Sugar addiction: Is it real? A narrative review

Abstract

In animal studies, sugar has been found to produce more symptoms than is required to be considered an addictive substance. Animal data has shown significant overlap between the consumption of added sugars and drug-like effects, including bingeing, craving, tolerance, withdrawal, cross-sensitisation, cross-tolerance, cross-dependence, reward and opioid effects. Sugar addiction seems to be dependence to the natural endogenous opioids that get released upon sugar intake. In both animals and humans, the evidence in the literature shows substantial parallels and overlap between drugs of abuse and sugar, from the standpoint of brain neurochemistry as well as behaviour.

Full text

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DiNicolantonioJJ, etal. Br J Sports Med 2017;0:1–5. doi:10.1136/bjsports-2017-097971
ABSTRACT
In animal studies, sugar has been found to produce
more symptoms than is required to be considered an
addictive substance. Animal data has shown significant
overlap between the consumption of added sugars and
drug-like effects, including bingeing, craving, tolerance,
withdrawal, cross-sensitisation, cross-tolerance, cross-
dependence, reward and opioid effects. Sugar addiction
seems to be dependence to the natural endogenous
opioids that get released upon sugar intake. In both
animals and humans, the evidence in the literature shows
substantial parallels and overlap between drugs of abuse
and sugar, from the standpoint of brain neurochemistry
as well as behaviour.
It has been suggested that refined added sugars are
habit-forming just like cocaine, nicotine, alcohol,
tobacco and caffeine.1–3 In fact, chronic smokers
suppress their cigarette cravings better than their
food cravings.4 Some individuals report increased
sweet cravings after giving up cigarettes,5 likely
accounting for the typical weight gain associated
with quitting smoking.6 In fact, oral glucose may
even decrease tobacco cravings7 and withdrawal
discomfort.5 One study in cocaine-addicted individ-
uals noted that their liking and wanting for food
was even greater than that for cocaine.8 As sweet
foods are the most craved foods, this suggests that
the reward and cravings from added sugars might
be comparable to that of addictive substances.
Indeed, food cravings have significant overlap
with drug cravings,1–3 9 and animal studies show that
sweetness, such as sugar or saccharin, is preferred
even over that of addictive drugs like cocaine.10–14
Once sugar is introduced (even in lab rats already
addicted to cocaine) the rats will almost always
switch over to consuming sugar. This is because the
reward from sugar surpasses that of even cocaine.2
Consuming sugar produces effects similar to that of
cocaine,15–19 altering mood,20 possibly through its
ability to induce reward and pleasure,2 leading to
the seeking out of sugar.2 Others have shown that
foods high in sugar produce drug-like psychoactive
effects.2 21–23
A natural reward from sugar is another evolu-
tionary adaptation, as it would have driven humans
to search out and consume sugar whenever it
was found in the food supply.10 24 The increased
consumption of foods high in sugar (such as ripened
fruit and honey) would have increased the chances
for survival during periods of food scarcity, as sugar
helps us to lay down fat, and when found in nature
generally indicates foods that would have provided
ample amounts of calories.24 Those individuals with
the greatest fat stores likely had a strong evolu-
tionary advantage when it comes to survival during
times of food scarcity. Thus sugar cravings likely
imparted a strong evolutionary advantage.
Unfortunately humans never adapted to the
intense reward that follows the consumption of
highly refined added sugars, and the 24/7 availability
of these sugars provides us with little reprieve. In
other words, we can run from sugar but we cannot
hide. The most common forms of added sugar are
sucrose (table sugar) and high-fructose corn syrup.
Each contains the simple sugars glucose and fruc-
tose. This unnatural reward from consuming sugar
(surpassing that of drugs of abuse) over-rides our
self-control mechanisms predisposing us to sugar
addiction.10 Indeed, sweet substances are extremely
rewarding to humans and other mammals, but there
does appear to be genetic differences in the strength
of this preference for sweetness.10 25–29 And with the
recent ‘sweetening of the world’s diet’, there has
followed a dramatic rise in the consumption of
sugar.30–33 Added sugars have penetrated the food
supplies of virtually every isolated corner of the
world.
The reason why we may not be able to give up
the sweet stuff is because sweet sensations are
one of the most intense sensory pleasures that
humans experience in the modern day.10 Our
seeking out of sugary substances exceeds any
metabolic need.10 And there is no physiological
requirement for consuming a single gram of added
sugar as there is technically no such thing as an
‘essential carbohydrate’ (unlike that for protein
or fat).34 Nonetheless as we previously discussed,
fructose consumption played a critical role in
human evolution. Although individuals can clearly
thrive and survive without any added sugars, the
human species likely would not have survived for
very long without the craving and consumption of
natural sources of fructose.
The issue of attractiveness of sweets in humans
is further complicated by the fact that individ-
uals perceive sweetness differently. The tendency
to experience addiction to refined sugars is likely
rooted in both the sweet taste perception and the
preference of each individual, likely reflecting
genetic factors.35 Thus although humans have the
ability to become addicted to sugar, the tendency to
do so is likely multifactorial.
DOES SUGAR BEHAVE LIKE A DRUG?
Nowadays, sugar has been refined to the state of a
chemical-like substance. Indeed, when sugar cane is
crushed and drained of all its liquid contents, boiled
down to a syrup, shaken and then stripped of all its
vitamins, minerals and molasses, we are left with
pure white crystals. This extraction and refinement
process is similar to that of other addictive white
crystals, that is, cocaine from the coca leaf, and
opium from the poppy seed/pod.36 Thus, it is the
Sugar addiction: is it real? A narrativereview
James J DiNicolantonio,1 James H O’Keefe,1 William L Wilson2
Review
To cite: DiNicolantonioJJ,
O’KeefeJH, WilsonWL.
Br J Sports Med Published
Online First: [please include
Day Month Year]. doi:10.1136/
bjsports-2017-097971
1Saint Luke’s Mid America Heart
Institute, Kansas, USA
2Lahey Health and the Wilson
Institute of Neurobiology,
Burlington, USA
Correspondence to
DrJames JDiNicolantonio,
Saint Luke’s Mid America Heart
Institute, Kansas City, USA;
jjdinicol@ gmail. com
Accepted 1 August 2017

2DiNicolantonioJJ, etal. Br J Sports Med 2017;0:1–5. doi:10.1136/bjsports-2017-097971
Review
refinement of sugar that significantly adds to its addictive prop-
erties.
During our evolutionary history we only had access to fruc-
tose in honey, fruits and certain vegetables, and in these sources
fibre and other substances are present that slow and limit the
absorption of the fructose. With low levels of fructose consump-
tion typical of our evolutionary history, about half is converted
to glucose and a quarter is converted to lactate. Very little fruc-
tose is converted into fat when consumption is at a low level
and fatty acid synthesis is also not upregulated. Thus throughout
our evolutionary history humans consumed a small amount of
fructose on a regular basis and this did not cross the fat storage
threshold. It is only when they occasionally binged on fructose
after finding a beehive or large supply of ripened fruit would they
store extra fat. Importantly, the natural antioxidants contained
in these natural foods would have decreased the formation of
‘inflammatory’ fat stores (unlike that with the consumption of
added sugars).
But does sugar behave like a drug of abuse? It has been noted
that the same increase in dopamine D1 receptor binding and
decreased D2 receptor binding in the striatum that occur with
cocaine administration also occur with intermittent access to
sugar or glucose.17 Rats with intermittent access to sugar also
have the same decrease in D2 receptor mRNA in the nucleus
accumbens that occurs with morphine and cocaine. Moreover,
the same increase in μ-receptor binding that occurs with cocaine
and morphine occurs with intermittent sugar intake. And finally
the same release of dopamine and reduction in extracellular
acetylcholine in the nucleus accumbens (indicating tolerance)
that occurs with injecting morphine occurs with bingeing on
sugar.17 Figure 1 provides a schematic of sugar addiction.
The sugar–drug connection goes even further as ‘addiction
transfer’ may occur between sugar and drugs of abuse and
alcohol.37 Some overweight patients may transfer their addic-
tion to high-sugar foods over to addictive drugs after weight
loss surgery. In one study, weight loss surgery patients who
reported preweight loss surgery problems with high-sugar
foods were the most likely to have new-onset substance use
disorders after surgery.37 Box 1 summarises how added sugars
(refined sugar and high-fructose corn syrup) behave like drugs
of abuse.
In order to understand if sugar is addictive, we need to under-
stand drug addiction. Take for example opiate addiction, which
can be diagnosed if naloxone (an opiate antagonist) produces
subsequent withdrawal signs. Shockingly, this is exactly what
occurs when animals are fed sugar and then given naloxone.
More importantly, the withdrawal that occurs with naloxone in
these animals eating sugar is similar to that found with nico-
tine or morphine. Sugar addiction seems to be a dependence on
the body’s own natural endogenous opioids that get released on
sugar intake.38 Indeed, there are substantial parallels and overlap
Figure 1 Schematic of sugar addiction
Box1 How added sugars behave like addictive drugs of
abuse
►Behaves like a chemical or drug—due to its ‘pure’ white
crystalline form, which is readily absorbable leading to
unique metabolic harms1
►Habit-forming just like alcohol, tobacco, cocaine, nicotine,
tea, coffee and chocolate1–3
►Induces reward and cravings comparable to addictive drugs,
being more rewarding than cocaine3
►Alters mood,4 induces reward and pleasure,3 leading to the
seeking out of sugar3
►Produces drug-like psychoactive effects3 5–7
►Produces cravings comparable to that of cocaine, sex and
cigarettes3 8 9
►Can produce dependence/addiction (eg, bingeing,
withdrawals and cravings) indicating sugar can be
addictive10

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DiNicolantonioJJ, etal. Br J Sports Med 2017;0:1–5. doi:10.1136/bjsports-2017-097971
Review
between drugs of abuse and sugar, from the standpoint of brain
neurochemistry as well as behaviour.
So back to the question, is sugar addictive? The term addic-
tion is generally reserved for drugs of abuse (ie, cocaine, heroin,
morphine, nicotine and alcohol) and is many times used synon-
ymously with dependence.17 The Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition (DSM-5) defines
‘substance use disorder’ (ie, addiction) if at least two to three
criteria (symptoms) exist from a list of 11. This was a change
from DSM-IV, which categorised both substance abuse and
substance dependence as separate disorders, and substance
abuse only required one criterion. In DSM-5 these two catego-
ries have been combined into ‘substance use disorder’. It is also
interesting to note that binge eating disorder has been added to
DSM-5. Sweet and high-fat foods are preferred by those with
binge eating disorders and that those preferences are mediated
by the endogenous opioid system.39
In animal models, sugar produces more symptoms (eg, crav-
ings, bingeing, tolerance and withdrawal) than is required to be
considered an addictive substance.36 So we can be quite confident
that sugar is indeed addictive in animal models. In fact, animal
data demonstrate significant overlap between the consump-
tion of added sugars and drug-like effects,10 40–42 producing
(1) bingeing, (2) craving (a strong desire to ‘use’), (3) tolerance
(gradual escalation in intake with repeated use), (4) withdrawal
(adverse physiological signs with discontinuation of use), (5)
cross-sensitisation (increased response to drugs of abuse), (6)
cross-tolerance (animals become tolerant to the analgesic effects
of morphine after chronic intake of sugar and saccharin),43 44
(7) cross-dependence (suppression of withdrawal symptoms with
certain drugs),38 45 46 (8) reward47 48 (intense dopamine release
in the brain),17 49–51 and (9) opioid effects, such as the release
of endogenous opioids on consuming sweet substances,44 46 52
symptoms of narcotic withdrawal when an opiate blocker is
given, and other neurochemical changes in the brain.17 36
A person may become addicted to sugar due to dependence on
his or her own endogenously released opioids.38 This is particu-
larly revealing when looking at patients with anorexia who may
be ‘addicted to starvation’ by the same dependence pathway
that occurs when eating sugar (ie, addiction to endogenously
released opioids that occurs during starvation).53 If anorexia can
be classified as a disease, and is apparently the body’s addiction
to its own endogenously released opioids, then sugar addiction
(dependence to endogenously released opioids on consumption
of sweets) should also be able to fall under the classification of
a disease.
IS SUGAR ADDICTIVE IN HUMANS?
In the purest sense, addiction is simply a psychological depen-
dence, but also a physiological dependence to sugar.17 While
there is not a universal agreement for the definition of addic-
tion, certain characteristics must be present in order to diagnose
an addiction (ie, cravings, tolerance and withdrawal), otherwise
known as the ‘addiction triad’. In order for sugar to be truly
considered addictive, it must be able to induce a withdrawal.
And in order for humans to have withdrawals from sugar, a
threshold must be reached. Thus, a certain dose of sugar needs
to be consumed for a certain of time whereby neurochemical
changes occur in the brain. This period of time likely varies from
person to person based on genetic differences.
It just so happens that after several weeks to months of chronic
sugar intake, the period in between sugar intake may cause
‘dopamine deficiency’ in the brain due to downregulation of the
dopamine D2 receptors and a reduction in binding of dopamine
to those receptors.54 But why is dopamine deficiency in the brain
a problem?
When the brain is low in dopamine, this can then lead to
withdrawals. And it is the withdrawal that can lead to continued
perpetual sugar intake leading to addiction. But the withdrawals
from sugar are less obvious compared with addictive drugs.
Indeed, people are not visibly ‘strung-out’ on sugar, nor do they
have life-threatening or even physically apparent withdrawal
signs. But this does not mean that sugar withdrawal does not
exist in the brain. In fact, the lack of dopamine in the brain
during periods between sugar consumption has been suggested
to lead to attention deficit hyperactivity disorder (ADHD)-like
symptoms such as, hyperactivity, attention-deficit, distraction
and decreased performance.54 In essence, ADHD-type symp-
toms could be a sign of ‘withdrawal’ from eating refined added
sugars.
In fact, obesity, ADHD and drug addiction to cocaine and
heroin all share the same downregulation of the dopamine D2
receptors in the brain. This suggests that all three conditions
have the same underlying issue (dopamine deficiency). During
periods off sugar, a mild state of depression may ensue due
to dopamine deficiency, which can be temporarily relieved by
consuming more sugar (hence the term ‘sugar fix’). This leads to
an endless and vicious cycle of dopamine highs and lows, perpet-
uating continued sugar intake and dependence on its intake.
Sugar and high glycaemic carbohydrates also have an effect on
brain serotonin. After consuming a meal high in sugar or carbo-
hydrates, there is a surge in brain serotonin. In other words,
people may overconsume sugar because it makes them feel better.
Over time this may lead to depletion of serotonin in the brain
perpetuating sugar dependence. As we have discussed, these
patients also tend to be dopamine-deficient with downregula-
tion of dopamine receptors. This combination may well explain
the association of obesity with many other brain disorders like
depression, anxiety disorders, bipolar disorder and ADHD.55
After consuming large amounts of sugar, a drop in blood
glucose may cause further sugar dependence. Throughout our
evolutionary history, low blood glucose levels meant ‘it’s time to
eat’, and if given the chance it made perfect sense to eat some-
thing with sugar or starch, the fastest way to restore normal
glucose levels. Ramped up hunger and sweet cravings were
Mother Nature’s means of accomplishing this critical task. But
today with a constant supply of added sugar readily available,
advocating the consumption of sugar as a treatment of low blood
glucose levels may make the situation worse. Since it is now
estimated that around 110 million Americans have insulin resis-
tance,56 much of the population could be at particular risk for
sugar addiction.
SUGAR ADDICTION MIGHT PREDISPOSE TO DRUG
ADDICTION
Sugar produces drug-like effects that may increase the risk for
drug addiction.17 Indeed, sugar may have a ‘gateway effect’ as it
cross-sensitises with drugs of abuse.17 However, these effects are
not always reproducible and more work in humans is required
to fully elucidate these effects. The consumption of sugar has
even caused an increase in the intake of alcohol during periods
of sugar abstinence.17 Rats given daily amphetamine injections
become hyperactive after tasting sugar.17 And this occurs even
when low doses of amphetamine are used. Sugar has also been
found to cross-sensitise with cocaine,17 and can lead to sensiti-
sation to the dopamine agonist quinpirole.17 These data suggest

4DiNicolantonioJJ, etal. Br J Sports Med 2017;0:1–5. doi:10.1136/bjsports-2017-097971
What is already known?
►Substances of abuse are acknowledged throughout the
medical community to have the potential to be addictive.
►Sugar consumption has increased in parallel with its
introduction in the food supply.
►Sugar may drive increased food consumption, obesity and
diabetes.
What are the findings?
►Animal studies have confirmed that the reward for sugar can
surpass that of cocaine.
►In animal studies, sugar produces more symptoms than is
required to be considered an addictive substance.
►In animal studies there is overlap between the consumption
of added sugars and drug-like effects (eg, bingeing, craving,
tolerance, withdrawal, cross-sensitisation, cross-tolerance,
cross-dependence, reward and opioid effects).
►Sugar addiction may be a dependence to the natural
endogenous opioids that get released on sugar intake.
►In both animals and humans there are substantial parallels
and overlap between drugs of abuse and sugar, from the
standpoint of brain neurochemistry as well as behaviour.
Review
that sugar consumption may sensitise the brain dopamine system,
contributing to addiction and polysubstance abuse.17 More-
over, animals that prefer sweetness will self-administer cocaine
at a greater rate,17 which may be due to sugar’s dopaminergic,
cholinergic, opioid-mimicking effects and stimulant-mimicking
effects like dexamphetamine, methylphenidate and modafinil
(although smaller in magnitude).17
Postingestive glucose can activate the brain dopamine reward
circuit independently of sweet taste,57 and that sweet appetite
may even be stimulated by the presence of glucose in the gastro-
intestinal tract.58
Unlike drug or alcohol addiction, in general sugar addiction has
little direct negative social impact on individuals or their fami-
lies. Sugar addiction does have one clear impact on our collective
health—it makes us fat and metabolically sick. The fructose in
sucrose, honey, high-fructose corn syrup and fruits has little
impact on fat storage when it is consumed in small amounts.59
This was clearly how humans interacted with simple sugars most
of the time in the past. Our ancient ancestors would binge on
fruit or honey when it was available, but these episodes were
clearly sporadic. In today’s world with the 24/7 availability of
highly processed food loaded with added sugars, these episodes
of craving and bingeing would almost be constant, leading to a
markedly increased intake of fructose. Excessive consumption
of fructose promotes fat storage especially in the liver .60 This
supports the old adage ‘the dose makes the poison’.
Based on the aforementioned evidence, sugar meets many of
the criteria for a substance of abuse and could be potentially
addictive in humans. Changes that occur in the brain neuro-
chemistry with drugs are similar, although smaller in magnitude,
to those that result from sugar intake. Because of the nature of
addiction, simply telling people to consume less sugar is unlikely
to be successful. The focus of the medical profession should
be on finding treatments that suppress or eliminate these crav-
ings. Varenicline (Chantix) is approved by the Food and Drug
Administration as an aid to quitting cigarette smoking, and it
also markedly decreases cravings for sugar.61 There are a few
case reports suggesting that varenicline might be effective for
weight loss.
Certain supplements such as chromium picolinate and L-glu-
tamine have been reported to curb sweet cravings, but to date
research on these supplements has been limited. Chromium
picolinate appears to be especially effective for patients with
binge eating disorder and depression.62 Unfortunately as is the
case of many supplements, at the present time we are lacking
large controlled studies using these supplements.
In conclusion, now is the time to kick the habit and say
goodbye to the sweet stuff for good. Hopefully in the future we
will have more effective medical treatments that will help us in
this critical endeavour.
Contributors JJD performed the literature search and wrote the initial manuscript.
JHO’K and WLW reviewed, edited and wrote sections of the final manuscript.
Competing interests JJD is the author of The Salt Fix and operates the website
thesaltfix. com WLW sells a supplement that contains both L-glutamine and
chromium picolinate. JHO’K owns and operates a nutraceutical company.
Provenance and peer review Not commissioned; externally peer reviewed.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2017. All rights reserved. No commercial use is permitted unless otherwise
expressly granted.
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