Table 1 Characteristics of the studies selected for meta-analysis of the effects of anthocyanins on cardiometabolic risk factors
Study | Country year | Participants | Type and dose of anthocyanin | Duration (week) | Sample size |
|---|---|---|---|---|---|
Alnajjar M, et al. [46] | UK 2020 | Overweight male and postmenopausal female, BMI 31 ± 4, aged 62 ± 7, with or without diabetes, were not on any special religious or prescribed diet, with stable weight, without thromboembolic or coagulation problems, thyroid disease, renal or hepatic disease, severe gastrointestinal disorders, pulmonary disease (e.g., chronic bronchitis, COPD), alcohol or any other substance abuse, eating disorders or psychiatric disorders, not were taking oral steroids, tricyclic antidepressants, neuroleptics anticoagulants, digoxin and anti-arrhythmic, or chronically using anti-inflammatory (e.g., high doses of aspirin, ibuprofen) | Three capsules of 0.47 g of Mirtoselect® [a standardized bilberry extract (36% (w/w) anthocyanins)] per day, which equates to ~ 150 g of fresh bilberries per day, formulated in gelatin capsules | 3 | Total: 16, with (n = 9) or without (n = 7) type 2 diabetes two groups: Control group: 16 Anthocyanin group: 16 Lost to follow-up: 0 |
An JH, et al. [30] | Korea 2016 | Aged 20–80 years with prediabetes with no history of renal impairment, liver disease, uncontrolled hypertension, triglyceride > 500 mg/dL, other acute or chronic disease, no starting or changing lipid-lowering agent within two months, no take of medications known to affect glycemic control and lipid profiles or herbal supplements | Rubus occidentalis extract (RO, Black raspberry) Definite anthocyanins levels of RO extract investigated in this study were not available | 12 | Total: 44, three groups: Control group: 1 900 mg RO extract: 1 1800 mg RO extract: 17 Lost to follow-up: 5 |
Asgary S, et al. [68] | Iran 2014 | hypertensive patients aged 30–67 years with BMI ≤ 30, without type 1 or 2 diabetes, chronic pancreatitis, liver cirrhosis, kidney stones, renal failure, use of non-steroidal anti-inflammatory drugs, use of antioxidant or vitamin supplements, intense physical activity (> 5 h/week), smoking habit, being vegetarian or having any restrictive dietary requirements and pregnancy | Pomegranate juice (PJ) Definite anthocyanins levels of PJ investigated in this study were not available | 2 | Total: 21, two groups: Control group: 10 Pomegranate juice group: 11 Lost to follow-up: 0 |
Bakuradze T, et al. [24] | Germany 2019 | Healthy male volunteers, aged 20–50, BMI = 19–25, non-smokers, no practice of excessive sports, no intake of pharmaceutical drugs or food supplements | 750 mL bolus of anthocyanin-rich fruit juice Total anthocyanins: 274.5 mg/L | 8 | Total: 62, two groups: Control group: 31 fruit juice group: 31 Lost to follow-up: 5 |
Basu A, et al. [34] | USA 2010 | Obese adults with metabolic syndrome, older than 21 years, not using hypoglycemic, hypo lipidemic, anti-inflammatory, or steroidal medications; no history of liver, renal, or thyroid disorders or anemia, not consuming antioxidants or fish oil supplements on a regular basis | 50 g freeze-dried blueberries that were reconstituted in 480 mL water and vanilla extract Total anthocyanins: 742 mg | 8 | Total: 66, two groups: Control group: 32 blueberry group: 34 Lost to follow-up: 18 |
Basu A, et al. [35] | USA 2010 | Adults with metabolic syndrome, no medications for any chronic disease (cancer, congenital heart disease, diabetes mellitus), or medications known to affect lipid metabolism or possess anti-inflammatory effects, pregnant or lactating, used any form of tobacco products, consumed alcohol on a regular basis, used mega doses of antioxidants or fish oil supplements (> 1 g/day), or had any abnormalities in hematology, liver, renal, and thyroid function tests | Strawberry beverage Total anthocyanins: 154 mg | 8 | Total: 30, two groups: Control group: 15 Strawberry beverage group: 15 Lost to follow-up: 3 |
Basu A, et al. [36] | USA 2011 | Adults with metabolic syndrome, no medications for any chronic disease (cancer, cardiovascular disease, diabetes mellitus), pregnant or lactating, used any form of tobacco products, consumed alcohol (> 1 oz/day), used mega doses of antioxidants or fish oil supplements (> 1 g/day), or had any abnormalities in hematology, liver, renal, and thyroid function tests | 480 mL cranberry juice Total anthocyanins: 12.4 mg | 8 | Total: 36, two groups: Control group: 18 cranberry juice group: 18 Lost to follow-up: 5 |
Basu A, et al. [37] | USA 2014 | Hyperlipidemic adults with abdominal adiposity and fasting serum lipids that met any 2 of the following 4 criteria: (1) total cholesterol > 200 mg/dL; (2) LDL-C > 100 mg/dL; (3) TGs > 150 mg/dL; and (4) HDL-C < 50 mg/dL for women and < 40 mg/dL for men Without medications for any chronic disease (cancer, cardiovascular disease, diabetes mellitus), pregnant or lactating, used any form of tobacco products, consumed alcohol (> 1 oz/day), used mega doses of antioxidants or fish oil supplements (> 1 g/day), no abnormalities in hematology, liver, renal, and thyroid function tests | 474 mL of freeze-dried strawberries (FDS) beverages Total anthocyanins: low-dose FDS: 78 mg high-dose FDS: 155 mg | 12 | Total: 66, four groups: low-dose control: 15 low-dose FDS: 15 high-dose FDS: 15 high-dose control: 15 Lost to follow-up: 6 |
Chan SW, et al. [54] | China 2021 | Patients with type 2 diabetes, with HbA1c ≥ 7%, controlled with oral hypoglycemic agents, BMI > 23 kg/m2, with no evidence of cardiovascular disease, overt vascular complications, evidence of renal, liver disease, not taking other nutritional supplements | Spray-dried water/ethanol extract of European Bilberry (Vaccinium vitis-idaea L.) containing ≥ 25% anthocyanidins 4 capsules – 350 mg Total anthocyanins: 1.4 g | 4 | Total: 20, two groups: Control group: 20 Anthocyanin group: 20 Lost to follow-up: 0 |
Kent K, et al. [42] | Australia 2017 | Elderly with mild to moderate dementia Alzheimer without uncontrolled hypertension, uncontrolled diabetes, any other unstable physical or mental health condition or dysphagia | 200 mL anthocyanin-rich cherry juice Total anthocyanins: 138 mg | 12 | Total: 49, two groups: Control group: 25 cherry juice group: 24 Lost to follow-up: 7 |
Curtis PJ, et al. [23] | United kingdom 2009 | Healthy postmenopausal women, not taking hormone replacement therapy for ≥ 6 mo, BMI: 20–32, nonsmokers, No history of diabetes; hepatic, renal, cardiac, pulmonary, digestive, hematological, neurological, thyroidal, or psychiatric disease; or taking anti-inflammatory or steroidal medication, or vaccines and antibiotics | Elderberry extract capsule Total anthocyanins: 500 mg | 12 | Total: 57, two groups: Control group: 29 anthocyanin group: 28 Lost to follow-up: 5 |
Davinelli S, et al. [43] | Italy 2015 | Overweight smokers without history of chronic diseases, no taking anti-inflammatory drugs, cardiovascular medications, lipid-altering drugs, and hormone replacement therapy | 3 capsules of 150 mg standardized maqui berry extract Total anthocyanins: 162 mg | 6 | Total: 42, two groups: Control group: 16 Anthocyanin group: 26 Lost to follow-up: 0 |
Dohadwala, et al. [66] | USA, 2011 | Patients with stable coronary artery disease, confirmed by angiography, exercise test, or documented history of myocardial infarction, without body weight > 115 kg, congestive heart failure, or acute medical illness, not taking vitamins exceeding 2 times the Recommended Dietary Allowance or food supplements within 1 mo of study | Cranberry juice (480 mL/d) Total anthocyanins: 94 mg | 4 | Total: 47, two groups: Control group: 23 Anthocyanin group: 24 Lost to follow-up: 3 |
Duthie SJ, et al. [67] | United kingdom 2006 | healthy female, without taking medication or vitamin and mineral supplements | 750 ml of cranberry juice Total anthocyanins: 2.8 mg/l | 2 | Total: 20, two groups: Control group: 9 Anthocyanin group: 11 Lost to follow-up: 0 |
Erlund I, et al. [47] | Finland 2008 | Adults with cardiovascular risk factors, at least one of the following conditions: mild hypertension, elevated blood glucose, elevated serum total cholesterol or triacylglycerol, and low HDL cholesterol Without regular use of medications (except hormone replacement therapy) or dietary supplements, smoking, intestinal disorders, obesity, and vegetarianism | Whole bilberries (100 g) and a nectar containing 50 g crushed lingonberries, Black currant or strawberry purée (100 g, containing 80% black currants) and cold-pressed chokeberry and raspberry juice (0.7 dL juice, containing 80% chokeberry) Total anthocyanins: 515 mg | 8 | Total: 72, two groups: Control group: 36 Berry group: 36 Lost to follow-up: 0 (one excluded from analysis) |
Gurrola-Díaz CM, et al. [65] | Mexico 2010 | Individuals with and without metabolic syndrome, aged 30–71 years | 100 mg Hibiscus sabdariffa extract powder (HSEP) Total anthocyanins: 19.24 mg | 4 | Total: 152, six groups: Healthy Control (without metabolic syndrome): Diet group:27 HSEP group:26 Diet + HSEP group: 20 Lost to follow-up: 7 Metabolic syndrome group: Diet group:11 HSEP group:18 Diet + HSEP group: 22 Lost to follow-up: 21 |
Jeong HS, et al. [38] | Korea 2014 | Patients with metabolic syndrome, 18 and 75 years old | 750 mg Black Raspberry Definite anthocyanins levels of RO extract investigated in this study were not available | 12 | Total: 77, two groups: Control group: 38 Black raspberry group: 39 Lost to follow-up: 4 |
Kianbakht S, et al. [48] | Iran 2013 | diabetic outpatients aged 40–60 years, resistant to conventional oral anti-hyperglycemic drugs, with FBG: 200–250 mg/dl and HbA1c: 7- 8, despite using a combination of conventional oral anti-hyperglycemic drugs, without cardiac, renal, or hepatic diseases or concomitant infections | 350 mg whortleberry fruit hydroalcoholic extract Total anthocyanins: 86.56 mg / 10 g extract | 8 | Total: 86, two groups: Control group: 44 Whortleberry group: 42 Lost to follow-up: 12 |
Kianbakht S, et al. [55] | Iran 2014 | Outpatients aged 20–60 years with newly diagnosed primary hyperlipidemia without taking anti-hyperlipidemic agents; herbal medications; triglyceride or/and total cholesterol > 350 mg/dL; no history of cardiac, renal, hepatic and hematological diseases, hypothyroidism, diabetes mellitus, tachycardia, vertigo and seizure; gallstones or gall bladder surgery; not using estrogen, steroid, betablocker and thiazide; | 350 mg whortleberry fruit hydroalcoholic extract Total anthocyanins: 86.56 mg / 10 g extract | 8 | Total: 105, two groups: Control group: 54 Whortleberry group: 51 Lost to follow-up: 25 |
Kim H, et al. [39] | USA 2018 | metabolic syndrome patients, without previous hospitalizations due to metabolic syndrome, current pregnancy or lactation, recent history of significant weight change, weight loss medications, dietary supplements, smoking, binge drinking, and allergy to açaí berries | 325 mL açaí beverage Total anthocyanins: 307 mg/L | 12 | Total: 43, two groups: Control group: 22 açaí group: 21 Lost to follow-up: 6 |
Lee I, et al. [49] | Taiwan 2018 | Type 2 diabetic subjects, 50–75 years old, HbA1c 7–10%, triglycerides < 4.5 mmol/l Without kidney or hepatic disease, severe systemic disease such as immune disorders, cancer, acute or chronic inflammatory disease; smoking, insulin or steroid use | 500 mg cranberry extract Definite anthocyanins levels of RO extract investigated in this study were not available | 12 | Total: 30, two groups: Control group: 15 Cranberry group: 15 Lost to follow-up: 0 |
Lee M, et al. [44] | Korea 2016 | 19–65 years old with BMI > 23, and waist circumference > 90 cm (male) or 85 cm (female). Without using anti-obesity or lipid-lowering medication, no history of cardiovascular or obesity-related diseases, no more than 10% loss of body weight within the previous 3 months | 2.5 g Black soybean testa extracts (BBT) Total anthocyanins: 32 mg | 8 | Total: 80, two groups: Control group: 31 BBT group: 32 Lost to follow-up: 17 |
Li D, et al. [50] | China 2015 | Type 2 diabetes aged 56–67 years, without recently diagnosed diabetes, pregnancy, coronary artery disease, and other known chronic diseases | Anthocyanin capsules Total anthocyanins: 320 mg | 24 | Total: 58, two groups: Control group: 29 Anthocyanin group: 29 Lost to follow-up: 0 |
Lynn A, et al. [22] | United Kingdom 2014 | Healthy, non-smoking, age 30–50 y, without taking medication for heart disease, hypertension or diabetes, regular consumption of cherries or cherry juice and the use of antioxidant supplements | Cherry juice concentrate [30 ml diluted with 220 ml of water] Total anthocyanins: 273.5 mg | 6 | Total: 47, two groups: Control group: 21 Cherry juice group: 25 Lost to follow-up: 1 |
Murkovic M, et al. [25] | Austria 2004 | Healthy volunteers not regularly taking antioxidant supplements | Spray-dried elderberry juice capsule Total anthocyanins: 100 mg | 2 | Total: 34, two groups: Control group: 17 Cherry juice group: 17 Lost to follow-up: 0 |
Naruszewicz M, et al. [56] | Poland 2017 | Patients who survived myocardial infraction and have received statin therapy for at least 6 months | 3 × 85 mg/day of chokeberry flavonoid extract Total anthocyanins: 25% | 6 | Total: 44, two groups: Control group: 22 Chokeberry group: 22 Lost to follow-up: 0 |
Novotny JA, et al. [26] | USA 2015 | nondiabetic, nonsmokers with fasting TGs < 300 mg/dL not using cholesterol-lowering medications, BP medications, history of bariatric or weight-loss surgery, recent weight loss, history of gastrointestinal or malabsorption disorders, kidney disease, liver disease, gout, hyperthyroidism, untreated or unstable hypothyroidism, cancer, pancreatic disease, or other metabolic disorders | 240 mL of low-calorie cranberry juice Total anthocyanins: 10.3 mg | 8 | Total: 60, two groups: Control group: 30 Cranberry group: 30 Lost to follow-up: 4 |
Puupponen‐Pimiä R, et al. [40] | Finland 2013 | Metabolic syndrome | 300 g fresh berries comprising of 100 g of strawberry puree, 100 g of frozen raspberries, and 100 g of frozen cloudberries Total anthocyanins: 70.7 ± 52 mg | 8 | Total: 37, two groups: Control group: 17 Berry group: 20 Lost to follow-up: 5 |
Qin Y, et al. [57] | China 2009 | Dyslipidemiac subjects met 2 of the following 4 criteria: TC > 200 mg/dL, TGs > 150 mg/dL, LDL-C > 100 mg/dL, HDL-C < 40 mg/dL with no history of CVD or other severe chronic disease or use of any drugs known to affect lipid metabolism | Anthocyanins capsule Total anthocyanins: 320 mg | 12 | Total: 120, two groups: Control group: 60 Anthocyanins group: 60 Lost to follow-up: 5 |
Riso P, et al. [29] | Italy, 2013 | Healthy male subjects, aged 47.8 ± 9.7 years with BMI 24.8 ± 2.6 kg/m2, with at least one risk factor for CVD based on American Heart Association guidelines without secondary hypertension, obesity, diabetes, renal insufficiency, known food allergies, chronic constipation, diarrhea or any other gastrointestinal problem or disease, not taking drugs, dietary supplements, specific probiotics, prebiotics or medications, not taking high ([5 portions/day) or low (\2 portions/day) intake of fruit and vegetables and habitual alcohol consumption (\3drinks per week), not following a specific diet | Wild blueberry (WB) drink was prepared by suspending 25 g of WB freeze-dried powder in 250 mL of water Total anthocyanins: 375 mg | 6 | Total: 20, two groups: Control group: 20 Anthocyanin group: 20 Lost to follow-up: 2 |
Shidfar F, et al. [51] | Iran 2012 | Nonsmoking T2D men with BMI < 30 kg/m, HbAlc < 9%, serum triglyceride < 400 mg/dl, and serum total cholesterol < 240 mg/dl, with no history of symptomatic heart disease, myocardial infarction, angina pectoris or stroke, surgery, liver, renal, or thyroid disease; use of steroids or change in the use of medication | 240 ml cranberry juice Definite anthocyanins levels of RO extract investigated in this study were not available | 12 | Total: 60, two groups: Control group 30 Cranberry group: 30 Lost to follow-up: 2 |
Soltani R, et al. [58] | Iran 2014 | hyperlipidemic patients with TC: 200–300 mg/dL and/or TGs: 150–199 mg/dL and/or LDL-C: 130–190 mg/dL, being non-smokers, free of diseases affecting serum lipids (e.g., diabetes, thyroid disorders, and pancreatitis), not using drugs or supplements affecting serum lipids (e.g., statins, fibrate derivatives, estrogens, progestins, beta-blockers, thiazide diuretics, and fish oil) within the last 3 months, free of liver or kidney disease, | Fruit extract of Vaccinium arctostaphylos L. capsule Total anthocyanins: 90 mg | 4 | Total: 54, two groups: Control group: 27 Vaccinium group: 27 Lost to follow-up: 4 |
Soltani R, et al. [52] | Iran 2015 | T2D patients, being diagnosed for at least 2 years, age of 18–80 years, HbA1c 7–10%, not being alcohol or substance abuser, not using insulin or insulin secretagogue | Anthocyanins capsule Total anthocyanins: 600 mg | 6 | Total: 60, two groups: Control group: 30 Anthocyanin group: 30 Lost to follow-up: 0 |
Stote KS, et al. [53] | USA 2020 | Men diagnosed with T2D for ≥ 6 mo; HbA1c: 6.5–9; BMI > 25. Without chronic kidney disease, liver cirrhosis, gastrointestinal disease, pancreatic disease, or malabsorption syndromes, losing > 10% of weight within the past 12 mo, participating in a heavy exercise program | 22 g freeze-dried blueberries Total anthocyanins: 261.8 mg | 8 | Total: 55, two groups: Control group: 28 Blueberry group: 27 Lost to follow-up: 3 |
Stull AJ, et al. [45] | USA 2010 | Obese, nondiabetic, and insulin-resistant subjects, BMI: 32–45 kg/m2, without history of diabetes, thyroid or chronic liver, renal, or cardiovascular disease, allergic reactions to blueberries, not using medications known to affect glucose metabolism; drug and/or alcohol abuse, not consuming berries, grapes, and wine > 3 times/wk; and > 5% fluctuation in body weight preceding 2 mo | Smoothie containing 22.5 g blueberry bioactives with 45 g of blueberry powder Total anthocyanins: 668 mg | 6 | Total: 32, two groups: Control group: 17 Blueberry group: 15 Lost to follow-up: 0 |
Stull AJ, et al. [41] | USA 2015 | Metabolic syndrome patients without diabetes, liver, kidney or heart disease, smoking, not using nonprescription drugs, vitamins, dietary and herbal supplements | Skim milk-based smoothie with 45 g freeze-dried blueberry powder added Total anthocyanins: 290.3 mg | 6 | Total: 46, two groups: Control group: 23 Blueberry group: 23 Lost to follow-up: 2 |
Sumner MD, et al. [64] | Patients with ischemic coronary heart disease with ≥ 1 reversible myocardial perfusion defect without history of other heart diseases or significant co-morbidity, current use of tobacco products, or alcohol or drug abuse | 240 mL of pomegranate juice Definite anthocyanins levels of RO extract investigated in this study were not available | 12 | Total: 45, two groups: Control group: 26 Pomegranate group: 19 Lost to follow-up: 4 | |
Wright OR, et al. [27] | Australia 2013 | Healthy male volunteers aged 18–65 years with a BMI 25–35 with stable blood pressure in the normal, high-normal, or mildly hypertensive or being stable on medication if are hypertensive; with no chronic diseases or medical conditions, not already consuming purple carrots or purple carrot products | Sachets of dried purple carrot Total anthocyanins: 118.5 mg | 4 | Total: 16, two groups: Control group: 8 Purple carrot group: 8 Lost to follow-up: 0 |
Xu Z, et al. [59] | China 2020 | Dyslipidemic subjects | Purified anthocyanin capsules Total anthocyanins: 40–80-320 mg | 12 | Total: 176, four groups: Control group: 46 Anthocyanin (40 mg):45 Anthocyanin (80 mg):42 Anthocyanin (320 mg):43 Lost to follow-up: 5 |
Yang L, et al. [32] | China, 2020 | Prediabetes or early untreated diabetes, aged 40–75 years, HbA1c: 5.7–6.4%, without medical history of diabetes, untreated thyroid disease, polycystic ovarian syndrome, serious liver or kidney dysfunction, infection, or traumatic injury or surgeries, not using glucocorticoids | Purified anthocyanins Total anthocyanins: 230 mg | 12 | Total: 160, two groups: Control group: 80 Anthocyanin group: 80 Lost to follow-up: 22 |
Yang L, et al. [33] | China, 2021 | Prediabetes or early untreated diabetes, aged 40–75 years, HbA1c: 5.7–6.4%, without medical history of diabetes, untreated thyroid disease, polycystic ovarian syndrome, serious liver or kidney dysfunction, infection, or traumatic injury or surgeries, not using glucocorticoids | Purified anthocyanins Total anthocyanins: 230 mg | 12 | Total: 160, two groups: Control group: 80 Anthocyanin group: 80 Lost to follow-up: 22 |
Yang L, et al. [31] | China 2017 | Prediabetes or early untreated diabetes, aged 40–75 years, HbA1c: 5.7–6.4%, without medical history of diabetes, untreated thyroid disease, polycystic ovarian syndrome, serious liver or kidney dysfunction, infection, or traumatic injury or surgeries, not using glucocorticoids | Purified anthocyanins Total anthocyanins: 230 mg | 12 | Total: 160, two groups: Control group: 80 Anthocyanin group: 80 Lost to follow-up: 22 |
Yarahmadi M, et al. [28] | Iran 2014 | athletes with athletic history of at least 3 years, not using antioxidant supplements during the past month | Anthocyanins pill Total anthocyanins: 100 mg | 6 | Total: 54, two groups: Control group: 27 Anthocyanin group: 27 Lost to follow-up: 10 |
Zhang P-W, et al. [63] | China 2015 | NAFLD patients, 25–65 years, without excessive alcohol consumption, cirrhosis, viral hepatitis, cardiovascular disease, cancer, and any consumption of nonsteroidal anti-inflammatory drugs, corticosteroids, or prescriptive medicines that affect liver function, lipid, or glucose metabolism | Purified anthocyanins from bilberry and black currant Total anthocyanins: 320 mg | 12 | Total 74, two groups: Control group: 37 Anthocyanin group: 37 Lost to follow-up: 11 |
Zhang X, et al. [60] | China 2016 | Hypercholesterolemic individuals, with total cholesterol:200–310 mg/dL, without a history of CVD, hypertension, diabetes mellitus, thyroid disorder, smoking or the use of any drug that could influence the measurement of lipid parameters, inflammatory markers, or chemokines | Purified anthocyanins Total anthocyanins: 320 mg | 24 | Total: 150, two groups: Control group: 75 Anthocyanin group: 75 Lost to follow-up: 4 |
Zhao Y, et al. [61] | China 2021 | Dyslipidemic subjects, 35–70 years, without history of atherosclerosis, coronary disease, or other severe vascular disease, infection, autoimmune disease, cancer, traumatic injury, or surgery within 1 month; liver or renal dysfunction; prescription of lipid-lowering medications within 6 months; intake of phytochemical supplements including anthocyanin and grape seed extracts within 2 months | Purified anthocyanin concentrated from skins of wild Norwegian bilberries and black currants Total anthocyanins: 40–80-320 mg | 12 | Total: 176, four groups: Control group: 46 Anthocyanin (40 mg):45 Anthocyanin (80 mg):42 Anthocyanin (320 mg):43 Lost to follow-up: 7 |
Zhu Y, et al. [62] | China 2013 | Hypercholesterolemic adults, aged 40–65 y, with total cholesterol:200–310 mg/dL, without history of cardiovascular disease, diabetes, hypertension, thyroid disorders, smoking or the use of any drugs that could influence lipid parameters and inflammatory markers | Purified anthocyanin mixture Total anthocyanins: 320 mg | 24 | Total: 150, two groups: Control group: 75 Anthocyanin group: 75 Lost to follow-up: 4 |