Episode 1: Neurobiology of food addiction

Three students at UMass have created a podcast to educate people about the misconceptions in food science. In this episode, they discuss food addiction and its similarities and differences to drug addiction. They explain that certain foods high in sugar and fat can act in a similar way to drugs, leading to compulsive consumption and loss of control. They also discuss concepts like glucose metabolism in the brain, dopamine, and the dopamine motive system. The podcast aims to provide a comprehensive understanding of food addiction and address common questions. However, they clarify that they are not experts and the information comes from outside researchers. Hi, welcome to the UMass Food Science Podcast. I'm Gunalan, a food science student at UMass. I and my classmates, Gunja and Suvita, have created this podcast as a part of our interest in educating people about the misconceptions in food science and equipping them with a better knowledge of food by sharing the findings from the research publications. This episode is about food addiction and a few misconceptions surrounding it. This episode will provide you with a comprehensive knowledge of the neurobiology of food addiction and most importantly, some of the key questions we are going to concentrate on includes, what is food addiction? What are the similarities and dissimilarities between drug and food addiction? Is food addiction a valid concept? The idea is that when the information is delivered through your podcast, it will reach a wide audience and more people can listen to it, even when they are doing any automatic tasks like cooking or walking. I'd like to begin by apologizing for the extended duration of this podcast episode. To discuss the concepts of food and drug addiction, we need to review some basics such as dopamine and its motive mechanism. If you already have a background in these topics, feel free to skip using the timestamps in the transcript. If you ever feel like I am using too much technical terms that might be difficult to understand, please bear with me while I simplify things at the end so that everything is crystal clear. Any information in this podcast has zero barriers to understanding, meaning that you don't need to have any technical knowledge to understand all the things that we are going to talk about. First, let's set a theme for this podcast. There have been continuous arguments over the past two decades, both within and outside the scientific community, on whether food and drug addiction are the same or if they are different, because it seems that both drug addiction and obesity result from repeated behaviors and habits that the individual has difficulty controlling despite awareness of undesirable consequences. Food consumption is rewarding in part through the activation of the mesolimbic dopamine pathways. Certain foods, especially those high in sugar and fat, act in a similar way to drugs, leading to compulsive food consumption and loss of control over food intake. We are going to find answers to all these questions from first principles. Before we move on to the episode, I'd like to share a few disclaimers. In the field of biology, specifically in brain science, it is difficult to pinpoint a single cause for the problem. Since there are many pathways and conflicting interactions involved, it is not as simple as identifying a dysregulation and taking a drug to target it. This is not a straightforward process, and as a non-expert, I cannot provide advice on the matter. Also, I want to clarify that the information discussed in this podcast comes from outside researchers and not from our research at UMass. I've included references in the attachment section for you to learn more about the topic. Let's start with the question. So what is food addiction and what do we know about it? Food addiction refers to maladaptive, ingestive behaviors resulting from a shift from primarily homeostatic to hedonic regulatory mechanisms of food intake. What is the homeostatic system? It is basically consuming food for nutrient needs and the hedonic system is consuming food for pleasure experience. We'll discuss more on this in the later part of the episode. For now, before we move into the main theme, let us revise a few concepts to understand the similarities and dissimilarities between food and drug addiction that are glucose metabolism, dopamine mechanism, and dopamine motive system. The first concept we are going to discuss is glucose metabolism in the brain. Glucose metabolism refers to the process by which the brain utilizes glucose, a type of sugar, as its primary source of energy. This metabolic process is crucial for the proper functioning of the brain, including the activities of the prefrontal cortex and the dopamine signaling pathways. To better understand this concept, we can think of a glucose as the fuel that powers the brain, similar to how gasoline powers a car. Just as a car requires a constant supply of gasoline to run smoothly, the brain needs a steady stream of glucose to function efficiently. If the brain does not have enough fuel, that is glucose, it is difficult to power the prefrontal cortex and the dopamine signaling pathways. The second concept we want to understand is dopamine. I think when I say dopamine, many of you might have heard about dopamine from the superman lab podcast. If not, I would highly recommend it, regardless of your background, because it occurs to me understanding that dopamine is a basic math that everyone should know. But for now, let's take a quick look at its mechanism. Dopamine is like an internal currency or reward for every activity we do. Whether it's moving from one place to another, or enjoying a good meal, dopamine is responsible for the feeling of reward we experience. It is basically the letter was in our head that says, yay, you did it. The key thing to understand here is that the dopamine does not increase after consuming food or drugs. I repeat, the dopamine does not increase after consuming food or drugs, but rather right before we consume them as a form of reward. Let's say if you predict a reward and receive it, the dopamine levels will increase above the baseline levels and then return to normal. However, if the reward is incorrectly predicted, the system will be punished and dopamine levels will drop below the baseline as a form of internal correction. The third concept is dopamine motive system. The brain's reward and decision making pathways are governed by two key neural circuits, the direct go pathway and the indirect no go pathway. The direct go pathway is a neural circuit that originates in the ventral tegmental area of the midbrain and projects to the nucleus accumbens in the ventral seatum. This pathway is primarily mediated by dopamine neurons and is responsible for driving goal directed and reward seeking behaviors. When this pathway is activated, it promotes the execution of actions that lead to positive outcomes or rewards. And second is the indirect no go pathway. The indirect no go pathway, on the other hand, originates in the nucleus accumbens and projects to the globus pallidus and the substantial nigra pass reticulata. This pathway is primarily mediated by gamma ergic neurons, that is, gamma amino butyric acid neurons, and is responsible for inhibiting or suppressing actions that may lead to negative outcomes or punishments. Again, go pathway activation leads to positive outcomes or rewards and no go pathway activation leads to negative outcomes or punishments. There are two ways in which this dopamine is released. One is tonic and the other one is basic. Tonic means slow and gradual. Receptors activated by a tonic input typically adopt slowly throughout the stimulation period, conveying information about its duration. Basic means sudden and transient, conveying information about sudden changes in stimulus intensity and rate and promoting rapid adaptation to the stimulus. To put it simply, tonic sounds beep, beep, beep. And basic sounds beep, beep, beep, beep, beep. That is what's happening inside our bodies. In the context of addiction, tonic craving can be likened to the constant underlying desire or urge that an individual feels towards consuming addictive substance or foods. This type of craving is persistent and can be thought of as the background noise that influences long-term consumption habits and the difficulty in abstaining from the addictive behavior. On the other hand, basic craving is acute, intense desire that is triggered by specific cues or contacts such as the sight or smell of palatable food or the environment associated with the drug use. The one thing you want to understand here is that basic dopamine release is critical for reinforcing specific behaviors by signaling unexpected rewards or reward predicting cues. This type of signaling is highly implicated in the associative learning processes that are central to addiction where specific cues become linked to the drug use experience. In drug addiction, basic dopamine responses are often hijacked by the drugs of abuse which can lead to strengthening of drug-associated cues and behaviors. For example, drugs like cocaine directly increase basic dopamine signaling leading to strong reinforcement of drug-taking behavior. Again, while tonic dopamine signaling provides a motivational backdrop, it is the basic dopamine signaling that plays a more direct role in the learning and reinforcement process that are critical to addiction. The dopamine is essential to appropriate feeding in mice and also in any other animals. The dopamine deficient mice or inactive do not eat and die within typically four weeks of birth. Treatment with L-Dopa which is a precursor of dopamine increases food and water consumption. There is a gene called DRD2 which is nothing but dopamine receptor D2 that encodes D2 receptors that is dopamine receptors that mediate all this dopamine reward functions. If it sounds complex, bear with me while I simplify this for you. Besides dopamine, serotonin another neuromodulator also plays a role in regulating consumption. It was found that lower levels of serotonin also called 5-HT are associated with a higher appetite and it is positively correlated to BMI. If you wonder if only these two neurotransmitters regulate the intake of food and drugs, the answer is no. There are many other hormones such as leptin, ziralin and insulin regulate this process. However, these are not the context for our episode. The reason is human eating behavior is modulated by two distinct but related mechanisms as we have discussed earlier. Homeostatic mechanisms which include hormonal regulators of hunger, satiety and adiposity levels such as leptin, ziralin and insulin which act by stimulating or inhibiting appetite in order to maintain an adequate energy balance and non-homeostatic or hedonic mechanisms also known as reward system is activated by dopamine. This is important because both foods that are highly palatable and drugs seems to utilize these pathways and take advantage of them. Listeners may have a question here. Well, you have said that our eating behavior is regulated by two mechanisms but how does our body discriminate between homeostatic and hedonic systems and regulate them? Well, to answer that a study investigated that the difference in the regional connectivity at resting state between obese and lean subjects and found at baseline that is which is at zero level they observed that connectivity between the left insula and the hypothalamus was stronger in obese subjects and connectivity between the amygdala and the ventromedial prefrontal cortex was stronger than lean subjects. After a 48-hour fast they observed increased connectivity between hypothalamus and dorsal anterior cingulate cortex in lean subjects and decreased connectivity in obese subjects suggesting that nutrient deprivation is processed differently in obesity. Also, there is another study which is in line with this found that caloric rich foods appear to affect the brain reward system independently of taste as the dopaminergic response to sucrose is greater than the response to sucralose in mice that cannot detect sweet taste. Basically, they just knocked out the sweet taste receptor genes in mice. Again, you don't have to remember all these brain parts or its mechanisms. This is just for contacts who want to learn more but you may have to remember one thing from this section that is our body can regulate nutritional needs and hedonic pleasures differently. And the last concepts we want to know is before we move on to the main question is the mechanism of addiction. The chronic usage of drugs like cocaine dampens the dopamine signaling therefore in order to get that same pleasure relative to the high level raised upon by consumption of the drug the person has to consume or take higher levels in comparison with the previous magnitude of the exposure or consumption. This pattern of behavior is described as chasing the remembered high because our body needs to remember what is the maximum rise in dopamine when you previously consume any drug and need to consume more than the previous level to have any considerable effects on dopamine. Failure to consume that level of drug would lead to depressive like symptoms, lack of motivation, obsessive-compulsive disorder and impulsivity. Impulsivity is nothing but the tendency to act without thinking. In general, people are attracted to food because it is rewarding and it produces pleasure. The brain recalls not only the taste of the food but also the sense of satisfaction itself as well as the suggestions or behaviors that preceded it. This is where it gets really interesting so it's not only the food or the substance used but also how much pleasure you felt during that moment that decides the reward. This memory grows stronger as the cycle of prediction, seeking and obtaining pleasure becomes more reliable. In scientific terms, we call this process called conditioning. In simple words, the addiction mechanism can be summarized as whenever we consume any highly palatable foods or drug substances which creates a sense of pleasure accompanied by an increase in dopamine and creates a memory of it leading to biological, social or psychological despair. And because of this disparity, our system again urges us to consume it. Then it creates a vicious cycle and the cycle goes on and on and on. And next one of the questions we want to find answers for in this area is how obesity is related to addiction and does all the obese people are food addictor? The short answer is no, they are not same. In fact, they are two different mechanisms. It is fair to say that they are two different compartments and one may or may not interfere with the other only at certain conditions. The reason we want to understand this is that it seems that it is one of the common misconceptions in this area outside of the scientific community. So let's take a closer look. First off, let's define obesity clearly. Obesity is directly related to the decrease in energy expenditure associated with the increase in the consumption of foods. Again, it is decrease in energy expenditure associated with the increase in the consumption of foods with high palatability and energy density. And food addiction is defined by behavioral patterns and experiences relating to eating rather than by weight status. Moreover, it is considered to be separate from those established clinical conditions with which it markedly overlaps, notably eating disorders marked by binge eating. Obesity does not necessarily imply food addiction. Food addiction can also exist in lean subjects. And similarly, obese people do not always have to be food addictive. To put it simply, people with greater than 30 body mass index are obese. Interestingly, fMRI studies, which is nothing but brain imaging studies that detect the activity of the brain by measuring the blood flow to the brain region, to the particular brain region. When the brain works, the blood, particularly oxygenated blood, goes to that part of the brain. And the fMRI take an imaging of it. So that's how fMRI works. So fMRI studies found that higher responsivity to food use in reward and attention region is predictive of future weight gain. And that weight gain is associated with altered reward region activity. They found that body mass index was predicted by greater lateral orbitofrontal cortex activation to food cues and observed a positive correlation between BMI and speed of behavioral response to both apathizing and anapathizing food stimuli. BMI also possibly correlated with response in brain regions that are implicated in attention and reward, such as anterior insula and central operculum lateral orbitofrontal cortex, ventral prefrontal cortex, and superior parietal lobe during the initial orientation to food cues. So let us get into our main theme. Our food addiction and drug addiction are the same. And what are the similarities between them? The increasing studies suggest that a loss of executive function and inhibitory control, a common theme in drug addiction, is likewise associated with obesity. A greater reduction of neural activity to high energy-dense food cues than to lower energy-dense food cues was observed post-surgery, particularly in the ventral tegmental area, ventral striatum, putamen, posterior cingulate, and dosomedial prefrontal cortex. The findings are similar to the substance usage disorder individuals. Overweight adolescents also have reduced cognitive flexibility and poorer decision-making ability in comparison with the healthy weight-matched controls. The poorer decision-making of obese persons means that they are more heavily influenced by immediate rewards and less responsive to future consequences, such as increased weight resulting in poorer food choices. Similar deficits are seen in drug-addicted individuals. The reason a part of the scientific community calls food an addiction is that it's not that people who consume sugar or high energy-dense foods do not know that it is bad and it causes health problems. They knew it. They knew it and they consume it and they cannot stop it because it is so much hardwired in their system. They no longer have control over their decision-making. I think it's fair to say that their system's biology controls them as opposed to their mental thinking. Overcoming these impulses only with willpower is extremely difficult. That's the reason we see a lot of people are having a difficult time reducing weight and overcoming it. Maladaptive eating patterns are associated with a tendency to heavily discount future rewards and focus on immediate gratification, referred to as delayed discounting. Similar attributes have been found in individuals addicted to cocaine, smoking, opiates, and gambling. Heightened delay discounting can increase consumption of both drugs and hyperpalatable foods and reduce attention to long-term health goals such as weight management and healthy eating. To determine whether an addition to drug is comparable to an addition to food, studies examined dopamine release and the availability of DRD2, again, which is dopamine receptor genes in the brains of the obese humans. Studies using PET, which is positron emission tomography, which is another brain imaging technology, and raptopride imaging on human subjects with alcohol, cocaine, heroin, and methamphetamine substance use disorders shows that a defined trait of addition is reduced dopamine release as well as decrease in the dopamine receptors availability in the nucleus accumbens regions of the ventral striatum and the dorsal striatum, again, it is the reward processing areas of the brain, resulting in a decreased neural response to brain forces to compensate for this deficiency of reward. Drug users typically administer themselves larger quantities of the drug over a short period to experience the same reward effect. So is it scientifically correct to say that overeating is an addition? Can we call a food an addition? I think ultimately a few studies concluded that the value of identifying overlapping brain systems involved in regulating the motivational properties of palatable food and drugs of abuse rests on whether such knowledge facilitates the development of therapeutics that reduce problematic overeating and drug use. Available evidence is promising in this regard. For example, the cannabinoid receptor 1, which is antagonist reminoband developed as an anti-obesity drug, facilitates smoking cessation in humans. Similarly, the anti-obesity drug, lorcaserine, has a retaining 2C receptor antagonist, which facilitates smoking cessation. Antagonist is nothing but a substance that interferes with or inhibits the physiological action of another. These findings again suggest that common underlying brain processes are likely involved in overeating and drug use. To summarize in one sentence, although reviewing the studies seems like both food addiction and drug addiction are similar, but we also need to review the arguments proposed that say both are dissimilar. So for now, we are going to discuss the studies that say both food addiction and drug addiction are not the same. So what are the dissimilarities between food and drug addiction? So to answer that, I looked at one of the beautiful studies that is again published in Nature, which proposes as a possible explanation that in the case of food, a consistent increase in the frequency of calorific feeding that may have effects on the dopamine system, similar to those of the infrequent, but much stronger effects of addictive drugs, which explain why consuming drugs are so dangerous because of its relapse conditions. Again, relapse is nothing but returning to the normal state of substance usage after a temporary non-usage period. So it seems that food stimuli modulate endogenous opioids and cannabinoids in the system as a function of palatability as well as it cause delayed decrease of dopamine as a function of increase glucose and insulin. In contrast, the drugs of abuse often increase dopamine through direct pharmacologic effects or indirectly through the opioid nicotine or gamma-aminobutyric acid or cannabinoid systems. Again, to summarize, drugs increase dopamine specifically through direct actions and food in contrast increases dopamine through indirect actions and indirect pathways and systems. Also, there is a couple of two different studies with one study found that participants with cocaine dependence upregulated the norepinephrine transporters in the thalamus of the cocaine users and another study which later found that decrease in the norepinephrine transporters availability was found in the thalamus in obese regions. These findings present a notable difference in neurotransmission between individuals with substance use disorder and those with obesity. The motivation to seek reinforcement is maintained until the animal receives a reinforcer or a predictor that leads to a burst of neuronal findings further enhancing conditional learning. In the case of food, changes in metabolic factors such as leptin or xylene reduces the sensitivity of the dopamine motive system for the food and its predictors after satiety. In the case of healthy individuals and it seems that in obese individuals it is somewhat at least tightly regulated but while in the case of drug it is so different where further stimulation of the system appears to be unreinforced when dopamine levels are overly elevated leading to a higher risk of loss of control with repeated exposure compared to reinforcing foods. So reviewing these studies of the both sides I think we are at the end of the episode to answer the most important question that are what can we conclude from all these findings? Can we conclude that food addiction and drug addiction are same or is it different? I think we can't say that food addiction and drug addiction are the same because attempts to pinpoint the neurobiology of food addiction in humans have generated no consistent or replicated findings overall failing to support the model and in many areas seemingly quite strong enough to contradict it. Currently as opposed to drug mechanisms very little is known about the neurobiological mechanisms that regulate the choice to consume palatable energy dense food at the expense of healthier but less palatable options and the role that intermittency of access to palatable food can play in influencing such choices. But why can't we conclude so? The first reason is that the central feature of the substance addiction do not philosophically translate to food and drug consumption. The second reason is because the assertion that foods have paraplegical effects on the brain demands strong and convincing evidence which has not been found. Another argument often used against the notion of the food that produced disorder is the question of which ingredient in the food is the responsible agent. Again we don't have any answer for this because it seems that calling sugar as an responsible agent is a reductionist approach. Again another brilliant article which is published in Nature authored by researchers Paul C. Fletcher and Paul J. Kenney noted that I'm quoting their points in the article. Indeed core features of substance usage disorders can differ dramatically depend on which substances being used reflecting different underlying neurobiological process at play. For example cocaine use disorder is characterized by cycles of binge consumption interspersed by periods of abstinence with amounts of cocaine use sufficiently to induce intoxication and often exceeding the amounts that the user wish to limit themselves to resulting in overt signs of overdosing. By contrast tobacco use disorder is characterized by remarkably stable and highly regular patterns of daily use with no overt signs of intoxication and binge like consumption not a general feature of the habit. Yet considering the well-known detrimental health consequences of tobacco smoking and the struggle that habitual smokers experience when trying to quit it is difficult to argue that a tobacco smoker is any less addicted than someone who binges on cocaine. It is worth pointing out that until recently tobacco smoking was also the subject of much heated debate about whether it constituted a simple habit or warranted the moniker of full-blown addiction. Before that the same type of debate centered on cocaine when viewed from this perspective it should come as no surprise that overweight individuals who struggle to control their food intake will show brain and behavior abnormalities that are similar in some aspects to the prototypic features of psychomotor stimulant, alcohol, tobacco or OPR addiction yet differ from these disorders in much the same way that this drug addition differs from each other. So what are the future directions and how do we move the field forward? Again here I'm quoting Fletcher and Kenning. First it begins not by assuming that overeating is a form of addiction although it allows for the possibility that ultimately there may emerge evidence to suggest that at least certain forms of such over consumption may show high levels of overlap. Rather the initial aim should be a systematic approach using insights from a drug addition literature to focus and sharpen scientific questions relating to obesity. Second the emphasis should move away from focusing exclusively on similarities between excessive food and substance use and would acknowledge to the importance of difference in the patterns of use. If you can't remember all this that's fine you only need to remember that food like drugs is mediated by dopamine systems and the same regions of the brain. So far through the studies we only know they have some similarities but we don't know exactly what how and why behind the specific pathways of food addiction. Moreover until now there is little to no evidence to say that food addiction is a valid concept. To further simplify just because we do not have enough studies on dissimilarities that doesn't mean we should say that both food addiction and drug addiction are similar. That's all from my side guys. I hope you have learned something valuable and if you want to learn more about what the science-based approaches and tools to overcome food addiction are until the next episode.