Delphinidin is a blue-purple anthocyanidin found in berries and dark fruits that provides exceptional antioxidant protection, anti-inflammatory benefits, and supports cardiovascular health, vision, and cellular defense against oxidative damage.
Alternative Names: Delphinidin-3-O-glucoside, Delphinidin-3-O-galactoside, Myrtillin, Delphin, Tulipanin
Categories: Anthocyanidin, Anthocyanin (when glycosylated), Flavonoid, Polyphenol, Plant Pigment, Antioxidant
Primary Longevity Benefits
- Potent antioxidant activity
- Anti-inflammatory effects
- Cardiovascular protection
- Neuroprotective properties
- Anti-cancer potential
Secondary Benefits
- Vision health enhancement
- Blood glucose regulation
- Improved insulin sensitivity
- Antimicrobial properties
- Gut microbiome modulation
- Skin protection from UV damage
Mechanism of Action
Delphinidin exerts its biological effects through multiple molecular mechanisms that contribute to its diverse health benefits. As a polyphenolic compound with a distinctive chemical structure featuring three hydroxyl groups in the B-ring (a tri-hydroxylated B-ring), delphinidin possesses unique properties that distinguish it from other anthocyanidins and contribute to its potent biological activities. The primary mechanisms through which delphinidin exerts its effects include: 1) Superior antioxidant activity: Delphinidin is one of the most potent antioxidants among anthocyanidins due to its tri-hydroxylated B-ring structure, which provides exceptional electron-donating capacity. It neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS) through multiple mechanisms including hydrogen atom transfer, single electron transfer, and metal ion chelation.
The presence of three hydroxyl groups in the B-ring creates an optimal structure for radical scavenging and metal chelation, making delphinidin particularly effective at preventing oxidative damage to cellular components including lipids, proteins, and DNA. In comparative studies, delphinidin consistently demonstrates higher antioxidant capacity than other anthocyanidins like cyanidin and malvidin. 2) Activation of endogenous antioxidant defense systems: Beyond direct antioxidant effects, delphinidin upregulates cellular antioxidant defenses by activating the Nrf2 (Nuclear factor erythroid 2-related factor 2) signaling pathway. Upon activation, Nrf2 translocates to the nucleus and binds to antioxidant response elements (AREs), promoting the expression of antioxidant and detoxifying enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1).
This indirect antioxidant effect provides more sustained protection against oxidative stress than direct radical scavenging alone and may contribute significantly to delphinidin’s long-term health benefits. 3) Anti-inflammatory effects: Delphinidin exhibits potent anti-inflammatory properties through inhibition of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway. By preventing the phosphorylation and degradation of IκB (inhibitor of κB), delphinidin blocks the nuclear translocation of NF-κB, thereby reducing the expression of pro-inflammatory genes and the production of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). Additionally, delphinidin inhibits the activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), further contributing to its anti-inflammatory effects.
Delphinidin also modulates MAPK (mitogen-activated protein kinase) signaling pathways, particularly p38 MAPK and JNK (c-Jun N-terminal kinase), which are involved in inflammatory responses. Research suggests that delphinidin may be more effective than other anthocyanidins at inhibiting inflammatory pathways, possibly due to its unique chemical structure. 4) Cardiovascular protection: Delphinidin improves endothelial function by enhancing nitric oxide (NO) bioavailability through multiple mechanisms. It activates endothelial nitric oxide synthase (eNOS) via the PI3K/Akt pathway, leading to increased NO production.
Simultaneously, delphinidin’s antioxidant effects reduce superoxide levels, preventing the formation of peroxynitrite and preserving NO bioavailability. Delphinidin also inhibits NADPH oxidase, a major source of vascular superoxide production. Additionally, delphinidin protects against LDL oxidation, a key step in atherosclerosis development, and modulates cholesterol metabolism by affecting the expression of genes involved in cholesterol synthesis, transport, and excretion. Delphinidin exhibits antiplatelet and antithrombotic effects by inhibiting platelet aggregation and adhesion, potentially reducing the risk of thrombotic events.
The tri-hydroxylated B-ring structure of delphinidin appears to be particularly important for its vascular effects, as comparative studies have shown that delphinidin has stronger effects on endothelial function than other anthocyanidins. 5) Anti-cancer potential: Delphinidin demonstrates anticancer properties through multiple mechanisms, including induction of cell cycle arrest and apoptosis in cancer cells via activation of p53, modulation of Bcl-2 family proteins, and activation of caspases. It inhibits cancer cell proliferation by suppressing various signaling pathways including PI3K/Akt/mTOR and MAPK/ERK. Delphinidin also inhibits angiogenesis by reducing VEGF (vascular endothelial growth factor) expression and matrix metalloproteinases (MMPs) activity, potentially limiting tumor growth and metastasis.
Furthermore, delphinidin exhibits epigenetic regulatory effects by inhibiting DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), potentially reversing aberrant epigenetic modifications associated with cancer. Research suggests that delphinidin may be particularly effective against certain cancer types, including colon, prostate, and breast cancer. The tri-hydroxylated B-ring structure appears to be important for its anticancer effects, as delphinidin often shows stronger antiproliferative and pro-apoptotic effects than other anthocyanidins in comparative studies. 6) Neuroprotective mechanisms: Delphinidin can cross the blood-brain barrier to a limited extent and exert neuroprotective effects through multiple mechanisms.
It reduces oxidative stress in neuronal cells, inhibits neuroinflammation by suppressing microglial activation, and prevents protein aggregation associated with neurodegenerative diseases. Delphinidin enhances brain-derived neurotrophic factor (BDNF) levels, supporting neuronal health and plasticity. It also modulates neurotransmitter systems, including dopaminergic, cholinergic, and GABAergic pathways, potentially improving cognitive function and mood. Additionally, delphinidin inhibits neuronal apoptosis through regulation of Bcl-2 family proteins and caspase activation.
The superior antioxidant capacity of delphinidin may make it particularly effective for neuroprotection, as oxidative stress is a key factor in many neurodegenerative conditions. 7) Metabolic regulation: Delphinidin enhances insulin sensitivity through activation of insulin signaling pathways and AMPK (AMP-activated protein kinase). It improves glucose uptake in skeletal muscle and adipose tissue by increasing GLUT4 translocation to the cell membrane. Delphinidin inhibits digestive enzymes such as α-amylase and α-glucosidase, slowing carbohydrate digestion and absorption, which helps regulate postprandial glucose levels.
It also protects pancreatic β-cells from oxidative stress-induced damage and may stimulate insulin secretion. Additionally, delphinidin modulates adipokine production and reduces adipose tissue inflammation, potentially contributing to improved metabolic health. 8) Vision health support: Delphinidin has specific benefits for ocular health, particularly for the retina. It improves retinal blood flow, protects retinal cells from oxidative damage, and may help maintain the integrity of the blood-retinal barrier.
Delphinidin’s ability to absorb blue light may also provide protection against light-induced retinal damage. Additionally, it may help regenerate rhodopsin, the photopigment essential for vision in low-light conditions. These effects may be particularly relevant for age-related macular degeneration and diabetic retinopathy. 9) Skin protection: Delphinidin provides protection against UV-induced skin damage through multiple mechanisms.
It absorbs UV radiation, scavenges ROS generated by UV exposure, and inhibits the expression of matrix metalloproteinases (MMPs) that degrade collagen and elastin. Delphinidin also reduces UV-induced inflammation and prevents DNA damage in skin cells. These effects may help prevent photoaging and reduce the risk of skin cancer. 10) Antimicrobial properties: Delphinidin exhibits antimicrobial activity against various pathogens, including certain bacteria, viruses, and fungi.
It may disrupt bacterial cell membranes, inhibit viral attachment and entry, and interfere with microbial enzymes. These effects may contribute to the potential benefits of delphinidin for urinary tract health and immune function. The bioactivity of delphinidin is influenced by its metabolism, with both the parent compound and its metabolites contributing to the observed health benefits. Delphinidin undergoes extensive metabolism in the gut and liver, producing various phenolic acids and phase II conjugates.
These metabolites may have distinct biological activities and contribute significantly to the overall effects of delphinidin. Additionally, the complex interplay between delphinidin and the gut microbiome adds another layer of complexity to its mechanism of action, as individual variations in gut microbiota composition may influence the metabolic fate of delphinidin and consequently its biological effects. It’s important to note that most research has been conducted using delphinidin glycosides (anthocyanins) rather than the aglycone form, as the glycosides are more stable and represent the form typically found in foods and supplements. The glycosylation pattern can influence the bioavailability and biological activity of delphinidin, with different glycosides potentially having distinct effects.
Optimal Dosage
Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.
Determining optimal dosages for delphinidin is challenging due to several factors, including its variable bioavailability, individual differences in metabolism, and the diverse sources from which
it can be obtained. Unlike single-compound pharmaceuticals, delphinidin is typically consumed as part of complex plant extracts or whole foods with varying delphinidin content and glycosylation patterns. For general health maintenance and antioxidant support, dietary intake of delphinidin-rich foods (bilberries, blackcurrants, maqui berries, etc.) is often recommended rather than isolated delphinidin supplements.
When supplemental forms are used, dosages typically range from 25-200 mg of delphinidin (usually as glycosides) daily, depending on the specific source and the intended health benefit.
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Cardiovascular health | 50-150 mg of delphinidin daily | Clinical studies showing cardiovascular benefits have typically used berry extracts providing approximately 50-150 mg of delphinidin daily. Effects on endothelial function, blood pressure, and vascular inflammation have been observed at these doses. Bilberry extract standardized to contain 25-36% anthocyanins (with delphinidin glycosides as major components) has shown benefits for vascular health in several studies. |
| Vision health | 30-120 mg of delphinidin daily | Bilberry extract standardized to contain 25-36% anthocyanins (with delphinidin glycosides as major components) has traditionally been used for vision support, particularly for night vision and eye fatigue. Clinical evidence suggests potential benefits at these doses with consistent use. Delphinidin’s specific effects on retinal blood flow and protection against light-induced damage may be particularly relevant for vision health. |
| Cognitive function/Neuroprotection | 50-200 mg of delphinidin daily | Limited clinical studies suggest benefits for cognitive parameters with doses in this range, particularly when using bilberry or blackcurrant extracts. Long-term consistent use (12+ weeks) may be necessary to observe significant cognitive benefits. Animal studies suggest neuroprotective effects at equivalent human doses within this range. |
| Anti-inflammatory support | 50-150 mg of delphinidin daily | May help reduce inflammatory markers with consistent use. Higher doses within this range may be more effective for acute inflammatory conditions, while lower doses may be sufficient for general anti-inflammatory support as part of a healthy lifestyle. |
| Antioxidant support | 25-100 mg of delphinidin daily | Lower doses may be sufficient when combined with a diet rich in other antioxidants. For targeted antioxidant support, doses in the higher end of this range may be more effective. Delphinidin has been shown to have particularly high antioxidant capacity compared to other anthocyanidins due to its tri-hydroxylated B-ring structure. |
| Blood glucose management | 50-150 mg of delphinidin daily | Limited clinical evidence suggests potential benefits for glucose metabolism at these doses. Effects may include improved insulin sensitivity, reduced postprandial glucose responses, and protection of pancreatic β-cells from oxidative stress. |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Children (under 12) | Not recommended as isolated supplements | Consumption through whole foods (berries, etc.) is preferable. No established supplemental dosage for this age group due to limited safety data. |
| Adolescents (12-18) | Not generally recommended as isolated supplements | Dietary sources preferred. If used for specific health conditions, dosing should be adjusted based on weight and under medical supervision. |
| Adults (18-65) | 25-200 mg of delphinidin daily | Dose depends on specific delphinidin source, health status, and therapeutic goals. Start with lower doses and increase gradually as needed. For general health maintenance, doses at the lower end of this range may be sufficient. |
| Seniors (65+) | 25-200 mg of delphinidin daily | May be particularly beneficial for cardiovascular, vision, and cognitive health in this age group. Start with lower doses and monitor for tolerability. Some research suggests seniors may benefit from doses in the higher end of this range for vision and cognitive support. |
| Pregnant/lactating women | Not recommended as isolated supplements | Moderate consumption of delphinidin-containing foods is generally considered safe, but concentrated supplements should be avoided due to insufficient safety data. |
By Source
| Source | Dosage | Notes |
|---|---|---|
| Bilberry extract | 80-480 mg of anthocyanins daily (320-1920 mg of extract standardized to 25% anthocyanins), providing approximately 25-150 mg of delphinidin glycosides | Traditionally used for vision health and vascular support. European studies have typically used 240-480 mg of anthocyanins daily for therapeutic effects. Bilberry contains a high proportion of delphinidin glycosides compared to other berry sources. |
| Blackcurrant extract | 100-300 mg of anthocyanins daily, providing approximately 30-90 mg of delphinidin glycosides | Rich in delphinidin glycosides (primarily delphinidin-3-rutinoside and delphinidin-3-glucoside) that may have particular benefits for eye health, inflammation, and vascular function. |
| Maqui berry extract | 50-200 mg of anthocyanins daily, providing approximately 20-80 mg of delphinidin glycosides | Exceptionally rich in delphinidin glycosides, particularly delphinidin-3,5-diglucoside and delphinidin-3-sambubioside-5-glucoside. Limited clinical studies suggest benefits for eye health, inflammation, and glucose metabolism. |
| Blueberry extract | 100-500 mg of anthocyanins daily, providing approximately 15-75 mg of delphinidin glycosides | Contains a diverse profile of anthocyanins including delphinidin glycosides. Clinical studies have used a wide range of doses, with higher doses typically showing more significant effects on cognitive function and vascular health. |
| Muscadine grape extract | 100-300 mg of anthocyanins daily, providing approximately 20-60 mg of delphinidin glycosides | Contains significant amounts of delphinidin-3,5-diglucoside. Limited clinical evidence suggests potential benefits for cardiovascular health and inflammation. |
Dosing Considerations
| Factor | Impact | Recommendation |
|---|---|---|
| Individual variability | Significant differences in response to delphinidin exist between individuals, influenced by gut microbiome composition, genetic factors affecting metabolism, and overall health status. | Personalized approach starting with lower doses and adjusting based on individual response. Genetic testing for polymorphisms in genes involved in delphinidin metabolism may help guide dosing in the future. |
| Timing | Taking delphinidin with meals may reduce its absorption due to interactions with food components, but may enhance its effects on postprandial glucose and lipid metabolism. | For maximum absorption, take between meals. For effects on postprandial metabolism, take 15-30 minutes before meals. Morning administration may be optimal due to potentially higher intestinal permeability early in the day. |
| Duration | Many benefits of delphinidin, particularly for vision, cardiovascular, and cognitive health, may require consistent long-term use to become apparent. | For chronic conditions, consistent daily use for at least 8-12 weeks is recommended before evaluating efficacy. Some benefits may continue to increase with longer-term use. |
| Standardization | Delphinidin content varies widely between sources and extraction methods, affecting potency and biological activity. | Use standardized extracts with specified anthocyanin content and, ideally, information about the delphinidin content or profile. Look for products that specify the percentage or amount of delphinidin glycosides rather than just ‘anthocyanins’ generally. |
| Bioavailability enhancement | Various formulation approaches can significantly enhance the bioavailability of delphinidin, potentially allowing for lower effective doses. | Consider enhanced bioavailability formulations (liposomal, nanoparticle, protein-bound) for improved efficacy, particularly when using lower doses. Co-administration with piperine (black pepper extract) may enhance absorption. |
| Metabolite contribution | Delphinidin is extensively metabolized to various compounds including gallic acid and other phenolic acids, which contribute significantly to its biological effects. | Consider the total biological activity rather than just the parent compound. Some formulations may be designed to enhance the production of specific beneficial metabolites. |
Research Limitations
Current dosage recommendations for delphinidin are limited by several factors: 1) Most clinical studies use specific anthocyanin-rich extracts rather than isolated delphinidin, making
it difficult to establish dose-response relationships for delphinidin
specifically ; 2) Significant variability in chemical composition and bioavailability between different delphinidin sources; 3) Limited long-term safety data for isolated delphinidin supplements at various doses; 4) Individual variability in metabolism and response to delphinidin; 5) The complex interplay between parent delphinidin and its metabolites, which may contribute significantly to biological effects; 6) Lack of standardized analytical methods for quantifying delphinidin in commercial products; 7) Limited clinical trials
specifically designed to determine optimal dosing for different health conditions. More research is needed to establish optimal dosing regimens for specific health conditions and to understand how factors such as formulation, timing, and individual characteristics affect the optimal dose.
Bioavailability
Absorption Rate
Delphinidin has very low bioavailability, with absorption rates typically reported between 0.1-1% of the ingested dose when measured as intact parent compound in plasma and urine. This limited bioavailability is primarily due to its chemical instability at physiological pH, susceptibility to metabolic transformations, and interactions with intestinal and microbial enzymes. The tri-hydroxylated B-ring structure of delphinidin, while contributing to its potent antioxidant capacity, also makes it more susceptible to oxidation and degradation compared to other anthocyanidins. However, recent research using isotope-labeled anthocyanins suggests that the bioavailability of delphinidin may be significantly underestimated when considering its extensive metabolism to phenolic acid derivatives and phase II conjugates, which can reach much higher concentrations in circulation than the parent compound.
Delphinidin can be absorbed in multiple regions of the gastrointestinal tract, with evidence for absorption in the stomach, small intestine, and colon, though the majority reaches the colon where it undergoes extensive microbial metabolism.
Enhancement Methods
| Method | Description |
|---|---|
| Protein complexation | Forming complexes with proteins (milk proteins, soy proteins, etc.) can protect delphinidin from degradation in the gastrointestinal tract and enhance its stability and absorption. Studies have shown 1.5-3 fold increases in bioavailability for protein-bound delphinidin compared to free forms. The protein-binding approach may be particularly effective for delphinidin due to its high susceptibility to degradation at physiological pH. |
| Liposomal encapsulation | Encapsulating delphinidin in phospholipid vesicles can protect it from degradation in the gastrointestinal tract and enhance its absorption through improved membrane permeability. Studies have shown 2-4 fold increases in bioavailability for liposomal delphinidin formulations. The liposomal approach may also help stabilize delphinidin at physiological pH. |
| Nanoparticle delivery systems | Various nanoparticle formulations (polymeric nanoparticles, solid lipid nanoparticles, etc.) can improve the solubility, stability, and cellular uptake of delphinidin. These systems can increase bioavailability by 3-5 fold depending on the specific formulation. Nanoparticles may also offer targeted delivery to specific tissues or protection from enzymatic degradation. |
| Cyclodextrin complexation | Forming inclusion complexes with cyclodextrins can improve the solubility and stability of delphinidin, potentially enhancing its bioavailability. This method has shown 1.5-2 fold increases in bioavailability for delphinidin. The cyclodextrin cavity provides a hydrophobic environment that can protect the delphinidin molecule from degradation. |
| Emulsion-based delivery systems | Oil-in-water emulsions can improve the stability and gastrointestinal fate of delphinidin, potentially enhancing its absorption. This approach has shown 1.5-3 fold increases in bioavailability in some studies. The emulsion droplets may protect delphinidin from degradation and enhance its interaction with the intestinal epithelium. |
| Piperine co-administration | Black pepper extract containing piperine may enhance delphinidin absorption by inhibiting certain enzymes involved in its metabolism (particularly UDP-glucuronosyltransferases) and by temporarily increasing intestinal permeability. Studies suggest a 30-60% increase in bioavailability of various polyphenols, including delphinidin, when co-administered with piperine. |
| Probiotic co-administration | Certain probiotic strains, particularly Lactobacillus and Bifidobacterium species, can enhance the conversion of delphinidin to more bioavailable metabolites. This approach focuses on optimizing the metabolic fate rather than direct absorption of parent delphinidin. Specific probiotic strains may be selected based on their ability to produce beneficial delphinidin metabolites. |
| pH-controlled release formulations | Formulations designed to release delphinidin in specific regions of the gastrointestinal tract where absorption is optimal (e.g., stomach or proximal small intestine) may enhance bioavailability. Enteric coatings or pH-responsive polymers can be used to target release to specific gastrointestinal regions. |
Timing Recommendations
Delphinidin is generally better absorbed when taken on an empty stomach or between meals to minimize interactions with dietary proteins and other food components that can reduce its absorption. However, taking delphinidin with meals may be preferable when the goal is to reduce the glycemic impact of the meal or to exert local effects in the gastrointestinal tract. For maximum absorption of parent delphinidin, morning administration may be optimal due to potentially higher intestinal permeability and metabolic activity early in the day. For effects mediated by delphinidin metabolites, consistent daily intake is more important than specific timing, as it allows for adaptation of the gut microbiota to enhance metabolite production over time.
The timing of delphinidin intake may also be influenced by the specific health goal; for example, taking delphinidin before exposure to bright light or screen time may be most effective for supporting eye health.
Metabolism And Elimination
Gastrointestinal Metabolism: In the stomach, delphinidin is relatively stable due to the acidic environment (pH 1-2), which favors the flavylium cation form. As it moves into the small intestine (pH 5-7), it undergoes structural transformations to less stable forms including the colorless carbinol pseudobase, quinoidal base, and chalcone forms. In the small intestine, delphinidin glycosides can undergo deglycosylation by brush border β-glucosidases, releasing the delphinidin aglycone, which is highly unstable at intestinal pH and rapidly degrades to phenolic acids and aldehydes, primarily gallic acid and phloroglucinol aldehyde. The tri-hydroxylated B-ring structure of delphinidin makes it particularly susceptible to degradation compared to other anthocyanidins.
Microbial Metabolism: The majority of ingested delphinidin reaches the colon, where it is extensively metabolized by gut microbiota. Microbial enzymes cleave glycosidic bonds and open the C-ring of the delphinidin structure, producing various phenolic acids including gallic acid, syringic acid, and phloroglucinol aldehyde. These microbial metabolites have better absorption profiles than the parent delphinidin and may contribute significantly to the biological effects attributed to delphinidin consumption. The specific pattern of metabolites produced depends on the individual’s gut microbiome composition.
Hepatic Metabolism: Absorbed delphinidin and its metabolites undergo phase II metabolism in the liver, primarily glucuronidation, sulfation, and methylation. These conjugated forms are the predominant circulating metabolites in the bloodstream. The specific pattern of conjugation varies depending on individual genetic factors affecting metabolizing enzymes. Gallic acid, a major metabolite of delphinidin, may undergo further metabolism to 4-O-methylgallic acid through methylation by catechol-O-methyltransferase (COMT).
Elimination: Delphinidin and its metabolites are primarily excreted in urine (for absorbed compounds) and feces (for unabsorbed compounds). The elimination half-life of parent delphinidin is relatively short (approximately 1-2 hours), while certain metabolites may have longer half-lives (up to 24 hours). Biliary excretion and enterohepatic recycling may also play a role in the disposition of delphinidin metabolites, potentially prolonging their presence in the body.
Factors Affecting Bioavailability
| Factor | Impact | Mitigation |
|---|---|---|
| Chemical structure | The tri-hydroxylated B-ring structure of delphinidin, while contributing to its potent antioxidant capacity, also makes it more susceptible to oxidation and degradation compared to other anthocyanidins. Additionally, the specific glycosylation pattern of delphinidin glycosides affects their stability, absorption, and metabolism. | Enhanced bioavailability formulations (liposomal, nanoparticle, etc.) can protect the delphinidin structure from degradation. Consuming delphinidin with other antioxidants may help preserve its structure during digestion. |
| Food matrix | The presence of dietary proteins, carbohydrates, lipids, and fiber can affect delphinidin stability, release, and absorption. Proteins may form complexes with delphinidin, potentially enhancing stability but reducing absorption unless specifically formulated for improved bioavailability. Dietary fiber may slow transit time, reducing absorption in the small intestine but potentially enhancing microbial metabolism in the colon. | Consider the timing of delphinidin intake relative to meals based on the desired effect. For maximum absorption, take between meals; for effects on postprandial metabolism, take with meals. |
| Processing methods | Thermal processing, fermentation, and mechanical disruption of plant tissues can affect delphinidin stability and bioaccessibility. Moderate heat treatment may enhance release from the food matrix, while excessive heat can cause degradation. Fermentation may enhance bioavailability through structural modifications and matrix degradation. Freezing and freeze-drying generally preserve delphinidin content better than other processing methods. | Choose minimally processed or appropriately processed delphinidin sources. Freeze-dried products often retain higher delphinidin content than heat-processed alternatives. |
| Gut microbiome composition | Individual variations in gut microbiota significantly affect the metabolism of delphinidin to bioavailable metabolites. The presence of specific bacterial species capable of delphinidin metabolism (e.g., Bifidobacterium, Lactobacillus, Bacteroides) can enhance the production of bioactive metabolites. Antibiotic use, diet, and health status can all influence gut microbiome composition and consequently delphinidin metabolism. | Consider probiotic supplementation to optimize gut microbiome composition for delphinidin metabolism. A diet rich in fiber and fermented foods may support a healthy gut microbiome. |
| Gastrointestinal pH and transit time | Variations in gastric and intestinal pH can affect the stability and solubility of delphinidin. Higher gastric pH (e.g., due to use of proton pump inhibitors) may reduce delphinidin stability. Faster gastrointestinal transit time reduces the opportunity for absorption in the small intestine and microbial metabolism in the colon. | Consider acidified formulations or taking delphinidin with acidic beverages to maintain optimal pH for stability. Factors that normalize gastrointestinal transit time may improve delphinidin bioavailability. |
| Concurrent medications | Drugs that alter gut transit time, microbiome composition, or liver enzyme activity may affect delphinidin bioavailability and metabolism. Antacids and proton pump inhibitors may reduce delphinidin stability by increasing gastric pH. Drugs that inhibit phase II conjugation enzymes may increase the bioavailability of unconjugated delphinidin and its metabolites. | Consider potential drug interactions when using delphinidin supplements. Separate the timing of delphinidin intake from medications that may affect its bioavailability. |
| Age and health status | Older adults may have altered gut microbiome composition and gastrointestinal function, potentially affecting delphinidin metabolism. Various health conditions, particularly those affecting liver function or gut health, can also impact delphinidin bioavailability. Inflammatory conditions may alter intestinal permeability and consequently delphinidin absorption. | Adjust delphinidin dosing based on age and health status. Enhanced bioavailability formulations may be particularly beneficial for older adults or those with compromised gastrointestinal function. |
| Habitual intake | Regular consumption of delphinidin-rich foods may lead to adaptation of the gut microbiota, potentially enhancing the metabolism of delphinidin to bioavailable metabolites over time. This adaptation may result in improved bioavailability and enhanced biological effects with consistent long-term intake. | Consistent daily intake of delphinidin may be more effective than intermittent high doses. Allow several weeks for potential adaptation of the gut microbiome. |
Pharmacokinetics
Absorption Sites: Delphinidin can be absorbed in multiple regions of the gastrointestinal tract. Some absorption occurs in the stomach, where the acidic environment stabilizes the compound. In the small intestine, delphinidin may be absorbed through passive diffusion or via glucose transporters (for glycosylated forms). The colon is a major site for the absorption of delphinidin metabolites produced by gut microbiota.
Distribution: After absorption, delphinidin and its metabolites are distributed throughout the body, with evidence for presence in various tissues including liver, kidney, brain (in limited amounts), adipose tissue, and ocular tissues. The volume of distribution is relatively large due to extensive tissue distribution. Delphinidin and its metabolites may bind to plasma proteins, which can affect their distribution and elimination.
Peak Plasma Time: Peak plasma concentrations of parent delphinidin typically occur 1-2 hours after oral administration, reflecting absorption primarily in the upper gastrointestinal tract. Metabolites may show different kinetics, with some appearing rapidly (1-4 hours) and others showing delayed peaks (6-24 hours) due to microbial metabolism in the colon.
Half Life: The elimination half-life of parent delphinidin is relatively short, approximately 1-2 hours. However, certain metabolites, particularly those produced by gut microbiota and subject to enterohepatic recycling, may have longer half-lives ranging from 6-24 hours. This extended presence of metabolites may contribute to the sustained biological effects observed with delphinidin supplementation.
Research Gaps
Despite significant advances in understanding delphinidin bioavailability, several knowledge gaps remain: 1) Limited data on tissue distribution and cellular uptake of delphinidin and its metabolites beyond plasma concentrations; 2) Incomplete understanding of the specific gut microbial species responsible for delphinidin metabolism and how to optimize
this process; 3) Limited information on how chronic consumption affects bioavailability through potential adaptation mechanisms; 4) Need for better analytical methods to comprehensively identify and quantify the diverse array of delphinidin metabolites in biological samples; 5) Incomplete knowledge of the relative contribution of parent delphinidin versus its metabolites to the observed health benefits; 6) Limited understanding of how genetic polymorphisms affect delphinidin metabolism and individual responses; 7) Need for more human studies using isotope-labeled delphinidin to accurately track its metabolic fate in vivo; 8) Limited comparative data on the bioavailability of different delphinidin glycosides and how glycosylation patterns affect absorption and metabolism.
Safety Profile
Safety Rating
Summary
Delphinidin has an excellent safety profile with minimal reported adverse effects at recommended doses. As a naturally occurring compound found in many common foods and beverages, dietary delphinidin has a long history of consumption with no significant safety concerns. Clinical studies using delphinidin-rich extracts at doses up to 150 mg of delphinidin daily have demonstrated good tolerability with few adverse effects. The safety profile of delphinidin is further supported by its relatively low bioavailability and rapid metabolism and elimination, which limits systemic exposure to high concentrations.
Delphinidin is generally recognized as safe (GRAS) when consumed in amounts consistent with a normal diet rich in berries and other anthocyanin-containing foods.
Side Effects
| Effect | Severity | Frequency | Notes |
|---|---|---|---|
| Gastrointestinal discomfort | Mild | Uncommon | May include mild nausea, stomach upset, or diarrhea, particularly at higher doses. Typically resolves with continued use or dose reduction. More common with certain sources (e.g., bilberry) than others. |
| Allergic reactions | Mild to severe | Rare | Individuals with known allergies to specific berries or plants containing delphinidin may experience allergic reactions. Discontinue use if symptoms such as rash, itching, or swelling occur. |
| Hypoglycemia | Mild to moderate | Rare | Theoretical risk in diabetic patients taking glucose-lowering medications, as delphinidin may enhance insulin sensitivity and glucose uptake. Monitor blood glucose levels when combining with antidiabetic medications. |
| Temporary discoloration of urine or stool | Mild | Common at higher doses | Not a safety concern but may cause alarm if unexpected. Discoloration is due to unabsorbed delphinidin or its metabolites and is harmless. |
Contraindications
| Condition | Recommendation | Notes |
|---|---|---|
| Known allergy to source plants | Strictly contraindicated | Individuals with known allergies to berries, grapes, or other delphinidin-rich foods should avoid supplements derived from those specific sources. |
| Scheduled surgery | Discontinue 2 weeks before | Due to potential mild antiplatelet effects, delphinidin supplements should be discontinued at least 2 weeks before scheduled surgical procedures to reduce any theoretical bleeding risk. |
| Pregnancy and lactation | Caution advised | While consumption of delphinidin-containing foods is generally considered safe during pregnancy, concentrated supplements lack sufficient safety data and should be used with caution or avoided. |
Drug Interactions
| Drug Class | Interaction Type | Severity | Management | Evidence Level |
|---|---|---|---|---|
| Antidiabetic medications | Potential enhanced hypoglycemic effect | Mild to moderate | Monitor blood glucose levels; dose adjustment of medications may be necessary | Moderate – based on animal studies and limited human data |
| Anticoagulants/Antiplatelets | Potential enhanced antiplatelet effect | Mild | Monitor for signs of increased bleeding; consider dose reduction or alternative supplements | Limited – based on in vitro studies and theoretical pharmacological mechanism |
| Proton Pump Inhibitors | Potential reduced stability and absorption | Mild | Consider taking delphinidin supplements with acidic beverages or using enteric-coated formulations | Limited – based on known pH-dependent stability of delphinidin |
| Drugs metabolized by UGT enzymes | Potential competition for metabolic enzymes | Mild | Monitor for altered drug effects; separate administration times if necessary | Limited – based on in vitro studies of delphinidin metabolism |
Upper Limit
No definitive upper limit has been established for delphinidin. Clinical studies have used doses up to 150 mg of delphinidin daily without significant adverse effects. The European Food Safety Authority (EFSA) has not established a tolerable upper intake level for delphinidin or anthocyanins in general due to lack of evidence for any adverse effects. Based on available research, doses up to 200 mg of delphinidin daily appear to be well-tolerated in most individuals.
Higher intakes from food sources (which may exceed 100 mg in diets rich in berries and other delphinidin-containing foods) have not been associated with adverse effects.
Long Term Safety
Long-term safety data beyond 12 months of continuous use is limited for concentrated delphinidin supplements. Available studies lasting up to 12 months have not identified significant safety concerns at doses up to 150 mg of delphinidin daily. Epidemiological data on populations consuming diets rich in delphinidin-containing foods suggest long-term safety of dietary delphinidin. No cumulative toxicity or adverse effects specific to long-term use have been identified in the available literature. Some evidence suggests potential beneficial effects of long-term delphinidin consumption on markers of oxidative stress, inflammation, and vascular health.
Special Populations
| Population | Safety Notes |
|---|---|
| Children | Limited safety data in pediatric populations. Consumption through whole foods is generally considered safe. Supplements should be used with caution and under medical supervision in children under 12 years. |
| Elderly | Generally well-tolerated. May have particular benefits for this population for vision, cardiovascular, and cognitive health. Start with lower doses and monitor for drug interactions, as polypharmacy is common in this population. |
| Pregnant/lactating women | Consumption of delphinidin-containing foods is generally considered safe during pregnancy and lactation. Limited safety data for concentrated supplements; use with caution or avoid during pregnancy and lactation. |
| Individuals with diabetes | Generally safe and potentially beneficial for glucose management. Monitor blood glucose levels when using alongside antidiabetic medications due to potential additive effects. |
| Individuals with autoimmune conditions | Limited data on safety in autoimmune conditions. Theoretical concern that immunomodulatory effects could potentially affect disease activity. Use with caution and medical supervision. |
| Individuals with impaired liver function | Delphinidin undergoes extensive hepatic metabolism. While no specific safety concerns have been identified, individuals with impaired liver function should use supplements with caution and under medical supervision. |
Toxicity Data
Acute Toxicity: Delphinidin has very low acute toxicity. Animal studies have shown no significant adverse effects at doses far exceeding those used in human supplementation. The LD50 (lethal dose for 50% of test animals) for various delphinidin-rich extracts is typically greater than 2000 mg/kg body weight in rodents, indicating a wide margin of safety.
Subchronic Toxicity: 90-day feeding studies in animals have shown no significant adverse effects at doses equivalent to several times the typical human supplemental dose. No-observed-adverse-effect levels (NOAELs) for various delphinidin-rich extracts typically range from 1000-2000 mg/kg body weight/day in rodents.
Genotoxicity: Standard genotoxicity assays (Ames test, chromosomal aberration tests, micronucleus tests) have been negative for delphinidin and delphinidin-rich extracts, indicating no significant mutagenic potential.
Carcinogenicity: No evidence of carcinogenic potential in available studies. Some research suggests potential anti-carcinogenic properties of delphinidin through various mechanisms including antioxidant activity, modulation of cell signaling pathways, and epigenetic effects.
Safety By Source
| Source | Safety Profile | Specific Concerns | Notes |
|---|---|---|---|
| Bilberry extract | Excellent safety record with extensive clinical use in Europe. Well-tolerated at doses providing up to 150 mg of delphinidin daily. | Rare reports of mild gastrointestinal discomfort. Theoretical concern for interaction with anticoagulant medications due to potential antiplatelet effects. | One of the most extensively studied sources of delphinidin for clinical applications, particularly for vision health. |
| Blackcurrant extract | Excellent safety profile with minimal reported adverse effects. | Few specific concerns. Mild gastrointestinal effects reported in some individuals at high doses. | Rich in specific delphinidin glycosides (delphinidin-3-rutinoside and delphinidin-3-glucoside) with a long history of traditional use. |
| Maqui berry extract | Generally recognized as safe based on traditional food use and limited clinical data. | Limited clinical safety data compared to more extensively studied sources like bilberry or blackcurrant. | Exceptionally rich in delphinidin glycosides, particularly delphinidin-3,5-diglucoside and delphinidin-3-sambubioside-5-glucoside. |
| Blueberry extract | Excellent safety profile with minimal reported adverse effects. | Few specific concerns. Mild gastrointestinal effects reported in some individuals at high doses. | Contains a diverse profile of anthocyanins including delphinidin glycosides, but at lower concentrations than bilberry or blackcurrant. |
| Muscadine grape extract | Generally recognized as safe based on traditional food use and limited clinical data. | Limited clinical safety data compared to more extensively studied berry sources. | Contains significant amounts of delphinidin-3,5-diglucoside, with a different glycosylation pattern than many berry sources. |
Regulatory Considerations
Delphinidin is generally recognized as safe (GRAS) for food use by regulatory authorities worldwide. In the United States, various delphinidin-containing extracts are permitted as food additives and dietary supplement ingredients. The European Food Safety Authority (EFSA) has evaluated various anthocyanin-rich extracts for safety but has not established specific intake recommendations or upper limits for delphinidin specifically. Delphinidin-containing extracts are permitted as food colorants (E163) in the European Union.
No major regulatory warnings exist for delphinidin-containing foods or supplements when used as directed. Regulatory status may vary for different sources of delphinidin (bilberry extract, blackcurrant extract, etc.) and specific formulations.
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating | Research Notes |
|---|---|---|---|
| Vitamin C (Ascorbic Acid) | Vitamin C can regenerate oxidized delphinidin, extending its antioxidant capacity. It also stabilizes delphinidin by preventing oxidation and maintaining acidic conditions that favor the stable flavylium cation form. Additionally, vitamin C and delphinidin provide complementary antioxidant protection in different cellular compartments and against different types of reactive species. The regeneration effect may be particularly important for delphinidin due to its high susceptibility to oxidation. | 4 | Multiple in vitro and food chemistry studies demonstrate enhanced stability and antioxidant capacity when delphinidin and vitamin C are combined. Clinical studies using berry extracts (naturally containing both compounds) show superior antioxidant effects compared to isolated compounds. The combination appears to be particularly effective for protecting against oxidative stress in ocular tissues. |
| Other Anthocyanins | Different anthocyanins can act synergistically with delphinidin through complementary antioxidant mechanisms and by targeting different signaling pathways. The diverse chemical structures of various anthocyanins allow for a broader spectrum of biological activities when combined. Additionally, different anthocyanins may compete for metabolic enzymes, potentially enhancing the bioavailability of delphinidin. | 4 | Studies using berry extracts containing multiple anthocyanins consistently show greater biological effects than would be expected from the sum of individual compounds. The specific combination of anthocyanins found in bilberries, blackcurrants, and other natural sources appears to provide optimal synergistic effects. Delphinidin’s unique tri-hydroxylated B-ring structure complements the activity of other anthocyanins with different hydroxylation patterns. |
| Lutein and Zeaxanthin | Lutein and zeaxanthin are carotenoids that accumulate in the macula of the eye, where they filter blue light and provide antioxidant protection. Delphinidin complements these effects through its own blue light absorption properties and superior radical scavenging capacity. Additionally, delphinidin may enhance blood flow to ocular tissues, potentially improving the delivery and uptake of lutein and zeaxanthin. | 3 | Clinical studies using combinations of anthocyanins (including delphinidin) with lutein and zeaxanthin show enhanced benefits for visual function and protection against age-related macular degeneration compared to either component alone. The combination appears to provide more comprehensive protection for ocular tissues through complementary mechanisms. |
| Omega-3 Fatty Acids | Omega-3 fatty acids provide complementary anti-inflammatory effects through modulation of eicosanoid production and resolution of inflammation. While delphinidin primarily affects inflammatory signaling pathways like NF-κB, omega-3s address the lipid mediators of inflammation. The combination may provide more comprehensive anti-inflammatory benefits and enhanced vascular protection. | 3 | Animal studies show enhanced cardiovascular and anti-inflammatory benefits when combined. Limited human data with specific combination, though epidemiological studies suggest additive benefits of diets rich in both compounds. The combination may be particularly beneficial for conditions involving both oxidative stress and inflammation, such as age-related eye diseases and cardiovascular disorders. |
| Resveratrol | Resveratrol activates SIRT1 and AMPK pathways, which complement delphinidin’s effects on cellular energy metabolism and vascular function. While delphinidin primarily acts through antioxidant mechanisms and direct enzyme inhibition, resveratrol works through sirtuin activation and epigenetic modulation. The combination may provide enhanced benefits for cardiovascular health, metabolic function, and cellular longevity. | 3 | Preclinical studies demonstrate synergistic effects on vascular function, oxidative stress biomarkers, and inflammatory signaling. Limited clinical studies with the combination show promising results for cardiovascular health. Both compounds are found naturally in certain berries and grapes, suggesting evolutionary co-optimization of their effects. |
| Probiotics (specific strains) | Certain probiotic strains, particularly Lactobacillus and Bifidobacterium species, can enhance the metabolism of delphinidin to bioactive metabolites in the gut. This addresses the issue of variable metabolism among individuals and may enhance the overall biological activity of delphinidin, particularly in individuals with gut microbiomes less efficient at delphinidin metabolism. | 3 | Emerging research shows that specific probiotic strains can enhance the production of phenolic metabolites from delphinidin. Preliminary clinical studies suggest improved bioavailability and enhanced biological effects when delphinidin is combined with specific probiotic strains. The combination may be particularly beneficial for conditions involving both gut health and systemic inflammation. |
| Piperine (Black Pepper Extract) | Piperine enhances the bioavailability of delphinidin by inhibiting UDP-glucuronosyltransferases and other enzymes involved in delphinidin metabolism. It also temporarily increases intestinal permeability, potentially leading to higher plasma concentrations and enhanced biological effects of delphinidin. | 3 | Studies with various polyphenols show 30-60% increases in bioavailability when co-administered with piperine. Specific studies with delphinidin demonstrate enhanced absorption and prolonged presence in circulation when combined with piperine. This combination may be particularly important for delphinidin due to its naturally low bioavailability. |
| Quercetin | Quercetin can enhance the antioxidant and anti-inflammatory effects of delphinidin through complementary mechanisms. While delphinidin primarily affects NF-κB signaling and histone acetyltransferase activity, quercetin has stronger effects on MAPK pathways and Nrf2 activation. Quercetin may also inhibit enzymes involved in delphinidin metabolism, potentially extending its half-life and bioavailability. | 3 | In vitro and animal studies demonstrate enhanced anti-inflammatory and antioxidant effects when delphinidin and quercetin are combined. Limited human studies suggest improved vascular function with the combination compared to either compound alone. The combination may provide more comprehensive protection against oxidative stress and inflammation. |
| Zinc | Zinc can act as a cofactor for antioxidant enzymes that complement delphinidin’s direct antioxidant effects. Additionally, zinc plays a crucial role in retinal function and may enhance delphinidin’s effects on vision health. Both compounds also support immune function through complementary mechanisms. | 2 | Limited direct studies on the combination, but mechanistic research suggests potential synergy. Both compounds have established roles in vision health and antioxidant defense systems. The combination may be particularly beneficial for age-related macular degeneration and other ocular conditions. |
| Alpha-Lipoic Acid | Alpha-lipoic acid is both water and fat-soluble, allowing it to function in multiple cellular compartments. It can regenerate other antioxidants including delphinidin, extending their activity. Additionally, alpha-lipoic acid activates Nrf2 signaling through different mechanisms than delphinidin, potentially leading to enhanced upregulation of endogenous antioxidant defenses. | 2 | Preliminary studies suggest enhanced antioxidant effects when combined. The combination may be particularly beneficial for conditions involving mitochondrial dysfunction and oxidative stress, such as diabetic complications and neurodegenerative disorders. |
| Phospholipids (Lecithin) | Phospholipids can form liposomal or micellar structures that encapsulate delphinidin, enhancing its stability in the gastrointestinal tract and improving its absorption through enhanced membrane permeability. This approach addresses one of the key limitations of delphinidin – its poor bioavailability and stability at physiological pH. | 3 | Studies on liposomal and phospholipid complex formulations of delphinidin show 2-4 fold increases in bioavailability compared to conventional forms. The technology has been successfully applied to various delphinidin sources including bilberry and blackcurrant extracts. The phospholipid complex may also enhance delphinidin’s ability to cross the blood-retinal barrier, potentially improving its effects on ocular health. |
Antagonistic Compounds
Stability Information
Shelf Life
Powder Extract: 12-24 months when properly stored
Liquid Extract: 6-18 months when properly stored
Capsules: 18-30 months when properly stored
Tablets: 18-30 months when properly stored
Notes: Shelf life estimates assume proper storage conditions and sealed containers. Actual stability may vary based on specific formulation, processing methods, and storage conditions. Delphinidin generally has shorter shelf life than other anthocyanidins due to its tri-hydroxylated B-ring structure, which makes it more susceptible to oxidation and degradation.
Storage Recommendations
Temperature: Store at cool temperatures (2-8°C). Refrigeration is strongly recommended for all delphinidin-containing products, particularly liquid extracts. Avoid temperatures exceeding 25°C as higher temperatures significantly accelerate degradation. Freeze-thaw cycles should be strictly avoided as they can dramatically reduce delphinidin stability.
Humidity: Keep in low humidity environments (<50% relative humidity). Delphinidin can absorb moisture, which accelerates hydrolysis and degradation reactions. Desiccants should be included in packaging to maintain low humidity.
Light: Protect from all light, especially UV light, which rapidly catalyzes oxidation reactions and structural transformations. Amber or completely opaque containers are essential for preserving delphinidin stability. If transparent packaging is used for marketing purposes, secondary packaging must provide complete light protection.
Packaging: Store in airtight, light-resistant containers to minimize exposure to oxygen, moisture, and light. Nitrogen-flushed packaging is strongly recommended to displace oxygen. Aluminum foil pouches or HDPE bottles with oxygen scavengers provide optimal protection. Consider individual blister packaging for products intended for regular use to minimize exposure of the bulk product.
Notes: Once opened, products should ideally be used within 1-3 months, even if the total shelf life is longer. Refrigeration after opening is essential, particularly for liquid extracts. For bulk materials, consider dividing into smaller portions to minimize repeated exposure to air and light.
Degradation Factors
| Factor | Impact | Mechanism | Mitigation |
|---|---|---|---|
| pH | Very high | Delphinidin is extremely pH-sensitive, more so than other anthocyanidins due to its tri-hydroxylated B-ring structure. It is most stable in highly acidic conditions (pH 1-3) where it exists predominantly as the flavylium cation. As pH increases, it undergoes structural transformations to less stable forms including the colorless carbinol pseudobase (pH 4-5), quinoidal base (pH 6-7), and chalcone forms (pH > 7). These transformations are reversible at first but can lead to irreversible degradation over time, particularly at higher pH values. | Maintain strongly acidic conditions in formulations using food-grade acids (citric, malic, tartaric). Use pH-stabilized formulations or enteric coatings for oral supplements to protect from alkaline conditions in the intestine. Buffer systems can help maintain optimal pH during storage. Consider microencapsulation techniques to create a protective acidic microenvironment. |
| Temperature | High | Elevated temperatures dramatically accelerate hydrolysis, oxidation, and structural rearrangements of delphinidin. Degradation rates approximately double for every 10°C increase in temperature. The glycosidic bond is particularly susceptible to thermal hydrolysis, leading to formation of the unstable delphinidin aglycone which rapidly degrades further. The tri-hydroxylated B-ring structure makes delphinidin more thermally sensitive than other anthocyanidins. | Use cold processing methods when possible. Store finished products at refrigerated temperatures (2-8°C). Consider freeze-drying rather than heat drying for powder production. Avoid exposure to high temperatures during manufacturing, shipping, and storage. Use temperature-controlled shipping methods. |
| Oxygen | Very high | Oxidation of delphinidin leads to formation of brown polymeric pigments and loss of biological activity. Oxygen can also generate reactive oxygen species that further accelerate degradation. The tri-hydroxylated B-ring structure of delphinidin makes it particularly susceptible to oxidation compared to other anthocyanidins, as the three adjacent hydroxyl groups can readily donate electrons to oxygen. | Use oxygen-free processing when possible. Include antioxidants in formulations. Use nitrogen flushing or vacuum packaging. Include oxygen absorbers in packaging for sensitive products. Consider oxygen barrier packaging materials. Minimize headspace in packaging. |
| Light (especially UV) | Very high | Light energy, particularly UV radiation, rapidly catalyzes oxidation reactions and structural transformations of delphinidin. Photodegradation can occur through direct absorption of light energy or through photosensitized reactions involving other compounds. Delphinidin’s extended conjugated system makes it particularly susceptible to photodegradation. | Use opaque or amber containers that completely block UV and visible light. Store products away from all light sources. Include UV-blocking agents in formulations if necessary. Secondary packaging should provide additional light protection. |
| Metal ions (especially iron and copper) | High | Transition metal ions can catalyze oxidation reactions and form complexes with delphinidin, altering its stability and color. The tri-hydroxylated B-ring structure of delphinidin is particularly effective at chelating metal ions, which can lead to both stabilization and degradation depending on conditions. Copper ions are especially problematic for delphinidin stability. | Use chelating agents like citric acid or EDTA in formulations. Ensure processing equipment is made of appropriate materials (e.g., stainless steel or glass rather than reactive metals). Consider metal-binding agents in formulations. Test raw materials for metal contamination. |
| Enzymes | High | Polyphenol oxidases, peroxidases, and glycosidases can rapidly degrade delphinidin. These may be present in raw materials or introduced during processing. β-glucosidases specifically cleave the glycosidic bond in delphinidin glycosides, releasing the unstable delphinidin aglycone. Polyphenol oxidases can rapidly oxidize the tri-hydroxylated B-ring structure. | Heat inactivation of enzymes in raw materials, blanching of fresh plant materials before extraction, use of enzyme inhibitors in certain formulations. Acidic conditions can help inhibit many degradative enzymes. Consider adding specific enzyme inhibitors to formulations. |
| Co-pigmentation | Moderate (can be positive or negative) | Delphinidin can form complexes with other compounds (flavonoids, phenolic acids, metals) that can either stabilize or destabilize it depending on the specific interaction. Co-pigmentation typically involves stacking interactions that protect the delphinidin molecule from nucleophilic attack and hydration. Certain co-pigments can significantly enhance delphinidin stability. | Understand and control co-pigmentation effects in specific formulations. Certain co-pigments (e.g., ferulic acid, rosmarinic acid) can be added intentionally to enhance stability. Formulation design should consider potential interactions between ingredients. |
| Water activity | High | Higher water activity provides a medium for degradation reactions and can accelerate hydrolysis of the glycosidic bond in delphinidin glycosides. Water also facilitates molecular mobility, increasing the rate of degradative reactions. Delphinidin is particularly susceptible to hydrolysis in aqueous environments with moderate to high water activity. | Maintain very low water activity in dry products (below 0.3 if possible). Use appropriate humectants and drying techniques to achieve optimal moisture content. Consider water activity when designing formulations and packaging. Include desiccants in packaging. |
Stability In Different Formulations
| Formulation | Relative Stability | Notes |
|---|---|---|
| Freeze-dried powders | Moderate to high | Freeze-drying preserves delphinidin structure by avoiding high temperatures. The low moisture content and water activity in properly freeze-dried products further enhances stability. Addition of carrier materials like maltodextrin can provide additional protection. Freeze-dried powders typically retain 70-85% of initial delphinidin content after 12 months when properly stored at refrigerated temperatures. |
| Spray-dried powders | Low to moderate | Brief exposure to high temperatures during spray drying can cause significant degradation of delphinidin. The resulting low moisture content provides some stability benefits, but initial processing losses can be substantial. Carrier materials and encapsulation techniques can improve stability. Typical retention of 50-70% of initial delphinidin content after 12 months when properly stored. |
| Capsules | Moderate to high | Hard shell capsules provide good protection from environmental factors. HPMC (vegetable) capsules may offer better protection from moisture compared to gelatin. Stability can be further enhanced by including stabilizers and antioxidants in the fill material. Typical retention of 65-80% of initial delphinidin content after 24 months when properly stored. |
| Tablets | Low to moderate | Compression forces and heat generated during tableting can potentially degrade delphinidin. Stability depends on excipients used and manufacturing conditions. Enteric-coated tablets may protect delphinidin from degradation in gastric acid. Typical retention of 50-70% of initial delphinidin content after 24 months when properly stored. |
| Liquid extracts (alcohol-based) | Low to moderate | Ethanol provides some protection against microbial growth and can help maintain acidic conditions favorable for delphinidin stability. However, liquid formulations are generally more susceptible to degradation than dry forms. Antioxidants and proper packaging are essential. Typical retention of 40-60% of initial delphinidin content after 12 months when properly stored under refrigeration. |
| Liquid extracts (water-based) | Very low | Most vulnerable to degradation due to higher water activity and potential for microbial growth. Stability can be improved by maintaining acidic pH, adding preservatives and antioxidants, and using refrigeration. Typical retention of 30-50% of initial delphinidin content after 12 months when properly stored under refrigeration. |
| Liposomal/Nanoparticle formulations | High | Encapsulation in liposomes or nanoparticles can significantly enhance stability by protecting delphinidin from environmental factors. These delivery systems can also improve bioavailability. Typical retention of 75-90% of initial delphinidin content after 12 months when properly stored. |
| Protein-bound complexes | High | Complexation with proteins (milk proteins, soy proteins, etc.) can enhance stability by protecting delphinidin from degradation factors. The specific stability benefits depend on the protein type and binding characteristics. Typical retention of 70-85% of initial delphinidin content after 12 months when properly stored. |
Stability Testing Methods
| Method | Description | Application |
|---|---|---|
| HPLC analysis | High-Performance Liquid Chromatography with UV-Vis or mass spectrometry detection for quantitative determination of delphinidin and its degradation products over time. | Primary method for monitoring chemical stability and establishing shelf life. Can identify specific degradation pathways and products. Typically uses a C18 column with acidified mobile phases to maintain delphinidin stability during analysis. |
| pH differential method | Spectrophotometric method based on the structural transformations of delphinidin at different pH values. Measures absorbance at pH 1.0 and pH 4.5 to determine monomeric delphinidin content. | Rapid screening method for delphinidin content. Less specific than HPLC but useful for routine quality control. Particularly suitable for distinguishing monomeric delphinidin from polymerized pigments. |
| Accelerated stability testing | Storage at elevated temperatures (30-40°C) and humidity (75% RH) to predict long-term stability under normal conditions. | Used for shelf-life estimation and formulation development. Allows rapid assessment of stability-enhancing strategies. Typically conducted over 3-6 months to predict 1-2 year shelf life. For delphinidin, accelerated conditions should be less extreme than standard protocols due to its high sensitivity to degradation. |
| Real-time stability testing | Storage under recommended conditions with periodic testing over the intended shelf life. | Provides the most accurate stability data but requires longer timeframes. Essential for confirming predictions from accelerated testing. Typically conducted over 1-3 years depending on the intended shelf life. |
| Photostability testing | Exposure to defined light conditions (typically following ICH Q1B guidelines) to assess vulnerability to photodegradation. | Determines packaging requirements and light protection needs. Essential for all delphinidin formulations due to high photosensitivity. Typically involves exposure to both UV and visible light sources. |
| Color stability assessment | Visual and instrumental color measurements (L*a*b* color space) to track changes in color parameters over time. | Important for products where color is a key quality attribute, particularly for food colorants and beverages. Changes in color can be an early indicator of delphinidin degradation. |
| Antioxidant capacity assays | Measurement of ORAC, DPPH, or FRAP values to assess functional stability over time. | Complements chemical analysis by monitoring biological activity retention. Important for products marketed for antioxidant benefits. Can help establish correlation between chemical stability and functional properties. |
Stabilization Strategies
| Strategy | Examples | Mechanism |
|---|---|---|
| pH control | Citric acid, malic acid, tartaric acid buffer systems | Maintains optimal acidic pH (1-3) where delphinidin exhibits maximum stability in the flavylium cation form. Buffer systems help maintain pH even when exposed to external factors. For delphinidin, more acidic conditions are generally better for stability compared to other anthocyanidins. |
| Antioxidant addition | Vitamin C, vitamin E, rosemary extract, ferulic acid | Sacrificial antioxidants that preferentially react with oxygen and free radicals, protecting delphinidin from oxidation. Different antioxidants may protect in different phases (aqueous vs. lipid) of the formulation. Combinations of water-soluble and lipid-soluble antioxidants often provide the best protection. |
| Copigmentation | Addition of phenolic acids, flavonoids, or metal ions | Forms complexes with delphinidin that can enhance stability through molecular stacking and hydrogen bonding, protecting reactive sites from degradation. Ferulic acid, rosmarinic acid, and chlorogenic acid are particularly effective copigments for delphinidin. |
| Microencapsulation | Spray drying with maltodextrin, cyclodextrin complexation, liposomal encapsulation | Physical barrier that protects delphinidin from environmental factors and may control release. Different carrier materials offer varying degrees of protection against specific degradation factors. For delphinidin, carriers that create an acidic microenvironment are particularly beneficial. |
| Protein complexation | Milk proteins (casein, whey), soy proteins | Forms complexes that protect delphinidin from degradation factors and may enhance bioavailability. The specific binding characteristics depend on the protein type and environmental conditions. Proteins with high affinity for polyphenols, such as certain milk proteins, are particularly effective. |
| Freeze drying | Lyophilized extracts with cryoprotectants | Removes water at low temperatures, preserving structure and minimizing degradation during drying. Addition of cryoprotectants like trehalose or maltodextrin can further enhance stability during the freeze-drying process. For delphinidin, freeze-drying is generally preferred over other drying methods due to its temperature sensitivity. |
| Modified atmosphere packaging | Nitrogen flushing, vacuum packaging, oxygen absorbers | Reduces oxygen exposure during storage, preventing oxidative degradation. Particularly important for powder formulations with high surface area. For delphinidin, complete oxygen removal is more critical than for other anthocyanidins due to its higher susceptibility to oxidation. |
| Chelating agents | EDTA, citric acid | Binds metal ions that could catalyze oxidation reactions and delphinidin degradation. Particularly important when processing equipment may introduce trace metal contamination. For delphinidin, copper ion chelation is especially important due to its high sensitivity to copper-catalyzed oxidation. |
| Enzyme inhibition | Heat treatment, acidification, specific enzyme inhibitors | Prevents enzymatic degradation of delphinidin by inactivating or inhibiting enzymes like β-glucosidases, polyphenol oxidases, and peroxidases. Critical during initial processing of raw materials. For delphinidin, polyphenol oxidase inhibition is particularly important due to its tri-hydroxylated B-ring structure. |
| Water activity control | Desiccants, humectants, appropriate drying techniques | Reduces water availability for degradation reactions and microbial growth. Optimal water activity for delphinidin stability is typically below 0.3. For delphinidin, maintaining very low water activity is more critical than for other anthocyanidins due to its higher susceptibility to hydrolysis. |
Sourcing
Synthesis Methods
| Method | Commercial Viability | Notes |
|---|---|---|
| Total chemical synthesis | Very low | Complete chemical synthesis of delphinidin is technically possible but extremely complex and not commercially viable due to its complex structure, multiple chiral centers, and the need for selective glycosylation. Natural extraction remains the preferred method. The tri-hydroxylated B-ring structure adds additional complexity to synthesis compared to other anthocyanidins. |
| Semi-synthesis from other flavonoids | Low | Partial synthesis starting from other flavonoids with subsequent hydroxylation and glycosylation has been explored in research settings but is not widely used commercially due to complexity and cost considerations. |
| Biotechnological production | Emerging | Research is ongoing into using engineered microorganisms or plant cell cultures to produce delphinidin. This approach shows promise for future commercial applications but is currently limited to research and development stages. Metabolic engineering of E. coli and yeast strains has shown some success in producing delphinidin in laboratory settings. |
Natural Sources
| Source | Concentration | Notes |
|---|---|---|
| Bilberry (Vaccinium myrtillus) | High (100-300 mg per 100g fresh berries) | One of the richest sources of delphinidin glycosides, particularly delphinidin-3-glucoside, delphinidin-3-galactoside, and delphinidin-3-arabinoside. European bilberry contains higher delphinidin content than North American blueberries. Commercial extracts are typically standardized to 25-36% anthocyanins, with delphinidin glycosides comprising approximately 30-40% of total anthocyanins. |
| Blackcurrant (Ribes nigrum) | Very high (130-400 mg per 100g fresh berries) | Rich in delphinidin-3-rutinoside and delphinidin-3-glucoside. Contains a unique profile of delphinidin glycosides with specific health benefits for vision and vascular health. Commercial extracts typically standardized to 20-35% anthocyanins, with delphinidin glycosides comprising approximately 30-50% of total anthocyanins. |
| Maqui berry (Aristotelia chilensis) | Exceptionally high (300-600 mg per 100g fresh berries) | One of the richest known sources of delphinidin glycosides, particularly delphinidin-3,5-diglucoside and delphinidin-3-sambubioside-5-glucoside. Native to Chile and traditionally used for various health benefits. Commercial extracts typically standardized to 25-35% anthocyanins, with delphinidin glycosides comprising approximately 70-80% of total anthocyanins. |
| Blueberry (Vaccinium spp.) | Moderate (30-160 mg per 100g fresh berries) | Wild blueberries typically contain higher delphinidin content than cultivated varieties. Contains delphinidin glycosides along with other anthocyanins. Delphinidin typically comprises approximately 15-30% of total anthocyanins in blueberries. |
| Muscadine grape (Vitis rotundifolia) | Moderate to high (50-200 mg per 100g fresh fruit) | Contains significant amounts of delphinidin-3,5-diglucoside, which is not typically found in common grape varieties (Vitis vinifera). The skin contains the highest concentration of delphinidin glycosides. |
| Concord grape (Vitis labrusca) | Moderate (40-150 mg per 100g fresh fruit) | Contains delphinidin-3-glucoside primarily in the skin. Concentration varies significantly by ripeness and growing conditions. |
| Elderberry (Sambucus nigra) | Moderate (30-120 mg per 100g fresh berries) | Contains delphinidin glycosides along with cyanidin glycosides. Traditionally used for immune support. Delphinidin typically comprises approximately 10-20% of total anthocyanins in elderberries. |
| Pomegranate (Punica granatum) | Low to moderate (10-50 mg per 100g fresh arils) | Contains delphinidin-3,5-diglucoside primarily in certain varieties. Concentration varies significantly by variety, with some containing very little delphinidin. |
| Black rice (Oryza sativa L.) | Low to moderate (10-60 mg per 100g dry weight) | Contains delphinidin-3-glucoside in the bran layer. Concentration varies significantly by variety, with some containing very little delphinidin compared to cyanidin. |
| Blue flowers (Viola spp., Delphinium spp.) | Variable (50-300 mg per 100g fresh flowers) | Many blue flowers contain delphinidin glycosides as their primary pigments. Not typically used as commercial sources for supplements but historically used in traditional medicine and as natural dyes. |
Extraction Methods
Acidified alcohol extraction
Acidified water extraction
Ultrasound-assisted extraction
Microwave-assisted extraction
Pressurized liquid extraction
Enzyme-assisted extraction
Supercritical CO2 extraction with polar co-solvents
Quality Considerations
- High-quality delphinidin extracts should be standardized to contain a specific percentage of total anthocyanins, typically 25-36% depending on the source, with information about the delphinidin content or profile. Advanced products may specify the content of specific delphinidin glycosides (e.g., delphinidin-3-glucoside, delphinidin-3-rutinoside) or the percentage of delphinidin relative to total anthocyanins.
- Extracts should be tested for heavy metals, pesticide residues, microbial contamination, and mycotoxins. Berries and other delphinidin sources can accumulate environmental contaminants, particularly when wild-harvested. Organic certification may provide additional assurance of minimal pesticide residues.
- Excessive heat during processing can degrade delphinidin. High-quality extracts use controlled temperature extraction methods (typically below 60°C) to preserve compound integrity. Freeze-drying is preferred over heat drying for preserving delphinidin content. Processing in acidic conditions helps maintain delphinidin stability.
- Delphinidin extracts should be stored in cool, dry conditions in airtight, light-resistant containers to prevent oxidation and degradation. Vacuum packaging or nitrogen flushing may be used for bulk storage. Refrigeration can significantly extend shelf life, particularly for liquid extracts.
- HPLC fingerprinting should be used to verify the delphinidin profile, which is characteristic of the source material. This can identify adulteration or substitution with less expensive sources. DNA barcoding may provide additional authentication for botanical source materials.
Sustainability
- Cultivation of delphinidin-rich berries and plants generally has moderate environmental impact. Many sources (bilberry, maqui berry) can be wild-harvested, though this raises concerns about sustainable harvesting practices. Agricultural production of delphinidin-rich crops can be integrated into sustainable farming systems.
- Wild harvesting of berries should follow sustainable practices to prevent depletion of natural resources. Fair labor practices are important, particularly for labor-intensive berry harvesting. Indigenous knowledge and traditional uses of delphinidin-rich plants should be respected and acknowledged, particularly for sources like maqui berry which have traditional importance to indigenous communities in Chile.
- Development of enhanced extraction methods from food processing waste (berry pomace) and exploration of alternative sustainable sources are active areas of research. Biotechnological production methods may offer more sustainable alternatives in the future.
Commercial Forms
| Form | Delphinidin Content | Typical Use |
|---|---|---|
| Standardized berry extracts | 5-30% of total extract weight | Dietary supplements, functional foods, natural colorants |
| Spray-dried powders | 1-15% of total powder weight | Food additives, beverage mixes, less concentrated supplements |
| Freeze-dried berry powders | 0.3-3% of total powder weight | Whole food supplements, food ingredients |
| Liquid extracts | 0.5-5% (varies widely) | Tinctures, liquid supplements, food colorants |
| Enhanced bioavailability formulations | 3-20% (complexed with various delivery systems) | Premium supplements, clinical applications |
| Delphinidin-rich fractions | 30-80% of total anthocyanins | Research, pharmaceutical applications, premium supplements |
Scientific Evidence
Evidence Rating
Summary
Delphinidin has been extensively studied in preclinical models, demonstrating significant antioxidant, anti-inflammatory, and vascular protective properties. Human clinical evidence has grown in the past decade, with several randomized controlled trials supporting benefits for vision health, cardiovascular function, and potentially metabolic parameters. Epidemiological studies consistently associate higher intake of delphinidin-rich foods with reduced risk of age-related eye diseases, cardiovascular disease, and certain cancers. The strongest clinical evidence exists for vision and vascular health benefits, with moderate evidence for antioxidant and anti-inflammatory effects, and emerging but promising evidence for metabolic and neuroprotective properties.
While most studies use delphinidin-rich extracts rather than isolated delphinidin, advances in analytical techniques and study design have improved our understanding of the specific contributions of delphinidin to the observed health benefits. The tri-hydroxylated B-ring structure of delphinidin appears to confer unique biological properties compared to other anthocyanidins, particularly regarding its superior antioxidant capacity and vascular effects.
Key Studies
Meta Analyses
Ongoing Trials
Evidence By Application
| Application | Evidence Strength | Key Findings | Optimal Sources |
|---|---|---|---|
| Vision health | Strong | Multiple randomized controlled trials support the use of delphinidin-rich extracts for improving visual function, reducing eye fatigue, and potentially protecting against age-related macular degeneration. Mechanisms include improved retinal blood flow, protection of retinal cells from oxidative damage, and absorption of blue light. Delphinidin’s effects on rhodopsin regeneration may be particularly relevant for night vision and visual adaptation. | Bilberry extract, maqui berry extract, blackcurrant extract |
| Cardiovascular health | Moderate to Strong | Clinical trials show improvements in endothelial function, blood pressure, and vascular inflammation with delphinidin-rich extracts. Mechanisms include enhanced nitric oxide bioavailability, reduced oxidative stress, and inhibition of inflammatory signaling in vascular cells. Delphinidin’s tri-hydroxylated B-ring structure appears to confer stronger vascular effects compared to other anthocyanidins. | Bilberry extract, blackcurrant extract, maqui berry extract |
| Anti-inflammatory effects | Moderate | Clinical and preclinical studies show reductions in inflammatory biomarkers with delphinidin supplementation. Unique mechanisms include inhibition of histone acetyltransferase activity and prevention of NF-κB acetylation, which may provide more sustained anti-inflammatory effects than direct pathway inhibition. | Blackcurrant extract, bilberry extract, maqui berry extract |
| Antioxidant support | Strong | Extensive in vitro and in vivo evidence demonstrates superior antioxidant effects of delphinidin compared to other anthocyanidins, due to its tri-hydroxylated B-ring structure. Clinical studies show reductions in markers of oxidative stress with delphinidin-rich extracts. | All delphinidin-rich sources; maqui berry may have particularly high antioxidant capacity |
| Metabolic health/Glucose regulation | Preliminary to Moderate | Emerging clinical evidence suggests benefits for glucose metabolism and insulin sensitivity. Mechanisms include enhanced GLUT4 translocation, inhibition of digestive enzymes, and protection of pancreatic β-cells from oxidative stress. | Blackcurrant extract, bilberry extract, maqui berry extract |
| Neuroprotection/Cognitive function | Preliminary | Animal studies and limited human data suggest potential benefits for cognitive function and neuroprotection. Mechanisms include reduced oxidative stress and inflammation in neural tissues, enhanced BDNF levels, and modulation of neurotransmitter systems. | Bilberry extract, blackcurrant extract |
| Anti-cancer potential | Preliminary | Strong preclinical evidence for anticarcinogenic effects through multiple mechanisms including inhibition of angiogenesis, induction of apoptosis, and cell cycle arrest. Delphinidin’s ability to inhibit VEGF and bFGF receptor phosphorylation may be particularly relevant for preventing tumor angiogenesis. | Various delphinidin-rich extracts; specific optimal source not yet established |
Research Gaps
Limited studies on isolated delphinidin versus complex extracts, making it difficult to attribute effects specifically to delphinidin, Insufficient dose-response studies to establish optimal therapeutic dosages for specific conditions, Limited long-term safety and efficacy data beyond 12 months, Incomplete understanding of how different glycosylation patterns affect the bioavailability and biological activity of delphinidin, Limited research on the relative contribution of parent delphinidin versus its metabolites to observed health benefits, Insufficient clinical trials in specific populations such as children, pregnant women, or those with specific chronic diseases, Need for more comparative studies between delphinidin and other anthocyanidins to better understand its unique properties
Future Research Directions
Development and clinical testing of enhanced bioavailability formulations to overcome the limited absorption of delphinidin, Investigation of the role of gut microbiome in determining individual response to delphinidin and strategies to optimize this aspect, Larger, longer-duration clinical trials for chronic disease prevention and management, particularly for vision and vascular health, Comparative studies of different delphinidin glycosides to identify optimal forms for specific health conditions, Research on direct supplementation with delphinidin metabolites to bypass variability in gut metabolism, Development of personalized approaches based on individual metabolic profiles and gut microbiome composition, Further investigation of delphinidin’s unique epigenetic effects, particularly its inhibition of histone acetyltransferase activity
Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.