IP Library › Granted Patent US 12,648,924
Granted Patent B2
US 12,648,924 · App. 17/794,756 · Granted Jun 9, 2026

Prevention and treatment of effects of aging and age-associated disorders with ketone supplementation

Inventors: Andrew Paul Koutnik (Tampa, FL); Dominic Paul D'Agostino (Tampa, FL)
Assignee: University of South Florida
A61K31/22A61K9/0053A61K45/06A61P43/00
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Quick Facts
Patent No.
US 12,648,924
App. No.
17/794,756
Granted
Jun 9, 2026
Kind
B2
Abstract

Methods and compositions for preventing, reducing, delaying, or reversing effects due to aging or preventing, treating, or reducing time to recovery from a disease associated with aging, as well as anemia, hypoalbuminemia, hypocholesterolemia, malnutrition/anorexia/starvation, and/or splenomegaly in a subject in need thereof are disclosed. The method can include administering a therapeutically effective amount of a ketogenic supplement to the subject, wherein the subject is fed ad libitum. The ketogenic supplement can include R,S 1,3-butanediol acetoacetate diester or derivatives thereof.

Claims (29)

1 . A method for reducing, delaying, or reversing effects due to aging in a subject in need thereof, the method comprising:

administering a therapeutically effective amount of a ketogenic supplement to the subject, in an amount of greater than 5% by weight of the subject's diet or greater than 10% of the subject's total daily caloric intake,

wherein the ketogenic supplement comprises R,S-1,3-butanediol diacetoacetate

wherein the subject is age sixty-five (65) or over, and

wherein the subject is fed ad libitum.

2 . The method of claim 1 , wherein the subject exhibits elevated levels of insulin-like growth factor-1 (IGF-1), insulin, or a combination thereof, compared to an average level of IGF-1 or insulin in a population of subjects under age sixty-five (65); elevated levels of one or more cytokines compared to an average level of cytokine in a population of subjects under age sixty-five (65); elevated levels of poly-ubiquitination or FOXO3a compared to an average level of poly-ubiquitination or FOXO3a in a population of subjects under age sixty-five (65); or any combination thereof.

3 . The method of claim 1 , wherein the subject has anemia, hypoalbuminemia, hypocholesterolemia, inflammation, malnutrition/anorexia/starvation, splenomegaly, or a combination thereof.

4 . The method of claim 1 , wherein the ketogenic supplement further comprises a medium chain triglyceride, a beta-hydroxybutyrate, a beta-hydroxybutyrate precursor, an acetoacetate, an acetoacetate precursor, a beta-hydroxybutyrate mineral salt, a beta-hydroxybutyrate amino acid, a beta-hydroxybutyrate fatty acid, acetoacetate mineral salt, acetoacetate amino acid, acetoacetate fatty acid, a or a combination thereof.

5 . The method of claim 1 , wherein the ketogenic supplement is administered in an amount from 5% to 100% by weight of the subject's diet.

6 . The method of claim 1 , wherein the ketogenic supplement is administered in an amount up to 100% of total daily caloric intake based on the subject's diet.

7 . The method of claim 1 , wherein the ketogenic supplement is administered in an amount from 5% to 100% of total daily caloric intake based on the subject's diet.

8 . The method of claim 1 , wherein the ketogenic supplement is administered at about 0.001 g/kg/day to about 10 g/kg/day.

9 . The method of claim 1 , wherein the amount of ketogenic supplement is gradually administered to the subject, comprising an incremental dose elevation of at least 5% by weight of the subject's diet per day or at least 10% of total calorie intake per day.

10 . The method of claim 1 , wherein the ketogenic supplement is administered orally.

11 . The method of claim 1 , wherein the method further comprises administering a second agent selected from the group consisting of an antioxidant, a different anti-aging agent, an anti-inflammatory, a metabolic regulatory agent, or a combination thereof.

12 . A method for treating, or reducing time to recovery from a disease associated with aging in a subject in need thereof, the method comprising:

administering a therapeutically effective amount of a ketogenic supplement to the subject, in an amount of greater than 5% by weight of the subject's diet or greater than 10% of the subject's total daily caloric intake,

wherein the ketogenic supplement comprises R,S-1,3-butanediol diacetoacetate,

and

wherein the subject is fed ad libitum.

13 . The method of claim 12 , wherein the disease is anemia; hypoalbuminemia; hypocholesterolemia; inflammation; malnutrition/anorexia/starvation; splenomegaly; related to elevated levels of insulin-like growth factor-1 (IGF-1), insulin, or a combination thereof; related to elevated levels of one or more cytokines; related to elevated levels of poly-ubiquitination or FOXO3a; or a combination thereof.

14 . The method of claim 12 , wherein the ketogenic supplement further comprises a medium chain triglyceride, a beta-hydroxybutyrate, a beta-hydroxybutyrate precursor, an acetoacetate, an acetoacetate precursor, a beta-hydroxybutyrate mineral salt, a beta-hydroxybutyrate amino acid, a beta-hydroxybutyrate fatty acid, acetoacetate mineral salt, acetoacetate amino acid, acetoacetate fatty acid, a or a combination thereof.

15 . A method for reducing or delaying effects due to aging in a subject in need thereof, the method comprising:

administering a therapeutically effective amount of a ketogenic supplement to the subject, in an amount of greater than 5% by weight of the subject's diet or greater than 10% of the subject's total daily caloric intake,

wherein the ketogenic supplement comprises R,S-1,3-butanediol diacetoacetate,

wherein the subject is age thirty-five (35) or over, and

wherein the subject is fed ad libitum.

16 . The method of claim 15 , wherein the subject is healthy.

17 . The method of claim 15 , wherein the ketogenic supplement further comprises a medium chain triglyceride, a beta-hydroxybutyrate, a beta-hydroxybutyrate precursor, an acetoacetate, an acetoacetate precursor, a beta-hydroxybutyrate mineral salt, a beta-hydroxybutyrate amino acid, a beta-hydroxybutyrate fatty acid, acetoacetate mineral salt, acetoacetate amino acid, acetoacetate fatty acid, or a combination thereof.

Assignments (3)
GOVERNMENT INTEREST AGREEMENT Recorded Feb 26, 2025
From: UNIVERSITY OF SOUTH FLORIDA
To: THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE NAVY
Reel/Frame 070336/0271 →
GOVERNMENT INTEREST AGREEMENT Recorded Jun 17, 2024
From: UNIVERSITY OF SOUTH FLORIDA
To: THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE NAVY
Reel/Frame 067766/0537 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 25, 2023
From: KOUTNIK, ANDREW PAUL; D'AGOSTINO, DOMINIC PAUL
To: UNIVERSITY OF SOUTH FLORIDA
Reel/Frame 062483/0991 →
Continuity (2)
Provisional Application 62964952 · Jan 23, 2020
Related Publication 20230172891A1 · Jun 8, 2023
References Cited (127)
US 4559157A · Smith et al. · 1985 [cited by applicant]
US 4608392A · Jacquet et al. · 1986 [cited by applicant]
US 4820508A · Wortzman · 1989 [cited by applicant]
US 4938949A · Borch et al. · 1990 [cited by applicant]
US 4992478A · Geria · 1991 [cited by applicant]
US 5167649A · Zook · 1992 [cited by applicant]
US 6960648B2 · Bonny · 2005 [cited by applicant]
US 8124589B2 · Henderson · 2012 [cited by examiner]
US 10980764B1 · D'Agostino · 2021 [cited by examiner]
US 20020035243A1 · Imfeld et al. · 2002 [cited by applicant]
US 20020120100A1 · Bonny · 2002 [cited by applicant]
US 20030032594A1 · Bonny · 2003 [cited by applicant]
US 20170000754A1 · Weeber · 2017 [cited by applicant]
US 20170266148A1 · D'Agostino · 2017 [cited by examiner]
US 20210189914A1 · Barnes · 2021 [cited by examiner]
International Search Report and Written Opinion in PCT/2021/014673. Mailed Apr. 9, 2021. [cited by applicant]
Fearon, K., et al., Definition and classification of cancer cachexia: an international consensus. Lancet Oncol, 2011. 12(5): p. 489-95. [cited by applicant]
Evans, W.J., et al., Cachexia: a new definition. Clin Nutr, 2008. 27(6): p. 793-9. [cited by applicant]
Argiles, J.M., et al., Cancer cachexia: understanding the molecular basis. Nat Rev Cancer, 2014. 14(11): p. 754-62. [cited by applicant]
Warren, S., The Immediate Causes of Death in Cancer. Am J Med Sci, 1932. 183(13): p. 610-613. [cited by applicant]
Von Haehling, S., M.S. Anker, and S.D. Anker, Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016. J Cachexia Sarcopenia Muscle, 2016. 7(5): p. 507-509. [cited by applicant]
Penna, F., S. Busquets, and J.M. Argiles, Experimental cancer cachexia: Evolving strategies for getting closer to the human scenario. Semin Cell Dev Biol, 2016. 54: p. 20-7. [cited by applicant]
Tomasin, R., A. Martin, and M.R. Cominetti, Metastasis and cachexia: alongside in clinics, but not so in animal models. J Cachexia Sarcopenia Muscle, 2019. [cited by applicant]
Bennani-Baiti, N. and D. Walsh, What is cancer anorexia-cachexia syndrome? A historical perspective. J R Coll Physicians Edinb, 2009. 39(3): p. 257-62. [cited by applicant]
Dewys, W.D., et al., Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med, 1980. 69(4): p. 491-7. [cited by applicant]
Muscaritoli, M., et al., Prevalence of malnutrition in patients at first medical oncology visit: the PreMiO study. Oncotarget, 2017. 8(45): p. 79884-79896. [cited by applicant]
Caillet, P., et al., Association between cachexia, chemotherapy and outcomes in older cancer patients: A systematic review. Clin Nutr, 2016. [cited by applicant]
Wang, G., et al., Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle. Nat Med, 2018. 24(6): p. 770-781. [cited by applicant]
Huysentruyt, L.C., et al., Metastatic cancer cells with macrophage properties: evidence from a new murine tumor model. Int J Cancer, 2008. 123(1): p. 73-84. [cited by applicant]
Poff, A.M., et al., Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy. PLoS One, 2015. 10(6): p.e0127407. [cited by applicant]
Cahill, G.F., Jr., Starvation in man. N Engl J Med, 1970. 282(12): p. 668-75. [cited by applicant]
Sherwin, R.S., R.G. Hendler, and P. Felig, Effect of ketone infusions on amino acid and nitrogen metabolism in man. J Clin Invest, 1975. 55(6): p. 1382-90. [cited by applicant]
Thomsen, H.H., et al., Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS-induced inflammation in humans: anticatabolic impact of ketone bodies. Am J Clin Nutr, 2018. 1… [cited by applicant]
Nair, K.S., et al., Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. J Clin Invest, 1988. 82(1): p. 198-205. [cited by applicant]
Vandoorne, T., et al., Intake of a Ketone Ester Drink during Recovery from Exercise Promotes mTORC1 Signaling but Not Glycogen Resynthesis in Human Muscle. Front Physiol, 2017. 8: p. 310. [cited by applicant]
Shukla, S.K., et al., Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia. Cancer Metab, 2014. 2: p. 18. [cited by applicant]
Zou, X., et al., Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice. J Biol Chem, 2016. 291(5): p. 2181-95. [cited by applicant]
Roberts, M.N., et al., A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metab, 2018. 27(5): p. 1156. [cited by applicant]
Poff, A., et al., Targeting the Warburg effect for cancer treatment: Ketogenic diets for management of glioma. Semin Cancer Biol, 2017. [cited by applicant]
Newman, J.C. and E. Verdin, beta-Hydroxybutyrate: A Signaling Metabolite. Annu Rev Nutr, 2017. 37: p. 51-76. [cited by applicant]
Kovacs, Z., et al., Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats. Front Mol Neurosci, 2019. 12: p. 45. [cited by applicant]
Youm, Y.H., et al., The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med, 2015. 21(3): p. 263-9. [cited by applicant]
Koutnik, A.P., D.P. D'Agostino, and B. Egan, Anticatabolic Effects of Ketone Bodies in Skeletal Muscle. Trends Endocrinol Metab, 2019. 30(4): p. 227-229. [cited by applicant]
Wagner, F., P. Radermacher, and W. Stahl, Anesthesia and the immune response: evidence for an “isoflurane paradox”? Shock, 2010. 34(4): p. 437-8. [cited by applicant]
Nader, G.A., T.J. McLoughlin, and K.A. Esser, mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators. Am J Physiol Cell Physiol, 2005. 289(6): p. C1457-65. [cited by applicant]
Haun, C.T., et al., Pre-training Skeletal Muscle Fiber Size and Predominant Fiber Type Best Predict Hypertrophic Responses to 6 Weeks of Resistance Training in Previously Trained Young Men. Front Physiol, 2019. 10: p. 2… [cited by applicant]
Motulsky, H.J. and R.E. Brown, Detecting outliers when fitting data with nonlinear regression—a new method based on robust nonlinear regression and the false discovery rate. BMC Bioinformatics, 2006. 7: p. 123. [cited by applicant]
Sangisetty, S.L. and T.J. Miner, Malignant ascites: A review of prognostic factors, pathophysiology and therapeutic measures. World J Gastrointest Surg, 2012. 4(4): p. 87-95. [cited by applicant]
Baracos, V.E. and L. Arribas, Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol, 2018. 29(suppl_2): p. ii1-ii9. [cited by applicant]
Maltoni, M., et al., High-dose progestins for the treatment of cancer anorexia-cachexia syndrome: a systematic review of randomised clinical trials. Ann Oncol, 2001. 12(3): p. 289-300. [cited by applicant]
Loprinzi, C.L., et al., Body-composition changes in patients who gain weight while receiving megestrol acetate. J Clin Oncol, 1993. 11(1): p. 152-4. [cited by applicant]
Murphy, K.T., et al., Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia. Dis Model Mech, 2012. 5(4): p. 533-45. [cited by applicant]
Miokovic, T., et al., Heterogeneous atrophy occurs within individual lower limb muscles during 60 days of bed rest. J Appl Physiol (1985), 2012. 113(10): p. 1545-59. [cited by applicant]
Stephens, N.A., et al., Sexual dimorphism modulates the impact of cancer cachexia on lower limb muscle mass and function. Clin Nutr, 2012. 31(4): p. 499-505. [cited by applicant]
Cosper, P.F. and L.A. Leinwand, Cancer causes cardiac atrophy and autophagy in a sexually dimorphic manner. Cancer Res, 2011. 71(5): p. 1710-20. [cited by applicant]
Baracos, V.E., et al., Body composition in patients with non-small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis. Am J Clin Nutr, 2010. 91(4): p. 1133S-1137S. [cited by applicant]
Enns, D.L. and P.M. Tiidus, The influence of estrogen on skeletal muscle: sex matters. Sports Med, 2010. 40(1): p. 41-58. [cited by applicant]
Mauvais-Jarvis, F., D.J. Clegg, and A.L. Hevener, The role of estrogens in control of energy balance and glucose homeostasis. Endocr Rev, 2013. 34(3): p. 309-38. [cited by applicant]
Tsoli, M. and G. Robertson, Cancer cachexia: malignant inflammation, tumorkines, and metabolic mayhem. Trends Endocrinol Metab, 2013. 24(4): p. 174-83. [cited by applicant]
Bronte, V. and M.J. Pittet, The spleen in local and systemic regulation of immunity. Immunity, 2013. 39(5): p. 806-18. [cited by applicant]
Platzbecker, U., et al., Spleen enlargement in healthy donors during G-CSF mobilization of PBPCs. Transfusion, 2001. 41(2): p. 184-9. [cited by applicant]
Fouladiun, M., et al., Daily physical-rest activities in relation to nutritional state, metabolism, and quality of life in cancer patients with progressive cachexia. Clin Cancer Res, 2007. 13(21): p. 6379-85. [cited by applicant]
Bennegard, K., et al., Metabolic balance across the leg in weight-losing cancer patients compared to depleted patients without cancer. Cancer Res, 1982. 42(10): p. 4293-9. [cited by applicant]
Eden, E., et al., Glucose flux in relation to energy expenditure in malnourished patients with and without cancer during periods of fasting and feeding. Cancer Res, 1984. 44(4): p. 1718-24. [cited by applicant]
Holroyde, C.P., et al., Lactate metabolism in patients with metastatic colorectal cancer. Cancer Res, 1979. 39(12): p. 4900-4. [cited by applicant]
Holroyde, C.P., et al., Altered glucose metabolism in metastatic carcinoma. Cancer Res, 1975. 35(12): p. 3710-4. [cited by applicant]
Tracey, K.J., et al., Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med, 1988. 167(3): p. 1211-27. [cited by applicant]
Gupta, D. and C.G. Lis, Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J, 2010. 9: p. 69. [cited by applicant]
Utech, A.E., et al., Predicting survival in cancer patients: the role of cachexia and hormonal, nutritional and inflammatory markers. J Cachexia Sarcopenia Muscle, 2012. 3(4): p. 245-51. [cited by applicant]
Ettinger, W.H., Jr., et al., Interleukin-6 causes hypocholesterolemia in middle-aged and old rhesus monkeys. J Gerontol A Biol Sci Med Sci, 1995. 50(3): p. M137-40. [cited by applicant]
Gilbert, H.S., et al., Characterization of hypocholesterolemia in myeloproliferative disease. Relation to disease manifestations and activity. Am J Med, 1981. 71(4): p. 595-602. [cited by applicant]
Bonaldo, P. and M. Sandri, Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech, 2013. 6(1): p. 25-39. [cited by applicant]
Sharples, A.P., et al., Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake. Aging Cell, 2015. 14(4): p. 511-23. [cited by applicant]
Lecker, S.H., A.L. Goldberg, and W.E. Mitch, Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol, 2006. 17(7): p. 1807-19. [cited by applicant]
Karin, M. and Y. Ben-Neriah, Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol, 2000. 18: p. 621-63. [cited by applicant]
Li, Y.P. and M.B. Reid, NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes. Am J Physiol Regul Integr Comp Physiol, 2000. 279(4): p. R1165-70. [cited by applicant]
Hoffmann, A., et al., The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science, 2002. 298(5596): p. 1241-5. [cited by applicant]
Guttridge, D.C., et al., NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science, 2000. 289(5488): p. 2363-6. [cited by applicant]
Digby, J.E., et al., Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms. Arterioscler Thromb Vasc Biol, 2012. 32(3): p. 669-76. [cited by applicant]
Feingold, K.R., et al., Inflammation stimulates niacin receptor (GPR109A/HCA2) expression in adipose tissue and macrophages. J Lipid Res, 2014. 55(12): p. 2501-8. [cited by applicant]
Dhingra, S., et al., IL-10 attenuates TNF-alpha-induced NF kappaB pathway activation and cardiomyocyte apoptosis. Cardiovasc Res, 2009. 82(1): p. 59-66. [cited by applicant]
Sandri, M., et al., Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 2004. 117(3): p. 399-412. [cited by applicant]
Beharry, A.W., et al., HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy. J Cell Sci, 2014. 127(Pt 7): p. 1441-53. [cited by applicant]
Deemer, S.E., et al., Concentration-Dependent Effects of a Dietary Ketone Ester on Components of Energy Balance in Mice. Front. Nutr., 2019. [cited by applicant]
Davis, R.A.H., et al., Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet. FASEB J, 2019. 33(2): p. 2409-2421. [cited by applicant]
Zentella, A., K. Manogue, and A. Cerami, Cachectin/TNF-mediated lactate production in cultured myocytes is linked to activation of a futile substrate cycle. Cytokine, 1993. 5(5): p. 436-47. [cited by applicant]
Vander Heiden, M.G., L.C. Cantley, and C.B. Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 2009. 324(5930): p. 1029-33. [cited by applicant]
De Wilde, J., et al., The embryonic genes Dkk3, Hoxd8, Hoxd9 and Tbx1 identify muscle types in a dietindependent and fiber-type unrelated way. BMC Genomics, 2010. 11: p. 176. [cited by applicant]
Sun, R., et al., Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPbeta-regulated atrogin1 expression in cancer cachexia. Am J Physiol Cell Physiol, 2016. 311(1): p. C101-15. [cited by applicant]
Montalvo, R.N., B.R. Counts, and J.A. Carson, Understanding sex differences in the regulation of cancerinduced muscle wasting. Curr Opin Support Palliat Care, 2018. 12(4): p. 394-403. [cited by applicant]
Fukawa, T., et al., Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nat Med, 2016. 22(6): p. 666-71. [cited by applicant]
Norman, K., et al., Effect of sexual dimorphism on muscle strength in cachexia. J Cachexia Sarcopenia Muscle, 2012. 3(2): p. 111-6. [cited by applicant]
D'Agostino, D.P., et al., Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. Am J Physiol Regul Integr Comp Physiol, 2013. 304(10): p. R829-36. [cited by applicant]
Kesl, S.L., et al., Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond), 2016. 13: p. 9. [cited by applicant]
Dansinger, M.L., et al., Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA, 2005. 293(1): p. 43-53. [cited by applicant]
Weber, D.A.-G., S. Tulipan, J. Catalano, L. Feichtinger, RG. Kofler, B., Ketogenic diet in the treatment of cancer—Where do we stand? Molecular Metabolism, 2019. [cited by applicant]
Poff, A.M., et al., Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer, 2014. 135(7): p. 1711-20. [cited by applicant]
Schakman, O., et al., Role of IGF-I and the TNFalpha/NF-kappaB pathway in the induction of muscle atrogenes by acute inflammation. Am J Physiol Endocrinol Metab, 2012. 303(6): p. E729-39. [cited by applicant]
Costelli, P., et al., IGF-1 is downregulated in experimental cancer cachexia. Am J Physiol Regul Integr Comp Physiol, 2006. 291(3): p. R674-83. [cited by applicant]
Walsh, M.E. and H. Van Remmen, Emerging roles for histone deacetylases in age-related muscle atrophy. Nutr Healthy Aging, 2016. 4(1): p. 17-30. [cited by applicant]
Penna, F. and P. Costelli, New developments in investigational HDAC inhibitors for the potential multimodal treatment of cachexia. Expert Opin Investig Drugs, 2019. 28(2): p. 179-189. [cited by applicant]
Pigna, E., et al., HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses. Skelet Muscle, 2018. 8(1): p. 6. [cited by applicant]
Pigna, E., et al., Histone deacetylase 4 protects from denervation and skeletal muscle atrophy in a murine model of amyotrophic lateral sclerosis. EBioMedicine, 2019. 40: p. 717-732. [cited by applicant]
Shimazu, T., et al., Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science, 2013. 339(6116): p. 211-4. [cited by applicant]
Hobler, S.C., et al., IGF-I stimulates protein synthesis but does not inhibit protein breakdown in muscle from septic rats. Am J Physiol, 1998. 274(2): p. R571-6. [cited by applicant]
Broussard, S.R., et al., IL-1beta impairs insulin-like growth factor i-induced differentiation and downstream activation signals of the insulin-like growth factor i receptor in myoblasts. J Immunol, 2004. 172(12): p. 77… [cited by applicant]
Broussard, S.R., et al., Cytokine-hormone interactions: tumor necrosis factor alpha impairs biologic activity and downstream activation signals of the insulin-like growth factor I receptor in myoblasts. Endocrinology, 2… [cited by applicant]
Frost, R.A., C.H. Lang, and M.C. Gelato, Transient exposure of human myoblasts to tumor necrosis factoralpha inhibits serum and insulin-like growth factor-I stimulated protein synthesis. Endocrinology, 1997. 138(10): p.… [cited by applicant]
Samani, A.A., et al., The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev, 2007. 28(1): p. 20-47. [cited by applicant]
Von Haehling, S., et al., Ethical guidelines for publishing in the journal of cachexia, sarcopenia and muscle: update 2017. J Cachexia Sarcopenia Muscle, 2017. 8(6): p. 1081-1083. [cited by applicant]
Chu, et al; Int J Clin Exp Med 2015; 8(5) 7684-7688; (R)-3-oxobutyl 3-Hydroxybutanoate (OBHB). [cited by third party]
Newport, et al; Alzheimer's Diment 2015; 11(1) 99-103; A new way to produce hyperketonemia: use of a ketone ester in a case of Alzheimer's disease. [cited by third party]
Almeida-Suhett et al; Nutritional Neuroscience, 25:6, 1287-1299 (2022; The ketone ester, 3-hydroxybutyl-3-hydroxybutyrate, attenuates neurobehavioral deficits and Improves neuropathy following controlled cortical impact… [cited by third party]
Merck Manual of Diagnosis and Therapy 18th Ed 2006 p. 1815. [cited by third party]
Rebello, et al; BBA Clinical 3 (2015) 123-125; Pilot feasibility and safety study examining the effects of medium chain triglyceride supplementation in subjects with cognitive impairment: a randomized controlled trial. [cited by third party]
Hashim, e al; J. Lipid Res. 2014, 55:1818-1826; Ketone Body Therapy: From the Ketogenic Diet to the Oral Administration of Ketone Ester. [cited by third party]
Ingle et al, Journal of Food Science, vol. 64, No. 6, 1999 pp. 960-963; Dietary Energy Value ol Medium Chain Triglycerides. [cited by third party]
De La Rubia Orti et al; Journal of Alzheimer's Disease 65 (2018) 577-587; Improvement of Main Cognitive Functions in Patient's with Alzheimer's Disease After Treatment of Coconut Enriched Mediterranean Diet: A Pilot Stu… [cited by third party]
Gandotra et al; Int J Sch Cog Psychol 2014, 1:2 (10 pages); Efficacy of Adjunctive Extra Virgin Coconut Oil Use in Moderate to Severe Alzheimer's Disease. [cited by third party]
Merck Manual of Diagnosis and Therapy, 18th Edition 2006, p. 1815. [cited by third party]
Hashim et al; J. Lipid Res. 2014, 55:1818-1826; Ketone Body Therapy: From the Ketogenic Diet to the Oral Administration of Ketone Ester. [cited by third party]
Newport, et al; Alzheimers Diment 2015; 11(1) 99-103; A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease. [cited by third party]
Almeida-Suhett, et al; Nutritional Neuroscience, 26:6, 1287-1299 (2022); The ketone ester, 3-hydroxybutyl-3-hydroxybutyrate, attenuales neurobehavioral deficits and improves neuropathology following controlled cortical … [cited by third party]
Rebello, et al; BBA Clinical 3 (2015) 123-125; Pilot feasibility and safety study examining the effects of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled tr… [cited by third party]
Ingle, et al; Journal of Food Science, vol. 64, No. 6, 1999 pp. 960-963; Dietary Energy Value of Medium Chain Triglycerides. [cited by third party]
De La Rubia Orti et al; Journal of Alzheimer's Disease 65 (2018) 577-587; Improvement of Main Cognitive Functions in Patient's With Alzheimer's Disease After Treatment of Coconut Oil Enriched Mediterranean Diet: A Pilot… [cited by third party]
Gandotra et al; Int J SCH COG Psychol 2014 1:2 (10 Pgs); Efficacy of Adjunctive Extra Virgin Coconut Oil Use in Moderate To Severe Alzheimer's Disease. [cited by third party]