I have ET with joint pain in my knees and elbows. N-acetylcysteine (NAC) has effectively reduced my pain by 90%. However, I found a study ncbi.nlm.nih.gov/pmc/articl... that links NAC to an increased osteoarthritis risk. The study states:
"Our study sample comprised 12,928 people who used NAC and 51,715 NAC nonusers. NAC users had a significantly higher incidence of osteoarthritis (adjusted hazard ratio: 1.42, P < .001) than did NAC nonusers. Also, in analyses stratified by age group and sex, all subgroups exhibited a significantly higher incidence of knee osteoarthritis (P < .0001) among NAC users than among NAC nonusers. The use of oral NAC was associated with nearly four-fold increased the risk of knee OA in the young age group."
Since I have arthritis in one knee, I stopped taking NAC, but the pain is returning. I'd appreciate your thoughts on the study and any suggestions for non-NSAID joint pain relief. I have tried curcumin but did not notice much if any improvement. All thoughts, comments, and suggestions welcome.
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BlastedKnees
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The study was for pts starting without OA, so it may translate differently for one who already has it.
In your case, have you had an objective Dx of OA other than the pain? The study looked for changes here, so maybe you can monitor the non-pain factors for any changes while on NAC if using this study as a guide.
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This statement makes me uneasy:
"the large sample size yielded reliable and accurate results."
Nothing in the world is an unqualified "accurate". Maybe more accurate than something else, but we need that comparison.
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The 1st thing I looked for was the dosing. This came up:
" because data on the dose and administration forms of oral NAC were not available... the dose-response relationship could not be determined". Big problem.
What dose were you taking?
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Another concern is described here:
"The relatively homogenous population living in Taiwan increases the internal validity and reliability of the findings, but the ability to generalize our findings to other populations is unknown"
It would be good to reproduce this in a larger and more heterogeneous country to get an "external validity". This is a common concern in narrow populations of study.
Thanks for the in-depth review of the study. I had similar comments - while no study is 100% conclusive, on the whole they can only use general intuition to guess why it may have the affects they see in the quantitative numbers from self-reported doctors visits for OA etc. I didn't catch the bit on dosing but that's another good catch. However, it's still worth considering and caused me to think twice about using NAC, which is the only thing that's made a significant difference in reducing my joint pain.
I did have a Dx of OA - MRI on the knee and talked to a specialist. In my case however I'm tall (6'5"), so it's highly likely just based on lever action of having long limbs that I'll have OA and worn cartilage from the additional stress. My family however has a history of OA which makes it a near certainty I'll have to deal with OA regardless.
I'm taking the recommended dose per manufacturer - 600mg twice daily outside of meals. To say it works is an understatement. I went from some constant joint pain to nearly none within a week. I stopped taking NAC and had an inflammation event in one knee within 48 hours. So I'm loathe to give it up, but then again I view the possible mechanical damage as worse than some aches and pains...
I've been thinking about your dilemma. Below are some misc thoughts (just my opinions)
- I understand if this is too much info.
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A life changing therapy (NAC) vs its potential risk. I have a mild version of the same choice. Curcumin seems to help my malaise, but overdoing it could over thin the blood (a reversible outcome). I plan to discuss with my specialist next visit. My current solution is to take just one/day to compromise. But I'm also experiencing some possibly irreversible effects from my vax reaction. No way to take that one back.
In the Taiwan study above another big missing item is outcome upon discontinuing NAC. Is the OA effect reversible or not so? Important detail
Another variable not broken out is length on therapy. The study required a min 28 days. This suggests the effect is rapid, but is it proportionate to time or does it stabilize after ~ 1 month?
One of their three outcomes is Dr. or Hospital visits, rather than objective OA. This suggests a subset of pts had pain increased as their outcome as that is the reason to visit a Dr; objective OA not required, but pain is. But does objective OA always lead to pain?
Similar to here, with IFN therapy, it's usually beneficial, but watch for the objective liver counts.
One option could be to measure your OA after your NAC therapy, assuming it was for more than 28 days. If it is unchanged it suggests a lower risk for you of objective OA per the study. If it is increased, does it improve after time off therapy? If so it suggests reversible whereby a smaller dose might prevent a recurrence.
Not too much info at all, I really appreciate the thoughts. From reading your posts (and Hunter's) I get the feeling we're all a lot alike - analytical and working to make the best sense of imperfect data to find the best options we have available.
I'm trying to balance the positive effects of NAC with the risk of further OA. In my case, the way I'm leaning is that I'm more concerned with the potential deterioration of my knees than with the pain that I get at times.
Before I started taking NAC, there were days where I went to bed fine and woke up with kneecaps that felt like someone beat them with hammer all night. But then I forced myself to push through some activity and it helped push out the pain / inflammation. Only exceptions are where I get some weird ones like in the balls of my feet... that sucked for a month. I did see a rheumatologist but nothing came back from those tests. As soon as you tell any doctor you have an MPN, they're very happy to blame it for any odd symptoms...
I'm going to try the L-Glutathione as a potential replacement and see how that does. I haven't done my full homework yet so hopefully there's less to be concerned about. I just hate the fuzziness in the NAC study - good to have the info, but frustrating to not have it pinned down to a specific mechanism of the medicine that can cause OA.
Sorry to hear about the vax reaction. I hope it's just a long-winded reaction and fades over time. My mother has Guillain-Barre and a flu vaccine knocked her for a loop a few years ago and paralyzed one side of her face. It took months but wore off and now she's fine, although she's not keen on needles these days.
As you've likely seen, L-Glutathione requires particular formulas to be bio available.
You also likely have seen this one:
"glutathione and its precursor N-acetylcysteine have demonstrated significant protective effects in events of prolonged, exacerbated oxidative stress as seen in chronic inflammatory musculoskeletal disorders such as osteoarthritis"
They equate the two therapies. As you say, maybe they are different in relevant ways.
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Your mother had existing GBS aggravated by the vax, is that right? There is a US program for vaccine injury compensation, and GBS from flu vax is on it, and her severe reaction seems to qualify, but there are many details. Neuro injuries can take a very long time to heal I've been told, and experiencing. Glad she has mended. ok.
I got Parsonage Turner from the flu vax. I described some of what came next in my "cope with hope" post. I believe in my case it interacted with the IFN.
I still have musculoskeletal issues and am debating whether to restart the NAC. At my peak trauma period it seemed to make things worse.
In addition, the fact that it was "a retrospective cohort study from 2000 to 2013" indicates that they are reporting a correlation, rather than a cause and effect, as might be the case if it were a prospective double-blinded study.
Another caveat is the question of why the patients taking NAC were taking it. They may have been taking it FOR knee pain that had not yet been diagnosed with OA, because we know that knee pain can begin long before the signs of OA are evident even on x-ray.
In my case, I had a meniscus tear in '96, and only developed demonstrable OA changes about 10 years later...
I have used curcumin for some time now to relieve joint pain. It is recommended by my rheumatologist and my Integrative Medicine doctor. The Integrative Medicine doctor also recommended a pro-resolving mediator (SPM Active) and L-Glutathione for systemic inflammation. Note that L-Glutathione is the anti-inflammatory agent in the body that NAC increases.
I would agree with the review by EPguy regarding NAC. I did not review the study, but would suggest looking at the actual data. Correlation does not equal causation. Sometimes correlative data is used in ways that are not accurate.
Suggest reviewing your use of NAC with a medical professional who is knowledgeable about complimentary health interventions. Note that many Western-trained doctors are not familiar with complimentary health interventions. It is not part of their training. It is important to find a doctor with the expertise that you need. Also worth noting that anything that is biologically active enough to help you can also hurt you, and interact with things. It is best to get expert consultation.
Thanks for replying, I had seen your earlier mentions in other posts about curcumin (the curcuwin formulation) and tried it for a couple months but didn't notice a difference. Even NSAIDs that I used pre-diagnosis didn't do a ton to resolve the joint aches / flareups. NAC is the only thing that put a complete stop to it.
Before starting NAC I had a chat with the oncology pharmacist that works with my MPN specialist to ask about any conflicts with other medications. She said no issues and my specialist has several other patients using NAC with favorable results. I didn't ask about the study yet but that's my next stop. My experience has been that there are so many studies that the medical establishment doesn't have the time to keep up.
I was reading about L-glutathione and will give it a try. Anything you've ready about potential downsides? I haven't done the deep dive yet.
The short dive is that L-Glutathione is what NAC produces in the body. The Integrative Medicine doc suggested just going straight to the desired anti-inflammatory agent. I have used NAC to the same effect when L-Glut was not available.
My own thought and where my doc went is that there is potential value in intervening in multiple pathways. Inflammation occurs via various pathways. It makes good intuitive sense to control it via various pathways. The combination I am using is curcumin. L-Glutathione, and SPM Active (a proresolving mediator).
The curcumin is particularly effective for me. That is how I respond. We are all different. Sometimes trial and error is the only way to figure out what works. I am glad to hear you found something that works for you.
I believe that you have that correct. My Integrative medicine doc acknowledged that NAC works too. She was just suggesting to take out the middleman and go straight to the desired effect.
Consulting an Integrative Medicine doc is a great idea if you are interested in a more holistic approach and want to include complementary health interventions. Here is the list that i know of. fonconsulting.com/resources... And in a similar vein, Functional Medicine docs. ifm.org/find-a-practitioner/
The interesting bit in the study you posted below comparing NAC and glutathione was that the hierarchy of effectiveness seems to be:
1. sublingual glutathione
2. NAC
3. Capsule form glutathione
Capsule form glutathione being the least effective as it gets destroyed by the stomach before being absorbed. NAC survives the stomach well but isn’t as directly effective as glutathione (if it can be absorbed). Sublingual glutathione is absorbed directly through either liquid or a lozenge form in the mouth and is the most effective of all.
Amazon sells the same version of sublingual glutathione (Sublinthion) that was used in the study.
FYI - the other thing that worked is hyaluronic acid injections into the knee. I avoided surgery that one doc recommended. My knees were restored to almost full function.
Thanks, I appreciate the suggestions. Making a list of what others use. I'll see how L-Glutathione does for awhile to see if that's a good substitute. The fact that the NAC study doesn't say much about the specific mechanism (except to postulate that maybe it has something to do with factor p53) makes it hard to look for any relationship. How long have you been using L-Gl if you don't mind me asking?
I have been using L-Glut for about 3 years. I am using it in combination with the curcumin and SPM Active so it would hard to sort out its individual impact. There is some trial and error involved. Hope you find what works for you.
BlastedKnees, suggest researching annatto tocotrienol for your joint pain. I use 375 mg a day to tap into it's many benefits. I have no joint issues. In addition to the annatto tocotrienol check out boron for your arthritis, search Nothing boring about Boron. I use 12 mg a day. Not noted in that search information is boron also helps prevent loss of height. So far so good. Always check with your health care professional before using any supplement.
Thanks for this, I'll have a look. The core issue is that I have inflammation related joint pains, but also have some knee degradation that I don't want to accelerate. So I'm looking to treat the inflammation and not exacerbate the cartilage wear. What type of joint pain is annatto tocotrienol helping you with?
Blasted, I've been using annatto tocotrienol for many years along with boron as a preventitive. I'm 78 and have full motion of all my joints and experience no pain. As you research it's effect on cartilage, especially articular cartilage, you'll be pleased to know it is also a bone building enhancement. Annatto tocotrienol also is anti inflammatory among other attributes.
Interesting thread. For what it’s worth I have been using a high dose of a combo of NAC + glycine (8+8 grams/ day) based on some very interesting positive ( but small) human studies. Before starting the regimen I often had lower back and knee pain. I no longer have any joint/knee pain in spite of playing competitive hard court tennis. I’ve been on NAC + glycine for 2 years now. This by no means is meant as a recommendation as there are no long term studies with a large number of subjects. You can find the studies with the following search terms: NAC AND glycine AND Sekhar
Holy moly, 8 grams per day is some serious dosing. I'll have a search on that but something tells me I won't be able to get my head around the high intake. Particularly as I don't want to potentially irritate the cartilage issue. I haven't looked yet, but they have no issues with oxidative stress in the studies?
The combo is clearly active. From the reports it seems the goal of the combo remains raising glutathione levels. They do suggest an action of Glycine alone but it largely points to increasing glutathione from what I can see.
"This is why GlyNAC is a natural solution for correcting glutathione deficiency, because it provides the raw materials to help cells to make their own glutathione"
Are there reports on the combo vs NAC, or vs other high bioavail Glut formulas? Is primary the goal still focused on Glut levels? Or is there a unique branch that Gly addresses? I know here are rarely clear answers to these sort of things.
I'm all in for a supplement that will reduce days like I'm having today. I'm increasingly inclined to consult an integrative med doc as Hunter has discussed.
While glycine is one of the 3 amino acids in glutathione, glycine has additional roles in one-carbon metabolism. The intervention testing program (ITP, a great website) has tested glycine in large cohorts of mice to evaluate if the compound extends life span. It did extend median life span by a modest 5%. phenome.jax.org/projects/ITP1
The combination NAC+Gly extended the life span of mice by a stunning 24%, which is among the strongest effects I have seen for supplements in survival studies. Note, this was a modestly sized study in a commonly used mouse strain (C57BL/6) with a homogeneous genetic background, unlike the genetically diverse mice used in ITP studies:
It is noteworthy that there is an ongoing clinical trial with NAC at lower doses in MPN patients. Angela Fleischman at UC Irvine is the lead on this and she is aware of the studies of high dose NAC + glycine.
Thanks again for all this information. I went through a few studies on NAC / Glycine combo. The results are encouraging. One thing I note is that they use very high levels of Gly and NAC. Given NAC has warnings for blood thinning effects, this would concern me with taking doses in the range of 2g - 8g per day. Have you seen anything that addresses that risk?
The message is NAC is not the best way to increase Glutathione. Maybe the Fleischman trial should have selected the combo or at least the high bio avail GSHs. I think one reason for using NAC is its establishment already as an FDA medicine for another purpose.
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