Rheumatoid arthritis may be triggered by autoimmune friendly fire against a urinary tract infection bacteria called Proteus mirabilis, which could help explain why sufferers randomized to a plant-based diet experience such remarkable benefit.
Why Do Plant-Based Diets Help Rheumatoid Arthritis?
Rheumatoid arthritis is a chronic systemic autoimmune disease affecting millions, characterized by persistent pain and stiffness, and progressive joint destruction—particularly in the hands and feet, leading to crippling deformities. What can we do to prevent it and treat it?
In a famous 13-month long randomized controlled trial of plant-based diets for rheumatoid arthritis, patients were put on a vegan diet for three and a half months, and then switched to an egg-free lactovegetarian diet for the remainder of the study. Compared to the control group, who didn’t change their diet at all, the plant-based group had a significant improvement in morning stiffness within the first month, cutting the number of hours they suffered from joint stiffness in half. Pain dropped from five out of ten down to less than three out of ten. A drop in disability; they reported subjectively feeling better, significant improvement in their grip strength, fewer tender joints, less tenderness per joint, and less swelling, with the added benefit of losing about 13 pounds and keeping most of that weight off throughout the year. They also had a drop in inflammatory markers in their blood, sed rate, C-reactive protein, and white count. The question is why. What does diet have to do with inflammatory joint disease?
Well, rheumatoid arthritis is an autoimmune disease in which your body attacks the lining of your own joints. Why would it do that? Well, there’s a different autoimmune disease called rheumatic fever, in which your body attacks your own heart. Again, why would your body do that? It appears to be a matter of friendly fire.
Rheumatic fever is caused by strep throat, which is caused by a bacteria that has a protein that looks an awful lot like a protein in our heart. So when our immune system attacks the strep bacteria, it also attacks our heart valves, triggering an autoimmune attack by “molecular mimicry.” The protein on the strep bacteria is mimicking a protein in our heart, so our body gets confused and attacks both. That’s why it’s critical to treat strep throat early to prevent our heart from getting caught in the crossfire.
So researchers thought maybe rheumatoid arthritis might be triggered by an infection as well. A clue to where to start looking was the fact that women seem to get rheumatoid arthritis three times more frequently than men. What type of infection do women get more than men? Urinary tract infections, so researchers started testing the urine of rheumatoid arthritis sufferers, and lo and behold found this bacteria called Proteus mirabilis. Not enough to cause symptoms of a UTI, but enough to trigger an immune response. And indeed, there’s a molecule in the bacteria that looks an awful lot like one of our own molecules in our joints, so anti-Proteus antibodies against the bacteria may inadvertently damage our own joint tissues, leading eventually to the joint destruction. Therefore, therapeutic interventions aimed at the removal of this bacteria from the bodies of patients, with consequent reduction of antibodies against the organism, should lead to a decrease in inflammation.
Well, as we saw before, urinary tract infections originate from the fecal flora; the bugs crawl up from the rectum into the bladder. And so, how might one change the bugs in one’s colon? By changing our diet. Some of the first studies over 20 years ago on trying to fundamentally shift people’s gut flora were done using raw vegan diets, figuring that’s about as fundamental a shift from the standard Western diet as there is. And indeed, within days one could significantly change someone’s gut flora. And you put rheumatoid arthritis sufferers on that kind of diet, and they experienced relief, and the greater improvements were linked to greater changes in their gut flora. But the diet was considered so intolerable that half the patients couldn’t take it and dropped out–perhaps because they were trying to feed people things like buckwheat-beetroot cutlets buttered with a spread made out of almonds and fermented cucumber juice.
Thankfully, regular vegetarian and vegan diets work too, changing the intestinal flora and improving rheumatoid arthritis, but we didn’t specifically have confirmation that plant-based diets brought down anti-Proteus antibodies, until now. Those who responded to the plant-based diet showed a significant drop in anti-Proteus mirabilis antibodies compared to the control group. Maybe it just dropped immune responses across the board? No, antibody levels against other bugs remained the same, so the assumption is that the veg diet reduced urinary or gut levels of the bug.
A shift from an omnivorous to a vegetarian diet has a profound influence on the composition of the urine–for example, higher levels of lignans in the urine of those eating vegetarian. Up until now, it was just thought that lignans protected people eating more plant-based from getting cancer, but now we know lignans can also have antimicrobial properties as well, so may be helping to clear Proteus from the system. Either way, this suggests a new type of therapy for the management of rheumatoid arthritis. This new treatment includes anti-Proteus measures such as dietary manipulations in the forms of vegetarian diet.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- J Kjeldsen-Kragh. Rheumatoid arthritis treated with vegetarian diets. Am J Clin Nutr. 1999 Sep;70(3 Suppl):594S-600S.
- R Peltonen, WH Ling, O Hänninen, E Eerola. An uncooked vegan diet shifts the profile of human fecal microflora: computerized analysis of direct stool sample gas-liquid chromatography profiles of bacterial cellular fatty acids. Appl Environ Microbiol. 1992 Nov;58(11):3660-6.
- J Kjeldsen-Kragh, T Rashid, A Dybwad, M Sioud, M Haugen, O Førre, A Ebringer. Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet. Ann Rheum Dis. 1995 Mar;54(3):221-4.
- A Ebringer, T Rashid. Rheumatoid arthritis is caused by a Proteus urinary tract infection. APMIS. 2014 May;122(5):363-8.
- A Ebringer, T Rashid. Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper. Front Biosci (Elite Ed). 2009 Jun 1;1:577-86.
- MT Nenonen, TA Helve, AL Rauma, OO Hänninen. Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. Br J Rheumatol. 1998 Mar;37(3):274-81.
- R Peltonen, M Nenonen, T Helve, O Hänninen, P Toivanen, E Eerola. Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet. Br J Rheumatol. 1997 Jan;36(1):64-8.
- R Peltonen, J Kjeldsen-Kragh, M Haugen, J Tuominen, P Toivanen, O Førre, E Eerola. Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet. Br J Rheumatol. 1994 Jul;33(7):638-43.
- C Wilson, H Tiwana, A Ebringer. Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity. Microbes Infect. 2000 Oct;2(12):1489-96.
- A Ebringer, T Rashid. Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection. Clin Dev Immunol. 2006 Mar;13(1):41-8.
- A Ebringer, T Rashid. Rheumatoid arthritis is linked to Proteus--the evidence. Clin Rheumatol. 2007 Jul;26(7):1036-43.
- H Adlercreutz, T Fotsis, C Bannwart, K Wähälä, T Mäkelä, G Brunow, T Hase. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem. 1986 Nov;25(5B):791-7.
- BW Senior, GA Anderson, KD Morley, MA Kerr. Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy controls. J Infect. 1999 Mar;38(2):99-106.
- L Guilherme, J Kalil. Rheumatic fever: from sore throat to autoimmune heart lesions. Int Arch Allergy Immunol. 2004 May;134(1):56-64.
- L Guilherme, J Kalil, M Cunningham. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006 Feb;39(1):31-9.
- G Furneri, LG Mantovani, A Belisari, M Mosca, M Cristiani, S Bellelli, PA Cortesi, G Turchetti. Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis. Clin Exp Rheumatol. 2012 Jul-Aug;30(4 Suppl 73):S72-84.
- M Saleem, HJ Kim, MS Ali, YS Lee. An update on bioactive plant lignans. Nat Prod Rep. 2005 Dec;22(6):696-716.
Images thanks to Pacific Northwest National Laboratory via Flickr.
Rheumatoid arthritis is a chronic systemic autoimmune disease affecting millions, characterized by persistent pain and stiffness, and progressive joint destruction—particularly in the hands and feet, leading to crippling deformities. What can we do to prevent it and treat it?
In a famous 13-month long randomized controlled trial of plant-based diets for rheumatoid arthritis, patients were put on a vegan diet for three and a half months, and then switched to an egg-free lactovegetarian diet for the remainder of the study. Compared to the control group, who didn’t change their diet at all, the plant-based group had a significant improvement in morning stiffness within the first month, cutting the number of hours they suffered from joint stiffness in half. Pain dropped from five out of ten down to less than three out of ten. A drop in disability; they reported subjectively feeling better, significant improvement in their grip strength, fewer tender joints, less tenderness per joint, and less swelling, with the added benefit of losing about 13 pounds and keeping most of that weight off throughout the year. They also had a drop in inflammatory markers in their blood, sed rate, C-reactive protein, and white count. The question is why. What does diet have to do with inflammatory joint disease?
Well, rheumatoid arthritis is an autoimmune disease in which your body attacks the lining of your own joints. Why would it do that? Well, there’s a different autoimmune disease called rheumatic fever, in which your body attacks your own heart. Again, why would your body do that? It appears to be a matter of friendly fire.
Rheumatic fever is caused by strep throat, which is caused by a bacteria that has a protein that looks an awful lot like a protein in our heart. So when our immune system attacks the strep bacteria, it also attacks our heart valves, triggering an autoimmune attack by “molecular mimicry.” The protein on the strep bacteria is mimicking a protein in our heart, so our body gets confused and attacks both. That’s why it’s critical to treat strep throat early to prevent our heart from getting caught in the crossfire.
So researchers thought maybe rheumatoid arthritis might be triggered by an infection as well. A clue to where to start looking was the fact that women seem to get rheumatoid arthritis three times more frequently than men. What type of infection do women get more than men? Urinary tract infections, so researchers started testing the urine of rheumatoid arthritis sufferers, and lo and behold found this bacteria called Proteus mirabilis. Not enough to cause symptoms of a UTI, but enough to trigger an immune response. And indeed, there’s a molecule in the bacteria that looks an awful lot like one of our own molecules in our joints, so anti-Proteus antibodies against the bacteria may inadvertently damage our own joint tissues, leading eventually to the joint destruction. Therefore, therapeutic interventions aimed at the removal of this bacteria from the bodies of patients, with consequent reduction of antibodies against the organism, should lead to a decrease in inflammation.
Well, as we saw before, urinary tract infections originate from the fecal flora; the bugs crawl up from the rectum into the bladder. And so, how might one change the bugs in one’s colon? By changing our diet. Some of the first studies over 20 years ago on trying to fundamentally shift people’s gut flora were done using raw vegan diets, figuring that’s about as fundamental a shift from the standard Western diet as there is. And indeed, within days one could significantly change someone’s gut flora. And you put rheumatoid arthritis sufferers on that kind of diet, and they experienced relief, and the greater improvements were linked to greater changes in their gut flora. But the diet was considered so intolerable that half the patients couldn’t take it and dropped out–perhaps because they were trying to feed people things like buckwheat-beetroot cutlets buttered with a spread made out of almonds and fermented cucumber juice.
Thankfully, regular vegetarian and vegan diets work too, changing the intestinal flora and improving rheumatoid arthritis, but we didn’t specifically have confirmation that plant-based diets brought down anti-Proteus antibodies, until now. Those who responded to the plant-based diet showed a significant drop in anti-Proteus mirabilis antibodies compared to the control group. Maybe it just dropped immune responses across the board? No, antibody levels against other bugs remained the same, so the assumption is that the veg diet reduced urinary or gut levels of the bug.
A shift from an omnivorous to a vegetarian diet has a profound influence on the composition of the urine–for example, higher levels of lignans in the urine of those eating vegetarian. Up until now, it was just thought that lignans protected people eating more plant-based from getting cancer, but now we know lignans can also have antimicrobial properties as well, so may be helping to clear Proteus from the system. Either way, this suggests a new type of therapy for the management of rheumatoid arthritis. This new treatment includes anti-Proteus measures such as dietary manipulations in the forms of vegetarian diet.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- J Kjeldsen-Kragh. Rheumatoid arthritis treated with vegetarian diets. Am J Clin Nutr. 1999 Sep;70(3 Suppl):594S-600S.
- R Peltonen, WH Ling, O Hänninen, E Eerola. An uncooked vegan diet shifts the profile of human fecal microflora: computerized analysis of direct stool sample gas-liquid chromatography profiles of bacterial cellular fatty acids. Appl Environ Microbiol. 1992 Nov;58(11):3660-6.
- J Kjeldsen-Kragh, T Rashid, A Dybwad, M Sioud, M Haugen, O Førre, A Ebringer. Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet. Ann Rheum Dis. 1995 Mar;54(3):221-4.
- A Ebringer, T Rashid. Rheumatoid arthritis is caused by a Proteus urinary tract infection. APMIS. 2014 May;122(5):363-8.
- A Ebringer, T Rashid. Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper. Front Biosci (Elite Ed). 2009 Jun 1;1:577-86.
- MT Nenonen, TA Helve, AL Rauma, OO Hänninen. Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. Br J Rheumatol. 1998 Mar;37(3):274-81.
- R Peltonen, M Nenonen, T Helve, O Hänninen, P Toivanen, E Eerola. Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet. Br J Rheumatol. 1997 Jan;36(1):64-8.
- R Peltonen, J Kjeldsen-Kragh, M Haugen, J Tuominen, P Toivanen, O Førre, E Eerola. Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet. Br J Rheumatol. 1994 Jul;33(7):638-43.
- C Wilson, H Tiwana, A Ebringer. Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity. Microbes Infect. 2000 Oct;2(12):1489-96.
- A Ebringer, T Rashid. Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection. Clin Dev Immunol. 2006 Mar;13(1):41-8.
- A Ebringer, T Rashid. Rheumatoid arthritis is linked to Proteus--the evidence. Clin Rheumatol. 2007 Jul;26(7):1036-43.
- H Adlercreutz, T Fotsis, C Bannwart, K Wähälä, T Mäkelä, G Brunow, T Hase. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem. 1986 Nov;25(5B):791-7.
- BW Senior, GA Anderson, KD Morley, MA Kerr. Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy controls. J Infect. 1999 Mar;38(2):99-106.
- L Guilherme, J Kalil. Rheumatic fever: from sore throat to autoimmune heart lesions. Int Arch Allergy Immunol. 2004 May;134(1):56-64.
- L Guilherme, J Kalil, M Cunningham. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006 Feb;39(1):31-9.
- G Furneri, LG Mantovani, A Belisari, M Mosca, M Cristiani, S Bellelli, PA Cortesi, G Turchetti. Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis. Clin Exp Rheumatol. 2012 Jul-Aug;30(4 Suppl 73):S72-84.
- M Saleem, HJ Kim, MS Ali, YS Lee. An update on bioactive plant lignans. Nat Prod Rep. 2005 Dec;22(6):696-716.
Images thanks to Pacific Northwest National Laboratory via Flickr.
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Why Do Plant-Based Diets Help Rheumatoid Arthritis?
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Content URLDoctor's Note
I have to admit I had never even heard of Proteus mirabilis. That’s why I love doing this work—I learn as much as you do!
I explored another unconventional theory as to why plant-based diets are so successful in treating inflammatory arthritis in Potassium and Autoimmune Disease.
There’s another foodborne bacteria implicated in human disease, the EXPEC in chicken leading to urinary tract infections—another game-changer: Avoiding Chicken To Avoid Bladder Infections.
This reminds me of the Neu5Gc story (The Inflammatory Meat Molecule Neu5Gc), that mystery pig brain disease (Eating Outside Our Kingdom) and the crazy tick bite meat allergies thing (Alpha Gal and the Lone Star Tick).
Lots more videos coming up on the role our gut flora play in health and disease—stay tuned!
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