this program is a presentation of uctv for educational and non-commercial use only welcome to life in balance strategies for optimal health from the science of Integrative Medicine why do we talk about a life and valve imbalance that quality of life and vibrancy to be mentally alert and physically fit requires a lot of attention to being imbalanced and I talked about how part of life is is working out balances the being happy about certain things facing some of the more challenges that we feel that life really is something that you're always working with we're it's an moving process and one thing about a tightrope is the way they do this is they keep moving and I think I mentioned last week that a key thing about life that working on a tightrope is the pole that they have and I looked up why they had the pole does anybody remember what I said last week absolutely it lowers the center of gravity and as you go through this course you're gonna be adding information your pole is getting longer and longer and your center of gravity will lower and you'll have a life imbalance how many of you did something like this last week in recognition as all the things that Ellen Hughes suggested just any tiny thing like eat a little bit less food a smaller plate I see some hands this is good so this can be something where you can apply all of the things that you're learning and that's especially true tonight so we want to promote health prevent disease we want to learn what kind of choices that we can make there's so much under our control that we can do in making choices for ourselves and our families to have a life in balance so last time we heard about sort of an overview from Ellen Hughes on individual health and vitality with sort of a focus on vital aging we are what we eat and we are the kinds of things that we take and sometimes we don't eat a healthy enough diet so some of us think about supplements and that's what we're gonna hear about tonight so tonight we have the wonderful pleasure of hearing from dr. Stephen bent he's going to be talking about from popular wisdom to scientific evidence evaluating the efficacy of herbs and supplements let me tell you a little bit about Steve Fenn he's an associate professor of medicine psychiatry epidemiology and biostatistics here at UCSF that means he's very smart he's a staff physician at the VA Medical Center and he's on the affiliated faculty for the Osher Center and that's only because I have not figured out a way to kind of pull him into our center but we're having him here tonight and he really is a wonderful friend of the Osher Center because of his area of expertise his main area research is on the evaluation of the safety and the efficacy of herbal remedies and he's been most recently focusing on herbal remedies and diets and issues around autism he served as the project director of the one of the first large randomized clinical trials that looked at herbal therapies for benign prostate hyperplasia I was at National Institutes of Health at that time I knew all about his study and the study that he conducted saved this country from making a mistake that would have cost 30 million dollars so this is the 30 million dollar man it was hearing about his trial we went back we were about to launch a brand-new study that would have been your tax dollars and it was one my first acts when I was at the National Center for Complementary and alternative medicine to say stop we were not kind of proceeded with that study we need to do a dosing trial and I actually the study was all ready to go out into the field and I said wait a minute we have new information we have to pull back regroup we're not gonna do that we're gonna do better science and it was all because of Steve and so this you have no idea what a pleasure it was to come here to UCSF and get to meet him I won't tell you all about the studies that he's done with velarium and kava and omega-3 fatty acids because I think he's going to share that with us tonight but he's really a wonderful colleague a wonderful speaker and it is really my pleasure to introduce Steve Steven bent thank you very much Margaret that was very nice and it's really a pleasure to be here tonight and to share with you what I know about vitamins herbs and supplements and I'm gonna start with a little disclaimer just to let you know that I have no financial or other conflict of interests related to any of these products or the companies that make them and then the other thing I wanted to make clear up front is that there are literally thousands of vitamins herbs and supplements and clearly I'm not gonna be able to cover even a small chunk of that group today but what I really hope to be able to do is cover the most commonly used herbs and supplements and then by doing so give you some insight into the process of how we evaluate whether these are safe and effective so that you can apply that knowledge to other situations when you're thinking about using herbs and supplements in your own life so my main goals today are to review the scientific evidence regarding the most commonly used vitamin supplements and herbs to have you understand the three products that I think you should consider using maybe you can take a moment right now and see if you can think yourself which three things that you might think would be the most interesting orbes vitamins or supplements to use and see if we agree at the end of the presentation and then have you understand the general process of evaluating evidence so why are vitamins and herbs and supplements so commonly used while there's lots of reasons but one of them is clearly marketing who would not want to be a mega man who would not want to lose 56 pounds in just six months and go from that physique to the more cut physique on the opposite side in just a few months by taking this diet pill it's very tempting and then here's another product that I think is is actually not quite as as as comical it's called cancer off 126 this is a product that is currently sold over the internet that website herb dot-com is active and this product proposes to help remove melanoma breast cancer lung cancer intestine cancer and many other things for $30 a month and this brings up a significant issue that for some herbs and supplements that make false claims it can really delay people getting to the appropriate care so there's certainly many downsides as well as some potential benefits to the vitamins herbs and supplements but fortunately none of these products are among the most commonly used herbs and supplements that I'm going to just discuss with you today this is the list of the top 10 most commonly used vitamins herbs and supplements in this country and this comes from the National social life health and aging project which was a survey of over 3,000 adults living in the United States and this they were asked which of these products that they used commonly and as you can see the most common not surprisingly is the multivitamin or about a quarter of the population in this age group was using it and then down near the bottom some herbs that are used by a much smaller percent of the population but that's still those are very significant numbers of people when you're talking about the entire US population so we're gonna go through these ones today and then again hopefully that that process will give you insight into other vitamins and supplements so we're gonna start with the multivitamin and again who wouldn't want to take a centrum and have a partner and a full head of hair and big smile on your face riding off on a bicycle or something into the future marketing is a very powerful tool but but how did how did this country you get started on multivitamins well they were really introduced in the 1940s and since about the 1970s between a quarter and a half of the adult population takes a multivitamin and I wonder if I could just ask how many people in this room take a multivitamin so probably somewhere between a quarter and a half so it's pretty significant they were originally formulated based on something called the RDA which you've probably heard of the recommended daily allowance that term has actually been changed was changed in 1997 to the DRI which is the dietary reference index and what those amounts are formulated for is to prevent nutritional deficiencies so for example vitamin D is given an amount to prevent rickets which is a bone disease if you don't have enough vitamin D but they were not formulated with insight into what's the optimal level to create optimal health they were just formulated to prevent disease there are some formulas that are higher potency and there's some specialty formulas that are multivitamins for people with diabetes or mature people and there are some multivitamins that have herbs but for the most part there is a very long list of vitamins and minerals that are consistent between almost all the multivitamin products that are sold in this country and they're almost in all of them have about the same amount which is a hundred percent of the RDA for most of these vitamins and minerals so what are the experts say about multivitamins well a decade ago the New England Journal of Medicine which is obviously a well-known medical journal published an editorial called eat right and take a multivitamin and they thought that all adults in this country should take a multivitamin based primarily on the benefits of folic acid for preventing birth defects so they wanted everybody to take one so that women who could become pregnant would prevent having birth defects and then a few years later that Journal of the American Medical Association another widely read and regarded journal published a similar review that's again concluded that all adults should take one multivitamin daily and this is based primarily on the health benefits again of folic acid for birth defects and vitamin D and calcium for preventing osteoporosis but what's the evidence behind these recommendations well certainly there's a little bit of scientific rationale and that is that many chronic diseases have common risk factors such as smoking dietary problems a sedentary lifestyle and obesity and many of these risk factors share a common metabolic pathway and that is that they can cause oxidative damage and inflammation and we know from animal studies and in vitro studies that many of the vitamins prevent oxidative damage and they prevent inflammation so people thought well if we know these products prevent this pathway then why don't we give it to everybody and maybe we'll make people healthier or make them live longer but what's the evidence from clinical trials well amazingly there have only ever been two large randomized control trials that have examined the use of a combination of vitamins to prevent cancer or death it's really kind of shocking that we have this widespread recommendation to take multi Raiden's but there's only ever been two large studies and no trials have examined the formulations of multivitamins that are commonly used today the two trials that were done had much smaller numbers of vitamins and supplements in the product here are the two trials so the first one was done in China between 1986 and 1991 is a very large study of about 30,000 patients between ages 40 and 69 about Half Men and half women this was a nutritionally deprived population which means that they had poor access to fruits and vegetables and there were seven groups with varying combination of these different components of vitamins so a very complex study the second one was done in France between 1994 and 2000 this was a somewhat smaller study but still a very large study with 12,000 patients about a third of the men similar age range and there were four five vitamins vitamin C e beta-carotene selenium and zinc that were in the vitamin product that were given to these patients and the women in this study had higher baseline levels of beta-carotene and vitamin C but lower levels of zinc and selenium than the men so there were some differences in the baseline composition between the men and the women so this is the location of the study in China and it's just point that out to show you that was in a very rural area of China where the patients enrolled were quite poor and were nutritionally deprived and this is the the summary figure from that that study from those studies this is a commonly used figure when looking at the efficacy of interventions and what's shown on the bottom is what's called the relative risk and if the relative risk is one that means that the risk in the group that got the vitamin and the group that got the placebo was the same because the way relative risks are done is you put the risk in one group divided by the risk in the other so if the risks of developing some outcome are the same then that's one if the risk is lower than one that generally means that the patients getting the intervention or the vitamins had a lower risk of whatever outcome were interested in so in this case we're looking at cancer and this is the French study so this is a French study in all the men and this is the risk of cancer in the patients taking the vitamins and as you can see their risk was zero point six nine or 0.6 nine or 69 percent of the risk in the other group that means that they had a 31% reduction in the risk of cancer and that's enormous there's hardly anything that we've ever developed that creates that much of a decrease in risk interestingly in the same study there was no decrease in risk in cancer in the women and then in the prostate cancer which was thought because the man had a decreased risk of cancer maybe it was all due to prostate cancer but what you can see here is these bars indicate the statistical confidence in the study so if the bars overlap this one bar here of these error bars that means that this results weren't statistically significant so there was no decrease in the risk of prostate cancer in men in the Chinese study this is the Chinese study for gastric cancer which is one of the more common cancers in China there was a borderline decrease in the risk of cancer with a risk decrease being 16% so there was a 16% decreased risk of cancer gastric cancer in the Chinese study and then esophageal cancer is another common cancer in China and there was no difference in risk in that study so just looking at this figure what we conclude can conclude is a significantly decreased risk of cancer in men in the French study and probably a decrease in Kent at gastric cancer in China and all patients so what about death well not surprisingly the studies had a very similar outcome when we looked at death and so again in the French study the men had a statistically significant very large decrease in death a 37% decrease in the risk of death if you were taking multivitamins not true for women and then in the Chinese study this is a little difficult to interpret visually but what this means is that there was a statistically significant decrease in cancer in the Chinese study the Box just it gives you an idea of the power the size of the study but because the bar doesn't overlap one that means it was statistically significant and that indicates that it was a 9% in the risk of death so we have two different studies two very different countries one showing a marked decrease at risk of cancer and death and men but not in women and the other showing probably a decreased risk of death in all patients men and women yes these were both prospective randomized controlled trials the only two that ever been done with multivitamins it was approximately 40 to 60 at enrollment and then they followed patients for another five to ten years so the question that I had about this that I think is the obvious question is who were these French men why were they the ones getting all the benefit and and some what the people thought well maybe there's something different about them but it turns out that 60% of them were from upper management physicians very well-educated very good access to food forty percent of them had university degrees they did have lower serum levels of beta carotene and vitamin C than the women and perhaps there was something about that and the repletion of those vitamins that perhaps helps those men but it's a little bit of a puzzling finding did you have a question sir yes I think those are very good observations and this is there are concerns about the methodology of these studies which we're gonna review a minute but what what he's pointing out very wisely is that you'll see that this bar is very long which means that there's less people and less power because we have less confidence the results we don't really know if the result is really here or if it's there or if it's there because we don't have as many patients in that study as we do in this larger Chinese study where the bar is much smaller so and again it's puzzling that it happened only in men and in men that were at a relatively young age for developing cancer but these are the findings we have so the question is what do we how do we interpret this what do we do about this and as you said there are some methodological concerns one of them is that there was an inadequate description of blinding meaning that we we don't know for sure if the people knew that they were getting vitamins or a placebo and certainly if you know you're getting vitamins perhaps there are some perceived benefits and a strong placebo effect that might occur with and there was no information about the use of other supplements besides the multivitamins that were used in the study so perhaps people were taking other things that either improved or worsened their health so the NIH reviewed this topic very recently in 2006 and they said based on all the available evidence that it suggests that there's a potential benefit of multivitamins in the primary prevention of cancer in those with poor nutritional status really based on the Chinese study and applicability to the United States is limited and their conclusion was that the strength of evidence is insufficient to support the presence or absence of a benefit from the routine use of multivitamins by adults in the US for primary prevention of cancer cardiovascular disease hypertension cataracts or age-related macular degeneration and no studies to date have examined the efficacy of the most commonly used over the county multivitamins that are available in this country so unfortunately not a very conclusive finding here so and I think what this really does is this explains what happens in clinical practice as a as a clinician and an internist I don't routinely give my patients much advice about multivitamins if they're taking them take them and I think there's the practice of many physicians Fishes just don't go out and say hey you really need to take your multivitamin want you to take your multivitamin because they don't really know we don't really know if they work or not so if people are motivated to take them then they end up taking them but physicians don't usually try to convince them to take them and I would say based on my own personal opinion reviewing this evidence you know if this is all we have there's all the evidence we have those are some pretty impressive reductions in mortality in the French men and in China made nine percent reduction reduction in death is still pretty impressive so I think until we have more evidence available I think it's probably very reasonable to use a multivitamin especially for patients who have some risk factors for being nutritionally deprived yes so there were no no evidence of negative effects in these studies the side effects were very minimal that we report in these studies but I'm gonna go over individual vitamins just now and there are some interesting concerns about using individual antioxidant vitamins so and but remember that in these studies the Chinese study used a multivitamin that had seven components and the French study had a vitamin that had five components and the ones that are sold in this country have about thirty components so they're very different products so we really don't know and I think the NIH wisely said there just isn't enough evidence for us to make a firm recommendation it's really up to individuals and their physicians to decide why it's which is why it's kind of a murky field we really don't know all right so let's look so before I move on one one other study the only significant study that's been done in this country was the Women's Health Initiative and this is a massive study that involves a hundred and sixty one thousand participants but remember this study is not a randomized controlled trial in this study they just ask people what are you taking they're not randomized to placebo or vitamins just people are taking vitamins are compared to people who aren't and in this study if you were taking a multivitamin your risk of cancer mi which is a heart attack stroke or death was almost the same in other words very close to one as the women who weren't taking multivitamins so from the information we have in this country it appears that people who are taking multivitamins do not achieve a benefit in the reduction of camps or heart disease or stroke or death but we don't know because this design is not nearly as good as a randomized controlled trial and that's a topic we'll touch on a little bit later but it relates to the fact that people who choose multivitamins are probably choosing to do lots of other things that are good for their health so we don't know that it's the multivitamin alone that is conferring a benefit if we find one and in this case we didn't even find a benefit okay the one thing that we know for sure about multivitamins is that they're very good at preventing congenital birth defects so it's very clear that multivitamins containing folic acid reduce the risk of neural tube defects so this is about a 50% reduction in risk and a similar reduction risk of cardiovascular defects limb defects cleft palate and iourney tract abnormalities and children so clearly we want all women of childbearing age who are considering pregnancy to be taking a multivitamin with folic the same is true of pediatric cancer so we know from many studies at the risk of of certain kinds of pediatric cancer is much lower and these these summary bars are on this side of one which indicates a decreased risk of pediatric cancer and women who were taking the supplement their children has a reduced risk I alluded to a little bit before about rather than looking at the big multivitamin pill what about the individual components so there was a very large review article published three years ago in JAMA that compared that looks for all studies that examined whether these vitamins were beneficial for improving health it was an enormous undertaking they looked first they found 16,000 references including 850 trials and 68 of them were judged to be very high quality and were included in the review over 200,000 participants in these studies the mean duration was about three years and about 70% of the included studies were judged to have a low risk of bias meaning they thought they were high quality studies most of them now this figure I don't expect you to be able to interpret other than looking at this same figure we've looked at before where this is the risk of one meaning if it's on one the vitamins don't do anything and what what I hope you can visually see is that most of the studies found that these individual antioxidant vitamins had a risk close to one meaning that they didn't do anything and rather than looking at in and if you if you sum them all together if you say let's take all of these studies of those five antioxidant vitamins and we'll summarize them together what was the risk in patients who took one or more of those vitamins versus the risk and patients who didn't and the risks and those taking vitamins was 1.05 and that's a statistically significant increase in the risk of death so if you were someone who was taking one of those vitamins you had a 5% increase in the risk of death overall so let's look at them individually rather than combined so if you look at all the studies of beta-carotene the risk of death and those taking Barrett beta-carotene was 1.07 or 7% increased risk of death or beta-carotene user in those studies for vitamin A a 16% increase in the risk of death for vitamin E a 4% increase in the risk of death these are all statistically significant meaning that the confidence intervals are these bars did not overlap one they were all on the wrong side of one for vitamin C that the estimate was that it was an increased risk of death but this confidence in it will overlap to one so we don't really know for vitamin C if it increases your risk of death and the same thing for selenium this one actually showed possibly a trend towards a reduced risk of death but again the confidence interval meant that there was no statistically significant result there so we can't tell for sure if selenium helps but what we can say for sure based on the evidence we have is it taking beta-carotene vitamin A and vitamin E is not a good idea and vitamin C we don't really know yet so if you're taking any of those I would encourage you to eliminate one thing from your medicine cabinet and and I think that's an important message yes so in all of these studies it's any death and that's all that's all most generally true with any type of study that the outcome of death is there's one overall death outcome where they take all kinds of death and then they usually look individually at cancer death cardiovascular death accidental death depending upon the intervention but this was overall death yes probably not and and we don't know which ones are better and why there was again there was this belief that we know that these risk factors cause oxidative damage and we know that all these things have antioxidant properties so we thought of course they're gonna work but it turns out when you do them in the study they didn't work so we'll explore a little bit more later about why that might be the case yes I'm not you know I'm not that familiar with root cause analysis other than when it's applied to sort of like medical errors or problems like that but in the study they certainly looked for for side effects and other kinds of side effects and it wasn't clear why or what type of death was you know being caused by this whether it was heart disease or cancer was a mixed picture of different reasons people had an increased risk of death so I wanted to show you some of the more recent evidence that came out since the publication of that big summary review and these are all very exciting expensive studies that we were all hoping for a positive result the first one is called the select trial the selenium and vitamin E cancer prevention trial this was an enormous study paid for by the NIH 35,000 people 427 sites it's almost impossible to conceive of doing that study it's just the millions and millions of dollars that winning is just amazing so it enrolled people over the age of 50 man over the age of 50 and if you're African American over the age of 55 because I'm sorry over 50 if you're african-american because they're an increased risk of prostate cancer so they enrolled them in a younger age because of the increased risk of prostate cancer you had to have no prior history of prostate cancer yet have a low PSA less than four which is the the upper limit of normal and a normal digital rectal exam no prior history of hypertension or stroke let's take a little break for trivia since we're talking about all these vitamins what food has the highest amount of vitamin E no not very good anybody know which nut almonds almonds how about for selenium that's much harder which one Brazil nuts Wow I wouldn't inform the audience we have here so almonds are the highest nutritional source of vitamin E and Brazil nuts offer selenium of course since vitamin E doesn't help us we don't really want eat almonds for that reason although there may be other good things in almonds so this study that I was talking about this enormous study had four groups a selenium and placebo group a vitamin E plus placebo group a vitamin e plus selenium group and a double placebo group so you were taking two pills and you didn't know if your two pills work both the vitamins are both the placebo or one of one vitamin one placebo these patients had six-month visits where they self-reported cancer which was then confirmed by a medical record review and the primary endpoint was prostate cancer incidence we we thought everyone hoped that these vitamins were going to reduce the risk of prostate cancer the median follow-up was five and a half years so this is the disappointing result of that study and what's shown here on this figure is the years after randomization so this is time and this is the probability of developing prostate cancer so the risk of the the number of people that got prostate cancer increased over time these are the four groups and the highest line here the one had the most prostate cancer of all was the vitamin E group the other three were overlapping and actually there was no statistically significant difference between any of these lines but there was a hint of this one being slightly increased risk so let's look at the numbers and the numbers these are the these are the groups vitamin E selenium and then both of them together the risk of prostate cancer was one point one three so a 13% increase in risk but as you can see it overlapped one so it wasn't quite statistically significant but it was very scary and close to statistically significant so all if anything it likely increases the risk of prostate cancer the same true for selenium the point estimate here is on the wrong side of one and for both of them together again on the wrong side of one oh these these none of these are statistically significant if you look at all cancer again very close to one cardiovascular disease close to one and death a little lower than one but again a wide confidence interval so we really can't tell so the editorialists for this study which was also in the New England Journal of Medicine said physicians should not recommend vitamin E or selenium or any other antioxidant for the Prevention of prostate cancer it may be time to give up the idea that the protective influence of diet which is clearly observed in populations transitioning to a Western diet can be emulated by isolated dietary molecules I think that's a very powerful statement so I want to sort of dissect that with you so what this editorialist is saying is that when people move to this country they get a much higher risk of certain kinds of cancer and cardiovascular disease and people thought well maybe let's just give everybody a few vitamins and we'll get the wrist back to normal and and the problem is it doesn't seem to work it doesn't seem that we can give somebody a pill and reduce their wrist back to what it was when they ate a healthy diet so we ought to have to give up on the idea that as Americans we can have this for our breakfast lunch and dinner take one of these and be healthy it just doesn't seem to work so let's look at another very large study that came out last year this was the physicians Health Study another enormous study 14,000 patients male physicians age greater than 50 were randomly assigned to vitamin C E or placebo again for groups where you either got one vitamin the other or two placebos or both vitamins this one was a mean follow-up of eight years it was started in 1997 so again this is an enormous undertaking everyone was very eager to get some positive results finally from the vitamins that's those overlapping lines again that we hate to see so this is the cumulative incidence of prostate cancer in these men the lines for vitamin E and placebo vitamin E overlapped no difference and the same thing is true of overall cancer looking at vitamin C and placebo vitamin C overlapping lines and these are the numbers for that study so for prostate cancer very close to one meaning no effect for vitamin C also close to one for all cancer slightly increased risk not statistically significant and then the one that really is concerning again is the risk of death looks like it's pretty close to elevated although not statistically significant so what I'd like to recap just what we've done so far is multivitamins certainly for prenatal use for women who are considering pregnancy and possibly for nutritionally deficient and we really don't know for everyone else wait am and C and E a clear no so this x-ray shows a very common problem in this country it's degenerative joint disease of the knee what you can see is this is someone's knee this is the medial compartment or the inside portion of their knee and there's very little cartilage here you see this side there's a nice space between the bones and that's a cushiony cartilage in this side that cartilage is unfortunately all gone and so this patient is almost certainly experienced a lot of pain in their knee when they walk and a potential cure for this was popularized in 1996 in this book called the arthritis cure and it interestingly glucosamine and chondroitin sulfate are naturally found in cartilage and someone had the somewhat crazy idea that well if you if you don't have enough cartilage in your knee you want you just grind it up and eat some right which makes really no sense at all because the cartilage doesn't get absorbed in your stomach and then travel to your knee that's just not how it works so we don't really know how this might work even if it does work so there were about 20 randomized controlled trials done over the past 10 to 20 years involving about 2,500 patients and if you summarize all those together they appear to show about a 28% reduction in pain scores and people who have degenerative joint disease but many of these studies like many of the studies in supplements and herbs were limited by methodological flaws so a group in this study in this country set out to do a high-quality randomized control trial looking at glucosamine and chondroitin sulfate this was called the gait study glucosamine chondroitin arthritis intervention trial it was a randomized double-blind placebo and AFTRA controlled trial it lasted 24 weeks in 16 centers you had to be over age 40 you had to have knee pain for at least six months and for most days in the past month and you had to have an x-ray evidence like the x-ray I showed you of degenerative joint disease it was a somewhat complicated study design there were five groups so you either got randomized to glucosamine chondroitin sulfate both celebrex which is an anti-inflammatory which has some adverse cardiovascular effects that weren't known at the time or placebo and the primary outcome measure was reduction in this thing called the Womack which is a pain score that people filled out about how much pain they were having and there were numerous kinds of secondary outcome measures but the main one was pain so if you looked at all the patients enrolled the average age was 58 about 64 percent female most people have had symptoms for about a decade and had been diagnosed with a degenerative joint joint disease about five years ago and that score in sort of mild to moderate pain so this wasn't severe knee pain but kind of mild to moderate pain this is the somewhat complex summary figure but again it's using the same principle that we have used over and over again which is this one line so if outcome is along the one line it means that the intervention did nothing in this case if the outcome is on this side it means the intervention was better and if the outcome is on this side it means the intervention was worse because we're talking about pain scores here so if as you can see these bars indicate statistical confidence so for all randomized patients glucosamine was no better than placebo and you'll see the same trend here again for chondroitin the bars overlap this dotted line so no better than placebo no better than placebo for the combination and interestingly even celebrex an anti-inflammatory was borderline significance for reducing pain so just barely so even this drug that's commonly used for knee pain was barely effective in this study the only group that showed a benefit was a subgroup analysis in patients with more severe pain so rather than mild to moderate pain if you look at the group of patients that had severe pain and you use the combined supplement glucosamine and chondroitin sulfate there was a statistically significant benefit so unfortunately there were also some methodological problems with this study and one of them I just don't understand how it happened but they used something called glucosamine hydrochloride which is a different glucosamine than the one that's commonly used in all of the over-the-counter products and I just don't know how in an NIH study with millions and millions of dollars they made that mistake at the outset but they had the wrong glucosamine so people said you know why the reason it didn't work is you had the client of glucosamine that's not very good and also patients had relatively mild pain so if they didn't roll patients with more severe pain perhaps we would have seen a benefit but the what people have concluded about this study is that combined therapy appears to be beneficial and patients with moderate to severe symptoms and it might be reasonable to try glucosamine or combine therapy if you do you should use glucosamine sulfate and you should consider this rata product called Donna which was the one that was used in most of the prior studies that showed a benefit okay let's move on to the next one on the list folic acid or folate so folic acid has a very interesting story again this is something that happened just in the last decade where people were really excited about folic acid there were a number of epidemiological studies that showed that this substance called homocysteine was associated with a higher risk of heart disease and stroke so if you measured someone's blood and you found that they had an elevated level of homocysteine we found out that those people had a higher risk of heart disease and stroke and we knew from basic science studies that it was very easy to lower homocysteine levels if you just gave people folic acid in b12 their homocysteine levels came down so people thought this is great well just what all we have to do is give the population forecast in b12 we're gonna lower that homocysteine and we're gonna lower all this risk of heart disease and stroke and I'll pause again for a trivia break weird it does anybody know where you get folic acid from what leafy greens is one but the highest that one has the highest concentration of folic acid is a little more obscure Vegemite Vegemite as you may recall from the very popular song by man at work do you speak in my language he just smiled and gave me a Vegemite sandwich so Vegemite is actually made up of brewers yeast so brewers yeast has very high concentrations of folic acid so in any case based on the evidence that I talked to you about and the fact that in this National Health and Nutrition Examination the United States that occurred between 1988 1991 it showed that many adults in this country did not meet the RDA for folic acid so they're forecast adults were low and based on that study the FDA mandated the addition of folic acid to breads cereals flours corn meals pastas rice green and other products so you may not know this but you are getting folic acid whether you like it or not if you eat any of these and the reason they did that was to try to reduce the risk of birth defects because they figured women who weren't taking multivitamins at least would be eating bread and by doing that we would reduce the risk of birth defects and in fact it worked there was a very large reduction in neural tube defects after the institution in this policy so when people started thinking about this homocysteine issue they were very excited and as recently as 2005 the American Heart Association said that the lowering of the population mean level of homocysteine is is estimated of prevented 17,000 deaths in this country every year so they were really excited people physicians were recommending that everybody should be taking folic acid routinely and unfortunately v initial randomized controlled trials found no convincing evidence of a benefit so in this country we decided we're gonna do the definitive study to show that it really works and this was called the way facts study it enrolled 5000 women u.s. health professionals that had prior cardiovascular disease or three risk factors for heart disease and they were randomized to folic acid and b6 and b12 or placebo the main outcome was a composite measure meaning combined heart attack stroke coronary revascularization or cardiovascular disease death what kind of figure do you think we're gonna see oh no it didn't work so it didn't work so this the line for active treatment the folic acid and the B vitamins and the placebo again are overlapping we didn't prevent heart disease death and stroke by giving folic acid the homocysteine levels went down everyone's levels went down but unfortunately it didn't prevent death so when homocysteine levels are elevated it means you're at risk for heart disease but unfortunately when you lower that homocysteine level it doesn't prevent your risk for heart disease though so of the earlier five studies that were smaller there were men included in that study that's a good question it's possible with the the risk is different in men as we saw in the French study that maybe vitamins are have a different effect in men so in the toriel for this article the editorialists said as shown with antioxidant vitamins with post menopausal hormone therapy and that's a whole other story that that was thought for a long time to reduce the risk of heart disease and death and it doesn't and more recently HDL raising agents which is a whole nother story unfortunately although high HDL is good if you give someone a medicine that raises their HDL it doesn't work to prevent death the success of cardiovascular therapies cannot always be predicted based on experimental and observational data meaning just because people have high homocysteine levels and heart disease just because we lower their homocysteine levels it doesn't mean it's gonna work so you really need a randomized controlled trial of an intervention to show that you have a benefit in some outcome so the editorial stick in recommended B vitamins are not recommended for CA D prevention and there's no role for screening for elevated homocysteine levels no so that's a very good question I'm and I think I probably said something very confusing there so statin medications like lipitor they the primary well actually we don't know exactly how they work but they lower substantially lower LDL so LDL is the bad cholesterol HDL is the good one we want HDL to be high so when you take statin drugs HDLs do go up a little bit but the main action is that the LDL goes way down but there are some other drugs that just raise HDL that have no effect on LDL and when they've studied those drugs that just have HDL rising raising properties they didn't work and we thought each high HDL is good so if we raise your HDL it's gonna be better but it doesn't necessarily work that way and what this what this editorialist is saying is we know the mechanism of action of lots of things there's a pathway and if we alter that pathway we think that we're going to improve the outcome but what we really need are studies that look at the outcome because just because we alter the pathway and we may be doing something good but we may be doing something else bad and so we really need to have studies that look at prevention of disease not change in your cholesterol level or change in your homocysteine level we need studies with outcomes okay sure very good question okay so recapping again the next two chondroitin glucosamine maybe if you have severe degenerative joint disease it might be worth a try but folic acid no for cardiovascular disease another trivia question for you where does the name omega-3 come from we use that name a lot anybody know yes does it come from the Omega house one of my favorite movies Animal House this was a may house no they did not invent that name does it come from the fish where it is in high concentrations no it actually comes from the chemical name so omega-3 fatty acids just described that these are the omega-3 fatty acid family and in the third carbon there's a double bond here so the omega end is this end and if you go one two three bonds that's where the first double bond is in the omega-3 family and they make a six family you have to go all the way to carbon six before you get your first double bond so very technical but it's always kind of interesting and interestingly omega-3 fatty acids are found in high concentrations in fish and certain nuts but they're actually not made by fish they fish get them because fish eat phytoplankton so phytoplankton is what makes omega-3 fatty acids and then the fish eat that incorporates into the fish's body so there some companies that are now mining phytoplankton and putting phytoplankton in capsules thinking that that might help your health we don't know the answer to that yet though so the story of omega-3 fatty acids is that modern diets have a markedly increased ratio of omega-6 to omega-3 fatty acids so omega-6 fatty acids have been introduced in massive amounts into the modern American diet and it didn't used to be there used to be much higher ratio of omega-3 fatty acids and we know from from earlier studies that omega-3 fatty acids have some very interesting evidence that suggests it might help protect protect you from having heart disease omega-3 is found in fish in certain nuts omega-3 omega-6 fatty acids are found in corn oil safflower sunflower oil soybean and khat seed oil and a lot of these things are used in commercial cooking and baking products nowadays so there's some population studies that have shown that people who take a lot of omega-3 fatty acids in their diet have a much lower risk of cardiovascular disease one of the first studies in this regard was done on an Eskimo population and they studied this population and their diets tere intake was very high in fat but it was all fish fat and they had almost no cardiovascular disease they couldn't find that anybody in these various colonies had died from stroke or heart disease so people thought wow maybe it's the omega-3 fatty acids that's reducing the risk of death and we know from other studies and other settings that people that have high levels of DHA and EPA which are two of the omega-3 fatty acids can have as much as a 90% decreased risk of death again these are observational studies so it might not be it's just that they're eating fish it might be that the Eskimos are outside and getting exercise and sunshine or no sunshine or whatever it is that they're getting so this is one of my favorite studies it's ever been done and it's called the dart trial and and it was it's old it was done in 1989 and it was published in Lancet which is a European journal and it stands for the diet and reinforcement trial so this study took 2,000 men who were less than age 70 who had just had a heart attack they were on average 41 days after a heart attack attack and the study randomized them to diet advice didn't give them any pills just gave them advice okay it's a simple very simple study and they were randomized to either get advice about fat and that was reduce your fat intake to less than 30% of your total calories or have two weekly portions of fish a fatty fish or increase your cereal fiber to 18 grams a day and it was kind of a complicated to say they had nine groups so you either got like this advice and that one or this and that one or that and I would say there are nine different groups of getting various kinds of advice but they summarized it out into into looking at the groups that got fat advice or not fish advice or not and fiber advice or not and if you looked at all the people who got fat advice meaning reduce reduce your intake of fat about the same number of people died in the group that got the advice versus the group that didn't now look at the fish advice if you were told to eat fish your risk of death look at how many more people died who didn't get fish advice and this was this was highly statistically significant this remember this indicates a 29% reduction in the risk of death and it was statistically significant and then for fiber if you were told to eat more cereal you actually had an almost increased risk of death in this study which is which is interesting so people were very excited about this and one thing to know about there is what is that fish advice I've kind of like to have that fish advice myself and what they told patients was to eat at least two weekly portions 200 to 400 grams of fatty fish and those are things like mackerel herring kipper pilchard sardines salmon or trout 22 percent of the patients that study could not take fish and they were told to take fish oil capsules so almost a quarter the patients were taking fish oil supplements and there was a four-fold increase in the levels of EPA one of the omega-3 fatty acids at two years and the estimated intake was about 600 to 900 milligrams of combined omega-3 fatty acids so based on this study in 2002 the American Heart Association recommended that all adults should eat fatty fish at least two times per week and that patients with heart disease should consume a gram of DHA plus EPA so if you weren't eating enough fish that you should actually take a supplement with with the omega-3 fatty acids now interestingly there have been a few smaller studies since then that have not had as positive results and this is the Cochrane Collaboration is a group that specializes in reviewing all of the evidence on a particular topic so they reviewed all of the evidence on omega-3 fatty acids they found 48 randomized controlled trials some of them very small and the relative risk of dying in those studies was 0.87 which means a reduced risk of death two percent reduced risk of death but it wasn't statistically significant and the same thing for heart disease a slightly lower than one number but not statistically significant so they concluded that there's not enough evidence to say the pichia people should stop taking rich sources of omega-3 fats but further high-quality trials are needed to confirm the previously suggested protective effect of omega-3 fatty acids for those at increased cardiovascular risk so basically based on all of the evidence at this point we really don't know for sure but I personally think that that dart study was very intriguing okay how about sunshine so what we get from sunshine is vitamin D and we get a lot less vitamin D than we used to so it used to be that we were out you know working in the fields or hunting and gathering and our bodies produce vitamin D from our Sun exposure but most of us now spent a lot of time indoors at the computer and we're outside we wear long-sleeved shirts and our hats and our SPF 50 sunscreen so we get a lot less vitamin D in fact if you look at population levels of vitamin D they've decreased by about half in the last two decades and that corresponds exactly to win the dermatology Association started having major campaigns about wearing sunscreen so we're all getting less vitamin D than we used to and interestingly vitamin D has been known for a long time to be important for bone metabolism and vitamin D and calcium there been a number studies looking at whether vitamin D and calcium prevents bone disease primarily osteoporosis or thin bones so somebody said well why don't we take all those studies that were used for bone disease and look at whether people lived longer so they pooled all the studies which was about 60,000 participants and the vote dose of vitamin D in those studies was between 400 international units so vitamin D is dosed in units and not milligrams to 2,000 international units and the largest study there was about 36,000 women accounted for more than half of the total participants it was postmenopausal women between the ages of 50 and 80 who were taking calcium 1,000 milligrams of vitamin D 400 versus placebo and the mean follow up was 5 years again this is another one of these summary charts but what what I want to point out that if you look at the largest studies and the smallest studies the summary estimates are both on the side of protection and if you pool them all together the summary relative risks for people who were given vitamin D as a supplement was 0.93 which indicates a 7% reduction in the risk of death so again if you can take a vitamin and reduce your risk of death by 7% that's a pretty good deal so this is not considered to be conclusive and there's probably you've probably heard there's a lot of interest in vitamin D right now people are started thinking well vitamin D might prevent heart disease it might prevent Alzheimer's disease it may prevent autism there's a lot of interest so there's a lot of studies that are getting started and ongoing but this is all we have so far so we don't know the answer there was another small study that was done after this review it was about a thousand women aged age greater than 55 they were randomly assigned to placebo placebo and calcium or calcium and vitamin D d3 is the vitamin that that's commonly used in these studies there's a d2 it's a slightly different form this was followed for four years in the primary outcome was nan skin cancer and this shows you they looked at the analysis in two different ways they looked at the number of cancers at four years and first they looked at years one to four and there were more cancers in the placebo group and a calcium group than in the vitamin D group and then if he looked at years two to four thinking that whatever cancer developed in the first year probably was already there and wasn't it related to the vitamin even into the years two to four there were far fewer cancers in the people taking vitamin D and graphically that looks like this so this is the incidence of cancer meaning if you're one you don't have cancer and the further you go down here means the more people got cancer in that group so the most cancer was in the placebo group then slightly less than the calcium only group but significantly last year in the calcium and D group to recap where we are so far multivitamins or let's just add those ones at the end so omega-3 fatty acids I put maybe and vitamin D maybe and so you'll get to decide for yourselves whether you think that's a good idea i put zinc on the list just because it's one of the most commonly used things and i wanted to show you the incredibly long list of things that people use ink for it's too long for me to even read but there's so many different outcomes and so many different small poorly organized studies that we really don't know whether it works or not so all I can tell you about zinc is that it's inconclusive and there really there are some concerns that zinc being a metal could have some toxic effects and we just don't have enough data to know whether it's a good idea to be using zinc so this is the last one I'm gonna talk about it's anybody know what this one is that's a saw palmetto yeah you guys have a handout that's not fair so this grows in the southwest united states it was originally used by Native Americans widely used in Europe for benign prostatic hyperplasia which is enlargement of the prostate and Men happens in all men as we age and it interferes with urination it is the fifth most commonly used in the urban the US least it was several years ago now it's more like the ninth or tenth and prior studies showed mixed results so we decided to do a study here we did a randomized double-blind placebo-controlled trial we enrolled patients over the age of 50 who had at least moderate symptoms of urinary problems and they were given either saw palmetto 160 milligrams twice a day for a year or placebo fortunately this is the dose that we was used in all the prior studies so we didn't have any questions about dosing we knew this was the dose that people thought worked so the patients that we recruited there were a hundred and twelve in the saw palmetto group an 113 the placebo group and you know keep in mind that this study is much smaller than the other studies we've been talking about that have many thousands of patients so this was you know the first the first what we thought was very high quality study to look at this outcome patients were about 60 years old this indicates that they had moderate symptoms this is a symptom score and their prostate size was again indicating kind of moderate disease and then this is a figure that has the the similar trend of overlapping lines there's a little bit wider spread in the lines just because we spread out the figure but the bar error bars indicate the statistical significance for each point as you can see these bars are large enough that there is no confidence that this line is any different than this one and what this shows is the saw palmetto group this is the symptom score meaning patients reported how severe their symptoms were higher is worse lower is better and the symptom scores were almost the same in the sample Mehta group in the placebo group and the no statistically significant difference so taking saw palmetto did not make men's symptoms get any better what I find really interesting about this figure is that these two points up here are the beginning of the placebo run in period so everyone in the study got placebo for the first for the first month from here to here and their symptom scores went down from a mean of about 17 to about 15 so improve about two points and then really didn't improve much at all after that they didn't know that they were taking placebo they were told they were taking a study medication that they'd be taking placebo at some point during the study but they didn't know when um and they improved so really a striking and that this is seen in almost all studies of this condition so you know a condition that's clearly mechanical the prostate gets big and it blocks off urinary flow yeah giving a placebo somehow relaxes the prostate and makes people urinate better and the same thing was seen with urinary flow so this is men urinate into a machine that measured the strength of their urinary flow again the lines are almost identical no significant difference between the two groups and again you can see this is the placebo run in period so here more flow is better so even on placebo between here and here their their symptoms were better on on placebo so they got better while they were taking placebo this was this was the beginning of the study this is the placebo pair and this is the first measurement after placebo it's a it's an incredibly interesting field and yes the placebo effect has been widely documented in many different conditions and people use that figure of about a twenty thirty percent improvement and whatever you're studying and what I find interesting about this is is that the first slide we looked at was symptom scores so people are reporting how they were feeling so it's kind of like okay I can understand that you're taking up to see what maybe maybe you'd sort of feel better you know but this is actually a mechanical this is just measuring your urinary flow and it's it's a very mechanical process so it doesn't just affect how we're it actually affects physiological functions in our body so the placebo the mind is very powerful thing absolutely yes so there there are a number of other different herbs that are commonly used one is pumpkin seed there's another one called pygeum africanum and then there's a another one where they've taken out what they think are the active ingredients in saw palmetto bay testosterone and tried to put that in different compounds and the answer is that there is not much evidence for any of those other ones for most of them there's a few small studies that people are concerned about the methodology that shows some effect there is a very large study that Margaret was alluding to that was approved after this study that is looking at saw palmetto pygeum africanum versus placebo so our study caught causes the NIH to say hey 160 milligrams a day doesn't seem to work let's do a dose ranging study where we give people more saw palmetto and then more of this other compound and see if if we can find if there's any beneficial effect and that study hasn't been finished yet and I actually don't know do you know when it's gonna be done so I think result to be coming out in a few years another interesting thing about our study is our site was the only one that's been published so far that looked at blinding so at the end of the study we asked people which group do you think you were in and 40% of the people patients thought of the placebo group 40% thought they were taking saw palmetto and 46% of patients in the placebo group believed they were taking the herb so so about half patients in each group thought they were taking taking the real or the fake so blinding was effective it the they didn't really know what they were taking garlic I'm just gonna briefly mention because it's so commonly talked about and used there is very good evidence that garlic lowers cholesterol lowers cholesterol by about six percent but you have to take a lot of garlic and it's much smaller reduction than you get with taking cholesterol medications so if you really have a cholesterol problem taking a lot of garlic probably isn't going to do the trick but but it does help it actually lost the lowers blood pressure so we know that garlic does have effects but they're relatively modest benefits in both cholesterol and blood so here's my summary of the top 10 herbs multivitamins yes for premium vitamins and possibly for nutritionally deficient clearly know for vitamin C and E maybe a trial of the glucosamine chondroitin sulfate is worthwhile folic acid you don't need unless you're thinking of getting pregnant omega-3 and vitamin D I say maybe and I think those are gonna be really interesting ones for us to watch over the next few years zinc I'd say no I think saw palmetto is no although there'll be more information coming in in the few next few years and garlic has a small benefit the bottom line to summarize all this these are the the three things that I asked you to think about in the beginning so one I would say is multivitamins clearly for female patients of childbearing age and maybe for all adults we just don't know omega-3 fatty acids maybe if you have cardiovascular disease and maybe just for all adults and the same thing for vitamin D maybe we should all be taking some vitamin D we won't know the answers fortunately there is a large NH study and I hope it won't have overlapping lines the way all the earlier ones did that I showed you tonight it's looking at vitamin D and omega-3 it's called the vital study it just started recruitment its recruiting men over 60 and women over 65 because women are healthier than men so they live longer so they have to get women who are older 20,000 participants as well who they hope to enroll they're gonna sign them to four groups you've seen this design before vitamin D or placebo omega-3 or placebo both or neither and the target completion is unfortunately 2016 so we have to wait about five or six years before we get those results so in the meantime you have to decide if you're going to take vitamin D and omega-3 or not based on the evidence we have and and we don't have definitive answers if you are gonna take either one I sort of think that the NH study probably has a pretty good idea of what you should take if you're going to take it so a two thousand international units of vitamin D would probably reasonable dose and about a gram so if you combine these two numbers and ends up being about one gram about a gram of omega-3 fatty acids is probably a reasonable thing a reasonable dose to take another bottom-line point is I think it's really important to reduce clutter and polypharmacy so when I have patients that are taking these I tell them clearly to stop I don't want people taking more pills than they have to be taking and right now there seems to be insufficient evidence for all of these things so how do you decide whether you should take other supplements that people advertise and tell you about and the bottom line is it's very difficult and scientific studies take sort of four general forms and this is a really complicated discussion that they could take several lectures or even a full course but these are the four main types of studies one is a case study where someone says I knew a guy who had really bad back pain and he started doing acupuncture and it got all better that's a case series same thing could be true with you know I knew a patient who had cancer and they started taking high-dose vitamin D and our cancer went away okay that that is sort of interesting it's provocative but it's not cyant all the scientific evidence the only thing that really is high-quality evidence for intervention is the randomized controlled trial and unfortunately those are time consuming and expensive and we don't have a lot of randomized controlled trial data for most vitamins herbs and supplements there are some herbs and supplements that do have a few small randomized controlled trials showing benefit so I've heard people in the in the herbal and supplement industry say hey you really ought to take you know valerian for preventing sleep because there was this small study of 50 patients and it it helped in those 50 people and it's really I feel like it's just not enough to have a few small studies those are sort of things that get us interested and cause us to do the much bigger study they can really gives us definitive evidence so you'll hear a lot of little studies that give interesting tidbits but in general I don't think that's enough to document safety or efficacy because a lot of these studies have poor methods and are small I would be wary of claims of dramatic benefits so when people tell you you're gonna lose 50 pounds in six months or you're gonna wash away your cancer I would be very wary of that these are some very good sources to seek further information I think this is the best website for alternative therapies it's called natural standard calm and they have very unbiased and I think critical high-quality review of all prior evidence for almost all of the supplements you would consider taking there's another source called natural medicines comprehensive database which is quite good and this website is a laboratory that takes supplement products and tests them to make sure they have in them what they say they have in them to make sure they have no contaminant contaminants or things like heavy metals or other drugs so well the problem with herbs and supplements is they're not well regulated by the FDA and people aren't testing these products regularly so there have been lots of studies showing for example if you take Chinese herbal creams that are used for eczema or rashes and you examine those many of those products will have things like steroids in them so they'll they'll people will put drugs many of the weight loss products they're available have diuretics diuretic drugs so yeah you're gonna lose weight but it because you're urinating and you're drying yourself out so so unfortunately there are a lot of risks to taking herbs and supplements now even if some of them are believed to be effective that's not true for vitamins most vitamins are produced by large companies that have very good good safety standards as always I think you should discuss things like this with your doctor or your health professional so they can help you figure out if it if it's effective and remember for General Health nothing beats exercise a healthy diet and stress reduction really if we could focus more on those things to make people healthy I think we get a lot more bang for our buck and and I'm I'm a big fan of of this concept of active versus passive preventive measures and I think a lot of times in our society we're looking for the pill we're looking for the treatment where we can go lie in someone's room and they're gonna take care of me and fix me and what we really need to get people to do is to learn how to how to enrich their own health and and by being active both physically and mentally and I think that we'll get a lot more a lot more health in this country and internationally if we do that so thank you very much for your attention I appreciate and so I'd be more than happy to take any questions yes yeah so so calcium is often considered more of a medicine but it wasn't list it wasn't in the top ten and it's commonly used calcium is definitely known to prevent osteoporosis so if you take calcium supplements you reduce your risk of osteoporosis there are there are some concerns about taking very high dose calcium that calcium is found in plaques in heart disease and an asterisk laurel acts the same is true for vitamin D so when we take vitamin D we raise our serum calcium levels and people don't know if mega doses of calcium or vitamin D are going to be safe for the cardiovascular disease outcomes so if you take five hundred to a thousand milligrams of calcium a day it's known to be safe for cardiovascular disease and it's known to reduce your risk of bone disease yes so the question was Co Q 10 and coq10 is another commonly used supplements it stands for coenzyme q10 and there have been some very interesting early studies looking at the prevention of sudden death in patients who have arrhythmias or congestive heart failure and I would describe those is among the most exciting preliminary studies there's been a few small randomized controlled trials that have shown benefits and I think that's another one that we should be watching for I don't yet recommend it because there because it's all preliminary evidence very small studies but but but if for people with heart disease and congestive heart failure it's it's something to consider and discuss with your doctor yes that's a great question so so the question is more about vitamin D and both what dose should we be using and then what are the effects of vitamin D vitamin D is considered to be a neuro endocrine hormone it has it has effects over 200 different pathways people have reported of the effects of vitamin D so it appears to go directly in and affect the DNA and affect regulatory mechanisms within the DNA and so people don't really know because there's so many different mechanisms we don't know how it works if it does work but you know the thing that I think is so interesting about vitamin D is is that that we make it right so you just have to go out in the Sun and your body makes vitamin D and it makes it fast and very high doses so you just need about 20 minutes of sun exposure full sun exposure a day and you can get a very nice dose of vitamin D so I kind of have a feeling that you know our bodies have evolved to do things that are important for us and if we're making all this vitamin D it's probably good for us that's my you know this is this is non scientific kind of off the record and then in terms of dosing there have been a couple of studies that so you can either take a little bit of vitamin D every day to keep your levels normal or you can give someone a massive dose once a year or once every six months and their levels will go really high and then they'll gradually trend down back to low and there have been two recent studies that looked at giving elderly patients massive doses of vitamin D and interestingly in both of those studies it increased the risk of fracture and falling we don't know why so the people who did those small pilot studies said you know for future studies we should probably be giving a little bit of vitamin D every day and not the massive doses but that's not nobody knows for sure that's just these are two initial studies that came out yes right behind you there so resveratrol I don't know as much about that I'm pretty sure that's the substance that's found in red wine yeah you know there's lots of studies showing that red wine a little bit of red wine reduces a risk of heart disease and so people are trying to isolate the active components out of that and use that as a as a treatment but I don't know the studies well enough on that to comment on whether that's effective but I think it's interesting that's interesting sure I do in other words our medical schools teaching more nutrition yeah gosh I you know I I don't know that I went to medical school from 1989 to 93 so a long time ago and I did not get I got almost no nutritional teacher yeah about one or two hours I think I hope they've evolved but you know nutrition is a big topic and I know yeah well that's true I I hesitated to put that on there because you can consult a lot of different physicians and get a lot of different answers about this topic and diet topics too you know okay yes so I became very interested in autism because I've always been interested in complementary alternative medicines and primarily herbs and supplements and I started working with some people who who were involved in autism and the prevalence of use there is incredibly high so if you look at at all families of children with autism more than 90 percent of them have tried some herb or supplement and I think you find that in almost any condition where there aren't very good treatments right so you know autism is a very difficult disease and and there aren't any cure all that the treatments are slow and hard and they're not you know a mild to moderately effective so people are looking for the answer you know can I try something else kind of try this herb can I try something that'll reduce my lead levels can I try chelation therapy and so I thought this is a really important condition to to study this and first document the prevalence of it and then find out which ones are the most promising and so the ones that I've been focusing on are omega-3 fatty acids in vitamin D and we did an initial study of omega-3 fatty acids a small pilot study that show that it reduced hyperactivity in these children and there's some ADHD studies that also show that omega-3 fatty acids may reduce hyperactivity it was a great study in patients who were considered to be pre schizophrenic and they're people who sort of showed some early schizophrenic traits and they randomized them to omega-3 or placebo and there was markedly reduced incidence of converting to schizophrenia and people taking omega-3 really interesting very preliminary but interesting so maybe there are some neurological benefits and effects from it too you've been waiting to ask a question there yeah that's a really interesting question so what about what about we're talking about randomized controlled trials what about your personal experience your clinical trial of one when I take it I feel better and it works for me and I personally think I've sort of come around on that one but I think that's pretty powerful you know we don't we don't need a clinical trial to tell us that parachutes work right you know there's never been a study but they're pretty darn effective right if you don't use a parachute you die and if you use them you usually make it down so you know I think that there's some things that so clearly work that you really notice the difference it it really doesn't matter if it's the placebo effect if I feel better than then great I used to say when I did that saw palmetto study and improved that didn't work that I really ruined a perfectly good placebo you know there were plenty of men they were getting a great benefit and now they're oh great it doesn't work so I'm gonna stop taking it so I think that with any therapy you have to evaluate the risks and the benefits and so for something that's potentially very risky like chelation therapy for autism I would definitely not do that until there's scientific evidence a benefit but for something that's likely to have mental effects problems like rubbing a little vitamin E on your wound because you think it might help the healing wall if that seems to work for you then great and for things that are known to be minimally risky I think if you try it and it works well for you then that's great my patients who are on saw palmetto who tell me it works for them I say go for it that's great yeah so so the question is do any of these herbs and supplements interact with with regular prescription medications and that is that's an enormous question it's an enormous field and we don't have a lot of good information about that so the answer is probably we certainly know of some herbs and supplements that have very bad reactions so st. John's wort which probably actually works for depression interacts with just about everything and for example it interacts with oral contraceptive pills so in young women who are having depression who takes on John's wort they may not realize it and then they may become pregnant because the pill the oral contraceptives are no longer working it interacts with chemotherapy it interacts with medications for HIV so although it's it's potentially a good medication for a depression a mild beneficial effect it has all these interactions so it's it's probably too big a question to answer and one but the bottom line is we don't know for most things so that is a potential risk whenever you take something it could interact with all the other medications you're on good question I think we have a couple of questions maybe you could ask them after I wanted to mention something or ask you about something and just highlight something that if you if you billet how many of you belong to Costco or sometimes go to some of the big box stores I've noticed and I don't know if you've noticed you talked about omega-3 mm-hmm and sometimes they'll have a sale of omega-6 and what did you say omega-6 was so Omega six is is another one of this family of fatty acids and it's commonly found in a lot of the cooking products we use now like corn oil and safflower oil so I just yes thought to be not good for you to have a lot of omega-6 so I'm just gonna suggest that when you go to Costco and they're selling nature made big jars and it says omega-6 that's you have to really listen they look back at your notes because it's omega-3 and you'll also see at CVS and Costco and these that they have Omega six and three and it's it's lower cost because you could also just go to your kitchen and drink some cottonseed oil or some soybean oil which I don't cook with and you've got to be really careful about that I just I just wanted to highlight that because I think part of what we can take home from these classes is you you know sometimes if it looks too good to be true it probably is too good to be true it's not the Omega threes I was also gonna mention that the urologists that we're working on the saw palmetto study and saw Steve's results about that dose of the hundred and sixty milligrams most of the these were scientists throughout the country many of them were also taking saw palmetto and so when during the coffee I went up and I said well tell me what you're doing they said well we take it about every day and then we forget and then we noticed we're getting up at night and then we take more and I said well if you're taking more than 160 why were you dosing this study and so we then did some looking at NIH of how they choose to do some of these studies or dose in the bottles and I talked to the companies that make these and it's riskier for them to use a higher dose and so they will sometimes in some of these supplements use of very modest dose thinking that people might take more but they can it protects them against liabilities so it made dosing become incredibly important to us that and it adds to the complications that we as Steve saying that the best studies are the RCTs the randomized controlled trials but before you do that and I was really Steve's work that taught us that before we would launch that big study we would do a dosing study and the fact that the saw palmetto study went on to look at saw palmetto and pudgy 'm suggests that they found and it was I think the higher dose that they're using the study so it's complicated but you do want to look at the labels I think and remember what Steve said so you said something about D to remember you said D to D oh yeah what D because if you go to Costco you can get either one yeah it might just yeah D two gets converted to D 3 by a certain pathway but D 3 is the one that's been used in the studies that found a benefit so that's the one that I would recommend if you're going to try taking vitamin D yeah right so yeah that's I guess that's why I wanted to share this a little consumer wisdom cuz I was at Costco when I looked at slitting my word and then it was actually just at omega fatty it didn't even it was you had to look closely and it was six and I almost went up to them and said why are you saying it was in a big jar I don't I don't know the I don't know the different components in the pathways for D very well all I know is that the d3 is what was used in the earlier studies yeah the other thing I want to say is I don't mean to come across as being anti herb I think clearly there are lots of herbs that have medicinal effects some people have estimated that a third of the drugs that we use originally came from plants so there probably are lots of things out there that do things and some of them are beneficial we just haven't evolved the science yet to know which ones are beneficial and to create products that are reliably effective and safe I want to thank also bring some websites on a sheet of paper next week that you can go to that have fact sheets there's an office of dietary supplements and they update them and the Osher Center also where one of the things we're planning on doing is to try to help people get access you know be a place where you can come to to get to those websites where you can get the latest on some of these findings because the the studies do come out and he's already hinted at one that would be very good I'll mention two that the National Institutes of Health is really looking at the omega-3s for also for just mood states positive effect you know because of some of the early studies that suggested evidence for mental health so and they're also studying it for heart disease at the National Heart Lung and Blood Institute so people are very interested but interest doesn't mean that those lines won't be you know parallel and most of us as scientists we'd love to see the lines we would love to get some exciting effects if maybe one more question and I know people need to go right so that's a good question and I think it's interesting the questions about which omega-3 should we be using so the fish ones are EPA and DHA those are the two fish omega-3 fatty acids there is a concern that if you're using a lot of fish you may be getting a lot of mercury and so it's important to pick a product that's been tested to not have mercury and you can go to consumer lab calm to get that information and there are a number of very good products the other one is ala and the ala comes from nuts and flaxseed and there is not as much evidence about ala so people think well maybe three fatty acids kind of the same stuff so al is probably like the fish oils but we don't know as much about that yet so there's a lot of procs that'll it's the community a lot of people convinced you to take flaxseed and and nuts that contain high levels of ala and maybe it's beneficial but we don't know as convincingly as we do about fish and as I say we don't even really know that for the fish oils
