Impact of sugar on the body, brain, and behavior

Abstract

Sugar is highly palatable and rewarding, both in its taste and nutritive input. Excessive sugar consumption, however, may trigger neuroadaptations in the reward system that decouple eating behavior from caloric needs and leads to compulsive overeating. Excessive sugar intake is in turn associated with adverse health conditions, including obesity, metabolic syndrome, and inflammatory diseases. This review aims to use recent evidence to connect sugar's impact on the body, brain, and behavior to elucidate how and why sugar consumption has been implicated in addictive behaviors and poor health outcomes.

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1. ABSTRACT
Sugar is highly palatable and rewarding,
both in its taste and nutritive input. Excessive sugar
consumption, however, may trigger neuroadaptations
in the reward system that decouple eating behavior
from caloric needs and leads to compulsive overeating.
Excessive sugar intake is in turn associated with
adverse health conditions, including obesity, metabolic
syndrome, and inammatory diseases. This review
aims to use recent evidence to connect sugar’s impact
on the body, brain, and behavior to elucidate how
and why sugar consumption has been implicated in
addictive behaviors and poor health outcomes.
2. INTRODUCTION
The past several years have been marked
by a growing awareness of the unsavory effects
of excessive sugar consumption. As of 2015, the
World Health Organization recommends reducing
added sugar to less than 5% of daily caloric intake to
lower the risk of unhealthy weight gain and obesity
(1). Last year, the American Academy of Pediatrics
recommended that parents should not feed fruit juice
to infants younger than one year because of its high
sugar content (2). This advice reects a growing body
of research investigating added sugar as an instigator
of obesity and metabolic syndrome (a combination of
risk factors like high blood pressure, high triglycerides,
high fasting blood glucose, etc. that increase the
likelihood of cardiovascular disease, type 2 diabetes
mellitus, and non-alcoholic fatty liver disease (3).
Other research has examined sugar as a potentially
addictive substance. However, the public is still
ooded with mixed messages from advertising, health
organizations, and popular press about sugar’s impact
on human health. Unbiased scientic ndings from the
past several years have begun to help clear up this
consumer confusion.
Sugar typically refers to a category of simple
carbohydrates that includes monosaccharides like
fructose and glucose, and disaccharides, like sucrose
and lactose, which have different effects on the body
and brain. The present review focuses primarily on
added sugars, namely sucrose and high fructose corn
syrup (HFCS), because of their negative impact on
health and because they predominate in the typical
western diet. Sucrose, or table sugar, is a disaccharide
made up of one-part glucose and one-part fructose. In
contrast, HFCS is comprised of 42% or 55% of free
Impact of sugar on the body, brain, and behavior
Clara R Freeman1, Amna Zehra1, Veronica Ramirez1, Corinde E Wiers1, Nora D Volkow1,2, Gene-Jack
Wang1
1Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of
Health, Bethesda, MD, 20892, 2Ofce of Director, National Institute on Drug Abuse, National Institutes of
Health, Bethesda, MD, 20892
TABLE OF CONTENTS
1. Abstract
2. Introduction
3. Sugar on the body, brain, and behavior
3.1 Fructose vs. glucose
3.2 Hedonic response to sugar and rewards of sugar intake
3.3 Hedonic response: fructose vs glucose
3.4 Sugar addiction
3.5 Sugar, obesity, and cognitive functioning
4. Sugar compared
4.1. Sugar vs. fat
4.2 Sugar vs. complex carbohydrates
5. Conclusions and future directions
6. Acknowledgement
7. References
[Frontiers In Bioscience, Landmark, 23, 2255-2266, June 1, 2018]

Sugar’s impact on the body, brain, and behavior
2256 © 1996-2018
fructose, complemented by free glucose (4). Because
most added sugar consumption comes from sucrose
or HFCS, we typically consume both fructose and
glucose together. However, research on the individual
monosaccharides, fructose and glucose, has revealed
large differences in how they affect the body.
The present review aims to explore sugar
and its physiological effects on the brain and body,
which may play a role in its adverse health effects.
First, we discuss different types of sugar and how they
are processed by the body and brain. Second, we
address sugar’s hedonic effects, addictive properties,
and connections with obesity, primarily focusing on
imaging studies in humans with support from the
animal literature. Third, we aim to compare how sugar
is metabolized and processed compared to other
macronutrients such as fat and ber-rich complex
carbohydrates to further emphasize any singular
effects attributable to sugar.
3. SUGAR ON THE BODY, BRAIN, AND
BEHAVIOR
3.1 Fructose vs. glucose
Monosaccharides differ in how they are
processed by the brain and inuence brain activity.
Although some consumers may believe that fructose is
healthier because it comes from fruit (5), this notion is
misguided. The body does not respond in the same way
to fructose in fruit as to added fructose. As an added
sugar, fructose is particularly implicated in metabolic
syndrome, hypertension, insulin resistance, lipogenesis,
diabetes and associated retinopathy, kidney disease,
and inammation (4,6,7,8,9). Accordingly, reduction of
fructose in the diet of at risk individuals appears to reduce
these symptoms. When added fructose was replaced
by glucose (in the form of starch) in the diets of obese
children, liver fat, de novo lipogenesis, diastolic blood
pressure, triglycerides, and LDL cholesterol decreased
while insulin sensitivity improved (10,11). Furthermore,
in fruit, fructose is accompanied by antioxidants,
avonols, potassium, vitamin C and high ber, which
may collectively outweigh any negative consequences
of fructose content (4, 12). Importantly, the quantities of
fructose in a piece of fruit and a sweetened beverage
are drastically different. For example, the fructose in
a peach represents approximately 1% of the fruit’s
weight whereas fructose accounts for half the weight
of HFCS (7).
Differences in health effects between glucose
and fructose may be caused by the different metabolic
pathways they follow. Digestion and absorption of
sugars takes place in the top half of the digestive tract
(13). Most of the glucose in the blood stream is not
stored in the liver but rather, through the action of
insulin, quickly passes through to muscle, adipose,
and other peripheral tissues where it can immediately
be used as energy (13). Fructose, on the other hand, is
a less direct source of energy. Independent of insulin,
the liver converts fructose to glucose, lactate, and/or
fatty acids before passing it to the blood stream where
it can be oxidized in other tissues for energy (14,15,8).
Compared to glucose, fructose produces smaller
increases in plasma glucose and circulating satiety
hormones such as glucagon-like peptide-1 (GLP-1)
and insulin (16). Fructose also attenuates suppression
of ghrelin, an appetitive hormone, while glucose does
not (17). Therefore, fructose allows overconsumption
of calories by failing to activate the body’s signals to
stop eating.
Beyond weight gain and obesity, other
diseases are linked to fructose’s metabolic pathway.
High dietary fructose can increase de novo lipogenesis
in the liver (18) in a way that is reminiscent of ethanol
(19). This is because fructose bypasses the main
rate limiting step of glycolysis to act as a precursor
for fatty acid synthesis (20,21,8). This bypass may
also explain the increased rates of non-alcoholic
fatty liver disease and resulting insulin resistance
associated with fructose ingestion (20). Fructose
also seems to contribute to inammation in the body.
When in excess in the intestinal lumen, fructose
generates advanced glycation end products (AGE’s),
which are related to neurodegenerative diseases,
atherosclerosis, and chronic inammatory diseases
such as asthma, diabetes, and associated cognitive
decline (22,9,23,24,25).
Glucose and fructose have differing impacts
on the brain. Compared to other organs, the brain has
vastly disproportionate energy requirements relative
to its weight. Neurons have an especially high energy
demand for generating postsynaptic potentials and
action potentials, necessitating large amounts of energy
(26). Glucose from the bloodstream is the main source
of energy for the brain (26,27). Glucose transporters
in astrocytes and the epithelial cells of the blood
brain barrier (BBB) are responsible for transporting
glucose into the brain (16,26). Neurons then absorb
glucose from astrocytes using glucose transporters. In
contrast, fructose cannot directly supply the brain with
energy as it crosses the blood brain barrier to a much
lesser degree than glucose (16,26). However, fructose
administered intraperitoneally in rodents crossed
the BBB to some degree and triggered neuronal
activation. This fructose was metabolized into lactate,
an alternate energy source, in the hypothalamus (16).
Fructose’s ability to cross the BBB has not yet been
studied in humans, so more research is needed on the
direct effects of fructose in the brain. Nonetheless, the
differential effects of the two monosaccharides may
be attributed in part to glucose’s more immediate and
direct availability to the brain as an energy source as
compared to fructose.

Sugar’s impact on the body, brain, and behavior
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3.2 Hedonic response to sugar and rewards of
sugar intake
While the hypothalamus regulates food
intake in terms of energetic needs, the dopamine
reward/motivation circuitry involving striatal, limbic and
cortical areas also drives eating behavior (28). Other
neurotransmitters including serotonin, endogenous
opioids, and endocannabinoids confer the rewarding
effects of food in part by modulating its hedonic
properties (29). Ingestion of palatable food releases
dopamine (DA) in the ventral and dorsal striatum and
dorsal striatal DA release is proportional to the self-
reported level of pleasure gained by eating the food
(30). Highly palatable foods, namely those rich in sugar
or fat, can strongly trigger these reward/motivation and
hedonic systems, encouraging food intake beyond the
necessary energy requirements (31). While this may
have been evolutionarily advantageous by encouraging
fat storage when food was scarce, overeating becomes
a liability in our current environment, which has no
shortage of highly caloric and processed foods.
There are two principal rewarding aspects of
sugar consumption: nutrition and taste. Rodent studies
have indicated that these two aspects are distinct and
dissociable and may follow different neural pathways
(32,33). One path for the nutritive rewards of sugar
comes from melanin-concentrating hormone (MCH)
neurons in the lateral hypothalamus (32). In rodents,
these neurons re in response to extracellular glucose
levels, independent of gustatory input, and project to
dopamine neurons in the midbrain that in turn project to
the ventral and dorsal striatum. Though animals typically
prefer sucrose over sucralose (non-nutritive sweetener),
transgenic mice who lack MCH neurons do not, showing
that this pathway is essential for encoding nutritive
reward. When MCH neurons are optogenetically
stimulated during the consumption of sucralose, the
mouse brain is tricked into responding as if it is receiving
caloric energy with a resultant increase in striatal DA
and even preference of sucralose over sucrose (32).
The nutritive reward value of sugar is associated with
increases in DA release in the dorsal striatum (34). When
infused intra-gastrically in mice to avoid the confounds of
taste, glucose elicited DA release in the dorsal striatum
while sucralose did not (34).
The sweet taste of sugar is also rewarding—
offering an explanation as to why articial sugars
like sucralose are still consumed despite their lack
of nutritive value. The reward of the sweet taste,
however, activates a different neural pathway than the
caloric input. While the nutritive reward of sugar in mice
causes DA release primarily in the dorsal striatum,
the sweetness reward is concentrated in the ventral
striatum (32). Consumption of sucralose in mice was
associated with increased DA in the ventral striatum
except when tainted by a bitter additive, suggesting
that the reward is derived from the palatable taste
rather than another feature of sucralose (34).
Although both the nutritive and taste rewards
of sugar are, to some extent, neurologically distinct, they
occur in tandem and are interrelated. A recent study
showed that mice modied to have disrupted DA D-2
receptor (DRD2) signaling in the nucleus accumbens
(NAc) shell of the ventral striatum exhibited more
perseverative and impulsive sucrose-taking, increased
sucrose reinforcement, increased reinforcement/
reward learning of glucose-paired avors, and
worsened learning exibility (35). Additionally, these
mice were less efcient in metabolizing glucose. This
suggests that DRD2 in the NAc are essential both for
regulating peripheral glucose levels as well as the
reinforcement/reward learning of glucose consumption
(35), which explains why dysregulation of this system
may lead to overeating.
3.3 Hedonic response: Fructose vs. glucose
Just as fructose and glucose have different
metabolic pathways, they have different hedonic effects
on the brain and behavior. Fifteen minutes after subjects
received a drink of either pure fructose or glucose
during a functional MRI (fMRI) scan, those receiving
glucose showed a signicantly reduced amount of
cerebral blood ow (CBF) in the hypothalamus, insula,
anterior cingulate cortex, and striatum when compared
to baseline (17). They also showed greater functional
connectivity between the hypothalamus, thalamus,
caudate, and putamen. The increased connectivity
between the hypothalamus and the dorsal striatum after
glucose was interpreted to reect engagement of the
nutritive reward pathway. The reduction in hypothalamic
activity and increased connectivity with reward centers
was accompanied by a perceived increase in fullness
and satiety. In contrast, consuming a fructose drink was
not associated with reduced CBF in the hypothalamus,
but instead with reduced CBF in the thalamus,
hippocampus, posterior cingulate cortex, fusiform gyrus,
and visual cortex. Although those in the fructose group
did have increased connectivity between the thalamus
and hypothalamus, there was no increase detected
with the dorsal striatum as observed in the glucose
group. Correspondingly, fructose consumption did not
signicantly reduce hunger. Fructose consumption has
also been associated with a stronger fMRI response in
the visual cortex to high calorie foods compared that
with glucose consumption (14). As fructose delivers
a sweet taste without an immediate nutritive input, it
follows that fructose consumption should be associated
with increased appetitive behavior and reactivity to food.
3.4 Sugar and addiction
Sugar has been characterized by some as
an addictive substance, with properties comparable to

Sugar’s impact on the body, brain, and behavior
2258 © 1996-2018
that of drugs of abuse. Nonetheless, explicit evidence
of pure sugar addiction has thus far been limited to
research with rodents. Rat studies have shown that
sugar addiction may be induced by intermittent access
to sugar and in many ways resembles opiate addiction
(36). Rats with 12-hour access to sugar followed by
12 hours of food deprivation showed “bingeing”,
“withdrawal”, “craving”, and cross sensitization to drugs
of abuse, like amphetamine1 (37,38). When these
sugar exposed mice were given naloxone, an opioid
antagonist, they showed withdrawal symptoms as
observed with mice chronically exposed to opioid drugs
(39,36,40). Because the same reward-related brain
structures (i.e., NAc shell, caudate nucleus), respond
to the positive valence and saliency of both sugar and
drugs, there is reason to believe that their mechanisms
of producing addictive behavior as well as physical and
psychological responses are related (41,42,43,44).
In fact, using a free-choice lever pressing paradigm,
Lenoir and colleagues showed that rats nd high levels
of sweetness from non-nutritive saccharin or sucrose
more rewarding than cocaine even for rats that were
already dependent on cocaine (45).
Like other rewarding stimuli, intake of
sucrose induces DA release in the NAc, but after
repeated exposure and conditioning, DA efux is more
prominent in dorsal striatal areas, which are important
for habitual behaviors (46,47). Parallel to changes seen
in opiate addiction, sugar addiction in rats is marked
by an upregulation of dopamine D1 and mu-1 opioid
receptors in the NAc shell, and a decrease of DRD2
in the striatum (48,49,50). However, this effect is much
more pronounced in the NAc of sugar-taking rats while
more evenly distributed across the dorsal and ventral
striatum for morphine-exposed rats (50). Still, deep-
brain stimulation in the NAc shell prevented relapse of
both cue-induced sugar and cocaine consumption in
rats (51).
Evidence of similar predispositions for
sugar and drug-taking further highlight their shared
mechanisms. Alcohol and drug abusers tend to have
a greater preference for sweet foods, especially those
with a family history of alcoholism or drug addiction,
suggesting a genetic component to this association
(52,53). A recent study exploring the heritability of
high sugar consumption and substance use disorders
(SUDs) found that these two phenomena were
correlated, and that both genetic and environmental
factors (59% and 41% correspondingly) explained the
variability in the relationship (54).
3.5 Sugar, obesity, and cognitive functioning
Some scientists argue that the obese brain
is addicted to food, particularly highly processed food
containing added sugar or fat. In both rodents and
humans, lower DRD2 in the striatum is seen in obesity
as in drug addiction (55,56). However, others argue
that only the subset of obesity corresponding to binge
eating disorder (BED) involves food addiction (57).
Cravings for sweets and carbohydrates can partially
mediate the signicant association between addictive-
like eating symptoms and binge eating episodes
(58). As cravings are a core feature of addiction, this
is a necessary component to implicate sugar as a
potentially addictive substance.
The typical pattern of response to glucose
and fructose is somewhat altered in obese individuals.
Compared to lean adolescents, obese adolescents
showed reduced perfusion in the prefrontal cortex
(PFC) and increased perfusion in the hypothalamus
and striatum following a glucose drink (59). In the
fructose drink condition, obese adolescents once again
had reduced CBF in the PFC and increased CBF in the
striatum, especially the NAc, while lean adolescents
did not (59). There also appears to be evidence of
insufcient down regulation of appetite following
caloric intake in adult obese individuals. Using positron
emission tomography (PET) with (11C)raclopride to
measure DA release and DRD2 occupancy in the
striatum, Wang and colleagues showed that obese
individuals had a reduced DA response in the ventral
striatum after consuming a glucose drink (controlling
for sweet taste with a sucralose condition) compared
to lean participants (60, Figure 1). Because DRD2
mediates the inhibition of aversive responses,
i.e. hunger, the reduced DA release with caloric
consumption in obese individuals might contribute to
excess food intake.
Added sugar consumption has also been
associated with cognitive impairments, especially
worsened hippocampal memory function. Rats on
a high sugar/low fat, or a high sugar/high fat diet
show hippocampal-dependent memory decits (61).
This relation appears to be mediated by increased
hippocampal inammation, which is especially
pronounced in the high sugar/low fat condition (61).
Associations in humans support these ndings: greater
relative carbohydrate intake predicted a heightened
risk of mild cognitive impairment or dementia in elderly
people, while carbohydrate intake in school children
was negatively associated with nonverbal intelligence
tests (61).
In contrast, the ketogenic diet (KD), a high-fat,
low-protein and low-carbohydrate diet (e.g., a 4:1 or
3:1 ratio of fat to carbs and protein), has gained traction
to manage different neurological and psychiatric
disorders and promote weight loss. This diet induces
a state of ketosis so that the brain uses ketone bodies
for energy rather than glucose. The diet has shown
consistent clinical benet in patients with epilepsy,
possibly due to the increase of acetone in the brain,
which has anticonvulsant effects (62,63,64,65,66).

Sugar’s impact on the body, brain, and behavior
2259 © 1996-2018
Figure 1. Top: Statistical signicance of dopamine (DA) changes in nucleus accumbens for the contrast glucose > sucralose intake (ΔBPND). Bottom:
Correlation between BMI and brain DA changes. Reproduced with permission from (60).
Other less studied neurological conditions in which
KD has been used are Alzheimer’s Disease, where
daily use of a ketogenic compound lead to cognitive
improvements 45-90 days later (67), and Parkinson
Disease (68). The effects of KD have also been studied
in psychiatric disorders including ADHD, depression,
autism, anxiety, bipolar disorder, and schizophrenia,
but there is currently insufcient evidence available as
to whether the diet shows clinical efcacy (69). Further
research is needed to establish how the benets of the
ketogenic diet may be related to the detrimental effects
of high sugar consumption.
4. SUGAR COMPARED
4.1 Sugar vs. fat
Sugar consumption alone will not lead to
weight gain or obesity--even rats exhibiting addictive
behavior towards sugar do not gain weight (70,71).

Sugar’s impact on the body, brain, and behavior
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The same is true for fat--rats given intermittent access
to fat will binge on it, but will not gain signicant weight
(70). However, like sugar, fat also increases food
palatability, which can lead to hyperphagia. Higher
fat content in food is a large, signicant predictor
of problematic, addictive-like eating in humans
(71). Lower DRD2 may be a risk factor not only for
compulsive sugar-taking but also for fat bingeing; rats
with knocked down DRD2 exhibited more compulsive
eating of highly palatable fat-rich foods (72). Further, it
appears that greater amounts of fat may increase the
likelihood that a food will be consumed problematically,
even in those who do not report consuming food in an
addictive-like way (73).
While fat or sugar alone may not induce
weight gain, together they do. Highly processed
foods, which are often over-consumed, tend to contain
both fat and added sugar (e.g. ice cream, pizza, etc).
Sugar-coating of fatty foods can further increase their
palatability, contributing to overeating and weight
gain. Therefore, sugar and fat eaten together is a
very potent combination with implications for obesity.
Interestingly, rats who binged on a fat-sweet diet
gained weight but did not display the same withdrawal
effects as the sugar-addicted rats (70). Fat intake
may protect against opiate-like withdrawal symptoms
associated with excessive sugar consumption,
despite the other problematic health effects of the
sugar/fat combination.
4.2 Sugar vs. complex carbohydrates
Irrespective of sugar, not all carbohydrates
are associated with adverse health effects. While
some complex carbohydrates, like starches, are
broken down into monosaccharides, others, like the
ones found in fruits, vegetables, and ber-rich whole
grains and legumes, follow a different metabolic
pathway. Unlike sugars, which can be absorbed
in the upper half of the GI tract, certain complex
carbohydrates are not digestible by human enzymes
and must be broken down by microbes in the large
intestine (74,13,75,76,77). Gut microbes produce
short chain fatty acids (SCFAs) as a byproduct of the
fermentation of these complex carbohydrates. The
primary SCFAs produced are acetate, propionate, and
butyrate, which can be used by the body as an energy
source. Complex carbohydrates are more lling than
sugars because SCFAs can increase the release of
hormones and peptides from enteroendocrine cells
that result in increased satiety, thus reducing food
seeking behavior (78).
In direct contrast to the effects of excessive
sugar intake, especially fructose, SCFAs seem to have
multiple health benets including anti-inammatory
effects, antidiabetic effects via suppression of insulin
signaling, inhibition of fat storage, and decreased body
fat and weight (79,75,13,76). As previously mentioned,
sugar ingestion seems to increase the inammatory
response in the body. Excessive sugar intake has been
associated with an increase in diabetes and associated
cognitive impairment mediated by an increase
in inammation (23). Diabetes also involves the
impairment of insulin signaling along with the presence
of low-grade inammation (23). These aspects of the
pathogenesis of diabetes seem to parallel the effects
of fructose on the body (20). Fructose metabolism may
cause inammation by increasing fatty acid oxidation
in the liver and increasing transcription of inammatory
factors (7,8). Therefore, the SCFAs produced by gut
microbes in the digestion of complex carbohydrates
could be a source of protection against the inammatory
effects of a high fructose diet.
The anti-inammatory effects of SCFAs are
also seen in the brain. Gut microbes seem to regulate
the central nervous system via pathways involving the
immune system and the vagus nerve (78,76). SCFAs can
elicit cell signaling by binding to G-protein receptors found
in multiple locations, including nerve bers of the portal
vein, enteroendocrine cells of the intestines, glial cells in
the brain, and adipocytes. This binding seems to suppress
a neuroinammatory response: butyrate treatment has
been shown to protect against lipopolysaccharide (LPS)
inammatory responses in microglia. Despite these
ndings of indirect anti-inammatory effects, propionate
has been shown to promote microglial activation (78) and
the full effects of complex carbohydrate metabolism on
the brain are still unclear. Future research is necessary to
determine whether SCFAs cross the blood brain barrier
to have a more direct effect on the brain and behavior,
including how they might counterbalance the effects of
sugar and food-seeking.
5. CONCLUSIONS AND FUTURE
DIRECTIONS
Sugar is a highly palatable food that triggers
our reward systems due to both caloric input and
taste. Taken in excess, sugar can trigger these reward
systems too strongly, inducing compulsive eating. The
nutritive and taste reward centered in the striatum
and the homeostatic signaling from the hypothalamus
become less effective at communicating with each other
to signal satiety. Added fructose is especially disruptive
because it is not immediately available as an energy
source for the brain, providing a sweet taste without
the accompanying benecial and timely nutritive input.
The following dysregulation of eating behavior in many
ways parallels the compulsive consumption of drugs
in addiction.
When we examine glucose and fructose
separately, added fructose is associated with many
more health risks than glucose. Fructose can
increase food-seeking and lead to fat production and

Sugar’s impact on the body, brain, and behavior
2261 © 1996-2018
storage. It may also be related to neurodegenerative
inammatory disease like diabetes and Alzheimer’s.
As an alternative to sugar, complex carbohydrates in
fruits, vegetables, legumes and ber-rich grains are
fermented by gut microbes, producing SCFAs, which
may counterbalance the inammatory effects of sugar.
The evidence of sugar addiction in rat models
does not clearly translate to humans. Because fat
seems to protect against sugar withdrawal symptoms
in rats, we may be unable to identify pure sugar
withdrawal in humans due to our naturally varied
diet. Nonetheless, overlap between the risk factors,
neurobiological substrates, and behavioral effects
of drug addiction and sugar bingeing suggest that
added sugar is a problematic substance that might
trigger behaviors akin to those of addictive drugs.
The combination of sugar and fat is especially potent
for triggering food overconsumption and weight gain.
While each alone will not cause weight gain, sugar and
fat together are highly palatable and can induce weight
gain and obesity.
Although it is clear that excess added sugar,
fructose in particular, has adverse health effects, further
research is needed to study the mechanisms of these
effects, including how sugar affects the brain. One
particularly pressing line of research is to understand
the direct effects of fructose and SFCAs on the brain.
Although there is preliminary evidence that SFCAs may
counter the inammatory effects of fructose, we still do
not know to what extent they are able to cross the blood
brain barrier and how they are processed in the brain.
This research may have important implications for type
2 diabetes, which has been associated with dementia
and cognitive impairment, as well as for Alzheimer’s
and other diseases (23).
Another future direction of clinical concern is
research trials on dietary interventions for neurological
and psychiatric health, as recent studies increasingly
show adverse effects of dietary sugar on mental health
problems, such as ADHD (80), and sleep duration (81).
More randomized controlled trials on the effects of the
ketogenic diet and similar diets in psychiatric disorders
are needed.
In summary, reducing added sugar
consumption may help to promote healthy eating
behavior and maintain overall physical and behavioral
health. Future research in the form of RCTs is needed
in humans to fully understand the systems-wide effects
of sugar.
6. ACKNOWLEDGEMENTS
The work is supported by the Intramural
Research Program of the National Institute on Alcohol
Abuse and Alcoholism (Y1AA3009).
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Note: 1 Interestingly, rats with 24-hour access to
sugar do not become addicted, perhaps because
free-access prevents the cycle of bingeing,
withdrawal, and craving (Avena, 2008).
Key Words: Sugar, Addiction, Brain, Eating
Behavior, Review
Send correspondence to: Gene-Jack
Wang, National Institute on Alcohol Abuse
and Alcoholism, Laboratory of Neuroimaging,
National Institutes of Health, 10 Center Drive,
Room B2L124, Bethesda, MD, 20892, USA, Tel:
301-496-5012, Fax: 301-496-5568, E-mail: gene-
jack.wang@nih.gov