 Well, thank you, and I'm happy to have the opportunity to address this interesting meeting. By way of disclosures, I've received research grants in the past from Denone, as well as Abbott, and the National Calamans Beef Association. I'm going to talk today very briefly about milk proteins and proteins in general with regard to health in the elderly. I've been asked to try to cut this down a little, and so I'm going to give an overview first here to tell you that there's two main messages that I want to get across today. One related to the role of protein in the diet in general and in health status in elderly, and I'm going to zip through a variety of slides to make the general point that we have focused very extensively on lean body mass changes in the elderly and the loss of muscle mass, and in fact the evolving definition of sarcopenia or the extreme muscle loss that occurs in certain percentage of elderly that is associated with a variety of health outcomes that are all negative, is predicated on lean body mass. What I want to really focus on more today is that the dietary protein and resulting amino acids has a variety of physiological functions, and that we have to look well beyond the effect on lean body mass alone as the criterion on which to base how much protein intake is recommended for the healthy lifestyle in elderly individuals. And then at the second aspect of the talk, it's going to focus more on protein quality and recent efforts to advance the quantification of protein quality in a numerical way. Well, with regard to lean body mass, the crucial question that we have to ask with regard to protein intake in lean body mass is whether increased protein intake translates to more lean body mass and improved health outcomes. And I can tell you that with regard to the elderly, this is a difficult issue. We know that the mechanism of action by which protein intake affects lean body mass or muscle accretion is by stimulation of muscle protein synthesis. There's a very simple demonstration here from a study we did many years ago that the net gain or loss of muscle protein is determined by the balance between protein synthesis and protein breakdown and in the absence of any dietary intake, in a circumstance where there's a net breakdown of muscle protein due to the rate of breakdown exceeding the rate of synthesis. And we, in just protein or amino acids, the rate of synthesis is stimulated so that we enter into a positive balance. So this is the fundamental basis. But how this translates to the effect of dietary intake of protein on long-term lean body mass is less clear. And I will specify upfront that we really don't have controlled prospective trials in which high levels of protein intake have been given over prolonged periods of time. So we have to look at shorter studies where there have at least been some dietary controls. And if we look at, there have been several studies, and this is one done by Dillon et al. in which elderly individuals were given dietary supplements of essential amino acids twice per day in addition to their diet. And this is, we don't know really what the rest of the diet was. And this is one of the limitations of supplemental studies, but we have to live with that limitation. And what this study showed was that there was in fact a gain in lean body mass in these individuals when they had an increased intake of essential amino acids. The thing that I would note here is that the change is fairly significant. But this is a change which plateaus and it doesn't continue to keep increasing. And in fact, other studies have not shown very significant changes in lean body mass over time with supplemental protein or amino acids. So how much effect this exerts in a long term is difficult to say in terms of lean body mass and elderly. Certainly the more loss of muscle that has occurred in older people, the harder it is to improve lean body mass simply through diet alone. Population-based studies are difficult to interpret often, but this is a result of the heart ABC study in which a large number of subjects were followed over a three-year period and divided into quintiles of protein intake. In all of these subjects, there was a loss of muscle protein over the three years in the elderly. Those that had the highest level of protein intake had significantly less muscle loss than those that had lower. The highest intake here wasn't what we'd really consider high level of protein intake in the range of 1.2 grams of protein per kilogram per day. But it provides some supportive evidence that there may be some sparing of the lean mass loss with increased dietary protein intake. But really, I think that the major point in relation to this, as I said in the introduction, is that I think the focus on lean body mass is probably not the main target when we look at health outcomes in elderly, that it's really very difficult to show significant changes in lean body mass even with resistance exercise in elderly, and that it seems that strength and physical function have much more of a direct relevance to health outcomes than lean mass per se, and that in older individuals there can be a wide range of strength and physical function for the same lean body mass, and this seems to be more important in terms of health outcomes. And this shows just a large group of subjects about close to 1,000 in which mortality and strength was looked at in individuals under the age of 60 and over the age of 60, and again, divided in terms of those that had the lower third of protein intake, the middle third, and the highest level of protein intake. And we look at the all-cause mortality as well as cancer mortality that clearly the individuals having the lower third of protein intake, a lower third of, excuse me, strength, not protein intake strength, those that had the lowest strength had the worst outcomes. Now, all the epidemiological studies suffer from the same problem, and that is, of course, we don't know that the loss of strength caused the mortality, but rather those that were sickest and on their way to dying probably lost muscle strength. So these kind of epidemiological studies are not very conclusive with regard to health status and the importance of strength, but I'm presenting it because it's pretty much all we have. We do know that in very tightly controlled situations that we can influence strength and level function with a dietary intake of amino acids and protein. The mechanism that I think is important to understand with regard to muscle protein synthesis is that the process of protein synthesis and breakdown remodels the muscle, so that as the protein synthetic rate is stimulated by a higher level of protein intake, even if the rate of breakdown is increased to the same extent, so that there's no real change in lean body mass, we still get an improvement in body strength, and this is from the laboratory at Srinair, in which the muscle strength is normalized for muscle mass and shown to be directly related to the rate of turnover of the muscle protein, so that the important aspect of protein intake on muscle strength is stimulating the turnover of muscle protein so that the muscle fibers are remodeled to function more effectively than occurs at a lower rate of protein turnover. What we see when we look at trials where this strategy has been undertaken is that we do see increases in physical function and older people giving either protein or amino acids as supplements. In this study, which was a 24-week study, we saw this is from a group in the Netherlands in which there was a significant increase with whey protein supplements given over a period of 24 weeks. Again, in free-living subjects, we don't really know what the rest of the intake is because it hasn't been controlled, but it's certainly supportive of the notion that stimulating protein turnover through increased protein intake can improve muscle strength. This study is one we did in our own laboratory in which everything was controlled completely because these individuals were maintained completely in bed rest for 10 days so that every bit of food and every bit of activity was completely controlled. You can see that this type of bed rest that is common in the hospital in elderly and why we endeavored to investigate this was because of the hospitalization procedure in the United States of generally enforcing bed rest in elderly. We see that these are different functional tests that are here on the side and that functional capacity was greatly reduced in these individuals when given a placebo, when they were given extra essential amino acids, it almost completely eliminated the decline in the functional capacity. So in this study there was a complete control of all extraneous variables and we see a direct effect of higher levels of essential amino acid intake on protein, on muscle function. I'm going to go through very briefly a variety of other areas that we have to consider when coming to the conclusion as to what level of protein intake we should recommend for older individuals. I'm going to skip that slide because it's an epidemiological slide and show that there's been a representative slide of a lot of work it was referred to in the previous slide that protein, in particular, has been shown to reduce blood pressure. In this case, this study was done by Ray Townsend in Philadelphia in which just one single supplement had a significant effect on both systolic and donostolic pleasure of lowering blood pressure and hypertensive patients. There's a complete literature in this area on the cardiovascular benefits of higher protein intake. We also know that if we give supplemental essential amino acids that plasma triglycerides decrease in elderly. And at the same time, we see a decrease in liver fat and this is work done in our laboratory in which elderly individuals were given a supplementation of essential amino acids for a month and we see a significant reduction of almost 50% in liver fat and as in the previous slide, dietary triglycerides. So that we have mechanisms related to risk factors not only directly related to blood pressure but also triglyceride and hepatic fat that can be modulated by increased intake of amino acids and protein. There's a considerable literature on bone health and protein intake. I think that many years ago it used to be thought that the acidification of the blood resulting from higher protein intake would cause a loss of mineral density in the bone but a number of studies have shown this to not be the case and in fact that higher levels of protein intake are beneficial for bone health. This is one representative study in which subjects were given either a placebo or a 30 gram whey protein supplement over two years and what we can see is the effect on bone, of the bone mineral density of those given placebo over this two year time period had a significant loss and those that had the dietary protein supplements in fact had this loss of bone mineral density prevented over this two year time period. So that we don't really need to rely on epidemiological studies. We have controlled studies, prospectively randomized control studies that demonstrate a beneficial effect in older individuals of increased protein and amino acid intake and I'm highlighting here results there are a number of studies that support each of these various areas of benefits. We've heard already about satiety today and thermogenesis and some reference of the partitioning of nutrients to muscle. So the point is that there's a wide variety of effects of higher protein intake that have physiological benefit in terms of health status in the elderly and that we have to go well beyond lean body mass or what's really been used to determine protein requirements and namely nitrogen balance which is only a surrogate for a lean body mass measurement as not relying on that as the sole criterion on which we base our dietary planning for older individuals. But the question of how much protein is optimal is really up in the air. We really don't know. We have different recommendations from the experts. We have the recommended dietary allowance which is 0.8 grams of protein per kilogram per day and we also have the acceptable macronutrient distribution range of 10 to 35 percent of the calories constituted as protein. These are both published in the same document published by the Food and Nutrition Board of the National Academy of Science. The acceptable mac... The rationale behind this is expressing it as percent is to understand the fact that protein is not eaten as an isolated compound but rather as part of an overall diet so that if we have a low protein intake by necessity then you have to have a high carbohydrate fat intake. One of the things that's a little confusing here is that if we look at the RDA in relation to this AMDR that there is a sort of a dichotomy here because if we take the recommended caloric intake from the same document and look at the RDA as a percent of caloric intake we come up with 9.1 percent and realize that in the same document the minimal recommended percentage of protein intake in the diet was 10 percent. So that we can look at the RDA really as a minimal value that we should be able to be sure that everyone eats but that in terms of the dietary recommendations really it's at the low end of what the experts have recommended as dietary intake and this is from a paper from Victor Felgoni which emphasizes that point where it's a little complicated here but I want to go through it because I think it's important to understand the relation between recommendations and dietary intake. This is the lower level intake of the AMDR 10 percent of the calorie intake and this is the high end so it's quite a wide range. What this represents is actual protein intake taken from the NHANES data so that we can see in America most people are eating closer to 15 percent well above the RDA and what these values represent is he took the dietary guidelines from the USDA and broke down the meal plans into how much protein was in each of the meal plans and that came out closer to 1.5 grams per kilogram per day or in the range of 20 percent of calories which is kind of in the midpoint of the AMDR so that all of these things kind of come into the same area which is well above the RDA so the perspective that we should be eating more protein than recommended in terms of the RDA is really not a very extreme position it's supported by both what people are actually eating what the USDA guidelines recommend and in the pretty much the midpoint of the acceptable macronutrient distribution range we clearly need perspective studies in which higher levels of protein intake are eaten over prolonged period of time to really definitively address the question of how much protein should be eaten but I think that we can conclude from all of these different areas of physiology in which increased protein intake can have beneficial effects that we should be targeting a level of protein intake that's above the 0.8 grams of protein per kilogram per day The second aspect I'd like to touch briefly on is a project that I've been involved with with a number of people under the auspices of the FAO to revise the approach to quantifying protein quality The PDCOS is a system which currently has existed and this new scoring system has meant this a plant to try to come up with a way to quantify protein quality and the report came out was published this year by the FAO of the digestible indispensable amino acid score and there are two aspects of the score of a quality of protein One is the profile and abundance of the essential amino acids and in particular the relation of the profile of the essential amino acids in the protein to the requirements for the individual essential amino acids and the second aspect is the true ilial digestibility of the individual amino acids in the test protein So the way in which this varies from PDCOS is in this case not much other than the PDCOS is truncated at 1 meaning that any protein that provides that if you eat 0.66 grams of protein per kilogram per day of that protein, of the test protein that you can obtain a percentage of the essential amino acids that exceeds 100% then the PDCOS truncated that value at 1 whereas the Dias does not truncate the scores given the opportunity to classify dietary proteins over a wide range of quality according to a numerical score So this shows the Dias scores of common proteins and I'm sorry that they're so small but I can tell you just in grouping them these are fundamentally the animal proteins other than soy protein is in here one of these is right about here I can't read it from here but soy protein is one of these it's the only vegetable protein that's in here there are four quality proteins that don't provide and so what this number means again to try to explain it more clearly if we look at some of the milk proteins here if you eat 0.66 grams of protein per kilogram per day of the milk proteins that you will eat 140% of all the essential amino acids requirement how can we use these quality scores in a practical way to rank proteins well the first aspect is can we really extrapolate from these numbers to actual functional activity and the answer is there's a lot of work to be done there's some suggestion that this is the case let's just take a look at the comparison of whey protein versus soy protein and this is a slide from Stu Phillips lab in which the effect or response of muscle protein synthesis to 20 grams of intake of either soy protein or whey protein is compared and in accord with their respective diast scores we see a significant stimulation of the protein synthesis with whey that is considerably greater than with soy so that in terms of the relative diast values we see a functional relationship in terms of protein synthesis there are other types of studies like this that support the notion that this scoring of protein quality throughout the whole range of proteins is a viable approach but clearly more work needs to be done to actually validate these diast scores as a true reflection of protein quality on a relative basis but if we take for the moment the assumption that they do reflect a difference in quality we know at the very least that they reflect the difference in the ability to deliver essential amino acids in a given amount of protein I'd like to show the last two slides here to make the point in relation to the energy intake required to deliver the amount of essential amino acids required to meet all basal requirements and if we express it just in the energy intake per gram of protein we see that there are certainly some variations in different types of proteins but that fundamentally the energy intake per gram of protein is not particularly extreme if we now correct each of these proteins for the diast score meaning the fractional contribution of each of these proteins to the total ability to provide essential amino acids we get an energy intake per gram of protein which is based on the ability to provide the essential amino acid requirements and we see quite a differentiation in the proteins that peanut butter while having a very high percentage of protein relatively speaking almost 25% that the caloric density of the peanuts nonetheless means that you need to eat actually more than the total energy requirement for the day to meet your protein requirement whereas some of the high quality proteins and we look at whole milk or whey protein here are much more effective in delivering the essential amino acid requirements for a given amount of caloric intake and so I think that as time evolves when we get a better validation of these diast scores as really corresponding to functional capacity this type of approach of trying to express or develop dietary plans in terms of the ability to deliver essential amino acids those calorie efficient manner will be quite an effective approach to the nutritional planning and recommendations this just shows the difference between the two graphs where we've looked at here just expressing the kilocal's required per gram of protein and then in this case the kilocal's required to meet minimal EAA requirements and then if we look at the requirement to meet EAA requirements we have quite a different picture of the nutrient density of these different food stuffs in terms of protein quality so to conclude an older individuals that intake of protein greater than the RDA promotes better health outcomes by affecting many systems and to just sort of answer a challenge that's always issued is that there are many studies that haven't shown much benefit and I may have cherry picked some of the ones that have shown benefit the important point I think with regard to deciding how much protein should be eaten here is to recognize that in no study that the RDA has been compared to a higher level of protein intake has the RDA ever shown to have better outcomes than a higher intake the second point is that the high quality proteins such as milk proteins enable the targeted essential amino acid intakes as defined by amino acid requirements with less caloric intake than lower quality proteins and therefore we can't just consider a protein a protein that we have to look at the quality of proteins and in that regard the milk proteins come out very much at the high end of the spectrum so with that I'll conclude and thank you for your attention