Steph’s Note: This week, we’re diving into a frequently contentious topic - herbals and supplements. Regardless of your feelings about these products, as a pharmacist, you WILL receive questions from patients about them. And you should be sufficiently prepared to give them an educated, carefully considered answer rather than hand waving based on your own opinions. If you’re not sure how to do that or where to get the info in order to do that, *waves* that’s why we’re here! Jenny Hoang, who previously educated us about Aucatzyl and CAR-T therapy, is back this time to give you the need to know info about herbals and supplements. Thanks, Jenny!

Being of Southeastern Asian descent, I’ve always had an interest in complementary alternative medicine. Looking through all the herbs and spices inside traditional medicine shops always made me feel like I was in some sort of candy store, where each selection had its own health superpower. But it wasn’t until pharmacy school that I began to truly understand the role that these supplements play in conventional medication therapy.

In fact, one of my favorite rotations was when I got to participate in a school of integrative medicine, where the students were learning traditional Chinese medicine and acupuncture. Upon first glance, this seemed like an odd elective rotation for a P4 student. After all, weren’t we supposed to reinforce the endless lectures on the pharmacotherapy of conventional medicine?

But in reality, I quickly found that my knowledge of conventional medicine came in handy given the patients seeking complementary treatments were also taking multiple prescription drugs. Knowing how to find, interpret, and educate patients on drug interactions was extremely valuable!

The students and professors at the school also spoke of their deep desire for conventional clinicians (including pharmacists) to have a better understanding of supplements. This is because patients tend to trust us and our advice, and our influence could bring complementary medicine more to the forefront of treatment. The FDA estimates that around 75% of Americans use supplements, so as pharmacists, it is essential for us to understand how prescription and complementary medications work and interact.

What are Supplements?

First, we must dive into a better understanding of what complementary alternative medicine is. Usually this term encompasses many holistic approaches such as acupuncture, herbal supplements, yoga, meditation, and more.

The term “natural medicine” is generally used to describe anything from plant-derived (or “herbal”) products to vitamins and minerals. Additionally, the FDA considers many products to be “dietary supplements,” which can be obtained via prescription or bought over the counter. Given how broad these definitions are, you can see how almost every one of your patients may be using some form of supplementation.

On the positive side, this means a large majority of Americans have access to and are taking supplements that can help them stay happier and healthier, even if they have little to no access to other healthcare services. But the downside of this is that it is extremely hard for healthcare providers to monitor utilization and advise patients on whether the supplements they are taking are safe and efficacious.

A Quick History of Supplements

This is where a quick understanding of the law comes into play. We know that the FDA regulates conventional prescription drugs for safety and efficacy. Supplements, however, are not regulated in the same manner. They are regulated by the Dietary Supplement Health and Education Act (DSHEA) of 1994, which requires manufacturers to ensure products are safe.

IMPORTANT TAKEAWAY HERE! Read that DSHEA bit again, and notice how this requirement differs from prescription drugs, which have to have proven safety and efficacy through rigorous clinical trials. Another effect of DSHEA-only regulation is that dietary supplement companies can release new products to the market whenever they like since FDA approval is not necessary.

The Cheerios box that got General Mills in trouble with the FDA back in 2009. You’ll notice new boxes don’t make such specific claims…this was bordering on Cheerios being a “drug”! (Image)

It is also important to understand that companies cannot claim that their supplement can treat or cure a condition (whereas prescription drugs may obtain an FDA-approved indication for specific disease states). However, companies can make claims about the supplement’s relationship to health. A seemingly subtle difference, but this is what that looks like.

For example, a company selling calcium supplements can claim that it helps build strong bones, but it cannot state that their product treats osteoporosis. Like I said, subtle…but a necessary distinction as there have been no studies of that calcium supplement on osteoporosis prevention and progression. So to claim that would be false information!

Even though supplements are not approved by the FDA, that doesn’t mean the FDA isn’t involved at all with them. Here’s what the FDA can do:

The FDA can periodically inspect the factories that produce the supplements to verify they are meeting manufacturing and labeling requirements.
The FDA also has the MedWatch service. This is a program that healthcare providers and patients alike can use to report adverse events in response to taking both prescription drugs and supplements. If MedWatch receives any pertinent information, they can issue safety alerts, such as recalls.

If you see this on a supplement’s label, you know it’s received the USP stamp of approval. (Image)

In addition to input from DSHEA and the FDA, the United States Pharmacopeia (USP) sets the standards for supplements by verifying strength, quality, and purity of the ingredients. Supplements can receive a USP-verified mark, which means the following:

The ingredients listed on the label are actually contained in the product in the amount and potency declared.
The supplement does not contain harmful contaminants like lead, mercury, or bacteria.
The supplement was tested against performance standards to guarantee that it will actually break down and release into the body for its intended effect.
The product was made according to the FDA’s current Good Manufacturing Practices (cGMP), which assures safe, sanitary, well-controlled, and well-documented manufacturing and monitoring processes.

As you can see, all of these processes help regulate purity of the supplement’s contents…but there’s no oversight or guarantee of efficacy or safety for a specific individual. This is where pharmacists come in handy with the knowledge and ability to help patients find the highest quality supplements that also suit their needs.

What’s in a Supplement’s Label

Similar to food items you find at a grocery store, supplement bottles must contain an information label on the back stating its ingredients, the quantity of ingredients per serving, serving size, calories, number of supplements per container, and so forth. Let’s check this one out below:

One of the first things that we as pharmacists should look at is the serving size or recommended daily intake at the very top. That is like the “sig,” and we can use it to help educate patients on how to take the product. Risks with supplements are often dose dependent, so this is especially important (along with drug interactions that we will talk about later).

Next, the suggested use section tells us how and when to take the supplement. This is where patients learn if the supplement should be taken with or without food.

Turning the bottle over to read the label is one of the easiest first things we can do as a pharmacist when helping a patient decide if they should take a supplement and, if so, how and when to do it. Other things to note on the bottle include the health claim or functional description of what the supplement is intended to do. This is where we can use our clinical judgement to decide if the claims make sense.

Moving along, there is a section for precautions, such as avoiding use in heart disease. These are super useful talking points when discussing use with a patient.

Finally, there are storage instructions to keep the supplement in the best form for consumption.

Questions to Ask When Assessing Supplements

As pharmacists, one of our main jobs related to supplements is helping decide if they are safe for patients to use alongside their other medications and disease states. Our ability to ask the right questions should lead us to the most beneficial supplement for a patient.

Because of this, it is important to have a few questions in mind to ask yourself as you help the patient decide if its best to take a supplement or not.

Does the supplement work?

Many companies make grandiose claims about ingredients, so it’s important to do some research to see if there have been any studies on efficacy. I’ve found that the National Center for Complementary and Integrative Health is a good place to start.

Natural Medicine Comprehensive Database and PubMed are also helpful resources.

What is the mechanism of action?

This is usually a good question to consider when you are trying to determine if the supplement works. Sometimes the supplement’s main active ingredient mimics the mechanism of action of standard prescription drugs used for the same disease state. If they do, this is a good clue that the supplement may be effective.

A great example of a supplement that is used for its similar mechanism of action is berberine in diabetes. Berberine has been shown to have many properties such as activating AMP-activated protein kinase and inhibiting gluconeogenesis, along with its anti-inflammatory and antioxidant effects. We know that metformin, a frequently used prescription drug for diabetes, also activates AMP-activated protein kinase and inhibits liver gluconeogenesis.

What this means is that both metformin and berberine act on similar metabolic pathways to inhibit the process of making more glucose (gluconeogenesis), which if left unmanaged causes sugar spikes in diabetes. So you can see how there would be some folks who think that they can just take berberine instead of metformin, assuming it will have the same therapeutic effects. Or they might even take both berberine and metformin for additive effects.

Either of these scenarios could have undesirable consequences, including uncontrolled diabetes due to lack of berberine efficacy, increased risk of adverse effects from increased levels of metformin in the presence of berberine, and/or increased risk of hypoglycemia from the combination.

Is the supplement safe to use?

Just as mechanism of action can help us decide if it’s an effective supplement, it can also help us understand if it is safe to use. Adding on a supplement with the same mechanism and/or adverse effect profile as the patient’s current prescriptions can lead to serious drug interactions.

A great example of a supplement that should be carefully monitored is kava. Kava is known for its anxiolytic benefits. However, kava has been found to inhibit enzymes needed for the metabolism of many drugs, leading to higher systemic concentrations. Kava also depletes glutathione, an essential antioxidant for metabolizing alcohol.

If kava use is unregulated or unmonitored in a patient with preexisting liver disease or alcohol use disorder, they could be at a significantly higher risk of alcohol/drug overdose. As a result, it is extremely important to ask patients about preexisting conditions to get a better picture of whether a supplement is right for them.

What is a safe dose?

Like prescription drugs, supplements must be taken correctly. This is especially important if we want to prevent overdoses. The NIH has a useful nutrient recommendation database with recommended dietary intakes based on things like age and gender. Some vitamins are water soluble, meaning there’s a little more leeway when it comes to taking too much at one time as excess product is flushed out of the system through urine. But this is not the case with fat soluble vitamins, which include vitamins A, D, E, and K. Being fat soluble, they get stored in the body’s tissues, and overdoses may lead to adverse effects ranging from diarrhea, vomiting, and hairloss to more severe symptoms like kidney stones and hemorrhaging.

So the next time a patient asks about supplements, be sure to help them decide on an appropriate dose.

What medications and/or other supplements are they currently taking?

Just like we must watch for drug-drug interactions, it is important to also consider any additive adverse effects when combined with the patient’s current medication/supplement list. NatMed Pro has a drug-supplement interaction checker, which can come in handy.

You may recall that many drugs are metabolized through common enzyme pathways, such as the CYP450 enzymes. It’s essential to know if a supplement inhibits or accelerates these metabolic pathways. For example, the notorious St. John’s Wort supplement used for depression is well known to strongly induce CYP3A4, CYP2C9, and CYP1A2. So it can interfere with the efficacy and safety of many drugs that are also metabolized through these common pathways.

When you realize that “over the counter” doesn’t necessarily mean “safe.” (Image)

Just for a few examples… St. John’s Wort can decrease the efficacy of many birth controls and lead to increased risk of pregnancy. It is also serotonergic, so it should be completely avoided with MAO inhibitors. There’s also danger at high doses with SSRIs and SNRIs. It can lower the seizure threshold and increase risk of seizures, so it should be avoided with medications like bupropion. St. John’s Wort can also cause photosensitivity, so pharmacists should counsel patients on sun protection and increased caution with other photosensitive medications, like retinoids or sulfa drugs.

Yep, believe it or not, St. John’s Wort is available OTC. Even with all of those potential effects. The takeaway here? Always remember to treat supplements like prescription drugs and check for interactions!!

The tl;dr of Supplements and Herbals

As you can see, there are numerous supplements that can benefit patients. However, it is important to remember that they have adverse effects and drug interactions that we need to be aware of. Because of this, pharmacists play a key role in assisting patients with discerning if a supplement is right for them given their unique disease states and prescription medications. We can help them find supplements that are not only safe but also effective.

So the next time you are helping a patient look at some supplements remember to ask yourself:

Does this supplement work?
What is the mechanism of action?
Is it safe to use?
What is a safe dose?
What other medications or supplements are they currently taking?

Useful resources include the supplement’s label, NIH, FDA/Medwatch, NatMedPro (aka Natural Medicines Comprehensive Database), and your favorite clinical resources, such as Clinical Pharmacology and UptoDate/Lexicomp.

Supplements are very accessible, but so are pharmacists. So next time a patient comes by to ask about them, be sure to help guide them through the process of getting the appropriate ones that will help - not harm - them.

The Pharmacist’s Introduction to Herbals and Dietary Supplements