(Source : Medscape, 30 May 2012)
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.[3-5]
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.