Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1978 Aug;62(2):468–479. doi: 10.1172/JCI109148

The Metabolic Response to Hypocaloric Protein Diets in Obese Man

Errol B Marliss 1, Frederick T Murray 1, Azima F Nakhooda 1
PMCID: PMC371785  PMID: 670403

Abstract

Exogenous protein in the absence of other calories can cause protein-sparing, but the mechanisms involved are controversial. It has been postulated that low insulin and high fat-derived substrate levels are necessary and sufficient conditions for such protein-sparing. We therefore established such conditions with differing protocols of protein input to define the role of protein input in mediating the response. Three groups of obese, nondiabetic subjects received the following diets: (1) 82.5±1.0 g protein/day (400 cal/day) for 21 days, n = 7; (2) the same, but as a refeeding diet for 7 days after 21-28 days of total fasts, n = 7; and (3) commencing with the same input, but with daily stepwise decrements over 14 days to 19.4±2.2 g/day, then maintained an additional 7 days, n = 4. Diet 3 gave approximately the amount and pattern of protein lost during total fasting.

The circulating hormone and substrate responses of diets 1 and 3 were comparable and resembled those of total fasts, in that plasma glucose and insulin fell and free fatty acids rose. Blood levels of alanine, pyruvate, and other glucogenic amino acids fell and blood levels of branched-chain amino acids rose transiently. Blood 3-hydroxybutyrate levels and urinary excretion were greater in diet 3 than diet 1, but less than in total fasting. Nitrogen balance in diet 1 was transiently negative, but in equilibrium from 12 to 21 days. In diet 3, it was constantly negative at −6 g/day, the values also observed at 21 days of fasting. Mean 3-methylhistidine excretion decreased by 170 μmol/day in diet 1 and 107 μmol/day in diet 3, reflecting decreased muscle protein catabolism. The refed, protein-depleted subjects, diet 2, showed an increase in plasma glucose without alteration in insulin levels. Free fatty acid and ketone body levels decreased to those of the steady state observed in diet 1. Glucogenic and branched-chain amino acids decreased transiently. Nitrogen balance became positive, and the low 3-methylhistidine excretion increased by 152 μmol/day.

The differing responses of nitrogen balance could not be accounted for on the basis of levels of insulin or of fat-derived substrates. The primary determinants of the protein-sparing observed appeared to be the protein supply itself, and the magnitude of the decrease in endogenous protein catabolism. The positive balance on refeeding after prior depletion of protein stores was likely due to the exogenous supply, combined with decreased catabolism and considerably increased reutilization.

Full text

PDF
468

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Apfelbaum M., Boudon P., Lacatis D., Nillus P. Effets métaboliques de la diète protidique chez 41 sujets obèses. Presse Med. 1970 Oct 24;78(44):1917–1920. [PubMed] [Google Scholar]
  2. Baird I. M., Parsons R. L., Howard A. N. Clinical and metabolic studies of chemically defined diets in the management of obesity. Metabolism. 1974 Jul;23(7):645–657. doi: 10.1016/s0026-0495(74)80023-5. [DOI] [PubMed] [Google Scholar]
  3. Bell J. D., Margen S., Calloway D. H. Ketosis, weight loss, uric acid, and nitrogen balance in obese women fed single nutrients at low caloric levels. Metabolism. 1969 Mar;18(3):193–208. doi: 10.1016/0026-0495(69)90039-0. [DOI] [PubMed] [Google Scholar]
  4. Bistrian B. R., Blackburn G. L., Flatt J. P., Sizer J., Scrimshaw N. S., Sherman M. Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast. Diabetes. 1976 Jun;25(6):494–504. doi: 10.2337/diab.25.6.494. [DOI] [PubMed] [Google Scholar]
  5. Bistrian B. R., Blackburn G. L., Stanbury J. B. Metabolic aspects of a protein-sparing modified fast in the dietary management of Prader-Willi obesity. N Engl J Med. 1977 Apr 7;296(14):774–779. doi: 10.1056/NEJM197704072961402. [DOI] [PubMed] [Google Scholar]
  6. Bistrian D. R., Winterer J., Blackburn G. L., Young V., Sherman M. Effect of a protein-sparing diet and brief fast on nitrogen metabolism in mildly obese subjects. J Lab Clin Med. 1977 May;89(5):1030–1035. [PubMed] [Google Scholar]
  7. Blackburn G. L., Flatt J. P., Clowes G. H., Jr, O'Donnell T. F., Hensle T. E. Protein sparing therapy during periods of starvation with sepsis of trauma. Ann Surg. 1973 May;177(5):588–594. doi: 10.1097/00000658-197305000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blackburn G. L., Flatt J. P., Clowes G. H., O'Donnell T. E. Peripheral intravenous feeding with isotonic amino acid solutions. Am J Surg. 1973 Apr;125(4):447–454. doi: 10.1016/0002-9610(73)90080-9. [DOI] [PubMed] [Google Scholar]
  9. Felig P., Owen O. E., Wahren J., Cahill G. F., Jr Amino acid metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):584–594. doi: 10.1172/JCI106017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Felig P., Pozefsky T., Marliss E., Cahill G. F., Jr Alanine: key role in gluconeogenesis. Science. 1970 Feb 13;167(3920):1003–1004. doi: 10.1126/science.167.3920.1003. [DOI] [PubMed] [Google Scholar]
  11. Flatt J. P., Blackburn G. L. The matabolic fuel regulatory system: implications for protein-sparing therapies during caloric deprivation and disease. Am J Clin Nutr. 1974 Feb;27(2):175–187. doi: 10.1093/ajcn/27.2.175. [DOI] [PubMed] [Google Scholar]
  12. Fox I. H., Halperin M. L., Goldstein M. B., Marliss E. R. Renal excretion of uric acid during prolonged fasting. Metabolism. 1976 May;25(5):551–559. doi: 10.1016/0026-0495(76)90009-3. [DOI] [PubMed] [Google Scholar]
  13. Genuth S. M., Castro J. H., Vertes V. Weight reduction in obesity by outpatient semistarvation. JAMA. 1974 Nov 18;230(7):987–991. [PubMed] [Google Scholar]
  14. Greenberg G. R., Marliss E. B., Anderson G. H., Langer B., Spence W., Tovee E. B., Jeejeebhoy K. N. Protein-sparing therapy in postoperative patients. Effects of added hypocaloric glucose or lipid. N Engl J Med. 1976 Jun 24;294(26):1411–1416. doi: 10.1056/NEJM197606242942601. [DOI] [PubMed] [Google Scholar]
  15. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  16. Ho R. J. Radiochemical assay of long-chain fatty acids using 63Ni as tracer. Anal Biochem. 1970 Jul;36(1):105–113. doi: 10.1016/0003-2697(70)90337-4. [DOI] [PubMed] [Google Scholar]
  17. Hoover H. C., Jr, Grant J. P., Gorschboth C., Ketcham A. S. Nitrogen-sparing intravenous fluids in postperative patients. N Engl J Med. 1975 Jul 24;293(4):172–175. doi: 10.1056/NEJM197507242930404. [DOI] [PubMed] [Google Scholar]
  18. Jeejee hoy K. N., Anderson G. H., Nakhooda A. F., Greenberg G. R., Sanderson I., Marliss E. B. Metabolic studies in total parenteral nutrition with lipid in man. Comparison with glucose. J Clin Invest. 1976 Jan;57(1):125–136. doi: 10.1172/JCI108252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kedenburg C. P. A lithium buffer system for accelerated single-column amino acid analysis in physiological fluids. Anal Biochem. 1971 Mar;40(1):35–42. doi: 10.1016/0003-2697(71)90081-9. [DOI] [PubMed] [Google Scholar]
  20. Kuku S. F., Zeidler A., Emmanouel D. S., Katz A. I., Rubenstein A. H. Heterogeneity of plasma glucagon: patterns in patients with chronic renal failure and diabetes. J Clin Endocrinol Metab. 1976 Jan;42(1):173–176. doi: 10.1210/jcem-42-1-173. [DOI] [PubMed] [Google Scholar]
  21. Long C. L., Haverberg L. N., Young V. R., Kinney J. M., Munro H. N., Geiger J. W. Metabolism of 3-methylhistidine in man. Metabolism. 1975 Aug;24(8):929–935. doi: 10.1016/0026-0495(75)90084-0. [DOI] [PubMed] [Google Scholar]
  22. O'Connell R. C., Morgan A. P., Aoki T. T., Ball M. R., Moore F. D. Nitrogen conservation in starvation: graded responses to intravenous glucose. J Clin Endocrinol Metab. 1974 Sep;39(3):555–563. doi: 10.1210/jcem-39-3-555. [DOI] [PubMed] [Google Scholar]
  23. Owen O. E., Felig P., Morgan A. P., Wahren J., Cahill G. F., Jr Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574–583. doi: 10.1172/JCI106016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Owen O. E., Reichard G. A., Jr Ketone body metabolism in normal, obese and diabetic subjects. Isr J Med Sci. 1975 Jun;11(6):560–570. [PubMed] [Google Scholar]
  25. Stinbaugh B. J., Marliss E. B., Goldstein M. B., Fox I. H., Schloeder F. X., Halperin M. L. Mechanism for the paradoxical aciduria following alkali administration to prolonged-fasted patients. Metabolism. 1975 Aug;24(8):915–922. doi: 10.1016/0026-0495(75)90082-7. [DOI] [PubMed] [Google Scholar]
  26. Streja D. A., Marliss E. B., Steiner G. The effects of prolonged fasting on plasma triglyceride kinetics in man. Metabolism. 1977 May;26(5):505–516. doi: 10.1016/0026-0495(77)90094-4. [DOI] [PubMed] [Google Scholar]
  27. Streja D. A., Steiner G., Marliss E. B., Vranic M. Turnover and recycling of glucose in man during prolonged fasting. Metabolism. 1977 Oct;26(10):1089–1098. doi: 10.1016/0026-0495(77)90035-x. [DOI] [PubMed] [Google Scholar]
  28. Yang M. U., Van Itallie T. B. Composition of weight lost during short-term weight reduction. Metabolic responses of obese subjects to starvation and low-calorie ketogenic and nonketogenic diets. J Clin Invest. 1976 Sep;58(3):722–730. doi: 10.1172/JCI108519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Young V. R., Havenberg L. N., Bilmazes C., Munro H. N. Potential use of 3-methylhistidine excretion as an index of progressive reduction in muscle protein catabolism during starvation. Metabolism. 1973 Nov;23(2):1429–1436. doi: 10.1016/0026-0495(73)90257-6. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES