The in vivo effects of N-acetyl cysteine (NAC), S-allyl cysteine, S-ethyl cysteine (SEC), S-methyl cysteine (SMC), and S-propyl cysteine (SPC) against hyperlipidemia development and oxidation stress in Balb/cA mice consuming a high saturated fat diet were examined. The influence of these agents on plasma levels of glucose, insulin, uric acid, TG, cholesterol, and the activity of three lipogenic enzymes--glucose-6-phosphate dehydrogenase, malic enzyme, and FA synthase--was determined. All mice consumed the coconut oil-basd, high saturated fat diet, water, and cysteine or one of the five cysteine-containing compounds for 4 wk. The diet with 18% saturated fat significantly elevated the activity of three lipogenic enzymes and significantly increased TG and cholesterol biosynthesis in plasma and liver (P < 0.05). When compared with the water and cysteine groups, the treatments from five cysteine-containing agents significantly reduced high saturated fat diet-increased malic enzyme and FA synthase activities, and significantly lowered TG levels in plasma and liver (P< 0.05); however, only NAC, SAC, and SMC treatments significantly reduced cholesterol levels in plasma and liver (P < 0.05). The five cysteine-containing agents significantly restored high saturated fat diet-decreased glutathione peroxidase (GPX) activity in liver (P< 0.05); however, only SMC and SPC significantly restored GPX activity in heart and kidney (P< 0.05). These agents also significantly improved high saturated fat diet-related hyperglycemia, hyperuricemia, and oxidation stress (P < 0.05). These data support the hypothesis that these compounds are potential multiply-protective agents for hyperlipidemia prevention or therapy.