The Manganese Story: An Interview with Dorothy Klimis-Tavantzis, Ph.D.

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The Manganese Story: An interview with Dorothy Klimis-Tavantzis, Ph.D

Robert Crayhon: Joining me now is an expert on manganese, Dr. Dorothy Klimis-Tavantzis. Dr. Klimis Tavantzis, could you give us your educational background?

Dr. Klimis-Tavantzis: I started at Beaver College where I received my Bachelors in Biology and Chemistry. Then I went on and graduated from Penn State with a masters in Human Physiology and got a Ph.D. in Nutrition. My training is basically in the area of lipids, lipoprotein, and in the area of manganese nutrition.

Robert Crayhon: You've authored many papers on both the area of manganese, lipoproteins and diet frequency questionnaires. And most recently the editor and contributor of a book called Manganese in Health and Disease from CRC Press in Florida 1994. What got you interested in this trace mineral?

Dr. Klimis-Tavantzis: When I was a graduate student my mentor was Dr. Arnold Leach Jr. who is "the manganese man." He discovered the role of manganese-dependent enzymes in glycogen transferases. I took some courses with him and got interested in what he was doing. I read on manganese and I saw that there was nothing being done about manganese and lipids and lipoproteins.

Robert Crayhon: What is the role of manganese in lipoproteins and the prevention of heart disease?

Dr. Klimis-Tavantzis: As you know, manganese plays a role in many areas such as carbohydrates, proteins, lipids. When I started there were very few reports in the 50's about the in-vitro role of manganese in cholesterol biosynthesis. But I just asked the question "What is its role in vivo?" and I did some experiments to check whether manganese was effective in cholesterol biosynthesis in rats. I used rats because they are good models for lipid metabolism and you can extrapolate to humans from rats. So, I discovered manganese did not play a big role in cholesterol biosynthesis because the enzymes that it would activate were not dependent on manganese. So in vivo, in the human body, magnesium may be connective or consumptive for manganese and the enzyme can keep going. Those were my first studies.

Robert Crayhon: So if manganese is deficient it won't affect blood lipid levels, because if there's enough magnesium then there's no problem. But we know many Americans are not getting enough magnesium....

Dr. Klimis-Tavantzis: That's right, and not enough manganese either. If you look at their whole diet...if you look at Dr. Penington's research from the early 90's in which she surveys the American population, we find that in many of the sub-populations and the population as a whole that we are clinically deficient in most of the trace minerals, chromium, magnesium, manganese...especially teenage women and the elderly. I am also improving this with my work in manganese nutrition.

Robert Crayhon: What happens when someone is deficient in both magnesium and manganese?

Dr. Klimis-Tavantzis: We can get many defects in both lipid and carbohydrate metabolism.

Robert Crayhon: When you talk about defects, do you mean that because manganese is involved with some of the enzymes that make cholesterol, low manganese would lead to low cholesterol levels?

Dr. Klimis-Tavantzis: Yes. Manganese is not just involved in cholesterol metabolism but also in fatty acid metabolism and biosynthesis. What we see with manganese deficient chickens and rats is that the liver becomes very fatty. Why? Are they making more cholesterol and less fatty acids? Are they diverting precursors? Or is it that they're not mobilizing fatty acids out of the liver?

Robert Crayhon: Great questions...Let's speak generally if we could about sub-clinical deficiency of manganese. We supposedly have an intake of 2.2-2.7 mg of manganese per day according to your textbook.

Dr. Klimis-Tavantzis: Well, actually the general population has lower than 2 mg because of the ESSDDI (Estimated Safe and Suggested Daily Dietary Intake) for manganese is between 2-5 mg. But we're finding that the population is very borderline rather than clinically deficient, plus or minus 0.5 mg. Teenagers consume about 1-1.5 mg, especially women.

Robert Crayhon: What effect does this suboptimal intake have in them short and long term?

Dr. Klimis-Tavantzis: This is the question. Well, maybe I should continue with the lipid impact of low manganese intake. I found that some people have some defective glycoproteins. We looked at glycoprotein composition and metabolism and found that manganese didn't affect LDL but it did affect the HDL. The HDL cholesterol decreased which is bad, because HDL carries cholesterol back from your arteries to your liver for catabolism. You want to have high levels of HDL.

We also found that with manganese deficiency the HDL particle was changing structurally. It changed the lipoprotein content. The HDL particle has lipo Al, A2 and C proteins. Lipo C is recognized by the liver and it can pick up the cholesterol from the HDL get rid of it or unload it. If there is a problem with the lipo C then the cholesterol will not be unloaded from the HDL particles. We found that the lipo C decreased in HDL particle. We are just doing this experiment right now. We've also found changes in the other lipoproteins. In other words we are finding changes in the lipoproteins.

Robert Crayhon: So you're saying that the HDL C will go down meaning there will be less dumped in the liver. Dr. Klimis-Tavantzis: Right

Robert Crayhon: What happens to lipo A and B?

Dr. Klimis-Tavantzis: We're not finding many changes in lipo A and B.

Robert Crayhon: So what you've said is really two separate things. With low manganese the HDL doesn't carry as much cholesterol and the HDL C goes down so it doesn't dump as much as it's supposed to.

Dr. Klimis-Tavantzis: My hypothesis on what is happening is that because of this lipoprotein changing in structure and configuration, something is happening to the HDL so that it is not able to pick up as much cholesterol from the arterial tissues.

Robert Crayhon: Let's look at manganese at another angle, in terms of heart disease and that's the mucopolysaccharide content of arterial tissue.

Dr. Klimis-Tavantzis: We know that manganese activates specific enzymes all over the body, not just the arteries. So I put animals on a diet with manganese supplementation for 13 weeks which is a very short time. We sized their arteries and we studied the role of manganese in vascular health. A student of mine did this wonderful work where he looked under the electron microscope at the different layers of the artery and he found some incredible changes happening as far as injury to the epithelium. What we found was that the damage done during manganese deficiency was 200 times more than what we were seeing with a manganese supplemented diet. It was an extreme thing that was happening with only 13 weeks! The question was -- what was happening? What we found was happening was the tissue in the media was much more loosely packed in the manganese-deficient rats. Another student extracted glycosaminoglycans from the arteries and found that the total concentration was lower in the def icient rats. She found that chondroitin sulfate was much lower in concentration. We think the manganese deficient rats are making chondroitin sulfate but not as many chains. Not only that but we're finding the chondroitin sulfate changes whereby we have greater concentration of 6 sulfate than 4 sulfate.

Robert Crayhon: So there is a biological difference between chondroitin 6 and chondroitin 4. And you're saying that maybe chondroitin 6 is weaker. If you could set the manganese RDA for optimal intake, what would it be for teenagers and women?

Dr. Klimis-Tavantzis: I would say around the higher range of 5 mg.

Robert Crayhon: Are there reliable dietary sources of manganese?

Dr. Klimis-Tavantzis: Well blueberries are very high in manganese. All the berries and cereals. Teenagers can have cereal in the morning and put berries on them.

Robert Crayhon: What about the soil content of manganese? Does that vary around the country?

Dr. Klimis-Tavantzis: Yes, and the food supply is coming from everywhere. We need to look at food tables which take food samples from all over the country and average them.

Robert Crayhon: We know from studies on selenium that the soil content from one place to another can vary by a factor of 100, so how do we really know what is in the berries? Should we be eating other manganese-rich foods like nuts and seeds?

Dr. Klimis-Tavantzis: Yes, nuts, seeds, cereals, and tea -which is the highest.

Robert Crayhon: If manganese is important for chondroitin sulfate, is manganese therefore an important wound healing nutrient?

Dr. Klimis-Tavantzis: Yes, we have to make sure that people who have wounds take manganese.

Robert Crayhon: What would you say to somebody who deals with epileptics in their practice? Is there some association between epileptics having lower levels of manganese? Is there reason to give them manganese supplements or lots of blueberries?

Dr. Klimis-Tavantzis: I would definitely give them lots of blueberries! Although there is not a clearcut answer to which came first -- the chicken or the egg. But I don't work with Carl in this area and there aren't any clearcut studies and very little human studies. Now that we know that there are a lot of borderline deficient people, more clinical studies can be done with controls.

Robert Crayhon: In your book there was mention of a couple of studies showing women who gave birth to children with neural tube defects have lower hair levels of manganese.

Dr. Klimis-Tavantzis: Yes, but with neural tube defects, we are just beginning to research the role of manganese. We don't know the whole story yet. Obviously, demands do increase. I'm not sure if currently recommended levels are adequate for pregnant women.

Robert Crayhon: What about assessing levels of manganese in patients who want to check?

Dr. Klimis-Tavantzis: Actually, this is a problem. When I was doing my graduate work, plasma was not a good tissue. The techniques were not as accurate then, but with my work now there are a lot of better graphics and ways to analyze manganese with the plasma from 2 to 20 parts per million. There are accurate methods now. I would give samples to a government lab.

Robert Crayhon: We know that in regard to magnesium and calcium for example, serum levels are interesting in acute care, but in terms of everyday nutrient levels they're not very valuable. Is manganese valuable in plasma? Or do we need to look at red blood cells or white blood cells?

Dr. Klimis-Tavantzis: We look at red blood cells. Robert Crayhon: So you'll recommend to look at red blood cell index. But, I have to ask for the nutritionist out there with patients who don't have enough money for the blood tests...those hints we got from the studies on the pregnant women. low in manganese.

Dr. Klimis-Tavantzis:Yes, I would recommend that from the studies we've done, you can look at the diet because there is a pretty good relation between their diet and what's going on.

Robert Crayhon: But from the two studies on hair you can't comment on hair manganese? Because I've done hundreds of hair analyses and found that hair is routinely low in manganese.

Dr. Klimis-Tavantzis: Yes, the hair too. But then you have to take the hair to a very reliable lab.

Robert Crayhon: What about manganese toxicity? We know that not getting enough is bad. What about too much?

Dr. Klimis-Tavantzis: They say that 25 mg of manganese in the diet over a period of time can bring about problems, but we haven't seen manganese related toxicity through dietary intake. Only people who work in mines, factories, or other work related areas seem to get into trouble.

Robert Crayhon: I don't generally recommend more than 10 mg per day without medical supervision. But I've seen many people in the popular nutrition press who recommend 50 mg of manganese per day.

Dr. Klimis-Tavantzis: I would not suggest that. What is their basis? They are risking lives.

Robert Crayhon: Any loose ends you want to wrap up on manganese?

Dr. Klimis-Tavantzis: I think there is great potential for the role of manganese. What I've come to conclude is that the next step as far as lipids are concerned is that manganese does play a role in glycoprotein structure, but now what we need to see is how and we need to look at the receptors and see how the HDL particles have been or not been picked up. But I think the real crucial role is on the epithelial of the arteries. I would like to make recommendations to the public and change our estimated safety net for the RDA and make certain population of the US have sufficient levels. I think that in the long run all these minerals interact among themselves and with other factors, bring about degenerative disease.

Robert Crayhon: You've outlined a striking role for manganese. Dr. Klimis-Tavantzis, thank you very much for all your excellent work and for sharing your thoughts with us.

Dr. Klimis-Tavantzis: My pleasure, Robert.

Townsend Letter for Doctors & Patients.

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By Robert Crayhon

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