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Too much estrogen being metabolized through CYP1B1 into 4-OHE1(E2) and the estrogen quinones can potentially be bad if your body has slower phase II (COMT, GSTP1, GSTM1, NQO1) enzymes.[ref][ref] The connection between smoking and estrogen-related cancers: Smoking significantly increases the risk of breast cancer and prostate cancer

Ishida J, et al

Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

Without enough selenium, your body cannot turn the "spent" oxidized version back into the active "reduced" version