Research Group for ME/CFS, Chronic Disease, Aging and Cancer

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I was having inconsistent results with the protocol, many experiences lined up with what was expected or predicted to happen, 
I got the weird headache to begin with, it became a problem at times that reminded me to take the sodium benzoate, I got the strong fever within the first few days,  experienced changes in symptom profile and energy levels.   But it seemed to not last or intensify and I had patterns of ups and downs, a light fever feeling that came maybe once a week then disappeared within 2 days seemingly regardless of if I increased the level of oat bran that I was consuming, say from 1 gram to 2 grams.  

This lead me to test different variables, the first was the quality and contents of the supplements,  at first reishi and green tea, I noticed pains in my right side after switching to Life Extension mega green tea extract,  made into empty capsules ( this allowed EGCG from an unknown, probably low amount, up to 30mg or higher ).  I settled with Life Extension brand reishi capsules after various discussions and looked at other products.  

One of the things I tried recently was going on a very restrictive diet, of the same sorts of food as I was already on,  getting calories below 1500 or maybe 1000 per day, I had a suspicion that this would re-induce the fever and it basically did,  but another factor that I decided may have been important, and the only factor that I hadn't considered at length yet was beta glucans.  Most likely its effects stack up over time,  so just trying to take 2 instead of one, as a once off, might not be a good indicator of any scaling effects.  I decided to switch the brand of Lions Mane I was using, because I remembered that it said on the bottle ' 450mg per 3 capsules ',  I am now switched to Time ultra lions mane which have 50% beta glucans content. I noticed that fever was induced shortly after switching to these, but still not an intense one.  During or following the fever I usually have higher energy levels and feel better aside from certain odd feelings that I recognize as something different to standard ME symptoms. 

The other factor I have been observing is diet, when it gets lax and I start to eat more carbohydrates or sugar e.g. one small pizza ( 150g ) I notice that a day or 2 later I feel more rough / less energy, and this seems to disrupt the fever process. Exercise beyond a threshold might also have this interrupting effect ( harder to confirm that ). 

48 hours ago I was feeling ok and was quite active in various ways, I decided to test the diet hypothesis, I ate a bread roll, 2 Cadbury Darkmilk chocolate bars ( around 85g each at around 48% sugar content ), then half of a 450g pizza.  Almost immediately my cognitive function seemed to be 'jammed' and I later got a headache ( though the headache part could have been due to the high temperatures we've been having, so not a fair test exactly there ).  I generally felt all sorts of PEM symptoms heavily come on, which I am still experiencing 48 hours later, and I feel exhausted in general,  yesterday I slept halfway through the day for example. 


Re: still doing the protocol - observations + possible discoveries
« Reply #1 on: June 18, 2021, 09:19:04 PM »
Welcome .. and thanks for sharing your journey here! :)

These are great observations - the carbohydrate sensitivity in this model is largely caused by high GDH in the pancreas triggering hyperinsulinism. 

This is similar to what has been described in the literature as "hyperinsulinism and hyperammonemia syndrome" 

Hyperinsulinism/Hyperammonemia Syndrome in Children with Regulatory Mutations in the Inhibitory Guanosine Triphosphate-Binding Domain of Glutamate Dehydrogenase1 | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic (oup.com)


This also provides a general clue that your dosing protocol may benefit from adjustments that provide better regulation of GDH.

This gets quite interesting, as there are a number of pathways suggested as being directly involved to maintain an elevated GDH, not just the protein expression. Some of these are related to hormonal influences and dysregulation, especially around DHT metabolism.

There have been some improvements around this in v3.31, which help to normalise DHT (and allopregnanolone) metabolism, via targeting abnormal 5-AR and 3a-HSD.
 
Additionally, there are influences for GABA : glutamate balance, such as serum Vitamin D. We're targeting a serum level of above 120nmol/L.

One earlier and very important error that was also corrected in the updated protocol - the EGCG dose in v3.2 was originally based on a small number of people who had been using spironolactone.

Spironolactone also reduced GDH, however this connection was not well understood at the time of drafting 3.2. Subsequently, the EGCG dose has been significantly increased around no longer using spironolactone. 

When there is dysregulated mitochondrial energy and mTOR, owing largely to GDH + diet (although excessive doses of vitamin B12 can be expected to cause the same issue), the apoptosis signalling induced by reishi triterpenes is expected to be impaired. The cells appear to display behaviour where they won't voluntarily die until their proliferation tasks are completed.

The diet and supplement schedule aims to allow the cells to voluntarily signal for apoptosis.

The reishi product selection was also a huge problem. I spent some time in the lab a week ago trying to get to the bottom of it. At this stage, only the Life Extension Reishi Complex met the criteria. To prevent further complications, I'm sticking to that product only until more pass the same lab testing process. We also saw completely different metabolite profiles in reishi spore products and fruiting body. They look nothing alike on the HPLC, let alone LCMS.

A combination of an alcohol extract of the fruiting body and broken spores provides the desired metabolite profile. I'll be making a post about this when I get the full results from the lab.

Can you share your supplement choices and dosages / timing? I'd be curious if you can replicate the carbohydrate tests with lower GDH. :D
NB. I am NOT a doctor and all information provided is for educational purposes only.

Please consult your physician before attempting anything you read here.


Re: still doing the protocol - observations + possible discoveries
« Reply #2 on: June 20, 2021, 09:27:15 AM »
Ok I see. I wrote this out before so I can copy 

- LFE reishi   3 or 4 capsules a day
- LFE super R-ALA  3 or 4 a day
- ' gold label ' organic lions mane made by brainpower something ( has a furry white mushroom picture on the front ), supposedly 'made in England', found it on Amazon. 
was on 3 or 4  a day but I now use it as a booster. 
-  ( now )  Time ultra Lions Mane capsules,  50% beta 1,3/1,6 D glucan,  425 mg,  3 or 4 times a day. 
-'hatton hill' oat bran   1 to 2 grams  1 to 4 times a day,  depends
- LFE mega green tea extract decaffinated, cut down to size 1 capsules.    Made various weights,  40mg  75mg 100mg 150mg ( EGCG, actual weight is 110% more + 80mg ) 
- Thorn basic B complex  1 a day
- Vitabiotics vitamin D 1000IU 1 a day
- xSpan labs NAC 600mg about 3 a day 
- Nutra Vita 400 IU vitamin E ( now changed it to Nu U because cheaper )  1 a day 

-  Vitamin C  1000mg,  sometimes.... it burned my tongue yesterday.   

I have tried different types of the green tea from about 20mg going up to 150mg,  I didn't notice much difference in energy or symptoms over this range,  it does seem to affect fever / pain ( when I am capable of getting the fever ), but this effect seems like it caps out at about 75mg with no benefit going higher.  When I was using the original green tea capsules ( veda ? )  of unknown but low EGCG content,  I got fevers but I didn't get the sharp pains all the way up my right side.  I've been generally taking the 100mg or 75mg, I was trying to take it before even eating small amounts of carbs as I heard that might help. I'm not keen to repeat the pizza, bread and chocolate experiment ! 


The strange thing is I didn't notice any sensitivity to carbohydrates or sugar before starting this protocol,  actually I sometimes felt a strong craving to eat a lot of sugar, I knew that eating a lot of meat and later BCAAs improved my energy though.  This type of reaction to pizza, bread etc would have been really obvious though because it came on quite fast and was debilitating.   I speculate that there is some sort of adaption mechanism, that switches off when you change diet and stop eating lots of sugar etc,  the other explanation could be that something in the protocol somehow causes this intolerance of high blood sugar ?  that would be interesting in itself because it might be a new discovery in biology. 


Its been about 4 days since I ate that food, i've gone back to near keto diet but... still really knocked down,  last night I felt like I hit zero point of energy, where I couldn't do anything without feeling weird symptoms, so I just lied in bed for a while watching videos, then I slept for 12 hours.  No fever yet and I wouldn't expect it to happen in this state.  Surely the ROS should be mostly gone by now ?  I wonder if it could be the viruses activating. 


Re: still doing the protocol - observations + possible discoveries
« Reply #3 on: June 22, 2021, 04:02:39 AM »
The fever has came back on pretty strong in the past couple of hours, I had some subtle signs yesterday that made me think it might do. 
Perhaps more interesting though is I got up late yesterday ( 5pm ) and went to bed early ( 3am ), then I had trouble sleeping, strange dreams,  got up quite early ( 9am ),  this seems to match my previous observations about there being phases where I don't sleep as long. 

Its been about 6 days now since I ate all that unhealthy food that I described and the subsequent symptom relapse.  3 days since the last major energy overexertion.   In other words I am able to predict when the fever will occur,  so its not random :)

This makes me think about something that people commonly say about chronic fatigue syndrome. Perhaps if we go with the virus theory, 
by forced resting it allows some increased capacity for an elevated immune response even without the assistance of these organic compounds we are taking ? new article about long covid in guardian newspaper