Response from Gayle Nicholas Scott, PharmD
Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia; Clinical Pharmacist, Chesapeake Regional Medical Center, Chesapeake, Virginia
Coconut oil and a related medical food, Axona® (Accera, Inc; Broomfield, Colorado), are being promoted as treatments for Alzheimer disease (AD). Obtained from the kernel of the coconut palm (Cocos nucifera),[1] coconut oil contains medium-chain fatty acids, predominately lauric acid but also caprylic, myristic, and palmitic acids. Medium-chain triglycerides are the esterified form of medium-chain fatty acids; the terms are often used interchangeably.[2] The active ingredient of Axona is caprylic triglyceride. In the published research available, the product is called AC-1202.
Proponents claim that coconut oil and Axona provide ketones as an alternative to glucose for cerebral metabolic processes. Advocates of these treatments describe AD as “diabetes of the brain” and contend that the AD brain is better able to use ketones than glucose.[6] This theory is not widely accepted among AD clinicians and researchers,[7] but some speculate that ketogenesis might improve free radical-mediated pathologies associated with AD.[8]
Normally, metabolic energy comes from glucose. When glucose availability is reduced, the liver produces ketone bodies (primarily acetoacetate and beta-hydroxybutyric acid [beta-OHB]) as energy sources. Unlike the heart and skeletal muscle, the brain cannot use fatty acids as an energy source because it requires glucose or ketone bodies.[8]
Medium-chain triglycerides are more ketogenic than long-chain triglycerides, such as those in animal fat. Ketogenic diets, which are diets high in fat and low in carbohydrates and proteins, have been used since the time of Hippocrates for treatment of epilepsy; the mechanism is still unknown.[8] Ketogenic diets are still used in refractory epilepsy, but poor tolerance of the gastrointestinal side effects and dislike for the diet limit effectiveness.[9] Medium-chain triglyceride diets are better tolerated than classic ketogenic diets, which include more long-chain triglycerides. Because medium-chain triglycerides are highly ketogenic, patients can consume more carbohydrates, making the diet more palatable.[8]
Several theories have been proposed for beneficial effects of ketones in AD, including prevention of amyloid plaques, reduction of proinflammatory mediators associated with neurodegeneration, and a neurotrophic effect of cerebral ketone metabolism.[10] Studies with encouraging results using ketogenic diets in AD have been published.[10-13] In a 6-week clinical study of 23 elderly patients with mild cognitive dysfunction, a diet very low in carbohydrates, which increased ketone levels, improved memory function better than a high-carbohydrate diet.[10] In another preliminary clinical study of 20 persons with AD or mild cognitive impairment, administration of a medium-chain triglyceride beverage was associated with improvement on some cognitive measurements in response to acute elevation of beta-OHB levels 90 minutes after treatment in 2 single-dose study visits, but only in patients without the apolipoprotein E gene (n = 9).[14]
A literature search for coconut oil and AD revealed no clinical studies. A search for the medical food Axona yielded 1 manufacturer-sponsored study and 2 substudies.[3-5] In a 90-day, randomized, double-blind phase 2 study, 152 persons diagnosed with mild to moderate AD received Axona10-20 g/daily or placebo. The primary endpoint was improvement on the AD Assessment Scale-Cognitive subscale (ADAS-Cog). At 45 days, patients receiving the study drug showed improvement on the ADAS-Cog, as noted in company advertising. However, scores were similar in both groups at day 90 and after a 2-week washout period on day 104. In patients without the apolipoprotein E gene, Axona was superior to placebo at both time points.[3]
According to the Alzheimer’s Association, the manufacturer of Axona elected to market the product as a medical food rather than conducting phase 3 studies in a larger population to prove effectiveness. Medical foods do not require phase 3 studies.[15]
Both coconut oil and Axona are high in calories and saturated fat, but some research suggests that coconut oil neither increases weight nor adversely affects lipid levels.[2,16,17] Gastrointestinal adverse effects, particularly diarrhea, were frequent causes of discontinuation in the phase 2 study.[3] Coconut oil costs about $12 for 16 oz. Axona costs about $85 per month.
Currently, neither coconut oil nor Axona can be recommended for AD due to lack of credible effectiveness research. For patients or family members who insist on these products, suggest starting with a low dose and gradually increasing the dose to avoid adverse gastrointestinal effects. Healthcare providers should monitor for adverse effects and effectiveness and possibly increased lipid levels.
References
- Marina AM, Man YB, Nazimah SA, Amin I. Antioxidant capacity and phenolic acids of virgin coconut oil. Int J Food Sci Nutr. 2009;60 Suppl 2:114-123. Abstract
- Liau KM, Lee YY, Chen CK, Rasool AH. An open-label pilot study to assess the efficacy and safety of virgin coconut oil in reducing visceral adiposity. ISRN Pharmacol. 2011;2011:949686.
- Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 2009;6:31.
- Henderson ST, Poirier J. Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 2011;12:137.
- Crumpacker DW. Retrospective evaluation of constructive praxis measurements among APOE4(-) subjects enrolled in the study of AC-1202(Axona®) in mild to moderate Alzheimer’s disease (AD). Am J Geriatr Psychiatry. 2012;20:S129. [abstract]
- Johnson L. Coconut oil touted as Alzheimer’s remedy. http://www.cbn.com/cbnnews/healthscience/2012/January/Coconut-Oil-Touted-as-Alzheimers-Remedy/ Accessed April 1, 2012.
- Daviglus ML, Bell CC, Berrettini W, et al. National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline. Ann Intern Med. 2010;153:176-181. Abstract
- McPherson PA, McEneny J. The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress. J Physiol Biochem. 2012;68:141-151. Abstract
- Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2012;3:CD001903.
- Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, Clegg DJ. Dietary ketosis enhances memory in mild cognitive impairment. Neurobiol Aging. 2012;33:425.e19-27.
- Van der Auwera I, Wera S, Van Leuven F, Henderson ST. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab (Lond). 2005;2:28.
- Yao J, Chen S, Mao Z, Cadenas E, Brinton RD. 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer’s disease. PLoS One. 2011;6:e21788.
- Studzinski CM, MacKay WA, Beckett TL, et al. Induction of ketosis may improve mitochondrial function and decrease steady-state amyloid-beta precursor protein (APP) levels in the aged dog. Brain Res. 2008;1226:209-217. Abstract
- Reger MA, Henderson ST, Hale C, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging. 2004;25:311-314. Abstract
- Alzheimer’s Association. Alternative treatments. http://www.alz.org/alzheimers_disease_alternative_treatments.asp Accessed April 1, 2012.
- Assunção ML, Ferreira HS, dos Santos AF, Cabral CR Jr, Florencio TM. Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity. Lipids. 2009;44:593-601. Abstract
- Feranil AB, Duazo PL, Kuzawa CW, Adair LS. Coconut oil is associated with a beneficial lipid profile in pre-menopausal women in the Philippines. Asia Pac J Clin Nutr. 2011;20:190-195. Abstract