This Is MS Multiple Sclerosis Community: Knowledge & Support

Hi Heapsreal,

I agree with what you have said. The original reason I tried Avonex was due to the success my doctor had treating patients with cfs on the assumption that EBV was the underlying cause.
Same idea different path for MS and I think if you dig deep enough you will see Lymphoma gets an inclusion as well.

Are there people in the MS community trying interferon inducers? these are substances that stimulate our natural production of interferon and are used in cfs/me to help strengthen the immune system in particular their natural killer cell function. I have had some help with cycloferon and many others have used immunovir, they seem to help with lowering viral load to the herpes viruses implicated in cfs/me like ebv/cmv/hhv6. The substances to need to be cycled on and off as the immune system gets use to the stimulation and gets a tolerance to it.

I've never heard of Interferon inducers before. The premise I worked on is that a gammaherpes virus (in my case EBV) is binding to an autoreactive B cell and that infected cell moves from lymph tissue around the tonsil region into the CNS. The infected cell gives off 2 molecules of oxygen which is called superoxide. The superoxide reacts to the Nitric oxide in the CNS and produces peroxynitrite. The reaction is exponential e.g 10 units O2 x 10 units NO = 100 units peroxynitrite. This is highly destructive and results in many enzymes being disabled and the citric acid cycle fails to work properly resulting in insufficient non essential amino acids being produced, insufficient ATP being produced and some nuclear receptors including the RXR/VDR complex being disabled.
Interferon is a signalling agent that alerts T cells to attack invaders. EBV is a pyrimidine loaded virus rather than purine loaded and this helps it to evade the T cells. Valtrex terminates the RNA of a replicating EBV by binding guanine to cysteine in the RNA tail. Valtrex seems to work on the lytic cycle of EBV infection at point of replication. Interferon works on the latent cycle of infection. The difference is cells burst and spread daughter cells in the lytic cycle and cells just divide in the latent cycle. If you just focus on interferon then you will most likely have no impact on the lytically produced cells. That's why I say Avonex and Valtrex is the best strategy for me.
As an aside I have found the use of coenyme Q10 to be surprisingly helpful. Currently I take two capsules at bedtime and 1 more in the morning. Be careful of contraindications with other medications especially Warfarin. ie Check with a doctor.
I've also stopped the carrot juice. I think a one month program of a daily glass taken in conjuction with Valtrex and Interferon was very beneficial but in the end it's hard to keep taking it because it feels like its building up in your system.
I've now gone 6 weeks without Valtrex or Interferon but have used the coenzyme Q10 instead. I think the uric acid reading must still be high because I can feel the gouty toes a little. That makes sense because Uric acid is just ATP+GTP+nucleic acids. The coenzyme Q10 boosts ATP production hence higher uric acid levels. Uric acid is a scavenger of peroxynitite so I an symptom free at the moment. I don't expect this will last as I am not addressing the EBV infected B cells just the symptoms but it's nice to have a holiday from my decade long routine that has kept me well.

Hi Scott,
Very interesting post.
So how comes you have decided to stop your avonex and valtrex? If its working for you I would keep going indefinitely!

I did look into the Q10 enzyme with my blood thinners and with Arixtra it seems to be ok (my haemotologist is watching me closely anyway and so far so good) Thanks for the heads up.

I am going to look into adding Valtrex to my regime although I don't think I will take the interferon just yet but stick with the Q10.

Once I get hold if some I will keep you posted. Only worry is ever since I got the 2 EBV infections that caused mono/glandular fever it did mess up my liver so I always have to watch it closely (which I do) I haven't yet been tested again for IgG antibodies against EBV but will this week x

The only reason I've taken a "holiday" is because it has been so effective. The downside of it working is I have elevated my uric acid level too much. This happens because Valtrex is a Purine. When Uric acid gets above the normal level you are susceptible to gout and that's where I am now. I spend more time trying to manage that than think about MS. Uric acid is a scavenger of Peroxynitrite so I feel comfortable that I have a window where I can back off the medication and find a happy compromise. The risk I create is I am not attacking the EBV and my symptoms might come back over time.
I am comfortable having a break because I spent over a month taking a daily glass of Carrot juice to boost my intake of two retinoids; all-trans retinoic acid and 9-cis retinoic acid. The first has the capacity to punch holes in the capsid of EBV which makes it vunerable to attack by T-cells that were on alert due to the interferon and the latter is required to activate the Retinoid X receptor. If the RXR is inactivated then the VDR (Vitamin D receptor ) can't work. This point seems to have been missed by a lot of the work on VDR. The focus is on adding Vitamin D3 or using drugs and strict diets (Marshall protocol) and that seems like a work around to me. I think I made a major hit on the EBV when I did this.
I took Avonex every week for 12 years and Valtrex twice daily for over 10 years. I'm at a different place to most because I have lowered my viral load through this aggressive approach. I need to work out what happens next. It doesn't concern me that I might be exposing myself to the risk of MS symptoms returning because I can turn them off by resuming my regime but the gout symptoms (a bit like an arthritis) do need some management.
Regards

Hi again,

I think there is happy amount of Q10 and then it becomes an issue. The limit probably differs between individuals and might change over time. Gradually I increased to 2x 150g at night and 1x 150g in the morning. I took the holiday from my normal medicine so I could get a feel for what was happening. My gouty toes started to remind me they were there so I dropped the Valtrex to see what happened. My thinking was Q10 will aid the production of ATP (particularly during sleep) and the higher ATP should be elevating my production of uric acid so I had a protective cover form the problems brought on by too much peroxynitrite. I still think the reasoning is valid.
The problem I found is the high dose of Q10 made me too agitated at night to sleep well and I was constantly wanting to rid my body of waste products at a troubling pace!
The other side effect is now I get quite thirsty quite often. This is unusual for me. Most of my life I have never felt particularly thirsty. I would always shake my head at people who were running around with water bottles as I seemed to not need to and I couldn't understand why they drank so much. A couple of different things might be at work here; 1)maybe my lack of thirst was an oddity specific to me,2) maybe I'm some sort of dumb martyr who was too stupid to drink fluids when he should have and didn't recognise it or 3)perhaps the jostling of medications over the past few months has triggered something into action and that is giving me a normal response to thirst. I would be interested to know if others with MS have a lower need to drink water than healthy people. It might be one of those symptoms that we just don't think about or it could just be me.
I can make an argument that it is point 3 by looking at the citric acid cycle (krebs cycle) which it has been established is disabled by peroxynitrite. It is enzymes that are disabled by peroxynitrite, particularly those ending in dehydrogenase or dehydrogenate. When they don't work we can't make non essential amino acids or sufficient ATP. Dehydration comes from the same root word so perhaps if our bodies don't librate hydrogen as quickly as others then we don't get as thirsty as they do.
Another aspect might relate to the RXR/VDR complex. Maybe the combination of the attack on EBV using retinoids, Valtrex and Interferon has triggered a change in activity in the diverse range of functions controlled by RXR. (Wikipedia has a great table show how many glands and functions are run by this master switch). I can't tell for sure so this is just a "thinking out loud" exercise. I will get some tests done and that will tell the truth of the matter.
Because I have cut back the Q10 to 1 at night I have reintroduced 1 Valrex and 1 probenecid (to keep it circulating) in the morning. I'm still off the Interferon because I want to see what happens with these other changes.
I did note that heapsreal raised Rituximab as a B cell Knock out to destroy the EBV infected cells. This is something I had discussed with my doctor previously as I think it has merit. His attitude might be coloured as this drug hastened his sisters death from throat cancer due to an adverse reaction. He pointed out that 'mab' on the end of the name stands for monoclonal antibody. These are designer antibodies that are targeted at only 1 receptor on the 'V' part of the 'Y' shaped call. A bit like putting a cork in a bottle, it will turn off (or on) a disease. The issue arises when it binds, say, to both receptors. This can prove fatal. We should all watch the development of monoclonal antibodies closely as I think this is where the real answer lies if EBV is the true problem.
Regards

Hi Again,

I backed off the Q10 and felt better but I think another modification is needed as I stopped getting the kick to energy levels I had when I really drove the dose up. I'll try 2x 150g at night and continue with the Valtrex and Probenecid in the morning. Something tells me I should resume another four week burst of carrot juice to boost my 9-cis retinoic acid levels and hopefully assist the RXR/VDR complex. My alternative approach would be just to resume the Avonex injections but as I am still very well I want to see what happens. I've gone almost two months without interferon and this is a record for me. As I have said previously I don't believe what I do is a cure but it does keep the beast in the cage. I suspect in the end I will need to add the Avonex back into the routine as the T cells must be slipping back into their bad habits by now. The other benefit of carrot juice is I will also be dosing with all-trans retinoic acid and that can put holes in the EBV capsid. If I take the carrot juice in the morning hopefully it is able to work synergistically with the Valtrex and deal with the lytic cycle EBV which should be vulnerable because of the all-trans retinoids.
I'll let you know how I go but I suspect I will ultimately revert to the old tried and true Valtrex and Avonex plus a bit of Q10 plus the probenecid to stop getting the gout.

Regards

So scott...Could you just list again everything you were doing when you felt well? (before adding Q10 etc)

Then what you have added.....

I hope you are able to keep it under control but I fear you may need to revert to avonex x

Hi LR1234,
Please don't think I don't feel well. I'm trying to optimise my health and I have been taking advantage of my understanding of what I am doing to get to a less interventionist level.
At the core of my approach, I just take a weekly injection of Avonex and a Valtrex tablet each morning and night. I have been doing this for a decade and have stayed very well. For most of that time I thought that is all I needed to do as I remained well even compared to my non MS peers.
My issues with gout were diagnosed last year and can now think back and recognise that a few aches and pains that I attributed to MS were really to do with gout. My gout symptoms come from the gram a day of Valtrex. Gout is caused by high uric acid levels being absorbed back into the system and crystalising. A sign of MS is low uric acid levels, i.e MS and gout should be mutually exclusive. My problem has been trying to find a way to maintain a high uric acid level by maintaining the Valtrex as an anti-EBV agent without getting gout. This is difficult balancing act as there is no roadmap to follow.

If I wanted to get to a "recovered" state I would take a weekly Avonex injection and a tablet morning and night of Valtrex. I wouldn't worry about gout for around 8 years. I have at times megadosed on Valtrex and taken up to 6 in 24 hours. I wouldn't recommend doing that until you know how it affects you. It's not possible for me to comment on other conventional injections like Copaxone because I've never tried them but all the literature I've read suggests you need your T cells to be activated by Interferon if you follow my approach.
If I was on nothing and just starting out I would try this approach-
1) get checked for an IgG positive response to EBV, get as many nonessential amino acid levels checked as possible, get vitamin d levels checked and importantly get uric acid levels checked. If they are all low then you are where I started.
2) Commence a low dose of Valtrex ( Say 1 a day) if tolerated increase to 2 per day
3) Once the Valtrex is tolerated (was easy for me) add I large glass of Carrot juice per day for 4 weeks. I'm sure you will be sick of it by the end. I had a massive amount of mucous stirred up and developed a raging sore throat after 10 days. I needed antibiotics in conjuction for a week to help.
4) start taking Avonex. This can be very rough but that is because the system becomes armed to attack any sort of infection and you may have many!
5) When that is going well try Coenzyme Q10. Again start at a small dose because it can make you feel aggitated and sensitive in the tummy.

I am still happy to take a very aggressive approach to how I manage myself. That includes dropping medications to see what happens. I'm very impressed with Q10 because I understand how it adds a phosphate molecule to the ATP to replenish it. I definitely get something from that. Nonetheless, at the core all I do is Avonex and Valtrex. When I have worked out the happy balance to manage gout I'll let you know.
As always triple check for contraindications. eg Vitamin D theories hold great sway at the moment but if you take a drug based approach to that (Marshall protocol) then you shouldn't take Interferon. If you are on Warfarin then don't take Q10.

I'm sorry if my posts had become a bit off track. Every little change can mean something ( thirst increases with Q10 -why? Is it just me?). I'll try to be clearer in the future.
Regards

I should also have added that when your uric acid level starts to read at normal levels you should add 1 probenicid to 1 Valtrex. This should stop the gout developing. A bit late for me as I am the guinea pig and now have uric acid crystals in the joints. It's easier to avoid than get rid of!
Shouldn't be an issue for a new starter for some years.

Regards

I didn't think you were getting worse....its just good for us to see exactly what you were doing before you had the pesky gout!

I will get all that stuff checked this week and see what they come back as!

I think if I was going to take Valtrex, it would be 500mg only as I am much smaller than yourself (I would imagine!)
I will see what the tests say x

I found this also regarding UA....It really does seem high UA is beneficial in MS although kidney stones are a complication too. I think my levels are normal and not low.
The treatment of multiple sclerosis with inosine.
Markowitz CE, Spitsin S, Zimmerman V, Jacobs D, Udupa JK, Hooper DC, Koprowski H.
Source
Neurology Department, University of Pennsylvania, Philadelphia, PA, USA.
Abstract
OBJECTIVE:
The objective of this study is to evaluate the safety and tolerability of inosine in patients with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives are to assess the effects of inosine administration on serum urate (UA) levels, the progression of neurologic disability, the cumulative number of new, active lesions on magnetic resonance imaging (MRI), and changes in serum levels for markers of inflammation.
DESIGN:
Oral administration of inosine was used to raise serum levels of the natural peroxynitrite scavenger UA in 16 patients with RRMS during a 1-year randomized, double-blind trial.
OUTCOME MEASURES:
The endpoints studied were relapse rate, disability assessed by the Kurtzke Expanded Disability Status Scale (EDSS), MRI, and analysis of serum levels of nitrotyrosine, and oxidative and pro-inflammatory makers.
RESULTS:
Increased serum UA levels correlated with a significant decrease in the number of gadolinium-enhanced lesions and improved EDSS. A number of MRI intensity-based parameters were altered by inosine treatment, in certain cases correlating with changes in serum UA levels. In a patient with low serum UA and high lesion activity, raising UA levels by inosine treatment decreased serum nitrotyrosine while increasing the ratio of Th2 to Th1 cytokines in circulating cells. The only side-effect correlated with inosine treatment was kidney stone formation in 4/16 subjects.
CONCLUSIONS:
These data suggest that the use of inosine to raise serum UA levels may have benefits for at least some MS patients. The effect of this treatment is likely to be a consequence of inactivation of peroxynitrite-dependent free radicals. Close monitoring of serum UA levels as well as other measures are required to avoid the potential development of kidney stones.

Hi LR1234,

If your uric acid levels are ok then I would suggest Valtrex still be used as it terminates the EBV virus at the point of replication. The kidney stones in the article you suggest are similar in origin to the gout-ie uric acid crystals. This means 1 probenecid should be added per 1 Valtrex to keep the uric acid circulating and prevent crystal formation. You will still need to assess your tolerance of each tablet so don't fly headlong at it.

Regards

If you read this article

http://en.wikipedia.org/wiki/Inosine

then it validates what I've been saying. The only problem I have with it is they don't have a logical process to explain why. I'd rather use an antiviral to elevate my Purine level because I will get the benefit of the attack on Peroxynitrite plus I will be attacking the virus which Inosine alone won't do.

I didnt think valtrex increased uric acid levels?? Immunovir and immunemodulator/antiviral increases uric acid levels, this occurrs as inosine is ued in the making of immunovir. There is another antiviral that is helpful against ebv and is possibly effective against cmv(virus i have) and hhv6 and is called famvir, its side effect profile is as good as valtrex. The other antiviral used in cfs/me mainly for hhv6 and cmv and is also effective against ebv is valcyte, although is said to be more toxic and regular blood tests are needed to monitor its effects. I have been on famvir for a few years and it has been helpful but of late spinning my wheels, i have recently started valcyte in a low dose with famvir and although a bumpy ride at the moment, i feel that it is helping some. Just to clarify i have cmv and ebv, neg to hhv6.

I havent seen it in this thread but i easily miss things when reading , but of interest is probenecide that is used for gout, can help increase the blood levels and half life of antiviral and antibiotic medications. My doc has also said to me that high uric acid levels with high cholesterol is a sign of oxidative stress going on and these labs showing elevation work as an antioxidant in the body to help fight oxidative stress.

cheers!!!

Valtrex will elevate Uric acid because it is a Purine

see http://medical-dictionary.thefreedictionary.com/Valtrex

Of course, it depends on the dose and the length of use. My dosage equates to a gram a day and the use has been long term

Inosine is also a Purine. It's base is hypoxanthine. Xanthine is the preoxidised state before Uric acid.
see medical-dictionary.thefreedictionary.com/inosine

The real difference is Valtrex terminates the RNA of EBV by binding guanine to cysteine at the point of replication hence it prevents the virus replicating from the lytic state.

I haven't read anywhere that Inosine does that.

As both are purines and elevate uric acid they will scavenge Peroxynitrite which is toxic to system. Peroxynitrite is formed by the combination of Super Oxide (from EBV infected B cells) and Nitric oxide which occurs naturally in the CNS.

It doesn't surprise me that both offer some relief but we still need to limit the EBV.

Regards