1) How exactly does an immune modulator work and how do I know if a medication or supplement fits into that category?
2) What are the ones that PWC's most currently take?
3) What effects do you guys notice (good, bad or indifferent?)
4) If I have Hashimoto's would that rule out immune mods for me?
5) Are these a short or long-term treatment?
That's a good set of questions, @Gingergrrl
One this site there's a list here
of immunomodulators used in ME/CFS (though the weblink for each immunomodulator no longer works).
Perhaps the immunomodulators that you hear about the most, and the ones which are regularly used by ME/CFS specialists, are: oxymatrine, Nexavir, Imunovir, low-dose naltrexone and Valcyte.
Here is some info on these immunomodulators:
Oxymatrine is a herbal extract from the plant Sophora flavescens. Oxymatrine is inexpensive, especially if you buy the White Tiger brand. You can also buy Dr Chia's Equilibrant brand of oxymatrine. Dr Chia said he found around 25% of his enterovirus-associated ME/CFS patients had significant improvement on oxymatrine. He has reported cases of bedbound ME/CFS patients going back to work after a couple of months on oxymatrine. However, 50% of patients did not respond at all to oxymatrine, and the remaining 25% only saw some mild improvements.
Here is some info on Dr Chia's oxymatrine treatment of ME/CFS patients, from a presentation given by Chia in 2010:
Case Studies of Oxymatrine Treatment
• 59 y/o M with severe CFS following GI and resp. infections. Bedridden for 18 months.
• Epigastric and RLL tenderness.
• EV serology negative, + EV VP1 in stomach biopsy.
• Took oxymatrine for 2 1⁄2 months.
• Fevers to 104 C for 4-5 days, myalgia better, mental clarity.
• In next 2 months, back to work for 3 years with energy level 9-10/10. Mild RLQ tenderness.
• 25 y/o F with ME/CFS x 5 years. E. level 3-4/10, diffuse myalgia, cognitive dysfunction, HA, abdominal symptoms, sinus congestion, sore throat, CVB4 Ab 1:640 (<1:10).
• Took one tablet of oxm/day. Increase of myalgia for one week, then gradually down to 0 in 10 d. 1 week later, jogging 3 times a week.
• Felt normal in 2 months. Stopped oxm.
• Symptoms relapsed in 2 months. Improved after taking 1 tablet/day.
• 48 y/o F, marathon runner, became ill with resp./GI., flu-like symptoms while training for race.
• Bedridden for 2 years after race. Able to sit up, do business for 1-2 hours c home computer, phone.
• Took oxm 3 bid. Increase HA, myalgia, GI symptoms for 2 weeks. Felt normal by 3 months.
• Stopped oxm. Within 36 hours, marked increase of pre-existing symptoms. Couldn’t tolerate 1⁄2 tab.
• 6 weeks later, started on 90 ug pegylated interferon-2a q week, then back on oxm and worked up dose to 6/day. Myalgia resolved in 3 weeks. On combo for 6 months, then oxm for 18 months. Total treatment – 27 months.
• In remission for >8 months. Mild symptoms 1/30 days.
The graph below shows the cytokine changes Chia found in the responders to oxymatrine (top 7 lines) and the non-responders to oxymatrine (bottom 10 lines). Those who got better on oxymatrine showed a shift to the desired Th1 immune response. This shift to Th1 is measured by an increased in the ratio (IL-12 p35 + IL-12 p40) / IL-10, which on the graph is shown on the vertical axis. Those non-responders who did not improve on oxymatrine showed no shift to Th1. This suggests that it is the immunomodulatory effect of oxymatrine, the shift towards a Th1 immune response, that causes the improved symptoms in ME/CFS patients.
In the responders, Chia also found a reduction in the amount of enteroviral VP1 protein in the stomach biopsy tissues after oxymatrine treatment, indicating that oxymatrine reduces viral loads. The image below shows the enteroviral VP1 protein (the brown stain) before and after oxymatrine (Equilibrant brand) treatment.
One thing about oxymatrine though is that if you have improved on it, should you then stop taking it, you may quickly (within a few days to a month) fall back to the illness level you had before you started it. Chia has observed this many times.
Once the benefits of oxymatrine have manifested, Dr Chia says men can stop taking it after 3 to 6 months; but women usually have to continue taking oxymatrine, otherwise they relapse and get worse again. Ref: 1
Note that Chia has advised against the used of oxymatrine in patients with autoimmune tendencies:
Autoimmunity and Oxymatrine
: Dr. Chia suggested that patients with autoimmune tendencies should not take Oxymatrine. Autoimmune tendency means a strong family history of autoimmune diseases such as rheumatoid arthritis, lupus, autoimmune thyroiditis (especially Grave’s disease), multiple sclerosis, and if the patients have joint pain with positive rheumatoid factor and persistently positive ANA. With the use of other potent Chinese herbs and oxymatrine over the last several years, we have seen two patients develop rheumatoid arthritis (presented at the Reno meeting and London IiME, London meeting).
I believe that the main reason that CFS patients are symptomatic are due to continuing inflammatory response toward viruses living within the cells, enteroviruses in most of the cases I see. The attack is dominated by Th2, which needs to be shifted toward Th1, as is with the use of the herbs. However, an excessive shift toward Th1 in a patient who has autoimmune tendencies could potentially start off an unregulated Th1 response (autoimmune response) that will require immunosuppressant to rebalance the immune response. This is why the herbal product should not be used in patients with autoimmune tendency.
Source: Dr. Chia On Oxymatrine, Autoimmunity, ME/CFS and FM
Around 50% of patients taking oxymatrine will feel worse for a month or two before they get better. The transition to feeling better is often marked by several days of high fever that suddenly appear after around one or two months on oxymatrine. After these few days of fever, that is when you get the improvements, and are thereafter on the home run.
I have to say, though, that I have not heard many stories on this forum about spectacular successes with oxymatrine. I tried oxymatrine myself, but failed to see either any initial worsening or later improvements in symptoms. But because Chia found oxymatrine only works well for around 25% of patients, 3 out 4 patients trying it will get no benefits, or just mild benefits.
Nexavir is a brand name for a porcine liver extract which has anti-inflammatory, immunomodulatory and antiviral properties (it shows in vitro effects again EBV and HHV-6).1
Other brands of the same drug include: 4ME, Kutapressin, Hepapressin and Biopressin.
Nexavir costs around £120 ($190) per month. Nexavir is given by subcutaneous injection typically once every two days. It is very safe, very well tolerated, and patients usually feel good while taking it.
Nexavir is employed by several ME/CFS doctors, including Dr Cheney, Dr Enlander and Dr De Meirleir. Nexavir treatment protocols vary, but in one study, ME/CFS patients were given one subcutaneous 2 ml injection of Nexavir for the first 25 days of treatment; then one injection was given every two days for the next 50 days; and thereafter one injection was give three times a week for the next 105 days. This study reported a 42% remission rate in these patients at the end of this course of Nexavir treatment.1
However a 42% remission rate seems high, so I wouldn't trust this study too much.
Dr De Meirleir reports that around 70% of his ME/CFS patients experience at least a 20 point increase on the Karnofsky scale
as a consequence of taking Nexavir.1
Dr Enlander says that Nexavir helps about 30% of his ME/CFS patients, and when combined with other compounds including vitamin B12 and glutathione injections, Dr Enlander reports Nexavir helps 67% of his ME/CFS patients.1
With Nexavir, I believe people may just take a course of this drug for several months, and then stop. Whereas others may keep taking it.
Dr Cheney believes that Nexavir will stop working if you don't take regular breaks from it. Indeed, Dr Cheney and Dr Klimas believe this is the case with many immunomodulators: they say that you need to take immunomodulators on a start-stop basis to maintain their efficacy, and to avoid developing a tolerance them. (Though this would not apply to oxymatrine, which once it works, should not be stopped, otherwise you will get worse again).
I myself took a 4 month course of Nexavir (the 4ME version). I found I made significant improvements in my ME/CFS around the time I took this drug and in the year that followed, and these improvements have persisted. However, since I also started regularly taking several new helpful supplements that year (like selenium and N-acetyl-glucosamine, which I believe may be a microglial activation inhibitor), I cannot be sure that it was Nexavir that caused this improvement. The only way to know would be to take another course of Nexavir, and see if I get further improvements. This is something I plan to do.
Imunovir (inosine pranobex) is an immunomodulatory and antiviral drug used by ME/CFS specialists such as Dr Cheney, Dr Klimas and Dr De Meirleir. Dr Chia often uses Imunovir in conjunction with oxymatrine.†
Imunovir is a combination of three components: inosine, acetamidobenzoic acid, and dimethylaminoisopropanol. (These components are chemically bonded together as a molecular complex). However, Dr De Meirleir and Dr Cheney feel that taking inosine alone instead of Imunovir provides equally good results. Inosine is an inexpensive dietary supplement available without prescription, so this makes it cheaper and easier to take inosine rather than the drug Imunovir.
Dr Cheney’s "pulsing" protocol for Imunovir / inosine:
Week one: take 6 tablets a day, Monday through Friday, and none on the weekend. Week two: take 2 tablets a day, Monday through Friday, and none on the weekend. Repeat this cycle. But do not treat every month. Do two months on and then one month off of this "pulsing" dose. This medicine works best when you do not treat regularly. If you treat continuously at the same dose, it stops working. It is an immune modulator, and Dr. Cheney suspects all immuno-modulators are like this. If taken continuously they stop working.
Though even with pulsing, some patients report that the effects of Imunovir / inosine diminish with long-term use.
The low-dose naltrexone (LDN) protocol involves taking small doses (around 3 or 4 mg) of naltrexone at bedtime. Because such low doses are used, this protocol works out pretty cheap.
LDN is thought to have an anti-inflammatory effect in the brain (by reducing microglial activation).†
LDN is used off-label to treat autoimmune diseases (LDN is believed to reduce B cells), so may be particularly helpful to ME/CFS patients with autoimmune conditions or tendencies. LDN acts on opioid growth factor (OGF) and on the receptor for OGF.†
Some ME/CFS patients initially feel a lot worse when starting LDN, and they have to greatly lower their dose (to 0.25 mg or even less), and then slowly titrate the dose up over many months. There are plenty of accounts of ME/CFS patients doing well on LDN.
I tried LDN, but found no noticeable improvements or worsening in my symptoms.
Note that LDN may not work unless you also take vitamin D3
Valcyte (valganciclovir) is a powerful antiviral and immunomodulatory drug that is effective against many herpes family viruses: EBV, HHV-6, CMV, VZV, HSV-1 and HSV-2.†
When trialling Valcyte for ME/CFS, Prof Montoya found that many of his patients shifted their immune response towards the Th1 mode, indicating that as well as being an antiviral, Valcyte also has an immunomodulatory propeties. Montoya said he is not presently able to determine whether the benefits of Valcyte for ME/CFS arises from its immunomodulation and/or its antiviral effects.†
Valcyte is pretty expensive, though some members of this forum have found good prices for Valcyte from online pharmacies.
Valcyte is not generally a well tolerated drug, and ME/CFS patients often report feeling bad while taking it. Valcyte can also have some serious side effects, and patients taking Valcyte must be regularly monitored in case these side effects start emerging.