Table 1.

The effect of nutraceuticals containing TCM on managing diabetes through RCT

Chinese medicine	First author	Country	Design	Other ingredients	Relevant inclusion criteria	Subjects	Interventions	Relevant outcomes	Results
Cinnamon	Akilen et al. [37]	UK	Prospective, double-blind, placebo-controlled RCT	Starch powder	T2DMs, age ≥ 18 years, two consecutive FBG ≥ 7.0 mmol/L, HbA1c ≥ 7%, oral hypoglycaemic agents	n 58 (F = 33 and M = 25) Age = 54.43 (SD 12.53) years (placebo), 54.90 (SD 10.14) years (cinnamon)	Duration = 12 weeks Placebo or 2 g (500 mg × 4) cinnamon powder daily	Primary = FBG and HbA1c	There was a significant reduction in FBG compared to baseline in the cinnamon group but the changes were not significant when compared to placebo group (P = 0.318, changes = 14.0 (SD 33.0) mg/dL), the mean HbA1c was significantly decreased (P < 0.005*, changes = 0.36 (SD 0.90)  %) in the cinnamon group compared with placebo group
	Sharma et al. [38]	India	Prospective, double-blind, placebo-controlled RCT	N/A	Age ≥ 30 years, FBG level between 140–400 mg/dL, standard diet and exercise for 1 month	n 58 (F = 56 and M = 94)	Duration = 3 months Two arms: (1) 3 g/day dose of cinnamon as a 1 g capsule (2) 6 g/day of cinnamon as a 2 g capsules	Primary = FBG and HbA1c	There was a significant reduction in FBG (3 g P < 0.001*, 6 g P < 0.01*) and HbA1c (3 g P < 0.005*, 6 g P < 0.001*) level in both groups
	Mirfeizi et al. [39]	Italy	Multicenter stratified, triple‐blind, placebo-controlled RCT	Caucasian whortleberry (Vaccinium arctostapphylos L.), starch	T2DMs, HbA1c > 7% and FBG ≥ 140 mg/dL despite the oral blood glucose-lowering agents	n 102 (F = 79 and M = 23) Age = 55 (SD 10) years (placebo), 52 (SD 13) years (cinnamon), 55 (SD 10) years (whortleberry)	Duration = 3 months Placebo or (1) cinnamon supplements of 1 g/day, (2) whortleberry supplements of 1 g/day	Primary = FBG, PBG and HbA1c Secondary = Fasting insulin and HOMA-IR scores	There was a significant decrease in FBG (cinnamon P < 0.006*, whortleberry P < 0.002*), PBG (cinnamon P < 0.003*, whortleberry P < 0.001*) and HbA1c (cinnamon P < 0.010*, whortleberry P < 0.007*) level in both groups, Fasting insulin and HOMA-IR also showed a significant effect (P < 0.05*)
Cinnamon	Gupta Jain et al. [40]	India	Parallel, triple-blind, placebo-controlled RCT	Wheat flour	Metabolic syndrome, stable	n 116 (F = 52 and M = 64) Age = 45.1 (SD 8.4) years (placebo), 44.3 (SD 7.2) years (cinnamon group)	Duration = 16 weeks Placebo group (wheat flour, 2.5g/day) or the cinnamon intervention group (3 g/day)	Primary = FBG, PBG and HbA1c	Significantly greater decrease in FBG (P = 0.001*), and HbA1c (P = 0.011*) in the cinnamon group, but no significant effect in PBG (P = 0.055)
Curcuminoids	Na et al. [18]	China	Double-blind, placebo-controlled RCT	Demethoxy-curcumin, bisdemethoxycurcumin, sesquiterpene ketones and alcohols	Overweight/obese with T2Ds, BMI ≥ 24.0 kg/m2, FBG ≥ 7.0 mmol/L or PBG ≥ 11.1 mmol/L, current optimal therapeutic regimens lasting at least 6 months	n 100 (F = 50 and M = 50) Age = 54.72 (SD 8.34) years (placebo), 55.42 (SD 6.40) years (curcuminoids)	Duration = 3 months Placebo or a 150mg curcuminoids capsule twice daily, 30 min after breakfast and supper, respectively	Primary = FBG and HbA1c Secondary = HOMA-IR	Curcuminoids supplementation has a significantly decreased in FBG (P< 0.01*), HbA1c (P = 0.031*) and insulin resistance index (P< 0.01*) in both groups.
	Panahi et al. [41]	Iran	Double-blind, placebo-controlled RCT	Piperine, demethoxycurcumin, bisdemethoxycurcumin	Not originally receiving lipid-lowering therapy, diagnosis of MetS	n 100 (F = 50 and M = 50) Age = 43.46 (SD 9.70) years (placebo), 44.80 (SD 8.67) years (complex group)	Duration = 8 weeks Placebo or daily dose of 1g (500 mg b.i.d.) of C3 Complex (5mg piperine added to each 500mg curcumin capsule)	Primary = FBG and HbA1c	Curcuminoids supplementation caused a significant reduction of FBG (P < 0.001*) and in serum levels of HbA1c (P = 0.048*)
Ginger	Mozaffari-Khosravi et al. [19]	Iran	Double-blind, placebo-controlled RCT	N/A	T2DMs for at least 10 years, FBG < 180 mg/dL and 2 h-blood-sugar < 250 mg/dl, BMI < 40 kg/m2, no consumption of any supplements during 2 months	n 81 (F = 50 and M = 31) Age = 51.05 (SD 7.70) years (placebo), 49.83 (SD 7.23) years (ginger)	Duration = 8 weeks Placebo or daily 3 1-g capsules containing ginger powder	Primary = FBG and HbA1c Secondary = QUICKI index	A significant decrease of FBG in the ginger in comparison with the placebo (P = 0.003, changes = − 18.17 (SD 35.82) mg/dL), in line with the variation in mean HbA1c [P = 0.02*, changes = − 0.4 (SD 1.2)%] and improvement of QUICKI index (P < 0.005*, changes = 0.02 (SD 0.01) mg/dL)
	Attari et al. [42]	Iran	Double-blind, placebo-controlled RCT	N/A	Obese women aged 18–45 years, BMI of 30–40 kg/m2	n 70 (F) Age = 34.54 (SD 7.91) years (placebo), 35.25 (SD 7.30) years (ginger)	Duration = 12 weeks Placebo or 2 g ginger powder as 1 g tablets/day	Primary = FBG	Ginger supplementation significantly reduced serum glucose as compared to the baseline both in the placebo and ginger group (P < 0.0001*, changes = − 7.51 (SD 9.69) mg/dL)
Propolis	El-Sharkawy et al. [43]	Egypt	Parallel masked, RCT	N/A	T2DMs for at least 5 years, stable doses of oral hypoglycemic drugs and/or insulin for at least 6 months, Chronic Periodontitis	n 50 (F = 17 and M = 33) Age = 51.2 (SD 6.5) years (placebo), 48.9 (SD 8.3) years (propolis)	Duration = 6 months Placebo or Propolis 400 mg capsule daily, both groups with SRP	Primary = FBG and HbA1c	There were statistically significant changes in FBG (P < 0.01*) and HbA1c levels after 3 and 6 months of therapy compared with the placebo group
	Samadi et al. [44]	Iran	Double-blind, placebo-controlled RCT	N/A	5–10 years history of T2DMs, using the conventional therapy of oral medications	n 57 (F = 28 and M = 29) Age = 56.07 (SD 9.02) years (placebo), 51.30 (SD 6.57) years (propolis)	Duration = 12 weeks Placebo or propolis pills 300 mg	Primary = FBG and HbA1c Secondary = fasting insulin, insulin sensitivity, HOMA-IR, QUICKI index	Significantly decreased in the mean of FBG (P = 0.001*, changes = − 17.76 (SD 27.72) mg/dL), HbA1c (P = 0.004*, changes = − 0.77 (SD 1.34)%), fasting insulin, insulin sensitivity, HOMA-IR, QUICKI and β-cell function (all P < 0.05*) between the two groups
Silybum marianum (L.)	Gargari et al. [45]	Iran	Parallel, placebo-controlled, triple-blind RCT	N/A	Aged 25–50 years, diabetes at least 6 months, taking hypo glycaemic medications, BMI of 27–35 kg/m2, stable habitual diet for past 3 months	n 40 (F = 20 and M = 20) Age = 46.10 (SD 4.30) years (placebo), 43.50 (SD 5.76) years (silymarin supplement)	Duration = 45 days Placebo or 140 mg silymarin supplement three times daily with main meals	Primary = FBG	Silymarin supplement showed a significant influence in FBG (P < 0.003*, changes = − 17.8 (− 28.77, − 7.02) mg/dL)
	Ebrahimpour-koujan et al. [46]	Iran	Phase II-III, parallel, placebo-controlled, triple-blind RCT	N/A	Aged 25–50 years, diabetes at least 6 months, taking hypo glycaemic medications, BMI of 27–35 kg/m2, stable habitual diet for past 3 months	n 40 (F = 20 and M = 20) Age = 46.10 (SD 4.30) years (placebo), 43.50 (SD 5.76) years (silymarin supplement)	Duration = 45 days Placebo or 140 mg silymarin supplement three times daily with main meals	Primary = FBG Secondary = fasting insulin, HOMA-IR and QUICKI index	There was a significant reduction in the levels of fasting insulin, HOMA-IR and QUICKI index compared to the placebo group (all P < 0.05*)
Aloe vera	Zarrintan et al. [47]	Iran	Double-blind, placebo-controlled RCT	N/A	Aged 30–65 years, T2DMs for at least 6 months, taking only glucose-lowering drugs not using insulin	n 43 (F = 19 and M = 25)	Duration = 2 months Placebo or 1000 mg of Aloe vera supplements daily	Primary = FBG and HbA1c	No significant effect in the levels of the FBG and HbA1c
Andrographis paniculate	Widjajakusuma et al. [48]	Indonesia	Parallel, double-blind, placebo-controlled RCT	Syzygium polyanthum, maltodextrin	Aged ≥  30 years, T2DMs, taking no other medicines, on any other hypoglycemic treatment for minimum 2 weeks before the study	n 54 (F = 32 and M = 22) Age = 55.25 (SD 10.04) years (placebo), 53.74 (SD 9.25) years (EM tablets)	Duration = 8 weeks Placebo or 450 mg EM tablets, 500 mg Met tablets (all group), twcie a day	Primary = FBG, PBG and HbA1c	There was a significant decrease in FBG (4 weeks P < 0.043*) and PBG (4 weeks P = 0.002*, 8 weeks P = 0.017*) in the extract supplementation group, but no significant effect in HbA1c level for 4 weeks (P = 0.715)
Cornus mas L.	Soltani et al. [49]	Iran	Double-blind, placebo-controlled RCT	Tribasic calcium phosphate powder	Aged 18–80 years, T2DMs for at least 2 years, HbA1C > 7% and < 10%	n 60 (F = 21 and M = 39) Age = 49.93 (SD 6.12) years (placebo), 49.16 (SD 5.62) years (Cornus mas)	Duration = 6 weeks Placebo or Cornus mas extract capsules, 2 capsules twice daily, 150 mg anthocyanins each capsule	Primary = FBG and HbA1c Secondary = fasting insulin	No statistically significant in FBG (P = 0.130, changes = − 14.63 (SD 36.87) mg/dL) compared to the placebo group, but significant increase in insulin level as well as decrease in HbA1c
Daidzein	Ye et al. [50]	China	Double-blind, placebo-controlled RCT	Isoflavones	Aged 30–70 years, FBG of 5.6 − 7.0 mmol/L, a 2-h PG of 7.8 − 11.0 mmol/L, newly diagnosed diabetes	n 151 (F) Age = 56.3 (SD 11.1) years (placebo), 56.4 (SD 9.9) years (Daidzein), 57.0 (SD 9.68) years (Genistein)	Duration = 24 weeks Placebo or (1) 50 mg of Daidzein, or (2) 50 mg of Genistein daily, and daily dose 10 g of soy protein isolated for all group	Primary = FBG, PBG and HbA1c Secondary = fasting insulin, postprandial insulin, HOMA-IR and QUICKI index	No significant difference in all outcomes among 3 groups at baseline, 12 weeks and 24 weeks in IGR women without any drug treatment (all P > 0.05)
Flaxseed	Javidi et al. [51]	Iran	RCT	N/A	BMI of 25–34.9 kg/m2, fasting serum glucose of 100–125 mg/dl, not use of insulin and other glucose lowering medications or herbal supplements for at least 3 months before the study	n 92 (F = 52 and M = 40) Age = 50.55 (SD 11.54) years (placebo), 52.93 (SD 8.9) years (20 g), 52.15 (SD 9.15) years (40 g)	Duration = 12 weeks Placebo or (1) 20 g flaxseed powder daily, or (2) 40 g flaxseed powder daily	Primary = FBG Secondary = fasting insulin and HOMA-IR index	There was a significant reduction in FBG (20 g P = 0.002*, changes = 8.63 (13.74) mg/dL, 40 g P = 0.001*, changes = 10.30 (SD 16.22) mg/dL)) in all groups, HOMA-IR (P = 0.033*, changes = 0.27 (SD 0.65)%) in 20 g group compared to the baseline, but no significant in fasting insulin (all P > 0.05) between the 3 groups
Garlic	Atkin et al. [52]	UK	Double-blind, placebo-controlled crossover pilot RCT	N/A	T2DMs, aged 18–70 years, not treated with insulin	n 26 (F = 9 and M = 17) Age = 61 (SD 8) years	Duration = 12 weeks Placebo or aged Garlic extract (kyolic), 4 capsules/day (1200 mg) for 4 weeks, then a 4 weeks washout period and entered the crossover arm	Secondary = HOMA-IR index	No significant effect in HOMA-IR in all groups compared to the baseline and placebo group
Glycyrrhiza Glabra L.	Alizadeh et al. [53]	Iran	Double-blind, placebo-controlled RCT	N/A	Aged 30–60 years, BMI > 25 kg/m2	n 64 (F = 37 and M = 27) Age = 33.6 (SD 4.8) years (placebo), 36.0 (SD 11.9) years (supplement)	Duration = 8 weeks Placebo or Licorice. 1.5 g daily, a low-calorie diet for both group	Primary = FBG Secondary = fasting insulin and HOMA-IR index	No changes in FBG in all groups compared to the baseline and placebo (P > 0.05), but the levels of insulin (P = 0.02*) and HOMA-IR (P < 0.01*) showed significant effect compared to the baseline
Ginkgo biloba extract	Aziz et al. [54]	Malaysia	Double-blind, placebo-controlled RCT	N/A	Aged 25–65 years, T2DMs for at least 1 year, with glycemic status uncontrolled by Met therapy alone	n 47 (F = 39 and M = 8) Age = 48.2 (SD 10.3) years (placebo), 48.7 (SD 9.6) years (GKB)	Duration = 90 days Placebo or GKB extract, 120 mg/capsule, in addition to usual Met dose (placebo = 1.24 (SD 0.67) g/day, GKB = 1.36 (SD 0.45) g/day	Primary = FBG and HbA1c Secondary = fasting insulin and HOMA-IR index	The FBG level was significantly lower than baseline values (P < 0.001*), and GKB extract also significantly decreased in the fasting insulin and HOMA-IR (all P < 0.05)

Chinese medicine	First author	Country	Design	Other ingredient	Design	Relevant inclusion criteria	Subjects	Interventions	Relevant outcomes	Results
Morus alba	Trimarco et al. [55]	Italy	Monocentric, double-blind, cross-over, placebo-controlled RCT	Berberine, red yeast rice powder	Monocentric, double-blind, cross-over, placebo-controlled RCT	Aged 18–70 years, hypercholesterolemia not requiring statins or in statin intolerant	n 23 Age = 59.5 (SD 6.3) years	Duration = 8 weeks Two randomized: (1) Combination A (placebo) for 4 weeks followed by 4 weeks of Combination B (Morus alba), (2) Exchange squence	Primary = FBG and HbA1c Secondary = fasting insulin and HOMA-IR index	There was a significant reduction for FBG (P < 0.0001*), only after treatment with the Combination B, as well as HbA1c (P < 0.002*), insulin (P < 0.006*) and HOMA-IR index (P < 0.006*)
Nigella sative	Heshmati et al. [56]	Canada	Double-blind, placebo-controlled RCT	N/A	Double-blind, placebo-controlled RCT	Aged 30–60 years, T2DMs for at least 6 months, taking anti-diabetic medications	n 72 Age = 47.5 (SD 8.0) years (placebo), 45.3 (SD 6.5) years (NS oil)	Duration = 12 weeks Placebo or NS oil capsules 3 g/day, three times a day	Primary = FBG and HbA1c Secondary = fasting insulin and HOMA-IR index	FBG changed significantly in the intervention group compared to baseline, but HbA1c, insulin and HOMA-IR changed significantly in intervention group compared to the placebo group after 12 weeks intervention
Psyllium	Abutair et al. [57]	Palestine	RCT	N/A	RCT	Aged > 35 years, newly identified T2DMs patients (maximum 1 year)	n 40 (F = 20 and M = 20)	Duration = 8 weeks Both groups remain regular diet, and intervention group provided with 10.5 g of psyllium soluble fiber daily	Primary = FBG and HbA1c Secondary = fasting insulin and HOMA-IR index	There was a significant effect in FBG level in the intervention group compared to the placebo group, as well as the level of HbA1c, insulin and HOMA-IR (all P < 0.001*)
Red ginseng	Oh et al. [58]	Korea	Double-blind, placebo-controlled RCT	N/A	Double-blind, placebo-controlled RCT	Aged 20–75 years, FBG of 5.6–7.8 mmol/l with at least two follow-up measurements	n 42 (F = 14 and M = 28) Age = 53.5 (SD 1.9) years (placebo), 53.2 (SD 1.8) years (red ginseng)	Duration = 4 weeks Placebo or three fermented red ginseng (FRG) capsules/day with 2.7 g/day	Primary = FBG, PBG and HbA1c Secondary = fasting and postprandial insulin	FBG level was reduced by FRG (P = 0.039*), but did not show a treatment effect when compared to the placebo. No differences in fasting insulin were found, but FRG led to a significant effect in PBG (P = 0.008*) and postprandial insulin (P = 0.040*) levels compared to the placebo.