Effectiveness of royal jelly supplementation in glycemic regulation: A systematic review

Table 3 Animal and in vitro trials examining effects of long-term royal jelly treatment

Ref.	Study design	Subjects	Treatment	Outcome measures	Effectiveness
Ghanbari et al[14]	Randomized controlled trial	N = 8 healthy male Wistar rats aged 10-12 wk (control)	100 mg/kg BW royal jelly dissolved in 1 mL of water daily for 6 wk	Hyperinsulinemia: ELISA test on plasma sample	Treatment significantly improved insulin levels (d = 1.67) and hyperglycemic fasting blood glucose (d = -2.72) levels to levels similar to healthy control group
		N = 8 diabetic male Wistar rats aged 10-12 wk		Hyperglycemia: Fasting plasma glucose
		N = 8 healthy male Wistar rats aged 10-12 wk receiving treatment
		N = 8 diabetic male Wistar rats aged 10-12 wk receiving treatment
Fujii et al[32]	Controlled trial	N = 80 male streptozotocin-diabetic rats aged 5 wk equally split into three experimental groups and one control group	Each experimental group had one of 1, 10, and 100 mg/kg body weight royal jelly administered orally by force for 4 wk. Control group received purified water	Hyperglycemia: Blood glucose (unknown whether fasting)	Royal jelly administration overall slightly decreased blood glucose levels in non-dose dependent manner (no information on statistical significance)
				Body weight	No significant change in body weight between groups
Membrez et al[33]	Randomized controlled trial	N = 15 male db/db mice aged 6-8 wk in control group	1 g/kg body weight of sebacic acid was added to chow food in one experimental group, and 10 g/kg body weight SA to second experimental group’s chow for 6 wk	Hyperglycemia: OGTT and fasting (plasma samples)	In more heavily supplemented group: Hyperglycemia significantly improved (d = -1.86) and improved glucose clearance (d = -3.20), HbA1c significantly decreased (d = -1.89), ketone bodies significantly increased (d = 1.16), dose response relationship observed, gluconeogenic and lipogenic enzyme expression significantly decreased (insufficient information for SMD estimation), food intake was significantly decreased (d = -1.82).
		N = 30 male db/db mice aged 6-8 wk equally split in two experimental groups		HbA1c: Plasma samples
				Liver gene expression: RNA extracted from liver samples
				Food intake: Chow consumed
Takikawa et al[7]	In vitro	L6 myotubes grown in cell culture and collected from healthy male mice 7 wk of age	Cell cultured myotubes treated with 10H2DA	Glucose clearance: GLUT4 translocation to plasma membrane	Significantly improved GLUT4 translocation to plasma membrane in skeletal muscle cells compared to non-treated myotube cells (d = 0.4698)
			Mice fed 1.6 mmol/kg 10H2DA
Yoneshiro et al[34]	Controlled trial	N = 8 3-wk old healthy male mice (control)	High fat diet with 5% lyophilized royal jelly powder for 17 wk	Body weight gain	Body weight gain due to white adipose tissue significantly reduced compared to HFD group (d = -2.82)
		N = 11 3-wk old healthy male mice fed HFD		Hyperlipidemia: Plasma sample	Significantly decreased levels of NEFA compared to HFD (d = -1.6072)
		N = 11 3-wk old healthy male mice fed high fat diet with treatment		Hyperglycemia: Plasma sample	Significantly improved hyperglycemia compared to HFD group (d = -2.04)
				Insulin resistance: HOMA-IR	HOMA-IR significantly decreased compared to HFD group, not significantly different from control group (d = -1.23)
Zamami et al[15]	Controlled trial	N = 6 6-wk old healthy male Wistar rats (control, received water)	Two experimental groups: One fed 100 mg/kg and the other 300 mg/kg of dilute enzymatically treated royal jelly supplementation daily for 8 wk	Insulin resistance: HOMA-IR	High fructose diet induced insulin resistance in rats
		N = 5 6-wk old healthy male Wistar rats as vehicle-treated group (received high fructose consumption)		Food intake	Plasma insulin levels and HOMA-IR similar between healthy control group and fructose drinking rats supplemented with 300 mg/kg royal jelly. Dose dependent relationship observed d = -0.7063 (effect size of 300 mg/kg royal jelly on fructose drinking rats)
		N = 6 + 6 6-wk old healthy male Wistar rats (received high fructose consumption) in two treatment groups		Body weight	No significant difference in body weight and FBG between groups
				Plasma triglycerides	Plasma triglycerides significantly decreased compared to control dose-dependently (d = -1.62)
Watadani et al[35]	Controlled trial	N = 7 female KK-Ay mice 5 wk of age in control group	3 mg/kg 10H2DA for 4 wk	Hyperglycemia: Plasma glucose samples collected in intervals after OGTT	Significantly improved glucose clearance (d = -1.33) and fasting blood glucose (d = -1.23)
		N = 8 female KK-Ay mice 5 wk of age in treatment group		Body weight: Adiposity index of abdominal, mesenteric and retroperitoneal fat tissue	Body weight did not differ between groups
				Insulin resistance: HOMA-IR	Significantly improved insulin sensitivity (d = -4.44)
				Glucose regulatory proteins: AMPK, G6Pase, Pck1 levels, GLUT4, GS/GSK in tissue homogenates	Significantly increased levels of G6Pase (d = 1.22) and Pck1(d = 0.77) mRNA in liver cells. Significantly increased levels of pAMPK in muscle (d = 3.13), but no change in liver. Insignificant increase in GLUT4 in muscle cells. No change in GS/GSK levels between groups
Yoshida et al[36]	Controlled trial	16 female KK-Ay mice split into control and experimental groups	10 mg/kg royal jelly in 1/15M phosphate buffer 5 d/wk for 4 wk		Significantly improved rates of glucose clearance (d = -1.25)
					Insignificantly decreased body weight
					Significantly increased pAMPK levels in liver (d = 2.39) and skeletal muscle (d = 1.73). Significantly decreased G6Pase mRNA levels in liver (d = -1.65), but no change in Pck mRNA levels. Insignificantly increased GLUT4 levels in skeletal muscle
					Significantly decreased plasma NEFA (d = -1.42). No change in plasma TG
					No significant change in plasma insulin

GLUT4: Glucose transporter type-4; 10H2DA: 10-hydroxydecanonic acid; OGTT: Oral glucose tolerance test; HOMA-IR: Homeostatic model assessment of insulin resistance; GS(K): Glycogen synthase (kinase); AMPK: AMP-dependent kinase; NEFA: Non-esterified fatty acids; HFD: High fat diet.