A vegan diet is a type of plant-based diet which eliminates any animal-origin food. In contrast, some types of vegetarian diets remove meat and fish but the consumption of milk, dairy products, and eggs were included. Since milk and fish are refrained in vegan and some vegetarian types of diet, it is important to supplement vitamin D in order to ingest adequate amounts of this vitamin which not only is important to help absorb calcium and phosphorus from food but also plays a role in the immune system. Its deficiency can interfere with antibacterial and anti-inflammatory responses of immune system. As such, a lack of vitamin D may play a role in the development of RA [
67] and counteract the benefits of vegetarian diets including vegan. Based on the results of a study conducted on mice with vitamin D receptor (VDR) deficiency, it was found that inflammation increased, leading to a pro-inflammatory monocyte phenotype associated with cartilage damage [
68]. In different studies, it has been revealed that the risk of autoimmune diseases is lower in the vegan diet because there are no animal products consumed. Vegetarian diets contain less arachidonic acid than diets with high or moderate intake of meat, whereas vegan diets contain virtually no arachidonic acid [
69]. Arachidonic acid is an essential fatty acid derived from endogenous and exogenous sources. It contributes in the production of eicosanoids and several of them have pro-inflammatory efficacy. Since it is converted into various mediators, such as prostaglandin E2 (PGE2), which is involved in the development of RA, the consumption of exogenous sources (nutrients of animal origin) should be minimized. It was confirmed by population studies that a high consumption of foods of animal origin in the Western diet is associated with the event of RA [
70]. In this case, it suggests that people with a vegan diet may have a low risk of RA [
71]. As mentioned earlier, fruits and vegetables are high in polyphenols, organic compounds that have been shown to alleviate the inflammation process in diseases such as RA [
36]. It has been reported that oral application of 1 gram of resveratrol co-administered to RA patients with their conventional drug improved the disease induced symptoms by reducing clinical markers (i.e., the 28-joint count for swelling and tenderness) as well as serum levels of certain biochemical markers (i.e., C-reactive protein, TNF-alpha, and IL-6) [
72]. Another polyphenolic compound in legumes is genistein which also has anti-oxidative activity. It has been shown to help to reduce reactive oxygen species in RA patients [
73]. In contrast, increased consumption of nutrients of animal origin and decreased intake of dietary fiber may increase the risk of developing autoimmune disease [
6]. Plant-based diets can reduce the inflammatory response by lowering C-reactive protein levels, alleviating joint inflammation and pain and are also low-fat and fiber-rich diets, which can develop the composition and the variety of intestinal bacteria in patients with RA [
64]. Increased release of pro-inflammatory cytokines such as interleukins (IL-1, IL-6, and TNF-α) can lead to chronic inflammation [
75]. In this regard gut microbiota plays an important role in the physiological and immunological homeostasis. There are approximately 10-100 trillion microorganisms in the human intestine [
76] representing a dynamic microbial ecosystem, with bacteria in the gut varying between 500-1000 different species [
77]. Disruption of gut microbiota homeostasis may be associated with various inflammatory diseases, including RA [
67]. As mentioned earlier, adequate dietary fiber intake may have a positive effect on the microbiota. Fibrous foods in the daily diet are reduced to SCFA by commensal bacteria. Butyrate, a SCFA, decreases intestinal permeability and bacterial translocation, increasing tight junction protein expression which limits local and systemic inflammation [
1,
58]. It is known that patients with RA are at higher risk for cardiovascular disease and have higher plasma oxidized low-density lipoprotein (LDL) levels. There is a positive correlation between the development of RA and total cholesterol levels in females but not in males. The effect of total cholesterol on improvement of subsequent disease in women has been shown to be significant for seropositive as well as seronegative RA [
12]. A study revealed that vegetarians had lower plasma lipids compared to omnivore counterparts, with the lowest levels reported among vegans [
78]. In that study, plasma total cholesterol and LDL cholesterol were 32% and 44% lower among vegans than among omnivores. A higher consumption of nutrients rich in fiber and antioxidants is associated with lower blood cholesterol concentrations [
79]. In contrast, increased animal products in the diet and decreased dietary fiber may increase the risk of developing autoimmune disease [
6]. Research data show that a low-fat vegan diet recovers some RA symptoms, such as pain rating, joint tenderness and swelling. Moreover, a randomized clinical trial showed that a gluten-free vegan diet reduced the level of immunoglobulin G in patients with RA, thereby improving the signs and symptoms of RA [
80]. In studies conducted with RA patients on a vegan or vegetarian diet, a remarkable development in disease symptoms was observed [
27]. Nevertheless, it needs to be stated that nutrients deficiencies may arise depending on the restriction of all foods of animal-origin. Hence it seems important to supervise RA patients on vegan diet and provide the correct intake of critical nutrients (e.g. protein, vitamin D, vitamin B12, omega-3 polyunsaturated fatty acids) to avoid impairment of physiological functions.