Takeaway
The Medication Connection: Prescribed medicines can significantly impact the body, both directly and indirectly, by altering nutrient availability.
Albumin's Role: Albumin is the primary carrier in the blood for distributing nutrients, essential compounds, prescribed medications, and other substances.
Vitamin Availability: Many prescribed medications can alter the absorption and utilization of vitamins.
Albumin and vitamins are essential for body function as albumin is either a primary or secondary carrier for most vitamins.
The Essentiality of Albumin and Vitamins
Many factors can alter albumin’s structural shape and therefore its ability to carry nutrients, pharmaceuticals and other compounds.
Vitamins are essential for the metabolism of proteins, fats and carbohydrates, and to support energy production, growth and cell maintenance.
Human and Bovine Albumin Commonality
Human (HSA) and bovine (BSA) albumins have 76% commonality and similarity in their 3D structures. A significant differentiator is the number of tryptophan binding sites –
- Human - one tryptophan binding site - Trp-214 in subdomain IIA;
- Bovine - two tryptophan binding site - Trp-134 in subdomain IIA and Trp-212 in subdomain IIIA.
Co-operative Drug-nutrient Interactions
Subdomain IIA is the preferred binding site for both folate and methothrexate, however folate only binds to IIA whilst methothrexate binds to IIA and IIIA. When both drugs are present, folate binds to IIA and methotrexate binds to IIIA which is deemed a cooperative interaction to minimize alteration to albumin’s structure. https://doi.org/10.1021/acsomega.7b01437
Distribution of Vitamins and Their Binding Sites
Table of vitamins and their known binding sites on albumin
Vitamin
Binding site
Thiamine
Subdomain IIA - Trp 214
Riboflavin
Subdomain IIA
Niacin
Sudlow site 1, Subdomain IIA
Pantothenate
No apparent evidence of carriage by albumin
Pyridoxine
Subdomain IIA - Lys-190
Biotin
No apparent evidence of carriage by albumin
Folate
Sudlow site I, Subdomain IIA - on or near Tyr-214
Cobalamin
Subdomain IIA
vitamin C
Binding site I (Sudlow site 1), Subdomain IIA
vitamin A/retinol
Subdomain IIA - Trp 214, Subdomain IIIA - Asp 451
vitamin D
Metabolites - calcitriol and cholecalciferol; Domains 2 + 3, preferred option domain 2
vitamin E
α-tocopherol – Fatty Acids 3+4 sites, Subdomain IIIA
Tocopherol - Site II Subdomain IIIAvitamin K
Unable to verify domains, subdomains or binding sites
Note - Vitamin E is a generic name that refers to two tocochromanols, tocopherol (Toc) and tocotrienol (T3). Albumin mediates the difference in the cellular uptake of Toc and T3.
Bilirubin binding to albumin at subdomain IB inhibits lipid peroxidation, and protects α-tocopherol from peroxyl radicals.
Note - Vitamin E is a generic name that refers to two tocochromanols, tocopherol (Toc) and tocotrienol (T3). Albumin mediates the difference in the cellular uptake of Toc and T3.
Bilirubin binding to albumin at subdomain IB inhibits lipid peroxidation, and protects α-tocopherol from peroxyl radicals.
Table of domains and subdomains and their vitamin distribution
Subdomain
Vitamins
IA
IB
IIA
B1, B2, B3, B6, B9, B12, Vit C, Vit A
IIB
IIIA
Vit A, Vit E
IIIB
Domains
IIIA
Vitamin D metabolites (calcitriol, cholecalciferol)
IIIB
Vitamin D metabolites (calcitriol, cholecalciferol)
Clinical Concerns
There is no regulatory requirement that the albumin subdomain(s) and binding sites for each prescribed medicine be included in the Product Information documents.
The evidence in relation to albumin-based drug-nutrient interactions is remarkably limited. A range of factors, including nutrients and pharmaceuticals, can alter albumin structure and therefore it’s carrying capacity. Our knowledge of albumin-based vitamin binding sites and vitamin-induced changes to albumin structure, is in dire need of further clarification.
There may also be nutrient-nutrient competition for some of albumin’s binding sites, and their access process also requires clarification. Is nutrient access based on first-come, or is there a pecking order and if so what is it?
How can we apply the likely albumin-based drug-nutrient interactions evidence in our clinical reports? At this stage I suggest increased monitoring of nutrients that share the same subdomain as each prescribed medicine. The limitations with this suggestion are that it does not take into account -
- drug-induced, or possibly nutrient-induced, impacts on the domain(s) and/or subdomain(s) it is, and is not, occupying;
- some nutrients and drugs being able to share the same subdomain as they access different binding sites.
Albumin-based drug-nutrient interactions also further emphasize the importance of a comprehensive Diet History that includes nutrient supplements. If there is contradiction between oral intake and blood test findings, then external sources should be considered. The mechanisms of action of external sources likely include inhibiting transporters, and/or altering access to albumin.
Clinical Questions
What actions will you initiate as you a review a person whose prescribed medications profile includes one or more drugs that utilize albumin as a carrier, will you -
- clarify and monitor adequacy of intake of nutrients carried by albumin that are potentially affected by their prescribed medicines?
Conclusions
Albumin and vitamins are both directly and indirectly impacted by the prescribed medicines that can alter their effectiveness and availability.
Bibliography
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Panja, S., Khatua, DK. & Halder, M. 2018. Simultaneous Binding of Folic Acid and Methotrexate to Human Serum Albumin: Insights into the Structural Changes of Protein and the Location and Competitive Displacement of Drugs. ACS Omega 3(1):246-253. http://dx.doi.org/10.1021/acsomega.7b01437. Epub 2018 Jan 9. PMID: 30023775; PMCID: PMC6045412.
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Cite: Coleman, Y. 2025. Albumin and vitamins. MedNut Mail https://medicationsandnutrition.com/albumin-and-vitamins/ Accessed (date)
Albumin and vitamins
Professional Notice
The information in this article is provided to support Health Professionals. It is not an exhaustive protocol and Health Professionals are advised that adequate professional supervision is accessed to ensure that Duty of Care obligations with respect to safe administration of medicines is met for each consumer.
Core Philosophy
Whilst medications have profoundly improved global health outcomes, they typically also introduce nutritional challenges. By proactively identifying and addressing these nutritional harms, we can bridge the gap towards achieving better health outcomes.
