“Where Did The Protein Go?”-The Ultimate Metabolic Question To Answer In Order To Improve Chief Complaints In Chronically Ill Patients
As I suggested at the end of the last newsletter, I felt, at that point, I had said everything there was to say in terms of providing a “big picture” introduction to Entry Level Clinical Nutrition™ and was ready to move on to an in depth review of the various components. However, shortly after writing that newsletter, some conversations with you about some of your most difficult patients, the release of some key papers on determinants of quality of life, plus the purchase of the book Protein Turnover by J.C. Waterlow (1) made me realize that a major foundational issue still needed to be addressed. Interestingly, I did address this issue in my reviews of the various papers on the acute phase response and sickness behavior in a somewhat superficial, academic fashion. However, given my current opinion that optimal understanding of this issue can greatly clarify why chronically ill patients feel poorly and what we need to do to help them feel better, I feel this issue requires further exploration.
Could it be that the vast majority of symptoms reported by chronically ill patients can be explained, both in terms of why they exist and what to do about them, by answering a simple question:
Where did the protein go?
Over the years, this question has been not only posed, but answered many times – not only by me but by many others – using different but very common phrasing:
Is the patient anabolic or catabolic?
Why consider this question again using different words? To answer this, first consider the definitions of the words “anabolic” and “catabolic” as found in Dorland’s Illustrated Medical Dictionary, 28th Edition. The dictionary defines the word “anabolism” in the following way:
“any constructive metabolic process by which organisms convert substances into other components of the organism’s chemical architecture.”
How about “catabolic?” The dictionary defines the word “catabolism” with the following:
“any destructive metabolic process by which organisms convert substances into excreted compounds.”
While these definitions are interesting, do they really give us specific information about why our chronically ill patient is ailing and what to do about it? Not really. In turn, by using the above definitions of anabolic and catabolic, I feel, at best, we gain some basic academic understanding of our patients rather than “in the trenches” specifics that provide true insight into why the chief complaints exist and what we can do about them.
Fortunately, many authors have examined these terms from a more clinical perspective. In my opinion, one of the best examples is the book by Mauro G. Di Pasquale entitled Amino Acids and Proteins for the Athlete: The Anabolic Edge, Second Edition (2). In the following quote, Di Pasquale gives these words a more clinical perspective by pointing out how they relate to protein metabolism:
“Protein balance is a function of intake relative to output (utilization and loss). Body proteins are in a constant state of flux with both protein degradation and synthesis constantly going on. Normally these two processes are equal with no net loss or net gain of protein taking place. Protein intake usually equals protein lost.
However, increases of both protein synthesis and protein breakdown (as many do) might have a positive or negative anabolic effect. The overall effect is anabolic if the increase in protein synthesis is greater than the increase in protein breakdown, and catabolic if protein breakdown exceeds protein synthesis. It would also be useful to quantify the anabolic effect so we can tell which substances and procedures would be more effective than others for increasing muscle mass and strength.”
While I feel this definition of anabolic and catabolic provides more of a clinical perspective than the purely academic one found in the aforementioned dictionary, it is still too general to provide the specific patient-driven information we desire. Of course, further reading of Di Pasquale’s outstanding text does provide more specific information on the clinical implications of anabolic and catabolic states, particularly in relationship to cellular function, stress hormones, and athletic performance. However, in terms of addressing the needs of chronically ill patients, I am still feeling like I want more specificity.
In turn, I feel the best way to gain this patient-oriented specificity is to ask the question in a different way:
Where did the protein go?
As I have been discussing in previous installments of this series and will point out in much more detail shortly, the acute phase response and its impact on chronically ill patients dictates that knowing the balance between protein synthesis and breakdown is only a very basic beginning. What we really need to know are the very specific endpoints of protein breakdown. For, while it is academically satisfying to know that protein, during a catabolic state, is broken down and excreted as suggested in the above definitions, this information does not even begin to tell us why this protein breakdown plays such a large role in creating our patients’ chief complaints.
In contrast, if we go beyond the terms “breakdown” and “excretion” and consider in very specific detail “where the protein goes,” we gain a more helpful, more clinically relevant picture. For, by asking this question of where the protein goes, we are led to the following question:
Was it used to build functional tissues related to improved quality of life such as muscles, ligaments, gut lining, glutathione, phase I and II detoxification enzymes, red and white blood cells, etc. or produce glucose via gluconeogenesis and tissues designed to cope with stressors such as inflammatory cytokines (TNFα, IL-6), acute phase proteins (C-reactive protein), and proinflammatory neurotransmitters (quinolinate, glutamate), etc.?
In addition, knowing the answer to this question leads us to another equally important question concerning therapeutic use of protein and amino acid supplements:
Was the supplemental protein/amino acids we provided used to build functional tissues related to improved quality of life such as muscles, ligaments, gut lining, glutathione, phase I and II detoxification enzymes, red and white blood cells, etc. or produce glucose via gluconeogenesis and tissues designed to cope with stressors such as inflammatory cytokines (TNFα, IL-6), acute phase proteins (C-reactive protein), and proinflammatory neurotransmitters (quinolinate, glutamate), etc.?
Interestingly, while the first version of the above question is important, the second version may even be more so because not knowing the answer to the latter could lead to a situation where the patient gets worse with our therapies, which is certainly a situation we want to avoid completely.
Yes, asking the question of whether our patients are anabolic or catabolic is helpful from a big picture, conceptual perspective. However, if we ask where the protein went in terms of the parameters discussed in the above questions, I feel we now have access to information that can explain virtually every major symptom typically reported by chronically ill patients and give us a specific roadmap concerning safe and cost-effective resolution. Of course, I realize that this hypothesis may, at first glance, seem far-fetched and outrageous. Nevertheless, it is my goal in this newsletter to begin to present evidence that supports my contention that this somewhat far-fetched and outrageous hypothesis is true.
Of course, I also realize that it could be interpreted that I am suggesting a panacea – that if my hypothesis is correct, a simple supplemental and lifestyle protocol can be created that optimizes functional protein and, in turn, fixes everyone. I want to assure you that this is definitely not what I have in mind. For, it is also my hypothesis that, if what I am proposing is true, what is clinically required to optimize production of functional protein will still require a functional medicine approach involving many of the aspects of Entry Level Clinical Nutrition™ such as reduction of inflammation, optimization of insulin/glucose metabolism, correction of dietary macro- and micronutrient deficiencies, etc. and will vary in content and complexity from patient to patient. You may ask, though, if the clinical steps necessary to address chief complaints from a functional medicine/Entry Level Clinical Nutrition™ standpoint still need to be addressed whether or not the question I am posing is answered, why bother answering it. My reply? It is my belief that if we understand the most foundational, most essential metabolic reasons why the patient is suffering and what is needed to reduce the suffering, it will be easier and more time and cost efficient for us to determine what functional medicine/Entry Level Clinical Nutrition™ steps need to be employed. Furthermore, I sincerely believe that this understanding will give us greater predictive abilities clinically in terms of telling the patient the likelihood that what we are proposing, both diagnostically and therapeutically, will lead to successful resolution of the concerns that brought the patient to our offices in the first place.
RESEARCH THAT SUPPORTS MY CONTENTION
Loss of functional protein and overall quality of life
Loss of protein related to quality of life can be derived from more than one organ system, as I pointed out in the discussion in the last newsletter, based on the fact that the gut lining can be used to supply protein and amino acids for gluconeogenesis. However, the vast majority of papers that focus on the idea that loss of protein has a direct link with overall quality of life no matter what the clinical presentation also focus almost exclusively on muscle mass and its loss during aging and chronic illness. As you may recall from other newsletters I have written on the subject of Entry Level Clinical Nutrition™, the term used to describe age- and chronic illness-related loss of muscle mass is sarcopenia. Of all the papers in my possession that discuss the link between muscle mass and overall quality of life, there is one, as you will see from the title, that suggests it most emphatically. In “Sarcopenia and the elusive fountain of youth” by Hanauer (3) the author states:
“Sarcopenia, the age-related decrease in skeletal muscle mass and strength, is a major risk factor for frailty, loss of independence, and physical disability in the elderly. Therapies that prevent or reverse sarcopenia and other hormone-related changes associated with aging have the potential to reduce the morbidity of aging adults and their resultant dependency on families and society.”
More recently, Studenski et al (4) looked at markers for quality of muscle function, gait speed, and suggested it can also be related to overall survival in older adults. In their paper, “Gait speed and survival in older adults,” the authors conclude:
“In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.”
Interestingly, though, in the accompanying editorial, Cesari (5) suggests, as I have above, that gait speed tells us more than just the quality of function of the lower extremities. Instead, it can be an important marker of overall metabolic health and quality of life:
“Gait speed should not be regarded solely as a measure of lower extremity function. Gait speed has been associated with clinical (eg, comorbidities) as well as subclinical conditions (eg, atherosclerosis or inflammatory status) and is able to predict several health-related events even apparently unrelated to physical function (eg, cognitive impairment, hospitalization, institutionalization). Gait speed may serve as a marker of physiological reserve and potentially could quantify overall health status.”
However, my hypothesis goes beyond the idea that loss of muscle mass is related to chronic illness and quality of life. It also dictates that when we see loss of muscle mass, we need to not only acknowledge that this is a significant issue in terms of resolution of patient chief complaints, but we must also ask the important question:
Where did the protein go?
If the protein is not in the muscle, where is it? To fully understand why our patients are ailing and what to do about it, we can no longer be satisfied with the standard answer that, as noted in the introduction, has been given for years –“it was metabolized.” We must also ask – “What was it metabolized to?” Did it go to gluconeogenesis to make glucose? Did it go to the liver to make inflammatory cytokines and acute phase proteins such as C-reactive protein? Was it oxidized to produce ATP? As I have been suggesting, I strongly feel that, if we can provide concise answers to these questions, we will greatly enhance our ability to not only help patients restore lost muscle mass but much, much more in terms of truly optimizing key determinants of long term quality of life such as overall metabolic and functional reserve.
Have other researchers suggested a major link between muscle mass and long term health? Most certainly!! In “Physiological functions should be considered as true end points of nutritional intervention studies” by Genton et al (6) the authors state:
“Nevertheless, because muscle strength consistently predicts morbidity and mortality, it is suggested that this variable is used as a hard marker of malnutrition-related morbidity and mortality.”
Several researchers have also quantified this relationship by relating grip strength measurements and overall health. For example, Sasaki et al, in “Grip strength predicts cause-specific mortality in middle-aged and elderly persons,” (7) the authors point out:
“Grip-strength measurement is useful for assessing approximate overall muscle strength of middle-aged and elderly people, and longitudinal studies revealed that it also predicts health-related prognosis.”
In turn, Sasaki et al (7) conclude:
“Grip strength is an accurate and consistent predictor of all causes of mortality in middle-aged and elderly persons.”
In a more recent paper, Norman et al point out the following in their paper “Hand grip strength: Outcome predictor and marker of nutritional status” (8):
“Numerous clinical and epidemiological studies have shown the predictive potential of hand grip strength regarding short and long-term mortality and morbidity. In patients, impaired grip strength is an indicator of increased postoperative complications, increased length of hospitalization, higher rehospitalization rate and decreased physical status. In the elderly in particular, loss of grip strength implies loss of independence. Epidemiological studies have moreover demonstrated that low grip strength in healthy adults predicts increased risk of functional limitations and disability in higher age as well as all-cause mortality. As muscle function reacts early to nutritional deprivation, hand grip strength has also become a popular marker of nutritional status and is increasingly being employed as an outcome variable in nutritional intervention studies.”
Before continuing, please note again the quotes above that point out the important relationship between muscle strength, grip strength, and nutritional status. To me this suggests that once we have determined where the protein went, employment of therapeutic modalities that revolve around clinical nutrition may be the best way to put the protein back where it should be in terms of optimal function and resolution of chief complaints.
If protein is not in key functional organs such as muscle and gut lining, where does it go?
Conversion to acute phase proteins (APP)
Now that, hopefully, I have convinced you that losing protein from key functional organs such as muscle and gut lining is one of the most important, if not the most important determinant of quality of life in your chronically ill patients, we must answer the question – Where did the protein go? The traditional answer to this question, as suggested above, is that it was “metabolized and/or excreted.” While I feel this answer is adequate from a strictly academic and biochemical perspective, I also feel it is inadequate in terms of gaining information on how to alleviate chief complaints in our chronically ill patients. For, as I suggested above, knowing where it is going is just as important as knowing where it came from. Fortunately, published papers from the critical care nutrition community have answered this question very precisely over the years. From a very basic perspective, the mechanics of the acute phase response, which I have outlined previously, is a good beginning in terms of informing us where the protein went. Now, though, I want to focus on aspects of the acute phase response that relate specifically to protein metabolism.
It should come as no surprise that, given the acute phase response has been primarily defined in terms of its proinflammatory components and the creation of inflammatory positive acute phase proteins such as C-reactive protein, much of the protein lost from functional organs in chronically ill patients is used to produce pro-inflammatory acute phase proteins. In Protein Turnover by Waterlow (1) the following is stated:
“An interesting hypothesis was proposed by Reeds et al. to relate the acute phase protein (APP) response to the muscle wasting that occurs in so many clinical conditions. At its peak synthesis of APPs after a stress, from the data of Fleck et al., could amount to as much as 0.85 g of protein per kg per day. The APPs contain larger amounts of the aromatic amino acids than muscle, and Reeds calculated that it would require the breakdown of 2 g of muscle protein to provide amino acids for the synthesis of 850 mg of APPs. The other amino acids that are produced in excess from muscle in order to meet the need for the aromatics will be oxidized and the nitrogen excreted in the urine. This would account for a large part of the ‘catabolic’ loss after trauma or in septic states.”
Before continuing, I would like to emphasize two key points from the above quote. First, the quote does point out what we have classically learned about protein during catabolic, ailing situations; some of it is oxidized (metabolized) and the nitrogen component is excreted in the urine. However, as I have been suggesting, knowing that protein is “metabolized” during catabolic physiology only tells us part of the story. For, much more of this protein that leaves muscle goes to the formation of proinflammatory acute phase proteins. How much? As the text states, during stress, protein is converted to acute phase proteins at a rate of 0.85 g of protein per kg per day at peak levels. To put this into perspective, please note that the classic recommendation for total daily intake of protein is 0.8 g or protein per kg body weight. In turn, based on the quote above, in your chronically ailing patients, it is very possible that more than the daily intake of protein is being converted to proinflammatory proteins every day. To me, these numbers are staggering. Knowing this, it should come as no surprise that loss of functional protein can play an overwhelming role in determining mortality and quality of life issues.
Of course, with the above in mind, you may wonder why the body would do something so self destructive? As I have mentioned repeatedly over the years, the answer is that given the nature of its highly stressed environment, the body is responding in a way that makes perfect sense physiologically (while it may be difficult for us to understand at a more superficial level) as suggested in the following quote from the Waterlow (1) book:
“A convincing argument was put forward by Reeds et al. that ‘the mobilization of muscle protein confers an adaptive advantage to the organism.’ They showed that the acute phase proteins (APP) are richer in aromatic amino acids than muscle protein, and to produce 1 g of acute phase proteins would require the breakdown of about 2 g of muscle protein. From an approximate estimate of the amount of acute-phase proteins produced in response to a typical injury they calculated that the nitrogen ‘wasted’ in the APP response might amount to 130 mg N per kg body weight, a figure very close to the typical catabolic loss of N following trauma.”
Another excellent description of what happens to functional protein under stress was provided in the book chapter “Overview of nutrition and wound healing” by Molnar that can be found in Nutrition and Wound Healing by Molnar (9):
“During periods of metabolic stress, the body is able to effectively catabolize the carcass (muscle, skin, bone) to support visceral protein synthesis of acute phase proteins, immunoglobulins, inflammatory cells, and collagen, needed to fight infection and heal the wound. In the case of proteins, intricate shuttling mechanisms have developed to allow redistribution of the substrate from the periphery to the viscera.”
Before continuing, please note again the mention of “bone” in the quote above. Could it be that osteoporosis in most patients is not really a disease at all in the classical sense but actually a response by the body to deal with metabolic stress? To me, this is exactly what the statement above is suggesting.
Below you will find a diagram from the Molnar (9) book chapter that provides an excellent overview of what was pointed out in the above quote.
The next paper I would like to highlight is the one by Reeds et al mentioned in two of the above quotes entitled “Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on the nitrogen loss in traumatic stress?” (10). In the quote that follows the authors make it clear, as I have been suggesting, that the classic assumption that protein is “lost” during catabolic illness states is only true to a minor extent. In fact, most of the protein is not “lost” but is, to a great extent, converted to protein-based inflammatory mediators:
“It is important to recognize that the utilization of amino acids for acute-phase protein synthesis should not, a priori, lead to excessive amino acid nitrogen loss from the body. Thus, even though the rate of turnover of the acute-phase proteins, has not, to our knowledge, been measured in humans, their increased turnover will not necessarily lead to an increased amino acid loss, because the amino acids so released should be recycled into protein.”
Again, with this quote in mind, I want to emphasize that it should come as no surprise that muscle function is so closely linked with quality of life issues given that, under metabolic stress, so much muscle protein is converted to inflammatory mediators.
If you have not already done so, it is my hope that the preceding section helped you to fully appreciate the major impact that conversion of functional protein to inflammatory mediators has on patient quality of life in general and, specifically, the creation of the chief complaints presented by your chronically ill patients. Unfortunately, though, this conversion still does not fully explain why loss of functional protein happens so often in these patients. Another reason why functional protein is lost with chronic illness is that it can readily be converted to glucose in a process we all know as gluconeogenesis. In his outstanding chapter on the subject, Leverve (11) presents an excellent definition of gluconeogenesis which points out that, by strict definition, the process does not only involve conversion of protein/amino acids to glucose:
“The term gluconeogenesis means new glucose synthesis from a nonglucose compound. Thus, we call gluconeogenesis the glucose formation from either fructose, glycerol, lactate, proprionate, or amino acids, although the source and the pathways are quite different.”
The author also provides an excellent introductory statement that explains why the body places such a high priority on the ability to convert amino acids to glucose:
“In terms of mass, glucose synthesis is probably the most important biosynthetic process in living systems. It is a general feature of plants, microorganisms, and animals, and the ability of heterotrophic cells to synthesize glucose or glycogen from lactate, pyruvate, and also from nearly all amino acids present in proteins is one of the most fundamental biosynthetic pathways of cellular metabolism.”
With the above stated, it certainly follows that gluconeogenesis is occurring very often in both sickness and health. Leverve (11) points out:
“The physiologic need for hepatic gluconeogenesis is related to the condition where there is lack of exogenous glucose, i.e., the fasting state.”
In addition to the fasting state, gluconeogenesis is a common feature of exercise physiology:
“Glycogenolysis and gluconeogenesis are both involved in the increase in hepatic glucose production, glycogenolysis being predominant in short-term exercise and gluconeogenesis being the major pathway in prolonged exercise or during recovery.”
Therefore, the existence of gluconeogenesis in our chronically ill patients is not the issue. The true issue is the fact that, with illness, gluconeogenesis can occur excessively. Leverve (11) states:
“It has long been known that gluconeogenesis is enhanced in severe illness, injury, and diabetes, whereas it is decreased in long-term starvation. In stressed patients, the occurrence of an increased gluconeogenesis together with hyperglycemia is known as insulin resistance.”
Before continuing, please note again the last statement in the above quote. Over the years, we have had a tendency to make an overly simplistic conclusion that the elevated serum glucose typically seen with insulin resistance is purely an issue of ingesting too much carbohydrate. While this is partially true, there is also another important component to insulin resistance that is all too often, in my opinion, ignored by nutritional practitioners. Much of the observed insulin resistance and resultant elevated serum glucose occurs as a consequence of a metabolic derangement where functional protein is being converted to glucose, delivering, as I have pointed out, a major negative blow to quality of life. Of course, with the above stated, it might be logically assumed that if more glucose is given to the patient, gluconeogenesis processes will decrease. Unfortunately, this is not the case, as noted by Leverve (11):
“The increased gluconeogenesis is not suppressible by infusion of high amounts of glucose.”
In contrast, it again needs to be emphasized that gluconeogenesis is occurring excessively in our patients due to several metabolic imbalances that need to be fully understood before we can hope to correct them. Fortunately, as I have been pointing out repeatedly in this series, we can thank the critical care nutrition community for fully explaining the nature of these imbalances to us. In the following quote, Leverve (11) presents an overview of why gluconeogenesis is occurring excessively in our patients:
“The increased use of amino acids for gluconeogenesis has been recognized for a long time, since stress and the hypercatabolic state are associated with an increase in urinary nitrogen loss. In fact, it was shown that in burn patients the entire increment in glucose production could be accounted for by the increase in gluconeogenic precursor uptake by the liver.”
Thus, while we can justifiably conclude that serum glucose levels are primarily an issue of diet in our healthy patients, in our chronically ill patients this is decidedly not the case. Rather, much of what we see in terms of elevated serum glucose is the result of several metabolic imbalances that result in the conversion of functional protein to glucose.
The next paper I would like to discuss presents an excellent overview of the metabolic imbalances referred to above and how they relate to gluconeogenesis. While what you are going to read is somewhat of a review of the information on the acute phase response that was presented in previous newsletters, I feel it is important to discuss this information again so as to provide an excellent perspective on why gluconeogenesis is so common in our chronically ill patients. On a personal note, this paper and the others that appeared in a special edition on nutrition from the journal New Horizons: The Science and Practice of Acute Medicine was my first exposure to the outstanding work of critical care nutritionists and first suggested to me that the nutritional needs and metabolic imbalances of the acute care patient are very similar to those of the outpatient chronically ill patient. In “Overfeeding the critically ill child: Fact or Fantasy?” by Chwals (12) the following is noted:
“In response to a variety of local or systemic injury stimuli (such as trauma, sepsis, and acute inflammatory conditions), a series of metabolic changes occur that characterize the acute stress state. Among the early features of the injury response are the release of cytokines, followed rapidly by important alterations in the hormonal environment. Increased counterregulatory hormone concentrations are associated with insulin and growth hormone (GH) resistance. As a result of this response, a sequence of metabolic events is initiated that includes the catabolism of endogenous stores of protein, carbohydrate, and fat to provide essential substrate intermediates and energy necessary to fuel the ongoing response process. Amino acids from catabolized proteins flow to the liver, where they provide substrate for the synthesis of acute phase proteins and glucose (gluconeogenesis). The acute metabolic stress response, then, represents a hypermetabolic, hypercatabolic state that results in the loss of endogenous tissue. Growth, which is an anabolic process, is inhibited during periods of acute metabolic stress. As the acute metabolic stress response resolves, adaptive anabolic metabolism ensues to restore catabolic losses.”
In our chronically ill patients, the metabolic stress response never resolves, for reasons such as poor diet, chronic GI problems, excess body weight, lack of weight bearing and aerobic exercise, lack of sleep, and toxicology. This leads to a chronic hypermetabolic, hypercatabolic state that perpetuates loss of endogenous tissue sometimes for decades. Chwals (12) continues his overview:
“Insulin is a potent anabolic hormone responsible for glycogen synthesis and the storage of carbohydrate, lipogenesis and the storage of fat, and new protein synthesis. Insulin and insulin-like growth factor I (IGF-1) are essential hormones for somatic growth in infants and children. Acute metabolic stress is characterized by substantial increases in serum concentrations of catecholamines, glucagon, and cortisol, which are referred to as counterregulatory hormones because they oppose the anabolic effects of insulin. Serum concentrations of these metabolic stress-related hormones increase as a result of cytokine release.
Glucagon induces glycolysis and gluconeogenesis. These effects counteract the anabolic effects of insulin. Increased glycolysis results in increased serum lactate and alanine concentrations. These amino acids provide the substrate necessary for the endogenous regeneration of glucose (Cori cycle and alanine cycle). These cycles are major contributors to altered carbohydrate metabolism during acute metabolic stress.
Cortisol induces muscle proteolysis and promotes gluconeogenesis. Glucocorticoids cause the muscle proteolysis associated with cytokine release and have been shown to be a predictor of protein breakdown and hypermetabolism in acutely stressed adults. The major amino acid sources for gluconeogenesis are alanine and glutamine from skeletal muscle and gut. Hepatic uptake of these amino acids is accelerated during acute metabolic stress. Like glucagon, cortisol also causes insulin resistance. Although insulin concentrations may be increased during acute metabolic stress, insulin’s anabolic effects are inhibited.”
Again, even though I realize that the above is largely a review of information on the acute phase response presented previously, I hope you found it helpful in terms of further understanding exactly what happens metabolically when patients are ailing, either acutely or chronically. In addition, it is my hope that this quote effectively demonstrates that gluconeogenesis is not the isolated metabolic entity often suggested in basic nutrition and physiology books but part of an overall catabolic state that plays a major role in creating the signs and symptoms seen in many if not most chronically ill patients.
Following you will find a diagram from the Chwals (12) paper that provides an excellent overview of the metabolic specifics of the catabolic state we see in our patients and the role that gluconeogenesis plays in this process.
In the next newsletter I will continue this discussion of “Where did the protein go?” with more information on gluconeogenesis and another way protein is lost, oxidation.
Moss Nutrition Report #237 – 02/01/2011 – PDF Version
- Waterlow JC. Protein Turnover Cambridge, MA: CABI; 2006.
- Di Pasquale MG. Amino Acids and Proteins for the Athlete: The Anabolic Edge, Second Edition Boca Raton: CRC Press; 2008.
- Hanauer SB. Sarcopenia and the elusive fountain of youth. Nature Clin Pract: Gastroenterology and Hepatology. 2009;6(1):1.
- Studenski S et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50-58.
- Cesari M. Role of gait speed in the assessment of older patients. JAMA. 2011;305(1):93-94.
- Genton L et al. Physiological functions should be considered as true end points of nutritional intervention studies. Proc Nutr Soc. 2005;64:285-296.
- Sasaki H et al. Grip strength predicts cause-specific mortality in middle-aged and elderly persons. Am J Med. 2007;120:337-342.
- Norman K et al. Hand grip strength: Outcome predictor and marker of nutritional status. Clin Nutr. 2010;Epub ahead of print Oct 29.
- Molnar JA. Overview of nutrition and wound healing. In: Molnar JA, ed. Nutrition and Wound Healing. Boca Raton: CRC Press; 2007.
- Reeds et al. Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states? J Nutr. 1994;124:906-910.
- Leverve XM. Amino acid metabolism and gluconeogenesis. In: Cynober L, ed. Metabolic and Therapeutic Aspects of Amino Acids in Clinical Nutrition, Second Edition. Boca Raton: CRC Press; 2004:83-95.
- Chwals WJ. Overfeeding the critically ill child: Fact or fantasy? New Horizons. 1994;2(2):147-155.