Table 1.

A summary of human trials showing the potential health beneficial effects of anthocyanins.

Anthocyanin	Anthocyanin Dose	Time	Subject Profile	Study Type	Major Findings	Reference
MEDOX® (Purified anthocyanins) a	320 mg/day	12 weeks	160 subjects with prediabetes or early untreated T2DM (40–75 years; 54 males and 106 females)	Randomized, double-blind, placebo-controlled trial	-↓ HbA1c, LDL-c, and ApoB; -↑ ApoA1; -↓ insulin resistance; -More effective at improving glycemic control, insulin sensitivity, and lipids profile among patients with elevated metabolic markers.	[68]
MEDOX® (Purified anthocyanins) a	320 mg/day	12 weeks	138 subjects with prediabetes or newly diagnosed T2DM (40–75 years; 45 males and 93 females)	Randomized, double-blind, placebo-controlled trial	-↑ adipsin and ApoA1; -↓ visfatin, HbA1c, C-peptide, C-peptide index, and ApoB.	[69]
MEDOX® (Purified anthocyanins) a	320 mg/day	12 weeks	121 patients with fasting hyperglycemia (average age: 61 years old; 42 males and 79 females)	Randomized controlled trial	-↑ IGFBP-4 fragments; -↓ FGB and postprandial C-peptide; -↓ LDL-c and ApoB.	[70]
MEDOX® (Purified anthocyanins) a	320 mg/day	4 weeks	14 healthy (35.2 ± 3.16 years old; 8 males and 6 females), 14 T2DM at-risk (50.1 ± 3.15 years old; 8 males and 6 females), and 12 T2DM (57.7 ± 2.5 years old; 8 males and 4 females) individuals	Open-label design	-↓ FGB, LDL-c, and uric acid in the T2DM at-risk group; -↓ IL-6, IL-18, and TNF-α in the T2DM group.	[71]
MEDOX® (Purified anthocyanins) a	20, 40, 80, 160, and 320 mg/day	14 days	111 healthy adults (18–35 years old; 39 males and 72 females)	Randomized, double-blind, placebo-controlled trial	-↓ FBG; -↓ IL-6, IL-10, and 8-iso-PGF2α; -IL-10 and 8-iso-PGF2α decreased with increasing anthocyanin dose.	[72]
MEDOX® (Purified anthocyanins) a	40, 80, and 320 mg/day	12 weeks	169 dyslipidemic subjects (35–70 years old; 45 males and 124 females)	Randomized, double-blind, placebo-controlled trial	-↑ SOD activity in the high dose group after 6 weeks (320 mg/day); -IL-6, TNF-α, 8-iso-PGF2α, 8-OHdG, and MDA decreased with increasing anthocyanin dose.	[65]
MEDOX® (Purified anthocyanins) a	40, 80, and 320 mg/day	12 weeks	176 dyslipidemic subjects (35–70 years old; 46 males and 130 females)	Randomized, double-blind, placebo-controlled trial	-↓ plasma levels of 6 ceramide species (Cer 16:0, 18:0, 20:0, 22:0, 24:0 and 24:1) in a dose-dependent manner; -Cer 16:0 and Cer 24:0 reduction was correlated with the decreases in non-HDL-c, ApoB and TC in the high dose group (320 mg/day).	[73]
MEDOX® (Purified anthocyanins) a	40, 80, and 320 mg/day	12 weeks	176 dyslipidemic subjects (57.41 ± 7.95 years old; 46 males and 130 females)	Placebo-controlled, double-blind, randomized trial with multiple doses	-↑ cholesterol efflux capacity, HDL-c, and ApoA1 in the high dose group (320 mg/day); -Cholesterol efflux capacity, HDL-c, and ApoA1 increased with increasing anthocyanin dose.	[74]
MEDOX® (Purified anthocyanins) a	320 mg/day	24 weeks	150 hypercholesterolemic subjects (40–65 years old; 63 males and 87 females)	Randomized, double-blind, placebo-controlled trial	-↓ NAP-2, ENA-78, IL-8, SDF-1α, and MCP-1; -↓ LDL-c; -↑ HDL-c; -↓ hs-CRP, IL-1β, and soluble P-selectin.	[75]
MEDOX® (Purified anthocyanins) a	320 mg/day	4 weeks	12 lean (33.0 ± 3.2 years old; 6 males and 6 females), 9 overweight (49.9 ± 4.2 years old; 5 males and 4 females), and 8 obese (43.3 ± 4.5 years old; 4 males and 4 females) participants	Clinical trial	-↓ MCP-1 across all groups; -↓ IL-6 in the obese group; -Trend for reducing TNF-α across all groups.	[76]
MEDOX® (Purified anthocyanins) a	320 mg/day	4 weeks	51 subjects (25 normal subjects (38.2 ± 2.7 years old; 13 males and 12 females) and 26 MetS subjects (56.6 ± 2.6 years old; 14 males and 12 females))	Clinical trial	-↓ FBG, TG, and LDL-c in the MetS group; -↓ hs-CRP in the MetS group; -↓ ADP-induced platelet activation (↓ P-selectin expression) in the MetS group.	[77]
MEDOX® (Purified anthocyanins) a	320 mg/day	4 weeks	35 subjects (15 normal subjects (37.3 ± 2.9 years old; 10 males and 5 females) and 20 MetS subjects (56.2 ± 2.9 years old; 11 males and 9 females))	Clinical trial	-↓ FBG, TC, TG, and LDL-c in the MetS group; -↑ PPAR-γ expression in the MetS group; -↓ hs-CRP, TNF-α, IL-6, and IL-1A in the MetS group; -↓ COX-2 and PECAM-1 in both groups; -↑ SOD in the MetS group.	[78]
MEDOX® (Purified anthocyanins) a	320 mg/day	4 weeks	26 pro-thrombotic overweight and obese individuals (39 ± 11 years old; 9 males and 17 females)	Randomized, double-blind, placebo-controlled, crossover design dietary intervention trial	-↓ ADP-induced platelet activation-related conformational change and degranulation (↓ PAC-1 and P-selectin expression); -↓ thrombogenic progression (↓ monocyte-platelet aggregate formation and PECAM-1 expression); -↓ platelet aggregation, collagen, and arachidonic acid.	[79]
MEDOX® (Purified anthocyanins) a	320 mg/day	4 weeks	16 sedentary pro-thrombotic individuals (38 ± 12 years old; 3 males and 13 females)	Randomized, double-blind, placebo-controlled, cross-over design dietary intervention trial	-↓ ADP-induced platelet activation-related conformational change and degranulation (↓ PAC-1 and P-selectin expression); -↓ thrombogenic progression (↓ monocyte-platelet aggregate formation and PECAM-1 expression).	[80]
MEDOX® (Purified anthocyanins) a	320 mg/day	16 weeks	27 individuals with MCI (n = 8) or stable non-obstructive coronary artery disease (n = 19) (55–70 years old; 18 males and 9 females)	Open-label study	-↓ RANTES; -Improved verbal memory function (learning, recall, and recognition) and cognitive speed.	[81]
Anthocyanins-rich blackcurrant extract	150, 300, and 600 mg	Acute	14 men and 9 postmenopausal women (46 ± 14 years old) consuming a high-carbohydrate meal	Randomized, double-blind, crossover trial	-↓ postprandial glycemia, serum insulin, and serum GIP in the high dose group (600 mg).	[82]
Anthocyanins-rich blackcurrant extract	3.2 mg/kg/day (~240 mg/day)	5 weeks	34 healthy individuals (38 ± 11 years old; 21 males and 13 females)	Double-blind placebo-controlled trial design	-↓ post-exercise-induced MDA and plasma ROS-generating capability; -↓ post-exercise plasma TNF-α and IL-6; -↑ post-exercise plasma IL-10; -↑ salivary mucosal anti-bacterial defense proteins (BD2 and secretory IgA).	[66]
Anthocyanins-rich black soybean testa extract	31.45 mg/day	8 weeks	63 overweight or obese individuals (30.59 ± 9.25 years old; 50 males and 30 females)	Randomized, double-blinded, placebo-controlled clinical trial	-↓ waist circumference, hip circumference, TG, LDL-c, and non-HDL-c; -↓ TC/HDL-c and LDL-c/HDL-c.	[83]
Anthocyanins-rich Queen Garnet plum juice	200.8 mg/day	4 days	16 overweight subjects (65.9 ± 6.0 years old; 3 males and 13 females) consuming a high-fat high energy meal	Crossover, randomized, controlled, double-blind clinical trial	-↑ 2 h postprandial flow-mediated dilatation and microvascular post-occlusive reactive hyperemia; -↓ hs-CRP and IL-6.	[84]
Anthocyanins-rich Queen Garnet plum juice	47 and 201 mg/day	8 weeks	31 subjects with MCI (75.3 ± 6.9 years old; 12 males and 19 females)	Randomized, controlled, double-blind clinical trial	-↓ TNF-α in the high dose group (201 mg/day).	[85]
Anthocyanins from blueberry	258 mg/day	16 weeks	37 older adults with MCI (≥68 years old; 17 males and 20 females)	Randomized, double-blind, parallel groups, placebo-controlled trial	-Improved semantic access and visual-spatial memory; -Trend for enhanced psychomotor speed of processing; -Cognitive benefits were correlated with parent anthocyanin compounds.	[86]
Anthocyanins-rich black rice extract	19.08 mg/day	12 weeks	48 subjects with subjective memory impairment (63.88 ± 7.59 years old; 16 males and 32 females)	Double-blind randomized, placebo-controlled trial	-Improved subjective memory; -Trend for improving cognitive function.	[87]
Anthocyanins-rich cherry juice	138 mg/day	12 weeks	49 older adults with mild-to-moderate dementia (≥70 years old; 25 males and 24 females)	Randomized controlled clinical trial	-Improved verbal fluency, short-term memory, and long-term memory; -↓ Systolic blood pressure.	[88]
Anthocyanins-rich bilberry extract	840 mg/day	6 weeks	13 patients with current mild-to-moderate ulcerative colitis (19–61 years old; 10 males and 3 females)	Open, prospective, non-blinded, and non-controlled pilot trial	-↓ IFN-γ-receptor 2, IFN-γ, and TNF-α expression in the colon; -↓ phosphorylated (activated) p65-NF-κB in the colon; -↓ STAT1 expressing cells; -↓ serum MCP-1 and TNF-α; -↓ Th17-specific cytokine protein expression (IL-22) in the colon; -↑ IL-10 expression in the colon.	[67]
Anthocyanins-rich blackcurrant extract	210 mg/day	7 days	14 older adults (73.3 ± 1.7 years old; 6 males and 8 females)	Randomized, double-blind, placebo-controlled, crossover design study	-↓ carotid-femoral pulse-wave velocity, central blood pressure, brachial systolic blood pressure, brachial mean blood pressure, brachial pulse pressure, and augmentation index.	[89]
Anthocyanins-rich red fruit juice b	205.5 mg/day	8 weeks	57 healthy male volunteers (20–50 years old)	Prospective, randomized, placebo-controlled parallel design	-↑ NQO-1 and HO-1 transcript levels in peripheral blood lymphocytes; -Modified microbial community; -↑ relative abundance of beneficial bacteria Adlercreutzia; -Potentially harmful taxa were not enriched.	[90]
Anthocyanins-rich aronia extract	30 mg/day	12 weeks	66 healthy male volunteers (18–45 years old)	3-arm, randomized, double-blind, placebo-controlled, parallel trial	-↑ flow-mediated dilation; -Modulated gut microbiota composition; -↑ growth of butyrate-producing bacteria Anaerostipes.	[91]
Anthocyanins-rich bilberry extract	88.5 mg/day	12 weeks	109 healthy adults (20–60 years old; 34 males and 75 females)	Randomized, double-blind, placebo-controlled, parallel-group comparison trial	-↓ post-visual display terminal load HFC-1; -Ameliorated and relieved the tonic accommodation of ciliary muscles caused by visual display terminal tasks and near-vision tasks.	[92]
Delphinol® (Purified anthocyanins) c	60 mg/day	8 weeks	16 healthy female subjects (27–57 years old)	Randomized, double-blind, placebo-controlled pilot study	-↑ skin brightness and collagen content; -↓ facial skin redness.	[93]

Where: ↓ indicates reduction; ↑ indicates increase; 8-iso-PGF_2α, 8-iso-prostaglandin F_2α; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; ADP, adenosine diphosphate; Apo, apolipoproteins; BD2, beta-defensin 2; COX-2, cyclooxygenase 2; ENA-78, epithelial neutrophil-activating peptide; FBG, fasting blood glucose; GIP, glucose-dependent insulinotropic polypeptide; HbA1c, glycated hemoglobin A1c; HDL-c, high-density lipoprotein cholesterol; HFC-1, high-frequency component 1; HO-1, heme oxygenase 1; hs-CRP, high-sensitivity C-reactive protein; IFN-γ, interferon-gamma; IgA, immunoglobulin A; IGFBP-4, insulin-like growth factor binding protein 4; IL, interleukins; LDL-c, low-density lipoprotein cholesterol; MCI, mild cognitive impairment; MCP-1, monocyte chemoattractant protein 1; MDA, malonaldehyde; MetS, metabolic syndrome; NAP-2, neutrophil-activating peptide 2; NF-κB, nuclear factor-kappa B; NQO-1, NAD(P)H quinone oxidoreductase 1; PAC-1, procaspase 1; PECAM-1, platelet endothelial cell adhesion molecule 1; PPAR-γ, peroxisome proliferator-activated receptor gamma; RANTES, regulated on activation, normal T-cell expressed and secreted; ROS, reactive oxygen species; SDF-1α, stromal cell-derived factor 1-alpha; SOD, superoxide dismutase; STAT1, signal transducer and activator of transcription 1; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TG, triglycerides; TNF-α, tumor necrosis factor-alpha. ^a The MEDOX^® food supplement capsules (Medapalett Pharmaceuticals, Biolink, Sandnes, Norway) contain purified anthocyanins isolated from bilberries (Vaccinium myrtillus) and blackcurrant (Ribes nigrum) (33.0% of 3-Ο-β-glucosides, 3-Ο-β-galactosides, and 3-Ο-β-arabinosides of cyanidin; 58.0% of 3-Ο-β-glucosides, 3-Ο-β-galactosides, and 3-Ο-β-arabinosides of delphinidin; 2.5% of 3-Ο-β-glucosides, 3-Ο-β-galactosides, and 3-Ο-β-arabinosides of petunidin; 2.5% of 3-Ο-β-glucosides, 3-Ο-β-galactosides, and 3-Ο-β-arabinosides of peonidin; 3.0% of 3-Ο-β-glucosides, 3-Ο-β-galactosides, and 3-Ο-β-arabinosides of malvidin; and 1.0% of 3-Ο-rutinoside of cyanidin and delphinidin). ^b The anthocyanins-rich red fruit juice (Eckes-Granini GmbH, Niederolm, Germany) was produced from red grape juice, lingonberry juice from concentrate, apple, blueberry, and strawberry puree, Aronia juice from concentrate, and acerola puree (100% fruit content). The total anthocyanin content of red fruit juice was 274 mg/L, comprising 33% of malvidin-3-glucoside, 14.3% of cyanidin-3-galactoside, 11.6% of peonidin-3-glucoside, 10.3% of petunidin-3-glucoside, 7.7% of delphinidin-3-glucoside, 6.8% of cyanidin-3-arabinoside, 6.4% of cyanidin-3-glucoside, 3.8% of delphinidin-3-arabinoside, 2.5% of malvidin-3-galactoside, 2% of petunidin-3-galactoside, and 1.6% of delphinidin3-galactoside. ^c The Delphinol^® food supplement capsules (Oryza Oil & Fat Chemical Co., Ltd., Aichi, Japan) contain purified anthocyanins isolated from maqui berry (Aristotelia chilensis). Each capsule contains ≥ 35% anthocyanin glycosides and ≥25% delphinidin glycosides.