As a pharmacist, I’ve done a lot of medication reviews with patients over the years. I always ask about supplements, and because of my many years of practice (and blogging) I’ve heard of many of them. Patients are sometimes reluctant to disclose, possibly fearing disapproval or judgment. A nonjudgmental attitude is essential.
I’ve sometimes found myself staring at long lists of supplements alongside equally long lists of prescription drugs. Many consumers, especially older adults, genuinely believe dietary supplement products are (at worst) harmless, taking a “can’t hurt” perspective to combining “natural” supplements with prescribed medications. But supplements cannot always be taken safely with medications: It’s not uncommon to find combinations that might blunt a prescribed drug’s effect, raise one’s bleeding risk, or cause other unintended consequences. A medication history that doesn’t include dietary supplements is an incomplete one.
Recent reviews have underscored just how common and under-recognized these interactions are. Surveys of older adults report that many take multiple prescription drugs along with one or more dietary supplements, yet few report this use to their healthcare providers. The result is a growing potential for supplement–drug interactions—some theoretical, others well-documented. A newly published review in Cureus, (h/t Edzard Ernst) for example, documents the extent of this issue, with many examples.
Despite all my past posts, this is a topic I haven’t covered enough: How often supplement-drug interactions occur, which combinations are most concerning, the likelihood of harm, and what kinds of evidence support these concerns. Understanding the scope of the problem, and the evidence base, can support better, safer use of supplements alongside prescription drugs.
Understanding how drugs and supplements interact
When we use the term “drug interaction” we’re describing situations where one substance changes the way another works in the body. That can mean a change in how a drug is absorbed, distributed, metabolized, or eliminated (a pharmacokinetic interaction), or a change in how it acts on its target (a pharmacodynamic interaction).
Supplements can influence drugs in the same ways. Some herbal products, for instance, affect the same liver enzymes that also metabolize many medications, either speeding them up (which can then make a drug less effective) or slowing them down (which reduces the body’s ability to eliminate the drug, potentially causing side effects or toxicity). Others may have additive or opposing effects on the body’s systems. For example, combining ginkgo or fish oil with blood “thinners” like warfarin have the potential to increase bleeding risk, while taking St. John’s wort can lower levels of several prescription drugs by boosting the metabolism of the drugs and reducing blood levels.
Not every supplement–drug combination causes problems, and not every reported or anticipated interaction causes meaningful effects. But understanding how and why these interactions occur helps explain why they’re so important to identify—especially in older adults who may take plenty of both.
Frequency of Interactions
Interactions between supplements and medications are more common than many people realize. Studies suggest that among adults who take prescription drugs, anywhere from 15% to over 30% also use dietary supplements—often several at once. The more products someone takes, the greater the chance of an interaction. Older adults are particularly at risk because they tend to take more medications and may be more sensitive to their effects. Yet many of these combinations go unnoticed, since supplements are often viewed as “natural” and not mentioned to doctors or pharmacists.
Commonly-identified drug-supplement interactions
Some supplement–drug interactions are well established and supported by strong clinical evidence. St. John’s wort is one of the most studied examples: It induces cytochrome P450 enzymes (particularly CYP3A4), which can reduce blood levels and effectiveness of many drugs, including oral contraceptives, antidepressants, transplant anti-rejection drugs, and HIV medications. Ginkgo biloba and garlic supplements can increase bleeding risk when combined with anticoagulants or antiplatelet drugs such as warfarin or aspirin. Ginseng may interfere with blood sugar control, potentially counteracting diabetes medications or increasing hypoglycemia risk. Calcium, magnesium, and iron supplements can reduce the absorption of thyroid medication and some antibiotics if taken together.
Fish oil, while widely consumed and generally safe, may also enhance the effects of “blood-thinning” drugs when taken in high doses. I have blogged the story of the grapefruit juice interaction before. It can inhibit CYP3A4 and cause dangerously high blood levels of certain medications like statins and calcium channel blockers.
While some of these risks are small, the point is that “natural” doesn’t always mean “inert.” The potential for real pharmacologic effects (and therefore interactions) is very real. As I and others have pointed out, many dietary supplements, particularly herbal remedies, can be viewed as unrefined, unpurified, and unstandardized drugs. That lack of consistency increases the risk to patients, because we can’t count on supplements to meet the same quality standards as medicines, or to interact with them in predictable ways.
A new review paper
A newly published review in Cureus, entitled Pharmacological Interactions Between Nutritional Supplements and Prescription Medications in Older Adults: A Comprehensive Review sets out to summarize what’s known about supplement-drug interactions in the older adult population. The authors conducted a literature search ultimately including 16 studies (original research and review articles) that describe clinically relevant interactions. While the authors describe their search and review as comprehensive, the review was narrative in nature, with limited assessment of study quality. Still, it identified some consistent themes. The authors note the following:
The findings from these 16 primary and secondary sources identify three themes in the use of nutritional supplements in older adults: the high prevalence of use and polypharmacy, the identification of common supplement-drug interactions and high-risk patient groups, and the critical role of communication gaps in exacerbating these risks.
The findings are both familiar and concerning. The supplements most often implicated were herbal products, particularly St. John’s wort, ginkgo biloba, garlic, ginseng, and echinacea. The most frequently affected medication classes were anticoagulants, antihypertensives, antidepressants, and antidiabetic drugs. Reported effects ranged from reduced therapeutic efficacy (for example, St. John’s wort lowering blood levels of some drugs) to increased bleeding risk with ginkgo or garlic when combined with warfarin or aspirin. The authors also noted that up to one-third of older adults in various studies were taking at least one supplement–drug combination with potential for harm. The review highlights the need for awareness among healthcare providers and patients regarding these interactions, and the need for health professionals to screen for supplement use. The authors recommend enhanced education and communication strategies to mitigate risks, as well as further research to better understand the science of supplement-drug combinations.
What isn’t known
Not all potential interactions cause real-world harm. The actual incidence of serious clinical harm seems to be far lower than what a paper analysis of potential interactions would suggest. Many identified interactions are theoretical, based on known pharmacologic mechanisms or lab data, rather than direct evidence of harm. Others are reported in case studies, and whether or not they can be generalized is unclear. On one hand, this could be a consequence of poor supplement quality – where we don’t know if what’s on the label is in the bottle. This makes risk assessment, and evidence-based advice nearly impossible. Or it may be that the clinical consequence of supplement-drug interactions may be limited to specific combinations of products. Given the lack of regulation in the supplement market and the poor (overall) data, it is difficult to say.
The end result is a knowledge gap for patients and health professionals: we can identify plausible mechanisms and credible signals of risk, but it’s much harder to know how often real-world harm occurs. For clinicians, this uncertainty reinforces the need to understand if supplement use is occurring, open dialogue with patients, and a healthy skepticism toward assumptions that supplements can only provide benefit. Given the risks, you can see why health professionals are generally leery of combining supplements with drugs.
Conclusion
The first step in reducing the risk of supplement–drug interactions is simple awareness. Supplements need to be treated like medicines: products with drug-like potential that can have risks and can interfere with other treatments. Every medication review must include a discussion about vitamins, minerals, and herbal products—not just prescription and over-the-counter drugs.
Patients can reduce their own risk by being transparent with their health care providers. Keeping an up-to-date list of products and doses for your physician and pharmacist is so helpful. Pharmacists can use evidence-based tools to assess risks, and can put reported interactions into perspective. In some cases, separating doses by a few hours may be enough to prevent any problems. In others, a supplement may need to be avoided completely.
People generally take supplements with good intentions: To improve their health or address gaps in their diet. But when supplements are combined with prescription drugs, good intentions alone will not be enough to prevent problems.The safest approach is one that’s transparent, informed, and guided by good evidence.