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{{for multi|the genus of hoverflies|Axona (fly)|the French river|Aisne (river)}} |
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{{Drugbox |
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{{unbalanced|reason=Article focuses too much on "medical food" aspects rather than natural occurrence, physical/chemical properties, normal biochemical role, etc.|date=April 2015}} |
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| verifiedrevid = 429764297 |
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| IUPAC_name = octanoate |
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{{Chembox |
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| image = Caprylic triglyceride.svg |
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| Watchedfields = changed |
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| imagename = Caprylic triglyceride |
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| verifiedrevid = 445340351 |
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| image2 = Caprylidene-3D-balls.png |
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| Name = |
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| width = 260 |
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| ImageFile = Caprylic triglyceride.svg |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| ImageSize = 260 |
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| ImageFile1 = Caprylidene-3D-balls.png |
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| ImageSize1 = 270 |
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| IUPACName = Tri-''O''-octanoylglycerol |
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| SystematicName = Propane-1,2,3-triyl tri(octanoate) |
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| OtherNames = Glycerol trioctanoate; Tricaprylin; octanoate |
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|Section1={{Chembox Identifiers |
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| Abbreviations = |
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| CASNo = 538-23-8 |
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| CASNo_Comment = |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 6P92858988 |
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| PubChem = 10850 |
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| PubChem_Comment = |
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| ChemSpiderID = 10393 |
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| ChemSpiderID_Comment = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| EINECS = |
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| EC_number = |
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| UNNumber = |
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| DrugBank = |
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| KEGG = D01587 |
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| KEGG = D01587 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| MeSHName = |
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| ChEBI = 76978 |
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| RTECS = |
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| SMILES = O=C(OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC)CCCCCCC |
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| InChI = 1/C27H50O6/c1-4-7-10-13-16-19-25(28)31-22-24(33-27(30)21-18-15-12-9-6-3)23-32-26(29)20-17-14-11-8-5-2/h24H,4-23H2,1-3H3 |
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| InChI = 1/C27H50O6/c1-4-7-10-13-16-19-25(28)31-22-24(33-27(30)21-18-15-12-9-6-3)23-32-26(29)20-17-14-11-8-5-2/h24H,4-23H2,1-3H3 |
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| smiles = O=C(OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC)CCCCCCC |
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| InChIKey = VLPFTAMPNXLGLX-UHFFFAOYAW |
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| InChIKey = VLPFTAMPNXLGLX-UHFFFAOYAW |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = VLPFTAMPNXLGLX-UHFFFAOYSA-N |
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| StdInChIKey = VLPFTAMPNXLGLX-UHFFFAOYSA-N |
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| Beilstein = |
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| CAS_number = 538-23-8 |
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| Gmelin = |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| 3DMet = |
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| ATC_prefix = None |
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}} |
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| ATC_suffix = |
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|Section2={{Chembox Properties |
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| PubChem = 10850 |
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| C=27 | H=50 | O=6 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| MeltingPt = |
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| ChemSpiderID = 10393 |
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| MeltingPt_notes = |
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| C=27|H=50|O=6 |
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| BoilingPt = |
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| molecular_weight = 470.68 g{{·}}mol<sup>−1</sup> |
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| BoilingPt_notes = |
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| synonyms = Glycerol trioctanoate; Tricaprylin |
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| LogP = |
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| bioavailability = |
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| Solubility = |
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| protein_bound = |
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| SolubleOther = |
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| metabolism = |
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| Solvent = |
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| elimination_half-life = |
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}} |
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| excretion = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category= |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_US = Rx-only |
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| routes_of_administration = Oral |
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}} |
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}} |
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'''Axona''' was previously marketed as a ] for the clinical dietary management of the impairment of metabolic processes associated with mild to moderate ]. It is a proprietary formulation of ] ] (]), a ]. Cericin,<ref></ref> the company that makes Axona, states that during digestion, ] is broken down into ], which provide an alternative energy source for the brain. Its use is based on the idea that the brain's ability to use its normal energy source, ], is impaired in Alzheimer's disease. Axona was first sold in March 2009. |
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'''Caprylidene''' (trade name '''Axona''') is a ] that was approved in March ] by the ] for the "clinical dietary management of the metabolic processes associated with mild to moderate ]".<ref name=AxonaApproval/> Glucose metabolism by the brain is impaired in Alzheimer's disease, and it is proposed that ] bodies may provide an alternative energy source. Caprylidene is a powdered form of caprylic triglyceride, a ] (MCT) in which three molecules of ] are ]ified with ].<ref name=AxonaDrugsCom/> |
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In 2013, US Food and Drug Administration (FDA) determined Axona was misbranded because the product was labeled and marketed as a medical food but does not meet the statutory definition of a medical food. Axona has not been approved by the FDA as a drug to treat Alzheimer's and the efficacy of managing the health of Alzheimer's patients by use of this medical food has been questioned by experts in the field, including the ]. |
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==Description== |
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Axona is a ] marketed to assist with dietary management of mild to moderate Alzheimer's disease.<ref></ref><ref name=Henderson>{{cite journal |doi=10.1186/1743-7075-6-31 |title=Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: A randomized, double-blind, placebo-controlled, multicenter trial |year=2009 |last1=Henderson |first1=Samuel T |last2=Vogel |first2=Janet L |last3=Barr |first3=Linda J |last4=Garvin |first4=Fiona |last5=Jones |first5=Julie J |last6=Costantini |first6=Lauren C |journal=Nutrition & Metabolism |volume=6 |pages=31 |pmid=19664276 |pmc=2731764 |doi-access=free }}</ref> Axona is formulated for oral administration and is sold by prescription. The largest ingredient in Axona is ],<ref name=Henderson/> also known as fractionated coconut oil, a ].<ref name=Cunnane/> ] is ] (GRAS) by the FDA.<ref>Staff, FDA. Page Last Updated: April 2013. </ref> |
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A ] in the US is an official FDA product classification, and was originally defined by Congress as part of the Orphan Drug Amendments of 1988 as "a food which is formulated to be consumed or administered through a feeding tube under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."<ref name=FDA>Staff, FDA. May 1997; Revised May 2007 </ref> Medical foods are not drugs and cannot be marketed as treating or preventing a disease or condition; the FDA does not evaluate the efficacy and safety of medical foods.<ref name=FDA/> |
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==Proposed mechanism of action of Axona== |
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Alzheimer's disease is clinically characterized by a progressive decline in memory and language, and pathologically by accumulation of ]s and ]s. Because Alzheimer's disease is also characterized by a reduced ability of some areas of the brain to use glucose,<ref name=Cunnane/><ref name=Mosconi>{{cite journal |doi=10.1007/s00259-005-1762-7 |title=Brain glucose metabolism in the early and specific diagnosis of Alzheimer?s disease |year=2005 |last1=Mosconi |first1=Lisa |journal=European Journal of Nuclear Medicine and Molecular Imaging |volume=32 |issue=4 |pages=486–510 |pmid=15747152|s2cid=25670318 }}</ref><ref name=Hoyer>{{cite journal |doi=10.1007/BF03159971 |title=Oxidative energy metabolism in Alzheimer brain |year=1992 |last1=Hoyer |first1=Siegfried |journal=Molecular and Chemical Neuropathology |volume=16 |issue=3 |pages=207–24 |pmid=1418218}}</ref><ref name=Meier-Ruge>{{cite journal |doi=10.1159/000213592 |title=Changes in Brain Glucose Metabolism as a Key to the Pathogenesis of Alzheimer's Disease |year=1994 |last1=Meier-Ruge |first1=W. |last2=Bertoni-Freddari |first2=C. |last3=Iwangoff |first3=P. |journal=Gerontology |volume=40 |issue=5 |pages=246–52 |pmid=7959080}}</ref> some scientists have proposed that treatments targeting metabolic deficits in the brain of Alzheimer's patients may have efficacy.<ref>{{cite journal |doi=10.2174/156720512799015064 |title=Metabolic Dysfunction in Alzheimers Disease and Related Neurodegenerative Disorders |year=2012 |last1=Cai |first1=Huan |last2=Cong |first2=Wei-na |last3=Ji |first3=Sunggoan |last4=Rothman |first4=Sarah |last5=Maudsley |first5=Stuart |last6=Martin |first6=Bronwen |journal=Current Alzheimer Research |volume=9 |pages=5–17 |pmid=22329649 |issue=1 |pmc=4097094}}</ref><ref>{{cite journal |doi=10.1007/s12264-012-1270-2 |title=Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease |year=2012 |last1=Gu |first1=Xue-Mei |last2=Huang |first2=Han-Chang |last3=Jiang |first3=Zhao-Feng |journal=Neuroscience Bulletin |volume=28 |issue=5 |pages=631–40 |pmid=22968595|pmc=5561922 }}</ref><ref>{{cite journal |doi=10.1016/j.jns.2012.05.033 |title=Mitochondria and Alzheimer's disease |year=2012 |last1=Piaceri |first1=Irene |last2=Rinnoci |first2=Valentina |last3=Bagnoli |first3=Silvia |last4=Failli |first4=Ylenia |last5=Sorbi |first5=Sandro |journal=Journal of the Neurological Sciences |volume=322 |pages=31–4 |pmid=22694975 |issue=1–2|s2cid=11871039 }}</ref> |
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The makers of Axona claim that after oral administration of Axona, the ] in Axona are processed by ]s in the ], and the resulting medium-chain fatty acids (MCFAs) are absorbed into the blood supply leading to the liver. The MCFAs rapidly pass directly to the ], where they undergo oxidation to form ]s. Since the liver does not use ketones, they are released into the circulation to be used by nonliver tissues. ] can cross the blood-brain barrier and are then taken up by brain cells. While glucose is the brain's chief energy source, ketones normally serve as the "backup" energy source.<ref name=Cunnane>{{cite journal |doi=10.1016/j.nut.2010.07.021 |title=Brain fuel metabolism, aging, and Alzheimer's disease |year=2011 |last1=Cunnane |first1=Stephen |last2=Nugent |first2=Scott |last3=Roy |first3=Maggie |last4=Courchesne-Loyer |first4=Alexandre |last5=Croteau |first5=Etienne |last6=Tremblay |first6=Sébastien |last7=Castellano |first7=Alex |last8=Pifferi |first8=Fabien |last9=Bocti |first9=Christian |last10=Paquet |first10=Nancy |last11=Begdouri |first11=Hadi |last12=Bentourkia |first12=M’Hamed |last13=Turcotte |first13=Eric |last14=Allard |first14=Michèle |last15=Barberger-Gateau |first15=Pascale |last16=Fulop |first16=Tamas |last17=Rapoport |first17=Stanley I. |journal=Nutrition |volume=27 |pages=3–20 |pmid=21035308 |issue=1 |pmc=3478067}}</ref> |
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Ketones act as an alternative energy source for brain cells that have an impaired ability to use ] (sugar) as a result of Alzheimer's disease,<ref name=Henderson/> and the makers of Axona claim that this may have medical benefits.{{cn|date=January 2022}} |
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==Clinical trials== |
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Axona has been evaluated in ]s, paid for and conducted by Cerecin, only one of which was published in an ] in 2009.<ref name=Henderson/><ref name=Reville>John Reville for Wall Street Journal. July 19, 2012. </ref> |
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==Sales and marketing== |
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The product launched in 2009.<ref>Elaine Watson for Nutraingredientsusa.com July 19, 2012. </ref> By 2012 it was being administered to about 30,000 patients in the US.<ref name=Reville/> |
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==Criticism== |
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A 2011 story by ABC News noted widespread concern about Axona in the medical community, with some calling it "]."<ref>Carrie Gann for ABC News Medical Unit. Aug. 31, 2011 |
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Accessed May 10, 2012</ref> |
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The theory that the brain in Alzheimer's disease patients is better able to use ketones than glucose is not widely accepted among AD clinicians and researchers.<ref>Gayle Nicholas Scott for Medscape. May 30, 2012 </ref><ref>{{cite journal |pmid=20445638 |year=2010 |last1=Daviglus |first1=ML |last2=Bell |first2=CC |last3=Berrettini |first3=W |last4=Bowen |first4=PE |last5=Connolly Jr |first5=ES |last6=Cox |first6=NJ |last7=Dunbar-Jacob |first7=JM |last8=Granieri |first8=EC |last9=Hunt |first9=G |last10=McGarry |first10=K |last11=Patel |first11=D |last12=Potosky |first12=AL |last13=Sanders-Bush |first13=E |last14=Silberberg |first14=D |last15=Trevisan |first15=M |title=NIH state-of-the-science conference statement: Preventing Alzheimer's disease and cognitive decline |volume=27 |issue=4 |pages=1–30 |journal=NIH Consensus and State-of-the-science Statements}}</ref> |
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The ] has classified Axona an "alternative treatment", has "expressed concern that there is not enough evidence to assess the potential benefit of medical foods for Alzheimer’s disease", and notes that the safety of Axona is not regulated in the way that drugs are.<ref>Staff, Alzheimer's Association Accessed May 10, 2012</ref> |
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Glenn Smith, Ph.D, a clinical neuropsychiatrist at the Mayo Clinic, also noted that Axona's safety and efficacy are not known, and noted that "the Alzheimer's Association doesn't recommend the use of medical foods, including Axona, for the treatment of Alzheimer's disease."<ref>Glenn Smith for the Mayo Clinic. Aug. 4, 2011 Accessed May 10, 2012</ref> |
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In 2013, FDA determined that Axona is misbranded under section 403(a)(1) of the Federal Food, Drug, and Cosmetic Act because the labeling is false and misleading in that the product is labeled and marketed as a medical food but does not meet the statutory definition of a medical food.<ref name=FDA2></ref> |
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==See also== |
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==See also== |
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==References== |
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==References== |
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{{reflist|refs= |
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{{reflist}} |
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<ref name=AxonaDrugsCom> Drugs.com. Cited 30 November 2009.</ref> |
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<ref name=AxonaApproval> CenterWatch. Cited 30 November 2009.</ref> |
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}} |
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==Further reading== |
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* Accera. (February 2011). (Prescribing Information). Retrieved April 26, 2011 from www.about-axona.com. |
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* Henderson ST. (July 2008). . ''Neurotherapeutics'' '''5''' (3): 470-480. {{pubmed|18625458}}. |
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== External links == |
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{{nervous-system-drug-stub}} |
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