Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.

Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.

Effects of anthocyanin, astaxanthin, and lutein on eye functions: a randomized, double-blind, placebo-controlled study.

We examined the effects of a test food containing anthocyanin, astaxanthin, and lutein on the eye function in healthy Japanese adults with eye fatigue after operating visual display terminals. Forty-four subjects were randomly but equally assigned to the active or placebo group. Two active or placebo capsules were taken once daily for 6 weeks. Accommodative function, tear film break-up time, visual acuity, the value of Schirmer's test, macular pigment optical density level, muscle hardness, and a questionnaire were evaluated before and after a 6-week intervention. Each group included 20 subjects in the efficacy analysis. The active group showed a significant improvement in the percentage of pupillary response of an average of both eyes and dominant eye pre- and post-visual display terminal operation at 6 weeks compared with the placebo group. Moreover, the active group showed a significant improvement in the scores of "A sensation of trouble in focusing the eyes" and "Difficulty in seeing objects in one's hand and nearby, or fine print" compared with the placebo group between before and after ingestion. Therefore, 6-weeks consumption of the test food inhibited a decrease in the accommodative function caused by visual display terminal operation (UMIN000036989).

Evaluation of the Immunomodulatory and Anti-Inflammatory Activities of Honey Bee Larva Powder.

Honey bee larva powder (HLP) has traditionally been used as a daily supplement and tonic for health promotion with an uncertain scientific basis. In this study, B16-F10 tumor-bearing mice were established to evaluate the immunomodulatory activity of HLP. The proliferation and apoptosis assays were performed to evaluate the anti-inflammatory activity of honey bee larva extract (HLE) in RAW 264.7 macrophage. The in vivo experimental results demonstrated that the oral administration of freeze-dried HLP (4 and 6 g/kg) significantly enhanced the spleen index, the percentage of CD4+cells, and the ratio of CD4+ and CD8+ T lymphocytes (CD4+/CD8+) in the peripheral blood compared with those in the tumor control mice. The in vitro studies demonstrated the potent immunomodulatory activities of HLE through the induction of RAW 264.7 macrophage proliferation and the mitigation of doxorubicin (DOX)-induced toxicity. HLE also exhibits anti-inflammatory activity by decreasing the production of nitric oxide (NO) and the cytokine level of interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage. The present study provides important scientific evidence for the immunomodulatory and anti-inflammatory activities of HLP and HLE.

Anti-tumor and anti-metastasis activities of honey bee larvae powder by suppressing the expression of EZH2.

Honey bee larvae products have been widely used as traditional daily supplements and complementary medicine for health promotion. However, there is little scientific evidence about their bioactivities. This study was designed to examine the anti-tumor and anti-metastasis effects of honey bee larvae powder (HLP) and explore the underlying mechanism. A subcutaneous transplantation model (murine breast cancer cell 4T1-LUC) and lung metastasis model (murine melanoma cell B16-F10) were established to evaluate the anti-tumor and anti-metastasis effects of HLP. Honey bee larvae powder extract (HLE) was obtained by 70% ethanol extraction, and its chemical composition was determined according to physiochemical methods. Cell Counting Kit-8 assay was performed to test the cytotoxicity of HLE, and qRT-PCR assays were conducted to examine the mRNA levels of tumor marker EZH2 in HLE-treated tumor cells. In vivo xenograft tumor assays in BALB/c mice revealed dose-dependent suppression of tumor growth and lung metastasis showing an inhibition rate of 37.5% and 70.4% at 6 g/kg HLP-administered group with no toxicity to the animals. In vitro studies indicated that HLE showed no cytotoxicity to cancer cells at doses up to 1000 µg/mL, however, it significantly decreased EZH2 mRNA levels in HLE (1000 µg/mL)-treated B10-F10 cells (28.49%) and 4T1-LUC cells (26.75%). Further studies to elucidate the mechanisms involved and to isolate the active components of honey bee larva may provide more valuable information for its development and application in cancer treatment.

A phytoestrogen supplement prevents the altered gene expression associated with pregnancy implantation induced by IL-1ß in endometrial epithelial cells.

Phytoestrogens stimulate expression of the uterine estrogen receptor and regulate uterine functions in reproductive tissues. However, comprehensive understanding of the beneficial impacts of phytoestrogens on uterine biology at the molecular level remains unexplored. Interleukin-1ß (IL-1ß) expression is increased in the inflamed decidua and is associated with first trimester pregnancy loss. AglyMax-Sup has the same composition as that of the phytoestrogen supplement AglyMax but with added vitamins and other components. Expression of genes associated with implantation may be enhanced by AglyMax-Sup compared with AglyMax. We tested the hypothesis that AglyMax-Sup has greater effects on implantation compared with AglyMax, using RT-PCR and Western blotting in the endometrial epithelial cell line. Furthermore, we investigated the protective effect of AglyMax-Sup on IL-1ßinduced changes in estrogen-responsive gene expression in endometrial epithelial cells. The purpose of this study was to compare the effects of the phytoestrogen supplement AglyMax-Sup with those of AglyMax on estrogen-responsive gene expression. AglyMax and AglyMax-Sup significantly (p<0.05) induced gene expression of glycodelin-A, HoxA10, IL-11, LIF, MEG-E8 and TGFß1. AglyMax-Sup induced high levels of these genes compared with the levels induced by AglyMax. The enhanced expression of LIF, IL-11, integrin αV, and HOXA10 induced by AglyMax-Sup was abolished by the ER antagonist fulvestrant and the ERK inhibitor PD98059. Meanwhile, IL-1ß inhibited progesterone plus estrogen-induced TGFß1, glycodelin-A, HOXA10, and integrin αV expression. IL-1ß-induced suppression of these expression was reversed by AglyMax-Sup. These results indicate that expression of genes associated with implantation may be increased by AglyMax-Sup compared with AglyMax. AglyMax-Sup might abrogate IL-1ß-mediated changes that can affect embryo implantation via the MAPK pathway.