2010: New Aspects of Protein Function and Metabolic Health
George A. Scheele, M.D.
THE HSPH PROTEIN PRIMER MAKES THE FOLLOWING POINTS
The Harvard School of Public Health published this primer on dietary protein in 2008. The publication points out the following:
- Until recently, protein got little attention.
- Surprisingly little is known about protein and health.
- Around the world, millions of people do not get enough protein. Protein malnutrition leads to the condition known as Kwashiorkor (1). This kind of far-advanced protein deficiency can lead to growth failure, loss of muscle mass, decreased immunity, weakening of the heart and respiratory system, and death.
- Adults need a minimum of 1 gram of protein for every kilogram of body weight per day to keep from slowly breaking down their own tissues. This means that the average 70 kg man (154 lbs) needs 70 grams of dietary protein a day.
- Almost any reasonable diet in the US will give you enough protein each day. Eating a variety of foods will ensure that you get all of the amino acids you need.
- It explains “complete proteins,” those animal proteins that contain all twenty of the amino acids that are required for protein synthesis.
- It explains “incomplete proteins” as those coming from fruits, vegetables, grains and nuts that lack one or two amino acids.
- Because of the existence of “incomplete proteins” nutritionists recommend that all people eat a variety of proteins.
- Other than protein allergies relatively little evidence has been gathered regarding the effect of protein on the development of chronic diseases.
- There is evidence that people who eat high protein, low carb diets have an easier time to regulate their body weight than those who eat high carb, low protein diets. This is because high protein/fat diets inhibit gastric emptying and therefore satiate hunger better.
- One large prospective study – the nurses’ Health study – showed that women who ate the most protein (about 110 grams per day) were 25% less likely to have had a heart attack or to have died of heart disease than the women who ate the least protein (about 68 grams per day over a 14-year period. And the high protein diet also protected against higher fat consumption as well. Please note that these data are somewhat misleading, because 68 grams of protein per day is more than normal in women and 110 grams per day is super-high. Unfortunately, there was not another study arm that administered a protein deficient diet.
- Protein has a gentle, steady effect on rise in blood sugar and subsequent fall in blood sugar that occurs after eating a rapidly digested carbohydrate like white bread or baked potato.
WHAT IS MISSING FROM THE PROTEIN PRIMER
- The primer does not explain why amino acids are divided into “nonessential” and “essential” even though biochemists have known about this difference for 70 years.
- The primer does not explain why higher animals (rodents, mammals and humans) cannot produce all the amino acids that are required for protein synthesis.
- While the primer discusses complete and incomplete proteins as a function of representation of amino acids, it pays no attention to the ratio of negative-charged and positive-charged amino acids.
- The primer pays no attention to the importance of the food chain in moving essential and positive-charged amino acids up from primitive organisms (bacteria, yeast and plants) to higher animals (rodents, mammals and humans).
- The primer pays no attention to the importance of evolution in dietary health and vice versa.
WHY IS THE PROTEIN PRIMER INCOMPLETE
- The simple answer to this question is that all of the nutrition studies that have been performed in the advanced and underdeveloped worlds have focused on total protein in the blood stream or the breakdown of protein into albumin and globulin in the blood stream.
- Since albumin is highly negatively charged and globulins represent a spectrum of negative and neutral-charged proteins, these studies completely disregarded positive-charged proteins, the most vulnerable of proteins sustained by the food chain.
WHERE IS THE DATA THAT SHOWS THAT POSITIVE-CHARGED PROTEINS ARE THE MOST VULNERABLE IN THE FOOD CHAIN?
- The only nutritional study that looked carefully at all the proteins synthesized in a given organ, in this case the rat pancreas, was that conducted by Scheele and coworkers in 1984.
- This group used 2D gel electrophoresis (2) to separate the approximate 10,000 proteins synthesized in this tissue. Twenty five of these proteins were digestive enzymes and isoenzymes representing proteases (trypsinogens, chymotrypsinogens, and proelastase forms), glycosidases (amylase forms), lipases (lipase and phospholipase forms), ribonucleases, and deoxyribonucleases. Scheele and coworkers had identified these enzymes in 2D gels representing 5 species (guinea pig, rat, rabbit, dog and human). These enzymes represented the most abundant proteins synthesized in the exocrine pancreas.
The 1984 study (3) varied the following parameters:
- 7 isocaloric diets increasing protein at the expense of carbohydrate. Percentage protein varied from 0%, 10%, 22%, 30%, 45%, 64% and 82% as starch varied 75%, 65%, 53%, 45%, 30%, 11%, and 0%. Sucrose(10%) and fat (3%) were held constant.
- Diets were administered for the following periods of time: 0 days (control); 1 day, 2 days, 4 days, 8 days, and 12 days.
- Six animals were studied per time period.
- All animals were weighed daily
- Radioactivity was used to measure total protein synthesis and fractional rates of protein synthesis for each of 20 enzymes. Absolute synthetic rates could be determined for each of these enzymes by multiplying total protein synthesis rates by individual fractional rates of synthesis.
- For each diet and administration period, total protein synthesis was measured as a function of tissue mass (DNA content) and fractional synthetic rates were measured for each of the 20 enzymes, which spanned isoelectric points from 4.3 to 9.3.
- Together with preparations this study required about 2 years of time to execute and analyze.
- Reflections on the impact of these discoveries have taken 25 years to understand the implied correlations associated with their importance.
- More than 1,000 data points on 20 specific pancreatic digestive enzymes, spanning isoelectric points from 4.3 to 9.3, and comparing 7 different isocaloric diets over 12 days were recorded and analyzed in this single study.
THE RESULTS OF THIS STUDY SHOWED THAT
- Under conditions of early protein deficiency the results showed that serious disruptions occur in the feedback mechanisms that regulate pancreatic adaptation to changing diets. Under conditions of early protein deficiency, positive-charged proteins initially suffered more than negative-charged proteins. The synthesis of negative-charged proteins continued but the synthesis of positive-charged proteins was greatly diminished to levels that are more than 90% diminished from levels observed in health. Furthermore, we showed that these changes in protein expression resulted in serious impairments in cellular function (3).
- The high resolution analysis of proteins spread on 2D gels, provided the first diagnostic test for changes in protein patterns due to early protein deficiency. The dramatic decreases observed in the expression of positive-charged proteins within days of placing experimental animals on protein deficient diets, served as a wake-up call suggesting that protein health may be more difficult to maintain than previously thought (4).
- From analyses of these studies, it became abundantly clear that the vulnerable shoulder of the food chain is represented by positive-charged amino acids. It also became abundantly clear that reversal of the early forms of protein deficiency could be most effectively combated by providing the essential and positive-charged amino acids that are crucial to the diet of higher animals and humans (5).
- Earlier work has called attention to the deleterious effects of excess refined sugars and processed carbohydrate on metabolic processes that lead, in part, to the Metabolic Syndrome. However, because high carbohydrate diets are often low in protein, we have analyzed the other half of the equation, the pathological effects of deficiencies in amino acids, proteins and metabolic pathways on the development of the Metabolic Syndrome, which is associated with chronic degenerative diseases that lead to accelerated aging and premature death (5).
- We believe that selective impairments in protein expression in humans may result in serious disease states, including overweight disorders, high blood pressure, high cholesterol levels and Type II diabetes, characterized by numerous risk factors and symptoms associated with the Metabolic Syndrome (5).
- This disruption in health appears to be due to the constitutive deficiency of essential and positive-charged amino acids in the food chain that lead to deficiencies in enzymes that drive metabolic pathways. Furthermore, the patterns of protein deficiency (loss of positive-charged proteins) observed in the exocrine pancreas can be expected to occur in other organs and physiological systems throughout the body, including those that regulate inflammation, blood pressure, cholesterol metabolism, glucose metabolism, resistance to infectious organisms, weight control and the like (5).
- According to Dr. Scheele’s scientific investigations, the most likely reason that amino acids are divided into essential and nonessential groups is that essential amino acids serve as the major signal for satiety in the appetite centers of the brain and stomach. Existing evidence demonstrates that the major signals of satiety are branched chain amino acids (Leucine, Isoleucine and Valine), Phenylalanine, and Tryptophan, including its metabolites 5-Hydroxy Tryptophan and Serotonin. These molecules include essential amino acids and their metabolites (5). It follows from this that the absence of essential and positive-charged amino acids serves as the orexigenic (hunger) signal that is quintessentially essential in survival.
- The evolutionary implications of these new findings are profound. Once higher organisms developed muscles these contractile organs conferred an enormous advantage on higher organisms (vertebrates and higher animals) to find and ingest food. However, this higher efficiency in the acquisition of food (dietary substrates in the environment) necessitated the co-development of potent mechanisms to signal hunger and satiety. Why? Because without strong “hunger” signals, vertebrates would not have the drive or need to find, locate and ingest food to avoid starvation. Without strong “satiety” signals, vertebrates would not have the need to stop eating to avoid obesity. Thus the regulation of “fasting” and “eating” became one of the most highly developed physiological systems that determine body health, including the athletic (muscular) prowess necessary for food ingestion and procreation. The evolution of mechanisms that developed during evolution of higher animals to signal hunger (orexigenic signals) and satiety (anorexigenic signals) depended on the relative absence and abundance, respectively, of essential and positively-charged amino acids and their metabolites in the blood circulation and extracellular space. Once these physiological mechanisms developed to signal hunger and satiety, it became essential that vertebrates lose the ability to synthesize the amino acids that signal hunger. In reality the evolutionary development of hunger/satiety signals paralleled the loss of biosynthetic mechanisms to produce these same hunger/satiety factors.
In order to maximize fitness for dietary health and procreation, it is necessary to achieve balanced synthesis of enzymes to drive metabolic pathways and optimize mobility and digestive functions of the body. Since vertebrates (higher organisms containing muscles) are deficient in essential and positive-charged amino acids, it is profoundly important that sufficient amounts of essential and positive-charged amino acids are acquired from the environment and ingested into the body. When dietary health is compromised, by eating excessive amounts of processed carbohydrates and refined sugars at the expense of dietary protein containing adequate amounts of essential and positive-charged amino acids, the deficiencies in positive-charged amino acids lead to the loss of positive-charged proteins that are essential to optimize health in all of the physiological systems of the body, including the metabolic health of individual organs and tissues, neurotransmitters in the brain, and hormones in the blood circulation that are necessary for optimal function of multicellular organisms. Most important among these functions are mobility mechanisms in finding and ingesting food as well engaging in procreation.
Based on his extensive studies on amino acids and proteins in rodents, mammals and humans, Dr. Scheele proposes that evolutionary adaptations to the food chain and procreation constitute the two fundamental drivers behind speciation, which provides a new dynamic in understanding Charles Darwin’s ”On the Origen of Species.”
THE NEXT PRIMER ON PROTEIN HEALTH
- The next primer on protein health will underscore the importance of essential and positive-charged amino acids in the food chain and their impact on metabolic health including the prevention and relief of chronic degenerative diseases associated with the Metabolic Syndrome, accelerated aging and premature death.
- Pitchumoni, C.S. and Scheele, G.A. (1993) Interdependence of nutrition and exocrine pancreatic function, In The Pancreas, Biology, Pathobiology and Diseases (V.L. Go, J.D. Gardiner, H.A. Reber, E. Lebenthal, E.P. DiMagno, G.A. Scheele, eds.) Raven Press, New York, NY pp 449-473.
- Scheele, G. (1975) Two dimensional gel analysis of soluble proteins – Characterization of guinea pig exocrine pancreatic proteins. J. Biol. Chem. 250: 5375-85.
- Schick, J., Verspohl, R., Kern, H. and Scheele, G. (1984) Two distinct genetic patterns of response in the exocrine pancreas to inverse changes in protein and carbohydrate in the diet, Am. J. Physiol. 248: G611-616.
- Scheele, G. (1993) Regulation of pancreatic gene expression in response to hormones and nutritional substrates, In The Pancreas, Biology, Pathobiology and Diseases (V.L. Go, J.D. Gardiner, H.A. Reber, E. Lebenthal, E.P. DiMagno, G.A. Scheele, eds.) Raven Press, New York, NY pp 103-120.
- Scheele, G. (2011) The Obesity Cure: Weight Control, Metabolic Health and Revitalized Youth With Power Amino Acids. Bookmasters and Altas Books. http://www.atlasbooks.com/theobesitycure/
For additional papers on the biochemistry of exocrine pancreatic cells, please see Dr. Scheele’s bibliography of 110 papers, which may be obtained upon request.
George Scheele, MD
December 21, 2010
George A. Scheele, M.D.
Dr. Scheele is a world-renowned physician, inventor, author and two-time Nobel Associate, who has pioneered in understanding the critical role of amino acids in regulating metabolic health and body weight. He recently introduced Factor4 Weight Control® with essential ingredients to treat the four nutritional traps that lead to overweight disorders and obesity.
As a graduate of Princeton University and Johns Hopkins Medical School he served as Professors of Medicine on the faculties of The Rockefeller University, Yale University School of Medicine and Harvard Medical School. Dr. Scheele invented new concepts and techniques which “cracked the code” in understanding how Power Amino Acids® correct the deficiencies in amino acids, positive-charged proteins, and metabolic pathways that normalize body weight and restore metabolic health.
A pioneer in the development of the fields of Cell Biology and Molecular Biology and their impact on understanding chronic human diseases, he participated in work that won two Nobel Prizes in Medicine awarded in 1974 and 1999.
As a leader in nutritional science and medical research with 40 years of innovative scientific research and 10 years of breathtaking achievements in the fields of obesity and metabolic disease, Dr. Scheele’s passion has always been to “Make the World a Better Place”. After moving to La Jolla in 1998, he has utilized his vast experience to develop superior health-care products for individuals living in today’s fast-paced world.
Dr. Scheele is currently the Founder, President, and CEO of NovaLife, Inc. a San-Diego based biotech company that has pioneered in the development of innovative health-care products for people who suffer from obesity and metabolic diseases, including diabetes, lipid disorders, cardiovascular disease, autoimmune disorders, and aging.
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