Food chemistry and nutrient bioavailability: Bridging science and human nutrition

Introduction

Human nutrition depends not just on the amount of nutrient present in foods, but on how much of that nutrient becomes available to the body after ingestion (bioavailability) (Stevenson, 2006) [40] . The chemical form of a nutrient (e.g., heme vs. non-heme iron), its molecular interactions in the food matrix, the presence of inhibitors or enhancers, processing history, and host factors (digestion, microbiome, physiology) all determine ultimate nutritional value (Xing et al., 2022) [46] . Food chemistry provides the mechanistic basis for these interactions and offers levers through formulation or processing to improve nutrient delivery (Zhang et al., 2025) [50] . Recent reviews emphasize that the food matrix concept must be central to dietary guidance and product design because matrix-mediated interactions can substantially alter bioaccessibility and bioefficacy.

Key concepts: bioaccessibility vs. bioavailability

 Bioaccessibility refers to the fraction of a nutrient released from the food matrix in the gastrointestinal tract and made available for absorption (Santos et al., 2019) [36] .  Bioavailability is the fraction of the ingested dose that is absorbed and reaches systemic circulation in an active form (Paul, 2019) [26] .

Distinguishing these is critical because many food-chemistry interventions improve bioaccessibility without necessarily enhancing absorption or systemic utilization (which may be limited by transporters, first-pass metabolism, or microbial transformation). Quantifying each step requires complementary analytical and biological methods (Fennema et al., 2017) [10] .

Food matrix effects chemistry in context

The "food matrix" describes the structural and compositional context in which nutrients reside (proteins, lipids, carbohydrates, fibres, and other bioactives) (Aguilera, 2019) [1] . Matrix components affect solubility, release during digestion, and physical accessibility to enzymes and uptake transporters (Dima et al., 2020) [8] . For example, carotenoids are fatsoluble and their micellarization during digestion depends strongly on lipid presence and particle size; calcium and iron availability may be reduced by binding to oxalates or phytates in certain matrices (Corte-Real and Bohn, 2018) [6] . Dairy matrices illustrate that the whole food can have different health effects than isolated nutrients because proteins, lipids and minerals interact synergistically or antagonistically (Aguilera, 2019) [1] . Because matrix interactions are complex and often compound-specific, food-chemistry characterization (particle size, lipid phase, binding affinities) is a prerequisite to predict bioaccessibility (Peyron et al., 2018) [29] .

Processing: a double-edged sword

Food processing alters chemical and physical structure sometimes improving, sometimes reducing bioavailability (Ribas-Agustí et al., 2018) [33] . Thermal treatments can denature proteins (improving digestibility), but may degrade heat-labile vitamins (e.g., vitamin C, B vitamins). Cooking of carotenoid-rich vegetables increases carotenoid bioaccessibility by disrupting cell walls, while boiling leafy greens can leach water-soluble vitamins (Bhat et al., 2021) [2] . Fermentation often enhances micronutrient availability by degrading phytates and producing bioactive metabolites (Samtiya et al., 2021) [35] . Advanced processing (highpressure, extrusion, enzymatic hydrolysis) can be tailored to increase release of target nutrients from the matrix; however, processing can also generate undesirable compounds or complex the nutrient with other food components, reducing uptake (Aguilera, 2019) [1] . Thus, processing must be considered as a tunable variable rather than simply "good" or "bad."

Chemical modulators: inhibitors and enhancers of absorption

 Inhibitors: Phytates, oxalates, certain polyphenols and dietary fibres can chelate minerals (e.g., Fe, Zn, Ca) and reduce their intestinal uptake (Zhang et al., 2022) [46] . Tannins can bind proteins and digestive enzymes, decreasing protein digestibility (Cirkovic Velickovic and Stanic-Vucinic, 2018) [5] .  Enhancers: Vitamin C enhances non-heme iron absorption by reducing Fe (III) to Fe (II) and forming soluble complexes (Pan et al., 2024) [25] . Dietary lipids improve micelle formation required for carotenoid and fat-soluble vitamin absorption. Certain fermentation products (organic acids) can improve mineral solubility.

Understanding stoichiometry and kinetics of these chemical interactions within the gut environment is critical to predict net effects (Hsu et al., 2019) [13] .

Methods to assess bioavailability: strengths and limitations

 In vitro digestion models (static or dynamic gastrointestinal simulators) estimate bioaccessibility and micellarization under controlled conditions; they are useful for screening but lack host absorption processes (Gonçalves et al., 2021) [11] .  Ex vivo and cell culture models (e.g., Caco-2 intestinal cells) test transport and cellular uptake but cannot fully capture whole-body kinetics or microbial interactions (Pearce et al., 2018) [27] .  In vivo human studies remain the gold standard (isotopic tracers, balance studies, clinical biomarkers), but are costly and ethically constrained (Penner et al., 2009) [28] .

 Mathematical modeling and prediction algorithms are emerging to integrate physicochemical data and experimental results into bioavailability estimates; standardization and validation remain active needs. Recent guidance proposes frameworks for harmonized prediction equations and reporting to improve comparability across studies (Soliman et al., 2022) [38] .

Technological strategies to improve nutrient delivery 7.1 Fortification and chemical form selection

Selecting more bioavailable chemical forms (e.g., ferrous fumarate vs. elemental iron) and matching fortificant carriers to the food matrix reduces antagonistic interactions. Fortification success also requires consideration of sensory changes and stability (Mattar et al., 2022) [21] . Fortification is one of the most widely applied strategies to combat micronutrient deficiencies, but its success largely depends on the chemical form of the nutrient selected (Dwyer et al., 2015) [9] . The stability, solubility, and interaction of the fortificant with the food matrix determine both sensory quality and bioavailability (Lavelli et al., 2021) [17] . For example, ferrous fumarate and ferrous sulfate are preferred for iron fortification due to higher solubility and absorption compared with elemental iron, although they may cause color and flavor changes in certain foods (Hurrell, 2002) [14] . Similarly, zinc sulfate is commonly used over zinc oxide because of greater bioavailability in aqueous systems (Wedekind et al., 1992) [45] . The choice of vitamin form also matters; vitamin A is typically fortified as retinyl palmitate for stability in oils, while vitamin D is added in fat-soluble forms that integrate better into lipid matrices, enhancing absorption (Maurya et al., 2022) [22] . Careful selection must balance nutritional efficacy, chemical compatibility, sensory attributes, and cost-effectiveness (Rajasekaran and Kalaivani, 2013) [30] . Moreover, matching fortificants to specific dietary staples of target populations ensures optimal delivery and minimizes inhibitors such as phytates or tannins, ultimately making fortification a science-driven intervention for improving public health nutrition (Osendarp et al., 2018) [24] .

Encapsulation and delivery systems

Micro-and nano-encapsulation protect labile nutrients from degradation, mask off-flavors, and enable controlled release at target gut locations improving stability and sometimes absorption (Samakradhamrongthai, 2024) [34] . Advances in food-grade nanoparticles, liposomes, protein-or polysaccharide-based carriers, and pH-responsive release systems have shown promise for vitamins, polyphenols, and omega-3 fatty acids (Mankan et al., 2025) [19] . Regulatory, safety, and scale-up considerations remain key barriers to widespread food application (Rashidinejad, 2024) [31] .

Processing optimization and ingredient pairing

Combining ingredient science (e.g., adding small amounts of oils to vegetable mixes to aid carotenoid uptake, coformulating vitamin C with plant-based iron sources) and tailored processing (mild thermal treatment, enzymatic phytase treatment) can markedly improve net nutrient availability while maintaining sensory quality (Hofmann et al., 2020) [12] .

The gut microbiome as a mediator of nutrient fate

The gut microbiota acts as a metabolic "organ" that transforms dietary components, synthesizes vitamins, modifies bile-salt mediated lipid digestion, and influences mineral solubility (Vernocchi et al., 2020) [42] . Microbial fermentation of fibres yields short-chain fatty acids that modulate intestinal physiology and nutrient transporter expression (Wang et al., 2019) [43] . Moreover, the microbiome can convert some polyphenols into more or less absorbable metabolites (Marín et al., 2015) [20] . Recent systemic reviews and mechanistic studies underline that inter-individual microbiome differences can contribute to variability in nutrient responses to identical diets, suggesting a role for personalized nutrition strategies informed by microbiome profiling (Lampe et al., 2013) [16] .

Translating food-chemistry knowledge into publichealth nutrition

Bridging mechanistic science and population nutrition requires: (a) robust, standardized methods to measure bioavailability across matrices and populations; (b) contextaware fortification/processing strategies appropriate for local diets; and (c) policies that consider not only nutrient content but expected bioavailable fraction. For instance, staple food fortification programs should be designed with matrix and inhibitor considerations in mind and validated by bioavailability studies in target populations rather than assuming uniform uptake. Modeling frameworks that combine food composition, processing data, and physiological factors can improve policy decisions and predict population-level impacts (Sanz et al., 2025) [37] .

Challenges and future directions 1. Standardization and comparability: Diverse in vitro

methods and inconsistent reporting hamper cross-study synthesis. Community-wide standards for assay design, reporting and validation would accelerate progress (McMullen et al., 2019) [23] .

Bridging scales:

Integrating molecular-level chemistry with whole-organism outcomes (PK/PD, biomarkers) remains difficult; multi-scale models and better translational studies are needed (Kuepfer et al., 2012) [15] .

Personalization:

Accounting for host genetics, age, disease status, and microbiome composition could improve nutrient recommendations but will require large, well-characterized cohorts (Bianchetti et al., 2023) [3] .

Safe application of new technologies:

Nanoencapsulation and other advanced delivery systems show efficacy in controlled studies, but longterm safety, regulatory frameworks, and consumer acceptance must be addressed prior to widespread adoption (Soni et al., 2022) [39] . [41] Carotenoids (βcarotene, lycopene)

Carrots, tomatoes

Heat processing disrupts cell wall; lipids aid micelle formation Increased bioaccessibility after cooking, especially with added oil Zheng et al., 2022 (CRFSFS) [51] Polyphenols (flavonoids) Tea, cocoa Complexation with proteins and fibres

Decreased absorption and bioefficacy

Zhang et al., 2024 (Food Chemistry) [47] Vitamin B12 [44] Omega-3 fatty acids Fish oils, fortified foods

Encapsulation in nanoemulsions

Improved stability and intestinal uptake Lei et al., 2024 (Frontiers/MDPI) [18] Minerals (Zn, Fe) Fermented cereals

Phytase activity during fermentation

Increased mineral solubility and absorption Toydemir et al., 2022 (Foods) [41] Vitamin D Fortified dairy Fat matrix facilitates absorption Higher serum response vs. supplements in water-based matrices Cifelli et al., 2021 (Nutrients) [4] Conclusion Food chemistry provides essential mechanistic understanding to predict and improve nutrient bioavailability. Matrix composition, processing, chemical interactions, delivery technologies and the gut microbiome all interact to determine the nutritional value of foods. Progress requires integrated approaches standardized assays, translational human studies, systems modeling, and responsible technological deployment to convert lab discoveries into measurable improvements in public health nutrition. Collaborative efforts across food chemists, nutritionists, microbiologists, and policy makers will be necessary to close the gap between nutrient content and nutrient benefit.

References

1. Aguilera JM. The food matrix: implications in processing, nutrition and health. Critical Reviews in Food Science and Nutrition. 2019;59(22):3612-3629.
2. Bhat ZF, Morton JD, Bekhit AEDA, Kumar S, Bhat HF. Thermal processing implications on the digestibility of meat, fish and seafood proteins. Comprehensive Reviews in Food Science and Food Safety. 2021;20(5):4511-4548.
3. Bianchetti G, De Maio F, Abeltino A, Serantoni C, Riente A, Santarelli G, et al. Unraveling the gut microbiome-diet connection: exploring the impact of digital precision and personalized nutrition on microbiota composition and host physiology. Nutrients. 2023;15(18):3931-3931.
4. Cifelli CJ, Miller GD, McGregor RA. Dairy foods, bioactive compounds, and the food matrix: Impact on human health. Nutrients. 2021;13(7):2344-2344.
5. Cirkovic Velickovic TD, Stanic-Vucinic DJ. The role of dietary phenolic compounds in protein digestion and processing technologies to improve their antinutritive properties. Comprehensive Reviews in Food Science and Food Safety. 2018;17(1):82-103.
6. Corte-Real J, Bohn T. Interaction of divalent minerals with liposoluble nutrients and phytochemicals during digestion and influences on their bioavailability -a review. Food Chemistry. 2018;252:285-293.
7. Diacova T, Forde C, Linder T. Best practices and considerations for conducting diet-gut microbiome studies: An umbrella review. Advances in Nutrition. 2025;16(2):305-324.
8. Dima C, Assadpour E, Dima S, Jafari SM. Bioavailability of nutraceuticals: Role of the food matrix, processing conditions, the gastrointestinal tract, and nanodelivery systems. Comprehensive Reviews in Food Science and Food Safety. 2020;19(3):954-994.
9. Dwyer JT, Wiemer KL, Dary O, Keen CL, King JC, Miller KB, et al. Fortification and health: challenges and opportunities. Advances in Nutrition. 2015;6(1):124-131.
10. Fennema OR, Damodaran S, Parkin KL. Introduction to food chemistry. In: Fennema's Food Chemistry. Boca Raton: CRC Press; 2017. p.1-16.
11. Gonçalves A, Estevinho BN, Rocha F. Methodologies for simulation of gastrointestinal digestion of different controlled delivery systems and further uptake of encapsulated bioactive compounds. Trends in Food Science & Technology. 2021;114:510-520.
12. Hofmann T, Lowry GV, Ghoshal S, Tufenkji N, Brambilla D, Dutcher JR, et al. Technology readiness and overcoming barriers to sustainably implement nanotechnology-enabled plant agriculture. Nature Food. 2020;1(7):416-425.
13. Hsu CY, Wang PW, Alalaiwe A, Lin ZC, Fang JY. Use of lipid nanocarriers to improve oral delivery of vitamins. Nutrients. 2019;11(1):68-68.
14. Hurrell R. How to ensure adequate iron absorption from iron-fortified food. Nutrition Reviews. 2002;60(Suppl):S7-S15.
15. Kuepfer L, Lippert J, Eissing T. Multiscale mechanistic modeling in pharmaceutical research and development. Advances in Systems Biology. 2012;543-561.
16. Lampe JW, Navarro SL, Hullar MA, Shojaie A. Interindividual differences in response to dietary intervention: integrating omics platforms towards personalised dietary recommendations. Proceedings of the Nutrition Society. 2013;72(2):207-218.
17. Lavelli V, D'Incecco P, Pellegrino L. Vitamin D incorporation in foods: Formulation strategies, stability, and bioaccessibility as affected by the food matrix. Foods. 2021;10(9):1989-1989.
18. Lei Y, Zhang L, Wang Q. Nanoencapsulation and delivery of bioactive ingredients in foods: Approaches and perspectives. Frontiers in Nutrition. 2024;11:114128.
19. Mankan E, Karakas CY, Saroglu O, Mzoughi M, Sagdic O, Karadag A. Food-grade liposome-loaded delivery systems: current trends and future perspectives. Foods. 2025;14(17):2978-2978.
20. Marín L, Miguélez EM, Villar CJ, Lombó F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. BioMed Research International. 2015;2015(1):905215905215.
21. Mattar G, Haddarah A, Haddad J, Pujola M, Sepulcre F. New approaches, bioavailability and the use of chelates as a promising method for food fortification. Food Chemistry. 2022;373:131394-131394.
22. Maurya VK, Shakya A, Bashir K, Kushwaha SC, McClements DJ. Vitamin A fortification: recent advances in encapsulation technologies. Comprehensive Reviews in Food Science and Food Safety. 2022;21(3):2772-2819.
23. McMullen PD, Pendse SN, Black MB, Mansouri K, Haider S, Andersen ME, et al. Addressing systematic inconsistencies between in vitro and in vivo transcriptomic mode of action signatures. Toxicology in vitro. 2019;58:1-12.
24. Osendarp SJ, Martinez H, Garrett GS, Neufeld LM, DeRegil LM, Vossenaar M, et al. Large-scale food fortification and biofortification in low-and middleincome countries: a review of programs, trends, challenges, and evidence gaps. Food and Nutrition Bulletin. 2018;39(2):315-331.
25. Pan X, Köberle M, Ghashghaeinia M. Vitamin Cdependent uptake of non-heme iron by enterocytes, its impact on erythropoiesis and redox capacity of human erythrocytes. Antioxidants. 2024;13(8):968-968.
26. Paul A. Drug absorption and bioavailability. In: Introduction to Basics of Pharmacology and Toxicology: Volume 1: General and Molecular Pharmacology: Principles of Drug Action. Singapore: Springer Singapore; 2019. p.81-88.
27. Pearce SC, Coia HG, Karl JP, Pantoja-Feliciano IG, Zachos NC, Racicot K. Intestinal in vitro and ex vivo models to study host-microbiome interactions and acute stressors. Frontiers in Physiology. 2018;9:1584-1584.
28. Penner N, Klunk LJ, Prakash C. Human radiolabeled mass balance studies: objectives, utilities and limitations. Biopharmaceutics & Drug Disposition. 2009;30(4):185-203.
29. Peyron MA, Sayd T, Santé-Lhoutellier V. Nutrient bioaccessibility is reduced in elderly with oral deficiency combining in vitro mastication and digestive approaches. In: 5th International Conference on Food Oral Processing; 2018 Jul. p.156-p.
30. Rajasekaran A, Kalaivani M. Designer foods and their benefits: a review. Journal of Food Science and Technology. 2013;50(1):1-16.
31. Rashidinejad A. The road ahead for functional foods: promising opportunities amidst industry challenges. Future Postharvest and Food. 2024;1(2):266-273.
32. Rezagholizade-Shirvan A, Amini N, Babazadeh A. Encapsulation of bioactive compounds: food applications and characterization methods. Food Research International. 2024;172:112-120.
33. Ribas-Agustí A, Martín-Belloso O, Soliva-Fortuny R, Elez-Martínez P. Food processing strategies to enhance phenolic compounds bioaccessibility and bioavailability in plant-based foods. Critical Reviews in Food Science and Nutrition. 2018;58(15):2531-2548.
34. Samakradhamrongthai RS. The interaction and applications. In: Aroma and Flavor in Product Development: Characterization, Perception, and Application. Cham: Springer Nature Switzerland; 2024. p.309-328.
35. Samtiya M, Aluko RE, Puniya AK, Dhewa T. Enhancing micronutrients bioavailability through fermentation of plant-based foods: a concise review. Fermentation. 2021;7(2):63-63.
36. Santos DI, Saraiva JMA, Vicente AA, Moldão-Martins M. Methods for determining bioavailability and bioaccessibility of bioactive compounds and nutrients. In: Innovative Thermal and Non-Thermal Processing, Bioaccessibility and Bioavailability of Nutrients and Bioactive Compounds. Cambridge: Woodhead Publishing; 2019. p.23-54.
37. Sanz Y, Cryan JF, Deschasaux-Tanguy M, Elinav E, Lambrecht R, Veiga P. The gut microbiome connects nutrition and human health. Nature Reviews Gastroenterology & Hepatology. 2025;1-22.
38. Soliman ME, Adewumi AT, Akawa OB, Subair TI, Okunlola FO, Akinsuku OE, et al. Simulation models for prediction of bioavailability of medicinal drugsthe interface between experiment and computation. AAPS PharmSciTech. 2022;23(3):86-86.
39. Soni M, Maurya A, Das S, Prasad J, Yadav A, Singh VK, et al. Nanoencapsulation strategies for improving nutritional functionality, safety and delivery of plantbased foods: recent updates and future opportunities. Plant Nano Biology. 2022;1:100004-100004.
40. Stevenson LW. Hemodynamic goals are relevant. Circulation. 2006;113(7):1020-1033.
41. Toydemir G, Boyacioglu D, Hall R. Effect of food processing on antioxidants, their activity and bioavailability. Foods. 2022;11(23):3795-3795.
42. Vernocchi P, Del Chierico F, Putignani L. Gut microbiota metabolism and interaction with food components. International Journal of Molecular Sciences. 2020;21(10):3688-3688.
43. Wang M, Wichienchot S, He X, Fu X, Huang Q, Zhang B. In vitro colonic fermentation of dietary fibers: fermentation rate, short-chain fatty acid production and changes in microbiota. Trends in Food Science & Technology. 2019;88:1-9.
44. Weaver CM, Martin BR, Allen LH. Overview: the food matrix and its role in the diet. Critical Reviews in Food Science and Nutrition. 2025;65(4):500-514.
45. Wedekind KJ, Hortin A, Baker DH. Methodology for assessing zinc bioavailability: efficacy estimates for zinc-methionine, zinc sulfate, and zinc oxide. Journal of Animal Science. 1992;70(1):178-187.
46. Xing Y, Gao S, Zhang X, Zang J. Dietary hemecontaining proteins: structures, applications, and challenges. Foods. 2022;11(22):3594-3594.
47. Zhang J, Chen R, Huang Q. Food matrix-flavonoid interactions and their impact on bioavailability. Food Chemistry. 2024;425:136-149.
48. Zhang P, Li Q, Zhao Y. Influence of foods and nutrition on the gut microbiome: current knowledge and future perspectives. Nutrients. 2022;14(12):2451-2451.
49. Zhang YY, Stockmann R, Ng K, Ajlouni S. Revisiting phytate-element interactions: implications for iron, zinc and calcium bioavailability, with emphasis on legumes. Critical Reviews in Food Science and Nutrition. 2022;62(6):1696-1712.
50. Zhang Z, Kumar Sharma A, Chen L, Zheng B. Enhancing optimal molecular interactions during food processing to design starch key structures for regulating quality and nutrition of starch-based foods: an overview from a synergistic regulatory perspective. Critical Reviews in Food Science and Nutrition. 2025;65(24):4805-4821.
51. Zheng J, Zhou J, Xu Z. The effects of food processing on food components and their bioactivities. Comprehensive Reviews in Food Science and Food Safety. 2022;21(4):3902-3925.