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.




Wednesday 26 October 2016

Metabolic Therapeutics: the science behind exploiting weaknesses in cancer metabolism.

In the third episode of the Beating Brain Cancer podcast we had the great pleasure of interviewing Dr. Angela Poff, Research Associate in the Department of Molecular Pharmacology and Physiology at the University of South Florida.


Dr. Angela Poff


Dr. Poff works in the Laboratory of Nutritional and Metabolic Medicine under the mentorship of Dr. Dominic D'Agostino. Her research focuses on the development and testing of non-toxic metabolic therapies for cancer and neurological disorders.

Dr. Poff's research focuses primarily on vivo research using rodent models with metastatic cancer derived from human glioblastoma cell lines.

The aim of her work is to observe the effects of nutritional ketosis, exogenous ketones and hyperbaric oxygen therapy and outline the underlying synergistic anti-cancer mechanisms behind these treatments.

The audio recording of this interview is available here: http://www.braincanceroptions.com/metabolic-therapeutics

Wednesday 19 October 2016

Cannabinoids and Cancer: a hot topic often surrounded by controversies

I recently had the privilege of interviewing Dr. Wai Liu at St. George's University Hospital to talk about cannabinoids and cancer. More details of the interview can be found on my website here:

Monday 26 September 2016

Exercise updates, photodynamic therapy and the iKnife.

Exercise was a huge seizure trigger for me since acquiring brain tumour related epilepsy. Over time my seizure threshold has improved thanks to a high DHA ketogenic diet. Yesterday I was able to run for the first time in 4 years. I managed 20 minutes plus a light resistance workout. Today I ran 30 minutes without stopping at a decent pace. 


I never thought this would be possible when I look back at where I've come, suffering those horrible grand mal seizures and now being on no medication with complete seizure control. 

Never forget that our brains are made of fat and cholesterol. As I have written on several occasions, in and around malignant brain tumours we see dysregulated lipid composition when compared to healthy, disease free brains. This is often how neurosurgeons actually identify tumour tissue for resection, as described from the study below and from use of the iKnife, which identifies malignant tissue and can be combined with a form of photodynamic therapy. 

Photodynamic therapy- 5-ALA: http://www.cam.ac.uk/research/news/glow-in-the-dark-brains-aid-tumour-surgery
The tissue that 'glows' represents diseased tissue and the differences in lipid composition are clear. The smoke coming from the iKnife during resection of the tumour can analyse the lipid composition of tissue using a mass spectrophotometer http://publishing.rcseng.ac.uk/doi/full/10.1308/rcsbull.2016.88


Epilepsy and neurodegerative diseases can all me managed more effectively with manipulation of dietary fatty acids. I believe this has been an essential part of my strategy to manage my disease and the epilepsy I have acquired as a result. I have been fine-tuning this approach over time and I have regular blood tests to monitor the efficacy of this approach. I wrote about this in more detail in my post on fatty acids and brain tumours which can be found here: http://mybraincancerstory.blogspot.co.uk/2016/07/fatty-acids-and-brain-tumours.html 




The iKnife:







Sunday 7 August 2016

Mornings are fun.

Despite exercise being a seizure trigger I enjoy my morning walks. Its at a pace which doesn't overstimulate my brain and I find it very calming. Walking allows me to reflect and to enjoy natural beauty. We have so many beautiful green spaces in this country and its a beautiful, sunny day today. The shorts will be on later and I'll do some sunbathing to top up the vitamin D. :)


Friday 5 August 2016

Aspirin for brain cancer. Evaluating efficacy

Some new videos on my Youtube channel evaluating the efficacy of different forms and doses of aspirin for brain cancer management and as a potential anticonvulsant:

I'm trying to get used to recording presentations using my computer. I'm not sure how to edit videos yet without hassle but I tried my best here. I hope people find this interesting, there are 3 videos in the series.

Aspirin for brain cancer- part 1

Aspirin for brain cancer- part 2



Aspirin for brain cancer- part 3




Wednesday 20 July 2016

Thursday 14 July 2016

New insights from a new website?


I have created a website to provide a place to share data I have collected to support a metabolic protocol to managing brain cancer. I hope that this information can empower patients by providing the resources they need to take control of their treatment, whatever that may be.

I have decided to name it:

'Metabolic Therapy Resources for Brain Cancer Management'

This website will grow and evolve as I gather more information and when I have time to update it. Feel free to contribute with additional materials others might find useful in their search for evidence based metabolic approaches to this devastating disease. Please share with anybody you know who has been diagnosed with a brain tumour of any grade and type.

Monday 11 July 2016

Fatty acids and brain tumours


After a recent study came out suggesting that brain tumours can adapt and use fatty acids for energy I thought I would attempt to clear up a few things concisely and succinctly. I'm writing a research proposal at the moment that I'm very excited about if my plans ever come to fruition from sufficient funds but firstly I wanted to tackle this confusion over the fatty acid study that came out recently entitled; 

'Fatty acid oxidation is required for the respiration and proliferation
of malignant glioma cells.'




Firstly I would like to point out that the title is a misleading half truth which validates one very important point but does by no means conclude that all fats are created equal. I could point out several questionable aspects of the study design, however I cannot fault the actual investigation, more the application and the sweeping conclusions made that I find a little irresponsible and misleading. The conclusions by no way invalidate a ketogenic diet, but the findings definitely support a well structured ketogenic diet and validate the significant benefits that come with ensuring fatty acids are balanced appropriately.

I found some of the conclusions equally baffling, including this one. Also strangely no real mention of glutamine even though one of the study aims was to identify the metabolic fuel requirements of human glioma cells.:


They mention how the fatty acid binding drug etomoxir can be used therapeutically to inhibit fatty acid oxidation and reduce proliferation and viability of mouse glioma-initiating cells which is certainly an interesting finding and I applaud them for that, however I question the safety of this drug in terms of the detrimental effect is has on the liver over time and the possible depletion of DHA which I will explain has countless anti tumour benefits.

The drug could potentially be a useful strategy for late stage disease where there is little time to intervene without this pharmalogical approach. It would be wrong for me to disregard this approach completely as the findings to support use of this drug in vivo are certainly interesting despite my reservations.





In my opinion they should have renamed the study

'Fatty acid oxidation primarily via n-6 PUFAs such as linoleic acid can be required for the respiration and proliferation of malignant glioma cells.'



Let's explore some of these misleading statements about all fats through investigation of lipid distribution in both normal, and neoplasms of the brain:

- In the brain, lipids are major structural components with fatty acids making up about 50% of the total mass of neural membranes.

- Long chain PUFA (polyunsaturated fatty acid) such as docosahexaenoic acid (DHA, an omega 3 fatty acid) and arachidonic acid (AA, an omega 6 fatty acid) are abundant in the brain, constituting close to 20% of the dry weight of the brain, including 6% for AA and 8% for DHA. Just imagine, this doesn't even include the CFS (cerebro-spinal fluid) which probably contains quite a lot of DHA I would think.

IMG- http://www.slideshare.net/SpinalCordCom/infographic-17-interesting-facts-about-the-human-brain


The type of fat used in the study is linoleic acid, which is an omega 6 fatty acid that goes through conversion to arachidonic acid. An imbalance of docosahexaenoic acid (an omega 3 fatty acid) and arachidonic acid in favour of omega 6 is a huge problem for normal neurological functioning.

IMG- https://en.wikipedia.org/wiki/Linoleic_acid


IMG- http://www.ncbi.nlm.nih.gov/pubmed/23981365


- Brain turnover of AA and DHA is closely linked and maintenance of a favourable or homeostatic DHA:AA ratio is critical for normal brain function.

- Crucially, deprivation of omega 6 PUFAs is shown to increase brain DHA metabolism while maintaining AA levels by down-regulating enzymes involved in its metabolism.

- It is important to note here that in a standard UK diet (SUK!) that we have at least a 15-16:1 ratio in favour of omega 6 fatty acids, which are typically inflammatory (with omega 3 fatty acids being anti-inflammatory). This is far from ideal and contributory to many health problems, particularly for the brain and heart. The optimal ratio of 3:6 is said to be 3:1 in favour of omega 6 but I try and aim for as close to 1:1 as possible for brain cancer management.

You can read more here: http://www.ncbi.nlm.nih.gov/pubmed/12442909




IMPORTANT POINT!!!!- MALIGNANT GLIOMA IS CHARACTERISED BY LIPID METABOLISM IMBALANCE


IMG- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461378/


This is actually true of most, if not ALL brain tumours, as is explored further here:
http://www.omicsgroup.org/journals/docosahexaenoic-acid-a-potential-modulator-of-brain-tumors-2167-7956.1000e119.php?aid=19902

How can we exploit this to our benefit and what does this mean?

Consider this:

- The omega 3 and 6 ratio is dramatically increased in malignant glioma, suggestion deregulation of fundamental lipid homeostasis in brain tumour tissue. - full paper available here, well worth a read: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461378/



ALTERED LIPID METABOLISM IS ASSOCIATED WITH A WORSE PROGNOSIS IN THESE TUMOURS. WE CAN CHANGE THIS WITH THE FATS WE CONSUME!!!


Think more oily fish, less bacon for a more favourable omega 3:6 ratio- IMG http://www.fourfourtwo.com/performance/nutrition/think-fast-and-fish-out-pass

Is this one potential contributory factor for the development of these tumours or a simple consequence? We may never know, but it is likely there is something we can do about this imbalance to put the odds back in our favour. I feel we are missing a trick if we do not scrutinise the fatty acid profile of ketogenic diets for the management of these tumours. If you eat nuts for example, maybe opt for walnuts that have a more favourable ratio of omega 3 and 6 compared to almonds. It would also be preferential to not cook them or to cook with olive oil as it can be oxidised. Some argue differently but I would err on the side of caution personally. For balance I will include this even though I don't necessarily agree:


Source- https://www.oliveoilsource.com/page/heating-olive-oil

It is well established that the essential fatty acids, cis-linoleic acid (LA, an omega 6 fatty acid), and a-linolenic acid (ALA, an omega 3 fatty acid), the pre-cursors of AA and DHA, respectively, have to be obtained from the diet because our bodies cannot synthesise them.

Accumulation of long chain fatty acid metabolites (like the linoleic acid used in this study) has been consistently associated with the worst survival in malignant glioma. This is nothing new, and certainly not a breakthrough, as has been suggested recently. Specifically, extensive research indicates that DHA levels are reduced by up to 50% in malignant glioma samples compared to normal brain tissue. Don't forget that some omega 6 is good and beneficial if it comes from the right sources like coconut oil for example where there are countless additional benefits. The key is the ratio and the quality of the source.

PUFA metabolism- https://openi.nlm.nih.gov/detailedresult.php?img=PMC3335257_JNUME2012-539426.001&req=4


With this in mind (linoleic acid), consider this fact:

'The decrease in DHA observed in malignant glioma was accompanied by unchanged AA levels AND A 4-FOLD INCREASE IN LINOLEIC ACID, RESULTING IN AN OVERALL INCREASE IN x-6/x-3 FATTY ACID RATIO COMPARED TO NORMAL BRAIN.

IMG- http://ebooks.cambridge.org/reading_experience.jsf?bid=CBO9781139680783&cid=CBO9781139680783d4e5810

The fatty acid composition of the diet will also have a clear effect on how the disease spreads within the brain.

'The migratory properties of malignant glioma cells can be modified by altering the ratio of AA:DHA in growth medium, with increased migration observed in AA-rich medium.'- http://www.ncbi.nlm.nih.gov/pubmed/23981365

IMG- https://commons.wikimedia.org/wiki/File:Glioblastoma_-_very_high_mag.jpg

It would be interesting therefore, if the study I am scrutinising used linoleic acid WITH a-linolenic acid (to have a balance of omega 3 and 6 fatty acids), to see how this changed cells in vitro. I predict their results would not have validated their hypothesis under these conditions. I am surprised the paper was accepted in light of this and flaws I have not even mentioned regarding flaws in their methods.

Source- http://www.fatsoflife.com/fats-and-health/fat-basics/

My next point involves what are called FATTY ACID BINDING PROTEINS- they are intracellular fatty acid binding proteins that have complex roles which I won't detail too much but I will just say for clarification that the protein involved specifically to the brain is called FABP7. It is also called B-FABP- Brain fatty acid binding protein.

'Altering the DHA:AA ratio in the culture medium affects cell migration in a FABP7 specific manner, with an increased DHA:AA ratio associated with reduced cell migration.'- HUGE POINT ONCE AGAIN!

In glioblastoma FABP7 is highly expressed at sites of infiltration and surrounding blood vessels.

IMG- http://www.jbc.org/content/285/47/37005.full


Closely observe this image and you will understand my argument completely. The whole paper is available to view so readers can dissect it thoroughly if they wish.




Is DHA (docosahexaenoic acid) the saviour for brain cancer sufferers? Well, it could certainly be part of the solution. Let's shed some light onto this...

We know that unlike the fat used in the fatty acid study appearing to lambast all fats and question the over-simplistic Warburg effect, DHA has inhibitory effects on pro-inflammatory pathways such as COX-2, which is believed to be important for cancer proliferation and invasion.

A correlation between COX-2 expression and glioma grades has been described, with one report indicating that 71% of glioblastoma tumours had >50% COX-2 positive cells compared to 44% of anapaplastic astrocytomas and 30% of low grade astrocytomas. This suggests to me that the higher grade tumours definitely need to ramp up the DHA and keep omega 6 fatty acids as low as they can safely in an attempt to correct this imbalance in order to maintain lipid homeostasis to reduce expression of COX-2.

The linoleic acid used in the study would cause a further decrease in DHA, remember that linoleic acid is actually important for tumour survival and infiltration. The study should have specifically stated that it is only certain omega 6 fatty acids in isolation, and not fatty acid oxidation in general that can drive tumour growth. I would even go as far as to say that such statements are not only misleading, but they are irresponsible and it is poor science when you do not consider your words and exclude such crucial variables.
Its all about achieving an appropriate balance of eicosanoids- http://www.nature.com/nchembio/journal/v6/n6/fig_tab/nchembio.375_F1.html



In summary:

- DHA levels are decreased in malignant glioma tumour samples resulting in a higher AA:DHA in tumour compared to normal brain tissue.

- The up-regulation of FABP7 combined with the higher relative availability of AA may thus favour tumour infiltration.

- It is conceivable that strategies aimed at correcting the DHA:AA ratio may result in the inhibition of tumour cell migration/infiltration and reduce tumour recurrence.

- The inhibitory effect of DHA on the migration of FABP7 positive malignant glioma cells in vitro lends further support to the idea that it may be possible to control malignant glioma infiltration through manipulation of the lipid environment.

- As glioblastoma tumour tissues also have elevated levels of the omega 6 PUFA linoleic acid it would be worthwhile to investigate the effect of linoleic acid on the migration of FABP7 positive and FABP7 negative malignant glioma cells.






Future proposals:

- A better understanding of the consequences of lipid alterations in malignant glioma may shed light on the mechanisms driving tumour recurrence thereby revealing new approaches for the treatment of malignant glioma.

- Neuroimaging of AA and DHA: potential for astrocytoma detection and grading.

- Analysis of the cerebrospinal fluid to determine concentration of DHA:AA

- Potential of an intravenous, balanced eicosanoid ketogenic diet with a therapeutic dose of DHA to replace chemotherapy. This may be ambitious, and may be seen as a wild claim, however I personally believe this could work as it has done for some children with drug resistant epilepsy as noted here:





http://www.sciencedirect.com/science/article/pii/S0887899414007656

and here:

http://www.epilepsy.com/article/2015/5/can-you-give-ketogenic-diet-intravenously





 So....

How do you effectively manage a brain tumour? A good start would likely be attempting to fix this clear imbalance of lipids in the brain by optimising your omega 3 and 6 ratio. The same goes for a host of neurodegenerative diseases that display similar characteristics. 

We now have already established that:

'An increase in the AA:DHA ratio has been consistently reported in malignant glioma, suggesting that tumorigenicity is associated with enhanced DHA loss/metabolism, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461378/

It has been suggested that this is...

'to the extent that brain DHA loss cannot be compensated by liver or diet.'


I would tend to disagree with that last statement, as I believe consistent monitoring via a blood spot test can help humans to replicate both the in vitro and in vivo models that have shown therapeutic benefit through dietary manipulation of eicosonoids (fatty acids). I also supplement with a high quality, high DHA fish oil when I need it at therapeutic doses and store it in a way that it is not oxidised. It is marketed at pregnant women as they typically need more DHA, like brain tumour patients!


I don't take it all the time as my diet is naturally very high in omega 3 fatty acids, but it seems to be efficacious. https://www.amazon.co.uk/Minami-Nutrition-MorDHA-Prenatal-Capsules/dp/B0041TRPLS 



Below is my latest blood test result from a recent fatty acid profile. Something is clearly working for me. You can get a comprehensive fatty acid profile yourself through www.omegaquant.com




I hope I have provided whoever reads this with a useful critique of this fatty acid study. It is important for me to stress that the study in no way invalidates a well structured ketogenic diet, quite the opposite actually. I may have seemed a little harsh, but this is more to do with the working than the study itself, which was actually fairly comprehensive and thorough despite my many misgivings about some of the methodology and claims. The study, perhaps without the researchers realising it,  underlines the importance of balancing eicosanoids on a ketogenic diet, which I couldn't agree more with. 

I wish you all good health and happiness in your lives. I have some important updates regarding my own research in the near future and I am hopeful I can continue to get more of the incredible support I have received so far. I make no money from this and I am going to be digging around for funding as I really believe in metabolic therapy and I desperately want to turn around these dysmal statistics. I'm writing up my research proposal and I will keep you updated on my progress here. Wish me luck!!