The ability of green tea to alleviate autoimmune diseases: fact or fiction?

Keywords::

• autoimmune disease
• EGCG
• green tea
• prevention
• treatment

Autoimmune diseases are a major health threat affecting 3–8% of the population in the industrialized world. While the etiology of autoimmune diseases is unclear, genetic, infectious and environmental factors are implicated. Nutrition is viewed as a modifiable environmental factor to potentially prevent and/or alleviate autoimmune diseases. Green tea consumption is suggested to have many health benefits, probably owing to its high content of polyphenols, known as catechins, among which epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active. A limited number of animal studies have demonstrated that green tea/EGCG can, to a varied degree, improve autoimmune diseases. These diseases include, ranking in order of the available information in literature, rheumatoid arthritis, inflammatory bowel disease (IBD), Sjögren’s syndrome and Type 1 diabetes (T1D; sharing the same animal model) and experimental autoimmune encephalomyelitis (EAE, murine model for human multiple sclerosis [MS]). Employing collagen- or adjuvant-induced arthritis rodent models, investigators have observed that administering green tea polyphenols (GTP, mainly EGCG) or EGCG alleviates the disease as demonstrated by reduced disease incidence, severity, pathology, serum autoantibody levels, and production or gene expression of relevant inflammation mediators/markers [1–4]. As with the IBD model, IL-2 knockout mice [5] or dextran sodium sulfate-treated mice [6] fed GTP, along with acetic acid-treated mice fed EGCG [7], or trinitrobenzene sulfonic acid-induced mice receiving peritoneal injection of EGCG [8], showed less severe colitis, improved body weight, and reduced levels of various inflammation mediators/markers in colon and circulation. Sjögren’s syndrome, an autoimmune disease affecting salivary glands, is being studied using nonobese, diabetic (NOD) mice, an animal model used widely for T1D. Green tea supplementation in NOD mice, either as GTP [9] or EGCG [10], was shown to ameliorate Sjögren’s syndrome as indicated by reduced submandibular gland lymphocytic infiltration and serum autoantibody levels, in addition to a delayed onset and reduced incidence of diabetes. In a study using NOD mice as a model for T1D, EGCG delayed the onset of diabetes, but had no effect on insulitis [11]. MS or EAE are well-characterized T-cell-mediated autoimmune diseases. In the only published study, Aktas et al. found that giving EGCG to EAE mice reduced their clinical symptoms, brain pathology and pathological immune responses [12].

Epigallocatechin-3-gallate is T-cell suppressive, particularly with CD4⁺ T cells [13] and is also anti-inflammatory. These EGCG properties coincide with reported beneficial effects of green tea/EGCG on autoimmune diseases. However, the working mechanisms underlying EGCG’s protective role in autoimmune diseases are insufficiently understood. Rapid progress over the past few years has greatly revised our view of the pathogenesis of autoimmune diseases. In particular, the long-standing Th1/Th2 paradigm has been challenged, and the roles of Th17 and regulatory T cells (Treg) are now increasingly emphasized. In a recent study [14], we found that dietary EGCG in EAE mice dose-dependently attenuated the disease’s severity. We also observed suppressed proliferation of autoreactive T cells, reduced production of proinflammatory cytokines, decreased Th1 and Th17 populations, and increased Treg populations in lymph nodes, spleen and the CNS. EGCG-induced shifts in CD4⁺ T-cell subsets in EAE mice are accompanied by corresponding changes in their regulation network. We speculate that this working mechanism of EGCG in EAE may also apply, partly or entirely, to other T-cell-mediated autoimmune diseases.

Since human data are absent, we can only extrapolate from the available animal study results to predict future application in humans. In this context, it is important to know how effective doses determined in animal studies can be once translated to equivalent doses for humans. Doses for animals should clearly not be directly applied to humans without adjustment, because metabolic rates are very different between animals and humans. For example, we found that the effective EGCG dose for inhibiting T-cell response [13] or alleviating EAE [14] is 360 mg/kg bodyweight in mice, which is equivalent to 26 mg/kg bodyweight in humans based on an isocaloric calculation (1820 mg/day for a person of 70 kg). Although it is not feasible to achieve this dose of EGCG by drinking tea since it translates to 2.5 l of tea a day, it should be easy to achieve this dose by consuming purified EGCG capsules (400-mg capsules are available). As shown in a clinical trial, most chronic lymphocytic leukemia patients who received 400–2000 mg of EGCG twice a day for 6 months tolerated these levels of EGCG without significant side effects [15].

Practice recommendations

Based on the positive results from animal model and cell-based studies, EGCG may potentially have a therapeutic value in human autoimmune diseases. Since drinking tea in usual quantities is unlikely to deliver adequate amounts of EGCG to achieve effective levels in the body, ingesting EGCG or enriched GTP supplements is a practical solution. Given the fact that EGCG is relatively safe and already used as a common dietary supplement for an array of health benefits, patients of autoimmune diseases might consider trying EGCG, rather than waiting until its efficacy is proved by future clinical trials. Currently, no upper limit is set on the intake of EGCG, and tolerance varies among individuals, therefore appropriate doses for each individual should be carefully determined, ideally by stepwise dosing while closely monitoring the patient’s reactions. In particular, liver function should be checked regularly as high doses of EGCG have been shown to cause hepatotoxicity in both humans [16] and animals [17]. In addition, taking EGCG with meals is recommended to help reduce its side effects.

Conclusion

While observations from animal studies are strongly suggestive of a therapeutic potential for using green tea EGCG in treating autoimmune diseases, evidence in humans is absent, which indicates a need for future clinical trials for corroboration. At present, allowing patients to take EGCG supplements under close scrutiny seems to be a favored choice by weighing the potential benefit versus harm.

Financial & competing interests disclosure

The authors’ research is supported by USDA National Institute of Food and Agriculture grant 2010-65200-20360, and USDA, Agriculture Research Service contract #58-1950-7-707. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.