Tick, Tock, Curcumin O'Clock

'Treatments based on the phytochemical curcumin have much potential for use in cancer treatments because of their effects on a wide variety of biological pathways, including those regulating the cell division cycle and circadian clocks. Cancer incidence and progression are influenced by circadian clock cells in multiple organs and tissue types. 

'According to chronotherapeutic studies aimed at optimizing cancer treatments based on the circadian cycle it is known that circadian clocks modify the effectiveness of cancer treatments. Thus, it is important to determine whether curcumin and similar chemotherapeutic treatments being tested against cancer in clinical trials are influenced by the circadian clock. Similarly, it is important to determine whether curcumin alters the timing activity of circadian clock cells. To understand how curcumin treatments and combinatorial therapies using curcumin with standard therapies can be made more effective, we characterized the impact of the circadian clock on the timing of cell death and cell division in curcumin-treated C6 glioma cells.'


http://cancerres.aacrjournals.org/content/75/15_Supplement/1772.abstract

Cancer cells adapting to use ketone bodies for fuel?

A response to an interesting study:

The bad news is: 

Cancer is very good at adapting in order to proliferate in challenging environments so this study throws up interesting talking points. 

The good news is: 

1. It will always be effective for all types of epilepsy. - including brain tumour related epilepsy (and related symptoms)

2. There are many different approaches within metabolic therapy that are effective. Central Nervous System cancers are unique in many ways. 

3. We are not rodents and other animals with more spontaneous tumours are continuing to display very encouraging long term results. 

4. Human cancer cells injected into mice have had to adapt to foreign conditions anyway so I would presume this may also be a factor to consider. 

5. The quality and type of ketogenic diet is vitally important and continues to be ignored in rodent studies (and the few human clinical trials out there). Quality of fats used is generally poor in these studies. Some even use vegetable fats!!

The study is very interesting and needs to be researched further but we need to further expand our horizons to get truly relevant data. 

Researchers often have a very narrow focus, these rodents typically aren't even monitored for seizure activity which is a very important consideration. 

I have been asked? Would be interesting to seperate the unique ketosis benefits from the normoglycemia?

Certainly, but we must remember that they are interrelated they and that it remains a fact that if quality fats are included we see that in and around malignant brain tissue we continue to see very low amounts of DHA (which is also cytotoxic to brain cancer cells). Ensuring that quality fats, particularly DHA (which makes up at least 20% of healthy brain tissue, still appears to make perfect sense when we devise an appropriate ketogenic diet. 

Personally I get frustrated at times with these ketogenic diet studies using poor quality ingredients. Im my humble opinion it should be no dairy, less omega 6, more omega 3- especially DHA. This is perhaps even more important than the ketones. I know individuals who have utilised a metabolic approach that is not strict keto and have achieved remission simply following these 'rules' so in a way I agree with the study that it isn't all about ketones. 

If the ketones are powerful metabolic tools long term, which I still believe they can be, we must consider this fact...

All ketones are not created equal. Lifestyle factors are also important and this plays a bigger role in humans, especially vitamin D status.

I've written this in about 2 minutes but when I have time after Christmas I will add all my research to back up the individual points made. It's a great study for discussion and I'm glad it's been brought to my attention. I like to question everything and I am continually adapting my methods to suit new research. 

I'm also really looking forward to Christmas Day so...

MERRY CHRISTMAS AND A HAPPY NEW YEAR!!!

Preparations for hyperbaric oxygen therapy!

Preparation for HBOT. No exogenous ketones required. Ketones need to be high and blood glucose low during treatment. 90% fat, 10% protein to have the most benefit in order to obliterate any microscopic cancer cells that might be left. I don't always maintain this kind of reading but I have learned to time it for when I need to. Hyperbaric oxygen therapy for cancer management requires this kind of restriction, I definitely won't want to maintain this after for long even though I feel good at the moment.

Professor Thomas Seyfried has informed me that: 

'It will be very important that your GKI is 1.0 or below when you receive HBOT (our GKI paper is attached).  Our preclinical data on GBM show that oxygen therapy can increase tumor growth except when ketones are high and glucose is low.  Use HBOT only at the time of day when your blood ketone levels are highest and you glucose is lowest.  You will need to determine time this for yourself. I think this will be the most important consideration.' 

Here is the paper... 

http://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-015-0009-2

Interestingly he also gave insight into some of my burning questions regarding exogenous ketones, DHA, and curcumin. He has stated...

'Your liver will produce D-b-hydroxybutyrate from the fats in the KD.  If you take exogenous ketones, it is best if they also contain D-b-hydroxybutyrate.  Some exogenous ketone preparations contain both the D- and the L- forms of b-hydroxybutyrate.  According to Richard Veech, The L- form will not be as therapeutic as the D- form.  However, exogenous ketones can help lower blood glucose that is important.  I have not yet evaluated the effects of exogenous ketones in or preclinical model of GBM.  The therapeutic effect of treatments can sometimes be different in the brain environment than outside the brain.

I am not sure what to say about combining DHA with HBOT while under the calorie restricted KD.  We are actually doing these experiments now in our preclinical model of GBM.  We think this combination will be effective, but we need to examine the data first before I can make any firm recommendations.  There are dosage and timing issues that need to be evaluated.  I think a low dosage of DHA while in ketoses might be helpful when under HBOT.  I am not sure what to say about curcumin, as we have not tested this.

We are also working on a new drug/KD combination that might be the most effective therapy yet for managing GBM.  Unfortunately, progress is slow due to limited funding.  I am convinced that long-term non-toxic management of GBM will be better when using metabolic therapies that when using current standards of care.  However, we are still at an early stage of development in this new frontier of GBM therapy.  You are one of the pioneers.'

I learned a lot from this and I hope he doesn't mind me sharing his wisdom. I greatly appreciate his work and admire his compassion.

Here is my food diary today, I made a few changes. The coconut flour is a different brand but nutritionally this isn't far off what today has been like so far: 

For breakfast I had ghee in a big bottle of hot water, sipping this over 1 hour. 

After this I had breakfast which was actually mackerel in olive oil but nutritionally all I could find that was similar is tinned sardines in oil (I did check though, the nutritional info would be almost exactly the same!) 

Then early afternoon I had 2 eggs with 50g ghee mixed with coconut flour in the oven for 10 minutes. I added coconut flour back in recently as well as the olive oil because these ingredients no longer give me headaches as my brain has healed. 

Here is the now infamous article on a combination of the ketogenic diet, hyperbaric oxygen therapy, and ketone esters as a potent synergistic protocol to manage metastatic cancer in rodents. 

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065522

And here is a dog with cancer following a ketogenic diet at the Ketopet Sanctuary being treated with hyperbaric oxygen therapy. He seems happy. 

Ketopet diet:

This brilliant work is being put into practice by Quest Nutrition who are getting very encouraging results. The main problem when we try to translate this strict approach to humans is compliance. I am trying to lead the simple life of a dog and moving forward this includes sleep regulation and less exposure to artificial light. 

HBOT and keto

I will be having hyperbaric oxygen therapy on January 4th to compliment my ketogenic diet. There are also plans to open up a ketogenic cafe at the centre. The owner is very interested in my story and approach. I'm aiming to set up a fundraising page to ensure that more brain cancer patients have access to this while on ketogenic diets. 

I will give daily updates of my progress and details of the protocol once I start. These are very exciting times. 

It's all coming together nicely...

I'm finally going to start having hyperbaric oxygen therapy and I will be combining this with a few other metabolic strategies to attempt to get my brain looking and feeling as healthy as possible. I'm very excited about the potential of this protocol and I will be documting the progress of other patients that I am monitoring doing similar things. I feel this will make for compelling reading. It's very exciting. I will be taking lots of pictures when I'm there. 

Special days for seriously ill young adults- Willow

I have written a piece for Willow Foundation which will likely be in the Arsenal match day programme for the Manchester City game on the 21st. My interview about my special day will also be appearing on the big screen before the match but this isn't about me at all now. If I felt that I would seriously need a personality transplant. I feel incredibly fortunate at this moment despite continued uncertainty. The least I can do is express what a fantastic charity this is for so many. 

They work tirelessly to provide individuals with life limiting illnesses special days with their loved ones. I have had friends with the same type of cancer as me pass away recently but the small consolation is that their families have special memories with them from special days provided by Willow. The positive impact of these days is immeasurable for these people. Its a wonderful distraction in dark times where you can smile through uncertain times. If you know anyone in this situation or if you can support the charity in any way why not check them out?


https://www.willowfoundation.org.uk/about-willow-0

A long overdue post on Magnesium

I could not stress enough how magnesium supplementation is an ESSENTIAL part of my approach to manage my epilepsy. Control of my horrible, terrifying and debilitating seizures I had suffered in the past has been tremendously liberating and magnesium supplementation has certainly played a crucial role in that success.

Magnesium is an abundant mineral in the body serving many biochemical functions and it is an essential electrolyte for all living organisms. It plays an important physiological role particularly in the brain, heart, and skeletal muscles. Normal dietary magnesium intake is estimated to be 300–350 mg per day for adults.

Magnesium supplementation has been shown to be beneficial in treatment of, among others, preeclampsia, migraine, depression, coronary artery disease, and asthma. http://physrev.physiology.org/content/95/1/1.abstract

In regards to epilepsy specifically it is worth noting this…

‘The concentrations of copper, magnesium, and zinc were all significantly altered in patients with epilepsy who received antiepileptic drugs compared with untreated patients with epilepsy. Designing treatments to selectively restore zinc levels may be a strategy for treating patients with epilepsy. It is still unclear whether these ions are causal to, or a cofactor in, the development of epilepsy. Knowledge of the effects of various antiepileptic drugs on trace element homeostasis could potentially be used to effectively guide appropriate therapeutic strategies in the future.’ http://nutritionreviews.oxfordjournals.org/content/73/11/760.abstract

I take magnesium chloride as a critical part of my seizure management approach. I take this orally mixed with water- 10 sprays at least 3-4 times a day. Each dose of 10 sprays = 150mg of Magnesium. I also have other natural treatment components complimenting this supplement nicely.

I choose magnesium chloride because for me personally it is the best form I have tried to control my seizure activity (which it does quite remarkably!), and it is convenient. I believe that the benefits of magnesium chloride are described quite nicely in the brilliant book 'The Magnesium Miracle' by Carolyn Dean M.D., N.D.

On magnesium chloride... 'Some say it may be the best magnesium for ingestion. That's because minerals need to be dissolved in gastric acid to go into solution. And, magnesium chloride has extra chloride molecules to produce hydrochloric acid in the stomach to enhance its absorption.'- personally I find that you have to build up to the dose I use to prevent any discomfort. 

It is also worth noting that our water supply in many countries is lacking in the magnesium it once had. There is a lot of calcium, but little magnesium in this water so I feel I benefit from adding additional magnesium to my filtered water. 

I have also recently tried magnesium citrate which I tolerate very well but it actually lowers my seizure threshold for some reason. This brand is excellent for general use. It can also be helpful if you have constipation, which some people experience on ketogenic diets. Find out which type of magnesium works for you and which one you tolerate best as an individual. I won't be having this any more but you may like it. 

It is interesting how magnesium citrate doesn't help at all with my seizure activity (and can even trigger seizures-possibly due to poor absorption) but magnesium chloride is brilliant and controls it completely. Potassium citrate helps with alkalising my urine and doesn't interfere with my epilepsy but I need to make sure potassium, sodium, calcium and magnesium ratios are right for me. I'm sure it should be the same for others but they wouldn't get instant feedback that someone with reflex epilepsy would get. Reflex epilepsy is when seizures only occur as triggers rather than being seemingly spontaneous or from a cause that cannot be changed. I found this useful but not sure how accurate the claims are:

I feel it is important to state that I eat a variety of insects that are reasonable sources of magnesium (particularly the exoskeleton), and occasionally I do eat macadamia nuts. Initially I struggle to tolerate nuts however since I have had significant healing of my scar tissue and I have improved my omega 3 to 6 ratio in my blood I find them much easier to tolerate. 

The same is true with foods containing salicylates which I find very interesting. I also consume a fair amount of oily fish and I can now add olive oil to it which is a nice feeling. I have read that olive oil can help to activate AMPK but perhaps not at the amounts we can consume without feeling nauseous. I do have other ways of managing this so I am not overly concerned at present in that respect. I can also tolerate avocados again and enjoy as an occasional snack. 

Magnesium supplementation is essential for most people these days and moreso for those with any type of epilepsy, a compromised blood brain barrier, or acquired brain injury.

We know that… ‘Magnesium is required for over 300 enzyme systems and is critical for many cellular functions including oxidative phosphorylation, glycolysis, DNA transcription and protein synthesis. Studies suggest that the modern Western diet and lifestyle may lead to magnesium deficiency, and this appears to be associated with a wide range of medical conditions. Magnesium deficiency decreases seizure thresholds in animal models of epilepsy and indeed low magnesium concentration in the perfusate is a common method of generating spontaneous epileptiform discharges from rat hippocampal slices.’

Magnesium is a potential modulator of seizure activity because of its ability to antagonize excitation through the N-methyl-d-aspartate receptor. http://www.sciencedirect.com/science/article/pii/S092012111200040X

Some studies have shown that people with epilepsy have lower magnesium than people without epilepsy. 

-         

-        There are case reports of seizures being controlled with magnesium supplementation in people with specific conditions, and recently in an open randomized trial, children with infantile spasms responded better to adrenocorticotropic hormone (ACTH) plus magnesium than to ACTH alone. http://www.sciencedirect.com/science/article/pii/S092012111200040X

-        Oral Mg supplementation may prove to be a worthwhile adjunctive medication in treating drug intractable epilepsy. http://www.ncbi.nlm.nih.gov/pubmed/22547512

Seizures are clearly associated with ionic changes in the brain. I am rushed to write this post as I have a great deal on at the moment, but I will detail the main points with supportive research to explain the rationale behind my approach. Magnesium chloride replaces standard medication for me and I have found it to be incredibly effective alongside a strict ketogenic diet. Here are just some of the reasons why.

-         Magnesium is a CNS depressant, with numerous functions intracellularly and extracellularly.

-          Oral magnesium can act as a natural statin and reduce plasma blood glucose levels http://www.sciencedirect.com/science/article/pii/S1262363615000580

-          Magnesium supplementation has been shown to raise seizure threshold in animal and human studies. http://onlinelibrary.wiley.com/doi/10.1002/jcph.626/abstract;jsessionid=96A16B1C52CB56D9E7C67CEEC60C561F.f04t03?userIsAuthenticated=false&deniedAccessCustomisedMessage=

-        Similar to the ketogenic diet, magnesium has had nearly a century of clinical use to treat epilepsy. It been used as prophylaxis and treatment of seizures associated with eclampsia however because of the availability of well studied anticonvulsant drugs it has not been tested widely in the treatment of epileptic seizures. http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=9341631&fileId=S0317167100013457

-          Eclampsia is defined as de novo seizure in a woman with the hypertensive complication of pregnancy known as preeclampsia (PE), and is a leading cause of maternal and fetal morbidity and mortality worldwide. http://scholarworks.uvm.edu/graddis/336/

-        The pathogenesis of eclampsia during PE likely involves breakdown of the BBB and subsequent neuroinflammation, resulting in a state of greater seizure susceptibility that is ameliorated by MgSO4 treatment. This situation of a compromised blood brain barrier could be translated to brain cancer patients where more magnesium is required to combat likely deficiency. Brain cancer patients can have a ‘leaky brain’, particularly if they have had radiotherapy and chemotherapy.

-        Magnesium sulfate is an evidence-based anticonvulsant drug used to prevent and control eclampsia. http://onlinelibrary.wiley.com/doi/10.1111/jog.12697/abstract?userIsAuthenticated=false&deniedAccessCustomisedMessage=

-        Although magnesium sulfate is one of the most commonly used agents for seizure prophylaxis in preeclampsia, its efficacy relative to other anticonvulsants is incompletely investigated. http://www.sciencedirect.com/science/article/pii/0002937894900221

-        Hypomagnesaemia is a recognized cause of generalized seizures. http://www.sciencedirect.com/science/article/pii/S1090379815001798

-        Patients with hypomagnesemia suffer from a wide range of symptoms including muscle cramps, cardiac arrhythmias and epilepsy. http://www.jle.com/fr/revues/mrh/e-docs/the_art_of_magnesium_transport_305521/article.phtml

As we can see, magnesium sulphate is the most studied form of magnesium for the management of epilepsy:

-        Magnesium sulfate infusions can be safely used in pediatric refractory status epilepticus. Magnesium sulfate can be considered in the management of children with febrile illness-related epilepsy syndrome. http://cno.sagepub.com/content/2/1/2329048X14550067.short

Compared to anti epileptic medication (AEDs)…

-        Magnesium sulfate is a significantly more effective prophylactic agent than phenytoin for N-methyl-D-aspartate-induced seizures. http://www.sciencedirect.com/science/article/pii/0002937894900221