A composition for reducing polypharmacy or for preventing or ameliorating a condition, a disease or a disorder, or chronic diseases that cluster in patients (CDCP), wherein the composition comprises one or more non-FDA approved agent selected from a sesquiterpenoid, a sesquiterpene, zerumbone, lactucin, lactuopicrin, 8-deoxylactucin, picriside A, crepidiaside A, jacquinellin, jacquinellin glycoside, chamissonolide, helenalin, alantolactone, dehydrocostus lactone, costunolide, a sesquiterpene sulfate, reduced glutathione, auraptene, ethacrynic acid, curcumin, a curcuminoid, hispolon, dehydroxyhispolon, methoxyhispolon, bisdemethylcurcumin, hispolon methyl ether, hydroxyhispolon, methoxyhispolon methyl ether, a triterpenoid, Betulinic acid, zingerone, reservatrol, vanillin, rosmarinic acid, a methoxyflavone, a sesquiperetene, n-acetylcysteine, trimethylglycine, folinic acid, folic acid, an amino acid, an ATF4 modulator, flavone, a flavonoid, quercetin, a shogaol, 6-shogaol, a gingerol, 6-gingerol, zingerol, kavalactone, sulforaphane, allyl-, butyl- and phenylethyl-isothiocyanate, chlorophyllin, alpha-lipoic acid, allicin, plumbagin, protandim, capsaicin, a capsaicinoid, piperine, asafetida, eugenol, piperlongumine, pellitorine, zingiberine, tBHQ, CDDO-lm, MC-LR, epigallocatechin-3-gallate, a compound found in wasabi, modihydrocapsaicin, cafestol, 16-O-methyl cafestol, xanthohumol, isoxanthuhumolol, 5-O-caffeoylquinic acid, N-methylpyridinium, resveratrol, nootkatone, caffeic acid phenethyl ester, 3-O-Caffeoyl-1-methylquinic acid, silymarin, kahweol, garlic organosulfur compounds, lycopene, carnosol (rosemany), an avicin, oltipraz, CDDO, a neurite outgrowth promoting prostaglandin, vitamin D, a B vitamin, andrographolide, an amino acid, s-allylcysteine, Vitamin A, Vitamin C, Vitamin E, 6 carotene, trans-2-hexenal, cyclopentenone, ajoene, Dihydro-CDDO-trifluoroethyl amide, Hypochlorous acid, Fragrant unsaturated aldehydes, trans-cinnamaldehyde, safranal, 2,4-octadienal, citral, and trans-2,cis-6-nonadienal, 2-OHE, 4-OHE, bucillamine, momordin, momordol, momordicin I, momordicin II, momordicosides, momordicin-28, momordicinin, momordicilin, momordenol, momorcharin, cucurbitacin B, charantin, charantosides, goyaglycosides, α-eleostearic acid, 15,16-dihydroxy-α-eleostearic acid, antirheumatic gold(I) compounds, an avicin, dithiolethione, an approved drug, an OTC drug, and/or a compound, agent or drug extracted from cloves, black pepper, red chili, ginger, garlic, onion, fennel, bay leaves, nutmeg, saffron coriander and cinnamon, cinnamic aldehyde, zingerbene, agoraspirol, amorphine, anhydro-β-rotunol, aromadendrine, azulene, bisabolene, bisabolol, cadalene, cadinene, cadrina-1,4-diene, caryophyllene, cedrene, cedrol, cerapictol, ceratopicanol, clovene, copaene, cubebene, eudalene, eudesmol, farnesene, farnesol, germacrene, guaiazulene, guaiol, gurjunene, hexahydrohumulene, himachalene, hinesol, humulene, junipene, longifolene, lubiminol, khusimone, khusinol, khusimol, nootkatone, santalene, santalol, santanol, santonene, selinene, solavetivone, spatulenol, sterpurine, sulcatine, thujopsene, valerenol, vetispirene, vetivazulene, vetivene, vetiverol, vetivone, viridiflorine, and viridiflorol as well as their derivatives and analogs.