Analytical determination of proanthocyanidin (PAC) content and its association with label-declared PAC amounts and cranberry material in dietary supplements: A multi-lab study using the 4-dimenthylamino-cinnamaldehyde method

Authors: PANDEY, DEEPESH - University Of Maryland; VAVILALA, SUMA - University Of Maryland; GUSEV, PAVEL - University Of Maryland; ANDREWS, KAREN - University Of Maryland; OH, LAURA - University Of Maryland; EKONG, JOSIAH - University Of Maryland; CHUNG, MEI - Tufts University; Wu, Xianli; DWYER, JOHANNA - National Institutes Of Health (NIH); PEHRSSON, PAMELA - Retired ARS Employee

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/4/2026
Publication Date: 5/6/2026
Citation: Pandey, D., Vavilala, S., Gusev, P., Andrews, K., Oh, L., Ekong, J., Chung, M., Wu, X., Dwyer, J., Pehrsson, P. 2026. Analytical determination of proanthocyanidin (PAC) content and its association with label-declared PAC amounts and cranberry material in dietary supplements: A multi-lab study using the 4-dimenthylamino-cinnamaldehyde method. Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2026.101582.
DOI: https://doi.org/10.1016/j.tjnut.2026.101582

Interpretive Summary: Cranberry dietary supplements are widely used to help prevent recurring urinary tract infections, particularly amid rising concerns about antibiotic-resistant pathogens. However, there is ongoing uncertainty about how much of the key active compounds (proanthocyanidins, or PACs) they contain and how consistently different laboratories measure these compounds. In this study, 53 popular U.S. cranberry supplements were tested across four independent commercial laboratories to measure soluble PACs and to evaluate the real-world variability of the most widely used colorimetric DMAC method as implemented by industry labs. Only three products provided the 36mg per day of soluble PACs that has been associated with reduced urinary tract infection reoccurrence in clinical trials, and many products that listed PAC content on the label delivered substantially less than claimed. Further, most solid dosage forms passed standard disintegration or rupture tests, indicating the pills break apart and release active constituents successfully in the body, although some products containing clinically studied ingredients did not, which could limit how much PAC becomes available in the body. Overall, the findings from four labs were in agreement with PAC measurements revealing substantial under-delivery and mislabeling of PAC content in many cranberry supplements, while also demonstrating that the existing industry-standard DMAC approach, when used with appropriate controls, can provide clinically meaningful differentiation of PAC potency, underscoring the need for improved formulations and more accurate, transparent labeling.

Technical Abstract: Background: Proanthocyanidins (PACs) represent the primary bioactive compounds in cranberries recognized for reducing urinary tract infection (UTI) recurrence. Accurate PAC measurement is essential for reliable labeling, evaluating therapeutic efficacy, and guiding consumer choices. The DMAC (4-dimethylamino cinnamaldehyde) assay remains the predominant method used to quantify PACs in cranberry dietary supplements (DS). However, the influence of methodological variability in commercial laboratories on measured PAC values remains unclear. Objective: To quantify PAC content and evaluate label accuracy in commonly consumed U.S. cranberry DS, and to assess inter-laboratory variability using commercially implemented DMAC protocols. Methods: Fifty-three cranberry DS products (containing extracts, concentrates, or whole fruit powders) were analyzed for PACs by four commercial laboratories using harmonized extraction solvents and two standards (procyanidin A2, n=4 labs; cPAC, n=2 labs), while allowing lab-specific DMAC workflows for soluble PAC quantification. Insoluble PACs were quantified by butanol-hydrochloric acid assay in one laboratory. Statistical analyses included pairwise comparisons, meta-analysis and heterogeneity testing. Results: Overall, 3 of 53 products exhibited soluble PAC levels at or above 36 mg/day, the level associated with UTI risk reduction. Notably,13 of 16 (81.3%) extract-based products provided PAC concentrations well below this level despite their average soluble PAC level being higher than in concentrate-based DS (mean [95% CI] mg/day: 18.4 [3.94, 32.8] vs. 3.87 [2.41, 5.34], p=0.032), and higher, although not statistically significantly than amounts in the whole fruit powder based products (6.01 [0.93, 11.1], p=0.082). Products that declared PAC content on the label contained, on average, significantly less PACs than stated (mean+/-SD: -32+/- 51.4%, n=14). Inter-laboratory variability (expressed as %relative standard deviation [RSD]) for in-house controls and products with >3.3 mg/day PAC ranged from 22.1 to 31.6%. Concentrate and fruit powder-based products contained higher insoluble PAC than the extract-based products (p=0.02). Most DS cranberry products analyzed (77.8%) passed disintegration tests. although some formulations with the ingredients investigated in clinical trials failed. Conclusions: This multi-laboratory analysis reveals notable discrepancies between labeled and analytically measured soluble PAC content in most commercial cranberry DS, including many extract-based products marketed for UTI prevention. While inter-laboratory variability was high for products with low PAC content, variability was acceptable for products containing = 3.3 mg/day soluble PAC. Current industry DMAC practices can distinguish clinically relevant PAC potencies. However, the findings highlight the need for more stable formulations that align with the label claims and greater transparency in disclosing PAC amounts on labels to better inform consumers.