Hi Interrupted,
I managed to get a copy of the book. It's called "The Sinatra Solution, Metabolic Cardiology" by Stephen T Sinatra. Like all worthwhile books it was in the bargain bin for $10. It is a very dense book, full of anecdotal evidence and good science. It is not about MS rather it is about heart disease. A massive part of the book is about Q10 and it's role in the formation of ATP which is at the heart of my approach. Having read half this book, I am already concluding that had I not been taking large doses of Q10 I would already be dead as a result of my recent adventure.
Sinatra was chief Cardiologist and director of medical education at Manchester Memorial Hospital in Connecticut for around 20 years (see- http://www.echn.org/Locations/Mancheste ... pital.aspx ).
The point he is making is nothing works without ATP and you need Q10, L-carnitine and D-ribose plus magnesium working synergistically to treat most forms of heart failure by boosting ATP. He spends a lot of time detailing examples but, honestly, I rather he just stuck to the science of it all.
Nonetheless, what he says makes sense. He never doses Q10 as high as I suggest but he prefers intravenous treatment although he is happy with certain soft gel forms.
For the conditions: Fibromyalgia, CFS or Mitochondrial Cytopathies he suggests a multivitamin foundation program with 1g of fish oil, 300-360mg of Q10, 2000-3000mg of L-carnitine, 15g of D-ribose and 400-800mg of Magnesium.
When I have finished book I will try to write a (coherent) note because it dovetails into what I have been doing and I think the dose suggestions may be of assistance to you.
Regards
Beyond Avonex and Valtrex
Re: Beyond Avonex and Valtrex
Hi,
Well, I better have a go at summarising Sinatra’s book in the context of what we look at. A lot of me will creep into this.
Essentially, it is all about the ability to utilise energy. The first question then is “where does the energy come from?” Energy is assumed to be stored but it’s not true. We see batteries storing a bit of potential energy but in nearly all circumstances energy should be viewed as the utilisation of released energy not accessing stored energy.
So energy is made and used now. It has many forms. In our case, it is about the cellular energy potential. If you can make it, you use it. If you can’t make it then there is nothing to utilise. The energy in a cell is consumed as soon as it is made.
As this is a complicated area I will try to break it down, starting at energy itself and working out to the process.
The human body has lots of reactions going on in it but in all healthy cells we have chemical event that occurs many times per minute in every cell; Sodium inside the cell wants to get out of the cell and potassium outside the cell wants to get in. They end up on the wrong side of the cell wall by passing through one way channels that are specific to the size of their respective molecules. Chemical reactions draw them to the channels but they just want to get back to where they came from. There is one large gateway in a cell wall that can accommodate this. It is known as the Sodium/Potassium pump. Something has to drive the pump. It cannot drive itself. We will come back to this.
If I draw an analogy, imagine a water tank on top of a tower. The water sitting in the tank doesn’t appear to have energy but does have potential energy to be released. If we connect a hose to a tap on the tank and turn it on then gravity and the weight of the water released will make it rush out the end of the hose. That rushing water is releasing potential energy. It could be used to drive a turbine, create a jet of water etc so the potential energy of the water and gravity can be released by activating the tap. The same thing happens when Sodium and Potassium pass through the gateway. It is the flow that is really the release of potential energy. The flow creates an electrical charge that drives other cellular reactions. We then need something that represents the tap on the tank to let the flow occur.
As I said earlier the pump cannot drive itself. Every action to drive flow in either direction needs a hand to turn the tap. In the case of a cell, a phosphate molecule changes the behaviour of the gateway. The phosphate is the hand that turns the tap. It is donated to the pump to activate it by a chemical compound called Adenosine triphosphate (known as ATP).
Although you don’t need to remember it ATP looks like this-
3 phosphate molecules (P) + D-Ribose + Adenonine (a purine)
The D-Ribose is a sugar that binds
ATP is made in the inner membrane of the part of every cell called the mitochondria. We will come back to this.
One of the phosphates is only weakly bound and can be split away from the ATP and attach to the Sodium Potassium pump like this animation shows-
http://highered.mheducation.com/sites/0 ... works.html
The movement of sodium and potassium are the two flows that release the energy like the flow from the water tank earlier. The tap is the gateway and the hand that turns the tap is the phosphate. The phosphate is critical to drive the pump. Only ATP can deliver enough phosphate to the pump. ATP is critical to the release of energy.
So where does ATP come from?
It is too simple to say ATP is made in the cell. A cell consists of different parts. The main part of the cell is called the cytosol, the fluid portion of the cell that surrounds all the other parts. Most of the ATP is found in the cytosol but when it has donated a phosphate molecule the resulting ADP (Adenosine Diphosphate) returns to the mitochondria to be converted to ATP.
With the help of magnesium, ATP can move freely around the cellular space. 5-10 per cent of the ATP in a cell is inside the mitochondria at any one time, the rest in the cytosol. As the majority of reconversion happens in the mitochondria the turnover is rapid.
As ATP is mainly made from ADP in the mitochondria how does it get from the cytosol to the mitochondria and how does ATP get out of the mitochondria back to the cytosol?
The mitochondria has two sets of membranes; a smooth outer membrane and an inner membrane which is arranged in folds. Inside the mitochondria, fatty acids and other chemicals that are products of glucose metabolism use oxygen delivered by blood to help convert ADP back to ATP. Some of the spare oxygen molecules are not used and they become what we call free radicals. If there is not enough of the ingredients to make ATP the build up of oxygen molecules will make a lot of reactive oxygen species which affects health.
Mitochondrial membranes are impermeable. Nothing will get through except by one method; Carnitine can move freely across the membrane. Both ADP and ATP use a chemical process to hitch a ride on Carnitine from one side to the other of the membrane. So most ATP is made in the mitochondria and spent in the cytosol.
We can see Oxygen, fatty acids, ADP, some glucose and carnitine all contribute to making ATP.
What, however, makes the spark in the mitochrondria that starts the process? It is a vitamin-like, fat soluble compound called called Coenzyme Q10. It is made by all the tissues of the body by an amino acid called tyrosine. We get it from vegetables, fish, shell fish and meat. Our bodies cannot survive without it. It is an antioxidant that protects proteins and DNA.
It also drives the conversion of ADP to ATP in the inner membrane of the mitochondria. It does this by accepting electrons from one source and delivering them to a target through a pathway called the electron transport chain.
Without coenzyme Q10 we can’t make ATP adequately.
If we can’t make enough ATP what does the cell do as a response? It first tries to combine 2 molecules of ADP to make one of ATP and one of AMP (adenosine mono phosphate) to maintain energy viability. The AMP degrades and is washed out of the cell. When the ATP is spent it repeats the process lowering the pool of energy. If you return to the ATP picture earlier you will see it is made of 3 phosphates and Ribose (sugar) to bind and Adenonine which is a purine. As the cell viability falls we have less and less available purine. Purines are the key ingredient to make Uric acid. Too much Uric acid leads to gout. Too little uric acid means a scavenger of reactive oxygen species made from free radicals is depleted. The whole body becomes very vulnerable.
A common marker of multiple sclerosis is low Uric acid. It is extremely rare to have gout and MS. You would need to ingest massive amounts of Purines to alter that relationship.
If I wanted one marker to use I would measure Uric acid. If it is very low against the acceptable range. That would tell me that ATP depletion is a fundamental problem.
I would utilise the advice in the book “Metabolic Cardiology” by Stephen T. Sinatra, a US cardiologist.
For chronic fatigue (page 230) he uses
A multivitamin foundation program with 1 g per day of fish oil
300-360mg Coenzyeme Q10 (I think this is an IV dose) – I would think about working up to 750mg tablets a day
2-3000mg L-Carnitine
15g D-Ribose (you would need to find a good health shop or go on line)
400-800mg of Magnesium
Naturally, I would be testing for Epstein Barr Virus (the cause of Glandular Fever). You do not need a currently active infection. It is a herpes virus. Once infected it highjacks the B cells to reproduce and never goes away. An EBV infected B Cell is a prolific producer of the oxidant Superoxide. If you produce too much superoxide it can lead to the formation of Peroxynitrite.
Peroxynitrite can disable glyceralderhde-3-phosphate which is an important step in the second stage of glucose metabolism. If that fails, again, you will fail to produce ATP. Ironically, the best scavenger of Peroxynitrite is Uric acid. Unfortunately that is already affected.
If EBV is apparent, then I would consider using a 500mg twice a day of Valacyclovir. Some people really struggle with this and I suspect it is co-infections causing a herximer response. It may be too difficult and a doctor is best qualified to deal with that.
There are a range of other things to look at as we know but I would start at this level.
I hope this helps.
Regards
Well, I better have a go at summarising Sinatra’s book in the context of what we look at. A lot of me will creep into this.
Essentially, it is all about the ability to utilise energy. The first question then is “where does the energy come from?” Energy is assumed to be stored but it’s not true. We see batteries storing a bit of potential energy but in nearly all circumstances energy should be viewed as the utilisation of released energy not accessing stored energy.
So energy is made and used now. It has many forms. In our case, it is about the cellular energy potential. If you can make it, you use it. If you can’t make it then there is nothing to utilise. The energy in a cell is consumed as soon as it is made.
As this is a complicated area I will try to break it down, starting at energy itself and working out to the process.
The human body has lots of reactions going on in it but in all healthy cells we have chemical event that occurs many times per minute in every cell; Sodium inside the cell wants to get out of the cell and potassium outside the cell wants to get in. They end up on the wrong side of the cell wall by passing through one way channels that are specific to the size of their respective molecules. Chemical reactions draw them to the channels but they just want to get back to where they came from. There is one large gateway in a cell wall that can accommodate this. It is known as the Sodium/Potassium pump. Something has to drive the pump. It cannot drive itself. We will come back to this.
If I draw an analogy, imagine a water tank on top of a tower. The water sitting in the tank doesn’t appear to have energy but does have potential energy to be released. If we connect a hose to a tap on the tank and turn it on then gravity and the weight of the water released will make it rush out the end of the hose. That rushing water is releasing potential energy. It could be used to drive a turbine, create a jet of water etc so the potential energy of the water and gravity can be released by activating the tap. The same thing happens when Sodium and Potassium pass through the gateway. It is the flow that is really the release of potential energy. The flow creates an electrical charge that drives other cellular reactions. We then need something that represents the tap on the tank to let the flow occur.
As I said earlier the pump cannot drive itself. Every action to drive flow in either direction needs a hand to turn the tap. In the case of a cell, a phosphate molecule changes the behaviour of the gateway. The phosphate is the hand that turns the tap. It is donated to the pump to activate it by a chemical compound called Adenosine triphosphate (known as ATP).
Although you don’t need to remember it ATP looks like this-
3 phosphate molecules (P) + D-Ribose + Adenonine (a purine)
The D-Ribose is a sugar that binds
ATP is made in the inner membrane of the part of every cell called the mitochondria. We will come back to this.
One of the phosphates is only weakly bound and can be split away from the ATP and attach to the Sodium Potassium pump like this animation shows-
http://highered.mheducation.com/sites/0 ... works.html
The movement of sodium and potassium are the two flows that release the energy like the flow from the water tank earlier. The tap is the gateway and the hand that turns the tap is the phosphate. The phosphate is critical to drive the pump. Only ATP can deliver enough phosphate to the pump. ATP is critical to the release of energy.
So where does ATP come from?
It is too simple to say ATP is made in the cell. A cell consists of different parts. The main part of the cell is called the cytosol, the fluid portion of the cell that surrounds all the other parts. Most of the ATP is found in the cytosol but when it has donated a phosphate molecule the resulting ADP (Adenosine Diphosphate) returns to the mitochondria to be converted to ATP.
With the help of magnesium, ATP can move freely around the cellular space. 5-10 per cent of the ATP in a cell is inside the mitochondria at any one time, the rest in the cytosol. As the majority of reconversion happens in the mitochondria the turnover is rapid.
As ATP is mainly made from ADP in the mitochondria how does it get from the cytosol to the mitochondria and how does ATP get out of the mitochondria back to the cytosol?
The mitochondria has two sets of membranes; a smooth outer membrane and an inner membrane which is arranged in folds. Inside the mitochondria, fatty acids and other chemicals that are products of glucose metabolism use oxygen delivered by blood to help convert ADP back to ATP. Some of the spare oxygen molecules are not used and they become what we call free radicals. If there is not enough of the ingredients to make ATP the build up of oxygen molecules will make a lot of reactive oxygen species which affects health.
Mitochondrial membranes are impermeable. Nothing will get through except by one method; Carnitine can move freely across the membrane. Both ADP and ATP use a chemical process to hitch a ride on Carnitine from one side to the other of the membrane. So most ATP is made in the mitochondria and spent in the cytosol.
We can see Oxygen, fatty acids, ADP, some glucose and carnitine all contribute to making ATP.
What, however, makes the spark in the mitochrondria that starts the process? It is a vitamin-like, fat soluble compound called called Coenzyme Q10. It is made by all the tissues of the body by an amino acid called tyrosine. We get it from vegetables, fish, shell fish and meat. Our bodies cannot survive without it. It is an antioxidant that protects proteins and DNA.
It also drives the conversion of ADP to ATP in the inner membrane of the mitochondria. It does this by accepting electrons from one source and delivering them to a target through a pathway called the electron transport chain.
Without coenzyme Q10 we can’t make ATP adequately.
If we can’t make enough ATP what does the cell do as a response? It first tries to combine 2 molecules of ADP to make one of ATP and one of AMP (adenosine mono phosphate) to maintain energy viability. The AMP degrades and is washed out of the cell. When the ATP is spent it repeats the process lowering the pool of energy. If you return to the ATP picture earlier you will see it is made of 3 phosphates and Ribose (sugar) to bind and Adenonine which is a purine. As the cell viability falls we have less and less available purine. Purines are the key ingredient to make Uric acid. Too much Uric acid leads to gout. Too little uric acid means a scavenger of reactive oxygen species made from free radicals is depleted. The whole body becomes very vulnerable.
A common marker of multiple sclerosis is low Uric acid. It is extremely rare to have gout and MS. You would need to ingest massive amounts of Purines to alter that relationship.
If I wanted one marker to use I would measure Uric acid. If it is very low against the acceptable range. That would tell me that ATP depletion is a fundamental problem.
I would utilise the advice in the book “Metabolic Cardiology” by Stephen T. Sinatra, a US cardiologist.
For chronic fatigue (page 230) he uses
A multivitamin foundation program with 1 g per day of fish oil
300-360mg Coenzyeme Q10 (I think this is an IV dose) – I would think about working up to 750mg tablets a day
2-3000mg L-Carnitine
15g D-Ribose (you would need to find a good health shop or go on line)
400-800mg of Magnesium
Naturally, I would be testing for Epstein Barr Virus (the cause of Glandular Fever). You do not need a currently active infection. It is a herpes virus. Once infected it highjacks the B cells to reproduce and never goes away. An EBV infected B Cell is a prolific producer of the oxidant Superoxide. If you produce too much superoxide it can lead to the formation of Peroxynitrite.
Peroxynitrite can disable glyceralderhde-3-phosphate which is an important step in the second stage of glucose metabolism. If that fails, again, you will fail to produce ATP. Ironically, the best scavenger of Peroxynitrite is Uric acid. Unfortunately that is already affected.
If EBV is apparent, then I would consider using a 500mg twice a day of Valacyclovir. Some people really struggle with this and I suspect it is co-infections causing a herximer response. It may be too difficult and a doctor is best qualified to deal with that.
There are a range of other things to look at as we know but I would start at this level.
I hope this helps.
Regards
-
Interrupted
- Family Elder
- Posts: 240
- Joined: Sun Jan 14, 2007 3:00 pm
- Location: UK
- Contact:
Re: Beyond Avonex and Valtrex
Hi Scott,
A very interesting read, thank you. Taking on board those last supplement dosages...
Here's my update; briefly as have a heck of a headache today!
24hr ECG showed 8 'episodes' of rapid heart - the GP will get back to me on what they will/won't do this week.
Static ECG was fine. (Though if the problem is a 'weak' heart, i'd assume a 24hr BP test would be more enlightening!)
Currently taking; Myhill Methylation list and Mitochondrial Failure list still + Valtrex 250mg (finally tolerating it, hurrah) and Doxycycline/Azithromycin ABX still.
Currently doing an elimination diet. I have been thinking hard about my symptoms recently and they are very 'allergy' so, as i've never done a proper elimination diet, i'll be doing my best to live off salad, kale, pear, turkey, deep sea fish and veg for the next month - literally just to see if any of these really unnecessary extra symptoms disappear!
Hope you are still doing well!
A very interesting read, thank you. Taking on board those last supplement dosages...
Here's my update; briefly as have a heck of a headache today!
24hr ECG showed 8 'episodes' of rapid heart - the GP will get back to me on what they will/won't do this week.
Static ECG was fine. (Though if the problem is a 'weak' heart, i'd assume a 24hr BP test would be more enlightening!)
Currently taking; Myhill Methylation list and Mitochondrial Failure list still + Valtrex 250mg (finally tolerating it, hurrah) and Doxycycline/Azithromycin ABX still.
Currently doing an elimination diet. I have been thinking hard about my symptoms recently and they are very 'allergy' so, as i've never done a proper elimination diet, i'll be doing my best to live off salad, kale, pear, turkey, deep sea fish and veg for the next month - literally just to see if any of these really unnecessary extra symptoms disappear!
Hope you are still doing well!
28/07/10, 04/10/10, 16/11/10 - CCSVi Dopplers x3 ** 12/10/10 - Poland procedure. Symptoms worsened. No improvement.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
Re: Beyond Avonex and Valtrex
Hello again,
I was worried about you. Good to hear you're doing a few things. I wonder what happened with Valtrex.
The Sinatra approach is very forgiving on using conventional treatments in conjunction with his regime. The book is an interesting read but you need to like that style. I've added around 1500mg of acetyl L-Carnitine to my regime. Overall, I feel very untroubled by exercise and generally alert. I did run out of Q10 for two days and wilted. I think I will continue using both as I feel there is a benefit but I don't know how to be objective about it. I still have funny hands and a tight psoas but that's from demylination and it will take time. I'm still on sick leave so my days are all about Pilates and staying relaxed.
I think I will fully recover but remyelinating is going to take time.
Regards
I was worried about you. Good to hear you're doing a few things. I wonder what happened with Valtrex.
The Sinatra approach is very forgiving on using conventional treatments in conjunction with his regime. The book is an interesting read but you need to like that style. I've added around 1500mg of acetyl L-Carnitine to my regime. Overall, I feel very untroubled by exercise and generally alert. I did run out of Q10 for two days and wilted. I think I will continue using both as I feel there is a benefit but I don't know how to be objective about it. I still have funny hands and a tight psoas but that's from demylination and it will take time. I'm still on sick leave so my days are all about Pilates and staying relaxed.
I think I will fully recover but remyelinating is going to take time.
Regards
-
Interrupted
- Family Elder
- Posts: 240
- Joined: Sun Jan 14, 2007 3:00 pm
- Location: UK
- Contact:
Re: Beyond Avonex and Valtrex
Hope a good Christmas was had by all 
Quick update: Had quite a good Xmas, currently managing 500mg Valtrex without continued breathing/tachy trouble (hurrah!) and genuinely feel that I have slightly improved energy from a month ago. I've certainly been doing more most days. Those close to me have commented. Pretty heartening!
That said, i'm still having crash days, still battling vertigo, still have legs going awry, eyes have definitely got worse but overall i'm walking my dog for 10 mins 4-5 out of 7 days a week which has really cheered me up (considering the last 6 months). No more collapses the last two weeks. I do have a pain in in the right side of my mid-back that's been artound as long as the Valtrex, hoping it's muscular and not a kidney gripe, but hopefully have FBC after first Avonex so that should pick up any issue. Can't really ask doc for one with relation to this, because i'm not supposed to be on it.
Docs haven't goth back to me on the ECG result 'incidents' yet. Avonex arrived this morning.
Now I just need to get back on my hardcore allergy elimination diet and stop falling prey to Christmas junk food remainders!!!
How have you been Scott?
Quick update: Had quite a good Xmas, currently managing 500mg Valtrex without continued breathing/tachy trouble (hurrah!) and genuinely feel that I have slightly improved energy from a month ago. I've certainly been doing more most days. Those close to me have commented. Pretty heartening!
That said, i'm still having crash days, still battling vertigo, still have legs going awry, eyes have definitely got worse but overall i'm walking my dog for 10 mins 4-5 out of 7 days a week which has really cheered me up (considering the last 6 months). No more collapses the last two weeks. I do have a pain in in the right side of my mid-back that's been artound as long as the Valtrex, hoping it's muscular and not a kidney gripe, but hopefully have FBC after first Avonex so that should pick up any issue. Can't really ask doc for one with relation to this, because i'm not supposed to be on it.
Docs haven't goth back to me on the ECG result 'incidents' yet. Avonex arrived this morning.
Now I just need to get back on my hardcore allergy elimination diet and stop falling prey to Christmas junk food remainders!!!
How have you been Scott?
28/07/10, 04/10/10, 16/11/10 - CCSVi Dopplers x3 ** 12/10/10 - Poland procedure. Symptoms worsened. No improvement.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
Re: Beyond Avonex and Valtrex
Hi Interrupted,
I'm on the mend. That attack I had was a monster so it will take time to fully recover. The sensations have varied as I have progressed. When I was in hospital and prior to that I was troubled by my hands and had a lot of discomfort in my torso due to a tight psoas muscle. The hands became a moving feast when I tried to describe them and now they are like I'm wearing a pair of gloves but generally ok now. Enormous amounts of daily exercise helped the psoas and now I just have the odd period where I feel like I was "kicked in the guts" a few days prior but generally I'm better. The interesting thing for me is I have avoided fatigue.
The more I think about it the more convinced I am cycling ATP properly and that is the reason I can easily separate different symptoms. I would have been very distressed if I had fatigue on top of what I went through. It also leads me to think that more than one thing is going on at the same time. A decade of using Valtrex obviously needs to be factored in as that would have had a big impact on EBV replication by now. It also tells me that it isn't the only thing or I would not have been hit recently.
Leonard posted a terrific piece recently(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906243/) which suggest the EBV primes the cell to release pro inflammatory mediators when a second stimulus is provided. The article doesn't say what the second stimulus might be except in a lab setting but it would help explain why EBV is important to us but not others.
The three books I read (Wahls, Buhner and Sinatra) all have overlapping features without straying into each others area. All are worth reading (particularly Buhner and Sinatra) but you have to be comfortable reading that style. I can't buy D-Ribose down the street but I have adopted Aceytl L-Carnitine and added it to my Q10. (that's from Sinatra), I have added NAC (that's from Buhner) and I have dropped all dairy and Gluten and added a lot of fat (that's from Wahls). The overall effect is I seem to have plenty of energy and I'm getting better. Wahls doesn't like eggs so she omits them but I had been brainwashed by a cigarette smoking, whisky drinking mother that eggs were bad for you all my life and now I love them-no problem. Needless to say, avoid your allergens as staying in a non inflammatory state is critical.
Exercise has helped a great deal. My Pilates studio has been closed for 2 and a half weeks and I have been hit with horrible dead arm aches in the break. The first time I thought it was a heart attack. Cheap massage has helped but I cant wait to get back to structured exercise. When I was in hospital the physios described me a having layers of weakness over tightness. Couldn't have been more apt. I think my unstable structure is leading to pinched nerves. Sometimes its really debilitating but it helps when you know what's going on.
I am still on sick leave and removing stress must help as well.
I'm glad to hear you're feeling better. Good luck with the Interferon. It can be a monster. My best way of thinking of it is as a signaling agent to wake up the immune system. If you have a range of bugs underlying things you may find it hard work.
Let us know how you get on.
Regards
I'm on the mend. That attack I had was a monster so it will take time to fully recover. The sensations have varied as I have progressed. When I was in hospital and prior to that I was troubled by my hands and had a lot of discomfort in my torso due to a tight psoas muscle. The hands became a moving feast when I tried to describe them and now they are like I'm wearing a pair of gloves but generally ok now. Enormous amounts of daily exercise helped the psoas and now I just have the odd period where I feel like I was "kicked in the guts" a few days prior but generally I'm better. The interesting thing for me is I have avoided fatigue.
The more I think about it the more convinced I am cycling ATP properly and that is the reason I can easily separate different symptoms. I would have been very distressed if I had fatigue on top of what I went through. It also leads me to think that more than one thing is going on at the same time. A decade of using Valtrex obviously needs to be factored in as that would have had a big impact on EBV replication by now. It also tells me that it isn't the only thing or I would not have been hit recently.
Leonard posted a terrific piece recently(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906243/) which suggest the EBV primes the cell to release pro inflammatory mediators when a second stimulus is provided. The article doesn't say what the second stimulus might be except in a lab setting but it would help explain why EBV is important to us but not others.
The three books I read (Wahls, Buhner and Sinatra) all have overlapping features without straying into each others area. All are worth reading (particularly Buhner and Sinatra) but you have to be comfortable reading that style. I can't buy D-Ribose down the street but I have adopted Aceytl L-Carnitine and added it to my Q10. (that's from Sinatra), I have added NAC (that's from Buhner) and I have dropped all dairy and Gluten and added a lot of fat (that's from Wahls). The overall effect is I seem to have plenty of energy and I'm getting better. Wahls doesn't like eggs so she omits them but I had been brainwashed by a cigarette smoking, whisky drinking mother that eggs were bad for you all my life and now I love them-no problem. Needless to say, avoid your allergens as staying in a non inflammatory state is critical.
Exercise has helped a great deal. My Pilates studio has been closed for 2 and a half weeks and I have been hit with horrible dead arm aches in the break. The first time I thought it was a heart attack. Cheap massage has helped but I cant wait to get back to structured exercise. When I was in hospital the physios described me a having layers of weakness over tightness. Couldn't have been more apt. I think my unstable structure is leading to pinched nerves. Sometimes its really debilitating but it helps when you know what's going on.
I am still on sick leave and removing stress must help as well.
I'm glad to hear you're feeling better. Good luck with the Interferon. It can be a monster. My best way of thinking of it is as a signaling agent to wake up the immune system. If you have a range of bugs underlying things you may find it hard work.
Let us know how you get on.
Regards
-
Anonymoose
- Family Elder
- Posts: 1190
- Joined: Tue Oct 09, 2012 6:33 am
Re: Beyond Avonex and Valtrex
Hopping over from Leonard's thread...
How could I have forgotten it was the n acetyl glucosamine? I guess my brain has reached full capacity. New stuff goes in and old stuff goes out. :rolls eyes:
Anyway, that trigger ties into my recent suspicion that candida might be playing a part in ms for some of us too. NAG feeds candida and morphs it to its more creepy/damaging form. (Not a detail person so you'll have to seek more accurate description elsewhere). Here's a link. http://informahealthcare.com/doi/abs/10 ... alCode=mmy. Your relapse after high dosing NAG in addition to your occasional mention of white tongue seem to fit the picture I'm getting. OOoo. And maybe your slowish recovery is because of those antibiotics you were taking which would also give candida a leg up in your gut. I jumped on Leonard's thread because it's really his idea...gut flora & ebv contributing together.
Anywho, have a brain munch and let me know what you think.
How could I have forgotten it was the n acetyl glucosamine? I guess my brain has reached full capacity. New stuff goes in and old stuff goes out. :rolls eyes:
Anyway, that trigger ties into my recent suspicion that candida might be playing a part in ms for some of us too. NAG feeds candida and morphs it to its more creepy/damaging form. (Not a detail person so you'll have to seek more accurate description elsewhere). Here's a link. http://informahealthcare.com/doi/abs/10 ... alCode=mmy. Your relapse after high dosing NAG in addition to your occasional mention of white tongue seem to fit the picture I'm getting. OOoo. And maybe your slowish recovery is because of those antibiotics you were taking which would also give candida a leg up in your gut. I jumped on Leonard's thread because it's really his idea...gut flora & ebv contributing together.
Anywho, have a brain munch and let me know what you think.
Re: Beyond Avonex and Valtrex
On Leonards post I posted a link to an article on arachidonic acid. As I said there, it points out is EBV infected cells are primed for a further stimulus to lead to arachidonic acid release. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906243/ .
The article makes the point that it's not the EBV itself but that is integral. It is EBV infected polymorphonuclear leucocytes that when stimulated that start a response.
It's the second stimulus that does the damage as the cell is already primed. It's a great article. They don't identify the second stimulus but I guess it could be from a number of sources. The justification for controlling EBV is stronger having read this as, if the cell is not primed, then the second stimulus is neutered.
One of the stimuli they tried was Zymosan. This is found on the surfaces of fungi.
This is the composition of fungal cell walls
- http://en.wikipedia.org/wiki/Cell_wall
- Not all species of fungi have cell walls but in those that do, the plasma membrane is followed by three layers of cell wall material. From inside out these are:
• a chitin layer (polymer consisting mainly of unbranched chains of N-acetyl-D-glucosamine)
• a layer of β-1,3-glucan (zymosan)
• a layer of mannoproteins (mannose-containing glycoproteins) which are heavily glycosylated at the outside of the cell.
So here we have two differing sources of inflammation. The Zymosan in the experiment triggered an response in EBV infected cells and NAG does it anyway. I guess the point is there are many possible triggers for inflammation. Deal with them as best you can.
Regards
The article makes the point that it's not the EBV itself but that is integral. It is EBV infected polymorphonuclear leucocytes that when stimulated that start a response.
It's the second stimulus that does the damage as the cell is already primed. It's a great article. They don't identify the second stimulus but I guess it could be from a number of sources. The justification for controlling EBV is stronger having read this as, if the cell is not primed, then the second stimulus is neutered.
One of the stimuli they tried was Zymosan. This is found on the surfaces of fungi.
This is the composition of fungal cell walls
- http://en.wikipedia.org/wiki/Cell_wall
- Not all species of fungi have cell walls but in those that do, the plasma membrane is followed by three layers of cell wall material. From inside out these are:
• a chitin layer (polymer consisting mainly of unbranched chains of N-acetyl-D-glucosamine)
• a layer of β-1,3-glucan (zymosan)
• a layer of mannoproteins (mannose-containing glycoproteins) which are heavily glycosylated at the outside of the cell.
So here we have two differing sources of inflammation. The Zymosan in the experiment triggered an response in EBV infected cells and NAG does it anyway. I guess the point is there are many possible triggers for inflammation. Deal with them as best you can.
Regards
-
Anonymoose
- Family Elder
- Posts: 1190
- Joined: Tue Oct 09, 2012 6:33 am
Re: Beyond Avonex and Valtrex
Details, details. The part that gets me about going that deep is you get stuck in the minutiae of one particular angle that seems to fit and could be completely off base, missing the big picture (been there, done that). Or you could be right.
Too bad there isn't a standard panel of tests you can take to identify all possible contributors. Without it, we are left taking risks trying to correct the problems we know we have.
Be well.
Too bad there isn't a standard panel of tests you can take to identify all possible contributors. Without it, we are left taking risks trying to correct the problems we know we have.
Be well.
Re: Beyond Avonex and Valtrex
That's the truth of it.
I guess the point I'm trying to make is once you have established a predisposition, many things can be the activator. I'm sure we are staring at the right things but we don't know how they fit together. Do age, gender, racial background, geography, past infections, current infections, deficiencies, metabolic imbalances, stresses, physiology, diet and anything else I missed play a role or don't they? Does it makes a difference if you treat each problem separately? Is my story the same as yours or almost without commonalities? Is it a single problem or many problems with a common presentation?
I suspect most of us, when we were diagnosed, expected there would be a set of possible contributors already established by now but there just isn't an universally accepted point of view. The opinions hurled at me twenty years ago have all failed the test of time but still dominate clinicians conversation because they don't have anything else to add. In a sense, they are waiting for us to tell them because we present such a diversity of problems. If it was just one thing we would all be better. "Multiple" is the word to focus on.
The answer will be in the minutiae but there is rather a lot of that to look at. This site helps because we have more conversations in detail than you can have in a clinic. Maybe we will get lucky.
In a perfect world, if we tried something that someone else suggested we would tell each other, as you and I tend to do. How many others try something and never say what happened. How much more could we learn? I thought I had my problem licked for good till I made a mistake (my view). Now I have a set of demyelination issues to deal with but I still don't have fatigue. Is there any benefit in all that? Maybe there is which is why I write it down. If there isn't I wish I knew what else happened to others because that's where the minutiae counts.
There are many common issues and solutions that have relevance for someone newly diagnosed and we need to share that knowledge because they simply won't know and won't have anywhere to turn. If we don't share our mistakes others will repeat them. It's not just about successes.
Regards
I guess the point I'm trying to make is once you have established a predisposition, many things can be the activator. I'm sure we are staring at the right things but we don't know how they fit together. Do age, gender, racial background, geography, past infections, current infections, deficiencies, metabolic imbalances, stresses, physiology, diet and anything else I missed play a role or don't they? Does it makes a difference if you treat each problem separately? Is my story the same as yours or almost without commonalities? Is it a single problem or many problems with a common presentation?
I suspect most of us, when we were diagnosed, expected there would be a set of possible contributors already established by now but there just isn't an universally accepted point of view. The opinions hurled at me twenty years ago have all failed the test of time but still dominate clinicians conversation because they don't have anything else to add. In a sense, they are waiting for us to tell them because we present such a diversity of problems. If it was just one thing we would all be better. "Multiple" is the word to focus on.
The answer will be in the minutiae but there is rather a lot of that to look at. This site helps because we have more conversations in detail than you can have in a clinic. Maybe we will get lucky.
In a perfect world, if we tried something that someone else suggested we would tell each other, as you and I tend to do. How many others try something and never say what happened. How much more could we learn? I thought I had my problem licked for good till I made a mistake (my view). Now I have a set of demyelination issues to deal with but I still don't have fatigue. Is there any benefit in all that? Maybe there is which is why I write it down. If there isn't I wish I knew what else happened to others because that's where the minutiae counts.
There are many common issues and solutions that have relevance for someone newly diagnosed and we need to share that knowledge because they simply won't know and won't have anywhere to turn. If we don't share our mistakes others will repeat them. It's not just about successes.
Regards
-
Interrupted
- Family Elder
- Posts: 240
- Joined: Sun Jan 14, 2007 3:00 pm
- Location: UK
- Contact:
Re: Beyond Avonex and Valtrex
Update - "Ahh Avones, I have not missed you."
Onward from the previous, 'out and about more' hurrah type update. It all went wrong. I had a stressful week getting an assignment in, got through that fine, then started to feel awful. Could have been the stress and late nights or could have been viral. Legs started getting weak, vision worsening (at the time I thought it was screen stare from typing but now I don't think so), exhaustion.
THEN a few days later I was booked in for my first Avonex injection. I remembered Avonex (albeit vaguely after a decade) and was not thrilled at facing that while feeling so rough. And yep, late evening, the shivering started, the blurry vision and that skull splitting, weight of the 1a headache. Now I get bad migraines frequently, but this was just crucifying me all night, plus I couldn't bear anything touching my skin (but I can live with that and the fluey stuff). It took two days to see the back of it. And my poor body has been acting like it's in shock ever since, my legs are weak as water, my vision is painful, sore and dry, my comprehension and cognition is all over the show and I keep getting almost convulsive shakes. And the depression... yes apparently Avonex and Valtrex together is a nasty combination for that, even if you've never had any for of it before.
So yup that's where i'm at...
Valtrex seemed briefly to do my stamina some good, briefly gave me heart and breathing problems which passed, and overall clinically depresses me a smidge. I also suspect my vision and cognitive problems are stemming from here. I may drop back to 250mg/day or switch to straight Acyclovir 2x250mg/day.
Avonex is just evil in my book but hopefully will not always be for me. Currently knocking out my legs and making me extremely weak, causing the shakes and sore muscles. Very scared of taking it again, swore I wouldn't but probably will.
The reason i'm mostly upset is that i've lost my ability to have a little walk with my dog every day. Little things mean a lot etc.
Onward from the previous, 'out and about more' hurrah type update. It all went wrong. I had a stressful week getting an assignment in, got through that fine, then started to feel awful. Could have been the stress and late nights or could have been viral. Legs started getting weak, vision worsening (at the time I thought it was screen stare from typing but now I don't think so), exhaustion.
THEN a few days later I was booked in for my first Avonex injection. I remembered Avonex (albeit vaguely after a decade) and was not thrilled at facing that while feeling so rough. And yep, late evening, the shivering started, the blurry vision and that skull splitting, weight of the 1a headache. Now I get bad migraines frequently, but this was just crucifying me all night, plus I couldn't bear anything touching my skin (but I can live with that and the fluey stuff). It took two days to see the back of it. And my poor body has been acting like it's in shock ever since, my legs are weak as water, my vision is painful, sore and dry, my comprehension and cognition is all over the show and I keep getting almost convulsive shakes. And the depression... yes apparently Avonex and Valtrex together is a nasty combination for that, even if you've never had any for of it before.
So yup that's where i'm at...
Valtrex seemed briefly to do my stamina some good, briefly gave me heart and breathing problems which passed, and overall clinically depresses me a smidge. I also suspect my vision and cognitive problems are stemming from here. I may drop back to 250mg/day or switch to straight Acyclovir 2x250mg/day.
Avonex is just evil in my book but hopefully will not always be for me. Currently knocking out my legs and making me extremely weak, causing the shakes and sore muscles. Very scared of taking it again, swore I wouldn't but probably will.
The reason i'm mostly upset is that i've lost my ability to have a little walk with my dog every day. Little things mean a lot etc.
28/07/10, 04/10/10, 16/11/10 - CCSVi Dopplers x3 ** 12/10/10 - Poland procedure. Symptoms worsened. No improvement.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
Re: Beyond Avonex and Valtrex
Hi Interrupted,
Are you using anything to block Avonex's side effects? I found that taking 400 mg of ibuprofen just before my shot to be helpful. A second dose about 4 or 5 hours later helped too.
Are you using anything to block Avonex's side effects? I found that taking 400 mg of ibuprofen just before my shot to be helpful. A second dose about 4 or 5 hours later helped too.
Re: Beyond Avonex and Valtrex
Hi Again,
I said Avonex can be a monster. The original box had a leaflet in it which said each shot contained a large amount of antiviral activity. They don't do that anymore out here. All interferon does is alert the immune system that it needs to respond to an infection. Waking your immune system up by loading with a signaling agent just means it will attack anything that is foreign. The more pathogens it suddenly sees the more exaggerated the response. A simple way to look at it is to imagine how your body ached when you were coming down with something. The ache you feel is interferons triggering an immune response. It doesn't cure anything itself just start a process.
I suggest you need to wind back to treating the mitochrondrial health first by using Q10, L-carnitine and later N-Aceytl-Cysteine. Then I would look at Candida which Anonymoose has flagged was an issue with her use of Valtrex in particular. You can treat candida with diet and Nilstat powder but it takes time.
Also check for mycoplasmas, Chlamydias and any of the other infections we have spoken about before. The lesson is the interferon will arc up the response to infection. Any one who says Avonex suppresses the immune system is confusing it with Prednislone and assuming they are similar. They most definitely are not.
When you feel better I'd reintroduce the Valtrex to see how you go and then look at Avonex after that. Clearing out the background infections will be critical if you are trying it the way I did. You can try NHE's suggestion as that does help with discomfort.
Regarding depression, try boosting your intake of foods that are high in Tryptophan. That will probably also help you get B vitamins as well. I'm not a fan of palliatives like antidepressants unless you have no option as they can be their own nightmare.
Tell me about your walking?
Regards
I said Avonex can be a monster. The original box had a leaflet in it which said each shot contained a large amount of antiviral activity. They don't do that anymore out here. All interferon does is alert the immune system that it needs to respond to an infection. Waking your immune system up by loading with a signaling agent just means it will attack anything that is foreign. The more pathogens it suddenly sees the more exaggerated the response. A simple way to look at it is to imagine how your body ached when you were coming down with something. The ache you feel is interferons triggering an immune response. It doesn't cure anything itself just start a process.
I suggest you need to wind back to treating the mitochrondrial health first by using Q10, L-carnitine and later N-Aceytl-Cysteine. Then I would look at Candida which Anonymoose has flagged was an issue with her use of Valtrex in particular. You can treat candida with diet and Nilstat powder but it takes time.
Also check for mycoplasmas, Chlamydias and any of the other infections we have spoken about before. The lesson is the interferon will arc up the response to infection. Any one who says Avonex suppresses the immune system is confusing it with Prednislone and assuming they are similar. They most definitely are not.
When you feel better I'd reintroduce the Valtrex to see how you go and then look at Avonex after that. Clearing out the background infections will be critical if you are trying it the way I did. You can try NHE's suggestion as that does help with discomfort.
Regarding depression, try boosting your intake of foods that are high in Tryptophan. That will probably also help you get B vitamins as well. I'm not a fan of palliatives like antidepressants unless you have no option as they can be their own nightmare.
Tell me about your walking?
Regards
-
Interrupted
- Family Elder
- Posts: 240
- Joined: Sun Jan 14, 2007 3:00 pm
- Location: UK
- Contact:
Re: Beyond Avonex and Valtrex
Hi, thank you for all the advice, very much appreciated. I'll have to go point by point for my brain to follow...
NHE - Hi, yes, 2 brufen every few hours and paracetamol for the chills etc, but they don't touch it. I remember it being that way before. The only thing that began to shift that monster headache was my migraine pills. My predisposition to everything ending up in nasty headaches does concern me a bit.
Scott - Ah darn, I thought it did have anti-viral properties... If this isn't the case, that's a big bit of oops news on my part. Is it something they have removed? Because you generally read comments about people finding they don't get colds etc. when taking it?
Not that i'm averse to 'not' taking it, but here it's not something I can just start and stop at will. If I stop it, I won't have it offered again. I went with it to make it seem like I was playing ball with my Neuro on something, and because I thought it complemented the Valtrex on the anti-viral front. That said, if I say the effects are too much, I can stop.
Mitochondrial health, I hope I am, as in previous convo's. I'm still on both the Myhill supplement protocols. Including Q10. I've taken NAC for years, since trying the ABX.
Candida - I wholeheartedly agree that it's a stealthy bugger and people can have problems with it, without even knowing. I've tried to tackle it many times, it's always flagged on CFS boards with good reason too. But tbh, if i'm eating a healthy diet and taking anti Candida probiotics it's under control. I don't think it's one that that can be got rid of totally very easily because one sniff of sugar and it's back. I can't get hold of Nystatin here, i've tried before.
Again, the mycoplasmas etc. I can't check for them - I have no way of doing so. Unfortunately I literally cannot do anything about this aspect.
The is why i'm going this route, basically just doing all I can, with what I can. Valtrex and Acyclovir are things I can just about manage to get hold of off the book. I'd love to be able to start at the beginning, but i've got very little to work with so I feel that all I can do is try and stop the ebv replicating and chip away at it
Walking - Typically the bottom of my back will start to numb. L'hermittes will start. Legs will start to weaken. Power goes and they buckle.
This time i'm getting searing pain in my thigh muscles too, which is making me think it's brought on by the Avonex.
NHE - Hi, yes, 2 brufen every few hours and paracetamol for the chills etc, but they don't touch it. I remember it being that way before. The only thing that began to shift that monster headache was my migraine pills. My predisposition to everything ending up in nasty headaches does concern me a bit.
Scott - Ah darn, I thought it did have anti-viral properties... If this isn't the case, that's a big bit of oops news on my part. Is it something they have removed? Because you generally read comments about people finding they don't get colds etc. when taking it?
Not that i'm averse to 'not' taking it, but here it's not something I can just start and stop at will. If I stop it, I won't have it offered again. I went with it to make it seem like I was playing ball with my Neuro on something, and because I thought it complemented the Valtrex on the anti-viral front. That said, if I say the effects are too much, I can stop.
Mitochondrial health, I hope I am, as in previous convo's. I'm still on both the Myhill supplement protocols. Including Q10. I've taken NAC for years, since trying the ABX.
Candida - I wholeheartedly agree that it's a stealthy bugger and people can have problems with it, without even knowing. I've tried to tackle it many times, it's always flagged on CFS boards with good reason too. But tbh, if i'm eating a healthy diet and taking anti Candida probiotics it's under control. I don't think it's one that that can be got rid of totally very easily because one sniff of sugar and it's back. I can't get hold of Nystatin here, i've tried before.
Again, the mycoplasmas etc. I can't check for them - I have no way of doing so. Unfortunately I literally cannot do anything about this aspect.
The is why i'm going this route, basically just doing all I can, with what I can. Valtrex and Acyclovir are things I can just about manage to get hold of off the book. I'd love to be able to start at the beginning, but i've got very little to work with so I feel that all I can do is try and stop the ebv replicating and chip away at it
Walking - Typically the bottom of my back will start to numb. L'hermittes will start. Legs will start to weaken. Power goes and they buckle.
This time i'm getting searing pain in my thigh muscles too, which is making me think it's brought on by the Avonex.
28/07/10, 04/10/10, 16/11/10 - CCSVi Dopplers x3 ** 12/10/10 - Poland procedure. Symptoms worsened. No improvement.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
13/02/12 - Wheldon ABX protocol for 1.5yrs. Fairly stable but no improvement. Unable to source alternate ABX needed.
Re: Beyond Avonex and Valtrex
Hi Again,
I guess we don't want to get caught up in semantics here but anti viral properties is a very broad term. From memory the leaflet said anti viral activity. That's a property but interferon is not a killer cell or any sort of viral disabler itself. Interferon signals something else to activate to do the work. The activation will be indiscriminate which is why the reaction can be so adverse. It is not a targeted medication with a specific job to attack something.
If you're doing the right things then I guess just have another go and see if its more tolerable. My first injection was a terrible one but it did settle down to a predictable horrid effect and I could plan to take it before I went to bed and chewed Panadol rapid for a day. My old notes clearly show I was no better or worse on it on its own but a combination definitely helped. I did take Avonex for some time before I found Valtrex so staggering the introduction may be important.
On the walking issue, does it seem to be constant or related to the Avonex dosing?
I think you could benefit from exercises that focus on neural flossing. Here's a couple of different things to try - and They are generally very gentle and a small number of repetitions is fine.
If it starts in the lower back that suggests the core muscles in the pelvic area need strengthening. try this each day as well - . It is always better to have someone guide you through doing it properly rather than assume you are doing it correctly. I've been doing these exercises for years and still get picked up on technique from time to time. Your brain loves to fool you into becoming over confident. If you don't do them properly then you are practicing your mistakes and there is no benefit. You'll feel it if you do them properly.
There are obviously many more exercises with increasing complexity and fitness requirements but I'd start here if I was you.
I also found this video when I was looking up the others and I thought it was really valuable whether you had MS or not. The order we do things in and how we choose to breath through those movements has a massive impact on back pain.
Regards
I guess we don't want to get caught up in semantics here but anti viral properties is a very broad term. From memory the leaflet said anti viral activity. That's a property but interferon is not a killer cell or any sort of viral disabler itself. Interferon signals something else to activate to do the work. The activation will be indiscriminate which is why the reaction can be so adverse. It is not a targeted medication with a specific job to attack something.
If you're doing the right things then I guess just have another go and see if its more tolerable. My first injection was a terrible one but it did settle down to a predictable horrid effect and I could plan to take it before I went to bed and chewed Panadol rapid for a day. My old notes clearly show I was no better or worse on it on its own but a combination definitely helped. I did take Avonex for some time before I found Valtrex so staggering the introduction may be important.
On the walking issue, does it seem to be constant or related to the Avonex dosing?
I think you could benefit from exercises that focus on neural flossing. Here's a couple of different things to try - and They are generally very gentle and a small number of repetitions is fine.
If it starts in the lower back that suggests the core muscles in the pelvic area need strengthening. try this each day as well - . It is always better to have someone guide you through doing it properly rather than assume you are doing it correctly. I've been doing these exercises for years and still get picked up on technique from time to time. Your brain loves to fool you into becoming over confident. If you don't do them properly then you are practicing your mistakes and there is no benefit. You'll feel it if you do them properly.
There are obviously many more exercises with increasing complexity and fitness requirements but I'd start here if I was you.
I also found this video when I was looking up the others and I thought it was really valuable whether you had MS or not. The order we do things in and how we choose to breath through those movements has a massive impact on back pain.
Regards