2009-05-04 Tyler Barker PhD Knee Surgery And Antioxidant
ACL Surgery, Inflammation and Antioxidants
An Interview with Tyler Barker PhD
May 4, 2009, By Kirkham R. Hamilton, PA-C
© copyright 2009, Prescription 2000, Inc., www.prescription2000.com
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KIRK HAMILTON: Welcome to Staying Healthy Today Radio, a health oriented show committed to bringing you key experts in the fields of nutrition, prevention and integrated medicine.
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Today’s show topic is “Do The Antioxidant Vitamins C And E Help Reduce Inflammation And Improve Healing After Anterior Cruciate Ligament Knee Surgery?” Our guest today is Dr. Tyler Barker. He has a PhD in Nutrition and Exercise Science from Oregon State University. He earned a B.S. degree in Exercise and Sports Science at the University of Utah, and later received his Master’s in Kinesiology from Kansas State University. Presently, he is doing collaborative work with Dr. Merritt G. Traber on the role of antioxidants in ACL surgery. They have recently published an article entitled “Modulation of Inflammation by Vitamin E and C Supplementation Prior to Anterior Cruciate Ligament Surgery” in Free Radical Biology and Medicine, 2009, vol.46, issue 5, p. 599-606.
I would like to welcome Dr. Barker to Staying Healthy Today Radio. Again, Dr. Barker, thank you for taking the time to do this interview.
DR. TYLER BARKER: It’s my pleasure. Thanks for having me.
KIRK HAMILTON: Oh, this is good. I have a personal interest in this story because I’ve had ACL repairs bilaterally, or actually replacements in December of 2006 and January of 2007. So I’m interested in seeing your work. Can you share with me a little bit about your educational background and then what your present job is?
DR. TYLER BARKER: I received my Bachelor’s of Science from the University of Utah, my Master’s from Kansas State University and recently finished my PhD from Oregon State University. My research interest includes the influence of oxidative stress and inflammatory cytokines on muscle atrophy and muscle weakness, and that’s what led us into looking at the atrophy and weakness response following an ACL injury and surgery.
KIRK HAMILTON: And what exactly do you do now at the hospital?
DR. TYLER BARKER: At the hospital I primarily just do research. Doing research in a clinical setting.
KIRK HAMILTON: Tell me why you picked out the two antioxidants vitamins E and C to investigate in ACL repair.
DR. TYLER BARKER: There’s a lot of antioxidants that somebody could either consume in their diet or in a supplemental form. We chose vitamins E and C because they are two of the most potent dietary antioxidants. Vitamin C is water soluble and vitamin E is a lipid soluble antioxidant, and importantly, vitamin C helps recycle or regenerate vitamin E. That’s kind of the rationale why we chose those two antioxidants. Also, in other studies in humans as well as in experimental animal studies, they’ve both been demonstrated to reduce oxidative stress and inflammatory cytokines.
KIRK HAMILTON: Well let’s talk about ACL surgery for a minute. Why do you want to reduce inflammation if it’s a natural part of the healing process?
DR. TYLER BARKER: That’s a very good question. Inflammation is instrumental on recovery, so ideally you do want an inflammatory response. However, too much can actually be deleterious and with regards to the ACL, the inflammatory response, both locally and systemically, very little is known with regards to inflammatory cytokines, so that’s one reason we chose to look at it, is to identify what is the inflammatory response? Is there one than can be measured systemically? And can it be modulated by antioxidants such as vitamins E and C? That recent paper that we had published in Free Radical Biology and Medicine examined that. However we’re still exploring whether this alteration that is induced by these antioxidants is beneficial on recovery with regards to muscle strength and muscle size.
KIRK HAMILTON: What would be the advantage of using the nutraceuticals vitamins C and E versus taking a regular NSAID?
DR. TYLER BARKER: That’s a good question. It’s in addition to those inflammatory regulating properties of those NSAIDs. The one thing that is also beneficial about the antioxidants is by definition they help reduce oxidative stress, so sometimes the inflammation and oxidative stress are very related. It just kind of helps or assists with protection.
KIRK HAMILTON: You talk about the synergism between vitamins E and C. Can you elaborate on that a little bit?
DR. TYLER BARKER: Well what happens is that vitamin E will act with a free radical, which is a molecule capable of independent existence in your body, and it’s capable of eliciting damage in a body. So what happens is vitamin E gets converted to a free radical type form and then vitamin C helps regenerate vitamin E back to it scavenging form.
KIRK HAMILTON: Why did you choose the type of vitamin E you did and I believe it was 200 I.U. twice daily, so is that 400 I.U. per day total? Is that what it was?
DR. TYLER BARKER: Yes.
KIRK HAMILTON: In your study? Tell us about why you chose the D-alpha tocopherol and D-alpha tocopherol succinate.
DR. TYLER BARKER: Basically they’re both alpha tocopherol, and what happens is in your body you have alpha tocopherol transfer protein in the liver and it preferentially secretes alpha tocopherol in that form. The reason we chose that form as well was in experimental animal models they have been demonstrated to reduce oxidative stress, inflammatory cytokines, as well as muscle atrophy and muscle weakness. So that’s kind of the rationale why we chose that form of vitamin E.
KIRK HAMILTON: And where did you pull the dose from?
DR. TYLER BARKER: We have previously found that that dose and form reduced oxidative stress in humans following exercise.
KIRK HAMILTON: And was that taken with meals, away from meals, or does it matter? The vitamin C and/or E?
DR. TYLER BARKER: With meals, just to help with the absorption.
KIRK HAMILTON: The same question could be asked for vitamin C. Did you use any particular form of vitamin C, or was it just plain old ascorbic acid?
DR. TYLER BARKER: Just plain old ascorbic acid.
KIRK HAMILTON: And where did you get 1000 mg/d? Was that your total dose? Where did that come from?
DR. TYLER BARKER: The same rationale. We had found that the combination with vitamin E helped to reduce oxidative stress following exercise.
KIRK HAMILTON: Now before this study, did you evaluate levels at all in the subjects of vitamins C or E? Or did you just do the intervention?
DR. TYLER BARKER: No. Prior to enrollment and before supplementation we measured vitamins E and C with regards to alpha tocopherol and ascorbic acid plasma concentrations prior to intervention. And basically they were within adequate levels. In all the subjects that we recruited one of the criteria to be involved in this study was that they were not consistently, or had not been taking any supplements, for at least a year up to the time of the injury.
KIRK HAMILTON: Can you share with us just the basics of this study and the results? Did they start taking it (vitamins C & E) two weeks before the surgery?
DR. TYLER BARKER: Yes. So the subjects started the supplements two weeks prior to surgery and they continued for three months post-surgery. Each supplements were combined so both vitamins E and C were combined into one capsule. One capsule was taken twice a day each time with a meal.
KIRK HAMILTON: So I assume that compliance was pretty good.
DR. TYLER BARKER: Yes, and the one way we measured compliance is, after the study’s all done and everything like that, and it was a double blind study so we didn’t know which supplement or treatment the subjects had, nor did they, so then when we started breaking the code when they were finished, we could tell if the subjects were taking their supplements or not by measuring vitamins E and C in the blood.
KIRK HAMILTON: So tell us about which inflammatory cytokines that you were measuring and what you found with the supplementation.
DR. TYLER BARKER: Okay. So we looked at a variety of proinflammatory cytokines as well as anti-inflammatory cytokines. With regards to the proinflammatory cytokines we looked at TNF alpha, IL-1 beta, ‘IL’ meaning interleukin and TNF meaning tumor necrosis factor. We also looked at interleukin-6 or IL-6 and several other ones. With regards to the anti-inflammatory cytokines, we looked at IL-10, IL-4, and so on. Now what we found is that by three and seven days post surgery there was a significant increase in IL-6, meaning there is a proinflammatory response following surgery. Immediately following surgery we found that there was a significant increase in interleukin-10, or a significant increase in an antiinflammatory response, which with regards to IL-10 was blunted with vitamin E and vitamin C supplementation. So, the interesting thing is we didn’t find any significant increase in TNF alpha or IL-1 beta. Those are two inflammatory cytokines which help increase other pro and antiinflammatory cytokines, but they are also very transient in the blood. So, I’m wondering since our post surgery blood draw was 90 minutes after the tourniquet was taken off, so both IL - beta and TNF alpha, it is possible that they increased but then decreased before our IL-10 response.
KIRK HAMILTON: What would be the best healing response that you would like to get to reduce inflammation and improve wound healing? I mean, I guess that’s the goal essentially of this whole thing.
DR. TYLER BARKER: And that’s kind of the goal we are working towards right now is trying to find out if we modulate the inflammatory response. Is it actually beneficial or are we at a point today where the inflammatory response is helping recovery? We did find some interesting things such as we found that subjects that had higher vitamin C levels in the blood prior to surgery had greater strength gains of the injured limb post-surgery. Meaning that those individuals that had a better diet, possibly more fruit or vegetable intake, had greater vitamin C in their plasma, as well as throughout their entire body, displayed a greater recovery of strength. So that limb recovered faster.
KIRK HAMILTON: Was this irregardless of supplementation?
DR. TYLER BARKER: It was irregardless of supplementation. So that’s a really interesting finding that we are going to be trying to get out soon. However, with regards to your specific question, I think some more studies need to be performed in order to answer that question.
KIRK HAMILTON: Well let me ask you this. Would you take vitamin E and C at this dose if you were going into ACL surgery?
DR. TYLER BARKER: Yes, I would.
KIRK HAMILTON: Are these dosages you take on a daily basis, or would you just do it prior to this kind of event?
DR. TYLER BARKER: I would consume a really healthy diet consisting of a variety of fruits and vegetables, and I would also supplement with a nice multivitamin that consisted of vitamin C and E.
KIRK HAMILTON: Were there any adverse side effects to these levels of vitamin C and E that you could determine?
DR. TYLER BARKER: Not that we found in this study. So, it would be ideal to do a larger study with more outcomes to analyze the benefits of supplementation and also maybe was it detrimental.
KIRK HAMILTON: Could you run by one more time what happens just after surgery with either the inflammation or the immune response? I lost a little bit of the chemistry.
DR. TYLER BARKER: Okay. What we found is immediately following ACL surgery, there is a significant increase in interleukin-10 or IL-10. Specifically 90 minutes post-surgery. Now supplementation blunted that response so IL-10 did not increase in the subjects that had vitamins E and C prior to surgery. Three and seven days post-surgery we found a significant increase in interleukin-6, or IL-6, in both the placebo and antioxidant group. So we are still trying to figure out in more studies the mechanism why that antiinflammatory response was blunted with antioxidant supplementation. From other literature proinflammatory cytokines cause an increase in IL-10 as well as oxidative stress causes an increase in IL-10, so what we’re designing right now is another study with more frequent post-surgery blood draws with a similar antioxidant supplementation protocol to see if antioxidant supplementation blunted the proinflammatory response or oxidative stress.
KIRK HAMILTON: What is seems to me that you’re saying is the only take-home thing would be that those that had higher vitamin C levels coming in, irregardless of supplementation, had an improved muscle strength response after the fact.
DR. TYLER BARKER: Yes,
KIRK HAMILTON: And that would be an important factor in keeping our quads strong so you can come back quickly. Do you see antioxidant supplementation being used in other orthopedic surgeries in the future?
DR. TYLER BARKER: I think so. I think one area that is interesting right now would be an antioxidant supplementation protocol in maybe the aging population who’s coming in for total knee or total hip replacements where there’s going to be the profound inflammatory response, as well significant atrophy and weakness, in addition to the sarcopenia response with aging. I think that would be valuable information both from a practical standpoint as well as from a clinical standpoint.
KIRK HAMILTON: Any type of nutritional approach and basic approach that would keep muscle mass there in a strong state just up to surgery is going to benefit any person essentially coming out of it, correct?
DR. TYLER BARKER: I believe so, yes.
KIRK HAMILTON: Are there any other comments you want to make on this research? It’s fascinating to me.
DR. TYLER BARKER: Eat your fruits and vegetables, and have a nice well-rounded diet. If you have to supplement, supplement.
KIRK HAMILTON: Do you think there will be a day where the orthopedic surgeon will have an IV bag full of a few micronutrients and even low-dose antioxidants? Do you see that coming?
DR. TYLER BARKER: I’m not an orthopedic surgeon. I have seen some literature where they’ve demonstrated that IVs with those have helped improve recovery from various surgeries. I’d like to see that, but again, I’m not an orthopedic surgeon. I’m not sure if there’s any rules or regulations that would potentially influence that.
KIRK HAMILTON: You know mine is an anecdotal story of one, but years of working in a practice where we use vitamins and minerals and we give IVs of nutritional agents before and after, and we give vitamin C in gram doses. Actually some of the original work if you ever want to type in a name called Robert Cathcart. He was an orthopedic surgeon who actually got into giving high dose vitamin C for the yuppie flu, and then started applying it to some of his patients, and when they would come back and put a cast on - there’d be swelling so you’d make a cast loose. Well, the cast would fall off the next day after giving high doses of vitamin C, and that’s my own personal experience in our practice . What we find, and you can’t prove it. I mean, our patients usually go into surgery and they come out better and their doctors will make comments. And again, they are cases of one. We use intravenous infusions anywhere – oh, the low end would be 15,000 mg up to 60,000 mg depending. And now in my own case, because I am kind of an aggressive vitamin C person, when I had every knee surgery, whether they were just meniscal repairs, I would always have an infusion right after I got out and I would get anywhere from 50 to 75 grams, which is 75,000 mg, IV over a few hours and then I would keep my oral doses up. And what you find is you do that for several days and I can only compare myself to one. I was always a very good patient so I did the right things other than that beforehand. But my surgeons were always very, very pleased and I had to take minimal pain medicine and I would be up and running. In my ACL repairs, I did the same thing, and I told the surgeon what I was doing. It’s not that it’s magic, but I tend to get back quicker than most people. Now, there’s a lot of will in that. Milligram doses are fine for basic things of prevention of chronic illness, but if you want do an acute situation, that’s where the higher doses IV tend to – you just see it in front of you. So someday the dream would be to have those things done in a good study setting at much larger doses. I’ve done it and I think there’s benefit, and I would always love to be involved with someone who could do a real study with some real people in a real controlled setting.
DR. TYLER BARKER: So, you’re in Sacramento?
KIRK HAMILTON: Yes, I’m in a primary care practice in Sacramento, California, called Health Associates Medical Group, and have doing this about 25 years. We have a group of physicians and chiropractors and nurses, and so we do primary care, regular medicine, but we have an emphasis on lifestyle first, and then nutrients and IV therapies are a part of our armamentarium. Because people come for that.
DR. TYLER BARKER: So do you guys have – are you guys doing studies, and if so, do you have an IRB?
KIRK HAMILTON: It’s anecdotal, passed on, you know, from doc to doc, and then we get the different doctor groups that do these kind of things. But I take things from the literature. That’s what I do, and you extrapolate and then you see what works and what other people say.
DR. TYLER BARKER: What was that person’s name you mentioned?
KIRK HAMILTON: Robert Cathcart. He invented, I believe, the Cathcart prosthesis. He was an orthopedic surgeon. But if you – it used to be under Orthomed.com, his work on vitamin C and you probably could Google and find out some information about him.
I would like to thank Dr. Barker for that very interesting interview. And if I could state a take home messages from that, it is that whenever we have a surgery such as a knee surgery, muscle strength and health is very important for recovery. There are inflammatory compounds called cytokines that can increase muscle damage with the trauma of the surgery. And in this study, 500 mg of vitamin C twice a day along with 200 I.U. of vitamin E twice a day helped blunt some of those inflammatory cytokines immediately after surgery. Now whether this improves wound healing or not is the question that needs to be answered by further trials and I am sure Dr. Barker and his colleagues will continue forth researching this. Another take-home message that I take out of this is that Dr. Barker said that those with the highest levels of vitamin C coming into the surgery either by supplementation or not supplementing had the greatest muscle strength upon outcome. And if you’ve ever had knee surgeries or had any kind of knee injuries, your surgeons and physical therapists will always tell you about strengthening your quadriceps muscles and the muscles around your knee and give you specific exercises to do that. So the more that that muscle stature is maintained, the better off you’re going to be coming in and out of surgery. Vitamin C 1000 mg a day and vitamin E of 400 I.U. per day are very small safe doses, so I think it is very reasonable along with a multivitamin and mineral to take that pre- and post-surgery.
So, in closing, again I want to thank you all for listening, and I want to encourage you to Stay and Be Well until the next time you come and hear an interview on Staying Healthy Today Radio. Thank you very much.
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