I hope to write some critiques of treatments that are in advertisements to give some perspective to claims. So one thing that I get is called Clinical Geriatrics. It's a subscription I get from my membership in the American Geriatric Society. This last issue there was a supplement (i.e. advertisement) about a new nutritional supplement called Axona that will help patients with Alzheimers.
So what is Axona?
Axona is essentially a variety of fatty acids (fats) that get metabolized to ketones. So what? Well the brain can use ketones as well as glucose in helping us think. Since the brain that has Alzheimer's has trouble using glucose, maybe supplying some ketones will provide more energy to the brain.
So does Axona work?
That depends on what the goals are. If the goal of an Alzheimer's patient or family is to keep the patient functional, out of a nursing home, engaged in hobbies and relationships then the answer is unknown. If the goal is to see a miniscule improvement on a research cognitive scale (ADAS-cog), then the answer is, according to the manufacturer's 1 study, yes. At 45 days there was a 1.91 point difference between the two groups (out of 70 points). By 90 days this improvement disappeared.
Conclusion
Axona may have an effect on cognition that a researcher may be able to detect, but I am doubtful that any family member or patient would notice. In any case, the benefit disappears by 90 days according to the manufacturer's own data. And according to the data, for every 8-9 patients treated, 1 will get a side effect (like diarrhea).
My conclusion is that this nutritional supplement is interesting, but not worth trying yet.
edit: As one comment points out, this medication/food supplement is a single triglyceride (>95%). But I think it is made from a variety of oils (palm oil and others) due to the warning on label regarding food allergies.
Edit (6/12/2011)
I realized that this is my most viewed post on my blog and I would like to update it a little. There are several things I would like to see studied/researched about any specific intervention for dementia before I get too excited about it: The intervention has to
1. Show a difference between placebo and treatment in long term studies (i.e. more than 6 months)
2. It has to show an effect in both research scales and clinically oriented outcomes
3. Clinical significance (as opposed to statistical significance) has to be defined separately from the study
4. The study has to be large enough to define subgroups (i.e. those who achieve the threshold of clinically significant change/improvement)
5. A Number Needed to Treat needs to be able to be calculated
6. Ideally a way to tell if the treatment is working or not working would be researched along with effectiveness
7. Discontinuation studies need to be done that are not simply open label studies in order to allow people to feel comfortable stopping a med that will likely not benefit the majority of subjects.
These seven criteria will allow a patient/physician to know what a medication is supposed to achieve and whether it is clinically meaningful, what percentage of people actually achieve it, when it is not working so it can be stopped and the risk involved of stopping it.
To be fair to Axona, no medication/treatment meets these criteria so it is hard for me to get excited about any pharmacological intervention. I'm not a fan of starting a medication without knowing if it is working, whether it is doing anything clinically meaningful, how likely someone is to get benefit, when to stop it and risks involved.
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5 comments:
You might want to do a bit more researching before you blog. The active ingredient is a single triglyceride. The effects of Axona on the Alzheimer's patient are most definitely noticeable to the family members. I speak from personal experience, and I know quite a few other caregivers who would agree, also from personal experience. Axona mimics the effects of a ketogenic diet. The mechanisms underlying the impact of ketones on the brain are many and varied, and are being studied with a great deal of interest by the scientific community.
As for diarrhea, have you considered the side effects of the only other meds available for treating Alzheimer's? Or how much good these meds do, even if the patient can tolerate the side effects?
Great comments. Without a doubt, Alzheimer's meds are not necessarily safe. Drop out rates in trials due to side effects went up to almost 60%. And efficacy was not much better than Axona. In many ways, I would definitely consider Axona safer than, let's say, Aricept. One day I'll write a post how Pfizer offered me $500 per lunch meeting with doctors to push Aricept and why I decided not to do that.
The second question raised was whether Axona could be effective even though the studies showed marginal benefit. The answer is definitely yes. There is good reason to believe that the critera used by the FDA to approve drugs (ADAS-cog, NPI, CIBC plus) may not really be the best markers of effectiveness. Right now, family impression is as good as any in my opinion. So if someone feels it works, and since it is relatively safe, then use it. But it is not possible that a 2 point change on a 70 point research scale can be detectable by nonresearchers or that it reflects any meaningful change.
There may be promise, but the data collected by the manufacturer to get approval don't show it.
Josh, we participate in a number of studies on Alzheimer's. One of the first things I learned is that the tests administered to the patient by neurologists may not have any relevance to the way in which the patient functions in real life. The researchers themselves told me that. That's why patients are only accepted into these studies if they have caregivers who spend at least several days a week with them and are willing to participate in the studies, too. I spend nearly as much time answering questions about my ADLO's behavior for analyses such as CIBC-Plus, ADCS-ADL, and QoL-AD as my ADLO spends in the neuropsych testing. I would put far more value on those than on ADAS-cog.
I'll give you a small example. My ADLO has scored as having "severe" short term memory loss for four years -- the lowest score possible. Yet I can say "remind me to look for your sweater in your bureau in the morning", and in the morning, he'll say "I'm supposed to remind you to look for something in my bureau." This is not an isolated incident, this is typical behavior -- he remembers lots of what goes on. He keeps track of appointments on the calendar, for example, and remembers to get up early on the appropriate day and to put on clothes suitable for the appointment before he looks at the calendar on that day. The list goes on and on. I wouldn't consider his short term memory loss to be anywhere near as severe as it could be.
So in my experience, what I observe with my ADLO and what shows up on ADAS-cog are two totally different things.
Also, I believe you are incorrect about clinical trial results for conventional AD meds. For example, in the 30-week study on Aricept, on average, all patients declined steadily from baseline. However, the two drug treatment groups only declined by about 1 point, whereas the placebo group declined roughly 4 points. This resulted in a significant difference in the level of decline that was seen, of 2.8 and 3.1 units for the two Aricept dosage levels.
The Axona treatment groups, on the other hand, actually improved from baseline in two separate Phase IIb trials, and the results were statistically significant. The placebo group declined as expected.
As for side effects, while the incidence of treatment-related gastrointestinal side effects from Axona was similar to that of other AD drugs in the double-blind phase of the first IIb trial, a reformulated version used in the open-label extension study greatly reduced these side effects.
As for food allergies, I've asked Accera about a couple of those for a friend of mine whose ADLO has some allergies. Accera has gone way overboard on the warnings. For example, they warn about soy allergies solely because they use lecithin as an emulsifier. There is actually no reason to believe that any significant amount of a soy allergen is present in their product. Try looking at the list of ingredients in the prescribing information, not guessing about what Axona contains from allergy warnings.
If you want to understand the theory behind the way Axona works, Dr Henderson has published a number of outstanding papers, very thorough, comprehensive, and detailed. Also, look into recent advances in our understanding of mitochondrial dysfunction in neurodegenerative disorders, and the impact of raising ketone body levels by ketogenic diet, calorie limitation, and ketone body infusion.
Please note the full ingredient list on Axona - http://www.about-axona.com/hcp/about/faq/#faq_9 What are all these extra ingredients ?!?! Not explained anywhere so looks like a cereal box - pumped up with vitamins to appear more healthful. Plus, there is no assurance that Axona comes from pure virgin coconut oil ....and it may be from another source.
Let's see, coconut oil, eaten safely for thousands of years, or Axona with its side effects untested by the FDA, - Duh, easy choice.
Next consider the price - natural and delicious coconut oil at $25 a month per person for best quality virgin, or $110 a month plus doctor visits and the time spent to procure it. Do you want to increase corporate profits or reward organic coconut grove farmers?
It's simple and drug free - just not monetized by big pharma. Now visit CoconutBeachDiet.com for more details and enjoy getting older for a change!
My husband was started on Axona on March 25, 2014 by his neurologist. (He is also on the Exelon patch (9.5) and Namenda (10 mgs bid.) One month later on April 25, 2014 at a regular six month dental checkup, he had FIVE cavities. He has had no cavities in years. Absolutely nothing else in his diet or medications had changed except adding Axona.There seem to be no other reports of dental cavities as side effects of Axona. We instituted an aggressive dental regimen, including trips to the dentist every 3-4 weeks, daily brushing/flossing/hydroflossing, and brushing with prescription toothpaste with fluoride. Today (9-9-14), he was found to have yet another cavity. I can't say that we've seen any memory improvement since he started on Axona either. Tomorrow I shall call the neurologist to find out how to discontinue using Axona.
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