Protein: A Deep Dive with Dr. Jeff Bland

Well, welcome everyone. Thanks so much for being part of this big, bold health education program. Protein. I know it's a big, big topic with lots of information that we could include in this discussion. We got an hour. You know, we called it a deep dive and I think we better qualify. When we talk about deep, we're not going to be like real deep. We're going to be modestly deep. Because in an hour, I don't think we could, we can fulfill the criteria of being fully deep. But hopefully you'll have enough new information from this discussion that it kind of adds to your body politic and body of information as it relates to this very important concept of protein nutriture and protein in the human body and its constituent implications in terms of, of our health. So let's start with the first question I think everyone would probably want to know, and that is when we look at the human body, how are things kind of broken down in terms of body composition and where does protein reside in that compositional matrix that makes up the human body? So first of all, we're about 50% water, salt water, I might add, come from the oceans. We're about 20 to 25% fat. If you're in pretty good shape, we're about 14% bone. And that leaves the residual about 16% to 20% muscle as protein. But I think it's important to recall that protein in our body is more than just muscle. Protein includes the connective tissues made out of collagen. That's a form of protein. It includes the blood, plasma proteins and enzymes that make up much of what our blood is composed of. It makes up the enzymes within cells and the matrices of cells. All of those things become part of our total body protein. So it's not just muscle in and itself that when you talk about protein, and these are going to be important discussions because protein is also found as the building block of our immune system as well. So when we talk about where does protein play a role in the human body, it's in all organs and all structures. Even as you know, bone, which is mineralized hydroxyapatite, is built on a protein background. And so therefore protein is ubiquitous and important all across the body. So with that in mind, let's jump into this deep dive here for a second and see what we can find out about protein at a deeper level. So hang with me here. And away we'll go onto our journey into the protein family. And again, I thank my colleagues at Bigville Health for the support of this program and, and for the Production of the graphic materials I'm going to be presenting. So what do we hope to get across over the course of the Next now say 55 minutes? We want to understand the structure and function of protein and so we'll deep dive into that. We want to understand how protein needs can vary throughout the life cycle. What are the needs of protein that we have for proper nutriture and our function. We want to address protein needs, including deficiencies, excesses, quality of protein, sustainability of protein, protein, all part of this discussion. And we want to explore therapeutic uses of protein and the building blocks of protein, which are amino acids, as you know, in the clinical setting. So big kind of ambitious list of learning objectives, but I think we can make some good inroads as we move forward. So let's talk about the role of protein in the body and we could break it down into three categories and we'll discuss a little of each of these categories. Structural proteins, and I've already alluded to them when I talked about collagen and the, the kinds of elastin proteins that make up connective tissues and ligaments and become fabric upon which the bone is built. We have regulatory proteins. Now what do I mean by regulatory proteins? These are proteins that involve the regulation of metabolic function. And so these are often called enzymes. And then we have functional proteins. And those are small polypeptide molecules that influence the structure and function of the body, not as structure and not as regulatory, but as other functional operational activities. So these would be like the peptide hormones, for instance, and neurotransmitters, things that we'll talk about that are also part of this protein family. Now if I was to class all of this together into one big bucket, how would I then define proteins as contrasted to carbohydrates or lipids? Fats? And I would say that proteins are information molecules. They have an extraordinary amount of information encoded within them that imparts then some message to another component of the body. Generally this is through some kind of a receptor mediated process. But we could talk a little bit about how proteins then become very important structural and informational components of our system. Now, what is unique about protein as contrasted to carbohydrate and fat? Well, many things obviously, but I'm going to make it as simple here as I can. And that is that proteins are the only macronutrient that have the element nitrogen in them. And I think this is going to turn out to be a very important learning point for you, if you're not kind of thinking about that, that you don't have the element nitrogen in lipids to any significant extent. You don't have nitrogen in carbohydrate to any significant extent. But you'll find it obviously is a major element in the amino acids that build up the protein as building blocks. So the question is, how does nitrogen get into our food supply? And that's a very interesting question because you can eat nitrogen containing foods. Those are protein containing foods that come from animals or plants. But the ultimate source of nitrogen getting into our foods and ultimately getting into our body, because we don't breathe nitrogen in the air and then convert nitrogen directly into the body materials like, remember, we breathe carbon through carbon dioxide and, and, and we, and well, actually it's plants that breathe carbon dioxide and plants convert through the process of photosynthesis that carbon and carbon dioxide into the protoplasm that makes carbohydrate and fats, and that we eat that as a secondary source and then we exhale carbon dioxide as a process of respiration. So carbon gets into our hydrogen and oxygen. You get into our cycles through the process of eating foods that have undergone photosynthesis and ability to build those macronutrients. Nitrogen, however, gets into our foods through a different process by which we call it nitrogen fixation. And plants in, can breathe certain kinds of plants, the nitrogen fixing plants, and it's actually not the plants themselves. This is part of the soil microbiome that the nitrogen fixing plants, like legumes are a good example. Sample beans have in their root nodules specific adaptation to store and to habitate by nitrogen fixing bacteria. So their microbiome, so to speak, has nitrogen fixing unique genes in those bacteria that breathe nitrogen and convert that ultimately into nitrogen forms that can be made into, into protein. So nitrogen is a kind of a limiting nutrient in some respects as it relates to the production of protein in our food. Now how do we then get nitrogen into the agricultural system? If we want to accelerate the uptake of nitrogen into our agricultural products, then we start thinking about giving supplemental nitrogen. And how do we do that? That's nitrogen containing fertilizers. So that is ammonia, ammonium salts that then are spread out, spread on our fields, that then induce higher nitrogen content and then that becomes the feedstock from which the, the plant can start to build up its own protein reserves. So nitrogen is kind of a challenging nutrient because to get nitrogen in the air, which is diatomic nitrogen, it's N2 bonded together, two nitrogen atoms bonded together by a triple bond. It's hard to break that triple Bond, it's very strong to get it into single nitrogens like into ammonia or into ammonium fertilizers. And so that's a very energy intensive process to make these fertilizers and to feed more nitrogen into our plants. So the alternative of that course is to use agricultural methods that foster this nitrogen fixing bacteria and regenerate the soils in terms of nitrogen. And that's been all the time the kind of the juxtaposition between NPK fertilization and in agribusiness and the use of nitrogen fixing bacteria in soil economy by proper husbandry of the soil. So we'll talk more about that later. But I want to kind of at least set the tone that nitrogen is unique and it's only found in protein and it's difficult to get into this, the system. Secondly, how do you get rid of nitrogen? So we have a difficulty getting nitrogen into the body as protein. And now we have some complication getting it out because if it sticks around in the body, it can bruise produce as we're going to see later, toxic byproducts. And so in the human we get rid of nitrogen in a very unique way through the production of urea through the urea cycle. Now that is an interesting and important differentiation between us and other animals. Often fish and other animals can get rid of nitrogen by just excreting it through the skin like as ammonia. Your cat, as you know, if you have a cat and you have a cat box, you probably notice it's a very strong aroma. So the, the cat produce is more ammonia, less urea. We produce urea as a byproduct of nitrogen excretion. And so that has to do with the metabolism of nitrogen containing compounds that come from protein through the urea cycle, which is principally located in the liver of the body that manages this nitrogen breakdown. And we'll talk more about that later. So what are the composition of proteins and their function? We've talked about the fact that the proteins are made up of these building blocks called amino acids. And those amino acids can be broken into two families. One are called non essential. That doesn't mean that they're not important. It means that the body can make these from other things and so you don't have to eat them as specific members of the amino acid family. And then there's the essential amino acids, these eight or nine other amino acids of the 2022 family that have the inability to be made in the body so they have to be eaten directly. They're almost like vitamins in that respect they can't be made, so they have to be consum as such in our diet. So we'll talk about quality of proteins. And quality of proteins often will relate to how plentiful are these essential amino acids within the protein to make it more able to deliver to the body a complete ratio or portfolio of these amino acids. And we put the amino acids together into chains. Those chains are called peptide linkage chains. And so when you put many of them together, that's called polypeptides. And these polypeptides can be of different length. They can be just a few long, like three or four long, or they might be hundreds long, as we find in some proteins and enzymes where they're much longer chains of these amino acids if they're fairly small in number, and we call those peptides. And peptides can have their own activity. They can serve as hormones, cell signaling agents like chemokines, cytokines, lipoproteins, neurotransmitters. Going to talk a little bit about how protein nutriture gets distributed out through all these families, how the body is working to allow that family of amino acids to be seen in different forms, in different ways, for different functions. And then I've talked already about the structural proteins, collagen and elastin enzymes. And there are also forms of protein that are connected to sugars. We'll talk about those. Those are called glycoproteins. And they have important roles to play as well. And they also have some potential pathology associated with him as, as we'll talk about as well. So what are the essential versus the non essential and the conditionally essential amino acids? And what do I mean by conditionally essential? These are amino acids that under certain circumstances would be considered necessary to be consumed directly in that form in the diet because the body's not making enough to meet its needs. You have, those are straight essential, those are ones that for sure cannot be made in our body. Histidine, isoleucine, leucine, these are isoleucine, leucine, valine are so called branch chained amino acids. You'll hear that term BCAAs, branch chained amino acids. They play a very important role, as we'll see in, in muscle metabolism and in general sufficiency of protein adequacy. Then you have histidine and methionine. Methionine is a sulfur containing amino acid along with its counterpoint, cysteine. And then you have the aromatic amino acids, phenylalanine and threonine. And Tryptophan, well, tryptophane is actually indole. So phenylalanine and tyrosine are your immuno acids that are precursors to, to the dopamine family of neurotransmitters. And tryptophan is the precursor to the serotonergic neurotransmitters. And then lysine is a very important amino acid in this family because it is often a lim amino acid in people who eat poor quality protein diets. So we always concern ourselves with the adequacy of lysine in the diet and particularly in people that may be eating unusual types of vegan diets where they're not getting adequate lysine. So we're just breaking down these amino acids into the, the families of essential, conditionally essential and non essential. Those are those that can be made in the body. Cysteine is made from methionine. So if you have adequate methionine, then you'll hopefully have adequate cyste. So what about the protein structure and its relationship to function? So proteins, these amino acid linkages, I call them polypeptides, have three basic kind of configurations in the body. First is your primary structure. That's how each amino acid is connected to the next. And, and the nature of a name of a protein is going to be built around the sequence of those beads on the pop bead of the protein, the amino acids in sequence. So you have alanine, glycine, glutamine, those are linked one to the other will give rise to the specific protein that will have a specific name. And that protein will be coded for as it relates to the sequence of those amino acids on that chain by the genes. This is part of our genetic inheritances to code for how those amino acids will be aligned to make our proteins in our body structural as well as catalytic or informational proteins. Then once the chain is put together, it's put together on the ribosome in a cell, then it undergoes conformational changes. It kind of folds back up on itself and it forms what's called secondary structures, hydrogen bonding and so forth. And then that's further twisted as is kind of simple represented in this little cartoon on the left. It's further twisted into this ball like conglomerate, very defined structure that we call the tertiary structure. And that's the active form of that protein in, in terms of its, its structure and function. So in order for proteins to do their works, they have to have the right amino acids in a row. They have to be twisted in the right way and they have to be agglomerated in the right way to produce then the active protein. So that's the protein structure and function relationships between the primary structure, which is the sequence of amino acids on the chain, which is controlled by our genes. And so if you talk about single protein nucleotide polymorphisms, you've heard about this with genetic testing. That's SNPs. SNPs are genes that regulate the production of a protein such that one amino acid along that chain is different than the native way that that protein would be made. So that might be a, a substitution of a glycine for a phenylalanine along the chain. And that would be then a nucleotide, single nucleotide polymorphism that would occur in that gene that would then alter slightly the structure and function of that protein once it's manufactured within the cell. Now if, if that amino acid change was occurring in a region of the protein that didn't have a lot of direct effect on its function that's away from its, say, active site, it may have a very little effect. That SNP not have much influence on your function. But if that SNP happens to be at a place in the production of that, that ultimate protein, it's very critical for its function. Now that SNP might have significant impact on your overall function and, and subsequently your health. So all these things kind of tie together in this emerging understanding of the, the molecular and cellular biology of proteins. Now to make this even a little bit more confusion confusing. When proteins are produced in the body, they often are not formed in the active configuration. The body has this intelligence about it, it's remarkable. It said, I'm only going to make that protein active when it's needed. So I'm going to put a reservoir out there of inactive protein. These are called zymogens, excuse me, the, the inactive protein needs to be converted then into the active protein. This would be like an example would be the DIG enzyme trypsin. Trypsin is actually stored in cells as trypsinogen, which is the non active form that then has to be broken down, cleaved into delivering trypsin. So the body has this very important regulatory ability to kind of control when active enzymes are going to be available and when they're not going to be available. And I think this is another place where one might actually have some defect in your function is not regulating the delivery of proteins at the right time, at the right place. It's all part of this regulatory matrix. But it starts obviously with first having the right structure of the protein because you had the right amino acids available at the right time for that protein to be synthesized. Its primary structure. So a good example that's often used is insulin. You know about C peptide. C peptide is a diagnostic tool for looking at the activity of insulin in the body and, and how it's being used in a and how it's available. Well, it turns out that insulin is first produced by the body as insulinogen. Insulinogen is not the active form of insulin. It's a little like this trypsinogen model I was describing earlier. So insulinogen is converted into active insulin when the this tail of the A polypeptide is cut off and that leads to the release of C peptide. So when the body's making active insulin, it's going to be also producing more C peptide. And so now we have active insulin and C peptide and we can measure C peptide in the blood to see how active the insulin function is occurring. Kind of the kinetics of insulin production is occurring within the body. And it can be an indirect measure of insulin availability and insulin insulin sensitivity or insulin deficiency. Now to further complicate the story, proteins, once they're made in the body, don't always just stay that form, they can be modified. And this is called post translational modification. And I think this is an important additional story for us because some of the post translational modification of a protein can lead to improved protein function. Others of the protein post translational modification can cause the protein to lose its function or have altered function. So let's talk about a form that you're familiar with of post translational influence on a protein that can result in it having less effective function. That would be the glycosylation of a protein like hemoglobin. So hemoglobin is a major blood protein, as you know. And when hemoglobin is formed, it can undergo a chemical reaction with glucose that's called a glycosylation reaction to post translationally modify the hemoglobin protein into a now glycosylated form. Now you know about this, whether you know it or not, you know about this because this is what we call hemoglobin A1C. That's one of the ways that proteins can be glycosylated. And the higher the blood sugar level in your body, the more glucose is available and the more glucose can chemically react with with hemoglobin to produce this glycosylated end product. So it's an indirect measurement of blood sugar, the higher the amount of available glucose, the more react post translationally with hemoglobin. And by the way, when it does it, it lowers the ability of hemoglobin to do its job. So it's having an adverse effect on oxygen delivery, oxygen transport and so forth. So this is an example of how post translational modification of proteins can produce an adverse effect. What is another way that post translational modification of proteins occurs? Oxidation. So this is like barbecuing beef at too high a temperature and, and burning the protein. And you now to oxidize the protein amino acid matrix include and produce new oxidized derivatives post translational derivatives of protein that have potential adverse effects. It can be hepatotoxins, they can be carcinogens. So we now know that all these processes of altered protein structure post translational, some of those are regulated very carefully. And like neation of proteins, that's a very closely regulated process that has to do with the epigenetic regulation of our body. But then other post translational effects are occurring randomly by exposure to toxins, oxidants, glycosylation factors, various things that want to chemically react with protein to modify its function. So this is my glycosylation with hemoglobin example I've already shared with you. And when we measure hemoglobin A1C, we're measuring this combination of glucose sugar with protein lyseal amino groups in hemoglobin to produce this glycosylated hemoglobin, which is now able to be measured because it's not your native hemoglobin, it's a non native hemoglobin. Now this is very important I think if you give this a little thought. We know that when you start post translationally modifying proteins through this kind of non controlled process, that you're producing funny proteins. And what does the body do if it sees a funny protein? It generates an immune response. Because that's what the immune system is supposed to do, is recognize foreigners and to try to get rid of them. So what happens with people that have diabetes and, and they have high hemoglobin A1c and protein glycosylation going on is that their body then responds by producing more antibodies against these glycosylated proteins. And so you see a comorbidity with people with diabetes under control, diabetes that have more autoimmune disease because they're actually responding to their in, in their production of these funny proteins because they haven't regulated their blood sugar well, and that sugar is then actively reacting with proteins like hemoglobin to produce funny proteins that are then recognized by the immune system as not being there, as being part of what should be there as foreigners, and they start to react against them. So I've already talked about protein oxidation or protein rancidity, to use a kind of colloquialism, and how also can alter then protein structure and function. And we know that proteins are being continuously oxidized. These oxidized proteins, like oxidized lipoproteins, you've all heard of LDL oxidation. This is associated with various disorders including atherosclerosis, Parkinson's and, and biological aging. And so we now recognize that control of protein oxidation, that's the right antioxidant potential in the body, is very, very important in maintaining prot quality in the body. We also know that amino acids can conjugate themselves with various proteins and they can produce new, new molecules. One, one of them is so called cyclic citrullinated protein or abbreviated ccp. And this is found in people that have rheumatoid arthritis, where citrulline, the amino acid, has conjugated itself with a protein to produce this funny protein that is now associated with the immune dysfunction in rheumatoid arthritis. And so levels of CCP are used as a diagnostic determinant for, for rheumatoid arthritis. So how do proteins differ? Well, they differ in many ways, but one way that proteins differ from fats and carbohydrates is they contain sulfur. And that sulfur is in the form of the amino acids methionine, cysteine and cysteine. These particular sulfur containing amino acids then are involved with what's called the transulfuration pathway. It's a metabolic pathway that regulates how sulfur travels through the body as an essential nutrient. And we see sulfur ending up in very important places like glutathione. You've heard of glutathione as a one of the principal cellular antioxidants our body. It also is found in S adenosyl methionine, by the name the letter S. You know, it's sulfur. It's found in N acetylcysteine, homocysteine, and it's excreted ultimately as urany sulfate or sulf. So this transulfuration pathway is very important in maintaining proper antioxidant potential of the body and protecting against protein oxidation. I'm not going to go through the transulfuration pathway, but for those of you who are geeks metabolic geeks. You'll notice at the far lower right is how glutathione is being synthesized and, and acting in the body. Ultimately by starting off with methionine in this methionine cycle and how it gets transported down, you'll notice there is a connection of the methionine cycle. If you look to the left of the methionine cycle, what do you see? You see the, the letters thf and what does THF stand for? Tetrahydrofolate. So the methionine cycle in transulfuration is tightly tied to the folate cycle. So if you're folate insufficient, like 5 methyl tetrahydrofolate insufficient, it has a defective role to play on your methionine metabolism and that may limit or lower your, your ability to produce glutathione. So all these are interconnected. This is a network of metabolism. But you have to have the proper levels of sulfur amino acids and also the proper levels of folic acid, B6 and B12 to support this, this whole pathway. And that really is this whole methionine cascade going down through homocysteine, as you know. Once again, homocysteine, if it builds up in the body, can be a toxin. So it has to be properly metabolized down into ultimate glutathion, homocysteine and taurine. Other biomolecules that are very beneficial for the body. They're all these sulfur containing derivatives from the amino acid methionine. And you can measure how efficiently your body's doing that, in part by the level in your blood of homocysteine. So if homocysteine is elevated, it suggests that there are then defects or alterations in this cascade of events that ties to the transulfuration pathway in the production of very important things like glutathione and taurine. Well, how do you digest protein once you consume it and get it down into amino acids? It occurs through a process that starts in the stomach with acidification. They have specialized cells in the lining of the stomach that produce hydrochloric acid. These are called the parietal cells. The parietal cells have this, a very important role to acidify what's called the chyme, that's your partially digested food material sitting in the stomach. And the acidification of that is very important because the enzymes like trypsin, they're going to break down protein, require proper acidity in order to do that. So if you have hypochlorohydria, which is low stomach acid production. You may be a protein mal digester which makes you an amino acid malabsorber. And you may be suffering then from what's called exocrine pancreatic enzyme insufficient deficiency syndrome. Now we started talking about this, oh gee whiz, in my case probably back in the early 80s about this excrement pancreatic enzyme insufficiency. It was pushed back pretty strongly by traditional gastroenterology at the time. But over the decades now it's become recognized that this is a clinically important condition in many people who have poor stomach acid output or who have poor for exocrine pancreatic enzyme output. And they're not absorbing their, their protein correctly as form of amino acids. And now we see promotion of drugs to treat this exocrine pancreatic enzyme insufficiency. We've been talking about the use of digestive aids for decades, the pancreatin digestive aids. For people that have undigested food in their stool, who have maldigestion. We have used things like betaine hydrochloride as a supplement along with pancreatin. Generally porcine source is the better source for the improvement of protein digestion. So if a person has a difficult time digesting their meals, this is an important kind of clinical concept to be aware of. So we talk about breaking down protein into its form through proteolysis and then into its amino acids which are absorbed and then ultimately the amino acids are metabolized through your recycle in the liver. I'm not going to obviously do a big metabolic discussion of amino acid metabolism, but just say that this has been a major breakthrough in, in basic human biochemistry is understanding how amino acids can be broken down, ultimately entering into our energy processing system of the body, the so called citric acid cycle, and how they can then influence our energy production. So proteins going to amino acids, amino acids go to our energy cycles. So these become fuel for the as well as structural components for the body. And we'll speak more about this because some of these amino acids, the ones that are in kind of pink red color here, are so called glucogenic amino acids. They're the ones that can be broken down and converted into blood sugar. And we'll talk more about that later. But we often think of sugar comes from carbohydrate and protein is around structure. But now we know that actually the constituents of protein, protein, amino acids can be broken down ultimately through this process of glucogenesis to produce blood sugar. So you can have blood Sugar abnormalities from altered protein metabolism. And so here's how it all looks in Big Cycle. Don't you love that? Yeah. These are the things we have to memorize and, and repeat on demand on tests. If we're in biochemistry, I promise you we're not going to go through this. The only thing I just wanted to point out, if you look at the colors like the dark Bl phenylalanine and tyrosine and tryptophan, these are essential amino acids that go on to be produced neurotransmitters like the serotonin and the dopamine family. And so these play multiple roles, not just the energy economy, not just building enzymes, not just building structure, but actual functional signaling roles on the body as precursors to neurotransmitters. So you might ask, well, what would happen if you were protein deficient? Well, could it adversely affect your mood because it could lower serotonin levels in your brain? And the answer is yes. Those kind of studies have been done showing that protein insufficiency or protein that's not adequate in the delivery of tryptophan could lead to lower serotonin and to lower impact on your affect, your mood. What about a substance you've heard a lot about called nitric oxide? You'll notice nitric oxide. No, you'll see it in red there in the kind of the middle of the diagram. What is it come from? It comes from the metabolism of the amino acid arginine. So if you were arginine insufficient and you, you didn't have proper metabolism of arginine by nitric oxide synthase, the enzyme that modifies arginine into nitric oxide. Now you have inefficient nitric oxide. Why is that important? Because nitric oxide is very important for blood pressure control, for cellular metabolic, in vascular function of your heart and blood vessels. So we, we start to, to see that the amino acid insufficiency there could produce a downstream adverse effect on messages that your body needs to perform at a high level. And then lastly I said that the, the nitrogen in our amino acids is ultimately eliminated from the human body through what's called the urea side cycle. The urea cycle is how urea is ultimately produced. And urea then is ultimately transported across the nephron of the kidney, ending up in the urine. And it's a major urinary metabolite of nitrogen excretion. So if you eat a very high protein diet, you're going to then put more pressure on the urea cycle and more pressure on your kidneys to eliminate that nitrogen byproduct called ure urea. And that's another important theme about what happens if you eat too much protein for your body's capability of properly managing it. Could it have adverse effects on your kidney? Could it have adverse effects on buildup of urea in the body that has its own potential toxic influence? And the answer of course is yes. Everything has a proper zone of regulation, including dietary protein. So excesses for an individual could then overload the system and lead to liver problems, lead to kidney problems, lead to central nervous system problems, lead to immunological problems. So the right amount of the right type of protein, very important. And we know that singular amino acids have therapeutic potential as I've mentioned, with arginine and citrulline and the impact on nitric oxide with branch chain amino acids, leucine, isoleucine and veiling effect on muscle protein synthesis on neurotransmitter precursors. Tryptophan for serotonin and phenylalanine and tyrosine for the catecholamine. And we'll talk even about what for a long time was considered an unimportant amino acid because it's not essential, it's, it's ubiquitous and that's glycine. But it turns out that glycine can have very important therapeutic effects as well on liver function and what are called the glycination reactions that are related to detoxification. So even a simple amino acid may be conditionally essential and benefit from supplementation. Patient. So how do we assess protein adequacy? Well we have disorders that are associated with protein inadequacy that have names Quashiokor and in marasmus. To a, to a degree we see this mostly in very seriously protein and calorie malnourished populations. But it can appear anywhere in the world where a person is not getting adequate protein nor calories and they're diet. The other which is more prevalent in the western world is sarcopenia. SAR is flesh. Penia is loss of. So this is the loss of flesh, the loss of muscle mass. And it's one of the principal issues related to age induced frailty and to people losing balance and falling which is as you know, a, a serious risk factor as we, we grow older to, to both mortality and morbidity. And sarcopen sark flesh loss of is related to things like metabolic syndrome, to insulin resistance and to oxidative stress. And so how do you then use protein properly in A total dietary lifestyle application to maintain muscle mass as we, as we age. And so we'll talk about that and functional amino acid deficiencies as well as amino acid excesses or what are called, called acidurias. How do you measure then the quality of the protein that you're consuming in your diet? Because not all proteins from different dietary sources have the same biological value. So how do you measure it? Well, there are ways that people now have defined objective ways of assessing protein quality. The so called biological value or protein efficiency ratio per protein digestibility, corrected amino acid scores or the digestible indispensable amino acid score score. Now these are all ways that proteins can be quantified. You can have proteins analyzed to get the number for each of these variables. So you can categorize or compare protein quality, one protein against another. And we're going to talk about that in a moment. With various types of dietary proteins. I just want you to be aware of this scaling system. Now one of the problems that occurred early on in the establish of these scaling systems was that a lot of this work was done with rodents and how rodents used protein to keep their muscles and their bodies functional. And so protein scores were often built around or amino acid scores around rodent metabolic studies which were the most extensive that had been done. And it turns out that this was later found to have a difficulty because even though the government had used these criteria, it was found later that the rodent has a unique way that it manages sulfur amino acids. It has a, in its liver, it has a much higher level of need for sulfur amino acids in do humans. And so some of these studies then that led to protein digestibility and efficiency ratios were built around rodent data and then categorized for humans proteins at a lower value than really they should have been. So that has been kind of in the process of, of correction. And it's good because sulfur amino acids are lower generally in vegetarian diets. So what it did is by recorrection it made the vegetarian diets protein content actually higher quality in humans than we thought. If we were feeding it to rodents, we get a different score. But if we're feeding it to humans, the value is higher. So that actually kind of changed our perception of the quality of protein and vegetable proteins versus animal proteins. And we'll talk about that. What are the amounts of proteins that are needed? What are the ratio of essential amino acids? So you have a complete dietary protein that you're not missing or getting excess of one amino acid to another. And what about the presence in certain foods of protein digestion inhibitors. We know that in certain vegetable products and cereal grains that it contains various types of digestive inhibitors that prevent the digestive enzymes from properly breaking down carbohydrate protein and or carbohydrate. And so that can lead to mal digestion which can lead to malabsorption syndrome. So we want to look, when we're looking at dietary protein sources, at foods that don't have high levels of these protein digestion inhibitors, phytic acid being an example. So this is the animal versus vegetable protein debate that's been going on for some time, probably not over yet. And I've talked about one of the components, which is the methionine sulfur amino acid component. Because initially a lot of this study on looking at the variable quality of vegetable versus animal proteins was built on work that was done in rodents. And now we have seen that that was probably a false model for human metabolism because the human liver does more efficient job in managing sulfur amino acid metabolism than the rodents. So the levels of need in the human are lower than we had expected there would be from rodent studies. So now we see vegetable proteins actually having higher protein efficiency ratios and higher utilization than were previously defined. One of the the individuals that was at the forefront of this research that deserves a lot of our credit and adulation is Dr. Vernon Young at MIT. Young and Scrimpt Shaw, two investigators did much of the early protein work from which the dietary goals and dietary levels were established by the government. Taking on this and looking at the the data around complete proteins that had all the essential amino acids. Francis Mar then authored a book in the in 1970 that was really a frame shifting book called Diet for a Small Book Planet. And you recall in this book she proposed that there are cultures around the world, world that don't have a lot of animal products available in their diet and have lived very successfully on vegetable diets, vegetable rich diets. And when looking at their diets, it was found that their intake of things like grains and beans, beans and rice, that kind of things, legumes and grains gave a complimentary protein that could then be a vegetable based protein about equivalent in amino acid ratios of the essential amino acid to that found in animal based proteins. And that was really a major step forward in kind of understanding how protein adequacy can be maintained in vegetarians if they have the proper balance of the amino acids from different foods. Grains and legumes being kind of the complementary protein that she described in Diet for a Small Planet. And if we look at the blue zones. And look at blue zone diet principles. These regions around the world that are associated with longevity, many of them are, in fact the majority of them are very high in plant based protein intake, a modest amount of animal protein intake and the plant proteins they have are these complementary proteins that I've described by blending the way that they use foods that have these complementary amino acids. And that has to do with the lysine and sulfur amino acid adequacy as the limiting amino acids in making a complete protein. So I, I think those who are just saying you can only get great protein out of animal products are, are really not looking at the literature correctly. Granted you have a higher per and a slightly higher digestibility in animal proteins than that of most vegetable proteins. But at the level we're consuming vegetable proteins today in our diet, the adequacy for delivery of these essential amino acids as a complementary protein is being met. And there are many individuals who are on plant based protein diets who are more than adequate in, in muscle building and, and, and protein sufficiency. One of the interesting foods that we've been studying as it relates to plant proteins is Himalayan Tartary Buckwheat. It's a, about a 2 to 3,000 year old food in, in the human diet. It turns out it's one of the highest a plant protein, non grains. It's actually a fruit seed and it's gluten free obviously. It by the way gluten is a, is a protein as you probably know. It's generally found in cereal grains and it has you know, this obvious potentiality to produce immune sensitivity or, or immune allergic reactions in some individuals. But Tartary Buckwheat is a gluten free seed that then it's carbohydrate matrix with protein. It's about 15% protein, which makes it one of the highest protein starch delivering foods on our planet. And its amino acid profile is extraordinary because it matches up and syncs up very closely with animal proteins in terms of the essential amino acids. So it delivers the essential amino acids and it delivers them in a very high percentage. If you think of animal foods, you know, having between 20 and 25% calorie percent as protein. Here we have 15%. It's coming very close as a vegetable protein to that of animal dry proteins. So let's compare some of the more common protein sources that you're probably familiar with. Casein, lactobumin, that's whey pea protein and soy protein. These are ones that you probably heard a lot About So let's look at the puts and takes of these various types of proteins with casein. It's a milk protein. It's one of the principal milk proteins. There are two forms of casein. There's an A1 casein that is found in the milk of domestic cows and this is found to have very high allergenicity. Now you probably know there's another form of casein which is called A two casein that comes from a different strain of cows that are not generally in the dairy herds of American cows. They're found in the dairy herds of New Zealand cows House. So A two casein doesn't have nearly the allergenicity as does A one casein. What happens with A one casein is it, it can induce immunoglobulin E and non immunoglobulin E mediated immune issues so more allergic potential. It also can be converted to a peptide in the, in the digestion that's called beta casomorphin 7 or a BCM7. And BCM7 has been associated with gut inflammation and increased permeability or so called leaky gut. So for most of us we like to avoid supplementing with with the A1 casein protein. There's another milk protein however that has is, is absent of these allergenicity related problems of, of A one casein and that's high quality whey protein or lacto mument. There are different qualities in production regard to the amount of residual A1 casing in what has been labeled to be whey protein. And depending on how it's processed you can have either virtually no A1 casein residue or it can have measurable amounts. By the way, I'm not talking about lactose here. This is not lactose intolerance. I'm talking about protein intolerance. And so very high quality way generally more expensive in the marketplace because it's been more rigorously treated to remove the the A1 casein. These are very high in essential amino acids, very high digestibility and high protein efficiency ratios in the range of 90 plus percent and, and pers of of approaching 1 which is the best you can have. If we look at soy protein, it's a vegetable protein. It's, it's been commonly included in all sorts of things. Soy protein does have all essential amino acids, although it's fairly low in sulfur amino acids and, and, but it is reasonably high in lysine, one of the other essential amino acids. But it has unfortunately a very high allergy potential. It also Contains soy phytochemicals, gen genistine and dzine and these are known to have estrogenic like impacts hormonally impact. So although soy protein was used as soy protein isolate in infant formula for some time, as the results of research started more and more defining the potential of genocide and diazine having potential xenohormetic hormonal effects on developing infants. It was removed as a protein source from most of the infant formulas. So what's an alternative to soybeans protein? Well, pea protein has now gained a lot of prominence and and there are different grades and different types of C pro pea protein but in in the the best states it's a very low allergy. Vegetable protein contains all essential amino acids. It's reasonably low in methionine but it's high in lysine. But it, it still has a fairly good amino acid score of 0.9. Recall of the top is 1.0 and a biological value of 86. So it's one of the best better vegetable protein ingredients. How does that contrast or compare to tartery buckwheat protein? Well as I mentioned, tartary buckwheat protein is a gluten free source. It's high in all the essential amino acids. It's high in protein as a source and it has no digestive enzymes inhibitors such as phytic acid. So it is, it's another really great kind of combo low vegetable protein for complementary protein activities. So if I would say what is the best kind of protein you could deliver as a protein supplement? It would be a complementary protein that would blend together the virtues and values of high quality whey protein with pea protein and tartery buckwheat protein. I think this represents kind of an optimal ratio with high end branch chain amino acid for muscle protein production. High digestibility with the lactobulin, good essential amino acid balance for immune support from the pea protein and sustained delivery due to a slower digestion. So time releases amino acids into the body. Low allergy potential. And then lastly the tartary buckwheat protein. There's an interesting feature of tartary buckwheat protein that uniquely defines it and that is it's I think one of the highest if not the highest food that's rich in gamma aminobutyric acid or be GABA G A B A GABA is kind of a neurotransmitter. It's really important for mood support it and it turns out that tertiary buckwheat has this non protein amino acid at the highest level. This gaba. So it's also very high in the immune active polyphenols and flavonoids and low allergy potential. So the combination of these together forms a really, really powerful complementary amino acid mixture with many different functional benefits in terms of immune function, muscle protein synthesis and metabolism. Metabolism. So how much high quality protein do we need each day? Well, that's, that's a debated question, obviously. I don't think there's a single answer. But let me give you some thoughts about this. The general guidelines are somewhere between 0.8 to 1.5 grams of per kilogram. That's 2.2 pounds of ideal body weight of protein per day. That's a lot of numbers. What does that mean? First of all, I, I think it, for me, although they say 0.8 grams, I think I would start at 1 gram per kilogram per 2.2 pounds. And why did I say ideal body weight? Because if a person is very high percentage body fat, let's say that they have 60% of their body weight or 50% of their body weight is fat. This would be obviously called morbid obesity. In that case, you would not define their protein needs based upon their body weight because, because that their ideal weight would be much less because their body fat doesn't need protein. So when we talk about protein needs, we want to, to tie it to the body composition and say the amount of protein a person needs should be tied to their ideal body weight to height, type of ratio. And that will translate to somewhere between 40 and 100 grams per day of protein, depending upon your size and your metabolism and the type of protein you're consuming. For most individuals, the amount they're getting in their diets today, based upon national government studies, is around 80 grams a day. So the, the, the diet that we're all on today, it's kind of the standard diet is produced, is providing fairly high levels of protein. Is that the right protein, however, for optimal activity relate to the amino acid mix composition, to its digestibility and its availability for all the functions that I've described that protein plays a role in, in the body. And the answer to that question, I would say is problematic because of the nature of how we are getting our proteins from our diet and, and how they are delivered ultimately to the sites of need in our various tissues. If you look at food equivalents to come up with a critical amount of amino acids that can be digested and absorbed, food equivalents for producing the amount of protein that I've just described on a daily basis is around A half a pound of beef steak, one large chicken breast, three quarters of a pound of salmon, two cups of tofu, two cups of tartary buckwheat. Protein composition. So these are all within the, the range of what one could get in the diet and it's finding the right balance. And I want, I want to again emphasize that too much protein may be just as advantageous or disadvantageous, excuse me, as too little protein. There is a maximal benefit amount of protein that's based upon the individual personalized level on activity genealogy, dietary type, frequency of ME digestive ability. We do know however, as I mentioned earlier, that excess protein can be converted in the body into blood sugar. So you can exacerbate blood sugar problems with too much protein, particularly branch chain amino acids that are rich in leucine and isoleucine and valine. These are glucogenic amino acids that can stimulate blood sugar formation. These are the glucogenic amino acids that I've already described. So I don't think I need to go through them again. I just want you to recognize that that protein can be converted into sugar and protein can be converted into fat. So it's, it doesn't just stick by itself as an amino acid. You know, with, in the absence of metabolism. Now there are obviously special needs for protein athletes, pregnancy lactation seniors who are undergoing muscle loss, vegetarians who may not be eating the proper balance of complementary proteins in their diet. So that's why I think this is a very, very personalized approach that is required for optimizing protein intake for the individual. And you, you can start, start off first looking at the amount of protein you're getting, looking at the source of the protein and then asking questions about your activity levels, about your digestive ability, about pregnant or lactating, about are you losing muscle mass, all these things through kxia. All these things then become part of developing the appropriate formula and amount and date diet that will support protein needs in the individual. So I've talked about excessive protein intake. We know from studies done on kidney disease that too much protein can, can particularly in people with chronic kidney disease can be disadvantageous. The the DASH diet Dietary approach to stopping hypertension the DASH diet is a lower protein diet more in the range of 30 to 50 grams of protein a day. And it's been found to have beneficial effects on kidney function in people with chronic kidney disease. We know that excessive protein calcium excretion and, and cause bone loss or be associated with bone loss. We know there's a dehydration Potential with excessive protein, with people not intaking enough fluid. So if you do increase your protein, make sure you're getting adequate fluid water intake. And then we talk about protein breakdown products. And this is a very important part of our story because your intestinal microflora can break down protein and amino acids into secondary byproducts. And they have names that don't sound so good, right? Like cadaverine, putresine, indoxyl sulfate, trimethylamine, N oxide or tmao. These are toxic byproducts from protein baked bound product from a toxic bowel situation, excessive protein and, and mal. Mal digestion. They can also be broken down pro dietary proteins into fragments. These are called the peptides that appear in the digestive tract from incomplete protein digestion. And certain of those peptides, certain of those fragments have been called exorphants meaning they have endorphin like activity things like gluteal morphins and caseomorphins. So that comes from gluten containing grains or from casing containing dairy products. They can be broken down into these exorphants in the gut that didn't get absorbed and have effects on our nervous system. Nervous system. They can cause foggy brain, they can cause toxic brain syndrome. They can have adverse effects on, on our perception. So these are examples of this was first kind of recognized in Japan where the Japanese culture didn't grow up with dairy products. They didn't have cows. But we started introducing the western diet into Japan, you know, post World War II and things like ice cream and milk products started to become more prevalent and they started seeing in children many more of these behavioral problems, learning disabilities and so forth. And they started wondering where are they coming from? And the research then tied this to the. In, in part to the increased intake of, of dairy products through the production of these exorphants. So that's a whole interesting topic as it relates to protein byproducts that are then inducing kind of mimicking effects of endorphins and, and producing some of these secondary effects that's different than the intestinal microbial byproducts that I talked about the endotoxic byproducts from my previous discussion. And then lastly glutamate, glutamic acid is a, an amino amino acid found particularly high in MSG monosodium glutamate as you know. And that is associated with toxicity in of itself. Everyone knows what they used to call Chinese restaurant syndrome. I think that's a little bit off putting now. So we Just talk about MSG sensitivity and the reason it was called that it was in soy sauce at high levels. You have a lot of, of MSG and soy sauce traditionally. And so that could induce in certain people with unique genetic sensitivities to glutamate this neurotoxicity. So I, I want to just bring to your attention. You know, everything has two sides of the story and if we start increasing our protein intake, we have to be aware of these secondary effects. One of the amino acids that has a significant potential adverse effect is tryptophan. And I'm not going to go through the metabolic byproducts of tryptophan other than to say that it can be broken down in a substance called indoxyl, which is produced by gut bacteria in the, in a dysbiotic bacterial microbiome. Microbiome. Indoxil is a liver toxin. It's also a central nervous toxin. It's also capable tryptophan to be broken down into what's called quinoline or quinolinic acid. Quinolinic acid is also a neurotoxin. So too much tryptophan or mal digestion and absorption of tryptophan can induce these kinds of problems. And that is again, everything has a beneficial effect because we've seen tryptophan being used supplementary for the increase in the level of serotonin for the treatment of the blues and, and dysphoria for depression. So we know that there are beneficial effects of tryptophan but we also know there can be adverse downstream effects in excess the neurotoxin quinolinic acid that I, I mentioned through one of the metabolic pathways called the kyrenic acid acid pathway. So I'm not going to go into this in great detail just to suffice it to say that when we're talking about amino acid supplementation, you know, we want to take these with the sobriety that each one of us are uniquely different in the way we metabolize these amino acids and how they ultimately end up in downstream products. In a recent study with long Covid, it was found that individuals had had very low levels of serotonin in their blood as a consequence of altered dietary tryptophan metabolism and uptake because of the SARS CoV2 virus, it influenced then the ACE2 receptor and, and how that influenced the intraocyte in the gut mucosa and altered then transport and metabolism of, of tryptophan into serotonin. So this concept of long Covid symptoms having A neurocognitive relationship to altered tryptophan metabolism through the effect of the virus on the gut function and gut transport and metabolism is an interesting advancing concept within the field of long Covid therapy. Lastly, years ago I had the Privilege of meeting Dr. Rosemary Waring, a medical school neurology professor at a prestigious medical school in Britain, who was the first to start talking about the toxic effects of the amino acid cysteine and methionine and its relationship to Parkinsonism and to other types of neuro neurological problems. So again this has to do with individuals who have unique metabolism of the amino acid methionine or maybe excess methionine in their diet, overloading these pathways and producing these neurotoxic secondary effects. So I just again trying to emphasize that we want to be in, in balance as we're, as we're using these bioactive ingredients, the amino acids. And that is also relates to the dietary peptides which are gaining a lot of attention recently. These bioactive peptides. We see collagen peptides being used in collagen hydrolysates for skin and for, for hair and vision. Anti hypertensive peptides from fish protein hydrolysates. We see incomplete protein breakdown products I already talked about with caseomorphins and gluteomorphins. So peptides are kind of in the news now, both in the good and bad of peptides that have regulatory effects. And what we start to recognize is much to the difference of what I learned in gastrointestinal physiology in the 60s that proteins were not absorbed. You had only to absorb fully broken down amino acids from protein. Now we recognize that there is a fraction of our dietary protein that is absorbed into our blood in people that have intact healthy digestive systems. It's absorbed in our blood as small peptide like molecules. And something like maybe 5 to 10% of our dietary protein doesn't get fully absorbed as amino acids. It can be absorbed and see small small peptide molecules which may have regulatory effects on body's function. And this occurs through so called M cell vesicle formation in the small intestine and micropinocytosis which then absorbs these small peptide fragments into the body. And these may have messenger molecule effects on our health. So again protein digestion and assimilation, very, very important part of our story. And this is now part of this dietary peptide absorption recognition. I won't go through this whole thing, but just suffice to say that different types of food derived peptides can be delivered to the amino to the gastrointestinal lining and they can then be absorbed across these biochemical barriers and then ultimately get into the blood and have influences on on function. Lastly, just to close out this hour I've had the privilege of spending with you, let me talk about sustainability and environmental impact of protein. I mentioned early on that protein is unique because it contains nitrogen and nitrogen comes through the atmosphere through diatomic nitrogen gas. 80% of our atmosphere being nitrogen gas, which nitrogen is a diatomic molecule that's bonded by triple bonds. So to break it apart and make nitrogen available to be incorporated into growing plants is a very energy intensive process and can either be done naturally through plants that are nitrogen fixing organisms that have these root nodules, the leguminous plants that I talked about, or it can be done synthetically by converting nitrogen in the air into various fertilizers to deliver nitrogen which requires a huge amount of energy. And so as we really talk about global climatic change and energy economy because energy comes from petrochemicals oven being used to break apart the bonds of nitrogen and to make ammonia and other ammonium salts so that we can incorporate them into fertilizer. So if we really look at the energy economy, the climate and sustainability question of protein, we want to stay as close to the ground as we can done with letting plants do the work because plants have these nitrogenous capability of fixing nitrogen and doing the work that requires huge amounts of energy from the Haber process to convert air nitrogen into food nitrogen. So I just want you to be aware of the fact that there is this very interesting implication of protein as energy sustainable argument that again talks back to plant proteins, those that go through organic and sustainable and now regenerative agriculture methods. That's one of the reasons that we're so excited with our Himalayan tertiary buckwheat to be into a regenerative agriculture system so that we are enriching the soil microbiome to help the plant to be a nitrogenous fixer of nitrogen and ultimately to, to improve economy while energy economy while improving protein levels. So all this is part of the, of the big system of thinking. Well, I hope in the course of this hour which I've, I've probably given you more information that you felt you really wanted in a one hour presentation. I hope I've given you news to use that you can take forward. We'll be obviously addressing this in in more detail as we move forward with Big Bull Health Health. But thanks so much for being with us and I hope I've helped you to make some intelligent decisions about protein and protein nutriture in your own diet. Thanks so much.