. 2023 Sep 13;82(9):1292–1307. doi: 10.1093/nutrit/nuad116

Table 2.

Summary of clinical studies with citrus fruits

Reference	Type of study	Type of citrus	Doses and duration	Participants	Key results
Kegele et al (2019)²⁷	RCT	C. sinensis	First group (n = 35): 0.5 g of extract Second group (n = 35): 1 g of extract Third group (n = 36): placebo for 3 mo	Male and female adults with abdominal fat >20% of body weight	Muscle mass increased by 0.58% in the 0.5 g group and 7.81% in the 1 g group. Fat mass decreased by 0.64% in the 0.5 g group and by 11.89% in the 1 g group.
Li et al (2020)²⁸	RCT	C. sinensis	First group (n = 8): 200 mL of red orange juice Second group (n = 8): placebo twice/d for 2 wk	n = 16 healthy men and premenopausal women aged 20–45 y with BMI >25 kg/m²	There was no significant change in HDL, LDL, TG, TC, and BP levels compared with baseline.
Cardile et al (2015)²⁹	RCT	C. sinensis	First group (n = 30): Moro orange juice extract Second group (n = 30): nothing for 12 wk	n = 60 healthy people with a BMI between 25 and 35 kg/m²	Body weight^, BMI^, WC^, and HC^ values decreased in the supplement group. No change was found in the control group.
Niv et al (2012)³⁰	RCT	C. sinensis	First group (n = 29): 500 mL of fresh pasteurized orange juice Second group (n = 19): 500 mL levan-containing orange juice per day for 2 mo	n = 48 healthy people (aged 18–60 y)	There was no significant change in body weight, HDL, LDL, TG, TC, and BP values in both groups.
Azzini et al (2017)³¹	Cross-sectional Study	C. sinensis	Volunteers were given red orange juice 500 mL/d for 12 wk.	n = 20 women with a mean age of 36 ± (standard deviation) 7 y and a mean BMI of 34.4 ± 4.8 kg/m².	There was no significant change in body weight, HDL, LDL, TG, TC, BP, WC, and HC values at the end of 12 wk.
Briskey et al (2022)³²	RCT	C. sinensis	First group (n = 90): diet + 400 mg/d moro orange juice extract capsule + exercise Second group (n = 90): diet + exercise for 6 mo	A total of 180 overweight (25 < BMI < 35 kg/m²) healthy men and women aged 20–65 y	There was a significant decrease in body weight^, BMI^, WC^, and HC^ in both groups, and this decrease was higher in the extract group. There was no significant change in HDL, LDL, or TC levels.
Simpson et al (2012)³³	RCT	C. sinensis	First group (n = 16): 250 mL orange juice Second group (n = 16): 250 mL orange-flavored beverage per day for 12 wk	n = 32 overweight women aged 20–45 y with HOMA-IR >1.5 and a BMI of 27–35 kg/m²	There was no significant change in LDL, HDL, TC, SBP, DBP, apo-A1, and apo-B levels; HOMA-IR; and body weight of the groups at the end of 12 wk.
Basile et al (2010)³⁴	Cross-Sectional Study	C. sinensis	For 8 wk, men were given 750 mL/d orange juice, and women were given 500 mL/d orange juice.	n = 21 healthy women aged 20–53 y and 20 healthy men aged 21–44 y	There was no significant change in orange juice consumption, body weight, and BMI in either sex. Although WC^* decreased in women, no change was found in men. TC^* and LDL^* levels were decreased in both sexes. HDL^* increased in women, whereas TG^* and DBP^* levels decreased significantly in men.
Cesar et al (2010)³⁵	Cohort Study	C. sinensis	First group: normocholesterolemic (n = 31) Hypercholesterolemic (n = 14): 750 mL of orange juice Second group (n = 8): nothing daily for 60 d	n = 53 male and female adults aged 36–44 y	No significant changes were found in the groups in BMI, WC, and HDL levels. TC^ and LDL^ levels were decreased in the hypercholesterolemic group. TG^* level increased in the control group.
Asgary et al (2014)³⁶	RCT	C. sinensis	First group (n = 11): 500 mL commercial orange juice Second group (n = 11): 500 mL fresh orange juice twice daily for 4 wk	n = 22 healthy volunteers (7 men and 15 women) aged 18–59 y	No significant change was found in the weight, BMI, WC, apo-B, HDL, TC, and TG levels of both groups. A significant decrease in LDL^* level was found in the fresh orange juice group.
Pittaluga et al (2013)³⁷	Cohort Study	C. sinensis	First group (n = 15): 250 mL of fresh red orange juice Second group (n = 7): nothing 3 times/d 1 h before each meal for 4 wk	n = 22 healthy individuals who exercised regularly for 6 mo and were fed a Mediterranean diet	There was no significant change in BMI, body fat mass, and heart rate in both groups.
Büsing et al (2019)³⁸	Cohort study-cross-over	C. sinensis	First group (n = 12): orange juice (43 kcal/100 mL and 8.8 g sugar/100 mL) Second group (n = 14): cola drink (44 kcal/100 mL and 11.1 g sugar/100 mL) 3 times/d for 2 wk	n = 26 healthy adults	There was no significant change in body weight between groups.
Hägele et al (2018)³⁹	Cohort Study-Cross-over	C. sinensis	Orange juice (43 kcal/100 mL and 8.9 g sugar/100 mL) in an amount to meet 20% of the daily energy needs 3 times/d for 2 wk was given to the first group with meals and the second group between meals. After 1 wk of washout, the application was repeated by crossing.	n = 26 healthy adults (13 women, 13 men) aged 20–45 y	There was no significant change in body weight, HOMA-IR, and TG groups and between groups. Consumption of orange juice with meals decreased body fat mass^, and consumption between meals increased body fat mass^. Fat mass^* change was different between groups.
Stookey et al (2012)⁴⁰	RCT- crossover	C. sinensis	On 2 separate days, the groups were crossed and individuals consumed 500 mL of water or orange juice with breakfast.	Aged 11–17 y with a BMI <85th percentile. n = 7 adolescents and 10 adults (19–38 y) with a BMI 18.5–24.9 kg/m²	At 180 min after breakfast, the plasma insulin to glucose ratio^* increased in adolescents and adults compared with those drinking orange juice. 30 min after breakfast, fat oxidation^* decreased compared with those drinking water at breakfast with an orange drink in both age groups. But NPREE and NPRER did not change.
Sakaki et al (2021)⁴¹	Cohort Study	C. sinensis	The survey data were followed from 2004 to 2008 with an interval of 2 y.	n = 7301 children aged 9–16 y were included in the study.	Orange juice consumption was not associated with BMI and weight.
Aptekmann et al (2010)⁴²	Cohort Study	C. sinensis	First group (n = 13): 500 mL of orange juice Second group (n = 13): nothing daily for 3 mo	n = 30 physically active premenopausal women aged 30–48 y	Weight^, BMI^, SFT^* (triceps, thigh), lactate, TC^, and LDL^ levels decreased in the experimental group compared with the control group; HDL^, TG^, and SFT^* values (biceps) increased.
Simpson et al (2016)⁴³	RCT	C. sinensis	First group (n = 18): 250 mL of orange juice Second group (n = 18): orange-flavored beverage for 12 wk	n = 36 healthy men aged 40–60 y with BMI 27–35 kg/m²	BMI, weight, WC, HC, WHR, HOMA-IR, % body fat, TC, HDL, LDL, TG, apo-A1, and apo-B values did not change significantly between groups.
Ribeiro et al (2017)⁴⁴	RCT	C. sinensis	First group (n = 39): 500 mL of orange juice and a low-calorie diet (500 kcal reduced) Second group (n = 39): only a low-calorie diet for 12 wk	n = 78 individuals aged 18–50 y with BMI: 30–40 kg/m²	Weight, BMI, WC, HC, WHR, body fat, FG, HDL, TG, AST, and ALT values did not change. At wk 8 and 12, insulin^* and HOMA-IR^* values were decreased in the experimental group compared with the control group. At wk 12, LDL^* level decreased.
O’Neil et al (2011)⁴⁵	Cross-sectional study	C. sinensis	Data were obtained through surveys (NHANES) collected annually between 2003 and 2006. First group (n = 2183): 100% orange juice consumer Second group (n = 5067): nonconsumer	n = 7250 individuals between the ages of 2 and 18 y were included.	The group that consumed orange juice had lower levels of WC^* and LDL^* compared with the group that did not consume orange juice. Weight, BMI, SBP, DBP, TC, TG, HDL, apo-B, and insulin levels did not differ between groups.
Rumbold et al (2015)⁴⁶	RCT-crossover	C. sinensis	Participants were given 600 mL of skim milk or 600 mL (475 mL of orange juice and 125 mL of water) of orange juice after 30 min of cycling exercise.	Nine recreationally active women aged between 18 and 21 y and BMI of 19–25 kg/m² were included.	Vo²_peak was not different between groups. Relative energy intake^* at the test meal decreased in milk consumption.
Fidélix et al (2020)⁴⁷	Cohort Study	C. sinensis	Participants followed a regular diet with no orange juice for 30 d, 300 mL of orange juice/d for 60 d, and no orange juice again for 30 d.	n = 10 healthy women aged between 20 and 35 y	BMI, weight, and body fat did not change over the 120-d period. During the drinking period of orange juice, FG^, insulin^, HOMA-IR^, TG^, TC^, and LDL^ values decreased.
Rangel-Huerta et al (2015)⁴⁸	RCT	C. sinensis	First group (n = 100): 500 mL high-polyphenol orange juice Second group (n : 100): 500 mL of normal polyphenol orange juice for 12 wk	n = 100 individuals with a BMI 25–40 kg/m² or a WC >94 cm in men and >80 cm women	Weight^, BMI,^ WC^, and FPS^ increased in both groups. SBP^, DBP^, insulin^, TG^, and apo-B^* levels were decreased in the second group. Apo-A1^* was decreased in the first group. HOMA-IR, TC, HDL, and LDL levels were unchanged.
Aptekmann et al (2013)⁴⁹	Cross-sectional Study	C. sinensis	The data were created by analyzing data from those who drank ≥1 glass of orange juice/d and those who did not drink it at all in the last year. Consumers (n = 50); nonconsumers (n = 79)	n = 129 individuals aged 18–66 y	There was no significant difference in TG, HDL, apo-A1, BMI, weight, body fat, and WC values. Normolipidemic or hypercholesterolemic individuals who consumed orange juice had less TC^, LDL^, and apo-B^* compared with those who did not.
Dallas et al (2008)⁵⁰	RCT	C. sinensis C. aurantium C. paradisi	First group (n = 10): 4 capsules containing citrus mix extract Second group (n = 10): 4 capsules containing placebo for 12 wk	n = 20 healthy individuals aged 25–55 y with BMI 27–33 kg/m²	At the end of wk 4 and 12, the experimental group's BMI^, weight^, and body fat^* values had decreased compared with the placebo.
Silveira et al (2015)⁵¹	Cross-sectional Study	C. sinensis	First group (n = 17): normal weight and 750 mL of orange juice Second group (n = 12/6): overweight/obese group and 750 mL of orange juice daily for 8 wk	n = 35 healthy and nonsmoking individuals aged 18–29 y	In the first group, after 8 wk, TC^, HDL^, LDL^, apo-A1^, FG^, HOMA-IR^, and SBP^* decreased; weight, BMI, body fat, WC, apo-B, TG, and DBP values did not change. In the second group, TC, LDL, and DBP values decreased after 8 wk, whereas other values remained unchanged.
Penzak et al (2001)⁵²	Cross-sectional Cross-over	C. aurantium	Participants drank 8 oz (237 mL) of bitter orange juice (phase 1) or water (phase 2) 8 h before arriving at the study unit. After coming to the research unit, their measurements were taken, and 8 oz (237 mL) of bitter orange juice (phase 1) or water (phase 2) was given again. Measurements were repeated hourly for 5 h.	n = 12 healthy individuals aged 20–27 y	The bitter orange juice had no significant effects on SBP, DBP, or arterial pressure values, and heart rate compared with water.
Silver et al (2011)⁵³	RCT	C. paradisi	First group (n = 29): half a fresh grapefruit Second group (n = 28): grapefruit juice (127 g) Third group (n = 28): water (127 g) for 12 wk	n = 85 adults aged 21–50 y with BMI of 30–39.9 kg/m²	BMI^, WC^, and body fat percentage^* decreased in all groups at the end of 12 wk. There was no significant difference in REE, RQ, BMI, WC, HDL, TC, TG, SBP, or DBP values within and between groups.
Fujioka et al (2006)⁵⁴	RCT	C. paradisi	First group (n = 24): grapefruit capsule + 207 mL of apple juice (capsule) Second group (n = 21): placebo capsule + 237 mL grapefruit juice Third group (n = 24): half a fresh grapefruit + placebo capsule Fourth group (n = 22): placebo capsule + 207 mL of apple juice 3 times/d for 12 wk	n = 91 obese adult men and women with BMI = 30–40 kg/m²	The fresh grapefruit group had greater weight loss^* than the placebo group. HDL, TG, WC, and BP values did not change significantly.
Dow et al (2012)⁵⁵	RCT	C. paradisi	First group (n = 39): half a peeled grapefruit Second group (n: 32): nothing 3 times/d for 6 wk	n = 85 premenopausal healthy individuals with BMI ≥ 25–45 kg/m²	WC^**, WHR^, SBP^, TC^, and LDL^*** values decreased in the experimental group after the intervention. BMI, WC, weight, HC, WHR, SBP, DBP, heart rate, TC, TG, HDL, and LDL did not change between the groups after the intervention.
Taghizadeh et al (2016)⁵⁶	RCT	C. aurantifolia	First group (n = 24): 75 mg of Cumin cyminum L. (cumin) and lime capsule Second group (n = 24): 25 C. cyminum L. (cumin) and lime capsule Third group (n = 24): placebo twice daily for 8 wk	n = 72 healthy aged 18–50 y with BMI ≥ 25 kg/m²	In both experimental groups, weight^*, BMI^, and FG^** values decreased compared with the placebo group. In addition, the high-dose group LDL^* TC^*, and TG^ levels decreased compared with the low-dose and placebo groups. HOMA-IR, HOMA-β, and HDL values remained unchanged.
Hashemipour et al (2016)⁵⁷	RCT	C. aurantifolia	First group (n = 30): lemon peel–powder capsule Second group (n = 29): placebo for 4 wk	n = 60 healthy individuals aged 10–18 y with BMI > 85th percentile	WC, NC, BMI, DBP, SBP, FG, TC, and LDL values did not change between groups after the intervention. HDL^ increased in the placebo group. BMI^, SBP^, TC^, and LDL^* levels decreased before the intervention in the experimental group after the intervention. BMI^*** was also decreased in the placebo group.
Ferro et al (2020)⁵⁸	RCT	C. bergamia	First group (n = 51): C. bergamia extract + diet (<500 kcal) Second group (n = 51): placebo + diet (<500 kcal)	n = 102 individuals aged 30–75 y	BMI^, weight,^ and controlled attenuation parameter score^* decreased compared with the control group. WC, HC, TG, HDL, LDL, TC, FG, AST, and ALT values were unchanged. In subgroup analyses, men^, those older than 50 y^, those with android obesity^, and those with obese/overweight^** had decreased weight in the experimental group compared with the control.
Lin et al (2022)⁵⁹	RCT	C. reticulata	First group (n = 10): C. reticulata drink (50 mL and with 20% C. reticulata extract) Second group (n = 10): placebo drink (50 mL) twice a day for 6 wk	n = 20 healthy individuals (aged 18–70 y) with BMI ≥ 24 kg/m² or body fat > 30%	At the end of 4, 6, and 8 wk, body weight^* decreased in the experimental group. In addition, WC^* decreased at the end of the 6th wk and AST^* level decreased at the end of the 8th wk. Body fat, DBP, ALT, TC, TG, FG, and BMI levels did not change.

P < 0.05,

^**

P < 0.01,

^***

P < 0.001,

^****

P < 0.0001.

Abbreviations: ALT, alanine transaminase; apo-A1, apolipoprotein A1; apo-B, apolipoprotein B; AST, aspartate aminotransferase; BMI, body mass index; BP, blood pressure; DBP, diastolic blood pressure; FG, fasting glucose; HC, hip circumference; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; HOMA-β, homeostasis model assessment of β-cell dysfunction; hs-CRP, high-sensitive C-reactive protein; LDL, low-density lipoprotein; NC, neck circumference; NHANES, National Health and Nutrition Examination Survey; NPREE, nonprotein resting energy expenditure; NPRER, nonprotein respiratory exchange ratio; RCT, randomized controlled trial; REE, resting energy expenditure; RQ, respiratory quotient; SBP, systolic blood pressure; SFT, skinfold thickness; TC, total cholesterol; TG, triglyceride; Vo_2peak, peak oxygen uptake; WC, waist circumference; WHR, waist to hip ratio.