Sometimes you just guess right. Natelson and Shungu and company made two big guesses in this oh so interesting clinical trial.
The Shungu – Natelson team guessed right on two important questions in fibromyalgia
First, they guessed that people with fibromyalgia would have the same increased brain lactate levels that they’ve found that people with chronic fatigue syndrome do. Then they guessed that an “antidepressant” drug (Milnacipran; e.g. Savella) would be able to reduce that brain lactate.
They guessed right on both counts.
Natelson BH, Vu D, Mao X, Weiduschat N, Togo F, Lange G, Blate M, KangG, Coplan JD, Shungu DC, Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia : A Randomized, Double-blind, Placebo-controlled Trial, Journal of Pain (2015), doi: 10.1016/ j.jpain.2015.08.004.
The fibromyalgia patients in this study either took 8 weeks of Savella (n=17) or a placebo (n=17). Their brain lactate levels were measured before and after the treatment.
The study found that FM patients brain lactate levels were indeed elevated at rest – and not by a small amount (P<.0001). Relatively speaking the FM patient’s brains were loaded with lactate, relative to the healthy controls.
High Lactate – Low Energy
High lactate levels are usually associated with reduced oxygen levels in the tissues. When the cells don’t get enough oxygen to power the aerobic energy production process they turn to anaerobic energy production to produce energy.
During anaerobic energy production pyruvate is broken down into lactate, which then fuels the energy production process. This kind of energy production only works for short periods – two to three minutes in fit people – before fatigue and pain set in.
Lactate, therefore, is a natural outcome of anaerobic energy production. High blood lactate occurs when some lactate spills over into the blood.
High lactate levels are usually associated with strenuous exercise, however, not a “resting” brain. (Whether the brains or bodies of ME/CFS and FM patients can be described as ever being in a “resting state”, of course, is open to interpretation… :))
The study suggested that fibromyalgia patients brains – even at rest – were a bit low on the energy scale
The authors reported that the brain lactate levels found were similar to those found in people with chronic fatigue syndrome. In three studies over the past six years Shungu and Natelson have validated high levels of lactate in the ventricular regions of the brains of people with ME/CFS.
These findings suggest that aerobic energy production – the kind of energy production we rely on for most of our energy – is not exactly going gangbusters in ME/CFS and FM patients brains. That would fit in well with the cognitive issues (fibro-fog, brain-fog) so well known in these disorders.
Lower Lactate = Lower Pain
Savella lowered brain lactate levels significantly, and as it did so, it significantly reduced the FM patients pain. The lactate levels in the FM patients brains were still significantly higher than in the healthy controls brains but probability factors indicated they were remarkably reduced (p <0001 vs p <.01).
As noted, Savella didn’t lower the FM brain lactate levels to normal. Nor did it leave the FM patients pain-free. The significant reductions in both lactate and pain levels suggested, however, that further reductions in brain lactate levels could reduce pain levels further. It suggests that if researchers can figure out how to reduce brain lactate levels to normal the pain in FM might even disappear.
The reduced brain lactate did not significantly improve cognition, however. The authors, suspected that a larger study would find significantly improved levels of cognition.
Potential Biomarker
The authors noted that these high lactate levels could function as a biomarker for both ME/CFS and FM. This is one potential biomarker, it should be noted, that does not require exertion to produce it; the high lactate levels are found during rest. This could suggest that lactate accumulations in the brain – and the processes behind them – could constitute a fundamental part of ME/CFS and FM pathophysiology.
(Shungu’s finding of similarly increased lactate levels in depression (but not anxiety) as well as ME/CFS, however, has complicated the biomarker scenario. Shungu is currently engaged in a larger study which he believes will show that significantly higher lactate levels are found in ME/CFS than depressed patients. If he’s correct, high brain lactate levels may be a biomarker for ME/CFS – and fibromyalgia.)
Neuroinflammation?
Intriguingly, the authors suggested that the increased lactate levels may result from neuroinflammation; i.e. by over-activated glial cells pumping out pro-inflammatory factors that are increasing oxidative stress and generally producing havoc. (The “usual suspects” regarding inflammation in the brain basically end at the glial cells – the only immune cell found in the brain.)
Is neuroinflammation behind the pain in fibromyalgia?
The authors noted that activated glial cells have been tied to central sensitization – a key finding in fibromyalgia. Glial activation could also be behind a recent finding of “large increases” of IL-8 in the cerebrospinal fluid of FM patients.
If increased brain lactate levels are linked to glial cell activation in FM and ME/CFS, then evidence of significant neuroinflammation has been present for chronic fatigue syndrome since 2009. (Who knew?)
Savella – Antidepressant, Anti-Pain and Anti-inflammatory Agent?
But why would Savella – a serotonin and norepinephrine reuptake inhibitor – otherwise known as an antidepressant, be able to affect inflammation and glial functioning? Antidepressants were developed to effect neurotransmitter levels – not the immune system in the brain.
Research dating back at least to 2008 suggests, however, that antidepressants can also be potent anti-inflammatory agents. A 2012 study, in fact, found that all the SSRI”s tested (fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram) “potently” inhibited the microglia from pumping out pro-inflammatory factors (TNF-a, NO).
Of course, this brings up the question just what Savella is doing in the brains of the ME/CFS and/or FM subjects that are benefitting from it. If it’s helping with pain, this study suggests it’s probably reducing inflammation. (Since about a third of depression is associated with inflammation – the same may be true if it’s helping with depression.)
Since preliminary results from the Hornig/Lipkin microbiome studies suggest some people with ME/CFS may have problems with serotonin as well, it’s possible it’s working as a serotonin enhancer as well.
The Inflammation – Low Blood Flow Hypothesis
What’s happening here? Earlier Shungu proposed that high levels of oxidative stress were producing elevated levels of free radicals called isoprostanes in the brains of ME/CFS patients.
This oxidative stress could result from glial cell activation, low antioxidant levels, or perhaps most likely – both. Those isoprostanes then reduce blood flows and oxygen delivery to the brain by constricting the blood vessels in the brain. The low oxygen levels then reduce aerobic energy production and increase anaerobic energy production leading to high lactate levels.
Another hypothesis by Newton suggests that pH handling problems in the muscles could prompt blood vessel constriction and the restriction of blood flows in the brain.
(Low blood flows (ischemia) can also set up the blood vessels for a free radical explosion when more normal blood flows return. Could an ischemic environment contribute to the PEM that occurs when some people with ME/CFS try to concentrate – and thus send more blood flows to their brain?)
Conclusion
In this study Natelson and company provided evidence suggesting that a) FM is a neuroinflammatory disorder, b) Savella reduces pain levels by reducing inflammation in the brain and c) that FM and ME/CFS share a central brain factor. The study also suggested that focusing future treatments on reducing neuroinflammation might be a very good idea indeed.
quite a difference to this review http://www.examiner.com/article/cymbalta-and-savelia-minimal-help-with-unwanted-side-effects
The important aspect of this study for me was not how effective Savella is but how, when it was effective, it appeared to be effective because of it’s ability to reduce lactate and what that means for people with fibromyalgia.
That points treatment in the direction of reducing neuroinflammation – plus hopefully someone is using the new scanning techniques to assess the amount of neuroinflammation in FM patients brains.
https://www.researchgate.net/publication/5934934_Varicella-zoster_virus_infection_induces_the_secretion_of_interleukin-8
Fibromyalgia Drug Savella Should Be Pulled From Market, Says Public Citizen Group – See more at: http://www.drug-injury.com/druginjurycom/2010/01/savella-milnacipran-fibromyalgia-drug-public-citizen-fda-petition-drug-safety.html#sthash.9vYzgiEi.dpuf
http://www.drug-injury.com/druginjurycom/2010/01/savella-milnacipran-fibromyalgia-drug-public-citizen-fda-petition-drug-safety.html
read the comments, and other life threatening adverse reactions from this drug especially the heart, it was pulled in europe
I have no doubt but that some people have had bad reactions to this drug but Wikipedia says Savella is used widely including in Europe:
“Milnacipran was first approved for the treatment of major depressive episodes in France in December 1996. It is currently marketed (as Ixel) for this indication in over 45 countries worldwide including several European countries such as Austria, Bulgaria, Finland, France, Portugal, and Russia. It is also available in Japan (as Toledomin) and Mexico (as Dalcipran).
In January 2009 the U.S. Food and Drug Administration (FDA) approved milnacipran (under the brand name Savella) only for the treatment of fibromyalgia, making it the third medication approved for this purpose in the United States. In July and November 2009, the European Medicines Agency refused marketing authorization for a milnacipran product (under the brand name Impulsor) for the treatment of fibromylagia.[11]
EHLERS DANLOS SYNDROME IS CFS/FIBRO/GWI 100%
Cort, can you comment about any similarity between this info, and your last post about the gutt??
This is what I got from the internet:
“When you’re talking about body’s lactate production and lactate or lactic acid threshold, the difference is largely a matter of semantics. But, the body produces and uses lactate — not lactic acid.”
They are very similar – one is produced by our cells when we’re engaged in anaerobic energy production. The other can be produced by (anaerobic, I assume) bacteria in our gut. Both have similar effects on the body, I believe.
Lactate is the anion (whatever) that is – which is produced from lactic acid…
So they’re very similar…
Lactate in the brain / lactic acid in the gut – they seem very similar….
Thanks. Sometimes I think I need a medical degree just to understand all the research!
I don’t understand why we are so excited to learn that CFS/ME and FM involve neuroinflammation. That is the definition of Myalgic Encephalomyelitis – ” inflammation of the brain with pain.” They’ve known this since 1956 when they first coined the phrase which was later encoded in the WHO diagnostic codes as a neurological disorder. Wow. I guess we are right back to where we started. 1956. We’ve only lost 60 years.
To me, rather than suppressing the lactate in the brain with a drug we would have to take for the rest of our lives (with all its side effects), the research should be focused on finding out WHY there is so much lactate in the brain and then reversing THAT process to a normal, healthy one.
https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/
Bravo Kate! 🙂
Thanks Angela! 🙂
Well ,the research suggests the high lactate levels are due to neuroinflammation. So let’s work on treatments that reduce that.
Hi Matthias,
My point was that we have known it was neuroinflammation for 60 years and should have been looking for treatments and cures for that in the 1960s.
Science didn’t have the capability of determining whether neuroinflammation was actually present until just now recently In fact the techniques are being developed right now to do that; i.e. they are being validated. Even if ME/CFS was proposed to involve neuroinflammation there’s been no scientific means of validating that until around now.
A Japanese team used the new techniques pretty quickly to do a small study and others are now in the works.
Before it was supposition – now it has a change of being validated – and we’ll find out for sure over the next couple of years if it is in fact true.
Does that mean we can go back to calling it M.E. in the US soon, versus the 12 other names people have come up with, and the one worst name of all that is required by the govt? If they would just test my brain and spinal fluid, I’m sure they would see plenty that is abnormal. But up to now no one seems willing.
By the way, Cort and others, regarding this: I have found marked improvement from daily icing my head for about an hour. I was waiting to share until I had more consistent proof of improvement, but this seems relevant to the idea of brain inflammation. I often feel feverish, even if the numbers do not show it (my normal temp is in the 97 range, and when I’m feeling that way it is in the 98 range, so it’s a fever for me but not based on the standard numbers). At those times, I wrap a cold pack with velcro that is used for headaches around my head, and then put another cold pack on top so my entire brain is covered in cold. Most times, this is very soothing and I don’t want it to end, but on some days the change in temp to my skin is extremely painful. The rest of my body craves heat to soothe it, but my head usually needs cold. I wait until the packs have lost all their cold before removing, and on some days I need to reapply later. I got the idea from cancer patients applying a cold head device to prevent hair from falling out with chemo. It so far seems to improve my sleep quality dramatically, and to help my symptoms over time. But I am forgetful and so have not done it consistently enough yet to give a full report.
Additionally, I have just started trying 100mg 5-HTP (Tryptophan) which can be bought OTC, and will report back about that. It seems to help with pain from the very first time I took it, which shocked me, and this might be related to this study since Tryptophan also works on Serotonin levels but without all the terrible side effects of anti-depressant Rxs. I am trying it for sleep, which for me is extremely disordered. It has only been a few days, but I planned to report back if I saw significant change. I did see a significant improvement with 1500mg B1/day, which was discussed by Cort maybe almost 2 years ago now, so there are a handful of things that seem to help which patients can do themselves, without waiting for some doctor to get around to finally treating them a decade from now.
[I also find that consuming anti-oxidants, especially pomegranate juice or gogi berries, help a lot with energy, as do salt pills and compression stockings.]
Sunshine,
I have exactly the same temperature issue – my normal temp is 97.5, and by 98.6 I am feeling feverish and very unwell . Plus, now severe sweating when temp goes up. Will try the brain cold wrap! I do know that lower temperatures are neuroprotective, and people with brain injury receive treatment to lower body temp.
I think we’re often better educated about our disease than the majority of doctors in the U.S.
Tami,
So true. Most doctors seem so overwhelmed by day to day patient load/ insurance issues that there is no time to sort through our multiple, complex symptoms.
Tami that is exactly what I’ve found. I have been suffering for many many years. As a matter of fact when I heard the name Fibromialgia and polimialgia it was the first time I heard about it. I think it must be at least 20 years ago that I was diagnosed but I still find that it is ignored by even the best doctors and they keep on testing for all other kinds of illnesses. I have been diagnosed with CLL (Cronic Limphobia Leukemia) which they say treatment is’nt neccesary at the moment. I have each and every one of the symptoms and some more,of FM, and take all the prescribed meds, but it is never mentioned and very few people has ever heard about it.
Same with me, my temp runs 96.7 to 97.6 generally, when it’s over 98 I feel feverish–ice packs help my smouldering brain (feels as though it’s smouldering).
Thanks for the good information, Cort. Although I felt SO cheery the first couple of days on Savella, I needed to discontinue due to side effects, which for me (IF I’m remembering correctly) were cardiac in nature (RVR A Fib).
It’s interesting and exciting to know they can now identify the neuro-inflamation in our brains and are looking at the causes.
It is interesting that my low body temp began abruptly after a neck injury – age 49. My gynecologist says abnormal/fluctuating body temp can be caused by low estrogen/progesterone. Yes, check out the research! Or is it occult thyroid?? Or the HPA axis dilemma???
How very interesting….i too have noticed a lower body temperature since i became really ill, hovering around 97 to 97.5 until i have a crash when it drops to 96.5 or so. Body temperature would be affected by hypothyroidism which I do have but am treated for it so that is not the cause. I decided that this was the pathogens (those dirty bast*ds!) messing with my immune system….turning off my ability to produce a fever (or even a normal body temperature) – since fever can kill the pathogens……..this is sort of the idea behind whole body heat therapy for this and also for cancer – you get the body hot enough and it will kill cancer cells, bacteria, viruses, etc. I tried taking really hot baths to get my body temperature up to normal or even create a fever (with marginal success) but the treatment darn near killed me – I could not stay in the heat and was very weak and dizzy afterwards for quite a long time. So I don’t know if it worked, and that was a herx reaction, or if something else was going on entirely (a vascular problem, maybe).
The fact that so many of us are off on body temperature is significant. It is a biomarker, perhaps. I know that mine changed after I got sick; it was not always low. Maybe this is just another malfunction of the autonomic nervous system but I tend to think it is related to a dysfunctional immune system. Fever is our most basic weapon against infection and we have lost that weapon in this war. Or at least I have.
Kate,
Thanks for the important comments. I am reading research and learning that estradiol is very important in controlling body temperature and can also help balance neurotransmitters serotonin and norepinephrine. ( a natural Savella??????) Here is interesting research, Thurston et al. Are vasomotor symptoms associated with alterations in hemostatic and inflammatory markers? Menopause. 2011; 18(10) : 1044-1051
Severe vasomotor symptoms ( ie hot flashes/ temp instability / night sweats) may be linked to cardiovascular risk. One study suggests that ‘hot flashes’ ( with me – my temp goes up too) severity may be connected to alterations in inflammatory processes. – which plays a role in cardiovascular risk. Dysfunction of the endothelium ( inner lining) of the blood vessels has been linked to these vasomotor symptoms.
So, this research found the VMS to be associated with elevations in tPA-ag and FV11c – irrespective of estradiol 2 levels. So, I guess these are inflammatory markers?. Will check.
Perhaps EDS people have a dysfunctional endothelium??
Kate, your bad reaction to the heat treatment is common. Many FMers & ME/CFSers alike have autonomic nervous system problems (OI/POTS) along w low blood volume. Heat exacerbates those, causing dizziness & inability to remain upright.
My body temp runs close to normal (a smidge low) but in the afternoons I develop 99-99.5 degree “fever” that makes me feel particularly rotten all over. Fluish aches come with them. But I’m also VERY sensitive to cold especially when I have one of those fevers, I’m chilled. The idea of getting some relief sounds so good, just don’t know if my body could handle the ice therapy w out throwing me into vicious, convulsive chills. Maybe it’s worth a shot!
Thanks Hezza!
As for the cold treatment for you, maybe just stick to icing the head and keep the rest of you curled up in a blanket? Let us know…….
A reminder to protect your skin from the cold packs with a dish towel or something that will protect you from pain of direct contact with something frozen – the point is to cold down the brain, not damage the skin! Plus, a thin towel catches the drips when condensation starts to melt off.
Regarding the body temp issue, I was told by a top reproductional endocrinologist in NYC years ago that women in general always have a lower body temperature, that the 98.6 was established based on studies of men, like all medical studies were back in the day. However, since getting M.E. I have severe autonomic dysfunction, including a POTS Dx, and no ability to regulate my body temperature. So I fly back and forth from shivering to pouring sweat constantly. But my actual temperature doesn’t reflect how I feel, it is pretty much always lower than standard definitions of a “fever.” To me, the number is irrelevant, I have very clear and consistent symptoms of brain inflammation, and anything I do to lessen that (like reaching deep sleep where possible, or certain anti-inflammatory foods, and now the brain freezing) help tremendously with symptoms. The issue is not the actual temp for me, but the feeling of severe headaches, feverishness, and confusion that signal that my brain inflammation has become unacceptably high.
I have read about various M.E. patients being ignored as hypochondriacs while they spend years bedridden, and finally they die and an autopsy reveals – shock! – severe inflammation of the brain and brain stem into the spinal cord. I don’t want that to happen to me, but no doctor is doing a damn thing to prevent it. So I am taking matters into my own hands. I ice the whole head, but I find that icing the base of the neck, where the brain stem would be, seems to make the most immediate difference in how I feel, and the clarity of my brain.
I hope trying it out helps at least one person to feel better, or to come up with a new technique of their own. I need an excessive amount of heat, almost to scalding my skin for some reason, to ease joint pain and muscle stiffness (I guess just because it is so severe), but the head needs to be cooled down. When applying heat to the rest, I need to be sitting or lying down to manage the elevated heart rate it causes because of the autonomic dysfunction. None of this has much affect on my internal temperature, it still jumps up and down at will, independent of what I’m doing on the outside of my body.
Sunshine,
I felt so bad when i read your earlier post about how very ill you are. I wonder whatever happened to convalescent homes such as for TB? That’s what is needed for severe ME patients. Not a psych ward, just a nice room in a quiet place in the mountains, with a pretty view, where you can rest and then rest some more. And someone is there to take care of your basic needs like food.
I’m going to try the icing of the head. What a great idea! I too can “feel” the inflammation in my brain and it manifests also as a “concrete helmet” where my neck can no longer support my head and I recently realized this sensation often precedes a PEM crash. Like an aura precedes a migraine. As if my body recognizes, before my brain does, that I had better lie down.
So thank you for that tip. I too, cannot stand up after using heat on my body, i.e., a hot bath. Damn near killed myself last time I tried that!
God bless you Sunshine, and hang in there.
Kate
Thank you so much, Kate! A “sanitorium”/”spa” circa 1900 would be wonderful… but I think you only got to go there if you were very wealthy, or if you were some little tyke with TB working in a factory that a very wealthy person sponsored. 🙂 I hope trying the cold treatment on the brain will give you some relief – or at least not cause any harm! I do it all over, but cold right at the base of the head where it connects to the neck, near the brain stem, seems to do the best work for me.
Hi Sunshine,
I am going to try the cold right now. I know exactly the spot you mean, that is where my neck always feels like it is about to break from holding up my concrete helmet…… 🙁
The good news is that if it is knocking the neuroinflammation down a bit that there’s huge interest in finding other things to do that. Of course, there’s LDN but a lot of other candidates – one of the odder of those is minocycline…but Younger is looking at a variety of herbs and other supplements.
The Lipkin/Hornig microbiome study is reportedly finding low serotonin levels in the guts of some people.
If the neuroinflammation aspects are validated then perhaps with ME. Then again they seem to be showing up in FM as well. Maybe it’s one big disease with offshoots…(???)
I also find that ice packs at the base of my skull, kind of numbing to the pain that is so excruciating by the end of the day!
the rest of my body needs hot packs, but I have two cats for that! So I’m lucky there! They keep my knees , ankles and hips not quite so painful.
please, let me know how your trials are going with the 5 – HTP and also the high density of the one for asleep. I take a liquid B complex…
Also, have you tried this new Mito-Q?
has anybody here reading, tried this new Mito+Q?
thanks for taking the time to read over my note.
Meg.
Hi Meg,
I smiled about your feline heating pads. 🙂 Mine are canine. I’m icing my neck as Sunshine suggested and it was very helpful to falling asleep last night. Thanks Sunshine!
I may try the MitoQ but I need to quit doing multiple things at once. Im going to stick with current regimen for a while and may try it first of the year.
Well that did not stop them from treating other forms of encephalopathy…..
And yes, I do believe it is all one big disease. I would go so far as to include MS and Parkinson’s as part of the one big disease, and maybe a few others. They don’t know causes of any of these, and the symptoms (and some of the test results) are about 75-95% identical and only 5-25% different. So focus on what is similar and see if what works for one works for another. We would learn more from that than anything they are doing now.
Yes, agree with you – one big disease with some individual variation. I went to a number of conferences over the years: fibromyalgia, 2009 CFS in Reno, and several Chiari conferences. I spoke with a lot of patients. Too many similarities of symptoms to separate the groups by symptoms alone.
Interesting that many people in all 3 groups report scoliosis of some degree in themselves and/or their families. People with mild scoliosis are not always officially diagnosed. I was not officially diagnosed until age 52 – after requesting a full spine x-Ray.
Hi Merida,
Yes, the scoliosis link is interesting, I have mild scoliosis though not officially diagnosed. Mine is visible to the eye, don’t need an xray. Been commented on through the years but no diagnosis. I guess since there is nothing they can do they didn’t bother?
My mom has it more severely. It is on both sides of my family. Is anyone doing research on that link? How would that play into the pathogen based theory? I don’t know anything about Chiari or tethered cord. I keep seeing it discussed but just need to read up on it. Also mast cells……..so much to learn, so little energy. 🙁
Kate
I keep raising the question – what if carefully paced exercise, below the threshold at which the muscles “go anaerobic”, seems to lead to overall improvement, which is my experience?
Plus a low-carb diet.
What factors are acting and reacting on each other, and in what direction? I find that working from the symptoms in the muscles themselves, backwards, seems to lead to improvement; ie reduced pain, increased flexibility. And the threshold that is possible to reach without a pain relapse, seems to steadily rise.
So all these findings about lactate are hugely important in my honest opinion, but does the direction in which the “cure” takes place HAVE to be “from” a drug affecting the brain, outwards to the muscles? Can it also work the other way with the right “exercise” regime?
Of course there is quite a number of things in my overall tool-kit and I don’t know whether they are all essential for the improvement I have had. Stretch routines in a spa pool, Qi Gong massage, lots of magnesium. Maybe even Guaifenesin use on and off.
Phil, I too think that it is important to try to get SOME exercise. Deconditioning will exacerbate symptoms like joint pain and weakness and shortness of breath because we get out of shape and lose muscle! So when you work a little at getting back in condition you minimize those symptoms and get some of the benefits of exercise – or at least maybe slow down the deterioration. The problem is in not overdoing it. Once you get aerobic or overexert you begin to damage your body if you have CFS. It takes a long time to figure out those limits. And it probably isn’t a cure in my opinion, just something we can do to minimize the deterioration.
I think you are on the right track with what you are saying, but after 20 years of fruitless see-sawing between overdoing it and relapsing, and atrophying and gaining weight from lack of application, I believe I have found a balance that works so well for me, I am certainly doing far more than “minimizing the deterioration”.
At the age of 50, I am now riding familiar old cycling routes in elapsed times not too far off what I could do when I was 25 and very fit, pre fibro. For most of the last 20 years I did not ride at all, it was too painful. The improvement I have had, has been dramatic over a mere 2 years.
I can touch my toes now, when I was easily 10 inches away from that target. I can squat down without immediate unbearable pain. I can do a quad stretch, when previously I could barely touch my heel with my fingertips let alone grasp my ankle.
I am slowly building up my ability to run again, within my threshold of exertion. I believe that never in my life before, even when I was very fit, have I scientifically managed a significant increase in my aerobic threshold, and wish I had had this approach even back when I was very fit. In fact, I recall the great but ageing racing cyclist Francesco Moser in the 1980’s suddenly bouncing back to world-leading form in his late thirties – unusual in competitive cycling – by using the approach of concentrating on the aerobic threshold. This was novel and radical at the time and I wish I had paid more attention to it. It is only after 2 decades of fibro that I have seen the light…!
LOTS of low intensity exercise has been the key for me; for much of late 2014 and early 2015, I was doing 2 to 3 hours per day. Using the swimming pool, and stationary machines in the gym, much of the time, so that my weight was supported. I had set-backs that needed to be resolved – I kept having to increase the magnesium intake.
But bear in mind that the other things I mention I am doing, may also be essential to my improvement. I don’t know; I haven’t yet tried leaving out one thing at a time. Pretty much everything I do, I feel I can’t do without – like my massage sessions and my spa pool sessions.
What is your magnesium intake Phil? I tried magnesium powder without many results but I was taking the recommended dose on the bottle and I’ll bet I wasn’t taking enough.
I have been taking around 2000 mg per day of magnesium for months now. But in my case there may be factors that not everyone will have, that means I need this much.
Basically, I was shedding weight fast (I was severely overweight) and I suspect that the fat I was losing, had stored calcium and other elements that were in imbalance; and as I burned the fat, they all had to go somewhere, and that was into my muscle tissue.
I started to get devastating cramp attacks in my calf muscles at night in bed; and basically I upped the magnesium dosage until I had got rid of all periodic calf muscle twinges – which as I say, was somewhere around 2000 mg per day. Entirely an empirical, feel-my-way process. On good advice, I used different forms of magnesium, powders, hard tablets, different brands. Daily. I also got into the habit of taking some when I woke up during the night eg 3am. With some broth (in a thermos) so I was not taking it straight into an empty stomach. (Low carb diet and broth go together nicely).
The best advice I got, more recently, was to use spray-on magnesium oil directly onto the legs and feet and rub it in. This has absolutely beaten the last of the twinges. I don’t know how long I will have to keep up all this self-treatment; I will have to experiment with reductions in the dosage of the magnesium and even the actual activity I am doing. It absorbs a LOT of time daily.
So I did not take especially much magnesium as part of an informed approach initially; I was driven to trying it to overcome the cramping problem, and it worked. Otherwise my whole protocol was at risk. Possibly others who are not shedding weight like I was, might not have the same need.
Thanks Phil…:)
In case it’s helpful, I take 900mg of magnesium glycinate per day, and it helps immensely with sleep, heart troubles, pain, etc. I noticed a difference right away in the first day or few days of taking it. If I ever stop taking it, I do start to feel worse, and ultimately have terrible sleep and then remember – oh, have I forgotten to take it? – and then immediately it helps again. For me, it was not a cure, but a significant help in an arsenal of different supplements and other approaches, and I don’t seem to be able to do well without it. You have to be very careful not to OD, because magnesium at too high a level can cause serious arrhythmia problems, etc… so I personally would not try more unless I think my body is showing very clear signs of magnesium deficiency even at the high dose, and to be sure I would probably get a vitamin blood panel done and take a higher dose at a doctor’s recommendation. For me, I think I have multiple vitamin deficiencies (M.E. patients are often malnourished and starving in the sense that we tend to have poor absorption of multiple nutrients, likely due to inflammation of the intestines, or some metabolic problem, even if we might be overweight because calories are being absorbed), so it is more a matter of balancing each one that is wrong than leaning heavily on only one.
I buy a powered magnesium, and measure it out carefully to put in a daily electrolyte drink that I make. The electrolyte drink makes the largest difference in my day of anything. It has salt, potassium gluconate, magnesium glycinate, 1500mg B1 powder (VERY important for me), B12, Iodine, and recently also B5 and all 9 essential amino acids (which I think is making it’s own difference). In prior times, I have tried adding different supplements based on what I could afford, including D-Ribose (helpful but not financially sustainable), L-Citruline DL-Malate, Acetyl-Carnitine, etc…. The pills were killing my stomach, so making a huge bottle of water with these powders and a little juice made a big difference. Then separately I also have to take sublingual Vit. D3 because I have consistently deficient levels, and then several other supplements for immune support in pill form, CoQ10/ubiquinol, etc. I will share the electrolyte formula when I think I’ve perfected it, but people should know in the meantime that this is far more affordable than buying pre-made electrolyte drinks, totally natural so you don’t react with dyes and other artificial ingredients, doesn’t mess up the environment with bottles, and most importantly is WAY more effective than any drink you can buy on the market, including coconut water. M.E. patients need specific nutrients in specific amounts, and what is currently available doesn’t even come close to what we tend to need. Plus, each person is different, so making your own allows you to design a formula specifically for your body, and not someone else’s. I buy my supplement powders on Amazon, so I never even have to leave the house.
Could you share it in its imperfected form? You can get everything in powdered form? I would love to find out how you do this…
Phil,
A lot of magnesium can be hard on the kidneys. But your doctor can watch that – and perhaps he/she is.
I just had a renal system scan just in case, and it showed nothing wrong. I have been urinating far too frequently, yet failing to drink lots (and take magnesium) resulted in the cramp attacks I referred to.
I think this is all part of a big de-tox / system flush-out that is going on. Gradually the frequency of urination is reducing, along with all the other ways in which I am “getting better”. I am also starting to feel relief from the Black Dog depression that beset me most of the day too. I have since a teenager, believed that depression can be simply physical /chemical and nothing to do with “unhappiness” at all, this has helped me tolerate it. In fact one of the reasons I was a fitness freak before fibro hit me, is that I found it eliminated the depression I suffered from as a teen (and heavily into sedentary hobbies like chess and listening to music).
Phil,
That’s wonderful! Would you be willing to share your regimen, with details of what you are doing and how you measured the aerobic threshold? I am trying to do something similar but it is definitely a seesaw. If you have a roadmap you can share that would be great gift. As for the magnesium I cannot make up my mind about that. I feel better when I take it of course. But I know that the magnesium feeds biofilms which could make me sicker in the long run and more treatment resistant.
Currently I am taking magnesium but I think I will go back to concentrating on food sources versus supplements. Struggling with the whole issue of supplements. I think we are low in certain nutrients because (1) the pathogens are using those nutrients for biofilms and other purposes, and (2) gut issues result in malabsorption. I agree with Cort that fixing the gut may be job one. That is the beginning of fixing the immune system. I think that cortisol and other hormone irregularities also need a close look. And, of course, neuroinflammation.
I don’t get how the concept of exercise to the point of lactic acid buildup is supposedly to work for mostly bedridden patients. If you have to stay within a target heartrate as has been shown in multiple studies regarding what causes a crash, based on those calculations my HR is already too high just laying down, before I even got up to do anything. I already passed my peak, just laying down still! If we ignore those numbers and I start exercising well above them, I am too sick to do anything significant, and then apparently we’re supposed to stop within 2-3 minutes. This just seems utterly unreasonable, for anyone who has ever been familiar with the concept of traditional exercise in society. What movement could possibly be done in 2-3 minutes by a typically bedridden person, “only on the days when you don’t feel too sick to manage it!” as they stress (which is what – once a week?), that could mean anything significant? It would take 30 years at that rate to build up to the point you’re talking about where one is swimming or cycling for hours at a time! So I work out the way I know how, and then I crash. Because I can’t find any other way. “Exercising” by staying within my HR and energy and pain limits for 3 minutes a day makes me want to blow my brains out. I used to travel all over the work, and was very athletic. Either other people do not have the same illness I have, or I am missing something. I certainly don’t have the money for a physical therapist, or for massages, or any of that. I’ve been too sick to work for years now, and am broke. I have the willpower to do something on my own, but how, when just typing this is KILLING ME, and making my heart race, and my arms fill with lactic acid buildup and terrible muscle and joint pain from the tips of my fingers to my shoulders, and then on into my stomach?
How does someone with my severe immune-based M.E. build back actual muscle and aerobic capability, when I can barely do anything and my heart is out of control? Taking care of myself to keep myself alive uses way past the reserves I have in my body as it is. Adding onto what I am already doing to survive would probably finish me. But I don’t think I’m the only one. Nobody ever talks about the severe cases. I don’t want to get so deconditioned that I die from secondary causes, I know it’s important. But it’s hard as hell, and I have no help at all, I am completely alone.
I am incredibly sorry for you. I know Cort posted a story (or perhaps it was a commenter?) about a practitioner who does in fact try to re-mobilize extreme cases like you with extremely gentle movements in bed or a recliner. Cort, can you say more?
I do wish the underlying problem would be solved and a simple fix (drug, whatever) provided.
Thanks. I know, right? I wish there was a simple fix. But if there is, I just haven’t found it yet. I have found many things that are helpful, which is great, and fortunately I’m a good researcher. But because I’m doing this on my own, and don’t actually make enough money to survive yet since I’ve been unable to work for so long, it’s just really hard to keep up with all the many different things I’m supposed to take and do in a day to feel slightly better. Managing this disease (or diseases, more accurately) is at least 4 full-time jobs, and there is only one very sick broke person to do it. So I go back and forth between better times where I figure something out, and worse times where I barely am able to keep myself alive. I guess brain fog is fortunate, because I don’t remember half of it, and can be suffering in bed for close to a month before I realize something is wrong. So in a way, I’m grateful for that, because I don’t notice passage of time much. In some ways it feels like I only got sick a year or two ago, even though I have been very severely ill for over 6 years. If I ever get out of this and find a real treatment or even a cure, I will feel exactly like I am living the life of Rip Van Winkle!
I know exactly what you mean about the time being ill and bedridden.
I cannot exercise either. On better days I can manage to hobble out to the car with the help of my stick and my husband or son, and after a quick ride around hobble back again. Typing this is causing pain and strain in my arms too. Tried sitting up earlier and the neck was so bad had to come to bed.
As a matter of interest I have scoliosis too.
I am also diagnosed with Addison’s disease and Hashimotos and Diabetes aka Schmitz syndrome.
I recognise a lot of my ME symptoms among the symptoms of the other diseases and in others with ME/Fibro
God bless xx
I think when you are that sick it is rest you need, not exercise.
And even in bed, maybe you can get some gentle stretching in to keep you feeling better – if you can’t do it yourself maybe someone else can do it for you? Like shiatsu or Thai massage when they stretch your neck for you? A friend or neighbor or family member could do this for you, it would not require a professional massage if you can’t afford it. Or you can get a tennis ball and put that under your neck, back, etc. and as you lay on it you can accomplish a sort of self massage.
But for the most part, I would stop stressing over the exercise and just go ahead and rest. If you had mono or the flue you would get bed rest. So take care of yourself as if you are sick, because you are.
You might be right. I don’t have anyone in my life who can help, I am completely alone. But simple stretching in my bed, keeping the circulation going, and a modified yoga while laying down, do seem to help. I am also experimenting with an inversion table, which helps my blood fully circulate when I am to sick to do anything but lay down. I am planning to report back when I have used it longer as to whether it’s helpful, but so far it does seem to help a lot. Since I can’t afford a physical therapist to come to my home and move my limbs for me, which is what I really need, that seemed like the next best thing – a machine (see-saw, basically) that moves my body for me. Especially since blood pools in my legs from the POTS, it helps to move everything back up toward my heart and brain for a while. Daily stretching from bed is exhausting and painful, but also essential, if I am to prevent things from getting worse. I work very hard at trying not to get deconditioned, but it is extremely hard. I can’t afford things that might help movement and pain reduction, like a pool or hot tub, so I have to work with what I have, which is difficult.
I got a used Gazelle for $10, and that also helps a lot on better days when I can walk, because it’s easier than walking, but helps with circulation. It pretty much works on momentum, so I can just do a few minutes of gliding my legs back and forth, and that helps me get stronger to walk, and to get better range of motion in my hips again. It strengthens my arms just a little bit too. But I need to have my compression stockings on to do it, otherwise I would pass out, and sometimes just putting on the stupid stockings is all the energy I have for the day, then I have to go back to bed.
It’s a miracle I’ve even been tracking these comments for several days in a row and able to respond, but I think it’s my new experimentation with 5-HTP (tryptophan), which seems in the last few days to be making a big difference in how much I can do.
Hi Sunshine,
I’m so glad the 5 HTP is helping! I made a note to myself to try that after reading your previous post. I hope you will just do the best you can at moving, and then let it go and rest without any stress over letting it go! You are doing the best you can do. No one can ask more of you, not even you.
Sunshine, local counties and cities often have services for shut ins. To start, you might want to call Meals on Wheels and get signed up. Ask the people who deliver the meals to help you obtain services. Usually churches are the ones preparing the meals, and churches have other resources.
I am sure the county also provides home health care to folks in need, but you will need help getting through the maze of bureaucracy. The church ladies might help. One small step at a time.
And you are not completely alone. You have us, anyway. 🙂
Thank you. 🙂 Be careful on the 5-HTP (Tryptophan). It will certainly affect anyone sensitive to anti-depressants or serotonin, as I am. For the first few days, I had absolutely terrible disturbing nightmares which were different from my usual night terrors, and had episodes of racing heart, and severe panic attacks in the daytime. I kept at it though, because I also felt some immediate improvement in symptoms, and those issues seem to be getting less and less each day as my body adjusts. I will not raise the amount to 200mg for a while. I can’t say yet whether this is a miracle for me, but it is definitely helping the sleep at last, and I am at least dreaming and reaching deep sleep, which my body cannot repair itself without. I was exhausted those first few days though because even with the dreams, they were so disturbing I kept waking all night long, afraid to go back to sleep. They were weird dreams, about unscary topics, but for some reason the feeling accompanying them was sheer terror. ?
Apparently, this is a common side effect, so beware! I have been taking it maybe a week now, and last night I didn’t have any nightmares at all, and had decent sleep even without using my heavier sleep meds, which I am trying to scale back on in favor of over-the-counter things so I am not dependent on needing a doctor’s Rx, which all too often runs out before I am well enough to get myself back to an office. But I CAN usually get to the internet to order things online. By the way, the brand I tried was BRI Nutrition 5-HTP on Amazon, which had good reviews and was decently cheap. Although it’s been an adjustment, I am so far glad I tried it.
Will do. I had similar reaction to the LDN. Affected my sleep anyway
5-HTP gave me nightmares too both times I tried it (separated by an interval of several years) – so bad that I didn’t want to keep using it.
But the most really hellish side-effects I have ever experienced came from Prozac – Google “Akithesia”, this is what I got severe attacks of. My doctor encouraged me to try Prozac (at least, one form of it) but I won’t be trying any more anti-depressants after that one terrible experiment!
I think a heart rate of 65% of theoretical maximum has been my ideal zone – it is often referred to as the “fat burning” exercise intensity.
I decided to try this and a low carb diet, after Cort’s postings on lactic acid and oxidation and reperfusion injury being significant in FM sufferers. My logic was, perhaps the pains and the relapses are caused by exceeding a certain threshold of intensity; therefore exercise may in fact be beneficial if I do lots of it below that intensity. I do gentle walking, swimming, stationary cardio exercise machines; and increasingly, the bicycle.
Also, I reasoned that burning sugar for energy caused more damage than burning fat – Cort also posted on ketogenic diets improving FM. It all sort of gels.
I wish I understood more; you might be right about pathogens swallowing up much of the good nutrients we need. Maybe one day I will understand why what I am doing actually “worked” like it has. Maybe there are underlying problems still and I am just “getting around” these rather than being “cured”. Presumably if someone comes up with a fix for the pathogens or the leaky gut or whatever it really is, FM sufferers should be able to get better without the effort and the approach I have used.
But maybe going low-carb helps to fix the gut – I had the privilege of knowing Dr R. Bruce Duncan while he was alive, and he was very strong about sugars and refined carbs feeding Candida and Giardia and other pathogens in the gut.
But besides the question of the “right” level of exertion in “cardio” exercise, there is the question of the level of exertion of any one muscle at any one time. On this, I go by “feel” – I can feel the POTS-type symptoms setting in rapidly when I am exerting a limb too hard in the wrong position – for most of the last 20 years I could not squat without unbearable pain, and POTS-type cardio overload. What I have done with these postural-related issues, is get into a spa pool (almost daily, at one time, less now), and with my muscles nice and warm, and carefully positioning myself for the water to support my body weight, and take the limb/muscle gently to the verge of the POTS-type symptoms setting in – breathing for relaxation; and “holding” at the point where I am not provoking a pain relapse. It is really classic stretching technique adapted for the severe limitations of FM and POTS-type symptoms.
Over approximately 2 years, I have gained more and more “freedom” to exert my limbs and muscles in certain postures without the immediate terrible symptoms I used to get. I am still far from “normal”; there are numerous jobs that it would be impossible for me to do – massage therapist for example. How those guys do all that rubbing and kneading all day is beyond me; 5 minutes of trying to do it would kill me. But I keep working away at improving the problem areas, and who knows?
Many normal muscle stretches (on the mat, whatever) in the past, were absolutely pointless because there was nothing there to “stretch”, the muscles were like elastic soaked in concrete that had set. (I tore muscles very nastily many times early on in my FM experience 20 years ago, before I was effectively “mentally conditioned” to avoid sudden muscular efforts). But I can now do a lot of normal stretches with normal benefit, once I have got the muscles freed up with months of regular routines in the spa pool. I suspect that “everything” (or almost everything) I have been doing, combined, has been necessary to achieve all this.
For more on finding your anaerobic threshold check out the Exercise Resource Center on this page below – I think there’s something in there on that
http://www.cortjohnson.org/forums/resources/categories/pacing-exercise-and-management.168/
The problem of course is that we’re all very individual. I have some kind of metabolic problem where if I decrease carbs or sugar at all, it throws my heart and immune system completely out of whack. In a serious way. The longer I do it for, the worse I get. I kept listening to so many others telling me that sugar exacerbates Candida, high carbs are a problem, etc, and these things made sense to me so I kept at it. Without fail, every time I keep at it I end up in an emergency state. Last time I was in the hospital for weeks, and I decided finally THIS IS NOT RIGHT FOR MY BODY. We’re not all the same. I don’t know what’s going wrong in mine, but I know that I need a large amount of complex carbs to function, I never feel stronger and more normal than when I’m eating wheat daily (even though the gluten people will tell you that’s the cause of all problems), and although I do not enjoy eating sugary foods, if I keep some in my diet – at least in the form of very sweet fruits – I do a lot better than I do without. Take them away and I end up with vomiting, huge lymph glands, severe pain, and an extremely arrhythmic heart, plus so little energy I can’t even crawl or life my arm to drink a glass of water. It is terrifying. So I urge people to consider everyone’s stories, but listen to your own body. People with this disease classification do not actually all have the same disease, and many of us have multiple diseases which do not necessarily match up with others.
I wonder if the occasional need for sweets could reflect mitochondrial problems? The need to get some quick energy in there? Is that crazy?
I’m finding good results from lactose free dairy products – which are pretty much off most people’s lists – I find them calming…
Thanks Cort. I am just not able to keep up with you all. I appreciate the pointers!
My FM is pretty bad and none of the three Rheums I’ve seen over the years has reco’d Savella, maybe due to the risk profile noted above.
yep, I’ve been saying it for 3-4 years, the answer is in the brain / CNS…further proof of that.
Let’s stop wasting time on the immune system and silly notions about ampligen!
Wake up, people!!!!!
We need to focus where the evidence is leading!!!!
Well, yes, the argument here is that the brain is the problem but that it
‘s the immune system in the brain that has gone bonkers – so both apply.
The problem is the evidence is pointing all over the body. 🙂
antidepressents have helped my CFS big time.
Perhaps you mean “anti-inflammatories”, so to speak…:)
Cort
Can lactate levels in the brain be reduced by reducing the amount of lactic acid produced in the gut do you think? Does this tie in with your earlier piece featuring the benefits of E. coli and Mutaflor?
This what I found…
“When you’re talking about body’s lactate production and lactate or lactic acid threshold, the difference is largely a matter of semantics. But, the body produces and uses lactate — not lactic acid.”
They are very similar – one is produced by our cells when we’re engaged in anaerobic energy production. The other can be produced by (anaerobic, I assume) bacteria in our gut. Both have similar effects on the body, I believe.
Lactate is the anion produced from lactic acid.
To get really technical
Lactate is produced from the deprotonation of lactic acid.
Lactic acid has the ability to give a proton and lactate cannot.
In solutions (cellular fluid), lactate form is dominant.
Lactate is an anion; therefore has a -1 charge. Lactic acid doesn’t have a charge.
Lactate is the conjugate base of lactic acid.
Lactic acid has an intra-molecular hydrogen bond whereas lactate doesn’t have.
Lactic acid can pass through the lipid membranes whereas lactate cannot.
http://www.differencebetween.com/difference-between-lactate-and-vs-lactic-acid/
Yes, and lactate is converted to pyruvate ( which then goes thru the Citric acid / electron transport cycle to produce lots of ATP) with an enzyme called lactate dehydrogenase. I happen to be consistently low ( 60-70% of normal) on that enzyme. ( but there are 5 different forms)
Interesting that in the 1990s there were 2 journal articles on FM and glycolysis ( ie the inter conversion of lactate and pyruvate). One concluded that the lactodehydrogenase enzymes in muscles of FM patients were decreased. They suggested FM was a metabolic disorder. ( Eisinger et al. Glycolysis abnormalities in fibromyalgia. J Am Coll Nutr. 1994 Apr 13 (2): 144-8. )
I see from a 2009 article by Dr. Shungu that his team was thinking about various reasons for increased brain lactate: oxidative stress, mitochondrial dysfunction, and cerebral blood flow. He also comments that their study showed levels of brain lactate varied considerably in the CFS patients – ” more than half had increased lactate. . . ” ( http://nyp.org/advances-chronic-fatigue-syndrome )
Also, I have a piece of research here ( J. Of Cerebral Blood Flow and Metabolism) that in normal brains lactate increases (transiently) during brain activation.
Savella??? We had 2 emergency room admits in our support group related to it.
This must be a brain thing – thinking absolutely exhausts me.
Cort,
Do you understand this post? 🙂
Hi cort, can you let me know the doses of savella used? My partner is desperate for relief so we’ll have to give it a try and buy it overseas as it’s not available in NZ
They worked up to 50 mgs. twice a day…..Good luck!
The first milnacipran bottle contained 12.5 mg tablets allowing for the recommended milnacipran dose ramp up protocol as follows: one pill at night on the first night, one pill twice a day on the second day, then 2 pills at night and one in the morning on the third and fourthdays, then 2 pills twice a day on the fifth and sixth days. Then, on the seventh and eighth days, patients were instructed to take 2 pills in the morning and 4 pills at night and finally 4 pills twice a day on the ninth day.
Thereafter, they will be instructed to move to the second bottle and to take one pill (i.e., 50 mg) twice a day.
Save*
How does this relate to the success with LDN? It is an antioxidant so anti-inflammatory, right? So would LDN be doing basically the same thing as in this study? Other than stomach pain if my stomach is empty, I have had no side effects from LDN, and have seen marked improvement in both pain and cognition with it.
Yes, LDN is believed by Jarred Younger, to be reducing microglial activation. If the lactate accumulations are indeed caused by neuroinflammation; i.e. glial cell activity then LDN is believed to be doing the same general thing.
Because different “anti-inflammatories” such LDN and Savella could be tweaking the microglial cells a bit differently they could have somewhat different effects or work differently in different people depending on what their glial cells are doing.
I have another article here, “. . . we hypothesized that delta-opioid receptor is involved in neuro protection during O 2 deprivation, and that its activation/ inhibition may alter neuronal susceptibility to hypoxia stress.” ( Zhang et al. Neuroprotective role of delta- opioid receptors in cortical neurons. Am J Physiology Cell Physio. 2002 Jun; 282(6) : C1225-34 ) The delta opioid receptor activation protects against glutumate – induced injury. So, if LDN is altering opioid receptors, well this may then protect against high glutamate levels??
My understanding with the LDN is that by activating the opioid receptors on immune cells, it sort of reboots the immune system. A mini reboot every night…..timing is important.
That’s why they claim to have people actually recover from some autoimmune diseases like Hashimoto’s. They advise to get your thyroid checked regularly after initiating LDN because if you were hypothyroid you may have to reduce or eliminate your meds.
LDN is actually an opioid-receptor antagonist. It works by suppressing opioid production and causing the body to overcompensate and produce more opioids when the LDN has been metabolized.
When I hit 2.5 mg in my personal trial for FM, I got a tremendous worsening of my pain symptoms and d/c’d it and was back to “normal” in several days. The LDN groupies would say I increased my dosage too fast;I say subsets of FM don’t respond positively.
Thanks, Steve. What he said! Not having the literature in front of me i was bound to get the details wrong.
I’ll just add that when I first started the LDN I had to go the the ER in an ambulance. They thought I was having a heart attack, BP 188/115. they were feeding me nitroglycerin and aspirin on the way. But it was just due to severe nausea and distress, I assume caused by the herx. I had scale way back on the dosage. Doing ok with it at about 1.25 mg dose. Will work up from there. Very slowly!
And everyone should know that if you have Hashimoto’s thyroiditis, and not sure about other autoimmune disease, you must start at lower than the standard 4.5 mg LDN. I think they recommend starting at 1.5 mg in those cases. That was still too much for me. I had to start at 1 mg.
(I started at .5 but went up .5 every few weeks.)
I know the problem. The real problem is that we are all trying to become biochemists, nutritionists, pharmacologists, exercise physiologists, and who knows wtf else just to try to get relief from our illnesses because no one else knows wtf will help.
LOL I feel your pain. 🙂 But you are still making me giggle. 🙂
I will still add for those who have not tried it yet, that LDN for me was one of the few things that worked really well. It seems to commonly work well for people who have classic immune-type M.E. plus Fibro, not Fibro alone or other types of CFS that do no involve the immune system (but still if you’re desperate it may be worth a try), but of course even then some people don’t do well on it. For me it worked miracles, since before it I was on the floor in a fetal position moaning in pain, and after it I was able to live an actual life and to think much more clearly. I have never heard of anyone being started off at 4.5mg from the beginning, if so, your doctor doesn’t know what they’re doing. I started out very slow, and with food, and the dose needed to be split into twice a day – morning and night. The only side effect I had was some stomach aching when my stomach got empty. I worked my way up and my most effective dose is actually 6mg (3mg twice a day), which is more than most people can handle.
The other possibility is that there is a problem with the compounding pharmacy, that perhaps it is not being made with the right formula or as good quality ingredients, which could explain some of the wide discrepancies in experience. But certainly, not everything works for everybody, and I always believe one should listen to one’s own body and not force something that is causing a bad reaction. It is better to start from a small dose and build up very slowly, and as soon as you are having a bad reaction stop right there, and decide to stay at the dose if this seems normal until the problems clear, or discontinue immediately if something seems like an abnormal reaction.
I don’t want people to think LDN is nothing but a nightmare, because for me and for many people I know in my subset of the disease, as well as for many people in several studies, it has really helped tremendously. I have been taking it now for maybe 5 years, and every time I try to get off it (since insurance doesn’t cover it), I notice a huge difference in pain and cognition. I do a lot better on it, and still have no side effects but the aching on an empty stomach, and of course the lessening of the wallet.
Exactly. We are all desperately trying to solve a very complex problem. Nevertheless, there are many people here with important and illuminating observations. And careful, objective observation is the foundation of all good science?
Cort,
These interesting discussions are exhausting. ?
I agree, Merida. I have to try so hard to keep up!
Yep. Thank everyone for patience when i can’t keep up and ask a question that has already been answered. I’m a little overwhelmed by all this.
Cerebral blood flow is mentioned as a possible factor. Has anyone had any experience taking Plavix to prevent blood clots and increase blood flow? If you have taken it, what diagnosis allowed your MD to prescribe it?
Good question!
I remember hearing ( years ago) at some conference that a certain group of FM people responded well to heparin. The Fibromyalgia Syndrome ( edited by I Jon Russell, MD, PhD) reports research that FM patients have morphological abnormalities of red blood cells – the red blood cells in FM people have changes in their shape that tend to make them less flexible . So blood flow and oxygen delivery may be affected.
So, now I wonder ( again) about the RhD negative group who totally lack the red blood cell surface proteins that the RhD positive people have. I understand that these RhD proteins act as channels for the release of CO2. RBCs must release CO2 before they can pick up oxygen. At one FM/CFS meeting of 17 women, 55% were RhD neg. – much higher than even the Basques at 35%.
I am a regular contributor to these discussions, I have FM. Coincidentally, I got a DVT a few months ago as a complication of a calf muscle strain that immobilised my ankle, and was on Rivaroxaban for 3 months – an anti-clotting medication.
I did wonder whether it might show up any benefit because of the possible role of restricted blood flow in FM, but I cannot say I noticed anything. I am inclined to think that whatever the restricted blood flow problem is, it is not an issue of “clotting”, hence anti-clotting medications are not significant.
I am interested in the comment in this discussion, that even the red blood cells in FM people are often the “wrong” shape.
But I have long suspected that the problem is simply in blood vessels being shut off or constricted, by tension in surrounding tissues, especially the myofascia. And other intersticial fluid flows are also a likely problem. Are there “vessels” other than blood vessels, for these?
Is the “wrong-shape” blood cells a “cause”, or an “effect” of whatever the underlying problem is?
I agree that too much hard thinking in multiple directions at once is very taxing, is this an FM thing? I thought the demands of a job I had years ago, that had far too many simultaneous demands on my attention every day, resulting in chronic stress, was responsible for me getting FM in the first place. By the time I quit, my brain was “fried”, my capacity to handle these conflicting demands was gone, and it has never really come back. My brain is still good, though, at steady “getting around big-picture concepts” that a lot of others struggle with. These review comments on Urban Economics papers, are mine…..
http://www.voxeu.org/comment/105237#comment-105237
http://www.voxeu.org/comment/105244#comment-105244
The autonomic nervous system controls vasoconstriction, and many CFS-ME patients have POTS and other autonomic disorders.
As for “vessels” other than blood vessels, are you referring to lymph vessels?
Thanks Pam, I should have mentioned lymph vessels – but is that all there is besides blood vessels? Does all intersticial fluid transfer around the body occur through “lymph vessels” or are there other pathways that also could be getting restricted by FM tension or something?
Even the skin itself absorbs fluids and presumably is capable of some amount of transfer. I have found “magnesium oil” rubbed into the skin very helpful, more so than oral supplements.
PamJ,
Great point – another road leading to the autonomic nervous system.
Phil,
Great articles. Which brings out another point about”us.” Perceptive, sensitive, very intuitive. I have seen these qualities over and over again – in large support group, in my own family.
Merida, thank you for those comments; if you see something in those articles, it says something about you. I have my supporters around the world, who see something in what I am saying, yet some of the “brightest” in academia and policy advice do not want to know about it. And when it comes to ordinary lay people, almost nobody “gets it”. There is almost no pre-requisite I can see, for “getting it” – I cannot yet see the common denominator in those who do. Maybe it is simply the kind of mind that one has been born with, and/or formed by experience. My sister, a housewife, has no problem with it. I know a cargo handler who understands, and a nurse, and a baker. These people put the tenured professors, highly-paid consultants, and heads of bureaucracies to shame.
Phil,
Yes, I appreciated the articles – not that I understood everything. But you see links, connections, and complex interrelationships that others miss. This seems to be part of “the gift.” I have labelled this crazy disorder we have – The Gift and The Curse.” Geez. This gift and curse stuff runs thru my entire maternal line. Anyone else see this?
Merida, I never thought of this before, it is very interesting.
You mean we are in some way, like savants? Over-gifted in some aspects of mental perception, yet “disabled”?
What do others say – is this typical of people with fibro? I don’t know enough about others with it, to know. Two guys I do know, do fit the thesis in a similar way to what I do.
Great discussion.
I have been on cymbalta for a couple of years now with minimal s/e at the beginning.
I’m still on 30 mg but I’m having increased pain x 4 months so maybe it needs to increase.
I did not do well on LDN or methadone-severely sick.
Years ago I took a short kinesiology course focusing on Vo2, lactic acid etc.
In my opinion there are several possible contributing factors to ME and FM. I do believe there are mitochondrial issues, problems with transportation of O2 to the cells/muscles etc so probably we would test low on Vo2 and increased lactic acid build-up is probably a norm for us.
And I believe there is a large component of auto-immune/inflammatory process going on in our brains. My brain is so foggy today I have to stop every few words to see if I’m making sense!
We are having a federal election next Monday and If the party I’m voting for gets in then they have made, in writing, a commitment to working with and helping the CIHR (Canadian Institute for Health Research) for health reform to improve funding etc for ME/CFS research, issues around caregiver benefits etc. It’s very exciting considering only one responded with a non-form letter, or responded at all.
I could jump up and dance, well I can’t really do that but wow.
I did write to this party a month or so ago when there was a lot of talk on Cort’s blog re: getting noticed by the people with money and/or influence.
Maybe just maybe there was a seed planted in someone’s brain around all the issues people with ME and FM have. Maybe the person who wrote the letter actually knows someone with our struggles and really wants to be an agent of positive change, bring us out of the dark ages.
Katie,
My Wellbutrin worked well for 4-5 years – mood, energy, pain, better GI function. Then, it just seemed to quit. Yes, what a struggle, ehat a journey. Opiate pain meds worked well for me – now on very low dose. But the literature says they don’t work. Go figure. We have returned to the Middle Ages here in the U.S.
Has anyone had an MR angiogram to check blood flow in the carotid AND vertebral arteries?
Hi I have recently had steroid injections in my spine for an old injury. For 4/5 days afterwards my muscle pain and brain fog eases and have enery I have long forgotten about! This has happened 4 times (every 4 months) so far. This would lead me to believe that inflammation is involved in both the brain and the body. Unfortunately oral steroids do not appear to work for me.
Very interesting.
Thank you Phil, Cort, and everyone who has responded to my questions and posts. For some reason my reply button no longer takes me to the specific comment it only takes me to the article……and I am too foggy to keep paging through all the comments to respond in the right place. Is anyone else having this problem? Could we continue this conversation on a new page? Thanks
Thank you everyone who has responded to my questions and posts. For some reason my reply button no longer takes me to the specific comment it only takes me to the article……and I am too foggy to keep paging through all the comments to respond in the right place. Is anyone else having this problem? Could we continue this conversation on a new page? Thanks
I had the same issue, Kate. Just pick the most unusual word out of the person’s post, and do a page search for that word (probably “Find” at the bottom of the Edit menu, on the top of your screen). Keep clicking through until you find the one that you’re looking for. Like for one of the ones you were trying to reply to, “Shungu” would be a good choice, because not many comments have that word.
I’m very glad LDN works for you, Sunshine, it’s always good to hear people are getting some relief. Your observations about who it helps are interesting.
I got two forms of LDN, capsules from Israel, oddly subcontracted and sent from Italy, and 50 mg tabs from India, very cheap, I compounded myself. I had to get both of these this way, available without prescription, kind of a grey zone in the foreign mail, I guess, because no one would prescribe it. I didn’t like the docs I would have had to have seen. Both of these sources were reco’d by LDN groups and I have no reason to think they are poor quality. Maybe I went up to fast, maybe I’m a non responder. Since I’m on Tramadol now I don’t want to hassle trying to juggle taking an opioid and and opioid antagonist. I also had two terrifying nightmares on LDN and switched to AM before I dc’d.
I had considered ordering from India and other countries as well, but my doctor recommended against it. The reason is, the chemicals are very sensitive to heat. Spending that long in the mail in uncontrolled conditions in very hot countries could destroy or significantly alter the drug, causing it to be ineffective, or even harmful. Something to consider when we are looking into these alternatives for ourselves. It is stupid how hard it is to get a doctor to prescribe, how hard to get a pharmacy to give it, and then how hard it is to get an insurance company to pay for. Ridiculous, given there are studies out there proving effectiveness for some. But still, people need to listen to their bodies, maybe it was just as pure as any other LDN, and your body just hates it. So hard to say when we not only likely are all dealing with multiple different diseases, but we are not all dealing with the same source of drugs or supplements to treat with.
I have a friend ( retired biology professor) who lost his daughter and developed severe widespread body pain. His doc put him on LDN and it took all his pain away. What on Earth is that all about? Can anyone chart an explanation? Does severe stress affect the opioid system????
Is it just me who can’t read most of the down-thread comments because they are rendered in lines of single letters? I’m using Google Chrome, latest version. Sorry if this had been discussed already.
Wish there were a generic Savella. I’d like to try it.
Whoa, true, illegible on my Ipad also.
I was just going to comment that the further the reply comments get to the right, they become one long, single-character string of letters. Therefore, I cannot read many of the comments that are replies to replies to replies… 😛 Guess I’ll check out another browser (I always use Chrome on my MAC).
Great information, but rather confusing as to what one is to do. I’ll try and talk to my rheumatologist who treats my fibro about this. It’s like trying to get into Fort Knox though! Have to book six months ahead of time. Cheers! Judith
I’m going to try and get this fixed!