Americans are taking more prescription drugs than ever—along with more supplements. So it’s natural that questions about drug-nutrient interactions are also on the rise. Nearly half of Americans of all ages, and nine out of ten older Americans, now take at least one prescription drug, according to the Centers for Disease Control and Prevention (CDC). And more than half of American adults now take at least one dietary supplement, with multivitamins being the most common, according to a new CDC-sponsored study.

“Drugs are powerful substances that tend to work by blocking one pathway in the body,” says Robert Rountree, MD, Delicious Living’s medical editor and coauthor of the Clinical Natural Medicine Handbook (Mary Ann Liebert, 2008). “There’s a significant chance of an unexpected side effect. Often, you need to take a dietary supplement to replace depleted nutrients or protect against organ damage.”

Some nutrients can even enhance drugs’ effectiveness, says Leo Galland, MD, director of the Foundation for Integrated Medicine and founder of pilladvised.com. “But doctors are apprehensive about combinations of supplements and drugs because of mostly anecdotal reports of negative interactions. The supplement becomes the presumed culprit.”

Deciphering the data

Certainly, some drugs and supplements don’t mix well. The blood-thinning heart drug warfarin, or Coumadin, for instance, has the greatest number of actual and potential interactions with statin drugs, other blood thinners from aspirin to ginkgo, and even vitamin E, says Galland. And herbal St. John’s wort alters the action of several drugs, including birth control pills, and can cause toxicity when taken with SSRI antidepressants such as Prozac.

With most negative supplement-drug interactions, the supplement affects blood levels of a drug, says Galland: It either interferes with absorption, alters metabolism, or changes the way the drug is excreted.

“Let your doctors know what supplements you’re taking,” Galland advises—something he says most people don’t do, partly because they’re worried they’ll be told to stop taking them—and tell them before you stop or start any supplement. And go over the literature for any new prescription with your pharmacist, he adds.

At the same time, do your own homework. “Doctors aren’t taught much about nutrition or drug-nutrient depletion,” says Hyla Cass, MD, author of Supplement Your Prescription (Basic Health, 2007). What’s more, most official drug-nutrient interaction resources tend to leave out synergistic combinations, says Galland. He spent years creating pilladvised.com, an online database where you can enter prescriptions along with dietary nutrients you take and see clinical study digests documenting potential interactions, good and bad.

For each individual, especially the elderly or anyone taking several medications, specific reactions will be unique, says Galland. Here are some of the most common interactions, along with tips on how to navigate them.

Nutrient depletion

When a drug depletes a nutrient, supplementing to replace it can reduce side effects and increase the drug’s effectiveness, says Galland.

Birth control pills, diabetes drugs, diuretics, and statins + coenzyme Q10 (coQ10). Ironically, statin drugs, which are commonly prescribed for heart patients, deplete coQ10, a natural antioxidant that helps produce energy and may benefit heart health. (The natural statin alternative, red yeast rice, also depletes coQ10, Galland says.) For patients who also take a diuretic for high blood pressure or the drug metformin for diabetes, coQ10 depletion may be even greater, says Cass. And high-dose vitamin E can make the body burn through coQ10 faster because the body uses coQ10 to “recycle” oxidized E, Galland notes.

CoQ10 isn’t available in foods, so supplements are necessary to restore blood levels. If you’re taking any of the above medications, it’s a good idea to have your doctor check your levels and consider supplementing with 100 mg coQ10 daily, Galland says.

Acid reflux drugs, birth control pills, and diabetes drugs + B vitamins. Commonly used to treat diabetes, metformin can block B12 absorption, says Cass. But Galland says taking metformin with calcium appears to remedy this effect; the mineral seems to inhibit the drug’s binding of B12. Many antacids and acid reflux medications such as Prilosec also deplete B12, folic acid, and calcium, says Cass. And birth control pills, especially higher-dose ones, can deplete folic acid, B6, and other Bs, as well as minerals such as magnesium, increasing risk for heart disease and other problems. If you take acid reflux drugs or birth control pills, you may want to supplement daily with a high-quality B-complex product containing 20–50 mg B6.

Antacids, acid reflux drugs, and diuretics + minerals. Diuretics taken for high blood pressure, along with medications that relieve digestive symptoms, can flush out or reduce absorption of key nutrients like calcium, magnesium, potassium, and zinc, says Cass. For best absorption, time your intake of supplemental minerals (at doses your doctor recommends) as far from acid-reducing medications as possible, she advises.

Helpful nutrients

Some nutrients may enhance certain drugs’ effectiveness and even allow a reduction in the medication dose over time.

Fish oil + antidepressant, arthritis, and heart drugs
Of all the supplements studied, fish oil has the most positive drug interactions, says Galland. Omega-3 fatty acids in fish oil stimulate the production of anti-inflammatory substances in tissues, so they enhance the actions of anti-inflammatory drugs, including arthritis drugs and NSAIDs, he explains.

And they’re safe and even beneficial to take with heart medications such as statins and warfarin, as long as your doctor knows you’re taking them. In some cases, Galland says, fish oil can reduce inflammation to a point where you can lower the overall medication dose.

Several studies have shown fish oil can also improve depression symptoms for patients both on and off medications.

In particular, eicosapentaenoic acid (EPA) seems to enhance mood: A recent meta-analysis found that taking 2 grams of mostly EPA (60 percent or more of total omega-3s) benefited subjects with bipolar depression. A similar EPA dose enhanced unipolar depression medication benefits in an earlier study.

For heart health or depression, Galland recommends taking 2 daily grams of EPA in particular. In placebo-controlled studies, 3- to 4-gram doses have been proven to treat arthritis and colitis. To comfortably take such high doses, choose high-quality, concentrated fish oil supplements and carefully check labels for EPA amounts.

Folate + antidepressants
High-dose L-methylfolate, the natural form of folate, can make SSRI antidepressants more effective and is even an FDA-approved depression treatment, says Galland. Consult your doctor before considering a folate supplement of 400–800 mcg daily, Galland says. The SSRI studies used 5–15 grams L-methylfolate daily.

N-acetyl cysteine (NAC) + blood pressure and nitrate drugs
The antioxidant NAC is a precursor to glutathione, a major cell detoxifier. It also promotes healthy, flexible artery walls. Clinical studies show that NAC may improve the effectiveness of blood pressure–lowering drugs called angiotensin-converting enzyme (ACE) inhibitors, as well as nitrate drugs prescribed for angina, Galland says. Taking NAC also counteracts liver damage that can result from chronic use of acetaminophen, which depletes the liver of glutathione, says Rountree.

Negative interactions

St. John’s wort
The research is mixed about whether Hypericum perforatum may effectively treat short-term, mild-to-moderate depression. But it does affect enzymes in the liver and intestine, thus significantly altering blood levels of about 30 different drugs. In the case of birth control pills, for instance, the herb accelerates hormone breakdown and can reduce the effective dose by as much as half, causing the drug to fail, says Galland.

Ginkgo, garlic, and ginseng
The anticoagulant properties in these herbs can promote cardiovascular health but also may increase bleeding risk for heart patients taking warfarin. If you are taking warfarin, ask your doctor before starting any of these herbs or aspirin.

Calcium
Although helpful when paired with metformin, for example, this mineral can bind with other drugs to decrease absorption. For instance, it can reduce the effectiveness of many antibiotics, as well as thyroid medications and L-dopa drugs used to treat Parkinson’s disease. This may be of special note to older women: Two-thirds of women over 60 now take calcium supplements, up from 28 percent in the early 1990s, according to the CDC. In large doses, magnesium may have the same effect, says Cass. Take both minerals at a different time than these types of drugs, she recommends.

Although gratefully prescription-free at present, Delicious Living senior editor Susan Enfield plans to do homework before anyone in her family starts taking a doctor-recommended drug.