Cyanidin

Other Names

1-Benzopyrylium, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-, chloride2-(3,4-Dihydroxyphenyl)-1-benzopyrylium-3,5,7-triol2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy-1-benzopyrylium2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxychromenylium2-(3,4-Dihydroxyphenyl)chromene-3,5,7-triol2-(3,4-Dihydroxyphenyl)chromenylium-3,5,7-triol3,3′,4,5,7-Pentahydroxyflavylium cation3,3′,4′,5,7-Pentahydroxy-2-phenylbenzopyrylium chloride3,3′,4′,5,7-Pentahydroxyflavylium3,3′,4′,5,7-Pentahydroxyflavylium chloride3,5,7,3′,4′-PentahydroxyflavyliumcianidinaCyanidin cationCyanidin chlorideCyanidin(1+)CyanidineCyanidolCyanidol chlorideCyndFlavylium, 3,3′,4′,5,7-pentahydroxy-

Synopsis

Cyanidin: A Comprehensive Reference

1. Identity, Chemical Characterization, and Natural Sources

Chemical Identity and Nomenclature

Cyanidin is a naturally occurring anthocyanidin — the aglycone (sugar-free) form of a class of plant pigments known as anthocyanins. Its systematic chemical name is 2-(3,4-dihydroxyphenyl)chromenylium-3,5,7-triol. Anthocyanins belong to the flavonoid group of phenolic compounds, and the basic structure of their parent nucleus is a highly conjugated 2-phenylbenzopyran cation, in which two benzene rings are connected by three carbon atoms to form a C6–C3–C6 skeleton. The hallmark of cyanidin specifically is the presence of hydroxyl groups at positions 3 and 4 of the B-ring (catechol group), which confers particularly high antioxidant activity.

Currently, over 550 types of anthocyanidins are recognized, of which six are widely distributed in plants: cyanidin, delphinidin, pelargonidin, peonidin, malvidin, and petunidin — accounting for approximately 50%, 12%, 12%, 12%, 7%, and 7% of the anthocyanidin content in nature, respectively. Cyanidin is thus the single most abundant anthocyanidin in nature.

The color and stability of these pigments are influenced by pH, light, temperature, and structure. In acidic conditions, anthocyanins appear red, but turn blue when the pH increases. More specifically, cyanidin's color varies depending on the pH level of the solution: it is red when pH is below 3, blue at pH higher than 11, and violet at neutral pH.

Natural Botanical Sources

Anthocyanins are natural water-soluble pigments commonly found in the sap of plant cells, and they are the main factors underlying the red, blue, and purple colors of certain vegetables, fruits, and grains. Anthocyanins are naturally present in a wide range of plant tissues, including flowers, fruits, leaves, roots, and stems, where they work as pigments providing cyanic colors.

Cyanidin-based glycosides are found across a remarkably broad range of food plants. Dietary sources of anthocyanins include red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants. More specifically:

Elderberry (Sambucus nigra): Elderberries are rich in anthocyanins, the majority of which include cyanidin-3-glucoside and cyanidin-3-sambubioside, found in elderberry juice and polar extracts. The anthocyanin content of elderberries is one of the highest among common commodities.
Bilberry (Vaccinium myrtillus): Anthocyanosides in bilberry are composed of an aglycone bound to one of three glycosides (arabinoside, glucoside, or galactoside). Bilberry contains five aglycones that bind to glycosides forming more than 15 different anthocyanosides, including C-3 glucosides of delphinidin, malvidin, pelargonidin, cyanidin, and petunidin.
Plum: Studies from a large number of plum cultivars reveal that cyanidin-3-rutinoside is the predominant anthocyanin, along with its 3-glucoside.
Pomegranate: Cyanidin-3,5-diglucoside, cyanidin-3-glucoside, delphinidin-3,5-diglucoside, delphinidin-3-glucoside, and pelargonidin-3-glucoside have been identified as major anthocyanins in pomegranate juice.
Red cabbage (Brassica oleracea): Red cabbage anthocyanins are a complex assortment of structurally similar species, consisting of a characteristic cyanidin-3-diglucoside-5-glucoside scaffold, with a variety of caffeic, p-coumaric, sinapic, and ferulic acid acyl partners typically modifying the 3-C glucosyl units to yield structurally diverse anthocyanins.
Rosehip, saskatoon berry, and black beans: Cyanidin-3-rutinoside and 3-diglucoside are anthocyanins identified in rosehip. The major anthocyanins found in saskatoon berries were the 3-galactoside, 3-glucoside, and 3-arabinoside of cyanidin. Cyanidin-3-O-glucoside has been found to be the only anthocyanin to persist after cooking of black turtle beans.

Cyanidin can be found in great abundance in berries such as raspberry, bilberry, blackberry, blueberry, cranberry, elderberry, hawthorn, and loganberry. Other fruits such as apples, peaches, plums, and pears are also excellent sources. The fruits' skins generally contain the highest cyanidin concentration.

Principal Glycosylated Forms

In nature, cyanidin is almost never found in its free aglycone form. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form O-β-glucoside derivatives. The most studied glycoside is cyanidin-3-O-glucoside (C3G, also known by its trivial name chrysanthemin). C3G is soluble in water and belongs to the monomeric anthocyanin class, a category of flavonoids; it is derived from the cyanidin aglycone and is often present in dark-colored plants, fruits, and vegetables. Other important glycosides include cyanidin-3-galactoside, cyanidin-3-arabinoside, cyanidin-3-rutinoside, and cyanidin-3-sambubioside.

2. Traditional and Historical Use

Anthocyanins have been used in traditional medicine in many cultures for a long time. Because cyanidin is not isolated as a pure compound in traditional practice, its historical use is best understood through the traditional medicinal applications of the plants richest in cyanidin-based pigments — principally bilberry and elderberry.

Bilberry in European Tradition

Bilberries have enjoyed a long history as both food and medicine. Since they have high nutritive value, rich juice, and miniature seeds, they have long been used to make jams and jellies. Bilberry has many traditional medicinal uses, a number of which have been supported by fairly extensive pharmacological research. The fruit was traditionally consumed in dried, juice, or decoction form across Northern and Central Europe. Both the bilberry fruit and the leaves are used medicinally. The fruit is often used in the forms of decoctions, liquid extracts, and tablets, while the leaf is usually prepared as a tea.

Anthocyanin treatment is known to improve night vision. In World War II, British Air Force pilots reportedly consumed blueberry jam during night flights to obtain clear night vision. While this anecdote is often repeated, the clinical evidence for this specific use has since been scrutinized (see Section 5, Ocular Health).

Elderberry in European and Indigenous Traditions

Traditional folk medicine holds the elderberry plant in high regard and it has been known for its many dietetic and medicinal values throughout history. Both its flowers and fruit have been used for jelly, wine, juice, and coloring. Elderberry has been utilized as a food, a wine, a dye, and for a variety of medicinal applications, especially with symptoms presenting as the onset of a cold or flu.

Indigenous peoples of North America maintained extensive traditions surrounding elderberry. Elderberry is described as one of the most important traditional medicines in certain Indigenous communities, with all parts of the plant — roots, wood, berry, and flower — harvested at specific times of year. For the Northern Foothill Yokuts, the elderberry harvest in August coincided with the time to harvest sugar pine nuts, reflecting its central role in seasonal rhythms.

3. Key Constituents and Active Compounds

When cyanidin-rich botanical preparations are consumed, cyanidin itself (as its various glycosides) constitutes the principal bioactive. However, the parent plants also contain additional polyphenols. For example, bilberry fruit also contains catechin, epicatechin, condensed tannins, and oligomeric procyanidins (procyanidin B1–B4) in addition to its anthocyanosides. Elderberries are additionally a rich source of flavanols, phenolic acids, and procyanidins.

Cyanidin is standardly expressed and quantified as its chloride salt form in pharmacopoeial contexts. The British Pharmacopoeia and European Pharmacopoeia (BP/EP) specify a minimum of 0.30% anthocyanins expressed as cyanidin-3-glucoside chloride for fresh bilberry fruits, determined by absorption measurements at 528 nm on an acidified aqueous extract.

4. Mechanisms of Action

4.1 Antioxidant Activity and Free Radical Scavenging

Health benefits of anthocyanins have been widely described, especially in the prevention of diseases associated with oxidative stress, such as cardiovascular and neurodegenerative diseases. Among various common plant-derived polyphenolic flavonoids, cyanidin has one of the highest antioxidant activities. Cyanidin's antioxidant potency arises from the free hydroxyl groups on its B-ring, which readily donate hydrogen atoms or electrons to reactive oxygen species. The catechol B-ring with its ortho-dihydroxy arrangement is central to this activity; the resulting radical intermediate is stabilized by extensive electron delocalization across the flavylium cation structure.

4.2 Modulation of Nrf2 and NF-κB Signaling Pathways

Two master transcription factors — nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) — are central to how cyanidin exerts its antioxidant and anti-inflammatory effects. Cyanidin treatment not only increases Nrf2 transcription and expression, but also decreases NF-κB signaling. Molecular docking simulation has indicated that cyanidin has high affinity for Keap1 and NF-κB/p65, which may promote nuclear translocation of Nrf2 and inhibit that of NF-κB. By activating Nrf2, cyanidin upregulates downstream cytoprotective enzymes, including superoxide dismutase (SOD), catalase, and glutathione peroxidase. Total antioxidant capacity and the activity of superoxide dismutase, catalase, and glutathione peroxidase are increased, while the content of malondialdehyde, lipid peroxide, TNF-α, IL-1β, and IL-6 are decreased.

Cyanidin chloride suppresses NF-κB signaling and induces activation of the Nrf2 pathway in TNF-α-stimulated cancer cells. Nrf2 and NF-κB are two key transcription factors regulating antioxidative responses and cellular proliferation, respectively; knockdown of Nrf2 by siRNA transfection inhibited the effect of cyanidin on NF-κB signaling and apoptosis, suggesting functional crosstalk between Nrf2 and NF-κB.

4.3 Anti-Inflammatory Mechanisms

Anti-inflammatory activity of anthocyanins is mediated by modulation of various inflammatory cytokines or mediators such as IL-1, IL-6, IL-10, TNF-α, NF-κB, and COX-2. Cyanidin-3-glucoside (C3G) can attenuate LPS-induced pro-inflammatory cytokine production and plaque formation by inhibiting the activation of the NF-κB pathway and p65 translocation.

4.4 Antiproliferative and Apoptosis-Inducing Mechanisms

Pure anthocyanins and anthocyanin-rich extracts from fruits and vegetables have exhibited anti-proliferative activity towards multiple cancer cell types in vitro. Cell proliferation is inhibited by the ability of anthocyanins to block various stages of the cell cycle via effects on cell cycle regulator proteins (e.g., p53, p21, p27, cyclin D1, cyclin A). Anthocyanidins appear to be more potent inhibitors of cell proliferation than their glycosylated counterparts. Cyanidins also possess antiproliferative effects and apoptosis induction properties, which are part of their anticancer mechanisms of action. Anthocyanins have significant potential as anticancer agents due to their antioxidant properties, ability to induce apoptosis, inhibit cancer cell proliferation, inhibit angiogenesis, and reduce metastasis.

4.5 Gut Microbiota Interaction and Metabolite Generation

Following consumption, anthocyanin absorption occurs along the gastrointestinal tract, with the distal lower bowel being the place where most of the absorption and metabolism occurs. In the intestine, anthocyanins first undergo extensive microbial catabolism followed by absorption and human phase II metabolism. This produces hybrid microbial-human metabolites which are absorbed and subsequently increase the bioavailability of anthocyanins.

C3G engages in bidirectional interactions with the gut microbiota. It alters microbial composition and undergoes bacterial enzymatic metabolism to generate phenolic derivatives, including protocatechuic acid (PCA), which demonstrate enhanced systemic bioavailability and bioactivity. C3G and its microbial metabolite PCA have been shown to increase the ability of human adipocytes to remove plasma glucose by upregulating GLUT4. C3G and PCA treatments to adipocytes resulted in increased activity of adiponectin and peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear transcription factor involved in glucose disposal and glucose transporter regulation.

4.6 Rhodopsin Regeneration in the Eye

A specific mechanism relevant to visual function involves rhodopsin, the photosensitive pigment in retinal rod cells. Cyanidin 3-glycosides have been shown to have a stimulatory effect on the regeneration of rhodopsin in studies published in the Journal of Agricultural and Food Chemistry, providing a molecular basis for observed ocular effects.

5. Scientific Evidence by Health Area

5.1 Cardiovascular Health

Lipid profiles (human/clinical evidence — moderate strength): In a human study, mixed anthocyanins from bilberry and blackcurrant were given as an extract of 320 mg/day for 12 weeks to 60 middle-aged dyslipidemic Chinese subjects. Results showed significant improvements in LDL-cholesterol (average decrease of approximately 14%) and HDL-cholesterol (average increase of approximately 14%). No significant changes were seen in plasma total cholesterol, triglycerides, or apolipoproteins, but the plasma concentration of cholesteryl ester transfer protein (CETP) was significantly decreased, and the change in CETP correlated with changes in lipids. An in vitro study by the same group showed that cyanidin-3-O-glucoside lowered CETP activity in human HepG2 cells, and the researchers concluded that the bilberry and blackberry anthocyanin mixture improved lipids in human subjects by inhibiting CETP activity and changing cellular cholesterol efflux.

Blood pressure and vascular effects (preclinical evidence): Bilberry fruit anthocyanins have been reported to inhibit smooth muscle contraction and platelet aggregation, representing potentially antithrombotic and antihypertensive effects. Possible antihypertensive effects of bilberry are also suggested by the finding of inhibition of angiotensin-converting enzyme (ACE) activity in cells in vitro.

Myocardial effects (animal evidence): Cyanidin-3-O-glucoside (CG) is a polyphenol with potential health benefits; investigations have examined the cardioprotective effects of CG in an animal model of myocardial infarction (MI). Sham and MI rats were administered CG (10 mg/kg/day) daily for one week prior to surgery and 8 weeks post-surgery; echocardiography was performed to assess cardiac structure and function at 4 and 8 weeks. These findings are preclinical only and cannot be directly extrapolated to humans.

5.2 Metabolic Health, Obesity, and Type 2 Diabetes

Animal models (strong preclinical evidence, weak human evidence): Increased consumption of dark-coloured fruits and vegetables may mitigate metabolic syndrome. Studies have determined changes in metabolic parameters, and in cardiovascular and liver structure and function, following chronic administration of cyanidin-3-glucoside or Queen Garnet plum juice containing cyanidin glycosides in rats fed either a corn starch or a high-carbohydrate, high-fat diet. High-carbohydrate, high-fat rats developed signs of metabolic syndrome including visceral adiposity, impaired glucose tolerance, hypertension, cardiovascular remodelling, increased collagen deposition in the left ventricle, non-alcoholic fatty liver disease, increased plasma liver enzymes, and increased inflammatory cell infiltration in the heart and liver. Both cyanidin-3-glucoside and Queen Garnet plum juice reversed these cardiovascular, liver, and metabolic signs.

Gut microbiota and insulin resistance (animal evidence): Male C57BL/6J mice received HFHS + C3G (7.2 mg/kg/day, equivalent C3G in Saskatoon berry powder) diet for 11 weeks. The HFHS diet significantly increased plasma levels of glucose, cholesterol, triglycerides, insulin resistance, and inflammatory markers. The HFHS + Saskatoon berry powder diet increased the Bacteroidetes/Firmicutes ratio and relative abundance of Muriculaceae family bacteria in mouse feces. The HFHS + Saskatoon berry powder or HFHS + C3G diet attenuated glucose, lipids, insulin resistance and inflammatory markers, and increased the B/F ratio compared to the HFHS diet alone. These are animal data and require confirmation in human trials.

5.3 Ocular Health

Night vision (weak/inconsistent human evidence): In a systematic review of 30 clinical studies examining the bilberry effect on vision in reduced light conditions, Canter and Ernst found that testing of psychophysical outcome parameters was weak evidence due to a lack of strict study designs (e.g., non-randomized or non-placebo controlled trials).

Visual fatigue and accommodative function (small RCT evidence): A randomized, placebo-controlled, double-blind, parallel-group comparison study involved 32 healthy Japanese adults with eye fatigue after using visual display terminals (VDTs). Subjects were randomly allocated into either the active group receiving bilberry-derived anthocyanin (43.2 mg per capsule) or a placebo group, consuming one capsule once a day for 6 weeks. Consumption of the supplement containing anthocyanins extracted from bilberry for 6 weeks inhibited the decrease in accommodative function caused by oxidative stress due to VDT use. This was a small, single-center study; broader replication is needed.

Normal tension glaucoma (retrospective evidence): A study was performed to evaluate the effect of anthocyanins on visual function in patients with normal tension glaucoma (NTG). Retrospective analysis was carried out by a chart review of 332 subjects (209 men and 123 women) who were treated with anthocyanins (n = 132), ginkgo biloba extract (n = 103), or no medication (control, n = 97). This was a retrospective design with inherent confounders.

Venous/microcirculatory effects (uncontrolled trial evidence): A study of 47 patients with various venous diseases, giving 480 mg/day of bilberry extract, resulted in reduced capillary flow as well as elimination of microstagnation and blood stasis of the foot. A review of uncontrolled trials from 1979 to 1985 on a total of 568 patients with venous insufficiency of the lower limbs showed that anthocyanins were effective in decreasing symptoms and improving both venous microcirculation and lymph drainage. These are uncontrolled trials and evidence strength is accordingly limited.

5.4 Cancer Prevention and Anticancer Properties

Overall evidence characterization: predominantly in vitro and animal; no confirmed human clinical evidence for direct anti-tumour effects.

Anthocyanins have significant potential as anticancer agents due to their antioxidant properties, ability to induce apoptosis, inhibit cancer cell proliferation, inhibit angiogenesis, and reduce metastasis. Studies carried out in A549 and H1299 lung cancer cells, as well as in vivo in mice, confirm antiproliferative effects on lung cancer cells, reduction of tumor size, and suppression of cancer migration. Key proteins involved include MMP-2, MMP-9, COX-2, C-myc, cyclin D1, β-catenin, cyclin B, pERK, and VEGF, with apoptosis promoted by Bcl-2 and PARP.

In colorectal cancer cells specifically, cyanidin chloride treatment induced apoptosis as well as significant inhibition of cellular proliferation and colony formation in three colon cancer cell lines (HCT116, HT29, and SW620). In melanoma cells, elderberries are known for their high anthocyanins content, which have been shown to possess anti-proliferative and anti-cancer effects. An anthocyanin-enriched extract was obtained from elderberries and characterized by LC/DAD/ESI-MS analysis; five cyanidin-based anthocyanins were identified, among which cyanidin-3-O-sambubioside was the major compound (51%). This extract inhibited proliferation of metastatic B16-F10 murine melanoma cells in a concentration-dependent manner, with an IC50 of 264.3 μg/mL.

Clinical trials are needed to validate the potential anticancer activities of anthocyanins before clinical use. It is critical to note that in vitro IC50 values and animal models do not establish efficacy in humans, particularly given the low bioavailability of cyanidin when taken orally.

5.5 Neuroprotection and Cognitive Function

Evidence: largely in vitro and animal; no robust human clinical trials for direct cyanidin administration.

Inhibition of TLR4 by cyanidin in SK-N-SH neuroblastoma cells could be beneficial in preventing neuronal cell death in the process of Alzheimer's disease. However, this study is focused on cellular, biochemical, and molecular mechanisms in vitro; further study should investigate the protective effect of cyanidin in in vivo models.

In a mouse aging model, C3G dose-dependently enhanced total antioxidant capacity and activities of key antioxidant enzymes (GSH-Px and SOD), reduced malondialdehyde, and inhibited pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). These are animal data only.

5.6 Hepatoprotection

Evidence: animal models only. In an animal study, researchers evaluated the hepatoprotective ability of cyanidin and investigated its associated mechanisms. Cyanidin administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl4). High-dose cyanidin showed effects comparable to those achieved by the positive control (silymarin). Severe oxidative stress and inflammatory responses in the liver tissue induced by CCl4 were significantly mitigated by cyanidin supplementation.

5.7 Gastrointestinal / Peptic Ulcer

Evidence: primarily in vitro. The protective effect of cyanidin and C3G in alleviating peptic ulcer disease is primarily based on their antioxidant ability in in vitro studies. No robust human clinical trials specific to cyanidin and peptic ulcer disease have been reported.

6. Body Systems and Health Areas Associated with Cyanidin

Cardiovascular system: Lipid regulation, inhibition of platelet aggregation, angiotensin-converting enzyme inhibition, protection against myocardial ischemia (mainly preclinical).
Metabolic system: Modulation of insulin sensitivity, glucose transporter upregulation (GLUT4), improvement of adiponectin signaling, gut microbiota remodeling in the context of obesity and type 2 diabetes (animal evidence predominates).
Ocular system: Rhodopsin regeneration, accommodative function improvement, protective effects on retinal pigment epithelium (limited human and laboratory evidence).
Oncology: Antiproliferative and pro-apoptotic effects across multiple cancer cell lines, anti-angiogenic effects, modulation of cell cycle regulators (exclusively preclinical).
Central nervous system: Neuroprotection against amyloid-β toxicity, suppression of neuroinflammation via TLR4/NOX4/NF-κB pathways (preclinical).
Hepatic system: Protection against oxidative liver injury via Nrf2 activation and NF-κB suppression (preclinical).
Gastrointestinal system: Modulation of intestinal inflammation, protection of mucosal barrier integrity, promotion of beneficial gut microbiota diversity (animal and in vitro).

7. Bioavailability and Pharmacokinetics

Bioavailability is a critical limitation of cyanidin research. Evidence suggests that the consumption of anthocyanin-rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown.

The most definitive human pharmacokinetic study involved isotopically labeled C3G. Eight male participants consumed 500 mg isotopically labeled cyanidin-3-glucoside (¹³C5-C3G). Biological samples were collected over 48 hours, and ¹³C and ¹³C-labeled metabolite concentrations were measured by isotope-ratio mass spectrometry and liquid chromatography–tandem mass spectrometry. The mean percentage of ¹³C recovered in urine, breath, and feces was 43.9 ± 25.9% (range: 15.1–99.3% across participants). The relative bioavailability was 12.38 ± 1.38% (5.37 ± 0.67% excreted in urine and 6.91 ± 1.59% in breath).

Maximum rates of ¹³C elimination were achieved 30 minutes after ingestion, whereas ¹³C-labeled metabolites peaked at 10.25 ± 4.14 hours. The half-life for ¹³C-labeled metabolites ranged between 12.44 ± 4.22 and 51.62 ± 22.55 hours. Metabolites were identified as degradation products, phenolic, hippuric, phenylacetic, and phenylpropenoic acids. Anthocyanins are more bioavailable than previously perceived, and their metabolites are present in the circulation for up to 48 hours after ingestion.

The low intact-form bioavailability is modulated by the gut microbiome. The systemic bioavailability of anthocyanins was only 0.26–1.8% in animal studies when compared with intravenous administration. Anthocyanins are rapidly metabolized into several active metabolites by the host and/or gut microbiota, and evaluating their bioavailability is complex. The low bioavailability of anthocyanins causes the antiproliferative effect of anthocyanin extract to decrease in vivo.

8. Dosage Forms and Reported Dosages

Cyanidin is not typically administered as a purified compound in clinical or commercial practice; it is instead consumed through food or as standardized botanical extracts. Reported doses in research settings (stated as in the cited sources) include:

Mixed bilberry and blackcurrant anthocyanin extract: 320 mg/day for 12 weeks in a human trial involving 60 dyslipidemic subjects.
Bilberry-derived anthocyanin: 43.2 mg per capsule, one capsule per day for 6 weeks in a human RCT for eye function.
In an animal myocardial infarction model, cyanidin-3-O-glucoside was administered at 10 mg/kg/day for 1 week prior to surgery and 8 weeks post-surgery.
In a metabolic syndrome rat study, dosing of approximately 8 mg/kg/day cyanidin glycosides was used from week 8 to 16 of a 16-week feeding protocol.
In a gut microbiota/insulin resistance mouse study, C3G was administered at 7.2 mg/kg/day for 11 weeks.
In formal toxicology studies, 300 mg/kg cyanidin was administered orally for 14 days (acute, OECD 423), and 7.5, 15, and 30 mg/kg/day orally for 28 days (subacute, OECD 407) in Sprague-Dawley rats.
A study of 47 patients with venous diseases used 480 mg/day of bilberry extract.

No universally accepted human clinical dosage for purified cyanidin or C3G has been formally established by regulatory authorities as of the sources reviewed. All dosage figures above are from study-specific protocols.

9. Safety Considerations

Acute and Subacute Toxicology

Acute toxicity studies in rats (OECD 423) indicated an LD50 exceeding 300 mg/kg/day without adverse effects. Subacute toxicity at 7.5–30 mg/kg/day showed well-tolerated responses in both genders. No significant alterations in organ weights, hematological parameters, liver/kidney functions, or adverse histopathological findings were observed. Oral cyanidin administration demonstrated high safety and tolerance in rats, establishing a NOAEL at 30 mg/kg/day.

C3G is considered non-toxic within the range of regular dietary consumption. Safe intake levels (LD50) have been established in mice and rats at 25,000 mg/kg and 20,000 mg/kg, respectively, with no observed adverse effects; studies in rabbits administered anthocyanins orally (6 g/kg body weight) revealed no changes in blood pressure. C3G is considered safe and anti-mutagenic.

Pharmacokinetic Drug-Likeness

Pharmacokinetic analysis revealed that cyanidin showed good drug-likeness, fulfilled Lipinski's rule of five, and conferred favorable toxicity parameters.

Elderberry-Specific Safety Note

Although cyanidin in berries and extracts is considered safe, the elderberry plant itself warrants caution in unprocessed form. The seeds in the berries, stems, leaves, and roots contain the chemical cyanogenic glycoside sambunigrin, which metabolizes within the digestive tract with the help of bacteria into hydrogen cyanide, potentially leading to serious problems. This concern applies to raw, unprocessed plant material and not to commercial standardized extracts, which are processed to eliminate this risk.

Stability Limitations

The color and stability of these pigments are influenced by pH, light, temperature, and structure. The chemical instability of cyanidin glycosides under alkaline, high-temperature, and light-exposed conditions is a practical concern both for product formulation and for in vivo stability following ingestion, which in turn affects the achievable bioavailability of intact molecules at target tissues.

Overall Evidence Quality and Limitations

The bulk of the mechanistic and efficacy evidence for cyanidin derives from in vitro cell culture systems and animal models. Clinical trials are needed to validate the potential biological activities of anthocyanins before their use can be recommended for specific clinical indications. The low bioavailability of anthocyanins causes the effects observed in vitro to decrease substantially in vivo. Human trials examining anthocyanins typically use complex botanical extracts containing mixtures of anthocyanins, making attribution of effects to cyanidin specifically very difficult. The available human data — primarily from small, short-duration trials in defined populations — do not yet support firm conclusions about efficacy for most proposed health applications.

References

Health Conditions

Health conditions that Cyanidin may help support.

No conditions available.

Body Systems

Body systems that Cyanidin may help support.

No body systems available.