And thank you all for being here and in attendance. We have a lot of sessions that are quite interesting, all in competition, so it's also gratifying to see that nobody's getting up and leaving quite yet. So before I start the presentation, let me ask a question. How many of you actually take a supplement of any kind, whether it's a vitamin, a multivitamin, vitamin D, fish oils, on a daily basis? Okay, a few. How many of you take a supplement intermittently? Okay, how many of you ask your patients about whether they take a supplement or not? Good, I'm glad to see that. And perhaps the most important question is, how many of you have had a patient come to you and ask about a supplement, something they're, yes. Well, that is actually very, very interesting, because I think that's something that for many of us doesn't tend to happen very often, and then we face the problem and the challenge of, okay, what am I gonna talk about for them? Do I know enough to be an expert in an area? Can I talk to them about side effects? Can I talk to them about benefits? What do I do? So I'm hoping I'll be able to give you a little bit of information in that regard in this presentation. So why the persistent interest in supplements? Well, clearly, the same thing for our patients pertains to us, too, I think, that we hope that somehow supplements will give us something better, that perhaps it will keep our health good, or perhaps it will help improve health, but there's just something that's clearly a benefit, an improvement. There's also a perceived safety in the natural appeal. If it's natural, it has to be better than a chemical that's prescribed. There's accessibility and convenience. I do not have to go to see my clinician, my physician, to get a supplement. I can go down to the local grocery store, the supplement store, the pharmacy, and just pick it off the shelf. We also, unfortunately, are very heavily influenced by marketing and testimonials. Social media is full of supplements, and gee, they're all good. Have you ever seen a testimonial that says, this supplement was bad? It's rare. It happens, but it's rare. So clearly, we all search the internet, and we're all faced with this very positive aspect, and it's kind of like the supplement of the year, the supplement of the month, the supplement of the week. They're all having to deal with. There's also the desire to control one's own health, and this has been reported, actually, in the review that you see. I've referenced two reviews. There may be cultural and social factors about not taking a prescription. I think insulin is really notorious in this regard. There are many cultures that insulin is associated with something bad, an amputation, going blind, going on a dialysis, and unfortunately, increasingly, we're seeing something new, the lack of trust in the medical community. I know if you saw the recent New England Journal editorial that talked about trust, it was more specific and focused to vaccines, but that this is a huge issue that's evolving, certainly in the US, that I don't trust the medical society. I don't trust medicine in general. I want to do something on my own and feel that I'm in control. So if we look at prescriptions, we face another challenge, and that is that we have a problem with persistence in people taking what is prescribed, and I'll specifically focus to anti-obesity medications in this report that was just published earlier this year. It was a retrospective cohort study which looked at electronic medical records from January of 2015 to July of 2023 in a major health system in Ohio and Florida. They looked at roughly 1,900 adults. You can see the BMI that was accomplished with the medicine, even though their baseline BMI was considerably higher, and they looked at people who specifically were not only given prescriptions but actually picked them up in that time period between 2015 and 2022. At three months, only 44% were still taking the prescribed medication. You go out to six months, and it's now down to a third of the people. Go out to one year, and now it's less than 20%. So these are people who are achieving success. They're seeing weight loss, but they stopped taking the medication, and they looked at all sorts of medications. It wasn't just the most expensive ones of semaglutide, as you can see, which actually did the best at 40%, still taking it in a year, but they looked at naltrexone and bupropion, and they also looked at fentaramine and topiramate, and again, the falloff really didn't make a difference. There was some falloff with any medication that was actually prescribed. So why? Why did people stop taking it? Well, at least in the survey, when people answered, they cited expense as a major cause. Is that a surprise? Of course not. Insurance does not cover just weight loss medication alone. If you have diabetes, you might luck out if you wanted to lose weight, but at least in the US, weight loss medications do not tend to be covered by insurances, and out-of-pocket, even though someone may desire to get the medication, can actually be, obviously over time, just too expensive to maintain. Another major reason, I'm tired of injections. I want a pill. Sure, we do have some pills, but they're not as effective as injections overall, and then there's also symptoms, persistent nausea, abdominal discomfort, which continued, at least the reasons that were given by some people, that they discontinued. Additionally, we're also bombarded in the lay press by many concerns saying, well, you know, if you don't continue to take these obesity drugs, they're not going to be work. You're not going to be successful. It's not going to be effective. So people know that you do need to continue these medications for success, but that doesn't seem to stop the individuals who then, as I mentioned, actually do stop taking them. So how common is supplement use? Well, the actual numbers are unknown. Unfortunately, when you look at what's actually published data, what's science, these studies often reflect specific supplements. So they'll ask a question as to how many of you are taking vitamin D, and ignore the fact that there are other choices that the patient may actually be taking. So one of the challenges in what we see published is that questionnaires are not inclusive of all choices, and we don't have prescription data. We can look at anti-obesity medications, as I mentioned, and there's prescription data, electronic health records that can be looked at to actually get some sense that's more specific to use or lack of use. One of the reviews, again, recently published, 2018, looked at 22 US and Canadian studies. Of these studies, and they were specific to supplement use, 11 did not focus on any specific vitamins. So it seemed a little bit more inclusive of what was actually being ingested. And it suggested that of that population that was looked at, 85% used some supplement. 64, so two-thirds actually used a specific one. So vitamin E, a fish oil supplement. But this is a high rate. I mean, 85% actually is a very impressive rate of people using something beyond what we prescribe. In a better survey, I think, that reflected reuse of supplements, this is the NHANES data, and they looked at the years of 1999 to 2014, and they actually looked at the prevalence of any supplement use. So again, non-specific supplement use, what are you taking? And you can see that roughly about 52 to 58% were actually reporting using something. Any mineral use, so if we get a little bit more specific, again, about half the people. And the other thing that was a little surprising was that this intake was stable over years. So these people weren't taking something for a little while thinking, oh, it's good or not. They actually took it over the course of that period of time that was being looked at. The use of any vitamin products significantly increased from 47 to 52%, and you can see that is actually statistically significant. And use of some individual supplements, such as vitamin D, choline, lycopene, fish oil supplements significantly increased while some vitamins and minerals and non-mineral supplement use actually decreased. And there was a trend of supplement use which varied by age, by sex, by race, ethnicity, education, but interestingly enough, not necessarily by diabetes duration or diabetes comorbidities, at least in this particular NHANES study report. Others have, however, shown that perhaps there is a little bit more of a trend towards supplement use in some conditions. So this is a review looking at various diseases. Thyroid, as you can see, elevated cholesterol, hypertension, heart disease, but you'll notice, and I'm not sure if I can get, oh, here, this is showing up here, look at that diabetes. Diabetes actually did seem to actually stand out as people using supplements for a treatment or something additional to what they're prescribed if they did have diabetes. If we look at weight loss, again, looking at reports of over 2,000 people in this particular review, as you can see, these came out rather recently, 2021. Looking at adults trying to lose weight, about a third do report using some kind of a dietary supplement. And again, if we look at the populations, there's a trend towards use higher in young adults, in women, and in lower socioeconomic groups. In that same year, the review of supplements used, this was based on some 20,000 plus citations, which they felt they could only look at 315 that were randomized controlled trials, evaluating the efficacy of 14 purported dietary supplements, therapies, or combination. There was a little caveat in looking at the results, saying that there did appear to be inherent risk of bias in many of these reported studies, and that their sufficiency of data was somewhat questioned. So a lot of caveats to say, you know, we really looked at this, but we're not sure that these are good science-based studies. As you can see, part of the problem is what is defined as efficacy. And if we look at even just significant pre and post weight reports, that the intergroup differences in weight were tremendous. So some people felt there was success and efficacy if you only lost 0.3 kilograms, which I think any of us would say that just doesn't make much sense. But more significantly, almost up to five kilograms. Well, and I think we would agree that that study actually would achieve some significance. But if you look at that report, you can see, and they took a lot of different approaches. So it wasn't just supplements. As you can see, acupuncture was up there. Hard to imagine that acupuncture would help weight loss, but this was looked at. But other things such as chromium, ephedra, caffeine, green tea, things that I think are more in the mainstream, again, web-based literature, that suggests that there's weight loss. And you can see the problem. And again, I don't know if you can see the, I guess the mouse doesn't show up. But we can see that age ranges were fine. I mean, there was a wide range of age ranges reported in these studies. But most of them, this is not reported p-value. Look at the proportion of studies, a number of studies in which there wasn't any reported p-value. So it's hard to say is this significant or not. You can say it's significant, but that doesn't make sense if you don't have data to back it up. And then they also looked at the bias. So again, it's that difficulty of knowing if a 0.3 kilogram weight loss is significant. It may be in someone's bias that it is, but it's not something, again, that by any means is standardized. So what do we really have that's science? And I think one of the most popular supplements, and I looked at supplements particularly that hit the web in the past year from the beginning of January of this year. And this is berberine, which is widely touted in the internet as nature's ozempic. I will say it's also touted as a natural metformin. So we'll talk a little bit about that in a few slides. It's easily found in a number of plants, including barberry plants. It's also widely available, whether you get it online or whether you go to the local pharmacy, supplement store, and it's very inexpensive. So the price can range anywhere from $15 for a month's supply to $40, depending on the brand, the manufacturer, and also the dose that's being ingested. And again, the problem of what's the dose? So you'll see studies that are reporting at using just one gram a day. Others suggest up to 1.5 grams a day in divided doses. So again, a little bit of a lack of standardization. But there are also some side effects before we go to the benefits. And the side effects of berberine in humans are relatively mild. All that's been reported actually is nausea and vomiting, which not too surprising. In animal studies, a little bit more concerning because there are studies that would suggest that there is both an enlarged liver and kidney risk. So it's just organ enlargement, although not specific to organ dysfunction. And there also may be some reduced white blood cell count, again, of questionable clinical significance in an animal. How can you interpret that? It's not been reported in humans. Either the enlargement of organs or the white cell count defect. However, if we look at what's actually published with regard to use, first of all, the hydrochloride form is the most popular form of berberine. And this actually does have a long-term history of use. It's been used to treat diabetes for thousands of years, mostly in China. So obviously that begs the question that there must have been some efficacy. And if you look at one study that was published in Metabolism, granted it's over a decade ago, the results in that particular study were almost unbelievable. Documented decreases in A1C from 9.5 to 7.5. That's really, as I say, a little bit astonishing. Look at the change in fasting plasma glucose from 10.6 to 6.9. Decreases in postprandial glucose. Again, you look at those values and they're incredible. And this was actually seen in both newly diagnosed type two individuals with diabetes and poorly controlled diabetes. However, notice that it was a study that lasted only three months. So whether this is an initial effect or whether it can be persistent, I think begs the question. There is some suggestion, though, that berberine increases insulin receptor expression. It improves glucose utility both in vitro and in animal models. Berberine also increased insulin receptor messenger RNA, protein expression in a variety of human cell lines, as you can see, both with regard to general cell lines as well as specific to hepatitis B virus transfected human liver cells. So there's something happening. There is some signal there. It appears to be a favorable signal if you believe this particular report. There's also been an evidence of decrease in fasting glucose in A1c, similar to the amount that we see with metformin and rosiglitazone. So again, it goes back to what I mentioned, that sometimes this is called nature's metformin. You can also probably call it nature's rosiglitazone. There is evidence that hepatic function did improve. If you just measure hepatic enzymes, but not interhepatic fat specifically. And part of the antihyperglycemic effect of berberine is thought to be due to a decrease in the availability of glucose after a meal, specifically because it does suppress intestinal disaccharides, sucrase and maltase specifically, so that you do see reduced intestinal absorption of glucose. And again, if you believe some of the data that has been published, I mean, an 18% reduction in serum cholesterol, almost at what, 35, 36% decrease in triglycerides. I'm sorry, 21% in LDL cholesterol. And again, we're looking at studies that are three months in duration. Not only does it improve lipids, but it improves blood pressure. Systolic blood pressure and diastolic blood pressure. And again, these are published data. These are rather remarkable changes with p-values that are quite respectable. And there's also weight loss, you know, 7%. So I mean, look at this data and you think, my goodness, why shouldn't everybody be on berberine? It's much less expensive and with fewer side effects. So to ameliorate obesity, berberine additionally, there is an effect on appetite, and that's not understood nor well investigated, unfortunately. There's some evidence also that there's a promotion of thermogenesis of beige adipose tissue and brown adipose tissue. We've already talked about the improvement in glucose metabolism, the regulation of short-chain fatty acid production. It may also uprelate GLP expression. And there's some effect also on gut microbiota. I mean, some of this data seems almost too good to believe when you look at all the effects that it has been associated with. But again, this was actually reviewed very nicely just last year, as you can see in endocrinology. In humans, there's some additional evidence that there is expression of PPAR-gamma, CEB-P-alpha, adiponectin, and even leptin mRNA being downregulated in pre-adipocytes upon treatment with berberine. So again, these are in vitro studies, but they are well published. There's some difference in effect depending on dosages. So at a dose of basically up to a gram a day, berberine has been shown to be effective in reducing blood glucose. And the fact that this is probably more related to the alpha-glucosidase inhibition, decreasing glucose absorption may play a role here. If we look at a lower dose, so up to 500 milligrams per day, there is some attenuation of the synthesis of enteroendocrine peptides, which again are involved in glucose and energy homeostasis in people who are obese. And again, as I mentioned earlier, there's some evidence to suggest that there's modulation of gut microbiota by elevating intestinal peptides, such as the GLP-1, GLP-2, peptide YY, which you heard a lot about actually yesterday in one of our plenary sessions, and decreasing gastric inhibitory polypeptides. I mean, the evidence is there that there is, again, signaling. How robust the signaling in, I think, is a bit of a question. And whether it's long-lasting, of course, is also not answerable. There, however, are some challenges with berberine. And this relates to a study published in 2018 where the investigators actually ordered berberine online. So 15 different berberine brands that were bought online through U.S. dietary supplement vendors. They took each of these different brands and took three capsules out of each bottle and then analyzed, actually, by liquid chromatography tandem mass spec what actually was the content as well as what was the potency. So two things that were looked at. And as you can see, on average, the content varied tremendously. I mean, 75% plus or minus 25% variability of the product label claim. And the potency ranged anywhere from 33%. Some of them actually had 100% of what the label promised. Nine of the 15 tested products, so about 60%, fail to meet what are considered potency standards of 90 to 110% of labeled content as commonly required by pharmaceutical preparations by the U.S. Pharmacopeia Convention. And that's really a group that when you get a supplement and you see this little round kind of almost diamond-shaped thing that says USP, that's a way to actually guarantee content, and the claim has to be that whatever's on the label is within that 90 to 110%. So again, when you see 60% of these products not reaching goal, what are you actually getting? Let's move on to Lignans, they actually hit the web this past summer as being something to take, and the claim being that it's not just a fiber association, that these indeed are agents that are bioactive non-caloric phenolic plant compounds. Flax and sesame seeds are very rich sources of Lignans, but you can also find it in whole grains, nuts, fruits, vegetables, coffee, tea, and wine, which I think patients like to hear, although obviously in lower concentrations in those latter compounds. There are certainly ample evidence in the literature that higher consumption of certain plant-based foods, I mean if we eat fruits, if you eat vegetables, whole grains, and nuts, generally people tend to put on less weight, and Lignans are felt to be a major phytoestrogen class, which may also play some role actually in an anti-obesity effect of plant foods. The problem, however, is to claim that there's something more beyond fiber is a little bit difficult, and I just chose this particular example. If you look at what's actually in the supplement, what do you see that really is the highest in the content? It's fiber. The calcium, which some people have felt higher calcium intakes can actually contribute to less weight, gain or weight loss, pretty minimal. Sodium, we all know, well that doesn't really pertain to any weight loss, but you look at the amount of fiber in there, and that's huge. So again, it begs the question as to why do you think it's something beyond fiber and just the creation of fullness that actually makes this particular supplement so appealing? And there clearly are side effects. There's interference with absorption obviously of other medications that may be taken by the patient, and of course constipation obviously is not surprising. Let's move on to apple cider vinegar, another very popular supplement. And again, you can see in that cartoon that is just off that website as to all of the benefits that are touted by the intake of apple cider vinegar. Yes, it boosts weight loss. Curiously enough, it reduces stubborn belly fat. At least that's something that's being touted as an advantage, not just overall weight loss, but specific to where we get to be very concerned. Appetite suppression actually has been shown in a few studies, even human studies, people with diabetes specifically, regulating blood sugar. I like this one, enhances skin health, whatever that means. It's very easy to get. You can get it in pill form, as I have an example there on the left. You can get it in an oral liquid type of form also. So again, very inexpensive supplement that people are looking to, particularly with regard to weight loss more so than I think diabetes. We all know that it's a flavoring and preservative agent in foods. It does seem to contain a variety of flavonoids. You can see just some of the compounds that I have listed there with gallic acid, catechin, caffeic acid, and ferulic acid. So a lot of different flavonoids. Animal experiments that have been done have shown a variety of pharmacologic functions. There can be antioxidant effects, anti-inflammatory. We talked about the anti-glycemic, as well as anti-hypertensive and anti-hyperlipidemic. As with so many of these supplements, they kind of hit everything that you want to have benefit from. In human studies, particularly if you look at randomized controlled trials specific to lipid parameters, glycemic markers, the studies are equivocal. Some of them show that, yes, there are benefits. Others show there's really not much there. So it's a little hard to get a feel for what direction these studies tend to go in a group setting. And again, as many of these authors that publish these kinds of studies state that contradictory findings may be due to differences in study design or, yes, let's blame the patient characteristics of participants with regard to the age, sex, and other conditions. But there is some data that actually is quite good and very intriguing. So this is a 2007 study that's frequently quoted. It was done in a Japanese population looking at apple cider vinegar and its effect on weight and weight loss specifically. So you can see that they took a study cohort with a wide variety of BMIs, but they're high, obviously, for a Japanese population. Age range, as you can see, and some inclusion criteria, stable weight for one month, no other medications. It's a very curious study, even though it's very small in numbers, as so many of these studies are. But look at the distribution of males to females. It's two to one. Usually you see it the other way around, where you see more females being actually enrolled than males. So I think that was unique to this. And you can see, again, the BMI, the age range, and so on. And what they did is they actually had each of the individuals, the whole cohort was divided into three groups. And each of the individuals in the three groups, one was placebo, so you had a 500 cc liquid intake without any apple cider vinegar. Another group had what was called a low dose approach, which was 15 cc's mixed into that 500 cc's of water. And another group had a high dose, which was defined as 30 cc's. And they tried to do a three-week pretreatment period, 12-week treatment period, and a four-week post-treatment period, just to see the effects. And this is what they saw with regard to fat area. This is a change in fat area that was measured. In the very dark bars are actually the high dose apple cider vinegar intakers. In the lighter is the low dose, and in the white is the placebo. And so SFA, if you look on the left, is subcutaneous fat. Visceral fat is a group in the middle, and total fat is on the end. And this is actually rather appealing and surprising, and certainly would suggest that there was some benefit, at least with regard to measuring fat intake. The problem, however, is that this did not translate into any kind of significant weight loss. So you can see here, if we just look at, let's say BMI here, and at the very bottom, the high dose, and just kind of follow the numbers across, you can see where people started out, at a BMI of 27. And then if you look at week 12, which is the end of their treatment, 26.3, not a very impressive weight loss. And then if you look at what happens after they go off, well, they're kind of back to where they started. And that's the same thing, actually, with the other groups. So the weight loss itself was not impressive, despite the change in the fat area. Another group that was looked at was actually in a cohort of Lebanese adolescents and young adults who were overweight or obese. And this was an RCT. 120 participants, so not, again, a huge study, looked at over a rather short period of time of only four weeks. You know, again, one of the problems and challenges of all of the literature in this area. And again, they tried to divide people into placebo group and a group that was taking a higher and lower dose. In this case, there were two lower doses and one higher dose. So 5 cc's, 10 cc's, 15 cc's, and a smaller amount of water. This time, 250 cc's. And they tried to mimic the taste of apple cider vinegar by lacing the placebo group's water with lactic acid. So it would taste a little bit like vinegar and eliminate that potential confounder. And if we look at this group, there actually was a little bit more impressive change in weight. Again, if we take, let's say, group 3, which was the higher dose, the highest dose of apple cider vinegar, starting out, again, at weight kilogram, if we look at 77, and then by week 12, you can see 70. So that's a weight loss of 7 kilograms. Again, wide variability in success and response. But this does suggest that perhaps there might be something to this. You can look at the same results with regard to the BMI. And again, you can see that there does seem to be at least a little bit of a signal in this particular cohort that apple cider vinegar was successful in actually inducing a mild weight loss. Unfortunately, they did not look at what happened or report what happened after they went off again. And again, I think we all can be a little suspicious that we see the same thing as we do with all weight loss approaches, that the weight comes back up again. This is a systematic review of a number of different kinds of studies with different kinds of agents. I just wanted to point out on the very top, the apple cider vinegar group. What they looked at were reports that would combine the apple cider vinegar with another agent that's been reported to cause weight loss. We have cinnamon, we have curcumin, we have fenugreek seeds, and we'll talk a little bit about that in a second. Ginger. And then I think they also looked at just what happened if you took the apple cider vinegar alone. And you can see there's a little signal. Adding something to apple cider didn't make a difference. But again, if you looked at all of these studies combined, if you believe in meta-analyses as giving us direction, that the apple cider vinegar group, and that's actually the fifth little line down, was way to the positive of actually inducing some weight loss. And this was very recently published, as you can see, just last year. There was also an attempt to try and tease out actually not just weight loss, but the effect of apple cider vinegar on diabetes. And it's a little bit of a different picture if you look at this in the meta-analysis. So again, you see the same kind of distribution between apple cider vinegar and something else added to it, and then apple cider vinegar alone. And again, you can see, actually, in all of those top markers that they're all to the positive results, suggesting that perhaps for glucose, there indeed may be something positive to apple cider vinegar intake. And this isn't just with regard to HbA1c being improved, but also with regard to, I think we're missing a slide here. Hold on one second. Oh, fasting glucose. Also, generally looking like it's being improved, not as consistently as A1c, but again, the suggestion that apple cider vinegar did well with regard to its effect on glucose. The problem is to explain how this actually happened, because if you look at insulin resistance as measured by HOMA-IR, there's no effect whatsoever. There's not a direct insulin effect, and it kind of begs the question as to if you ingest the apple cider vinegar, is your appetite turned off, so you just don't take in anything more in terms of caloric intake? So the mechanism is a little hard to understand, and it certainly has not been looked at in any kind of degree. What are the potential side effects? Well, there clearly is a concern, and it's been well-published, that there is erosion of tooth enamel. So the recommendation is always to use it in some kind of diluted form, and perhaps even ingest it with a straw. There also have been some reports of esophageal erosion. Again, reemphasizing the need to use a diluted form or to use it in cooking and mixing it into a vinaigrette or an olive oil or, heaven forbid, a fizzy drink, but it's been recommended. I can't imagine somebody using it in a fizzy drink, but it has been recommended. For glycemic control, it doesn't take very much. The equivalent of the studies of what I actually just showed are just one to two tablespoons in water. So you don't need very much. A little bit of a concern, although quite rare, is that there also have been reports of hypokalemia with ingestion of apple cider vinegar. So again, something to keep in mind with regard to patients when you discuss potential side effects. And then I do want to continue and probably end with this supplement, and that is looking at fennel and fenugreek seeds. Again, very popular in the press, lay press and web, and there is some data that this actually can have some positive effect. It's an herb of the soy family, originated from India and North Africa, and fennel, which you see on the upper part is the bulb versus the fenugreek seeds, actually they've been used quite over a period of time to control appetite. About 50% of the seeds are mainly fiber. So again, it kind of breaks the same question as with the lignans. Is this really a fiber effect that's really causing people to feel full and then induce a reduced food intake? The seeds have been shown to have effects on lowering blood sugar in both clinical human as well as animal studies. And some of the challenges with this are that many of the previous studies have used the fennel essential oil or fenugreek fiber extracts, and oil is particularly difficult to get. So again, it kind of questions the practicality of using this. However, there are some interesting studies to actually show that this may be effective, whether indeed it's fenugreek tea or fennel tea. And this was actually done, as you can see, in Korean women who are felt to be overweight, and it was a crossover study. It's kind of an elegant study if you look at it. People were screened, and then week one, they actually were divided up into placebo tea intake, or a fennel tea intake, or a fenugreek tea intake. After another week with washout, they then were redistributed, so everyone kind of changed the particular groups that they were in. Again, a washout period, and then again, they had another week of everyone being kind of re-sorted out. If you look at the results, and you can see actually in the round kind of orange circles are the placebo group as compared to the other two lines, both with regard to the fennel tea as well as the fenugreek tea, that there was clearly evidence with some positive results. So hunger was reported as significantly lower for the fenugreek tea. Fullness at 90 minutes and 210 minutes, again, significantly higher for both teas rather than placebo as compared to placebo. The desire to eat, so these are all reports, obviously. There's no way to measure a sense of fullness or a desire to eat, but seemed to favor the teas. And prospective food consumption measured at 90 minutes and 210 minutes, which actually can be measured in terms of intake, did seem to be lower for both teas as compared to placebo. So for at least this particular patient or cohort, there did seem to be some positive effect of the fenugreek as well as fenugreek teas in affecting appetite. Again, one week, one can question is this long enough to know, but the report is there as measured. If we look at various herbs on glycemic control, particularly if we look at meta-analyses and trying to combine to get enough numbers, to get enough of a feel that there is certainly a positive signal, a number of studies have included other ingredients such as clove, thyme, turmeric, ginger, cinnamon, cumin. I mean, there's a huge variety of these different kinds of proponents that have been suggested to affect, actually, glycemic control. But if you look at this particular meta-analysis, the focus was actually on people who had diagnosed type 2 diabetes, and they specifically looked at studies that measured either effect on fasting glucose and or A1C and or insulin dosing. And so if you look at this, the graphic actually shows a little bit of cinnamon intake, but an attempt to see is there really a signal there that comes through. The results suggested that fasting glucose did improve, as you can see, with cinnamon, turmeric, ginger, black cumin, and saffron. Most significant fasting glucose improvement, and as you can see, defined by a fairly robust change and decrease, was with black cumin, cinnamon, and ginger. A1C seemed to favor, improvement in A1C seemed to be favored by ginger and black cumin. Insulin dose decreased with cinnamon and ginger. So you're getting a sense that these are not consistent in their effects overall, but that certain agents may be beneficial for some changes. The only one that showed consistently improvement over all parameters, so specifically a decrease in fasting glucose, a decrease in A1C, and a decrease in insulin dose that was needed to control glucose was ginger. So again, take that for what it is. But again, the authors were really reluctant to come through and say, yes, everyone should take ginger if you have diabetes or prediabetes or a tendency towards hyperglycemia, because they stated that the problem with so much is the difficulty in looking at so many multiple doses that people are using in these studies. Some studies show benefit, others do not. So how do you judge which one has the power to have the recommendation made? And again, variable factors, different baseline weights, different BMI changes, the combination of supplement use, and again, not accounting for differences in physical activity or lifestyle. So it's a great review. I can see it actually came out this year, earlier this year. So I would suggest everybody kind of refer to that if you really wanted to look at the so-called nitty gritty of all of these reports. So a systematic review, again, I referred to this earlier. And the problem that we have, again, is, as I mentioned, consistency, looking at what's real versus what's not real. And I think to take the final kind of perspective that if we look at an FDA drug base that actually looked at, you can see, just under 800 dietary supplements, the percentage of supplements specifically marketed for weight loss was significant. But again, the studies that we have to really feel that we have any kind of confidence in recommending any of these for someone really doesn't support any kind of high-quality evidence in the efficacy. So this is an area that clearly begs additional research, additional looking at, a challenge for all of us to discuss with our patients what should or should not be taken. You know, there's always the caveat, as I talk about with my patients, and I live in an area that has an institute called the Bastyr Institute. It's actually an institute based on supplement use, alternatives to prescription medicine. Although if you talk to their practitioners, they do indeed sneak in a pharmacologic agent here and there. But there's nothing wrong with trying something if there's a safety that can be, indeed, you personally feel comfortable that the patient can not have any side effects from. And so there's nothing lost. In fact, what you may gain is the confidence of your patient that you're willing to work with them in further improving their health. Thank you.

dietary supplements

healthcare challenges

supplement efficacy

weight loss

glycemic control

berberine

apple cider vinegar

herbal remedies