As we know most MSers take Acetyl-L-Carnitine + Q10 for their fatigue.
I give to my wife twice per day 50mg Thiamine Pyrophosphate (TPP) and once 100mg Alithiamine as she find they help her probably better than the ALC/Q10 she takes at different hours.
What do you people take for treating your fatigue?
TPP, alithiamine, Q10 & ALC for fatique
Re: TPP, alithiamine, Q10 & ALC for fatique
Hi Dim,
It may not be true that most MSers take those supplements for fatigue, you might have got those ideas from some things I wrote. I've elaborated on it in a book I wrote. The book is called Multiple Sclerosis: One Owner’s Manual.
https://www.amazon.com/Multiple-Scleros ... 645468002/
If you take a very simplistic approach, you could break MS into two areas-1) fatigue related issues and 2) everything else. Sometimes, solving fatigue makes some of the other issues more bearable.
If we say fatigue is a lack of energy then we have to ask what is energy and how is it made in the body.
For all activity in living things the key to energy is a molecule called ATP (adenosine triphosphate). When it loses phosphate from its structure, energy is released which allows other molecular activities to occur. Although science has known ATP existed for around 100 years by now , it did take a long time to work out what it was doing. The 1997 Nobel prize for chemistry was awarded to three men who finally unscrambled the puzzle of how it was made and what it did.
See - https://www.nobelprize.org/prizes/chemi ... s-release/
All the things we eat need to be converted into a form our body can use. Along the way, some elements of food become waste, some some become factors to assist cellular function and some go to the pathway that helps us make energy. If we discard all the other elements and just focus on the energy pathway, our body converts elements of foodstuffs into a sugar called glucose. A single molecule is made up of 6 carbon 12 Hydrogen and 6 oxygen atoms. Ignoring all the science stuff, we end up exhaling (or using) the carbon and oxygen and use the hydrogen atoms to drive the formation of ATP.
How do we do that? In every part of our body we have small membrane bound organelles called mitochondria. This is where the hydrogen atoms from our food are essential. They drive a complex molecular machine called an ATP synthase to make ATP.
On the way to getting to that stage, there a few cycles to transform those glucose molecules into the end stage atoms. The first is called glycolysis, which, after a few steps, requires additional oxygen. If it isn't available it becomes lactate and recycles back into glucose for a new cycle. There are a lot of steps and alternative pathways around this (which I will ignore) and the next relevant cycle is called the Krebs (or citric acid) cycle. This is where the hydrogen atoms are freed up to be taken to the last cycle. The transport agents that then carry the hydrogen to the last cycle are derivatives of B vitamins. The supplement your wife is taking descends from vitamin B1 (Thiamine). It will be a cofactor in a range of functions in the mitochondria. The transport agents for the hydrogen atoms derive from vitamins B2 and B3. All of them are important. Dark green leafy vegetables and meat are good sources for B vitamins.
The acetyl- L- carnitine helps transport fatty acids into the mitochondria so they can be 'burned' to release the hydrogen. That process (called Beta oxidation) releases the most hydrogen per cycle .
The CoQ10 is the major orchestrator of the movement of hydrogen electrons in the last stage in the process called the electron transport chain. Without it- you would be dead. If it is depleted- you would be fatigued. It's that fundamental.
However, those processes don't explain entirely why undue fatigue arises.
There is a very significant body of evidence building up that points the finger at Epstein Barr Virus (EBV) as a key element in MS. In my book, I tried to explain there is a possible mechanism for EBV to disrupt the orderly breakdown of ATP, leaving an excessive amount of adenosine. In our normal lives, ATP is always breaking down and adenosine is building up. We sleep to help clear the adenosine. If it doesn't clear, we remain unrefreshed and fatigued when we awaken.
Muscle fatigue also relates to ATP but its a different process and too involved for a web site chat.
I have treated my MS for over 20 years by focussing on EBV and taking the antiviral, valacyclovir. I don't have any cognitive fatigue and always have plenty of energy. I do have some muscle tightness in my left leg but I don't see it as a major fatigue issue. (that's a separate discussion about upper and lower motor neurons!).
So, what do I do that keeps me fatigue free?
I take
2x 500mg valacyclovir daily ( sometimes spelled as valciclovir)
2x 1000mg daily Aceytl-L-Carnitine
750mg daily of CoQ10 (that's a massive dose but the issue would be is it wasted not is it toxic)
2x500mg daily Magnesium glycinate ( needs to be glycinate, other forms would give you diarrhoea at that quantity)
I also take a curcumin supplement, but not as a fatigue treatment.
Hope that helps.
Regards,
It may not be true that most MSers take those supplements for fatigue, you might have got those ideas from some things I wrote. I've elaborated on it in a book I wrote. The book is called Multiple Sclerosis: One Owner’s Manual.
https://www.amazon.com/Multiple-Scleros ... 645468002/
If you take a very simplistic approach, you could break MS into two areas-1) fatigue related issues and 2) everything else. Sometimes, solving fatigue makes some of the other issues more bearable.
If we say fatigue is a lack of energy then we have to ask what is energy and how is it made in the body.
For all activity in living things the key to energy is a molecule called ATP (adenosine triphosphate). When it loses phosphate from its structure, energy is released which allows other molecular activities to occur. Although science has known ATP existed for around 100 years by now , it did take a long time to work out what it was doing. The 1997 Nobel prize for chemistry was awarded to three men who finally unscrambled the puzzle of how it was made and what it did.
See - https://www.nobelprize.org/prizes/chemi ... s-release/
All the things we eat need to be converted into a form our body can use. Along the way, some elements of food become waste, some some become factors to assist cellular function and some go to the pathway that helps us make energy. If we discard all the other elements and just focus on the energy pathway, our body converts elements of foodstuffs into a sugar called glucose. A single molecule is made up of 6 carbon 12 Hydrogen and 6 oxygen atoms. Ignoring all the science stuff, we end up exhaling (or using) the carbon and oxygen and use the hydrogen atoms to drive the formation of ATP.
How do we do that? In every part of our body we have small membrane bound organelles called mitochondria. This is where the hydrogen atoms from our food are essential. They drive a complex molecular machine called an ATP synthase to make ATP.
On the way to getting to that stage, there a few cycles to transform those glucose molecules into the end stage atoms. The first is called glycolysis, which, after a few steps, requires additional oxygen. If it isn't available it becomes lactate and recycles back into glucose for a new cycle. There are a lot of steps and alternative pathways around this (which I will ignore) and the next relevant cycle is called the Krebs (or citric acid) cycle. This is where the hydrogen atoms are freed up to be taken to the last cycle. The transport agents that then carry the hydrogen to the last cycle are derivatives of B vitamins. The supplement your wife is taking descends from vitamin B1 (Thiamine). It will be a cofactor in a range of functions in the mitochondria. The transport agents for the hydrogen atoms derive from vitamins B2 and B3. All of them are important. Dark green leafy vegetables and meat are good sources for B vitamins.
The acetyl- L- carnitine helps transport fatty acids into the mitochondria so they can be 'burned' to release the hydrogen. That process (called Beta oxidation) releases the most hydrogen per cycle .
The CoQ10 is the major orchestrator of the movement of hydrogen electrons in the last stage in the process called the electron transport chain. Without it- you would be dead. If it is depleted- you would be fatigued. It's that fundamental.
However, those processes don't explain entirely why undue fatigue arises.
There is a very significant body of evidence building up that points the finger at Epstein Barr Virus (EBV) as a key element in MS. In my book, I tried to explain there is a possible mechanism for EBV to disrupt the orderly breakdown of ATP, leaving an excessive amount of adenosine. In our normal lives, ATP is always breaking down and adenosine is building up. We sleep to help clear the adenosine. If it doesn't clear, we remain unrefreshed and fatigued when we awaken.
Muscle fatigue also relates to ATP but its a different process and too involved for a web site chat.
I have treated my MS for over 20 years by focussing on EBV and taking the antiviral, valacyclovir. I don't have any cognitive fatigue and always have plenty of energy. I do have some muscle tightness in my left leg but I don't see it as a major fatigue issue. (that's a separate discussion about upper and lower motor neurons!).
So, what do I do that keeps me fatigue free?
I take
2x 500mg valacyclovir daily ( sometimes spelled as valciclovir)
2x 1000mg daily Aceytl-L-Carnitine
750mg daily of CoQ10 (that's a massive dose but the issue would be is it wasted not is it toxic)
2x500mg daily Magnesium glycinate ( needs to be glycinate, other forms would give you diarrhoea at that quantity)
I also take a curcumin supplement, but not as a fatigue treatment.
Hope that helps.
Regards,
Re: TPP, alithiamine, Q10 & ALC for fatique
Thanks again Scott for your explainations.
I do give my wife since the beggining 3X500mg ALC and recently increased the Q10 to 3X150mg daily, but after I read the Klenner protocol I added to her regimen cocarboxylase (TPP) and alithiamine (very expensive) which seems to have at least the same effect in her energy levels, every 2-3 hours she takes an energy boost supplement.
By the way she takes mainly Magnesium threonate and small dose glycinate, I believe the first one is by far better than any other form for MS.
I do give my wife since the beggining 3X500mg ALC and recently increased the Q10 to 3X150mg daily, but after I read the Klenner protocol I added to her regimen cocarboxylase (TPP) and alithiamine (very expensive) which seems to have at least the same effect in her energy levels, every 2-3 hours she takes an energy boost supplement.
By the way she takes mainly Magnesium threonate and small dose glycinate, I believe the first one is by far better than any other form for MS.
Re: TPP, alithiamine, Q10 & ALC for fatique
I've taken PQQ and found it to be helpful for fatigue.
I've also taken Fisetin and found it to be helpful as well. Fisetin is an antioxidant that's found in several foods. The highest concentration is in strawberries. It helps promote BDNF.
Re: TPP, alithiamine, Q10 & ALC for fatique
I need more than one page to write what my wife takes daily.
She tried Fisetin and Luteolin, with no such effect as you say, now she takes Apigenin as it seems to be more powerful than both.
Anyway, she takes at different hours the following:
Vit A, B1 sublingual cocarboxylase & Allithiamine, B3 100mg, B complex sublingual coenzymated, C 250mg (ascorbyl 2 phosphate), D3 5000IU+K2, E & Tocotrienols, Chromium, Magnesium threonate & glycinate, Kelp, Selenium, Calcium, Zinc picolinate, Iron (limited dose for her deficiency).
Omega 3 2X950mg, CDP choline, Probiotics 500 billion, Q10 liposomal 3X150mg, NArALA 2X250mg, NAC 2X500mg, ALC 3X500mg, Inosine 500mg.
Ginkgo biloba, Curcumin (CurQfen + Fenugreek) 3X150mg, EGCG 2X450mg, Quercetin liposomal 3X250mg, Apigenin liposomal, Lions Mane, Phosphatidyl Serine, Monolaurin, Olive leaf extract, Milk Thistle.
I am sure her MS started due to recurrent EBV infections so my only concern is if/when I could give her Valtrex 2X500mg!
I was in a Fb Valacyclovir group where mainly women had very bad side effects from taking it so I stepped back for a while, plus I can't find a neurologist to prescribe it.
She tried Fisetin and Luteolin, with no such effect as you say, now she takes Apigenin as it seems to be more powerful than both.
Anyway, she takes at different hours the following:
Vit A, B1 sublingual cocarboxylase & Allithiamine, B3 100mg, B complex sublingual coenzymated, C 250mg (ascorbyl 2 phosphate), D3 5000IU+K2, E & Tocotrienols, Chromium, Magnesium threonate & glycinate, Kelp, Selenium, Calcium, Zinc picolinate, Iron (limited dose for her deficiency).
Omega 3 2X950mg, CDP choline, Probiotics 500 billion, Q10 liposomal 3X150mg, NArALA 2X250mg, NAC 2X500mg, ALC 3X500mg, Inosine 500mg.
Ginkgo biloba, Curcumin (CurQfen + Fenugreek) 3X150mg, EGCG 2X450mg, Quercetin liposomal 3X250mg, Apigenin liposomal, Lions Mane, Phosphatidyl Serine, Monolaurin, Olive leaf extract, Milk Thistle.
I am sure her MS started due to recurrent EBV infections so my only concern is if/when I could give her Valtrex 2X500mg!
I was in a Fb Valacyclovir group where mainly women had very bad side effects from taking it so I stepped back for a while, plus I can't find a neurologist to prescribe it.
Re: TPP, alithiamine, Q10 & ALC for fatique
By the way she has never taken other medications from the diagnosis in 2006, except LDN until 2021, when she had a bad relapse that left her with gait, balance and fatigue problems she never had before!
Re: TPP, alithiamine, Q10 & ALC for fatique
Hi Dim,
I don't doubt you have good reasons for introducing all those things, but most are not part of how I address fatigue. With so many things there is a risk that a graph of the dose benefit ends up looking like an inverted U. The issue is being sure that isn't happening.
A big difference between our approaches is the valacyclovir. There have been studies in the 1990s and early 2000s that looked at using valacyclovir to treat MS but the conclusion was it made no difference. When I read those studies I can see that what they wanted to happen didn't occur so the conclusion was self evident. Some studies were very short term, some had small populations, some seemed to want demyelination to reverse. A number of them noted that clinical improvements (i.e. patient well being improved) were not supported by MRI, so people possibly felt better but the discussion of that aspect is lacking.
Now EBV is moving towards the centre of thinking about the cause of MS, but there is still insufficient research to explain the mechanism of action of that virus. Like a lot of viruses it can mutate so we know there is, at least, a type 1 and a type 2 EBV. It has constant and variable regions in its structure so lots of variation is possible.
The other big issue is why (if EBV is the cause) do a small group of the population get MS while the great majority have no discernable long term illness from EBV exposure? As this would have to go back to the time of infection, there can be a huge time elapse before MS symptoms are noticeable -no one is looking at that early stage. This is a similar question to why did some people barely get a sniffle with Covid while others died of it. They are both viruses but they are very different.
In a note in my book, I looked at a cell called a plasmacytoid dendritic cell. This is the cell that introduces viruses to T cells and is the primary cell that activates the T cell. In the vast majority of people that introduction is accompanied by a strong type 1 interferon response. A report from 2012 https://www.sciencedirect.com/science/a ... via%3Dihub showed if the interferon signal was too weak that the necessary cytokines were not released and T cell response was muted. After a time, when the virus is well embedded the immune system responds too vigorously and an inflammatory reaction develops. The study implied this was a step in the development of MS.
A similar argument has been proposed to explain the variation in responses to the Covid virus. https://jamanetwork.com/journals/jama/f ... le/2768926
If this is how EBV begins its journey for MS patients, it would be logical to assume that whatever antiviral strategy is adopted, it will take time to work because there is another factor at work.
As to why those ladies didn't react well to valacyclovir?? There's too many variables that I don't know about. When I was introduced to valacyclovir, I was using Avonex (which I hated). That would have increased my type 1 interferon levels and acted as an antiviral. Maybe that made its introduction easier.
Most studies view valacyclovir as safe and efficacious but there are instances of negative reactions. That might be Herximer reactions. If they were the issue, you would use a doctor to advise how to gradually titrate the dose to prevent that. You wouldn't do it yourself.
I'm quite sure the valacyclovir stops EBV replication but it does not eliminate it. Many of the B cell treatments are used to delete the supposed autoreactive antibodies but they will also be ablating the home of the EBV and deplete the virus as well. If you believe the EBV argument then depleting B cells is depleting EBV.
As I don't like the list of possible side effects of B Cell treatments, I'm happy to stay with valacyclovir. It is working very well for me.
Regards,
I don't doubt you have good reasons for introducing all those things, but most are not part of how I address fatigue. With so many things there is a risk that a graph of the dose benefit ends up looking like an inverted U. The issue is being sure that isn't happening.
A big difference between our approaches is the valacyclovir. There have been studies in the 1990s and early 2000s that looked at using valacyclovir to treat MS but the conclusion was it made no difference. When I read those studies I can see that what they wanted to happen didn't occur so the conclusion was self evident. Some studies were very short term, some had small populations, some seemed to want demyelination to reverse. A number of them noted that clinical improvements (i.e. patient well being improved) were not supported by MRI, so people possibly felt better but the discussion of that aspect is lacking.
Now EBV is moving towards the centre of thinking about the cause of MS, but there is still insufficient research to explain the mechanism of action of that virus. Like a lot of viruses it can mutate so we know there is, at least, a type 1 and a type 2 EBV. It has constant and variable regions in its structure so lots of variation is possible.
The other big issue is why (if EBV is the cause) do a small group of the population get MS while the great majority have no discernable long term illness from EBV exposure? As this would have to go back to the time of infection, there can be a huge time elapse before MS symptoms are noticeable -no one is looking at that early stage. This is a similar question to why did some people barely get a sniffle with Covid while others died of it. They are both viruses but they are very different.
In a note in my book, I looked at a cell called a plasmacytoid dendritic cell. This is the cell that introduces viruses to T cells and is the primary cell that activates the T cell. In the vast majority of people that introduction is accompanied by a strong type 1 interferon response. A report from 2012 https://www.sciencedirect.com/science/a ... via%3Dihub showed if the interferon signal was too weak that the necessary cytokines were not released and T cell response was muted. After a time, when the virus is well embedded the immune system responds too vigorously and an inflammatory reaction develops. The study implied this was a step in the development of MS.
A similar argument has been proposed to explain the variation in responses to the Covid virus. https://jamanetwork.com/journals/jama/f ... le/2768926
If this is how EBV begins its journey for MS patients, it would be logical to assume that whatever antiviral strategy is adopted, it will take time to work because there is another factor at work.
As to why those ladies didn't react well to valacyclovir?? There's too many variables that I don't know about. When I was introduced to valacyclovir, I was using Avonex (which I hated). That would have increased my type 1 interferon levels and acted as an antiviral. Maybe that made its introduction easier.
Most studies view valacyclovir as safe and efficacious but there are instances of negative reactions. That might be Herximer reactions. If they were the issue, you would use a doctor to advise how to gradually titrate the dose to prevent that. You wouldn't do it yourself.
I'm quite sure the valacyclovir stops EBV replication but it does not eliminate it. Many of the B cell treatments are used to delete the supposed autoreactive antibodies but they will also be ablating the home of the EBV and deplete the virus as well. If you believe the EBV argument then depleting B cells is depleting EBV.
As I don't like the list of possible side effects of B Cell treatments, I'm happy to stay with valacyclovir. It is working very well for me.
Regards,
Re: TPP, alithiamine, Q10 & ALC for fatique
As you understand she takes all these supplements not only for fatigue but also for EBV, deficiencies, remyelination, overall good health etc
I stay in this "as I don't like the list of possible side effects of B Cell treatments, I'm happy to stay with valacyclovir"!
I want to introduce her to Valacyclovir but I need a doctor to supervise her, and this is the difficult part at least here.
I stay in this "as I don't like the list of possible side effects of B Cell treatments, I'm happy to stay with valacyclovir"!
I want to introduce her to Valacyclovir but I need a doctor to supervise her, and this is the difficult part at least here.