Green Tea
Green tea comes from leaves of the Camellia sinensis plant that have been steamed, pan fried, and dried, as opposed to withering and oxidation for oolong and black teas. Green tea has been used for medicinal purposes in China and Japan for thousands of years1.
Green tea’s main bioactive compound is epigallocatechin gallate (EGCG), a polyphenolic catechin with high antioxidant and anti-inflammatory activity2. EGCG’s protective effect is particularly notable in autoimmune diseases such as MS, as it represses autoimmune cells and generation of pro-inflammatory cytokines3. EGCG is able to pass through the blood-brain barrier4 and to accumulate inside the mitochondria of the neurons5, decreasing the cell destruction usually resulting from the high oxidative stress of the disease6.
EGCG at doses of up to 0.6% of the diet was shown to reduce clinical severity of disease in animal MS models by reducing neuronal damage from neurotoxic free radicals, brain inflammation7, immune cell infiltration, and demyelination, as well as modulating the balance among pro- and anti-autoimmune cells8. Similar results were observed at doses of 300 mcg/day9 and 22.5 mg/kg10.
The combination of EGCG at a dose of 600 mcg/day with the DMT glatiramer acetate (Copaxone®) demonstrated synergistic protective effects in neurons, including increased protection from neuronal cell death from inflammatory chemicals and regeneration of axons. These neuroprotective and neuroregenerative effects were translated in a live animal model of MS, where combination treatment significantly delayed disease onset, strongly reduced clinical severity – even after onset of symptoms – and reduced inflammatory infiltrates11.
A randomized, placebo-controlled clinical study in MS patients found that EGCG 800 mg/day in a base of 60 ml coconut oil was associated with decreased anxiety and improved functional capacity compared to control. The effect of EGCG was believed to be enhanced by the coconut oil due to the latter’s facilitation of ketone production. The ketone β-hydroxybutyrate (BHB) in particular activates receptors expressed by neuroinflammatory cells, reducing neuroinflammation and achieving a neuroprotective effect.
In another placebo-controlled clinical study with RRMS patients, a slightly lower EGCG dose of 600 mg/day (300 mg twice a day) for 12 weeks was shown to improve muscle metabolism during moderate exercise in men. The shift to carbohydrate- from fat-oxidation matched what is known about healthy individuals, and is considered advantageous for combatting the fatigue associated with MS12.
Two other randomized MS studies using EGCG at doses of 800-1200 mg/day – one in RRMS13 and one in PPMS/SPMS14 patients – did not identify treatment advantages for brain atrophy, lesion load, or disability progression.
In an animal safety study, 200 mg of green tea extract was not associated with adverse effects in pregnant rats or their fetuses. However, higher doses of 600 and 1000 mg were associated with significantly decreased body weights in both, with 20-day old offspring showing signs of degeneration in nerve and brain tissues15.
Each cup (8 fluid ounces or 240 ml) of brewed green tea is equivalent to approximately 50-100 mg of green tea extract.
References
1.(NCCIH). NCfCaIH. Green Tea. Health Information Accessed 28 Jan 2022. https://www.nccih.nih.gov/health/green-tea
2.Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol. Dec 15 2011;82(12):1807-21. doi:10.1016/j.bcp.2011.07.093
3.Wu D, Wang J, Pae M, Meydani SN. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases. Mol Aspects Med. Feb 2012;33(1):107-18. doi:10.1016/j.mam.2011.10.001
4.Lin LC, Wang MN, Tseng TY, Sung JS, Tsai TH. Pharmacokinetics of (-)-epigallocatechin-3-gallate in conscious and freely moving rats and its brain regional distribution. J Agric Food Chem. Feb 21 2007;55(4):1517-24. doi:10.1021/jf062816a
5.Schroeder EK, Kelsey NA, Doyle J, et al. Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal. Mar 2009;11(3):469-80. doi:10.1089/ARS.2008.2215
6.Platero JL, Cuerda-Ballester M, Ibanez V, et al. The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients. Nutrients. Jan 23 2020;12(2)doi:10.3390/nu12020305
7.Aktas O, Prozorovski T, Smorodchenko A, et al. Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J Immunol. Nov 1 2004;173(9):5794-800. doi:10.4049/jimmunol.173.9.5794
8.Wang J, Ren Z, Xu Y, Xiao S, Meydani SN, Wu D. Epigallocatechin-3-gallate ameliorates experimental autoimmune encephalomyelitis by altering balance among CD4+ T-cell subsets. Am J Pathol. Jan 2012;180(1):221-34. doi:10.1016/j.ajpath.2011.09.007
9.Sun Q, Zheng Y, Zhang X, et al. Novel immunoregulatory properties of EGCG on reducing inflammation in EAE. Front Biosci (Landmark Ed). Jan 1 2013;18:332-42. doi:10.2741/4104
10.Cai F, Liu S, Lei Y, et al. Epigallocatechin-3 gallate regulates macrophage subtypes and immunometabolism to ameliorate experimental autoimmune encephalomyelitis. Cell Immunol. Oct 2021;368:104421. doi:10.1016/j.cellimm.2021.104421
11.Herges K, Millward JM, Hentschel N, Infante-Duarte C, Aktas O, Zipp F. Neuroprotective effect of combination therapy of glatiramer acetate and epigallocatechin-3-gallate in neuroinflammation. PLoS One. 2011;6(10):e25456. doi:10.1371/journal.pone.0025456
12.Mahler A, Steiniger J, Bock M, et al. Metabolic response to epigallocatechin-3-gallate in relapsing-remitting multiple sclerosis: a randomized clinical trial. Am J Clin Nutr. Mar 2015;101(3):487-95. doi:10.3945/ajcn.113.075309
13.Bellmann-Strobl J, Paul F, Wuerfel J, et al. Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis: A Randomized, Placebo-Controlled Trial. Neurol Neuroimmunol Neuroinflamm. May 2021;8(3)doi:10.1212/NXI.0000000000000981
14.Rust R, Chien C, Scheel M, et al. Epigallocatechin Gallate in Progressive MS: A Randomized, Placebo-Controlled Trial. Neurol Neuroimmunol Neuroinflamm. May 2021;8(3)doi:10.1212/NXI.0000000000000964
15.El-Borm HT, Abd El-Gaber AS. Effect of prenatal exposure of green tea extract on the developing central nervous system of rat fetuses; histological, immune-histochemical and ultrastructural studies. Saudi J Biol Sci. Aug 2021;28(8):4704-4716. doi:10.1016/j.sjbs.2021.04.084