Ultra-processed Foods, Weight Gain, and Co-morbidity Risk

Abstract

Purpose of Review
The purpose of this review is to provide an update on the available data regarding the associations of Ultra-processed food (UPF) consumption with food intake and possible underlying mechanisms relating UPF consumption to weight gain and co-morbidities.

Recent Findings
In primarily observational studies, UPF consumption is consistently associated with an increased risk for weight gain among adults and children and increased risk for adiposity-related co-morbidities in adults. In a single mechanistic study, consumption of UPFs led to increased energy intake and weight gain relative to whole foods.

Summary
UPFs tend to be more energy-dense than nutrient-dense, and UPF consumption is associated with increased adiposity and co-morbidity risk. These data suggest that recommendations to limit UPF consumption may be beneficial to health — though further mechanistic studies are needed.

Full text

https://doi.org/10.1007/s13679-021-00460-y
ETIOLOGY OFOBESITY (M ROSENBAUM, SECTION EDITOR)
Ultra‑processed Foods, Weight Gain, andCo‑morbidity Risk
AnthonyCrimarco1 · MatthewJ.Landry1 · ChristopherD.Gardner1
Accepted: 3 September 2021
© The Author(s) 2021
Abstract
Purpose ofReview The purpose of this review is to provide an update on the available data regarding the associations of
Ultra-processed food (UPF) consumption with food intake and possible underlying mechanisms relating UPF consumption
to weight gain and co-morbidities.
Recent Findings In primarily observational studies, UPF consumption is consistently associated with an increased risk for
weight gain among adults and children and increased risk for adiposity-related co-morbidities in adults. In a single mecha-
nistic study, consumption of UPFs led to increased energy intake and weight gain relative to whole foods.
Summary UPFs tend to be more energy-dense than nutrient-dense, and UPF consumption is associated with increased
adiposity and co-morbidity risk. These data suggest that recommendations to limit UPF consumption may be beneficial to
health — though further mechanistic studies are needed.
Keywords Ultra-processed foods· Weight gain· NOVA· Weight management· Chronic disease
Introduction
Food processing includes any variety of operations to mod-
ify and alter raw foods from their natural state to make them
more suitable for consumption, cooking, or storage [1]. This
includes heating, freezing, washing, fermentation, grinding,
packaging, and other operations. Since prehistoric times, our
ancestors mastered the use of fire for the purpose of heat-
ing and cooking foodstuffs to preserve their organoleptic
and nutritional properties [2]. During more recent historical
events like the Industrial Revolution or the second World
War, the focus on food processing began to shift from home
cooking to more industrialized processes to emphasize the
preservation, safety, and nutritional quality of foods [2].
Food processing has been integral to providing safe, edi-
ble, and nutritious foods to the population for centuries. It is
useful for increasing the shelf life of foods, optimizing nutri-
ent availability and food quality, as well as to reduce losses
and waste [3, 4]. Since the nineteenth century, a number of
technologies in food processing were introduced, including
canning and pasteurization. This was followed by many types
of physical, thermal, and chemical processes, such as cen-
trifugation and sterilization of dairy products, or bleaching
vegetable oils [5]. The topic of food processing is complex,
and the different types of processes bring both benefits and
risks. For example, heat processing increases the shelf life
and decreases the pathogenic potential of raw milk, but pro-
motes the loss of nutritional value or the production of muta-
genic or carcinogenic molecules in others [2, 6]. Thus, dif-
ferent types of food processing bring both benefits and risks.
Advancements in food processing and changes to our
agro-industrial systems have led to the development of
numerous food products that contribute to the so-called
“Westernized diet.” These Westernized food products are
usually highly processed and energy-dense, and they con-
tain high amounts of added sugar, saturated fat, and salt,
but low amounts of fiber [7]. The concerns about the health
effects of industrial processing on diet quality and chronic
disease risk has resulted in food classification systems to
distinguish between different categories of processed foods
[8]. The most popular of those food classification systems is
the NOVA (not an acronym) system, which introduced the
term “ultra-processed foods” to describe the highest level of
food processing [8, 9]. Ultra-processed foods (UPFs) tend to
be highly palatable, convenient, shelf stable, and affordable,
This article is part of the Topical Collection on Etiology of Obesity
Anthony Crimarco and Matthew J. Landry are co-first-authors.
* Christopher D. Gardner
cgardner@stanford.edu
1 Stanford Prevention Research Center, School ofMedicine,
Stanford University, PaloAlto, CA, USA
/ Published online: 22 October 2021
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and are often marketed and advertised in appealing ways
[7, 10–13]. Since the term UPFs was coined, there were 72
articles published on the subject between 2009 and 2016
and another 565 articles from 2017 and 2021 (based on a
PubMed search of title words). The increased focus on the
health effects of UPFs has resulted in a number of studies
assessing the association between UPFs with weight gain
and/or co-morbidity risk.
There have also been recent studies that documented an
increased consumption of UPFs during the shelter-in-place
lockdowns that were implemented to prevent the spread of
the novel coronavirus (COVID-19) [14–16]. This was largely
attributable to an increase in fast foods and the consumption
of low-quality meals or snacks, such as sweets, chocolates,
sugar-added beverages, and processed meat. A recent review
indicated that only one study showed any improvement in
food quality intake (i.e., increased fruit and vegetable con-
sumption) among participants during the shelter-in-place
period [16].
Based on the growing interest and potential concerns
about the adverse health effects associated with consum-
ing UPFs, the purpose of this review is to examine recent
literature (i.e., within the last 5years) on UPF consumption
and its association with weight gain and/or co-morbidity
risk. We also discuss the potential mechanisms of how UPFs
increase the risk of gaining weight and developing chronic
diseases, as well as the limitations of the NOVA classifica-
tion system.
Defining Ultra‑Processed Foods
In food science and technology, the level of food process-
ing is based on the intensity and amount of operations uti-
lized to enhance shelf life, food safety, food quality, and
availability of edible parts of raw materials [17, 18]. There
are numerous definitions of food processing from organi-
zations like the International Food Information Council
(IFIC) [19] or the International Agency for Research on
Cancer—European Prospective Investigation into Cancer
(IARC-EPIC) [20]. In general, these classification systems
were designed by researchers to study the relationships
between industrial products and nutritional intake and/or
chronic disease risk [3]. The United States Department of
Agriculture (USDA) defines a processed food as “any raw
agricultural commodity that has been subject to washing,
cleaning, milling, cutting, chopping, heating, pasteurizing,
blanching, cooking, canning, freezing, drying, dehydrating,
mixing, packaging, or other procedures that alter the food
from its natural state” [21].
The NOVA system is one of the most popular food classi-
fication systems for categorizing foods and beverages in the
public health literature. One of the first systematic reviews
on food processing that was published in this journal con-
cluded that NOVA was the most specific, coherent, clear,
comprehensive and workable definition [22]. The NOVA
criteria involve classifying food products into four groups
based on the amount of processed ingredients: (1) unpro-
cessed or minimally processed foods, (2) processed culinary
ingredients, (3) processed foods, and (4) ultra-processed
foods (UPFs) [9]. See Fig.1 for the complete definitions
of all food categories. The UPF category is described as
“formulations mostly of cheap industrial sources of dietary
energy and nutrients plus additives, using a series of pro-
cesses” [9]. Some examples include reconstituted meats, fro-
zen pizzas, and confectionary foods, to name a few. The con-
cept of UPFs was originally coined and developed by a team
from the University of São Paulo in a 2009 commentary [8].
The main argument of the commentary was that the extent
to which foods are processed, rather than specific nutrients
Fig. 1 Spectrum of processing
of foods based on the NOVA
classification. The figure
provides examples of foods and
types of processing methods
within each NOVA classifica-
tion group. Definitions are
adapted from Monteiro etal.
(2018) [8]
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or food items, is the most important factor for determining
the relationship between nutrition and chronic diseases. This
work has now been formally adopted as a part of the national
dietary guidelines in Brazil [23] and has been acknowledged
in several leading reports, such as the Food and Agriculture
Organization (FAO) of the United Nations [24] or the Pan
American Health Organization (PAHO) of the World Health
Organization (WHO) [25].
Because the food manufacturing industry is not required
to state the processes used in its products on food labels and
the information required on food labels is not standardized
across countries, it can be difficult for consumers to identify
UPFs easily [7, 26]. For example, products like plain steel-
cut oats, plain corn flakes, and shredded wheat are classified
as minimally processed foods, but the same foods are con-
sidered processed when they also contain sugar, and ultra-
processed if they also contain flavors or colors [7]. A general
rule of thumb is to identify food substances or additives
whose primary function is to make the final product more
palatable or more appealing (i.e., “cosmetic additives”). This
includes items like hydrolyzed proteins, high-fructose corn
syrup, and interesterified oils, to name a few.
Because classification systems like NOVA largely rely on
categorizing a processed food category based on the content
of added sugars, saturated fat, and sodium, it is possible
to misclassify some nutrient-rich foods as ultra-processed
[27]. For example, in Drewnowski etal.’s analysis of vari-
ous foods using both the Nutrient Rich Food and NOVA
criteria, fortified ready-to-eat cereals, as well as beans and
nuts (in the form listed in the FFQ), were classified as ultra-
processed from the NOVA definitions [27]. Additionally,
when conducting diet assessments for research purposes
(e.g., food frequency questionnaires, 24-h recalls), it is not
typical to specify the level of processing involved in reported
foods, and thus misclassification may also result here [28].
For example, using the NOVA classification system, com-
mercially baked bread has been classified as ultra-processed,
whereas the same bread was considered processed when
homemade [29]. Foods that are processed by innovative,
non-traditional techniques, such as electric or magnetic
fields, may be deemed as minimally processed, despite the
use of non-traditional, complex processes [30–32]. Some of
the guidelines on UPFs may imply that food processing as
a concept has a negative connotation. Sadler etal. [3] note
that this could potentially “encourage consumers to seek out
unprocessed foods (e.g. raw milk) or process foods at home,
without sufficient food safety controls, and such consumer
rejection could also hamper sustainable innovations” [3].
More terms and definitions have recently been added
to address some of the classification problems within the
original NOVA criteria. The Siga classification of processed
foods extends the NOVA classification system by combin-
ing the original 4 categories of food processing with 5 more
specific subgroups [33]. This classification system accounts
for added sugar, fat, and salt contents; “at risk” additives;
“matrix” effects; ultra-processed ingredients; and the num-
ber of markers of ultra-processing (MUPs). Most of the lit-
erature to date still utilizes the original NOVA criteria; there
have not yet been many studies published utilizing the Siga
criteria [33].
Ultra‑Processed Food Consumption Levels
UPFs are expanding in food systems across the globe. A
number of articles have been published on the contribution
of UPF consumption to daily total energy intake in differ-
ent countries. Table1 shows selected recent articles on the
subject. In general, the majority of calories consumed in
high-income countries are from ultra-processed foods and
beverages. For example, in Canada, the UK, and the USA,
UPF products were estimated to contribute 45.0%, 50.4%,
and 57.9% of total energy intake, respectively [34–36]. For
other countries like Brazil, UPFs contributed 22.7% of total
energy intake. For other countries like Brazil, UPFs con-
tributed 22.7% of total energy intake. But it should be noted
that older studies (not shown in Table1) have indicated that
UPFs contributed anywhere from 21.5 to 51.2% of total
energy intake, depending on the sample [37, 38]. Most sam-
ples included children and adults, while two focused only on
children [39, 40]. Monteiroet al. (2018) assessed household
availability of NOVA food groups in 19 European countries
and analyzed the association between availability of UPF
and prevalence of obesity [35]. A strength of the study was
the use of standardized data and the use of population-based,
actual (non-modeled) estimates of the prevalence of obesity.
After adjusting for multiple confounding factors, each per-
centage point increase in the household availability of UPF
resulted in an increase of 0.25 percentage points in obesity
prevalence.
UPF consumption levels also appear to coincide with obe-
sity rates in some of the countries (Fig.2) [41]. For example,
the USA and UK had the highest rates of UPF consumption
and obesity. However, for other countries there are inconsist-
encies. Portugal had a relatively low UPF consumption rate
(10.2%), but still has an obesity rate of 20.8%, which is com-
parable to other European countries [41]. Although UPFs are
a significant source of energy intake, they are just one group
of foods among all the possible sources of energy intake in
the diet, and other factors also contribute to obesity rates.
Sociodemographic Characteristics
Prior studies have consistently shown that UPF consump-
tion differs among strata of sociodemographic characteristics
[34, 42–49]. Differences in consumption vary by gender,
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age, ethnicity, education, children within the household,
nativity, and time for meal preparation depending on the
sample (Table2). The literature has also suggested that an
individual’s or a household’s socioeconomic status may
be an important factor associated with the consumption
of greater ultra-processed foods; however, these associa-
tions vary by a country’s income level. Globally, differ-
ences between countries can be attributable to differences
Table 1 Select recent articles on ultra-processed food consumption levels from various countries
Articles Country Sample Key findings
Machado etal. [102] Australia 12,153 individuals from the National Nutrition
and Physical Activity Survey (2011–2012)
ages 2years and above
Consumption of ultra-processed foods consisted
of 42.0% of total energy intake
Harris etal. [103] Barbados Nationally representative population-based
sample of 364 adult Barbadians
Consumption of ultra-processed foods consisted
of 40.5% of total energy intake
Simões etal. [45] Brazil 14,378 adults ages between 35 and 74years
sampled at multicenter cohort from 6 public
universities
Consumption of ultra-processed foods consisted
of 22.7% of total energy intake
Nardocci etal. [34] Canada 9363 adults ages 18years or more from the
2004 Canadian Community Health Survey
Consumption of ultra-processed foods consisted
of 45.0% of total energy intake
Cediel etal. [49] Chile 4920 individuals ages 2years and above Consumption of ultra-processed foods consisted
of 28.6% of total energy intake
Cornwell etal. [39] Colombia 223 children ages 5–12years Consumption of ultra-processed foods consisted
of 34.4% of total energy intake
Monteiro etal. [35] Multiple European
countries
Households from the Living Costs and Food
Survey (LCFS) or the Data Food Networking
(DAFNE)
Consumption of ultra-processed foods consisted
of 26.4% of total energy intake. The range of
calories consumed from ultra-processed foods
were 10.2% of total energy intake in Portugal
to 50.4% of total energy intake from the UK
Setyowati etal. [104] Indonesia Children and adults (n = 145,360) grouped into
the following age groups: 0–4, 5–12, 13–18,
19–55, and > 55years
Consumption of ultra-processed foods consisted
of 15.7% of total energy intake
Marrón-Ponce etal.
[44]
Mexico 10,087 individuals from the 2012 Mexican
National Health and Nutrition Survey
Consumption of ultra-processed foods consisted
of 29.8% of total energy intake
Fangupo etal. [40] New Zealand 669 children ages 1–5years born in Dunedin,
New Zealand
Consumption of ultra-processed foods
consisted of 45.0%, 42.0%, and 51.0% of
energy intake to the diets of children at 12, 24,
and 60months of age, respectively
Steele etal. [36]USA 9317 individuals ages 1year and above Consumption of ultra-processed foods consisted
of 57.9% of total energy intake
Fig. 2 Comparison of select
countries totally energy intake
from UPFs and obesity rates.
Colombia and New Zealand
were not included in the graphs,
since those studies were based
on children only. The obesity
rates are based on 2016 data by
the World Health Organization
(WHO) [41]. Therefore, the
rates are not necessarily equiva-
lent to the dietary data from the
selected articles 0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
Portugal
Italy
Greece
France
Indonesia
Croaa
Cyprus
Slovakia
Spain
Hungary
Brazil
Lithuania
Malta
Chile
Mexico
Latvia
Austria
Norway
Barbados
Finland
Australia
Belgium
Canada
Ireland
Germany
United Kingdom
United States
Percent
Country
Total energy intake from ultra-processed foods and obesity rates by country
Percentage of energy intake from ultra-processed food consumpon Obesity rate
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in food price, affordability, and accessibility [50]. Within the
USA, higher consumption of UPF is associated with lower
income and education, and studies have documented that
UPF account for a larger proportion of grocery spending
within households participating in Supplemental Nutrition
Assistance Program compared to households not participat-
ing [51–53]. Similar results have been found within other
high-income countries [42, 47, 54]. The opposite is observed
within middle- and low-income countries as those of higher
socioeconomic status, those living within urban centers, and
those with greater educational attainment are associated with
greater UPF intakes [43, 44, 49]. In middle- and low-income
countries, there is likely to be more subsistence farming,
where families eat more of the food they grow or raise; these
foods would be more likely to be whole foods. Those with
higher incomes within these countries deviate from tradi-
tional dietary patterns as they can afford the purchase of
more Westernized foods that are more likely to be processed
or ultra-processed.
Associations ofUltra‑Processed Foods
withWeight Gain andDisease Risk inAdults
Although the majority of studies on the health effects of
UPFs are observational in nature, there is growing evidence
that they contribute to weight gain and increase the risk for
some chronic diseases [55]. A meta-analysis of 43 studies
(21 cross-sectional, 19 prospective cohort, 2 case–control,
and 1 conducted both as a cross-sectional and prospective
analysis) indicated that the consumption of UPFs was asso-
ciated with an increased risk of overweight (odds ratio: 1.36;
95% confidence interval [CI], 1.23–1.51; P < 0.001), obesity
(odds ratio: 1.51; 95% CI, 1.34–1.70; P < 0.001), abdominal
Table 2 Select recent studies examining sociodemographic factors associated with greater consumption of ultra-processed foods
Article Country Sociodemographic Factors Associated with Greater Consumption of UPF
Calixto Andrade etal. [105] France • Younger age
• Urban
Djupegot etal. [42]Norway • Men
• Native Norwegian
• Lower educational attainment
•  ≥ 3 children within the home
• Younger age
Nardocci etal. [42] Canada • Men
• Younger age
• Lower educational attainment
• Smokers
• Physically inactive
• Canadian-born individuals
Khandpur etal. [43] Columbia • Younger age
• Higher socioeconomic status
• Area of residence/geographic region
• Urban
Marrón-Ponce etal. [44] Mexico • Younger age
• Urban
• Higher socioeconomic status
• Lower educational attainment
• Geographical region
Machado etal. [48] Australia • Younger
• Australian or English country
• Physically inactive
• Smoker
• Lower educational attainment
• Urban
Cediel etal. [49] Chile • Younger
• Urban
• Geographic region
• Higher income
Baraldi etal. [53]USA • Non-Hispanic Whites and Non-Hispanic Blacks (compared to other
race/ethnicity groups)
• Higher educational attainment
• Younger age
• Lower income level
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obesity (odds ratio: 1.49; 95% CI, 1.34–1.66; P < 0.0001),
all‐cause mortality (hazard ratio: 1.28; 95% CI, 1.11–1.48;
P = 0.001), and metabolic syndrome (odds ratio: 1.81; 95%
CI, 1.12–2.93; P = 0.015) in adults [56]. A recent system-
atic review of 23 studies (10 cross-sectional and 13 pro-
spective cohort) also found an association between UPF
consumption and an increased relative risk for overweight/
obesity (+ 39%), high waist circumference (+ 39%), low
HDL-cholesterol levels (+ 102%), and metabolic syndrome
(+ 79%) [57]. An analysis on a subsample of adult men and
women from the PREDIMED-Plus cohort with obesity and
metabolic syndrome indicated that higher UPF consumption
was associated with greater accumulation of visceral fat,
android-to-gynoid fat ratio, and total body fat [58].
A number of other recent reviews that assessed UPF
consumption on weight gain, or increased health risk, have
reported similar findings (Table3). The majority of these
studies are cross-sectional; therefore, while increased UPF
consumption tends to be evident in people with greater adi-
posity and co-morbidities, the nature of the study design
does not indicate any direction of causality. It is worth noting
that obesity is a multifactorial disease with many related life-
style contributors. Given the majority of research on UPFs
is observational in nature, residual confounding is possible.
Some prospective cohort studies have also reported that
UPFs are positively associated with multiple indicators of
adiposity (i.e., BMI, waist circumference, and body fat per-
cent) [59, 60]. A retrospective cohort study indicated that
diets rich in UPFs were associated with a 79% increased
risk for obesity (HR 1.79; 95% CI 1.06─3.03) and a 30%
increased risk for abdominal obesity (HR 1.30; 95% CI
1.14─1.48 [59]. Additionally, higher consumption of UPFs
increased the risk of a gain in BMI, waist circumference, and
body fat of 5% or more during the follow-up period (median
of 5.6years) [59]. A cohort study with civil servants in Bra-
zil indicated that UPF consumption was associated with an
increased relative risk of 27% (95% CI: 1.07–1.50) weight
gain and 33% increased relative risk (95% CI: 1.12–1.58)
for waist-circumference gain [60]. Fazzino etal. [61] con-
ducted a prospective study among 82 individuals without
obesity and found that an increased consumption of UPFs
in a buffet meal were associated with greater weight gain
over the next 12months. These findings from cohort studies
build on the cross-sectional studies by providing evidence of
direction of causality for UPF consumption and weight gain.
In adults, results that are primarily from observational
studies generally report that consumption of UPFs is associ-
ated with an increased risk of hypertension [62], cardiovas-
cular disease [63], type 2 diabetes [64], metabolic syndrome
[65], higher risk of overall cancer [66], and all-cause mor-
tality [67]. Many of these studies adjusted for BMI in the
main analyses and/or included sensitivity analyses to adjust
for BMI, weight gain, physical activity levels, or a family
history of the specific health condition, suggesting that high
UPF diets increase one’s risk for co-morbidities independent
of body weight. In most of these studies, the participants
with the highest UPF consumption also consumed diets of
lower overall quality. Participants that consumed the most
UPFs had higher intakes of sugar, saturated fats, and salt, but
lower and/or inadequate intake of fiber and micronutrients
compared to those that had consumed fewer UPF products.
Therefore, it is plausible that the consumption of UPFs are
associated with many of today’s leading chronic diseases,
since poor diet quality is associated with all of the men-
tioned health conditions [68, 69]. However, there are also a
number of possible biological mechanisms unique to UPF
consumption, in addition to poor diet quality, that potentially
explain some of their effects on increased weight gain and/or
chronic disease risk, as discussed further below.
Ultra‑Processed Foods andHealth Outcomes
inChildren andAdolescents
While there is extensive evidence from several systematic
reviews and meta-analyses [56, 57, 70–72] linking UPFs to
health outcomes in adults, research is more limited in pedi-
atric populations. In 2017–2018, UPFs contributed greater
than two-thirds of energy intake among US children and
adolescents, a 5.6% increase over the prior 20years [73].
Additionally, research has found that frequent consump-
tion of UPFs was associated with food addition within
overweight children [74]. Together, poor diet quality and
excessive caloric intake can contribute to the development
of overweight and obesity among children.
Within several prospective studies, higher consump-
tion of UPFs during childhood was associated with more
rapid increase in BMI, fat mass index, weight, and waist
circumference in adolescence and early adulthood [75–77].
A 2018 systematic review reported that consumption of
ultra-processed foods during childhood and adolescence was
positively associated with adiposity [80]. Contrarily, several
studies have found no association between consumption of
ultra-processed foods and weight status or adiposity [78, 79].
Research suggests that null findings may be attributable to
factors associated with the etiology of obesity, such as physi-
cal activity, genetics, and family lifestyle, which were not
assessed within the studies [78, 79]. Given these findings,
reducing ultra-processed food consumption among children
may reduce the prevalence of overweight and obesity among
children; however, a clinical trial within a child population
is needed.
In addition to weight and adiposity outcomes, several
studies have found a positive association between greater
UPF consumption and blood lipids. A Brazilian cohort
found that children with the highest consumption of UPFs
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Table 3 Narrative reviews, systematic reviews, and meta-analyses summarizing recent evidence evaluating the association between ultra-processed food (UPF) intake and health outcomes
Reference Type of review Articles reviewed and study
design
Outcome Key findings
Askari etal. [70] Systematic review and
meta-analysis
13 cross-sectional, 1 prospective
cohort
Excess body weight and obesity UPF consumption was associated with increased risk of
overweight and obesity
Chen etal. [71] Systematic review 8 cross-sectional, 12 prospective
cohort
Any health outcome UPF consumption was associated with increased risk
of all-cause mortality, overall cardiovascular diseases,
coronary heart diseases, cerebrovascular diseases,
hypertension, metabolic syndrome, overweight and
obesity, depression, irritable bowel syndrome, overall
cancer, postmenopausal breast cancer, gestational
obesity, adolescent asthma and wheezing, and frailty.
No association with cardiovascular disease mortality,
prostate and colorectal cancers, gestational diabetes
mellitus, or gestational overweight
Costa etal. [106] Systematic Review 5 interventions, 6 cross-sectional,
and 15 prospective cohorts
Body fat (during childhood and
adolescence)
Consumption of UPF was positively associated with
body fat during childhood and adolescence
de Miranda etal. [107] Narrative review 1 randomized controlled trial,
15 prospective cohort, 12
cross-sectional, 1 prospec-
tive and cross-sectional, and 1
ecological
Metabolic health Consumption of UPF was positively associated with
metabolic syndrome, body weight change and obesity
indicators, blood pressure and hypertension, glucose
profile, insulin resistance and type 2 diabetes, other
metabolic risks and cardiovascular diseases and
mortality
Elizabeth etal. [55] Narrative review 1 randomized controlled trial, 1
case–control, 19 prospective
cohort, 19 cross-sectional, 3
ecological
All health outcomes Consumption of UPF was positively associated with
overweight, obesity and cardio-metabolic risks;
cancer, type 2 diabetes and cardiovascular diseases;
irritable bowel syndrome, depression and frailty
conditions; and all-cause mortality in adults. Among
children and adolescents, UPF consumption was
associated with included cardio-metabolic risks and
asthma
Lane etal. [56] Systematic Review and
Meta-Analysis
21 cross-sectional, 19
prospective, 2 case–control, 1
prospective and cross-sectional
Noncommunicable disease risk,
morbidity, and mortality
Consumption of UPF was associated with increased
risk of overweight, obesity, abdominal obesity, all-
cause mortality, metabolic syndrome, cardiometabolic
diseases, frailty, irritable bowel syndrome, functional
dyspepsia, breast and overall cancer, depression,
and wheezing in adults. Associated with metabolic
syndrome in adolescents and dyslipidemia in children.
No association with asthma in adolescents
Moradi etal. [108] Systematic review and
meta-analysis
9 cross-sectional and 3
prospective cohort
Overweight, obesity, and abdominal
obesity
UPF consumption was associated with increase in the
risk of overweight, obesity, and abdominal obesity
86 Current Obesity Reports (2022) 11:80–92
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at 3–4years of age had greater total cholesterol and triglyc-
erides 4years later, and another Brazilian cohort found ele-
vated LDL cholesterol and triglyceride levels several years
later [80, 81]. Additionally, a study of 210 adolescents in
Brazil reported that high consumption of UPFs was associ-
ated with the prevalence of metabolic syndrome, a cluster
of risk factors that increase the risk for cardiovascular dis-
ease, stroke, and diabetes [82]. However, a Spanish cross-
sectional study found no significant associations between
ultra-processed consumption and HDL or triglyceride levels
[83]. This null finding may be attributable to lipids being
measured in only a subset of the study population, which
could impact lipid levels.
In sum, current research suggests that consumption of
UPFs may lead to excessive calorie intake, weight gain, and
abnormal blood lipids in the short term and progress into
long-term health consequences in adulthood. Given that life-
long dietary patterns develop from childhood and continue
into adulthood [84, 85], efforts should be taken to reduce
children’s exposure and consumption of energy dense and
nutritionally poorer ultra-processed foods.
Potential Mechanisms ofHow
Ultra‑Processed Foods May Increase Weight
Gain andChronic Disease Risk
UPFs induce high glycemic responses, but have low sati-
ety potential [86]. One well-controlled randomized crosso-
ver study indicated that the consumption of UPFs led to
increased energy intake and weight gain relative to whole
foods [87]. In this study, 20 adults ate a diet consisting of
mostly UPFs (~ 80% of calories were from UPFs) and an
alternate diet of mostly whole grains and unprocessed foods
for 2weeks each. The researchers matched the diets for
total energy intake and macronutrient, but the UPF diet
resulted in a higher proportion of added total sugar (∼54%
versus 1%, respectively), insoluble to total fiber (∼16% ver-
sus 77%, respectively), saturated to total fat (∼34% versus
19%). A key finding from the study was that during the UPF
phase of the study, the participants consumed 500kcal/day
more than the alternate diet and the participants gained
0.9 ± 0.3 kg (P = 0.009) during the UPF diet and lost
0.9 ± 0.3kg (P = 0.007) during the unprocessed diet. The
changes in participants’ hunger related hormones (pancre-
atic peptide YY and ghrelin) during the UPF dietary phase
may explain the increased adlibitum energy intake [87].
It has also been suggested that specific features from food
processing, such as the inclusion of additives and alteration
of the food matrix makes the foods have a softer texture for
less chewing and amplifies sensory properties, which delays
satiety signaling, and thereby results in an overconsump-
tion of foods [58]. The higher sugar, fat, and salt content
Table 3 (continued)
Reference Type of review Articles reviewed and study
design
Outcome Key findings
Pagliai etal. [57] Systematic review and
meta-analysis
10
cross-sectional and 13
prospective cohort
Any health indicator Highest UPF consumption associated with increase in
the risk of overweight/obesity, high waist
circumference, low HDL, metabolic syndrome,
all-cause mortality, increased risk of CVD, cerebro-
vascular disease, and depression. No association with
hypertension, hyperglycemia, or hypertriglyceridemia
Santos etal. [109] Systematic Review 9 cross-sectional and 2
prospective cohort
Cardiometabolic risk factors UPF were positively associated with overweight and
obesity, high blood pressure, and metabolic syndrome
Silva etal. [110] Systematic Review 13 cross-sectional, 6 prospective
cohort, and 2 ecological
Noncommunicable chronic diseases UPF was positively associated with excess body weight,
hypertension, dyslipidemia, and metabolic syndrome
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in UPFs makes them more hyperpalatable, which in turn
could result in a healthy, nutrient-dense diet being displaced
with empty calories and a lower-quality diet that results in
weight gain [88].
UPFs also have been reported to contribute to a gut
environment that selects microbes that are associated with
inflammatory disease [89]. The modification of the food
matrix often changes the fiber and fat content of the foods,
which influences the microbiota composition and bacteria–
host interactions [88]. Minimally processed or natural foods
have intact fibrous cell walls that provide a substrate for
fiber-degrading bacteria in the colon and ensure a slow
release of nutrients along the digestive tract [90]. However,
the nutrients in UPFs are largely acellular, which instead
results in an environment that promotes inflammatory gut
microbiota that are associated with various cardiometa-
bolic conditions [89]. Thus, not only are UPF diets usually
low in dietary fiber, but even the way fiber is altered from
food processing impacts its effectiveness on promoting a
beneficial gut microbiome environment. As reported in an
animal model study, the consumption of a high-fiber diet in
pigs based on processed, extruded grains reduced bacterial
diversity compared to a diet based on unprocessed whole
grains [91]. A review of 7 trials indicated that higher UPF
diets were the most commonly associated with a reduced
abundance of microbes that are linked with beneficial health
outcomes and an increased abundance of microbes linked
with adverse health outcomes [92].
Another mechanism by which UPF consumption might
impact biology or metabolism could involve the endocrine-
disrupting chemicals, such as bisphenol A (BPA), often
found in the elaborate packaging materials used for UPF
products [88]. While the complete mechanisms of BPA
remain unknown, there is some evidence that BPA promotes
insulin resistance, oxidative stress, inflammation, and adi-
pogenesis, which in turn increases our risk for major CVD
conditions, including diabetes, overall and abdominal obe-
sity, and hypertension [93].
Gibney (2019 and 2020) argues that any adverse effects
observed from UPFs are due to nutritional factors, rather
than the degree to which foods are processed [29, 94]. Find-
ings from the SWAP-MEAT crossover intervention study
conducted by our lab group indicated that participants had
improvements in several cardiovascular disease risk factors
during 8weeks of consuming alternative plant-based meat
products relative to organic animal meats [95]. This was
due to the simultaneous decrease in saturated fatty acids
and increase in dietary fiber that the plant-based meats pro-
vided. It is not clear if the level of food processing increases
our risk for weight gain and other chronic diseases indepen-
dently from the nutritional composition of the foods them-
selves, since most UPFs by default are dense in energy and
poor in nutritional quality [96].
However, in our SWAP-MEAT study, there was a small
but statistically significant decrease in weight on the plant-
based meat phase vs. animal meat phase. However, our study
was designed to focus on a single substitution of plant-based
meat for animal meat. In a cohort study where the overall
level of UPF consumption was examined, across all food
types, the investigators reported that after controlling for
several components of nutritional quality, UPFs were associ-
ated with a higher risk of cardiovascular disease [63]. Simi-
larly, another study found an increased association between
the consumption of ultra-processed foods and type 2 diabe-
tes among individuals from the NutriNet-Santé cohort after
controlling for diet quality and energy intake [64].
Policies toReduce Ultra‑Processed Food
Consumption
Acknowledging the negative associations between health
and UPF, a number of countries have begun implementing
polices in an effort to reduce UPF consumption, including
taxes on sugar sweetened beverages or snacks, front-of-
package (FOP) warning labels, setting limits on sodium and
trans-fat content in food products, regulations to reduce or
ban the marketing of UPFs, and restricting access and pro-
motion of UPFs in schools [97]. Mexico was one of the first
countries to rigorously evaluate its tax policy on sweetened
beverages and found that purchases of taxed beverages fell
by 6% and the reductions from pre-tax trends were highest
among lower socioeconomic status household [98]. While
taxes on UPF foods are effective for reducing the sales of
such products, a particular gap in fiscal policy is the absence
of subsidies or incentives that promote the purchase of
healthier foods [97]. There is evidence that food taxes on
unhealthy foods combined with subsidies to purchase health-
ier foods improves the population’s diet quality and health
outcomes [99, 100]. However, implementing more forceful
policies remains a challenge, since the food industry and
other stakeholders are resistant to reducing UPF consump-
tion or are making efforts to undermine public actions to
improve health [97, 101].
Conclusions
Defining the extent of food processing that may be asso-
ciated with negative health outcomes remains a challenge
for the field. Various types of processing remain an integral
aspect of providing a safe food system. While the NOVA
classification remains the most frequently used method of
categorizing foods by level of processing, emerging classifi-
cation systems seek to build on the limitations of the NOVA
88 Current Obesity Reports (2022) 11:80–92
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classification to provide a more accurate assessment of pro-
cessing. Epidemiological research suggests that UPF con-
sumption is pervasive and contributes a substantial amount
of daily total energy intake in individuals around the world.
There has been an observed ecological trend that countries
with higher UPF consumption generally have a higher obe-
sity prevalence. However, this trend is not observed in all
countries, and differences may be attributable to sociode-
mographic characteristics or other related factors.
Despite the growing literature documenting the potential
increase in weight gain and adverse health outcomes in chil-
dren, adolescents, and adults from the consumption of UPFs,
there has only been one randomized clinical trial specifically
assessing the effects of UPF consumption [87]. Therefore,
most of what is known about UPFs is based on observa-
tional cohort studies, limiting conclusions to associations
rather than causation. Several plausible mechanisms includ-
ing increased energy intake, changes to the gut microbiome,
alterations in the gut–brain satiety signaling, and hormonal
effects have been proposed as plausible explanations of the
observed associations between UPF and both weight gain
and risk for chronic disease development. Further research
to examine the causal effect of consuming UPFs on weight
gain and adverse health outcomes is warranted. Given that
UPFs tend to be more energy-dense than nutrient-dense,
cautionary recommendations to limit UPF consumption
would be unlikely to lead to any additional risk or harm, and
would more plausibly lead to a nutritional benefit. Therefore,
while awaiting further research, recommendations to limit or
restrict UPF consumption would likely lead to more benefit
than harm.
Funding This work was supported by a training grant from the NIH
National Heart, Lung, and Blood Institute (T32 HL007034) and by the
Stanford Diabetes Research Center (NIH P30DK116074).
Availability of Data and Materials Not applicable.
Compliance with Ethical Standards
Conflict of Interest Gardner received a gift funding from Beyond Meat
which was used to conduct a research study.
Human and Animal Rights and Informed Consent. This article does
not contain any studies with human or animal subjects performed by
any of the authors.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, 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 link to the Creative Commons licence, and indicate if changes
were made. The images or other third party material in this article are
included in the article's Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
the article's Creative Commons licence 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 licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.
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