Supplements That Should Not Be Mixed

Supplements might not only interact with each other, but also with medications you may be taking. A healthcare provider can help assess your regimen.

By Toby Amidor, RD, CDN

Medically reviewed by Allison Herries, RDN

Many people take supplements to help with health conditions or improve their well-being. Vitamins, minerals, herbs, and probiotics are all types of supplements that may aid health (FDA, 2022). You might even take a combination of supplements. But there are certain combinations that shouldn’t be taken. Supplements might interact not only with each other, but also with medications you may be taking. That’s why knowing the potential interactions of supplements is important.

Supplement Combinations to Avoid

Supplements can have health benefits, but they may also have health risks. For example, sometimes the ingredients in certain supplements can alter lab tests or have negative effects during surgery (FDA, 2022). The risks that may come with taking supplements can be increased if you take more than one supplement. Here are some supplement combinations that you should talk to a healthcare provider about—and what you what you might need to do if you take both.

Magnesium and calcium

Magnesium is a mineral that is needed to help with hundreds of your body’s processes, including muscle and nerve function, blood sugar control, and blood pressure regulation. It is found in food like green, leafy vegetables as well as in legumes, nuts, seeds, and whole grains. It is also available in a variety of supplement forms, though taking them might not be advised (MedlinePlus, 2021).

Having low levels of magnesium has been associated with heart disease, diabetes, and osteoporosis (brittle bones). Too-low levels of magnesium is rare, but it is more likely among those who (MedlinePlus, 2021):

Have alcoholism
Have a gastrointestinal disease or surgery that causes your body to not properly absorb nutrients
Have type 2 diabetes
Are older

Calcium is another mineral important for bone health. It can be found in foods like milk, yogurt, and cheese. In the US, calcium is under-consumed by 30% of men and 60% of women (USDA, 2020). A supplement may be called for if there is insufficient dietary intake of the mineral. Not getting enough calcium can lead to reduced bone strength and osteoporosis (NIH, 2022).

Taking both minerals together can result in a decreased absorption of magnesium if you take very high doses of calcium (2600mg daily). It’s recommended that people at high risk for magnesium deficiency who take calcium supplements take the calcium at bedtime instead of during a meal. That’s because taking the calcium supplement during a meal could negatively affect how much dietary magnesium is being taken in (NMD, 2022).

Vitamin C and copper

Vitamin C helps create collagen, a protein that helps your wounds heal. People take vitamin C supplements for various reasons, including to help fight infection, reduce pain after surgery, or lower blood pressure (NMD, 2022).

The mineral copper is involved in energy production and helps create your connective tissue, which gives structure to the body. People with cardiovascular disease may take copper supplements as they have been shown to help change blood lipid levels, lowering the risk for atherosclerotic cardiovascular disease. The supplement has also been used in Alzheimer’s disease since copper deficiency has been seen among those with the condition (NIH, 2021).

There is some evidence that taking high amounts of vitamin C (over 1,500mg) can reduce copper absorption. The finding was based on research completed among young men, and it is likely that it only affects people whose intake of copper is low (NMD, 2022).

Iron and green tea

Iron is a mineral that is an essential part of red blood cells that transfers oxygen from the lungs to the tissues. Iron supplements are typically recommended for people who have iron-deficiency anemia, cancer, and certain gastrointestinal disorders, as well as for those who are pregnant (NIH, 2022).

Green tea has become popular to sip on and to take as an extract. It’s been touted to help improve mental alertness, alleviate digestive symptoms and headaches, and protect against cancer and heart disease (NIH, 2020).

Taking green tea with iron can reduce the absorption of the mineral. While the effect might not be significant for most people, if you take both, you can still consider taking them at separate times (NMD, 2022).

Supplements That Can Interact With Medications

Certain dietary supplements can change absorption, metabolism, or excretion of a medication. If that happens, it can affect the potency of your medication, which means you may get either too much or too little of the medication you need (FDA, 2022). Here are several common vitamins and supplements and which medications they may interact with.

Ashwagandha

Ashwagandha is an adaptogen, which is an herb that’s used in traditional Chinese medicine and Ayurvedic medicine. Ashwagandha—a small evergreen shrub found in dry areas like India, the Middle East, and parts of Africa—is touted to help the body fight stress and insomnia (NMD, 2022). But taking ashwagandha might interact with a variety of medications including:

Drugs for people with diabetes

Taking ashwagandha with antidiabetes drugs meant to lower blood sugar levels could increase the risk of low blood sugar (hypoglycemia) (NMD, 2022). Some herbs have been shown to help in the management of diabetes, but taking them on top of drugs that do that too can potentially lead to blood sugar that is too low (Gupta, 2017).

Drugs for high blood pressure

There is animal research that suggests that ashwagandha may lower systolic and diastolic blood pressure, putting people who take blood pressure-lowering medication at risk for hypotension, blood pressure that is too low (NMD, 2022).

Immunosuppressants

Human research has shown that ashwagandha can stimulate the immune system. In addition, animal research has shown that ashwagandha can decrease the effectiveness of the immunosuppression caused by cyclophosphamide, a drug used to treat cancer and nephrotic syndrome (NMD, 2022).

Zinc

Zinc is a mineral that has numerous roles, including in immunity, protein creation, wound healing, DNA creation, and sense of taste and smell. But zinc can interact with numerous medications including:(NIH, 2022)

Antibiotics

Certain antibiotics—specifically quinolone antibiotics (like Cipro) and tetracycline antibiotics (like Achromycin and Sumycin)—interact with zinc in the gastrointestinal tract and don’t allow the absorption of both the zinc and the antibiotic. If you need to take both, take the antibiotic at least two hours before or four to six hours after taking the zinc supplements.

Penicillamine

Zinc decreased the absorption and action of penicillamine, which is used to treat rheumatoid arthritis. If you need to take both, zinc supplements should be taken at least two hours before or after taking penicillamine.

Melatonin

Melatonin is a hormone your brain produces when it’s dark. It helps with the timing of your internal clock (circadian rhythm) and with sleep. Some people take melatonin supplements to help with sleep or jet lag (NIH, 2022). Melatonin may interact with several medications, including:

Blood thinners

Also known as anticoagulants, these drugs prevent blood clots from forming (MedlinePlus, 2022). There are some case reports of minor bleeding and decreased production of the protein prothrombin (one of many factors that help your blood clot) in people taking melatonin with warfarin (NMD, 2022).

Anticonvulsants

An anticonvulsant is a type of medicine given to individuals who may experience seizures. It is believed that melatonin may reduce the effectiveness of anticonvulsants. There is also some clinical research that suggests that melatonin can increase the frequency of seizures, especially children with neurological impairment (NMD, 2022).

Contraceptives

Some research suggests that oral contraceptives can increase the levels of melatonin, thereby increasing the effects and possible adverse effects of melatonin supplements (NMD, 2022).Potential adverse effects of melatonin include headache, dizziness, nausea, and sleepiness (NIH, 2022).

St. John’s Wort

This popular supplement is a plant native to Europe that has yellow, star-shaped flowers. The supplement tends to be taken to help with mental health conditions like depression. However, St. John’s wort has been associated with potentially serious interactions with certain drugs (NMD, 2022).

Taking St. John’s wort with certain antidepressants can lead to an increase in serotonin levels that can be life threatening. Symptoms can appear within minutes or hours and can include diarrhea, agitation, fast heartbeat, high blood pressure, and hallucinations (NIH, 2017).

St. John’s wort can also weaken antidepressants. Other medications that St. John’s wort can weaken include: (NIH, 2017)

Birth control pills
Cyclosporine (a drug used to prevent the body from rejecting organ transplants)
Digoxin (a heart failure medication)
Oxycodone (a pain medication)
Some HIV drugs, like indinavir
Some cancer medications, like irinotecan
Warfarin (a blood thinner)

When to Visit a Healthcare Provider

If you are taking any type of supplement or supplement combination and experience any negative side effects, you should stop using the supplement and see a healthcare provider (FDA, 2022). Potential serious reactions can include (FDA, 2022):

Itchy skin, rash, or hives
Swelling of the throat, lips, or tongue
Wheezing or shortness of breath
Fainting
Chest pain or irregular heartbeat
Nausea, vomiting, or diarrhea
Difficulty urinating, decreased urination, or dark urine
Blood in urine, stool, vomit, or sputum
Abnormal bleeding from the nose or gums
Fatigue
Loss of appetite
Yellowing of the skin or eyes
Severe joint, muscle, or abdominal pain

If you are unsure about the combination of supplements or the combination of supplements and medicines you are taking, you should have a healthcare provider assess the combination for any potential dangers. And if you are thinking of starting a supplement, you should consult with a healthcare provider as well, letting them know what other supplements and medications you take. This is especially true for people who are pregnant or breastfeeding, as well as for children, as these groups might be more susceptible to potential harms (FDA, 2022).

You should also talk to your provider about the supplements you take if you recently had or will soon be having surgery. Some supplements can have negative interactions with medications you need to take before, after, or during surgery and your regimen might need to be changed for the time being (FDA, 2022).

Summary

Taking a supplement that claims to help with certain health conditions can be as easy as buying something from online or your local health and wellness store. However, if you take more than one or take a supplement while on a medication, there might be a risk for negative interactions. Symptoms of negative interactions can include fatigue, yellowing of the skin, and severe muscle pain. If you experience any adverse reaction while taking a supplement, you should see a healthcare provider. If you’re thinking about starting a new supplement, you should visit a healthcare provider to figure out what’s best for you, letting them know of any other supplements or medications you take.

Sources:

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US Department of Agriculture. Dietary Guidelines for Americans 2020-2025 .
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Natural Medicines Database. Copper.
National Institutes of Health Office of Dietary Supplements. Iron.
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US Food & Drug Administration. Mixing Medications and Dietary Supplements Can Endanger Your Health.
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Gupta RC, Chang D, Nammi S, Bensoussan A, Bilinski K, Roufogalis BD. Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications. Diabetol Metab Syndr. 2017;9:59. doi:10.1186/s13098-017-0254-9
National Institutes of Health National Center for Complementary and Integrative Health. Zinc.
National Institutes of Health National Center for Complementary and Integrative Health. Melatonin: What You Need to Know.
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