Friday, 21 April 2017

Brilliant conference but keeping on top of things has been tough.

It was such a privilege to have spoken at the recent Metabolic Therapeutics Conference in Tampa, Florida with people I greatly admire. It provided me with a chance to share what I have learned from my experiences over time attempting to manage my cancer and epilepsy with metabolic protocols I have adapted and personalised.

These protocols have been based on the work of Dr. Dominic D'agostino, Dr. Thomas Seyfried and Dr. Angela Poff, who I have tremendous respect for. I must stress however that, while my epilepsy has been controlled very effectively with these therapies, it is very difficult to quantify how much influence ketosis in itself has impacted on my results regarding the cancer despite encouraging results. This approach is a multifaceted one, all I can say definitively is that my quality of life is much better than it would have been otherwise. I believe that fasting mimicking diets can potentially play a very important role in disease management and longevity but a ketogenic diet is just one form of this.

With GBM survivor David Shevock and Professor Thomas Seyfried in Tampa
It was also a great pleasure to meet a couple of other 'survivors' of even more aggressive types of brain cancer to mine (glioblastoma) who followed similar protocols. We draw inspiration off of each other and share theories based on the latest research, which is pretty useful at times. For example I made a lot of mistakes along the way which caused breakthrough seizures and while my understanding of brain tumour related epilepsy has been expanded upon as a result and I have impressive control through intuition and knowledge of changes to brain chemistry, I don't want anybody else to have to suffer with attempting to improve seizure control without this information. I wouldn't recommend attempting anything I have done without medical support and supervision.

This is why I am happy to help others to work out the things that we see these patients all have in common and then make individual adjustments for the differences- eg. type of seizures, location of tumour/brain damage, timing of seizures, confounding variables (type of drugs, tumours affecting hormone function, gender, age, environmental factors).

The first thing I had in mind about attending this conference was the fact that I had not flown since my diagnosis and that the changes in air pressure experienced during the flight can trigger seizures. I was also concerned about air quality in the plane. I had experienced a similar problem during hyperbaric oxygen therapy but had accounted for, in that case, oxygen toxicity seizures by using an 'air break' technique, which was very successful for allowing me to adapt to the treatment. In preparation for the flight I had decided a complete fast was necessary and I took exogenous ketones and magnesium with me just in case. Thankfully I had no issues on the flight which felt like an enormous accomplishment at the time. I was also concerned with the change in time zone but this affected me more a couple of weeks later which I was thankful for!

Air quality in planes is poor and can cause so called 'aerotoxic syndrome' -
http://www.bbc.co.uk/news/health-32786537

My talk was based around the how, what, and why I did what I did over the course of my disease from the beginning up until the point I had no visible or detectable disease present followed by considerations for the future relating to preventative approaches. I am well aware that this cancer is unforgiving and can be elusive. We have come a long way, and the MR Spectroscopy results have certainly been very interesting over time, but I remain cautious. I still have a highly sensitive type of epilepsy, which continues to irritate me to no end but I am thankful that I have been able to make micro-adjustments to keep the seizure activity largely under control. I still have partial seizures all throughout the day every day, but its just like getting tiny electric shocks and feelings of numbness around facial nerves which gives me feedback about what the causes might be and the ionic adjustments I need to make.

Presenting the intricacies of my approach: The how, what and why.
Having kept food diaries over the last few years, and having researched this to death, I feel I have developed an understanding of what might be going on in this area. My studies at university have underlined this fact as we look at action potentials quite often so I understand chemical synapse activity in the context of epilepsy and the mechanism of action of the drugs used in an attempt to manage the condition. I understand that with food and supplements you can achieve this without the undesirable side effects of the drugs that can cause side effects as a result of micronutrient deficiencies and a shift in brain chemistry- serotonin, dopamine changes and deficiency of magnesium, vitamin D, calcium, etc.

Messages are sent from one neurone to another in excitation, due to the movement of
sodium and calcium ions into cells, and potassium out of cells. (3)


Figure 1 Overview of the two main barriers in the CNS. blood-brain barrier and blood cerebrospinal fluid barrier (BCSF). ISF: Interstitial Fluid. CSF: Cerebrospinal fluid. (2)
These conferences are so important because I firmly believe we can only begin to truly move forward in our endeavours if we are able to collaborate with each other and learn to piece together different parts of the metabolic jigsaw in an attempt to find answers to the complex metabolic derangement we see in various disorders and conditions. This conference consisted of specialists in metabolic therapeutics who all have their very specific areas of interest within this field and there are many gaps remaining in our knowledge that need to be filled. I also see extreme views on either side of the argument (Warburg Effect or Reverse Warburg Effect) and I feel, as I do often with these things, that the truth usually lies somewhere in between. Few things are clear cut and when we're discussing physiological systems that don't work in isolation, its logical that the answer is never so clear and simple.

As a patient as well as a researcher I was delighted to have been invited to speak because as a cancer patient alone it can be very challenging and quite daunting to get a true grasp of what metabolism actually is, let alone how all of these biochemical processes that occur are related to the countless somatic mutations that we see. So many questions remain and we are still only just scratching the surface. I have also been burned in the past when I shared my story with others, there was confusion, misinformation, and many things were taken out of context to create a compelling narrative. I still don't see metabolic therapy as a 'cure' but it has potential to help manage the disease more effectively for some with the right protocols. I am not recommending any treatments of course and everything you choose to follow and/or believe from the information provided is your responsibility. I simply provide the research and you are free to take it or leave it!

Cancer anecdotes appear to be popping up everywhere, but I feel we need to reign in our enthusiasm a little and focus purely on the data. This data is very promising, but I notice many people are starting to get carried away and are oversimplifying what it all means. I have also noticed this when others have written about my story.

There is even a book coming out soon called 'Keto Cure', which I feel is an irresponsible title and ironically will serve as more of a hindrance to this research rather than support it. I like Jimmy Moore as a person, but there is no way I can support this endeavour and would like to take this opportunity to distance myself from anything like this. I use my words very carefully and cautiously on purpose. You will notice that I will never say the word 'cure', because I believe these therapies do not cure, but have the potential to manage the condition as you would with a chronic disease. I see it as being like HIV in how we must think of treating it, with multiple agents targeting multiple metabolic pathways and supporting the immune system. There is clearly a strong role of hyperbaric oxygen therapy, drugs targeting metabolic defects, and both nutritional and supplemental methods of inducing ketosis in all of this that would need to be personalised for the individual's tumour type and their unique physiology. Nothing works in isolation and the ketogenic diet on its own is certainly not a 'cure all', as some like to market it.

The claims on the cover of this book are not helpful. It is not written by scientists and
I can see researchers struggling to be taken seriously if we keep seeing this kind of thing.
My scans and documented findings from MR Spectroscopy have certainly been very interesting, but there are so many confounding variables that it would be irresponsible for me to make any claims about the virtues of ketosis from this alone. I am pushing for my tumour to be analysed again in the lab because my story has not been typical of the course suggested to me from discussions relating to the original histopathology results. I attended a conference last year with the British Neruro Oncology Society about how these results can actually vary greatly depending upon what determining factors a group of pathologists agree with and what criteria is being considered. It isn't an exact science by any means.


From BNOS 2016- Prof. Sebastian Brandner
Only 16% of tumours have been found to be diagnosed correctly upon reclassification under revised classification criteria.
I should have been less naive perhaps when sharing my story in the early days, but I am more wise now as a result of these experiences so I will stick to generating my own content here and with people I know I can trust who are more interested in the science than the story. If this is disproving anything related to that I am more than happy to be involved as I am constantly trying to prove myself wrong rather than right. This is what science is about, which is what I have explained in previous posts. Sometimes people get carried away I think.

I have so much more I could add about these experiences and what I have learned, but time appears to be moving so fast and so much is happening in a short space of time. As I returned home (to snow!) I gradually begun to develop flu like symptoms and progressively felt the accumulative effects of fatigue from my circadian missmatch I had been trying desperately to avoid. I was then to learn an even more valuable lesson...

As my symptoms became increasingly more debilitating in March I made efforts to take more magnesium and more exogenous ketones, which worked brilliantly to control the seizure activity, but left me with new symptoms that were worsening. On top of this, I was putting increasing pressure on myself with demands at university and I was beginning to forget the essence of why my specific approach had been so successful for so long. I had forgotten to treat the underlying problems and began to focus solely on the symptoms without truly looking after myself in the way that I should have been. Nothing beats quality sleep, happiness, nutrient dense food, consistency of good habits, clean air and sunshine. I think there may have been some psychobiological aspects of this too in how my mental state at this point was affecting my immune responses to pathogens.

The calcium entry causes synaptic vesicles to fuse with the membrane and release neurotransmitter
molecules into the synaptic cleft. (7) My ratio of calcium: magnesium was certainly not sufficient.
Too much magnesium, not enough calcium.
I was suddenly thrust back into the busyness of London without taking time to slow down and use my various nature and ketogenic 'paleo', evolutionary biology type' 'hacks' to cope. Of course I was still on my strict ketogenic diet, but I was slipping in terms of how my macros were being tracked and the timings of my meals (I eat only 1-2 times per day typically).

Before going on this trip I had my approach down to a fine art through 4 years of trial and error and I was starting to let myself down for the first time. Life was suddenly too fast paced for my brain to handle and there was I was starting to treat the symptoms as a 'plaster over the wound approach' rather than only using these supplements sparingly in emergencies.

You can't be half hearted with this, especially in my situation with 'reflex epilepsy' and no medication. You must live almost like a monk rather than having this struggle to cope in this toxic environment with a toxic mental approach. I should have become more introspective as I normally am. I'm a problem solver and usually I only take very calculated risks, but I was about to learn how, over the course of the next few weeks, I was no longer able to cover the symptoms and I suffered a bit of a breakdown. I'm not being overly dramatic by stating that this could have very well led to the end of my journey.

I decided to smile through the exhausting fatigue, stumbling through life and crying inside, feeling empty and hopeless. My sleep was very poor and eventually my mental state felt like it was being shattered into a million pieces on the floor. I was taking so much magnesium to cope and relying on caffeine to counteract the feelings of the magnesium that my brain and body eventually said no more. I started vomiting and experienced new kinds of seizures, feeling like I was about to pass out all the time and sleeping for long hours day and night. My vision also started to become blurred and I was worried about a recurrence of my tumour as I felt a pressure in my head where the tumour was. I felt increasing concern as these symptoms reminded me of my experiences just prior to my 'thunderclap headache' that occurred 4 years ago resulting in my brain haemorrhage.


'Thunderclap headache refers to a severe and explosive headache with peak intensity at onset—as sudden and as unexpected as a “clap of thunder”.' (4)


I was absolutely terrified, and walking out of university a few weeks ago I collapsed on the pavement, unable to move, and I thought I was going to have a grand mal seizure. I couldn't feel parts of my body, particularly on the left hand side, and my lips were constantly tingling. I could barely speak and I felt extremely dazed and confused but I was somehow able to dial 999 on my phone and was rushed to Accident and Emergency.


Magnesium can block synaptic transmission of nerve impulses. (1) 
Helps with depression and epilepsy, but too much can be problematic. 

There was nothing they could do and I was sent home after hours of waiting. My blood glucose and blood ketone readings were maintained the whole time, but I have never just paid attention to these arbitrary measures alone. Something was seriously wrong. I noticed my symptoms were consistent with peripheral neuropathy and hypermagnesaemia so after eventually pushing for an emergency MRI scan and then a reluctant CT scan only days later after a suspected possible small bleed on the brain I decided to diagnose the problem myself as I always had previously.

The solution was so obvious that I felt very stupid, but I have this personality that is prone to depressive states when my routine goes down the toilet so I became reliant on the magnesium to stabilise my mood. I noticed that my symptoms would improve slightly whenever I urinated and that when I took magnesium chloride sublingually I would go into a VERY deep sleep almost immediately. As an emergency I would always take the magnesium this way, under the tongue, because there are a lot of blood vessels in this area, meaning that absorption is rapid. I stopped supplementing with the magnesium and I concentrated on having more sodium and calcium, because I realised I was encountering a new problem, completely opposite to the problem I had when I started supplementing with magnesium a few years ago.

Sublingual drug delivery illicits a rapid response as it bypasses the liver (first pass metabolism).
There are many blood vessels under the tongue where the sublingual gland resides. (6)


I knew that magnesium depresses neuronal excitability and too much can have dangerous consequences that can cause coma and even death! People always say how unlikely this is as we are so deficient in magnesium and you can theoretically excrete the excess in the urine so it isn't too much of a concern but in my case it was a huge concern. Its a tricky balance because magnesium has so many benefits as I have noted previously, including neuroprotection and improvement of outcomes for many types of traumatic brain injury, but you have to be careful not to overdo it and damage neurons. (1) That would kind of be like blowing a fuse in the brain when the light is switched on.


After addressing all these issues by not taking any magnesium and taking in more calcium (this is excitatory) and sodium (allows flow of conduction) I feel absolutely fine and with the lifestyle tweaks I actually feel better than I have done at any time in the recent past. The balance is back in the range I need it to be and this ionic balance is definitely more important than the ketones. When you combine the two you may get more potent benefits, as I do, but we can't say this for sure with everyone. It was a tough lesson to learn, and pretty dangerous (I wouldn't recommend it), but I feel so strong as a result and my knowledge relating to epilepsy has taken another step forward. Silver linings. ;)



Graph of a normal action potential.



I made this table with the help of information from Epilepsy Society, to show how these drugs act.

I mention some of this here. I can now happily say that I've never felt better after this experience from what I learned and the changes I have made as a result. April has been a perfect month so far and I have been incredibly active and productive overall. Weird huh?



References


(1) Dribben, W.H., Eisenman, L.N. and Mennerick, S., 2010. Magnesium induces neuronal apoptosis by suppressing excitability. Cell death & disease1(8), p.e63.

(2) Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: Perspectives on tracking and neuroimaging - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/41721469_fig1_Figure-1-Overview-of-the-two-main-barriers-in-the-CNS-blood-brain-barrier-and-blood [accessed 20 Apr, 2017]

(3) http://oerpub.github.io/epubjs-demo-book/content/m46526.xhtml

(4) Dodick, D.W. Thunderclap headache. Journal of Neurology, Neurosurgery & Psychiatry. 2002;72:6-11.

(5) http://link.springer.com/article/10.1023%2FA%3A1022950321817?LI=true

(6) Kraan, H., Vrieling, H., Czerkinsky, C., Jiskoot, W., Kersten, G. and Amorij, J.P., 2014. Buccal and sublingual vaccine delivery. Journal of Controlled Release190, pp.580-592.

(7) https://cnx.org/contents/cs_Pb-GW@5/How-Neurons-Communicate

6 comments:

  1. As I shared regarding your concerns with our upcoming book title on my Keto Talk Facebook page, we're not putting forth the notion that a ketogenic diet is the "cure" for every ill of mankind. Neither Dr. Adam Nally or myself believes that. But for a lot of chronic illnesses, it can be a miracle cure for these conditions that are an extension of the spectrum of insulin resistance. For someone like yourself who has overcome extraordinary odds to heal your body through a wide variety of strategies to deal with terminal brain cancer, I can understand your concern. But Keto Cure is not referring to brain cancer at all. We would never do that and it would be a reckless statement for us to make. We are not making it. Appreciate your input and we think people will understand precisely what we're talking about. Be well, Andrew!

    ReplyDelete
    Replies
    1. " But Keto Cure is not referring to brain cancer at all"

      But the book specifically mentions Diabetes, Heart Disease, Cancer and more.

      SO - if not brain cancer what cancers are you referring to??

      Delete
  2. Regardless of the content in the book the title reads 'KetoCure' and as a subheading mentions cancer. Others agree with me that this is clearly misleading so you might want to change it.

    ReplyDelete
  3. Interesting update! Sorry to hear about the scare you had, but it sounds like you've learnt a lot from it. Do you measure your electrolyte balance somehow? And what form of calcium do you supplement with? BTW, the comment above (bone cancer in India) is spam - specifically "link spam" - trying to benefit from the profile of your blog. I suggest you delete it. All the best! Nick.

    ReplyDelete
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