Another week – another fascinating drug connection pops up in long COVID. A preprint of a long-COVID study, “Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine – and the development of Long Covid over a 10-month follow-up”, recently reported that metformin decreased the risk of coming down with long COVID by about 40%.
The size and duration of the trial were unlike virtually anything that’s been done in ME/CFS or FM – which is exactly what we want to see. The large (n=1,125 overweight or obese adults) phase 3, randomized, quadruple-blinded, placebo-controlled trial followed the participants monthly for almost a year. People who’d had a positive coronavirus test result within three days and had fewer than 7 days of symptoms were eligible to participate. Immediate-release metformin was increased over time to 1,500mg per day.
The first thing to notice was the high incidence of long COVID – almost 11% – in this group. The second is the lack of definition for what a diagnosis of long COVID means. It appears that the doctors decided on their own who had long COVID.
Whatever type of long COVID some of the participants ultimately had, being able to prevent almost half of it from showing up, with what the authors called “a very safe medication”, was a very good thing. Since figuring out what metformin is doing to reduce the rate of long COVID could tell us much about long COVID – and therefore ME/CFS/FM – let’s check out what metformin is and what it’s possibly doing to keep a substantial number of coronavirus patients from emerging with long COVID.
Metformin
Metformin turns out to be a most interesting drug. The first-line drug for type II diabetes, Metformin can do a lot more, though, than reduce insulin resistance, so much more that it’s hard to know what exactly it’s doing in long COVID. A good place to start is with pain and fibromyalgia.
The Fibromyalgia Connection
Metformin’s ability to boost immune functioning by activating AMPK and then the NLRP3 inflammasome appears to have significant pain-reducing potential. Many animal studies suggest the drug could provide a novel approach to pain reduction. At least five studies/papers on metformin and fibromyalgia/chronic pain have been published.
In a proof-of-concept, pilot trial, six women with FM received low-dose metformin (200 mg/daily) – a 6th of what the coronavirus study used). Significant improvements in pain, fatigue, morning tiredness, stiffness, anxiety, and depression were found.
Noting that AMPK appears to affect the sensory neurons via the mTOR and MAPK pathways – both of which impact the mitochondria – the authors proposed metformin might be enhancing the clearance of damaged mitochondria (autophagy). That’s an interesting connection given the recent finding of significant autophagy problems in ME/CFS.
Another study found that the genes associated with metformin production were expressed big time in FM – suggesting a close connection between the two. They proposed that “metformin may regulate the axis of inflammation to improve pain, fatigue, and other symptoms in patients with FM”.
Similarly, reporting on a large number of animal studies, a recent review paper, “Metformin: A Prospective Alternative for the Treatment of Chronic Pain“, asserted, “Data strongly suggest that metformin could open a new avenue for the treatment of pathological pain and some of its associated comorbidities.. They believe that metformin’s ability to inhibit mTOR expression may be helping it regulate the activity of out-of-control sensory neurons that are causing so much pain in FM and other diseases.
Finally, one study suggests that metformin makes sense in fibromyalgia for an entirely different reason: it’s possible that many people with FM are in a pre-diabetic state without knowing it.
A Chronic Fatigue Syndrome (ME/CFS) Connection?
Lower levels of autophagy (i.e. mitochondrial cleanup) can turn the mitochondria into ghosts – causing the cells to begin to deteriorate through lack of energy and start secreting pro-inflammatory cytokines. Autophagy, interestingly, also declines when cells become starved of resources – which has been proposed in ME/CFS – and plays an important role during exercise – a problematic area for ME/CFS and long COVID.
Plus, there’s an interesting possible rapamycin connection given that both metformin and rapamycin inhibit the mTOR pathway. Check a physician’s Rapamycin ME/CFS recovery story on Health Rising.
The Gist
- Metformin is a type-11 diabetes drug that turns out to have lots of interesting possibilities for long COVID, fibromyalgia, and ME/CFS.
- A very large, well-constructed study found that metformin reduced the risk of coming down with long COVID by about 40% in people who were overweight.
- Numerous animal studies suggest that metformin may be an effective pain drug as well. A pilot trial in FM found that low-dose metformin produced significant improvements in pain, fatigue, morning tiredness, stiffness, anxiety, and depression.
- Another study suggested that people with FM may be in a pre-diabetic state and that using metformin was able to take them out of that state may help to reduce pain.
- Like metformin, Rapamycin is an mTOR inhibitor that may be able to enhance autophagy – a process by which old, senescent mitochondria are removed so that the cell can function again. Rapamycin returned a physician with ME/CFS to health.
- Plus, metformin also appears to be able to improve gut health in ways that could be helpful in ME/CFS/FM.
- Unfortunately, metformin is still not being trialed in fibromyalgia or ME/CFS. After Paxlovid reduced the risk of long COVID, the NIH’s RECOVER Initiative started a Paxolivd trial in long COVID. Let’s hope this metformin finding produces the same result for this most interesting drug.
It has been shown to be involved in the control of peripheral sensitization of nociceptors and inflammatory nociception. Based on this evidence, manipulations that provoke AMPK activation may be a novel and effective treatment for acute and chronic pain states.
Metformin has one other possible trick up its sleeve: it turns out that it also has many positive effects on the gut, including several that are pertinent to ME/CFS. They include increasing the levels of butyrate and short-chain fatty acids, and bulking up the integrity of the gut wall.
In fact, a recent article proposes repurposing metformin to reduce inflammation and oxidative stress, and enhance gut barrier integrity and the gut microbiome in inflammatory bowel disease.
Conclusion
One wonders if this long COVID finding will do for metformin what other studies have been unable to. For whatever reason, the ample positive animal studies that have explored its effects on chronic pain have not resulted in the kind of large clinical trials needed to get Rapamycin into wide distribution. (In fact, no clinical trials were reported underway in chronic pain or long COVID in the clinicaltrials.gov database.)
This quite large long-COVID study has gotten quite a bit of media attention, however, and the idea that a drug might be able to both reduce the risk of long COVID, reduce pain levels and even improve gut functioning in post-COVID diseases like fibromyalgia and ME/CFS seems pretty darn compelling.
NINDS chief Walter Koroshetz reported that the RECOVER Initiative is designed to avoid the scattershot approach that’s dominant in medical research – which produces lots of leads but provides few definitive results. Instead, the RECOVER Initiative is going to methodically assess treatments in a way that provides definitive results.
One imagines that this study has pushed metformin to the top of the potential treatment trial list. After Paxlovid was found to reduce the incidence of long COVID, the RECOVER Initiative started a trial of it in long COVID. Let’s hope the same thing happens with this intriguing drug.
BIG (Little) Drive Update
Thanks to the approximately 500 people who have supported Health Rising as we move into the last 10 days of our drive.
When the metformin finding in long COVID came up, Health Rising was ready to provide linkages to fibromyalgia and ME/CFS as well because we’d already produced blogs on those topics and had done that work.
That’s why Health Rising is able to quickly clue you to the possibilities that this trial or that study provides for all these diseases. If that’s the kind of work that you want to see continue, please support us in a way that works for you. 🙂
Interesting.
It’s also worth mentioning that metformin has been shown to act against autoimmunity, so this could be another reason for its impact in reducing the occurrence of long covid.
Cort, Over the holiday’s I finally had time to view and digest the Norwegian film about Fluge and Mella’s Retuximab trial. (I was surprised that they did not incorporate your opinion, or even identify who you represented at the conference. Clearly, you have done 10 times the work of Dr. Baranick of Georgetown Med School in moving us closer toward effective treatments! Thank you!) I understand the power of the “placebo effect”, but the 43 year old named Laila was clearly cured of post infectious induced ME/CFS. She was clearly NOT a “Psych patient”. You could see in her face and eyes that she had battled ME/CFS for a decade. .She remembers the exact day she contracted the illness. She then ran a 10K after Retuximab treatment. This is the exact response many of the Incline Village patients experienced. They were back on skies, within a year. There are a subset of patients who respond to the med! Some non-responders may have had the disease too long to respond to their short protocol. Some non-responders may have ME/CFS due to multiple factors, and an infection was the last hole in the boat. I can not believe that Laila’s biochemistry is not being studied. Also, How can anyone ignore the biochemistry of the placebo responders? Do some of the non responders have one of the Lyme bacteria or Babesiosis (or, now have full blown MS?). This is amazingly frustrating. This woman is not an actor. How can a serious MD/Ph.D. studying Me/cfs ignore this woman’s response? If the disease is too complicated for Nath’s group (NIH) ,or Baranick’s group (G-Town), because it has five causes, they should move aside. Fund Prusty and Lipken. We fund Chinese labs. Why can’t we fund Prusty’s work? So, we have GI surgeons (Pridken), ENT specialists (Dantini), and Oncologists (Fluge and Mella) doing the heavy lifting as far as patient care. It’s ridiculous!
In Fluge and Mella’s drug trial 26% of Retuximab patients had “serious side effects”. But, 19% of the placebo controls receiving IV saline, had “serious side effects” What ???? An undergrad Stats major could tell you that something is wrong with the design of the protocol. In stats terms, I believe that their “n” was too small. They/we need to drug trial 3,000 well screamed ME/CFS patients. Come on NIH. Do something!
Just read this paper recently, it seems we are on the right track with the metformin/rapamycin angle:
Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?
“Initial respirometry studies of quiescent (unactivated) or chemically activated ME/CFS patient immune cells found mitochondrial respiration rates compared with healthy controls to be broadly reduced [111] or unchanged [112]. However, subsequent studies of metabolically active lymphoblastoid cell lines from ME/CFS patients using respirometry identified inefficient ATP synthesis by Complex V, the elevation of the proton leak, the maximal respiration rate and its major component (Complex I activity) [113]. These abnormalities were found to correlate with symptom severity and accurately distinguished ME/CFS from healthy control samples [113, 114].
***No deficiency in ATP levels nor in the absolute rate of ATP synthesis was observed but an elevation in the activity of the mammalian target of rapamycin complex 1 (mTORC1) was present and could account for the compensatory increase in maximal respiration rates.***
In agreement with this, whole-cell proteomics of these cell lines revealed an elevated expression of electron transport chain complexes and also in enzymes involved in the TCA cycle, fatty acid and amino acid catabolism (but not those of glycolysis).”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276562/
Yes Rick, that July 2022 publication in Cellular and Molecular Medicine is great. Thanks!
Thank you very much, Cort.
Could you ask Ron or Janet how this interfaces with the itaconate and
kynurenine pathway?
This would be brilliant. As usual, WE’LL SEE!
Only ten more days for donation to our journalistic guru, Cort. Please consider anything you can be comfortable with giving. Cort keeps us informed in a brilliant fashion. As my mother said to me one time in a very different situation…”THIS IS NO TIME TO BE CHEAP”. Make it monthly so it’s not overwhelming. I did that. Sincerely, Javen
hi C+ort, can you help me out please? i tryd to search metformin to see what it is but webmd gave different suggestions so i do not know wich metformin.
On https://www.webmd.com/drugs/2/search?type=drugs&query=rapamicin it even gave no excistence…
thanks again!
Given for diabetes. Obviously other attributes than we are learning. Been around a very long time.
I live in belgium so need to research meds on webmd. But i got no good answers and on 1 even did not exist.Here it are other names or do not excist. could you please give the product substance of those 2 meds then i can research in belgium. thanks!!!
Hallo Konijn, ik ben ook van België : als je medicatie wil opzoeken, kan je dit best doen via http://www.bcfi.be (referentiewebsite voor farmacologische producten in België). Je kan hier zowel op stofnaam als op merknaam zoeken en je krijgt meer uitleg over het product, de (contra-)indicaties etc.
bedankt Kristien! het probleem is dat (ik heb ook zo een site bv farmaceutisch kompas waar je op merk of stofnaam kan opzoeken) dat zeker niet alle medicamenten (zelfs met zeldde naam) in de VS en hier hetzelfde zijn. Ik kom niet meer op welke, maar ben er door de vele vele jaren heen al een paar tegen gekomen of krijg waarschuwing op 25% ME fb groep. toch bedankt voor de moeite!!! En de respons van webmd maakte me al voorzichtig, bij 1 verschillende opties en bij het andere ongekend…
metformin = glucophage
thanks!!!
Hoy Konijn. Ik neem metformax (850mg metformine) per dag reeds meer dan een jaar. Voorgeschreven door de internist omwille van boarderline licht verhoogde nuchtere suiker (die ik heb samen met CVS). Ik heb er in alle geval geen nadeel van ondervonden behalve 2 weken beetje wind.
bedankt armslag! heb je er een verbetering van je cvs van? dat zou ideaal zijn! ik geraak wel al heel lang niet mer bij specialisten maar is dat een goede ME internist? mag ik vragen wie? gewoon voor als ik toch zou kunnen… je moet natuurlijk niet zeggen wie als je dat liever niet doet!!!
Het is moeilijk te zeggen of Metformine effectief is, Konijn. Gezien ik allerhande op hetzelfde moment aan het nemen ben. (Artemisia, probiotics en de rest is mitochondriale enhancer: Mg, ubiquinol, B12, thiamine, acetylcarnitine, en aangezien Metf iets doet met suikertransport, kan het gewoon een goed effect op het metabolisme zijn) Men zei me dat ik de metformax als een langetermijn behandeling moet zien, maar ik heb geen “parallelle ik” waarmee ik kan vergelijken mocht ik de behandeling niet hebben. Ik kan wel zeggen dat ik nu voltijds kan werken (veelal zittend en zonder veel daarbuiten weliswaar). Ik zit in het programma van UZG. Daarmee zal je er wel komen.
My friends and I have been taking metformin for anti-aging, but we have not felt any improvement in the symptoms. Maybe it is not very effective for people who have already got sick.
Long term use of metformin may cause vitamin B12 deficiency. It is recommended to use it together with vitamin B12.
And thiamine! Metformin uses a thiamine transporter so it competes with thiamine for transport and it usually wins. Given the important of thiamine for metabolism, I think metformin can be useful, but pulsed and with a lot of thiamine, magnesium and other cofactors.
Being diagnosed with diabetes-II four years ago, I use Metformine. The FM pain was reduced from 4 days, after just grocery shopping, to just ONE day. I still produce lactate very fast, my CPET had to be stopped prematurely, I only got to 40%VO2max, but it hardly ever goes beyond ONE day of pain anymore. Metformine had too many side effects (keep that in mind too!!) so instead of 2 x 500 mg Metformine, I now get 500mg Metformine and 300 mg Invokana/canagliflozin (more expensive) that also lessens the FM pain and fewer side effects.
With my newly found freedom to go out more, I was on my (electric) bike almost everyday. I felt like a “little gray Speedy Gonzales” racing (max 25 km speed) through my village, challenging my muscles again. It felt wonderful!!
However it did not help with my fatigue. Just doing 1 or 2 miles emptied my energy levels too much. The rest of the day I had nothing left. I had to limit it to two times a week.
Those pills helped (in part) with FM, but not with ME/CFS.
Be aware of the side effects.
And long term use has not been studied yet when given pre-diabetes.
I took metformin in 2020 and 2021 for pre diabetic. It’s prescribed for twice a day but I took only once a day because it caused stomach discomfort. I don’t remember the dosage. After 2 years a1c and fasting glucose became good enough and my doctor told me to stop taking it. But it did not improve my fibromyalgia symptoms at all.
I’d be more inclined to try Berberine before trying another pharmaceutical.
Link to a random search between Berberine & Metformin.
https://www.bensnaturalhealth.com/blog/diabetes-health/berberine-vs-metformin/
Thanks Cort, this is a timely article for me because I was thinking of trying Berberine after a friend with type II Diabetes mentioned it to me. This information from the article Donna found in her random search has just put me off!
“ Both metformin and berberine can increase the body’s consumption of glucose. They can also both inhibit the first complex of the electron transport chain.
When they do this, the entire process becomes less efficient at producing ATP (adenine triphosphate). ATP is the source of energy in the body. As a result, the body will use energy in a way similar to that of a restricted-calorie diet or starvation mode.”
Since we may already be in starvation mode, I’m not sure taking Berberine or Metformin is a good idea!
It’s such a minefield trying to self medicate. Over the years I’ve found a handful of supplements that seem to genuinely help a bit. But sometimes I wonder if I would be better off not taking anything and waiting for something to be proven to be both helpful and safe for people with ME.
I agree with you Nicole about waiting for a more proven medication. May I ask what supplements help the bit with ME?
Roger, I’ve found glutathione, luteolin, high dose vitamin B1, curcumin and more recently a supplement called Ultrapome helpful. I had to be very careful with the glutathione and the luteolin, starting with small doses and I still don’t take as much as the suggested dose. I’ve also found vagus nerve stimulation to be helpful, especially with brain fog (see Stanley Rosenthal’s basic exercise on YouTube).
I do still experiment with new supplements but I’m much more cautious than I used to be.
Have you found anything that helps you?
Hi Nicole,
I’m commenting to your reply below. Thank you for listing the supplements that helped you. I agree about being careful to try new things, as my equilibrium is also delicate. I’ve found famciclovir 500mg, Rhodiola Rosea 1000mg, Acetyl L-Carnitine 500mg, and meditation to be helpful. This in addition to other basic supplements. But we need a medical breakthrough to get us beyond sustaining to fully living.
Thanks Roger. I hadn’t heard of Rhodiola Rosea before. Despite being cautious, I still find it difficult to resist trying a new supplement that sounds promising, just in case it’s the one that will make a big difference.
I’d be very careful with Metformin. There are also studies that it worsens gut health: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204317
Lucy Mailing writes about Metformin behind her paywalled patreon blog. She argues that it has some positive and some negative gut health effects. And for most healthy people probably the negative effects dominate. The metformin gut health connection is also not at all well enough understood. You are taking a big risk if you take metformin.
cfribance@gmail.com
‘Inflazome focused on one of these inflammasomes, NLRP3, which it saw was implicated in a range of inflammatory disease, and worked on developing a drug that would inhibit it, preventing out-of-control inflammation that can prove so damaging.’ The Irish Times.
https://www.irishtimes.com/business/health-pharma/prof-matt-cooper-it-s-not-about-the-money-it-s-about-the-patients-1.4367698
This study uses a select group. Namely people who are overweight or obese. Because this drug also reduces appetite and possibly better regulates their sugar in this group, it has a positive effect. You cannot generalize that to all long covid, ME / CFS or FM patients. I wonder if this drug also has an effect on people with an average or low weight.
I have the same question about the study. Since being overweight or obese increases the risk of diabetes or prediabetes, and this study’s inclusion criteria required participants to be overweight or obese, it is possible that some study participants had one of these conditions and that metformin offered protection against Long Covid to them, not to participants with normal glucose tolerance. That said, plenty of people who are not overweight have impaired glucose tolerance (which often goes undiagnosed) and metformin is a fairly safe drug, so I doubt that a 2-week course of it as described in the study would be particularly risky.
I even thought that obesity was an exclusion criteria for diagnosing ME/CFS. I agree that people who are not overweighted can have impaired glucose tolerance. I know that some ME/CFS/POTS patiënts have glucose in their urine.
Dihydroberberine + bitter melon reportedly can have some of the same effects as metformin, can upregulate ampk, could be worth trying. I am taking regular berberine i had on hand until it runs out and I can get the dihydro.
I tend to be hypoglycemic (have been my whole life). I am normal weight, with fibro, ME/CFS and Long COVID (trifecta!). I’d be wary of trying metformin in my case (my doctor told me my A1c was “too low” and not restrict sweets 🤣).
My family doctor was worried about my ongoing borderline high A1C & family history of Type 2 diabetes. In an effort to lower the A1C, he prescribed Metformin, 500 mg twice a day. I struggled to stay on the drug but after 3 weeks I had to finally acknowledge that I was heading towards a major Lactic Acidosis crash. Be careful & watch your ME symptoms if you try it.
Metformin made me very weak quickly. I weakened my muscles, tendons. I became very frail. I tried several times, with even small doses. It appeared that I was going into lactic acidosis based on my symptoms. I also take immunocal, which a undernatured whey protein. My cousin who has CFIDS can take 1500 grams of metformin, but if she tris even a small dose of Whey protein concurrently with metformin she gets the same symptoms. She would not stop Metformin because she crashes. I would not stop Immunocal because I crash without it too. So we both seem to have found different ways to improve, but can not try the alternative because apparently the combo creates a reaction with symptoms similar to lactic acidosis.
By the immunocal reduces glucose levels as well.
Did it get better again after stopping the metformin? Did you return to your previous level after stopping the metformin? Background: My doctor prescribed me metformin (I have ME/CFS) and I am worried about a persistent deterioration due to the medication. However, if it was reversible I would love to try it.
Hi Felix,
I only used it 2 to 3 days because it made so sick. I tried multiple times. I was back to baseline in about 3 to 5 days. The key is to stop if it makes you feel worse. Not try to push through. So with very short trials, I recovered. I do not know what would happen with longer trials. Never will.
My cou
Thank you so much for sharing your experience. After three months on 500mg/daily Metformin, I feel like I’m also in a bad lactic acidosis crash. Probably wouldn’t try it at this level again unless covid exposed.
What does a bad lactic acidosis crash feel like?
I am not questioning that some researchers may find value in the use of Metformin for ME/CFS. However, I do caution readers that one of the side effects of Metformin is significant intestinal motility – mainly as diarrhea – frequent and sometimes uncontrollable. It is not unusual for type II diabetics to request discontinuing usage because of this side effect.
I wonder if the low-dose form is better? I think one study used it. It’s kind of ironic that it’s supposed to improve gut functioning and yet can mess things up at the same time…
It was that remark that caught my attention. I guess it depends on which direction your gut needs correcting. It will be interesting to see the conclusions if the research.
The extended release form is a lot better in this regard as is ramping up…
Ivermectin is antiparasitic medicine for treating various parasitic infections.
https://www.tribuneindia.com/news/brand-connect/buy-ivermectin-for-humans-in-the-usa-trusted-vendor-464195
From our group, 9 out of 10 ME/CFS patients didnt tolerate Metformin (IR or Retard).
We all got fatigue and or diarrhea etc.
Maybe its different for FM and LC.
Ouch! Hopefully so….
I have CFS and have taken metformin for years for PCOS. It has not helped with any of the symptoms that I can tell. Of course I feel worse if I eat too much sugar/carbs, but most people with insulin resistance do. It makes sense if you have this problem that some fatigue is relieved by treating it with meds and diet. The PEM, brain fog, and sleep issues are all still severe. They prevent me from working or living a normal life. So I guess I’m not really hopeful about this drug being much of an answer.
One placebo cures 3 psychosomatic “illnesses” with zero physical markers and mostly cluster in the population of well off women with depression, anxiety, and personality disorders?? Color me absolutely shocked.
I hope you’re not a real clinician. I would hope that a real clinician would be a bit more discerning as well as less ugly. However, we know from experience that many aren’t. I’m not going to out you – but your email address indicates you’re associated with the Mayo Clinic. You’re should know that you’re a bit behind the times – long COVID is finally getting the Mayo Clinic to change its tune with regard to these diseases.
https://www.meaction.net/2022/09/22/mayo-grant/
I think you should put him/her. Let people know who to avoid.
You might want to bring yourself into the present tense of research, doc. First of all, you must be unfamiliar with research by Oaklander (and subsequently others) demonstrating that a significant portion of those diagnosed with FM actually have small fiber polyneuropathy, which can be diagnosed by skin biopsy, hence revealing “real” pathology (https://pubmed.ncbi.nlm.nih.gov/23748113/). Those diagnosed with FM no doubt represent a heterogeneous group, and there are likely numerous other pathophysiological explanations for the symptoms that categorize this syndrome.
Second, what makes metformin a “placebo?” Do you know what placebo means? It is an inert substance, not a drug.
Third, while I won’t be personally offended by your ignorance, I do think your comment is a sad and pathetic reflection on the state of our modern healthcare system and the consciousness of many providers. It might behove you to seek some psychological care yourself to determine why you feel so much disdain and hatred toward a large group of suffering people. [By the way, many of the people you are maligning have experienced significant trauma. If you are unfamiliar, please look into the ACE study and a significant body of subsequent research that will illuminate the very real physiological effects of traumatic stress.]
Where is your compassion? If you have none, you should really leave the field of medicine immediately and find something else to do that brings you joy, satisfaction, and pleasure. Life is too short to be as miserable as you apparently are and drag down your patients and colleagues with you.
Signed,
A Real Clinician myself — in psychiatry 😉
Wow. Check your arrogance, sir (pretty obvious you’re a male). You’re just the type who ends up with one of these REAL illnesses, then feels horrible for your previously judgmental and dismissive attitude.
I’m curious how long people need to take metformin to feel some relief? Should it be a few days or a few weeks?
I should have specified relief from fibromyalgia pain.
Several weeks was my experience and I’d had FM for 28 years before I took Metformin because of diabetes.
Ivemectin is important because of its broad spectrum of uses and its relative safety profile. Unlike many other drugs, it doesn’t have a lot of dangerous side effects and it is highly effective against parasites. https://ivermectin4sale.us/product/ivermectin-3-mg/
Too ill to read the comments, so perhaps someone already mentioned it.
One word regarding ME/Covid/Fibro & metformin: “microglia”.
Can’t remember/repeat the details but here’s an Interesting study:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585737/
I have taken Metformin since 2007, and it definitely helps me with more energy and less pain. I do occasionally get diarrhoea but only if I eat high sugar foods, which I’m not supposed to do anyway 🙂 so I feel that’s my fault not the medication’s.
Although I would rate this as a significant improver, it certainly doesn’t ‘fix’ my ME/CFS, as I suppose is pretty much the case for everything people try.
I’ve had severe ME for 2 decades. Wearing a CGM recently I’ve found my glucose levels go down to the 60 range around 3am. I reach my lactate threshold very quickly and I question if I clear lactate well. Would Metformin balance my glucose and help clear lactate or cause glucose to drop lower and increase lactic acid?
I would think the latter.
I am a CPP and was diagnosed with steroid-induced diabetes just over a year ago. I also have Adrenal Insufficiency. The only treatment for Adrenal Insufficiency is steroids, period. So I will be taking steroids for life. Just as a type 1 diabetic must have insulin to live, I require steroids to live.
I have been using 1000mg of Metformin a day for about a year now. I haven’t noticed a decrease in my pain, but I do not have Fibromyalgia or CFS. What has helped my pain is the 110 lbs I’ve lost. In addition, I’ve completely changed my diet. I no longer buy any prepackaged foods. I cook completely from scratch using only fresh foods. Rarely, do I use some canned foods.
My pain has improved because of my weight loss and dietary changes. Metformin may have helped with my weight loss, but I don’t feel it has helped with my chronic pain management.
In my opinion, this is just another misleading statement that is being told to the public to continue the government’s campaign to try and manipulate the public. The continuing campaign to stop the “opioid crisis” has been incredibly misleading. Blaming CPP for the crisis. The government continues to mislead the public by blaming the high rate of deaths on opioids. The percentage of opioid deaths from CPP who receive prescriptions from actual medical professionals is quite small. Most of the deaths are from illegal drugs that contain Fentanyl.
Articles like this are incredibly misleading. It would help to list the links to these studies.
There are probably a dozen links in the blog, Melissa – all you need to do is click on them. (I have no idea how opioid issues got into this conversation (?))
I have to say a big thank you to Cort for making these blogs. I’ve had ME for 2.5 years now (and Fibro since childhood) and have been slowly getting worse, though I’ve been lucky to remain fairly mild/moderate, I think largely due to quick diagnosis and adapting to pacing and starting LDN, pyridostigmine and other meds to help with sleep, and a host of supplements.
Despite all that I’ve been very close to giving up work entirely (I am on light duties 2 days a week, with extra breaks worked into the day) and was foreseeing being home/bed bound anytime.
Anyway since reading this article and doing a little more reading on it I started Metformin – initially started at 500 mg twice a day but that hit me hard with diarrhea and fatigue.
I dropped down to 250 mg twice a day and right away felt my fatigue and abilities improve. I was running around the driveway last week waiting for my kids school bus just to see how it felt because I felt I *could* do it! And I didn’t feel like total crap after 5 steps!
I’ve hardly needed to lay down in the middle of the day this past week and have been feeling so much better, and more capable. I have more hope right now for the future than I’ve had in a long time.
I’m planning on switching to the extended release version and seeing if on it I am able to possibly increase the dose slowly and possibly gain even more function.
For some reason since lowering the dose my bowels have gone the other way and I’m struggling with some constipation – but I can deal with that.
Also it doesn’t seem to be doing anything for pain – and because I am doing a little more than I’m used to my fibro is flaring a little. I certainly can’t claim I’m normal but I feel better energy-wise than I have in years.
Thank you for all you do Cort!
Great to hear Dana! Thanks for sharing your experience and good luck with getting your bowels in shape. For me vegetables are crucial; without lots of veggies they just lock up 🙂
How about that! Really good to hear! Thanks for letting us know and good luck!
Metformin is a biguanide medication that lowers blood glucose levels by inhibiting glucose synthesis in the liver, reducing intestine absorption, and boosting insulin sensitivity.
https://www.outlookindia.com/outlook-spotlight/buy-metformin-online-over-the-counter-news-278400
Thank you so much for this information which has confirmed my suspicions on metformin and its miraculous impact on me. I suspected long ago that i was already pre-diabetic (diabetes runs in my family) and the only time I found relief from fatigue was when taking metformin. For the first time in decades I felt like myself again. Keep up the great work by bringing awareness to these issues. God bless you 🌸
Good to hear! Thanks for sharing your experience, Rose 🙂
I have an excellent primary care doctor but she does not have experience treating ME/CFS. At my next appt on Monday I would like to request a prescription for Metformin. Can you give me some pointers that will help support this? Thanks in advance!
I have been on 500mg of Metformin for one week. I was prescribed to treat pre-diabetes. I was stunned by the experience of the most painfully debilitating fatigue lifting 20%. I was able to shower twice in this week, without PEM, socialize with a friend and spend some time in my studio painting. I had no idea this was being investigated for ME. I am 64. I have been sick for 40 years. The last decade, bedridden and continuing to decline. It was like a window opened for a week. I don’t know if it will continue. I am stunned.
Congratulations Linda! On a recent Patreon Unraveled talk Drs. Kaufman and Ruhoy really liked metformin! May your window stay open!
How kind of you to respond. I am interested to learn my accidental discovery has some traction. Thanks, as always, for your reporting.
Have you seen in literature pairing Metformin with thiamine and magnesium?
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Hi Cort, just wondering if you know why such a low dose of metformin was used in that fibromyalgia study? I’m trialling half a 500mg metformin tablet a day at the moment and haven’t noticed anything much so far (although it is early days). It’s hard to resist upping the dose! But perhaps the low dose is more effective for fibro for some reason?
I have no idea. I asked Ruhoy and Kaufman about metformin on their Patreon podcast and they both had quite positive thoughts about it. I don’t know if they spoke to dosage or not. They do entertain questions and you could give it a try.
Will do, thanks!
Hi Jennie, did you find out any more information regarding dosage of Metformin?
I didn’t unfortunately! I just experimented on myself with different dosages. I ended up deciding it wasn’t going to do much for me, apart from helping me sleep a little better, so I’m just taking 250mg at night.
Thanks for letting me know Jennie. Sorry it didn’t have more impact for you. Worth a shot.
Hello,
I’m wondering if anyone knows for CFS what time of day is recommended for anti inflammation? Presuming the dose is only once a day and extended release. I know for diabetes it is recommended at dinner. My understanding is that this is mostly to reduce side effects. Thank you to anyone who has more information.