Table 1 The effect of nutraceuticals containing TCM on managing diabetes through RCT

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)

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.