 Hello. Good afternoon. First of all, thank you for attending my talk. I really appreciate it. I would like also to give thanks to the Uncertain Health Imposition Organizer for accepting me to give this talk. And I would also like to give special thanks to Rob Wolf because he has helped me so much to come here. For those of you who don't know me, I'm an affiliate researcher at Lund University under Dr. Staffel's supervision. This is my vision of nutrition from an evolutionary perspective. I think that protein is bad, but I also think that protein is good. I think that carbohydrates are bad, but I also think that carbohydrates are good. I think that fats are bad, and I also think that fats are good. So for those of you who would like to enjoy the weather, you can go inside and you can skip the rest of the talk because this is a summary of what I'm going to talk. Well, we all know that worst indices are approaching pandemic proportions, despite the fact that, as has been mentioned before this day, every day we know more about nutrition, we know more about physiology, we know more about biology, we know more about science, but still the same. And atherosclerosis, the basis of cardiovascular disease, remains largely unexplained. And in Westerners, almost all Westerners above the age of 60, they have atherosclerosis, so this is very surprising. And even in small children, they have atherosclerosis even with a few months of age. And perhaps atherosclerosis is not more common now than 50 years ago. So that should make us think. There are, of course, all the worst indices affected by diet, as you all know. And one of the problems is that dietary prevention has largely focused on an optimal intake of macro and micronutrients. And I will give you an example. The Women's Health Initiative Dietary Intervention Trial shows no beneficial effect on a low fat, high fiber diet, eating five servings of fruit every day, five servings of vegetables, and six servings of whole grains. And regarding low fat diets, the Swedish Council on Health Technology Assessment concluded that there's only moderate evidence to support the advice of low carb or at least moderate low carb diet for type 2 diabetes. And the effect on glucose control and insulin sensitivity was uncertain. And we have heard today that there are several populations with a high intake of carbohydrates, but still they are very healthy. So perhaps there's something else in the fruit that we eat today than the macronutrient composition that is making us sick. So up to now we don't have good evidence for the dietary advice that we have, in part because it's almost impossible to conduct a double blind placebo control trial with food. Why? Because we cannot make a placebo food that's impossible, so we cannot compare one to the other without excluding confounding factors. So that's one of the reasons. And if we apply biology, plants don't want to be eaten. So if you talk to a biologist about this fact, he will understand it easily that plants don't want to be eaten and so they produce what they call secondary metabolites and I will call them bioactive compounds. An example could be the estrogen receptor that is bound by endogenous hormones, estrogen, but it's also bound by exogenous substances like, for example, phytoestrogen. So this is a good example how the plant and the animal kingdom interact between them. This is the defense mechanisms of plants. In this table you can see selected categories of some bioactive compounds. Of course it's not an official table, it's just a little review that I've done and there are a lot of other substances that are not included here. But for example we have antinutrients such as ferric acid and oxalic acid that decrease the bioavailability of some nutrients. We have endocrine disruptors like, for example, lectins, phytoestrogens or exorphins. They are exogenous opioid peptide derived from the digestion of certain proteins that they interact with endocrine receptors. We also can include immune disruptors like lectins, gliding, tomatin like proteins or saponies that they over-estimulate the immune system or they can disrupt physical barriers. I'm going to include as well some new substances like DNA and RNA binding molecules such as rice macro RNA that has been shown to alter the transcription of the LDL receptor. I will also include antioxidants, at least the isolated intake of certain antioxidants like, for example, vitamin C that has been shown to decrease the beneficial effect of exercising in type 2 diabetes patients. So perhaps the intake or the high intake of isolated antioxidants could be viewed as a reactive compound disrupting our physiology. And some flavonites, for example, the high intake of cursitine and chymphrol, has been shown to inhibit several key enzymes in metabolism. And I will give you a few examples of how these bioactive compounds interact with our physiology independently of the macronutrient content of the diet. So in this study, the researchers tested the effect of exogenous opioid peptides derived from the enzymatic digestion of wheat, in this case exorphine A5 and exorphine B5 versus saline solution on the glucose insulin and glucose response after a glucose meal. So we see here that, for example, exorphine B5 increases the production of insulin, also A5 in a significant difference with the saline solution, and exorphine B5 and A5 also increase the production of glucagon. And this scenario is what precisely we don't want in type 2 diabetes. This is a paradoxical effect to have high insulin and at the same time high glucose, glucagon levels, sorry. And this was independent of the, with no significant increasing glucose levels. And this effect was aggregated by naloxone. So this means that these opioids, they act through endogenous opioid receptors. And in these human studies, the researchers tested the effect of naloxone versus saline solution on the production of insulin, glucagon and glucose. And again, naloxone increased the production of insulin and it's enuated the decrease in glucagon. So we should see in physiology increased insulin and decreased glucagon. So this is what we see in type 2 diabetes. And in this case, again, with no significant difference in the glucose excursion. So at this point of the talk, I would like to highlight the role of the bioactive compounds inserting hormones. I would like to present some functions of leptin, some of them are well known, some of them perhaps not. So leptin, I think, is a master hormone. Leptin is able to decrease a hepatitis through the hypothalamus, of course, and it's also involved in lipid partitioning. What does this mean? It means that leptin drives the accumulation of the surplus of calories into lipid-tolerant adipose tissue and avoids the accumulation of surplus calorie into lipid-tolerant non-adipose tissue, such as the pancreas, heart, muscle, in the cell cells, or even the lung. And leptin is also able to increase beta-oxidation, increasing the mitochondric activity, and this is very important to avoid lipotoxicity as we will see later on. And another important role of leptin is the regulation of the glucagon production. So in several animal studies, they have been shown that leptin is able to decrease the glucagon production, and we will see some interesting data after. And also, leptin acts through the brain, so it's not really clear if there is a direct effect of leptin on the pancreas or through the brain. So perhaps insulin resistance is a protective mechanism against leptin resistance and lipotoxicity. So in this slide, we can see that when we have increased glucose, of course, the pancreas produces insulin, and this leads to phosphorylation of several enzymes, and finally, phosphorylation of AQT. This induces the translocation of the glutefoil transporter into the cell membrane and allowing the entrance of glucose in the cell. One of the first metabolites of increase the novel lipogenesis is malonyl coenzyme A that decreases the activity of the mitochondria. So this leads to increased amount of fatty acids and triglycerides. And one of the five products of the novel lipogenesis is ceramides. So ceramides inhibits the phosphorylation of the AQT protein, leading to an inhibition of the translocation of the glutefoil transporter into the cell membrane. So this decreases the entrance of glucagon, malonyl coenzyme A goes down, and this activates, again, beta oxidation in the cell. So perhaps it has been said before, insulin up, insulin down is not a big deal. So perhaps it's more about communication and endocrine interactions. And also, I would like to point out that perhaps obesity is also a protective mechanism against lipotoxicity. Because if we can accumulate the excess of calories in lipid torrent adipose tissue, we will avoid accumulation of excess of calories in vital organs. And here we can see the glucose excursion in animal model knocked out for the glucagon receptor. So we see that the glucose excursion for the knockout mice for glucagon receptor without beta cell, they have a normal glucose excursion. But on the other hand, normal mice, that means without knockout for the glucagon receptor, they have increased glucose excursion. And here they compare knockout mice before and after beta cell destruction. Of course, you see that before beta cell exhaustion, they produce insulin, but not after. And this does not affect glucose excursion. So perhaps there's a glucagon is a scenic one of type 2 diabetes and type 1 diabetes and not insulin. So why I'm talking about this? Because perhaps it's this barcative compounds that disrupt the communication between the hormonal and immune system is one of the factors leading to Western disease. And in type 2 diabetes patients what we see is that after carbohydrate meal, insulin goes up, glucose goes up, but I think that the hallmark of type 2 diabetes is attenuated, decreasing glucagon. Another kind of barcative compounds, for example, glidings, has been shown to increase the expression of tall interceptor 2 in gluten sensitivity patients in a significant way compared to select disease and control patients. And also gliding is able to decrease transcription of Fox P3. It leads to decrease production of tea regulatory cells in a significant difference with the select disease and control group. And as I said before, I think that micro RNA, there's a brand new research from last year that perhaps this opens a new research to understand interactions between the mammalian and plant kingdom interactions. So micro RNA from rice is able to interact with the mouse and the human LDL micro RNA to decrease production of LDL receptor. So this is another kind of new substances that has been shown or at least some studies that can interact with our physiology. So my question is, how many substances are yet to be discovered? I don't know. And soy and what we call nature romanticization because a lot of this is commonly believed that the soya is healthy and a lot of people look for ecological soya, biological soya because it doesn't have a pesticides or every side, etc. But if we look at the potency of phytoestrogens compared to certain insecticides, it's several thousand times more potent. So skipping this pesticides and eating this natural substances might be a problem. And I will quote part of this paper, the exposure to hormonal active xenobiotics virtually insignificant when compared with the intake of the phytoestrogens that are present in food and beverage. And it's even more insignificant when compared with 13 herbal potions using alternative medicine. So it speaks by itself. And good question is, but are these bioactive substances deactivated by cooking and by enzymatic digestion? I think that the answer is not all bioactive compounds are completely deactivated by cooking. For example, microRNA has been shown in a human sample from Chinese people to be in a high amount in blood. And gliding has been shown in high amounts in breast milk. And there's different data showing that you have to thoroughly process certain bioactive compounds in order to completely eliminate them. So again, just to point out that perhaps these substances are able to disrupt our physiology and perhaps it's more important than the amount of fats or the amount of carbohydrates or protein. So what may cause leptin resistance? This is an animal study with what, when they compare, the amount of leptin is required to decrease the calorific intake. And what they show is that, for example, there were one group that ate a high carb, grain based diet, low fat diet. And the other group had a high fat diet, low carbohydrate diet. It actually was a ketogenic diet. And they showed that after intrapertoral leptin, they needed much more amount to decrease calorific intake in the low fat, high carb, grain based diet. So when you compare that to the amount of leptin that you have to inject to administer intra-celebrate ventricular, it's the same. So what's going on with the carbohydrates? What's in the carbohydrates that disrupts the translocation of leptin to the brain? Perhaps bioactive compounds. And because I'm talking about food, this is as Linda has said before, the study conducted by Dr. Lim in the first group where he showed that paleo diet is more negotiating calorie per calorie diet and nutrient diet. So again, although they ate less carbohydrates, is it because of the carbohydrates or is it because of the bioactive compounds? We don't know. So this is a good question. And this is a new study, a review study that compared the type of carbohydrates from ancestral sources versus modern sources. And what he says is that the type of carbohydrates in modern sources of carbohydrates are in a cellular structure. That means there are not organelles in vesicles and that they are more free. So this can lead to change in the microbiota, leading to increased inflammation and leptin resistance. So we have food. Food is eaten, digested, absorbed, and interacts with our physiology and we have an effect. So what happens in the black box? Well, who matters if we eat a specific, a specific diet? And a biomarker is useful to a sedentary intervention. So as Linda said before, if you would expect at a high level of adiponectin in the Kitaban people, actually they have half the level compared to the Swedish match for males and females. So perhaps who cares if we eat a specific diet? So I think that the take home message that macromiconutrients, if we look at them, are we looking in the wrong place? It is not clear that all active compounds in food are safe for humans being on the long run. Some bite of compounds have endocrine disrupting activity. A specific diet produces beneficial effects we know, obvious health risks for most humans and go for variation. Even fruits, veggies, and tubers, they have active compounds. So if you eat a lot of variation in this food, you will be more free of disease. And this is my conclusion, specific foods, a quality for common sense. Why eat those substances, those fruits that are potential harmful for us having other options? And for the reading, this is a book where you can find most of this information. And thank you. We have time for one or two questions. Okay. Did you see the safe starch panel? Yes. Okay. What did you think the one gentleman, Peter, about he used white rice as an example of a starch that would be safe? But what you're presenting with the micro RNA would say that even when it's cooked, it's not safe. Is that correct? Yes. Well, perhaps it's safer than other sources of starch, but I would skip it. I prefer to eat another kind of food. Yes, if you put it in a scale, perhaps it's safer than the others. And perhaps one of the reasons is because the pollaming content of rice is much lower than other grains such as wheat, rye or barley. So perhaps that's one of the reasons, but I'm not sure. I don't know. Thank you. You're welcome.