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Dietary supplements are everywhere at the moment. No longer the sole province of specialty stores, drugstores, and natural foods grocers, they're being advertised on your Instagram feed as well as appearing on the shelves in recent years at beauty retailers. The industry is projected to reach over $100 billion by 2027 — and some of that growth has likely been fueled further by the pandemic and increased public concern about health and wellness.

However, evidence of the efficacy of supplements is often murky at best, and many supplements have little research to back up their marketing claims. The industry is not regulated as heavily as prescription and over-the-counter drugs so it can be hard to know which supplements to trust, especially when it comes to those marketed for mental health. In fact, the FDA recently issued warning letters to several brands for "selling dietary supplements that claim to cure, treat, mitigate, or prevent depression and other mental health disorders." Before we dive into a handful of ingredients to be extra cautious about, a reminder: When considering adding a supplement to your mental health regimen, always consult your health provider.

What to Know About Shopping for Supplements

A number of supplements, including those that are marketed in the beauty and wellness space, claim to have mental health-related benefits but they can potentially contain ingredients that could actually interfere with the functioning of pharmaceutical drugs, among other side effects. Furthermore, supplement brands are not required to note the ingredients in so-called proprietary blends, meaning a product could contain something like St. John's Wort, which can interact with many drugs used to treat depression, and you wouldn't know it. Therefore, supplements should be regarded with as much caution as one would use when considering taking a new medication.

"I take this general rule with all medications and supplements: that if they're supposed to have some effect on your brain in some way, there's probably going to be interactions between that and other drugs on your brain," says Bimal Ashar, an associate professor of medicine and clinical director of the Division of General Internal Medicine at Johns Hopkins University. "[Supplements] definitely should be reviewed with your provider if you’re taking other medications — even if you’re not, just so that they know that you are taking this — because you can have side effects even without drug interactions."

One last point from Ashar: "Really do your homework beforehand, and take that [information] with you to your appointment, rather than just going to your appointment and saying, 'Oh, I want to take this.' There's certainly new evidence coming out every day. But [your doctor] should take the time to look and see how [the supplement] fits into your overall health picture."

What to Know About the Interactions Between Some Supplement Ingredients and Medications

St. John's Wort is a flowering shrub that has long been used for depression, though medical studies of its efficacy are mixed and inconsistent. However, it has many drug interactions. Ashar notes that it "works on the liver and it interferes with the metabolism of a lot of drugs, including blood thinners" and it can reduce the efficacy of Wellbutrin, Xanax, methadone, birth control pills, and a number of other common medications.

Since it affects the body's monoamine neurotransmitter system in similar ways to the MAOI (monoamine oxidase inhibitor) class of antidepressants, James Giordano, a professor of neurology and biochemistry at Georgetown University, says that foods high in tyramine should be avoided while taking St. John's Wort.

Using St. John's Wort in concert with antidepressant drugs, such as SSRIs (selective serotonin reuptake inhibitors), SNRIs (serotonin and norepinephrine reuptake inhibitors), and MAOIs, can cause serotonin syndrome, a potentially life-threatening condition. "Serotonin syndrome, although somewhat rare clinically, is very often seen in those situations where individuals either mix prescription drugs that are serotenergically active or utilize serotenergically active drugs at a higher dose or an escalated dose in an unregulated way, and/or in these situations, where they're then mixing a phytomedicinal like hypericum perforatum, St. John's Wort, with the serotenergically acting drug," explains Giordano.

The effects of serotonin syndrome range from hypertension (high blood pressure) and tachycardia (a dangerously elevated heart rate) to seizures and respiratory failure. Giordiano describes it as being "characterized by increasing agitation, restlessness, changes in body temperature, and a very representative clinical sign called 'wet dog shakes.'" But it's not just that serotonin syndrome is just unpleasant to experience. "The level of agitation, the increase in anxiety, the variations of body temperature, which make the individual feel peculiar and feel uncomfortable, but the escalations in body temperature could be problematic — physiologically, pathologically problematic — and they could also result in changes in the rhythm of the heart," explains Giordano.

Another supplement that's frequently advertised as improving brain function is ginkgo biloba, a tree whose leaves are used to make an extract that has been used in traditional Chinese medicine for thousands of years. Though it is touted as a potential preventative and/or cure for dementia, there is no conclusive evidence to these ends, as the NIH notes. Many studies, including the 3000-person Ginkgo Evaluation of Memory Study, have been conducted, but results are often conflicting.

"Like I mentioned with St. John's Wort, ginkgo can interact with a lot of medications in and of itself," says Ashar. "It can cause dizziness, it can cause gastrointestinal problems. There's some thought that there's some blood thinning properties to it. So you absolutely do not want to mix it with blood thinners. And [it] also has some interaction with other psychiatric drugs as well." Similar to St. John's Wort, there is a potential risk of serotonin syndrome when taking ginkgo along with antidepressant medication.

Giordano believes ginkgo is reasonably safe when taken in moderate amounts for most people, assuming they’re not taking any other drugs (though it can cause side effects like constipation). However, "some people are very sensitive to ginkgo, and there's really no way of knowing beforehand who's going to be sensitive to this," says Giordano. Known as Ginkgo sensitivity syndrome, symptoms can include a low-grade headache, an upset stomach, and heart palpitations. "Very often the palpitations occur as a consequence of irregularities in their heartbeat and then as a consequence of that the blood pressure may rise and fall and the individuals will then feel dizzy," he says.

You may have seen kava root extract as an individual supplement at some juice bars and tea houses, as well as at natural foods and vitamin and supplement stores; it’' a member of the pepper family and native to the Pacific Islands. Giordano explains that the kava leaf contains "a number of active compounds, the most notable of which are something called the kavalactones," which are thought to interact with GABA receptors in the brain to produce kava’s purported calming effects. "Many people will use kava as a mood stabilizer. Some people will use it in the evening to sort of induce sleepiness or to induce relaxation," says Giordano.

There's clinical research to suggest it may be a moderately helpful short-term option for people with generalized anxiety disorder. But much more research is needed, and both doctors warn against using the supplement.

"You absolutely cannot mix [kava] with anything in a benzodiazepine class, something like Valium or Xanax," warns Ashar. He also cautions against its use with antidepressants, particularly tricyclic antidepressants, which can depress central nervous system function and possibly intensify the sedative effect of kava. It's also not recommended for use with the phenothiazine class of antipsychotics, which are used in the treatment of schizophrenia.

Additionally, it's important to note that similarly to how some people can be extra sensitive to ginkgo, "kava can be differentially metabolized by some individuals to produce a toxic metabolite that is very, very liver toxic," says Giordano. Without doing proper testing prior to kava use, there’s no way to know whether you’re one of those people. "For some individuals, it's dose-dependent, so in other words, the more kava you take, the worse the effect may be, and the more likely the effect may be," But for other individuals, even a low level of kava, including [a] single dose, "may be significant enough to induce these problems in the liver," says Giordano.

"The general advocacy about kava is that it should be taken with great caution," says Giordano. "And if upon taking kava, there are any hepatic signs and symptoms at all, if the individual is having bloating, if the individual becomes even mildly jaundiced, [it’s important] to seek medical attention."

He believes that because the risks are so high, kava should be avoided entirely until there's "definitive and widely available" pharmacogenomic screening for potential metabolic problems. 

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