Ketosis

Not to be confused with ketoacidosis.
Ketosis

Ketone bodies: acetone, acetoacetic acid, and beta-hydroxybutyric acid
Classification and external resources
ICD-9 276.2
DiseasesDB 29485
MeSH D007662

Ketosis /kɨˈtoʊsɨs/ is a metabolic state where most of the body's energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis where blood glucose provides most of the energy. It is characterised by serum concentrations of ketone bodies over 0.5 millimolar with low and stable levels of insulin and blood glucose.[1][2] It is almost always generalized with hyperketonemia, that is, an elevated level of ketone bodies in the blood throughout the body. Ketone bodies are formed by ketogenesis when liver glycogen stores are depleted (or from metabolising medium-chain triglycerides[3]). The main ketone bodies used for energy are acetoacetate and β-hydroxybutyrate,[4] and the levels of ketone bodies are regulated mainly by insulin and glucagon.[5] Most cells in the body can use both glucose and ketone bodies for fuel, and during ketosis free fatty acids and glucose synthesis (gluconeogenesis) fuel the remainder.

During the usual overnight fast the body's metabolism naturally switches into ketosis, and will switch back to glycolysis after a carbohydrate-rich meal. Longer-term ketosis may result from fasting or staying on a low-carbohydrate diet, and deliberately induced ketosis serves as a medical intervention for intractable epilepsy.[6] In glycolysis higher levels of insulin promote storage of body fat and block release of fat from adipose tissues, while in ketosis fat reserves are readily released and consumed.[5][7] For this reason ketosis is sometimes referred to as the body's "fat burning" mode.[8][9]

Degree of ketosis

The concentration of ketone bodies may vary depending on diet, exercise, degree of metabolic adaptation and genetic factors. Ketosis can be induced when a ketogenic diet is followed for more than 3 days. This induced ketosis is sometimes called nutritional ketosis.[10] This table shows the concentrations typically seen under different conditions[1]

blood concentration (millimolar) Condition
< 0.2 not in ketosis
0.2 - 0.5 slight/mild ketosis
0.5 - 3.0 induced ketosis
2.5 - 3.5 post-exercise ketosis
3.0 - 6.0 starvation ketosis
15 - 25 ketoacidosis

Note that urine measurements may not reflect blood concentrations. Urine concentrations will be lower with greater hydration, and after adaptation to a ketogenic diet the amount lost in the urine drops while the metabolism remains ketotic. In addition most urine strips only measure acetoacetate, while after adaptation the predominant ketone body is β-hydroxybutyrate.[11] Ketoacidosis is a metabolic derangement that cannot occur in a healthy individual who can produce insulin, and should not be confused with physiologic ketosis.

Metabolic pathways

When glycogen stores are not available in the cells, fat (triacylglycerol) is cleaved to provide 3 fatty acid chains and 1 glycerol molecule in a process known as lipolysis. Most of the body is able to use fatty acids as an alternative source of energy in a process called beta-oxidation. One of the products of beta-oxidation is acetyl-CoA, which can be further used in the citric acid cycle. During prolonged fasting or starvation, or as the intentional result of a ketogenic diet, acetyl-CoA in the liver is used to produce ketone bodies instead, leading to a state of ketosis.

During starvation or a long physical training session, the body starts using fatty acids instead of glucose. The brain cannot use long-chain fatty acids for energy because they are completely albumin-bound and cannot cross the blood–brain barrier. Not all medium-chain fatty acids are bound to albumin. The unbound medium-chain fatty acids are soluble in the blood and can cross the blood–brain barrier.[12] The ketone bodies produced in the liver can also cross the blood–brain barrier. In the brain, these ketone bodies are then incorporated into acetyl-CoA and used in the citric acid cycle.

The ketone body acetoacetate will slowly decarboxylate into acetone, a volatile compound that is both metabolized as an energy source and lost in the breath and urine.

Ketoacidosis

Main article: Ketoacidosis

Ketone bodies are acidic, but acid-base homeostasis in the blood is normally maintained through bicarbonate buffering, respiratory compensation to vary the amount of CO2 in the bloodstream, hydrogen ion absorption by tissue proteins and bone, and renal compensation through increased excretion of dihydrogen phosphate and ammonium ions.[13] Prolonged excess of ketone bodies can overwhelm normal compensatory mechanisms, leading to acidosis if blood pH falls below 7.35.

There are two major causes of ketoacidosis:

A mild acidosis may result from prolonged fasting or when following a ketogenic diet or a very low calorie diet.[16][17]

Diet

If the diet is changed from one that is high in carbohydrates to one that does not provide sufficient carbohydrate to replenish glycogen stores, the body goes through a set of stages to enter ketosis. During the initial stages of this process, blood glucose levels are maintained through gluconeogenesis, and the adult brain does not burn ketones. However, the brain makes immediate use of ketones for lipid synthesis in the brain. After about 48 hours of this process, the brain starts burning ketones in order to more directly use the energy from the fat stores that are being depended upon, and to reserve the glucose only for its absolute needs, thus avoiding the depletion of the body's protein store in the muscles.[18]

Ketosis is deliberately induced by use of a ketogenic diet as a medical intervention in cases of intractable epilepsy.[16] Other uses of low-carbohydrate diets remain controversial.[19][20] Induced ketosis or low-carbohydrate diet terms have very wide interpretation. Therefore Stephen S. Phinney and Jeff S. Volek coined the term "nutritional ketosis" to avoid the confusion.[10]

Carbohydrate deprivation to the point of ketosis has been argued both to have negative[21] and positive effects on health.[22][23]

Diagnosis

Whether ketosis is taking place can be checked by using special urine test strips such as Ketostix. The strips have a small pad on the end which is dipped in a fresh specimen of urine. Within a matter of seconds, the strip changes color indicating the level of acetoacetate ketone bodies detected, which reflects the degree of ketonuria, which, in turn, can be used to give a rough estimation of the level of hyperketonemia in the body (see table below). Alternatively, some products targeted to diabetics such as the Abbott Precision Xtra or the Nova Max can be used to take a blood sample and measure the β-hydroxybutyrate ketone levels directly. Normal serum reference ranges for ketone bodies are 0.5–3.0 mg/dL, equivalent to 0.05–0.29 mmol/L.[24]

Also, when the body is in ketosis, one's breath may smell of acetone. This is due to the breakdown of acetoacetic acid into acetone and carbon dioxide which is exhaled through the lungs. Acetone is the chemical responsible for the smell of nail polish remover and some paint thinners.

Urine
value 		Designation Approximate serum concentration
mg/dL mmol/l
0 Negative Reference range: 0.5–3.0[24] 0.05–0.29[24]
1+ 5 (interquartile range
(IQR): 1–9)[25] 		0.5 (IQR: 0.1–0.9)[26]
2+ Ketonuria[27] 7 (IQR: 2–19)[25] 0.7 (IQR: 0.2–1.8)[26]
3+ 30 (IQR: 14–54)[25] 3 (IQR: 1.4–5.2)[26]
4+ Severe ketonuria[28] – –

Controversy

Some clinicians[29] regard restricting a diet from all carbohydrates as unhealthy and dangerous.[30] However, it is not necessary to completely eliminate all carbohydrates from the diet in order to achieve a state of ketosis. Other clinicians regard ketosis as a safe biochemical process that occurs during the fat-burning state.[10] Ketogenesis can occur solely from the byproduct of fat degradation: acetyl-CoA. Ketosis, which is accompanied by gluconeogenesis (the creation of glucose de novo from pyruvate), is the specific state with which some clinicians are concerned. However, it is unlikely for a normal functioning person to reach life-threatening levels of ketosis, defined as serum beta-hydroxybutyrate (B-OHB) levels above 15 millimolar (mM) compared to ketogenic diets among non diabetics which "rarely run serum B-OHB levels above 3 mM."[31] This is avoided with proper basal secretion of pancreatic insulin. People who are unable to secrete basal insulin, such as type 1 diabetics and long-term type II diabetics, are liable to enter an unsafe level of ketosis, causing an eventual comatose state that requires emergency medical treatment.

The anti-ketosis conclusions have been challenged by a number of doctors and advocates of low-carbohydrate diets, who dispute assertions that the body has a preference for glucose and that there are dangers associated with ketosis.[32][33] The Inuit are often cited an example of a culture that has lived for thousands of years on a low-carbohydrate diet. However, in multiple studies the traditional Inuit diet has not been shown to be a ketogenic diet.[34][35][36][37] Not only have multiple researchers been unable to detect any evidence of ketosis resulting from the traditional Inuit diet, but the ratios of fatty-acid to glucose were observed to be well below the generally accepted level of ketogenesis.[34][35][36][37] Furthermore, studies investigating the fat yields from fully dressed wild ungulates, and the dietary habits of the cultures who rely on them, suggest that they are too lean to support a ketogenic diet.[38][39] With limited access to fat and carbohydrates, cultures such as the Nunamiut Eskimos—who relied heavily on caribou for subsistence—annually traded for fat and seaweed with coastal-dwelling Taremiut.[38]

The Inuit consumed as much as 15-20% of their calories from carbohydrates, largely from the glycogen found in raw meats.[34][35][36][40] Furthermore, the blubber, organs, muscle and skin of the diving marine mammals that the Inuit ate have significant glycogen stores that are able to delay postmortem degradation, particularly in cold weather.[41][42][43][44][45][46]

Whether a no-carbohydrate diet would be safe for non-Inuit is also disputed: Nick Lane [47] speculates that the Inuit may have a genetic predisposition allowing them to eat a ketogenic diet and remain healthy. According to this view, such an evolutionary adaptation would have been caused by environmental stresses.[48] This speculation is unsupported, however, in light of the many arctic explorers, including John Rae, Fridtjof Nansen, and Frederick Schwatka, who adapted to Inuit diets with no adverse effects.[49]

Schwatka specifically commented that after a 2- to 3-week period of adaptation to the Inuit diet he could manage "prolonged sledge journeys," including the longest sledge journey on record, relying solely on the Inuit diet without difficulty.[50] Furthermore, in a comprehensive review of the anthropological and nutritional evidence collected on 229 hunter-gatherer societies it was found that, "Most (73%) of the worldwide hunter-gatherer societies derived >50% (≥56–65% of energy) of their subsistence from animal foods, whereas only 14% of these societies derived >50% (≥56–65% of energy) of their subsistence from gathered plant foods," suggesting that the ability to thrive on low carbohydrate diets is widespread and not limited to any particular genetic predisposition.[51] While it is believed that carbohydrate intake after exercise is the most effective way of replacing depleted glycogen stores,[52][53] studies have shown that, after a period of 2–4 weeks of adaptation, physical endurance (as opposed to physical intensity) is unaffected by ketosis, as long as the diet contains high amounts of fat.[48] Some clinicians refer to this period of keto-adaptation as the "Schwatka Imperative" after the explorer who first identified the transition period from glucose-adaptation to keto-adaptation.[54]

Veterinary medicine

In dairy cattle, ketosis is a common ailment that usually occurs during the first weeks after giving birth to a calf. Ketosis is in these cases sometimes referred to as acetonemia. A study from 2011 revealed that whether ketosis is developed or not depends on the lipids a cow uses to create butterfat. Animals prone to ketosis mobilize fatty acids from adipose tissue, while robust animals create fatty acids from blood phosphatidylcholine (lecithin). Healthy animals can be recognized by high levels of milk glycerophosphocholine and low levels of milk phosphocholine.[55]

In sheep, ketosis, evidenced by hyperketonemia with beta-hydroxybutyrate in blood over 0.7 mmol/L, occurs in pregnancy toxemia.[56][57] This may develop in late pregnancy in ewes bearing multiple fetuses,[56][57] and is associated with the considerable glucose demands of the conceptuses.[58][59] In ruminants, because most glucose in the digestive tract is metabolized by rumen organisms, glucose must be supplied by gluconeogenesis,[60] for which propionate (produced by rumen bacteria and absorbed across the rumen wall) is normally the principal substrate in sheep, with other gluconeogenic substrates increasing in importance when glucose demand is high or propionate is limited.[61][62] Pregnancy toxemia is most likely to occur in late pregnancy because most fetal growth (and hence most glucose demand) occurs in the final weeks of gestation; it may be triggered by insufficient feed energy intake (anorexia due to weather conditions, stress or other causes),[57] necessitating reliance on hydrolysis of stored triglyceride, with the glycerol moiety being used in gluconeogenesis and the fatty acid moieties being subject to oxidation, producing ketone bodies.[56] Among ewes with pregnancy toxemia, beta-hydroxybutyrate in blood tends to be higher in those that die than in survivors.[63] Prompt recovery may occur with natural parturition, Caesarean section or induced abortion. Prevention (through appropriate feeding and other management) is more effective than treatment of advanced stages of ovine ketosis.[64]

See also

Notes

  1. ↑ 1.0 1.1 Volek & Phinney, page 91.
  2. ↑ thefreedictionary.com/ketosis citing:
    • The American Heritage® Medical Dictionary Copyright © 2007
    • Mosby's Medical Dictionary, 8th edition. © 2009
    • Dorland's Medical Dictionary for Health Consumers. © 2007
  3. ↑ http://www.ncbi.nlm.nih.gov/pubmed/903830
  4. ↑ Champe, Pamela C.; Harvey, Richard A. Lippincott’s Illustrated Reviews: Biochemistry. Lippincott Williams & Wilkins.
  5. ↑ 5.0 5.1 Johnston, DG; Pernet, A; McCulloch, A; Blesa-Malpica, G; Burrin, JM; Alberti, KG (1982). "Some hormonal influences on glucose and ketone body metabolism in normal human subjects.". Ciba Foundation symposium 87: 168–91. doi:10.1002/9780470720691.ch10. PMID 6122546.
  6. ↑ Kossoff, Eric H.; Freeman, John M.; Turner, Zahava; Rubenstein, James E. (2011). Ketogenic Diets: Treatments for Epilepsy and Other Diseases. Demos Health.
  7. ↑ Manninen, Anssi H (2004). "Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood "Villains" of Human Metabolism". J Int Soc Sports Nutr. 1 (2): 7–11. doi:10.1186/1550-2783-1-2-7. PMC 2129159. PMID 18500949.
  8. ↑ Attia, Peter (2013-07-18). "How to make a fat cell less not thin: the lessons of fat flux". The Eating Academy.
  9. ↑ Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A (2013). "Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets". European Journal of Clinical Nutrition 67 (8): 789–796. doi:10.1038/ejcn.2013.116.
  10. ↑ 10.0 10.1 10.2 Volek & Phinney, page 302.
  11. ↑ Galvin, R. Dennis; Harris, Janet A.; Johnson, Robert E. (1968). "Urinary Excretion of Beta-Hydroxybutyrate and Acetoacetate during Experimental Ketosis". Experimental Physiology 53: 181–193. doi:10.1113/expphysiol.1968.sp001958.
  12. ↑ Johnson RC, Young SK, Cotter R, Lin L, Rowe WB (1990). "Medium-chain-triglyceride lipid emulsion: metabolism and tissue distribution". Am. J. Clin. Nutr. 52 (3): 502–8. PMID 2118303.
  13. ↑ Marshall, William J.; Bangert, Stephen K. (2008). Clinical biochemistry: metabolic and clinical aspects. Elsevier Health Sciences. pp. 67–80. ISBN 978-0-443-10186-1.
  14. ↑ Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA (December 2006). "Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association". Diabetes Care 29 (12): 2739–48. doi:10.2337/dc06-9916. PMID 17130218.
  15. ↑ Kraut JA, Kurtz I (January 2008). "Toxic alcohol ingestions: clinical features, diagnosis, and management". Clinical Journal of the American Society of Nephrology 3 (1): 208–25. doi:10.2215/CJN.03220807. PMID 18045860.
  16. ↑ 16.0 16.1 Hartman AL, Vining EP (January 2007). "Clinical aspects of the ketogenic diet". Epilepsia 48 (1): 31–42. doi:10.1111/j.1528-1167.2007.00914.x. PMID 17241206.
  17. ↑ Delbridge E, Proietto J (2006). "State of the science: VLED (Very Low Energy Diet) for obesity". Asia Pac J Clin Nutr 15: 49–54. PMID 16928661.
  18. ↑ Eades, Michael R. (2007-05-22). "Metabolism and Ketosis". Protein Power.
  19. ↑ Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, Szapary PO, Rader DJ, Edman JS, Klein S (May 2003). "A randomized trial of a low-carbohydrate diet for obesity". N. Engl. J. Med. 348 (21): 2082–90. doi:10.1056/NEJMoa022207. PMID 12761365.
  20. ↑ Bravata DM, Sanders L, Huang J, Krumholz HM, Olkin I, Gardner CD, Bravata DM (April 2003). "Efficacy and safety of low-carbohydrate diets: a systematic review". JAMA 289 (14): 1837–50. doi:10.1001/jama.289.14.1837. PMID 12684364.
  21. ↑ Plaskett, L. G. (September 2003). "On the Essentiality of Dietary Carbohydrate". Journal of Nutritional & Environmental Medicine 13 (3): 161–168. doi:10.1080/13590840310001619405.
  22. ↑ Pérez-Guisado, J (2008). "Ketogenic diets: Additional benefits to the weight loss and unfounded secondary effects". Archivos latinoamericanos de nutricion 58 (4): 323–9. PMID 19368291.
  23. ↑ Westman, EC; Yancy Jr, WS; Mavropoulos, JC; Marquart, M; McDuffie, JR (2008). "The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus". Nutrition & metabolism 5: 36. doi:10.1186/1743-7075-5-36. PMC 2633336. PMID 19099589.
  24. ↑ 24.0 24.1 24.2 PTS PANELS™ Ketone Test Strips Information paper PS-002588E Rev. 2 10/05 by Polymer Technology Systems
  25. ↑ 25.0 25.1 25.2 Converted from molar values, using average of 10.3 g/mol as used in: PTS PANELS™ Ketone Test Strips Information paper PS-002588E Rev. 2 10/05 by Polymer Technology Systems, and subsequently rounded to same number of significant figures as molar value
  26. ↑ 26.0 26.1 26.2 Taboulet P, Deconinck N, Thurel A, Haas L, Manamani J, Porcher R, Schmit C, Fontaine JP, Gautier JF (2007). "Correlation between urine ketones (acetoacetate) and capillary blood ketones (3-beta-hydroxybutyrate) in hyperglycaemic patients". Diabetes & Metabolism 33 (2): 135–139. doi:10.1016/j.diabet.2006.11.006. PMID 17320448.
  27. ↑ Sekizawa A, Sugito Y, Iwasaki M, Watanabe A, Jimbo M, Hoshi S, Saito H, Okai T (2001). "Cell-free fetal DNA is increased in plasma of women with hyperemesis gravidarum". Clinical chemistry 47 (12): 2164–5. PMID 11719487.
  28. ↑ Burbos N, Shiner AM, Morris E (2008). "Severe metabolic acidosis as a consequence of acute starvation in pregnancy". Archives of Gynecology and Obstetrics 279 (3): 399–400. doi:10.1007/s00404-008-0715-3. PMID 18592261.
  29. ↑ McDougall, John (July 9, 2012). "The Paleo Diet Is Uncivilized (And Unhealthy and Untrue)". Forks over Knives.
  30. ↑ Karra, Cindy: Shape Up America! Reveals The Truth About Dieters, Shape Up America! (by former U.S. Surgeon General C. Everett Koop), 29 December 2003
  31. ↑ Volek and Phinney, p. 4
  32. ↑ Eaton SB, Konner M (1985). "Paleolithic Nutrition". New England Journal of Medicine 312 (5): 283–289. doi:10.1056/NEJM198501313120505. PMID 2981409.
  33. ↑ Yancy WS, Foy M, Chalecki AM, Vernon MC, Westman EC (2005). "A low-carbohydrate, ketogenic diet to treat type 2 diabetes". Journal of Nutrition and Metabolism 2: 34. doi:10.1186/1743-7075-2-34. PMC 1325029. PMID 16318637.
  34. ↑ 34.0 34.1 34.2 Peter Heinbecker (1928). "Studies on the Metabolism of Eskimos" (PDF). J. Biol. Chem 80: 461–475. Retrieved 2014-04-07.
  35. ↑ 35.0 35.1 35.2 Corcoran AC, Rabinowitch IM (1937). "A study of the blood lipids and blood protein in Canadian Eastern Arctic Eskimos" (PDF). Biochem. J. 31 (3): 343–8. PMC 1266943. PMID 16746345.
  36. ↑ 36.0 36.1 36.2 Ho KJ, Mikkelson B, Lewis LA, Feldman SA, Taylor CB (1972). "Alaskan Arctic Eskimo: responses to a customary high fat diet" (PDF). Am. J. Clin. Nutr. 25 (8): 737–45. PMID 5046723.
  37. ↑ 37.0 37.1 Sinclair, H. M. (1953). "The Diet of Canadian Indians and Eskimos" (PDF). Proceedings of the Nutrition Society 12 (01): 69–82. doi:10.1079/PNS19530016. ISSN 0029-6651. It is, however, worth noting that according to the customary convention (Woodyatt, 1921 ; Shaffer, 1921) this diet is not ketogenic since the ratio of ketogenic(FA) to ketolytic (G) aliments is 1.09. Indeed, the content of fat would have to be exactly doubled (324 g daily) to make the diet ketogenic (FA/G>1-5).
  38. ↑ 38.0 38.1 Speth, John D; Spielmann, Katherine A (1983). "Energy source, protein metabolism, and hunter-gatherer subsistence strategies" (PDF). Journal of Anthropological Archaeology 2 (1): 1–31. doi:10.1016/0278-4165(83)90006-5. ISSN 0278-4165.
  39. ↑ Ringberg, Tata M.; White, Robert G.; Holleman, Dan F.; Luick, Jack R. (1981). "Body growth and carcass composition of lean reindeer (Rangifer tarandus tarandusL.) from birth to sexual maturity" (PDF). Canadian Journal of Zoology 59 (6): 1040–1044. doi:10.1139/z81-145. ISSN 0008-4301. Body growth and carcass composition were measured in lean reindeer during the juvenile growth period between birth and 3 years of age. Mean carcass weight in these lean reindeer was 56 ± 4% of body weight and the deposition of body muscle and bone mass was linearly correlated with body weight after the 1st month of age. The weight of the brain relative to body weight and carcass weight declined, while the relative changes in heart, liver, kidneys, parotid glands, and tissues of the gastrointestinal tract were small after the neonatal period. The extractable fat content in carcasses increased from 4.4 to 11.4% of wet weight or approximately 100 g fat at birth and 3.5 kg fat in adult reindeer. Fat-free dry matter represented a constant percentage (18–20%) of wet carcass weight independent of body weight after the neonatal period, while a significant inverse relationship between carcass fat and body water was found.
  40. ↑ Yiu H. Hui (February 1985). Principles and issues in nutrition. Wadsworth Health Sciences Division. p. 91. Retrieved 2014-05-19. Eskimos actually consume more carbohydrates than most nutritionists have assumed. Because Eskimos frequently eat their meat raw and frozen, they take in more glycogen than a person purchasing meat with a lower glycogen content in a grocery store. The Eskimo practice of preserving a whole seal or bird carcass under an intact whole skin with a thick layer of blubber also permits some proteins to ferment into carbohydrates.
  41. ↑ Pfeiffer, Carl J. (1997). "Renal cellular and tissue specializations in the bottlenose dolphin (Tursiops truncatus) and beluga whale (Delphinapterus leucas)" (PDF). Aquatic Mammals 23 (2): 75–84. Retrieved 2014-04-25.
  42. ↑ Lockyer, Christina (1991). "Body composition of the sperm whale, Physeter cation, with special reference to the possible functions of fat depots" (PDF). Journal of the Marine Research Institute 12 (2). ISSN 0484-9019. Retrieved 2014-04-25. The significant levels of carbohydrate, probably mostly in the form of glycogen, in both blubber and muscle, may represent an instant form of energy for diving via anaerobic glycolysis.
  43. ↑ Hochachka, P.; Storey, K. (1975). "Metabolic consequences of diving in animals and man". Science 187 (4177): 613–621. doi:10.1126/science.163485. ISSN 0036-8075. PMID 163485. In the terminal stages of prolonged diving, however, even these organs must tolerate anoxia for surprisingly long times, and they typically store unusually large amounts of glycogen for this purpose.
  44. ↑ Lawrie 2014, pp. 92-. "A much delayed onset of rigor mortis has been observed in the muscle of the whale (Marsh, 1952b). The ATP level and the pH may remain at their high in vivo values for as much as 24h at 37ºC. No adequate explanation of this phenomenon has yet been given; but the low basal metabolic rate of whale muscle (Benedict, 1958), in combination with the high content of oxymyoglobin in vivo (cf 4.3.1), may permit aerobic metabolism to continue slowly for some time after the death of the animal, whereby ATP levels can be maintained sufficiently to delay the union of actin and myosin in rigor mortis."
  45. ↑ Peter J. Bechtel; UNKNOWN. AUTHOR (2 December 2012). Muscle as Food. Elsevier Science. pp. 171–. ISBN 978-0-323-13953-3. Retrieved 19 May 2014. Freezing does stop the postmortem metabolism but only at about -18ºC and lower temperatures. Above -18ºC increasing temperatures of storage cause an increasing rate of ATP breakdown and glycolysis that is higher in the comminuted meat than in the intact tissue (Fisher et al., 1980b). If the ATP concentration in the frozen tissue falls below ~ 1 µmol/g no contraction or rigor can occur because they are prevented by the rigid matrix of ice.
  46. ↑ Lawrie 2014, p. 298.
  47. ↑ Lane, Nick (2005). Power Sex Suicide Mitochondria and the Meaning of Life. pp. 254–256. ISBN 0-19-280481-2.
  48. ↑ 48.0 48.1 Phinney SD (2004). "Ketogenic diets and physical performance". Nutrition & Metabolism 1 (1): 2. doi:10.1186/1743-7075-1-2. PMC 524027. PMID 15507148.
  49. ↑ McClellan WS, Du Bois EF (February 13, 1930). "The Effects on Human Beings of a Twelve Months' Exclusive Meat Diet" (PDF). Journal of the American Medical Association.
  50. ↑ Schwatka, Frederick (1965). The Long Arctic Search. Ed. Edouard A. Stackpole. New Bedford, Mass.: Reynolds-DeWalt. p.115.
  51. ↑ Cordain L, Miller JB, Eaton SB, Mann N, Holt SH, Speth JD (2000). "Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets". Am. J. Clin. Nutr. 71 (3): 682–92. PMID 10702160.
  52. ↑ Ivy JL (Jun 19, 1998). "Glycogen Resynthesis After Exercise: Effect of Carbohydrate Intake". Int J Sports Med 19: S142–5. doi:10.1055/s-2007-971981. PMID 9694422.
  53. ↑ Burke LM, Collier GR, Hargreaves M (August 1993). "Muscle glycogen storage after prolonged exercise: effect of the glycemic index of carbohydrate feedings". Journal of Applied Physiology. 2 75 (2): 1019–1023. PMID 8226443.
  54. ↑ Volek and Phinney, p. 237.
  55. ↑ Klein MS, Buttchereit N, Miemczyk SP, Immervoll AK, Louis C, Wiedemann S, Junge W, Thaller G, Oefner PJ, Gronwald W (February 2012). "NMR metabolomic analysis of dairy cows reveals milk glycerophosphocholine to phosphocholine ratio as prognostic biomarker for risk of ketosis". J. Proteome Res. 11 (2): 1373–81. doi:10.1021/pr201017n. PMID 22098372.
  56. ↑ 56.0 56.1 56.2 Pugh, D. G. 2002. Sheep and goat medicine. Saunders, Philadelphia. 468 pp.
  57. ↑ 57.0 57.1 57.2 Kimberling, C. V. 1988. Jensen and Swift's diseases of sheep. 3rd Ed. Lea & Febiger, Philadelphia. 394 pp.
  58. ↑ Marteniuk J. V., Herdt T. H. (1988). "Pregnancy toxemia and ketosis of ewes and does". Vet. Clin. North. Am. Food Anim. Pract 4: 307–315.
  59. ↑ Reid R. L. (1960). "Studies on the carbohydrate metabolism of sheep. IX. Metabolic effects of glucose and glycerol in undernourished pregnant ewes and in ewes with pregnancy toxaemia". Aust. J. Agr. Res. 11: 42–47. doi:10.1071/ar9600042.
  60. ↑ Van Soest, P. J. 1994. Nutritional ecology of the ruminant. 2nd Ed. Cornell Univ. Press. 476 pp.
  61. ↑ Overton TR, Drackley JK, Ottemann-Abbamonte CJ, Beaulieu AD, Emmert LS, Clark JH (1999). "Substrate utilization for hepatic gluconeogenesis is altered by increased glucose demand in ruminants". J. Anim. Sci. 77 (7): 1940–51. PMID 10438042.
  62. ↑ Sasaki S., Ambo K., Muramatsu M., Tsuda T. (1975). "Gluconeogenesis in the kidney-cortex slices of normal fed and starved sheep". Tohoku J. Agr. Res. 26: 20–29.
  63. ↑ Henze P, Bickhardt K, Fuhrmann H, Sallmann HP (1998). "Spontaneous pregnancy toxaemia (ketosis) in sheep and the role of insulin". Zentralbl Veterinarmed A 45 (5): 255–66. doi:10.1111/j.1439-0442.1998.tb00825.x. PMID 9719756.
  64. ↑ Kahn, C. M., ed. (2005). Merck Veterinary Manual (9th ed.). Whitehouse Station: Merck & Co.

References

External links