How do acetylsalicylic acid and warfarin interact with various nutrients?

By Dr. Sushama R. Chaphalkar, PhD.Reviewed by Lily Ramsey, LLMMar 28 2024

In a recent review published in Nutrients, researchers discussed 45 drug-nutrient interactions (DNIs) that modify micro-nutritional status, particularly focusing on how acetylsalicylic acid (ASA) and warfarin may affect patients through various mechanisms.

They comprehensively address the complexities of DNIs, highlighting the influence of factors such as polymorphisms, gut microbiota, and dietary components, and offer practical recommendations for clinicians to manage DNIs effectively in vulnerable populations.

Study: Potential Drug–Nutrient Interactions of 45 Vitamins, Minerals, Trace Elements, and Associated Dietary Compounds with Acetylsalicylic Acid and Warfarin—A Review of the Literature. Image Credit: AleksSafronov/Shutterstock.com

Background

DNIs are less studied than drug-drug interactions but remain clinically relevant. Medications may directly or indirectly affect micro-nutritional status through physicochemical, physiological, or pathophysiological mechanisms.

These interactions include bio-inactivation, altered absorption, effect, or excretion. Medications may compete with micronutrients, induce physiological changes, or indirectly affect health.

While DNIs may be beneficial or detrimental, they're often underreported, and there’s a dearth of large-scale, comprehensive studies in the field.

Researchers in the present article review the DNIs of ASA (an antiplatelet drug) and warfarin (an anticoagulant), drugs widely used in cardiology, which may potentially impact patients' micronutrient status through various mechanisms.

The “hidden hunger” of micronutrients

“Hidden hunger” implies the deficiency of micronutrients. Micronutrients are essential for basic physiological functions, including vitamins (water-soluble and fat-soluble), minerals, and trace elements.

The American Institute of Medicine provides dietary reference intake recommendations for these nutrients and additional compounds, such as taurine and ergothioneine, essential for properly functioning longevity proteins.

ASA and DNIs

The interaction between ASA and various micronutrients is complex and multifaceted, with both reported and questionable interactions. While some interactions between ASA and micronutrients are well-established, others remain uncertain and warrant further research.

Reported interactions of ASA include increased urinary excretion of thiamine, modulation of niacin flush, alterations in folate renal excretion and serum concentration, potential impacts on cobalamins absorption, and effects on vitamin C absorption and excretion.

Fat-soluble vitamins like tocopherols/tocotrienols may potentiate ASA's antiplatelet effect and provide gastric protection, while minerals such as sodium show decreased excretion at high ASA doses, potentially impacting blood pressure regulation.

Trace elements like iron may be affected, leading to an increased risk of anemia, while associated dietary compounds like taurine could potentially enhance ASA's antiplatelet effect and offer gastric protection.

However, some interactions remain questionable, such as those with riboflavin, pantothenic acid, and retinol. While niacin shows antiplatelet effects, the clinical significance remains unclear.

Similarly, minerals like phosphorus, calcium, magnesium, potassium, copper, zinc, selenium, and chromium have uncertain interactions with ASA. Associated dietary compounds like lycopene, α-carotene, β-carotene, β-cryptoxanthin, and astaxanthin show inconclusive interactions.

Additionally, some micronutrients like biotin, chloride, sulfur, iodine, manganese, molybdenum, fluoride, arsenic, boron, nickel, silicon, and vanadium show no reported interactions with ASA.

ASA's effects on mitochondrial oxidative phosphorylation raise concerns about the potential metabolic misuse of micronutrients, but the clinical relevance in humans requires further assessment.

Warfarin and DNIs

While some interactions between warfarin and certain nutrients have been reported, others remain questionable or unstudied. Niacin has been associated with a synergistic effect for water-soluble vitamins, leading to critically elevated international normalized ratio (INR) in some cases.

Folate deficiency may arise from avoiding vitamin-K-rich foods, potentially impacting patients' health. Conflicting evidence regarding the interaction between high-dose vitamin C and warfarin necessitates careful monitoring.

Among fat-soluble vitamins, retinol and tocopherols/tocotrienols have shown interactions with warfarin, leading to adverse events such as hemorrhagic events and arterial calcification. Vitamin D status may influence warfarin's anticoagulant effect and risk of arterial calcification.

Further, magnesium has been linked to stabilizing INR levels, potentially affecting warfarin therapy outcomes. Low vitamin K foods high in potassium may pose a risk for patients with chronic kidney disease due to hyperkalemia.

Astaxanthin shows reported interactions with warfarin, but the exact mechanisms remain unclear. Several nutrients such as riboflavin, cobalamins, calcium, and trace elements like iron, lutein, zeaxanthin, lycopene, β-carotene, and β-cryptoxanthin do not demonstrate clinically significant interactions with warfarin based on available evidence.

Further research is needed to fully understand the potential interactions between warfarin and other elements like thiamine, pantothenic acid, sulfur, manganese, molybdenum, and others, which currently lack data.

Conclusion

Moving towards a predictive, preventive, and personalized healthcare model, clinicians can leverage omics technologies to detect signs of disease early and stratify the risk of DNIs.

These findings highlight the importance of considering dietary factors and nutrient intake in patients undergoing ASA or warfarin therapy to optimize treatment outcomes and minimize adverse events.

However, the review is limited by a lack of unified methodology, the small scale of human cohort studies, reliance on animal models, and missing data on certain micronutrient interactions.

In conclusion, the interplay between nutrient intake, individual physiology, and medication use calls for considering DNIs in clinical practice, particularly in vulnerable populations. It emphasizes the need for personalized approaches to nutritional assessment and management.