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47 Responses to “Failed Experiment: Methotrexate & Over the Counter Folic Acid”

    1. @SuaveDJ says:

      rawarrior I’ve been taking 5mg a day five days a week!

    2. @Sx3inSC says:

      rawarrior good morning Kelly! Sending you big ((HUGS)) to start your Monday. #PBWY

    3. Steph P says:

      I had the same experience with OTC folic vs prescription. In Canada you can only get prescription for 5mg Folic. Anything less is OTC only. Couple summers ago there was a manufacturing shortage of the prescription version and was forced to use the OTC. Adding 5 extra pills to my arsenal was bad enough but when it didn’t work as well I really wasn’t amused.

    4. KayLeFevre says:

      I’m sure there is a tendency to skip this important little yellow pill, but look how vital it is to your well-being! I swear when my rheumy finally put me on this my hair loss stopped too. Thanks for this important reminder!

    5. Diane says:

      My prescription is for 5mg folic acid 7 days a week…with 17.5mg MTX

    6. Hi Kelly, I’ve been on 5mg of folic acid every day except mtx day, for almost 18 years now. I asked my rheumy, aka Dr Dishy, about the differences between rheumies regarding the folic acid dose, days to take it etc and he said that he says every day to ensure that we get some into our systems, allowing for forgotten doses etc.

    7. Kelly says:

      Hi Kelly, I might also recommend a bone denisty scan upon diagnosis with RA and then again in a couple of years. In less than 4 years, I already show signs of osteopenia. Methotraxate depleats your bodys stores of Folic Acid and therefore depleats your bones of that needed mineral.

      • kelly- the tack room says:

        I take (2) 1mg tabs 7days- an Kelly you are correct in advising a bone density. took 3 OBGYN’s to order one and low and behold – found out from my “friends” at Mikes Health Connection- local vit. shop that when I take my vit. with meds the meds prohibit the absourbstion so always take vit. 1-2 hrs before or after meds.- esp. calcium – why the Dr’s dont know this – is beyond me – one would think this would be part of the dialog so as not to create “another” issue with the patient. I want to note that the owner and staff at Mikes have been a wealth of information and help to me through this journey and am so grateful-

      • Lora Floyd says:

        Oh, and BTW, Folic Acid can drain you of B12, so yes you can take too much. I take a supplement of B12, which seems to have help my mood. I’m not so depressed.

    8. Teresa says:

      I have taken both but did not notice a difference. But I will remember this article and continue with prescription. Thanks for posting. My rheumy said you cannot over dose on FA. Your body will pee out what you don’t need.

    9. Terri Loudermilk says:

      My dose of folic acid is 1mg per day with 17.5 methotrexate weekly. I was told there is a shortage on the injectable mtx so I’ve had to switch to the pill form – it is much harder on my stomach. I will definitely talk to my Rheumy on Friday about upping my folic acid dose.
      Thank you Kelly for the information. And my thanks to those who commented.
      P.S. The jokes will be spreading around my office in no time.

    10. Lora Floyd says:

      I’ve been taking OTC folic acid since my onset. I think your first mistake was getting it from an unreiliable source. I get mine from The Vitamin Shop and have not had any problems (yet). My blood work comes back great. Because I don’t have insurance OTC is my only affordable option. Again, thanks for all you do.

      • A brand can be reliable OTC. There is another post in progress about supplements which states this, but my point today is that unless they already know it’s a trusted brand, a patient can’t be sure of dosage OTC because testing is not required by law. I’m glad you pointed out that there are some brands and sources more dose reliable than others. It’s just hard for consumers to know for sure.

    11. Molly says:

      I’ve read a lot that patients don’t take Folic acid on their methotrexate day, can someone tell me why?

    12. Bob West says:


      There are several problems with this story, some of which the readers have picked up on, and some not.

      1. I agree with Lora Floyd that the SOURCE of OTC FA makes a difference. Walmart FA could have been tainted somehow, or just at a lower dose than advertised (FWIW I get my supplements from GNC and It’s having made you sick might have been simply the concomitant higher impact of MTX with lower active FA in your blood. If you examine the biochemical pathway, FA and MTX are opposing one another via the enzyme DHFR. With FA supplements, it appears you merely titrate out the MTX, assuming the latter acts as a competitive inhibitor. If you up the dose and frequency of FA, you must up the dose of MTX to gain an inhibitory effect of the latter. Otherwise, the one is defeating the role of the other. This argument assumes that FA acts solely on DHFR and not outside of the one-carbon metabolism pathway.

      2. What Lora Floyd said about FA causing B12 depletion is also true. Both vitamins are involved in the same metabolic pathway which produces purines thymine, serine and glycine (I teach to med students). Thus, starvation of this pathway via MTX will impact B12 by depriving it of its substrate N-methyl tetrahydrofolate. The consequences would be a buildup of homocysteine (bad?) and depletion of methionine- required for proteins, and for the methyl donor S-adenosyl methionine (SAM). Thus, depletion of FA by MTX causes multiple downstream biochemical effects that would seriously impact cell function.

      3. Teresa’s point about not overdosing on FA is likely correct. The body stores fat soluble vitamins but not water soluble ones; they are quickly eliminated in the urine.

      4. Other drugs and supplements you may be taking, including certain foods, may impact the concentration or activity of the FA or MTX. The more different drugs you take, the more complicated the entire metabolic scene becomes. This is one reason why it’s difficult to compare results between individuals (not to mention #genetics), not to mention different time periods for the same individual.

      5. From my limited understanding of this, I would say the most important variables to be controlled, assuming accurate drug quality, would be consistent and pinpoint dosing and scheduling of MTX and FA, along with supplementation of B12 and possibly methionine. Ask your doctor about the latter item, and also about potential hyperhomocysteinemia while on MTX.

      Did not mean to be long-winded, but this is a complex topic.


      • I’m sorry for any confusion about my situation. Yes, I did assume that as you said, the FA purchased at Walmart (NOT walmart brand) was a lower dose than advertised since I’ve been warned that is is commonly so. And I’ve had the b12 tested a few times by the GP and was not on any other supplements at the time that could interfere. What I swallow is highly monitored due to the clinical trial. I hope everyone can see that I never recommended or endorsed the high doses that many use of FA – 5 mg per day. Even while taking several OTC (very low dose) tablets, I’m sure I have never approached that dose, so over dosage was not something that entered my mind and does not sound like a possibity in my case.

        As the provided link states, there is not a protocol for this – as is true for so much of care for Rheumatoid disease. Youre correct that dosing is the most important issue. Since we do not take any tests to monitor that, it’s something that patients need to talk to doctors about – which was the point of the post. Accurate dosing is more difficult with OTC in the US, but not impossible of course.

        Also, a friend who is a chemist (working in rheumatology) has told me about experiments that prove increasing FA does not inhibit effectiveness of mtx. There are references to studies that have shown BOTH viewpoints in the article that I linked to in the post. Which tells me that our doctors may not be sure about this chemical balancing act.

    13. mj says:

      In the first 6 months of this mess of RA, I was terrible at remembering to take my pills. Finally got a pill box. I don’t know if it was the diligence with routine, and not skiping my FA, or adding of 200mg of planquinil, but I have returned to a fairly nice new normal. For me, keeping my routine constant, weather it is pills, food, sleep, exercise or mood, has become critical to my flare management. Just my 2 cents!

    14. Lene says:

      Interesting… would folic acid work if you have stomach issues from Humira (and pain meds, etc) do you think? I normally rely on acidophilus – the good kind from the helathfood store – and it works very well, but I could use an extra cushion.

    15. carolf says:

      I take 4 tabs of 1mg folic acid once a week and 15 mg of Methotrexate the next day. It is a prescription. I go to a Natural path as well and he studies what supplements I need. I never realized the difference in quality. This is a great site. When I get discouraged during a flare it is great to have an up beat site! Thanks,Carol

    16. Wayney says:

      I do not take MTX but I do take Arava. When I switched from MTX to Arava, my rheumy said I could stop FA if I wanted. There’s not much of a recommendation to take it with Arava from what I’ve seen. He did say if I had hair loss with Arava, I could restart the FA. When I did lose some hair from Arava, I restarted the FA. My generic scripts were $7 a month. The pharmacy I went to had a brand of OTC FA that was 800mcg in a bottle of 100 for less than $3. My rheumy and I discussed it and he said I could try the OTC brand to see if it helped and there were a few ways I could take it. 1)start at 800mcg per day to see if it worked. If not option 2)take an alternating dose of 800mcg one day and 1600mcg (1.6mg) the next. If that didn’t work, option 3)take 1600mcg a day. I never had to increase from the 800mcg. After that store went out of business, I began taking the 1mg prescription tabs. I still do even though my Medicare Part D plan does not consider the folic acid to be a covered med so I have to pay extra for it. Which is ridiculous!

    17. ben corde says:

      I’m on 5mg folic acid daily and 20mg methotrexate plus 200mg hydroxychloroquine daily.(And of course fish oil) Never had an illness or any side effects in three years. No joint damage progression in three years.Aches and pains still happen but occasional painkillers sort this.Muscle strength and stamina so much improved I feel 20 years younger. CRP hovers around the top end of the normal range at between 8 and 12 and ESR is anywhere between 10 and twenty. Rheumy says this is normal for age and the CRP is not bad enough to warrant change of medication while joint damage is nil. No charge or mail fee for repeat prescription home delivery by NHS Prescription every time for us. It’s cheaper and you have the medical backing. Incidentally, on a slight tangent, I believe homeopathy is all in the mind. It only works for a very small minority who believe it has made them feel better when in reality it does far more harm than good in delaying proper medication or treatments.

    18. Paul McIntosh says:

      Yes Bob complicated, body appears to store folic acid in the form of folate polyglutamates and FA supplements absorbed differently, preferentially. See link below chapter 8 on Folate, p213 references to MTX mimicking folate deficiency, gastrointestinal intolerance

    19. Kim says:

      Folic Acid does work to help with the nausea of MTX. You have to take a good kind like you said and you have to be consistent about it but it does work. OTC does not! I concur.

    20. Lisa says:

      When I stopped methotrexate last October I also stopped folic acid. I was still taking sulfasalazine and Enbrel. I started getting a lot of mouth ulcers and my rheumy said to start the FA again. They cleared up in a few days. From what I’ve read, sulfasalazine can also interfere with FA absorption. I take 1mg daily. Good post!

    21. Worn Out says:

      Interesting. My rheumy actually took me off methotrexate as I simply could not handle it. I was taking folic acid, but it was over the counter. I had no idea it was even available as a prescription.

      • I’ve heard this from several people – that is the point of my posting. If needed, the treatment program (mtx & folic) may still be an option for you to try one day if your dr thinks so. There is another more detailed post about folic acid options also – it is listed in the links below the post – “folic acid debate” —

    22. Elena says:

      When I was first diagnosed last year I was on 15mg MTX weekly and 1mg Folic Acid daily. When I told my doctor I was quite fatigued he doubled the FA daily. It helped a bit, but after researching the combo I wondered if the FA was cancelling out the MTX. My Dr. said no. Still taking the same dosage, but fatigue lingers for two days after taking MTX. I also take B Complex plus C, B-12, B-6 and Vitamin D 2,000 daily. Yesterday I bought double the dosage of the B vitamins to see if that helps.

      • Hi Elena. I’ve read studies and been told by experts that they don’t cancel out, but others seem unsure. Also, fatigue is something that has various factors behind it. I’ve never found that methotrexate helps my fevers or fatigue symptoms much. I still have daily fevers with it for example. So methotrexate, while it’s the most used & has the most broad affect agaisnt autoimmunity, does not treat all symptoms in all patients. So fatigue may be a side effect or may be the disease activity.

        I don’t know if it will matter, but make sure to tell your doc about new level of vitamins in case of any conflict.

        • Elena says:

          Kelly, I think the MTX definitely increases my fatigue and that’s why my dr. doubled the FA dose. Good point…I will tell him about my vitamin dosages next week when I go back. I’m also going to request a thyroid test as well, just to be sure.

    23. Carrie says:

      I am injecting Methotrexate (25mg) each week and am taking 2mg of folic acid a day. The folic acid has helped with mouth sores as well as help with stomach upset. The doc prescribed it before I could ask for it. I previously had been taking methotrexate by mouth before going to the injections. I did not notice much difference while I was taking the pill form of methotrexate. My stomach had major problems with it, though. I do notice a difference using the injections, though, and don’t have as much problems with my stomach. I believe it is VERY important to take folic acid for so many reasons. Taking folic acid helps with the hair loss too. I have Hashimoto’s, Sjogrens, and RA and I am still surprised I have hair left.

      • Thanks, Carrie, I have the same history as you – with those med levels and diagnoses. I’ve had the same experience w/ mouth sores, hair loss and stomach issues w/ the drug. And the same result w/ the FA: it helps a lot. More than I knew obviously. It’s so important that people know it’s an option to take prescription FA or to alter the dose, with their dr’s agreement, of course

    24. Ginny Granade says:

      I was put on prescription folic acid when first prescribed methotrexate pills. Later switched to the injections, but even though the methotrexate wipes me out for about 18 hours, I’ve never had the first bit of nausea or upset stomach. After reading this, will not try otc folic acid! Thanks, Kelly

    25. Heather Cannova says:

      Methotrexate is a folic acid inhibitor. You have to be careful with how much folic acid you take because it can work against your methotrexate. There is no real consensus on how much to take but my doc has raised it at times when I have been losing my hair or I have felt run down. It did help. However, he lowered it when I was feeling better.

      Just a note. Hope this helps.

    26. Kari says:

      I had the same problem with Folic Acid – I tried the over the counter also and was sick sick sick!

    27. Lisa says:

      Never knew there could be that much of a difference. I think I have taken 2 mg prescription folic acid for about, oh, I have had RA almost 18 years, so at least 15 years. I will stick with it. I too have noticed a difference sometimes with sores in mouth, on top of head, (and other unmentionable places) and extra folic acid has always cleared it up. I was never able to take mtx orally, but always did shots.

    28. Jenn says:

      It is also great in keeping your hair from falling out and severe headaches at bay. I don’t understand mtx dosage but I guess I might be on 15 mg and taking 3 mg of folic acid.

    29. Mr. C. says:

      I’m on 20mg of MTX after working my way up from 7.5mg over a 3 visits and about 4 months. 1MG of prescription folic acid per day, every day. After I learned to make sure I ate enough before taking the MTX and the first two doses knocking me for a loop I have had no noticeable side effects. Hair was already starting to thin but doesn’t seem to be any worse.

    30. calugg says:

      Thanks for the heads-up on the Folic Acid. I started Folic Acid AND MTX yesterday for the very first time (10 mgs). I’m a newbie, officially diagnosed on Tuesday, but started on Prednsone 3 weeks ago.

      I will say I’ll take the butt-kicking fatigue with MTX if I can turn off the butt-kicking burning joints, fatigue and brain fog of unmoderated RA. Until I started the Prednisone, I had never been so ill for so long in my life.

    31. Roxy says:

      I think the issue is less OTC vs. Prescription folic acid, and more the form of the folic acid you take.
      My rheumatologist gave me a folic acid prescription with my 20 mg. methotrexate prescription, and I had horrible nausea and fatigue. I came across an article about a common problem metabolizing folic acid, so switched to a different OTC form — the nausea went away and I felt a lot better. The form I am taking is usually referred to as MTHF, short for 5-MethylTetraHydroFolate. Thorne and Life Extension are two brands I have obtained online.
      As others said above, folate interferes with some mx actions, so it Is not advised for those taking mx for cancer.
      There is a good resource on supplement quality: The site tests supplements to see if they contain the claimed ingredients, and they also have general information about supplement use. Some articles are free to all, but the most helpful require a subscription (worth it to me, as I take quite a few supplements).
      Hope this is helpful to someone out there…

    32. Elizabeth says:

      When I asked my rheumatologist if I could just take the OTC folic acid, I was told no, that it would have to be the RX strength. I do have a question though. I tend to have IBS issues. I sort of know that some foods I eat can trigger this BUT I’d love to know now that I’ve been diagnosed with R.A. and take 5 pills of methotraxate per week…if any of this could also contribute. I see my rheumatologist in a couple of weeks so this will be one of my questions to her as well.

    33. How do you know an elephant has been in your refrigerator?

      There are footprints in the butter.

    34. carol Kelleher says:

      This is the greatest web site. what took me so long to find it?

    35. Barney says:

      I’m on 5mg folic acid daily and 20mg methotrexate plus 200mg hydroxychloroquine daily.(And of course fish oil) Never had an illness or any side effects in three years. No joint damage progression in three years.Aches and pains still happen but occasional painkillers sort this.Muscle strength and stamina so much improved I feel 20 years younger. CRP hovers around the top end of the normal range at between 8 and 12 and ESR is anywhere between 10 and twenty. Rheumy says this is normal for age and the CRP is not bad enough to warrant change of medication while joint damage is nil. No charge or mail fee for repeat prescription home delivery by NHS . Prescription every time for us. It’s cheaper and you have the medical backing. Incidentally, on a slight tangent, I believe homeopathy is all in the mind. It only works for a very small minority who believe it has made them feel better when in reality it does far more harm than good in delaying proper medication or treatments.

    36. Debra says:

      I have been in a state of natural remission from my RA for the past 6 years. My rheumatologist does not believe that I am not in any pain since I was pregnant with my 2nd child. Now he is recommending me take the dreaded methotrexate again without a clear definition for what he will be measuring against in terms of inflammation. I don’t want to take them…

    37. dee washington says:

      On avara 20 mg and taking 800 mg folic acid and 10,000 units biotin reversed hair loss was almost bald
      I know I dont have enough folic acid when my tongue is sore. I take a walgreens over the counter. Folic acid is a water soluable vitamin- read about this vitamin type

    38. Darewin F Rose says:

      Dont know who this might help but i was diagnosed with RA 2 years ago. Have been carefully and happily following the doctor’s orders the whole time especially concerning taking the folic acid. Just recently my GP ran a DNA panel on me on another matter and it turned out that I was missing a biomarker that shows I don’t absorb most folic acid. We have now switched over to l-methylfolate and my body is showing signs of improvement now that it can absorb the right type of folic acid. So just because a doctor may have you on a prescription folic acid does not mean that it’s doing your body one bit of good. This is something you might want to talk with your rheumatologist or your general practitioner and have the test done to clarify what your body will and will not absorb.

    39. Jill says:

      I do believe that methylfolate is a superior form of folic acid. IF you take folic acid please test yourself for the biomarker mentioned above. Also please don’t buy any supplements from Walmart, or China or Amazon! Biotics research lab makes supplements with same quality as prescriptions (they have a pharmaceutical license) visit Get

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