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D29
In Vitro Percutaneous Absorption of Pine Bark Extract (Pycnogenol) in Human Skin
Abstract
One promising class of antioxidant compounds is polyphenols, contained abundantly in pine bark extract (Pycnogenol®—pine bark extract). This medicinal extract is utilized for its anti‐inflammatory properties. Its pharmacological action in skin depends on the kinetics of its absorption. In this study the dermal bioavailability of pine bark extract was investigated. Viable human skin, adapted on continuously perfused Franz cells, was applied with 5% (w/v) pine bark solution. Samples were taken at 0.5, 1, 2, 4, 6, 8, 10, and 12‐hour intervals and analyzed for detection of pine bark extract constituents by high performance liquid chromatography (HPLC) (reversed phase column, isocratic conditions) coupled with an electrochemical detector (EC). Several constituents of pine bark extract such as gallic acid, protocatechuic acid, catechin, p‐hydroxybenzoic acid, vanillin, and one unidentified constituent were detected. These findings indicate that pine bark extract is readily absorbed by human skin and can be used for topical application.
... Pine extract is important in the fields of food, medicine, and health [126]. Sarikaki et al. [127] extracted Pinus brutia bark under different scCO 2 extraction conditions by adding 3% ethanol and performing ultrasonication. The results showed that 46.8% (-)-catechin was extracted, and almost 100% (-)-catechin gallate and (-)-epicatechin were extracted. ...
... Wood Effective Constituent [121] Candeia (Eremanthus erythropappus) α-bisabolol [122] Candeia (Eremanthus erythropappus) (−)-α-bisabolol [123] Candeia (Eremanthus erythropappus) α-bisabolol [125] Pinus brutia (-)-catechin, (-)-epicatechin, (-)-catechin gallate [126] Maritime pine (Pinus pinaster) phenolic compounds [127] Maritime pine (Pinus pinaster) Catechin, epicatechin [130] Eucalyptus globulus phenolics [131] Eucalyptus. grandis × Eucalyptus. ...
Wood processing is a crucial step of wood utilization, but the adding of environmentally hazardous feedstocks and the use of unreasonable technology allow it to harm the environment and human health. Supercritical CO2 (scCO2) is a non-toxic, odorless, and safe solvent, which is widely used in studies and industrial production, but there is no review summarizing wood processing with scCO2. The unique structure and chemical properties of wood combined with scCO2 technology produce positive results. In this paper, wood processing with scCO2 is summarized, including wood impregnation, wood drying, wood thermochemical conversion, and wood extraction. The green and efficient characteristics of wood processing with scCO2 are explained in detail for researchers, engineers, and investors to provide a clean wood processing method. Further study is needed to reduce its energy consumption and commercialize it eventually.
... A previous study reported that KRPBE contained catechin, taxifolin, and oligomers of catechin and epicatechin [29]. Extract of the raw pine bark of P. maritima collected in France has been reported to contain a variety of phenolics, including catechin, protocatechuic acid, taxifolin, and vanillin [30]. Consistent with our findings in this study, taxifolin, catechin, and protocatechuic acid were previously reported to be the major monomeric phenolics in P. radiata bark [6]. ...
Hardy kiwifruits (Actinidia arguta Planch.) have high amounts of antioxidants, including ascorbic acid (vitamin C) and phenolics. The anti-cholinesterase activity and neuroprotective effects of three
different cultivars of hardy kiwifruits, cv. Mansu (A. arguta × A. deliciosa), cv. Haeyeon (A. arguta), and cv. Chiak (A. arguta), on PC-12 and SH-SY5Y cells were evaluated. Extraction of phenolics and
vitamin C was carried out using 80% (v/v) aqueous ethanol and metaphosphoric acid assisted with homogenization, respectively. Hardy kiwifruit of cv. Mansu showed higher total phenolic, total
flavonoid, and vitamin C contents and antioxidant capacity compared to the other two cultivars of hardy kiwifruits, cv. Haeyeon and cv. Chiak. Analysis of high-performance liquid chromatography
results revealed the presence of procyanidin B2, (−)-epicatechin, neochlorogenic acid, cryptochlorogenic acid, rutin, hyperoside, isoquercitrin, and astragalin in hardy kiwifruits. The three cultivars of hardy kiwifruits had a wide range of vitamin C content of 55.2−130.0 mg/100 g fresh weight. All three cultivars of hardy kiwifruits had protective effects on neuronal PC-12 and SHSY5Y cells exposed to hydrogen peroxide by increasing cell viability and reducing intracellular oxidative stress. Furthermore, the hardy kiwifruits inhibited acetylcholinesterase and butyrylcholinesterase. Collectively, these results suggest that hardy kiwifruits rich in antioxidants like phenolics and vitamin C have good potential as functional materials in neuroprotective applications.
... Additionally, SFE is considered environment-friendly [20]. However, pine bark extracts contain a variety of polar phenolic compounds such as (-)-catechin, (-)-epicatechin, taxifolin, and phenolic acids (21,22). These polar compounds are difficult to extract under SFE conditions, particularly with CO 2 , the most widely used supercritical fluid, which is more suitable for the extraction of nonpolar solutes [20]. ...
Purpose
To summarize the main findings from research on food uses of Pine Bark Phenolic Extracts (PBPE), their origin, methods of extraction, composition, health effects and incorporation into food products.
Methods
A narrative review of all the relevant papers known to the authors was conducted.
Results
PBPE are mainly extracted from the bark Pinus pinaster. They are generally rich in procyanidins and their effects on health in the form of nutritional supplements include effect on some forms of cancer, on diabetes, on eye and skin health. Their method of extraction influences greatly their composition and yield, and commercially suitable methods are still to be developed. Incorporation into food products raises challenges related to bioavailability and subsequent bioactivity and sensory properties of the final products.
Conclusion
PBPE represent an opportunity for the development of functional foods with phenolic-rich bioactive compounds.
... Considering the usage of D. nervosa, which has been used as an external drug for the treatment of bone fracture, the percutaneous absorption was crucial to the effect of D. nervosa, especially the constituents of percutaneous absorption [7][8][9]. As far as we know, the constituent in vivo has not been investigated; therefore, it is worthwhile to identify the constituents of percutaneous absorption after D. nervosa for external use. ...
Duhaldea nervosa ( D. nervosa ) has been used for treatment of bone fracture by external use. Thus, the percutaneous absorption was crucial to the effect of D. nervosa, especially the constituents of percutaneous absorption. However, the constituents in vivo were never investigated to date. In this study, an efficient method was developed for the identification of constituents of percutaneous absorption using UHPLC-Q-Exactive Orbitrap MS and microdialysis technique. A total of 20 constituents including 15 chlorogenic acid analogues, 3 amino acids, and 2 organic acids were unambiguously or tentatively identified based on high-resolution mass data including MS and MS ² , chromatography retention time, and bibliography data. To the best of our knowledge, this is the first study to report the constituents of percutaneous absorption from D. nervosa , which will be very helpful for understanding the bioactive compounds and quality control.
... A previous study reported that KRPBE contained catechin, taxifolin, and oligomers of catechin and epicatechin [29]. Extract of the raw pine bark of P. maritima collected in France has been reported to contain a variety of phenolics, including catechin, protocatechuic acid, taxifolin, and vanillin [30]. Consistent with our findings in this study, taxifolin, catechin, and protocatechuic acid were previously reported to be the major monomeric phenolics in P. radiata bark [6]. ...
Korean red pine (Pinus densiflora) is one of the majorPinusspecies in Korea. Red pine barkis removed prior to the chipping process in the wood industry and discarded aswaste. However, red pine bark contains a considerable amount of naturally occurring phenolics including flavonoids and therefore may have a variety of biological effects. In this study, we investigated if Korean red pine bark extract (KRPBE) could protect neuronal PC-12 cells from oxidative stress and inhibit cholinesterase activity.Analysis of reversed-phase high-performance liquid chromatography results revealed four phenolics in KRPBE:vanillin, protocatechuic acid, catechin and taxifolin.Total phenolic and flavonoid contents of KRPBE were 397.9 mg gallic acid equivalents/g dry weight (DW) and 248.7 mg catechin equivalents/g DW, respectively. Antioxidant capacities of KRPBE measured using ABTS, DPPH, and ORAC assays were 697.3, 521.8, and 2,627.7 mg vitamin C equivalents/g DW, respectively. KRPBE and its identified phenolics protected against H2O2-induced oxidative cell death in a dose-dependent manner. Acetylcholinesterase and butyrylcholinesterase, which degrade the neurotransmitter acetylcholine to terminate neurotransmission in synaptic clefts, were inhibited by treatment with KRPBE and its identified phenolics. Taken together, these results suggest that KRPBE and its constituent antioxidative phenolics are potent neuroprotective agents that can maintain cell viability in the context of oxidative stress and inhibit cholinesterase activity.
... Showed good activity of absorption through human skin[88]Model:Other associated symptoms such as fatigue, constipation, pains in the body and anxiety were also improved.[89]Model: Human Diseases induced by: Previously Induced ...
The world is becoming uninhabitable owing to wide globalization. A large number of industries are contributing in water, soil, air, and environment pollution. Increased use of chemicals and accidental chemical spills are also hampering their surroundings. CFC containing tools and technologies are increasing due to higher demand in the market resulting ozone layers are highly affected which make the UV free towards the earth. Several environmental toxins and UV-radiation are the primary reasons for skin dysfunctions as a result skin loses its tone, strength, flux, density, and glamour that further lead to wrinkles and aging. Chronic UV exposure may also lead to skin cancers. pycnogenol, On the other hand, has been a major source for both flavonols and polyphenols which is very potent against several diseases. Evidences suggest that pycnogenol prevents from multiple skin dysfunctions. Its components are equally potent against skin cancers as well. Moreover, several harmful downstream kinases and proteins are also inhibited by this component. In addition, it has been strongly proven beneficial in reducing ageing by preventing free radical generations, at the same time; it also helps in cell regeneration and replication. Thus, in this study we tried to identify the correlate possible molecular theories on ageing and related skin diseases. Finally, a possible benefit of pycnogenol using on skin disorders would be established.
... Piknogenol deriden de kolaylıkla absorpsiyona uğrayabilmektedir. Polietilen glikol ile hazırlanan %5'lik piknogenol solüsyonunun 10 kadavraya topikal uygulandıktan sonra transdermal biyoyararlanımı incelendiğinde; gallik asit, protokateşik asit, kateşin, p-hidroksibenzoik asit, vanilin, taksifolinin absorbe olduğu tespit edilmiştir (Oliff, 2010;Sarikaki et al., 2004). Gönüllü insanlarda yapılan çalışmada piknogenolün oral alımından 2-3 saat sonra, sülfatasyon ve glukronidasyona uğradığı ve idrarda ferulik asit, taksifolin olarak ve M1 δ-(3,4-dihidroksi-fenil)-γvalerolakton) ve M2 (δ-(3-metoksi-4-hidroksi-fenil)γ-valerolakton) metabolitleri halinde atıldığı tespit edilmiştir (Oliff, 2010;Duweler & Rohdewald, 2000). ...
Pycnogenol, natural dried extract obtained from the bark of Pinus pinaster, is commonly consumed as a dietary food supplement due to its strong antioxidant and antiinflamatory effects. It is believed that some natural compounds might reduce the development of cancer through the antioxidant activity. The studies have supported the therapeutic role of Pycnogenol. Pycnogenol does not have toxic effect when consumed at the recommended doses, however, it should be noted that its high doses or long-term consumption of Pycnogenol may have toxic effects. It is predicted that the further studies needs to be performed to clarfy the mechanisms of Pycnogenol. In this review, the information on the pharmacokinetic and pharmacological properties of Pycnogenol and mechanisms of action, toxicity and safety of Pycnogenol were presented.
A cosmetic is a formulation containing substances of natural or artificial origin intended to boost the appearance of any part of the body for which it is designed to gain the esthetic appeal to the members of the audience. Such products are meant for use on the face to supplement one’s appearance and are often designated as makeup. Several undesirable effects are concomitant to synthetically based cosmetics owing to their content of harmful synthetic ingredients. Attention has then been shifted toward herbal bioactive-based cosmetics containing phytoconstituents possessing antioxidant and free-radical scavenging actions exploited to control skin disorders like dry skin, eczema, ageing, inflammations, etc., and in aromatherapy. Cosmetics appear as solids, semisolids, or liquids and in a broad sense, could be formulated as solutions, creams/emulsions, lotions, suspensions, ointments, pastes, powders, gels, sticks, pencils, tablets, capsules, or aerosols. They can be itemized according to the part of the body they are meant to be used at, such as products for the skin, hair, nails, teeth, and eye or on the basis of their function as emollients, cleansing, decorative, deodorant/antiperspirants, and protective preparations. Herbal bioactive ingredients suitable for preparing cosmetics could be extracted from various parts of organic materials, especially plants that are in abundance. With innovations in research and development and technology, these phytoconstituents are standardized and their novel products are patentable. The future and market for herbal bioactive-based cosmetics are high.
Background:
There is a need for novel skin antiseptic agents to combat the health-care burdens associated with surgical site infection (SSI) and bacterial resistance. The purpose of this proof-of-principle pilot study was to investigate the potential of the phenolic compound protocatechuic acid (PCA) as a topical antimicrobial for surgical skin antisepsis.
Methods:
The Kirby-Bauer method of disc diffusion was used to investigate the in vitro antimicrobial activity and comparative effectiveness of PCA and 7 related compounds against SSI pathogens. To explore the in vivo efficacy of topical PCA for providing deep, penetrating skin antisepsis, living Cutibacterium acnes was intradermally injected into the skin of female BALB/c mice. Mice were assigned to treatment with daily applications of topical PCA at 3 doses (78, 39, and 19.5 mM) or no treatment (n = 2 mice per group). After 96 hours, infected skin samples were harvested to compare mean C. acnes counts by treatment.
Results:
Compared with other polyphenols, PCA demonstrated the broadest spectrum of antimicrobial activity against tested SSI pathogens, including drug-resistant organisms. At 96 hours following infection, the mean C. acnes burden in untreated mice was 6.65 log colony-forming units (CFUs) per gram of skin. Compared with the untreated group, daily topical application of 78 mM of PCA was associated with a significantly lower C. acnes CFU burden in mice skin (mean, 5.51 log CFUs per gram of skin; p = 0.0295). Both lower dosages of topical PCA failed to show an effect.
Conclusions:
PCA demonstrated laboratory efficacy against pathogens implicated in SSI, including drug-resistant organisms. In vivo, topical PCA demonstrated dose-dependent skin penetration and antimicrobial activity against mouse skin C. acnes loads. Human clinical studies exploring the antimicrobial efficacy of topical PCA for preoperative shoulder skin antisepsis are warranted.
Clinical relevance:
Topical PCA may have the potential to improve current shoulder SSI treatment and prevention protocols.
Background
A great number of plants have been studied in recent times in order to identify and isolate new components with nutraceutical properties. In addition, there is a growing interest in the re-valorization of industrial byproducts as a source of bioactive molecules.
Scope and Approach
This present study highlights the potential of pine bark extract as a source of antioxidant and treatment diseases. Pine bark has a great content of bioactive molecules including polymeric flavanols, tannic acid, flavonoids and other phenolic acids such as caffeic or protocatechuic acid. Herein, we look at the most recent uses of pine bark extracts in the food industry and for biomedical purposes.
Key Findings and Conclusions
Regarding the food industry, pine bark extracts have been successfully used as antioxidants in the meat industry and have been proposed as interesting additives for the juice industry and Songzhen noodles production. On the other hand, different Pinus spp bark extracts have been tested against a wide range of disorders -cancer, diabetes mellitus, hypertension, atherosclerosis, neuroprotective effect and other oxidative stress and inflammatory-related diseases. Both in vitro and in vivo assays suggest a promising future for pine as an adjuvant therapy.
In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
The Oxygen Radical Absorbance Capacity (ORAC) assay was used to determine the total antioxidant capacity of tea. Green and black teas (n = 18) had a mean antioxidant capacity of 761.1 ± 85.3 μmol Trolox Equivalents (TE) per g dry matter. However, their antioxidant capacity varied from 235 μmol to over 1526 μmol Trolox equivalents (TE)/g dry matter, and total phenolics ranged from 32 to 147 mg/g in different commercial teas. One tea phenolics extract had an antioxidant capacity of 4796 μmol TE/g dry matter and 625 mg total phenolics/g. On a dry matter basis, an antioxidant capacity of 761 μmol TE/g is considerably higher than any of the other fruits and vegetables measured in our laboratory. However, since dry tea is not consumed directly, brewing conditions may influence the final antioxidant capacity in the tea as consumed. We tested both green and black teas by placing one tea bag (1.95 g) in 150 ml (5 oz.) of boiling water. In the first brewed cup, approximately 84% of the total antioxidant activity was solubilized within the first 5 min of brewing. An additional 13% of the antioxidant activity was extracted into the second glass of 150 ml with an additional 5 min of brewing. At the dilutions obtained after the first brewing, the tea as consumed would contain approximately 8.31 μmol TE per ml. This total antioxidant capacity compares to other drinks from fruits and vegetables that had antioxidant capacity values ranging from 1.6 to 15 μmol TE/ml. At these antioxidant levels, consumption of 150 ml of tea could make a significant contribution to the total daily antioxidant capacity intake. (-)-Epicatechin and (+)-catechin, two components from tea, had an antioxidant capacity of 2.36 and 2.49 μmol/μmol or 8.13 and 8.58 μmol/mg, respectively. In 16 tea samples we observed a mean of 10.0 ± 0.6 μmol TE/mg total phenolics. Tea can be an important source of what has been referred to as “non-nutrient” antioxidant phytochemicals. However, with the variation that exists in antioxidant capacity with various tea preparations, measures of antioxidant capacity intake are critical to the study of intake and health outcomes and/or biomarkers of health outcomes.
A co-culture system was used to study the effect of reactive nitrogen species (RNS) generated by RAW 264.7 macrophages grown on filters and activated by lipopolysaccharide and interferon-γ, on the α-tocopherol levels in ECV 302 endothelial cells. The results indicate that: RNS generated by activated macrophages or by direct administration of peroxynitrite lead to a significant loss of α-tocopherol in endothelial cells; pre-incubation with procyanidin extracted from pine bark (Pycnogenol) protects α-tocopherol of endothelial cells and enhances by about 15% basal endogenous levels of α-tocopherol. These results demonstrate flavonoids participate in the cellular antioxidant network and suggest that Pycnogenol may play an important role in the protection of endothelium from oxidative stress induced by reactive nitrogen species.
Pycnogenol, an extract from French maritime pine bark (PBE), is a complex mixture of bioflavonoids with reported protective effects against disease. PBE is an effective scavenger of reactive oxygen species, and its main constituents are procyanidins of various chain lengths. To find out the biochemical basis of action of on enzyme activity, involvement of its redox activity and direct binding to the enzyme in its subsequent action on enzyme activity have been investigated. PBE dose-dependently inhibited the activities of xanthine oxidase, xanthine dehydrogenase, horseradish peroxidase, and lipoxygenase, but it did not affect the activities of glucose oxidase, ascorbate oxidase, or elastase. To characterize the mechanism of PBE action, studies were focused on xanthine oxidase and glucose oxidase. Under non-denaturing conditions, PBE changed the electrophoretic mobility of xanthine oxidase but not of glucose oxidase. Gel filtration chromatography confirmed higher molecular weight complexes of xanthine oxidase and xanthine dehydrogenase in the presence of PBE. It was found that hydrophobic bonding might be the dominant mode of interaction between PBE and xanthine oxidase. The importance of the binding in the effect of PBE on enzyme activity was supported by the observation that PBE binds to and inhibits catalase, but not superoxide dismutase. However, no correlation was found between superoxide/hydroxyl radical scavenging activity and the inhibitory effect on xanthine oxidase activity of PBE, various purified flavonoids, or other complex mixtures of bioflavonoids. The results indicate that PBE selectively inhibits xanthine oxidase through binding to the enzyme rather than by the redox activity.
Considerable evidence points to the health benefits of the phytochemical constituents of fruit, vegetables, beverages, and grains in protection against cardiovascular disease and certain cancers. This may be accounted for through contributions from their constituent antioxidants (vitamin E, vitamin C, β-carotene, other carotenoids and the non-nutrient flavonoids, ubiquitous phytochemical components of the diet), as well as through other anticarcinogenic and cardioprotective effects independently of their antioxidant effects. Indeed, the epidemiological evidence for a risk-reducing role of vitamin C for cancer is not as strong as that for fruit and vegetables (1).Dietary components may contribute to antioxidant function in several ways that relate to their structural chemistry (2): i) by directly scavenging free radicals through hydrogen/electron donation, depending on their reducing properties, or reduction potentials; ii) by intercepting the propagatory chain reactions of lipid peroxidation and scavengin...
cer. Chemoprevention is a means by which the use of naturally occurring and/or synthetic compounds com- pletely prevents, blocks or reverses the occurrence of the disease. Prevention of cancer through dietary intervention has received considerable attention in the recent past and is viewed as a potential strategy for the management of cancer (1, 2). Ever since the finding from this laboratory in 1988 and 1989 about anticarcinogenic and antimutagenic activity of polyphenolic agents present in green tea (3-3, preven- tion of cancer through the consumption of this widely used beverage is receiving increasing attention. Green tea, de- rived from the plant
The Oxygen Radical Absorbance Capacity (ORAC) assay was used to determine the total antioxidant capacity of tea. Green and black teas (n = 18) had a mean antioxidant capacity of 761.1 ± 85.3 μmol Trolox Equivalents (TE) per g dry matter. However, their antioxidant capacity varied from 235 μmol to over 1526 μmol Trolox equivalents (TE)/g dry matter, and total phenolics ranged from 32 to 147 mg/g in different commercial teas. One tea phenolics extract had an antioxidant capacity of 4796 μmol TE/g dry matter and 625 mg total phenolics/g. On a dry matter basis, an antioxidant capacity of 761 μmol TE/g is considerably higher than any of the other fruits and vegetables measured in our laboratory. However, since dry tea is not consumed directly, brewing conditions may influence the final antioxidant capacity in the tea as consumed. We tested both green and black teas by placing one tea bag (1.95 g) in 150 ml (5 oz.) of boiling water. In the first brewed cup, approximately 84% of the total antioxidant activity was solubilized within the first 5 min of brewing. An additional 13% of the antioxidant activity was extracted into the second glass of 150 ml with an additional 5 min of brewing. At the dilutions obtained after the first brewing, the tea as consumed would contain approximately 8.31 μmol TE per ml. This total antioxidant capacity compares to other drinks from fruits and vegetables that had antioxidant capacity values ranging from 1.6 to 15 μmol TE/ml. At these antioxidant levels, consumption of 150 ml of tea could make a significant contribution to the total daily antioxidant capacity intake. (−)-Epicatechin and (+)-catechin, two components from tea, had an antioxidant capacity of 2.36 and 2.49 μmol/μmol or 8.13 and 8.58 μmol/mg, respectively. In 16 tea samples we observed a mean of 10.0 ± 0.6 μmol TE/mg total phenolics. Tea can be an important source of what has been referred to as “non-nutrient” antioxidant phytochemicals. However, with the variation that exists in antioxidant capacity with various tea preparations, measures of antioxidant capacity intake are critical to the study of intake and health outcomes and/or biomarkers of health outcomes.
Tea is an important dietary source of flavonols in countries such as the Netherlands, the United Kingdom and Japan. Flavonols may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumor development in animal studies. The association between flavonol intake and cancer risk was investigated in three prospective studies (Zutphen Elderly Study in the Netherlands, a Finnish cohort, and the Netherlands Cohort Study). Only one study (Finnish cohort) showed an inverse association with cancer mortality. The intake of flavonols with subsequent cardiovascular disease was studied in six prospective epidemiological studies. In some populations (Seven Countries Study, Zutphen Elderly Study, a Finnish cohort) a clear protective effect was observed. In a large US cohort, a protective effect was only found in a subgroup with previous history of coronary heart disease, whereas in Welsh men, flavonol intake, mainly from tea, was associated with an increased risk of coronary heart disease. These conflicting results may be due to confounding by coronary risk factors associated with tea consumption. The question of whether flavonols protect against cardiovascular disease remains still open; a protective effect of flavonols against cancer is less likely.