Can I Avoid RA Drugs or Should I Go On Drugs? 'Paddison Program' FAQ Opinion; Also: Methotrexate Explanation & References

Can I Avoid RA Drugs or Should I Go On Drugs? 'Paddison Program' FAQ Opinion;  Also: Methotrexate Explanation & References


Can I Avoid RA Drugs or Should I Go On Drugs? 'Paddison Program' FAQ Opinion; Also: Methotrexate Explanation & References

Hopefully, the 8-minute synopsis will clarify the 'Paddison Program' (PP) approach to medications & dispel misunderstandings, misperceptions, miscommunications, misimpressions, misreadings . . . of the approach. 🙏


If you're seeking clarification on Clint Paddison's OPINION on medications — in the context of a dietary/ lifestyle approach — kindly consider viewing the full 8 minutes.

Do You Need To Take RA Medications?


🙏 🍀 🌺 🌞



6️⃣8️⃣ Dr. Michael Greger ('Sense & Sensibility') Shares "How Not to Die":

6️⃣7️⃣ Journalist Sumit Bose, Another RA-er Who's Documenting His RA Journey:

6️⃣6️⃣ 'Microbiome/ Gut Health Book List' from AARA:

6️⃣5️⃣ Practical, Brief Video Tips for RAers/ Autoimmuners:

6️⃣4️⃣ Supplements/ Nutrients (B12, Vit. D, Potassium, Protein . . . ) for RAers/ Autoimmuners & Plant-Based Dieters (Vegans, Vegetarians, . . . ):

6️⃣3️⃣ Sally, 'The Galloping Grandma':

6️⃣2️⃣ Why Does the Medical System Ignore the Importance of Diet? A Fable Told by John Robbins:

6️⃣1️⃣ Dr. Brooke Goldner's Free 3-Day Webinar, '6 Steps to Reversing Autoimmune Disease with Supermarket Foods': August 3/Thu, 7/Mon, 10/Thu 2017:

6️⃣0️⃣ 'No' to Fish Oil Too?:



5️⃣9️⃣ Top Rheumatoid Arthritis Blogs & Websites (from 'Feedspot'):

5️⃣8️⃣ Psoriatic Arthritis & Skin Psoriasis: Nicole S. O’Shea's Journal (& Journey):’sheas-journal-journey

5️⃣7️⃣ Anyone experience with Pulmonary Nocardia (Nocardiosis)?:

5️⃣6️⃣ Osteoarthritis: Prevented with Diet & Exercise? University of Surrey (U.K.) study in 'Nature Reviews Rheumatology':

5️⃣5️⃣ "Guide for Rheumatologists" V 1.5.6 (for 'Paddison Program'-ers):

5️⃣4️⃣ Life is all about how we see things. Context is everything. Perspective is everything.:

5️⃣3️⃣ 2017 Food Revolution Summit: April 29 (Sat.) to May 7 (Sun.) Now Underway:

5️⃣2️⃣ Reg, Coordinator of 'Redcar Arthritis Care Group', Shares His Thoughts about Movement/ Exercise & Arthritis:

5️⃣1️⃣ Cornetto Trio? From Maya Angelou to Confucius to 'Oprah'!?:

5️⃣0️⃣ "What Doctors Don't Know About the Drugs They Prescribe" by Ben Goldacre:



4️⃣9️⃣ 2017 Food Revolution Summit: April 29 (Sat.) to May 7 (Sun.):

4️⃣8️⃣ "People who say it cannot be done should not interrupt those who are doing it.":

4️⃣7️⃣ "When someone shows you who they are, believe them.":

4️⃣6️⃣ Ankylosing Spondylitis (AS):

4️⃣5️⃣ Have you been on the "Paddison Program Forum"?:

4️⃣4️⃣ Anyone on the "Paddison Program Forum"?:

4️⃣3️⃣ "How U.S. Health Care Became Big Business": Medical Journalist, Dr. Elisabeth Rosenthal talks with NPR's Terry Gross:

4️⃣2️⃣ Quinoa, Buckwheat, Sweet Potatoes, Leafy Greens, . . . 'Baseline Phase' of PP Diet Fulfills Nutritional Requirements (Diverse & Complete):

4️⃣1️⃣ Healing Power of Resilience, Optimism, & Hope: Moving Forward from Trauma, PTSD, Physical & Psychological Abuse & Illness — Dave Pelzer:—-dave-pelzer

4️⃣0️⃣ Warm welcome, Hopeyj19!:



3️⃣9️⃣ From Wheelchair to Bikram Yoga (in 10 Months):

3️⃣8️⃣ "A Kitchen Fairy Tale" by Iida, How She Healed Herself with a Plant-Based Diet (according to 'Tribe Magazine'):

3️⃣7️⃣ Can I Avoid RA Drugs or Should I Go On Drugs? 'Paddison Program' FAQ Opinion; Also: Methotrexate Explanation & References:

3️⃣6️⃣ EarthToLor: Psoriasis, RA, Depression, Weight Gain; Triple Therapy & More; Potatoes & Rice:

3️⃣5️⃣ New Arthritis Podcast: "Can Arthritis Potentially End a Musical Career?":

3️⃣4️⃣ Cardiologist, Dr. Monica Aggarwal, Reduces Her RA Inflammation via Plant-Based Nutrition, Diet, Lifestyle:

3️⃣3️⃣ AndySwarbs Shares His RA Hero's Journey — Joe Campbell Style:—-joe-campbell-style

3️⃣2️⃣ Olive Oil — not Popeye's 'Olive Oyl':—-not-popeyes-olive-oyl

3️⃣1️⃣ Our Beloved AndySwarbs, a Hero's Journey:

3️⃣0️⃣ Erika's Rheumatologist Confirms Erika's CCP Reduced (from 144.3 to 27) via Diet — turning_pain_n2_purpose:—-turning_pain_n2_purpose



2️⃣9️⃣ "Super Juice Me!" Documentary by Jason Vale:

2️⃣8️⃣ "Fat, Sick & Nearly Dead" Documentary by Joe Cross:

2️⃣7️⃣ Juvenile Idiopathic Arthritis (JIA): Jenn, Cole, & Joseph Share Hope & Practical Experience:

2️⃣6️⃣ Jenn, Cole, & Joseph: JIA-ers Who Share Hope & Practical Experience:

2️⃣5️⃣ Empathetic 'Knee Photo' for Deejojo:

2️⃣4️⃣ "Tis but a scratch . . .":

2️⃣3️⃣ Placing Dietary & Lifestyle Approaches 'In Context'/ 'In Perspective':

2️⃣2️⃣ Roxana, 'The Sofia Vergara of Peru' (& now 'The States'), Improves Her Hashimoto's (Hypothyroid) & Rheumatoid Arthritis (RA):

2️⃣1️⃣ Any 'Ankylosing Spondylitis'-ers (AS)?:

2️⃣0️⃣ Catching Up with 'Healing Josefine' -- Over 2 Years & 80+ Vlogs:



1️⃣9️⃣ Dr. Pam Popper on: Hypothyroidism; Iodine, Thyroid Function & Thyroid Disease:

1️⃣8️⃣ Self-Management Event in Southampton on Feb. 14 & 15 from 'Arthritis Action':

1️⃣7️⃣ X-Ray Yoga:

1️⃣6️⃣ Gentle Chair Yoga for RA, X-Ray Yoga for Wonderment:

1️⃣5️⃣ Suicide -- Career & Otherwise:

1️⃣4️⃣ Meditation, Mindfulness, Movement, Breathing, Relaxation, Stress Reduction . . .:

1️⃣3️⃣ 13 Bite-Size Thoughts for Autoimmuners -- Newly Diagnosed (or Not):

1️⃣2️⃣ "When You Know Better, You Do Better!":

1️⃣1️⃣ Dietary/ Lifestyle Considerations for Rheumatologists to 'Ruminate On':

🔟 Spoon Theory, Spoonie, Spooning:



9️⃣ Douglas Lisle: 'The Pleasure Trap':

8️⃣ Dean Ornish, Neal Barnard, T. Colin Campbell, Caldwell Esselstyn, John McDougall, Michael Klaper, Michael Greger:

7️⃣ "Poofed" Info, References, Links, Your Replies, etc. (at ALL 'Kai-- Posts'):

6️⃣ FREE Whole Foods Plant-Based Diet/ Lifestyle (WFP-BD/L) Info for Interested Autoimmuners/ RAers:

5️⃣ Vogons, Vulcans, Vegans:

4️⃣ Microbiome, Pooing, Toilet Humour:

3️⃣ For All Autoimmuner's: FREE 7-Part Documentary with Tom O'Bryan:

2️⃣ FREE 3-Part 'Serology (RF, ACPA, Anti-CCP, ANAs, ANCA) in Rheumatology' Series from Dr. Robert Coughlan's 'Rheumatology Toolbox':

1️⃣ "Live Your Life. . . ":

Kai-- Profile: [Click on blue "Read more" text (at top of page) to read full profile.]


Last edited by

34 Replies

  • The 'Paddison Program' (PP) (to my understanding), has always encouraged us dietary/ lifestyle implementers to work hand-in-hand with our medical team.

    [From listening to podcasts & following the PP process, I've never heard (or gotten the impression) to 'pop off' meds or ignore my rheumatologist/ medical team or any of the other misinterpretations I've heard elsewhere. 😳 🙃 ]

    We implement our d/l approaches in conjunction with our meds — not in place of our meds.


  • Lyn has reduced (halved) her Methotrexate:



    [Bit more at: 13 Bite-Size Thoughts for Autoimmuners -- Newly Diagnosed (or Not): ]


  • Sally, 'The Galloping Grandma' blogger ( TheGallopingGrandma.wordpre... ) lowers her methotrexate too:



    🙏 🍀 🌺 🌞


    [ ]


  • Pareto principle — 80/20 rule ( ):

    The Pareto principle (also known as the 80/20 rule, the law of the vital few, or the principle of factor sparsity) states that, for many events, roughly 80% of the effects come from 20% of the causes.



    5-Ways to Lower Pain:

    1️⃣ Meds ⭐️

    2️⃣ Diet ⭐️

    3️⃣ Exercise ⭐️

    4️⃣ Supplements

    5️⃣ Stress Reduction



    Baseline Phase of PP: FREE Whole Foods Plant-Based Diet/ Lifestyle (WFP-BD/L) Info for Interested Autoimmuners/ RAers:

    Under Dr. Michael Klaper, Q&A: Diet, Arthritis, & Autoimmune Diseases, “The Baseline Safety Diet”:


  • Additionally, if you're interested in viewing the PP perspective on Methotrexate, this page (with references) may be of interest if your researching Methotrexate in conjunction with dietary/ lifestyle approaches:

    [The research References (& Comments) towards bottom of source page, may also be of interest. 🤓 ]

    In meantime, the Methotrexate text is copied & pasted here for easy reference:



    "Methotrexate is one of a group of drugs known as DMARDs, or disease modifying anti-rheumatic drug. This category of drug works by suppressing the immune system and is considered a first-line drug for treating Rheumatoid Arthritis.

    Because inflammation is an overactivity of one part of the immune system, the intent of using the drug is to reduce inflammation in rheumatoid arthritis. The major side effects of Methotrexate, however, have everything to do with causing inflammation of the digestive tract. This is important to understand, because the integrity and function of the intestinal lining is quite central to controlling inflammation. The most recognized risk of Methotrexate is increased intestinal permeability; this leaks to what is known as leaky gut [ii][iii] [iv] [v] [vi] [vii] [viii] and is a cause of inflammation [ix]

    Methotrexate also has been shown to reduce the number and diversity of gut microbiome [x] which has been shown to promote joint inflammation [xi]. Intestinal inflammation [xii] [xiii] and inflammatory bowel disease have also been found to promote rheumatoid arthritis [xiv]. Oxidative stress of intestinal lining [xv] from Methotrexate, and inflammation of the mucous lining of intestines (Intestinal mucositis) [xvi] also contribute to the side effects and immune dysfunction that can detract from it as a useful drug for many individuals. Some research has described the side effect as gastrointestinal toxicity with mitochondrial damage [xvii] which is what promotes oxidative stress of the intestinal lining, because the mitochondria are what produce energy for the columnar cells lining the gut. Because of this combination of factors, the side effects include diarrhea, anorexia, nausea, vomiting, abdominal pain, inflammation, ulcerations of the mucous membrane of mouth and throat [xviii]."


  • Why doesn't this text go on to explain if there are gastrointestinal problems on tablets injections can be prescribed? Taken this way it also solves the 'reduction of gut microbiome' theory, if this is eventually proven to be the case.

  • Whilst it is referenced, this is a very one-sided article and the references have been 'cherry picked' to convey the negatives of the drug without any of the positives. The article focuses on side effects and suggests that the drug causes inflammation rather than controlling it, yet there is a wealth of evidence for methotrexate being very good at controlling the disease activity in RA and preventing joint damage (far more evidence than there is for the Paddison Programme).

    For more balanced information on methotrexate, please see the following article on our website:

    For an article to be balanced, it should not only reference any statements it makes, but should also follow the most up-to-date and accurate evidence, rather than choose evidence that supports a pre-conceived idea. This is why all our articles go through a rigorous process, which includes being written by the most appropriately qualified author and being peer and reader reviewed.


    (NRAS Information and Support Manager)

  • 👍 Many thanks, Victoria-NRAS. Much appreciated. 🙏

    NRAS article copy & pasted below (in 3 segments) for easy reference: Methotrexate in Rheumatoid Arthritis:

  • Side/ related query regarding content of video 📹 (posted above):

    Is there a perspective/ opinion that NRAS can share about the video's content, the substance, of what is being said?


    [I ask, because to my layman's ear 👂 (non-science/ non-medical), it all sounds logical, sensible, sound . . . 🤔 ]

    Any insights 👁 👁 you're comfortable sharing, would be greatly appreciated, Victoria-NRAS. 🙏 👍


    [I understand (& respect 🙏 ) the many years of hands-on experience you (& NRAS staff & members) have with RA & the knowledge, experience, insight, wisdom . . . you've acquired over years. Whatever information, insights, opinions . . . you can share would be invaluable & much, much appreciated. 🙏 ]


    Thank you kindly, for your thoughtful consideration, Victoria-NRAS. 🙏 👍 ]


  • Hi Kai

    Thank you for including text from our methotrexate article. I prefer to give a link, as although it's an extra click, it means people will always see the most up-to-date version.

    I'm sure you will appreciate that in moderating this site while also running a busy helpline, I sadly do not have the time to watch and make notes on all videos posted on here, to then spend time going through all the statements made to see what the level of evidence is to support or refute them. This is much more time consuming with a video, as you have to effectively write up a transcript to go through it point by point.

    I should also point out that I am a lay person as well, so am not best-placed for analysing this for you. However, my colleague Clare did comment on another thread, giving feedback from NICE on levels of evidence for the Paddison Programme:

    This doesn't refer specifically to these videos, but will hopefully cover some of the key points.

    Kind regards



  • Thank you kindly for your time, Victoria-NRAS. 🙏

    I've copied & pasted Clare-NRAS reply to post 'Feeling sorry for people here': (for easy reference):

    [Thank you kindly, Clare-NRAS. 🙏 ]




    Hi Andy

    As we discussed when you came to visit NRAS recently we are delighted that you have found a way of managing your RA that appears to work for you but thought it might be helpful for others here on HU to see what we did further to our conversation about this programme that you are advocating.

    RA is a very individual disease and it is not a one size fits all solution therefore everyone must be respectful of each person's way of managing their condition and finding their own solutions to managing symptoms and disease progression. When someone feels passionately that something they have found works for them it is easy to try and advocate it for everyone else but that can be upsetting and distressing for others. I would recommend and encourage that careful consideration is used when posting and that the language used should be positive and encouraging and could not be perceived as judgmental or condescending. I doubt it was ever your intention Andy to cause offense.

    As we promised we did some research to see if there was an robust evidence to support this Clint Paddison’s claims.

    NRAS findings:

    The programme is a commercial product and involves a monthly subscription to follow it.

    NRAS made enquiries with senior people at NICE/RCP (Royal College of Physicians) that we have worked with on the NICE Guideline Review group. The expert response we received was as follows:

    Thank you for passing on the information about the Paddison program.

    At the scoping stage for the update of the NICE rheumatoid arthritis guideline, no new evidence that would alter the existing recommendations relating to dietary modifications were identified. During stakeholder consultation, one stakeholder suggested that there may be some evidence relating to Vitamin D supplementation or Omega 3 and Omega 6 levels. A couple of small studies on Omega 3 and 6 had been identified in the surveillance review that informed the update, but the conclusion was that the sample size of the existing evidence was too small and more large studies were required. No comments were received relating to bacteria / acid secretion / acidosis etc. as referenced in the Paddison program document.

    On review of the references provided, the majority of the studies may be informative epidemiology or background to inform research in the area, and may indicate a possible association between some of these factors. However, many are narrative reviews or comments in journals and are opinions on the area rather than primary research or systematic reviews.

    None of the references included were aiming to assess the effectiveness of the Paddison program itself. In order to be considered within a systematic review to inform on the effectiveness of the programme, a randomised controlled trial of the programme would be required ideally. In the cases of dietary interventions, it may be that the control group does not receive a placebo. Although this would introduce bias to the results, a large well performed study with investigator blinding and objective outcomes reported where possible, would minimise the bias.

    The two references that may contribute to an effectiveness review for a treatment are references 15 and 16 which look at alkaline and potassium supplementation respectively. Unfortunately these are each single references on each of the possible interventions and have relatively small sample sizes. Furthermore the trial on alkaline supplements does not have a placebo in the control group which would mean that this would be considered as high risk of bias. In isolation neither of these studies would be considered enough evidence for alkaline or potassium supplementation.

    I hope this is of some assistance. National Guideline Centre| Care Quality Improvement Department | Royal College of Physicians

    I hope everyone finds this helpful and I wish to reiterate that as a consequence of the above, being an evidence based organisation, NRAS will not be altering our current dietary information.

  • As much as I appreciate, Clare's thoughtful response to another post (& as insightful as it is), unfortunately, it doesn't touch on/ address my query about the 8-minute video. No worries. 🙏


    I was merely interested in your/ NRAS staff's knowledge, experience, insight, wisdom, perspective . . . on the substance/ essence of that video.


    It (the content of the video) seems to make so much sense to me. I merely wondered what your perspective(s) on it was?

    I mean, it sounds like it would dove-tail beautifully with any NRASer's, rheumatologist's, scientist's, medical person's, or layman's way of 'thinking'.

    Simple, step-by-step logic.

    That is, it seems sensical, sensible — nothing 'off the mark' or nonsensical or risky or illogical or remotely impractical . . .

    In short, it sounded to me like a practical points most everyone(?) could agree on? 🤔


    That is, it seems there was nothing said that anyone could find fault with. 🤔 [Merely my simple understanding of the aural words I'd heard — without scrutinising a transcript.]


    I understand this is an additional task for an already busy NRAS staff; already busy with other responsibilities/ duties. No worries. Fully understand. 🙏

    Without a transcript, I guess it could be difficult to share your experience, opinion, insights based on just 8-minutes of aural dialogue.

    I understand/ appreciate great care/ thought must be given before expressing any comments/ opinions — in your positions. 🙏 I respect & appreciate that. 🙏

    Thank you for your time & thoughtful comment, Victoria-NRAS.

    Much appreciated. 🙏 🌺 🍀 🌞


  • Thank you Kai

    If we had the time to look into individual posts/links in this level of detail, or to run by medical advisors etc we would, but sadly with the forum as active as it is, we just don't have the time to look into everything in that level of detail.

    Thank you for your understanding.


  • [Part 1 of 3]


    Methotrexate in Rheumatoid Arthritis:


    Background and mechanism of action

    Methotrexate (MTX) was introduced in 1947. Because it slows down the growth of rapidly dividing cells it was used in high doses to treat people with leukaemia and other forms of cancer. In the early 1950s it was used in much lower doses to treat people with the skin condition psoriasis. Some people who had an inflammatory arthritis associated with their psoriasis noted that their joints improved as well as their skin, as did a few people with rheumatoid arthritis (RA) who were given MTX. However some people with psoriasis developed cirrhosis of the liver after long-term treatment. As a group these people had a very high alcohol intake which was probably a major contributory factor, although recent work suggests that people with psoriasis who receive MTX may be more vulnerable than people with RA to liver damage. As a result of the liver problems MTX was used rarely by rheumatologists for some years.

    Methotrexate began to be used increasingly in RA in the 1980s and clinical trials demonstrated its efficacy in the mid-1980s. Studies have shown that it is generally well-tolerated in comparison with other disease-modifying drugs (DMARDs) used to treat RA. There have been numerous studies of its use since then both used alone (monotherapy) and in combination with other standard DMARDs and biologic drugs, reviewed below. In recent years it has become clear that the earlier in the course of RA that a DMARD is started the better the long-term outcome. MTX is now regarded as the “gold standard” against which conventional DMARDs and the newer biologic drugs are measured, and it is generally agreed that it should be used early in the course of RA in most people with the condition. There is also evidence that its use will reduce the risk of death from cardiovascular disease in people with RA.


    How does it work?

    Methotrexate has numerous effects on processes in the body which could be relevant in RA including interference with folate metabolism and reduction in proliferation of cells. More recently it has been recognised that it can reduce the production of damaging polyamines and increase the production of adenosine which has anti-inflammatory effects. However, it is not possible to pin-point a single effect which explains its effectiveness. At the doses used in RA, i.e. generally between 7.5 and 25mg weekly, it does not have a significant anti-cancer or immunosuppressive effect.

    It is likely that genetic factors influence both the response to MTX and the risk of side-effects. Although progress is being made in identifying these factors, there is at present no reliable way of predicting who will respond well, and who is at increased risk of side-effects.


    How is it taken?

    Methotrexate is usually given once weekly as an oral dose. Practice varies but it is usually started at around 10-15mg weekly and the dose is then increased as necessary by 2.5mg at a time over the next few months. Most people will respond to 10-25mg weekly but some may need 30mg weekly. Occasionally even higher doses are used. In general higher doses are more effective but also more likely to cause side-effects. MTX can be given as a weekly injection when people experience bad nausea with tablets, or if the response is inadequate when taken by mouth.

    MTX depletes the body of folic acid and the frequency of side-effects can be reduced by taking supplements of folic acid. It is usually prescribed at 5-10mg once weekly but sometimes at 5mg every day except that on which MTX is taken. Taking higher doses may reduce the efficacy of MTX and most rheumatologists recommend taking the folic acid one or two days after the MTX, and in particular not taking it on the same day as the MTX.


  • Thanks for the copying & pasting Kai, I sometimes have problems accessing links.🙏

  • Very welcome, trailblazer. 🙏 🌺 (Please don't hesitate to give a scream if having difficulty accessing links. Am happy to copy things over for you. 👍 No worries. 👍 ) Hope you're doing well & in good spirits 👻 👻 . . ☺️ . . 🐣 🐥 🐤

  • Thank you Kai, I'm good thank you. Hope your doing well. I'm just trying to juggle family (my cousin was critically ill in hospital), work, my diet food intolerances (healing my gut) and 'life happens', can get a wee bit hectic at times!

  • Yes indeed, life certainly does happen . . 😳 😁 🙃

    Very sorry to hear about cousin in hospital & having so much to juggle . . . No fun 😔 . Our thoughts 💭 💭 💭 are with you, trailblazer. 🙏


    . . . . 🔮

    . 🔮 . . . . 🔮


    . ¯\_(ツ)_/¯

    . . . . . . . . . . 🔮💥


    All we can do is try not to drop the glass balls. 😯 😳


    Wishing you the very best, dear lady. 🙏 🍀 🌺 🌞


  • Don't know if you'd already stumbled on to this:

    PP Guide for Rheumatologists?

    The PDF file, Low-Fat, Whole-Foods, Plant-Based “Paddison Program” Diet and Lifestyle Approach for Rheumatoid Arthritis: A Guide for Rheumatologists (Version 1.5.6), is at:

    Some of the Guide's content is in 5 segments towards bottom of post: Erika's Rheumatologist Confirms Erika's CCP Reduced (from 144.3 to 27) via Diet — turning_pain_n2_purpose:—-turning_pain_n2_purpose


    [Found it to be nice 'capsulized summary' particularly if your Rheumatologists is curious/ interested in what you're doing. 🤔 👍 ]


    (Hope this helps. 🙏 ☺️ )


  • [Part 2 of 3]




    Comparison with other DMARDs

    A detailed review of clinical trials of DMARDS concluded that MTX was well tolerated compared with the others. MTX was also more effective in reducing symptoms, clinical evidence of active arthritis, disability and joint damage on x-ray when compared with combined results for leflunomide, sulfasalazine, hydroxychloroquine, gold, ciclosporin and azathioprine..


    Use of MTX in combination with other DMARDs

    Over the past 15 years a number of studies have investigated the use of combinations of DMARDs with or without concurrent corticosteroid. MTX is a key component of the most effective combinations which include the triple combination of methotrexate, sulfasalazine (SSZ) and hydroxychloroquine (HCQ). The use of such combinations has been endorsed in the NICE Clinical Guideline and EULAR recommendations on the management of RA. Use of combination DMARD therapy can be particularly helpful when it is not possible to use biologic drugs e.g. in people with recent cancer or chronic infection.


    Effect on x-rays

    Rheumatologists are keen to see that a drug slows down the rate of deterioration in joint damage seen on x-ray, as there is a close correlation between the degree of joint damage and both disability and the need for operations.

    Several studies have shown that MTX is better at slowing x-ray deterioration than placebo or older synthetic DMARDs., However, it does not prevent the progression of joint damage in all people and use of a TNF-inhibitor with MTX is more effective in this regard than MTX alone.


    Use of MTX in combination with biologic drugs

    MTX is classified as a synthetic DMARD i.e. it has a defined chemical structure and is manufactured using conventional chemical processes. By contrast biologic drugs are typically produced in a living system such as animal cells and have a complex protein structure. Several biologic drugs have been licensed for the treatment of RA and approved by NICE for use in the NHS in certain situations. A detailed review of clinical trials concluded that using MTX in conjunction with the biologic drug was generally more effective than giving the biologic drug alone.

    Anti-TNFα drugs are biologic therapies that neutralise the effect of TNFα, a pro-inflammatory agent which plays a major role in causing inflammation in RA. There are now five agents licensed in the UK for the treatment of RA: infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi).

    Rituximab (Mabthera) targets a subset of B cells, reducing their capacity to take part in immune processes which damage the joint.

    Abatacept (Orencia) inhibits activation of T cells and so reduces their ability to participate in damaging inflammatory processes.

    Tocilizumab (RoActemra) blocks the effects of the cytokine IL-6, another pro-inflammatory agent which plays a major role in causing inflammation in RA.


  • [Part 3 of 3]


    Frequently asked questions


    What are the possible side-effects?

    Up to 30% of people experience side-effects which limit the dose of MTX which they can take, and some of them stop treatment as a result. In others the symptoms are an inconvenience but the benefits from taking the drug make it worth continuing. Nausea, loss of appetite, sore mouth and diarrhoea are fairly common (up to 10%). The level of liver enzymes can be checked by a blood test and mildly increased levels are also fairly common (up to 20%). If this increase is more severe the drug will have to be stopped, or the dose reduced. Headaches (up to 10%) and some hair loss (about 3%) can also occur.

    Potentially more serious side-effects such as reduction in the numbers of white blood cells or platelets can also be detected by a blood test. These problems occur in up to 5% of people on MTX. Rarely the drug can induce pneumonitis: inflammation in the lungs (about 1%). People with pre-existing lung disease seem to be at increased risk of this problem. Pneumonitis causes shortness of breath and troublesome cough, and people who develop this should stop the drug and consult their doctor as a matter of urgency.

    MTX is largely removed from the body by the kidney, so its use in people with significantly impaired kidney function is potentially hazardous.

    It is doubtful whether MTX increases the risk of serious infection in the doses typically used to treat people with RA.


    Can you drink alcohol when on treatment with MTX?

    As noted at the beginning of this article, there are concerns that MTX may increase the risk of cirrhosis, particularly in those who drink alcohol to excess. If the levels of liver enzymes are persistently raised MTX is usually stopped. Experience over the past fifteen years is generally re-assuring and there is no convincing evidence that the frequency of cirrhosis in people with RA treated with MTX is greater than in the population at large. However the risk is likely to be greater in people with other risk factors for cirrhosis such as heavy alcohol intake or infection with hepatitis B or C.

    Because of the possibility of an increased risk of liver damage with MTX the safest policy is to avoid alcohol if you are on MTX. Many rheumatologists believe however that it is safe to have up to ten units of alcohol per week i.e. a total of ten glasses of wine or five pints of beer or lager. People on MTX would be very unwise to exceed the maximum limit recommended for the population at large i.e. 14 units for women and 21 for men per week.


    Can methotrexate injure the unborn child?

    Yes, although this is not inevitable and the magnitude of risk cannot be stated reliably. A child conceived by a mother who is taking MTX may be born with deformities and the risk is such that termination of pregnancy has to be considered. It is therefore vital that women on MTX ensure that they use effective contraception. If a woman on MTX decides she would like to have a child, it is recommended that she stops the MTX for a period of at least three months before she tries to conceive, and some authorities recommend waiting six months. There is uncertainty regarding the risk of deformity in children conceived by men taking MTX but the manufacturer recommends that men should use effective contraception for three months after stopping MTX before trying to conceive.

    Women can start taking MTX again once the child is born, but should not breast-feed while on the drug. It may be necessary therefore for a mother to choose whether breast-feeding or re-starting MTX is more important to her at that time.


    Does MTX interact with other drugs?

    The antibiotics trimethoprim and sulphamethoxazole (often combined as co-trimoxazole) also have anti-folate effects (ie they impair the function of folic acid) and should be avoided or used with great caution by people on MTX as there is a risk of severe bone marrow depression leading to serious infection or bleeding.

    There is also increased risk of toxicity if MTX is taken with acitretin (a treatment for severe psoriasis); the epilepsy drug phenytoin, the anti-psychotic drug clozapine and the anti-malarial pyrimethamine.

    When MTX use became widespread there were concerns that non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin might increase the risk of side-effects when taken with MTX. However most people with RA cannot manage without regular NSAIDs as their joint stiffness is not relieved by ordinary painkillers, and further experience in tens of thousands of people with RA treated world-wide suggests that this is very rarely a problem with the doses of MTX used to treat RA.


    Can people on MTX have immunisations?

    It is generally recommended that people on MTX have the flu vaccine annually and are immunised against pneumococcus.

    It is recommended that people on MTX do not receive live vaccines, and should not do so until three months after stopping MTX. Live vaccines include oral polio and typhoid vaccines, measles, mumps, rubella (MMR), varicella (chickenpox/shingles) and yellow fever. BCG immunisation should not be given either. The inactivated polio vaccine (IPV) and killed typhoid vaccine can be given and there is no problem with hepatitis A and B, tetanus, anthrax, cholera, plague or rabies.

    This advice may affect your choice of holiday as some countries insist on evidence of immunisation against yellow fever before a person is allowed to enter their country.


    Further reading

    Immunisation for people with rheumatoid arthritis


    What tests are recommended for people on MTX?

    The British Society for Rheumatology (BSR) recommends that people starting MTX should have a full blood count, kidney and liver function tests and a chest x-ray before starting treatment. Blood count and liver function tests should be checked by blood test every two weeks until six weeks after the last dose increase. Thereafter tests should be done monthly until the disease and dose of methotrexate have been stable for one year when the frequency may be reduced in some cases.


    Further reading

    British Society for Rheumatology methotrexate monitoring guidelines

    Arthritis Research UK (ARUK) methotrexate drug information sheet


    References available on request

    Robin Butler MD FRCP, Consultant Rheumatologist. Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry

    Original article: 01/08/2006

    Reviewed: 09/12/2014

    Next review due: 09/12/2017


  • I'm not sure why it's necessary to c&p the content when both Victoria & yourself gave the link to the NRAS MTX info? Surely it would be preferable to supply us with PP's full content on MTX, that is unless this is the full content, in that case if this is typical of the PP's info on DMARDs etc it's misleading, even duplicitous. I haven't read it in full but I wouldn't think the PP info is full of negatives.

  • Here is another short recent overview of important practical facts about mtx (2013). What is central is the fact that inflammation is what the meds target, just as the alternative treatments. Less inflammation less illness progression and joint damage. There is no silent progression of RA without inflammation which has often been brought up here. The fact that meds may give a wrong picture of the inflammatory situation can be helped by MRI and US exams often enough.

  • Sorry, forgot the link

  • This is clearly a US site with info in this case for RD patients in the US. Nobody here in the UK being treated under the NHS will be considered for biologics after only 3 months on DMARDs as stated in para 5, another DMARD but not an anti-TNF/biologic. The guidelines don't tally between here & the US. Other than that I don't see any benefit in posting this particular info. This from another US site, which I've chosen specifically being info for US patients, is more realistic & accurate factual info I think you'll find

  • The point with the post was more to emphasize the importance of keeping inflammation down, refering here to dietary measures that have had success in many treatments of RA.

  • Thank you kindly, Simba1992. 👍 Much appreciated. 🙏


    This is my (layman's) understanding also:

    "Less inflammation less illness progression and joint damage." ✔️

    "There is no silent progression of RA without inflammation. . . " ✔️


    (Merely my understanding as well. 🙏 )

    [Article noted is cut & paste below for easy reference.]


  • The Facts on Methotrexate for Rheumatoid Arthritis Treatment:


    For people who have more than mild symptoms of rheumatoid arthritis, or RA, methotrexate (Rheumatrex, Trexall) is one of the most commonly prescribed drugs. It's a leader in a class of drugs known as DMARDs – for disease-modifying anti-rheumatic drug – and it works to slow the progression of joint damage from the disease.


    How Methotrexate Helps Ease Inflammation

    Methotrexate works by reducing the function of the cells that are causing inflammation in the joint tissues. "Its use can reduce inflammation and therefore should help relieve pain and protect from joint damage," notes Sean A. Whelton, MD, a rheumatologist and associate professor of medicine at MedStar Georgetown University Hospital in Washington, D.C. Less inflammation in the joints should mean less joint pain and less joint swelling. You should also feel less fatigue and less morning stiffness.

    People with swollen and painful joints whose rheumatoid arthritis has not improved with initial, non-drug therapies will most likely be prescribed methotrexate for RA management. But it may take weeks to several months until the full benefits of methotrexate are noticeable, says Barbara Young, PharmD, MHA, editor of consumer medication information for the American Society of Health-System Pharmacists in Bethesda, Maryland. While you’re waiting for the effects to start, you may be given other medications, such as corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), to help you manage your RA symptoms.

    The goal is to feel more and more improvement over a few months, reaching a level of stabilization after four to six months. But methotrexate doesn’t work for everyone. The drug is a slow but steady process, taking about 5 to 6 weeks to start working, says Dr. Whelton. "I find about half of people will experience relief with methotrexate alone, while the other portion usually adds other medications to treat their RA."

    According to a research review, published in January 2013 in the journal BMC Medicine, that analyzed predictors for methotrexate success, men respond better than women, non-smokers respond better than smokers, and people who take methotrexate as their first DMARD do better than people who have already tried another drug in this category. The review also found that those who take methotrexate in an early and mild stage of RA do better than those who start the drug after they have had RA for a long time. The researchers point out that if doctors can identify who is unlikely to respond to methotrexate, those patients can be spared exposure to a potentially toxic drug.

    If you do not have a significant improvement in joint inflammation and well-being after about three months of RA treatment, your doctor will probably consider adding another drug to your treatment, especially a biologic drug such as etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade). The treatment goal is to achieve early, complete (or near complete) control of joint inflammation so there’s less risk for long-term damage to the joints over the years.


    Dealing With Methotrexate Side Effects

    Because methotrexate affects rapidly dividing cells that line the mouth and stomach, very common side effects such as painful mouth ulcers, nausea, and diarrhea may result. "People on methotrexate may also suffer from fatigue," adds Whelton.

    Call your doctor right away if you have diarrhea, mouth sores, dehydration, bleeding, shortness of breath or cough, any signs of an infection, or a rash.

    Methotrexate can lower your white blood count, which can make you more likely to get an infection. It can also cause hair loss and make you bruise more easily. Some people get headaches and fatigue for a day or two after taking methotrexate, which is usually taken by mouth once a week. "Another dosage schedule for methotrexate oral is to take the weekly dose in divided doses every 12 hours for 2 doses (within 24 hours)," says Dr. Young.

    Because methotrexate can lead to spontaneous abortions, women taking this RA drug should take precautions to prevent pregnancy. Women should also use a contraceptive if their sexual partner is taking methotrexate. "Reliable contraception must be continued for three months after men stop taking methotrexate and for women until after they have had their menstrual cycle return," Young says. "Women must notify their physician immediately if they think that they may be pregnant while they (or their partner) are taking methotrexate."

    To prevent mouth pain, ulcers, and nausea, a low dose of folic acid, a B vitamin, once a day, can be considered. In addition, your doctor will want to do blood work, including a chemistry profile, every month to monitor your white blood count. After a few months of monitoring, you should be able to reduce the frequency of blood tests to once every two to four months. People living with rheumatoid arthritis and kidney disease may be especially susceptible to the side effects of methotrexate and instead may need to take a different medication for RA treatment.


    Long-Term Issues: Possible Liver Problems

    It's important to screen on a regular basis for liver irritation, says Whelton. "While mild liver inflammation is not uncommon, serious liver disease is rare." Blood tests can check for liver problems. If your liver test is abnormal, your doctor may lower your dose of this RA drug or stop it temporarily. Later on, your doctor might start you on methotrexate again at a lower dose.

    Alcohol increases the risk for liver inflammation when taking methotrexate and should be avoided. The combination of alcohol and methotrexatemay lead to liver damage.


  • Thank you Kai! :-}

  • Please note, this is extracted from a US website

    Is Methotrexate Effective For Rheumatoid Arthritis?

    Methotrexate for RA Effectiveness Side effects Takeaway


    1. Methotrexate can be used for long-term treatment.

    2. The drug is less likely than other DMARDs to cause serious side effects.

    3. Methotrexate may work in follow-up treatment even if it didn’t work initially.

    Rheumatoid arthritis (RA) is a chronic autoimmune disorder. If you have this condition, you’re familiar with the swelling and painful joints it causes. These aches and pains aren’t caused by the natural wear and tear that occur with aging. Instead, your immune system mistakes the lining of your joints for foreign invaders and then attacks your body. No one knows for sure why this happens or why some people have this disease.

    There’s currently no cure for RA, but there are ways to treat it. Your doctor might prescribe medications that slow down the progression of the disease or suppress your immune system. They may also give you drugs that reduce inflammation and pain in your joints.

    The current recommendation for initial treatment of RA is with disease-modifying antirheumatic drugs (DMARDs). One of these drugs is methotrexate. Check out how this medication works, including how effective it is in treating RA.


    Treating RA with methotrexate

    Methotrexate is a type of DMARD. DMARDs are a class of medications often used in the early stages of RA. A few drugs in the DMARD class were specifically made for treating RA, but methotrexate was developed for a different reason. It was originally created to treat cancer, but it’s been found to work for RA too. It’s sold under the brand names Rheumatrex and Trexall. It comes as an oral tablet and a solution for injection.

    Methotrexate and other DMARDs work to reduce inflammation. They do this by suppressing your immune system. There are risks linked with keeping your immune system in check this way, though, including an increased risk of infections.

    While methotrexate comes with the chance of side effects, it also offers great benefits for people with RA. DMARDs can prevent joint damage if you use them early enough after your RA symptoms first appear. They can also slow down further joint damage and alleviate symptoms of RA. Most doctors and people with RA think the benefits of this medication are worth the risks.

    Methotrexate is a long-term drug when used for RA. Most people take it until it no longer works for them or until they can no longer tolerate its effects on their immune system.



    Methotrexate is the go-to drug for most doctors treating RA. This is due to how well it works. According to Johns Hopkins, most people take methotrexate for a long time compared to other DMARDs—up to five years. This reflects how effective it is in treating the condition and how well most people tolerate it.

    The numbers show that methotrexate helps most people with RA. According to the National Rheumatoid Arthritis Society, more than half of people taking it see a 50 percent improvement in the course of their disease. And more than one-third of people see a 70 percent improvement. Not everyone will find relief with methotrexate, but it works better for more people than other DMARDs.

    If methotrexate treatment didn’t work for your RA the first time, there’s still hope. A study

    In combination with other drugs

    Methotrexate is often used with other DMARDs or other medications for pain and inflammation. It has shown to be a great partner. Certain combinations of two or more DMARDs—always with methotrexate as one component—work better than methotrexate alone. Keep this in mind if you don’t respond to methotrexate by itself. You can talk to your doctor about a combination therapy.


    Side effects of methotrexate

    Besides the fact that it works for many people, doctors like to use methotrexate because serious side effects are uncommon. But like all medications, methotrexate can cause side effects. Common side effects can include:

    upset stomach


    thinning hair

    You may be able to lower your risk of these side effects if you take a folic acid supplement. Ask your doctor if this supplement is right for you.

    Learn more: * Can folic acid reduce the side effects of methotrexate?

    In rare cases, methotrexate can cause serious side effects. These can include:


    low white blood cell levels (can lead to infections)

    low red blood cell levels (can cause fatigue)

    low platelet levels (can lead to bleeding)

    lung disease

    During treatment with methotrexate, your doctor may check your blood cell counts, liver function, and lung function. If you have serious side effects, your doctor may stop your treatment.

  • Again, from a US website


    Can Folic Acid Help Reduce The Side Effects Of Methotrexate?

    Folate Methotrexate and folic acid Folic acid Interaction Why treat RA? Takeaway


    If you have rheumatoid arthritis (RA), your doctor may have prescribed methotrexate for treatment. According to the American College of Rheumatology, methotrexate is one of the most commonly used drugs to treat RA. However, it can decrease the levels of an important vitamin in your body called folate. This leads to a side effect of methotrexate called folate deficiency. Your doctor may suggest you take a folic acid supplement, which is a man-made form of folate.


    What is folate?

    Folate is a B vitamin that has a role in many important functions in your body. It helps your body make new red blood cells and other healthy cells. It’s also necessary for DNA repair.

    Folate can be found in many different foods. These foods include:

    leafy vegetables such as spinach, broccoli, and lettuce



    certain fruits such as bananas, melons, and lemons

    legumes such as peas, beans, lentils, soybeans, and peanuts


    organ meat such as beef liver and kidney

    orange juice and tomato juice

    Although it’s good for you to get folate by eating a variety of these foods, simply eating more of these foods will not be enough to make up for the folate that you lose from methotrexate.


    Why would my doctor prescribe methotrexate and folic acid together?

    Symptoms Of Folate Deficiency

    Some symptoms caused by folate deficiency include:

    anemia (decreased number of red blood cells)



    stomach pain


    liver problems

    stomatitis (mouth sores)

    Methotrexate interferes with the way your body breaks down folate. When you take methotrexate, you can develop levels of folate that are lower than normal. This is because methotrexate causes your body to get rid of more folate as waste than usual. This effect causes folate deficiency. Your doctor can prescribe the supplement folic acid to help prevent a folate deficiency.


    What is folic acid?

    Folic acid is the man-made form of folate. Taking folic acid can help to make up for, or supplement, the folate that your body loses when you take methotrexate. Folic acid supplements can help decrease the side effects from folate deficiency. They’re available over the counter and cost about as much as other vitamins and supplements.

    These supplements come in a form that you take by mouth. The usual starting dosage is 1 mg per day. Your doctor will determine a dosage of folic acid that’s right for you.

    Learn more: Folate vs. folic acid » **


    Does folic acid affect how methotrexate treats RA?

    Taking folic acid with methotrexate does not decrease methotrexate's effectiveness in treating your rheumatoid arthritis. When you use methotrexate to treat RA, it helps decrease pain and swelling by blocking certain chemicals in your body that lead to inflammation. Methotrexate does block folate, but the way it treats RA seems to be mostly unrelated to blocking folate. Therefore, taking folic acid to make up for the folate you lose from taking methotrexate helps reduce the side effects of folate deficiency without affecting your treatment of RA.


    Why is it important for me to treat RA?

    What Is An Autoimmune Disorder?

    Your immune system usually protects your body by fighting off germs and other substances that invade your body when you are sick. An autoimmune disorder is when your immune system mistakes your body’s tissues for invaders and attacks them.

    RA is an autoimmune disorder. In RA, your immune system specifically attacks the synovium, which is the lining of the membranes that surround your joints. The inflammation from this attack causes the synovium to thicken. If you don’t treat your RA, this thickened synovium can lead to cartilage and bone destruction. The tissues that hold your joints together, called tendons and ligaments, can weaken and stretch. This can cause your joints to lose their shape over time, which can affect how well you can move around. The inflammation associated with RA can damage other parts of the body as well. These include your skin, eyes, lungs, heart and blood vessels. Treating your RA can decrease these effects and improve your quality of life.


    Talk with your doctor

    Many doctors prescribe methotrexate to treat RA. Sometimes this drug leads to folate deficiency, which can cause some bothersome side effects. However, these side effects can often be avoided by taking folic acid. Treating your RA is very important, so making your treatment as easy as possible is important. If your doctor prescribes methotrexate for your RA, talk to them about your risk of folate deficiency and the possibility of using folic acid to prevent side effects.

  • Finally, taken from a US website


    Folate Vs. Folic Acid

    Uses Amounts Deficiency Supplements Takeaway


    When it comes to knowing what important minerals and vitamins you should be getting more of, it’s easy to get confused. In the case of folic acid and folate — terms that are often used interchangeably — you may be surprised to learn just how much these two substances differ.

    Folate is also known as vitamin B-9. It is found naturally in foods. Folic acid is the synthetic form of folate, found in supplements and also added to processed, or “fortified,” foods. The term folate is often used to describe both natural and synthetic versions.


    Why Do You Need Folate?

    Folate is water soluble in any form. This means that it dissolves in water and doesn’t stick around in the body after a portion of what is ingested is absorbed, passing instead through urine. Because of this, you need to continually get folate in your diet to replenish the body’s stores.

    Folate serves a variety of purposes in the body. It helps to keep your cells functioning properly, as well as helping to form your red blood cells and DNA. It can also prevent anemia, heart disease, and birth defects, primarily neural tubal defects.


    How Much Do You Need?

    The recommended daily allowance for folate depends on your age and gender, among other things. The amount generally increases by age, although women of childbearing age have the highest requirement levels.

    Children between 1 and 3 years old should get around 150 mcg per day. This should go up to 200 mcg between the ages of 4 and 8, 300 mcg between the ages of 9 and 13, and 400 mcg from 14 onwards.

    Pregnant and lactating women should up this amount to 600 mcg per day, according to the National Institutes of Health (NIH).


    What Happens When You Have a Deficiency?

    Folate deficiencies are uncommon, according to the NIH. That’s because most people take in enough folate from the foods they eat. People who have a deficiency likely suffer from other issues that prevent their body from absorbing vitamins, like alcoholism or other nutritional deficiencies.

    Signs of a folate deficiency might include:


    soreness or ulcers on the tongue

    changes in your hair or skin pigmentation

    elevated homocysteine levels

    your baby having birth defects


    Should You Take Supplements?

    Most people with a generally healthy diet do not need to take folic acid supplements to help meet their folate requirement. However, because pregnant women need to get upwards of 600 mcg per day, experts recommend they take a prenatal vitamin that includes folic acid.

    For the rest of us, it’s simply a matter of eating more of the right foods.


    Lentils, lima beans, and chickpeas are excellent sources of folate. Chickpeas are the main ingredient in everyone’s favorite dip, hummus. And hummus has plenty of other health benefits, including its high-fiber content, which may help lower your “bad” cholesterol levels.

    Green Veggies

    You can also get your folate fix from asparagus, broccoli, okra, spinach, and asparagus. Mushrooms and enriched foods (like spaghetti, white rice, and bread) are other good sources of folate, which makes this recipe for an asparagus and shiitake mushroom noodle bowl very convenient!


    Which two fruit juices are absolutely brimming with folate? Orange juice and tomato juice. So feel free to enjoy a Bloody Mary (virgin, of course)!


    The Takeaway

    Folate is an essential vitamin that you can only get from your diet. Folic acid is a synthetic version that you can buy as a nutritional supplement. Deficiencies are rare, and most people get enough from the right foods. However, pregnant women might want to make sure they’re getting enough by taking a folic acid supplement.

  • Interesting.

  • Thanks, Isn't it.

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