Quality assessment of Cranberry (Vaccinium macrocarpon) based food supplements: HPTLC, HPLC and PAC quantification as effective tools for quality management

Quality assessment of Cranberry (Vaccinium macrocarpon) based food supplements: HPTLC, HPLC and PAC quantification as effective tools for quality management | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Quality assessment of Cranberry (Vaccinium macrocarpon) based food supplements: HPTLC, HPLC and PAC quantification as effective tools for quality management Alexa Brouns, Matthias Lechtenberg, Andreas Hensel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8523151/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cranberry-based food supplements with extracts from the fruits of Vaccinium macrocarpon are widely marketed for urinary tract health. As food supplements containing plant extracts, the so-called botanicals, are known to have quality problems the present study assembled efficient analytical protocols for evaluation of cranberry products for unambiguous identity testing and quantitation of procyanidins. Twelve cranberry-containing food supplements available in the D-A-CH region were included into the study. The analytical investigation comprised uniformity of mass testing of single-dosed capsule preparations, identity fingerprinting by HPTLC and HPLC and photometric quantification of the procyanidin content. Major deficiencies were detected such as labelling inconsistencies and deviations in capsule mass which indicated poor manufacturing control. The chromatographic analysis revealed that three products did not show specific anthocyanin fingerprints being typical for V. macrocarpon . In addition, deficiency was obvious concerning batch-to-batch conformity of certain brands. The results highlight the urgent need for specific analytical methods in quality control to verify botanical authenticity. Results again underscore critical regulatory gaps between the pharmaceutical-like presentation of such food supplements and their actual quality. Harmonized quality standards and stricter regulatory oversights are urgently needed to ensure transparency, consumer safety, and product integrity in the botanical supplement market. Cranberry fingerprint food supplements procyanidin quality Vaccinium macrocarpon Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Cranberries, the fruits from Vaccinium macrocarpon Ait. (Ericaceae), originating from the high moors of North America are used for its preventative effect against uncomplicated urinary tract infections (UTI). The positive effects of cranberries for UTI are due to the inhibition of early host-pathogen interaction, especially in regard to the adhesion of FimH-dominated uropathogenic Escherichia coli (UPEC) to bladder and kidney cells of the human host (Scharf et al. 2017 ; Gbinigie et al. 2020 ). These antiadhesive properties have been discussed to be due to a direct interaction of oligomeric proanthocyanidins (PAC) with the mannose-binding side of UPEC. Due to the low bioavailability of PAC after oral intake this mode of action might not contribute to a high extend to the positive effects of cranberry extract for UTI (Scharf et al. 2017 ; Scharf et al. 2020 ). In contrast, recent studies indicated an indirect antiadhesive effect, as cranberries stimulate the secretion of the highly mannosylated glycoprotein Tamm-Horsfall Protein (syn. THP, uromodulin) in the distal part of the kidney, which again interacts with the mannose-binding side of UPEC, preventing the adhesion of UPEC to uroplakin-receptors on the bladder epithelium (Scharf et al. 2019 ). For this, cranberry extracts are assessed nowadays as inductors of the innate immune defense within the urinary tract. For medical use, the European Medicines Agency (EMA) has published two monographs for liquid cranberry preparations within the traditional use and distinguishes between two indications, namely for the treatment of acute, uncomplicated UTI with mild symptoms, and additionally for prevention of recurrent uncomplicated UTI (European Medicines Agency - Herbal Medicinal Products Committee 2022 ). The phytochemical composition of cranberries is mainly characterized by the presence of oligomeric A-type PAC, anthocyanins, flavonoids, mainly flavonols, organic acids, and xyloglucan-like polysaccharides; for review see (Scharf et al. 2020 ; Xu et al. 2025 ). Cranberries contain also a high molecular weight fraction, known as non-dialyzable material (NDM) that has been reported to exert antiadhesive activity against different bacteria, as e.g. Helicobacter pylori strains to gastric epithelial cells (Burger et al. 2000 ; Burger et al. 2002 )d mutans and S. sobrinus to saliva-coated hydroxyapatite beads (Yamanaka et al. 2004 ). The nature of NDM is not clear but it is discussed to be a mixture of polymeric A-type PAC in combination with denatured proteins and xyloglucan (Neto et al. 2017 ). In regard to positive effects against bacterial pathogens in the urinary tract and the THP-stimulation in the kidney, especially A-type PAC are in the focus (Howell et al. 2005 ). Cranberry A-type PAC differ structurally from PAC found in other tannin-rich plants, such as green tea, grapes, or cocoa, dominated by B-type PAC, which do not exert antiadhesive activity (Howell et al. 2005 ). Cranberries typically contain six major anthocyanins, specifically the 3- O -glycosides of the anthocyanidins cyanidin and peonidin, which are linked to β-D-glucose, β-D-galactose, or α-L-arabinose (Foo et al. 2000 ). This specific anthocyanin-pattern (structural features see Fig. 1 ) can be used for identity testing of cranberry extracts, as it differs clearly from other fruits from the Ericaceae plant family and other anthocyanin containing plant material. Even though cranberry extracts are widely used for medical applications and a variety of clinical studies with positive outcome for UTI treatment have been reported, no cranberry-containing herbal medicinal products (HMP) have been registered in Germany. Instead, a steadily growing market for cranberry-based dietary supplements and food products has emerged. However, the European Food and Safety Authority (EFSA) has not approved any health claims for cranberry products until now (European Commission 2025 ). This has led to the marketing of cranberry-based food supplements with vague indications for use, most of which are promoted to consumers as providing benefits for the urinary tract system. In many cases it is not clear for the consumer if such a product is a registered drug-like HMP or a food supplement. This again leads to the problem of product quality. While HMP have controlled and reproducible quality due to legislation, registration and the underlying GMP guidelines, food supplements are covered by the national food laws and are therefore not subject to the strict requirements for efficacy, safety and quality that apply to authorized medicinal products. This lack of approval in combination with a presentation of food supplements similar to authorized drugs makes it difficult for consumers and health professionals to assess the quality of food supplements. Recent analytical investigations of food supplements containing plant extracts, the so-called botanicals, indicated strong quality deficiencies in many cases, ranging from food fraud without any active ingredients to strongly underdosed products and to products containing serious falsifications or even toxic adulteration (Lechtenberg and Hensel 2019 ; Gaspar et al. 2021 ; Sendker et al. 2022 ; Brouns et al. 2025 ). Therefore, many international societies and governmental institutions repeatedly ask for stringent analytical batch-to-batch control of food supplements by specific and validated analytical protocols, establishment of a nutrivigilance system and governmental reactions against manufacturer in case of quality violence. Cranberry food supplements are the top-selling products in the segment of food supplements. Differences between products are due to the respective PAC content. The dried press cake, obtained from the fruits after the juice has been squeezed out, contains about 0.8 to 1.5% PAC (American Botanical Council 2017 ). Many of the food supplements use this pre-extracted bulk material as “active ingredient”. On the other side cranberry drinks are characterized by PAC content of 3 to 5%, while pure cranberry juice should contain 12 to 24% PAC (American Botanical Council 2017 ). Falsification of cranberry products with other lower-cost PAC-enriched extracts have been described (e.g., peanuts from Arachis hypogaea , grape seeds from Vitis vinifera ) (American Botanical Council 2017 )). Also, adulterants with anthocyanin-enriched extracts are known (e.g. mulberry from Morus spp., hibiscus from Hibiscus sabdariffa , black beans from Phaseolus vulgaris , black rice from Oryza sativa ) (American Botanical Council 2017 ). Additionally, anthocyanin-enriched extracts from other Vaccinium species (e.g. V. corymbosum , V. oxycoccos , V. vitis-idaea ) might be suitable to simulate cranberry, but can clearly be differentiated by the respective anthocyanin fingerprint (Brown et al. 2012 ). As until now no monograph for cranberries has been published in the European Pharmacopoeia, the aim of this analytical project was to compile relevant analytical methods for the authentication of cranberry extracts, evaluating the typical anthocyanin pattern of the fruits by HPTLC and HPLC and colorimetric quantification of total PAC content. This collection of methods was used to assess the quality of food supplements obtained from different sources. 2. Materials and Methods 2.1 Materials and reference standards If not stated otherwise, solvents, reagents, and consumables were obtained from VWR International (Darmstadt, Germany). All solvents and reagents were of analytical quality. Water was produced by a Millipore Simplicity 185 system (Merck, Darmstadt, Germany). Procyanidin A2 (lot 16753) was obtained in reference standard quality from Phytolab (Vestensberggreuth, Germany). Cy3Gal (lot 18), Cy3Glc (lot 48) and Peo3Gal (lot 03) were obtained in reference standard quality from ExtraSynthese (Genay, France). V. vitis-idea was obtained as dried lingonberries from Galke (Bad Grund, Germany), lot 47545 (IPBP No. 917). Authenticated plant material from Vaccinium macrocarpon was obtained from the medicinal plant garden of University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany. Authentication was performed by AH and AB. Voucher samples are stored at the archives of the institute (IPBP 916). Authenticated plant material from Vaccinium oxycoccos was obtained from a controlled garden area in Münster, Germany (GPS positioning 51.9942, 7.5937). Authentication was done by Mr. André Niermann, voucher sample IPBP 918). 2.2. Cranberries, cranberry juices, cranberry containing food supplements Twelve different cranberry products were obtained on a commercial base for internet shops, pharmacy stores and herbal trade shops (Table 1 ). Product #01 represents a concentrated cranberry juice (puree), #11 are dried cranberries, the other products represent food supplements in capsule form. Declaration of supplement facts and specific claims of the respective products are displayed in Table 1 . Table 1 Overview of the analyzed cranberry-based food supplements No. Supllier or distributor name Shelf life LOT/ batch number Nutrition facts, content, serving size Further labeling (translated into English) #01 Anton Hübner GmbH & Co KG Donath Vollfrucht Cranberrry ungesüßt 19.04.2023 --- Cranberry puree #02 Bergland Pharma GmbH & Co KG Bergland Cranberry Lutschtabletten 06/2025 L2172/1 Cranberry juice powder (36%) a 15 mg b 3 capsules c Contains additionally Acerola powder with vitamin C (10%), #03 Avitale GmbH Avitale Cranberry Kapseln 10/2025 L2291/3 Crannberrypowder AV36 400 mg a 18 mg b 2×1 capsule per day c Contains aditionally excipients #31 Avitale GmbH Avitale Cranberry Kapseln 09/2026 L3249/1 Crannberrypowder AV36 400mg a 18mg b 2×1 capsule per day c Contains aditionally excipients #04 Dm- drogerie markt GmbH + Co. KG Mivolis Cranberry + Vitamin C 10/2025 393001 Cranberry-Extract 300 mg a 18 mg b 2×1 capsule c Contains additionally excipients and vitamin C #41 DM Drogerie Markt GmbH + Co. KG Mivolis Cranberry + Vitamin C 03/2026 39009 Cranberry-Extract 300 mg a 18 mg b 2×1 capsule c Contains additionally excipients and vitamin C #05 Pro medico Handels GmbH pure encapsulations – Cranberry Extrakt 05/2025 2260666 Cranberry extract (CranMax): 500 mg a 1 capsule per day c Contains additionally cranberry fibers and cranberry seed oil, excipients #06 11A Nutrithek GmbH Cranberry 36 12/2025 25122 Cranberry extract: 53 mg a 36 mg b 1 capsule per day c Contains additionally excipients #07 Hecht Pharma GmbH Cranberry 400mg GPH-Kapseln 08/2027 405.77 Cranberry Concentrate (400 mg = 10 g Cranberrys) a 3×1 capsule c Contains additionally excipients #08 Naturafit GmbH Cranberry 400 12/2024 41221 Cranberry Powder: 400 mg (= 10 g pure Cranberry) a 4 capsules per day after food c Contains additionally excipients #09 Quiris Healthcare Cystorenal plus 09/2024 0090894 Cranberry extract: 300 mg (25:1) a 12 mg b 3×1 capsule c Contains additionally pumpkin seed extract 4:1 (18%) vitamin C, vitamin B2, excipients #10 NeoElementum OÜ CardioBalance 06/2024 1042023 Cranberry extract 225 mg a 2×1 capsule per day c Contains additionally chokeberry extract: 200 mg (20:1), Calcium butyrate 200 mg *, magnesium 150 mg, Gymnema Sylvestre 100 mg *, L-Arginine 150mg, extract from hawthorn leaves and flowers 150 mg (6:1), Hibiscus flower powder 50 mg, Olive leaf extract 50 mg (10:1), Grape seed extract 50 mg (8:1), Blackcurrant fruit extract 25 mg (4:1), Coenzyme Q10 20 mg, Vitamin B6 1.4 mg, Folic acid 100 µg #11 Adler Vital Cranberries 29.10.2023 NOV2322W3 #12 Vitarmonyl Laboratoires Cranberry 06/2025 1637YAA Cranberry extract: 200 mg a 6 mg b 2×1 capsules per day c Contains additionally excipients a mg Cranberry extract or concentrate per capsule/unit; b total [mg] procyanidin per capsule/unit; c serving size; * specified in the enclosed product leaflet, but not on the primary packaging box 2.3. Cranberry dry reference extract (CDE) Authenticated fruits from V. macrocarcpon were harvested and frozen immediately. Fifty grams of the frozen fruits were pulverized crushed in an ice-cold mortar and extracted with 500 mL of ethanol 96% (v/v) for 30 min by use of a rotor-stator extractor (Ultra Turrax, IKA, Germany). The suspension was filtered (VWR filter paper 413) and the clear solution was evaporated to dryness under vacuo , followed by lyophilization to yield 5% (w/w, related to the fresh plant material) of the cranberry dry reference extract, which is termed as CDE in the following. 2.4. Fingerprinting by HPTLC (PAC, anthocyanins, chlorogenic acid, hyperoside) For identity testing of cranberry extract HPTLC analysis was used based on a protocol of the USP (United States Pharmacopeia Convention 2023 , 2024 ). Procyanidin A2 (1 mg/mL in MeOH), Cy3Gal, Cy3Glc, Peo3Gal, chlorogenic acid and hyperoside (0.2 mg/mL MeOH) served as reference standards. Cranberry dry extract (CDE) was used as reference extract. Test samples, for which a defined PAC content was specified by the manufacturer (#02, #03, #31, #04, #41, #06, #08, #12) were investigated by preparing solutions as follows: an aliquot of the contents of the capsules, equivalent to 8.5 mg of total PAC, is transferred to a 10 mL centrifuge tube. Seven milliliters of water are added. For #05, #07, #08, #10 and CDE 50 mg sample material is mixed with 7 mL of water. The respective suspensions are sonicated for 10 min and subsequently centrifuged for 5 min at 3600 × g. The clear supernatant is used for further processing. A solid-phase extraction cartridge (C18, 500 mg/3 mL, Macherey-Nagel, Germany) is conditioned with 3 mL of MeOH. Subsequently, 3 mL of water are loaded on the cartridge and sucked into until the solvent level is 1 to 2 mm above the stationary phase. 1.5 mL of the test solution is loaded onto the cartridge and sucked into the column. The eluate is discarded. The stationary phase is rinsed with 1 mL of water-MeOH (8:2, v/v). The eluate is discarded. Finally, 1 mL of MeOH is used to elute the retained compounds. This eluate is collected as the test solution for subsequent HPTLC. Mobile phase for HPTLC: ethylformiate, formic acid, water, toluene (60:8:6:3, v/v/v/v). Spotting volume: 5µL for references and 15 µL for samples, 8 mm. Development: 70 mm. Drying: 5 min by air stream at RT. Detection 1: 100 to 105°C for 5 min, followed by spraying with a solution of diphenylboryloxyethylamine (10 g/L) in MeOH, evaluation in day light and λ = 366 nm. Detection 2: spraying with a mixture of 170 mL ice-cooled MeOH in 20 mL of glacial acetic acid, 10 mL of sulfuric acid and 1 mL of anisaldehyde, followed by heating of the TLC plate to 100° C for 5 min. Evaluation in day light. 2.5. Fingerprinting of anthocyanins by HPLC HPLC system: Shimadzu LC10A with system controller (SCL10A), autosampler (SIL10A), pumps (LC10AT), degasser (JASCO DG-2080-53), oven (CTO10A) and UV-VIS detector SPD10A. Stationary phase: GeminiNX 110 Å, 5 µm, 250 mm (Phenomenex, USA), (alternatively with same selectivity Kromasil 100 Å, 5 µm, 250 mm, Phenomenex, USA). Mobile phase: (A) water, formic acid (91.5:8.5, v/v); (B) water, MeOH, acetonitrile, formic acid (41.5:22.5:22.5:8.5, v/v/v/v/); gradient: t 0min : 80% (A), t 35min : 75% (A), t 46min : 35% (A), t 57min : 0% (A). Flow rate: 1.0 mL/min. Injection volume: 10 µL for reference solutions, 30 µL for test solutions. Oven temperature: 30°C. Detection: λ = 535 nm. To recognize possible adulteration with the small cranberry ( V. oxycoccos ), the respective fruits from authenticated plants were harvested and treated as described for preparation of CDE, using 10 g fruits extracted with 100 mL EtOH 96% (v/v). For adulteration with lingonberry ( V. vitis idaea ), the dried fruits were frozen using liquid nitrogen and subsequently pulverized. One gram of the pulverized material was mixed with 10.0 mL of water and extracted in an ultrasonic batch for 15 min. The extract was centrifuged (3600 × g, 5 min) and the clear supernatant collected for solid-phase extraction (SPE) [SPE was employed to concentrate the anthocyanins, since a direct extraction of the fruits with MeOH yielded insufficient anthocyanin concentrations]. An SPE cartridge (C18, 500 mg, 3 mL; Macherey-Nagel, Germany) was conditioned with 3 mL MeOH, followed by 3 mL water. Subsequently, 4 mL of the aqueous extract were loaded onto the cartridge and eluted. Subsequently, 1.0 mL of a mixture of water/MeOH (80:20, v/v) was loaded onto the cartridge and eluted. Finally, the anthocyanins were eluted with 1.0 mL of MeOH. The eluate served as the test solution for HPLC analysis. Test solutions from cranberry food supplements: The equivalent of an average mass from one capsule of the test products was weighted exactly into a flask and was extracted with 25.0 mL of a mixture of MeOH and hydrochloric acid (98: 2 v/v). After centrifugation (3600 × g, 5 min), 5.0 mL of the clear supernatant were diluted with phosphoric acid in water (10% w/w) to 20.0 mL to serve as test solution for HPLC. Test solution from cranberry dried fruits: 1 g of dried fruits were extracted with 10.0 mL of MeOH: water (1:1 v/v) by ultrasonic treatment for 15 min. Subsequently, the suspension was centrifuged (3600 × g, 5 min). The clear supernatant serves as test solution. Test solutions from cranberry liquid preparations: 10 mL of the liquid samples were transferred to a sample tube and were centrifuged (3600 × g, 5 min). The clear supernatant served as test solution for HPLC. The HPLC protocol was validated for the parameters system precision (± 0.54%), linearity in the range of 5 to 100 µg/mL and recovery rate 100.7 ± 1.7% by using Pn3Gal (Supplementary Data File, Figure S1 ). 2.6. Quantification of PAC (United States Pharmacopeia Convention 2023 , 2024 ) Reagent solution: 4-(Dimethylamino)-cinnamaldehyd (DMAC, 1 mg/mL) in 0.4 mol/L sulfuric acid. The solution must be prepared fresh every day. Standard stock solution: procyanidin A2, 90 µg/mL in MeOH. Standard solutions: A minimum of five calibration solutions, ranging from 10 to 30 µg/mL procyanidin A2 in MeOH, were prepared from the standard stock solution by dilution with MeOH. Test solution from cranberry capsule preparations: A portion of the capsule content, equivalent to 36 mg of total PAC, was transferred to a 100 mL flask, suspended in MeOH, sonicated for 10 min, followed by shaking for 10 min. 10 mL of the resulting suspension were centrifuged for 5 min at 1950 × g. The clear supernatant is diluted with MeOH to a test solution being nominally equivalent to a PAC content of 0.02 mg/mL. For the samples without a PAC declaration 2.0 g of sample material were transferred to a 100 mL flask, suspended in 100.0 mL MeOH and sonicated for 10 min. The suspension was centrifuged (1950 × g, 5 min). The clear supernatant was used for further analysis. The reagent solution (250 µL) was mixed with 50 µL of the test sample solutions in a 96-well plate. A PAC-free solvent control, containing MeOH, is used as a blank. The resulting absorbance was determined constantly for 5 min at λ = 640 nm immediately after mixing the reagents. The highest absorbance is recorded. Absorbance values obtained from the standard solutions are used for calibration (R 2 > 0.98) to calculate total PAC content as procyanidin A2. The total PAC content per capsule is calculated as follows: $$\:PAC\:content\:\left(\%\:of\:specified\:content\right)=c\times\:{V}_{U}\:\times\:({W}_{AF}/\text{W})\:\times\:\:({V}_{F}/{V}_{A})$$ c: concentration (mg/mL) of sample solution, calculated as procyanidin A2 from the calibration; V U : volume (mL) of sample stock solution; W AF : average filling (mg) per capsule; W: weight of the capsules content (mg) for preparation of the sample stock solution; V F :: final volume (mL) of the sample solution; V A : volume (mL) of the aliquot of the sample stock solution. For validation of the protocol, the recovery rate (> 99%) was determined by spiking test solutions with procyanidin A2 reference standard (n = 3). All assays were performed in two independent investigations with n = 3 technical replicates. For final evaluation the respective mean values were used. Validation of the protocol was performed concerning linearity of detection signals in the range of 10 to 30 µg/mL of procyanidin A2 (Supplementary Data File, Figure S2). 2.7. Uniformity of mass for single-dose preparations (Bundesinstitut für Arzneimittel und Medizinprodukte 2024) Twenty randomly selected capsules are weighted. The content of each capsule is removed by a gentle air stream. The capsule shells are weighed, and the net filling mass is determined. The test meets the requirements of if not more than two capsules deviate +/- 7.5% from the average filling mass. None of the capsules may deviate more than +/- 15% from the mean value. In cases of average filling mass of < 300 mg the respective limits are +/- 10% and +/-20%. 3. Results and discussion Analytical investigations of a series of twelve cranberry containing food supplements (Table 1 , #01 to #12), representing the cranberry market in the D-A-CH region, was performed. Beside cranberry puree (#01), dried cranberry fruits (#11), and lozenges (#02) most of the investigated products were capsule preparations. Table 1 displays a detailed overview on the characteristics of the different products. The test samples were obtained from internet trading as well as from community pharmacies and herbal shops. Freshly harvested, authenticated and air-dried plant material from V. macrocarpon served as reference. Table 1: Overview of the analyzed cranberry-based food supplements No. Supllier or distributor name Shelf life LOT/ batch number Nutrition facts, content, serving size Further labeling (translated into English) #01 Anton Hübner GmbH & Co KG Donath Vollfrucht Cranberrry ungesüßt 19.04.2023 --- Cranberry puree #02 Bergland Pharma GmbH & Co KG Bergland Cranberry Lutschtabletten 06/2025 L2172/1 Cranberry juice powder (36%) a 15 mg b 3 capsules c Contains additionally Acerola powder with vitamin C (10%), #03 Avitale GmbH Avitale Cranberry Kapseln 10/2025 L2291/3 Crannberrypowder AV36 400 mg a 18 mg b 2×1 capsule per day c Contains aditionally excipients #31 Avitale GmbH Avitale Cranberry Kapseln 09/2026 L3249/1 Crannberrypowder AV36 400mg a 18mg b 2×1 capsule per day c Contains aditionally excipients #04 Dm- drogerie markt GmbH + Co. KG Mivolis Cranberry + Vitamin C 10/2025 393001 Cranberry-Extract 300 mg a 18 mg b 2×1 capsule c Contains additionally excipients and vitamin C #41 DM Drogerie Markt GmbH + Co. KG Mivolis Cranberry + Vitamin C 03/2026 39009 Cranberry-Extract 300 mg a 18 mg b 2×1 capsule c Contains additionally excipients and vitamin C #05 Pro medico Handels GmbH pure encapsulations – Cranberry Extrakt 05/2025 2260666 Cranberry extract (CranMax): 500 mg a 1 capsule per day c Contains additionally cranberry fibers and cranberry seed oil, excipients #06 11A Nutrithek GmbH Cranberry 36 12/2025 25122 Cranberry extract: 53 mg a 36 mg b 1 capsule per day c Contains additionally excipients #07 Hecht Pharma GmbH Cranberry 400mg GPH-Kapseln 08/2027 405.77 Cranberry Concentrate (400 mg = 10 g Cranberrys) a 3×1 capsule c Contains additionally excipients #08 Naturafit GmbH Cranberry 400 12/2024 41221 Cranberry Powder: 400 mg (=10 g pure Cranberry) a 4 capsules per day after food c Contains additionally excipients #09 Quiris Healthcare Cystorenal plus 09/2024 0090894 Cranberry extract: 300 mg (25:1) a 12 mg b 3×1 capsule c Contains additionally pumpkin seed extract 4:1 (18%) vitamin C, vitamin B2, excipients #10 NeoElementum OÜ CardioBalance 06/2024 1042023 Cranberry extract 225 mg a 2×1 capsule per day c Contains additionally chokeberry extract: 200 mg (20:1), Calcium butyrate 200 mg *, magnesium 150 mg, Gymnema Sylvestre 100 mg *, L-Arginine 150mg, extract from hawthorn leaves and flowers 150 mg (6:1), Hibiscus flower powder 50 mg, Olive leaf extract 50 mg (10:1), Grape seed extract 50 mg (8:1), Blackcurrant fruit extract 25 mg (4:1), Coenzyme Q10 20 mg, Vitamin B6 1.4 mg, Folic acid 100 µg #11 Adler Vital Cranberries 29.10.2023 NOV2322W3 #12 Vitarmonyl Laboratoires Cranberry 06/2025 1637YAA Cranberry extract: 200 mg a 6 mg b 2×1 capsules per day c Contains additionally excipients a mg Cranberry extract or concentrate per capsule/unit; b total [mg] procyanidin per capsule/unit; c serving size; * specified in the enclosed product leaflet, but not on the primary packaging box Deficiency in product declaration of cranberry food supplements At a first glance the test sample #10, which represents a combination of different plants extracts revealed strong differences in the declaration of the product concerning the information given on the primary packaging material and the information leaflet (Supplementary Data, Figure S3). Two ingredients, specified on the product leaflet, have not been specified on the capsules box. From this point of view product #10 does not meet the legal requirements concerning information of the consumer. Uniformity of mass of single dose cranberry products As the presentation of the food supplements is similar to that of medicinal products, test on uniformity of mass for single-dose preparations according to the European Pharmacopoeia (Bundesinstitut für Arzneimittel und Medizinprodukte 2024) was performed for the solid oral dosage forms. One sample (#08) did not meet the requirements, as one capsule deviated more than 15% from the mean. This result indicates the need for improvement of the technical production of capsules and tablets in the field of food supplements, as similar investigations a few years ago have also shown serious shortcomings for solid formulations concerning uniformity of mass (Gaspar et al. 2021 ). Identity testing by HPTLC HPTLC fingerprinting according to the methodology of USP-NF 2024 (United States Pharmacopeia Convention 2023 , 2024 ) was employed for identity testing of the samples, using chlorogenic acid, hyperoside, procyanidin A2, cyanidin-3- O -galactosid (Cy3Gal), cyanidin-3- O -glucosid (Cy3Glc) and peonidin-3- O -galactosid (Peo3Gal) as reference compounds (Fig. 1 ). Detection was performed after spraying with diphenylboryloxyethylamine and monitoring at day light at λ = 366 nm, and after derivatization with anisaldehyde-sulfuric acid (Fig. 2 A to C). After derivatization with diphenylboryloxyethylamine the reference standards hyperoside (hyp), Cy3Gal, Cy3Glc and Peo3Gal showed characteristic-colored bands at Rf-values between 0.2 and 0.6. The cranberry dry extract exhibited bands matching Cy3Gal, Cy3Glc and Peo3Gal, as well as hyperoside. At λ = 366 nm the fluorescent bands for chlorogenic acid (chl.ac) (R f = 0.65) and hyperoside (Rf = 0.6) were clearly visible, while Cy3Gal, Cy3Glc and Peo3Gal are not visible under these conditions. The CDE lane revealed multiple bright fluorescent zones in the middle to upper R f region. The evaluation of the test samples was based on the presence, intensity and distribution of these characteristic zones in the chromatograms. Sample #02 corresponds to the reference profile, although the zones appeared weaker. Sample #03 showed partial similarity to the reference. In contrast, sample #04 did not correspond and for #05 and #08 no detectable zones were observed. A clear match with the reference profile was observed for sample #06. Sample #09 and #10 revealed partial correspondence, but as these products contain combinations of different plant derived ingredients a clear verification is not possible by HPTLC. After derivatization with anisaldehyde / sulfuric acid reagent, procyanidin A2 (PA2) gets visible and appears as an intense red zone at R f = 0.9, which appears prominently in CDE. The presence of a matching band at R f = 0.9 in samples #02, #03, #31, #04, #41, #06, #07, #09, #12 indicates the presence of PA2. PA2 is not detectable in test samples #05, #08 and #10 (Fig. 2 C). At this point it can be stated that this HPTLC protocol provides valuable qualitative and semiquantitative insights and allows efficient comparison of the different chromatographic profiles of test samples. However, for certain samples the interpretation of the band pattern remained inconclusive due to weak or overlapping zones. To strengthen the analytical reliability further confirmation using HPLC is recommended. The complementary use of HPTLC and HPLC provides higher analytical confidence and ensures the unambiguous authentication of sample identity. Fingerprinting of anthocyanins by HPLC For further analysis, HPLC of the test samples was performed with special regard to the cranberry-specific anthocyanin pattern, based on a protocol of the United States Pharmacopeia (United States Pharmacopeia Convention 2023 ). The method was validated for precision, linearity and recovery rate (Supplementary Data File, Figure S1 ). Cranberry dry extract CDE was used as reference for qualitative investigation. The six anthocyanins 1 to 6 (Fig. 1 ) being typical for V. macrocarpum fruits were used for product authentication. Assignment of the peaks was performed by the respective reference standards. An exemplary chromatogram of V. macrocarpon is displayed in Fig. 3 . Cy3Gal ( 1 ), Cy3Ara ( 3 ), Pn3Gal ( 4 ) and Pn3Ara ( 6 ) represent the four main peaks, Cy3Glc ( 2 ) and Pn3Glc ( 5 ) elute as minor peaks at t R 9 to 24 min. The respective aglycons appear as minor peaks at a later retention (40 to 50 min) or are not present at all (Fig. 3 ). For unambiguous identification of V. macrocarpon USP requires the presence of anthocyanins 1 to 6 . Additionally, it is required that no other peak than those already mentioned between Cy3Gal ( 1 ) and Pn3Ara ( 6 ) has a higher intensity than the peak for Cy3Glc ( 2 ). Furthermore, the ratio of the major peonidin-glycosides ( 4 and 6 ) to the major cyanidin-glycosides ( 1 and 3 ) must be between 0.5 and 1.9. Figure 3 shows a typical anthocyanin chromatogram of V. macrocarpon . To identify potential adulterations, comparative analysis of the anthocyanin profile of lingonberries ( V. vitis-idaea ) and the small cranberry ( V. oxycoccos ) was performed (Fig. 3 ). Both species belong to the Ericaceae family and the same genus and exhibit similar morphological characteristics to V. macrocarpon , suggesting the possibility of adulteration (Brown et al. 2012 ). As displayed in Fig. 3 both extracts exert different anthocyanin pattern and can be differentiated easily by monitoring the six anthocyanins characterizing the cranberry extracts. Lingonberries test solution elutes several peaks with only one dominant peak, which was identified as Cy3Glc ( 1 ). V. oxycoccos elutes a chromatogram that is more comparable to that of cranberries. However, the presence of a greater number of peaks, arranged in a distinct ratio to each other, allows also a clear differentiation between the different species (Fig. 3 ). Subsequently, the test samples were analyzed by the validated HPLC protocol (Fig. 4 ). Three of the twelve test samples (#03, #04, #10) exhibited anthocyanin profiles which are different from that of V. macrocarpon . Test sample #03 revealed a complex anthocyanin fingerprint, not typical for cranberry. As this sample did not conform to the specification, a second batch of the same product (#31) was obtained from the same supplier on a commercial basis. Analysis of this second batch again revealed no typical cranberry anthocyanin pattern. Surprisingly, the two batches (#03 and #31) from the same product brand revealed completely different anthocyanin composition (Fig. 5 ). It seems astonishing that this product not only contains none of the typical cranberry natural products, but also lacks batch-to-batch conformity. Similar results were also obtained for different batches from test sample #04. Product #04 had an anthocyanin pattern which does not conform to that specified for cranberries (Fig. 4 ). This result is also in accordance with the data obtained from the TLC testing (Fig. 2 ). The respective adulteration of #04 could not be assigned to a distinct plant species. Surprisingly, analysis of a second batch of the same product (#41) revealed an anthocyanin pattern, which again did not meet the cranberry requirements, but was also different form the elution pattern observed for #04 (Fig. 5 ). This again means, that no batch-to-batch conformity is given for the product. Test sample #10 is a combination product with different botanical ingredients (chokeberries, hibiscus flowers, olive leaves, grape seed, blackcurrant extracts), a clear statement on identity of cranberry in this product is not possible. The presence of cranberry is possible, but due to the combination with other plant extracts which also contain anthocyanins a clear statement cannot be made for this product. For the other test products (#01, 02, 05, 06, 07, 08, 09, 11 and 12) identity of cranberry fruits was confirmed by the HPLC testing. Quantification of PAC ( United States Pharmacopeia Convention 2023 ) The quantification of PAC is based on a colorimetric reaction of 4-(dimethylamino)cinnamaldehyde (DMAC) in an acidic medium with the analytes. The assay exploits the reaction of DMAC with flavanols, leading to the formation of a chromophore, which can specifically be monitored at λ = 620 nm. The intensity of the resulting absorption is directly proportional to the concentration of the PACs in the solution. For quantitative evaluation of PAC content standard calibration was used and the respective results were expressed as procyanidin A2 equivalents (Prior et al. 2010 ; Cardellina II and Gafner 2018; Vidal-Casanella et al. 2021 ). Evaluation of the test samples indicated relevant quality deficiencies concerning the PAC content. In none of the samples for which a defined PAC content has been specified, this amount of PAC could be quantified (Table 2 ). Table 2 Summary of quality investigation of cranberry-based food supplements with regard to identity, uniformity of mass of single dosed preparations and total PAC-content No. Identity [TLC, HPLC] Uniformity of mass [Ph. Eur.] Content PAC PAC specification [mg/ unit] Total PAC content per unit [mg], calc. as procyanidin A2; mean (range), n = 2 Recommended daily dose, corresponding to PAC content [mg] per day Total PAC content per day [mg], calc. as procyanidin A2 According analysis #01 + n.a. no declaration n.a --- --- --- #02 + n.a. 15 0.95 (0.35–1.55) 3 capsules 45 2.9 #03/31 - / - + 18 5.41 (5.34–5.49) 2 capsules 36 10.8 #04/41 - / - + 18 7.35 (5.67–9.03) 2 capsules 36 14.7 #05 + + no declaration 1.27 (1.17–1.36) 1 capsule --- 1.3 #06 + + 36 11.26 (10.38–12.13) 1 capsule 36 11.3 #07 + + no declaration 3.02 (2.91–3.12) 3 capsules --- 9.1 #08 + - no declaration 1.16 (0.45–1.86) 4 capsules --- 4.6 #09 + + 12 1.29 (0.55–2.04) 3 capsules 36 3.9 #10 (+) + no declaration 6.29 (4.87–7.71) 2 capsules --- 12.6 #11 + n.a. no declaration n.a --- --- --- #12 + + 6 0.65 (0.24–0.88) 2 capsules 12 1.3 n.a.: not analyzed; - : negative result; + positive resul Samples for which no specific PAC content was provided by the supplier had been evaluated according the corresponding USP monograph for that product type (e.g. Cranberry fruit juice concentrate). Among all samples, only sample #07 complies with the USP specification, which requires a minimum PAC content of 0.6% (w/w), calculated as procyanidin A2. Although this product meets the official quality criteria, the actual PAC dosage provides by the serving size is substantially lower than the intake levels typically regarded as effective. Therefore, only a limited recommendation can be made. Table 2 summarizes the respective results and compares manufacturers declaration with the results found in our investigations. However, some limitations of the DMAC method must be noticed. The assay only quantifies soluble PACs, while insoluble PACs which are bound to fiber material, pomace or proteins remain undetected. As a result, the PAC content of products derived from cranberry press cake, where a considerable amount of PACs are bound to insoluble matrix constituents, may be underestimated (Brendler and Gafner 2017 ). Additionally, another limitation of the DMAC assay relates to the choice of the calibration standard. Procyanidin A2 is used as a reference standard for calibration. As cranberry products contain a heterogenous mixtures of PACs with varying degrees of polymerization, the use of procyanidin A2 reduces accuracy with respect to absolute PAC quantification. For this reason, DMAC-derived PAC concentrations should be interpreted as relative rather than absolute values (Brendler and Gafner 2017 ). Cranberry-based food supplements are widely marketed for urinary tract health, although their regulatory classification as food supplements rather than herbal medicinal products results in less stringent quality requirements. Substantial quality deficiencies have been detected in the present study. One product failed to meet legal labeling obligations due to inconsistencies between packaging and leaflet information. Testing of uniformity of mass revealed deviations exceeding governmental limits for one test sample, which shows insufficient manufacturing protocols. Identity testing by HPTLC seems to be a highly efficient way to have a close insight into the overall composition of the extracts and HPLC can specifically analyze the anthocyanin pattern as complex fingerprint authentication demonstrated a variability in anthocyanin profile. These findings underscore the lack of standardized raw materials and show again the critical gap between the pharmaceutical-like presentation of food supplements and their actual analytical and regulatory quality. In contrast to medicinal products, food supplements are not subject to the strict requirements and legislation of drug legislation, for this the national governmental institutions strictly controls manufacturers on the different levels of raw materials, products, production technology, quality control, quality assurance, pharmacovigilance and organizational structures. Food supplements are regulated by the national food laws, which shift responsibility for the marketed products towards the manufacturer (European Union 2025). For food supplements registration only online notification of the governmental institution before placing the product on the market is required; no assessment, testing or further authorization is carried out. As a result, a non-transparent and low-quality market for food supplements is obvious, especially for botanicals. While vitamins and minerals substances are listed and regulated in Directive 2002 /46 (European Parliament and the Council 2002), the botanicals are still on hold and therefore unregulated. Although the European Food and Safety Agency (EFSA) is responsible for the evaluation of health claims, food supplements are frequently advertised and marketed with health claims in practice. This makes it even more challenging for consumers to differentiate between medicinal products and food supplements. Previous studies have already demonstrated that the quality of botanicals is unacceptable (Gaspar et al. 2021 ; Brouns et al. 2025 ). This assumption was confirmed by the study presented here, which also highlights the urgent need for harmonized quality standards, transparent labeling and improved regulatory standards to ensure consumer safety. Abbreviations CDE cranberry dry extract Cy3Gal Cyanidin-3- O -galactoside Cy3Glc Cyanidin-3- O -glucoside EMA European Medicines Agency HPLC High pressure liquid chromatography HPTLC High performance thin layer chromatography PAC proanthocyanidin Pn3Gal paeonidin-3- O -galactoside Ph. Eur. European Pharmacopoeia TLC thin layer chromatography UPEC uropathogenic Escherichia coli UTI uncomplicated urinary tract infections. Declarations Author Contribution AB: data curation, formal analysis, investigation, methodology, writing; ML review and editing, supervision; AH: conceptualization, funding, writing. All authors reviewed the manuscript Acknowledgement AcknowledgmentsThe technical assistance of Mr. A. Niermann for providing plant material is acknowledged. Data Availability All data supporting the findings of this study are available within the paper and its Supplementary Information. References Directive (2002) /46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements American Botanical Council (2017) Cranberry Adulteration Bulletin: Botanical Adulterants Program. http://abc.herbalgram.org/site/MessageViewer;jsessionid=00000000.app20047a?em_id=41167.0&NONCE_TOKEN=1D35BD88E5B2E3C4E32E7A88021C55A9 . Accessed 20 November 2025 Brendler T, Gafner S (2017) Adulteration of Cranberry (Vaccinium macrocarpon). https://doi.org/10.59520/bapp.bapb/IYWq8096 Brouns A, Lechtenberg M, Hensel A (2025) Passionflower ( Passiflora incarnata ): Quality of Food Supplements Versus Registered Herbal Medicinal Products. Planta Med 532–540. https://doi.org/10.1055/a-2591-3765 Brown PN, Turi CE, Shipley PR, Murch SJ (2012) Comparisons of large ( Vaccinium macrocarpon Ait.) and small ( Vaccinium oxycoccos L., Vaccinium vitis-idaea L.) cranberry in British Columbia by phytochemical determination, antioxidant potential, and metabolomic profiling with chemometric analysis. Planta Med 78:630–640. https://doi.org/10.1055/s-0031-1298239 Bundesinstitut für Arzneimittel und Medizinprodukte (ed) (2024) European Pharmacopoeia: 2.9.5 Uniformity of mass of single-dose preparations, 11th edn. Deutscher Apotheker, Stuttgart Burger O, Ofek I, Tabak M, Weiss EI, Sharon N, Neeman I (2000) A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus. FEMS Immunol Med Microbiol 29:295–301. https://doi.org/10.1111/j.1574-695X.2000.tb01537.x Burger O, Weiss E, Sharon N, Tabak M, Neeman I, Ofek I (2002) Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr 42:279–284. https://doi.org/10.1080/10408390209351916 Cardellina IIJ, Gafner S (2018) Cranberry Products Laboratory Guidance Document. https://doi.org/10.59520/bapp.lgd/KyrL6352 European Commission (2025) Food and Feed Information Portal Database - Health Claims - EU Register. https://ec.europa.eu/food/food-feed-portal/screen/health-claims/eu-register European Medicines Agency - Herbal Medicinal Products Committee (2022) Vaccinii macrocarpi fructus: EMA/HMPC/49135/2017. https://www.ema.europa.eu/en/documents/herbal-monograph/final-european-union-herbal-monograph-vaccinium-macrocarpon-aiton-fructus_en.pdf Foo LY, Lu Y, Howell AB, Vorsa N (2000) A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli. J Nat Prod 63:1225–1228. https://doi.org/10.1021/np000128u Gaspar DP, Lechtenberg M, Hensel A (2021) Quality Assessment of Bilberry Fruits ( Vaccinium myrtillus ) and Bilberry-Containing Dietary Supplements. J Agric Food Chem 69:2213–2225. https://doi.org/10.1021/acs.jafc.0c07784 Gbinigie OA, Spencer EA, Heneghan CJ, Lee JJ, Butler CC (2020) Cranberry Extract for Symptoms of Acute, Uncomplicated Urinary Tract Infection: A Systematic Review. Antibiot (Basel) 10. https://doi.org/10.3390/antibiotics10010012 Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M (2005) A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry 66:2281–2291. https://doi.org/10.1016/j.phytochem.2005.05.022 Lechtenberg M, Hensel A (2019) Determination of glucosinolates in broccoli-based dietary supplements by cyclodextrin-mediated capillary zone electrophoresis. J Food Compos Anal 78:138–149. https://doi.org/10.1016/j.jfca.2019.02.007 Neto CC, Penndorf KA, Feldman M, Meron-Sudai S, Zakay-Rones Z, Steinberg D, Fridman M, Kashman Y, Ginsburg I, Ofek I, Weiss EI (2017) Characterization of non-dialyzable constituents from cranberry juice that inhibit adhesion, co-aggregation and biofilm formation by oral bacteria. Food Funct 8:1955–1965. https://doi.org/10.1039/C7FO00109F Prior RL, Fan E, Ji H, Howell A, Nio C, Payne MJ, Reed J (2010) Multi-laboratory validation of a standard method for quantifying proanthocyanidins in cranberry powders. J Sci Food Agric 90:1473–1478. https://doi.org/10.1002/jsfa.3966 Scharf B, Dobrindt U, Sendker J, Hensel A (2017) Inhibitory activity of Cranberry extract on the bacterial adhesion in human urine: an ex vivo study. In: 65th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA 2017). Georg Thieme Verlag KG. https://doi.org/10.1055/s-0037-1608435 Scharf B, Sendker J, Dobrindt U, Hensel A (2019) Influence of Cranberry Extract on Tamm-Horsfall Protein in Human Urine and its Antiadhesive Activity Against Uropathogenic Escherichia coli. Planta Med 85:126–138. https://doi.org/10.1055/a-0755-7801 Scharf B, Schmidt TJ, Rabbani S, Stork C, Dobrindt U, Sendker J, Ernst B, Hensel A (2020) Antiadhesive natural products against uropathogenic E. coli : What can we learn from cranberry extract? J Ethnopharmacol 257:112889. https://doi.org/10.1016/j.jep.2020.112889 Sendker J, Chen B, Lechtenberg M, Hensel A (2022) Nahrungsergänzungsmittel auf Basis von Safran – wie sieht die Qualitätssituation aus? Z für Phytotherapie 42:178–185. https://doi.org/10.1055/a-1716-9696 United States Pharmacopeia Convention (2023) Cranberry fruit juice dry extract capsules. https://doi.org/10.31003/USPNF_M20456_02_01 United States Pharmacopeia Convention (2024) Cranberry Fruit Powder. USP-NF. https://doi.org/10.31003/USPNF_M13915_02_01 Vidal-Casanella O, Nuñez O, Hernández-Cassou S, Saurina J (2021) Assessment of Experimental Factors Affecting the Sensitivity and Selectivity of the Spectrophotometric Estimation of Proanthocyanidins in Foods and Nutraceuticals. Food Anal Methods 14:485–495. https://doi.org/10.1007/s12161-020-01878-1 Xu J, Li C, Wu W, Kong L, Xiao L, Ma W, Zhang L (2025) Cranberry Research Progress: A Systematic Review of Chemical Composition, Pharmacological Mechanisms, Clinical Applications, and Nutritional Significance. Int J Mol Sci 26. https://doi.org/10.3390/ijms26199707 Yamanaka A, Kimizuka R, Kato T, Okuda K (2004) Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation. Oral Microbiol Immunol 19:150–154. https://doi.org/10.1111/j.0902-0055.2004.00130.x Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8523151","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":580353216,"identity":"78413448-a96a-4244-b91e-352fab923253","order_by":0,"name":"Alexa Brouns","email":"","orcid":"","institution":"University of Münster","correspondingAuthor":false,"prefix":"","firstName":"Alexa","middleName":"","lastName":"Brouns","suffix":""},{"id":580353217,"identity":"bc0a49c5-5c23-4515-a2b3-ccdb869d00e6","order_by":1,"name":"Matthias Lechtenberg","email":"","orcid":"","institution":"University of Münster","correspondingAuthor":false,"prefix":"","firstName":"Matthias","middleName":"","lastName":"Lechtenberg","suffix":""},{"id":580353219,"identity":"349f724c-acdb-4c86-853b-b63d1d821a85","order_by":2,"name":"Andreas Hensel","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYDACCTBpIcfAwNiAJMxGUIuEMUILG5FaEhFWENLCP7v52MMfFRLpG243NzDdbLPJk5/ffOwDQ5kNbkvuHEs35jkjkbvhzsEG5ty2tGKDY2zJMxjOpeG25kaOmTRjG1DLjcT237lthxM3sPEYMzC2HcapQ/5G/jfJn/8k0g1uJIJs+Z84v43/M1DLf5xaDG7ksEnwNkgkQLUcSGw4xsMM1HIApxbDG2lm0jzHJAxngrTknEtO3HAszZgh4VwyTi1yN5KfSf6osZHnu5H+gDmnzC5xfvPhxwwfyuxwex87SCBVwygYBaNgFIwCFAAA7VlTXp4I7TkAAAAASUVORK5CYII=","orcid":"","institution":"University of Münster","correspondingAuthor":true,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Hensel","suffix":""}],"badges":[],"createdAt":"2026-01-05 15:53:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8523151/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8523151/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101351121,"identity":"fa3a6f21-9a0f-4e91-84b8-cedffc7fabca","added_by":"auto","created_at":"2026-01-28 18:40:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":55322,"visible":true,"origin":"","legend":"\u003cp\u003eStructural features of anthocyanins \u003cstrong\u003e1\u003c/strong\u003e to \u003cstrong\u003e6\u003c/strong\u003e to be used identification of cranberry fruits from \u003cem\u003eVaccinium macrocarpon\u003c/em\u003e. Cy3Gal/Glc/Ara: Cyanidin-3-\u003cem\u003eO\u003c/em\u003e-galactoside/glucoside/arabinoside; Peo3Gal/Glc/Ara: paeonidin-3-\u003cem\u003eO\u003c/em\u003e-galactoside/glucoside/arabinoside.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8523151/v1/f3cd26482b4f0cdfad9681f7.png"},{"id":101351126,"identity":"6b7cbab0-516c-4659-882d-e354209d2a46","added_by":"auto","created_at":"2026-01-28 18:40:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2983323,"visible":true,"origin":"","legend":"\u003cp\u003eStructural features of anthocyanins \u003cstrong\u003e1\u003c/strong\u003e to \u003cstrong\u003e6\u003c/strong\u003e to be used identification of cranberry fruits from \u003cem\u003eVaccinium macrocarpon\u003c/em\u003e. Cy3Gal/Glc/Ara: Cyanidin-3-\u003cem\u003eO\u003c/em\u003e-galactoside/glucoside/arabinoside; Peo3Gal/Glc/Ara: paeonidin-3-\u003cem\u003eO\u003c/em\u003e-galactoside/glucoside/arabinoside.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8523151/v1/93bb2f2076549924c3ab55db.png"},{"id":101351127,"identity":"c83be0d3-696f-4c85-9813-22f3ffb9078d","added_by":"auto","created_at":"2026-01-28 18:40:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":99882,"visible":true,"origin":"","legend":"\u003cp\u003eHPLC fingerprinting of anthocyanins from different Vaccinium species: Cranberries from \u003cem\u003eVaccinium macrocarpon\u003c/em\u003e, fruits from \u003cem\u003eV. oxycoccus\u003c/em\u003e, and lingonberries from \u003cem\u003eV. vitis-idaea\u003c/em\u003e. Left side: overview chromatograms, right side: enlargement of the relevant elution time of anthocyanins \u003cstrong\u003e1\u003c/strong\u003e to \u003cstrong\u003e6\u003c/strong\u003e between tR 8 to 24 min.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8523151/v1/be4703cb8f79b675a0fbd2db.png"},{"id":101351123,"identity":"2b77278c-9c9b-48c2-9282-10814c8791f4","added_by":"auto","created_at":"2026-01-28 18:40:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":136858,"visible":true,"origin":"","legend":"\u003cp\u003eHPLC fingerprinting of the anthocyanin patter of test samples #01 to #12. Test samples #03 and #04 do not conform to the declaration of the products.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8523151/v1/7c726f07433c256ca2ed2b31.png"},{"id":101351128,"identity":"e7b0dfc0-4bcc-4479-a05a-f45662faac22","added_by":"auto","created_at":"2026-01-28 18:40:28","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":65545,"visible":true,"origin":"","legend":"\u003cp\u003eHPLC fingerprinting of anthocyanins patter from two different batches of the same test samples #03 (03 and #31) and #04 (#04 and #41) obtained from the same supplier at different times. Data indicate different anthocyanin patterns from batch to batch, and identity of extract from cranberry fruit is not given.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8523151/v1/7cccf0c43afff1b321dfef7e.png"},{"id":107425538,"identity":"b74b307a-76a0-4ccc-99ff-b344d1c06b48","added_by":"auto","created_at":"2026-04-21 11:12:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3923093,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8523151/v1/42340d41-4c97-4b02-a98d-9e19577c97e3.pdf"},{"id":101351125,"identity":"19510961-2564-48ad-ad1c-7cdb0517ebf1","added_by":"auto","created_at":"2026-01-28 18:40:28","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":677470,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryData.docx","url":"https://assets-eu.researchsquare.com/files/rs-8523151/v1/744b9b81a5b9bf17d01aa424.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Quality assessment of Cranberry (Vaccinium macrocarpon) based food supplements: HPTLC, HPLC and PAC quantification as effective tools for quality management","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eCranberries, the fruits from \u003cem\u003eVaccinium macrocarpon\u003c/em\u003e Ait. (Ericaceae), originating from the high moors of North America are used for its preventative effect against uncomplicated urinary tract infections (UTI). The positive effects of cranberries for UTI are due to the inhibition of early host-pathogen interaction, especially in regard to the adhesion of FimH-dominated uropathogenic \u003cem\u003eEscherichia coli\u003c/em\u003e (UPEC) to bladder and kidney cells of the human host (Scharf et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Gbinigie et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). These antiadhesive properties have been discussed to be due to a direct interaction of oligomeric proanthocyanidins (PAC) with the mannose-binding side of UPEC. Due to the low bioavailability of PAC after oral intake this mode of action might not contribute to a high extend to the positive effects of cranberry extract for UTI (Scharf et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Scharf et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). In contrast, recent studies indicated an indirect antiadhesive effect, as cranberries stimulate the secretion of the highly mannosylated glycoprotein Tamm-Horsfall Protein (syn. THP, uromodulin) in the distal part of the kidney, which again interacts with the mannose-binding side of UPEC, preventing the adhesion of UPEC to uroplakin-receptors on the bladder epithelium (Scharf et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). For this, cranberry extracts are assessed nowadays as inductors of the innate immune defense within the urinary tract.\u003c/p\u003e \u003cp\u003eFor medical use, the European Medicines Agency (EMA) has published two monographs for liquid cranberry preparations within the traditional use and distinguishes between two indications, namely for the treatment of acute, uncomplicated UTI with mild symptoms, and additionally for prevention of recurrent uncomplicated UTI (European Medicines Agency - Herbal Medicinal Products Committee \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe phytochemical composition of cranberries is mainly characterized by the presence of oligomeric A-type PAC, anthocyanins, flavonoids, mainly flavonols, organic acids, and xyloglucan-like polysaccharides; for review see (Scharf et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Xu et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Cranberries contain also a high molecular weight fraction, known as non-dialyzable material (NDM) that has been reported to exert antiadhesive activity against different bacteria, as e.g. \u003cem\u003eHelicobacter pylori\u003c/em\u003e strains to gastric epithelial cells (Burger et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2000\u003c/span\u003e; Burger et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2002\u003c/span\u003e)d \u003cem\u003emutans\u003c/em\u003e and \u003cem\u003eS. sobrinus\u003c/em\u003e to saliva-coated hydroxyapatite beads (Yamanaka et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2004\u003c/span\u003e). The nature of NDM is not clear but it is discussed to be a mixture of polymeric A-type PAC in combination with denatured proteins and xyloglucan (Neto et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn regard to positive effects against bacterial pathogens in the urinary tract and the THP-stimulation in the kidney, especially A-type PAC are in the focus (Howell et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). Cranberry A-type PAC differ structurally from PAC found in other tannin-rich plants, such as green tea, grapes, or cocoa, dominated by B-type PAC, which do not exert antiadhesive activity (Howell et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCranberries typically contain six major anthocyanins, specifically the 3-\u003cem\u003eO\u003c/em\u003e-glycosides of the anthocyanidins cyanidin and peonidin, which are linked to β-D-glucose, β-D-galactose, or α-L-arabinose (Foo et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2000\u003c/span\u003e). This specific anthocyanin-pattern (structural features see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) can be used for identity testing of cranberry extracts, as it differs clearly from other fruits from the Ericaceae plant family and other anthocyanin containing plant material.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eEven though cranberry extracts are widely used for medical applications and a variety of clinical studies with positive outcome for UTI treatment have been reported, no cranberry-containing herbal medicinal products (HMP) have been registered in Germany. Instead, a steadily growing market for cranberry-based dietary supplements and food products has emerged. However, the European Food and Safety Authority (EFSA) has not approved any health claims for cranberry products until now (European Commission \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). This has led to the marketing of cranberry-based food supplements with vague indications for use, most of which are promoted to consumers as providing benefits for the urinary tract system. In many cases it is not clear for the consumer if such a product is a registered drug-like HMP or a food supplement. This again leads to the problem of product quality. While HMP have controlled and reproducible quality due to legislation, registration and the underlying GMP guidelines, food supplements are covered by the national food laws and are therefore not subject to the strict requirements for efficacy, safety and quality that apply to authorized medicinal products. This lack of approval in combination with a presentation of food supplements similar to authorized drugs makes it difficult for consumers and health professionals to assess the quality of food supplements.\u003c/p\u003e \u003cp\u003eRecent analytical investigations of food supplements containing plant extracts, the so-called botanicals, indicated strong quality deficiencies in many cases, ranging from food fraud without any active ingredients to strongly underdosed products and to products containing serious falsifications or even toxic adulteration (Lechtenberg and Hensel \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Gaspar et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Sendker et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Brouns et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Therefore, many international societies and governmental institutions repeatedly ask for stringent analytical batch-to-batch control of food supplements by specific and validated analytical protocols, establishment of a nutrivigilance system and governmental reactions against manufacturer in case of quality violence.\u003c/p\u003e \u003cp\u003eCranberry food supplements are the top-selling products in the segment of food supplements. Differences between products are due to the respective PAC content. The dried press cake, obtained from the fruits after the juice has been squeezed out, contains about 0.8 to 1.5% PAC (American Botanical Council \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Many of the food supplements use this pre-extracted bulk material as \u0026ldquo;active ingredient\u0026rdquo;. On the other side cranberry drinks are characterized by PAC content of 3 to 5%, while pure cranberry juice should contain 12 to 24% PAC (American Botanical Council \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Falsification of cranberry products with other lower-cost PAC-enriched extracts have been described (e.g., peanuts from \u003cem\u003eArachis hypogaea\u003c/em\u003e, grape seeds from \u003cem\u003eVitis vinifera\u003c/em\u003e) (American Botanical Council \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e)). Also, adulterants with anthocyanin-enriched extracts are known (e.g. mulberry from \u003cem\u003eMorus\u003c/em\u003e spp., hibiscus from \u003cem\u003eHibiscus sabdariffa\u003c/em\u003e, black beans from \u003cem\u003ePhaseolus vulgaris\u003c/em\u003e, black rice from \u003cem\u003eOryza sativa\u003c/em\u003e) (American Botanical Council \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Additionally, anthocyanin-enriched extracts from other Vaccinium species (e.g. \u003cem\u003eV. corymbosum\u003c/em\u003e, \u003cem\u003eV. oxycoccos\u003c/em\u003e, \u003cem\u003eV. vitis-idaea\u003c/em\u003e) might be suitable to simulate cranberry, but can clearly be differentiated by the respective anthocyanin fingerprint (Brown et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs until now no monograph for cranberries has been published in the European Pharmacopoeia, the aim of this analytical project was to compile relevant analytical methods for the authentication of cranberry extracts, evaluating the typical anthocyanin pattern of the fruits by HPTLC and HPLC and colorimetric quantification of total PAC content. This collection of methods was used to assess the quality of food supplements obtained from different sources.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Materials and reference standards\u003c/h2\u003e \u003cp\u003eIf not stated otherwise, solvents, reagents, and consumables were obtained from VWR International (Darmstadt, Germany). All solvents and reagents were of analytical quality. Water was produced by a Millipore Simplicity 185 system (Merck, Darmstadt, Germany). Procyanidin A2 (lot 16753) was obtained in reference standard quality from Phytolab (Vestensberggreuth, Germany). Cy3Gal (lot 18), Cy3Glc (lot 48) and Peo3Gal (lot 03) were obtained in reference standard quality from ExtraSynthese (Genay, France). \u003cem\u003eV. vitis-idea\u003c/em\u003e was obtained as dried lingonberries from Galke (Bad Grund, Germany), lot 47545 (IPBP No. 917).\u003c/p\u003e \u003cp\u003eAuthenticated plant material from \u003cem\u003eVaccinium macrocarpon\u003c/em\u003e was obtained from the medicinal plant garden of University of M\u0026uuml;nster, Institute of Pharmaceutical Biology and Phytochemistry, M\u0026uuml;nster, Germany. Authentication was performed by AH and AB. Voucher samples are stored at the archives of the institute (IPBP 916). Authenticated plant material from \u003cem\u003eVaccinium oxycoccos\u003c/em\u003e was obtained from a controlled garden area in M\u0026uuml;nster, Germany (GPS positioning 51.9942, 7.5937). Authentication was done by Mr. Andr\u0026eacute; Niermann, voucher sample IPBP 918).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Cranberries, cranberry juices, cranberry containing food supplements\u003c/h2\u003e \u003cp\u003eTwelve different cranberry products were obtained on a commercial base for internet shops, pharmacy stores and herbal trade shops (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Product #01 represents a concentrated cranberry juice (puree), #11 are dried cranberries, the other products represent food supplements in capsule form. Declaration of supplement facts and specific claims of the respective products are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOverview of the analyzed cranberry-based food supplements\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSupllier or distributor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ename\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eShelf life\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLOT/ batch number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNutrition facts, content, serving size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFurther labeling (translated into English)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnton H\u0026uuml;bner GmbH \u0026amp; Co KG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDonath Vollfrucht Cranberrry unges\u0026uuml;\u0026szlig;t\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.04.2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e---\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry puree\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBergland Pharma GmbH \u0026amp; Co KG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBergland Cranberry Lutschtabletten\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e06/2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL2172/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry juice powder (36%) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e15 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e3 capsules \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally Acerola powder with vitamin C (10%),\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAvitale GmbH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAvitale Cranberry Kapseln\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10/2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL2291/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCrannberrypowder AV36 400 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e18 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e2\u0026times;1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains aditionally excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAvitale GmbH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAvitale Cranberry Kapseln\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e09/2026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL3249/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCrannberrypowder AV36 400mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e18mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e2\u0026times;1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains aditionally excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDm- drogerie markt GmbH\u0026thinsp;+\u0026thinsp;Co. KG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMivolis Cranberry\u0026thinsp;+\u0026thinsp;Vitamin C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10/2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e393001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry-Extract 300 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e18 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e2\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally excipients and vitamin C\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDM Drogerie Markt GmbH\u0026thinsp;+\u0026thinsp;Co. KG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMivolis Cranberry\u0026thinsp;+\u0026thinsp;Vitamin C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e03/2026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry-Extract 300 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e18 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e2\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally excipients and vitamin C\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePro medico Handels GmbH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epure encapsulations \u0026ndash; Cranberry Extrakt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e05/2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2260666\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry extract (CranMax): 500 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally cranberry fibers and cranberry seed oil, excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11A Nutrithek GmbH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCranberry 36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12/2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry extract: 53 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e36 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHecht Pharma GmbH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCranberry 400mg GPH-Kapseln\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e08/2027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e405.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry Concentrate (400 mg\u0026thinsp;=\u0026thinsp;10 g Cranberrys) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e3\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNaturafit GmbH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCranberry 400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12/2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry Powder: 400 mg (=\u0026thinsp;10 g pure Cranberry) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e4 capsules per day after food \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuiris Healthcare\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCystorenal plus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e09/2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0090894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry extract: 300 mg (25:1) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e12 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e3\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally pumpkin seed extract 4:1 (18%) vitamin C, vitamin B2, excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeoElementum O\u0026Uuml;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCardioBalance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e06/2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1042023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry extract 225 mg\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e2\u0026times;1 capsule per day\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally chokeberry extract: 200 mg (20:1), Calcium butyrate 200 mg *, magnesium 150 mg, Gymnema Sylvestre 100 mg *, L-Arginine 150mg, extract from hawthorn leaves and flowers 150 mg (6:1), Hibiscus flower powder 50 mg, Olive leaf extract 50 mg (10:1), Grape seed extract 50 mg (8:1), Blackcurrant fruit extract 25 mg (4:1), Coenzyme Q10 20 mg, Vitamin B6 1.4 mg, Folic acid 100 \u0026micro;g\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdler Vital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCranberries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.10.2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNOV2322W3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVitarmonyl Laboratoires\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCranberry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e06/2025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1637YAA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCranberry extract: 200 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e6 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e2\u0026times;1 capsules per day\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eContains additionally excipients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ea\u003c/sup\u003e mg Cranberry extract or concentrate per capsule/unit; \u003csup\u003eb\u003c/sup\u003e total [mg] procyanidin per capsule/unit; \u003csup\u003ec\u003c/sup\u003e serving size; * specified in the enclosed product leaflet, but not on the primary packaging box\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Cranberry dry reference extract (CDE)\u003c/h2\u003e \u003cp\u003eAuthenticated fruits from \u003cem\u003eV. macrocarcpon\u003c/em\u003e were harvested and frozen immediately. Fifty grams of the frozen fruits were pulverized crushed in an ice-cold mortar and extracted with 500 mL of ethanol 96% (v/v) for 30 min by use of a rotor-stator extractor (Ultra Turrax, IKA, Germany). The suspension was filtered (VWR filter paper 413) and the clear solution was evaporated to dryness under \u003cem\u003evacuo\u003c/em\u003e, followed by lyophilization to yield 5% (w/w, related to the fresh plant material) of the cranberry dry reference extract, which is termed as CDE in the following.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Fingerprinting by HPTLC (PAC, anthocyanins, chlorogenic acid, hyperoside)\u003c/h2\u003e \u003cp\u003eFor identity testing of cranberry extract HPTLC analysis was used based on a protocol of the USP (United States Pharmacopeia Convention \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2023\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Procyanidin A2 (1 mg/mL in MeOH), Cy3Gal, Cy3Glc, Peo3Gal, chlorogenic acid and hyperoside (0.2 mg/mL MeOH) served as reference standards. Cranberry dry extract (CDE) was used as reference extract.\u003c/p\u003e \u003cp\u003eTest samples, for which a defined PAC content was specified by the manufacturer (#02, #03, #31, #04, #41, #06, #08, #12) were investigated by preparing solutions as follows: an aliquot of the contents of the capsules, equivalent to 8.5 mg of total PAC, is transferred to a 10 mL centrifuge tube. Seven milliliters of water are added. For #05, #07, #08, #10 and CDE 50 mg sample material is mixed with 7 mL of water. The respective suspensions are sonicated for 10 min and subsequently centrifuged for 5 min at 3600 \u0026times; g. The clear supernatant is used for further processing. A solid-phase extraction cartridge (C18, 500 mg/3 mL, Macherey-Nagel, Germany) is conditioned with 3 mL of MeOH. Subsequently, 3 mL of water are loaded on the cartridge and sucked into until the solvent level is 1 to 2 mm above the stationary phase. 1.5 mL of the test solution is loaded onto the cartridge and sucked into the column. The eluate is discarded. The stationary phase is rinsed with 1 mL of water-MeOH (8:2, v/v). The eluate is discarded. Finally, 1 mL of MeOH is used to elute the retained compounds. This eluate is collected as the test solution for subsequent HPTLC.\u003c/p\u003e \u003cp\u003eMobile phase for HPTLC: ethylformiate, formic acid, water, toluene (60:8:6:3, v/v/v/v). Spotting volume: 5\u0026micro;L for references and 15 \u0026micro;L for samples, 8 mm. Development: 70 mm. Drying: 5 min by air stream at RT. Detection 1: 100 to 105\u0026deg;C for 5 min, followed by spraying with a solution of diphenylboryloxyethylamine (10 g/L) in MeOH, evaluation in day light and λ\u0026thinsp;=\u0026thinsp;366 nm. Detection 2: spraying with a mixture of 170 mL ice-cooled MeOH in 20 mL of glacial acetic acid, 10 mL of sulfuric acid and 1 mL of anisaldehyde, followed by heating of the TLC plate to 100\u0026deg; C for 5 min. Evaluation in day light.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Fingerprinting of anthocyanins by HPLC\u003c/h2\u003e \u003cp\u003eHPLC system: Shimadzu LC10A with system controller (SCL10A), autosampler (SIL10A), pumps (LC10AT), degasser (JASCO DG-2080-53), oven (CTO10A) and UV-VIS detector SPD10A. Stationary phase: GeminiNX 110 \u0026Aring;, 5 \u0026micro;m, 250 mm (Phenomenex, USA), (alternatively with same selectivity Kromasil 100 \u0026Aring;, 5 \u0026micro;m, 250 mm, Phenomenex, USA). Mobile phase: (A) water, formic acid (91.5:8.5, v/v); (B) water, MeOH, acetonitrile, formic acid (41.5:22.5:22.5:8.5, v/v/v/v/); gradient: t\u003csub\u003e0min\u003c/sub\u003e: 80% (A), t\u003csub\u003e35min\u003c/sub\u003e: 75% (A), t\u003csub\u003e46min\u003c/sub\u003e: 35% (A), t\u003csub\u003e57min\u003c/sub\u003e: 0% (A). Flow rate: 1.0 mL/min. Injection volume: 10 \u0026micro;L for reference solutions, 30 \u0026micro;L for test solutions. Oven temperature: 30\u0026deg;C. Detection: λ\u0026thinsp;=\u0026thinsp;535 nm.\u003c/p\u003e \u003cp\u003eTo recognize possible adulteration with the small cranberry (\u003cem\u003eV. oxycoccos\u003c/em\u003e), the respective fruits from authenticated plants were harvested and treated as described for preparation of CDE, using 10 g fruits extracted with 100 mL EtOH 96% (v/v).\u003c/p\u003e \u003cp\u003eFor adulteration with lingonberry (\u003cem\u003eV. vitis idaea\u003c/em\u003e), the dried fruits were frozen using liquid nitrogen and subsequently pulverized. One gram of the pulverized material was mixed with 10.0 mL of water and extracted in an ultrasonic batch for 15 min. The extract was centrifuged (3600 \u0026times; g, 5 min) and the clear supernatant collected for solid-phase extraction (SPE) [SPE was employed to concentrate the anthocyanins, since a direct extraction of the fruits with MeOH yielded insufficient anthocyanin concentrations]. An SPE cartridge (C18, 500 mg, 3 mL; Macherey-Nagel, Germany) was conditioned with 3 mL MeOH, followed by 3 mL water. Subsequently, 4 mL of the aqueous extract were loaded onto the cartridge and eluted. Subsequently, 1.0 mL of a mixture of water/MeOH (80:20, v/v) was loaded onto the cartridge and eluted. Finally, the anthocyanins were eluted with 1.0 mL of MeOH. The eluate served as the test solution for HPLC analysis.\u003c/p\u003e \u003cp\u003eTest solutions from cranberry food supplements: The equivalent of an average mass from one capsule of the test products was weighted exactly into a flask and was extracted with 25.0 mL of a mixture of MeOH and hydrochloric acid (98: 2 v/v). After centrifugation (3600 \u0026times; g, 5 min), 5.0 mL of the clear supernatant were diluted with phosphoric acid in water (10% w/w) to 20.0 mL to serve as test solution for HPLC.\u003c/p\u003e \u003cp\u003eTest solution from cranberry dried fruits: 1 g of dried fruits were extracted with 10.0 mL of MeOH: water (1:1 v/v) by ultrasonic treatment for 15 min. Subsequently, the suspension was centrifuged (3600 \u0026times; g, 5 min). The clear supernatant serves as test solution.\u003c/p\u003e \u003cp\u003eTest solutions from cranberry liquid preparations: 10 mL of the liquid samples were transferred to a sample tube and were centrifuged (3600 \u0026times; g, 5 min). The clear supernatant served as test solution for HPLC.\u003c/p\u003e \u003cp\u003eThe HPLC protocol was validated for the parameters system precision (\u0026plusmn;\u0026thinsp;0.54%), linearity in the range of 5 to 100 \u0026micro;g/mL and recovery rate 100.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7% by using Pn3Gal (Supplementary Data File, Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Quantification of PAC (United States Pharmacopeia Convention \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2023\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2024\u003c/span\u003e)\u003c/h2\u003e \u003cp\u003eReagent solution: 4-(Dimethylamino)-cinnamaldehyd (DMAC, 1 mg/mL) in 0.4 mol/L sulfuric acid. The solution must be prepared fresh every day. Standard stock solution: procyanidin A2, 90 \u0026micro;g/mL in MeOH. Standard solutions: A minimum of five calibration solutions, ranging from 10 to 30 \u0026micro;g/mL procyanidin A2 in MeOH, were prepared from the standard stock solution by dilution with MeOH.\u003c/p\u003e \u003cp\u003eTest solution from cranberry capsule preparations: A portion of the capsule content, equivalent to 36 mg of total PAC, was transferred to a 100 mL flask, suspended in MeOH, sonicated for 10 min, followed by shaking for 10 min. 10 mL of the resulting suspension were centrifuged for 5 min at 1950 \u0026times; g. The clear supernatant is diluted with MeOH to a test solution being nominally equivalent to a PAC content of 0.02 mg/mL.\u003c/p\u003e \u003cp\u003eFor the samples without a PAC declaration 2.0 g of sample material were transferred to a 100 mL flask, suspended in 100.0 mL MeOH and sonicated for 10 min. The suspension was centrifuged (1950 \u0026times; g, 5 min). The clear supernatant was used for further analysis.\u003c/p\u003e \u003cp\u003eThe reagent solution (250 \u0026micro;L) was mixed with 50 \u0026micro;L of the test sample solutions in a 96-well plate. A PAC-free solvent control, containing MeOH, is used as a blank. The resulting absorbance was determined constantly for 5 min at λ\u0026thinsp;=\u0026thinsp;640 nm immediately after mixing the reagents. The highest absorbance is recorded. Absorbance values obtained from the standard solutions are used for calibration (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.98) to calculate total PAC content as procyanidin A2. The total PAC content per capsule is calculated as follows:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:PAC\\:content\\:\\left(\\%\\:of\\:specified\\:content\\right)=c\\times\\:{V}_{U}\\:\\times\\:({W}_{AF}/\\text{W})\\:\\times\\:\\:({V}_{F}/{V}_{A})$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003ec: concentration (mg/mL) of sample solution, calculated as procyanidin A2 from the calibration; V\u003csub\u003eU\u003c/sub\u003e: volume (mL) of sample stock solution; W\u003csub\u003eAF\u003c/sub\u003e: average filling (mg) per capsule; W: weight of the capsules content (mg) for preparation of the sample stock solution; V\u003csub\u003eF\u003c/sub\u003e:: final volume (mL) of the sample solution; V\u003csub\u003eA\u003c/sub\u003e: volume (mL) of the aliquot of the sample stock solution.\u003c/p\u003e \u003cp\u003eFor validation of the protocol, the recovery rate (\u0026gt;\u0026thinsp;99%) was determined by spiking test solutions with procyanidin A2 reference standard (n\u0026thinsp;=\u0026thinsp;3).\u003c/p\u003e \u003cp\u003eAll assays were performed in two independent investigations with n\u0026thinsp;=\u0026thinsp;3 technical replicates. For final evaluation the respective mean values were used.\u003c/p\u003e \u003cp\u003eValidation of the protocol was performed concerning linearity of detection signals in the range of 10 to 30 \u0026micro;g/mL of procyanidin A2 (Supplementary Data File, Figure S2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7. Uniformity of mass for single-dose preparations (Bundesinstitut f\u0026uuml;r Arzneimittel und Medizinprodukte 2024)\u003c/h2\u003e \u003cp\u003eTwenty randomly selected capsules are weighted. The content of each capsule is removed by a gentle air stream. The capsule shells are weighed, and the net filling mass is determined. The test meets the requirements of if not more than two capsules deviate +/- 7.5% from the average filling mass. None of the capsules may deviate more than +/- 15% from the mean value. In cases of average filling mass of \u0026lt;\u0026thinsp;300 mg the respective limits are +/- 10% and +/-20%.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and discussion","content":"\u003cp\u003eAnalytical investigations of a series of twelve cranberry containing food supplements (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, #01 to #12), representing the cranberry market in the D-A-CH region, was performed. Beside cranberry puree (#01), dried cranberry fruits (#11), and lozenges (#02) most of the investigated products were capsule preparations. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e displays a detailed overview on the characteristics of the different products. The test samples were obtained from internet trading as well as from community pharmacies and herbal shops. Freshly harvested, authenticated and air-dried plant material from \u003cem\u003eV. macrocarpon\u003c/em\u003e served as reference.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: \u003c/strong\u003eOverview of the analyzed cranberry-based food supplements\u003c/p\u003e\n\u003ctable width=\"1087\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e\u003cstrong\u003eSupllier or distributor\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003e\u003cstrong\u003ename\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003eShelf life\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003eLOT/ batch number\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003e\u003cstrong\u003eNutrition facts, content, serving size\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003e\u003cstrong\u003eFurther labeling (translated into English)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eAnton H\u0026uuml;bner GmbH \u0026amp; Co KG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eDonath Vollfrucht Cranberrry unges\u0026uuml;\u0026szlig;t\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e19.04.2023\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry puree\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eBergland Pharma GmbH \u0026amp; Co KG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eBergland Cranberry Lutschtabletten\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e06/2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eL2172/1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry juice powder (36%)\u003csup\u003e a\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e15 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e3 capsules \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally Acerola powder with vitamin C (10%),\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eAvitale GmbH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eAvitale Cranberry Kapseln\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e10/2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eL2291/3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCrannberrypowder AV36 400 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e18 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e2\u0026times;1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains aditionally excipients\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eAvitale GmbH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eAvitale Cranberry Kapseln\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e09/2026\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eL3249/1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCrannberrypowder AV36 400mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e18mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e2\u0026times;1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains aditionally excipients\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eDm- drogerie markt GmbH + Co. KG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eMivolis Cranberry + Vitamin C\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e10/2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e393001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry-Extract 300 mg \u003csup\u003ea \u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e18 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e2\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally excipients and vitamin C\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eDM Drogerie Markt GmbH + Co. KG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eMivolis Cranberry + Vitamin C\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e03/2026\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e39009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry-Extract 300 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e18 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e2\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally excipients and vitamin C\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003ePro medico Handels GmbH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003epure encapsulations \u0026ndash; Cranberry Extrakt\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e05/2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e2260666\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry extract (CranMax): 500 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally cranberry fibers and cranberry seed oil, excipients\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e11A Nutrithek GmbH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eCranberry 36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e12/2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e25122\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry extract: 53 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e36 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e1 capsule per day \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally excipients\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eHecht Pharma GmbH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eCranberry 400mg GPH-Kapseln\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e08/2027\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e405.77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry Concentrate (400 mg = 10 g Cranberrys) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e3\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally excipients\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#08\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eNaturafit GmbH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eCranberry 400\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e12/2024\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e41221\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry Powder: 400 mg (=10 g pure Cranberry)\u003csup\u003e a\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e4 capsules per day after food \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally excipients\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eQuiris Healthcare\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eCystorenal plus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e09/2024\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0090894\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry extract: 300 mg (25:1) \u003csup\u003ea \u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e12 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e3\u0026times;1 capsule \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally pumpkin seed extract 4:1 (18%) vitamin C, vitamin B2, excipients\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eNeoElementum O\u0026Uuml;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eCardioBalance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e06/2024\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e1042023\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry extract 225 mg\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e2\u0026times;1 capsule per day\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally chokeberry extract: 200 mg (20:1), Calcium butyrate 200 mg *, magnesium 150 mg, Gymnema Sylvestre 100 mg *, L-Arginine 150mg, extract from hawthorn leaves and flowers 150 mg (6:1), Hibiscus flower powder 50 mg, Olive leaf extract 50 mg (10:1), Grape seed extract 50 mg (8:1), Blackcurrant fruit extract 25 mg (4:1), Coenzyme Q10 20 mg, Vitamin B6 1.4 mg, Folic acid 100 \u0026micro;g\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eAdler Vital\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eCranberries\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e29.10.2023\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eNOV2322W3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e#12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eVitarmonyl Laboratoires\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eCranberry\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e06/2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e1637YAA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"198\"\u003e\n\u003cp\u003eCranberry extract: 200 mg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e6 mg \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e2\u0026times;1 capsules per day\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"397\"\u003e\n\u003cp\u003eContains additionally excipients\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea \u003c/sup\u003emg Cranberry extract or concentrate per capsule/unit; \u003csup\u003eb\u003c/sup\u003e total [mg] procyanidin per capsule/unit; \u003csup\u003ec \u003c/sup\u003eserving size; * specified in the enclosed product leaflet, but not on the primary packaging box\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDeficiency in product declaration of cranberry food supplements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt a first glance the test sample #10, which represents a combination of different plants extracts revealed strong differences in the declaration of the product concerning the information given on the primary packaging material and the information leaflet (Supplementary Data, Figure S3). Two ingredients, specified on the product leaflet, have not been specified on the capsules box. From this point of view product #10 does not meet the legal requirements concerning information of the consumer.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eUniformity of mass of single dose cranberry products\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAs the presentation of the food supplements is similar to that of medicinal products, test on uniformity of mass for single-dose preparations according to the European Pharmacopoeia (Bundesinstitut f\u0026uuml;r Arzneimittel und Medizinprodukte 2024) was performed for the solid oral dosage forms. One sample (#08) did not meet the requirements, as one capsule deviated more than 15% from the mean. This result indicates the need for improvement of the technical production of capsules and tablets in the field of food supplements, as similar investigations a few years ago have also shown serious shortcomings for solid formulations concerning uniformity of mass (Gaspar et al. \u003cspan class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIdentity testing by HPTLC\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHPTLC fingerprinting according to the methodology of USP-NF 2024 (United States Pharmacopeia Convention \u003cspan class=\"CitationRef\"\u003e2023\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2024\u003c/span\u003e) was employed for identity testing of the samples, using chlorogenic acid, hyperoside, procyanidin A2, cyanidin-3-\u003cem\u003eO\u003c/em\u003e-galactosid (Cy3Gal), cyanidin-3-\u003cem\u003eO\u003c/em\u003e-glucosid (Cy3Glc) and peonidin-3-\u003cem\u003eO\u003c/em\u003e-galactosid (Peo3Gal) as reference compounds (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Detection was performed after spraying with diphenylboryloxyethylamine and monitoring at day light at \u0026lambda;\u0026thinsp;=\u0026thinsp;366 nm, and after derivatization with anisaldehyde-sulfuric acid (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA to C).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter derivatization with diphenylboryloxyethylamine the reference standards hyperoside (hyp), Cy3Gal, Cy3Glc and Peo3Gal showed characteristic-colored bands at Rf-values between 0.2 and 0.6. The cranberry dry extract exhibited bands matching Cy3Gal, Cy3Glc and Peo3Gal, as well as hyperoside. At \u0026lambda;\u0026thinsp;=\u0026thinsp;366 nm the fluorescent bands for chlorogenic acid (chl.ac) (R\u003csub\u003ef\u003c/sub\u003e = 0.65) and hyperoside (Rf\u0026thinsp;=\u0026thinsp;0.6) were clearly visible, while Cy3Gal, Cy3Glc and Peo3Gal are not visible under these conditions. The CDE lane revealed multiple bright fluorescent zones in the middle to upper R\u003csub\u003ef\u003c/sub\u003e region. The evaluation of the test samples was based on the presence, intensity and distribution of these characteristic zones in the chromatograms. Sample #02 corresponds to the reference profile, although the zones appeared weaker. Sample #03 showed partial similarity to the reference. In contrast, sample #04 did not correspond and for #05 and #08 no detectable zones were observed. A clear match with the reference profile was observed for sample #06. Sample #09 and #10 revealed partial correspondence, but as these products contain combinations of different plant derived ingredients a clear verification is not possible by HPTLC.\u003c/p\u003e\n\u003cp\u003eAfter derivatization with anisaldehyde / sulfuric acid reagent, procyanidin A2 (PA2) gets visible and appears as an intense red zone at R\u003csub\u003ef\u003c/sub\u003e = 0.9, which appears prominently in CDE. The presence of a matching band at R\u003csub\u003ef\u003c/sub\u003e = 0.9 in samples #02, #03, #31, #04, #41, #06, #07, #09, #12 indicates the presence of PA2. PA2 is not detectable in test samples #05, #08 and #10 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC).\u003c/p\u003e\n\u003cp\u003eAt this point it can be stated that this HPTLC protocol provides valuable qualitative and semiquantitative insights and allows efficient comparison of the different chromatographic profiles of test samples. However, for certain samples the interpretation of the band pattern remained inconclusive due to weak or overlapping zones. To strengthen the analytical reliability further confirmation using HPLC is recommended. The complementary use of HPTLC and HPLC provides higher analytical confidence and ensures the unambiguous authentication of sample identity.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFingerprinting of anthocyanins by HPLC\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor further analysis, HPLC of the test samples was performed with special regard to the cranberry-specific anthocyanin pattern, based on a protocol of the United States Pharmacopeia (United States Pharmacopeia Convention \u003cspan class=\"CitationRef\"\u003e2023\u003c/span\u003e). The method was validated for precision, linearity and recovery rate (Supplementary Data File, Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). Cranberry dry extract CDE was used as reference for qualitative investigation. The six anthocyanins \u003cstrong\u003e1\u003c/strong\u003e to \u003cstrong\u003e6\u003c/strong\u003e (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) being typical for \u003cem\u003eV. macrocarpum\u003c/em\u003e fruits were used for product authentication. Assignment of the peaks was performed by the respective reference standards. An exemplary chromatogram of \u003cem\u003eV. macrocarpon\u003c/em\u003e is displayed in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Cy3Gal (\u003cstrong\u003e1\u003c/strong\u003e), Cy3Ara (\u003cstrong\u003e3\u003c/strong\u003e), Pn3Gal (\u003cstrong\u003e4\u003c/strong\u003e) and Pn3Ara (\u003cstrong\u003e6\u003c/strong\u003e) represent the four main peaks, Cy3Glc (\u003cstrong\u003e2\u003c/strong\u003e) and Pn3Glc (\u003cstrong\u003e5\u003c/strong\u003e) elute as minor peaks at t\u003csub\u003eR\u003c/sub\u003e 9 to 24 min. The respective aglycons appear as minor peaks at a later retention (40 to 50 min) or are not present at all (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor unambiguous identification of \u003cem\u003eV. macrocarpon\u003c/em\u003e USP requires the presence of anthocyanins \u003cstrong\u003e1\u003c/strong\u003e to \u003cstrong\u003e6\u003c/strong\u003e. Additionally, it is required that no other peak than those already mentioned between Cy3Gal (\u003cstrong\u003e1\u003c/strong\u003e) and Pn3Ara (\u003cstrong\u003e6\u003c/strong\u003e) has a higher intensity than the peak for Cy3Glc (\u003cstrong\u003e2\u003c/strong\u003e). Furthermore, the ratio of the major peonidin-glycosides (\u003cstrong\u003e4\u003c/strong\u003e and \u003cstrong\u003e6\u003c/strong\u003e) to the major cyanidin-glycosides (\u003cstrong\u003e1\u003c/strong\u003e and \u003cstrong\u003e3\u003c/strong\u003e) must be between 0.5 and 1.9. Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows a typical anthocyanin chromatogram of \u003cem\u003eV. macrocarpon\u003c/em\u003e. To identify potential adulterations, comparative analysis of the anthocyanin profile of lingonberries (\u003cem\u003eV. vitis-idaea\u003c/em\u003e) and the small cranberry (\u003cem\u003eV. oxycoccos\u003c/em\u003e) was performed (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Both species belong to the Ericaceae family and the same genus and exhibit similar morphological characteristics to \u003cem\u003eV. macrocarpon\u003c/em\u003e, suggesting the possibility of adulteration (Brown et al. \u003cspan class=\"CitationRef\"\u003e2012\u003c/span\u003e). As displayed in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e both extracts exert different anthocyanin pattern and can be differentiated easily by monitoring the six anthocyanins characterizing the cranberry extracts. Lingonberries test solution elutes several peaks with only one dominant peak, which was identified as Cy3Glc (\u003cstrong\u003e1\u003c/strong\u003e). \u003cem\u003eV. oxycoccos\u003c/em\u003e elutes a chromatogram that is more comparable to that of cranberries. However, the presence of a greater number of peaks, arranged in a distinct ratio to each other, allows also a clear differentiation between the different species (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eSubsequently, the test samples were analyzed by the validated HPLC protocol (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThree of the twelve test samples (#03, #04, #10) exhibited anthocyanin profiles which are different from that of \u003cem\u003eV. macrocarpon\u003c/em\u003e. Test sample #03 revealed a complex anthocyanin fingerprint, not typical for cranberry. As this sample did not conform to the specification, a second batch of the same product (#31) was obtained from the same supplier on a commercial basis. Analysis of this second batch again revealed no typical cranberry anthocyanin pattern. Surprisingly, the two batches (#03 and #31) from the same product brand revealed completely different anthocyanin composition (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). It seems astonishing that this product not only contains none of the typical cranberry natural products, but also lacks batch-to-batch conformity.\u003c/p\u003e\n\u003cp\u003eSimilar results were also obtained for different batches from test sample #04. Product #04 had an anthocyanin pattern which does not conform to that specified for cranberries (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). This result is also in accordance with the data obtained from the TLC testing (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The respective adulteration of #04 could not be assigned to a distinct plant species. Surprisingly, analysis of a second batch of the same product (#41) revealed an anthocyanin pattern, which again did not meet the cranberry requirements, but was also different form the elution pattern observed for #04 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). This again means, that no batch-to-batch conformity is given for the product.\u003c/p\u003e\n\u003cp\u003eTest sample #10 is a combination product with different botanical ingredients (chokeberries, hibiscus flowers, olive leaves, grape seed, blackcurrant extracts), a clear statement on identity of cranberry in this product is not possible. The presence of cranberry is possible, but due to the combination with other plant extracts which also contain anthocyanins a clear statement cannot be made for this product.\u003c/p\u003e\n\u003cp\u003eFor the other test products (#01, 02, 05, 06, 07, 08, 09, 11 and 12) identity of cranberry fruits was confirmed by the HPLC testing.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eQuantification of PAC (\u003c/em\u003eUnited States Pharmacopeia Convention \u003cspan class=\"CitationRef\"\u003e2023\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe quantification of PAC is based on a colorimetric reaction of 4-(dimethylamino)cinnamaldehyde (DMAC) in an acidic medium with the analytes. The assay exploits the reaction of DMAC with flavanols, leading to the formation of a chromophore, which can specifically be monitored at \u0026lambda;\u0026thinsp;=\u0026thinsp;620 nm. The intensity of the resulting absorption is directly proportional to the concentration of the PACs in the solution. For quantitative evaluation of PAC content standard calibration was used and the respective results were expressed as procyanidin A2 equivalents (Prior et al. \u003cspan class=\"CitationRef\"\u003e2010\u003c/span\u003e; Cardellina II and Gafner 2018; Vidal-Casanella et al. \u003cspan class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eEvaluation of the test samples indicated relevant quality deficiencies concerning the PAC content. In none of the samples for which a defined PAC content has been specified, this amount of PAC could be quantified (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eSummary of quality investigation of cranberry-based food supplements with regard to identity, uniformity of mass of single dosed preparations and total PAC-content\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNo.\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eIdentity\u003c/p\u003e\n\u003cp\u003e[TLC, HPLC]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eUniformity of mass\u003c/p\u003e\n\u003cp\u003e[Ph. Eur.]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eContent PAC\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePAC specification [mg/ unit]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal PAC content per unit [mg], calc. as procyanidin A2;\u003c/p\u003e\n\u003cp\u003emean (range), n\u0026thinsp;=\u0026thinsp;2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRecommended daily dose, corresponding to PAC content [mg] per day\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal PAC content per day [mg], calc. as procyanidin A2\u003c/p\u003e\n\u003cp\u003eAccording analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.a.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eno declaration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.a\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.a.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.95 (0.35\u0026ndash;1.55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#03/31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e- / -\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.41 (5.34\u0026ndash;5.49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#04/41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e- / -\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.35 (5.67\u0026ndash;9.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eno declaration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.27 (1.17\u0026ndash;1.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 capsule\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.26 (10.38\u0026ndash;12.13)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 capsule\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eno declaration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.02 (2.91\u0026ndash;3.12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#08\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eno declaration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.16 (0.45\u0026ndash;1.86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.29 (0.55\u0026ndash;2.04)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e(+)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eno declaration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.29 (4.87\u0026ndash;7.71)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.a.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eno declaration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.a\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e---\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e#12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.65 (0.24\u0026ndash;0.88)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 capsules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003en.a.: not analyzed; \u003cstrong\u003e-\u003c/strong\u003e: negative result; + positive resul\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSamples for which no specific PAC content was provided by the supplier had been evaluated according the corresponding USP monograph for that product type (e.g. Cranberry fruit juice concentrate). Among all samples, only sample #07 complies with the USP specification, which requires a minimum PAC content of 0.6% (w/w), calculated as procyanidin A2. Although this product meets the official quality criteria, the actual PAC dosage provides by the serving size is substantially lower than the intake levels typically regarded as effective. Therefore, only a limited recommendation can be made. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the respective results and compares manufacturers declaration with the results found in our investigations.\u003c/p\u003e\n\u003cp\u003eHowever, some limitations of the DMAC method must be noticed. The assay only quantifies soluble PACs, while insoluble PACs which are bound to fiber material, pomace or proteins remain undetected. As a result, the PAC content of products derived from cranberry press cake, where a considerable amount of PACs are bound to insoluble matrix constituents, may be underestimated (Brendler and Gafner \u003cspan class=\"CitationRef\"\u003e2017\u003c/span\u003e). Additionally, another limitation of the DMAC assay relates to the choice of the calibration standard. Procyanidin A2 is used as a reference standard for calibration. As cranberry products contain a heterogenous mixtures of PACs with varying degrees of polymerization, the use of procyanidin A2 reduces accuracy with respect to absolute PAC quantification. For this reason, DMAC-derived PAC concentrations should be interpreted as relative rather than absolute values (Brendler and Gafner \u003cspan class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eCranberry-based food supplements are widely marketed for urinary tract health, although their regulatory classification as food supplements rather than herbal medicinal products results in less stringent quality requirements. Substantial quality deficiencies have been detected in the present study. One product failed to meet legal labeling obligations due to inconsistencies between packaging and leaflet information. Testing of uniformity of mass revealed deviations exceeding governmental limits for one test sample, which shows insufficient manufacturing protocols. Identity testing by HPTLC seems to be a highly efficient way to have a close insight into the overall composition of the extracts and HPLC can specifically analyze the anthocyanin pattern as complex fingerprint authentication demonstrated a variability in anthocyanin profile. These findings underscore the lack of standardized raw materials and show again the critical gap between the pharmaceutical-like presentation of food supplements and their actual analytical and regulatory quality. In contrast to medicinal products, food supplements are not subject to the strict requirements and legislation of drug legislation, for this the national governmental institutions strictly controls manufacturers on the different levels of raw materials, products, production technology, quality control, quality assurance, pharmacovigilance and organizational structures. Food supplements are regulated by the national food laws, which shift responsibility for the marketed products towards the manufacturer (European Union 2025). For food supplements registration only online notification of the governmental institution before placing the product on the market is required; no assessment, testing or further authorization is carried out. As a result, a non-transparent and low-quality market for food supplements is obvious, especially for botanicals. While vitamins and minerals substances are listed and regulated in Directive \u003cspan class=\"CitationRef\"\u003e2002\u003c/span\u003e/46 (European Parliament and the Council 2002), the botanicals are still on hold and therefore unregulated. Although the European Food and Safety Agency (EFSA) is responsible for the evaluation of health claims, food supplements are frequently advertised and marketed with health claims in practice. This makes it even more challenging for consumers to differentiate between medicinal products and food supplements. Previous studies have already demonstrated that the quality of botanicals is unacceptable (Gaspar et al. \u003cspan class=\"CitationRef\"\u003e2021\u003c/span\u003e; Brouns et al. \u003cspan class=\"CitationRef\"\u003e2025\u003c/span\u003e). This assumption was confirmed by the study presented here, which also highlights the urgent need for harmonized quality standards, transparent labeling and improved regulatory standards to ensure consumer safety.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCDE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecranberry dry extract\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCy3Gal\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCyanidin-3-\u003cem\u003eO\u003c/em\u003e-galactoside\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCy3Glc\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCyanidin-3-\u003cem\u003eO\u003c/em\u003e-glucoside\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Medicines Agency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHPLC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHigh pressure liquid chromatography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHPTLC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHigh performance thin layer chromatography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eproanthocyanidin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePn3Gal\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epaeonidin-3-\u003cem\u003eO\u003c/em\u003e-galactoside\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePh. Eur.\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Pharmacopoeia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTLC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethin layer chromatography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUPEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003europathogenic \u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUTI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003euncomplicated urinary tract infections.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u0026nbsp;\u003c/h2\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eAB: data curation, formal analysis, investigation, methodology, writing; ML review and editing, supervision; AH: conceptualization, funding, writing. All authors reviewed the manuscript\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eAcknowledgmentsThe technical assistance of Mr. A. Niermann for providing plant material is acknowledged.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eAll data supporting the findings of this study are available within the paper and its Supplementary Information.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDirective (2002) /46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmerican Botanical Council (2017) Cranberry Adulteration Bulletin: Botanical Adulterants Program. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://abc.herbalgram.org/site/MessageViewer;jsessionid=00000000.app20047a?em_id=41167.0\u0026amp;NONCE_TOKEN=1D35BD88E5B2E3C4E32E7A88021C55A9\u003c/span\u003e\u003cspan address=\"http://abc.herbalgram.org/site/MessageViewer;jsessionid=00000000.app20047a?em_id=41167.0\u0026amp;NONCE_TOKEN=1D35BD88E5B2E3C4E32E7A88021C55A9\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 20 November 2025\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrendler T, Gafner S (2017) Adulteration of Cranberry (Vaccinium macrocarpon). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.59520/bapp.bapb/IYWq8096\u003c/span\u003e\u003cspan address=\"10.59520/bapp.bapb/IYWq8096\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrouns A, Lechtenberg M, Hensel A (2025) Passionflower (\u003cem\u003ePassiflora incarnata\u003c/em\u003e): Quality of Food Supplements Versus Registered Herbal Medicinal Products. Planta Med 532\u0026ndash;540. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1055/a-2591-3765\u003c/span\u003e\u003cspan address=\"10.1055/a-2591-3765\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown PN, Turi CE, Shipley PR, Murch SJ (2012) Comparisons of large (\u003cem\u003eVaccinium macrocarpon\u003c/em\u003e Ait.) and small (\u003cem\u003eVaccinium oxycoccos\u003c/em\u003e L., \u003cem\u003eVaccinium vitis-idaea\u003c/em\u003e L.) cranberry in British Columbia by phytochemical determination, antioxidant potential, and metabolomic profiling with chemometric analysis. Planta Med 78:630\u0026ndash;640. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1055/s-0031-1298239\u003c/span\u003e\u003cspan address=\"10.1055/s-0031-1298239\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBundesinstitut f\u0026uuml;r Arzneimittel und Medizinprodukte (ed) (2024) European Pharmacopoeia: 2.9.5 Uniformity of mass of single-dose preparations, 11th edn. Deutscher Apotheker, Stuttgart\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurger O, Ofek I, Tabak M, Weiss EI, Sharon N, Neeman I (2000) A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus. FEMS Immunol Med Microbiol 29:295\u0026ndash;301. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1574-695X.2000.tb01537.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1574-695X.2000.tb01537.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurger O, Weiss E, Sharon N, Tabak M, Neeman I, Ofek I (2002) Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr 42:279\u0026ndash;284. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/10408390209351916\u003c/span\u003e\u003cspan address=\"10.1080/10408390209351916\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCardellina IIJ, Gafner S (2018) Cranberry Products Laboratory Guidance Document. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.59520/bapp.lgd/KyrL6352\u003c/span\u003e\u003cspan address=\"10.59520/bapp.lgd/KyrL6352\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Commission (2025) Food and Feed Information Portal Database - Health Claims - EU Register. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ec.europa.eu/food/food-feed-portal/screen/health-claims/eu-register\u003c/span\u003e\u003cspan address=\"https://ec.europa.eu/food/food-feed-portal/screen/health-claims/eu-register\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Medicines Agency - Herbal Medicinal Products Committee (2022) Vaccinii macrocarpi fructus: EMA/HMPC/49135/2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ema.europa.eu/en/documents/herbal-monograph/final-european-union-herbal-monograph-vaccinium-macrocarpon-aiton-fructus_en.pdf\u003c/span\u003e\u003cspan address=\"https://www.ema.europa.eu/en/documents/herbal-monograph/final-european-union-herbal-monograph-vaccinium-macrocarpon-aiton-fructus_en.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFoo LY, Lu Y, Howell AB, Vorsa N (2000) A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli. J Nat Prod 63:1225\u0026ndash;1228. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1021/np000128u\u003c/span\u003e\u003cspan address=\"10.1021/np000128u\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaspar DP, Lechtenberg M, Hensel A (2021) Quality Assessment of Bilberry Fruits (\u003cem\u003eVaccinium myrtillus\u003c/em\u003e) and Bilberry-Containing Dietary Supplements. J Agric Food Chem 69:2213\u0026ndash;2225. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1021/acs.jafc.0c07784\u003c/span\u003e\u003cspan address=\"10.1021/acs.jafc.0c07784\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGbinigie OA, Spencer EA, Heneghan CJ, Lee JJ, Butler CC (2020) Cranberry Extract for Symptoms of Acute, Uncomplicated Urinary Tract Infection: A Systematic Review. Antibiot (Basel) 10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/antibiotics10010012\u003c/span\u003e\u003cspan address=\"10.3390/antibiotics10010012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHowell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M (2005) A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry 66:2281\u0026ndash;2291. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.phytochem.2005.05.022\u003c/span\u003e\u003cspan address=\"10.1016/j.phytochem.2005.05.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLechtenberg M, Hensel A (2019) Determination of glucosinolates in broccoli-based dietary supplements by cyclodextrin-mediated capillary zone electrophoresis. J Food Compos Anal 78:138\u0026ndash;149. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jfca.2019.02.007\u003c/span\u003e\u003cspan address=\"10.1016/j.jfca.2019.02.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeto CC, Penndorf KA, Feldman M, Meron-Sudai S, Zakay-Rones Z, Steinberg D, Fridman M, Kashman Y, Ginsburg I, Ofek I, Weiss EI (2017) Characterization of non-dialyzable constituents from cranberry juice that inhibit adhesion, co-aggregation and biofilm formation by oral bacteria. Food Funct 8:1955\u0026ndash;1965. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1039/C7FO00109F\u003c/span\u003e\u003cspan address=\"10.1039/C7FO00109F\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrior RL, Fan E, Ji H, Howell A, Nio C, Payne MJ, Reed J (2010) Multi-laboratory validation of a standard method for quantifying proanthocyanidins in cranberry powders. J Sci Food Agric 90:1473\u0026ndash;1478. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jsfa.3966\u003c/span\u003e\u003cspan address=\"10.1002/jsfa.3966\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScharf B, Dobrindt U, Sendker J, Hensel A (2017) Inhibitory activity of Cranberry extract on the bacterial adhesion in human urine: an ex vivo study. In: 65th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA 2017). Georg Thieme Verlag KG. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1055/s-0037-1608435\u003c/span\u003e\u003cspan address=\"10.1055/s-0037-1608435\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScharf B, Sendker J, Dobrindt U, Hensel A (2019) Influence of Cranberry Extract on Tamm-Horsfall Protein in Human Urine and its Antiadhesive Activity Against Uropathogenic Escherichia coli. Planta Med 85:126\u0026ndash;138. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1055/a-0755-7801\u003c/span\u003e\u003cspan address=\"10.1055/a-0755-7801\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScharf B, Schmidt TJ, Rabbani S, Stork C, Dobrindt U, Sendker J, Ernst B, Hensel A (2020) Antiadhesive natural products against uropathogenic \u003cem\u003eE. coli\u003c/em\u003e: What can we learn from cranberry extract? J Ethnopharmacol 257:112889. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jep.2020.112889\u003c/span\u003e\u003cspan address=\"10.1016/j.jep.2020.112889\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSendker J, Chen B, Lechtenberg M, Hensel A (2022) Nahrungserg\u0026auml;nzungsmittel auf Basis von Safran \u0026ndash; wie sieht die Qualit\u0026auml;tssituation aus? Z f\u0026uuml;r Phytotherapie 42:178\u0026ndash;185. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1055/a-1716-9696\u003c/span\u003e\u003cspan address=\"10.1055/a-1716-9696\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUnited States Pharmacopeia Convention (2023) Cranberry fruit juice dry extract capsules. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.31003/USPNF_M20456_02_01\u003c/span\u003e\u003cspan address=\"10.31003/USPNF_M20456_02_01\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUnited States Pharmacopeia Convention (2024) Cranberry Fruit Powder. USP-NF. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.31003/USPNF_M13915_02_01\u003c/span\u003e\u003cspan address=\"10.31003/USPNF_M13915_02_01\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVidal-Casanella O, Nu\u0026ntilde;ez O, Hern\u0026aacute;ndez-Cassou S, Saurina J (2021) Assessment of Experimental Factors Affecting the Sensitivity and Selectivity of the Spectrophotometric Estimation of Proanthocyanidins in Foods and Nutraceuticals. Food Anal Methods 14:485\u0026ndash;495. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12161-020-01878-1\u003c/span\u003e\u003cspan address=\"10.1007/s12161-020-01878-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu J, Li C, Wu W, Kong L, Xiao L, Ma W, Zhang L (2025) Cranberry Research Progress: A Systematic Review of Chemical Composition, Pharmacological Mechanisms, Clinical Applications, and Nutritional Significance. Int J Mol Sci 26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms26199707\u003c/span\u003e\u003cspan address=\"10.3390/ijms26199707\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamanaka A, Kimizuka R, Kato T, Okuda K (2004) Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation. Oral Microbiol Immunol 19:150\u0026ndash;154. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.0902-0055.2004.00130.x\u003c/span\u003e\u003cspan address=\"10.1111/j.0902-0055.2004.00130.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cranberry, fingerprint, food supplements, procyanidin, quality, Vaccinium macrocarpon","lastPublishedDoi":"10.21203/rs.3.rs-8523151/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8523151/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCranberry-based food supplements with extracts from the fruits of \u003cem\u003eVaccinium macrocarpon\u003c/em\u003e are widely marketed for urinary tract health. As food supplements containing plant extracts, the so-called botanicals, are known to have quality problems the present study assembled efficient analytical protocols for evaluation of cranberry products for unambiguous identity testing and quantitation of procyanidins. Twelve cranberry-containing food supplements available in the D-A-CH region were included into the study. The analytical investigation comprised uniformity of mass testing of single-dosed capsule preparations, identity fingerprinting by HPTLC and HPLC and photometric quantification of the procyanidin content. Major deficiencies were detected such as labelling inconsistencies and deviations in capsule mass which indicated poor manufacturing control. The chromatographic analysis revealed that three products did not show specific anthocyanin fingerprints being typical for \u003cem\u003eV. macrocarpon\u003c/em\u003e. In addition, deficiency was obvious concerning batch-to-batch conformity of certain brands. The results highlight the urgent need for specific analytical methods in quality control to verify botanical authenticity. Results again underscore critical regulatory gaps between the pharmaceutical-like presentation of such food supplements and their actual quality. Harmonized quality standards and stricter regulatory oversights are urgently needed to ensure transparency, consumer safety, and product integrity in the botanical supplement market.\u003c/p\u003e","manuscriptTitle":"Quality assessment of Cranberry (Vaccinium macrocarpon) based food supplements: HPTLC, HPLC and PAC quantification as effective tools for quality management","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-28 18:40:23","doi":"10.21203/rs.3.rs-8523151/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6eef1374-397c-4e15-99cc-479f5d807406","owner":[],"postedDate":"January 28th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-21T11:11:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-28 18:40:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8523151","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8523151","identity":"rs-8523151","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}