User:Anthony.Sebastian

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Anthony Sebastian, M.D. Professor of Medicine University of California San Francisco (UCSF) Anthony_Sebastian@msn.com UCSF Faculty Affiliations: Department of Medicine Division of Nephrology My Faculty Webpage Profile on UCSF Website Profile on Nature Network

Sundry links: UCSF Profile Page Curriculum Vitae Updated Nov 2009 Curriculum Vitae Updated Nov 2009 Narrative of Sebastian Research Contributions Partial listing of research publications, some downloadable PDFs TonySeb's Commonplace Blog Blog: Science Thoughts Latest Textbook Chapters Essay: Consciousness versus Experiencing Consciously Google Search CZ How to run a CZ election Active users list

Most recent research publications

Strohle A, Hahn A, Sebastian A. (2010) Latitude, local ecology, and hunter-gatherer dietary acid load. implications from evolutionary ecology. American Journal of Clinical Nutrition 92(4):940-945. Schmidlin O, Forman A, Leon A, Sebastian A, Morris RC Jr. (2011) Salt Sensitivity in Blacks. Evidence That the Initial Pressor Effect of NaCl Involves Inhibition of Vasodilatation by Asymmetrical Dimethylarginine. Hypertension 58: published online before print, 25 July 2011. Kendall Moseley MD, Connie Weaver, PhD, Lawrence Appel MD, Anthony Sebastian MD, Deborah E. Sellmeyer MD. (2012) Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. Journal of Bone and Mineral Research. September. J Park-Sigal, BR Don, A Porzig, R Recker, V Griswold, A Sebastian, QY Duh, AA Portale, D Shoback, and M Schambelan. (2012) Severe hypercalcemic hyperparathyroidism developing in a patient with hyperaldosteronism and renal resistance to PTH. J Bone Miner Res, October 16, 2012. | Abstract. Frassett LA, Sebastian A. (2012) How metabolic acidosis and oxidative stress alone and interacting may increase the risk of fracture in diabetic subjects. Medical Hypotheses. 79(2):189-192. Frassetto LA, Sebastian \A. (2013) Commentary to accompany the paper entitled 'Nutritional disturbance in acid-base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney', by Jean-Philippe Bonjour. Br J Nutr Jun pp. 1-3.

Brief Biography

Though I packed my university curriculum with biology subjects, I majored in chemistry, at UCLA, receiving a B.S. in 1960. I knew that I needed a good background in chemistry as a foundation for learning biology. After graduation, I worked in the chemical industry for one year, then entered the UCSF School of Medicine, graduating in 1965 as co-runner-up for the Gold-Headed Cane Award. I remained at UCSF for post-graduate studies, including a fellowship in Nephrology under the mentorship of Dr. R. Curtis Morris, Jr.

I have maintained a productive collaborative relationship with Dr. Morris until the present time. My research, in collaboration with Morris and others, has focused on acid-base and electrolyte physiology and pathophysiology, emphasizing an integrated approach encompassing endocrine, nutrition, skeletal, and cardiovascular physiology. My contributions earned election to the American Society for Clinical Investigation and the Association of American Physicians. In recognition of our joint contributions in research and patient care, Morris and I together received the Belding H. Scribner Medal for lifetime achievement, from the American Society of Nephrology.

In the teaching arena, I established a medical student elective course in Renal Pathophysiology, which I directed and taught in for 13 years. For 10 years, I served as faculty facilitator in small-group sessions in the Foundations of Patient Care course.

In the administrative arena, I served on the Medical School’s Curriculum Committee for five years; helped launch the Chancellor’s Diversity Committee; received a Champion of Diversity Award; and, beginning in the mid-70’s, helped Dr. Morris administer the Moffitt/MZ General Clinical Research Center, culminating as co-director of the unit. In 2002, I received the UCSF School of Medicine’s Alumnus of the Year Award.

I work now part-time (salary-wise, not time-wise) as Professor of Medicine (recalled), and spend most of my time working in continued research projects with three collaborative groups, writing manuscripts and book chapters, peer-reviewing manuscripts, serving on the Steering Committee of UCSF's Clinical and Translational Science Institute's Strategic Opportunities Support Center, reviewing molecular medicine proposals for grant support from UCSF's Resource Allocation Program, and writing and editing for Citizendium.

I write to learn, and read to write. I consider writing rewriting.

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Acid-Base Physiology and Pathophysiology ‡  Biology ‡  Biological Chemistry ‡  History of Biology ‡  Blood Pressure Regulation and Hypertension   Evolutionary Biology ‡  Evolutionary Psychology   Human Physiology ‡  Potassium Physiology and Pathophysiology ‡  Potassium in Nutrition and Human Health ‡  Nutritional Anthropology   Nephrology ‡  Paleolithic Nutrition ‡  Systems biology ‡  Metabolism ‡  Principles Underlying the Living State ‡  Philosophy of Mind ‡  Nutrition ‡  Technical Writing   History of Medicine ‡  Linguistics ‡          ‡ Content contributions made in those areas.

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Peer-Reviewed Articles: Original Research

• Sebastian A, McSherry E, Ueki I, Morris RC Jr: Renal amyloidosis, nephrotic syndrome, and impaired renal tubular reabsorption of bicarbonate. Ann Int Med 69:541 548, 1968

• Sebastian A, McSherry E, Morris RC Jr: On the mechanism of renal potassium wasting in renal tubular acidosis associated with the Fanconi syndrome (Type 2 RTA). J Clin Invest 50:231 243, 1971

• Morris RC Jr, McSherry E, Sebastian A: Modulation of experimental renal dysfunction of hereditary fructose intolerance by circulating parathyroid hormone. Proc Nat Acad Sci, USA 68:132 135, 1971

• Sebastian A, McSherry E, Morris RC Jr: Renal potassium wasting in renal tubular acidosis: Its occurrence in types 1 and 2 RTA despite sustained correction of systemic acidosis. J Clin Invest 50:667 678, 1971

• McSherry E, Sebastian A, Morris RC Jr: Renal tubular acidosis in infants: The several kinds, including bicarbonate wasting, classic renal tubular acidosis. J Clin Invest 51:499 514, 1972

• Short E, Morris RC Jr, Sebastian A, Spencer M: Exaggerated phosphaturic response to circulating parathyroid hormone in patients with familial x linked hypophosphatemic rickets. J Clin Invest 58:152 163, 1976

• Sebastian A, McSherry E, Morris RC Jr: Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis. J Clin Invest 58:454 469, 1976

• Hulter HN, Ilnicki LP, Harbottle JA, Sebastian A: Impaired renal H+ secretion and NH3 production in mineralocorticoid deficient glucocorticoid- replete dogs. Am J Physiol 232:F136 F146, 1977

• Sebastian A, Schambelan M, Lindenfeld S, Morris RC Jr: Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism. N Engl J Med 297:576 583, 1977

• Hulter HN, Sigala JF, Sebastian A: K+ deprivation potentiates the renal alkalosis producing effect of mineralocorticoid. Am J Physiol 235:F298 F309, 1978

• Hulter HN, Ilnicki LP, Harbottle JA, Sebastian A: Correction of metabolic acidosis by the kidney during isometric expansion of extracellular fluid volume. J Lab Clin Med 92:602 612, 1978

• Hulter HN, Licht JH, Sebastian A: K+ deprivation potentiates the renal acid excretory effect of mineralocorticoid: Obliteration by amiloride. Am J Physiol 236:F48 F57, 1979

• Hulter HN, Licht JH, Glynn RD, Sebastian A: Renal acidosis in mineralocorticoid deficiency is not dependent on NaCl depletion or hyperkalemia. Am J Physiol 236:F283 F294, 1979

• Schambelan M, Sebastian A, Biglieri EG: Prevalence, pathogenesis, and functional significance of aldosterone deficiency in hyperkalemic patients with chronic renal insufficiency. Kidney Int 17:89 101, 1980

• Hulter HN, Sebastian A, Sigala JF, Licht JH, Glynn RD, Schambelan M, Biglieri EG: Pathogenesis of renal hyperchloremic acidosis resulting from dietary potassium restriction in the dog:role of aldosterone. Am J Physiol 238:F79 F91, 1980

• Hulter HN, Licht JH, Glynn RD, Sebastian A: Pathophysiology of chronic renal tubular acidosis induced by administration of amiloride. J Lab Clin Med 95:637 653, 1980

• Hulter HN, Licht JH, Bonner EL Jr, Glynn RD, Sebastian A: Effects of glucocorticoid steroids on renal and systemic acid base metabolism. Am J Physiol 239:F30 F43, 1980

• Hulter HN, Glynn RD, Sebastian A: Renal and systemic acid base effects of chronic dichloroacetate administration in dogs. Metabolism 29:997 1002, 1980

• Sebastian A, Sutton JM, Hulter HN, Schambelan M, Poler SM: Effect of mineralocorticoid replacement therapy on renal acid base homeostasis in adrenalectomized patients. Kidney Int 18:762 773, 1980

• Schambelan M, Sebastian A, Rector FC Jr: Mineralocorticoid resistant renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): Role of increased renal chloride reabsorption. Kidney Int 19:716 727, 1981

• Hulter HN, Bonner EL Jr, Glynn RD, Sebastian A: Renal and systemic acid base effects of chronic spironolactone administration. Am J Physiol 240:F381 F387, 1981

• Hulter HN, Sigala JF, Sebastian A: Effects of dexamethasone on renal and systemic acid base metabolism. Kidney Int 20:43 49, 1981

• Hulter HN, Toto RD, Bonner EL Jr, Ilnicki LP, Sebastian A: Renal and systemic acid base effects of chronic hypoparathyroidism in dogs. Am J Physiol 241:F495 F501, 1981

• Hulter HN, Ilnicki LP, Licht JH, Sebastian A: On the mechanism of diminished urinary carbon dioxide tension caused by amiloride. Kidney Int 21:8 13, 1982

• Jones JW, Sebastian A, Hulter HN, Schambelan M, Sutton JM, Biglieri EG: Systemic and renal acid base effects of chronic dietary potassium depletion in humans. Kidney Int 21:402 410, 1982

• Hulter HN, Sebastian A, Toto RD, Bonner EL Jr, Ilnicki LP: Renal and systemic acid base effects of the chronic administration of hypercalcemia producing agents: Calcitriol, PTH, and intravenous calcium. Kidney Int 21:445 458, 1982 Brenner RJ, Spring DB, Sebastian A, McSherry E, Genant HK, Palubinskas AJ, Morris RC Jr: Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis. N Engl J Med 307:217 221, 1982

• Hulter HN, Toto RD, Ilnicki LP, Sebastian A: Chronic hyperkalemic renal tubular acidosis induced by KCl loading. Am J Physiol 244:F255 F264, 1983

• Hulter HN, Toto RD, Ilnicki LP, Halloran B, Sebastian A: Metabolic alkalosis in models of primary and secondary hyperparathyroid states. Am J Physiol 245:450 461, 1983

• Kurtz I, Maher T, Hulter HN, Schambelan M, Sebastian A: Effect of diet on plasma acid base composition in normal humans. Kidney Int 24:670 680, 1983

• Toto RD, Hulter HN, Mackie S, Sebastian A: Renal tubular acidosis induced by dietary chloride. Kidney Int 25:26 32, 1984

• Maher T, Schambelan M, Kurtz I, Hulter HN, Jones JW, Sebastian A: Amelioration of metabolic acidosis by dietary potassium restriction in hyperkalemic patients with chronic renal insufficiency. J Lab Clin Med 103:432 445, 1984

• Hulter HN, Toto RD, Sebastian A, Mackie S, Cooke CR, Wilson, TE, Melby JC: Effect of extracellular fluid volume depletion on renal regulation of acid base and potassium equilibrium during prolonged mineral acid administration. J Lab Clin Med 103:854 868, 1984

• Sebastian A, Schambelan M, Sutton JM: Amelioration of hyperchloremic acidosis with furosemide therapy in patients with chronic renal insufficiency and type 4 renal tubular acidosis. Am J Nephrology 4:287 300, 1984

• Berger BE, Cogan MG, Sebastian A: Reduced glomerular filtration and enhanced bicarbonate reabsorption maintain metabolic alkalosis in humans. Kidney Int 26:205 208, 1984

• Hulter HN, Licht JH, Sebastian A: Effects of dietary potassium depletion and mineralocorticoid excess on renal Cl conservation in the dog. Am J Physiol 248:F104 F112, 1985

• Hernandez RE, Cogan MG, Schambelan M, Colman J, Morris RC Jr, Sebastian A: Dietary NaCl determines severity of potassium depletion-induced metabolic alkalosis. Kidney Int 31:1356-1367, 1987

• Schambelan M, Sebastian A, Katuna BA, Arteaga E: Adrenocortical hormone secretory response to chronic NH4Cl-induced metabolic acidosis. Am J Physiol 252:E454-E460, 1987

• Carneiro AV, Sebastian A, Cogan MG: Reduced glomerular filtration rate can maintain a rise in plasma bicarbonate concentration in humans. Am J Nephrol 7:450-454, 1987

• Petri M, Bockerstedt L, Colman J, Whiting-O'Keefe Q, Sebastian A, Hellmann D: Serial assessment of glomerular filtration rate in lupus nephropathy. Kidney Int 34:832-839, 1988

• Yarbrough S, Nix L, Katz R, Korn M, Sebastian A: Food chloride distribution in nature and its relation to sodium content. J Am Diet Assoc 88:472-475, 1988

• Schambelan M, Sebastian A: Pathogenesis and pathophysiologic role of hypoaldosteronism in syndromes of renal hyperkalemia. Current Topics in Membrane and Transport 28:351-366, 1987

• Sebastian A, Hernandez RE, Portale AA, Colman J, Tatsuno J, Morris RC Jr: Dietary potassium influences kidney maintenance of serum phosphorus concentration. Kidney Int 37:1341-1349, 1990

• Don BR, Sebastian A, Cheitlin M, Christiansen M, Schambelan M: Pseudohyperkalemia caused by fist clenching during phlebotomy. N Engl J Med 322:1290-1292, 1990

• Cogan MG, Carneiro AV, Tatsuno J, Colman J, Krapf R, Morris RC Jr, Sebastian A: Normal diet NaCl variation can affect the renal setpoint for plasma pH-HCO-3 maintenance. J Am Soc Nephrol 1:193-199, 1990

• Moulinier L, Venet T, Schiller NB, Kurtz TW, Morris RC Jr, Sebastian A: Measurement of aortic blood flow by Doppler echocardiography: Day to day variability in normal subjects and applicability in clinical research. J Am Coll Cardiol 17:1326-1333, 1991

• Siegel D, Hulley SB, Black DM, Cheitlin MD, Sebastian A, Seeley DG, Hearst N, Fine R: Diuretics, serum and intracellular electrolyte levels and ventricular arrhythmias in hypertensive men. JAMA 267(8):1083-1089, 1992 JAMA (ed.esp.) 1:113-124, 1992

• Hagiwara S, Lane N, Engelke K, Sebastian A, Kimme DB, Genant HK: Precision and accuracy for rat whole body and femur bone mineral determination with dual X-ray absorptiometry. Bone and Mineral 22:57-68, 1993

• Sebastian A, Harrris ST, Ottaway JH, Todd KM, Morris RC Jr: Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med 330:1776-1781, 1994

• Kusumoto F, Venet T, Schiller NB, Sebastian A, Foster E: Measurement of aortic blood flow by Doppler Echocardiography:temporal, technician, and reader variability in normal subjects and the application of generalizability theory in clinical research. J Am Soc Echocardiol 8:647-653, 1995

• Frassetto L, Sebastian, A: Age and systemic acid-base equilibrium: Analysis of published data. J Gerontol 51A:B91-B99, 1996

• Frassetto LA, Morris RC Jr, Sebastian A: Effect of age on blood acid-base composition in adult humans. Role of age-related renal functional decline. Am J Physiol 271:F1114-F1122, 1996

• Frassetto L, Morris RC Jr, Sebastian A: Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab 82:254-259, 1997

• Sudhir K, Forman A, Yi SL, Sorof J, Schmidlin O, Sebastian A, Morris RC Jr: Reduced dietary potassium reversibly enhances vasopressor response to stress in African-Americans. Hypertension 29:1083-1090, 1997

• Frassetto LA, Todd KM, Morris RC Jr, Sebastian A: Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein content. Am J Clin Nutr 68:576-583, 1998

• Schmidlin O, Forman A, Tanaka M, Sebastian A, Morris RC, Jr.: Salt induced renal vasoconstriction in salt sensitive African-Americans. Hypertension 33:633-639, 1999

• Morris RC, Sebastian A, Forman A, Tanaka M, Schmidlin O: Normotensive salt-sensitivity: Effects of race and dietary potassium. Hypertension 33:18-23, 1999

• Morris RC, Schmidlin O, Tanaka M, Forman A, Frassetto L, Sebastian A: Differing effects of supplemental KCI and KHCO3: pathophysiological and clinical implications. Seminars in Nephrology 19:487-493, 1999

• Frassetto LA, Todd KT, Morris RC Jr, Sebastian A: Worldwide incidence of hip fracture in elderly women: Relation to consumption of animal and vegetable foods. J Geront Med Sci 55A:M585-M592, 2000.

• Frassetto LA, Nash E, Morris RC Jr, Sebastian A: Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion. Kidney Intl 58:748-742, 2000

• Sellmeyer DE, Stone KL, Sebastian A, Cummings, SR: A high ratio of dietary animal to vegetable protein increases the rate of bone loss and risk of fracture in postmenopausal women. Am J Clin Nutr 73:118-122, 2001

• Frassetto LA, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A: Diet, evolution and aging – the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Eur J Nutr 40:200-213, 2001

• Sellmeyer DE, Schloetter M, Sebastian A: Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. J Clin Endocrinol Metab 87:2008-2012, 2002

• Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris RC Jr Estimation of the net acid load of the diet of ancestral pre-agricultural Homo sapiens and their hominid ancestors. Am J Clin Nutr 2002;76:1308-16.

• Frassetto, L.A., R. C. Jr Morris, and A. Sebastian. Long-term persistence of the urine-calcium-lowering effect of potassium bicarbonate in postmenopausal omen. J Clin Endocrinol Metab 2005;90:831-834

• Cordain, L., Eaton, S. Boyd, Sebastian A., Mann, N., Lindeberg, S., Watkins, B.A., O’Keefe, J.H., and Brand-Miller, J. Origins and evolution of the Western diet: health implications for the 21st century Am J Clin Nutr 81:341-354, 2005

• Hwa C, Sebastian A, Aird WC. Endothelial biomedicine: its status as an interdisciplinary field, its progress as a basic science, and its translational bench-to-bedside gap. Endothelium 2005;12:139-51.

• Morris RC, Jr., Schmidlin O, Frassetto LA, Sebastian A. Relationship and interaction between sodium and potassium. J Am Coll Nutr 2006;25:262S-70S.

• Frassetto LA, Morris RC, Jr., Sebastian A. A practical approach to the balance between acid production and renal acid excretion in humans. J Nephrol 2006;19 Suppl 9:S33-S4

• Frassetto LA, Lanham-New SA, Macdonald HM, Remer T, Sebastian A, Tucker KL, Tylavsky FA. Standardizing terminology for estimating the diet-dependent net acid load to the metabolic system. Journal of Nutrition 2007;137:1491-2.

• Schmidlin, O., Forman, A., Sebastian A, and Morris, R. C. Jr. What initiates the pressor effect of salt in salt-sensitive humans? Observations in normotensive blacks. Hypertension 2007;49:1032-9

• Frassetto LA, Morris RC, Jr., Sebastian A. (2007) Dietary sodium chloride intake independently predicts the degree of hyperchloremic metabolic acidosis in healthy humans consuming a net acid-producing diet.] Am J Physiol Renal Physiol 293:F521-F525. PMID 17522265.
  • Abstract: We previously demonstrated that typical American net acid-producing diets predict a low-grade metabolic acidosis of severity proportional to the diet net acid load as indexed by the steady-state renal net acid excretion rate (NAE). We now investigate whether a sodium (Na) chloride (Cl) containing diet likewise associates with a low-grade metabolic acidosis of severity proportional to the sodium chloride content of the diet as indexed by the steady-state Na and Cl excretion rates. In the steady-state preintervention periods of our previously reported studies comprising 77 healthy subjects, we averaged in each subject three to six values of blood hydrogen ion concentration ([H]b), plasma bicarbonate concentration ([HCO(3)(-)]p), the partial pressure of carbon dioxide (Pco(2)), the urinary excretion rates of Na, Cl, NAE, and renal function as measured by creatinine clearance (CrCl), and performed multivariate analyses. Dietary Cl strongly correlated positively with dietary Na (P < 0.001) and was an independent negative predictor of [HCO(3)(-)]p after adjustment for diet net acid load, Pco(2) and CrCl, and positive and negative predictors, respectively, of [H]b and [HCO(3)(-)]p after adjustment for diet acid load and Pco(2). These data provide the first evidence that, in healthy humans, the diet loads of NaCl and net acid independently predict systemic acid-base status, with increasing degrees of low-grade hyperchloremic metabolic acidosis as the loads increase. Assuming a causal relationship, over their respective ranges of variation, NaCl has approximately 50-100% of the acidosis-producing effect of the diet net acid load.

• Schmidlin O, Forman A, Sebastian A, Morris RC, Jr. (2007) Sodium-selective salt sensitivity: its occurrence in blacks.] Hypertension 50:1085-92. PMID 17938378.
  • Abstract: We tested the hypothesis that the Na(+) component of dietary NaCl can have a pressor effect apart from its capacity to complement the extracellular osmotic activity of Cl(-) and, thus, expand plasma volume. We studied 35 mostly normotensive blacks who ingested a low-NaCl diet, 30 mmol/d, for 3 weeks, in the first and third of which Na(+) was loaded orally with either NaHCO(3) or NaCl, in random order (250 mmol/d). In subjects adjudged to be salt sensitive (n=18; Delta mean arterial pressure: >or=5 mm Hg with NaCl load), but not in salt-resistant subjects (n=17), loading with NaHCO(3) was also pressor. The pressor effect of NaHCO(3) was half that of NaCl: mean arterial pressure (millimeters of mercury) increased significantly from 90 on low NaCl to 95 with NaHCO(3) and to 101 with NaCl. The pressor effect of NaCl strongly predicted that of NaHCO(3.) As judged by hematocrit decrease, plasma volume expansion with NaCl was the same in salt-resistant and salt-sensitive subjects and twice that with NaHCO(3), irrespective of the pressor effect. In salt-sensitive subjects, mean arterial pressure varied directly with plasma Na(+) concentration attained with all Na(+) loading. In salt-sensitive but not salt-resistant subjects, NaHCO(3) and NaCl induced decreases in renal blood flow and increases in renal vascular resistance; changes in renal blood flow were not different with the 2 salts. Responses of renal blood flow and renal vascular resistance to NaHCO(3) were strongly predicted by those to NaCl. In establishing the fact of "sodium-selective" salt sensitivity, the current observations demonstrate that the Na(+) component of NaCl can have pressor and renal vasoconstrictive properties apart from its capacity to complement Cl(-) in plasma volume expansion.

• Frassetto LA, Morris RC, Jr., Sellmeyer DE, Sebastian A. (2008) Adverse effects of sodium chloride on bone in the aging human population resulting from habitual consumption of typical American diets.] J Nutr 138:419S-22S. PMID 18203914.
  • Abstract: A typical American diet contains amounts of sodium chloride far above evolutionary norms and potassium far below those norms. It also contains larger amounts of foods that are metabolized to noncarbonic acids than to organic bases. At baseline, in a steady state, diets that contain substantial sodium chloride and diets that are net acid producing each independently induce and sustain increased acidity of body fluid. With increasing age, the kidney's ability to excrete daily net acid loads declines, invoking homeostatically increased utilization of base stores (bone, skeletal muscle) on a daily basis to mitigate the otherwise increasing baseline metabolic acidosis, which results in increased calciuria and net losses of body calcium. Those effects of net acid production and its attendant increased body fluid acidity may contribute to development of osteoporosis and renal stones, loss of muscle mass, and age-related renal insufficiency. The inverted ratio of potassium to sodium in the diet compared with preagricultural diets affects cardiovascular function adversely and contributes to hypertension and stroke. The diet can return to its evolutionary norms of net base production inducing low-grade metabolic alkalosis and a high potassium-to-sodium ratio by 1) greatly reducing content of energy-dense nutrient-poor foods and potassium-poor acid-producing cereal grains, which would entail increasing consumption of potassium-rich net base-producing fruits and vegetables for maintenance of energy balance, and 2) greatly reducing sodium chloride consumption. Increasingly, evidence supports the health benefits of reestablishing evolutionary norms of dietary net base loads and high potassium and low sodium chloride loads. We focus here on the American diet's potential effects on bone through its superphysiologic content of sodium chloride.

• Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC, Jr., Sebastian A. (2009) Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet.] Eur J Clin Nutr 63:947-55. PMID 19209185.
  • Abstract: BACKGROUND: The contemporary American diet figures centrally in the pathogenesis of numerous chronic diseases-'diseases of civilization'. We investigated in humans whether a diet similar to that consumed by our preagricultural hunter-gatherer ancestors (that is, a paleolithic type diet) confers health benefits. METHODS: We performed an outpatient, metabolically controlled study, in nine nonobese sedentary healthy volunteers, ensuring no weight loss by daily weight. We compared the findings when the participants consumed their usual diet with those when they consumed a paleolithic type diet. The participants consumed their usual diet for 3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a paleolithic type diet comprising lean meat, fruits, vegetables and nuts, and excluding nonpaleolithic type foods, such as cereal grains, dairy or legumes, for 10 days. Outcomes included arterial blood pressure (BP); 24-h urine sodium and potassium excretion; plasma glucose and insulin areas under the curve (AUC) during a 2 h oral glucose tolerance test (OGTT); insulin sensitivity; plasma lipid concentrations; and brachial artery reactivity in response to ischemia. RESULTS: Compared with the baseline (usual) diet, we observed (a) significant reductions in BP associated with improved arterial distensibility (-3.1+/-2.9, P=0.01 and +0.19+/-0.23, P=0.05);(b) significant reduction in plasma insulin vs time AUC, during the OGTT (P=0.006); and (c) large significant reductions in total cholesterol, low-density lipoproteins (LDL) and triglycerides (-0.8+/-0.6 (P=0.007), -0.7+/-0.5 (P=0.003) and -0.3+/-0.3 (P=0.01) mmol/l respectively). In all these measured variables, either eight or all nine participants had identical directional responses when switched to paleolithic type diet, that is, near consistently improved status of circulatory, carbohydrate and lipid metabolism/physiology. CONCLUSIONS: Even short-term consumption of a paleolithic type diet improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans.

Book chapters

• Sebastian A, McSherry E, Morris RC Jr: Metabolic acidosis with special reference to the renal acidoses. The Kidney, edited by Brenner BM, Rector FC Jr. WB Saunders Company, Philadelphia, Chapter 16, 1976

• Morris RC Jr, McInnes RR, Epstein CJ, Sebastian A, Schriver CR: Genetic and metabolic injury of the kidney. The Kidney, edited by Brenner BM, Rector FC Jr. WB Saunders Company, Philadelphia, Chapter 27, 1976

• Schambelan M, Sebastian A: Hyporeninemic hypoaldosteronism. Advances in Internal Medicine, edited by Siperstein MH. Year Book Medical Publishers, Chicago, Vol 24, 1978

• Schambelan M, Sebastian A, Hulter HN: Mineralocorticoid excess and deficiency syndromes. Contemporary Issues in Nephrology, edited by Stein JH, Brenner BM. Churchill Livingstone, NY, Vol II, 1978 `Sebastian A, Hulter HN, Rector FC Jr: Metabolic alkalosis. Contemporary Issues in Nephrology, edited by Stein JH, Brenner BM. Churchill Livingstone, NY, Vol II, 1978

• Sebastian A, Hulter HN, Schambelan M: Renal hyperchloremic acidosis with hyperkalemia. Type 4 renal tubular acidosis (RTA). Proceedings, VIIth International Congress of Nephrology, edited by Barcelo R, Bergeron M, Carriere S, Dirks JH, Drummond K, Guttmann RD, Lemieux G, Mongeau J G, Seely JF. S. Karger, Montreal, 1978

• Sebastian A, Morris RC Jr: Renal tubular acidosis. Strauss and Welt's Diseases of the Kidney, edited by Early LE, Gottschalk CG. Little, Brown and Company, Boston, Vol II, 1979

• Morris RC Jr, Sebastian A: Disorders of the renal tubule that cause disorders of fluid, acid base, and electrolyte metabolism. Clinical Disorders of Fluid and Electrolyte Metabolism, edited by Maxwell MH, Kleeman CR. McGraw Hill Book Company, NY, 1979

• Gonick HC, Fraser D, Sebastian A: Renal tubular disorders. Current Nephrology, edited by Gonick HC. Houghton Mifflin Professional Pub, Boston, 1979

• Morris RC Jr, Sebastian A: Renal tubular acidosis and Fanconi's syndrome. Metabolic Basis of Inherited Disease, edited by Stanbury JB Wyngaarden JB, Fredrickson DS. McGraw Hill, NY. 1983

• Cogan MG, Liu F Y, Berger BE, Sebastian A, Rector FC Jr: Metabolic alkalosis. Med Clin N Amer, edited by Kurtzman NA, Batlle DC. WB Saunders, Philadelphia. 1983

• Sebastian A, Schambelan M, Hulter HN, Kurtz I, Hernandez RE, Biglieri EG, Morris RC Jr: Acid base and electrolyte disorders associated with adrenal disease. Fluid, Electrolyte and Acid Base Disorders, edited by Arieff A, DeFronzo R. Churchill Livingstone, NY. 1985

• Schambelan M, Sebastian A: Hypoaldosteronism. Current Therapy in Endocrinology and Metabolism, edited by Bardin CW, Krieger DT. BC Decker, Philadelphia. 1985

• Sebastian A, Schambelan M, Hulter HN, Maher T, Kurtz I, Biglieri EG, Rector FC Jr, Morris RC Jr: Hyperkalemic renal tubular acidosis. Renal Tubular Disorders, edited by Buckalew V, Gonick H. Marcel Decker Publishers, NY. 1985

• Frassetto, LA, R. Morris, and A. Sebastian. The natural dietary potassium intake of humans: The effect of diet-induced potassium-replete, chloride-sufficient, chronic low-grade metabolic alkalosis, or stone age diets for the 21st Century. Nutritional Aspects of Osteoporosis, 2nd Ed., edited by P. Burkhardt, B. Dawson-Hughes, and R. P. Heaney, Amsterdam: Elsevier/Academic Press, 2004, p. 349-365.

• Frassetto, L.A., C. Morris, and A. Sebastian. Effects of diet acid load on bone health. Nutritional Aspects of Osteoporosis, 2nd Edition, edited by P. Burkhardt, B. Dawson-Hughes, and R. P. Heaney, Amsterdam: Elsevier/Academic Press, 2004, p. 273-295.

• Sebastian A, Hernandez RE, Schambelan M: Disorders of renal handling of potassium. The Kidney, edited by Brenner BM, Rector FC Jr. WB Saunders Company, Philadelphia. 1986

• Schambelan M, Sebastian A: Adrenal Gland. Cecil Essentials of Medicine, edited by Andreoli TE, Carpenter CCJ, Plum F, Smith LH Jr. WB Saunders Company, Philadelphia. 1986

• Bastl C, Sebastian A: Adrenal hormones. Clinical Disorders of Fluid and Electrolyte Metabolism, edited by Maxwell MH, Kleeman CR, Narins RG. McGraw Hill Book Co, NY. 1987

• Schambelan M, Sebastian A: States of aldosterone deficiency or pseudodeficiency. Hormone Resistance and Other Endocrine Paradoxes, edited by Cohen M, Foa P. Springer-Verlag, NY 1987

• Morris RC Jr, Sebastian A: Potassium-responsive hypertension. Hypertension:Pathophysiology, Diagnosis, and Management, 2nd Ed., edited by Laragh JH and Brenner BM. Raven Press Ltd, NY 1995

• Frassetto LA, Morris RC Jr, Todd KT, Sebastian A:: Chronic low-grade metabolic acidosis in normal adult humans: Pathophysiology and consequences women’s health and menopause. Women’s Health and Menopause, edited by Paoletti R, Crosignani P, Kenemans N, Jackson A Kluwer Academic. 1999, p. 15-23

• Morris RC Jr, Frassetto LA, Schmidlin,O, Forman A, Sebastian A: Expression of osteoporosis as determined by diet-disordered electrolyte and acid-base metabolism. Nutritional Aspects of Osteoporosis, edited by Burckhardt P, et al., Academic Press, San Diego, 2001, p. 357-378

• Sebastian A, Frassetto LA, Sellmeyer DE, Morris RC Jr: An evolutionary perspective on the acid-base effects of diet: Acid-Base Disorders and Their Treatment, Gennari, J, et al., eds., Marcel Dekker, Inc., 2005

• Sebastian A, Frassetto LA, Morris RC Jr: The Acid-Base Effects Of The Contemporary Western Diet: An Evolutionary Perspective The Kidney: Physiology and Pathophysiology, 4th Edition, edited by Drs. Robert J. Alpern and Steven C. Hebert, Elsevier [In Press] 2007

• Eaton SB, Cordain L, Sebastian A.: The Ancestral Biomedical Environment Aird W.C, Ed. Endothelial Biomedicine. Cambridge: Cambridge University Press, 2007 (ISBN 9780521853767).

Favorite quotes

ANTHONY’S FAVORITE QUOTES

One of the symptoms of an approaching nervous breakdown is the belief that one’s work is terribly important. —Bertrand Russell, philosopher, mathematician, author, Nobel laureate (1872-1970)

Words constitute the ultimate texture and stuff of our moral being, since they are the most refined and delicate and detailed, as well as the most universally used and understood, of the symbolisms whereby we express ourselves into existence. —Iris Murdoch

Whereof one cannot speak, thereof one must be silent. —Ludwig Wittgenstein

The greatest obstacle to discovery is not ignorance - it is the illusion of knowledge. —Daniel J. Boorstin

If you don’t find God in the next person you meet, it is a waste of time looking for him further. —Mahatma Gandhi (1869-1948)

And there it is: the very favor of receiving life at all is handsome advance payment for all life’s miseries, each single one. —Knut Hamsun

Good prose is like a windowpane. —George Orwell (1903-1950)

To fall in love is to create a religion that has a fallible god. —Jorge Luis Borges, writer (1899-1986)

I believe that the extraordinary should be pursued. But extraordinary claims require extraordinary evidence. —Carl Sagan

The more I want to get something done, the less I call it work —Richard Bach

You don’t write because you want to say something, you write because you have something to say. —F. Scott Fitzgerald

Nature is the cure of illness. Leave thy drugs in the chemist’s pot if thou can heal the patient with food. —Hippocrates, 460-370 BC

You have not converted a man because you have silenced him. —John Morley, statesman and writer (1838-1923)

One must be drenched in words, literally soaked in them, to have the right ones form themselves into the proper patterns at the right moment. —Hart Crane, poet (1899-1932)

The universal opinion over thousands of years that the earth was flat never flattened its spherical shape by one inch. —Isaac Asimov

When I was young I observed that nine out of ten things I did were failures, so I did ten times more work. —Bernard Shaw

I have not failed. I’ve just found 10,000 ways that won’t work. —Thomas Edison

We can’t solve problems by using the same kind of thinking we used when we created them. —Albert Einstein, physicist, Nobel laureate (1879-1955)

By words the mind is winged. —Aristophanes

Words are miraculous things. They describe, captivate, provoke, vivify, encompass, pervade, inspire, preserve, and comfort. So much more than that, in fact, so as to leave me at a loss of . . . words. —Whitaker

I never desire to converse with a man who has written more than he has read. —Samuel Johnson, lexicographer (1709-1784)

Opportunity is missed by most people because it comes dressed in overalls and looks like work. —Thomas Edison

Love is a perky elf dancing a merry little jig and then suddenly he turns on you with a miniature machine gun. —Matt Groening

Reality is that which, when you quit believing in it, doesn’t go away. —Philip K. Dick

The map is not the territory. —Alfred Korzybski

The limits of my language means the limits of my world. —Ludwig Wittgenstein

What is man, when you come to think upon him, but a minutely set, ingenious machine for turning, with infinite artfulness, the red wine of Shiraz into urine? —Isak Dinesen (pseudonym of Karen Blixen), Seven Gothic Tales (1934) [p. 275.]

Every form correctly seen is beautiful. —Goethe

It is not the strongest of the species that survive, nor the most intelligent, but the one most responsive to change. —Charles Darwin

I can’t change the direction of the wind, but I can adjust my sails to reach my destination. —Jimmy Dean

The time to be happy is now; the place to be happy is here. —Robert G. Ingersoll

Nothing you do is important, but it is very important that you do it. —Mahatma Gandhi

Nothing’s more dangerous than an idea when it’s the only one you have. —Emile Chartier

The master in the art of living makes little distinction between his work and his play, his labor and his leisure, his mind and his body, his information and his recreation, his love and his religion. He hardly knows which is which. He simply pursues his vision of excellence at whatever he does, leaving others to decide whether he is working or playing. To him he’s always doing both. —Zen Buddhist Text

I do not feel obliged to believe that the same God who has endowed us with sense, reason and intellect has intended us to forego their use. —Galileo Galilei

You will not die because you are ill, but because you are alive. —Seneca

A new word is like a fresh seed sewn on the ground of the discussion. —Ludwig Wittgenstein

The most essential gift for a good writer is a built-in, shock-proof, shit detector. —Ernest Hemingway

The earth laughs in flowers. —e.e. cummings

If we don’t believe in freedom of expression for people we despise, we don’t believe in it at all. —Noam Chomsky, linguistics professor and political activist (1928- )

An atheist is man who has no invisible means of support. —John Buchan (Baron Tweedsmuir), In H. E. Fosdick On Being a Real Person (1943) ch. 10

The really happy man is the one who can enjoy the scenery when he has to take a detour. —Anonymous

As I stood before the gates I realized that I never want to be as certain about anything as were the people who built this place. —Rabbi Sheila Peltz, on her visit to Auschwitz

However beautiful the strategy, you should occasionally look at the results. —Winston Churchill (1874-1965)

School sponsorship of a religious message is impermissible because it sends the ancillary message to members of the audience who are nonadherents ‘that they are outsiders, not full members of the political community, and an accompanying message to adherents that they are insiders, favored members of the political community.’ —U.S. Supreme Court, Santa Fe Independent Sch. Dist. v. Doe, 530 U.S. 290 (2000)

The fact that a believer is happier than a skeptic is no more to the point than the fact than a drunken man is happier than a sober one. —George Bernard Shaw, writer, Nobel laureate (1856-1950)

Any Universe simple enough to be understood is too simple to produce a mind able to understand it. —John Barrow

The satiated man and the hungry one do not see the same thing when they look upon a loaf of bread. —Rumi, poet and mystic (1207-1273)

A celibate clergy is an especially good idea, because it tends to suppress any hereditary propensity toward fanaticism. —Carl Sagan

In order to make an apple pie from scratch, you must first create the universe. —Carl Sagan

The evidence, so far at least and laws of Nature aside, does not require a Designer. Maybe there is one hiding, maddeningly unwilling to be revealed. —Carl Sagan, Pale Blue Dot

The geneticist Theodosius Dobzhansky famously declared, “Nothing in biology makes sense except in the light of evolution.” One might add that nothing in biology makes sense in the light of intelligent design. —Jerry A. Coyne, evolutionary biologist

We don’t have an intelligent designer (ID), we have a bungling consistent evolver (BCE). Or maybe an adaptive changer (AC). In fact, what we have in the most economical interpretation is, of course, evolution. —Lisa Randall, physicist

Faith in the supernatural is a desperate wager made by man at the lowest ebb of his fortunes. —George Santayana, “Supernaturalism,” Little Essays, No. 108

Nothing is indescribable in words if you take the time and trouble. If your present language framework is inadequate, then you must carefully create a larger one. —Colin Wilson, The Mind Parasites, Monkfish, Rhinebeck, 2005

It is by extending oneself, by exercising some capacity previously unused that you come to a better knowledge of your own potential. —Harold Bloom, Introduction, Stories and Poems for Extremely Intelligent Children of All Ages, Scribner, New York, 2001

The first principle is that you must not fool yourself and you are the easiest person to fool. —Richard P. Feynman

Nothing in biology makes sense except in the light of evolution. —Theodosius Dobzhansky

Real life is physical. Give me books in¬stead: Give me the invisibility of the contents of books, the thoughts, the ideas, the images. Let me become part of a book; I’d give any¬thing for that. —Ariel Manto, a young journalist and polymath scholar, fictional narrator in the novel, The End of Mr. Y, by Scarlett Thomas

As some authors point out in Richard Dawkins, there really is no intermediate position: you either accept the universal principles of mainstream evolution, or you wander around in an intellectual wasteland. —David Penny, in “Why the resistance?”, review of book, Richard Dawkins: How a Scientist Changed the Way We Think, by Alan Grafen and Mark Ridley (eds), Oxford University Press, Oxford, UK, 2006.

I own with reason: for, if men but knew Some fixed end to ills, they would be strong By some device unconquered to withstand Religions and the menacings of seers. —Titus Lucretius Carus, On The Nature Of Things, 50 BC Translated by William Ellery Leonard

Intelligence is what intelligence tests measure. —Edward Boring, Harvard Psychologist

To know causality is the sole function of the understanding and its only power. Conversely, all causality, hence all matter, and consequently the whole of reality, is only for the understanding, through the understanding, in the understanding. —Arthur Schopenhauer

…programmed by quanta, physics gave rise to chemistry and then to life, programmed by mutation and recombination, life gave rise to Shakespeare, programmed by experience and imagination, Shakespeare gave rise to Hamlet. —Seth Lloyd

All my life through, the new sights of Nature made me rejoice like a child —Marie Curie

We especially need imagination in science. It is not all mathematics, nor all logic, but somewhat beauty and poetry. —Maria Mitchell

Words are only postage stamps delivering the object for you to unwrap. —George Bernard Shaw

But there is not an error into which a man can fall, which he may not press Scripture into his service as proof of the probity of. —From: James Hogg's "The Private Memoirs and Confessions of a Justified Sinner," 1824

Keeping an open mind is a virtue – but not so open that your brains fall out. —James Oberg, Space Engineer

"Science is the organized skepticism in the reliability of expert opinion." Richard Feynman

All truth passes through three stages: First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident" Arthur Schopenhauer (1788-1860)

Toleration is meaningless without tolerance for what some may consider detestable. --American Library Association

"The greatest danger for most of us is not that our aim is too high and we miss it, but that it is too low and we reach it" Michelangelo

Notes to myself

Bugzilla Anthony_Sebastian@msn.com abug175

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Welcome, new editor! We're very glad you've joined us. Here are pointers for a quick start. Also, when you get a chance, please read The Editor Role. You can look at Getting Started and our help system for other introductory pages. It is also important, for project-wide matters, to join the Citizendium-L (broadcast) mailing list. Announcements are also available via Twitter. You can test out editing in the sandbox if you'd like. If you need help to get going, the forum is one option. That's also where we discuss policy and proposals. You can ask any administrator for help, too. Just put a note on their "talk" page. Again, welcome and thank you! We appreciate your willingness to share your expertise, and we hope to see your edits on Recent changes soon.

Sarah Tuttle 12:49, 25 November 2006 (CST)

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