nutrients

Review
What Is the Evidence for “Food Addiction?”
A Systematic Review
Eliza L. Gordon 1, * ID
, Aviva H. Ariel-Donges 1 , Viviana Bauman 1 and Lisa J. Merlo 2
1 Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville,
FL 32603, USA; [email protected] (A.H.A.-D.); [email protected] (V.B.)
2 Center for Addiction Research and Education, Department of Psychiatry, University of Florida,
1149 Newell Drive, Gainesville, FL 32610, USA; [email protected]
* Correspondence: [email protected]; Tel.: +1-352-273-5234




Received: 10 March 2018; Accepted: 6 April 2018; Published: 12 April 2018


Abstract: The diagnostic construct of “food addiction” is a highly controversial subject. The current
systematic review is the first to evaluate empirical studies examining the construct of “food addiction”
in humans and animals. Studies were included if they were quantitative, peer-reviewed, and in the
English language. The 52 identified studies (35 articles) were qualitatively assessed to determine the
extent to which their findings indicated the following addiction characteristics in relation to food:
brain reward dysfunction, preoccupation, risky use, impaired control, tolerance/withdrawal, social
impairment, chronicity, and relapse. Each pre-defined criterion was supported by at least one study.
Brain reward dysfunction and impaired control were supported by the largest number of studies
(n = 21 and n = 12, respectively); whereas risky use was supported by the fewest (n = 1). Overall,
findings support food addiction as a unique construct consistent with criteria for other substance
use disorder diagnoses. The evidence further suggests that certain foods, particularly processed
foods with added sweeteners and fats, demonstrate the greatest addictive potential. Though both
behavioral and substance-related factors are implicated in the addictive process, symptoms appear to
better fit criteria for substance use disorder than behavioral addiction. Future research should explore
social/role impairment, preoccupation, and risky use associated with food addiction and evaluate
potential interventions for prevention and treatment.

Keywords: food addiction; eating behavior; process addiction; systematic review

1. Introduction
The term “addiction” is commonplace in present society, despite the lack of consensus on an
established clinical definition (see Table 1 for definitions set forth by various health-related professional
organizations). In clinical practice, there is no official diagnosis of “addiction.” Instead, the Diagnostic
and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) states that the term may be used to
describe severe substance use disorders [1].
Criteria for substance use disorder diagnoses include 11 biopsychosocial symptoms grouped into
four categories (see Table 2) [1]. Diagnostic criteria focus on the consequences (e.g., symptoms, distress,
and impairment in daily functioning) of addictive disorders, however, research has provided insight
into the actual process (e.g., the neurobiological correlates) of addiction. Some important findings
focus on neurological factors related to reward and motivation, including DeltaFosB (∆FosB; a gene
transcription factor), dopamine, and opioid expression [2–4].
Behavioral and biological indicators of addiction have also been observed in certain excessive
behaviors [1], and research highlighting these similarities has sparked interest in addictive behavior
more generally [5]. The proposed “behavioral addictions” reflect dependence on a behavior or feeling

Nutrients 2018, 10, 477; doi:10.3390/nu10040477 www.mdpi.com/journal/nutrients

Nutrients 2018, 10, 477 2 of 30

brought about by an action, as opposed to a substance [6]. Several studies have confirmed similarities
between behavioral and substance addictions regarding ∆FosB, dopamine, and opioid expression;
impaired control over the behavior; neglect of relationships and role obligations; and continued
problematic behavior in the face of negative health outcomes [5,7]. As a result, the DSM-5 recently
introduced a new diagnostic category, Non-Substance-Related Disorders, within the newly-named
Substance-Related and Addictive Disorders section of the manual. This category currently includes
only gambling disorder, however, several other behaviors were considered, including compulsive
overeating [5,8], problematic sexual behavior [9], and excessive Internet gaming [5,9]. Although
overeating was ultimately excluded from this category due to insufficient empirical evidence,
discussion regarding the addictive potential of food has continued. Indeed, organizations such as the
American Society of Addiction Medicine (ASAM) have chosen to include “food addiction” in their
list of possible addictive disorders [10], and a number of studies have observed clear biological and
behavioral similarities between drug use and overeating (i.e., altered dopamine expression, cravings,
relapse to highly palatable food) [11–13]. In a review of food addiction studies in humans, Meule
and Gearhardt [14] reported that four out of the 11 DSM-5 substance use disorder symptoms were
empirically supported by studies of highly palatable food, and that the remaining seven symptoms
were “plausible” based on the literature available at that time. Several additional studies on food
addiction have been published since that review.

Table 1. Definitions of addiction.

Source Definition
English Oxford Dictionary [15] “Physically and mentally dependent on a particular substance.”
“A chronic disorder with biological, psychological, social and
environmental factors influencing its development and maintenance.
Genes affect the degree of reward that individuals experience when
initially using a substance (e.g., drugs) or engaging in certain behaviors
(e.g., gambling), as well as the way the body processes alcohol or other
American Psychological
drugs. Heightened desire to re-experience use of the substance or
Association [16]
behavior, potentially influenced by psychological (e.g., stress, history of
trauma), social (e.g., family or friends’ use of a substance),
and environmental factors (e.g., accessibility of a substance, low cost)
can lead to regular use/exposure, with chronic use/exposure leading to
brain changes.”
“A primary, chronic disease of brain reward, motivation, memory and
related circuitry. Dysfunction in these circuits leads to characteristic
biological, psychological, social and spiritual manifestations. This is
reflected in an individual pathologically pursuing reward and/or relief
by substance use and other behaviors. Addiction is characterized by
American Society of Addiction inability to consistently abstain, impairment in behavioral control,
Medicine [10] craving, diminished recognition of significant problems with one’s
behaviors and interpersonal relationships, and a dysfunctional
emotional response. Like other chronic diseases, addiction often
involves cycles of relapse and remission. Without treatment or
engagement in recovery activities, addiction is progressive and can
result in disability or premature death.”
“A complex condition, a brain disease that is manifested by compulsive
substance use despite harmful consequence. People with addiction
(severe substance use disorder) have an intense focus on using a certain
American Psychiatric Association
substance(s), such as alcohol or drugs, to the point that it takes over their
[17]
life. They keep using alcohol or a drug even when they know it will
causes problems. Yet a number of effective treatments are available and
people can recover from addiction and lead normal, productive lives.”
Nutrients 2018, 10, 477 3 of 30

Table 2. Substance Use Disorder criteria, adapted from the Diagnostic and Statistical Manual of Mental
Disorders, 5th Edition (DSM-5) [1].

Impaired Control
1. Consuming a substance in greater amounts or over longer periods of time than intended.
2. Having a persistent desire or unsuccessfully attempting to decrease or limit substance use.
3. Spending a significant amount of time acquiring, using, or recovering from a substance.
4. Craving the substance or having a strong urge to use it.

Social Impairment
5. Being unable to fulfill obligations at work, school, or home due to use of a substance.
6. Continually using a substance despite its effects causing or exacerbating persistent or recurrent social or
interpersonal problems.
7. Giving up or reducing social, occupational, or recreational activities due to substance use.

Risky Use
8. Continually using a substance in situations in which it is physically dangerous (e.g., driving under the influence of
a substance).
9. Continually using a substance despite physical or psychological problems that are caused or made worse by the
substance use.

Pharmacological Criteria
10. Needing a substantially higher dose of the substance to achieve the desired effect; or experiencing a substantially
reduced effect of the substance when the usual dose is consumed (i.e., tolerance).
11. Experiencing negative physical and psychological symptoms when the substance is not consumed at the typical
dose or frequency (i.e., withdrawal).

Note. To meet DSM-5 criteria for a substance use disorder, clinical distress or impairment must be evidenced by two
or more of the above symptoms within a 12-month period. Severity is classified as mild (2–3 symptoms), moderate
(4–5 symptoms), or severe (≥6 symptoms).

Nonetheless, there have been inconsistencies regarding the definition of food addiction. A variety
of approaches have been used to measure it, such as self-report questionnaires [18]; patient
self-identification [19]; and the Yale Food Addiction Scale (YFAS), which is currently the best
available measure for evaluating food addiction based upon modified DSM criteria for substance use
disorders [20,21]. Some have erroneously conceptualized food addiction as either obesity or binge
eating [22–25], yet mounting evidence indicates that these constructs are distinct [26,27]. Though some
individuals with obesity may display neurological and behavioral similarities to individuals addicted
to drugs [24], estimates suggest that only approximately 24.9% of overweight/obese individuals
report clinically-significant symptoms of food addiction and 11.1% of healthy-weight individuals also
report these symptoms [28]. Similarly, while food addiction symptoms are associated with binge
eating behavior and account for 6–14.8% of the unique variance in binge eating disorder [28], current
estimates suggest that only approximately 56.8% of individuals with binge eating disorder report
clinically significant food addiction symptoms [29]. Although there is substantial overlap between
food addiction and binge eating symptoms, the two constructs are not synonymous [26,27].
The concept of food addiction remains controversial [25,30,31]. Some researchers question whether
food or eating can be addictive if it is necessary to our survival [25], while others point out the common
biological (e.g., brain reward pathways, ∆FosB expression), behavioral (e.g., relapse, using more
than intended), and psychological (e.g., preoccupation, impaired control) similarities between the
compulsive consumption of highly palatable foods and use of addictive drugs [2,32,33]. Nevertheless,
critics and proponents alike agree that more research is needed to confirm the validity of food
addiction [30,34]. A non-systematic review by Hone-Blanchet and Fecteau [31] comparing animal and
human models of food addiction to characteristics of substance use disorder concluded that there was
significant overlap between the two conditions, but that more research was needed. Extant published
systematic reviews on the concept of food addiction have either conflated obesity with food addiction or
excluded animal studies [22,28,29]. As such, a more recent and inclusive systematic review was needed.
The present systematic review aimed to summarize the peer-reviewed empirical literature examining
Nutrients 2018, 10, 477 4 of 30

the evidence for food addiction in both animal and human studies. The chosen method involved
assessing its association with key characteristics of addiction in relation to food: (a) neurobiological
changes, (b) preoccupation with the substance, (c) impaired control, (d) social impairments, (e) risky
use, (f) tolerance/withdrawal, (g) chronicity of the condition, and (h) relapse [1,10,17].

2. Materials and Methods

Data collection, review, reporting, and discussion were conducted according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [35,36]. The literature
search was carried out in PubMed and PsychINFO databases using varying combinations of the
following keywords: food addiction, addiction, process addiction, binge eating, hedonic eating,
compulsive overeating, compulsive eating, eating behavior, food, eat, feeding behavior/psychology,
food preferences, food habits, hyperphagia, eating disorders, obesity, overeat*. Meshterms were used
in the PubMed search. Filters were used in both databases according to the study’s predetermined
inclusion and exclusion criteria. Given that the “study type” filters on PubMed only identified articles
in print, a second search was done using the same search terms without filters in order to identify
recent articles published online before print. Additional studies were identified through review of the
references listed in the identified articles. Due to the proliferative nature of research on food addiction,
two searches were done: the first was completed on 29 June 2016, and the second was completed on 8
January 2018. Protocols were followed for both searches exactly as described above, with the exception
that the second search included only articles published since 30 June 2016.
Articles were included if their stated purpose was to test the validity of the food addiction
construct, and if they fulfilled the following modified PICOS (Participants, Interventions, Comparisons,
Outcomes, and Study Design) criteria [35,36]. Acceptable participants included humans or animals
of any age with no specific limitations on disease or diagnosis. Only quantitative, empirical,
peer-reviewed studies published in the English language were included. The American Psychological
Association’s defines “quantitative” studies as those which “provide numerical representation of
observations for the purpose of describing and explaining the phenomenon studied followed by
the application of . . . statistical methods” [37], (“Quantitative Study”). Therefore, studies using
self-report measures that produced a numerical outcome (e.g., Likert scale, yes/no, hunger ratings)
were considered quantitative. Empirical studies were defined as those “based on . . . systematic
observation, or experiment, rather than theory or general philosophical principle” [37] (“Empirical
Study”). Studies examining any type of intervention or comparison (e.g., randomized control trial,
cross-sectional) within these constraints were included in order to accurately reflect the heterogeneous
nature of the existing literature. Studies could be published online or in print, and no limits were
set on date of publication. Finally, because not all overweight/obese individuals or individuals with
eating disorders report addiction-like symptoms related to food [29], studies defining food addiction
solely by weight, BMI, or eating disorder diagnosis were excluded.
Articles selected from PubMed and PsychINFO were reviewed first by title, then abstract,
and finally full article for relevancy and eligibility using the inclusion criteria described above. The first
author independently assessed study eligibility, and articles whose eligibility was unclear were
reviewed by two experienced obesity researchers. The last included study was identified in January
2018. A flowchart for study inclusion is depicted in Figure 1.
The data extraction form used for this study was modeled after forms used in similar systematic
reviews (e.g., [28]) and was modified for the current paper. The following data were extracted:
author/year of publication, study type, sample characteristics, number of subjects in treatment/control
groups, main independent variable(s), and main outcome variable(s). Two of the current authors
assessed risk of bias on the study level using a modified combined scoring system based on those
reported by Jamaty and colleagues [38] and Pursey and colleagues [28]. These scoring systems were
combined in order to include relevant criteria for both animal [38] and human [28] studies. Criteria
included questions about sample selection, study design, and reporting of findings. The authors
Nutrients 2018, 10, 477 5 of 30

gave answers of “Yes”, “No”, or “Unclear” regarding each question for every article included in the
review. An answer of “non-applicable” was given for the question “Was there sufficient description
of the groups?” if a study did not have multiple groups. Quality scores were obtained by summing
the number of “Yes”, “No”, and “Unclear” ratings, then calculating the ratio of “Yes” ratings to the
sum of the “No” and “Unclear” ratings combined. “Not applicable” ratings were not included in
the calculation of the overall quality rating. Disagreements between authors were discussed until a
resolution was agreed upon.

Figure 1. Study selection flow diagram, presented according to the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) statement [35,36].

3. Results
The original database search produced a total of 2421 articles, and the updated search produced
577 articles. Three additional articles describing eight studies were identified from references in other
papers. After removing duplicate references and excluding articles that did not meet the predetermined
inclusion criteria, a total of 35 articles and 52 studies were identified (see Figure 1 and Appendix,
Table A1). Primary reasons for exclusion were study objective (i.e., did not aim to evaluate the validity
of the food addiction construct) and study type (i.e., not a quantitative empirical study). Publishing
dates of included articles ranged from 1999 to 2017. Twenty articles (comprising 22 studies) involved
human participants and 15 articles (comprising 30 studies) involved animal subjects (i.e., rats, mice,
and monkeys). Forty-nine studies focused on the addictive potential of certain foods, five studies
focused on the addictive potential of eating patterns, and two studies focused on the addictive potential
of both certain foods and eating patterns.
As seen in Appendix, Table A2, quality scores for included articles ranged from 0.8 (lowest ratio of
“Yes” ratings to “No” ratings plus “Unclear” ratings) [39] to a perfect score (all “Yes” ratings) [40–43].
Three articles disclosed competing financial interests, including Coca-Cola [44], the International
Sweeteners Association [44], sugar industry relations [44], pharmaceutical companies [13,40] and
involvement in addiction/impulse disorder organizations [13]. Nineteen articles reported no
competing interests and 13 made no statement (see Table A2). As competing financial interests
may bias study conclusions [45], data should be objectively considered with this context in mind.
Nutrients 2018, 10, 477 6 of 30

Of the 35 articles (52 studies) included in this review, 31 articles (47 studies) reported results
supporting the criteria for addiction, two articles (two studies) were mixed, and two articles
(three studies) reported unsupportive findings (see Appendix, Table A3). Results examining support
for each pre-specified addiction characteristic were evaluated separately and are described below.

3.1. Neurobiological Correlates of Addiction

3.1.1. ∆FosB
Sharma, Fernandes, and Fulton [46] showed that rats placed on a 12-week high-fat diet of
primarily hydrogenated coconut oil, maltodextrin, sucrose, and casein had significantly higher ∆FosB,
dopamine D2 receptor, and brain-derived neurotropic factor expression, and lower dopamine D1
receptor expression, in the NAc. These changes were observed before the onset of obesity and were
linked to behaviors suggestive of anhedonia. The authors concluded that the brain changes may have
put the animals at greater risk for addictive-like symptoms such as relapse. No human studies reported
findings related to ∆FosB.

3.1.2. Dopamine
Colantuoni and associates [47] compared brain chemistry changes in rats with intermittent,
excessive glucose intake to rats given a normal diet of chow. They found that exposure to the
highly palatable food in an intermittent eating pattern caused increased activation of dopamine
D1 (p < 0.05) and µ-opioid-1 receptors (p < 0.05), as well as decreased binding of dopamine D2
receptors, in the dorsal striatum (p < 0.05). Adams and colleagues [41] found that rats given a
high-fat/low-sucrose diet (primarily lard) also had decreased D2 receptor expression in the NAc,
but those given a low-fat/high-sucrose diet did not (high fat diet: F = 11.1, p = 0.009; high sucrose
diet F = 3.8, p = 0.074). Reduced D2 receptor expression (p < 0.01) in the striatum (along with other
indicators of down-regulation of reward functioning) was also observed in rats who volitionally
overate highly palatable foods (bacon, sausage, cheesecake, pound cake, frosting, chocolate) in a study
by Johnson and Kenny [48]. Authors of each study concluded that their results were consistent with
findings in substance use disorder literature.
In humans, Davis and associates [49] found that individuals who met the YFAS cutoff suggesting
clinically significant food addiction symptoms had higher multi-locus genetic profile (MLGP) scores
associated with increased dopamine signaling (p = 0.023), and that the relationship between the
MLGP scores and food addiction was mediated by reward-driven eating (95% CI: 0.00–1.12). Davis,
Levitan, Kaplan, Kennedy, and Carter [50] showed that an appetite suppressant that blocked dopamine
functioning was not effective in adults who screened positive for food addiction on the YFAS compared
with controls, suggesting altered dopamine signaling strength in adults with more food addiction
symptoms similar to what is seen among adults with substance use disorders.

3.1.3. Opioid Expression

Opioid receptors were reported to play a role in food reward in rats. Le Merrer and Stephens [51]
found that rats conditioned on sugar sweetened pellets no longer responded to the conditioned reward
when given an opiate antagonist (naltrexone; dose effect: F2,32 = 1.72, non-significant). Newman,
Pascal, Sadeghian, and Baldo [52] showed that rats who were fed sweetened shortening daily ate
significantly more standard chow than rats not fed the palatable food when given a µ-opioid receptor
agonist (DAMGO), suggesting that opioid receptor activity may be associated with overeating and
consumption of highly palatable foods.
As a measure of opioid function, Daubenmier and colleagues [53] analyzed the effects of an
acute opioid blockade drug (naltrexone) on cortisol and nausea in overweight/obese women. They
found that women who engaged in more emotional and restrained eating had greater levels of cortisol
(r = 0.37, p < 0.05), and women who engaged in binge eating had greater levels of nausea in response
Nutrients 2018, 10, 477 7 of 30

to the drug (p = 0.048), suggesting that these individuals “may have a down-regulated opioidergic
system” (p. 99). Cambridge and associates [40] similarly found a significant role for the µ-opioid
receptor system in motivation for food reward; they observed that a µ-opioid receptor antagonist
reduced motivation for, but not liking of, high calorie foods (e.g., chocolate) in people with obesity and
moderate binge eating (p < 0.05). Although the authors did not conclude that their results supported
food as an addictive substance, they did indicate a role for the µ-opioid system in food-related reward.

3.1.4. Other Neurobiological Changes

In a controlled study conducted on primates, Duarte and colleagues [54] found that chocolate
induced a persistent conditioned place preference response usually only seen in response to drug
rewards. Monkeys who received chocolate spent more time in environments where they had previously
received chocolate, whereas controls showed no place preference (F1,13 = 13.59, p = 0.003, η 2 p = 0.53).
Conditioning persisted even after a 15-day follow-up (F1,13 = 4.31, p = 0.06, η 2 p = 0.26), indicating that
chocolate, like drugs, can be used for this type of conditioning. In rats, Le Merrer and Stephens [51]
found that an AMPA receptor antagonist blocked the conditioned response to sweetened pellets
(F2,34 = 3.02, non-significant) in a manner comparable to drugs of abuse. Additionally, Newman and
colleagues [52] suggested that gamma-aminobutyric acid (GABA) receptor activity may be implicated
in food addiction; they found that rats given a daily dose of sweetened shortening ate significantly
more standard chow than rats not fed the palatable food when given muscimol, a GABA agonist that
induces feeding (ps < 0.01).
In a study comparing rats genetically prone to obesity against rats resistant to obesity, Mary
Brown and colleagues [55] reported a significant role for the NAc glutamatergic system in driving
overeating (ps < 0.05), similar to the glutamatergic mechanisms seen in animal models of relapse to drug
addictions. Additionally, Pérez-Ortiz and associates [56] found that rats fed a high-fat diet (primarily
lard, casein, and sucrose), exhibited increases in potential biomarkers of addiction (fumarate hydratase,
ATP synthase subunit alpha, and transketolase) in the NAc (p < 0.05). Adams and colleagues [41],
however, found that a high fat diet (primarily lard) reduced activity of cAMP response element-binding
protein (CREB; F1,10 = 5.4, p = 0.042) and its activated form (pCREB; F1,10 = 5.9, p = 0.036) in the NAc,
contrary to their prediction.
In an electroencephalographic (EEG) study by Imperatori and colleagues [57], participants with
three or more food addiction symptoms on the YFAS exhibited brain changes similar to those in people
with addictive disorders (e.g., increased functional connectivity in fronto-parietal areas; ps < 0.05).
A functional magnetic resonance imaging (FMRI) study by Gearhardt and colleagues [12] found that
YFAS symptom scores were correlated with increased activation in the amygdala, cingulate cortex,
and medial orbitofrontal cortex when participants were anticipating consumption of a chocolate
milkshake. When participants received the milkshake, those with higher YFAS scores had greater
activation in the dorsolateral prefrontal cortex (p = 0.007) and caudate (p = 0.004) and less activation in
the lateral orbitofrontal cortex (p = 0.009) compared to those with lower YFAS scores. Gearhardt and
colleagues concluded that this pattern of increased activation in areas of the brain related to reward
and decreased activation in areas related to inhibition is similar to that seen in substance dependence.
De Ridder and colleagues [58] compared resting-state EEG brain activity between (1) adults with
obesity who endorsed more than three YFAS symptoms (“High YFAS”), (2) adults with obesity who
endorsed less than three YFAS symptoms (“Low YFAS”), (3) adults without obesity or food addiction
(“Lean controls”), and (4) adults without obesity but with alcohol use disorder (“Alcohol addiction”).
Positive correlations were found between YFAS symptoms and the rostral anterior cingulate cortex
(rACC) for theta (r = 0.23, p = 0.041) and beta3 (r = 0.22, p = 0.041) frequency bands. Increased gamma
activity in the rostral anterior cingulate cortex (rACC) extending to the dorsal medial prefrontal
cortex (dmPFC) was associated with increased hunger ratings in the High YFAS group only (r = 0.72,
p = 0.002), and increased alcohol craving in the Alcohol addiction group (r = 0.72, p = 0.002), while
the rACC was negatively correlated with hunger in the Low YFAS group. Conjunction analyses
Nutrients 2018, 10, 477 8 of 30

further revealed similarities between the High YFAS group and the Alcohol addiction group in the
ACC/dmPFC and precuneus (Z = 2.24, p = 0.013), sgACC, orbitofrontal cortex (OFC), and temporal
lobe (fusiform/parahippocampal area) (Z = 2.78, p = 0.003). No correlations were found between
the Low YFAS and Alcohol addiction groups. The authors concluded that there were significant
neurobiological similarities between persons with food addiction symptoms and alcohol dependence.
In a gustatory cue exposure trial among overweight/obese adolescents, Feldstein Ewing and
associates [59] found that consumption of high-calorie beverages (Sprite, Fanta, or Coca Cola) produced
brain responses (e.g., increased activation in the nucleus accumbens, cerebellum, bilateral OFC, etc.)
similar to those observed in response to addictive drugs. Unlike Gearhardt and colleagues, however,
they found no significant relationship between YFAS symptoms and brain response.
Finally, Franken and colleagues [60] found that, similar to patterns seen in drug addiction,
individuals with more YFAS symptoms displayed more impairments in cognitive control and
performance monitoring on behavioral (Flanker task; r = 0.39, p = 0.001) and neurological (EEG;
p < 0.05) tests.

3.2. Preoccupation with Substance Use

Given obvious constraints, no animal studies assessed the characteristic of “preoccupation” as it
relates to food addiction. However, Tuomisto and colleagues [61] found that self-identified chocolate
addicts were significantly more susceptible to hunger compared to controls, possibly indicating a
heightened preoccupation with food (F1,26 = 11.65, p < 0.005). Additionally, Merlo and colleagues [18]
found that in children, food addiction symptoms (measured by the Eating Behaviors Questionnaire)
were significantly associated with greater preoccupation with food (r = 0.58, p < 0.001; measured by
the Children’s Eating Attitude Test).

3.3. Impaired Control

3.3.1. Substance Used in Larger Amounts or over a Longer Period than Intended
Burmeister, Hinman, Koball, and Hoffmann [62] found that in a sample of treatment-seeking
adults with obesity, the number of addictive-like eating symptoms endorsed on the YFAS was
associated with greater self-reported difficulty controlling eating in certain situations (e.g., when
nervous or in social settings; r = 0.59, p < 0.01). In their pediatric sample, Merlo and colleagues [18]
found a significant positive association between the uncontrolled eating subscale on the Three
Factor Eating Questionnaire and symptoms of food addiction (r = 0.60, p < 0.001) on the Eating
Behaviors Questionnaire.

3.3.2. Persistent Desire or Unsuccessful Efforts to Cut Down or Control Substance Use
No studies specifically evaluated this sub-criterion.

3.3.3. Great Deal of Time Spent Obtaining, Using, or Recovering from the Effects of the Substance
Furlong and colleagues [42] randomly assigned rats to either restricted, continuous, or no access
to sweetened condensed milk for five weeks. They reported that, compared to the continuous access
and no access (control) conditions, rats given restricted access to sweetened condensed milk exhibited
more habitual behavior and time attempting to obtain the treat (i.e., continuing to press a lever, despite
the absence of its conditioned reward). Mary Brown and colleagues [55] reported that rats who became
obese due to overconsumption of highly palatable food (consisting mostly of lard, casein, and sucrose)
also exhibited more perseverative behaviors related to highly palatable foods by lever pressing in the
absence of a reward (t = 3.76, p = 0.006), greater motivation for the palatable food (t = 3.755, p = 0.006),
and greater number of lever presses (t = 2.87, p = 0.007) compared to rats on the same diet who did not
become obese.
Nutrients 2018, 10, 477 9 of 30

3.3.4. Craving, or a Strong Urge to Use the Substance

Lenoir and associates [43] found that rats preferred saccharin over cocaine when given the choice
(ps < 0.05), and were more willing to work for saccharin in the face of increased cost (ps < 0.05),
indicating a strong desire to consume the sweetener.
Davis and colleagues [39] found that adults with obesity who met YFAS criteria for food addiction
reported significantly greater food cravings (p < 0.001), hedonic eating (p < 0.001), and snacking on
sweets (p < 0.001). In a separate study, Davis and associates [49] reported that participants with
clinically significant food addiction symptoms (based on the YFAS) had higher scores on a measure
of food cravings (F = 55.07, p < 0.001) compared to those without, and found that craving mediated
the relationship between dopamine signaling and clinically significant food addiction symptoms
(95% CI: 0.04–0.93), even after controlling for binge eating and emotional eating. Additionally, Davis
and colleagues [50] demonstrated that individuals who met the YFAS criteria for clinically significant
food addiction symptoms reported greater food cravings and appetite following a taste of their favorite
palatable food (e.g., potato chips, chocolate, cookies; p < 0.001).
In a study of bariatric surgery candidates with binge eating disorder, Lent and Swencionis [63]
found that food cravings were associated with higher scores on a measure of addictive personality
(r = 0.31, p = 0.005) and that addictive personality scores explained a significant amount of the variance
in cravings (R2 = 0.10, p = 0.005). Tuomisto and colleagues [61] found that self-identified “chocolate
addicts” were more subjectively aroused and reported experiencing greater cravings when presented
with chocolate related cues (e.g., sight, smell, taste) than controls (p < 0.001). Finally, Feldstein Ewing
and associates [59] observed significant increases in adolescent boys’ self-reported urges to eat after
tasting a sweetened beverage (e.g., Sprite, Fanta, or Coca Cola) compared to water (t (23) = 2.20, p = 0.04).

3.4. Social Impairment

3.4.1. Failure to Fulfill Major Role Obligations at Work, School, or Home due to Recurrent
Substance Use
No studies specifically evaluated this sub-criterion.

3.4.2. Continued Use Despite Social or Interpersonal Problems Caused/Exacerbated by Substance

Adams and colleagues [41] found that rats fed a calorie-restricted high-fat/low-sucrose diet began
seeking sucrose rewards more impulsively, even when impulsive behavior was punished with time-out
from other rats (F1,11 = 6.4, p = 0.028). However, rats fed the low-fat/high-sucrose diet did not show
the same level of impulsive behavior (F1,12 = 1.2, p = 0.297). No human studies specifically evaluated
this sub-criterion.

3.4.3. Reduction of Important Social, Occupational, or Recreational Activities due to Substance Use
No animal studies evaluated this sub-criterion; however, Lent and Swencionis [63] found that 60%
of their sample of bariatric surgery candidates endorsed choosing to spend time eating over conducting
other activities, and that this subgroup also had higher addictive personality scores (p < 0.01). In turn,
higher scores on their addictive personality measure explained a significant amount of the variance in
social isolation (R2 = 0.28, p < 0.001).

3.5. Risky Substance Use

3.5.1. Recurrent Substance Use in Physically Hazardous Situations

Johnson and Kenny [48] observed that rats given unrestricted access to a diet consisting of bacon,
sausage, cheesecake, pound cake, frosting, and chocolate continued to compulsively consume these
foods despite the presence of an aversive conditioned stimulus (i.e., a cue light that had previously been
paired with foot shock; F1,26 = 29.7, p < 0.001). In contrast, rats previously fed only regular chow and/or
Nutrients 2018, 10, 477 10 of 30

given restricted access to the high-fat/high-sugar diet significantly decreased their palatable food
consumption in the presence of the aversive conditioned stimulus (F1,26 = 44.9, p < 0.001). No human
studies evaluated this sub-criterion.

3.5.2. Continued Use Despite Knowledge of Physical or Psychological Problem Likely Caused or
Exacerbated by the Substance
No studies specifically evaluated this sub-criterion.

3.6. Pharmacological Criteria

3.6.1. Tolerance
Johnson and Kenny [48] found that rats who volitionally overate highly palatable food exhibited
reward dysfunction (e.g., downregulated dopamine D2 receptors, elevated reward thresholds) that
worsened as the rats gained more weight (F2,6 = 5.2, p < 0.05).
Among bariatric surgery candidates in Lent and Swencionis’s study [63], 68.5% reported
increasing quantities of food to reach satiation, and those who endorsed this symptom also had
higher scores on the addictive personality measure. Additionally, Spring and associates [64] showed
that among women who reported craving carbohydrates, a 100% carbohydrate sweetened beverage
(including sucralose, maltodextrin, dextrose, high maltose rice syrup, etc.) significantly dispelled
negative mood (t (789) = 2.17, p = 0.03). However, this effect decreased over multiple exposures,
indicating signs of tolerance among this sample (t (95) = −2.82, p = 0.01). Finally, Markus and
colleagues [44] reported that the most common foods associated with tolerance-like effects in their
study were high-fat sweet foods (3.2%) and high-fat savory foods (2.9%), and that the “intensity” of
tolerance was greater for these foods compared to low-fat sugary foods (ps < 0.05). The authors did
not report how “intensity” was measured.

3.6.2. Withdrawal
Mangabeira, Garcia-Mijares, and Silva [65] found that rats who preferred a sugar solution had
impaired differential reinforcement of low rate performance (a measure of impulsivity) when forced
into abstinence (p < 0.001), similar to animals in withdrawal from addictive drugs. Pickering, Alsiö,
Hulting, and Schiöth [66] found that when given a high-fat/high-sugar diet, obesity-prone rats
exhibited withdrawal symptoms, including spending less time in the center of an open-field test
(an indicator of anxiety; p < 0.05) and eating significantly less regular chow (p < 0.05) upon removal of
the high-fat/high-sugar diet. Sharma and colleagues [46] reported that upon withdrawal from their
diet, mice fed high-fat food (primarily hydrogenated coconut oil, maltodextrin, sucrose, and casein)
showed more signs of anxiety and increased basal cortisone levels (p < 0.01), and the rats were more
motivated for both sucrose and high-fat foods compared to rats fed a low-fat diet (p < 0.01). However,
Yakovenko, Speidel, Chapman, and Dess [67] reported that spontaneous withdrawal symptoms of
rats reported in other studies (forepaw tremor, teeth chatter, and head shake) were rare in their study.
While they did observe elevated startle (a symptom of ethanol withdrawal seen in the same line of
rats) dependent upon the prior dose of glucose intake (r = 0.63), it was not significantly different from
controls (p > 0.10).
Lent and Swencionis [63] found that, in their sample of bariatric surgery candidates, individuals
who scored significantly higher on an addictive personality measure also reported feeling more anxious
when they were not near food (p < 0.01). Finally, Markus and associates [44] reported that among 1414
participants who reported experiencing at least one YFAS symptom in the past year, 9.5% endorsed
“withdrawal-like” physiological effects in response to either high-fat savory foods (3.8%), high-fat
sweet foods (2.8%), low-fat sugary foods (1.6%), or low-fat savory foods (1.3%). The self-reported
“intensity” of withdrawal symptoms were significantly greater for high-fat savory and high-fat sweet
foods compared to low-fat sugary foods (ps < 0.05).
Nutrients 2018, 10, 477 11 of 30

3.7. Chronicity
McGee, Amare, Bennett, and Duncan-Vaidya [68] found that three days of a binge/compensate
pattern of eating sweetened vegetable shortening still had a significant impact on rats’ motivation for
sucrose over one month later (F2,19 = 7.72, p < 0.01), suggesting long-term effects of palatable food
consumption. Pickering and colleagues [66] reported that obesity-prone rats fed a high-fat/high-sugar
diet consumed significantly less chow during a three-week withdrawal period from those foods
(p < 0.05), possibly suggesting long-term changes to the rats’ reward system analogous to the chronic
state of dependence seen in drug addictions.
Konkolÿ Thege, Woodin, Hodgins, and Williams [5] described a longitudinal study in which they
evaluated the prevalence of six potentially-addictive behaviors among 4121 Canadian adults. They
found that only 6.3% of participants reported problems with excessive overeating for four consecutive
years compared to 58% reporting problems for one year only. The authors concluded that excessive
overeating may be more transient than drug addictions.

3.8. Relapse
Two articles by Pickering and colleagues [66] and Sharma and colleagues [46] reported that rats
and mice withdrawn from a highly palatable food diet demonstrated increased motivation for sucrose,
suggesting risk for relapse (F1,390 = 4.71, p = 0.0491 and ps < 0.01, respectively). No human studies
evaluated this criterion.

3.9. Additional Observations

3.9.1. Genetics
In a genome-wide investigation of food addiction, Cornelis and associates [69] observed that
food addiction scores on the modified YFAS were significantly associated with signaling in the
mitogen-activated protein kinase pathway, which has been identified as a possible drug addiction
pathway (p = 0.02); however, other addiction-related genetic underpinnings did not overlap (e.g., genes,
single-nucleotide polymorphisms) with food addiction (ps > 0.05).

3.9.2. Substance Sensitization

Le Merrer and Stephens [51] observed that mice exposed to sweetened pellets paired with a
specific context displayed signs of behavioral sensitization by showing greater progressive activity in
that context compared to mice that did not have the same pairing (p < 0.05). This activity persisted for
three weeks in the absence of the palatable food and was described as being similar to those seen in
models of drugs sensitization. These authors also reported that conditioned environments produced
greater food consumption.
In humans, Spring and colleagues [64] observed that participants who reported craving
carbohydrates endorsed increased “liking” for a pure carbohydrate beverage over time, compared
to a control high-protein beverage (t (98) = 1.98, p = 0.05), which the authors concluded suggested
sensitization to carbohydrates in this sample.

3.9.3. Cross-Sensitization
Le Merrer and Stephens [51] reported that rats sensitized to palatable food had a significantly
enhanced locomotor response when given cocaine and morphine (F1,18 = 6.18, p < 0.05), suggesting
a cross-sensitization effect. However, Yakovenko and colleagues [67] failed to find evidence for a
cross-sensitization effect of cookie consumption on alcohol intake among rats.
In a study on weight-loss surgery patients, Fowler, Ivezaj, and Saules [70] observed that
those who reported more problems with high glycemic index and high-sugar/low-fat foods before
Nutrients 2018, 10, 477 12 of 30

surgery were more likely to develop a new substance use disorder post-surgery (ps < 0.05),
indicating cross-sensitization.

3.9.4. Impulsivity
Adams and colleagues [41] found that rats fed a high-fat diet showed increased impulsivity in
working for a sucrose reward compared to rats fed a high-sugar diet (F1,11 = 6.4, p = 0.02). In humans,
Davis and associates [39] reported greater impulsivity among adults with obesity who met YFAS
criteria for food addiction compared to controls who did not (p < 0.001).

3.10. Overall Addiction

Four studies reported results relevant to an overall characterization of addiction. Tuomisto and
associates [61] compared self-identified “chocolate addicts” to “non-chocolate addicts” in two studies
and found that exposure to chocolate cues led to affective changes (e.g., anxiety, restlessness) similar to
those seen in substance addiction. Additionally, Schulte, Avena, and Gearhardt [13] evaluated whether
certain foods were more likely to be associated with addictive-like eating in undergraduates and in a
more diverse sample of adults recruited through Amazon MTurk, respectively. Participants in their
study completed the YFAS and then were asked to complete a forced-choice task of identifying which
foods were associated with addictive symptoms. The authors reported that the foods most likely
to be implicated in addictive-like eating patterns were processed foods high in fat and/or refined
carbohydrates. These foods, the authors stated, parallel pharmacokinetic properties of addictive drugs
(e.g., highly concentrated, rapid absorption rate).

4. Discussion
The concept of food addiction has sparked much controversy among researchers. While some
have questioned the validity of this construct [25,30], an increasing number of studies have produced
evidence of biological and behavioral changes in response to highly palatable foods that parallel
addiction criteria. The current study reviewed existing food addiction research and organized the
findings into key diagnostic constructs: (a) neurobiological changes, (b) preoccupation with the
substance, (c) impaired control, (d) social impairments, (e) risky use, (f) tolerance/withdrawal,
(g) chronicity of the condition, and (h) relapse. We found significant support for the construct of
food addiction in both animals and humans, with each primary criterion having support from at
least one study (see Appendix, Table A3), though some sub-criteria have not yet been studied. Of the
addiction characteristics assessed in this review, brain reward changes and impaired control had
the greatest number of supportive findings (21 and 12 studies, respectively). The current review
also found evidence for supplemental characteristics consistent with addiction, including genetic
susceptibility, substance sensitization and cross-sensitization, and impulsivity. More research is
needed to evaluate the diagnostic criteria with less empirical support, including risky use, chronicity,
relapse, preoccupation, and social impairment. Only four of the 35 eligible articles reported findings
contrary to the proposed criteria for addiction [5,41,59,67], yet two of these also included supportive
findings [41,59]. Overall, evidence supporting the validity of food addiction significantly outweighed
evidence against it.
Some have proposed that food addiction should be classified as a behavioral disorder (i.e., “eating
addiction”) similar to a gambling disorder [71]. However, most research studies, including the vast
majority of studies identified for this review, have conceptualized food addiction as a substance use
disorder (i.e., “refined food use disorder”, “highly palatable food use disorder”, or simply “food
use disorder” [14,19,72–75]. To address this question, Meule and Gearhart [14] compared diagnostic
criteria for gambling disorder—the only officially recognized behavioral addiction in the DSM-5—to
symptoms of food addiction and found that despite several similarities (e.g., unsuccessful efforts to
cut down), food addiction symptoms more closely resembled those of a substance use disorder due to
Nutrients 2018, 10, 477 13 of 30

the necessary consumption of a substance (food) and the inapplicability of certain behavioral criteria
(e.g., monetary loss: DSM-5 criteria 1, 6, and 5).
By definition, behavioral addictions involve dependence on a behavior, not a substance; however,
addictive-like consumption of highly palatable food involves both a behavior (eating) and substance
(food). Some classic substance addictions, such as tobacco use disorder, also appear to include
behavioral dependencies. For example, behavior modification is typically required in treatment for
tobacco use disorder due to the strong connection between the effects of the substance (tobacco)
and the act of using it (e.g., smoking) [76]. Nevertheless, tobacco is the primary driver of the
addiction, and it is therefore classified as a substance use disorder. In the current review, symptoms
suggestive of “addiction” to highly palatable foods were often intertwined with specific eating patterns
(i.e., restriction, binge eating) [42,52,67]. However, these behavioral patterns are also frequently
observed among individuals with alcohol and other drug use disorders. In addition, characteristics of
food addiction were found in the absence of such eating patterns (e.g., [48]) and were preceded by
consumption of highly palatable foods, suggesting a profile most similar to substance addiction. In light
of these findings, the results of the current review support Meule and Gearhardt’s [14] conclusion
that, while food addiction involves both behavioral and substance-related symptoms, it more closely
parallels criteria for substance use disorder.
Overall, the majority of the studies in the present systematic review evaluated foods with added
sweeteners (e.g., sugar, saccharine), and many experiments combined sweeteners with fats such as
hydrogenated oils or lard (see Appendix, Table A1). The current review found that the most common
foods associated with addictive symptoms were those high in added fats and/or refined carbohydrates
such as sugar. These findings are consistent with prior literature. Avena, Rada, and Hoebel [77]
found that neural adaptations in response to sugar consumption could lead to dependence in rats,
and Ifland and colleagues [19] concluded that refined foods (e.g., sodas, breakfast cereal, high-fructose
corn syrup) should be considered a “classic” addictive substance. Taking it one step further, Lustig
and colleagues [73] argued that sugar should be regulated as substance of abuse given the negative
health outcomes common to both sugar and alcohol at the individual and societal levels (e.g., liver
disease, associated medical costs). Schulte, Potenza, and Gearhardt [75] proposed that food addiction
more closely resembles a substance-based addiction as opposed to a behavioral addiction due to
the differential effects of certain foods types on eating behavior. Finally, Pursey and colleagues [34]
reviewed the literature on food addiction and concluded that the foods most commonly associated with
addictive-like symptoms in humans are those that are highly-processed, high on the glycemic index,
and contain large amounts of added fats and sugar. Although there is strong support for the addictive
potential of sugar in animal studies [77], data from human studies suggest that the combination of
sweet and fat is more commonly associated with addictive symptoms than sugar alone [34,44]. More
research is needed to identify the types and characteristics of food ingredients that may have addictive
effects in humans.
Few studies have evaluated whether food addiction can manifest in response to consumption of
unprocessed “whole foods.” Animal studies in the current review found no evidence for addictive-like
symptoms to rodent chow (e.g., [48]), and human studies reported increased addictive symptoms
toward refined/processed foods compared to non-processed foods [13]. Nevertheless, in a study
by Schulte and colleagues [13] evaluating the addictive potential of specific foods, nuts (typically
considered a whole food, without added sugars) were rated more addictive on average than
granola bars (typically processed, with added sugars and fats). Furthermore, there was an isolated
report describing individuals who displayed addictive-like symptoms toward carrots [78]. While
highly palatable foods are associated with more addictive-like symptoms than non-processed foods,
the possibility of these symptoms occurring in response to “natural” food merits further exploration.
Future research should also examine potential biological and hormonal factors that play a role in
food addiction symptoms. Studies in this review found that rodents genetically prone to obesity had
greater risk for developing certain food addiction symptoms (i.e., craving, impaired control) compared
Nutrients 2018, 10, 477 14 of 30

to obesity-resistant rodents [48,66]. In humans, symptoms of food addiction are more prevalent among
adults in the overweight and obese BMI categories (24.9%) compared to adults in the normal BMI
category (11.1%) [28]. However, a study comparing adults with overweight/obesity, found hormonal
differences (e.g., amylin, prolactin, thyroid stimulating hormone) between those who met criteria for
food addiction and those who did not [79]. These data indicate a need to further explore the biological
and hormonal factors associated with both weight and food addiction.
Finally, while multiple studies have shown that obesity, binge eating disorder, and food addiction
are separate constructs [26,27], their distinct etiologies leave much to be clarified. Future research
should continue to examine the neurological correlates and differences between obesity, eating
disorders, and food addiction. Potential theoretical and clinical implications of these differences
should be explored.
To our knowledge, this is the first systematic review on food addiction that was not limited to
definitions based on the YFAS or body weight status. Strengths include the use of human and animal
studies, rigorous methodology using PRISMA guidelines and inclusion of both animal and human
studies. Limitations include that our search was limited to two electronic databases and only included
studies published in English, and that animal studies limit generalizability to humans. In addition,
our risk of bias assessment may have resulted in lower scores for older studies, due to changes over
time in reporting standards (e.g., financial support, conflicts of interest). The study question may
also have produced biased results, as researchers interested in evaluating the validity of the food
addiction construct may be more inclined (consciously or not) to observe and report confirmatory
results. When combined with publication bias, this may have resulted in an underrepresentation of
studies producing contrary or null findings. Finally, our search criteria likely excluded evidence for
certain characteristics of addiction (e.g., social impairment, risky use, preoccupation) because these
constructs are relatively difficult to measure quantitatively. However, these symptoms have been
reported in qualitative studies (e.g., [80]) and are plausible when considering, for example, individuals
who continue to overeat post-bariatric surgery or despite exacerbated chronic medical conditions such
as diabetes or heart disease [14,26]. As recommended by Burrows and colleagues [26], future reviews
on food addiction could benefit from including both quantitative and qualitative studies.

5. Conclusions
The results of the current systematic review generally support the validity of food addiction
as a diagnostic construct, particularly as it relates to foods high in added sweeteners and refined
ingredients. The majority of studies in the current review reported evidence for symptoms related to
neurological changes and impaired control, with fewer studies evaluating preoccupation, chronicity,
relapse, social impairment, and risky use. Behavioral and substance-related aspects of food addiction
appear to be intertwined, but we suggest that the substance (highly-palatable food) component may be
more salient to the diagnostic classification of this phenomenon than the behavior (eating). We propose
that the food addiction construct merits serious attention in regard to its presentation, prevention,
and treatment in humans.

Acknowledgments: Publication of this article was funded in part by the University of Florida Open Access
Publishing Fund.
Author Contributions: The review protocol was developed by Eliza L. Gordon. Retrieval and screening of
articles for inclusion was undertaken by Eliza L. Gordon with assistance from Viviana Bauman. The risk of bias
assessment was undertaken by Eliza L. Gordon and Viviana Bauman. Significant revisions were completed by
Lisa J. Merlo. Additional revisions were provided by Aviva H. Ariel-Donges and Viviana Bauman. All authors
contributed content to and approved the final manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
Nutrients 2018, 10, 477 15 of 30

Appendix

Table A1. Characteristics of included studies.

n
First Author (Year) Study Type Sample Characteristics Independent Variable(s) Outcome(s)
(Experimental/Control)
Impulsivity and attention,
measured by the five-choice serial
Restricted, equicaloric
reaction time task; dopamine
Adams (2015) [41] Animal Male Long-Evans rats 16/8 high-fat/low-sugar vs.
signaling in the dorsal and ventral
low-fat/high-sugar diets
striatum; insulin and leptin levels
in the plasma
Adults with obesity in a
behavioral weight-loss program 7-week weight change; measures of
Female: 68.4% Food addiction symptoms psychological distress, disordered
Burmeister (2013) [62] Cross-sectional 57/0
Age: 47.4 years (YFAS continuous) eating, weight bias,
BMI: 38.2 kg/m2 and weight-focused attitudes
Caucasian: 84.2%
Adults with obesity and Brain responses to food images
Double-blind, Mu-opioid receptor
moderate binge eating (FMRI and behavioral measures);
Cambridge (2013) [40] placebo-controlled 16/14 antagonist (GSK1521498) or
Female: 53.3% motivation to expend energy to
parallel group study placebo
Age: 40.2 years view comparable images
“Intermittent excessive sugar
intake” (25% glucose solution
Receptor binding (e.g., dopamine,
Colantuoni (2001) [47] Animal Female Sprague-Dawley rats 10/5 with chow for 12 h followed
opioid)
by 12 h of food deprivation
each day)
Women of European ancestry
Enrichment of SNPs, genes,
Genome-wide participating in the Nurses’
Cornelis (2016) [69] 9314/0 Food addiction (mYFAS) and pathways implicated in
association study Health Study
drug addiction
Age: 25–55 years at start
Indices of hedonic-related eating
Women in a waitlist control for
behaviors (binge, emotional,
a randomized controlled trial of
Naltrexone-induced nausea external, or restrained eating);
a mindfulness intervention for
Daubenmier (2014) [53] Cross-sectional 16/17 and cortisol levels (measure intake of sweets/desserts,
stress eating
of central opioidergic activity) carbohydrates; interoceptive
Age: 40.9 years
awareness; adiposity;
BMI: 31.1 kg/m2
weight change
Nutrients 2018, 10, 477 16 of 30

Table A1. Cont.

n
First Author (Year) Study Type Sample Characteristics Independent Variable(s) Outcome(s)
(Experimental/Control)
Clinical co-morbidities (e.g., binge
Adults with obesity eating disorder, attention deficit
Female: 68.1% hyperactivity disorder),
Food addiction (YFAS
Davis (2011) [39] Cross-sectional Age: 33.6 years 18/54 psychological risk factors
dichotomous)
BMI: 38.5 kg/m2 (e.g., impulsivity), and abnormal
Caucasian: 81.4% motivation for the addictive
substance
Adults recruited for study on Composite index of elevated Food addiction (YFAS
overeating/overweight dopamine signaling (a dichotomous); eating-related
Davis (2013) [49] Case-control 21/99
Female: 68.3% multi-locus genetic profile sub-phenotypes of food addiction
Age: 25–47 years score) (e.g., binging)
Adults, predominately
Food addiction (YFAS
overweight/obese
Three-way mixed model, dichotomous); psychomotor Appetite, cravings,
Davis (2014) [50] Female: 67.7% 23/113
double-blind cross-over stimulant (methylphenidate) and consumption of favorite snack
Age: 32.7 years
vs. placebo
BMI: 33.9 kg/m2
Adults
Weight category (normal vs. EEG; hunger; behavioral inhibition;
Female: 79.3%
De Ridder (2016) [58] Cross-sectional 38/34 obese BMI); food addiction eating style; binge eating; food
Age: 45.1 years
(YFAS continuous) awareness
BMI: 33.2 kg/m2
Marmoset monkeys 15 min exposure to 50 g
Duarte (2014) [54] Animal 6/8 Conditioned-place-preference
Female: 50% chocolate
Youth, overweight/obese
Beverage type (sweetened
Male: 83.3%
Feldstein Ewing (2017) soft drink vs. water); food Urge to eat; FMRI response
Cross-sectional Age: 16.5 years 24/0
[59] addiction (YFAS continuous); patterns (BOLD activation)
BMI: 33.1 kg/m2
BMI; insulin resistance
Hispanic: 79%
Adults, 2.7 years post-bariatric
surgery Pre-surgical problems with
Female: 88.4% high-sugar/low-fat foods and Risk for new onset substance use
Fowler (2014) [70] Secondary data analyses 154/0
Age: 48.7 years foods with a high glycemic disorder post-surgery
BMI: 32.3 kg/m2 index
Caucasian: 94.2%
Students recruited for larger
Cognitive control (error
YFAS study Food addiction (YFAS
Franken (2016) [60] Cross-sectional 34/34 monitoring) via Eriksen flanker
Age: 20.4 years continuous)
task and EEG (ERN, Pe)
BMI: 21.7 kg/m2
Nutrients 2018, 10, 477 17 of 30

Table A1. Cont.

n
First Author (Year) Study Type Sample Characteristics Independent Variable(s) Outcome(s)
(Experimental/Control)
Continuous vs. restricted
Goal-directed performance and
Furlong (2014) [42] access to sweetened
Animal Male Long-Evans rats 24/12 neuronal activity in corticostriatal
study 1 condensed milk (3:1 ratio of
circuits
Nestle to water)
AMPA-receptor and Habitual performance following
Furlong (2014) [42]
Animal Male Long-Evans rats 8/10 dopamine D1-receptor restricted access to a highly
study 2
antagonists palatable food
FMRI patterns of neural activation
Young women
Food addiction symptoms similar to substance dependence (in
Gearhardt (2011) [12] Cross-sectional Age: 20.8 years 39/0
(YFAS continuous) response to actual and anticipated
BMI: 28.0 kg/m2
receipt of chocolate milkshake)
Adults with overweight or
obesity admitted to a medical Food addiction symptoms
center for obesity treatment (I-YFAS continuous and EEG modifications and
Imperatori (2015) [57] Cross-sectional 14/14
Female: 78.6% dichotomous); taste of connectivity
Age: 43.6 years chocolate milkshake
BMI: 28.5 kg/m2
Restricted vs. extended access Brain stimulation reward threshold;
Johnson (2010) [48] to “cafeteria style” diet (e.g., body weight change; caloric intake;
Animal Male Wistar rats 22/9
study 1 bacon, sausage, cheesecake, type of food consumed (cafeteria
frosting) vs. chow)
Reward hyposensitivity (measured
Restricted vs. extended access by striatal D2 receptor density);
Johnson (2010) [48] to cafeteria style diet; body brain stimulation reward threshold;
Animal Male Wistar rats Not reported
study 2 weight; knockdown of striatal body weight change; caloric intake;
dopamine D2 receptor type of food consumed (cafeteria
vs. chow)
Restricted vs. extended access
to cafeteria style diet followed Brain stimulation reward threshold;
by intermittent access (30 body weight change; caloric intake;
Johnson (2010) [48]
Animal Male Wistar rats Not reported min) to cafeteria food; type of food consumed (cafeteria
study 3
environmental stimulus vs. chow); compulsive-like eating
(light) predicting adversity behavior
(foot shock)
Nutrients 2018, 10, 477 18 of 30

Table A1. Cont.

n
First Author (Year) Study Type Sample Characteristics Independent Variable(s) Outcome(s)
(Experimental/Control)
Restricted vs. extended access
to cafeteria style diet; Brain stimulation reward threshold;
Johnson (2010) [48] knockdown of striatal caloric intake; type of food
Animal Male Wistar rats Not reported
study 4 dopamine D2 receptor; consumed (cafeteria vs. chow);
environmental stimulus compulsive-like eating behavior
(light) predicting foot shock
Over-involvement (causing
Adults
significant problems) in one Prevalence, substance use
Konkolÿ Thege (2015) [5] Longitudinal study Female: 54.7% 4121/0
of six excessive behaviors comorbidity, five-year trajectory
Age: 46.1 years
(including eating)
Behavioral sensitization (assessed
Le Merrer (2006) [51] Sweetened pellets while by locomotor activity in
Animal Male mice 20/10
studies 1 & 2 hungry vs. while satiated sweetened-pellet-paired
environment)
Le Merrer (2006) [51] Dopaminergic agonists
Animal Male mice 9-10/0 Pellet-induced conditioned activity
study 3 (SCH23390, sulpiride)
Opiate (naltrexone) and
Le Merrer (2006) [51]
Animal Male mice 20/0 AMPA (GYKI 52466) receptor Pellet-induced conditioned activity
study 4
antagonists
Cocaine or morphine; Cross-sensitization (pellet-induced
Le Merrer (2006) [51]
Animal Male mice 20/0 pretreatment of GYKI 52466, conditioned activity following
study 5
naltrexone, or SCH23390 cocaine or morphine injection)
Le Merrer (2006) [51] Sweetened-pellet-conditioned Consumption of sweetened pellets;
Animal Male mice 7–9/0
study 6 environment locomotor activity
Mutually exclusive choice
between sweetened water Preferred substance (saccharin,
Lenoir (2007) [43] Animal Young male Wistar rats 132/0
and intravenous cocaine; sugar, or cocaine)
history of cocaine preference
Adult bariatric surgery Maladaptive eating behaviors
candidates Addictive personality (Overeating Questionnaire;
Female: 85.6% (Eysenck Personality binge-eating questions from
Lent (2012) [63] Cross-sectional 97/0
Age: 41.0 years Questionnaire Addiction Questionnaire of Eating and
BMI: 45.2 kg/m2 Scale) Weight Patterns; Eating Attitudes
Caucasian: 67.0% and Behaviors Questionnaire)
Nutrients 2018, 10, 477 19 of 30

Table A1. Cont.

n
First Author (Year) Study Type Sample Characteristics Independent Variable(s) Outcome(s)
(Experimental/Control)
Impulsivity (assessed by differential
Withdrawal from prolonged
Mangabeira (2015) [65] Animal Male Wistar rats 14/14 reinforcement of low rate
sugar consumption
performance)
Depressive symptoms; BMI; YFAS;
Undergraduates
Food addiction (YFAS “problem foods” (high-fat savory,
Markus (2017) [44] Cross-Sectional Female: 69.9% 1495/0
dichotomous, continuous} high-fat sweet, low-fat sugary,
Age: 21.6 years
low-fat savory)
Addictive-like behavior
(i.e., heightened motivation;
Propensity to diet-induced
Mary Brown (2015) [55] Animal Male Sprague-Dawley rats Not reported excessive intake; increased food
obesity
seeking); synaptic impairments in
NAc
Motivation (operant performance for
sucrose on progressive ratio
Withdrawal from intermittent
McGee (2010) [68] Animal Male Long–Evans rats 16/8 schedule); craving (lever pressing for
access to a sweet fat mixture
palatable food); anxiety (elevated
plus maze)
Children
Female: 64%
Age: 13.8 years
BMI: 35.6 kg/m2
BMI; Food addiction
Caucasian: 60% 50/0 children and their Food- and eating-related attitudes
Merlo (2009) [18] Cross-sectional symptoms (Eating Behaviors
parent/guardian and behaviors
Questionnaire)
Parent/guardian
Female: 87%
Age: 43.2 years
BMI: 33.0 kg/m2
Bouts of sweetened-fat intake
(shortening with 10%
sucrose); predator stress;
Neuroadaptations in NAc shell
Newman (2013) [52] Animal Male Sprague-Dawley rats 10/11 intra-NAc shell infusions of
GABA systems
either d-amphetamine or
opioid agonist DAMGO;
GABA agonist, muscimol
Nutrients 2018, 10, 477 20 of 30

Table A1. Cont.

n
First Author (Year) Study Type Sample Characteristics Independent Variable(s) Outcome(s)
(Experimental/Control)
Palatable food seeking; expression
of potential addiction biomarkers
C57BL/6J male mice High fat diet followed by 12 h
Pérez-Ortiz (2016) [56] Animal 20/20 in the NAc: fumarate hydratase
Age: 4 weeks food deprivation
(FH), ATP synthase subunit alpha
(ATP5a1) and transketolase (TKT)
Pickering (2009) [66] Sugar content of pellets
Animal Male Wistar rats 12/0 Sugar consumption
study 1 (50% vs. 95%)
Pickering (2009) [66] High-fat high-sugar diet
Animal Male Wistar rats 9/3 Caloric intake; body weight change
study 2 (lard, sucrose)
High-fat high-sugar diet
Caloric intake; body weight change;
Pickering (2009) [66] (lard, sucrose); vulnerability
Animal Male Wistar rats 16/8 motivation for sugar; anxiety-like
study 3 for weight gain; withdrawal
behavior (open-field test)
from lard and sucrose diet
Undergraduates
Female: 67.5% Food items (e.g., chocolate,
Schulte (2015) [13] study 1 Cross-sectional Age: 19.3 years 120/0 broccoli) and types Food addiction symptoms (YFAS)
BMI: 23.0 kg/m2 (e.g., processed)
Caucasian: 72.5%
Adults
Food characteristics
Male: 59.4%
(e.g., proportions of fats, Self-reported problematic eating
Schulte (2015) [13] study 2 Cross-sectional Age: 31.1 years 384/0
carbohydrates; level of behavior
BMI: 27.0 kg/m2
processing)
Caucasian: 76.8%
High fat diet (58% kcal from
fat: including hydrogenated
coconut oil, maltodextrin, Motivation for sucrose or high-fat
Male mice
Sharma (2013) [46] study 1 Animal 12 (treated + control) sucrose, casein) vs. reward; caloric intake; body weight
Age: 6–7 weeks
ingredient-matched low fat change
diet (10.5% kcal from fat);
withdrawal from diet
High fat diet vs. low fat diet
Male mice Anxiety-like behavior (elevated
Sharma (2013) [46] study 2 Animal 30 (treated + control) (10.5% kcal from fat);
Age: 6–7 weeks plus maze); plasma corticosterone
withdrawal from diet
Nutrients 2018, 10, 477 21 of 30

Table A1. Cont.

n
First Author (Year) Study Type Sample Characteristics Independent Variable(s) Outcome(s)
(Experimental/Control)
Basal corticosterone; protein levels
for tyrosine hydroxylase,
High fat diet vs. low fat diet corticosterone releasing factor type
Male mice
Sharma (2013) [46] study 3 Animal 48 (treated + control) (10.5% kcal from fat); 1 receptor, BDNF, phospho-CREB
Age: 6–7 weeks
withdrawal from diet and ∆FosB in amygdala, NAc and
ventral tegmental area via western
immunoblotting
Women who are overweight or
Mood; drink preference
Double-blind within and obese
Negative mood; consumption (carbohydrate-rich vs.
Spring (2008) [64] between subjects Age: 28.0 years 61/0
of carbohydrate-rich beverage macronutrient-balanced) during
cross-over BMI: 27.6 kg/m2
negative mood state
Caucasian: 50.8%
Psychological symptoms
Self-identified “chocolate (e.g., depression, disinhibition,
Women
Tuomisto (1999) [61] addiction”; type of exposure disordered eating) measured by
Case-control Age: 35.4 years 16/15
study 1 to chocolate (look, smell, or questionnaires; self-reported
BMI: 26.7 kg/m2
taste) reactivity to cues (e.g., anxiety,
calmness); salivation, heart rate
Amount of chocolate consumed;
psychological symptoms
Women Self-identified “chocolate (e.g., depression, disinhibition,
Tuomisto (1999) [61]
Case-control Age: 35.4 years 16/15 addiction”; type of exposure disordered eating) measured by
study 2
BMI: 26.7 kg/m2 to chocolate (look or smell) questionnaires; self-reported
reactivity to cues (e.g., anxiety,
calmness); salivation, heart rate
Occidental low- and Line of ingestive phenotype
Yakovenko (2011) [67] high-saccharin-consuming rats (LoS vs. HiS); periodic access Withdrawal symptoms (acoustic
Animal 13–15/0
study 1 (LoS and HiS, respectively) to glucose solution followed startle); glucose consumption
Age: 60–90 days by 24 h food withdrawal
Line of ingestive phenotype
(LoS vs. HiS); periodic access
Yakovenko (2011) [67] LoS and HiS rats Withdrawal symptoms (e.g., startle
Animal 8/0 to glucose solution followed
study 2 Age: 60–90 days behavior); glucose consumption
by 24 h food withdrawal;
naloxone
Yakovenko (2011) [67] LoS and HiS rats Binge-like feeding of cookies Cookie, shortening, and ethanol
Animal 8/0
study 3 Age: 60–90 days and shortening consumption
Nutrients 2018, 10, 477 22 of 30

Table A2. Risk of bias assessment of included studies.

Quality Score [Y/(N + UC)]

Description of the Groups?
Were Confounding Factors
Was the Inclusion Criteria

Using Objective Criteria?

Were Outcomes Assessed

Is the Source of Financial

Was a Random or Pseudo

Is There a Description of
Is There a Description of

Assessors, with Possible

Random Sample Used?

Identified and Control

Conflicts of Interest?
Was There Sufficient

Support Described?
Are the Methods of
Statistical Analysis
Strategies Stated?

Investigators and
Withdrawals and
Clearly Defined?

Drop-Outs?

Described?
Adams (2015) [41] Y Y Y Y Y Y Y Y Y All Ys
Burmeister (2013) [62] N Y UC Y N/A Y Y N N 1
Cambridge (2013) [40] Y Y Y Y Y Y Y Y Y All Ys
Colantuoni (2001) [47] Y Y Y Y Y Y Y Y N 8
Cornelis (2016) [69] N Y Y Y N/A Y Y Y Y 7
Daubenmier (2014) [53] Y Y Y Y UC Y Y Y N 3.5
Davis (2011) [39] N Y UC Y Y UC Y N N 0.8
Davis (2013) [49] N Y Y Y Y UC Y Y Y 3.5
Davis (2014) [50] Y Y Y Y Y N Y N Y 3.5
De Ridder (2016) [58] N Y Y Y Y UC Y N Y 2
Duarte (2014) [54] Y Y Y Y Y Y Y Y N 8
Feldstein Ewing (2017) [59] N Y Y Y N/A N Y Y Y 3
Fowler (2014) [70] UC Y Y Y UC N UC Y Y 1.25
Franken (2016) [60] N Y Y Y Y Y Y N Y 3.5
Furlong (2014) [42] Y Y Y Y Y Y Y Y Y All Ys
Gearhardt (2011) [12] UC Y Y Y N N Y Y Y 2
Imperatori (2015) [57] UC Y Y Y Y UC Y N Y 2
Johnson (2010) [48] Y Y Y Y Y UC Y Y Y 8
Konkolÿ Thege (2015) [5] N N UC Y Y Y Y Y Y 2
Le Merrer (2006) [51] Y Y Y Y Y N Y N N 2
Nutrients 2018, 10, 477 23 of 30

Table A2. Cont.

Quality Score [Y/(N + UC)]

Description of the Groups?
Were Confounding Factors
Was the Inclusion Criteria

Using Objective Criteria?

Were Outcomes Assessed

Is the Source of Financial

Was a Random or Pseudo

Is There a Description of
Is There a Description of

Assessors, with Possible

Random Sample Used?

Identified and Control

Conflicts of Interest?
Was There Sufficient

Support Described?
Are the Methods of
Statistical Analysis
Strategies Stated?

Investigators and
Withdrawals and
Clearly Defined?

Drop-Outs?

Described?
Lenoir (2007) [43] Y Y Y Y Y Y Y Y Y All Ys
Lent (2012) [63] N N Y Y N/A Y Y Y Y 3
Mangabeira (2015) [65] Y Y Y Y Y UC Y Y N 3.5
Markus (2017) [44] N N Y Y N UC Y Y Y 1.25
Mary Brown (2015) [55] Y Y Y Y Y UC Y Y Y 8
McGee (2010) [68] Y Y Y Y Y Y Y Y N 8
Merlo (2009) [18] N Y UC Y Y UC Y Y N 1.25
Newman (2013) [52] Y Y Y Y Y UC Y Y Y 8
Pérez-Ortiz (2016) [56] Y Y Y Y Y Y Y Y N 8
Pickering (2009) [66] N Y Y Y Y Y Y Y N 3.5
Schulte (2015) [13] N N Y Y N/A Y Y Y Y 3
Sharma (2013) [46] Y Y Y Y Y UC Y Y Y 8
Spring (2008) [64] N Y Y N N/A Y Y Y N 1.67
Tuomisto (1999) [61] Y UC Y Y Y Y Y N N 2
Yakovenko (2011) [67] Y Y Y Y Y UC Y Y N 3.5
N = No, Y = Yes, UC = Unclear, N/A = Non-Applicable.
Nutrients 2018, 10, 477 24 of 30

Table A3. Evidence for and against addiction criteria.

Characteristic Supporting Evidence Null/Contrary Evidence

Animal studies:
1. Adams (2015) [41]
2. Colantuoni (2001) [47]
3. Duarte (2014) [54]
4. Furlong (2014) [42] study 2
5. Johnson (2010) [48] study 2
6. Johnson (2010) [48] study 4
7. Le Merrer (2006) [51] study 3
8. Le Merrer (2006) [51] study 4
9. Mary Brown (2015) [55]
10. Newman (2013) [52]
11. Pérez-Ortiz (2016) [56] Adams (2015) [41] (animal study)
Brain changes
12. Sharma (2013) [46] study 3 Feldstein Ewing (2017) [59] (human study)
Human studies:
13. Cambridge (2013) [40]
14. Daubenmier (2014) [53]
15. Davis (2013) [49]
16. Davis (2014) [50]
17. De Ridder (2016) [58]
18. Feldstein Ewing (2017) [59]
19. Franken (2016) [60]
20. Gearhardt (2011) [12]
21. Imperatori (2015) [57]

Human studies:
1. Merlo (2009) [18].
Preoccupation 2. Tuomisto (1999) [61] study 1. N/A
3. Tuomisto (1999) [61] study 2.
Nutrients 2018, 10, 477 25 of 30

Table A3. Cont.

Characteristic Supporting Evidence Null/Contrary Evidence

Animal studies:
1. Furlong (2014) [42] study 1—Spending a significant amount of time acquiring, using, or
recovering from a substance.
2. Lenoir (2007) [43]—Craving.
3. Mary Brown (2015) [55]—Spending a significant amount of time acquiring, using, or
recovering from a substance.
Human studies:
4. Burmeister (2013) [62]—Consuming a substance in greater amounts or over longer
periods of time than intended.
Impaired control 5. Davis (2011) [39]—Craving. N/A
6. Davis (2013) [49]—Craving.
7. Davis (2014) [50]—Craving.
8. Feldstein Ewing (2017) [59]—Craving.
9. Lent (2012) [63]—Craving.
10. Merlo (2009) [18]—Consuming a substance in greater amounts or over longer periods
of time than intended.
11. Tuomisto (1999) [61] study 1—Craving.
12. Tuomisto (1999) [61] study 2—Craving.

Animal studies:
1. Adams (2015) [41]—Continually using a substance despite its effects causing or
exacerbating persistent or recurrent social or interpersonal problems.
Social impairment N/A
Human studies:
2. Lent (2012) [63]—Giving up or reducing social, occupational, or recreational activities.

Animal studies:

Risky use 1. Johnson (2010) [48] study 3—Continually using a substance in situations in which it is N/A
physically dangerous.
Nutrients 2018, 10, 477 26 of 30

Table A3. Cont.

Characteristic Supporting Evidence Null/Contrary Evidence

Animal studies:
1. Johnson (2010) [48] study 1—Tolerance.
2. Mangabeira (2015) [65]—Withdrawal.
3. Pickering (2009) [66] study 3—Withdrawal.
4. Sharma (2013) [46] study 2—Withdrawal. Yakovenko (2011) [67]
study 1
Tolerance/Withdrawal Human studies: Yakovenko (2011) [67]
5. De Ridder (2016) [58]—Withdrawal. study 2 (animal studies)
6. Lent (2012) [63]—Tolerance; Withdrawal.
7. Markus (2017) [44]—Tolerance; Withdrawal.
8. Spring (2008) [64]—Tolerance.

Animal studies:

Chronicity 1. McGee (2010) [68]. Konkolÿ Thege (2015) [5] (human study)
2. Pickering (2009) [66] study 3.

Animal studies:

Relapse 1. Pickering (2009) [66] study 3. N/A

2. Sharma (2013) [46] study 1.

Human studies:
1. Tuomisto (1999) [61] study 1.
Overall 2. Tuomisto (1999) [61] study 2. N/A
3. Schulte (2015) [13] study 1.
4. Schulte (2015) [13] study 2.
Nutrients 2018, 10, 477 27 of 30

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