Wednesday, 23 August 2017

DCA and glioma

Human glioblastoma patients require at least a 6.25 mg/kg oral, twice-a-day dose of DCA (Dichloroacetate) to inhibit PDK (Pyruvate dehydrogenase kinase) and kill cancer cells as indicated in the study below (5).

http://artemisinin.pbworks.com/f/Metabolic+Modulation+of+Glioblastoma+with+Dichloroacetate.pdf



A reliable source of DCA can be found here:

https://www.dcalab.com


It comes in tablet form as well as a powder.



The main problems I see here is that you would need to have enough of the product to get the appropriate therapeutic dose and it is not cheap!


Simple background as to why DCA might be useful:

As many reading this will already know, most tumours display unique metabolism described as the 'Warburg Effect' which has long been associated with the resistance to apoptosis which characterises cancer. Even in tumours where glucose is maybe not the primary fuel, it appears to still play a key role as a major energy source. 

the Warburg Effect (9)


Cancer is clever, there are parallels with Darwinian natural selection (1), meaning it can adapt to use different fuels in the absense of others. With this in mind, I believe it is key to note that the best result is unlikely to come from a monotherapy approach. Nevertheless, this glycolytic phenotype in most cancers appears to be a common denominator and gives reason as to why all these molecular abnormalities occur, and as a result lead to defective mitochondria. The good news is that research suggests this suppression of mitochondrial function we see in cancer may be reversible with DCA at therapeutic doses.

Mitochondrial physiology (8)


DCA exerts its anti-cancer effects by inhibiting an enzyme called PDK (Pyruvate Dehydrogenase Kinase), a mitochondrial enzyme that is activated in a variety of cancers. Inhibition of PDK with DCA shifts the metabolism of cancer cells from glycolysis to glucose oxidation (7). As a result we would hope to see restoration of normal mitochondrial function and suppression of mitochondrial dependent apoptosis.



As I say, typically nothing works as effectively in isolation as with a multi-modal approach. Personally I would recommend a low carb, fasting mimicking diet, time restricted feeding and/or longer periods of just water fasting alongside DCA. 

Why?... 

Well, I get lots of people asking about how some tumours appear to be able to use fatty acids for energy after reading certain studies showing up regulation of lipogenic enzymes in cancer cells (4). It is well established that deregulated lipogenesis plays an important role in tumour cell survival (3) and as a result, FASN (fatty acid synthase) is also a therapeutic target. However... 

I wouldn't worry about this in the context of a continuous ketotic state or through implementation of a low carb diet and I will tell you why. Despite the fact that this phenomenon exists, research shows that the expression of FASN is highly dependent on nutritional conditions in lipogenic tissues. 

'FASN-catalysed endogenous FA biosynthesis in liver and adipose tissue is stimulated by a high carbohydrate diet, whereas it is suppressed by the presence of small amounts of FAs in the diet and by fasting.' (2,6) 




References

1. Greaves, M. and Maley, C.C., 2012. Clonal evolution in cancer. Nature481(7381), p.306.

2. Katsurada, A. et al. Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in liver. Eur. J. Biochem190, 427–433 (1990).

3. Mashima, T., Seimiya, H. and Tsuruo, T., 2009. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. British journal of cancer100(9), p.1369.

4. Menendez, J.A. and Lupu, R., 2007. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nature reviews. Cancer7(10), p.763.

5. Michelakis, E.D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E., Maguire, C., Gammer, T.L., Mackey, J.R., Fulton, D. and Abdulkarim, B., 2010. Metabolic modulation of glioblastoma with dichloroacetate. Science translational medicine2(31), pp.31ra34-31ra34.

6. Sul, H. S. & Wang, D. Nutritional and hormonal regulation of enzymes in fat synthesis: studies of fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase gene transcription. Annu. Rev. Nutr. 18, 331–351 (1998).

7. Sutendra, G. and Michelakis, E.D., 2013. Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology. Frontiers in oncology3.

8. Wallace, D.C., 2012. Mitochondria and cancer. Nature reviews. Cancer12(10), p.685.

9. Vander Heiden, M.G., Cantley, L.C. and Thompson, C.B., 2009. Understanding the Warburg effect: the metabolic requirements of cell proliferation. science324(5930), pp.1029-1033.
  


Thursday, 22 June 2017

Analytics for my cryotherapy project.

I had a training session today at university with the Firstbeat Bodyguard, a sophisticated device I will be using to track activity and various health markers as I embark on my month long Whole Body Cryotherapy experiment. 

The equipment is also designed to assess how appropriate my diet and lifestyle is for my specific requirements alongside additional monitoring of sleep and how well I recover from personalised workouts throughout the duration of the experiment. It will be particularly interesting for me to assess just how much of my energy expenditure in each 24 hour period comes from fat and how this varies over the course of the day. 

I am looking forward to sharing more as I progress on this journey of discovery. 








Some examples of data collection:

http://www.henkpeteroonk.nl/en/firstbeat-bodyguard-2

http://www.wearethecity.com/professional-women-manage-stress-recovery-avoid-burn-firstbeat-life-assessment-insight-thrive-trial/






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.

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