Hello Maff
As you suggested, I am posting here rather than at the end of your 'My Candida Hell' article.
I hope your holiday in Turkey was good.
Since our last spate of messages things have moved on a fair bit. On your advice, I tried Sarah Myhill, who wasn't taking on any new patients but recommended Shideh Pouria at the Burghwood Clinic in Surrey.
I saw her around three weeks ago. She took some blood tests which came back with some interesting results. They are certainly more sophisticated tests than I have had before at places like the Brain Bio Centre. They seem mainly to be aimed at CFS/ME, but are quite relevant to me too.
The most interesting finding was on a DNA adduct test which found that I had aluminium adducts. These apparently affect a gene responsible for an enzyme which is involved in the regulation of glutamate and ammonia detoxification in the brain, both of which have implications for anxiety and CNS problems.
So - a good result to have at least found something. There were other tests too -
L-carnitine was normal
Mitochondrial membrane TL protein studies again found aluminium, low zinc, potassium and magnesium in the membrane and mitochondrial clumping, which apparently relates to too many free radicals.
Superoxide Dismutase Studies had various low values - this again is apparently related to detoxification in the brain, and there is something up with glutathione-s-transferase.
The tests were with Acumen, which is run by the chap who used to run BioLab.
All this is way over my head, but it's good to see some actual data to represent the mess in my nervous system that is only ever experienced internally. The DNA adduct thing seems the most interesting.
It seems the treatment is along the lines of Patricia Kane's phospholipid exchange protocol. I am on a high fat/protein, low carb diet, and supplementing with phosphatidylcholine, 1 tsp a day.
I've been on this for about two and half weeks, and have been feeling pretty awful for the past ten days. I have no idea if this is to do with the diet, or would happen anyway.
I realise now that getting the right tests for these things is absolutely vital, and prodding around in the dark, trying to self-diagnose is quite unwise. The phospholipid exchange ideas make good sense, and there seems to be a fair bit of evidence, anecdotal and otherwise, that it might be effective.
I'll keep you posted on how I get on - would welcome your thoughts on the above.

John

Hi John,

Thanks for posting in the forums - as I mentioned in my email to you there is a bug in the version of the comments software the site is currently using which means we can have a maximum of 20 comments. This will be fixed when the site is updated, hopefully within a couple of months!

I had a great time in Turkey thanks. Seems like a long time ago now sadly...

I'm glad Dr. Myhill was able to refer you to a doctor who could take you on. I have to admit I am not familiar with Shideh Pouria or the Burghwood clinic but it sounds like you are in good hands - both Biolab and Acumen are excellent labs that have pioneered some very useful tests.

The aluminium DNA adduct is certainly an important finding and fits with the other results you mention. A DNA adduct is a chemical that forms a covalent bond (remember chemistry lessons from school!) to DNA molecules and can cause mutations in the genetic material that can cause dysfunction of proteins and enzymes in the first instance - unless the body is able to repair the damage before DNA replication occurs.

I would guess aluminium adducts would affect a variety of genes (the affects of DNA adducts vary between individuals due to specific genetic makeup and environmental factors) - glutamate and ammonia metabolism, as you say, would certainly have major implications for the CNS as ammonia is a potent neurotoxin and glutamate also becomes toxic at high levels or if it's major receptor (NMDA recptor) is sensitised, as seems to be the case in environmental illnesses.

Low zinc would be expected when toxic metals are elevated as the two are antagonistic. Zinc supplementation can displace toxic metals and help their excretion.

Low superoxide dismutase (SOD) would follow from low zinc as zinc is a cofactor for the synthesis of SOD in the body. SOD is a major endogenous antioxidant that protects cells from superoxide radicals - not just in the brain but throughout the body. Superoxide radicals are produced by mitochondria when they produce ATP (energy) - when the mitochondria are damaged and dysfunctional they produce larger quantities of superoxide radicals and so more SOD is used up.

Glutathione peroxidase is another antioxidant produced by the body and one of its functions is to neutralise hydrogen peroxide, which is the product of SOD's neutralisation of superoxide (along with water). Glutathione also binds to toxic metals and the glutathione-metal complex is then excreted in the bile. Glutathione-s-transferase is the enzyme that \"recycles\" glutathione from its oxidised form back to the reduced form that is needed for detoxification/neutralisation of free frdicals.

You see now how all your test results fit togther into a big picture...

Treatment along the lines of Patricia Kane's Detoxx Protocol would certainly seem appropriate as it helps to restore the membranes of cells and their organelles (including mitochondria) so they regain function and are able to efficiently utilise nutrients and excrete toxins, such as aluminium. I am planning on undertaking IV phospholipid exchange myself in the coming months (I cannot tolerate phosphatidylcholine orally - it irritates my gut). I'll let you know how I get on and look forward to reading about your progress...

Good luck!

Maff

Hello Maff

You've been incredibly generous with your impressive knowledge - thanks a million for explaining all that stuff. I unfortunately failed my chemistry 'o' level, so all this info is quite hard on my brain! but I'm making some kind of sense of it, and you're right, a picture does begin to emerge when you put all the bits together. I can see how studying it must become quite engrossing.

I'm interested to hear you'll be doing the phospholipid exchange therapy. Will you be self-administering or supervised? And will you use the Patricia Kane products, as she has an article on how not all p-choline is equal as most on the market is not absorbable (see the link to BodyBio PC Bulletin on her website www.patriciakane.net)

There seems to be a big deal about the ratio of omega 6 to omega 3 fats, and although we're told we get too many 6's and should therefore supplement with the 3's, it seems that PK advises a ratio of 4:1 omega 6 to omega 3 (as does the WHO) Apparently you can't get the 3's into you unless you have the 6's....

I find this a bit confusing. The P-choline I take is in the ratio of 4:1, but what about all the other fats I'm eating? Don't these need to be balanced? I'm just randomly eating bucket loads of nuts, olive oil, butter, yoghurt etc. I'm just wondering if the p-choline omega 6's and 3's stay together during digestion, and therefore are effective regardless of the ratio in the other fats.

Are you a fan of liver flushing? I think we have the same issues with the liver - as soon as I stir up toxins with detox, saunas, exercise, supplements etc, my symptoms become unbearable, and I remember you saying the same thing. Do you think this is down to the 2 phases of liver detox being out of kilter? I'm wondering if phase 1 is working quite well, but then phase 2 is failing to finally expel the toxins, and leaving things more toxic than before. I believe the PCholine both supports the liver and precipitates cell membranes to detox. I've certainly been feeling pretty horrible for the past couple of weeks, but not to the point of having to quit the PCholine. I've not been taking any of the other bits of the protocol - glutathione, mineral-ions, butyrate - because I've not been told to, but would like to get some glutathione in me to see if it clears some of the toxins.

Apologies for the rather disorganised message, but it's great to be able to discuss this stuff here. Look forward to hearing from you.

John

Further to my last post, I have found another way that aluminium interferes with glutamate brain chemistry that is very interesting. Glutamate is an excitatory neurotransmitter which is converted into GABA (calming) using an enzyme called glutamate decarboxylase. It seems that aluminium poisons this enzyme, and so prevents the production of GABA.
So there are two ways that aluminium could be causing trouble - by preventing the production of glutamine synthetase, to convert glutamate into glutamine and detoxify ammonia, and by interfering with glutamate decarboxylase to convert glutamate into GABA.
I got all this from www.heartfixer.com/AMRI-Nutrigenomics.htm - a long article, but scroll to about 2/5s of the way down, heading, 'Glutamate – GABA Imbalance Þ Excitotoxicity'

Hi John,

Sorry for the slow reply.

You would need to balance the omega-3 and omega-6 fatty acids in your diet as well to get the overall balance right, yes. There are many websites and books out there that list the ratio of these fats in a variety of food sources - 'Know Your Fats' by Mary Enig is a good book.

I am undecided on liver flushing to be honest. It certanly gets things moving and stimulates excretion of toxic bile...but it's a bit aggressive and for those who are quite ill it is likely to simply make things temporarily worse and certainly if there is a problem such as gut dysbiosis causing chronic toxicity then it definitely won't help until that problem is cleared up.

You're spot on with the PC, that's exactly how it works. The idea is that it restores the fluidity of cells membranes throughout the body with improves the functioning of hepatocytes (liver cells) while supporting the ability of ALL cells to excrete waste products and toxins.

I too am about to start the same protocol you are on - I go for my first IV PC infusion on October 13th and will no doubt have IV glutathione and other detoxifying nutrients such as vitamin C as well. I'll share my experiences on the site, most likely in a blog post.

Thanks for the excitotoxicity link - very interesting stuff! GABA/glutamate imbalance seems to be a recurring theme with these illnesses and so many environmental factors are able to influence it.

Good luck and keep us updated on your progress!

Hello Maff

Balancing the fats in the overall diet would be quite a job, and I wouldn't know where to start...I'll look into it. I am interested to hear that you will be using the IV Protocol, it's supposed to be more effective isn't it?

I have now been on a low carb, high fat diet with 1 tsp of oral PC a day for five weeks. I haven't felt any better, and have had some pretty rough days. As soon as I stop taking the PC for a day or so I calm down a bit. This is the normal pattern for me when I try any kind of intervention.

From what I can gather, taking 1 tsp of PC a day is a very small amount. This site dshedu.com/HowTo/PCDetox/ talks about the oral ramping schedule, and 1 tsp isn't even the entry level, which is 3 tsps a day.

I am very interested in the pathological detoxification theory. I know that glutathione is crucial to phase 2 of the detox, and the tests that I mentioned above showed that my glutathione s transferase had a diffuse pattern, part of the profile and a subunit missing. God knows what that all means, but my doc said 'you can't detoxify with that.' It seems that the glutathione s transferase problems are due to a DNA adduct.

I'm wondering whether the supplements you recommend here - silymarin, curcumin etc, might not work for me, as the levels of glutathione s transferase seem high enough, it's just the quality of it (the missing subunits), and that seems to be down to the DNA.

A while ago I took Bayberry for a couple of weeks and felt much better quite quickly (within 4 days), but then after 2 weeks had the most almighty crash. I also feel worse after exercise, and worse after saunas - what do you think? Would that suggest a pathological detoxifier? I guess the answer is to have the tests done...