets low in whole grains, fruit, nuts/seeds, and vegetables and diets high in
sodium and processed meat [7]. Tree nuts and peanuts, one of the top dietary risk factors
noted by the GBD study, may be particularly beneficial for CVD prevention due to their
bioactive components. Of note, peanuts are botanically defined as legumes; however,
they have a similar nutrient composition and culinary use as tree nuts and are, therefore,
usually included as nuts when estimating total nut intake [8]. The bioactive components
of tree nuts and peanuts include their macronutrient, fat-soluble bioactive, fiber, vitamin,
mineral and phenolic content [9]. Specifically, fat-soluble bioactives such as their fatty acid
content (monounsaturated and polyunsaturated fatty acids), fiber, magnesium, tocopherols
and tocotrienols, phytosterols, sphingolipids, carotenoids, chlorophylls and alkyl phenols,
and phenolic compounds (including flavonoids, phenolic acids, stilbenes, lignans, among
others) all likely contribute to their cardiovascular health-promoting effects [9].
In this narrative review, we describe the importance given to nuts in clinical practice
guidelines, the evidence we have in relation to the beneficial effects of frequent consumption
of nuts in the prevention of CVD, as well as the possible mechanisms involved. However, we
also emphasize the gaps that exist in the literature and discuss the possible studies that we
should develop in the future to increase the level of evidence and establish recommendations.

2. Nuts in Clinical Practice Guidelines for Cardiovascular Risk Reduction

Given their cardiovascular health-promoting properties, tree nuts and peanuts are
recognized by several international health organizations for cardiovascular risk reduction
for both primary and secondary prevention. Table 1 highlights the recommendations from
cardiovascular clinical practice guidelines (CPGs), including the Canadian Cardiovascular
Society, Joint British Societies for the Prevention of Cardiovascular Disease, the Australian
Heart Foundation, the American Heart Association and the European Society of Cardiol-
ogy [10–14]. Nuts are recommended as a healthy plant protein and fat source that should
be frequently consumed to lower low-density lipoprotein cholesterol (LDL-C), improve the
overall lipoprotein profile and decrease CVD risk.

Table 1. Examples of Recommendations for Nuts in CVD Clinical Practice Guidelines.

Guideline Association Nuts Recommendation

“Choose healthy sources of protein, mostly protein from plants
American Heart Association 2021 [10]
(legumes and nuts)”
Nutrients 2023, 15, 911 3 of 16

Table 1. Cont.

Guideline Association Nuts Recommendation

European Society of Cardiology and European Atherosclerosis “Food choices to lower low-density lipoprotein cholesterol and
Society 2019 [11] improve the overall lipoprotein profile are nuts and seeds”
“We suggest that all individuals be encouraged to moderate
energy (caloric) intake to achieve and maintain a healthy body
weight (Conditional Recommendation; Moderate-Quality
Canadian Cardiovascular Society 2016 [12]
Evidence) and adopt a healthy dietary pattern to lower their
CVD risk: Dietary patterns high in nuts (30 g/day) (Conditional
Recommendation; Moderate-Quality Evidence)”
Joint British Society Consensus for prevention of Cardiovascular
“Consider regular consumption of whole grains and nuts”
Disease 2014 [13]
“Eating patterns for heart health are based on:
• A variety of healthy protein sources including fish,
Heart Foundation seafood, lean meat and poultry, legumes, nuts and seeds
Australia 2019 [14] • Healthy fat choices with nuts, seeds, avocadoes, olives and
their oils for cooking”

Abbreviations: CVD = cardiovascular disease.

3. Regulated Nut Health Claims Allowed for Cardiovascular Risk Reduction

To encourage the consumption of foods that may be beneficial for health, governmental
agencies review the evidence and approve health claims that can provide consumers with
reliable information about the relationship between the consumption of food and a specific
health benefit. Several regulated disease risk reduction health claims have been approved
for nuts and CVD by the U.S. Food and Drug Administration (FDA), the European Food
Safety Authority (EFSA) and Food Standards Australia New Zealand (FSANZ), as shown
in Table 2 [15,16]. Health Canada has not approved a disease risk reduction claim for
nuts. The FDA and FSANZ both approved a health claim regarding nuts and CVD risk
reduction, particularly for the LDL-C lowering effects of nuts. However, EFSA did not
approve this type of claim and noted that, specifically for walnuts, the evidence provided
did not establish that the consumption of walnuts had an effect on LDL-C beyond what
could be expected from their fatty acid composition [17]. EFSA, however, established that a
cause-and-effect relationship between the consumption of walnuts and the improvement
of endothelium-dependent vasodilation exists and has approved a health claim for this
finding (Table 2) [17].

Table 2. Examples of Regulated Health Claims for Nuts and CVD Risk Reduction.

FDA EFSA FSANZ

1.5 ounces per day of nuts, as part of a diet low in General level health claim around
30 g per day of walnuts may
saturated fat and cholesterol and not resulting in heart health without causing weight
improve endothelium-dependent
increased intake of saturated fat or calories may gain allowed for tree nuts, peanuts,
vasodilation [17]
reduce the risk of CHD [15] ground nuts/butters/pastes [16]
Abbreviations: EFSA = European Food Safety Authority; FDA = Food and Drug Administration; FSANZ = Food
Standards Australia New Zealand.

4. Nuts and Cardiovascular Disease Outcomes

The scientific study of the role of nuts in preventing CVD started over 30 years ago,
first with a discovery that individuals in the Adventist Health Study who consumed nuts
more frequently (more than four times per week) had fewer coronary heart disease (CHD)
events compared to those who consumed nuts less than once per week [18]. Investigators
believed that this CHD risk reduction might be related to the favorable fatty acid profile
of nuts. Researchers from the same group then assessed if consuming walnuts (20% of
calories through replacing other fatty foods, meat and oils, margarine and butter) would
 Nutrients 2023, 15, x FOR PEER REVIEW 4 of 16

Nutrients 2023, 15, 911 4 of 16

calories through replacing other fatty foods, meat and oils, margarine and butter) would
affect blood lipids in healthy individuals [19]. They found that incorporating a moderate
affect blood
amount oflipids
walnutsin healthy
in the dietindividuals
decreased [19]. They
levels of found that incorporating
total cholesterol (TC) anda LDL-C
moderate[19].
amount of walnuts
The favorable in the diet decreased
modification of the lipidlevels of by
profile total cholesterol
frequent (TC) and LDL-C
nut consumption has[19].
beenThe
con-
favorable
firmed inmodification of theand
additional trials lipidsystematic
profile by reviews
frequentand nut meta-analyses
consumption has been
[20]. Theconfirmed
role of nuts
inin
additional
preventing trials
CVD and systematic
outcomes reviews and
in prospective meta-analyses
cohort studies has [20]. The extensively
also been role of nutsstud-
in
preventing CVD outcomes in prospective cohort studies has also been extensively
ied. Below we describe this evidence related to total CVD, CHD, stroke, HF, atrial fibril- studied.
Below
lationwe describe
(AF), PAD this
andevidence related The
total mortality. to total CVD, CHD,
definition of nutsstroke, HF, atrial
includes fibrillation
tree nuts, peanuts
(AF),
andPAD
seedsand total mortality.
(sunflower, pumpkin, The definition of nuts includes
etc.) as a culinary definitiontree
fornuts, peanutsAn
this review. and seeds
overview
(sunflower, pumpkin,
of the pooled summary etc.)data
as for
a culinary definition
each outcome for this in
is included review.
FigureAn 1. overview of the
pooled summary data for each outcome is included in Figure 1.

Figure
Figure Summary
1. 1. Summary of of
thethe
pooled
pooledeffect estimates
effect estimatesof of
prospective
prospective cohort
cohortstudies assessing
studies thethe
assessing associa-
associ-
tion between
ation betweenhighhigh
and and
low consumption
low consumption of nuts
of and
nutsrisk
andofrisk
cardiovascular diseasedisease
of cardiovascular outcomes and total
outcomes and
total mortality.
mortality. Figure adapted
Figure adapted from
from Figure Figure
2 in 2 in [21].
[21]. Pooled riskPooled riskis estimate
estimate is represented
represented by the
by the diamond.
diamond.
* To * To obtain
obtain summary summary
estimates forestimates
peripheralforarterial
peripheral arterial
disease, we disease, we used
used generic generic
inverse inverse
variance
variance (fixed effects) to pool the natural log-transformed RRs of the extreme
(fixed effects) to pool the natural log-transformed RRs of the extreme quantiles. Abbreviations: quantiles. Abbrevia-
tions: CI = confidence intervals; RR = relative risk
CI = confidence intervals; RR = relative risk.

4.1.
4.1. Total
Total Cardiovascular
Cardiovascular Disease
Disease
Total
Total CVDCVD is is a composite
a composite outcome
outcome of of
CVDCVD incidence
incidence (including
(including only
only nonfatal
nonfatal oror
a a
combination
combination ofof nonfatal
nonfatal andand fatal
fatal outcomes
outcomes ofof different
different CVDCVD outcomes)
outcomes) oror may
may include
include
CVD
CVD mortality
mortalityoutcomes
outcomes only, which
only, whichis is
a composite
a composite of of
different
differentfatal CVD
fatal CVD endpoints.
endpoints.AA
recent systematic
recent systematic review
review andand meta-analysis
meta-analysis ofof
prospective
prospective cohort
cohort studies
studiesthat
thatwere
werecom-
com-
missioned
missionedto to
update
update thethe
clinical practice
clinical guidelines
practice guidelinesforfor
nutrition
nutrition therapy
therapy forfor
the European
the European
Association
Associationforfor
thethe
Study
Studyof Diabetes (EASD)
of Diabetes found
(EASD) that in
found three
that cohortcohort
in three comparisons (in-
comparisons
cluding 210,839 participants and 14,136 events), high consumption of nuts was associated
with a 15% lower risk of CVD incidence (relative risk [RR] = 0.85, 95% confidence intervals
Nutrients 2023, 15, 911 5 of 16

[CI]: 0.80–0.91) compared to low consumption [22]. In 15 cohort comparisons (including

413,797 participants and 14,475 events), high consumption of nuts was associated with
a 23% lower risk of CVD mortality (RR = 0.77, CI: 0.72–0.82) compared to low consump-
tion [22]. The certainty of the evidence was assessed using the Grading Recommendations
Assessment, Development and Evaluation (GRADE). The GRADE for CVD incidence was
low quality due to a downgrade for indirectness (i.e., how applicable the evidence is to
the general population) but an upgrade for a dose-response gradient. The GRADE for
CVD mortality was moderate quality due to an upgrade for a dose-response gradient.
The dose-response analysis showed that the reduction in risk of CVD incidence was ob-
served up to 10 g/day with no further reduction in risk for higher consumption. For CVD
mortality, there was a greater reduction in risk at 15–20 g/day, with no further reduction
with higher consumption. When assessing different types of nuts, tree nuts, peanuts and
walnuts were all associated with a 13–19% lower risk of CVD incidence, whereas the associ-
ation for peanut butter was not significant (RR = 0.98, CI: 0.93–1.03). For CVD mortality,
only peanuts have been analyzed, and higher consumption was associated with a lower
risk of CVD mortality compared to low consumption [22]. The lack of association with
peanut butter may be in part because many peanut butters on the market have added salt,
fully hydrogenated oils or oils such as palm oil that can increase the saturated fat content,
which could negatively impact their health benefits as compared with whole sources of
peanuts; further research on natural peanut butter may provide additional insight into
this hypothesis.
A more recent 2022 umbrella review assessing the role of nuts in preventing several
chronic diseases found similar associations with CVD incidence and mortality [21]. For
CVD incidence, 11 cohort comparisons were assessed (including 376,228 participants and
18,655 events), and a 19% lower risk was observed comparing high to low consumption
(RR = 0.81, CI: 0.74–0.89) and 21% lower risk when assessing associations per serving
(28 g/day) (RR = 0.79, CI: 0.70–0.89). For CVD mortality, 16 cohort comparisons were
included (524,610 participants and 19,574 cases), and a 25% lower risk comparing high
to low consumption (RR = 0.75, CI: 0.71, 0.79) was observed and a 6% lower risk when
assessing nut intake by 28 g/day (RR = 0.94, CI: 0.93, 0.96) [21]. This umbrella review also
assessed dose-response relationships with CVD mortality and found that the optimal intake
levels of nuts are ~15–20 g/day and that there were limited further benefits of consuming
up to one serving (28 g/day), similar to the earlier meta-analysis [22]. However, it should be
mentioned that the high end of nut consumption across most cohorts is typically one serving
(28 g)/day, and little is known about the dose-response relationship with higher intakes.

4.2. Coronary Heart Disease

Similar to total CVD, CHD incidence may include fatal and nonfatal events, whereas
CHD mortality includes CHD mortality outcomes only. The systematic review and meta-
analysis conducted to update the EASD nutrition therapy guidelines assessed 7 cohort
comparisons (including 275,812 participants and 12,654 cases) and found that high nut con-
sumption was associated with an 18% lower risk of CHD incidence (RR = 0.82, CI: 0.69–0.96)
compared to low consumption [22]. For CHD mortality, 13 cohort comparisons were in-
cluded (396,014 participants and 7877 cases), and high consumption of nuts was associated
with a 24% lower risk (RR = 0.76, CI: 0.67–0.86) compared to low consumption. The cer-
tainty of evidence using GRADE was very low for CHD incidence owing to downgrades
for inconsistency (i.e., unexplained heterogeneity), indirectness and imprecision (i.e., the
minimally important difference for the clinical benefit [considered RR = 0.95 in this meta-
analysis]), and an upgrade for a dose-response gradient. The certainty of the evidence was
moderate for CHD mortality, owing to an upgrade for a dose-response gradient. When
assessing different types of nuts, tree nuts, peanuts and walnuts were all associated with a
15–23% lower risk of CHD incidence, and similar to CVD incidence, no association was
reported for peanut butter consumption (RR = 1.00, CI: 0.94–1.07). The findings were also
similar between CVD and CHD mortality, where peanut consumption was inversely asso-
Nutrients 2023, 15, 911 6 of 16

ciated with the risk of CHD mortality. Comparable to CVD mortality, the CHD mortality
dose-response analysis showed greater reductions in risk at around 15–20 g/day [13,22].
The 2022 umbrella review showed that for CHD incidence (including 12 cohort compar-
isons with 315,397 participants and 12,331 events), there was a 24% lower risk comparing
high to low consumption (RR = 0.76, CI: 0.69–0.84) and 25% lower risk when assessing
per servings associations of 28 g/day (RR = 0.75, CI: 0.64–0.88) [21]. For CHD mortality,
13 cohort comparisons were included (429,833 participants and 10,083 cases), and a 27%
lower risk comparing low to high consumption (RR = 0.73, CI: 0.67, 0.80) was observed and
a 6% lower risk when assessing nut intake by 28 g/day (RR = 0.94, CI: 0.93, 0.96) [21].

4.3. Stroke
Stroke outcomes include stroke incidence and mortality, and the main stroke subtypes,
ischemic and hemorrhagic stroke. The association between nut consumption and stroke
risk has been less consistent than that observed for total CVD and CHD. For stroke in-
cidence, the EASD systematic review and meta-analysis included 7 cohort comparisons
(of 302,888 participants and 12,646 events) and found no associations when comparing
high to low consumption (RR = 1.00, CI: 0.92–1.09) [22]. In contrast, for stroke mortality,
12 cohort comparisons were analyzed (including 351,618 participants and 2332 cases) and
comparing high vs. low categories of nut consumption was associated with a 17% lower
risk (RR = 0.83, CI: 0.75–0.93). The certainty of evidence using GRADE was very low for
stroke incidence owing to downgrades for indirectness and imprecision, and low for stroke
mortality, owing to downgrades for imprecision but an upgrade for a dose-response gra-
dient. Regarding specific types of nuts, peanut consumption was associated with a lower
risk of stroke incidence and mortality, but other nut types and peanut butter were not
significantly associated with either outcome. For stroke subtypes, no associations were
seen with ischemic stroke (RR = 0.99, CI: 0.89–1.10 in 7 cohort comparisons including
302,423 participants and 8401 cases) or hemorrhagic stroke (RR = 1.02, CI: 0.77–1.34 in
5 cohort comparisons including 188,750 participants and 3088 cases) [22].
Another meta-analysis including 11 cohort studies (9272 stroke cases) and 396,768 par-
ticipants also reported an inverse association in the high vs. low analysis (RR = 0.89,
CI: 0.82–0.97), but not in the linear dose-response analysis (RR = 0.93, CI: 0.83–1.05); how-
ever, there was some indication of a non-linear J-shaped association with a reduction in risk
up to approximately 10–15 g/day, but a slight positive association at 30 g/day [23]. There
was no indication of an increased risk at high intakes when stroke incidence and stroke
mortality were analyzed separately, suggesting that the direct association at high nut doses
observation could be an artefact. When subtypes of nuts were examined, no association was
observed for tree nuts in relation to the risk of stroke in the high vs. low and dose-response
analyses, while slight inverse associations were observed for peanuts [23], which were
both similar to those reported in the EASD meta-analysis [22]. It is unclear whether these
differences in results between subtypes are real or simply because of chance variation
due to the few studies available. Given largely overlapping confidence intervals between
summary estimates, it is possible that chance variation is playing a role; therefore, further
studies are needed. The 2022 umbrella review findings were also similar: no association
was seen with stroke incidence (RR = 1.00, CI: 0.92–1.09) in 7 cohort comparisons, including
302,888 participants and 12,646 cases, with an inverse association seen with stroke mor-
tality (RR = 0.82, CI: 0.73–0.92) in 12 cohort comparisons including 449,293 participants
and 4398 events [21]. Although results regarding nut consumption and stroke risk have
been more variable than for CHD, it seems there may be a modest inverse association
between higher nut intake and stroke risk. Most of the individual studies may not have
been sufficiently powered to detect an association. Nonetheless, a possible reason for the
weaker association between nut consumption and stroke than for CHD could be the fact
that many nuts are salted. Dietary salt consumption is one of the main determinants for
elevated blood pressure, and it is possible that adding salt to nuts could dilute some of the
Nutrients 2023, 15, 911 7 of 16

benefits they have, particularly for stroke, similar to the possible reasons for no association
seen with peanut butter and several CVD outcomes.

4.4. Heart Failure

Few prospective cohort studies have assessed the role of nut consumption in pre-
venting one of the major complications of CVD, HF. The EASD systematic review and
meta-analysis included two cohort studies with 53,877 participants and 4253 cases, and
for high vs. low categories of nut consumption, the RR was 1.00 (CI: 0.86–1.16) [22]. The
certainty of evidence by GRADE was very low for HF, owing to downgrades due to the
risk of bias (i.e., study quality as assessed by the Newcastle Ottawa Scale), indirectness
and imprecision. Similarly, the 2022 umbrella review included the same cohorts, and the
same effect estimates were observed [21]. Interestingly, a large prospective Swedish Cohort
study of 61,364 adults observed a non-linear inverse association with the risk of HF and a
12% reduction in risk (HR = 0.88, CI: 0.79–0.99) with consumption of nuts 1–2 times per
week with 17 years of follow-up [24].

4.5. Atrial Fibrillation

Similar to HF, fewer prospective cohort studies have examined the role of nuts in
preventing this important risk factor for stroke and HF. The EASD systematic review and
meta-analysis assessed two prospective cohort studies, including 53,965 participants and
10,867 cases [22]. Comparing high vs. low consumption of nuts, there was a 15% lower risk
of AF (RR = 0.85, CI: 0.73–0.99), similar to the 2022 umbrella review [21]. The certainty of
the evidence was very low, owing to downgrades due to indirectness and imprecision [22].
Similar to HF, the Swedish Cohort study also found a non-linear inverse relationship with
the risk of AF and consumption of nuts 3 or more times per week was associated with an
18% reduced risk of AF [24].

4.6. Peripheral Arterial Disease

Few studies have assessed the association between nut consumption and the risk of
PAD [25]. In the Atherosclerosis Risk in Communities Study, 14,082 men and women were
followed for 20 years, and 1569 incident cases of PAD were identified. There was no clear
association between the frequency of nut consumption and the risk of PAD, and the HR
was 1.04 (CI: 0.89–1.23) when comparing an intake of ≥2/week vs. almost never [26]. In an
analysis from the Women’s Health Initiative, including 138,506 postmenopausal women
and 1036 PAD cases identified during 19 years of follow-up, there was no association
between higher consumption of nuts and seeds and PAD (highest vs. lowest quartile of
nuts and seeds consumption was 0.93 [CI: 0.78–1.10]) [27]. Similarly, in a combined analysis
of 38,823 women in the Swedish Mammography Cohort and 45,472 men in the Cohort of
Swedish Men (aged 45–83 years) with 22 years follow-up and 3413 PAD cases, there was no
clear association between intake of nuts and PAD risk, and the HR was 1.05 (CI: 0.89–1.24)
for the highest vs. lowest category of intake [28]. We pooled the data from the 3 cohorts,
and the RR was 1.03 (CI: 0.96–1.09), also highlighting no clear association between nut
consumption and the risk of PAD (Figure 1). However, we cannot exclude the possibility
that there may be a U-shaped association between nut consumption and PAD.

4.7. Total Mortality

The 2022 umbrella review also assessed the association between nut consumption
and overall total mortality. In 16 cohort comparisons (including 819,448 participants and
85,870 deaths), both high vs. low categories of nut consumption (RR = 0.81, CI: 0.77, 0.85)
and per serving (28 g/day, RR = 0.78, CI: 0.72, 0.84) were associated with lower risk of total
mortality [21]. Similar to total CVD, the dose-response analyses indicated optimal intake
levels were approximately ~15–20 g/day, with limited further benefits up to 28 g/day. In
addition, a meta-analysis of 15 cohort studies indicated that 4.4 million premature deaths
Nutrients 2023, 15, 911 8 of 16

in the Americas, Europe, Southeast Asia and Western Pacific would be attributable to a nut
intake below 20 g/day [23].

4.8. Change in Nut Intake and Substitution Analyses

Changes in nut intake over time and the substitution of nuts for other dietary factors
have also been associated with a lower risk of CVD. For instance, Liu et al. examined
the association between 4-year changes in nut consumption and risk of CVD outcomes in
the subsequent 4 years in the Health Professionals Follow-up Study (HPFS) and Nurses’
Health Study (NHS) I and II [29]. They found that a per 1/2 serving/day increase in total
nut consumption was associated with a lower risk of CVD (HR = 0.92, CI: 0.86–0.98), CHD
(HR = 0.94, CI: 0.89–0.99) and stroke (HR = 0.89, CI: 0.83–0.95) and those that decreased
their nut consumption over time had an increased risk of CVD, CHD and stroke. The
1/2 serving/day increase in consumption for a different type of nuts showed that most
nut types were associated with a lower risk of CVD outcomes, with walnuts showing
the strongest association and peanut butter showing no association. The researchers also
examined the substitution effect per 1/2 serving/day of nuts and found that replacing red
meat, processed meat, refined grains, French fries and dessert with nuts was associated
with a lower risk of CVD, CHD and stroke [29]. In another analysis of HPFS and NHS,
substituting both unprocessed and processed red meat for nuts was associated with the
greatest reduction in total mortality [30].

5. Healthy Dietary Patterns That Contain Nuts

Several healthy dietary patterns that are recommended in CVD clinical practice guide-
lines contain nuts as a key food component. These include dietary patterns such as the
Mediterranean, Nordic, Dietary Approaches to Stop Hypertension (DASH), vegetarian
and Portfolio diets. Each of these dietary patterns has been shown to lower important
CVD risk factors in RCTs and is associated with a lower risk of CVD in prospective cohort
studies [31–38]. A healthy Mediterranean diet including nuts was also assessed with CVD
endpoints in the landmark Prevención con Dieta Mediterránea (PREDIMED) trial. In
this trial, over 7000 high-risk individuals for CVD were randomly assigned to an energy-
unrestricted Mediterranean diet supplemented with either extra virgin olive oil (EVOO) or
mixed nuts or the control diet (advice to curtail all types of fat) [39]. After approximately
5 years, both the Mediterranean diet groups supplemented with EVOO and nuts had a
30% reduction in CV events, mainly through reductions in stroke. Further analyses of
the PREDIMED study also found a reduced risk of PAD both in the EVOO (HR = 0.36,
CI: 0.21–0.65) and in the nuts group (HR = 0.54, CI: 0.32–0.92) when compared to the control
group [40]. Due to the design of the PREDIMED study, it is not possible to separate the
impact of nuts (or EVOO) from that of other dietary recommendations given to increase
adherence to a Mediterranean diet, as well as with other healthy dietary patterns, and it is
possible that other components of the diet could contribute in part to these findings.

6. Mechanisms Related to Nuts and Cardiovascular Risk Reduction

There are several mechanisms by which nuts can lower the risk of developing CVD,
such as through positively impacting intermediate cardiovascular risk factors, including
blood lipids, blood pressure, inflammation, and markers of glycemic control, among
others. Nuts are rich in unsaturated fatty acids, plant protein, phytosterols, fiber, some
minerals (including potassium, calcium and magnesium), vitamins (vitamin E and B6)
and phenolic and bioactive compounds, all of which may contribute to their CV health-
promoting benefits [9]. A systematic review and meta-analysis of 61 trials of tree nut
consumption found that at a median dose of 56 g/day, TC, LDL-C, apolipoprotein B (ApoB)
and triglycerides were significantly lowered, with no effect on high-density lipoprotein-
cholesterol (HDL-C). A dose-dependent effect was also reported, with stronger effects seen
for TC and LDL-C with nut intake over 60 g/day [20]. Importantly, the type of nut did
not appear to be important for the cholesterol-lowering results observed [20]. The effects
Nutrients 2023, 15, 911 9 of 16

on blood pressure and inflammation have been less consistent than those observed for
blood lipids, with the same systematic review and meta-analysis finding no significant
effects of tree nut consumption on blood pressure and C-reactive protein [20]. Other meta-
analyses have conversely shown that nut consumption, particularly pistachios, does have a
modest blood pressure lowering effects in people without type 2 diabetes [41], with another
meta-analysis finding that almond consumption lowered diastolic blood pressure [42].
This finding of stronger effects on blood lipids than on blood pressure is consistent with
the studies showing that LDL-C and ApoB are causal in the development of CHD [43],
while elevated blood pressure is a greater risk factor for stroke [44] and may explain the
more consistent finding with a lower risk of CHD than with stroke seen in the prospective
cohort studies described earlier. Furthermore, a systematic review and meta-analysis
that included 12 trials found that tree nuts at a median dose of 56 g/day can improve
markers of glycemic control in individuals with type 2 diabetes (including lowering HbA1c
and fasting glucose) [45]. Another systematic review and meta-analysis of 40 RCTs at a
median dose of 52 g/day, including diverse populations of adults (including healthy, those
with type 2 diabetes or with CVD risk factors), found that tree nuts or peanuts improved
markers of insulin sensitivity, however, the effect on fasting blood glucose and HbA1c
was not significant [46]. Other potential mechanisms include their role in adiposity [47],
possibly due to their satiating effect, increased efforts and/or time of mastication and hence
incomplete digestion in the intestines, and alpha-linolenic acid content of nuts, especially
walnuts, which might increase membrane fluidity of endothelial cells with the enhancement
of nitric oxide synthesis and ensuing improvement of endothelial function [48,49]. Overall,
there is good evidence that nut consumption consistently lowers atherogenic blood lipids
and may improve insulin sensitivity and endothelial function, with less consistent effects
on blood pressure, without adversely impacting adiposity. Regarding adiposity, a recent
systematic review and meta-analysis highlighted that the median nut intake in the trials
included in their analyses, as well as in the health claims noted in Table 2, that a dose of
42.5 g/day could be integrated into a daily dietary pattern without contributing to weight
gain [47].

7. Future Directions
The evidence for nut consumption and total CVD and CHD is more consistent in
prospective cohort studies compared to other CVD outcomes, with low to moderate cer-
tainty of evidence using the GRADE criteria. The GRADE criteria, however, may not be the
best grading system to use when evaluating the certainty of evidence from observational
studies, particularly in the field of nutritional epidemiology [50]. Future pooled analyses
that assess the certainty of evidence should consider integrating ROBINS-I to assess the
risk of bias [51] or consider also applying the NutriGrade system [52], both of which do not
provide excessive downgrading of observational evidence. In addition, given the scarcity
and sometimes conflicting results among studies, more studies are needed to clarify the
role of nut consumption in stroke, particularly stroke subtypes, HF, AF and PAD. Further
research on the type of nuts will eventually provide further insight into their role in CVD
prevention, including studies of peanut and other nut butters (including natural) and
salted vs. unsalted nuts. New analyses on nut intake should also report quantities of nut
intake (i.e., grams/day) so that these data can be used in updated meta-analyses. The
quantity of nuts is also more translatable for guiding dietary recommendations compared
to high vs. low categories. Individual cohort pooled meta-analyses would also be useful to
ensure consistency in analyses across cohort studies. Although RCTs of nut consumption
and blood lipids support the results from observational cohort studies showing reduced
CVD and CHD risk, there is some discrepancy between what doses of nuts have been
shown to reduce blood lipids in RCTs and what doses lower CVD and CHD risk in ob-
servational cohort studies. For example, in a meta-analysis of RCTs, there was a steeper
reduction in total and LDL-C between 50–100 g/d than at lower levels of intake [20], while
in the observational cohort studies, maximum risk reductions have been observed around
Nutrients 2023, 15, 911 10 of 16

15–20 g/d (approximately 4–5 servings/week) [21–23]. However, the highest nut intakes
reported in cohort studies have typically been around one serving/day (28 g/d), and it is
unknown whether CVD or CHD risk is reduced further with higher intakes. Considering
that relatively few people consume more than one serving of nuts per day in most popu-
lations [23,53], pooled analyses may also be needed to explore, with sufficient statistical
power, whether higher intakes are associated with further reductions in hard endpoints.
Further studies are also needed to clarify if other mechanisms than reductions in lipids (e.g.,
antioxidant or anti-thrombotic effects) may contribute to the vascular benefits observed at
the more modest nut consumption levels reported in the observational studies. Another
important consideration related to the discrepancy of nut levels consumed in trials and
cohort studies is the dietary assessment tool used, as food frequency questionnaires (FFQ)
commonly administered in cohort studies may not be as accurate in quantifying absolute
intake compared to trials, where diet records are typically used, and intervention groups
are usually provided nuts to guarantee the desired consumption. As diet records are not
feasible in large cohort studies, repeated measurements of FFQs will be important to repre-
sent long-term dietary habits and reduce measurement error, as well as allow assessment
of change in nut consumption in relation to health outcomes. FFQs should also consider
including more nut categories (walnuts, almonds, peanuts, seeds, etc.) to provide more
detailed information on nuts and nut types.
Using objective biomarkers of nut consumption alongside dietary intake assessment
methods will additionally be important in the future, as they are less prone to measurement
error from FFQs or 24-h recalls [54]. For example, in the PREDIMED study, plasma alpha-
linolenic acid (a polyunsaturated fatty acid that abounds in walnuts) levels were measured
to confirm adherence in the group receiving mixed nuts alongside an FFQ [39]. Novel
approaches, such as multi-omics, will likely play a larger role in the future for both assessing
adherence to diet and precision nutrition [55]. Metabolomics, in particular, is a promising
technique to help identify objective dietary biomarkers by providing a comprehensive
representation of overall dietary intake by measuring the metabolites in biological samples
(such as blood or urine). In prospective cohort studies, several metabolites, mainly lipid-
related, have been found to be markers of nut intake in general [56] or of specific types
of nuts, such as walnuts, and these metabolites have likewise been associated with a
lower risk of CVD [57]. The metabolites associated with nut consumption may be helpful
in identifying potential objective biomarkers of exposure to nuts in large prospective
cohort studies, as well as in clarifying underlying mechanisms implicated in disease risk.
Importantly though, these metabolomic profiles associated with nut consumption are
not highly correlated with self-reported nut consumption and also reflect the metabolic
response to consumption and are therefore not completely sensitive or specific markers.
Many of these metabolites may also not be able to distinguish between different types
of nuts. Thus, dietary intake assessment methods such as FFQs will still be important to
determine more specific information on nut consumption.
Other future directions include undertaking large CV outcome trials of nut-containing
dietary patterns, as was previously done with PREDIMED [39] and the current ongoing
PREDIMED-Plus trials [58] (both primary CVD prevention trials) and the CORDIOPREV
trial (a secondary CVD prevention trial) [59]. One limitation of these trials is that they
cannot separate the effect of the Mediterranean diet from that of nuts on health outcomes.
Thus, any further trials in this setting could benefit from having an additional intervention
group on a Mediterranean diet only (without nuts). Large trials should also consider long-
term measurements of renal function, as this area has been given insufficient attention and
kidney dysfunction has been causally related to CHD risk [60], therefore highlighting the
need for preventative approaches to also preserve renal function. Furthermore, determining
metabolomic signatures that can reflect adherence and metabolic response to these nut-
containing dietary patterns should be included within these types of trials. This method
was previously assessed using the Mediterranean diet in the PREDIMED study, where a
metabolic signature that robustly reflected adherence and metabolic response to the diet
Nutrients 2023, 15, 911 11 of 16

was determined [61]. The metabolic signature was then used to assess associations with
CVD risk and showed stronger inverse associations with CVD risk compared to dietary
intake alone in a Spanish and three US cohorts. Mendelian randomization analyses also
showed that the genetically inferred metabolic signature was significantly associated with
a lower risk of CHD and stroke [61]. These novel approaches hold promise for an objective
and complete evaluation of both adherence and metabolic responses to diet, including nuts,
and may allow more effective and individualized approaches to dietary interventions in
the future; however, further research is also needed in this area. Overall, a combination of
efforts, including well-conducted large prospective cohort studies, large RCTs of hard CV
endpoints and incorporation of multi-omics approaches and genetics, will help us better
understand the role of nuts in the primary and secondary prevention of CVD.

8. Summary and Conclusions

The overall findings and conclusions from this review are that nuts are a beneficial
food for CVD risk reduction, with consistent findings for the benefit for total CVD and
CHD in prospective cohort studies and likely benefits for stroke and AF, but additional
research is needed for HF, AF, PAD and stroke subtypes. Considering all evidence from
mechanistic studies, RCTs of intermediate risk factors and CV events, and prospective
cohort studies, at least one serving per day of nuts should be considered for CV risk
reduction, although further research on the optimal dose is needed. The type of nut may
not be important, though more research is needed to confirm this finding. However, a
general nut recommendation will provide more variety of options and be important for
any availability and affordability concerns for consumers.
In conclusion, future research is urgently needed as outlined above, particularly
for stroke subtypes, PAD and HF, and include individual cohort pooled analyses, large
RCTs of nut-containing dietary patterns and using -omics methodologies to better capture
adherence and metabolic responses to diet, including the consumption of nuts.

Author Contributions: Writing—original draft preparation, A.J.G. and D.A.; writing—review and
editing, all authors. All authors have read and agreed to the published version of the manuscript.
Funding: AJG is supported by a Canadian Institutes of Health Research (CIHR) Postdoctoral Fellow-
ship. DA has received funding from the South-Eastern Norway Regional Health Authority (grant
no: 2017076). JSS is partially supported by ICREA under the ICREA Academia programme. The
NUTS 2022 conference was organized by the Rovira i Virgili University, with all the expenses of the
organization covered by Barcelo Congresos, including the fees related to publishing the Proceedings
in Nutrients. Barcelo Congresos SA has received funds from the International Nut and Dried Fruit
Council (INC). Neither the researchers attending the NUTS 2022 Conference, nor the Rovira i Virgili
University have received funds from the INC. Researchers’ travel expenses and accommodation have
been covered by Barcelo Congresos. Researchers did not receive any additional financial support
related to their participation in the NUTS 2022 conference. Sponsors did not have any role in organiz-
ing the conference, selecting, or inviting the speakers, nor in the writing or reviewing the proceedings
of the conference.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments: SThis review highlights the main discussion points from the scientific session
“Nuts and Cardiovascular Disease Outcomes” by speakers John Sievenpiper and Dagfinn Aune at
the NUTS2022 Conference held in Reus, Spain on 20–21 October 2022.
Conflicts of Interest: AJG has received an honorarium from the Soy Nutrition Institute and the
Academy of Nutrition and Dietetics. JS-S reports serving on the boards of the INC and receiving
grant support from these entities through his institution. He has also received research funding
(nuts for free to the PREDIMED participants) from the CWC; La Morella Nuts, Spain; and Borges SA,
Spain. He has also received research funding (nuts for free to the PREDIMED-Plus participants) from
Nutrients 2023, 15, 911 12 of 16

the Almond Board of California, USA and Pistachio Growers of California, USA. He is a non-paid
member of the Instituto Danone International and was a member of the executive committee of the
Instituto Danone Spain. DJAJ has received research grants from Saskatchewan and Alberta Pulse
Growers Associations, the Agricultural Bioproducts Innovation Program through the Pulse Research
Network, the Advanced Foods and Material Network, Loblaw Companies Ltd., Unilever Canada
and Netherlands, Barilla, the Almond Board of California, Agriculture and Agri-food Canada, Pulse
Canada, Kellogg’s Company, Canada, Quaker Oats, Canada, Procter and Gamble Technical Centre
Ltd., Bayer Consumer Care, Springfield, NJ, Pepsi/Quaker, International Nut and Dried Fruit Council
(INC), Soy Foods Association of North America, the Coca-Cola Company (investigator initiated,
unrestricted grant), Solae, Haine Celestial, the Sanitarium Company, Orafti, the International Tree
Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Soy Nutrition
Institute (SNI), the Canola and Flax Councils of Canada, the Calorie Control Council, the Canadian
Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI)and the Ontario
Research Fund (ORF). He has received in-kind supplies for trials as a research support from the
Almond board of California, Walnut Council of California, the Peanut Institute, Barilla, Unilever,
Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg
Canada, WhiteWave Foods. He has been on the speaker’s panel, served on the scientific advisory
board and/or received travel support and/or honoraria from Nutritional Fundamentals for Health
(NFH)-Nutramedica, Saint Barnabas Medical Center, The University of Chicago, 2020 China Glycemic
Index (GI) International Conference, Atlantic Pain Conference, Academy of Life Long Learning, the
Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd., the
Griffin Hospital (for the development of the NuVal scoring system), the Coca-Cola Company, Epicure,
Danone, Diet Quality Photo Navigation (DQPN), Better Therapeutics (FareWell), Verywell, True
Health Initiative (THI), Heali AI Corp, Institute of Food Technologists (IFT), Soy Nutrition Institute
(SNI), Herbalife Nutrition Institute (HNI), Saskatchewan and Alberta Pulse Growers Associations,
Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Educa-
tion Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Barilla,
Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats,
Procter and Gamble, Abbott Laboratories, Dean Foods, the California Strawberry Commission, Haine
Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and
Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the
Canola and Flax Councils of Canada, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food
Policy Institute, Pulse Canada, the Soy Foods Association of North America, the Nutrition Foundation
of Italy (NFI), Nutra-Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation
Group (St. Michael’s Hospital), the Canadian College of Naturopathic Medicine, The Hospital for
Sick Children, the Canadian Nutrition Society (CNS), the American Society of Nutrition (ASN),
Arizona State University, Paolo Sorbini Foundation and the Institute of Nutrition, Metabolism and
Diabetes. He received an honorarium from the United States Department of Agriculture to present
the 2013 W.O. Atwater Memorial Lecture. He received the 2013 Award for Excellence in Research
from the International Nut and Dried Fruit Council. He received funding and travel support from
the Canadian Society of Endocrinology and Metabolism to produce mini cases for the Canadian
Diabetes Association (CDA). He is a member of the International Carbohydrate Quality Consortium
(ICQC). His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for
the Food Industry, his 2 daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian
book that promotes the use of the foods described here, The Portfolio Diet for Cardiovascular Risk
Reduction (Academic Press/Elsevier 2020 ISBN:978-0-12-810510-8)and his sister, Caroline Brydson,
received funding through a grant from the St. Michael’s Hospital Foundation to develop a cookbook
for one of his studies. He is also a vegan. CWCK has received grants or research support from the
Advanced Food Materials Network, Agriculture and Agri-Foods Canada (AAFC), Almond Board
of California, Barilla, Canadian Institutes of Health Research (CIHR), Canola Council of Canada,
International Nut and Dried Fruit Council, International Tree Nut Council Research and Education
Foundation, Loblaw Brands Ltd., the Peanut Institute, Pulse Canada and Unilever. He has received
in-kind research support from the Almond Board of California, Barilla, California Walnut Commis-
sion, Kellogg Canada, Loblaw Companies, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo,
Unico, Unilever, WhiteWave Foods/Danone. He has received travel support and/or honoraria from
the Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International
Nut and Dried Fruit Council, International Pasta Organization, Lantmannen, Loblaw Brands Ltd.,
Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, the Peanut Institute,
Nutrients 2023, 15, 911 13 of 16

Pulse Canada, Sun-Maid, Tate and Lyle, Unilever and White Wave Foods/Danone. He has served on
the scientific advisory board for the International Tree Nut Council, International Pasta Organization,
McCormick Science Institute and Oldways Preservation Trust. He is a founding member of the Inter-
national Carbohydrate Quality Consortium (ICQC), Chair of the Diabetes and Nutrition Study Group
(DNSG) of the European Association for the Study of Diabetes (EASD), is on the Clinical Practice
Guidelines Expert Committee for Nutrition Therapy of the EASD and is a Director of Glycemia
Consulting and the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. JLS has received
research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of
Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research
(CIHR), Diabetes Canada, PSI Foundation, Banting and Best Diabetes Centre (BBDC), American
Society for Nutrition (ASN), INC International Nut and Dried Fruit Council Foundation, National
Dried Fruit Trade Association, The Tate and Lyle Nutritional Research Fund at the University of
Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University
of Toronto (a fund established by the Alberta Pulse Growers), and the Nutrition Trialists Fund at
the University of Toronto (a fund established by an inaugural donation from the Calorie Control
Council). He has received in-kind food donations to support a randomized controlled trial from
the Almond Board of California, California Walnut Commission, American Peanut Council, Barilla,
Unilever, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, and WhiteWave Foods. He
has received travel support, speaker fees and/or honoraria from Diabetes Canada, Mott’s LLP, Dairy
Farmers of Canada, FoodMinds LLC, International Sweeteners Association, Nestlé, Pulse Canada,
Canadian Society for Endocrinology and Metabolism (CSEM), GI Foundation, Abbott, Biofortis,
ASN, Northern Ontario School of Medicine, INC Nutrition Research and Education Foundation,
European Food Safety Authority (EFSA), Comité Européen des Fabricants de Sucre (CEFS), and
Physicians Committee for Responsible Medicine. He has or has had ad hoc consulting arrangements
with Perkins Coie LLP, Tate and Lyle, and Wirtschaftliche Vereinigung Zucker e.V. He is a member
of the European Fruit Juice Association Scientific Expert Panel and Soy Nutrition Institute (SNI)
Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of
Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular
Society (CCS), and Obesity Canada. He serves or has served as an unpaid scientific advisor for the
Food, Nutrition, and Safety Program (FNSP) and the Technical Committee on Carbohydrates of
the International Life Science Institute (ILSI) North America. He is a member of the International
Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition
Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical
Trials foundation. His wife is an employee of AB InBev. All other authors have no conflicts of interest
to report.
Disclaimer: Where authors are identified as personnel of the International Agency for Research on
Cancer/World Health Organization, the authors alone are responsible for the views expressed in
this article and they do not necessarily represent the decisions, policy or views of the International
Agency for Research on Cancer/World Health Organization.

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