Local Research Study Shows Effective Over-the-Counter Treatment for Depression

Globally, more than 300 million people of all ages suffer from depression. It's the leading cause of disability and a major contributor to the overall global burden of disease. Yet treatment for depression can be limited by effectiveness, cost, availability and side effects. Now, a new clinical trial done at the University of Vermont shows that magnesium may be a safe, effective, and less expensive treatment option for mild to moderate depression. Read or listen to our interview below with one of the leaders of this clinical trial, Emily Tarleton, PhD, RD, CD. She is a Bionutrition Research Manager at the University of Vermont's Clinical Research Center.

Your clinical trial finds a link between depression and magnesium intake. What have you discovered through your work?

Emily Tarleton: We were following up on some cross-sectional and prospective trials. I found an inverse association between magnesium intake and depression, so we conducted a randomized clinical trial with the aim of determining whether supplemental magnesium really does influence symptoms of depression. And we found that over a six-week period of time, symptoms of both depression and anxiety improved significantly. And this was the case regardless of age, gender, baseline severity of depression, baseline magnesium status, or use of other treatments for depression, such as counseling or antidepressants. And we also found that it was really well-tolerated, and a majority of participants indicated that they would use it in the future, which was one of our main outcomes.

So for anyone who is a little bit new to the research world, what exactly is a randomized controlled trial?

Emily Tarleton: Right. So a randomized controlled trial is a trial in which we ... in this case, we were comparing people to themselves, so we gave them a treatment for the six weeks, which in this case was the magnesium supplement, and then we followed them the same way for another six weeks without the magnesium supplement so we could compare how they responded while on the supplement, but also what happened while they were off of the supplement. And it's randomized because they either started the supplements at week one or at week seven, so it's sort of a crossover design.

And this was just here in Vermont? Are these Vermonters who participated?

Emily Tarleton: Yes. We started small for this trial, and we used outpatient primary care clinics to recruit from through physicians and people had to have a baseline of still suffering from depression, so people who are currently experiencing symptoms, and we were able to do our study over the phone for the most part, and it was really ... people really liked the opportunity to try something new.

And magnesium is something that you can just buy, right, in the store? It’s over the counter?

Emily Tarleton: Right. And magnesium is also found in a lot of foods that we eat, so the reason we don't tend to get enough is because it's the healthy food people don't really like to eat a lot of, so things like green leafy vegetables and whole grains and nuts and legumes. As a society, unfortunately those aren't foods that we over-consume- so people tend to not get as much magnesium as they should.

Is this something where, outside of the world of mild to moderate depression, anyone could benefit from?

Emily Tarleton: Yes. Because magnesium is in these healthy foods, certainly anybody would benefit from consuming more of those foods in general. But magnesium has also been found to help with other chronic diseases. It's been associated with cardiovascular disease and diabetes. People with migraines sometimes take magnesium. Also the big connection is with muscle cramping, so some people who tend to have a lot of muscle cramping, leg cramps, will take magnesium and that seems to help for them as well. In general there aren't a lot of great studies or randomized clinical trials on showing a cause and effect of magnesium in these uses, but their research is ongoing.

In this study, and I just want to get a better understanding for what some of these participants went through, how often did they have to take the magnesium?

Emily Tarleton: We had them take the tablets every day. We suggested they take two in the morning and two in the evening just to avoid that stomach upset. Some people took all four at once, and that was fine for them. Other people liked to split it up. It really didn't seem to make a difference. Another thing we found was that the effect was significant regardless of overall compliance, so at the end of the study we did a pill count to see how compliant they were with taking the supplements, and the lower the compliance, people still had a good reaction, a good decrease in their symptoms. So, in a future study we could look at using even less of the supplement.

Are there plans for a future study?

Emily Tarleton: We would love to do another study. There's lots of ... of course, we'd like to do a longer-term, bigger randomized controlled trial with a more diverse population to really show that this happened. We didn't really have enough people. While I mentioned that we saw the effect regardless of age and gender and all those other little sub-studies, we didn't really have enough people to really prove that or not, so we'd love to do a bigger study to show if there is a difference by race or gender. Age is another big one we'd like to look at.

So as we talked about a little bit earlier, the treatment for depression is complex. It can be limited by cost, availability. There are side effects. It's a very complicated thing. What do you think ... and I realize that the study and the research is somewhat in its infancy. What do you think is the promise of magnesium as a treatment for people?

Emily Tarleton: Yeah. As you mentioned, we're just getting started and even within our study, magnesium of course like any other treatment didn't work for everyone. But, because of the positive effects that we saw and because they worked quickly with very few side effects, it can be an option that patients can explore with their primary care or any other healthcare provider that they're seeing. There really is little risk to taking magnesium because, like I said, the side effects are few. We also saw the change in symptoms of depression within two weeks of taking the supplements, so if within two weeks you don't see ... you're not feeling any better or you happen to be even feeling worse, you can certainly stop taking them. Because it's a mineral, it doesn't stay within the body for a long period of time. After a day or two, any extra magnesium you have will be flushed out. If for some reason you feel like, "Oh, I don't know. For some reason it's making me feel worse," it comes out of the body really quickly as well. As I mentioned, we were able to decrease those side effects just by changing the timing of the dose or decreasing the dose to less than we had originally started at. It's also inexpensive. You mentioned the cost. About a month's supply of the magnesium chloride that we used in the study is only about $12 to $14 a month. And over-the-counter so you can get it on Amazon. Another aspect people liked about the magnesium was the lack of stigma associated with taking it. Some people just really don't want to start an antidepressant for that reason. And you know, even people who start antidepressants oftentimes are put in a tough situation where they may be feeling a little bit better, but not where they want to be. Now they're in a position where they need to either increase their dosage or add another medication increasing those risks of side effects, or they're left with the other option which is stay where they are and not feel as good as they wanted to. That's just not a great position to be in. We did have people in our study that were already taking an antidepressant and we did see that there might be what we call this adjunct relationship where the magnesium actually helps the antidepressant work even better. And there are a couple of other studies to support that idea. This is another direction we can certainly go in. It could be an option in that sense too like, "Hey, I just really don't want to risk increasing my side effects," or "I just really don't feel I'm feeling at the point where I want to start an antidepressant yet." Magnesium might be an option.

For people who are maybe feeling depressed and who haven't seen their doctor yet or haven't really talked to anyone yet, what's the step for them? Is this something where they go to the grocery store and pick some of this up? What would they do next?

Emily Tarleton: Magnesium does actually interact with some medications, so you would want to talk to your healthcare provider before starting it. But, as we mentioned, it's also found in really healthy foods, and there are some theories that just certain nutrients in combination might help with depression as well. And we've seen studies on things like fish oils, vitamin B. We've looked at vitamin D as well. Zinc, folic acid, all these different nutrients people have found some sort of association as well. Eating healthy foods that have all of these nutrients may help, may be beneficial, and may help you feel good in general just because you're taking care of yourself in that sense.

We've talked about the study a lot, but I'm also kind of fascinated by your title. You're a Bionutrition Research Manager. What are some of the other things you work on in your role here?

Emily Tarleton: Yeah. The Clinical Research Center is located on Shepardson 2 at the main hospital, and we do inpatient and outpatient research and really, any investigator within the UVM or UVM Medical Center community can utilize our services, and we have a metabolic kitchen, as well, that we can do food trials.

What's a metabolic kitchen?

Emily Tarleton: It's a kitchen that is specific to research where we create these very controlled meals. Whether an investigator wants to control for a certain nutrient or they want to just control the overall calories people are consuming at a given time. So we do some long-term feeding trials where sometimes we're controlling the fatty acid content of the food, sometimes we're looking at the different effects of dairy, sometimes we're looking at the effects of glucose. So we're involved in various studies throughout the community, and it's really exciting to be involved at this level and sort of get to see the results of some of these other trials.

Is there anything else that you found in your research that you think it would be helpful for our listeners to hear?

Emily Tarleton: One of the things we found was that, as I alluded to, the US adult population really doesn't consume enough magnesium, and so we took a closer look at this and tried to figure out some reasons why that might be. There have been changes in agricultural processes over the last century that has actually decreased the amount of magnesium in the soil, therefore there's less magnesium absorbed by the plants and the vegetables that we eat. That's one reason. That also means that we have to increase the amounts of those vegetables to get the same amount of magnesium, but what we found was that our intake of vegetables has actually gone down slightly over the past couple of decades. So we're getting less in the plant to begin with and then we're consuming less of those vegetables which isn't a great combination. Those are sort of changes in the way our consumption patterns are as adults. We've also just decreased our whole grains and we're eating more processed vegetables, more processed grains and refined oils, which all have less magnesium as well. Socioeconomic status also plays a role in magnesium consumption, so those that are at the lower end of the socioeconomic status, they tend to not only eat more processed and refined foods, they also are less likely to take a supplement in general and a supplement that contains magnesium.

Is that because of cost or-?

Emily Tarleton: Usually it's cost. Yeah. And just a side note that many multivitamins don't have magnesium in them to begin with so if you're taking a general multivitamin, you can look at the bottle but not all of them contain magnesium. You can look for one that does have some, and usually it's a very small amount even if it does. Finally, there's also issues with absorption and excretion so we have to absorb the magnesium after we consume it, whether it's from food or a supplement. And then we have to not excrete it all. We have to maintain some of that absorption. Things like alcohol consumption, smoking, medications and several chronic diseases actually affect the absorption or the excretion of magnesium. As we've seen an increase in things like diabetes over time, it's actually known that people who have diabetes absorb less magnesium. There's research ongoing in these areas, as well. There are many reasons why we're not getting enough, and this is not only in the US but in other countries as well. They've seen the same trend.

We've just been talking with Emily Tarleton. She's a PhD and a registered and certified dietician at the University of Vermont Medical Center. She's a Bionutrition Research Manager at the University of Vermont Clinical Research Center. If you want to learn more about her studies and other things happening here, please visit uvmhealth.org/medcenter.

If you want to learn more about clinical trials and research currently happening at the University of Vermont and the University of Vermont Medical Center, visit our website.