Thank you for joining us today for this very special topic, Food for Thought, Mindful Nutrition in Mental Health. The objectives we're going to talk about are the importance of nutrition in psychiatry, the role of gut microbiota, and what we can do to help improve the situation. Next, each of us will talk on different aspects of nutrition and its intersection with mental health. Me and four of my colleagues will follow in order, and each one will touch on a different subject. It's fallen upon me to start the introduction, as well as present an overview, which my co-presenters will further explore. I'm Dr. Bharu. The concept of food as medicine is rooted in our most ancient of healing traditions, including Indian, Greek, and Chinese traditions and medicine. It is likely that the hunter-gatherer ancestors of ours learned about medicinal herbs by observing animals deliberately eating certain plants in their diet to treat different health issues. For all of nature and throughout the history of medicine, there has never been any real separation between food and medicine, as can be seen by some of the philosophies stated here. Next, certain well-established guidelines exist of what to eat in conditions such as cancers, diabetes, hypertension, obesity, osteoporosis, and stroke, and some others. Some of the medical specialties give advice about diet and its significance, more so than we do. Coming to the topic of nutrition, food, and our current DSM. Does our food and drink affect how we feel, think, and behave? The role of diet in the mental health is yet to be fully grasped and understood. So, how much nutritional information do we know, and how much of what we know do we incorporate in the management of patients that see us? We know that appetite and nutrition are addressed in two chapters in DSM-5. The first one is mood disorders, where appetite appears as a criterion in number three, and the other one is a full chapter devoted to feeding and eating disorders, in which seven different disorders have been enumerated. Next. Coming to first, nutrition and mental health, before we move on to other subjects. We now know that good nutrition may play an important role in the prevention, development, and management of certain mental health conditions, such as depression, anxiety, ADHD, and dementia, maybe even in OCD, bipolar, and psychotic disorders. We are also well aware that consuming a diet that provides adequate amounts of complex carbohydrates, essential fats, and fatty acids, amino acids, vitamins, minerals, and water can totally support healthy neurotransmitter activity, as well as protect the brain from the effects of oxidants, which we know affect mental health. Next. Speaking broadly, there are two groups of foods that have been identified which can have a negative effect on our brain function. The first group is that which tricks the brain into releasing neurotransmitters that may be lacking at that time, thus creating a temporary alteration in mood. Examples, the classic ones, are caffeine and chocolate. The other group is foods that may damage the brain by preventing the necessary conversion of other foods that the brain requires. Examples of this can be found in saturated fat, such as butter, lard, and palm oil. Next. A diet that is rich in essential fatty acids and low in saturated fats protects by slowing the progression of memory loss and other cognitive problems of the aging process. Thus, we know that if we eat right, we may be able to prevent or ameliorate some of the problems that come with aging, particularly memory loss and cognitive issues. We have also come to realize that people who live in the Arctic and subarctic regions, their levels of depression are rising just as their diets are changing from those of the traditional diets which used to be high in essential fatty acids and being replaced by processed foods. Next. We have now come to identify six different ways in which food, medication, and mental disorders intersect. And they are not in any particular order of importance, but these are the six that demand that we pay attention to them. The first one is the mental disorder itself can lead to dysfunctional eating habits, as is seen particularly in psychosis and in depression. We also know that deficiencies of certain nutrients may be a risk factor for mental disorders, and this will be talked about further in the latter slides. Diet and medications influence the gut microbiota, which in turn could affect metabolism as well as appetite and mood. And we have one particular co-presenter talking on this in great detail. We have psychotropic medications that may lead to deficiencies of nutrients. This is also commonly known. We also know that foods may alter the absorption, metabolism, and excretion of medications. And finally, deficient amount of some nutrients may prevent medications from effectively treating mental conditions. All of these we are going to bring about a little more detail in each of these topics. Next, please. This is another very important pathway that we should discuss somewhat more in detail, because these are the five different pathways that have been implicated in mental illness, and they can be modulated by diet. The keyword here is modulation by diet. And these five pathways that have been identified at the current time are chronic, low-grade inflammation, oxidative and nitrosative stress, microbiota gut-brain access, altered neurogenesis, and finally, mitochondrial dysfunction. Of course, to show we have a lot of work to do in this area yet. Next. Coming now to the interactions between food and psychotropic medications. The United States Food and Drug Administration have given us a guideline. That guideline being the fact that high-calorie and high-fat meals are more likely to produce the greatest adverse effects on the gastrointestinal physiology and subsequent systemic drug availability. Let's talk more about some of the items that are consumed on a regular basis by many of the population. Alcohol. We all now know that alcohol is a CNS depressant, and alcohol comes in various shapes and sizes. And if they are consumed along with sedative medications, the effect could be drowsiness, dizziness, and impaired cognition. On the other hand, there is a stimulant that is very commonly used by most people in the form of caffeine. Excessive intake of these caffeinated drinks can potentiate the adverse effects such as tachycardia, restlessness, and tremor, particularly when taken with stimulant medications. And we all know of the psychiatric emergencies that can come out if a person is prescribed MAOIs, along with if they eat tyramine-rich foods. Next, please. Here is a sampling of some of the medications with directions of when they should be consumed in relation to the timings and the quality of food. These, by the way, all come from the package insert indicator. Next, please. Coming now to the area of metabolism and how it affects by various medications. We know that amphetamines are better absorbed under alkaline conditions. What does that mean? Every time we prescribe an amphetamine, we have to tell the patient, go easy on those drinks, the sodas, the juices, and some of the fruits, which might create an acidic condition. The other important point to note is that highly protein-bound psychotropics, such as valproate, SSRIs, and antipsychotics can get easily displaced by other drugs or food stuff which bind to the same sites. And mind you, there's always a caution that is mentioned whenever lithium is prescribed, because with lithium, the changes can occur, which can affect if a person's dietary sodium changes from low to high on a day-to-day basis. Next, please. Some more metabolic interactions that we should know. These particularly pertain to the CYP enzymes. And as far as the 1A2 is concerned, we know that charbroiled meat and broccoli, if consumed for more than five days, induces the activity as seen as increased metabolism of caffeine. There are three medications which are partially metabolized by this enzyme, clozapine, olanzapine, and duloxetine. The other important point to note is that grapefruit juice inhibits the first-pass metabolism of various CYP3A substrates, remember, in the intestine, only during the first-pass metabolism. What does this mean? This means that it leads to increased systemic exposure, sufficient to produce adverse effects, particularly if taken along with buspiron and diazepam. Here is something to take home. Never, whenever you're prescribing buspiron or diazepam, tell the patient, grapefruit juice should not be part of your itinerary. Though, of course, there are other CYP3A substrates such as clozapine, alprazolam, and haloperidol, which have seen not to be affected by grapefruit juice. Next, please. One more example. We all know that meal rich in carbohydrates triggers the release of insulin, which might cause a slight increase in the influx of tryptophan into the brain. And guess what? Tryptophan affects serotonin. The other point is depression. Whenever there is depression, and if a person has high cholesterol in their blood, be careful when you're prescribing them a low cholesterol diet or giving them medications. And if they are on those medications, be aware that depression might be more challenging to treat. The third point to take home is that SSRIs inhibit absorption of calcium into bones, which means what? Check the blood calcium level. Make sure it is adequate enough so that at least we don't deprive the bones of their calcium. One more important point of folate. We have seen folate levels are reported to be low in those who have major depressive disorder. We also know that sometimes anti-depressant treatments do not work as well as they expected to be working on. The culprit could be folate. Make sure you prescribe folate anytime somebody is coming up with treatment-resistant depression. Next. We are now going to talk about a few specific conditions of which we know a little more and how they intersect with nutrition. The first one that comes to mind is depression. The International Society for Nutritional Psychiatry Research has given guidelines to us for the adjunctive treatment of major depressive disorder with omega-3 fatty acids. Remember, while earlier we were talking of folate, now we are in the realm of omega-3 fatty acids. The recommendation is either pure EPA or EPA combined with DHA. The combination ratio should be higher than 2 to 1. The dosage of this should be providing at least 1 to 2 grams of net EPA daily. This should be done for at least 8 weeks. I don't think that should be a problem when we are prescribing medications. The other important point which I found was in a SMILES trial which took place in Australia and New Zealand, where they found that about a third of the patients who enrolled in that trial and who incorporated dietary intervention, such as eating less of junk food and more nutrient-rich foods such as fish, produce and legumes, they achieved remission from depression. An important point to note as we go along. Coming to post-traumatic stress disorder, we're going to talk about the neurotransmitter glutamate, which we know is an excitatory neurotransmitter, something that we could probably use in our treatment of PTSD. Glutamate is available in diet in the form of monosodium glutamate, commonly known as MSG, and sources which are rich in this item are Parmesan cheese, soy sauce, walnuts, processed meats and dried shiitake mushrooms. Consuming a diet that is low in glutamate has been known to improve anxiety and PTSD. The other food that has shown some promise is that of blueberries. Blueberries protect against inflammation. Remember earlier the slide mentioned chronic low-grade inflammation? Here we are talking about that. Blueberries are known to protect against inflammation associated with PTSD through a decrease in the levels of inflammatory cytokines and by scavenging free radicals. This leads to an increase of serotonin without the increase of norepinephrine. Isn't that wonderful? Because by increasing serotonin without increasing norepinephrine levels, they're able to enhance resiliency behavior as indicated by reduced anxiety levels. Next, please. Coming to obsessive-compulsive disorder, here again we talk about serotonin and glutamate. Though glutamate has not been known to know much about it, let me tell you about glutamate. It plays a key role in the development of normal corticosteroids, palomocortical circuits, along with GABA, and variations can play a role in the development of obsessive-compulsive disorder. To that end, we have to make sure that we have a proper and not an abnormal amount of intake of glutamate. Along with that, let's talk about tryptophan. Increased dietary tryptophan has resulted in fewer depressive symptoms and anxiety in obsessive-compulsive disorders. SSRIs right now are supposed to be the main line of treatment for obsessive-compulsive disorder. However, 40% of those who are on SSRIs, even in higher doses, do not show a clinical response. Is abnormal glutamate metabolism that is at fault? We don't know yet. However, we do know that an acetylcysteine, commonly called NAC, which is a derivative of L-cysteine, has shown promise in the treatment of OCD, and various regular foods have cysteine. ADHD, attention deficit hyperactivity disorder, patients are known to have deficiencies in iron, magnesium, and zinc. And also, it has been reported that having an adequate amount of essential fatty acids and minerals, such as iron, provide benefits for ADHD symptoms. There was a study done by the University of Barcelona, where the kids were all supposedly on a Mediterranean diet, but when they put them in different groups, they realized that those who were skipping breakfast and consuming fast food, sugar, and soft drinks, they had a higher prevalence of diagnosed ADHD. And those who started eating more vegetables, fruit, fatty fish, showed decrease in the ADHD symptoms. Next. Lastly, we do not know much about nutrition and how it applies to bipolar disorder and psychotic disorders. All we know is that patients with bipolar disorder tend to have a poorer quality diet with increased sugar, high fat, and carbohydrate intake. And as far as schizophrenia concerns, it is seen that those with lower levels of polyunsaturated fatty acids in their body and lower antioxidant enzymes in their brains. What does this mean as far as nutrition goes yet to be decided and determined? That sort of brings me to the end of my talk, and now I'm going to hand over to Dr. Jonathan Bui. Thank you. Thank you, Dr. Bharu. I'm Dr. Jonathan Bui, and today I'll be discussing diets and their effects on health. Next slide, please. So there's a variety of different diets out there in the world. You have the Asian diets, Nordic diets, Mediterranean diets. There's a whole host. Of the diets to which I decided to focus upon, I really looked at those which have been very popular in the West and have been kind of either diets that people normally eat, such as the Mediterranean diets, or other weight loss diets or other fad diets that people have used, such as the ketogenic diet or the paleo diet. So next slide, please. Of the first diet I'm going to discuss, it is the DASH diet. It's the Dietary Approach to Stop Hypertension diet. It's essentially a diet that was designed in order to help patients lower their blood pressure, and it's based, for the most part, upon consuming plant proteins from nuts, legumes, as well as eating fruits, vegetables, and low-fat dairies. Aside, it also restricts the amount of red meats, sweets, as well as sugar-sweetened beverages. And aside from hypertension, as well, this diet has also been recommended for those to prevent cancer, osteoporosis, heart disease, strokes, and diabetes. Next slide, please. When it comes to this diet, though, there is a theoretical basis for how this diet can help improve mood. Notably, this diet is high in potassium, magnesium, and calcium, while having a low sodium content. One of the theoretical models for this is that having a high serum to potassium results in a progesterone secretion, which in turn can change neural activity and lead to overall low mood. So by limiting the amount of sodium you take, we can correct that balance, and therefore it leads to decreased progesterone secretion. That said, though, an interesting quirk of this is that it was previously thought that decreased sodium led to the activation of the renal angiotensin system, which in turn leads to activation of aldosterone secretion, which is itself associated with depression. That said, though, this diet does have high magnesium, which may offset this. In the past, magnesium has been used to supplement depression. What this really elucidates is that we need further research into the relationship between magnesium and sodium. Aside from that, magnesium is also beneficial on its own in that it can block the activity of NMDA, which in turn can induce an antidepressant effect and boost our mood. Furthermore, low magnesium levels on their own are associated with low serotonin. This diet is high in fruits and vegetables, which in turn means that there's a high antioxidant behavior, which again may improve mood. And indeed, the results of this study indicate that there is an improvement in mood and the POMS global score, as well as improvements in anger, confusion, fatigue, tension, and vigor per the POMS. That said, though, the study that did look at this, which was high quality in nature, did a crossover design study, which though given these results were great, but given the crossover design nature itself makes it hard to draw a causal link between the effects noted here and the intervention. But overall, this is the benefits that occurs from going to the DASH diet. Next please. The next diet I'm going to discuss is the Mediterranean diet, which is a diet that's in many ways variable in its nature. It largely consists of fish, fruits and vegetables, whole grains, legumes, and olive oil, but depending on where it's made, it can vary in its content. The Greek Mediterranean diet, for example, is different than the French Mediterranean diet. Indeed, this is a diet that can change based on location and culture. That said, though, the common characteristic of this diet is that it's rich in essential fatty acids, magnesium, lean protein, and antioxidants. Next slide please. So as for the benefits of this diet, it's supposed to have benefits for vigor and confusion per the POMS. As for mechanics, how it does so, this diet is rich in essential fatty acids, magnesium, lean protein, and antioxidants. Furthermore, this diet is supposed to be high in omega-3 as well. This is important because omega-3 can reduce the production of pro-inflammatory cytokines, that is to say, in leukin-1, in leukin-6, to the necrosis factor alpha, and thus can stabilize membranes and improve mood. Furthermore, omega-3 can also increase BDNF, or brain-derived neurotrophic factor, which in turn is involved with survival of existing neurons, as well as growth and differentiation of brain neurons as well, which again will have the impact of improving mood. The big thing overall is that this diet has also been noted to decrease cholesterol, and cholesterol in general is associated with depression, but for the most part, based on the studies that we have here, it did show that using this diet and having low cholesterol actually resulted in improvements of mood. The big issue with the study, though, is that, at least with the Waddle study that I listed here, is that the study which showed a benefit for Mediterranean diet didn't necessarily show any advantage over other cholesterol-lowering diet as well. Again, mood improved for both, but there wasn't any significant benefit between the two of them, which brings the question of whether or not it's the diet itself or the idea that you're taking a consistent diet, having improvements to your health, and overall having psychological improvements from being able to maintain a better healthy lifestyle. But again, that's the theoretical basis for how the Mediterranean diet can help improve mood. Next slide, please. The next one is the vegetable-based diet. These diets are grouped together, but they're more or less broken down into two subcategories, the vegetarian diet, which are those without meat, fish, or poultry, but you're allowed to use animal-derived products, so cheese, milk, and eggs. Contrast that with the vegan diet, which are more or less the same as above, but you can't use any animal products, so that's no milk, cheese, or eggs. Next slide, please. As for the benefits of this diet, it's been noted that there has been improvements of attention, depression, anger, and fatigue, as well as improving the stress and anxiety in these diets. The theoretical basis for why is that these diets are a good source of phytochemicals and antioxidants, the big things that phytochemicals, or chemical compounds, synthesize by plants in order to protect against pathogens. They're further subdivided into carotenoids and polyphenols. Polyphenols themselves are associated with increased brain serotonin levels, increased BDNF, reduction in MAOA A slash B, as well as reduction in inflammatory biomarkers. Furthermore, arachidonic acid is another important factor that can affect our mood, specifically that arachidonic acid is elevated in meat diets. This is important because arachidonic iodine and the ratio of it to e-coccipentanoic acid, as well as DHA, can affect mood. The other big thing as well, or the reason why, is because AA is associated with increased inflammation, and inflammation can impact mood, and by decreasing the ratio between AA and EPA slash DHA, we can decrease inflammation, which in turn can help improve mood. And finally, ascorbic acid, or vitamin C, is very rich in this diet. Ascorbic acid itself is involved in the serotonergic, dopaminergic, and neurodegenerative systems. It can block NMDA receptor, and it itself is also protective against free radical injury. So to summation, those are the benefits that's denoted from a vegetarian-based diet. The big issue with the studies, though, is that they were really done in low populations, so it's really hard to draw any definitive conclusion. But those are the benefits that were noted in the study. Next slide, please. The next diet that's been popular is the glycemic load-based diet. This isn't necessarily a diet plan, but rather a set of tools, such as calorie counting or carbohydrate counting, that guides food choice. The idea is that each food is given a number to reflect the carbohydrate content it has and how much it increases one's blood sugar. So the idea is that, in essence, you're trying to limit how much you raise your blood sugar by, and by maintaining it less than 55, as noted in the slides, you're supposed to be on a low glycemic diet, as opposed to over 70, which is high, and then in between is medium. And down below is a chart there indicating the glycemic index of various food items. Next slide, please. As for the benefits of this diet, there's been noted improvements to depression, confusion, vigor, as well as total mood disturbance in a low glycemic diet versus a high glycemic diet. As for the theoretical basis of why, it's that a high glycemic diet is thought to interfere with hormonal changes and availability of certain metabolic fields, such as free fatty acids and glucose. This, in turn, can mean that you can exacerbate hunger and hunger sensation, which can overall negatively impact one's mood. Furthermore, with a high glycemic diet, there's huge amounts of blood glucose fluctuations that occur as well, and that fluctuation itself can exert a negative effect upon the mood. And finally, the rapid elevation of postprandial blood glucose levels can produce prone inflammatory cytokines and free radicals, which, on its own, can then worsen mood. The limitations of the studies that examined this, though, were that there was a low population that was noted in the studies. So again, it makes it hard to draw a definitive conclusion, but these are the noted benefits for adopting a glycemic load-based diet, and the theoretical basis of how to improve one's mood. Next slide, please. Another popular diet is the ketogenic diet, which is a diet that's defined as having high fat, low protein, and low carbohydrates that can promote ketogenesis in the metabolic state of fasting, immobilizing stored energy and fat. It's very popular for weight loss, as well as dietary management of blood sugars. The big thing is that it is fairly restrictive, and it can be pretty difficult to adhere to. Next slide, please. As for the benefits, it has been noted to improve depression, tension, fatigue, and improve activity. And the reason why is because it's thought that the ketogenic diet could stabilize the blood glucose levels and reduce cravings for food, as well as improve energy levels. Indeed, reducing the sense of hunger can itself improve mood. And indeed, the idea is that by decreasing your hunger, you have fewer food cravings, given the limited choices you can eat, which in turn create a greater sense of satiety after meals, which in turn can be protective. The other big thing is that, again, the diet and the studies noted that there is a psychological benefit for losing weight, which is maybe how this diet has its effect. The big issue with the studies, though, is that for the most part, there was a limited completion subgroups in the control trial, as well, between groups and studies. Overall, these are the noted benefits that can occur from the diet based on that study. Next slide, please. Next is the paleo diet, which is another very popular diet these days, as well. It's basically based on the concept of what our foreancestors would have eaten in the past. It's the diet of hunter-gatherer societies. And the idea is that it's rich in meat, organ meats, root, green vegetable, seasonal fruits, nuts, and seeds. And overall, we're trying to avoid eating processed foods, as well as grain-based meals. Next diet, please. Theoretical benefits of this diet is that, well, one, it's high in fruits and vegetables, but it's also high in zinc and meat, as well. And zinc itself has been associated with numerous benefits, as well. It's been associated with the serotonergy and glutaminergic systems, as well as BDNF and antioxidant mechanisms. It's been noted that chronic administration of zinc increases serotonin receptor density in the hippocampus and frontal cortex, as well as increasing levels of BDNF, as well. Furthermore, zinc deficiencies has been associated with increase in reactive oxygen species, as well. And it's interesting that depressed patients do have noted higher levels of reactive oxygen species. Antidepressants, on their own, increase the activity of antioxidant enzyme, such as superoxide dismutase. Finally, zinc has been known to affect the glutaminergic system by also blocking NMDA receptors. The big benefits of this diet is that you get improvements in self-reported measures for anxiety, depression, as well as cognitive function and executive function. However, the studies themselves do have some questions of generalizability. The study that I noted here was that it was a study that was done in patients with multiple sclerosis, and another high-quality study was done in those with non-alcoholic fatty liver disease. So there's really a question of generalizability. But overall, these are the noted benefits, as well as a theoretical basis for how the paleo diet can be helpful when it comes to affecting our mood, as well as cognitive function. Next slide, please. And the last diet I'll be discussing is the zone diet. So this is a diet that's based upon having low carbohydrates and high protein. The idea is that you have basically two-thirds of your plate be filled with carbohydrates, the one-third of your plate filled with proteins, and just a dash of fat, as well. And the goal of this is to reduce inflammation and to have three clinical markers be in a good state to know that you're entering the zone, which is key for weight loss. These clinical markers are having the appropriate triglyceride HDL ratio, having a good AA to EPA ratio, and finally having a low hemoglobin A1C level. And if those are the acceptable markers, you're in the zone. Next slide, please. As for theoretical basis for how this diet can be helpful, the big thing is that it's supposed to reduce reactive oxygen species, as well as free radicals, which is protective for our mood. It's also high in vitamin C, which is, again, another antioxidant behavior. It finds it's high in polyphenols, as well, which, as we discussed in the prior section, can also be helpful psychiatrically. When it comes to the benefits, though, the one study I did examine noted that there wasn't really any significant benefits to mood states. However, though, an interesting note, the diet did show benefit when it was supplemented with omega-3. Specifically, when they did that, they noted there was decreased depression, anxiety, and anger while improving vigor through the palms. This is interesting on its own, because the zone diet also recommends taking omega-3 supplements, as well, but purely on its own, there wasn't really much benefit shown from mood states. Next slide, please. So bringing that all together, I've compiled here a summary of benefits of all of the seven various diets I discussed about. The big takeaways I had is that omega-3 is a really important supplement that can really help improve our mood, as well as the panel diet has some improvements for cognitive function and executive function, which is a bit unique compared to the other studies. Granted, it was in a patient with MS. The big takeaway I had, though, is that these are the benefits noted, but overall, the quality of the studies were of questionable significance, given that there was some issues, notably low population being kind of the biggest limiting factor of these studies, and they're trying to come to a conclusion. But in essence, this is the results of the studies I found, and it potentially could be something that we could recommend to our patients moving forward. So now that I've spent some time discussing the various diets and their effects, we can get down to the nitty-gritty and talk about specifically how our body processes foods. And with that, we'll move on to Dr. Nguyen. Thank you. Thank you, Dr. Bui. So like Dr. Bui said, my name is Dr. Nguyen, Lieutenant in the United States Navy. I'm here with my colleagues for this very large topic on nutrition and psychiatry. And if I can jog your memory a little bit, we've heard from Dr. Baru about the interface between the prescription treatments that we give our patients, how food affects metabolism of said treatments, and this is followed by different compositions of various food diets that Dr. Bui was just talking about. So hopefully by now you'll appreciate how large this topic is in regards to complexity as well as the various areas you can talk about. So I'm going to follow suit, and I'm going to make it even more complex by talking about the approximately 100 trillion microbes that live within our body. So in comparison, and just to give you an idea, we have upwards of only 37 trillion cells in our body, so they number us three to one. So moving forward, and hopefully I'll boil down some of this complexity later, is that we're naturally going to go over some definitions that we're going to use. And this picture really stuck out to me. This is something that I saw in my microbiology class in college. It's a picture of one bristle of a toothbrush with multiple films of microbes surrounding it. Don't think about it too much, as you might become adverse to your toothbrush. Don't do that to your dentist. That the microbiota is referred to both the habitat as well as the microbial community that lives within that particular instance. So here you can see that the bristle is the habitat, kind of the yellow hue, and the film is the blue colored hue that's in here. And so this is the microbiota, everything that you're seeing here. So if you translate this into your gut, whether it's the small bowel or the large bowel, that is the habitat. And any of the microbes and the diversity of microbes that live there is the microbiota. Microbiome gets a little bit even more microscopic in regards to that it measures all the genes and genomes that exist within that specific microbiota. And a lot of that is measured in 16S ribosomal RNA gene sequencing. And then here on after, you can probably guess, but a lot of the microbiota that I'm referring to is the microbial community in our GI system. So as this next slide depicts, there are colorful pictures on the right to hopefully give you an idea of the next term, which is microbiota diversity. This is basically how many species are found in a particular area of said habitat. This is important to think about because if you have one area of diversity, but everywhere else has a homogenous blend of the same microbe, for example, C. diff, it would likely lead to something called dysbiosis or otherwise known as microbial imbalance. And basic concept there is we don't like that. So moving on as well, the last definition I kinda wanna talk about is colonocytes, pretty straightforward, epithelial cells of the colon. Now, before I go on with the microbiome, I kinda wanna talk about the independence of the stomach, otherwise known as the enteric nervous system. I promise this has values to the concepts that are going to be introduced a little bit later, but let's think about the stomach as a brain really quick. So think about it in a more primitive sense where in an evolutionary sense, early on when we were a little bit more simple creatures, it makes a lot of sense that the initial receptors or sensors in our input or output system, or as we like to know, the GI tract, would be one of the first likely to develop. So this makes sense because a lot of those receptors and centers kinda help us differentiate between good and bad. And so good food and then those that are noxious and might not be so good for us. So with that just in mind, with an idea that you can have on the back of your mind as I'm talking, you can cut the vagal nerve and actually remove the said brain from the nervous system from your autonomic system. And the stomach will still function without innervation from the parasympathetic system. This brings me to the idea of the gut feeling. It's that apprehension we feel in our stomach sometimes that gets translated into a specific interpretation into our minds. So just to give you a little pun there. To really drive this home, I kinda wanna translate this into how food may affect our mood, right? I mean, part of the conversation here. So the question becomes, is it the experience of eating and tasting or is it the brain in our stomachs that helps modulate our mood? The answer is somewhere likely in between, but an interesting study from a Belgian experiment showed that if you took two healthy sets of volunteers, gave nasogastric tubes in both of them, right? And one was delivered with normal saline, the other one with fatty acids. And then thereafter tried to have emotional inductions or in layman's term, try to make them sad. Whether it was music, whether it was pictures, those that had the fatty acid infusion were more resilient to the fact that they were less responsive to become sad. So just sheer fact of proof of concept there that the stomach in itself, even if you bypass the chewing, bypass the tasting, the smelling, and you go straight to like the neural receptors in our stomachs, it does affect our mood. So now, this is one of the many things that can affect our mood, right? And this is a picture or a graph of, well, this is half of a picture that I kind of want to show you here. It is demonstrating the extensive negative as well as the positive inputs and consequences that are produced. You know, this is one of those areas such as genetics where the more you know about it, the more unknowns there are to be known. I kind of want to draw your attention to, oh, sorry, I realized I didn't change my slide here. So this is what I was talking about. I kind of want to draw your attention to the lower left and the right upper corner about short-chain fatty acid productions, right? So blue means that it's good. Red means that it's bad. So an increase in short-chain fatty acid production is good, whereas less of it is bad. And a lot of more of this is going to be what I'm going to be focusing on later on in regards to fermentation products from the microbes. And just for completeness sake, here's the lower half of the picture that shows other negative and positive effects of this. As you can see here, there's insulin resistance, there's increased cardiovascular disease, there's increased LPS, and then everything on the right is generally what folks want to aim for. So here is the slide in its entirety. A lot of these studies, when it comes to even something such as fermentation products, I just want to point out that most of these have the strongest evidence thus far in interventional studies or randomized control trials. So much of these products are metabolized and then collected and measured through stool samples. Moving on. So let's go back to the microbes, the 100 trillion microbes that live inside of us. I like to consider them the auxiliary DNA system because if you think about it, our colonocytes are basically our eukaryotic mammalian cells has this DNA and makes enzymes and then the products of basically our genetic makeup. And then those that live on or within us, otherwise known as the microbiomes, they live there to also help support us in this endeavor of, well, when it comes to our stomach, break down dietary fibers or even endogenous intestinal mucus to form what we call short chain fatty acids. The three I'm going to talk about today are butyrate, propionate, as well as acetate. So first on the list is butyrate. I aptly named it food from food for colonocytes because a lot of the product of butyrate comes from the management of homeostasis for the colon. So this is basically the energy source or the food for the colonocytes. My second bullet point here points to a study where they had germ-free mice, saw how the colonocytes of those mice were doing in regards to basically the lack of butyrate. They found that the energy metabolism in them was much lower, right? And in part it was because the butyrate wasn't there to help facilitate the TCA cycle. So after that, after they were able to introduce butyrate back into the germ-free colonocytes, it found that it rescues their deficit in mitochondrial respiration. So it prevents them from actually going to autophagy or basically eating itself up. So that's butyrate, food from food for colonocytes. So this next slide is did I have enough or otherwise known as the story of propionate, right? So the second molecule primarily is responsible to whether or not we've had enough food, right? And so when you think about the indigestible carbohydrates, one of the things that you should think about are fibers, right? Whether they are digestible, propionate is usually the by-product to tell us, hey, you've had enough, you shouldn't eat any more. This is again, one of the more short, most common and short chain fatty acids that live in the large intestine. And later on a study that has been seen in regards to propionate is that in organisms or I guess in rat studies where propionate is missing, right, they introduce usually a microbiome of increased propionate producing microbes. And they usually see that there is a recapitulation of a prior microbiome that allows for the perpetuation of the diversity of the microbiome. A lot of microbiome words in there, but nonetheless, I hope one of the things that you got across from propionate is that it helps with satiety. Next on the list is acetate hormones and reduced appetite. So this is the highest production of compound in regards to the short chain fatty acids, right? In both the small and the large bowel, right? E. coli is gonna be the major players that creates this specific acid fermentation. And what it does, it also helps keep the gut environment stable and nourishes other microbes that live within there, not just the colonocytes, but at the same time allows for an environment within the microbiome to mitigate dysbiosis for the most part. So that was a whirlwind of the three that I wanted to mention in regards to short chain fatty acids, fermentations from your stomach. So in the summary slide, hopefully you've guarded most of these points from previous in my talk here about that the first point is that the enteric nervous system is otherwise known as your second brain and not just the one between our ears. That more diversity is better than less. And a lot of this has to do with the mitigation of dysbiosis, right? If you remember back to the picture that I showed before with all the red arrows and all the blue arrows, you can remember, if not appreciate the complexity that comes with the idea of, well, nutrition and the metabolic products that come about. And then the three most important metabolic products that come about from your microbiome are gonna be the short chain fatty acids that has come about whether it's proprionate, butyrate or acetate. All right, moving on. I'm gonna hand it over to Dr. Gutierrez who's gonna be taking us into the world of nutraceuticals. Go ahead, Dr. Gutierrez. Hi, I'm Dr. Lino A. Gutierrez, Lieutenant Commander, U.S. Navy. I'm gonna switch gears a little bit and go into nutraceuticals. Next slide. And so during this portion of the workshop, we're gonna discuss the growing presence of nutraceuticals in the United States, delve into what literature says about a few nutritional supplements that are out there and some things that we should consider when looking at or starting future studies that relate to nutritional supplements. Next slide. So chances are you've been here standing in a seamlessly endless aisle of vitamins, nutritional supplements, whatnot in your local grocery store, whether you're searching for melatonin to help the kids sleep at night, some glucosamine to help with your joints or just a simple multivitamin, it could be overwhelming, but rest assured you are not alone. Next slide. Over half of all Americans use nutritional supplements. Yearly, this accounts for about $35 billion of spending. There are many reasons behind the overwhelming use and that includes maintaining or improving mental health, which goes anywhere from mood concerns, anxiety concerns to cognition. Next slide. The term nutraceutical was first coined in the 80s by Dr. DeFelice. When you combine the terms pharmaceutical and nutrition, it's defined as any substance that is a food or a part of food that provides medical or health benefits, including prevention, treatment of disease. Since the creation of that term, there have been many variations of the definition along with analogous terms like functional foods or health foods. And over the last 30 years, there's been an explosion in the number of dietary or nutritional-based interventional studies. If you go in and do a PubMed search just for the term nutraceuticals, use it as a general search, you'll come back with 19,000 hits in the year 2019 alone. If you restrict that to just the title, you still get over 1,000 articles in the year 2019. Nutritional supplements are marketed under the Dietary Supplement and Health Education Act of 1994, which means they're not regulated the same way as the prescription drugs that we prescribe. And that means that there just isn't a rigid quality control standard. And because of that, there can be substantial variability in what our patients are buying in the store, whether it's the potency of what they're trying to buy or the purity of these products. Next slide. And chances are you've seen a couple headlines that came out recently, FDA warning companies for making improper claims and also finding out that some of these products that are out on the market actually contain pharmaceutical ingredients in them, which can present a host of complications for our patients. Next slide. In 2015, the International Society for Nutritional Psychiatry Research issued an index paper on the field of nutritional psychiatry, really advocating for evidence-based nutritional change that it can be regarded as an efficacious and cost-effective means to improve mental health. And when you consider things that, you know, looking at the ability to maybe modulate some of these things behind our mood disorders, like the catecholamines involved in the catecholamine hypothesis of depression or inflammation throughout the body. Next slide. In 2016, there was a large systematic review of clinical trials from around the world that used nutraceuticals as adjuncts in the treatment of depression. And these were some mixed findings, but overall what they felt was there was current evidence to support the adjunctive use of omega-3 fatty acids, S-adenosylmethionine, and vitamin D and methylfolate. There were some positive isolated studies for a few, like creatine, folinic acid, and certain amino acid combinations. And remember, those are the building blocks to our neurotransmitters. And then mixed results for zinc, folic acid, vitamin C, and tryptophan. But no, and then not significant results for inositol. And in this workshop, we're going to just spend a little bit more time on three main ones, omega-3 fatty acids, SAMe, and vitamin D. Next slide. So omega-3 fatty acids, in the U.S., we spend about $5 to $6 billion annually on omega-3 fatty acids. About 8% of adults and about 1% of children use some type of supplement containing fish oil. Next slide. As was previously mentioned, low dietary intake of omega-3 fatty acids is associated with increased rates of depression globally. And an elevated omega-6 to omega-3 ratio is not just associated with depression, but is also associated with an increased risk in suicidal behavior. There is a fossil lipid hypothesis in which polyunsaturated fatty acids may be a possible ideological factor in the development of depressive disorders. And if you think about it, the CNS, it has the highest concentration of lipids in the body after adipose tissue. And the fatty acids account for half of the dry weight of the brain. Another thing to consider is that early humans often settled near freshwater sources or saltwater sources, relied heavily on food sources that were rich in omega-3 fatty acids. And it is believed that their diet had a one-to-one ratio of omega-6 to omega-3. And as we westernized and industrialized our diet, we've taken a drastic shift away from that ratio. Next slide. So there are three main sources of omega-3 fatty acids. Some does come from meat, and that comes in the form of linoleic acid. There's also alpha-linoleic acid, which comes in some nuts, chia seeds, and flax seed. And then there are the omega-3s that come mainly from fatty fish, like EPA and DHA. Next slide. A few studies have demonstrated the benefit of adding omega-3 fatty acids to antidepressant medications. And it's been shown that we can get better outcomes when we use it with citalopram or fluoxetine in a couple of studies. Studies have also shown, as it was mentioned earlier, EPA seems to be more efficacious than DHA. And that could be because EPA, not DHA, competes with arachidonic acid as a substrate for cyclooxygenase, which decreases the production of pro-inflammatory eicosanoids. Next slide. And so the FDA recommends that adult males get about 1.6 grams of omega-3 fatty acids and females get 1.1 gram. Although we do meet that requirement with our diet, it's usually in the form of the alpha-linoleic acids and not EPA or DHA. So when people do supplement with these omega-3 fatty acids, they're generally well-tolerated. In all the studies that we reviewed, there were no significant adverse events. Common side effects were nausea, diarrhea, indigestion, and constipation. Next slide. And then next up is S-adenosyl-L-methionine. It's a neurotraceutical that's been studied. It's not as well-known as some of the other ones out there, but there is some research out there to support its use. Next slide. And so SAMe is what it's also known as. It is a methyl donor found throughout the body. It's important in the synthesis, activation, or metabolism of other endogenous molecules in the body, such as hormones, nucleic acids, proteins, phospholipids, and neurotransmitters. And its activity is dependent upon other nutrients like folate, B6, and B12. Next slide. SAMe, in the United States, it's promoted for the use in depression, osteoarthritis, early-stage hepatic cirrhosis. There is no FDA approval for SAMe for the diagnosis, treatment, or prevention of any of these diseases, but it does carry an orphan drug designation by the U.S. FDA for AIDS-associated myelopathy. SAMe, it affects the activity of tyrosine hydroxylase, which is the enzyme used in the rate-limiting step of dopamine synthesis, and so that's one of the reasons why we think it might have such an effect in mood. Something to note is that it's been used for a few decades over in Europe and other parts of the world where it's actually considered a prescription. In other parts of the world, they do have an IM formulation, but here in the United States, we only use the enteral form. Next slide. And like omega-3 fatty acids, studies have shown that when it's used as an adjunct, it can improve outcomes of antidepressant use. There does seem to be a dose-related response. Some studies found that there was a better response when they went from 1,600 milligrams a day up to 3,200 milligrams per day. It's well tolerated, again had few significant adverse events in the studies and one thing to consider is that there is a risk in inducing mania in patients who have a history of bipolar depression. One thing that sets SAMe apart from the other nutraceuticals is cost. It can cost upwards of $5-$10 a day for some patients if they want to take up to the 3,200 milligrams per day. The final supplement we're going to discuss is that of vitamin D. It's been in the news a lot lately in the light of the COVID-19 pandemic, especially with recent findings showing that it can be associated with a number of health outcomes. It is the sunshine vitamin. Next slide. So vitamin D, it's a fat-soluble steroid. Its synthesis in the body begins with UV irradiation of 7-dehydrocholesterol. As a supplement, it comes in two forms, D2 which is ergocalciferol and D3 which is cholecalciferol and they're essentially equivocal as far as its use in the body. It is found in some fortified foods like milk and cereal which tend to have about 100 international units per serving. It's also found in fatty fish and in fish liver oils as well. When it comes to status, vitamin D deficiency is defined as less than 20 nanograms per milliliter of 25-hydroxyvitamin D in the blood. Vitamin D insufficiency is 21 to 21, I'm sorry, 21 to 29 nanograms per milliliter. And so for patients who are vitamin D deficient, the recommendation from many guidelines is to use 50,000 units per week for eight weeks to recheck the vitamin D level after that and then to continue with maintenance. And sometimes the maintenance can be up to 1,500 to 2,000 international units per day just to maintain a vitamin D level greater than 30 nanograms per milliliter. Otherwise a typical recommendation is 600 international units per day. Next slide. The association between vitamin D and depression continues to gain support. There's increasing evidence that vitamin D supplementation and augmentation is a benefit in those patients that have both clinical depression and vitamin D deficiency. There is no one mechanism to explain the relationship, but some of the risk factors that we should consider for vitamin D deficiency are race, as our skin tones increase that blocks out the UV radiation so that there's less vitamin D produced, obesity because of the increased amount of adipose tissue which can sequester some of the vitamin D, a history of malabsorptive syndromes and antiepileptic use which affects the metabolism of vitamin D. Next slide. We do know that vitamin D receptors are located in the brain primarily like the prefrontal cortex, hypothalamus, substantia nigra. It does have an effect on serotonin levels and it increases the expression of genes that encode for tyrosine hydroxylase. Again it's one of the enzymes that's very important in the synthesis of dopamine and norepinephrine. Next slide. Research has found that there's a 65% probability that an individual with depression will have a lower vitamin D concentration than an individual without depression if they're chosen at random. Like omega-3 vitamin D was shown to be an effective adjunct, one study showed that with fluoxetine use the combination was superior to either one alone. And then an additional study of vitamin D as an adjunct to antidepressants in patients with MDD, there was beneficial effects not just on depressive scores but also on glucose homeostasis and oxidative stress. Next slide. And then one thing I'd like to end this portion of our workshop on is talking about a concept that's important to nutraceuticals and that's that nutrients are not like drugs, the baseline status and the dose are important. And so when we look at things that we can get actual lab levels on whether it's vitamin D, folate, B12, it's important to know where does a person start. So when looking at studies we want to see was there a deficiency to begin with? Was the deficiency adequately corrected? And then if these two things aren't met we're likely to see a null response whether it's in a patient or in a study. If we don't adequately correct the level or if we don't identify patients who are actually deficient, we're likely not to get a positive response which is kind of what explains maybe why there's so many consistencies in the vast amount of studies that we have out there. And so to wrap up I'm going to be switching over and let Dr. Matt Hunter take us into some more practical considerations. Hello. I'm Dr. Hunter. I will provide a broader perspective of nutritional psychiatry that we can translate into meaningful intervention. Next. My objectives today are to define the terminology you see here and discuss their implications on mental health. Additionally, I will further highlight the link between food choices and mental health. I will then wrap up by touching on the practical implications of nutritional psychiatry, various nutritional hygiene tips, and end with other important aspects to consider when addressing diet with patients. Next. So let's start off by defining some terminology. Food desert is an area with limited access to healthy food. Food swamp is an area with adequate access to healthy food but features an overabundance of exposure to less healthy food. Food mirage is an area with access to healthy food but one can't afford it. Food insecurity is a more general term referring to inability to access a sufficient quantity or variety of food because of financial constraints. Okay, so we're going to dive right into one of the best references out there in helping a person understand and remember these concepts. Next. Next slide. But in all seriousness, a systematic review of the food desert literature from 2010 highlighted four aspects to consider. Access to supermarkets. This is more than just distance to and number of supermarkets, but also lack of transportation or ability to afford it, unsafe neighborhoods for walking, among others. Racial and ethnic disparities. Black neighborhoods have fewer supermarkets compared to white neighborhoods. Socioeconomic status. Food prices are higher and quality is poorer in the highest poverty areas. Choices in chain versus non-chain stores. Bottom line is non-chain stores are more expensive than chain stores, with non-chain stores being more prevalent in urban areas. Keep in mind that a consequence of a food desert is that people tend to make choices based off the food in their vicinity, which tend to be fast food or corner stores in these instances. Next. DoSomething.org is a global nonprofit organization with the goal of motivating people to make change through campaigns. You can see some of the astonishing facts from them here, but I want to touch on the last one briefly. Let's not forget the physical health implications of food deserts, which we know can subsequently lead to worsening mental health. A 2010 systematic review found that people who were obese had a 55% increased risk for developing depression. Next. As I present the next several slides, I want the focus to be on the general link of unhealthy food as a detriment and healthy food as a benefit to one's mental health. A global analysis of 149 countries showed food insecurity's association with poor mental health and psychosocial stressors. Conclusions drawn were that uncertainty over the ability to maintain food supplies or acquire food in the future can lead to stress response that contributes to anxiety and depression. Also, acquiring food in socially unacceptable ways can induce feelings of alienation, shame, and guilt that are associated with depression. Next. One more note on food insecurity with respect to COVID-19. A Canadian study in the early months of the pandemic studied the association between household food insecurity and self-perceived mental health status and anxiety symptoms. Results showed that, compared with individuals in food-secure households, those with moderate and severe food insecurity had higher prevalence of both fair or poor self-perceived mental health and moderate or severe anxiety symptoms. Next. I now want to take us through the effect of diet at various ages. A prospective cohort study of women evaluated the effects of healthy or unhealthy dietary pattern on internalizing problems and externalizing problems among the children. It was found that higher intake of unhealthy foods in mothers during pregnancy predicted externalizing problems among their children, and children with higher intake of unhealthy diets postnatally predicted both problem types. Next. As you can see here, as it pertains to adolescence, the issues with internalizing and externalizing behaviors carry through from childhood, based off of a Western diet versus one that contains more leafy green vegetables and fresh fruit. Next. Leading into adults now, a cross-sectional study of Norwegian adults showed that with better quality diets, you were less likely to be depressed, and those with higher intake of processed and unhealthy foods were more likely to be anxious. Moving along to the elderly, a prospective study of elderly Taiwanese people showed fruits and vegetables were protective against depressive symptoms four years later. I know there seems to be a lot of redundancy to this point, but showing consistency of diet's effects across the lifespan is the goal. Next. The next couple of slides provide a slightly different perspective, where the focus isn't on how poor diets lead to disorder, but rather how healthy dietary intervention can alleviate symptoms that are already present. You can see the parameters of the study in the first bullet point. The key takeaway is dietary intervention, which in this case is a Mediterranean diet along with fish oil supplementation, leads to reduced depressive symptoms. Next. As a final example, the randomized control trial here shows the impact of dietary intervention of nutrition counseling by a dietician compared with control group of social support. Results show that in the treatment of moderate to severe depression, the intervention group had significantly greater improvement between baseline and 12-week depression scores. Next. I want to transition to practical implications now. A Proceedings of Nutrition Society article from 2017 talked of the efficacy of dietary and nutraceutical interventions, but stated change to public policy was needed to translate these findings into population-wide changes in eating behavior. Given the necessity for public health measures, what can we as clinicians do on the micro level? Next. One of the most important things to do is start discussing nutrition as a standard of practice. Psychiatrists may have better luck affecting dietary change than medicine doctors. Patients may perceive their typical consequences of poor diet, like heart disease, cancer, diabetes, as happening far off in the future, but potentially seeing the consequences on poor mental health as impacting them more acutely. Next. In the setting of information overload on the various diets, a good evidence-based option for patients that has significant resources is USDA.gov. The USDA's Dietary Guidance for Americans are based on the preponderance of current scientific and medical knowledge. Next. The four core elements of the USDA guidelines are follow a healthy dietary pattern at every life stage, customize and enjoy nutrient-dense food and beverage choices to reflect personal preferences, cultural traditions, and budgetary considerations, focus on meeting food group needs with nutrient-dense foods and beverages, and stay within caloric limits. Limit food and beverages higher in added sugars, saturated fat, and sodium, and limit alcoholic beverages. Next. The great thing about the USDA website is its resources. The MyPlate plan gives you personal food group targets within your calorie allowance. Your food plan will be personalized to your demographics. There is also a start simple with MyPlate app one can utilize. The healthy eating on a budget resource can help you create a grocery game plan, shop smart, and prepare healthy meals at home. Next. I would now like to transition into nutritional hygiene. It's not just what you eat, but how you eat that is crucial. People forget eating should be a parasympathetic event, rest and digest. Many today are distracted when they eat, working, making phone calls, driving, maybe all three at the same time. I'd be willing to bet that there are many of you eating right now. Next. Some improvements for how one eats, regardless of what you are eating, include sit down, breathe, and smell your food. This helps you relax, trigger the parasympathetic nervous system, and stimulate salivary enzymes from the aroma. Strive for around 20 bites. This helps you relax. This ensures getting food to small particles before swallowing. Avoid over-consuming fluids while eating. People may use it as a lubricant to help swallow. This reinforces not chewing enough, which can stress the digestive tract's ability to derive nutrients from food. As a brief aside, don't forget about water in general. Dehydration is linked to worsening mood, increased perception of task difficulty, and lower concentration. Put the fork down between bites. This helps you stay mindful about when you are chewing and lessen temptation to take another bite prematurely. Enjoy a meal with a friend. This leads to slower chewing and longer pauses between bites. Take a quick walk afterward. This helps assimilate nutrients more efficiently and decrease blood sugar spikes. Next. I do want to point out that several of those tips help one derive nutrients from food. We all know that just because we consume something doesn't mean we absorb it, so we need to maximize our ability to do that. And additionally, know your patient. What and how one eats is not a one-size-fit-all approach. I want to wrap up with a quick note on rigid versus flexible dietary strategies, moderation, and willpower as food for thought in discussing nutrition with your patients. One study found individuals engaging in rigid dieting strategies as opposed to flexible reported symptoms of an eating disorder, mood disturbances, and excessive concern with body size and shape. You might think this should lead to a quote everything in moderation approach, but that has its problems too. Moderation is ambiguous and doesn't offer clear behavior guidelines. Additionally, the more people like a food, their definition of moderation becomes more forgiving. Their perceived ability to eat foods they like in moderation is also increased. Next. I made my last slide intentionally dense to end on an in vivo exercise in willpower. Did you already tune me out before I began speaking on this slide once you saw how long it was? You see, willpower is defined as the ability to ignore temporary pleasure or discomfort to pursue a longer-term goal. It operates like a muscle that can be exhausted from exerting self-control. Have you exhausted your willpower muscle to this point from exerting the self-control needed to stay focused during this presentation? Let us not forget you all volunteered to learn about this topic as well. A point worth making is that willpower is generalized, so refraining from gossip at work makes it more difficult to go to the gym afterward. Resisting the impulse to buy something at your favorite store makes it more difficult to turn down dessert later on. I personally apologize for depleting your willpower right now, which will no doubt lead to bad food choices you're going to make later today as a direct result of focusing on this presentation. So what does willpower have to do with our patients and nutritional psychiatry? Things like social stress take a particularly large toll on willpower. People who are lonely or socially rejected have worse control over their thoughts, emotions, and health-enhancing behaviors. Feeling stigmatized depletes willpower for both mental and physical acts of self-control. Social rejection even takes away the will to exert willpower. We all know how draining and daunting it is to make even the smallest decisions or commit to the most basic of goals for many of our patients, who no doubt live their lives in willpower-depleting states. The good news is that willpower can be improved by social support, adequate sleep, planning for obstacles, among other things. Additionally, committing small, consistent acts of willpower or self-control can generalize success to other areas. A study asking participants to create and meet artificial deadlines for eight weeks led to not only better time management, but also improved diet, physical activity, and reduced tobacco, alcohol, and caffeine use. I understand that rigid versus flexible dietary patterns, moderation, and willpower aren't traditional topics of nutritional psychiatry per se, but not considering and assessing these factors in the patient that sits in front of you will limit the impact of our nutrition interventions as a whole. Next. This is just my references for the prior slide, and I will then turn it back over to Dr. Bharu for our final remarks. Next. Here am I, back again. So what does this all mean to us? The last decade has seen a surge of information, but we now know that we have a long way ahead of us. The field of nutritional psychiatry is starting to generate data of the quality and consistency that needs to change public health recommendations and clinical practice. We now find there's an urgent need for governments to address food policy to support population health, not just in the physical field, but also in the mental field. Public health strategies, which have so far focused on improving nutrition for pregnancy and childhood, thinking about the physical medicine should also now take into consideration psychiatry and its implications. This evidence supports us, the investigation of psychobiotics as psychotropic medications. And finally, to complete the picture, we all need to put along and understand that dietary change should be a lifestyle strategy, just like healthy living, exercise, smoking cessation, amongst others, to help support what we all expect to achieve in mental health. We want to thank the APA for providing us the opportunity to present this matter today. And me and my co-presenters, we all thank you for joining us today. Hope you can implement some of what we all learned here. Thank you.

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