Several categories of supplements can cause problems when taken alongside prednisone, ranging from increased bleeding risk to dangerous drops in potassium. The interactions vary in severity, but the most important ones involve supplements that thin the blood, lower blood sugar, or deplete potassium, since prednisone already pushes your body in those same directions.
Licorice Root: The Highest-Risk Supplement
Licorice root is the single most concerning supplement to combine with prednisone. The active compound in licorice, glycyrrhizin, blocks an enzyme in your kidneys that normally deactivates cortisol. When that enzyme is blocked, cortisol builds up and starts triggering the same receptors that control sodium and potassium balance. The result is a condition called pseudohyperaldosteronism: your body retains too much sodium, dumps too much potassium, and your blood pressure climbs.
Prednisone already mimics cortisol and can cause potassium loss on its own. Adding licorice root on top creates a compounding effect. Severe potassium depletion (hypokalemia) can cause muscle weakness, cramping, irregular heartbeat, and in serious cases, cardiac complications. This applies to licorice root supplements and teas containing real licorice, not artificially flavored licorice candy.
Supplements That Increase Bleeding Risk
Prednisone raises the risk of gastrointestinal bleeding or perforation by about 40%, based on a systematic review published in BMJ Open. That elevated risk holds even when other factors like NSAID use and prior ulcer history are removed from the analysis. The likely mechanism is that corticosteroids impair tissue repair and delay wound healing in the gut lining.
Because of this baseline risk, supplements with blood-thinning or anti-inflammatory properties deserve caution. The ones most commonly flagged include:
- Fish oil (omega-3 fatty acids), which reduces platelet clumping at higher doses
- Turmeric and curcumin, which have both anti-inflammatory and mild anticoagulant effects
- Ginkgo biloba, which inhibits a platelet-activating factor and has been linked to bleeding events
- Garlic supplements (concentrated extract, not dietary garlic), which can interfere with clotting
- Ginger supplements in high doses, which have mild blood-thinning properties
None of these are guaranteed to cause a problem, but the combination creates overlapping risk. If you’re on prednisone for more than a few days and taking any of these, the cumulative effect on your stomach lining and clotting ability is worth discussing with a pharmacist.
Blood Sugar-Lowering Supplements
Prednisone is well known for raising blood sugar, sometimes significantly. This is one of the most common side effects, and it can push people with prediabetes or diabetes into poorly controlled territory. You might assume that a supplement lowering blood sugar would helpfully counteract this, but the interaction is more unpredictable than that. Prednisone’s effect on blood sugar fluctuates with dosing, and layering a glucose-lowering supplement on top makes it harder to know where your blood sugar actually stands at any given time.
Supplements with documented glucose-lowering effects include:
- Berberine, one of the most potent, with effects comparable to some prescription diabetes medications
- Bitter melon
- Fenugreek
- American ginseng
- Gymnema
- Milk thistle
- Aloe vera gel (taken orally)
- Prickly pear cactus (nopal)
- Banaba leaf
- Chromium
- Cinnamon extract
The concern isn’t that these supplements are dangerous on their own. It’s that combining them with prednisone creates a tug-of-war over blood sugar that’s difficult to monitor without frequent testing. If you’re diabetic and taking prednisone, your doctor is likely already adjusting your diabetes medications. Adding a supplement into that equation without their knowledge can lead to unexpected highs or lows.
Calcium and Vitamin D: The Exception
Not all supplement interactions with prednisone are negative. Calcium and vitamin D are two supplements that people on prednisone often need more of, not less. Corticosteroids accelerate bone loss, and even relatively short courses can chip away at bone density. A Cochrane review found that all patients starting corticosteroids should receive calcium and vitamin D as a preventive measure because of their low toxicity and cost.
The dosages used in clinical trials typically ranged from 500 to 1,000 mg of calcium per day and 400 to 500 IU of vitamin D per day, though some studies used higher vitamin D doses. If you’re going to be on prednisone for more than a couple of weeks, this is one of the few supplement additions that’s broadly recommended rather than cautioned against.
St. John’s Wort: Less Risky Than Expected
St. John’s Wort is a common offender when it comes to drug interactions. It speeds up liver enzymes that break down dozens of medications, often reducing their effectiveness. Prednisone is processed through the same enzyme pathway, so the theoretical concern was that St. John’s Wort would cause prednisone to clear from your body too quickly.
A clinical study tested this directly, giving male subjects St. John’s Wort for 28 days alongside prednisone. The result: no significant change in how the body absorbed or processed prednisone or its active form, prednisolone. Blood levels of both remained essentially the same before and after St. John’s Wort treatment. So while St. John’s Wort interacts with many drugs, prednisone does not appear to be one of them.
Why the Evidence Is Limited
One frustrating reality is that most supplements haven’t been formally tested alongside prednisone. As the NHS notes, herbal remedies and supplements aren’t tested the same way prescription drugs are, and there is very little published data on most specific combinations. The interactions listed above are based on known pharmacological effects of each supplement (blood thinning, potassium depletion, glucose changes) overlapping with known side effects of prednisone.
This means the absence of a warning doesn’t equal safety. If you’re taking prednisone for longer than a short burst and you use supplements regularly, bring the full list to your pharmacist. Pharmacists are often better equipped than prescribing doctors to flag interaction risks, and they can check combination databases that account for the specific dose and duration of your prednisone course.