Effect of oral intake of royal jelly on endothelium function in hemodialysis patients: study protocol for multicenter, double-blind, randomized control trial

Abstract

Background Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed. Methods This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety. Discussion This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples. Trial registration The Japan Registry of Clinical Trials jRCTs071200031. Registered on 7 December 2020.

Exploring the Therapeutic Potential of Royal Jelly in Metabolic Disorders and Gastrointestinal Diseases

“…At the clinical level, a randomized, placebo-controlled study demonstrated that a daily intake of RJ tablets (690 mg) for four weeks significantly improved the vascular endothelial activity of the participants' blood vessels, suggesting that RJ may exert antiatherogenic activity [106]. Another clinical study reported that the treatment of renal failure patients suffering from cardiovascular disease with a daily dosage of RJ (3600 mg) for a year considerably attenuated the progression of atherosclerosis in hemodialysis patients [15]. Figure 5 illustrates the mechanism of the antihypertensive activity of RJ.…”

“…Royal jelly (RJ) is a "rich source of nutrients" that nurse bees produce and feed to worker larvae and queen bees. RJ supplementation is beneficial for a variety of disorders, including diabetes [11,12], gastrointestinal diseases [13,14], and cardiovascular diseases [15,16]. The active ingredients of RJ, including its proteins, carbohydrates, and fats, as well as its minerals, amino acids, vitamins, enzymes, hormones, and polyphenols, are what provide its biological properties [17].…”