@article{ottaviani2024reliance,

title = {Reliance on self-reports and estimated food composition data in nutrition research introduces significant bias that can only be addressed with biomarkers},

author = {Javier I Ottaviani and Virag Sagi-Kiss and Hagen Schroeter and Gunter GC Kuhnle},

url = {https://elifesciences.org/articles/92941},

doi = {10.7554/eLife.92941.3},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {eLife},

volume = {13},

pages = {RP92941},

publisher = {eLife Sciences Publications Limited},

abstract = {The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.},

keywords = {biomarkers, dietary assessment, epicatechin, flavanols, nitrate},

pubstate = {published},

tppubtype = {article}

}

@article{ottaviani2023measuring,

title = {Measuring the intake of dietary bioactives: Pitfalls and how to avoid them},

author = {Javier I Ottaviani and Hagen Schroeter and Gunter GC Kuhnle},

year  = {2023},

date = {2023-01-01},

journal = {Molecular Aspects of Medicine},

volume = {89},

pages = {101139},

publisher = {Pergamon},

keywords = {biomarkers, flavanols},

pubstate = {published},

tppubtype = {article}

}

@article{brickman2023dietary,

title = {Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption},

author = {Adam M Brickman and Lok-Kin Yeung and Daniel M Alschuler and Javier I Ottaviani and Gunter GC Kuhnle and Richard P Sloan and Heike Luttmann-Gibson and Trisha Copeland and Hagen Schroeter and Howard D Sesso and others},

url = {https://pubmed.ncbi.nlm.nih.gov/37252983/},

doi = {10.1073/pnas.2216932120},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Proceedings of the National Academy of Sciences},

volume = {120},

number = {23},

pages = {e2216932120},

publisher = {National Academy of Sciences},

abstract = {Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion-repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.},

keywords = {flavanols, hippocampus},

pubstate = {published},

tppubtype = {article}

}

@article{ottaviani2023impact,

title = {Impact of polyphenol oxidase on the bioavailability of flavan-3-ols in fruit smoothies: a controlled, single blinded, cross-over study},

author = {Javier I Ottaviani and Jodi L Ensunsa and Reedmond Y Fong and Jennifer Kimball and Valentina Medici and Gunter GC Kuhnle and Alan Crozier and Hagen Schroeter and Catherine Kwik-Uribe},

url = {https://pubmed.ncbi.nlm.nih.gov/37615673/},

doi = {10.1039/d3fo01599h},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Food & Function},

volume = {14},

number = {18},

pages = {8217–8228},

publisher = {Royal Society of Chemistry},

abstract = {Flavan-3-ols are bioactive compounds found in a variety of fruits and vegetables (F&V) that have been linked to positive health benefits. Increasing habitual flavan-3-ol intake is challenged by the generally low consumption of F&V. While smoothies are a commonly endorsed, consumer-accepted means to increase the daily intake of these important foods, fruits used for smoothie preparation can have a high polyphenol oxidase (PPO) activity and thus potentially affect the content and bioavailability of flavan-3-ols. To assess whether or not consuming freshly prepared smoothies made with different PPO-containing fruit impacts the bioavailability of the flavan-3-ols, a controlled, single blinded and cross-over study was conducted in healthy men (n = 8) who consumed a flavan-3-ol-containing banana-based smoothie (high-PPO drink), a flavan-3-ol-containing mixed berry smoothie (low-PPO drink) and flavan-3-ols in a capsule format (control). The peak plasma concentration (Cmax) of flavan-3-ol metabolites after capsule intake was 680 $±$ 78 nmol L-1, which was similar to the levels detected after the intake of the low PPO drink. In contrast, the intake of the high PPO drink resulted in a Cmax of 96 $±$ 47 nmol L-1, 84% lower than that obtained after capsule intake. In a subsequent study (n = 11), flavan-3-ols were co-ingested with a high-PPO banana drink but contact prior to intake was prevented. In this context, plasma flavan-3-ol levels were still reduced, suggesting an effect possibly related to post-ingestion PPO activity degrading flavan-3-ols in the stomach. There was a substantial range in the PPO activity detected in 18 different fruits, vegetables and plant-derived dietary products. In conclusion, bioavailability of flavan-3-ols, and most likely other dietary polyphenol bioactives, can be reduced substantially by the co-ingestion of high PPO-containing products, the implications of which are of importance for dietary advice and food preparation both at home and in industrial settings.},

keywords = {biomarkers, epicatechin, flavanols, polyphenol oxidase},

pubstate = {published},

tppubtype = {article}

}

@article{momma20235b,

title = {5-(3′, 4′-Dihydroxyphenyl)-𝜸-Valerolactone Is a Substrate for Human Paraoxonase: A Novel Pathway in Flavan-3-ol Metabolism},

author = {Tony Y Momma and Gunter GC Kuhnle and Reedmond Y Fong and Jodi L Ensunsa and Alan Crozier and Hagen Schroeter and Javier I Ottaviani},

url = {https://pubmed.ncbi.nlm.nih.gov/37423968/},

doi = {10.1002/mnfr.202300281},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

abstract = {Scope: Dietary flavan-3-ols are known to mediate cardiovascular benefits. Currently, it is assumed that the levels of flavan-3-ol catabolites detected in humans, 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (γVL) and 5-(3',4'-dihydroxyphenyl)-γ-valeric acid (γVA), and their corresponding phase II metabolites, are determined exclusively by the action of the gut microbiome. However, a family of human proteins, paraoxonase (PON), can theoretically hydrolyze γVL metabolites into the corresponding γVAs. This study aims to determine if PON is involved in γVL and γVA metabolism in humans. Methods and results: A rapid conversion of γVL into γVA is detected in serum ex vivo (half-life = 9.8 $±$ 0.3 min) that is catalyzed by PON1 and PON3 isoforms. Phase II metabolites of γVL are also reacted with PON in serum. Following an intake of flavan-3-ol in healthy males (n = 13), the profile of γVA metabolites detected is consistent with that predicted from the reactivity of γVL metabolites with PON in serum. Furthermore, common PON polymorphisms are evaluated to assess the use of γVL metabolites as biomarkers of flavan-3-ol intake. 

Conclusion: PONs are involved in flavan-3-ol metabolic pathway in humans. PON polymorphisms have a minor contribution to inter-individual differences in the levels of γVL metabolites, without affecting their use as a nutritional biomarker.},

keywords = {absorption, epicatechin, flavanols, paraoxonase},

pubstate = {published},

tppubtype = {article}

}

@article{crowe2022flavan,

title = {Flavan-3-ols and Cardiometabolic Health: a Guideline Recommendation by the Academy of Nutrition and Dietetics.},

author = {Kristi M Crowe-White and Levi W Evans and Gunter GC Kuhnle and Dragan Milenkovic and Kim Stote and Taylor Wallace and Deepa Handu and Katelyn E Senkus},

year  = {2022},

date = {2022-01-01},

journal = {Advances in Nutrition (Bethesda, Md.)},

pages = {nmac105–nmac105},

keywords = {dietary recommendations, flavanols},

pubstate = {published},

tppubtype = {article}

}

@article{ottaviani2019evaluation,

title = {Evaluation of (-)-epicatechin metabolites as recovery biomarker of dietary flavan-3-ol intake},

author = {Javier I Ottaviani and Reedmond Fong and Jennifer Kimball and Jodi L Ensunsa and Nicola Gray and Anna Vogiatzoglou and Abigail Britten and Debora Lucarelli and Robert Luben and Philip B Grace and others},

year  = {2019},

date = {2019-01-01},

journal = {Scientific reports},

volume = {9},

number = {1},

pages = {13108},

publisher = {Nature Publishing Group UK London},

keywords = {biomarkers, dietary assessment, epicatechin, flavanols},

pubstate = {published},

tppubtype = {article}

}