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While it is known that B-vitamin supplementation effectively treats hyperhomocysteinemia, there is a need for well-designed, large trials to evaluate the effect of B-vitamin supplementation on long-term outcomes, such as age-related cognitive decline and the incidence of Alzheimers disease

Upon binding to an uncharged tRNA, GCN2 undergoes a conformational change and is activated, resulting in inhibitory phosphorylation of eukaryotic translation initiation factor 2 (eIF2), preventing translation initiation under amino acid deficiency (Figure 1) (Berlanga et al., 1999