Sugar (2) – Is sugar addictive?
The Reward mechanism:
When it comes to energy needs, the hypothalamus (a small region of the brain) is the one that regulates intake; however, this behavior is also stimulated by the dopamine reward circuit (1).
This circuit has been a fundamental part of our evolution, but in modern society, it can easily get out of control leading to unhealthy habits.
In a recent study (2), it was shown that participants were better able to remember the location of high-calorie foods. In other words, spatial memory, in which dopamine plays a leading role (3), could have evolved to prioritize the location of foods with the highest caloric content and not the most nutritious. In fact, the reported pleasure from eating palatable foods is proportional to the release of dopamine in the brain (ventral and dorsal striatum) (4), which suggest that our tendency is the pursuit of pleasure and not necessarily that of properly feeding the body.
Evolutionarily speaking, the dopamine reward system makes perfect sense, since apart from stimulating the search for foods that increase fat reserves for periods of scarcity — it also stimulates other behaviors that create greater chances of survival, such as the need to explore new territories or to transmit genes to ensure the continuity of the species. But this circuit evolved in a very different environment and with a very different availability of food.
In today’s society, where previously scarce foods abound and where we have recreational drugs, pornography and other habits that reinforce this circuit, the reward system has become the main mechanism that has led us to self-destruction.
Through this process, we learn an association between two events, the stimulus and its reward, leading us to respond to the first with the search for the second and learn to do it repeatedly, if this is rewarding.
Not being able to stop checking the cell phone, compulsive eating, gambling, promiscuity, the impulse to buy and drug addiction, among other things, are a consequence of the deregulation of the reward mechanism.
Both in humans and in animal experimentation, it is observed that the choices made are those that lead to an activation of dopaminergic neurons and the withdrawal of states associated with their inhibition. In other words, we live seeking to release dopamine.
When we eat healthy foods that do not create dopamine spikes, the urge to continue eating will decrease as we have obtained adequate nutrition, but as with other factors with potential for abuse such as drugs, use of devices or obsession with the sex, this does not happen with sugar.
The evidence that we have so far indicates that there are several mechanisms that explain the compulsive consumption of sugar.
Among these, we find the activation of neurological pathways between the intestine and the brain, epigenetic alterations and the stimulation of the dopamine reward circuit.
All of these are more related to the taste of sugar than nutrition, but even so, there also seems to be some kind of nutritional reward.
Let’s see a brief description of the possible mechanisms.
Nutrition reward:
In the lateral hypothalamus, are the neurons that express melanin concentrating hormone (MCH).
Animals prefer sugar to non-nutritive sweetener; however, when mice are genetically modified to lack MCH neurons, they do not, suggesting that this pathway encodes nutritional reward, regardless of taste (5).
This could also be confirmed by stimulating the MCH neurons of mice during the consumption of the non-nutritive sweetener sucralose (3). Tricking the mouse brain into responding as if it were receiving caloric energy, which resulted in increased levels of dopamine (striatal area), and even a preference for sucralose over sugar.
To finish corroborating this conclusion, when glucose was infused directly into the stomach in mice to avoid the stimulus of taste, the release of dopamine (dorsal striatum) was also caused, while sucralose did not achieve this effect (6).
Reward in taste:
In a study published in the journal Nature in 2020 (7), researchers found that sugar not only activates the taste buds, but also activates a neurological pathway that begins in the intestine sending signals that travel to the brain, whetting the appetite for sweeter foods. However, this pathway only responds to sugar and not to artificial sweeteners.
Another mechanism related to the sweet taste that can lead to higher sugar consumption may be the alteration of the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1).
To explore these mechanisms in a simpler organism, the researchers fed fruit flies (Drosophila melanogaster) a sugary diet (8).
One group was fed 30% sugar and the other 5%.
After 7 days, they compared the responses of the flies to three different concentrations of sweetness and found that the flies fed the high-sugar diet showed a substantially lower response to the sweet taste compared to the control group. However, a group of flies with mutations in the PRC2.1 complex, showed the same response to sweet taste in both diets, which indicates the important role of this epigenetic regulator in the alteration of taste.
Regarding these observations, researcher and study author Monica Dus stated:
“The mechanisms we discovered are similar to those that lead to depression and anxiety in people experiencing trauma”
“Eating sugar changes the taste system, for what the animal will be trapped in the choice of unhealthy foods, always choosing foods that have a higher sugar content, behavior that leads to weight gain and chronic diseases “
Finally, but in my humble opinion the most relevant for now, is the stimulation of the reward pathway and its main protagonist, dopamine.
Most striatal neurons (striatum) process various reward signals.
Stimulation of striatal neurons with dopamine D1 or D2 receptors leads to impulse or inhibition of choices, suggesting that striatal neurons link the dopamine reward signal with decision-making.
The striatum is made up of two main sections, the dorsal and the ventral striatum, and when it comes to taste or nutrition, the release of dopamine in response to the pleasure of consuming sugar is divided between these areas differently.
The response to nutrition focuses on the dorsal striatum, while the response to taste focuses on the ventral striatum (2). Now, when a component is added to alter the flavor, this does not happen (6), which seems to indicate that the pleasure response in the ventral striatum is due only to taste.
Apart from all these specificities, the important thing is to understand that the reduction in dopamine D2 receptors is clearly a characteristic of addiction and that this reduction, so closely related to drug use, has also been observed in compulsive eating (9,10,11,12).
A 2017 study (9) showed that mice modified to have disrupted D2 receptor signaling in the nucleus accumbens (the brain’s pleasure center), had more persistent and impulsive sugar intake, a worsening in learning flexibility and less efficiency in glucose metabolism. Suggesting that D2 receptors in the nucleus accumbens are essential both for regulating peripheral glucose levels and for learning the reward of their consumption (9).
(TakeAway: Both the nutritional reward and the taste of sugar appear to lead to increased consumption through several mechanisms, including unique neurological pathways for sugar, epigenetic changes, and high dopamine release in various brain regions.
Dopamine is a neurotransmitter that is directly related to compulsive behaviors, which would explain why the dysregulation of this system can lead to overeating and eventually, to what seems to have all the characteristics of addiction.)
So … is the sugar addictive?
“It is very similar to an addiction to opioids”
Dr Lewis Cantley
Impulsive eating induced by sugar is probably mainly due to overstimulation of the brain’s reward systems, which leads to excessive consumption independent of caloric needs. This could partly explain why sugar consumption has multiplied in an exaggerated way in the last couple of centuries (13).
When communication between hypothalamus homeostatic signaling and striatum-centered reward (taste and nutrition) is impaired, cravings and lack of satiety are experienced. These cravings could be involved in the relationship between compulsive eating and binge eating disorder (12,14) and, as cravings are a central feature of addiction, this is another behavior that indicates the addictive potential of sugar (14).
Binge eating and drug use:
Because the same reward-related brain structures respond to both sugar and drugs, the relationship is hard to deny (10,11,12,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31)
More studies:
- Both in obesity and in drug addiction, whether in humans or rodents, fewer D2 receptors are observed in the striatum (10,11).
- After consuming a glucose drink, obese people demonstrated a reduced response to dopamine in the striatum (32).
Since dopamine D2 receptors are also mediators in the suppression of appetite, this could be one more reason why there is a trend towards greater consumption.
- Alcohol and drug users tend to have a greater preference for sweet foods, especially those with a family history of alcoholism or drug addiction, suggesting a genetic component for this association (29,30).
- Another study that could confirm a genetic component is one that was done to demonstrate the relationship between inherited disorders of high sugar consumption and substance use.
This study found that these two phenomena were correlated and that genetic and environmental factors (59% and 41% respectively) explained the variability in the relationship (31).
- The simple fact of giving rats intermittent access to sugar, makes them dependent on this substance, with a type of addiction similar to that which occurs with opiates (19).
- Rats with access to sugar for 12 hours, followed by 12 hours of deprivation, had all the symptoms of dependence including binging, withdrawal, craving, and cross-sensitization to drugs of abuse (20,21).
- When animals exposed to sugar are given naloxone (an opioid antagonist), they show a withdrawal syndrome comparable to mice chronically exposed to opioid drugs (19,22,23).
- In a study using a free-choice lever, they showed that rats find high levels of sweetness more rewarding than cocaine (24).
- Like the changes seen in opiate addiction, sugar addiction in rats is characterized by upregulation of dopamine D1 and mu-1 opioid receptors in the nucleus accumbens, and a decrease in D2 receptors in the striatum (25,26,27). However, this effect is much more pronounced in the nucleus accumbens of sugar-eating rats, whereas for rats exposed to morphine, it is more evenly distributed in the striatum (27).
- When deep brain stimulation of the nucleus accumbens is elicited in rats, both relapse to cocaine and sugar use is prevented (28), which suggests that as with drugs, this is the effect sought through the consumption of sugar.
(TakeAway: Aside from the similarities in behavior and brain chemistry between sugar consumption and drugs of abuse, there are also similarities in withdrawal syndrome.
Sugar releases chemicals related to reward and pleasure, influencing areas specific to the brain as any addictive substance, with a clear association and overlap between its consumption and that of other drugs.)
That said, I leave you with the question:
… Do you think that sugar is addictive?
(Note to parents and especially grandparents: Based on science, we could conclude that excessive sugar consumption in children has the potential to create a dopamine-seeking mechanism that could eventually lead to substance abuse. So, those who tend to think and say, “let the child be happy, ” should consider seriously how much they are affecting that happiness, but in the long term.)
References:
1 – The dopamine motive system: implications for drug and food addiction.
2 – Human spatial memory implicitly prioritizes high-calorie foods.
3 – Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar.
5 – Sugar addiction: the state of the science.
6 – Separate circuitries encode the hedonic and nutritional values of sugar.
7 – The gut-brain axis mediates sugar preference.
8 – Persistent epigenetic reprogramming of sweet taste by diet.
10 – Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction.
12 – Food craving as a mediator between addictive-like eating and problematic eating outcomes. 13 – Sugar consumption in the last 200 year.
16 – Oral sucrose stimulation increases accumbens dopamine in the rat.
18 – Reward system and addiction: what dopamine does and doesn’t do.
21 – Intermittent access to a sucrose solution for rats causes long-term increases in consumption.
22 – A Behavioral and Circuit Model Based on Sugar Addiction in Rats.
23 – Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence. 24 – Intense sweetness surpasses cocaine reward.
25 – Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain.
26 – How can drug addiction help us understand obesity?
27 – Opiate-like effects of sugar on gene expression in reward areas of the rat brain
32 – BMI modulates calorie-dependent dopamine changes in accumbens from glucose intake.
Woow! This is a very nice article! Deep explanation of addictions, not only sugar! Congrats!
Thank you very much.