Matthew Phillips is Director of Neurology as Waikato Hospital.
He's published on predictive processing (brain function).
He also has a strong interest in ketogenic diets as treatments for neurodegenerative diseases. There's a 2021
paper here with Philllips as first author on a trial of a ketogenic diet in people with Alzheimers Disease.
a single-phase, assessor-blinded, two-period crossover trial
Note that it is claimed that the study is assessor-blinded. Participants were required to have a
a cohabiting trial partner willing to (at least partly) partake in a ketogenic diet.
Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects.
Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild.
So, there primary outcomes.
1. Addenbrookes Cognitive Examination
This was probably was given to the patient by a blinded assessor. No significant differences between the ketogenic diet and the normal diet
2. ADCS- Activities of Daily Living (ADCS-ADL)
This was administered to the trial partner. That is, the person living with then AD patient, the person who was required to '(at least partly) partake in a ketogenic diet' and therefore almost certainly was involved in the preparation of the food and giving it to the AD patient, was the one reporting on changes. It is almost irrelevant whether the nurse or whoever was writing down the partner's responses was blinded to the diet when the partner clearly was not. This was not an assessor-banded study, despite the claims that it was.
Even with that bias, the report benefit was minimal.
whereas they increased their ADCS-ADL (+ 3.13 ± 5.01 points, P=0.0067)
Actually, Table 2 shows us that the participants were assessed as increasing their ADCS-ADL by 0.13 of a point while on the ketogenic diet, it's just that the participants were assessed as decreasing their ADCS-ADL by 3 points on their usual diet. The scale is from 0 to 78. Even a change of 3.13 points on a 78 point scale is deeply within the realms of a placebo effect. Honestly, I'm surprised it was not substantially more of a benefit reported given the obvious motivation of the patients and their partners who completed the trial and the hope they would have had that they could do something to improve things.
3. Quality of Life in Alzheimers Disease
The Quality of Life in AD (QOL-AD) questionnaire was also administered to the trial partner. The QOL-AD assesses 13 items (scores
range from 13 to 52, with higher numbers indicating better quality of life)
QOL-AD (+ 3.37 ± 6.86 points, P= 0.023
So, this was also assessed by the partner of the patient and so was also the opposite of a blinded assessment. A difference in the change between the two treatments of 3 points on a scale of 52 is also barely noticeable and well within the change we would expect with an unblinded treatment and hopeful participants.
It's pretty clear that the study found no benefit likely to be real. And these are results from the 81% of the participants who started the trial. One participant stopped due to diarrhoea (this being blamed on the patient eating too much coconut oil) and four participants were withdrawn because they refused to alter their diet, causing conflict with their partner.
This is what was said about the participant who ate too much coconut oil:
Importantly, only one withdrawal was attributed to ill effects of the ketogenic diet, even though the trial partner was enthusiastic.
The 'enthusiastic' trial partner does not sound to have been in a state of equipoise.
This is what Phillips et al reported in the abstract:
High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia.
And this is what was reported in the Discussion:
Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily
function and quality of life.
Matthew Phillips
Researchgate entry says
My foremost passion is to explore the feasibility, safety, and efficacy of metabolic therapies, particularly fasting and ketogenic diet protocols, in creating alternative metabolic states that may lead to improvements in symptoms, function, and quality of life for people with neurological disorders.
If we think about the people with Alzheimers disease and their carers, dealing with a difficult new diet is not an easy thing. It can be expensive and time consuming at a time when the carer often has to give up work and when things most need to be easy. The text of Phillips' trial notes that the diet caused conflict between some patient and their carers, and diarrhoea in a person with Alzheimers disease probably was very hard for both the patient and the carer.
This is the advice that Phillips is giving medical professionals via the
Goodfellow Unit, claiming as he does so that he is a metabolic neurologist:
Take home messages
- People with Alzheimers display a brain-specific form of insulin resistance, resulting in deficient glucose metabolism.
- Alzheimers neurons also show significant mitochondria dysfunction, which precedes the appearance of plaques or tangles.
- Metabolic strategies, such as fasting and ketogenic diets, create ketones that can bypass the insulin resistance, and they stimulate multiple mechanisms focused on mitochondria renewal.
- In the first-ever randomized crossover trial of a ketogenic diet in Alzheimer’s, people showed statistically (and clinically) meaningful improvements in daily function and quality of life.
- Given the efficacy and safety data to date, it is reasonable to offer a modified ketogenic diet to people with Alzheimer’s disease.
I think this messaging is a failure of Phillips and the Goodfellow Unit. Phillips' trial is not strong enough to warrant recommendations that will make life harder for AD patients and their carers.
Given the essentially null results from the trial, the positive spin put on them in the report, the misleading characterisation of the trials as involving blinded assessors and Phillips' ongoing commitment to the idea and willingness to promote it, it looks to me as though Phillips is a man who sees what he wants to see when it comes to ketogenic diets. He also seems extremely sure of his opinion about their utility, even when the data does not support them.
Those two qualities may be relevant to his promotion of the concept of functional neurological disorders and his ability to carefully diagnose the people who come to him for help.