Can You Really Take Medicine with Milk?

Food–drug interactions form a crucial area of focus within clinical pharmacology. Oral drug administration is the most common method due to its convenience, but it also presents the highest variability in absorption. Many patients, particularly children, the elderly, or those with sensitive stomachs, often use milk as a swallowing aid. However, milk contains biologically active components that can affect drug absorption, distribution, and efficacy throughout the body. This review explores the interactions between milk and medications and the clinical implications for both healthcare providers and patients. ^[1]

Calcium and Magnesium in Milk: The Problem of Chelation

Milk is known to interact with certain drugs via chelation. It contains divalent cations, primarily calcium (Ca²⁺) and magnesium (Mg²⁺), which can form stable, insoluble complexes with specific medications in the gastrointestinal (GI) tract. These complexes reduce the bioavailability of the drugs, hindering their therapeutic effectiveness. ^[2]

Antibiotics such as fluoroquinolones and tetracyclines are especially prone to this interaction. The chemical structures of these drugs allow calcium and magnesium to bind with them, forming inactive compounds. Clinical research shows that co-administration of ciprofloxacin with milk reduces its blood concentration by up to 50%, potentially leading to treatment failure and increased antibiotic resistance. ^[3]

This interaction occurs regardless of drug dosage— even minimal milk consumption can significantly reduce absorption. Medical guidelines recommend avoiding milk and other dairy products for at least two hours before and after taking such medications. ^[2]

Milk and Gastric pH: A Hidden Variable in Drug Absorption

The mildly alkaline nature of milk can raise stomach pH, which may interfere with the absorption of drugs that require an acidic environment.

For instance, ketoconazole, an antifungal medication, exhibits poor solubility when stomach acidity is reduced. Similarly, atazanavir, an HIV drug, also requires a highly acidic pH for proper absorption. The use of milk or other pH-modifying substances can therefore impair the systemic absorption of such drugs, potentially compromising their therapeutic effect. ^[4]

The same principle applies to many basic drugs that must first dissolve in the acidic environment of the stomach before they can be absorbed in the intestine. ^[5]

Protein and Fat in Milk: Binding and Sequestration

Milk proteins, especially casein, exhibit drug-binding properties that can limit the availability of active drugs. Casein micelles—spherical protein structures—are particularly effective at sequestering drugs with lipophilic or zwitterionic properties, reducing the concentration of free drug available for absorption.

Levothyroxine, used to treat hypothyroidism, is one such drug. It is highly sensitive to binding interactions and environmental changes. When taken with milk, levothyroxine’s absorption is reduced by approximately 30%, largely due to binding with casein proteins and the accompanying change in gastric pH. ^[6]

Given its narrow therapeutic index, even a small decrease in levothyroxine absorption can lead to poorly controlled symptoms such as fatigue, weight gain, and mood disturbances. Regular monitoring of thyroid-stimulating hormone (TSH) levels becomes essential in such scenarios.

When Milk May Be Helpful: Gastrointestinal Protection

Not all interactions between milk and drugs are harmful. In some cases, milk can act as a protective agent for the gastrointestinal lining.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, as well as corticosteroids like prednisone, are known to irritate the stomach lining and may cause gastritis or ulcers. In these cases, taking medication with milk may help buffer gastric irritation and improve patient adherence. ^[7]

This benefit is particularly relevant for older patients or those with a history of ulcers or long-term NSAID use. However, this must be balanced against the potential for milk to interfere with other concurrently administered drugs.

Conclusion

The pharmacological impact of milk in oral drug delivery is significant. Calcium, magnesium, casein, and milk fat—along with milk’s influence on gastric ph—can substantially alter drug absorption, especially in drugs with narrow therapeutic indices or ph-dependent solubility. ^[1,2,4]

It is essential for clinicians and pharmacists to provide evidence-based counselling and screen for possible food–drug interactions. Patients, particularly those taking fluoroquinolones, tetracyclines, bisphosphonates, or levothyroxine, should be advised to avoid milk at dosing time. In contrast, for drugs that irritate the gastric lining, such as NSAIDs or steroids, co-administration with milk may be beneficial.

References:

1. Neuvonen PJ, Kivistö KT, Lehto P. Interference of dairy products with the absorption of ciprofloxacin. Clin Pharmacol Ther. 1991 Nov;50(5 Pt 1):498-502. doi: 10.1038/clpt.1991.174. PMID: 1934862.

2. Bushra R, Aslam N, Khan AY. Food-drug interactions. Oman Med J. 2011 Mar;26(2):77-83. doi: 10.5001/omj.2011.21. PMID: 22043389; PMCID: PMC3191675. Kumar S, Pandey A, Khanna P. A pharmacokinetic evaluation of the interaction between ciprofloxacin and calcium. Indian J Pharmacol. 2010;42(5):267–271. doi:10.4103/0253-7613.70608

3. Baishakhi Dey, et al. In vitro–in vivo studies of the quantitative effect of calcium, multivitamins and milk on single dose ciprofloxacin bioavailability, Journal of Pharmaceutical Analysis, Volume 5, Issue 6, 2015, Pages 389-395. https://doi.org/10.1016/j.jpha.2015.02.003

4. Nicolas JM, et al. Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions. Biopharm Drug Dispos. 2017 Apr;38(3):209-230. doi: 10.1002/bdd.2052. PMID: 27976409; PMCID: PMC5516238.

5. Wiesner A, Gajewska D, Paśko P. Levothyroxine Interactions with Food and Dietary Supplements—A Systematic Review. Pharmaceuticals (Basel). 2021 Mar 2;14(3):206. doi: 10.3390/ph14030206. PMID: 33801406; PMCID: PMC8002057.

6. Wiesner A, Gajewska D, Paśko P. Levothyroxine Interactions with Food and Dietary Supplements—A Systematic Review. Pharmaceuticals (Basel). 2021 Mar 2;14(3):206. doi: 10.3390/ph14030206. PMID: 33801406; PMCID: PMC8002057.

7. Jeong-Hyun Yoo, et al. Protective effect of bovine milk against HCl and ethanol–induced gastric ulcer in mice, Journal of Dairy Science, Volume 101, Issue 5, 2018, Pages 3758-3770. https://doi.org/10.3168/jds.2017-13872

By Isha Otukar, 5th year Pharm D Student

_MSM/DP