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2010-03-26 Stella L Volpe PhD RD Magnesium in Clinical Medicine and “Clinical Pearls” in Chronic Disease Management

An Interview with Stella L. Volpe, PhD, RD

March 26, 2010 By Kirkham R. Hamilton, PA-C
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KIRK HAMILTON: Hi, my name is Kirk Hamilton, your host of Staying Healthy Today, and our mission is simple: To provide you credible usable health information from interviews and our educational resources to help you Stay and Be Well in the busy modern world. Please take a few moments before or after listening to this interview to browse through the Prescription2000.com website, the home of Staying Healthy Today Radio, for our free educational services.

Today's show topic is "The Clinical Use Of Magnesium In Primary Care Medicine And "Clinical Pearls" In Managing Obesity, Diabetes, Metabolic Syndrome And Bone Loss."

Our guest today is Dr. Stella Volpe, a nutritionist, exercise physiologist, and professor at the University of Pennsylvania, where she teaches nursing students and continues to do clinically relevant research. In 2009, Dr. Volpe coauthored an article entitled "Therapeutic Uses of Magnesium" in the American Family Physician.

Welcome Dr. Volpe. Thank you for being on the show today.

DR. STELLA VOLPE: Thank you Kirk for having me.

KIRK HAMILTON: So tell me. What is your main title and your main functions at the University of Pennsylvania?

DR. STELLA VOLPE: Sure. I am faculty at the University of Pennsylvania, Division of Biobehavioral and Health Sciences in the School of Nursing, and my main functions are both research and teaching with a greater emphasis on research.

KIRK HAMILTON: What areas are you passionate about in research?

DR. STELLA VOLPE: For me, my two biggest areas of research are obesity and diabetes prevention, in particular type 2 diabetes prevention.

KIRK HAMILTON: Well let's hang on those two things for a moment. Is there a particular reason why? It's (diabetes) in epidemic proportion? Do you have a personal relationship with it? Why are you interested in diabetes per se?

DR. STELLA VOLPE: For me, researching something like diabetes and obesity in the way I do so, which is using exercise and/or nutrition to try to stave off, either what they can cause or at least try to prevent them from happening at all, is because both of them are so prevalent in the United States. Actually around the world, but especially in the United States, that I feel that this is something I can have an impact upon, and it's sort of something to where my research has evolved over the years as well.

KIRK HAMILTON: So tell me why do you think type 2 diabetes or, adult-onset diabetes formerly called, is so prevalent and growing dramatically? Give me three or four lifestyle reasons maybe.

DR. STELLA VOLPE: I can easily give you two and then I will add a couple to that. The first two are very easy for me. People's diets have certainly changed over the years. In particular, the portion sizes have increased dramatically. There have been in some cases 200% increases in portion sizes over the last thirty-some years. People's exercise habits, and when I say exercising I mean total physical activity throughout the day, has certainly decreased. And some of the examples I often use is that even sedentary behaviors in the past have become more sedentary. So an example would be watching TV. We used to have to get up and change the channels, those of us who remember that, and know that. Behavior has actually become even more sedentary. So we are less active overall and our sedentary behaviors have become even more sedentary. And also a fairly new area, probably within the last ten years of research, has been sleep. People are getting less sleep overall. And we know that lower sleep increases a person's risk of obesity and diabetes. And also increased stress levels can certainly impact that. But the biggest two for me would be diet and exercise, that that energy imbalance has tremendously changed over the years.

KIRK HAMILTON: Yeah, I've heard the term called non-exercise exercise. It would be like why do we have to park right next to where we're going? Why not, we don't park across the parking lot to walk across, or when I'm in an airport you know, I try and walk versus take the walking path that moves and all those kinds of things. But the extreme is what you just said, and I heard it from someone else, is that, we don't get up and even turn the TV on.

DR. STELLA VOLPE: We don't, right?

KIRK HAMILTON: And that's amazing.

DR. STELLA VOLPE: It is amazing. And by the way, there's more research coming out that's even saying that those of us who are active, but the rest of our day as inactive, that actually can be - make all the benefits of our exercise be reversed. So even more important to do the things like you said. Walk at the airport, park farther away, take the stairs when you can, sit on a balance ball as I do. Things like that make a difference throughout the day.

KIRK HAMILTON: I gotta catch this. So you're in the middle of your office and you're sitting on a balance ball.

DR. STELLA VOLPE: Yes. People often don't know where to sit when they come into my office. Because they look at my balance ball and they think - and they see that I have a sort of formal chair that they think I should be sitting on for them, but then I often offer them to sit on my balance ball chair because then, maybe they'll want to do it as well.

KIRK HAMILTON: And so the reason you do that is because you have to use some stabilizing energy with your legs or your back. Are you doing that to work, or are you doing that actually to take a break and exercise?

DR. STELLA VOLPE: I actually do this when I sit on the computer - when I sit at the computer. I have a ball at home and a ball at work in front of my computer so it does exactly as you said. I have to use my core. It helps me use my legs. I really pay more attention to my posture. So in that effect, even though it's not burning a lot more extra calories, it's certainly doing something a little bit more than it would have had I just been sitting on a regular chair.

KIRK HAMILTON: Tell me how inadequate sleep or inappropriate sleep might affect diabetes. I am curious.

DR. STELLA VOLPE: I'm certainly no sleep expert as far as research. However, the research has shown that the optimal amount of sleep is between 7 and 9 hours a night, and less than that - more than that can cause problems too, but less than that has been shown to actually result in increases in glucose levels in the blood as well as increases in lipid levels in the blood. And certainly increases in hormonal activity that might lead to obesity. There could be also the effect of not just the lack of sleep, but then when people are up longer they tend to eat more as well when they're up later. However, in a general sense they're finding that the lower amount of sleep can increase those risks because physiologically there are changes happening in the body that result in greater risks of diabetes and obesity.

KIRK HAMILTON: So we have increased portion size, we have less activity, and we have poor sleep. What else are lifestyle factors that may increase the risk to both diabetes and obesity?

DR. STELLA VOLPE: I don't have as much data on this one but I think stress can certainly do it. Bad stress. We all have stress in our lives and there are certainly good stresses and bad stresses and I think that it seems as if for example our society moves a lot faster and people are a lot busier than they had been. And so those stresses can certainly increase things like cortisol which could increase your fat deposition rate for example. And so that's another thing that I think - and I think you will agree with me Kirk on this since we've talked before, is that holistically that's how we have to look at things. And I'm sure that that's what you're getting at with me is that, I always like to look at the full picture when people ask me about obesity and diabetes. Even though my focus of research is diet and exercise, we have to look at someone's full picture when we want to say why might that person be overweight, obese, and/or have type 2 diabetes. So diet, portion sizes, inactivity, lack of sleep, more stress in a person's life I think all contribute to a person's risk of obesity and diabetes.

KIRK HAMILTON: Well it's interesting you brought up portion size. I just interviewed Dr. Jean Buzby a week or so ago and she's at the Economic Resource Service at the USDA, and that's where I got a lot of information for my book actually on dietary patterns over the last 100 years in the United States. And one of the things that obviously comes up is we have - we're in caloric excess, and there was just an article in the American Journal of Clinical Nutrition on 500 extra calories per day between 1970 and 2000 in the average adult which comes out to about a pound a week if you have 500 extra calories. It was interesting when I interviewed her she came up with the same things that I had come up with that, you know, we have increased concentrated sources of animal food still is going up as a concentrated source of calories; increased fats and oils have skyrocketed over the last 50 to 100 years; increased added sugars whether they be from high fructose or traditional cane or beet sugar; cheese has gone up; and the last one was refined grains has gone up even though total grains has gone down. And that's the same pattern for the world which is interesting as it industrializes. So the calorie thing is a tough one.

Let's jump a little bit and your article intrigued me that you co-authored in the American Family Physician. And one of the things that popped up aside from the title "Therapeutic Uses of Magnesium" which I am always interested in because we use a lot in our practice, this came under the Complementary and Alternative Medicine banner and I couldn't believe that. I mean - I've got a little chip on my shoulder you know, it's like you're using this in asthma, you're using this in allergic disorders, you're using it in arrhythmias and then you're going to lump magnesium uses in Alternative Medicine? To me it should be real medicine. Maybe I'm talking to the choir, but what do you think about that? Did you ever notice that?

DR. STELLA VOLPE: No, I agree with you. Before I answer your question, though, just to get this on the air, I want to be certain that I acknowledge the co-authors, Dr. Mary Guerrera from the University of Connecticut is the first author on this paper and Dr. Jun Mao, a colleague of mine at Penn School of Medicine is another author on this. And the reason why it's under Complementary and Alternative medicine, also known as CAM, is because even though I agree with you, anything that can help can be under medicine, but as you well know, minerals and vitamins, any type of nutritional supplement is not regulated as are medications, regular medications are, so when we think of anything that might be a nutritional supplement because it's not under that FDA part unless it's you know considered an investigational new drug, it is considered under CAM.

KIRK HAMILTON: Seems nuts to me. I mean you know you studied Lehninger biochemistry (Lehninger Principles of Biochemistry) in the first year or two, crammed it into your brain, and then if you manipulate it with a nutrient it's called Complementary and Alternative Medicine. You manipulate it with a drug, anti-arrhythmic drug, and it's called medicine. I don't know.

DR. STELLA VOLPE: Right.

KIRK HAMILTON: Alright, that's my pet chip on my shoulder, so we'll keep going -

DR. STELLA VOLPE: Well it's a great chip to have because when you think of it too, as you said in biochemistry, we know just how important minerals and vitamins are as coenzymes and cofactors in all metabolism so they're right there in the body as it is but that's the reason why.

KIRK HAMILTON: Why did you all choose magnesium you know as the one nutrient to pick out for the different clinical entities? You talked about asthma, arrhythmias, constipation, GERD, migraine headaches, menstrual cramps, metabolic syndrome. Why did you choose magnesium versus some other mineral to highlight in an article?

DR. STELLA VOLPE: I think it had a little bit to do with Mary's and my interest as well as Jun's interest because the three of us - I have a grant right now where Dr. Mao is a co-investigator and Dr. Mao and Dr. Guerrera have been colleagues for a long time. And they had been speaking at a conference and Jun discussed with Mary that you know Stella is doing this project, and I've written some articles on magnesium in the past, and so the three of us just connected in that way. And we chose to obviously, because it's a pretty short article as you see, we wanted to focus only on one mineral. We thought it would be too diffuse if we had done several, so we wanted to get out there to physicians, look at all the things magnesium can do, and look at some of the things that a deficiency can lead to.

KIRK HAMILTON: Well let's talk about then, are we magnesium deficient in our diet, or are we magnesium deficient in that the food doesn't have as much magnesium in it?

DR. STELLA VOLPE: More often it's that people do not take in enough. Now let me just say to you first, magnesium deficiency is somewhat rare, but I'll get back to that because I think you might ask me something about how you analyze magnesium in the blood. But I will say that -

KIRK HAMILTON: Good guess!

DR. STELLA VOLPE: And I think you may do that and I'd like to get to that regardless. But the other thing is that so most of the time it's because Americans aren't consuming enough magnesium. But certainly it could be that if a person's on say a diuretic, if a person is an alcoholic for example, that can increase magnesium loss. And just certainly we could have had some losses. Depending on how people are farming for example, there could be some magnesium losses in some of the fruits and vegetables that people are getting, but I would say for the most part it's that people aren't taking in enough.

KIRK HAMILTON: So why aren't people taking in enough and what are the dietary sources that people aren't eating?

DR. STELLA VOLPE: One of the dietary sources that is a great dietary source are whole grains and so a lot of people as you know are eating white bread instead of whole grain bread for example. And another source, a couple of other sources, include nuts as well as fish, and you know again just going back to what you alluded earlier, is that our meat consumption has gone up but our fish consumption probably not proportionately. And which fish as you know is a great source of omega-3 fatty acids, and people will tend not to snack on things like almonds or cashews. They will tend to snack on things like maybe candy. So it's sort of this, you know replacement of worse foods with foods that could have higher sources of magnesium.

KIRK HAMILTON: See here's the problem. If you "poke" these clinicians and say well, magnesium's important, and then you don't tell them how to assess it- the reason I think nutrients aren't used in clinical medicine more frequently is the assessment tools are not routinely done to make it easy for the clinician to do it. For example, we all measure iron no problem. People replace iron. But why don't you replace zinc or magnesium or all these other nutrients? And I think the reason is those tests in traditional medical circles aren't easily accessible. So you're going to get everybody's interest for all these wonderful complaints - asthma, arrhythmias, constipation and then the clinician's gonna go, why do I just tell them to eat more magnesium food, do I just throw in a magnesium supplement, what do I do? So how do they assess it?

DR. STELLA VOLPE: Magnesium is actually another mineral that is more commonly assessed in hospitals and by clinicians than for example obviously you know that zinc is not unfortunately. But it's serum magnesium that is assessed. There's nothing wrong with assessing serum magnesium. It, however, may not be the best indicator of our magnesium status. There's a little bit of a lag behind when serum magnesium will drop. So a better indicator of magnesium status is ionized magnesium, which you need a specific instrument to measure that. But if we started doing that more often I think it would be - then become more routine. It could become cheaper. I always use the example of remember when homocysteine first came out and people said well we can't assess that, it's much too expensive. But now it's - I wouldn't' say it's routinely tested, right, but it's more often tested than it used to be.

KIRK HAMILTON: Well I'm absolutely with you and I - unfortunately like ionized magnesium is hard to get in Quest Laboratories, let's say. So I use red blood cell magnesium, and I do it on almost everybody like, it's part of my chem profile. It's intracellular, you know. We're trying our best.

DR. STELLA VOLPE: Perfect. I was going to - I'm sorry that I'm totally interrupting you. However, red blood cell was the other one I was going to tell you is a very good measure.

KIRK HAMILTON: No, I interrupted you. That's - my fault

DR. STELLA VOLPE: No you did not at all. I was just going to tell you that that's another excellent way of measuring magnesium and that would get to it better than your serums.

KIRK HAMILTON: Well getting to like a - you know the "clinical meat" here, what are the best uses for magnesium as a clinician because we think a disease - I'm going to tell you if you expose a traditional person to this, they're not thinking of overall health. They're thinking I have an entity I need to give magnesium. So which has the most evidence of the asthma, the arrhythmia, constipation, the things that you listed, GERD, migraine headaches? What are the best ones to use magnesium for as far as data?

DR. STELLA VOLPE: I would say for example we know that constipation can quickly be helped by something like magnesium sulfate. That is very clear. That's very somewhat easy to do. You know, milk of magnesia for example. If - you know those things can help. The other thing that it seems to be better related to might also be the GERD. But when I say might, it's only because some of the studies have shown that it's very helpful, whereas others may have not. So the other one that we see much more often is when a person has a magnesium deficiency in the hospital. The other big worry is a dysarrhythmia so we know that magnesium, because of its relationship with heart function, that we know it directly will help if you supplement a person with magnesium. Now in a hospital that typically would be an IV. But if this person were just slightly below and needed to be supplemented daily with magnesium then they would get a magnesium supplement, but via the magnesium supplement they would get would be via a pharmacy, not just an over-the-counter one because they would need a higher amount.

KIRK HAMILTON: Okay.

DR. STELLA VOLPE: So I would say those, in particular the constipation, the heart and the GERD. What I'm studying is the metabolic syndrome. We have some good data to show that it might actually prevent that from going on to diabetes but that's sort of in the newer stages at this moment.

KIRK HAMILTON: Well let's talk about that for a moment because I know it's an area of interest of yours. First, can you just describe a little bit what metabolic syndrome is and then how magnesium might improve that condition, because if I remember a little of biochemistry, magnesium is involved in something like 300 enzyme systems, so it's you know a little magnesium helps a lot of different things. So how might it help metabolic syndrome? But what is metabolic syndrome?

DR. STELLA VOLPE: Metabolic syndrome sometimes people refer to it as pre-diabetes but it's officially called the metabolic syndrome. And basically there are five criteria and a person would be diagnosed with metabolic syndrome if they had three of these five. So for example a high waist circumference and we have - I won't give your listeners all the details because it would be a lot of numbers, but high waist circumference; a high triglyceride level; low high density lipoprotein cholesterol - the good cholesterol levels are low; high blood pressure; and/or elevated fasting glucose levels. So if they have three of those five, or if they're on a medication say for high triglycerides, high blood pressure or low HDL cholesterol, or high glucose then and again, any three of those five would characterize them as having metabolic syndrome. When it comes to magnesium we're not exactly sure the connection between magnesium and metabolic syndrome. We do know that it's probably related to perhaps a kinase, an enzyme that magnesium is a cofactor or coenzyme for, and that works with you know insulin resistance that low - not having magnesium around may increase a person's risk of not getting glucose into their cells because the insulin does not recognize the receptors at the cell, i.e. insulin resistance.

KIRK HAMILTON: With regards to magnesium, alright I understand the need for it in metabolic syndrome. Have you ever done any supplementation trials just with magnesium and what did you use?

DR. STELLA VOLPE: That's exactly the study I am conducting right now. And it's an NIH funded study by NIDDK and also the Office of Dietary Supplements. And it is a randomized controlled trial where we have individuals who have the metabolic syndrome, and, who also must be magnesium deficient. And it's double blind so we don't know who is taking which supplement, but either they are given 350 mg and we are using magnesium glycinate. And that has been shown to be absorbed very well. Or a placebo, an identical looking placebo, and we are measuring what our major outcome measure is - does it improve insulin resistance. And we do that by our individuals have to come into our clinical and translational research center pre- and at the end of six months. Although we are measuring them monthly for things like ionized magnesium and other measures. But the main outcome measure is insulin resistance and does it improve with the metabolic syndrome.

KIRK HAMILTON: How did you diagnose magnesium deficiency? You said that these people - number one, and number two was that elemental magnesium glycinate 350 mg, and did you give it with meals or away from meals? So now you've got three questions.

DR. STELLA VOLPE: Three questions and they're all great. So number one, we are measuring and the study is still going so we - you know I have no results to give to you unfortunately . But so we are measuring magnesium deficiency by several ways. We are doing something called the magnesium loading test pre- and post intervention. And that is when we infuse 1 mg/kg of - 1 mg rather of magnesium over an hour and then we collect urine one hour and then between two and four hours later. And the more a person holds onto that magnesium then that means that they're deficient. There's a certain percentage about 80% retention, means that they're deficient. We are also measuring ionized magnesium, red blood cell magnesium, ionized red blood cell magnesium as well as serum magnesium. So we're covering all our bases when it comes to diagnosing magnesium deficiency. We are giving 350 mg of magnesium glycinate as elemental magnesium correct. And just to let your listeners know whenever they look for a supplement they want to make sure that they see how much of the elemental amount of that mineral is available. Because the total amount, as you know means that it's - that's how much is bound to whatever they have to bind it to because you can't just provide a mineral by itself in a pill.

KIRK HAMILTON: I'm just curious. You've done five different assessments for magnesium. Which one are you going to say is the sine qua non for the - this is the one that's going to be deficient? Let's say one is deficient and four aren't. I mean do you have a favorite one, ionizable?

DR. STELLA VOLPE: I will tell you ionized is our favorite one. It really is. We feel more confident and more and more researchers are saying that is the one. So - but we did want to do them all to - there are a couple of reasons we wanted to do that actually. One, because we thought it also could be a very good methods paper to share with other researches to show, look here are the differences or perhaps here are the similarities. And so for us that's one thing. The other thing is we just wanted to be darned sure that we were covering our bases to ensure that we know that a person's either magnesium deficient or not.

KIRK HAMILTON: Did you give the magnesium - did you say take it with meals, away from meals, or in divided dose?

DR. STELLA VOLPE: They have to unfortunately take six pills because it's too much to put into one with the kind that we got. Pardon me, not six, three. So we're suggesting to our participants that they take them throughout the day. But we have to also realize what might be greater for their adherence. So we're encouraging them, say just to take for example, if it's best for them to take all three at breakfast then we're going to tell them to take all three at breakfast. And I know that this could cause a - we hope that it's not going to cause anything different in our study whether they spread them out or take them all together, because as you know if you spread things out the absorbability could be greater. However, we want adherence. So -

KIRK HAMILTON: Well the only thing that I can see happening is that they get loose stools if you give it all at once.

DR. STELLA VOLPE: Right, but so here's what I'll tell you though. So the good news is we did a small bioavailability study within my lab before the study started. And in that bioavailability study. What we did was we collected 24-hour urine's then for a week we took the supplements, and some of us took them all at once and some of us spread throughout the day. And none of us had any diarrhea symptoms and it improved the magnesium in I think all but maybe one person. So we - it didn't matter, is what I should say, of whether we took it altogether or whether we took it spread throughout the day.

KIRK HAMILTON: We're talking to Stella Volpe. She is a professor at the University of Pennsylvania and doing some excellent work with magnesium and metabolic syndrome. And I wanted to - we've talked a little bit about diabetes. We've talked about metabolic syndrome. We've talked about obesity. I wanted to get one other area of interest of yours, and that is bone loss. And you know maybe you could highlight some of the factors you think are why we have so much bone loss in a country that you know consumes lots of milk products and things like that, and maybe also - I'm interested in magnesium. To me it's like the "lost little sister" that doesn't get paid attention to sometimes in bone health. I'm wondering if you can comment on that.

DR. STELLA VOLPE: You're right about magnesium. It does sort of get pushed to the side. So, my belief as to why we have such a high rate of osteoporosis in our country and bone loss and osteopenia in our country are probably - well they are a number of things. Number one certainly people who are on a number of medications that can certainly lead to bone loss. However, when we look at diet and lifestyle factors I will get back to eating and activity again. My mantra. When we look at the fact that we're a society that has a high salt consumption and we know that higher salt can lead to increased urinary magnesium excretion. We also know that although slightly higher protein intake might not - won't lead to bone loss, very high amounts of protein can lead to some bone loss, so that's another thing we have. We tend to have a higher protein diet than we actually need - a much higher protein diet than we actually need. And in general for some, especially young women, milk consumption has - especially teens and college age women - has gone down some because oftentimes they will replace the consumption of milk or dairy anything higher in calcium with things like a diet soda. Which is offsetting their calcium to phosphorous ratio. So I think those are some of the problems. And then certainly lack of physical activity because physical activity, especially that which is weight-bearing, is going to increase a person's bone density and maintain that bone density.

KIRK HAMILTON: Are you an encourager of strength training?

DR. STELLA VOLPE: I am a big encourager of strength training. For people of all ages and both men and women because a lot of women think they should stay away from it, and as you well know that weight training can increase a person's bone density.

KIRK HAMILTON: How about magnesium in bone loss? Any role?

DR. STELLA VOLPE: Yeah, it does play a role. We tend to focus on calcium and vitamin D because we know that those are the biggest players in bone density and in reversing maybe some bone loss in some people. Magnesium does play a role in bone density. If a person was to tell me that they bought a calcium magnesium supplement with vitamin D I would not tell them oh that's a bad thing. The only thing that's kind of interesting that may surprise you, but you already may know it, is that magnesium may actually compete with calcium at the absorptive sites in the intestine. So you need to be careful that the amount of magnesium given in that supplement is not more than the calcium. So that's where people have to be aware that the balance of calcium/magnesium needs to be in good balance.

KIRK HAMILTON: Well, Stella, I think we have to move on here, and I appreciate you letting me to through a litany of questions and kind of running you through the ringer a little bit and jumping in.

DR. STELLA VOLPE: Oh you know I always enjoy speaking with you Kirk. That's what makes it fun.

KIRK HAMILTON: So and I have this vision of you talking to me on the phone sitting on a ball. Are we in a chair or are we on the ball?

DR. STELLA VOLPE: Oh on the balance ball of course. I expect you to send me a picture of you on the balance ball in your office.

KIRK HAMILTON: Uh, no.

DR. STELLA VOLPE: Then I'm sending you one.

KIRK HAMILTON: Okay, that is a great visual, and we'll leave it at that. We'd like to thank Dr. Stella Volpe from the University of Pennsylvania for sharing with us today on her excellent work with magnesium and multiple chronic diseases. And I would like to thank you, the audience for listening to this edition of Staying Healthy Today. And until next time, Stay and Be Well.

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