Emerging evidence supports that sleep disorders are the main risk factor for sporadic Alzheimer's disease (AD), and iron dysregulation may be the link between them. Our previous studies have confirmed that ketogenic diet (KD) can prevent chronic sleep deprivation-induced AD. However, it is uncertain whether exogenous ketones supplements (EKS), as an alternative intervention, have the same effects as KD. Thus, we investigated the prophylactic efficiency of EKS on chronic sleep deprivation-induced AD and reveal the underlying mechanism focus on iron metabolism. We observed that the prophylactic efficacy of EKS against chronic sleep deprivation-induced AD was comparable to that of KD. Meanwhile, our results suggest that both EKS and KD inhibited iron metabolism disorder through regulation of iron metabolism-related proteins. Moreover, we found that both EKS and KD reduced hippocampal mitochondrial dysfunction and iron-mediated lipid peroxides. Furthermore, EX527 (Sirt1 inhibitor), mostly abrogated these above protections of EKS, suggesting that the prophylactic effect of EKS on AD is partly dependent on Sirt1. Our findings provide novel evidence that EKS can be developed as functional foods to prevent or delay the development of AD, particularly in individuals with sleep disorders.

Krill oil (KO) exhibits various biological activities, such as anti-inflammatory and antitumor effects. However, the inhibitory effects of benign prostatic hyperplasia (BPH) in vitro and in vivo have not yet been studied. This study investigated the anti-BPH effects of KO extracted by an enzymatic hydrolysis method. KO treatment inhibited the proliferation of WMPY-1 and BPH-1 cells by induction of G₀/G₁ phase arrest through the modulation of positive and negative regulators in both prostate cell types. KO treatment stimulated phosphorylation of JNK and p38 signaling. In addition, KO changed the expression of BPH-related markers (5α-reductase, androgen receptor, FGF, Bcl-2, and Bax) and the activity of the proliferation-mediated NF-κB binding motif. KO-induced levels of proliferation-mediated molecules of prostate cells were attenuated in the presence of siRNA-specific p-38 (si-p38) and JNK (si-JNK). Furthermore, the administration of KO alleviated prostate size and weight and the cell layer thickness of prostate glands in a testosterone enanthate-induced BPH rat model. KO treatment altered the level of dihydrotestosterone in serum and the expression levels of BPH-related markers in prostate tissues. Finally, KO-mediated inhibition of prostatic growth was validated by histological analysis. These results suggest that KO has an inhibitory effect on BPH in prostate cells in vitro and in vivo. Thus, KO might be a potential prophylactic or therapeutic agent for patients with BPH.