Saturday, 4 August 2018

6 months to a year to live without chemo?.... apparently. Deuterium depletion protocol for my Mother

I haven't mentioned this much, but my Mother was diagnosed with oesophageal cancer not long after my diagnosis 5 years ago. There was no cancer, let alone any disease in my family before I was diagnosed with my malignant brain tumour. All the compelling evidence that we had compiled strongly supported the idea that for her, the cancer was directly caused by alendronate, a drug she was taking for her osteoperosis. We conducted extensive research into this at the time, and were shocked with what we found. After speaking to researchers who were looking into the association between alendronic acid use and incidence of oesophageal cancer and enquiring about the type of damage to the lining of the oesophagus things became even more clear. I actually wrote about this in a blog post from a couple of years ago...

https://mybraincancerstory.blogspot.com/2016/05/meeting-my-heroes-and-learning-about.html


After treatment (chemo and radiation).... and diet change... she appeared to recover without the need for surgery. The tumour seemed to disappear after the gruelling treatments, however about a month ago we discovered she had a tumour in the colon (which has since been removed with surgery) and disease that has spread to other areas including the lymph nodes, with nodules in the lungs. This is deeply unpleasant of course.

Following a long consultation with her oncologist, we were informed that the nodules in the lungs were most likely malignant and the degree of spread was such that any treatment from here on would only be palliative and that prognosis would be poor, even with treatment. We were given a prognosis of 6 months to a year, depending on whether on not she would decide to have chemotherapy and partly dependent upon results of a lung biopsy.

She decided not to have the biopsy as prognosis would be poor either way. We could understand that a biopsy could help to determine the lineage of this disease (if they are not just 'benign' nodules- some type of fibrosis possibly from radiation 5 years ago), but prognosis either way would still be far from favourable so we agreed it wasn't necessary for the path she felt was right for her. The other issue is quality of life. If you have a 'terminal' disease and treatment (for the few who actually respond to it) aims to give a few months more life while making you ill in the process, you have to ask what the point in that is.

We decided to opt for metabolic therapies instead and say no to chemotherapy in this instance. It was an informed decision based on all the information we had and my Mother feels 'happy' with this treatment plan. She felt so ill during treatment for her last cancer, and this cancer was most likely caused by treatment from the first so it just made a lot of sense to avoid it this time. We want to treat it by building her up rather than knocking her down with 'palliative' treatment that was likely to be ineffective even for this purpose.

Why not aim high and try and do what few even dare to consider? Treating cancer with kinder treatments to restore homeostatic mechanisms and support mitochondrial function.

My Mother is a smart woman and as such is skeptical of anything I say, which I love. We had long discussions about deuterium depletion and after outlaying my case for it with the underpinning mechanisms of these treatments she was open to trying it and became convinced that this was the right path for her to follow for her. We have nothing to lose trying this and in the worst case scenario her quality of life is likely to improve.

Without hesitation, we then immediately contacted Dr. Que Collins from the Centre for Deuterium Depletion and got to work with a protocol that would be suitable for her based on her personal situation and disease state. You can find out more about the centre and the relationship between deuterium and cancer see the link below:

http://www.ddcenters.com/conditions-cancer-2-2/


The deuterium depletion protocol that she has decided to follow looks like this:

Deuterium depletion water therapy (Preventa)

Nutrient dense, low deuterium ketogenic foods

Breathing therapy

Natural light therapy

Red and near infrared therapy

Body temperature cycling

Environmental mitigation

Metabolic supplementation
Deuterium Depleted Water used in clinical trials- Preventa

Red light therapy- JOOVV
https://joovv.com
This plan will evolve as we go on and her cancer markers will be assessed at regular intervals. I have decided to document her progress and how she feels throughout this 'journey'. This is all quite significant, because she has decided to NOT opt for the standard of care (biopsy, chemo, radiation), so any response is certainly meaningful and cannot be ignored.

We hope for the best. I love my Mother with all my heart and strongly feel this is the most logical step forward. I will keep you updated on her progress.

Monday, 23 July 2018

abcam Cancer and Metabolism Conference 2018- 1/3

I recently attended abcam’s Cancer and Metabolism conference in Cambridge and realise that I haven’t written about it yet. 


In a nutshell, the event covered major aspects of metabolic transformation in cancer and attempted to highlight potential therapeutic approaches to target cancer-specific metabolic pathways. The conference allowed me to build on my existing knowledge of metabolism and metabolic signalling in cancer and introduced me to more advanced concepts, novel methods, and emerging technologies to target these pathways.

I was also introduced to a collaborative European wide research project called TRANSMIT: Translating the role of Mitochondria in Tumorigenesis. 

The angle they are taking with TRANSMIT is viewing cancer as not only a genetic, but also a metabolic disease. 

TRANSMIT Project- https://www.transmit-project.eu

Personally I think it is a metabolic disease with metabolic solutions and the genetic mutations are as a result of mitochondrial dysfunction. With healthy mitochondria it is my belief that you simply do not get cancer. However… whether it is cause or effect, the focus on cancer metabolism is a huge step in the right direction for me and I am greatly encouraged by seeing this type of event take place and to be able to have these conversations. 

The research I came across at this conference was all work that could directly be translated to the patient (‘from bench to bedside’) so I found this more engaging than most conferences I have been to. 

More and more now scientists are not only investigating the conribution of oncogenes and tumour suppressor genes (an approach which, as the primary focus over the years has been woefully ineffective), but we are also focusing on the intricate metabolic plasticity that transformed cells undergo to survive the adverse, volatile tumour microenvironment conditions. 

The mitochondria is the star player here, and rightly so, because they act as key players in cancer metabolic restructuring due to their crucial role in powering all functions of the cell by producing complex molecules for function, growth and survival. When these normal processes become aberrant, causing dysfunction, as is the case with cancer, this biosynthetic powerhouse of the cell is forced to adapt through more anaerobic respiration, and so is forced to provide energy and metabolites to the cell in different ways. 

These cells are very clever and can learn how to survive by using different substrates to stay alive and will become more resiliant with time if provided with the fuel that it needs to thrive. It will then become more able to use alternative substrates for energy as it adapts and learns, and here we have parallels with Darwinian biology. In the absence of nutrients, cancer cells can even scavenge from cellular debris in a process called ‘macropinocytosis’, so this is worth considering with any metabolic therapy, most likely it seems when necrotic tissue is a hallmark of disease as it often is with glioblastoma. That’s my opinion anyway, seems to make sense. Cancer doesn’t want to die, as a result of these metabolic abnormalities we have an occurance of mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA. 

It is my belief therefore, that more solid tumours would be most responsive to any kind of metabolic approach, as they have clear margins, are less diffuse and invasive, and as such have likely not yet progressed to being able to use multiple substrates to become more resilient to targeted metabolic therapies. More aggressive malignancies will likely require a combination approach of dietary manipulation and drugs targetting key metabolic targets in line with what the tumour’s metabolic signature may dictate. 

Electron microscopy morphology of the mitochondrial network
in gliomas and their vascular microenvironment-
https://www.sciencedirect.com/science/article/pii/S0005272810007437


As I began listening to the talks, the main research challenges became eminently clear. 

Firstly, we need to continue to learn about the bioenergetic plasticity of cancer in general. We have established that mitochondrial function and respiration play fundamental roles in the development and progression of cancer. The main challenges here are noted below numerically and although of major importance as a primary substrate for most cancers, its not all about the glucose:

1. Many malignancies have been shown to be able to utilise not only glucose, but also glutamine for generating cellular energy and provide metabolic building blocks to proliferate.

2. As stated, many cancers generate most of their cellular energy via mitochondrial respiration and oxidative phosphorylation (OxPhos). Glutamine is the preferred substrate for OxPhos in tumour cells.

3. Cancer cells are remarkably adaptable at using different substrates for fuel. They can even use metabolic substrates donated by ‘stromal cells’ for cellular energy generation via OxPhos. Stromal cells are present in the tumour microenvironment and are not necessarily malignant themselves but can provide the tumour with substrates it needs to keep growing.

4. Bioenergetic plasticity of cancer is a major consideration if we want to attempt to predict, understand and monitor a metabolic approach to treating cancer more effectively.

See below a poster displaying an outline of the work various research groups are undertaking as part of the TRANSMIT project:



How might we achieve this:

1. By targeting metabolic enzymes and coenzymes

2. Learning more about metabolic features of cancer cells in general. This can help us with therapeutic efficacy testing and biomarker discovery. 


Primary aims that I could see from this research:

1. Help to overcome chemoresistance

2. Come up with metabolic intervention strategies. 

3. Better understand the role of the mitochondria in cancer initiation and progression. 

4. Understanding of metabolic signatures of tumours that may respond to the ketogenic diet or specific nutrient deprivation diets. 


Dietary and drug strategies covered:

1. An energy restricted ketogenic diet. (high fat, low carb, adequate protein)

Most cancer cells thrive on glucose as major energy source and partly posess dysfunctional mitochondria leading to a reduced ability to metabolise fat. This approach is being studied as an adjunct to the standard of care. It may reduce tumour growth and prolong survival. 

2. Amino acid deprivation diets.

- Glutamine (protein restriction, temporary inhibition of enzymes involed likely more suitable)
- Methionine, cysteine

3. Fasting and diets that mimic a fasted state.

4. Drugs and drug targets

- Glutaminase inhibitors as a major target for the majority of cancers. For brain cancer perhaps more important in neuroblastoma (considered a real glutamine hog) and tumours that use up glutamine as the primary or major fuel alongside glucose as major substrates.

- Tryptophan degrading enzymes (overcoming tumour immune resistance)

- Citrin blockers- citrin is upregulated in multiple cancers.

- Targeting other novel metabolic pathways (aspartate, folate, serine, sapienate)

- Dichloroacetate (DCA)- PDK inhibitor (Pyruvate dehydrogenase kinase)- mitochondrial enzyme activated in a variety of cancers. Pyrimidine biosynthesis and growth of SDH (Succinate dehydrogenase) deficient cells is also inhibited by this drug.

- Biguanides and Kinase Inhibitors (KI)- induce opposing effects on key metabolic pathways that fuel cancer (eg. inhibition of mTOR. MTOR regulates mRNA translation initiation). 


Areas of focus: TRANSMIT

1. Cancer bioenergetics of different tumours. 

I have MR Spectroscopy, for example, and we can identify different metabolic signatures pertaining to different types of brain tumour fairly accurately from this. There may be some problems looking at areas where there is brain damage however, showing false positive results as you may see high signalling activity. It can sometimes be difficult to differentiate between malignant activity and areas of brain damage. 

2. How metabolic factors influence how cancer cells adapt to survive and proliferate could identify mitochondrial metabolic biomarkers for characterising the transformation from benign to cancer cells. 


What TRANSMIT is working on more specifically:

-Metabolic reprogramming of cancer cells- ie coordination of glutaminolysis and glycolysis. 

- Work with cancer cell models, metabolic intervention strategies.

- Improve our understanding of cancer pathology. 

- Understanding the role of fumarate hydratase in tumorigenesis.

- The mitochondrial complex 1 driven regulation of the hypoxic response in cancer cells. 

- Identifying coenzymes in cancer cells. 

Saturday, 23 June 2018

Deuterium experiment part 1- Preparation.



This is the first stage of my deuterium depletion experiment. 

Please see links below the videos on Youtube to understand the link between deuterium and cancer and how you may effectively deplete deuterium from the body. 

The tests I have used will provide me with a baseline for levels of deuterium in the body. The kit I have used measures breath as a marker of deuterium in tissues and saliva or urine for deuterium in biological fluids. The two measures when taken together are used to determine the body's ability to deplete deuterium. 

Breath analysis


Deuterium depleted water (DDW)



Considerations about starting drinking the water.



Testing levels of deuterium in the body.

Tuesday, 12 June 2018

Orexin/hypocretic receptor signalling and cancer.

Let's consider Orexin/hypocretin receptor signalling and how we may exploit this system for brain cancer management.


As we can see in the diagrams below, orexin neutrons regulate various activities such as wakefulness, feeding, reward and thermogenesis.



A ketogenic diet, normalisation of sleep/wake cycles, fasting, stimulation of thermogenic pathways and giving the brain fuels it thrives on could act as key strategies we can adopt to take advantage of the fact that orexin appears to have potential as a novel, highly-specific treatment for various localised and metastatic cancers. This is not quite as simple as it may sound as you can always have too much of a 'good' stressor or thing before it becomes 'bad'- eustress vs distress.

We know of course that fat is a very efficient source of energy for the brain and ketone bodies are neuroprotective, the body energy level influences orexin neuronal activity to coordinate arousal and energy homeostasis. Management of chronic stress is also key as inputs from the lymbic system are important to regulate activity of orexin neutrons to evoke emotional arousal or fear-related responses.

Also consider that the brain has an abundance of mitochondria and the matrix water in the presence of cancer either by cause or effect appears to be high deuterium. Normal cells are very good at adapting to changes in levels of deuterium (in terms of reduction) but abnormal cells are not.

From my research on the subject it seems clear and viable that you can achieve greater mental stability by a kind of filtration process to deplete deuterium by drinking deuterium depleted water, as has been shown in studies of depressive disorders. We also see several studies on how deuterium depleted water can shrink tumours by restoring fumarate hydratase activity. Fumarate hydratase acts as a tumour suppressor. Here is an example of how fumarate hydratase and deuterium depletion control oncogenesis, effectively helping to put the breaks on cancer proliferation: http://cancerres.aacrjournals.org/content/74/19_Supplement/1426.short

I have little doubt that Orexin signalling cascades will also be affected by this in a positive way for cancer patients. A lot of this is theory, but it is backed by some sound science. I still have a lot of questions but I think I may have a few interesting theories on this.

Here is a nice review of orexin's unprecedented potential as a highly-specific treatment for various localised and metastatic cancers: http://journals.sagepub.com/doi/full/10.1177/2050312117735774

Sunday, 13 May 2018

Reaction to Tessa Jowell's death, thoughts on repurposed drugs and deuterium. Update on Sativex.



Links relating to subjects mentioned: Deuterium content of water increases depression susceptibility https://www.sciencedirect.com/science/article/pii/S0166432814004884 Ketogenic substrates, water and drugs promote deuterium depletion of mitochondrial metabolic matrix water, offering a means to prevent tumor cell growth.- https://www.sciencedirect.com/science/article/pii/S0306987715004399#f0005 AKT as Locus of Hydrogen Bond Network in Cancer.- https://www.ncbi.nlm.nih.gov/pubmed/28590011 Tumour Treating Fields- https://www.novocure.com/our-therapy/ Essential reading about water, especially if you're into all that reverse osmosis, alkaline stuff or drink tap water.- https://www.hindawi.com/journals/jchem/2013/472323/

Thursday, 8 March 2018

L-Carnitine, ketolytic enzymes and therapeutic ketogenic diets for cancer management.

L-Carnitine plays an absolutely vital role in the metabolism of fatty acids.

Mo Farah is recently, somewhat controversially been pruported to have had an injection of L-Carnitine before the 2014 London Marathon for performance gains. It is worth noting that Mo Farah is an endurance athlete, so fat is the predominant fuel source. Fat oxidation rate is high so if you can sustain this for a longer period of time you can improve limits of exhaustion.

Carnitine shuttle (1)
This IV administration by Mo Farah is now being seen by the media in this country as 'cheating within the rules' with increased scrutiny recently of 'marginal gains' in athletic performance and sport in general after the cycling 'scandal' with Team Sky riders making the most of Therapeutic Use Exemptions (TUEs) that are known to improve performance for endurance athletes.



What helps athletes often has great potential for cancer patients- ie. infusion of nutrients, certain drugs, nutritional supplements, hyperbaric chambers, cold induced thermogenesis, infrared saunas, etc.

It is interesting....

Like Mo Farah I also take L-Carnitine because it ensures efficient transfer of long-chain fatty acids to mitochondria for subsequent β-oxidation. The brain has an abundance of mitochondria and if you subscribe to the mitochondrial defect theory of cancer as I do its kind of a no brainer (pun intended) that you would want to make the most of everything you can do to do try and restore mitochondrial function here. This can potentially be very beneficial for ensuring that ketone bodies produced during fasting, or fats on the ketogenic diet actually get used so that we can attempt to attain more healthy mitochondria.

This is what I take
There is exhaustive evidence showing how supplementation with L-Carnitine could benefit cancer patients, mostly for reducing general fatigue during chemotherapy (2) but also for normalising lipid metabolism for more general health (3). Anti-dementia effects have been proposed and suggested when co-administering L-Carnitine with medium chain triglycerides (MCTs) and other agents (5, 6). A higher rate of absorption would result in rapid perfusion of the liver, and a potent ketogenic response.


Perhaps an important consideration: 

If you are thinking of taking this as a brain cancer patient however, it may be worth some exploration to see if your tumour has increased activity of ketolytic enzymes to see if it can use fats to proliferate. You can ask about this from histological findings. 

Ketone body ketolytic enzymes to assess expression of include (4): 

Succinyl CoA: 3 Oxoacid CoA Transferase (OXCT1)
3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and BDH2) 
Acetyl-CoA acetyltransferase 1 (ACAT1) 


This can be the case in more aggressive tumours rather than typically lower grade, more solid tumours. I suspect this may be because the tumour is more diffuse, and as such the cell membrane may lack integrity and become more permeable. This is a theory I have based on research looking at alterations of membrane integrity and cellular constituents in neuroblastoma and glioma cells (8). 

I could be completely wrong with that theory, but either way there is often an overexpression of Fatty Acid Synthase (FASN) in high grade gliomas (7), a key lipogenic enzyme in glioma stem cells (GSCs), as well as other important metabolic enzymes, meaning aggressive tumours will try to use whatever they can to grow and thrive and are excellent at adapting to use alternative fuels when you restrict main substrates. These tumours will use glucose, amino acids, fats and nucleic acids for energy, and while the demand will be different for each, as the tumour becomes more aggressive the amounts will change and it becomes more and more resistant to even the most aggressive treatments. 







6. Odle, J., 1997. New insights into the utilization of medium-chain triglycerides by the neonate: observations from a piglet model. The Journal of nutrition127(6), pp.1061-1067.