WEBVTT - Ep 98 Folate: Marmite, anyone? 0:00:02.040 --> 0:00:05.760 The number of cases of tropical macrositic anemia treated with 0:00:05.880 --> 0:00:10.040 marmite was not large, in all twenty two, many of 0:00:10.080 --> 0:00:12.520 which could be followed up only for a short time. 0:00:13.200 --> 0:00:16.919 The results of the treatment were, however, so striking that 0:00:17.000 --> 0:00:20.119 I feel justified in reporting them more, especially as I 0:00:20.160 --> 0:00:23.000 am leaving India and shall not be able to continue 0:00:23.000 --> 0:00:26.200 the work further. It is hoped that other workers will 0:00:26.200 --> 0:00:29.520 be encouraged to give the treatment a trial. At present, 0:00:29.680 --> 0:00:32.600 it is only possible to state that in marmite, and 0:00:32.720 --> 0:00:35.960 possibly in other yeast extracts, there appears to be a 0:00:36.080 --> 0:00:39.919 curative agent for this dread disease, which equals liver extract 0:00:40.000 --> 0:00:43.640 in potency and has the advantage in India of being 0:00:43.680 --> 0:00:46.120 comparatively cheap and of vegetable origin. 0:01:31.640 --> 0:01:35.240 I love that, and it's also I love how full 0:01:35.280 --> 0:01:36.160 of spoilers it is. 0:01:36.480 --> 0:01:40.760 It is so full of spoilers, and I'm gonna I'll 0:01:40.800 --> 0:01:44.919 tell you enough now to hopefully just like give teasers 0:01:44.920 --> 0:01:46.160 so that you'll want to learn more. 0:01:46.520 --> 0:01:47.360 Entice us all. 0:01:48.480 --> 0:01:52.720 So. That is from a paper by Lucy Wills published 0:01:52.760 --> 0:01:57.800 in nineteen thirty one, and it plays a huge role 0:01:58.040 --> 0:02:02.680 in the history of discovery of foll late and folic acid. 0:02:03.160 --> 0:02:06.280 Woooo the topic of today's episode. 0:02:06.720 --> 0:02:07.280 That's right. 0:02:08.040 --> 0:02:11.680 Hi, I'm Aaron Welsh and I'm Erin Allman Updike. 0:02:11.600 --> 0:02:13.799 And this is this podcast will kill you. 0:02:14.480 --> 0:02:16.560 A vitamin deficiency today. 0:02:16.880 --> 0:02:19.040 You know, I was thinking that it's been a really 0:02:19.080 --> 0:02:20.600 long time since we did this. 0:02:21.040 --> 0:02:24.040 Yeah, it's been I think since scurvy, right. 0:02:24.000 --> 0:02:26.120 I think I wrote that in my notes. Hasn't been 0:02:26.160 --> 0:02:31.399 scurvy question mark. Yeah, And there are so many more vitamins. 0:02:31.200 --> 0:02:33.799 It's it's amazing. So I'm glad that we're tapping back 0:02:33.840 --> 0:02:34.240 into this. 0:02:34.680 --> 0:02:34.960 Yeah. 0:02:35.080 --> 0:02:36.360 Yeah, it's gonna be a fun one. 0:02:36.520 --> 0:02:40.480 Yeah, it's really it's always there's always more there than 0:02:40.520 --> 0:02:44.240 we expect from the beginning. Keep learning this lesson somehow, 0:02:44.280 --> 0:02:44.560 I know. 0:02:44.840 --> 0:02:47.640 I know, And I will say, like, because we had 0:02:47.639 --> 0:02:50.080 talked about doing vitamin D and Ricketts, like we've been 0:02:50.080 --> 0:02:51.040 talking about that one. 0:02:50.880 --> 0:02:51.800 For a while now. 0:02:52.040 --> 0:02:55.160 Yeah, and so when you suggested fole ate and full 0:02:55.200 --> 0:02:59.480 like acid, I was like, Okay, that's fine, it's interesting 0:02:59.560 --> 0:03:02.120 at all. But then I was like reading about it, 0:03:02.160 --> 0:03:04.600 I was like, oh, it's so much more interesting than 0:03:04.639 --> 0:03:07.840 I even realized. I love when I'm so wrong about that. 0:03:09.840 --> 0:03:11.920 Well Erin what time is it? 0:03:11.919 --> 0:03:13.800 It is quarantiny time. 0:03:14.040 --> 0:03:17.200 That's fantastic news. What are we drinking this week? 0:03:17.520 --> 0:03:20.320 Well, we're drinking fortified. 0:03:20.560 --> 0:03:25.040 Fortified, and what is in fortified It. 0:03:25.200 --> 0:03:31.040 Is a long list of vegetables and fruits that have 0:03:31.160 --> 0:03:32.720 a lot of folate in them. 0:03:33.360 --> 0:03:34.680 Yep, let me tell you about it. 0:03:35.080 --> 0:03:39.760 We've got orange juice, papaya, banana, canalope, and maybe some 0:03:39.800 --> 0:03:46.200 spinach and of course vodka in ours. So a very 0:03:46.280 --> 0:03:48.880 high fol ate alcoholic smoothie for yeah. 0:03:49.160 --> 0:03:52.600 Yeah. I went to the NIH had like a table 0:03:52.800 --> 0:03:56.520 of fully containing foods by order, and I went through 0:03:56.640 --> 0:04:00.360 and I was like, hmm, boiled spinach. I don't know 0:04:00.400 --> 0:04:07.160 if that's gonna work. Hmmm, liver, Brussels sprouts, spaghetti, black 0:04:07.200 --> 0:04:10.320 eyed peas, to like, all delicious foods. But I was like, 0:04:10.400 --> 0:04:14.080 none of these really fit that well into a cocktail, 0:04:14.520 --> 0:04:17.320 and so I kept going down the list until I 0:04:17.440 --> 0:04:21.520 found a little more some more fun mixers. 0:04:21.240 --> 0:04:25.760 Yeah, a little more quarantiny friendly items. We'll post the 0:04:25.800 --> 0:04:28.680 full recipe for that quarantini as well as the non 0:04:28.760 --> 0:04:32.200 alcoholic placeba Rita, which is going to be so delicious. 0:04:32.320 --> 0:04:34.839 Oh yeah, on our website. This podcast We Kill You 0:04:34.839 --> 0:04:37.279 dot com and all of our social media channels. 0:04:37.760 --> 0:04:41.479 Also on our website, you can find the sources for 0:04:41.680 --> 0:04:44.920 all of our episodes. You can find transcripts. You can 0:04:44.960 --> 0:04:48.080 find bookshop dot org, affiliate account, and our Goodreads list. 0:04:48.400 --> 0:04:51.240 You can find music by Bloodmobile. You can find links 0:04:51.279 --> 0:04:54.720 to our merch and our Patreon. You can find alcohol 0:04:54.720 --> 0:04:58.800 free episodes. There's everything there and more. So check it 0:04:58.839 --> 0:04:59.880 out you should. 0:05:00.040 --> 0:05:02.000 It's a great website. 0:05:04.760 --> 0:05:06.120 I think it's time to get started. 0:05:06.400 --> 0:05:09.280 I think so too. I'm looking forward to this one. 0:05:09.360 --> 0:05:10.039 So let's take a. 0:05:10.080 --> 0:05:41.160 Quick break and then we'll get started. Full eight, or 0:05:41.440 --> 0:05:45.680 vitamin B nine as it's also called, No one ever 0:05:45.760 --> 0:05:51.960 calls it that is an essential vitamin, essential vitamin, meaning 0:05:52.160 --> 0:05:55.479 it's something that we need and we cannot make it ourselves, 0:05:56.080 --> 0:06:01.000 so we have to ingest it from dietary sources. Mostly 0:06:01.600 --> 0:06:05.960 like we kind of already said, leafy green vegetables that's 0:06:05.960 --> 0:06:12.160 like the number one most folate great, but also nuts, meats, 0:06:12.279 --> 0:06:13.760 lots of fruits, et cetera. 0:06:14.279 --> 0:06:17.160 I have a question about leafy greens, Okay, do they 0:06:17.160 --> 0:06:20.600 have to be boiled or cooked or anything? Or raw? 0:06:20.760 --> 0:06:23.600 Is also you can eat? You can get full late from. 0:06:23.680 --> 0:06:26.320 Yeah, you can get it from all. Okay, yeah, yeah, 0:06:26.520 --> 0:06:27.120 good question. 0:06:28.560 --> 0:06:32.360 And as I know, you'll talk about aarin in the 0:06:32.520 --> 0:06:35.240 US and Canada and a lot of other countries. Now, 0:06:35.480 --> 0:06:40.320 many of our grains are also fortified with folic acid. 0:06:41.080 --> 0:06:45.240 Now right off the top, let's define somethings, shall we. 0:06:46.600 --> 0:06:50.240 So fol late is actually kind of a generic term. 0:06:50.400 --> 0:06:53.920 It encompasses a lot of different forms of this vitamin 0:06:54.040 --> 0:07:00.520 B nine. There's dihydrofolate, there's tetrahydrofolate that gets convert into 0:07:00.560 --> 0:07:03.320 a lot of different forms of folate in our body. 0:07:03.680 --> 0:07:06.719 There's a lot of complicated names that have numbers and letters. 0:07:06.880 --> 0:07:11.840 These are all forms of folate. Folic Acid is the 0:07:12.000 --> 0:07:16.600 synthetic form of folate that is used in supplements and fortification. 0:07:18.240 --> 0:07:21.760 So folate is what you ingest, or various forms of 0:07:21.760 --> 0:07:24.480 folate is what you ingest from like your leafy greens, 0:07:24.640 --> 0:07:28.800 your meats, your nuts. When you ingest folate in its 0:07:28.880 --> 0:07:33.040 natural form, you only absorb about fifty percent of it. 0:07:34.040 --> 0:07:38.960 But the synthetic form folic acid is actually much more bioavailable, 0:07:39.040 --> 0:07:42.360 so you actually absorb one hundred percent of it through 0:07:42.440 --> 0:07:46.320 your gut wall. Why is that great question? I don't 0:07:46.320 --> 0:07:49.119 know this specific biochemistry of it. It's just more easily 0:07:49.160 --> 0:07:53.679 absorbed through our guts into our bloodstream. Okay, Now, either way, 0:07:54.240 --> 0:07:59.240 whether it's forms of folate or folic acid in our body, 0:07:59.520 --> 0:08:03.600 once we ingest this, it's absorbed in our guts in 0:08:03.640 --> 0:08:06.280 the very first part of our duodenum. It's like the 0:08:06.360 --> 0:08:10.240 first part of our small intestine, which I love. I 0:08:10.280 --> 0:08:13.000 don't know why, but I really get excited thinking about 0:08:13.000 --> 0:08:16.000 what specific parts of our intestines are absorbing what. 0:08:16.600 --> 0:08:18.880 That I've never thought about that, and now I want 0:08:18.920 --> 0:08:19.600 to know more. 0:08:19.840 --> 0:08:22.920 I know, I know, Sorry for just like starting a 0:08:22.920 --> 0:08:26.720 new little itch for you. Yeah, I do really love it. 0:08:27.880 --> 0:08:29.960 So this is if you would like to know, absorbed 0:08:29.960 --> 0:08:33.280 in the same part of our intestine as iron, and 0:08:33.360 --> 0:08:34.679 I think also vitamin C. 0:08:35.120 --> 0:08:36.040 That I could be wrong about that. 0:08:36.160 --> 0:08:41.400 Vitamin C one fascinating anyways, Once it makes its way 0:08:41.559 --> 0:08:45.319 through our gut wall, it travels mostly to the liver 0:08:46.559 --> 0:08:50.439 and has to be metabolized in order to be useful 0:08:50.480 --> 0:08:55.120 in order to serve its many functions. So whatever form 0:08:55.160 --> 0:08:57.600 of folate we ingest has to be converted in a 0:08:57.640 --> 0:09:03.000 series of reactions into that I mentioned earlier. Tetrahydrofolate, also 0:09:03.040 --> 0:09:11.400 called THHF, and this is the predominantly useful form of folate, which, okay, 0:09:11.520 --> 0:09:13.840 this is where I have to pause for a second 0:09:15.080 --> 0:09:17.840 and tell you that if we were to go into 0:09:17.840 --> 0:09:22.120 the really nitty gritty details of the metabolism of folate, 0:09:23.360 --> 0:09:25.600 it would be a lot of acronyms and a lot 0:09:25.600 --> 0:09:29.280 of biochemical pathways that are things I try to avoid. 0:09:31.640 --> 0:09:33.839 So we're going to talk about how. 0:09:33.679 --> 0:09:38.240 These compounds are used in a very broad picture way 0:09:38.600 --> 0:09:40.080 and why they're so important. 0:09:41.280 --> 0:09:43.040 I'm good with that, great, excellent. 0:09:44.200 --> 0:09:47.760 I do think it's worth noting that all of these 0:09:47.800 --> 0:09:53.120 forms of folate, including folic acid, eventually get converted into 0:09:53.160 --> 0:09:56.720 this THHF, which then goes on to be converted to 0:09:56.800 --> 0:10:03.320 other forms. It is by slightly different mechanisms, So folate 0:10:04.120 --> 0:10:07.840 in the natural form that you ingest from kale doesn't 0:10:07.880 --> 0:10:11.440 follow the exact same pathway as folic acid when it 0:10:11.559 --> 0:10:14.480 enters our body, but the end result is the same. 0:10:14.880 --> 0:10:15.240 Okay. 0:10:15.720 --> 0:10:18.720 So to get a little bit into the mechanisms of 0:10:18.800 --> 0:10:22.960 folate and why it's an essential vitamin that is so important. 0:10:24.559 --> 0:10:32.400 Fullate requiring reactions are collectively all called quote one carbon metabolism. 0:10:32.520 --> 0:10:35.880 It sounds very biochemistry e but it doesn't have to 0:10:35.880 --> 0:10:36.800 be that deep. 0:10:36.720 --> 0:10:40.040 As they say, they say, as they say. 0:10:40.880 --> 0:10:45.680 What one carbon metabolism entails basically is literally moving around 0:10:46.200 --> 0:10:48.800 one carbon or one methyl group. 0:10:49.800 --> 0:10:50.680 Okay, So. 0:10:52.400 --> 0:10:58.160 Tetrahydrofolate THHF, that active form of folate, through a series 0:10:58.280 --> 0:11:04.400 of many different interc connected cycles, essentially serves to move 0:11:04.559 --> 0:11:10.440 methyl groups single carbons with hydrogen around our cells like 0:11:10.600 --> 0:11:14.520 a courier. It can pick up one from one group 0:11:14.880 --> 0:11:17.360 and then run across the cell and give it to 0:11:17.600 --> 0:11:20.400 someone else. And then it might pick up a carbon 0:11:20.400 --> 0:11:24.040 group in a slightly different place on its structure and 0:11:24.080 --> 0:11:25.640 then bring it somewhere else. 0:11:26.800 --> 0:11:28.360 That's essentially what it's doing. 0:11:29.720 --> 0:11:32.880 But it turns out that the other players in our 0:11:32.960 --> 0:11:37.000 cells that folate THHF and all of its forms are 0:11:37.080 --> 0:11:41.720 helping to move carbons between are some of the most 0:11:42.040 --> 0:11:48.760 essential metabolic processes in our cells. So full late serves 0:11:49.080 --> 0:11:53.520 as an essential cofactor or co substrate. And we've talked 0:11:53.520 --> 0:11:58.360 about cofactors in our alcohol episode of ownings. It serves 0:11:58.400 --> 0:12:00.840 as a co factor in a whole whole bunch of 0:12:00.880 --> 0:12:05.640 different reactions. So I'll go over which reactions those are, 0:12:06.000 --> 0:12:09.160 and then I think it'll become very clear why we 0:12:09.200 --> 0:12:13.480 see the symptoms that we see from folate deficiency. First, 0:12:14.559 --> 0:12:18.160 folate is required for the synthesis of a bunch of 0:12:18.200 --> 0:12:22.440 different amino acids and proteins, so we need folate to 0:12:22.440 --> 0:12:25.440 be able to make amino acids to put together to 0:12:25.480 --> 0:12:29.880 make proteins. We also need folate to be able to 0:12:30.000 --> 0:12:34.880 make some kinds of RNA, which are also important to 0:12:34.880 --> 0:12:38.320 be able to make proteins because RNA is an essential 0:12:38.400 --> 0:12:45.080 part of protein synthesis also, and folate is essential for 0:12:45.160 --> 0:12:50.760 the synthesis of our actual DNA, so folate is required 0:12:50.840 --> 0:12:55.400 in the reactions to make purines and perimitings, which, if 0:12:55.520 --> 0:13:00.880 everyone can just remember Jurassic Park and the little DNA 0:13:00.960 --> 0:13:04.200 double helix and the ACTG that they go over in 0:13:04.280 --> 0:13:09.679 that follic acid is involved and required in the process 0:13:09.760 --> 0:13:12.600 to make the building blocks that make up our DNA. 0:13:13.360 --> 0:13:15.960 I didn't really look into this, or maybe I just 0:13:16.240 --> 0:13:19.120 didn't have my search terms right, but I think it's 0:13:19.559 --> 0:13:24.400 really fascinating to think about early life and fullate because 0:13:24.520 --> 0:13:28.920 there is diversity within organisms as to which ones can 0:13:29.000 --> 0:13:32.040 produce fullate of their own versus the ones that have 0:13:32.080 --> 0:13:35.960 to acquire it from these organisms, right exactly. 0:13:36.040 --> 0:13:40.040 So, like plants make folate, which is why we mostly 0:13:40.120 --> 0:13:44.440 get it from plants, some bacteria and archia also make folate, 0:13:44.640 --> 0:13:48.120 and a lot of fungi make folate, but animals. 0:13:47.800 --> 0:13:49.120 We just straight up can't do it. 0:13:49.440 --> 0:13:53.120 Yeah, it's really so interesting. 0:13:52.960 --> 0:13:56.720 And yet folate is required for all of life because 0:13:56.960 --> 0:13:58.280 it's required for DNA. 0:13:58.760 --> 0:13:59.800 It boggles the mind. 0:14:00.120 --> 0:14:03.120 I know. There's one other thing that folic acid is 0:14:03.160 --> 0:14:07.920 really important for. It's related to DNA. So folic acid 0:14:08.040 --> 0:14:12.400 is heavily involved in the process of DNA methylation. Methylation 0:14:12.559 --> 0:14:16.520 is a fancy term for moving those methyl groups, So 0:14:16.600 --> 0:14:20.880 folate is really involved in transferring methyl groups or carbon 0:14:20.920 --> 0:14:25.680 groups onto DNA. This process of methylation, what it does 0:14:25.720 --> 0:14:29.400 in our cells is it regulates gene expression. It essentially 0:14:29.520 --> 0:14:33.200 is like turning on and off a light switch, turning 0:14:33.280 --> 0:14:36.320 genes on when they need to be on and turning 0:14:36.400 --> 0:14:37.320 genes off. 0:14:37.160 --> 0:14:38.280 When they don't need to be on. 0:14:38.800 --> 0:14:46.600 Right, So, just knowing those things alone, the broad strokes, 0:14:47.640 --> 0:14:50.400 you can probably imagine some of the things that are 0:14:50.440 --> 0:14:54.680 going to happen. If you don't have enough folate, you 0:14:54.720 --> 0:14:58.040 aren't going to be able to build new cells because 0:14:58.080 --> 0:15:02.160 you're not going to be able to repl your DNA. 0:15:02.400 --> 0:15:05.000 You're also not going to be able to repair any 0:15:05.160 --> 0:15:09.920 damaged DNA or damaged cells because again you can't repair 0:15:10.400 --> 0:15:15.040 the building blocks of that DNA or potentially repair damage 0:15:15.040 --> 0:15:19.960 cells that require proteins or amino acids for repair. So 0:15:20.240 --> 0:15:23.880 a lack of folate is going to have effects literally 0:15:24.040 --> 0:15:28.720 anywhere and everywhere in our body. But primarily it's going 0:15:28.800 --> 0:15:32.560 to affect rapidly dividing cells. So it's going to affect 0:15:32.600 --> 0:15:35.880 areas of the body that need to make more cells 0:15:35.920 --> 0:15:41.160 and divide frequently, and it's going to affect growth, for example, 0:15:41.480 --> 0:15:42.920 a developing fetus. 0:15:43.600 --> 0:15:47.520 It also, I know this is absolutely jumping ahead, but 0:15:48.280 --> 0:15:51.880 hearing the explanation of how it all works and how 0:15:51.920 --> 0:15:57.560 important it is in rapidly dividing cells, it completely makes 0:15:57.600 --> 0:16:01.960 sense that we're harnessing sort of the power of a 0:16:02.160 --> 0:16:06.600 full eate deficiency to treat certain cancers. 0:16:08.120 --> 0:16:11.200 That was the last, like most exciting part about full ate. 0:16:11.360 --> 0:16:14.920 I'm so sorry. It's just like, don't be sorry. 0:16:15.000 --> 0:16:18.240 It means your brain put it all together exactly the 0:16:18.280 --> 0:16:19.080 way I hoped. 0:16:21.200 --> 0:16:23.240 Oh it is, it's so interesting. 0:16:23.600 --> 0:16:27.680 Yes, it's the full eate cycle. And truly, if you 0:16:27.720 --> 0:16:32.600 have even just a tiny modicum of interest in biochemistry 0:16:33.240 --> 0:16:37.280 or molecular biology, like getting down into the nitty gritty 0:16:37.440 --> 0:16:42.680 of these processes and these cycles, it really is fascinating 0:16:42.720 --> 0:16:46.000 because of how interconnected they are. But we're not going 0:16:46.080 --> 0:16:46.720 to do that today. 0:16:47.360 --> 0:16:50.240 Not everyone is that into it. Yeah, let's let's take 0:16:50.280 --> 0:16:53.240 a step back and go let's go back to what 0:16:53.360 --> 0:16:55.600 happens when you have a full eight deficiency. 0:16:55.960 --> 0:16:59.040 That's a great idea, let's get into it. So what 0:16:59.080 --> 0:17:04.560 are the symptoms of folate deficiency? Since folate is so 0:17:04.800 --> 0:17:08.040 essential for the production of DNA and the production of 0:17:08.080 --> 0:17:11.000 any cells that are going to rapidly divide, one of 0:17:11.119 --> 0:17:14.959 the most rapidly dividing sets of cells in our body 0:17:15.119 --> 0:17:20.600 are our blood cells, especially our red blood cells. So 0:17:21.080 --> 0:17:25.639 the again specifics of these reactions are very interesting in 0:17:25.680 --> 0:17:30.520 and of themselves. But for our red blood cells specifically 0:17:30.600 --> 0:17:34.520 to be able to divide, both folate and vitamin B 0:17:34.800 --> 0:17:39.960 twelve as well as iron, are all essential vitamins. So 0:17:40.280 --> 0:17:44.240 folate deficiency and not being able to divide our red 0:17:44.240 --> 0:17:47.520 blood cells correctly leads to a specific kind of anemia. 0:17:47.600 --> 0:17:54.960 That's called megaloblastic anemia. Megaloblasts are precursors to our red 0:17:55.000 --> 0:17:58.520 blood cells. So what happens in this type of anemia 0:17:58.600 --> 0:18:03.080 is that these red cell precursors can't keep dividing normally, 0:18:03.600 --> 0:18:06.960 So these like pre red blood cells just accumulate in 0:18:07.000 --> 0:18:10.439 our bone marrow and then they're ineffective. So you end 0:18:10.520 --> 0:18:13.520 up with anemia because you don't have enough actual functional 0:18:13.560 --> 0:18:14.399 red blood cells. 0:18:15.200 --> 0:18:18.439 I think this episode was the first time that I 0:18:18.480 --> 0:18:21.919 really began to realize just how many different types of 0:18:21.960 --> 0:18:26.560 anemia there are, and how many terms there are. And 0:18:26.640 --> 0:18:31.440 so you just defined megaloblastic anemia. I also came across 0:18:31.560 --> 0:18:36.040 two other terms in my readings. One is macrositic anemia 0:18:36.119 --> 0:18:38.359 and the other is pernicious anemia. 0:18:38.880 --> 0:18:40.399 I would love to define those for you. 0:18:40.800 --> 0:18:42.280 Thank you. I'm so excited. 0:18:42.560 --> 0:18:47.040 Yeah, So megaloblastic anemia, that's when I define when you 0:18:47.080 --> 0:18:53.600 have megloblast macrositic anemia. Macro means big site toe meaning cell. 0:18:53.960 --> 0:18:57.880 So a macrositic anemia is one where the cells are bigger, 0:18:58.000 --> 0:19:01.000 the red blood cells are bigger than they be. Oh, 0:19:01.160 --> 0:19:04.400 and this is in contrast to a microcytic anemia, where 0:19:04.400 --> 0:19:08.400 the cells are smaller than they should be a Megloblastic 0:19:08.440 --> 0:19:13.480 anemia is a type of macrositic anemia. Macrocitic anemia is 0:19:13.520 --> 0:19:18.480 like a more general term, Okay. Microcytic anemias can happen 0:19:18.520 --> 0:19:21.240 from a lot of other reasons. One of the most 0:19:21.240 --> 0:19:25.880 common ones is iron deficiency, because with iron deficiency, you're 0:19:25.920 --> 0:19:29.680 not having problems making DNA, you just don't have enough 0:19:29.720 --> 0:19:33.199 stuff to make beefy enough red blood cells. So you 0:19:33.240 --> 0:19:35.879 make these tiny, little wimpy ones because they're just like 0:19:36.080 --> 0:19:37.600 trying so hard. 0:19:37.640 --> 0:19:39.040 To be able to keep making cells. 0:19:39.200 --> 0:19:39.600 Got it. 0:19:40.720 --> 0:19:46.960 Pernicious anemia is another type of macrositic anemia, but it's 0:19:47.000 --> 0:19:52.359 specific to vitamin B twelve deficiency. Okay, and vitamin B 0:19:52.440 --> 0:19:57.040 twelve and folate work together so closely that the syndromes 0:19:57.040 --> 0:20:00.000 that are caused by deficiency with both folate and vitamin 0:20:00.119 --> 0:20:03.440 B twelve are really overlapping and can sometimes mimic each 0:20:03.440 --> 0:20:06.280 other and be difficult to distinguish, which is actually really 0:20:06.280 --> 0:20:12.520 important but probably a whole episode in and of itself. Now, 0:20:12.600 --> 0:20:15.600 another question that you might ask, or one might ask, 0:20:16.080 --> 0:20:19.359 is well, is it just red blood cells? And why 0:20:19.400 --> 0:20:22.679 is it just red blood cells? And the answer is no, 0:20:22.760 --> 0:20:23.280 it's not. 0:20:23.440 --> 0:20:24.679 Just red blood cells. 0:20:26.080 --> 0:20:30.439 Fullate deficiency does result in decrease white blood cells and platelets, 0:20:30.680 --> 0:20:33.320 and really in all tissues that are rapidly dividing, there's 0:20:33.359 --> 0:20:36.600 going to be impairment of cell division. It's just that 0:20:36.680 --> 0:20:39.600 our red blood cells, first of all, are very dependent 0:20:39.680 --> 0:20:43.159 on folate and B twelve and also have kind of 0:20:43.560 --> 0:20:47.359 very obvious and important outcomes in that it results in anemia. 0:20:47.960 --> 0:20:50.800 So that's one of the major and most well studied 0:20:51.440 --> 0:20:52.320 consequences of. 0:20:52.280 --> 0:20:57.119 Full ate deficiency. The other is neural tube defects. 0:20:58.119 --> 0:21:01.720 So I know you'll talk probably about this and how 0:21:01.920 --> 0:21:06.600 we came across this data, but we know from a 0:21:06.640 --> 0:21:11.840 lot of very well done clinical trials and supplementation studies 0:21:12.600 --> 0:21:17.960 that supplementation, specifically with folic acid, which is again the 0:21:18.000 --> 0:21:23.320 synthetic and easily absorbed form of folate. Supplementation with folic 0:21:23.359 --> 0:21:27.359 acid reduces the risk of neural tube defects. What is 0:21:27.400 --> 0:21:33.120 a neural tube defect, so glad I asked, So in 0:21:33.320 --> 0:21:40.240 a developing embryo, not during field development. This happens really 0:21:40.280 --> 0:21:45.040 really early in the very earliest days of embryonic development. 0:21:45.840 --> 0:21:49.679 One of the structures that forms is called the neural tube, 0:21:49.720 --> 0:21:52.600 and without getting into like a lot of developmental biology here, 0:21:52.640 --> 0:21:55.040 even though I would love to, and I think we 0:21:55.119 --> 0:22:00.000 will at some point in the future in another episode. 0:21:59.760 --> 0:22:04.360 But this neural tube essentially houses what will become our 0:22:04.480 --> 0:22:08.320 central nervous system, our brain, and our spinal cord. That's 0:22:08.359 --> 0:22:12.159 the very rough way of putting it, and I know that. 0:22:12.280 --> 0:22:15.800 In our solidamide episode, I talked a lot about how 0:22:15.880 --> 0:22:20.680 whenever we have something in our bodies that affects very 0:22:20.800 --> 0:22:24.400 very early stages, early days of development, when we are 0:22:24.600 --> 0:22:29.119 just a few cells large, has the potential to cause 0:22:29.280 --> 0:22:33.200 very big effects downstream in the fetus and the baby. 0:22:33.760 --> 0:22:38.280 So during the development of this neural tube, sometimes what 0:22:38.359 --> 0:22:41.440 can happen is it can fail to close completely at 0:22:41.480 --> 0:22:45.280 one end or the other. So this tube is essentially 0:22:45.320 --> 0:22:47.359 like you think of our spinal cord as a tube 0:22:47.400 --> 0:22:50.880 going from our head down to our butt. So that 0:22:50.920 --> 0:22:53.879 tube has to make itself into a hollow tube and 0:22:53.920 --> 0:22:57.800 then close on either end. If it fails to close 0:22:57.920 --> 0:23:01.360 on the anterior or the head end, then what can 0:23:01.359 --> 0:23:05.840 happen is something called an encephaly, which means like what 0:23:05.880 --> 0:23:09.840 that root sounds like and meaning without an cephal like 0:23:09.880 --> 0:23:13.320 the root for brain. So If the neural tube doesn't 0:23:13.359 --> 0:23:16.080 close on the anterior or the head side, then the 0:23:16.080 --> 0:23:19.640 brain and the skull are unable to form properly, and 0:23:19.720 --> 0:23:24.359 that condition and encephally is generally not compatible with life. 0:23:24.400 --> 0:23:27.880 If the neural tube doesn't close completely on the other side, 0:23:28.040 --> 0:23:32.040 the bottom side, the distal end, then that results in 0:23:32.080 --> 0:23:37.000 a condition called spina bifida and spina bifida which people may. 0:23:36.840 --> 0:23:39.480 Have heard of. It's actually a very. 0:23:39.200 --> 0:23:46.199 Wide ranging condition. It can cause very significant disability and 0:23:46.440 --> 0:23:50.719 inability to use the lower half of the body. Or 0:23:51.200 --> 0:23:54.520 it can also be entirely asymptomatic and something that's not 0:23:54.640 --> 0:23:59.119 diagnosed until adulthood. If ever, and it all depends on 0:23:59.280 --> 0:24:03.280 how much of the spinal cord remains exposed when that 0:24:03.400 --> 0:24:05.600 neural tube fails to close completely. 0:24:06.240 --> 0:24:10.520 I have a question what determines whether it fails to 0:24:10.600 --> 0:24:13.960 close at your head or at your butt. 0:24:14.480 --> 0:24:15.960 I really wish I knew the answer to that. 0:24:16.520 --> 0:24:19.560 Okay, I don't have an answer to that. Okay, Yeah, 0:24:20.320 --> 0:24:23.280 And I guess I should preface this next question by 0:24:23.359 --> 0:24:26.320 saying that we'll probably do a spina bifida episode at 0:24:26.320 --> 0:24:29.679 some point in the future. Yeah, But jumping ahead again, 0:24:30.960 --> 0:24:35.280 why is there such not why is there such variation, 0:24:35.640 --> 0:24:39.679 but what determines where it closes? 0:24:40.600 --> 0:24:42.679 Oh, Aaron, that's such a good question, and I do 0:24:42.720 --> 0:24:45.960 think it deserves an episode of its own to talk 0:24:46.080 --> 0:24:48.280 more about the details of spina bifida and all of 0:24:48.320 --> 0:24:53.720 the different forms and consequences. The short answer is, I 0:24:53.840 --> 0:24:56.960 don't know, And based on what I read about fol 0:24:57.040 --> 0:25:00.479 late and its effects on spina bifida, we don't know 0:25:00.600 --> 0:25:04.040 that we know all that much detail about why and 0:25:04.119 --> 0:25:08.560 how things go wrong in the closure of that neural tube. Okay, 0:25:09.480 --> 0:25:13.200 because then the question does come up is like, how 0:25:13.240 --> 0:25:16.240 does all of that, these different types of neural tube 0:25:16.240 --> 0:25:19.120 defects that can arise, how does that relate to folate? 0:25:19.520 --> 0:25:21.440 What does folate have to do with whether. 0:25:21.400 --> 0:25:25.239 Or not this tube closes completely and where or not 0:25:25.480 --> 0:25:29.040 it fails to close completely. Yeah, So what I can 0:25:29.160 --> 0:25:34.840 say is that demand for folate increases during pregnancy, as 0:25:34.920 --> 0:25:38.960 does the demand for a lot of other micronutrients, et cetera, 0:25:39.760 --> 0:25:43.960 because of the essential role of folate in cell replication. 0:25:45.640 --> 0:25:51.840 But beyond that, we don't know, Like, we still don't 0:25:51.880 --> 0:25:55.960 know the mechanism by which folic acid supplementation reduces neural 0:25:56.000 --> 0:26:00.600 tube defects specifically, but we know that it does and 0:26:01.280 --> 0:26:05.840 folate deficiency is not, by any means the only cause 0:26:06.040 --> 0:26:11.320 of neural tube defects, and fullic acid supplementation can never 0:26:11.520 --> 0:26:16.000 eliminate the risk of neural tube defects completely because these 0:26:16.040 --> 0:26:21.000 are very complex developmental mechanisms that are related to a 0:26:21.080 --> 0:26:23.760 lot of other genetic and environmental factors. 0:26:24.920 --> 0:26:30.040 Can we talk about the genetic factors of folate and 0:26:30.040 --> 0:26:36.360 folic acid? We can a little, because there's a lot 0:26:36.400 --> 0:26:41.200 of variation in your ability to metabolize folate or folic acid. 0:26:41.320 --> 0:26:44.240