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

Tuesday, 7 March 2017

Branched chain amino acids, the ketogenic diet pill, and ketosis

Recently I have been combining exogenous ketones with BCAAs on my restricted protein ketogenic diet protocol to see how I react over time. Nutritional ketosis produces an increased ratio of plasma branched chain amino acids to aromatic amino acids which is one of its main proposed mechanisms of action for seizure control. 




It has been suggested that the high ratio of plasma BCAAs/ARAAs could be useful for epileptics as it results in decreasing ARAAs- (ARAAs supposedly increase the excitability potential of the brain entering the central nervous system (Jirapinyo et al., 2004)). This shift resulting in a rise of BCAAs to ARAAs means that a state of ketosis will decrease the excitability potential of the brain and increase seizure threshold. The brain becomes more resilient to stress you could say and brain chemistry in general is more balanced as a result. I feel pretty good today but its just one day, one experiment, and the type I am taking also includes resveratrol and L-carnitine (which may have its own benefits). Resveratrol readily crosses the blood brain barrier and modulates the Wnt signalling pathway to impair glioma stem cell proliferation and inhibit angiogenesis (Cilibrasi et al., 2017)

I have been taking the BCAAs at the same time as my exogenous ketones because I have held the belief for a while now that exogenous ketones could improve drug delivery to the brain (much like the combination of aspirin and caffeine) and research already suggests that brain amino acid metabolism is more efficient in a ketotic state (Yudkoff et al., 2007). 

These branched chain amino acids compliment ketogenesis nicely and leucine and lysine in particular are strictly ketogenic amino acids which have shown potent anticonvulsant effects. Its complicated, I know, and the ratio of individual amino acids are important, so I'm still learning and testing blood ketones and blood glucose to assess efficacy.

I am particularly interested in this amino acid supplement from Dr. Heinz Reinwald, who has used it in some very interesting studies for the metabolic management of cancer and to compliment immunotherapy treatments such as in the study below.

Amino acid product and study:

https://www.drreinwald.de/fileadmin/media/downloads/MAP-Product_Info-Basic-E-Web.pdf


http://thescipub.com/abstract/10.3844/ajisp.2016.91.98


IMG- Glucogenic and Ketogenic amino acids:
https://en.wikipedia.org/wiki/Gluconeogenesis

The effects of all this, and nutritional ketosis in general, can be similar to that of the 'ketogenic diet pill' developed by researchers in Japan. The drug, sitipentol, works primarily by enhancing central Gaba neurotransmission and by inhibiting lactate dehydrogenase, an important enzyme involved in the energy metabolism of neutrons (Sada et al., 2015)

IMPORTANT!!! In cancer, lactate dehydrogenase expression is enhanced as a result of the Warburg Effect (Hirschhaeuser, Sattler, and Mueller-Klieser, 2011) so sitipentol could indeed be very useful not just for seizure control of drug resistant epilepsy, but also to compliment a metabolic protocol for cancer management to take advantage of this metabolic defect. 


IMG- Targeting Lactate Dehydrogenase A inhibits tumourigenesis and tumour progression in mouse models:
(Xie et al., 2014)
The side effects could be irritating, as with other anticonvulsants, but if you have active cancer the pay-off would be worth it in my opinion and I would take the drug in a heartbeat if I ever have a recurrence. It could be taken in cycles. I have back up plans as I have mentioned a few times, and this is near the top of my list of things I would add to my protocol to hit the cancer hard if the situation arises (hopefully not). 

I believe it would likely be effective at therapeutic doses that go beyond seizure control. I would even be more comfortable taking stiripentol than metformin for brain cancer management even though I think they both show great potential. I would simply be more confident of stiripentol offering the specific neurological effects I would be hoping for despite the side effects. I am not entirely convinced that metformin crosses the blood brain barrier at appreciable amounts despite its ability to lower blood glucose so I see sitipentol as being potentially more suitable for brain cancer specifically in theory. It just makes sense to me.


Stiripentol by Diatomit enhances beneficial effects of the therapeutic ketosis for cancer management by inhibiting lactate dehydrogenase and offers neuroprotection and increased seizure threshold by enhancing central Gaba neurotransmission: http://www.diacomit.eu/en/64-check

I had already undertaken extensive research into leucine after learning about its very promising results for drug resistant epilepsy in animals. I wrote a long article on this a while ago, but it was deleted which is a little frustrating, however there is a decent summation here of the potential of these ketogenic amino acids, even in isolation for seizure control.- https://www.epilepsy.org.uk/news/news/amino-acid-good-rescue-medication-64819

Supplementation with L-carnitine may be especially useful for patients taking valproic acid (Epilim) as an anticonvulsant because it can result in hormonal dysregulation in both females AND males. These effects in males are rarely documented or even discussed. Men taking VPA display significantly lower free carnitine/total carnitine but it also makes your sperms weaker swimmers (lower motility), lowers testosterone, and raises insulin and C-peptide concentrations (YIKES!) (Røste et al., 2005)

Carnitine also aids fatty acid metabolism of course being an essential cofactor required for long chain fatty acids to enter mitochondria. It aids oxidation of palmitic acid (Seim, Kiess and Richter, 2002) so one could potentially argue (I don't know, just a theory) that maybe that if this palmitic acid is used and not stored as body fat (which would promote systemic inflammation), that these studies suggesting palmitic acid promotes carcinogenesis (Pasqual et al., 2017) may be invalidated from a well constructed dietary perspective. It is also worth noting that the study looked at CD36, which is a fatty acid receptor for oxidised low density lipoprotein (the 'bad' cholesterol), which is often linked to atherosclerosis (Endemann et al., 1993) and shouldn't be a problem on a well structured ketogenic diet. Quite the opposite in fact.


IMG- Oxidation of fatty acids: carnitine (Flanagan et al., 2010)

People have different opinions on this, and it is likely that it is actually the ratio of LDL cholesterol and HDL cholesterol is more important or simply HDL on its own (if its too low this is the main problem it seems). On a well structured ketogenic diet LDL cholesterol is unlikely to change much (it may be a little elevated but particle size is the important consideration) but high density lipoprotein (the 'good' cholesterol), usually increases and insulin is normalised. 

This would mean that CD36 is unlikely to be expressed to respond, forming a 'foam cell' as shown below. This is called a foam cell because macrophages are recruited to the location of these fatty deposits on blood vessel cell walls. It is a pro-inflammatory response causing the cell to be filled with lipids and this action creates a 'foamy' appearance. 


IMG- Foam Cell https://en.wikipedia.org/wiki/Foam_cell
A well structured ketogenic diet is anti-inflammatory and also is unlikely to increase thrombosis and platelet aggregation. Risk factors for cardiovascular disease for example are actually improved being on a ketogenic diet, as is the lipid profile as a result. The ketogenic diet improves triglyceride levels, HDL, and LDL particle size- measures that have been seen as indicating risk. More information with a comprehensive list of references can be found here:



IMG- (Lüscher et al., 2014)

IMG- https://www.spectracell.com/clinicians/products/lpp/

The ketogenic diet is about using fat for energy and it is excess carbohydrates and trans fats which will cause this type of fat to be stored, creating inflammatory responses. I remain unconvinced that palmitic acid from foods such as ghee and coconut oil will promote carcinogenesis, especially when the fatty acid profile is balanced appropriately and the diet is personalised. Palmitic acid from grass fed and grain fed animals may also be different of course, just a thought. I am no expert of course (I'm always learning, nobody is a true expert), but the basic idea seems to make sense to me.


IMG- (St-Pierre et al., 2017)
Other anti-epileptic drugs have similar issues. As with everything though, it is always my belief that we can adjust these variables to bring endocrine functioning back to normal parameters AND allow the drugs to do exert their positive effects IF it is working for the patient to maintain seizure control. I was on VPA (Epilim) at one point when I took AEDs, and it does have survival benefits, but it is my firm belief that any micronutrient deficiencies the medication causes and any negative hormonal responses must be accounted for to achieve the best results not only for seizure control, but also quality of life and potential survival for improved survival.

Maybe I'll have amazing cognitive abilities and be superhuman in some way. It would be good to just feel more normal as I still feel like crap a lot of the time. Telekinesis would be pretty fun though or the ability to read a whole book on a complicated subject in a single day. Kind of like Doctor Strange, that was a cool film, enjoyed it. I like superheroes with intelligence rather than the meathead types.


IMG- http://www.twincities.com/2016/11/03/doctor-strange-review/

References:

Acharjee, S., Boden, W.E., Hartigan, P.M., Teo, K.K., Maron, D.J., Sedlis, S.P., Kostuk, W., Spertus, J.A., Dada, M., Chaitman, B.R. and Mancini, G.J., 2013. Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: a post-hoc analysis from the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation). Journal of the American College of Cardiology62(20), pp.1826-1833.

Cilibrasi, C., Riva, G., Romano, G., Cadamuro, M., Bazzoni, R., Butta, V., Paoletta, L., Dalprà, L., Strazzabosco, M., Lavitrano, M. and Giovannoni, R., 2017. Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway. PLOS ONE12(1), p.e0169854.

Endemann, G., Stanton, L.W., Madden, K.S., Bryant, C.M., White, R.T. and Protter, A.A., 1993. CD36 is a receptor for oxidized low density lipoprotein. Journal of Biological Chemistry268(16), pp.11811-11816.

Flanagan, J.L., Simmons, P.A., Vehige, J., Willcox, M.D. and Garrett, Q., 2010. Role of carnitine in disease. Nutrition & metabolism7(1), p.30.

Hirschhaeuser, F., Sattler, U.G. and Mueller-Klieser, W., 2011. Lactate: a metabolic key player in cancer. Cancer research71(22), pp.6921-6925.

Jin, J.X., Lee, S., Taweechaipaisankul, A., Kim, G.A. and Lee, B.C., 2017. Melatonin regulates lipid metabolism in porcine oocytes. Journal of Pineal Research62(2).

Jirapinyo, P., Kankirawatana, P., Densupsoontorn, N., Thamonsiri, N. and Wongarn, R., 2004. High plasma branched-chain amino acids: aromatic amino acids ratio in children on the ketogenic diet: a mechanism in controlling epilepsy. JOURNAL-MEDICAL ASSOCIATION OF THAILAND87(4), pp.432-437.


Lüscher, T.F., Landmesser, U.L.F., von Eckardstein, A. and Fogelman, A.M., 2014. High-density lipoprotein. Circulation research114(1), pp.171-182.

Pascual, G., Avgustinova, A., Mejetta, S., Martín, M., Castellanos, A., Attolini, C.S.O., Berenguer, A., Prats, N., Toll, A., Hueto, J.A. and Bescós, C., 2017. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature541(7635), pp.41-45.

Prospective Studies Collaboration, 2007. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. The Lancet370(9602), pp.1829-1839.


Røste, L.S., Taubøll, E., Mørkrid, L., Bjørnenak, T., Saetre, E.R., Mørland, T. and Gjerstad, L., 2005. Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy. European journal of neurology12(2), pp.118-124.

Sada, N., Lee, S., Katsu, T., Otsuki, T. and Inoue, T., 2015. Targeting LDH enzymes with a stiripentol analog to treat epilepsy. Science347(6228), pp.1362-1367.

Schwalb, M. et al. 2016. Clinical Observation of a Novel, Complimentary, Immunotherapeutic Approach based on a Ketogenic Diet, Chondroitin Sulfate, Vitamin D3, Oleic Acid and a Fermented Milk and Colostrum Product. American Journal of Immunology. Vol 12(4). pp.91-8.

Seim, H., Kiess, W. and Richter, T., 2002. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults. Metabolism51(11), pp.1389-1391.

St-Pierre, V., Courchesne-Loyer, A., Vandenberghe, C., Hennebelle, M., Castellano, C.A. and Cunnane, S.C., 2017. Butyrate is more ketogenic than leucine or octanoate-monoacylglycerol in healthy adult humans. Journal of Functional Foods32, pp.170-175.


Xie, H., Hanai, J.I., Ren, J.G., Kats, L., Burgess, K., Bhargava, P., Signoretti, S., Billiard, J., Duffy, K.J., Grant, A. and Wang, X., 2014. Targeting lactate dehydrogenase-a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell metabolism19(5), pp.795-809.

Yudkoff, M., Daikhin, Y., Melø, T.M., Nissim, I., Sonnewald, U. and Nissim, I., 2007. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu. Rev. Nutr.27, pp.415-430.



Friday, 9 December 2016

Future endeavours, talks, societies, ketosis and mood stabilising drugs.

Ok, so I haven't updated for a while which isn't ideal as I like to try and share what I've been up to lately. My shyness gets the better of me sometimes as well as that voice in my head that constantly says I'm never good enough and I don't deserve anything good to happen so why am I still doing well when others have tried their very best and they are no longer around. I know that I like to push things and think outside the box with every little thing that I try to be happy and to continue to keep the cancer beast away while controlling the epilepsy, but despite feeling very content I feel there is still something missing. Other days I feel deliriously happy for no reason, its just cool being alive and you realise what a gift that is, just feels like a selfish thought at times but keeps me sane.

I've lost a lot of friends to brain cancer recently and it makes me feel numb because the sad fact is that I am getting used to hearing sad news. Personally I have countless backup plans of novel approaches I have been researching that compliment metabolic approaches to managing this disease should the worst ever happen in future...ever the optimist eh? ;)

I am well aware of the effect of different emotional states on physiological systems so keeping my thoughts and feelings in check is something I definitely prioritise. It is of course partly why the placebo effect exists and why there is even a science dedicated to how our emotional state changes our biology. I don't get stressed, eustress yes but not distress.

How emotions are mapped in the body.
https://www.sciencedaily.com/releases/2013/12/131231094353.htm

"When under stress, cells of the immune system are unable to respond to hormonal control, and consequently, produce levels of inflammation that promote disease. Because inflammation plays a role in many diseases such as cardiovascular, asthma and autoimmune disorders, this model suggests why stress impacts them as well." https://www.sciencedaily.com/releases/2012/04/120402162546.htm

Eustress and distress- adapted versions of the Yerkes–Dodson curve for a difficult task https://www.researchgate.net/figure/236527629_fig3_Figure-3-Alternative-Presentation-of-Yerkes-Dodson-Curve-for-Difficult-Tasks-direction
https://www.projecttimes.com/articles/managing-stress-in-project-management.html

There is still no detectable sign of cancer on MR Spectroscopy but I believe this is a disease that needs to be managed indefinitely. I am often too fearful to completely relax, but at the same time being proactive brings me comfort.

This actually reminds me that I need to try and get hold of Innovate Pharmaceuticals to see if they can answer a few queries about their 'world's first' truly soluble liquid aspirin product which has incredibly promising applications for brain cancer treatment. I made a series of videos related to this on my Youtube channel so I could teach myself a bit more and share what I have learned. It is proposed that this specific product will be fast tracked into clinical trials as the safety profile is well established and preliminary data is so compelling.

I mentioned this in my second video on the subject here (2/3):


More recently I have been working on a few little projects since my last post, some have been more successful than others. I must admit I feel pretty frustrated at the lack of progress I am experiencing relating to my Research Project at university. I am focusing on a complex area of course with many differing opinions so it was never going to be straightforward but I am determined to succeed. It will require a lot of patience and some degree of persistence to push this through I imagine. I submitted my proposal at the start of this academic year and things have been progressing even if it has been stagnant at times. The research involves combinations of ketone esters and different mood stabilising drugs tested on glioblastoma cell lines in vitro.

beta-Hydroxybutyric acid. https://en.wikipedia.org/wiki/Beta-Hydroxybutyric_acid

Mood stabilising drugs can act as HDAC inhibitors.
Synergistic benefits with the ketogenic diet have yet to be explored to my knowledge.
https://www.scienceopen.com/document_file/f6db0986-f342-468f-8f68-948b47bfbbe7/PubMedCentral/f6db0986-f342-468f-8f68-948b47bfbbe7.pdf


(Left) the inhibition of histone deacetylases (hDACs) causes both transcriptional
and non-transcriptional effects, leading to profound alterations in cell homeostasis. Middle: the re-acetylation of histones upon hDAC inhibition stimulates gene transcription. (
Right) As a result of hDAC inhibition, NKG2D ligands (NKG2DLs) such as MhC class I-related chain A and B (MICA/B) or uL16-binding proteins (uLBPs) are upregulated, rendering glioblastoma multiforme (GBM) susceptible to recognition and lysis by natural killer (NK) cells. 

The whole point about being back at university is so that I can do my own research to add to the metabolic jigsaw of these approaches. I feel as though I need to contribute by having my own research paper published on this to spread the word about my ideas and findings from the many theories I have that make logical sense based on what we already know and understand. My brain never shuts up, its constantly thinking and trying to solve problems. I'm a problem solver and always have been, obstacles are to be overcome, they are no dead ends. If I don't know something I will make sure I know it and I'm not afraid to admit ignorance about even the most basic subjects. I genuinely believe that true intelligence is realising how stupid you are.

Speaking of problem solving, I am experiencing a certain amount of trepidation as we come closer to the date of the Metabolic Therapeutics Conference I have been invited to speak at in February. I feel truly humbled to be doing this and part of me thinks I don't deserve to be there when there are so many people speaking who I have admired greatly and have inspired me to experiment with their work and ideas on my personalised path to managing my disease and the epilepsy I acquired as a result from a messy brain haemorrhage.

Details of the conference can be found here: http://metabolictherapeuticsconference.com


My talk will be titled- 'Beyond Ketosis: Managing Anaplastic Astrocytoma and Brain Tumour Related Epilepsy with Metabolic Therapies.'

A bit of a mouthful, but I feel it describes my story well in a scientific way. Difficult to be concise with complicated subjects. I am a little anxious I must admit. I seriously need to get over this shyness, but it comes from a feeling of wanting to be a perfectionist and that nothing I do will ever be good enough. This is both a strength and a weakness as it motivates me to 'push the envelope' and see what novel approaches to the ketogenic diet I can come up with to optimise this approach for my personal requirements.

Biochemical individuality (more specifically nutritional individuality) is very important I feel, its just a shame I can't afford all of the lab tests I wish I could have to test a few more theories. I will always take calculate risks of course, nothing crazy. I was skeptical of the ketogenic diet from day 1 and the initial idea was to manage the epilepsy better as the medication wasn't working well and my quality of life was suffering. Thankfully my version of the diet worked well for me, I don't know if it will work for others but I do believe some aspects of it might when you look closer at brain cancer metabolism and human physiology.

On a completely separate note (well, not entirely), I have had some frustrations with exercise once more as the work has piled up. I get into nice routines where I start to get fitter but then my seizure threshold lowers as I progress. Hard to tell whether its a nutrition issue, sleep, or work load at university, but I'll get the answer soon I'm sure. Because the epilepsy was initially caused by my brain haemorrhage it can even be more complicated than 'tradional' brain tumour related epilepsy. Mine is a complex type of 'reflex epilepsy' caused by damaged nerves that will never fully heal. I adopt the plaster over a wound approach using diet, supplements, maintaining stable emotions and getting good quality sleep.

Being able to run now is a welcome progression so I can't get too dispirited about this. Yes, it is quite a conundrum and something I need to play around with to work out the most suitable approach but I'll find a way as I always do, I'm just keen to not make mistakes of forcing myself to do it at innapropriate times (for example after sunset, which is quite early at this time of year).

http://www.headway.ie/publications/introduction-to-the-brain/
I have some localised brain damage that runs quite deep accompanied by haemocidirin from the brain haemorrhage resulting from what was a very vascular brain tumour. When blood rushes to the area too quickly or the internal environment changes by any other means I can get increased seizure activity. I have learned how to manage this effectively but at times this can be a tricky balancing act. 
http://koalasleepcenters.com/tmj-disorder/
To complicate matters further my operation to remove most of the tumour involved cutting through tissues and bone in line with the temporomandibular joint (TMJ). This means the area is still fairly sensitive 3 1/2 years on. There are however unexpected benefits from this in terms of understanding seizure triggers and its great for understanding physiology. ;) Silver linings...

Moving on... I had the pleasure of attending an event with Yes to Life a few weeks ago which was pretty special as I got to meet Patricia Daly and Travis Cristofferson whom I have tremendous respect for. If you haven't read their excellent books you really should.


I am greatly encouraged that I was able to signpost the event to some of my friends at university who are all studying nutrition. We are starting to gather some real momentum to educate other students and staff about ketosis and the many applications of metabolic therapies. Unfortunately students on my particular course (Human and Medical Science) are not as enthusiastic as we don't tend to even cover nutrition in sufficient context. We skim over nutrigenomics and metabolic biochemistry, it is far from comprehensive and the foundations are based on some flawed data with very little coverage of fatty acid metabolism. We are even still being taught by some that the brain can only use glucose for energy which is certainly not true. Energy from fatty acids actually acts as a far more efficient fuel source for the brain, heart, and other organs and they thrive on it.

I am delighted to announce that my friend Isabella and I have set up a Ketogenic Diet Society at my university to discuss the mechanisms, history, and applications of the diet and to dispell a few persistent myths relating to saturated fat, cholesterol, red meat and any other questionable topics that pop up from time to time when discussing nutrition. Isabella is very knowledgable and has started to shake things up on her course by provoking further thought to challenge outdated information that is still being taught. This is no easy feat as I realised last year so as a result I have adapted my approach by engaging in respectful, quite and considered conversations with others who have differing views, even if they speak in a provocative tone. Your argument is stronger if you remain calm and lay out all the evidence.

With the society I am very keen to promote real food in the eating areas at university. Junk food is very convenient, students and lecturers are some of the unhealthiest people I have known with only a few rare exceptions. I may sound as though I am bashing the university, but it has a number of bonuses. For a start, it is the place where I first learned about the ketogenic diet before my diagnosis. Admittedly they appear to have regressed somewhat with the teaching, but there is no reason why we can't go back to move forward. I would also say that the university allows people to speak out and have a voice, being able to set up a ketogenic diet society and have these conversations is a great thing.

Overall despite my perhaps overly introspective thoughts on life, the universe and everything in it, I feel reasonably pleased with how things are going and I feel content, satisfied with my lot.

I have recently focused more attention on researching mood stabilising drugs as an adjunct treatment for brain cancer with a secondary interest of fasting with ketogenic amino acids. I have been playing around with leucine and lysine which are strictly ketogenic. If we can structure appropriate, considered protocols for these agents and manipulation of amino acids we could see some very interesting results. The promise of mood stabilising drugs for brain cancer management (significantly improved survival) is nothing new but it is still something that is under-utilised and the benefits are underappreciated. You can't make much money from these of course.

Ketogenic and glycogenic amino acids. Some are both of course.
https://amit1b.wordpress.com/the-molecules-of-life/about/amino-acids/

Going back to the importance of the amino acid profile of ketogenic diets, this reminds me of the 'hyperketogenic diet' approach proposed by Dr. Heinz Reinwald. I believe this could have even greater relevance for pancreatic cancer, whereby protein requirements would likely need to be reduced even further so to make up the deficit amino acids that are not providing energy for the tumour to grow would be supplemented. I believe he also uses Bravo yoghurts to support gut health, which is critical for immune system support and overall healthy functioning. Keeping those trillions of bacteria in the gut happy is always worth prioritising. I would need to look into this more but it appears to make sense. I'm obviously going to be skeptical of anything at first before I know everything about it and then I will probably remain skeptical until I see something that truly amazes me but its certainly very interesting.

Bravo yoghurt- https://www.bravo-europe.com

Details of the 'hyperketogenic diet'- I wouldn't normally share articles from other blogs, but the background is interesting. Always look into information written about in articles very stringently. This definitely provokes thought however.- https://bisforbananascisforcancer.wordpress.com/2014/01/23/fulda-conference-4-master-amino-acid-pattern-map-and-the-hyper-ketogenic-diet-in-cancer-and-epilepsy-dr-heinz-reinwald/#more-2358

Interestingly I have often suspected that in the early stages of my ketogenic approach I may have benefited greatly from being on such high doses of two anti-epileptic drugs- Sodium Valproate (Epilim) and Levetiracetam (Keppra). As well as being established drugs that have proven efficacy, these drugs are the most commonly prescribed for brain tumour related epilepsy largely due to the clear survival benefits. Incredibly, while this is clear, it is not really communicated or even understood by most neurologists I contacted at the time. They also did not understand all of the micronutrient deficiencies caused by continuous use of these drugs that can be easily remedied through supplementation of certain nutrients.

I have written about this previously so I won't go over it too much but ironically many of these micronutrients are actually anticonvulsive so supplementation to lessen the inevitable side effects of the drug should be standard procedure in my opinion. It is important to note that Epilim and Keppra are mood stabilising drugs because there is a clear pattern that emerges when you take a closer look at the potent anti cancer benefits of this class of drugs and their mechanisms of action in different types of brain cancer and neurodegenerative disease.