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Cited by 126Diet and metabolism studiesGut microbiota and healthDietary Effects on Health

Potential Synergies of β-Hydroxybutyrate and Butyrate on the Modulation of Metabolism, Inflammation, Cognition, and General Health

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Cavaleri, Franco, Bashar, Emran·2018·Journal of Nutrition and Metabolism
DOI 10.1155/2018/7195760PMC PMC5902005
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Abstract

The low-carbohydrate high-fat diet (LCHFD), also known as the ketogenic diet, has cycled in and out of popularity for decades as a therapeutic program to treat metabolic syndrome, weight mismanagement, and drug-resistant disorders as complex as epilepsy, cancer, dementia, and depression. Despite the benefits of this diet, health care professionals still question its safety due to the elevated serum ketones it induces and the limited dietary fiber. To compound the controversy, patient compliance with the program is poor due to the restrictive nature of the diet and symptoms related to energy deficit and gastrointestinal adversity during the introductory and energy substrate transition phase of the diet. The studies presented here demonstrate safety and efficacy of the diet including the scientific support and rationale for the administration of exogenous ketone bodies and ketone sources as a complement to the restrictive dietary protocol or as an alternative to the diet. This review also highlights the synergy provided by exogenous ketone,β-hydroxybutyrate (BHB), accompanied by the short chain fatty acid, butyrate (BA) in the context of cellular and physiological outcomes. More work is needed to unveil the molecular mechanisms by which this program provides health benefits.

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  • Elevation in serum ketones inhibits apoptotic proteins and improves mitochondrial activity, thus reducing apoptosis in neurodegenerative diseases.

    “This elevation in the serum ketones has been shown to inhibit apoptotic proteins and improve mitochondrial activity and thus reducing apoptosis in neurodegenerative diseases (Cavaleri and Bashar, 2018).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Cavaleri and Bashar, 2018

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  1. [1]Gjedde A. Crone C. Induction processes in blood-brain transfer of ketone bodies during starvation American Journal of Physiology–Legacy Content 1975 229 5 1165 1169 10.1152/ajplegacy.1975.229.5.1165 1200135 · DOI
  2. [2]Pollay M. Alan Stevens F. Starvation-induced changes in transport of ketone bodies across the blood-brain barrier Journal of Neuroscience Research 1980 5 2 163 172 10.1002/jnr.490050208 2-s2.0-0018848460 6772797 · DOI
  3. [3]Cunnane S. Nugent S. Roy M. Brain fuel metabolism, aging, and Alzheimer’s disease Nutrition 2011 27 1 3 20 10.1016/j.nut.2010.07.021 2-s2.0-78649962844 21035308 PMC3478067 · DOI
  4. [4]Reger M. A. Henderson S. T. Hale C. Effects of β-hydroxybutyrate on cognition in memory-impaired adults Neurobiology of Aging 2004 25 3 311 314 10.1016/s0197-4580(03)00087-3 2-s2.0-1242338801 15123336 · DOI
  5. [5]Costantini L. C. Barr L. J. Vogel J. L. Henderson S. T. Hypometabolism as a therapeutic target in Alzheimer’s disease BMC Neuroscience 2008 9 2 p. S16 10.1186/1471-2202-9-s2-s16 2-s2.0-57449113999 PMC2604900 19090989 · DOI · Paper page
  6. [6]Leonard W. R. Dietary change was a driving force in human evolution Scientific American 2002 287 6 106 116 10.1038/scientificamerican1202-106 2-s2.0-0036885140 12469653 · DOI
  7. [7]Innis S. M. Dietary (n−3) fatty acids and brain development Journal of Nutrition 2007 137 4 855 859 10.1093/jn/137.4.855 17374644 · DOI · Paper page
  8. [8]Cohen E. Cragg M. Hite A. Rosenberg M. Zhou B. Statistical review of US macronutrient consumption data, 1965–2011: Americans have been following dietary guidelines, coincident with the rise in obesity Nutrition 2015 31 5 727 732 10.1016/j.nut.2015.02.007 2-s2.0-84933527505 25837220 · DOI
  9. [9]Scholl J. Traditional dietary recommendations for the prevention of cardiovascular disease: do they meet the needs of our patients? Cholesterol 2012 2012 1 9 10.1155/2012/367898 2-s2.0-84858204845 PMC3299312 22482040 · DOI
  10. [10]Mullins G. Hallam C. Broom I. Ketosis, ketoacidosis and very-low-calorie diets: putting the record straight Nutrition Bulletin 2011 36 3 397 402 10.1111/j.1467-3010.2011.01916.x 2-s2.0-80051586843 · DOI
  11. [11]Layman D. K. Walker D. A. Potential importance of leucine in treatment of obesity and the metabolic syndrome Journal of Nutrition 2006 136 1 319S 323S 10.1093/jn/136.1.319s 16365106 · DOI
  12. [12]Lawson M. Shaw V. Ketogenic diet for epilepsy Clinical Paediatric Dietetics 2001 2nd Oxford, UK Blackwell Science Ltd. 222 232
  13. [13]Krikorian R. Shidler M. D. Dangelo K. Couch S. C. Benoit S. C. Clegg D. J. Dietary ketosis enhances memory in mild cognitive impairment Neurobiology of Aging 2012 33 2 425. e19 425. e27 10.1016/j.neurobiolaging.2010.10.006 2-s2.0-82755194976 PMC3116949 21130529 · DOI
  14. [14]Barañano K. W. Hartman A. L. The ketogenic diet: uses in epilepsy and other neurologic illnesses Current Treatment Options in Neurology 2008 10 6 410 419 10.1007/s11940-008-0043-8 2-s2.0-58649103488 18990309 PMC2898565 · DOI · Paper page
  15. [15]Sullivan P. G. Rippy N. A. Dorenbos K. Concepcion R. C. Agarwal A. K. Rho J. M. The ketogenic diet increases mitochondrial uncoupling protein levels and activity Annals of Neurology 2004 55 4 576 580 10.1002/ana.20062 2-s2.0-1642289587 15048898 · DOI
  16. [20]Schmidt M. Pfetzer N. Schwab M. Strauss I. Kämmerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial Nutrition and Metabolism 2011 8 1 p. 54 10.1186/1743-7075-8-54 2-s2.0-79960688044 PMC3157418 21794124 · DOI
  17. [21]Layman D. K. Baum J. I. Dietary protein impact on glycemic control during weight loss Journal of Nutrition 2004 134 4 968S 973S 10.1093/jn/134.4.968s 15051856 · DOI
  18. [22]Remesy C. Fafournoux P. Demigne C. Control of hepatic utilization of serine, glycine and threonine in fed and starved rats Journal of Nutrition 1983 113 1 28 39 10.1093/jn/113.1.28 6401804 · DOI
  19. [23]Krilanovich N. J. Benefits of ketogenic diets American Journal of Clinical Nutrition 2007 85 1 238 239 10.1093/ajcn/85.1.238 17209202 · DOI
  20. [24]Kim D. W. Kang H. C. Park J. C. Kim H. D. Benefits of the nonfasting ketogenic diet compared with the initial fasting ketogenic diet Pediatrics 2004 114 6 1627 1630 10.1542/peds.2004-1001 2-s2.0-13244275812 15574625 · DOI
  21. [25]Veech R. L. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism Prostaglandins, Leukotrienes and Essential Fatty Acids 2004 70 3 309 319 10.1016/j.plefa.2003.09.007 2-s2.0-1042299789 14769489 · DOI
  22. [26]McGarry J. D. Disordered metabolism in diabetes: have we underemphasized the fat component? Journal of Cellular Biochemistry 1994 55 S1994A 29 38 10.1002/jcb.240550005 2-s2.0-0028339336 7929616 · DOI
  23. [28]Owen O. Reichard G. Jr. Markus H. Boden G. Mozzoli M. Shuman C. Rapid intravenous sodium acetoacetate infusion in man metabolic and kinetic responses Journal of Clinical Investigation 1973 52 10 2606 2616 10.1172/jci107453 2-s2.0-0015864398 4729054 PMC302521 · DOI
  24. [29]Balasse E. O. Féry F. Ketone body production and disposal: effects of fasting, diabetes, and exercise Diabetes/Metabolism Reviews 1989 5 3 247 270 10.1002/dmr.5610050304 2-s2.0-0024549618 2656155 · DOI
  25. [30]Wilson R. Reeves W. Neutrophil phagocytosis and killing in insulin-dependent diabetes Clinical and Experimental Immunology 1986 63 2 p. 478 PMC1577392 3084140
  26. [31]Brownlee M. Vlassara H. Kooney A. Ulrich P. Cerami A. Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking Science 1986 232 4758 1629 1632 10.1126/science.3487117 3487117 · DOI
  27. [32]Ahmed N. Advanced glycation endproducts—role in pathology of diabetic complications Diabetes Research and Clinical Practice 2005 67 1 3 21 10.1016/j.diabres.2004.09.004 2-s2.0-11144324314 15620429 · DOI
  28. [33]Marceau P. Biron S. Hould F. S. Liver pathology and the metabolic syndrome X in severe obesity Journal of Clinical Endocrinology and Metabolism 1999 84 5 1513 1517 10.1210/jc.84.5.1513 10323371 · DOI
  29. [35]Moley K. Chi M. Y. Knudson C. Korsmeyer S. Mueckler M. Hyperglycemia induces apoptosis in pre-implantation embryos through cell death effector pathways Nature Medicine 1998 4 12 1421 1424 10.1038/4013 2-s2.0-0031728455 9846581 · DOI
  30. [36]Hays S. P. Smith E. B. Sunehag A. L. Hyperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants Pediatrics 2006 118 5 1811 1818 10.1542/peds.2006-0628 2-s2.0-33750959972 17079549 · DOI
  31. [37]Vlassara H. Advanced glycation end-products and atherosclerosis Annals of Medicine 1996 28 5 419 426 10.3109/07853899608999102 2-s2.0-0029793997 8949973 · DOI
  32. [38]Yki-Jarvinen H. Glucose Toxicity∗ Endocrine Reviews 1992 13 3 415 431 10.1210/edrv-13-3-415 2-s2.0-0026731869 1425483 · DOI
  33. [39]Madison L. L. Mebane D. Unger R. H. Lochner A. The hypoglycemic action of ketones. II. Evidence for a stimulatory feedback of ketones on the pancreatic beta cells Journal of Clinical Investigation 1964 43 3 408 415 10.1172/jci104925 14135491 PMC441933 · DOI
  34. [40]Baron A. Brechtel G. Edelman S. Effects of free fatty acids and ketone bodies on in vivo non-insulin-mediated glucose utilization and production in humans Metabolism 1989 38 11 1056 1061 10.1016/0026-0495(89)90040-1 2-s2.0-0024424731 2682134 · DOI
  35. [42]Noakes T. D. Low-carbohydrate and high-fat intake can manage obesity and associated conditions: occasional survey South African Medical Journal 2013 103 11 826 830 10.7196/samj.7302 2-s2.0-84885995683 24148165 · DOI
  36. [43]Ratliff J. Mutungi G. Puglisi M. J. Volek J. S. Fernandez M. L. Carbohydrate restriction (with or without additional dietary cholesterol provided by eggs) reduces insulin resistance and plasma leptin without modifying appetite hormones in adult men Nutrition Research 2009 29 4 262 268 10.1016/j.nutres.2009.03.007 2-s2.0-65349084973 19410978 · DOI
  37. [44]Volek J. S. Sharman M. J. Love D. M. Avery N. G. Scheett T. P. Kraemer W. J. Body composition and hormonal responses to a carbohydrate-restricted diet Metabolism 2002 51 7 864 870 10.1053/meta.2002.32037 2-s2.0-0036069120 12077732 · DOI
  38. [45]Major C. A. Henry M. J. de Veciana M. Morgan M. A. The effects of carbohydrate restriction in patients with diet-controlled gestational diabetes Obstetrics and Gynecology 1998 91 4 600 604 10.1016/s0029-7844(98)00003-9 2-s2.0-0032054370 9540949 · DOI · Paper page
  39. [46]Accurso A. Bernstein R. K. Dahlqvist A. Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal Nutrition and Metabolism 2008 5 1 p. 9 10.1186/1743-7075-5-9 2-s2.0-43149111330 PMC2359752 18397522 · DOI · Paper page
  40. [47]Feinman R. D. Pogozelski W. K. Astrup A. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base Nutrition 2015 31 1 1 13 10.1016/j.nut.2014.06.011 2-s2.0-84922230039 25287761 · DOI · Paper page
  41. [48]Badman M. K. Kennedy A. R. Adams A. C. Pissios P. Maratos-Flier E. A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss American Journal of Physiology-Endocrinology and Metabolism 2009 297 5 E1197 E1204 10.1152/ajpendo.00357.2009 2-s2.0-70350443243 19738035 PMC2781352 · DOI
  42. [49]Xu K. Sun X. Eroku B. O. Tsipis C. P. Puchowicz M. A. LaManna J. C. Diet-induced ketosis improves cognitive performance in aged rats Advances in Experimental Medicine and Biology 2010 Berlin, Germany Springer 71 75 PMC2874682 20204773
  43. [50]Ballard K. D. Quann E. E. Kupchak B. R. Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins Nutrition Research 2013 33 11 905 912 10.1016/j.nutres.2013.07.022 2-s2.0-84886416689 24176230 · DOI
  44. [51]Hawkins R. A. Mans A. M. Davis D. W. Regional ketone body utilization by rat brain in starvation and diabetes American Journal of Physiology-Endocrinology and Metabolism 1986 250 2 E169 E178 10.1152/ajpendo.1986.250.2.e169 2937307 · DOI
  45. [52]Seyfried T. N. Mukherjee P. Targeting energy metabolism in brain cancer: review and hypothesis Nutrition and Metabolism 2005 2 1 p. 30 10.1186/1743-7075-2-30 2-s2.0-27744502691 PMC1276814 16242042 · DOI
  46. [53]Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes Diabetes/Metabolism Research and Reviews 1999 15 6 412 426 10.1002/(sici)1520-7560(199911/12)15:6<412::aid-dmrr72>3.0.co;2-8 10634967 · DOI
  47. [54]Krebs H. The regulation of the release of ketone bodies by the liver Advances in Enzyme Regulation 1966 4 339 353 10.1016/0065-2571(66)90027-6 4865971 · DOI
  48. [56]Newport M. T. VanItallie T. B. Kashiwaya Y. King M. T. Veech R. L. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s disease Alzheimer’s and Dementia 2015 11 1 99 103 10.1016/j.jalz.2014.01.006 2-s2.0-84922709891 PMC4300286 25301680 · DOI
  49. [57]Westman E. C. Feinman R. D. Mavropoulos J. C. Low-carbohydrate nutrition and metabolism American Journal of Clinical Nutrition 2007 86 2 276 284 10.1093/ajcn/86.2.276 17684196 · DOI
  50. [59]Kodde I. F. van der Stok J. Smolenski R. T. de Jong J. W. Metabolic and genetic regulation of cardiac energy substrate preference Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology 2007 146 1 26 39 10.1016/j.cbpa.2006.09.014 2-s2.0-33846636024 17081788 · DOI
  51. [60]Plecko B. Stoeckler-Ipsiroglu S. Schober E. Oral β-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of β-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy Pediatric Research 2002 52 2 301 306 10.1203/01.pdr.0000019439.27135.2b 2-s2.0-0035992255 12149510 · DOI
  52. [61]White H. Venkatesh B. Clinical review: ketones and brain injury Critical Care 2011 15 2 p. 219 10.1186/cc10020 2-s2.0-84862739428 PMC3219306 21489321 · DOI
  53. [62]Vining E. P. Clinical efficacy of the ketogenic diet Epilepsy Research 1999 37 3 181 190 10.1016/s0920-1211(99)00070-4 2-s2.0-0032877719 10584968 · DOI
  54. [63]Kossoff E. H. Zupec-Kania B. A. Rho J. M. Ketogenic diets: an update for child neurologists Journal of Child Neurology 2009 24 8 979 988 10.1177/0883073809337162 19535814 · DOI
  55. [64]Cahill G. F. Jr. Fuel metabolism in starvation Annual Review of Nutrition 2006 26 1 1 22 10.1146/annurev.nutr.26.061505.111258 2-s2.0-33750110683 16848698 · DOI
  56. [65]Gasior M. Rogawski M. A. Hartman A. L. Neuroprotective and disease-modifying effects of the ketogenic diet Behavioural Pharmacology 2006 17 5-6 431 439 10.1097/00008877-200609000-00009 2-s2.0-33748298884 16940764 PMC2367001 · DOI · Paper page
  57. [66]de Oliveira Caminhotto R. Lima F. B. Low carbohydrate high fat diets: when models do not match reality Archives of Endocrinology and Metabolism 2016 60 4 405 406 10.1590/2359-3997000000177 2-s2.0-84989222476 27533617 · DOI
  58. [67]Abdelwahab M. G. Lee S. H. O’Neill D. Ketones prevent oxidative impairment of hippocampal synaptic integrity through K ATP channels PLoS One 2015 10 4 e0119316 10.1371/journal.pone.0119316 2-s2.0-84929991757 PMC4388385 25848768 · DOI
  59. [68]Yin J. X. Maalouf M. Han P. Ketones block amyloid entry and improve cognition in an Alzheimer’s model Neurobiology of Aging 2016 39 25 37 10.1016/j.neurobiolaging.2015.11.018 2-s2.0-84959499873 26923399 · DOI · Paper page
  60. [69]Zhang J. Cao Q. Li S. 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer’s disease via mitochondria protection mechanism Biomaterials 2013 34 30 7552 7562 10.1016/j.biomaterials.2013.06.043 2-s2.0-84880508862 23849878 · DOI
  61. [70]Siegel L. Robin N. I. McDonald L. J. New approach to determination of total ketone bodies in serum Clinical Chemistry 1977 23 1 46 49 832372
  62. [72]Misell L. Lagomarcino N. Schuster V. Kern M. Chronic medium-chain triacylglycerol consumption and endurance performance in trained runners Journal of Sports Medicine and Physical Fitness 2001 41 2 p. 210 11447364
  63. [73]Ööpik V. Timpmann S. Medijainen L. Lemberg H. Effects of daily medium-chain triglyceride ingestion on energy metabolism and endurance performance capacity in well-trained runners Nutrition Research 2001 21 8 1125 1135 10.1016/s0271-5317(01)00319-0 2-s2.0-0034803445 · DOI
  64. [74]Liu Y. M. C. Medium-chain triglyceride (MCT) ketogenic therapy Epilepsia 2008 49 s8 33 36 10.1111/j.1528-1167.2008.01830.x 2-s2.0-55349097907 19049583 · DOI
  65. [75]Jeukendrup A. E. Saris W. Schrauwen P. Brouns F. Wagenmakers A. Metabolic availability of medium-chain triglycerides coingested with carbohydrates during prolonged exercise Journal of Applied Physiology 1995 79 3 756 762 10.1152/jappl.1995.79.3.756 8567514 · DOI
  66. [76]Poff A. Ari C. Arnold P. Seyfried T. D’Agostino D. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer International Journal of Cancer 2014 135 7 1711 1720 10.1002/ijc.28809 2-s2.0-84904438541 24615175 PMC4235292 · DOI
  67. [78]D’Agostino D. P. Pilla R. Held H. E. Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2013 304 10 R829 R836 10.1152/ajpregu.00506.2012 2-s2.0-84878652279 23552496 · DOI
  68. [79]Gormsen L. C. Svart M. Thomsen H. H. Ketone body infusion with 3-hydroxybutyrate reduces myocardial glucose uptake and increases blood flow in humans: a positron emission tomography study Journal of the American Heart Association 2017 6 3 p. e005066 10.1161/jaha.116.005066 2-s2.0-85015064440 28242634 PMC5524028 · DOI
  69. [80]Henderson S. T. Vogel J. L. Barr L. J. Garvin F. Jones J. J. Costantini L. C. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial Nutrition and Metabolism 2009 6 1 p. 31 10.1186/1743-7075-6-31 2-s2.0-69449085062 19664276 PMC2731764 · DOI · Paper page
  70. [81]Arnaiz E. Jelic V. Almkvist O. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment Neuroreport 2001 12 4 851 855 10.1097/00001756-200103260-00045 2-s2.0-0035953137 11277595 · DOI · Paper page
  71. [82]Gong C. X. Liu F. Iqbal K. Impaired brain glucose metabolism leads to Alzheimer neurofibrillary degeneration through a decrease in tau O-GlcNAcylation Journal of Alzheimer’s Disease 2006 9 1 1 12 10.3233/jad-2006-9101 2-s2.0-33646002650 16627930 · DOI
  72. [83]Messier C. Impact of impaired glucose tolerance and type 2 diabetes on cognitive aging Neurobiology of Aging 2005 26 1 26 30 10.1016/j.neurobiolaging.2005.09.014 2-s2.0-28444433338 16236384 · DOI
  73. [84]Henderson S. T. Ketone bodies as a therapeutic for Alzheimer’s disease Neurotherapeutics 2008 5 3 470 480 10.1016/j.nurt.2008.05.004 2-s2.0-46749091229 18625458 PMC5084248 · DOI
  74. [85]VanItallie T. B. Nufert T. H. Ketones: metabolism’s ugly duckling Nutrition Reviews 2003 61 10 327 341 10.1301/nr.2003.oct.327-341 2-s2.0-0141919698 14604265 · DOI
  75. [86]Maalouf M. Sullivan P. G. Davis L. Kim D. Y. Rho J. M. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation Neuroscience 2007 145 1 256 264 10.1016/j.neuroscience.2006.11.065 2-s2.0-33846852428 17240074 PMC1865572 · DOI
  76. [87]Henderson C. B. Filloux F. M. Alder S. C. Lyon J. L. Caplin D. A. Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis Journal of Child Neurology 2006 21 3 193 198 10.2310/7010.2006.00044 2-s2.0-33745162585 16901419 · DOI
  77. [88]Sirven J. Whedon B. Caplan D. The ketogenic diet for intractable epilepsy in adults: preliminary results Epilepsia 1999 40 12 1721 1726 10.1111/j.1528-1157.1999.tb01589.x 10612335 · DOI
  78. [89]McNally M. A. Hartman A. L. Ketone bodies in epilepsy Journal of Neurochemistry 2012 121 1 28 35 10.1111/j.1471-4159.2012.07670.x 2-s2.0-84858701982 22268909 PMC3969728 · DOI
  79. [90]Murray A. J. Knight N. S. Cole M. A. Novel ketone diet enhances physical and cognitive performance Federation of American Societies for Experimental Biology Journal 2016 30 12 4021 4032 10.1096/fj.201600773r 2-s2.0-85002322997 27528626 PMC5102124 · DOI
  80. [91]Pinckaers P. J. Churchward-Venne T. A. Bailey D. van Loon L. J. Ketone bodies and exercise performance: the next magic bullet or merely hype? Sports Medicine 2017 47 3 383 391 10.1007/s40279-016-0577-y 2-s2.0-84978687301 27430501 PMC5309297 · DOI · Paper page
  81. [92]Larsen T. Nielsen N. I. Fluorometric determination of β-hydroxybutyrate in milk and blood plasma Journal of Dairy Science 2005 88 6 2004 2009 10.3168/jds.s0022-0302(05)72876-9 2-s2.0-22944460854 15905430 · DOI
  82. [93]Nielsen N. I. Larsen T. Bjerring M. Ingvartsen K. L. Quarter health, milking interval, and sampling time during milking affect the concentration of milk constituents Journal of Dairy Science 2005 88 9 3186 3200 10.3168/jds.s0022-0302(05)73002-2 2-s2.0-27544449473 16107409 · DOI
  83. [95]Clarke K. Tchabanenko K. Pawlosky R. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects Regulatory Toxicology and Pharmacology 2012 63 3 401 408 10.1016/j.yrtph.2012.04.008 2-s2.0-84862236426 22561291 PMC3810007 · DOI · Paper page
  84. [96]Clarke K. Tchabanenko K. Pawlosky R. Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate Regulatory Toxicology and Pharmacology 2012 63 2 196 208 10.1016/j.yrtph.2012.04.001 2-s2.0-84861137360 22504461 PMC3809901 · DOI
  85. [97]Van Hove J. L. Grünewald S. Jaeken J. D, L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase deficiency (MADD) The Lancet 2003 361 9367 1433 1435 10.1016/s0140-6736(03)13105-4 2-s2.0-0242348802 12727399 · DOI
  86. [98]Endo H. Niioka M. Kobayashi N. Tanaka M. Watanabe T. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: new insight into the probiotics for the gut-liver axis PLoS One 2013 8 5 e63388 10.1371/journal.pone.0063388 2-s2.0-84877798095 PMC3656030 23696823 · DOI
  87. [100]Tuohy K. M. Conterno L. Gasperotti M. Viola R. Up-regulating the human intestinal microbiome using whole plant foods, polyphenols, and/or fiber Journal of Agricultural and Food Chemistry 2012 60 36 8776 8782 10.1021/jf2053959 2-s2.0-84866405382 22607578 · DOI
  88. [101]Wong J. M. De Souza R. Kendall C. W. Emam A. Jenkins D. J. Colonic health: fermentation and short chain fatty acids Journal of Clinical Gastroenterology 2006 40 3 235 243 10.1097/00004836-200603000-00015 2-s2.0-33748209543 16633129 · DOI · Paper page
  89. [102]Velasquez-Manoff M. Gut microbiome: the peacekeepers Nature 2015 518 7540 S3 S11 10.1038/518s3a 2-s2.0-84923788626 25715278 · DOI
  90. [103]Kanauchi O. Iwanaga T. Mitsuyama K. Butyrate from bacterial fermentation of germinated barley foodstuff preserves intestinal barrier function in experimental colitis in the rat model Journal of Gastroenterology and Hepatology 1999 14 9 880 888 10.1046/j.1440-1746.1999.01971.x 2-s2.0-0032887944 10535469 · DOI
  91. [104]Yadav H. Lee J. H. Lloyd J. Walter P. Rane S. G. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion Journal of Biological Chemistry 2013 288 35 25088 25097 10.1074/jbc.m113.452516 2-s2.0-84883418106 23836895 PMC3757173 · DOI · Paper page
  92. [105]Kim H. J. Leeds P. Chuang D. M. The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain Journal of Neurochemistry 2009 110 4 1226 1240 10.1111/j.1471-4159.2009.06212.x 2-s2.0-67651146826 19549282 PMC2726719 · DOI · Paper page
  93. [106]Yamawaki Y. Fuchikami M. Morinobu S. Segawa M. Matsumoto T. Yamawaki S. Antidepressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus World Journal of Biological Psychiatry 2012 13 6 458 467 10.3109/15622975.2011.585663 2-s2.0-84865248291 21812623 · DOI · Paper page
  94. [107]Lin H. V. Frassetto A. Kowalik E. J. Jr. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms PLoS One 2012 7 4 e35240 10.1371/journal.pone.0035240 2-s2.0-84859587827 PMC3323649 22506074 · DOI · Paper page
  95. [109]Tuohy K. M. Probert H. M. Smejkal C. W. Gibson G. R. Using probiotics and prebiotics to improve gut health Drug Discovery Today 2003 8 15 692 700 10.1016/s1359-6446(03)02746-6 2-s2.0-0041620412 12927512 · DOI · Paper page
  96. [110]Canani R. B. Di Costanzo M. Leone L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice Clinical Epigenetics 2012 4 1 p. 4 10.1186/preaccept-1764710053667755 PMC3312834 22414433 · DOI
  97. [111]Alvaro A. Sola R. Rosales R. Gene expression analysis of a human enterocyte cell line reveals downregulation of cholesterol biosynthesis in response to short-chain fatty acids IUBMB Life 2008 60 11 757 764 10.1002/iub.110 2-s2.0-58149357347 18642346 · DOI
  98. [112]Finley J. W. Burrell J. B. Reeves P. G. Pinto bean consumption changes SCFA profiles in fecal fermentations, bacterial populations of the lower bowel, and lipid profiles in blood of humans Journal of Nutrition 2007 137 11 2391 2398 10.1093/jn/137.11.2391 17951475 · DOI
  99. [113]Canfora E. E. Jocken J. W. Blaak E. E. Short-chain fatty acids in control of body weight and insulin sensitivity Nature Reviews Endocrinology 2015 11 10 577 591 10.1038/nrendo.2015.128 2-s2.0-84941879755 26260141 · DOI · Paper page
  100. [114]Darzi J. Frost G. S. Robertson M. D. Do SCFA have a role in appetite regulation? Proceedings of the Nutrition Society 2011 70 1 119 128 10.1017/s0029665110004039 2-s2.0-79951743069 21266094 · DOI · Paper page
  101. [115]Hague A. Singh B. Paraskeva C. Butyrate acts as a survival factor for colonic epithelial cells: further fuel for the in vivo versus in vitro debate Gastroenterology 1997 112 3 1036 1040 10.1053/gast.1997.v112.agast971036 2-s2.0-0031055517 9041270 · DOI
  102. [116]Davie J. R. Inhibition of histone deacetylase activity by butyrate Journal of Nutrition 2003 133 7 2485S 2493S 10.1093/jn/133.7.2485s 12840228 · DOI · Paper page
  103. [117]Stefanko D. P. Barrett R. M. Ly A. R. Reolon G. K. Wood M. A. Modulation of long-term memory for object recognition via HDAC inhibition Proceedings of the National Academy of Sciences 2009 106 23 9447 9452 10.1073/pnas.0903964106 2-s2.0-67249137941 PMC2695069 19470462 · DOI
  104. [118]Gray S. G. Epigenetic treatment of neurological disease Epigenomics 2011 3 4 431 450 22126204
  105. [119]Segain J. De La Blétiere D. R. Bourreille A. Butyrate inhibits inflammatory responses through NFkappa B inhibition: implications for Crohn’s disease Gut 2000 47 3 397 403 10.1136/gut.47.3.397 2-s2.0-0033863238 10940278 PMC1728045 · DOI
  106. [121]Sabatino A. Morera R. Ciccocioppo R. Oral butyrate for mildly to moderately active Crohn’s disease Alimentary Pharmacology and Therapeutics 2005 22 9 789 794 10.1111/j.1365-2036.2005.02639.x 2-s2.0-27644432597 16225487 · DOI
  107. [122]Kotunia A. Wolinski J. Laubitz D. Effect of sodium butyrate on the small intestine Journal of Physiology and Pharmacology 2004 55 2 59 68 15608361
  108. [125]MacFabe D. F. Cain N. E. Boon F. Ossenkopp K. P. Cain D. P. Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: relevance to autism spectrum disorder Behavioural Brain Research 2011 217 1 47 54 10.1016/j.bbr.2010.10.005 2-s2.0-78049463483 20937326 · DOI · Paper page
  109. [126]MacFabe D. F. Cain D. P. Rodriguez-Capote K. Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders Behavioural Brain Research 2007 176 1 149 169 10.1016/j.bbr.2006.07.025 2-s2.0-33845391588 16950524 · DOI · Paper page
  110. [127]Kratsman N. Getselter D. Elliott E. Sodium butyrate attenuates social behavior deficits and modifies the transcription of inhibitory/excitatory genes in the frontal cortex of an autism model Neuropharmacology 2016 102 136 145 10.1016/j.neuropharm.2015.11.003 2-s2.0-84947918250 26577018 · DOI · Paper page
  111. [129]McNeil N. I. Cummings J. James W. Short chain fatty acid absorption by the human large intestine Gut 1978 19 9 819 822 10.1136/gut.19.9.819 30683 PMC1412179 · DOI
  112. [130]Velazquez O. C. Lederer H. M. Rombeau J. L. Butyrate and the Colonocyte. Dietary Fiber in Health and Disease 1997 Berlin, Germany Springer
  113. [131]Sandle G. Salt and water absorption in the human colon: a modern appraisal Gut 1998 43 2 294 299 10.1136/gut.43.2.294 2-s2.0-0031824797 10189861 PMC1727220 · DOI
  114. [132]Havenaar R. Intestinal health functions of colonic microbial metabolites: a review Beneficial Microbes 2011 2 2 103 114 10.3920/bm2011.0003 2-s2.0-80053026224 21840809 · DOI
  115. [133]Canani R. B. Terrin G. Cirillo P. Butyrate as an effective treatment of congenital chloride diarrhea Gastroenterology 2004 127 2 630 634 10.1053/j.gastro.2004.03.071 2-s2.0-4143152851 15300594 · DOI
  116. [134]Butzner J. Parmar R. Bell C. Dalal V. Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat Gut 1996 38 4 568 573 10.1136/gut.38.4.568 8707089 PMC1383116 · DOI
  117. [135]Li H. Gao Z. Zhang J. Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3 Diabetes 2012 61 4 797 806 10.2337/db11-0846 2-s2.0-84859529243 22338096 PMC3314370 · DOI
  118. [137]Hird F. Symons R. The mechanism of ketone-body formation from butyrate in rat liver Biochemical Journal 1962 84 1 212 216 10.1042/bj0840212 13907650 PMC1243643 · DOI
  119. [138]Linskens R. Huijsdens X. Savelkoul P. Vandenbroucke-Grauls C. Meuwissen S. The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics Scandinavian Journal of Gastroenterology 2001 36 234 29 40 10.1080/003655201753265082 11768558 · DOI · Paper page
  120. [139]Sartor R. B. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics Gastroenterology 2004 126 6 1620 1633 10.1053/j.gastro.2004.03.024 2-s2.0-2442453484 15168372 · DOI
  121. [140]Taggart A. K. Kero J. Gan X. (D)-β-hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G Journal of Biological Chemistry 2005 280 29 26649 26652 10.1074/jbc.c500213200 2-s2.0-22844439234 15929991 · DOI
  122. [141]Egan B. D’Agostino D. P. Fueling performance: ketones enter the mix Cell Metabolism 2016 24 3 373 375 10.1016/j.cmet.2016.08.021 2-s2.0-84990840497 27626197 · DOI
  123. [142]Murray A. J. Montgomery H. E. How wasting is saving: Weight loss at altitude might result from an evolutionary adaptation Bioessays 2014 36 721 729 24917038 PMC4143966
  124. [143]Blad C. C. Ahmed K. Ijzerman A. P. Offermanns S. Biological and pharmacological roles of HCA receptors Advances in Pharmacology 2014 62 219 250 10.1016/b978-0-12-385952-5.00005-1 2-s2.0-80052648068 21907911 · DOI
  125. [144]Offermanns S. Schwaninger M. Nutritional or pharmacological activation of HCA 2 ameliorates neuroinflammation Trends in Molecular Medicine 2015 21 4 245 255 10.1016/j.molmed.2015.02.002 2-s2.0-84925821034 25766751 · DOI
  126. [145]Offermanns S. Free fatty acid (FFA) and hydroxy carboxylic acid (HCA) receptors Annual Review of Pharmacology and Toxicology 2014 54 1 407 434 10.1146/annurev-pharmtox-011613-135945 2-s2.0-84891859045 24160702 · DOI
  127. [146]Offermanns S. Colletti S. L. Lovenberg T. W. Semple G. Wise A. Ijzerman A. P. International union of basic and clinical pharmacology. LXXXII: nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B) Pharmacological Reviews 2011 63 2 269 290 10.1124/pr.110.003301 2-s2.0-79955769365 21454438 · DOI
  128. [147]Milder J. B. Liang L. P. Patel M. Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet Neurobiology of Disease 2010 40 1 238 244 10.1016/j.nbd.2010.05.030 2-s2.0-77955845526 20594978 PMC3102314 · DOI
  129. [148]Storoni M. Plant G. T. The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis Multiple Sclerosis International 2015 2015 9 681289 10.1155/2015/681289 PMC4709725 26839705 · DOI
  130. [149]Sandberg M. Patil J. D’angelo B. Weber S. G. Mallard C. NRF2-regulation in brain health and disease: implication of cerebral inflammation Neuropharmacology 2014 79 298 306 10.1016/j.neuropharm.2013.11.004 2-s2.0-84891600336 24262633 PMC3958930 · DOI
  131. [150]Huang H. C. Nguyen T. Pickett C. B. Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription Journal of Biological Chemistry 2002 277 45 42769 42774 10.1074/jbc.m206911200 2-s2.0-0037044791 12198130 · DOI
  132. [151]Vriend J. Reiter R. J. The Keap1-Nrf2-antioxidant response element pathway: a review of its regulation by melatonin and the proteasome Molecular and Cellular Endocrinology 2015 401 213 220 10.1016/j.mce.2014.12.013 2-s2.0-84922335135 25528518 · DOI · Paper page
  133. [152]Wei N. Yuan D. He H. B. Saponins from Panax japonicas reduces myocardial infarction induced reactive oxygen species production and cardiomyocyte apoptosis via activation of the Nrf-2 pathway Advanced Materials Research 2014 881–883 339 346 10.4028/www.scientific.net/amr.881-883.339 2-s2.0-84893911601 · DOI
  134. [153]Lee J. S. Surh Y. J. Nrf2 as a novel molecular target for chemoprevention Cancer Letters 2005 224 2 171 184 10.1016/j.canlet.2004.09.042 2-s2.0-19444379739 15914268 · DOI
  135. [156]Lee J. M. Shih A. Y. Murphy T. H. Johnson J. A. NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons Journal of Biological Chemistry 2003 278 39 37948 37956 10.1074/jbc.m305204200 2-s2.0-0141621061 12842875 · DOI · Paper page
  136. [157]Thimmulappa R. K. Mai K. H. Srisuma S. Kensler T. W. Yamamoto M. Biswal S. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray Cancer Research 2002 62 18 5196 5203 12234984
  137. [158]Thimmulappa R. K. Scollick C. Traore K. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide Biochemical and Biophysical Research Communications 2006 351 4 883 889 10.1016/j.bbrc.2006.10.102 2-s2.0-33750826092 17097057 PMC2293275 · DOI
  138. [159]Tufekci K. U. Civi Bayin E. Genc S. Genc K. The Nrf2/ARE pathway: a promising target to counteract mitochondrial dysfunction in Parkinson’s disease Parkinson’s Disease 2011 2011 p. 314082 10.4061/2011/314082 2-s2.0-79955057180 PMC3049335 21403858 · DOI
  139. [160]He X. Kan H. Cai L. Ma Q. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes Journal of Molecular and Cellular Cardiology 2009 46 1 47 58 10.1016/j.yjmcc.2008.10.007 2-s2.0-57249104720 19007787 · DOI
  140. [161]Tan Y. Ichikawa T. Li J. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress–induced insulin resistance in cardiac cells in vitro and in vivo Diabetes 2011 60 2 625 633 10.2337/db10-1164 2-s2.0-79551575483 21270272 PMC3028364 · DOI
  141. [163]Lee J. M. Li J. Johnson D. A. Nrf2, a multi-organ protector? Federation of American Societies for Experimental Biology 2005 19 9 1061 1066 10.1096/fj.04-2591hyp 2-s2.0-21744445077 15985529 · DOI · Paper page
  142. [164]Neymotin A. Calingasan N. Y. Wille E. Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis Free Radical Biology and Medicine 2011 51 1 88 96 10.1016/j.freeradbiomed.2011.03.027 2-s2.0-79957959973 21457778 PMC3109235 · DOI
  143. [165]Yu S. Khor T. O. Cheung K. L. Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice PLoS One 2010 5 1 e8579 10.1371/journal.pone.0008579 2-s2.0-77649163840 PMC2799519 20062804 · DOI
  144. [166]Nagatomo H. Morimoto Y. Ogami A. Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro Inhalation Toxicology 2007 19 4 317 323 10.1080/08958370601144167 2-s2.0-33847168094 17365036 · DOI
  145. [167]Suzuki S. Toledo-Pereyra L. Rodriguez F. Cejalvo D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury Transplantation 1993 55 6 1265 1272 10.1097/00007890-199306000-00011 7685932 · DOI
  146. [170]Yoshida T. Watanabe M. Engelman D. T. Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury Journal of Molecular and Cellular Cardiology 1996 28 8 1759 1767 10.1006/jmcc.1996.0165 2-s2.0-0030218917 8877785 · DOI
  147. [171]Dhalla N. S. Elmoselhi A. B. Hata T. Makino N. Status of myocardial antioxidants in ischemia–reperfusion injury Cardiovascular Research 2000 47 3 446 456 10.1016/s0008-6363(00)00078-x 2-s2.0-0034683031 10963718 · DOI
  148. [172]Dong W. Jia Y. Liu X. Sodium butyrate activates NRF2 to ameliorate diabetic nephropathy possibly via inhibition of HDAC Journal of Endocrinology 2017 232 1 71 83 10.1530/joe-16-0322 2-s2.0-85007579959 27799462 · DOI
  149. [173]Chen X. Su W. Wan T. Sodium butyrate regulates Th17/Treg cell balance to ameliorate uveitis via the Nrf2/HO-1 pathway Biochemical Pharmacology 2017 142 111 119 10.1016/j.bcp.2017.06.136 2-s2.0-85022225906 28684304 · DOI
  150. [174]Hu X. Zhang K. Xu C. Chen Z. Jiang H. Anti-inflammatory effect of sodium butyrate preconditioning during myocardial ischemia/reperfusion Experimental and Therapeutic Medicine 2014 8 1 229 232 10.3892/etm.2014.1726 2-s2.0-84901300519 24944626 PMC4061237 · DOI
  151. [175]Yano S. Tierney D. F. Butyrate increases catalase activity and protects rat pulmonary artery smooth muscle cells against hyperoxia Biochemical and Biophysical Research Communications 1989 164 3 1143 1148 10.1016/0006-291x(89)91788-9 2-s2.0-0024453712 2590195 · DOI
  152. [176]Walsh M. E. Bhattacharya A. Sataranatarajan K. The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging Aging Cell 2015 14 6 957 970 10.1111/acel.12387 2-s2.0-84954384433 26290460 PMC4693467 · DOI · Paper page

Cited by

Sorted by citations

Authors
Cavaleri, F., & Bashar, E.
Affiliations
Biologic Pharmamedical Research, 688-2397 King George Hwy., White Rock, BC, Canada
Corresponding author
Cavaleri, Franco
ORCID
Venue
Journal of Nutrition and Metabolism
Publisher
Wiley
Published
2018
Volume
2018
Pages
1-13
ISSN
  • 2090-0724 (ISSN-L)
  • 2090-0732
DOI
10.1155/2018/7195760
PMC
PMC5902005
OpenAlex
W2795053146
Cited by
126
References
16
Citations by year
2026: 4 · 2025: 9 · 2024: 11 · 2023: 7 · 2022: 11 · 2021: 11 · 2020: 64 · 2019: 7 · 2018: 2
FWCI
2.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition and Metabolism (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords
beta-hydroxybutyrate, butyrate, ketogenic diet, low-carbohydrate high-fat diet, short-chain fatty acids, ketosis, inflammation, cognition, metabolic syndrome, dietary fiber, dietary adherence, gastrointestinal symptoms, negative energy balance

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