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The brain is particularly susceptible to oxidative stress due to its high oxygen demand, abundance of high-redox-active metals (such as iron and copper), and vulnerability of polyunsaturated fatty acids to oxidative damage, while the number of antioxidant factors is relatively limited [174, 175]

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While early data suggested modestly elevated colorectal cancer risk, more recent controlled studies show that when IGF-1 levels are normalized, cancer mortality aligns with baseline population rates

Furthermore, glutamate concentrations are reduced in frontal areas in experimental and clinical pain (Thompson and Neugebauer, 2019), and a frontal glutamatergic dysfunction has been implicated in depression as well (Moriguchi et al., 2019)