WEBVTT 00:00.000 --> 00:06.300 Hey everybody, it's Mikki here. You're listening to Mini-Mikkipedia on a Monday. 00:06.300 --> 00:13.760 I hope you had a great weekend. And in fact, last week, cracking week, as they all are, 00:14.320 --> 00:20.240 I got a text in a WhatsApp group that I'm part of just with a couple of my very smart friends. 00:20.700 --> 00:27.960 And one of them put a link to an article that was in the NZ Herald. And the headline reading, 00:27.960 --> 00:34.400 popular supplements could harm the aging brain. And I'm like, oh yeah, that's interesting. I 00:34.400 --> 00:40.200 wonder what's going on here. And she had a note in there saying, is this just healthy user bias 00:40.200 --> 00:46.120 that people who are concerned with their brain health might already have a small amount of 00:46.120 --> 00:50.880 sort of cognitive decline. They start taking supplements and then this sort of reverse 00:50.880 --> 00:56.540 association relationship occurs. And I'm like, I'd actually love to dig a little bit deeper 00:56.540 --> 01:01.140 into the article, see what it's saying. And then where are they even getting their information 01:01.140 --> 01:06.960 from? So the article itself was originally a Washington Post article that was published 01:06.960 --> 01:14.580 last week as well. And it was one article discussing vitamin D, omega-3 and glucosamine. 01:15.100 --> 01:21.260 However, these come from three different recent studies. So it wasn't just one study. 01:21.880 --> 01:26.180 And the caveat to all of this that I'm about to go into, 01:26.540 --> 01:31.380 that even though the original article acknowledges that the findings are preliminary, 01:32.220 --> 01:38.500 mostly observational, sometimes contradictory, and does not establish that these supplements 01:38.500 --> 01:44.640 cause cognitive decline. The thing with the headline is it's such clickbait for so many people 01:44.640 --> 01:50.060 who won't really read the finer details and will just look at some of the commentary that 01:50.060 --> 01:55.360 article provided. And of course, I will put the article in the show notes for you to have a look 01:55.360 --> 01:56.180 at yourself. 01:56.540 --> 02:03.140 Because as per usual, that headline asks a much stronger question than the evidence can currently 02:03.140 --> 02:11.080 answer. But humans being humans, we're going to think that it already has. So before getting into 02:11.080 --> 02:17.640 the individual supplements and studies, just sort of clarify what I mean by observational study 02:17.640 --> 02:23.720 versus a randomized controlled trial, which is the gold standard in this type of research when 02:23.720 --> 02:26.020 we're looking at one particular intervention. 02:26.540 --> 02:32.820 So an observational study is, as the name suggests, the researchers observe what people 02:32.820 --> 02:39.120 already do. So people taking a supplement can differ from non-users of supplements in dozens 02:39.120 --> 02:45.600 of ways. And this is something called the healthy user bias, like people who are interested in 02:45.600 --> 02:51.520 taking supplements are probably also interested in being active, in monitoring their drinking, 02:51.520 --> 02:55.920 and not smoking, and watching their sleep, and all of those sorts of things, which, 02:55.920 --> 03:02.680 of course, researchers can statistically adjust in their analyses of whatever results they find. 03:03.060 --> 03:09.220 But you cannot adjust away that healthy user lifestyle. And you also can't adjust away for 03:09.220 --> 03:15.980 things that aren't measured. So there'll be maybe these other underlying factors related to 03:15.980 --> 03:20.080 supplement use that we aren't even aware of. So we don't know how to adjust them. 03:20.080 --> 03:25.840 So this associations that are found in observational studies, as I'll go on, 03:25.920 --> 03:32.820 to explain, they don't necessarily, or they certainly don't, suggest causation. But often 03:32.820 --> 03:38.920 that's where our brain goes. And often that's where newspaper headlines tend to lead us. 03:39.520 --> 03:44.920 And a really great way to think about an observational study is that they set the scene, 03:44.920 --> 03:52.600 or they are hypothesis producing, in that the results of an association study should then be 03:52.600 --> 03:55.900 taken into that randomized controlled environment to test the results. And that's where the 03:55.900 --> 04:00.520 data comes from. And that's where the data comes from. And that is, in fact, a very good contrast, 04:00.680 --> 04:06.820 that randomized controlled trial, to an observational study. So researchers randomly 04:06.820 --> 04:13.580 assign a particular supplement or intervention to a group that there are no differences, 04:13.860 --> 04:19.200 no indifferences between the different groups in the study. So all groups, all people within the 04:19.200 --> 04:23.660 groups, there are sort of selection criteria for which you would be involved in a study. 04:23.660 --> 04:25.880 And then everyone is randomized to, 04:25.900 --> 04:32.040 a particular group. And because of that randomization process, no one is, as at that 04:32.040 --> 04:36.980 group level, no one is different from one group to the next. And it means that these groups are 04:36.980 --> 04:45.060 much more comparable. So if observational studies suggest harm, but a randomized controlled trial 04:45.060 --> 04:52.480 on that particular observation wasn't able to reproduce the harm or reproduce the finding, 04:52.480 --> 04:55.260 we have to be quite cautious about, 04:55.900 --> 05:01.580 including that the observational research was correct. Because literally that randomized 05:01.580 --> 05:06.900 controlled trial was designed to test the mechanism that the observational trial sort 05:06.900 --> 05:13.440 of brought up. Anyway, and that really is, has to be an underlying theme as I go through some of what 05:13.440 --> 05:18.800 this article was suggesting, and then actually what the studies associated with the article 05:18.800 --> 05:24.840 actually found. So let's think about vitamin D, for example, and this is a really important 05:24.840 --> 05:25.620 nutrient. 05:25.900 --> 05:31.480 Some people call it a hormone, and it is involved in many, many different pathways in the body. And 05:31.480 --> 05:36.320 of course, we talk about vitamin D a lot over here in New Zealand, particularly in winter, 05:36.320 --> 05:43.260 because we synthesize the majority of our vitamin D from the sun. But for many months of the year, 05:43.420 --> 05:49.300 the sun's UVB rays aren't strong enough for our body to synthesize vitamin D. And therefore, 05:49.300 --> 05:55.740 we need to take it as a supplement. Now, in the British Medical Journal Open study in 05:55.740 --> 06:02.820 2026, a database from the US Health and Retirement Study was used to look at vitamin D and cognitive 06:02.820 --> 06:11.160 decline. So there were over 5,000 adults, their average age was 67 and a half years. 40% of those 06:11.160 --> 06:18.680 users took vitamin D, and they followed these people for six years. And they assessed the 06:18.680 --> 06:25.140 population for global cognition, memory, and executive function. And this was not a randomized 06:25.140 --> 06:25.720 vitamin D study. It was a randomized vitamin D study. And they assessed the population for global 06:25.720 --> 06:26.260 cognition. And they assessed the population for global cognition. And they assessed the population 06:26.260 --> 06:26.480 for global cognition. And they assessed the population for global cognition. And so a lot 06:26.480 --> 06:27.180 of the countries were not following the data. And they assessed the population for global 06:27.180 --> 06:27.620 cognition. And they assessed the population for global murmurs, and calculates their average 06:27.740 --> 06:31.660 People simply reported whether they took vitamin D or not, which is how they came up with the number 06:31.660 --> 06:36.680 of people that actually took vitamin D. And what they found across that six years was that 06:36.680 --> 06:45.220 vitamin D users had a statistically faster decline in global cognition and executive function. Memory 06:45.220 --> 06:50.740 decline was not statistically significantly different. So the association appeared primarily 06:50.740 --> 06:55.700 in people who started with what the researchers classified as adequate vitamin D status, 06:55.700 --> 07:02.500 rather than those that were deficient or insufficient so let's have a look at what 07:02.500 --> 07:11.520 they actually found so global cognition was 0.052 points a year lower in vitamin d users 07:11.520 --> 07:19.340 and executive function was 0.021 points per year lower and to put that effect size into context 07:19.340 --> 07:27.000 the global cognition scale went up to 27 so the excess decline associated with supplement use 07:27.000 --> 07:37.740 across those six years was essentially 0.31 points so 0.31 out of a 27 point scale so whilst 07:37.740 --> 07:44.480 it was statistically significant can you really tell me that one third of a point across 27 points 07:44.480 --> 07:49.100 is clinically important i don't know i would probably argue not 07:49.100 --> 07:49.320 you 07:49.340 --> 07:54.120 and you've got to remember that sometimes a real strength of a study is the fact that they are 07:54.120 --> 07:59.640 looking at thousands of participants right so that is you know obviously a strength however 07:59.640 --> 08:04.880 the reverse is actually true as well is that when you get large databases like that you can detect 08:04.880 --> 08:09.780 very small differences and they can be statistically significant even if they're 08:09.780 --> 08:14.600 not clinically important and i think that's a really worthwhile thing to sort of bear in mind 08:14.600 --> 08:19.100 there were some big limitations to the study so they did not know the actual 08:19.100 --> 08:19.320 actual value of the study and they didn't know the actual value of the study and they didn't 08:19.340 --> 08:21.640 know it to a great extent also because of the fact that they were normally taking vitamin d 08:21.640 --> 08:27.300 dose in sufficient detail so you could have been taking 400 international units or iu you could be 08:27.300 --> 08:33.760 taking 2 000 iu or 5 000 iu and all of these people were sort of lumped into that broad category of 08:33.760 --> 08:40.460 vitamin d user you can see that it was such a vast difference between the dosing and also of course 08:40.460 --> 08:46.340 as with a lot of nutrition supplement use was self-reported in addition to that vitamin d users 08:46.340 --> 08:49.100 were already actually different from the non-users so vitamin d users were actually the ones that were 08:49.100 --> 08:54.520 For example, their baseline global cognitive scores were slightly higher. 08:54.800 --> 08:59.180 They were 16.3 out of that 27 versus 15.8. 08:59.500 --> 09:02.160 So residual confounding also remains possible. 09:02.760 --> 09:09.800 And when vitamin D users were compared specifically with people taking neither a vitamin D or 09:09.800 --> 09:19.280 a multivitamin, the difference fell to 0.044 points per year, which was no longer statistically 09:19.280 --> 09:19.980 significant. 09:20.580 --> 09:27.000 So on observational level, there was a slight difference in that global cognition and that 09:27.000 --> 09:34.200 executive functioning by 0.3 of a point across six years, but that was pretty much it. 09:34.500 --> 09:36.500 And this was just an observational trial. 09:36.500 --> 09:39.340 So what actually happens when we randomize vitamin D? 09:39.340 --> 09:42.820 And I think this is a really important point and an important comparison. 09:43.260 --> 09:51.120 There was a study called VITAL, and it randomized older adults, similar age, 60 plus, to 2,000 09:51.120 --> 09:56.180 international units of vitamin D3 a day versus taking nothing at all. 09:56.640 --> 10:03.660 And there was a cognitive sub-study within that that had 4,000 adults who were, as I 10:03.660 --> 10:08.880 said, aged over 60, and they found no significant difference in cognitive decline between these 10:08.880 --> 10:09.300 groups. 10:09.860 --> 10:13.140 And there was no interaction with baseline vitamin D status. 10:13.320 --> 10:14.600 So that's interesting as well. 10:14.720 --> 10:20.460 Like in the previous observational study, those people taking vitamin D tended to have 10:20.460 --> 10:24.800 an adequate status, whereas here, there was no sort of interaction with that vitamin D 10:24.800 --> 10:25.200 status. 10:25.860 --> 10:31.220 So the major take-home probably is that there isn't good evidence that taking vitamin D 10:31.220 --> 10:37.460 when you already have adequate vitamin D stores prevents cognitive decline. 10:38.260 --> 10:39.220 And this new... 10:39.340 --> 10:44.760 This new observational study, as highlighted by this newspaper report, it also doesn't 10:44.760 --> 10:49.160 establish that ordinary vitamin D supplementation causes cognitive decline. 10:49.520 --> 10:52.500 Yet that is sort of the message that's pervading that article. 10:53.160 --> 10:57.380 So the take-home for me that I think all of us should be thinking about is we need to 10:57.380 --> 11:03.420 correct a deficiency, we should aim for adequacy, and also don't automatically assume that pushing 11:03.420 --> 11:06.120 a nutrient higher and higher creates benefit. 11:06.640 --> 11:09.320 But if you are taking vitamin D, you don't really need to be worried about that. 11:09.340 --> 11:10.960 You don't need to be worried about your cognitive function. 11:11.420 --> 11:16.780 Now, this one really surprised me, the next supplement that they looked at, and that was 11:16.780 --> 11:18.580 omega-3 or fish oil. 11:19.040 --> 11:23.880 So there was a 2026 paper in the Journal of Prevention of Alzheimer's Disease, and they 11:23.880 --> 11:29.340 used the data from the Alzheimer's Disease Neuroimaging Initiative, or ADNI. 11:30.000 --> 11:34.360 And so that's an important context because this wasn't just a random sample of healthy 11:34.360 --> 11:35.200 older people. 11:36.100 --> 11:39.200 ADNI specifically follows people across that cognitive system. 11:39.340 --> 11:45.380 So we're looking at cognitively normal, subjective memory concerns, mild cognitive 11:45.380 --> 11:48.220 impairment, right through to Alzheimer's disease. 11:48.800 --> 11:59.040 And researchers compared 273 omega-3 users with 546 matched non-users, and they followed 11:59.040 --> 12:02.280 them for around or a medium of about five years. 12:02.820 --> 12:08.780 And what they found was that omega-3 use was associated with faster decline across three 12:08.780 --> 12:09.320 cognitive systems. 12:09.340 --> 12:18.660 And these are all indexes or questionnaires looking at cognitive function, MMSE, ADAS, 12:18.920 --> 12:21.780 COG-13, and CDR-SB. 12:22.180 --> 12:28.620 And they found that in the MMSE, or mini mental state examination, that declined by an additional 12:28.620 --> 12:33.740 0.266 points per year amongst omega-3 users. 12:33.740 --> 12:39.000 The ADAS, COG-13, or Alzheimer's Disease Assessment Scale. 12:39.340 --> 12:44.920 That worsened by 0.823 points per year. 12:45.420 --> 12:55.920 And the CDR-SB, or Clinical Dementia Rating Sum of Boxes Scale, that increased by 0.205 12:55.920 --> 12:57.540 points per year faster. 12:58.020 --> 13:03.560 So different to vitamin D, this isn't just some sort of numerical difference. 13:03.560 --> 13:07.560 There is a signal here, and it is worth investigating. 13:08.160 --> 13:08.960 But it is still... 13:09.340 --> 13:10.960 An observational signal. 13:11.060 --> 13:12.500 And I think that's really important to remember. 13:12.580 --> 13:14.580 This is still just observing individuals. 13:15.060 --> 13:22.900 And what they were able to do was use an imaging technology to examine the metabolic activity 13:22.900 --> 13:24.240 of the brain. 13:24.780 --> 13:30.060 And so what they used was something called FDG PET, P-E-T. 13:30.360 --> 13:32.680 And I'm probably going to get this wrong, but I'll give it a go. 13:34.920 --> 13:37.360 Fluorodeoxyglucose positron emission topography. 13:37.860 --> 13:39.320 That was actually easier than I thought. 13:39.340 --> 13:42.380 So fluorodeoxyglucose PET. 13:43.200 --> 13:46.820 And essentially what they do is they inject a radioactive glucose-like tracer. 13:47.180 --> 13:51.800 They see how much glucose that the different brain regions actually take up. 13:52.020 --> 13:55.340 And lower uptake can indicate lower metabolic activity. 13:56.540 --> 14:03.340 And researchers found greater FDG hypometabolism in Alzheimer's vulnerable brain regions among 14:04.220 --> 14:05.400 those omega-3 users. 14:06.060 --> 14:08.240 So that is really interesting. 14:08.240 --> 14:09.240 And they said... 14:09.340 --> 14:14.860 So they thought, looking, using another statistical analysis, that this could explain anywhere 14:14.860 --> 14:22.120 between 19 and 41% of the relationships that we found in those scales that I just walked 14:22.120 --> 14:22.680 you through. 14:23.060 --> 14:29.220 Now, they didn't find any amyloid or tau or gray matter atrophy, which could explain that 14:29.220 --> 14:29.780 association. 14:29.960 --> 14:34.180 And that's worth mentioning because these are conditions which are definitely associated 14:34.180 --> 14:36.760 with that sort of progression to Alzheimer's. 14:36.760 --> 14:38.460 But I guess the thing is... 14:38.460 --> 14:44.160 Even with the FDG PET results, is that this just measures glucose metabolism. 14:44.160 --> 14:50.340 It does not directly measure neuronal death, mitochondrial damage, lipid peroxidation, 14:50.800 --> 14:56.780 DHA oxidation, DHA is a type of an omega-3, and synaptic destruction. 14:57.480 --> 15:00.160 So it is worth noting that as well. 15:00.720 --> 15:06.720 And I guess some of the sort of key criticisms and objections to the study that I've seen 15:06.720 --> 15:08.160 online since it's come... 15:08.460 --> 15:11.080 Since it was published is... 15:11.080 --> 15:14.160 Well, the biggest one is that the omega-3 intake wasn't randomized. 15:14.940 --> 15:24.280 So the matching was principally around factors such as age, sex, APOE4, genetic sort of presence, 15:24.640 --> 15:26.460 and also, of course, diagnosis. 15:26.960 --> 15:30.160 So this wasn't a randomized controlled trial. 15:30.420 --> 15:38.440 Again, it was just an associative trial looking at people that were already in that age, 15:38.780 --> 15:46.080 And so even when you match participants according to different age and sex, 15:46.580 --> 15:50.800 and even diagnosis, you can't account perfectly for things like 15:50.800 --> 15:54.820 why somebody started taking a fish oil, their overall diet health, 15:55.220 --> 16:00.240 their health consciousness, cardiovascular disease, supplement use in general, 16:00.680 --> 16:07.000 any sort of other cognitive concerns, socioeconomic factors, exercise wasn't accounted for, 16:07.000 --> 16:08.000 overall metabolic... 16:08.460 --> 16:13.280 Health and their ability to utilize glucose, and other unmeasured differences. 16:14.080 --> 16:19.660 And when I said that, you know, the study has been sort of challenged by other scientists, 16:20.100 --> 16:25.340 there were letters that were published subsequently raising concerns about exposure classification. 16:25.940 --> 16:28.080 You know, how long had they been taking the fish oil? 16:28.640 --> 16:30.560 Residual confounding from other factors. 16:30.560 --> 16:37.780 The fact that the FDG hypometabolism was interpreted as synaptic dysfunction, 16:37.780 --> 16:43.060 not adequately accounting for omega-3 status, or the formulation of the omega-3, 16:43.060 --> 16:48.420 how much EPA, how much DHA that these omega-3s are contained. 16:48.420 --> 16:53.460 And also, this is super important, the inconsistency with previous evidence 16:53.460 --> 16:56.660 showing that omega-3 was beneficial for the brain. 16:56.660 --> 17:02.220 And then when we compare it to a randomized trial, again vital, 17:02.220 --> 17:07.400 vital actually randomized older adults to receive one gram of marine omega-3, 17:07.400 --> 17:14.780 omega-3 a day, that provided 460 milligrams of EPA, 380 milligrams of DHA. 17:14.780 --> 17:16.960 And that was versus a placebo. 17:16.960 --> 17:22.840 And they had more than 4,200 older adults included in their cognitive analyses. 17:22.840 --> 17:26.660 This was for around two to three years, and they found no significant difference in cognitive 17:26.660 --> 17:28.000 decline. 17:28.000 --> 17:33.540 And interestingly, they found no benefit from taking the omega-3 with cognitive change. 17:33.540 --> 17:37.020 And in fact, vital found that fish oil really didn't change. 17:37.020 --> 17:39.080 It didn't change cognition. 17:39.080 --> 17:45.380 So it did not demonstrate that it improved cognition, but importantly, it does not demonstrate 17:45.380 --> 17:51.520 substantial cognitive harm suggested by that observational ADNI study. 17:51.520 --> 17:53.240 And that is a big distinction. 17:53.240 --> 17:58.360 So if you have, I guess, these two studies sitting together, and you're wondering where 17:58.360 --> 18:03.520 the sort of strength of evidence is, it has to be in that randomized control trial where 18:03.520 --> 18:06.620 they gave them set doses of omega-3s. 18:06.620 --> 18:09.460 Rather than what we see in observational studies. 18:09.460 --> 18:17.120 We know that omega-3 is so helpful for inflammation, cardiovascular disease, improving lipid profiles, 18:17.120 --> 18:22.880 vascular function, endothelial function, blood pressure, so much. 18:22.880 --> 18:30.120 And having dietary omega-3 rich foods, salmon, mackerel, sardines, other fatty fish, super 18:30.120 --> 18:31.120 important. 18:31.120 --> 18:33.620 Or taking a supplement also can be super beneficial. 18:33.620 --> 18:35.680 And I certainly take an omega-3 supplement. 18:35.680 --> 18:36.480 Pillar performance. 18:36.480 --> 18:39.420 Not that it's an ad, but that's what I take. 18:39.420 --> 18:43.880 What I think we know right now is that taking an omega-3 supplement purely because you think 18:43.880 --> 18:48.080 it will prevent dementia, that's just not that strongly supported right now. 18:48.080 --> 18:53.800 But one observational analysis is nowhere near enough to tell someone taking fish oil 18:53.800 --> 18:55.820 that it's damaging their brain. 18:55.820 --> 19:01.500 And one last supplement that they looked at in the article was glucosamine. 19:01.500 --> 19:05.420 And in fact, I am very familiar with glucosamine. 19:05.420 --> 19:11.040 It was sort of all the rage maybe 15 to 20 years ago in relation to joint health and 19:11.040 --> 19:17.820 helping sort of lubricate in and around the joints, knee osteoarthritis, hip osteoarthritis, 19:17.820 --> 19:19.280 along with chondroitin. 19:19.280 --> 19:26.540 Now this one, in this particular study, which appeared in Nature Metabolism 2026, looked 19:26.540 --> 19:30.780 at glucosamine and its role in Alzheimer's disease. 19:30.780 --> 19:33.460 And so this wasn't an observational supplement study, actually. 19:33.460 --> 19:34.460 The reason it wasn't an observational supplement study, actually, is that it was a study that 19:34.460 --> 19:35.420 looked at glucosamine and its role in Alzheimer's disease. 19:35.420 --> 19:41.300 And the researchers, elegantly really, they combined post-mortem human brains, Alzheimer's 19:41.300 --> 19:48.880 mouse models, experimental manipulation of glycosylation, and human electronic health 19:48.880 --> 19:54.600 records to look at all of these different mechanisms and the impact of glucosamine on 19:54.600 --> 20:01.360 that hyperglycosylation process that may drive Alzheimer's disease. 20:01.360 --> 20:04.160 So glycosylation, what even is it? 20:04.160 --> 20:09.000 Glycols attach carbohydrate structures called glycans to proteins and other molecules. 20:09.000 --> 20:12.280 And that's just like normal biology. 20:12.280 --> 20:17.640 Researchers have found that excess glycan production, hyperglycosylation, has been found 20:17.640 --> 20:19.800 in Alzheimer's brains. 20:19.800 --> 20:25.680 And when researchers reduced glycan synthesis in Alzheimer's mice, cognitive performance 20:25.680 --> 20:26.940 improved. 20:26.940 --> 20:31.500 And when they gave glucosamine, cognitive impairment worsened. 20:31.500 --> 20:34.040 So this is looking at that preclinical diagnosis. 20:34.040 --> 20:40.100 This is a preclinical trial in mice showing that glucosamine worsened cognitive impairment. 20:40.100 --> 20:42.240 But what happens in humans? 20:42.240 --> 20:45.340 So researchers then looked at electronic health records. 20:45.340 --> 20:51.980 They had a sample of 24,000 or over 24,000 people with Alzheimer's-related dementias. 20:51.980 --> 20:57.080 And they had 41,000, close to 42,000 people with mild cognitive impairment. 20:57.080 --> 21:01.820 And they followed these people up, or they had records for them for approximately five 21:01.820 --> 21:02.820 years. 21:02.820 --> 21:06.920 And they found that the glycosamine use was associated with approximately 25% greater 21:06.920 --> 21:12.400 progression from mild cognitive impairment to Alzheimer's-related dementia. 21:12.400 --> 21:17.620 And among people who already had Alzheimer's or a related dementia, there was an increased 21:17.620 --> 21:20.500 mortality risk by 25%. 21:20.500 --> 21:23.400 That sounds certainly concerning, right? 21:23.400 --> 21:28.120 But I guess I think the real thing I want you to remember is that you don't want to 21:28.120 --> 21:30.880 extrapolate it to everybody taking glucosamine. 21:30.880 --> 21:31.880 The human component is still the real thing. 21:31.880 --> 21:32.600 So that's the first thing. 21:32.600 --> 21:33.600 The second thing I want you to remember is that you don't want to extrapolate it to 21:33.600 --> 21:34.600 the retrospective observational data. 21:34.600 --> 21:38.860 So it does not prove glucosamine caused dementia progression. 21:38.860 --> 21:43.840 And critically, the signal was particularly relevant to people who may already have existing 21:43.840 --> 21:48.040 mild cognitive impairment or established neurodegenerative disease. 21:48.040 --> 21:52.460 So if you are one of these healthy 50-year-old people who's taking glucosamine for your 21:52.460 --> 21:58.700 knee, there's no evidence to suggest that glucosamine is increasing your risk of Alzheimer's 21:58.700 --> 21:59.700 disease. 21:59.700 --> 22:01.660 So to sort of tie all this together, what was that herald? 22:01.660 --> 22:04.780 Well, what was that herald article really telling us? 22:04.780 --> 22:08.060 We've got three studies, but they're not showing the same thing. 22:08.060 --> 22:14.680 With the vitamin D, we saw observational association with a very small excess decline that was 22:14.680 --> 22:19.720 found, but there is good randomized controlled evidence that it does not demonstrate harm. 22:19.720 --> 22:24.820 And then with omega-3, there was this interesting observational signal of a faster cognitive 22:24.820 --> 22:30.420 decline and that hypometabolism of glucose in the brain, but that directly conflicts 22:30.420 --> 22:31.460 with a randomized control. 22:31.460 --> 22:41.620 And with glucosamine, this was probably the most interesting signal because there is experimental 22:41.620 --> 22:47.700 biology supporting it, plus observational human evidence, but there is still insufficient 22:47.700 --> 22:51.440 evidence to conclude that glucosamine causes dementia in humans. 22:51.440 --> 22:55.380 And really, I mean, supplements are biologically active. 22:55.380 --> 23:00.460 And this is much broader than just these three supplements, this just means that even though 23:00.460 --> 23:04.860 they're not inert and more isn't always better. 23:04.860 --> 23:10.260 And I guess it's also important to again, state that one observational study showing 23:10.260 --> 23:15.320 harm doesn't suddenly turn an established supplement into a toxin. 23:15.320 --> 23:20.660 You always want to ask who was studied, were they deficient in that particular nutrient? 23:20.660 --> 23:21.900 How old were they? 23:21.900 --> 23:25.200 Did they already have cognitive impairment in this case? 23:25.200 --> 23:26.600 What dose was used? 23:26.600 --> 23:28.620 Was supplementation actually measured properly? 23:28.620 --> 23:29.620 Was the exposure of the supplement actually measured properly? 23:29.620 --> 23:29.820 Was the exposure of the supplement actually measured properly? 23:29.820 --> 23:31.760 Was the exposure randomized? 23:31.760 --> 23:33.360 How long were they exposed? 23:33.360 --> 23:35.060 How big was the effect? 23:35.060 --> 23:40.060 Does the finding here agree with the randomized control trials, which really are gold standard 23:40.060 --> 23:42.980 when we're thinking about these one supplement studies? 23:42.980 --> 23:47.080 Is there a plausible mechanism with which this could even be an issue? 23:47.080 --> 23:49.780 And has the study been replicated? 23:49.780 --> 23:54.060 And that is how you interpret the study rather than the headline that the Herald is giving 23:54.060 --> 23:55.060 you. 23:55.060 --> 23:59.220 So vitamin D, you do want to supplement to correct or prevent deficiency where appropriate. 23:59.220 --> 24:02.220 And it is appropriate here in New Zealand, particularly during winter. 24:02.220 --> 24:07.460 There is not convincing evidence that higher vitamin D protects cognition once you're replete, 24:07.460 --> 24:13.280 but neither is there persuasive evidence from these data that usual supplementation damages 24:13.280 --> 24:14.280 the brain. 24:14.280 --> 24:18.360 And with omega-3, fish and seafood remain excellent foods. 24:18.360 --> 24:19.360 Obviously. 24:19.360 --> 24:23.880 Omega-3 supplementation hasn't convincingly prevented cognitive decline in randomized 24:23.880 --> 24:29.220 controlled trials, but current evidence also doesn't justify telling people that fish or 24:29.220 --> 24:30.220 vegetable oil is neurotoxic. 24:30.220 --> 24:35.400 And for what it's worth, it is one of my go-to supplements for a range of different reasons. 24:35.400 --> 24:38.400 And glucosamine, this is particularly interesting. 24:38.400 --> 24:43.040 If you are an individual with mild cognitive impairment or established dementia, you do 24:43.040 --> 24:44.880 want to watch this one. 24:44.880 --> 24:49.700 And I think what we have to wait for is replication of study findings. 24:49.700 --> 24:52.960 And ideally you'd have some intervention data here as well. 24:52.960 --> 24:55.080 So there's mini Mikkipedia for you. 24:55.080 --> 24:58.280 If you saw that article last week and were a little bit panicked by what it told you, 24:58.280 --> 25:02.620 hopefully this just alleviates some of your fears. 25:02.620 --> 25:06.160 And if you didn't see it, I've got the link in the show notes for you as well. 25:06.160 --> 25:07.160 Yeah. 25:07.160 --> 25:08.940 Keen to hear your thoughts. 25:08.940 --> 25:14.560 Hit me up on Instagram threads or X at Mikki Williden Facebook at Mikki Williden nutrition 25:14.560 --> 25:16.980 or head to my website, Mikki Williden.com. 25:16.980 --> 25:21.200 I've got this recipe portal with over a thousand recipes. 25:21.200 --> 25:22.560 It's 12 bucks a month. 25:22.560 --> 25:26.660 I'm constantly adding to it and they are macro friendly. 25:26.660 --> 25:27.660 They are carb appropriate. 25:27.660 --> 25:29.420 They are higher protein. 25:29.420 --> 25:30.680 They are higher fat. 25:30.680 --> 25:33.760 Some of them in the early days, there's something for everyone there. 25:33.760 --> 25:36.540 If you want some quick, easy, tasty meals to add to your repertoire. 25:36.540 --> 25:37.540 All right, guys, you have the best week. 25:37.540 --> 25:37.580 See you later.