Table 1.

Studies and their respective details investigating the hypoglycemic effect of cladode.

Reference	Aim/s	Participants	Intervention/Design	Results
Frati et al. [19]	To assess the effect of Opuntia ficus indica cladode on hyperglycemia in T2DM subjects.	T2DM participants (n = 8; 2 M and 6 F; mean age: 55 years)	Length: Acute (single consumption) Study design: Cross-over trial Treatment: 500 g of cladode given to fasted (12 h) subjects. Cladode prepared as broiled, blended, crude, and heated (60 °C) crude. Measurements: GLU at 40, 60, 120, 180 min following intervention.	Reductions in GLU (p < 0.01) reached at 120 and 180 min. Major hypoglycemic effects shown after cladode consumption ranged from 23.3 ± 4.4 to 25.4 ± 14.3 mg/dL. No difference in the hypoglycemic effects between cladode preparations (all p > 0.05).
Frati et al. [43]	To investigate the effect of Opuntia streptacantha cladode on hyperglycemia in T2DM subjects.	Group 1: T2DM participants (n = 16; 9 M and 7 F; mean age: 43.8 ± 11.4 years) Group 2: T2DM participants (n = 10; 6 M and 4 F; mean age: 46.2 ± 10.8 years) Group 3: T2DM participants (n = 6; 4 M and 2 F; mean age: 48.0 ± 11.7)	Length: Acute (single consumption) Study design: Randomized control-trial Treatment (fasted 12 h): Group 1: 500 g of broiled cladode. Group 2: 400 mL of water. Group 3: 500 g of broiled cladode (test 1), 400 mL of water (test 2), 500 g of broiled squash (zucchini) (test 3) Measurements: GLU at 0, 60, 120, 180 min following intervention.	Group 1: Reduction in GLU (p < 0.001) with mean reduction of 17.6 ± 2.2% of basal value at 180 min. Group 2: No change in GLU (p > 0.05). Group 3: Test 1—reduction in GLU (p < 0.001) with mean reduction of 16.2 ± 1.8% of basal value at 180 min; test 2, 3—no change in GLU (p > 0.05).
Frati et al. [18]	To evaluate the acute hypoglycemic effect of O. streptacantha Lem. intake in “healthy” and diabetic individuals.	Group 1: T2DM participants (n = 14; 9 M and 5 F; mean age: 43 years; age range: 36–65 years). Group 2: “Healthy” participants (n = 14; 9 MJ and 5 F; mean age: 33 years; age range: 15–45 years)	Length: Acute (single consumption) Study design: Randomized control trial Group 1 and 2 treatments: 500 g steamed cladode or 400 mL water (placebo) given to fasted subjects. Measurements: GLU, INS at 0, 60, 120, and 180 min following the intervention.	Group 1: Reduction in GLU (60 min: p < 0.005; 120 min: p < 0.005; 180 min: p < 0.005) reaching 40.8 + 4.6 mg/dL less than basal value. Reduction in INS (120 min: p < 0.005; 180 min: p < 0.005) reaching 7.8 + 1.5 µU/mL less than basal value. Group 2: No change in GLU and INS (p > 0.05).
Frati et al. [20]	To assess the acute hypoglycemic effect of O. streptacantha Lem. intake in “healthy” adults.	“Healthy” participants (n = 16) Group 1: (n = 5) Group 2: (n = 6) Group 3: (n = 5)	Length: Acute (single consumption) Group 1: 12 hr fasted + 100 g of cladode Group 2: OGTT (25 g GLU load), 100 g of cladode given after time 0, before GLU load. Group 3: OGTT (25 GLU load) + 100 g of cladode Measurements: GLU, INS at 0, 30, 60, 120 and 180 min following intervention.	Group 1: Attenuation of GLU at 60 min; 180 min (p < 0.025). No change in INS (p > 0.05). Group 2, 3: No change in GLU, INS (p > 0.05).
Guevara-Cruz et al. [21]	To investigate the effect of dietary patterns, featuring nopal cladode, on biochemical markers (GLU, INS).	MetS participants (n = 67; age: 20–60 years; satisfied 3 positive criteria for MetS).	2 weeks prior to treatment: Participants were put on a reduced energy diet, low saturated fat, and low cholesterol diet (50–60% CH, 15% PRO and 25–35% fat). Treatment: Length: 2 months Study design: Single-center, randomized, placebo-controlled, double-blind, parallel-arm study. Group 1: Controlled dietary pattern Group 2: Placebo Dietary pattern: 100 g of cladode, 4 g of chia seeds, 22 g of oats, 32 g of soybean proteins, 0.02 g of sweetener, and 1 g of flavoring. Placebo: 30 g of calcium caseinate, 30 g of maltodextrin, 0.02 g of sweetener and 1 g of flavoring. Pre/post measurements: GLU, INS.	Group 1: Reductions in GLU AUC (from 388.8 ± 115.2 mg/dL to 351.0 ± 115.2 mg/dL), and in AUC INS (from 26.4 ± 14.4 ng/mL to 17.4 ± 10.4 ng/mL) (p < 0.0001). Group 2: No difference in GLU, INS (p > 0.05).
Linarès et al. [44]	The study aimed to evaluate “NeOpuntia” on blood lipid parameters and MetS, including glycemia	MetS participants (n = 59; 0 M and 59 F; age distribution: 10.29% <35, 27.94% 35 to 45, 41.18% 45 to 55 and 29.59% >55; mean age: 47.3 ± 10.1 years) Group 1: Treatment (n = 35) Group 2: Placebo (n = 33)	Length: 6-weeks Study design: Monocentric, randomized, double-blind, placebo-controlled study Group 1: balanced diet (45% CH, 17% PRO and 38% fats; 2000 kcal), 3 x “NeOpuntia” capsule after meals/day. Group 2: balanced diet (45% CH, 17% PRO and 38% fats; 2000 kcal), 3 x placebo capsule after meals/day. Measurements: GLU at day 1, day 14 and day 42.	Group 1: Treatment group remained at the same GLU level. Group 2: Increase in GLU.
Godard et al. [45]	To assess the acute and hypoglycemic effect of OpunDia™ (O. ficus indica) in obese and pre-diabetic individuals.	Pre-diabetic and obese participants (n = 29; age: 20–50 years) Group 1: Treatment (n = 15) Group 2: Placebo (n = 14)	Length: Acute phase (single consumption) and chronic phase (16-weeks) Acute phase: Group 1: 400 mg bolus of OpunDia™ 30 min before OGGT (75 g GLU load). Group 2: 400 mg of the placebo 30 min before OGGT (75 g GLU load). Pre/post measurements: GLU Chronic phase: Group 1: 16-week supply of 200 mg OpunDia™ Group 2: 16-week supply of the placebo Pre/post measurements: GLU	Acute phase: Reductions in GLU in the treatment compared to placebo at 60 (205.92 ± 36.90 and 188.84 ± 38.43 mg/dL respectively), 90 (184.55 ± 33.67 and 169.74 ± 35.16 mg/dL respectively) and 120 min (159.24 ± 17.85 and 148.89 ± 24.86 mg/dL respectively) (p < 0.05). Chronic phase: No difference in GLU (p > 0.05)
López-Romero et al. [46]	To investiage the effect of nopal in breakfast (2 compositions) upon metabolic markers in T2DM and “healthy” individuals	Study 1: “healthy” participants (n = 4; 3 M and 4 F; mean age: 20.6.3 ± 1.2 years; mean BMI: 23.05 ± 0.8). Study 2: T2DM participants (n = 14; 4 M and 10 F; mean age: 48.0 ± 2.1; mean BMI: 28.9 ± 1.0; glycosylated hemoglobin levels mean: 6.5 ± 0.2%)	Study 1: Length: Acute (single consumption) Group 1 (treatment): 50 g of dehydrated nopal. Group 2 (placebo): 50 g of available carbohydrates from GLU. Study 2: Length: Acute (single consumption) Group 1 (treatment): High CH breakfast (HCB) or high soy-protein breakfast (HSBP) with or without (random) 300 g steam nopal. Group 2 (placebo): HCB or HSBP. HCB: 300 kcal, 89% CH, 6% PRO, 5% fat in apple juice (240 mL), white bread (55.6 g) and strawberry jam (21 g). HSP: 344 kcal, 42.4% CH, 40.7% PRO, 16.9% fat in soy hamburger (61.5 g) and soymilk beverage (230 mL) Pre/post measurements: GLU, Glycemic index, insulinemic index, glucagon-like peptide 1 (GIP-1) index.	Study 1: Glycemic index is 32.5 ± 4.0, insulinemic, Gastric Inhibitory Polypeptide index 6.5 ± 3.0, and GLP-1 index was 25.9 ± 18.0. Study 2: Group 1: Reduction in GLU AUC of HCB + nopal compared to only HCB (287 ± 30 and 443 ± 49 respectively). Reduction in GLU peaks HSPB + nopal at 30 min and 45 min (p < 0.05).

Key: GLU: blood glucose; INS: insulin; AUC: area under the curve; OGGT: oral glucose tolerance test; BMI: body mass index CH: carbohydrate; PRO: protein; M: males; F: females.