Confused by Drug-Nutrient Interactions? A New Tool Solves Common Practical Problems

Written by Kelly C. Heim, Ph.D.

Drug-nutrient interactions comprise a critical area of integrative medical practice. A drug-nutrient interaction occurs when a nutrient changes how the body absorbs, processes or responds to a medication. We’re also talking about herbs and nutraceuticals (not nutrients per se), but for simplicity, we’ll refer to all interactions between drugs and dietary supplements as “drug-nutrient interactions” here.


If you’re new to this topic, I encourage you first to familiarize yourself with the two types of interactions:

1. Pharmacodynamic interactions modify a medication’s pharmacological or clinical effects. These include:

  • Antagonistic interactions – when a supplement counteracts the function of a drug. For example, vitamin K blocks the effects of warfarin (Coumadin).
  • Additive interactions – when drug actions magnify because the nutrient shares similar effects or properties. For example, velvet bean extract contains L-DOPA, the same compound as levodopa.
  • Synergistic interactions – when the effect is greater than that of either agent alone. Theoretically, combining L-arginine with antihypertensive drugs could produce a drop in blood pressure through a synergistic interaction due to their complementary mechanisms of action.

2. Pharmacokinetic interactions modify a drug or nutrient’s absorption, distribution, metabolism or elimination.

  • Green tea may reduce levels of lisinopril in the bloodstream by as much as 85%, which could reduce the antihypertensive efficacy of this drug.
  • Calcium may interfere with the absorption of doxycycline, an antibiotic.
  • Chromium may interfere with levothyroxine absorption.

Pharmacokinetic interactions that compromise the absorption or metabolism of a nutrient are called drug-induced nutrient depletions. For example:

  • Proton-pump inhibitors may reduce the absorption of vitamin B12, calcium and iron.
  • Statins may reduce the synthesis of coenzyme Q10 (CoQ10).
  • Metformin may reduce vitamin B12.

The science on drug-nutrient interactions is always evolving with new drugs, new dietary supplement ingredients and new research.  Here’s the good news: you don’t need to be an expert if you use the right online resources to check for interactions.

A good drug-nutrient interaction checker is essential. Choosing one isn’t easy—every checker is different, with considerable variability in the nutrient coverage, interaction descriptions, sources of information and scientific rigor.

In a clinical setting, the most frustrating dilemma is the long list of theoretical drug interactions that might fill the screen when you enter a nutrient into a checker. The burden is on you to separate clinically meaningful information from questionable noise.

For example, entering “melatonin” into an online checker might retrieve a list like this:

  • Anticoagulants
  • Antiplatelet drugs
  • Anticonvulsants
  • Antidiabetic drugs
  • CNS depressants
  • Immunosuppressants
  • CYP1A2 substrates
  • CYP2C19 substrates
  • Oral contraceptives

This list adds up to about 2200 individual drug interactions with melatonin. Looking at current drug usage data, the majority of American adults who take medications are taking one of these drugs.

Should they all avoid melatonin?

Absolutely not.  There are two reasons why:

  • Most of the interactions are not contraindications. With rare exceptions and precautions in select situations, melatonin can be used safely with most drugs on this list.
  • Most interactions are not clinically relevant for the reasons I will describe below.

Long lists of warnings can increase the risk of clinical errors. Alert fatigue is a formally defined practitioner experience where the real warnings are missed. Unless the tool designates them as significant, they become easy to minimize or ignore.

Here’s the punchline: The scientific reliability of a checker isn’t about the volume of information – it’s about the quality of information. A more diligent and accurate translation of the science will greatly reduce the number of warnings you see, not increase them.


The general body of scientific evidence on drug-supplement interactions remains one of the least mature areas of medical knowledge. And somehow, you see more warnings than you have time to read. Where did all this information come from?

There isn’t much direct clinical research on drug interactions with dietary supplements. Therefore, many warnings come from educated guessing based on preclinical data.

Test tubes and cell culture models are prolific authors of unfounded alerts. In these environments, all herbs should interact with nearly all drugs. All herbs contain phytochemicals that inhibit drug-metabolizing enzymes (i.e., cytochrome p450) if very large doses are applied to a layer of liver or gut cells. These experiments are typically impossible to recapitulate in humans and were never intended to inform clinical decisions. Such interactions are frequently invalidated if clinical trials on drug-supplement combinations are performed. But even if the study is well-designed, we can seldom make generalizations because of dose and formulation differences.

There are currently no industry-wide requirements for scientific substantiation in drug-nutrient interaction checkers, and most clinicians don’t have the pharmacology background to make objective comparisons.


Pure Encapsulations® is proud to support integrative practices with a new Drug-Nutrient Interaction Checker (DNI Checker).

Pepid, a leading drug information and interaction resource developer for healthcare providers, licenses this tool and associated content. Our medical affairs team worked with Pepid to compile extensive drug-nutrient interactions and depletion data relevant to the ingredients and nutrients found in dietary supplements.

Unlike other Drug-Nutrient Interaction checkers, we provide a unique experience by reducing noise and delivering clinically relevant interactions that can:

  • Happen in real life. Most interactions are hypothetical. They are studied in vitro (in a test tube or cell culture) without validation in human studies. We take a rigorous, clinical, evidence-focused approach to deliver those interactions that could happen in realistic, clinical situations.
  • Occur at typical doses. All interactions are dose-dependent. Many interactions require unrealistically high doses or intravenous administration of a dietary supplement to occur. Our tool excludes these irrelevant situations, delivering alerts that pertain to doses commonly used in dietary supplements.
  • Affect the body in a significant way. Many interactions have harmless effects on the body that are not cause for concern. We alert you to meaningful interactions that change drug efficacy, safety, risks and/or key clinical parameters.

The following types of data are preferentially analyzed to bring you clinically relevant alerts without the burden of hypothetical noise:

  • Clinical trials on drug-nutrient combinations. These studies are the “gold standard” for confirming clinically relevant interactions, but only a small number have been performed to date. We rely on these whenever possible.
  • Clinical trials on the ingredient or nutrient showing redundant or antagonistic effects relative to known drugs may suggest potential theoretical interactions.
  • Human pharmacokinetic data are often the “missing link” when only in vitro data are available. These interactions may be clinically relevant if sufficient blood concentrations can be achieved. By comparing blood levels with the amount required to interact with a drug target, we can make educated approximations of clinical relevance in these situations.
  • Published case reports are considered when an interaction is detected as a probable cause of an adverse event.

All of the information in our DNI Checker is based on independent, authoritative sources or other scientific published, peer-reviewed data and research studies that have undergone critical review by medical experts.

Diving deeper into each interaction and depletion is made easy with live links to representative studies for each interaction. The tool also covers interactions and depletions found in the Prescriber’s Desk Reference ( for the specific pharmaceutical product.


Our Drug-Nutrient Interaction Checker (DNI Checker) provides clear guidance on appropriate actions.  You’ll see one of the following displayed for each interaction:

  • Avoid the combination
  • Administer several hours apart
  • Avoid high-dose supplementation
  • Monitor for increased drug effects and/or adverse effects
  • Monitor for diminished drug efficacy

We provide clinical relevance, links to studies, and finished product recommendations for nutrient depletions.


Our Drug-Nutrient Interaction Checker (DNI Checker) is a complimentary resource available now



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