The inability to properly digest proteins would also lead to the same lack of vitamin B12, high homocysteine, white matter lesions, dysregulated VEGF, and increased risk cancer in RA as we saw in patients with MS.
In the following study researchers found a high incidence of anemia and low vitamin B12 in not only RA patients, but in psoriatic arthritis and lupus as well. The researchers concluded that the incidences of anemia and decreased vitamin B12 levels were high in these three groups of patients.
Anemia, serum vitamin B12, and folic acid in patients with rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus.
Segal, R., Y. Baumoehl, O. Elkayam, D. Levartovsky, I. Litinsky, D. Paran, I. Wigler, B. Habot , A. Leibovitz, B.A. Sela, D. Caspi. 2004. Rheumatol Int. 2004 Jan;24(1):14-9. Epub 2003 Apr 29.
“Although anemia is frequent in inflammatory rheumatic diseases, data regarding vitamin B12 status is scarce. The purpose of this study was to analyze the incidence and nature of B12 and folic acid (FA) deficiencies in a cohort of rheumatic patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE)…The incidence of anemia was high: 49%, 46%, and 35%, in RA, SLE, and PsA, respectively. Low levels of serum B12 were also frequent (24%), with almost similar occurrence in the three disease groups…The incidences of anemia and decreased serum B12 levels were high in these three groups of rheumatic patients…”
In the following study the researchers stated that elevated homocysteine levels occur commonly in patients with rheumatoid arthritis.
Abnormal homocysteine metabolism in rheumatoid arthritis.
Roubenoff, R., P. Dellaripa, M.R. Nadeau, L.W. Abad, B.A. Muldoon, J. Selhub, I.H. Rosenberg IH. 1997. Arthritis Rheum. 40(4):718-22.
“…Elevated tHcy levels occur commonly in patients with RA, and may explain some of the increased cardiovascular mortality seen in such patients. Studies of the prevalence and mechanism of hyperhomocysteinemia in RA are warranted.”
In the following study the researchers concluded that the presence of white matter lesions was assoicated with homocysteine in patients with RA.
The role of homocysteine as a significant risk factor for white matter lesions in Japanese women with rheumatoid arthritis.
Futoshi Anana,Takayuki Masakib, Hiroshi Tatsukawac, Shuji Naganoc, Motohiro Oribed, Nobuoki Eshimae, Tetsunori Saikawaf, Hironobu Yoshimatsuba
Plasma total homocysteine (tHcy), which increases with diabetes, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of WML correlates with tHcy in rheumatoid arthritis patients. Based on brain magnetic resonance imaging findings, 65 rheumatoid arthritis patients were divided into 2 groups: WML-positive group (61 ± 6 years, mean ± SD; n = 25) and WML-negative group (60 ± 7 years, n = 40). The level of metabolic parameters was assessed by total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and homocysteine (tHcy). The duration of rheumatoid arthritis was longer in the WML-positive group than in the WML-negative group (P < .05). Plasma levels of triglyceride was higher whereas high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < .05 and P < .01, respectively). Fasting plasma glucose (P < .05) and tHcy (<.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the tHcy (odds ratio, 1.35; 95% confidence interval, 1.12-1.63; P < .0001). Our findings indicate that the presence of WML was associated with the tHcy in Japanese patients with rheumatoid arthritis.
Elevated homocysteine would lead to the same increased risk of cardiovascular disease in RA and association with COPD as we saw in MS.
In a study published in Arthritis and Rheumatism researchers found there was a 50% increased risk of death from ischemic heart disease and stroke in rheumatoid arthritis patients compared to the general population (Avina-Zubieta, 2008).
An additional study published in the Journal of Internal Medicine looked at the risk of ischemic heart disease associated with rheumatoid arthritis and concluded, “The risk of having a heart attack is 60% higher just a year after a patient has been diagnosed with rheumatoid arthritis…” (Wiley-Blackwell, 2010).
A study presented at the EULAR (European League Against Rheumatism) 2011 Annual Congress has confirmed the link between rheumatoid arthritis and COPD. An article discussing this study published in News-Medical stated, “Patients with rheumatoid arthritis are two times more likely to have COPD than healthy controls. The study, of 15,766 patients with RA and 15,340 controls, found that the prevalence of COPD was significantly higher in RA patients than healthy controls. Interestingly, the link was still significant after risk factors common in both RA and COPD patients, such as smoking, obesity and socioeconomic status, were controlled for” (News- Medical, 2011).
RA patients also have a greatly increased risk of developing lymphoma and other types of cancer, due to dysregulated VEGF.
An article from Arthritis Today discusses the link between RA and lymphoma (Flanigan, 2013): “In an investigation, published in Arthritis & Rheumatism, Swedish researchers mined a national registry of nearly 75,000 RA patients and analyzed medical records and case histories of a subset of 378 RA patients who had developed lymphoma between 1964 and 1995 and 378 lymphoma-free patients. They found a dramatic association between lymphoma and disease activity, which is determined by currently swollen or tender joints, increased levels of inflammatory markers and X-ray evidence of erosion in at least one joint.
Compared with patients with low RA activity, those with medium disease activity showed an eight-fold increase in the likelihood of developing lymphoma. For those with high activity, the probability took a staggering 70-fold jump…”
In the following study researchers discussed the connection between RA, angiogenesis, and VEGF. The researchers stated, “the potent pro-angiogenic cytokine vascular endothelial growth factor (VEGF) has been demonstrated to have a central involvement in the angiogenic process in RA.”
The role of the angiogenic molecule VEGF in the pathogenesis of rheumatoid arthritis.
Afuwape, A.O., S. Kiriakidis S, E.M. Paleolog. 2002. Histol Histopathol. 17(3):961-72.
“The expansion of the synovial lining of joints in rheumatoid arthritis (RA), and the subsequent invasion by the pannus of underlying cartilage and bone, necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. New blood vessel formation - ‘angiogenesis’ - is now recognised as a key event in the formation and maintenance of the pannus in RA. Although many pro-angiogenic factors have been demonstrated to be expressed in RA synovium, the potent pro-angiogenic cytokine vascular endothelial growth factor (VEGF) has been demonstrated to have a central involvement in the angiogenic process in RA. The additional activity of VEGF as a vascular permeability factor may also increase oedema and hence joint swelling in RA. Several studies, including those from the Kennedy Institute of Rheumatology Division, have shown that targeting angiogenesis in animal models of arthritis ameliorates disease…”
I thought this was interesting, Gilyena (FTY720) works, in part, by inhibiting VEGF-induced vascular permeability.
J Biol Chem. 2003 Nov 21;278(47):47281-90. Epub 2003 Sep 3.
Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability.
Sanchez T, Estrada-Hernandez T, Paik JH, Wu MT, Venkataraman K, Brinkmann V, Claffey K, Hla T.
"...Furthermore, oral FTY720 administration in mice potently blocked VEGF-induced vascular permeability in vivo. These findings suggest that FTY720 or its analogs may find utility in the therapeutic regulation of vascular permeability, an important process in angiogenesis, inflammation, and pathological conditions such as sepsis, hypoxia, and solid tumor growth."