Home LiteratureArticle Details
PMID: 12813917 Published · ppublish English Journal Article Review

Ketoacids? Good medicine?

Transactions of the American Clinical and Climatological Association ·Vol. 114 ·2003-00-00 ·Pages 149-61; discussion 162-3

Cahill GF, Veech RL

Abstract

D-beta-hydroxybutyrate, the principal "ketone" body in starving man, displaces glucose as the predominating fuel for brain, decreasing the need for glucose synthesis in liver (and kidney) and accordingly spares its precursor, muscle-derived amino acids. Thus normal 70 kg. man survives 2-3 months of starvation instead of several weeks, and obese man many months to over a year. Without this metabolic adaptation, H. sapiens could not have evolved such a large brain. Recent studies have shown that D-beta-hydroxybutyrate, the principal "ketone", is not just a fuel, but a "superfuel" more efficiently producing ATP energy than glucose or fatty acid. In a perfused rat heart preparation, it increased contractility and decreased oxygen consumption. It has also protected neuronal cells in tissue culture against exposure to toxins associated with Alzheimer's or Parkinson's. In a rodent model it decreased the death of lung cells induced by hemorrhagic shock. Also, mice exposed to hypoxia survived longer. These and other data suggest a potential use of beta-hydroxybutyrate in a number of medical and non-medical conditions where oxygen supply or substrate utilization may be limited. Efforts are underway to prepare esters of beta-hydroxybutyrate which can be taken orally or parenterally to study its potential therapeutic applications.

MeSH Terms
3-Hydroxybutyric Acid/metabolism,pharmacology Animals Cerebral Cortex/metabolism Diet Epilepsy/drug therapy,metabolism Fasting/metabolism Humans Ketone Bodies/metabolism,pharmacology Ketosis/metabolism Neuroprotective Agents/metabolism,pharmacology Starvation/metabolism
Chemicals
Ketone Bodies Neuroprotective Agents 3-Hydroxybutyric Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Cahill George F
Veech Richard L
References (33)
33 references, click to expand
  1. Efficacy of the ketogenic diet for infantile spasms.
    Pediatrics. 2002 May;109(5):780-3 PMID: 11986436
  2. Effects of ketogenic diet on development and behavior: preliminary report of a prospective study.
    Dev Med Child Neurol. 2001 May;43(5):301-6 PMID: 11368482
  3. Hormone-fuel interrelationships during fasting.
    J Clin Invest. 1966 Nov;45(11):1751-69 PMID: 5926444
  4. Brain metabolism during fasting.
    J Clin Invest. 1967 Oct;46(10):1589-95 PMID: 6061736
  5. Metabolic interactions of glucose, lactate, and beta-hydroxybutyrate in rat brain slices.
    Am J Physiol. 1969 Sep;217(3):784-92 PMID: 5807702
  6. Starvation in man.
    N Engl J Med. 1970 Mar 19;282(12):668-75 PMID: 4915800
  7. Medium-chain triglycerides as a therapy for intractable childhood epilepsy.
    Neurology. 1971 Nov;21(11):1097-103 PMID: 5166216
  8. Interspecies correlations of cerebral cortical oxygen consumption, acetylcholinesterase activity and chloride content: studies on the brains of the fin whale (Balaenoptera physalus) and the sperm whale (Physeter catadon).
    J Neurochem. 1973 Feb;20(2):253-67 PMID: 4633360
  9. Ketosis.
    Trans Am Clin Climatol Assoc. 1973;84:184-202 PMID: 4199621
  10. Effects of ketone body infusion on hypoglycemic reaction in postabsorptive dogs.
    Metabolism. 1974 Feb;23(2):151-8 PMID: 4810807
  11. Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats.
    Biochem J. 1974 Jan;138(1):1-10 PMID: 4275704
  12. Effect of ketone infusions on amino acid and nitrogen metabolism in man.
    J Clin Invest. 1975 Jun;55(6):1382-90 PMID: 1133179
  13. Effects of beta-hydroxybutyrate, glycerol, and free fatty acid infusions on glucagon and epinephrine secretion in dogs during acute hypoglycemia.
    Metabolism. 1976 Oct;25(10):1077-86 PMID: 967013
  14. Hydroperoxide metabolism in mammalian organs.
    Physiol Rev. 1979 Jul;59(3):527-605 PMID: 37532
  15. Physiological roles of ketone bodies as substrates and signals in mammalian tissues.
    Physiol Rev. 1980 Jan;60(1):143-87 PMID: 6986618
  16. Butanediol induced ketosis increases tolerance to hypoxia in the mouse.
    Stroke. 1980 Sep-Oct;11(5):506-13 PMID: 6775394
  17. Fat-derived fuels during a 24-hour fast in children.
    Eur J Pediatr. 1982 Mar;138(2):141-4 PMID: 7094934
  18. Effect of 3-hydroxybutyrate in obese subjects on very-low-energy diets and during therapeutic starvation.
    Lancet. 1983 Jan 1;1(8314-5):15-7 PMID: 6129367
  19. Brain metabolism: a perspective from the blood-brain barrier.
    Physiol Rev. 1983 Oct;63(4):1481-535 PMID: 6361813
  20. Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. Studies with quantitative western blotting and in situ hybridization.
    J Biol Chem. 1990 Oct 15;265(29):18035-40 PMID: 2211679
  21. Effect of 3-hydroxybutyrate on posttraumatic metabolism in man.
    Surgery. 1991 Feb;109(2):176-81 PMID: 1992551
  22. Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited.
    J Neurochem. 1999 Jan;72(1):238-47 PMID: 9886075
  23. Mechanisms underlying the anti-epileptic efficacy of the ketogenic diet.
    Epilepsy Res. 1999 Dec;37(3):171-80 PMID: 10584967
  24. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes.
    Diabetes Metab Res Rev. 1999 Nov-Dec;15(6):412-26 PMID: 10634967
  25. The ketogenic diet: a therapy in search of an explanation.
    Neurology. 2000 Jan 25;54(2):282-3 PMID: 10668683
  26. Ketone bodies, potential therapeutic uses.
    IUBMB Life. 2001 Apr;51(4):241-7 PMID: 11569918
  27. The ketogenic diet: a 3- to 6-year follow-up of 150 children enrolled prospectively.
    Pediatrics. 2001 Oct;108(4):898-905 PMID: 11581442
  28. A forkhead-domain gene is mutated in a severe speech and language disorder.
    Nature. 2001 Oct 4;413(6855):519-23 PMID: 11586359
  29. Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats.
    Jpn J Pharmacol. 2001 Oct;87(2):143-50 PMID: 11700013
  30. Measurement of beta-hydroxybutyrate in acute hyperketonemia in human brain.
    J Neurochem. 2001 Nov;79(3):539-44 PMID: 11701757
  31. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5440-4 PMID: 10805800
  32. The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones.
    J Child Neurol. 2000 Dec;15(12):787-90 PMID: 11198492
  33. Regulation of glucose uptake by muscle. 7. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, on the concentrations of hexose phosphates, nucleotides and inorganic phosphate in perfused rat heart.
    Biochem J. 1964 Dec;93(3):641-51 PMID: 4220951
Article Info
Journal
Transactions of the American Clinical and Climatological Association
Abbr.
Trans Am Clin Climatol Assoc
ISSN
0065-7778
Published
2003-00-00
Pages
149-61; discussion 162-3
Language
English
Region
United States
NLM ID
7507559
PMCID
PMC2194504
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com