Published 24th November 2022

The truth about vitamin supplements

Let’s talk about vitamins, shall we?  

Good information about vitamins is hard to find, and there’s a reason. With over 70% of Americans and 40% of Brits using them, it's a hugely lucrative market.

Numerous voices in the media and online push a pro-vitamin agenda without having the scientific evidence to support their claims.

Products containing many times the daily recommended dosages are widely available. Could overdosing on these supplements lead to serious health complications?

In this episode, Jonathan speaks with Prof. JoAnn Manson and Dr. Sarah Berry to better understand how vitamin supplements affect our health.

  • JoAnn Manson is a professor of epidemiology at the Harvard School of Public Health and one of the world's most cited researchers. She’s run multiple enormous studies, with over 20,000 participants, to uncover the real effects of vitamin supplementation on our health.

  • Dr. Sarah Berry is one of the world's leading experts on human nutrition. She's run more than 20 randomized clinical trials looking at how humans respond to different fats.

If you want to uncover the right foods for your body, head to joinZOE.com/podcast and get 10% off your personalized nutrition program.

Check out the trials mentioned in today’s episode: AREDS 2, COSMOS, Physicians' Health Study II, and VITAL.

Episode transcripts are available here.

You can follow Sarah. And you can follow ZOE on Instagram.

This podcast was produced by Fascinate Productions.

Transcript

[00:00:00] Jonathan Wolf: Welcome to ZOE Science and Nutrition, where world-leading scientists explain how their research can improve your health.

Let's talk about vitamins, shall we? Good Information about vitamins is hard to find and there's a reason. With over 70% of Americans and 40% of Brits using them, it's a hugely lucrative market. Numerous voices push a pro-vitamin agenda in the media and online without having scientific evidence to support their claims.

Have you heard the one about vitamin C curing colds? This theory spread across the Western world in the 1970s. Decades later, it's utterly debunked, but many still hold this belief. Cash incentives may explain the pro-vitamin argument, but what about those who think vitamin supplements should be avoided?

Can supplementing naturally occurring micronutrients really be dangerous?

Sure. Supplements markets lack regulation, especially in the US. No one really knows what's inside those pills they're popping. Products containing many times the daily recommended doses are widely available. Could overdosing on these supplements actually lead to serious health complications? Amidst the scare stories and the miracle cures, legitimate scientific research has been taking place, trying to uncover the real cost and benefit of vitamin supplementation on our health and our wallet. Our guest today is behind a lot of that research.

JoAnn Manson is a professor of epidemiology at the Harvard School of Public Health and one of the world's most cited researchers. Her achievements spanning more than 40 years are too many to list. We often talk on this podcast about how tiny most nutrition studies are. JoAnn's are the exception.

JoAnn has run multiple enormous studies with over 20,000 participants to find out how vitamins and supplements affect major health conditions. 

Talking of health conditions. I have to apologize for my sore throat when recording today's episode. Luckily, Sarah Berry joins me as a co-host. For those of you who aren't sure of how much of a big deal JoAnn is, you can judge it from Sarah's excitement.

JoAnn, thank you for joining me today. Why don't we start with a quick-fire round of questions from our listeners? And the first one is very simple. Should we all take vitamins every day? 

[00:02:37] JoAnn Manson: It's not essential if you have a healthy and balanced diet, and vitamin and mineral supplements will never be a substitute for a healthy diet.

[00:02:48] Jonathan Wolf: Brilliant. In that case, are vitamins and supplements just scams by manufacturers to make us pay for something that we don't need? 

[00:02:56] JoAnn Manson: No, I don't think it's a total scam. However, it has to be targeted and appropriate use, which we'll get into in more detail. 

[00:03:06] Jonathan Wolf: Brilliant, and I think we'll talk about that a lot.

Next question, should I take vitamin D in the winter months? 

[00:03:12] JoAnn Manson: Yes, it would be very reasonable to take 1000 to 2000 IU a day.

[00:03:18] Jonathan Wolf: And I should note that JoAnn does not like being forced to say yes or no in quite such a short period on such a complex topic. So we are gonna come back to that in a bit more detail.

Are collagen supplements a waste of money? 

[00:03:30] JoAnn Manson: Maybe. Okay. I don't know how well-studied the collagen supplements are. Most of my work has focused on vitamin-mineral, and supplements as well as some bioactive, such as omega-3s. 

[00:03:43] Jonathan Wolf: Wonderful. And may I just say that I'm incredibly excited to have you join us, part of that is because Sarah has been telling me for months how excited she was that you were going to join us.

And Sarah, why is that?

[00:03:56] Sarah Berry: Gosh. Well, JoAnn's been a real inspiration, I think, you know, to us female scientists, and I think JoAnn, your work in the area of nutritional research has been really foundational for a lot of the work that we've gone on to do. And I'm especially excited by your COSMOS and your VITAL trial that hopefully, we can go on to talk about, which are huge randomized control trials, Jonathan, that just hasn't been done before in the way that JoAnn's done these recently.

[00:04:23] JoAnn Manson: Thank you so much, Sarah. It's very kind of you, and I'm really honored to hear that. 

[00:04:27] Jonathan Wolf: JoAnn, we had a huge number of listeners saying that they were incredibly confused about supplements. What's caused this level of confusion? 

[00:04:35] JoAnn Manson: There have been so many mixed messages about dietary supplements over the years.

There are findings from observational studies just looking at what people do, what people consume, and their reporting, certain findings. And then randomized trials are done, which are experimental studies. For example, giving vitamin D, giving vitamin E or beta carotene to a group of participants, and half of them will get a placebo.

A flip of a coin assignment to treatment, and the results are often very different. So there is a different message that comes out a year later, and it's completely understandable that the public is confused. 

[00:05:16] Jonathan Wolf: Brilliant. Which supplement would the majority of the population benefit from taking and why? 

[00:05:23] JoAnn Manson: I think at this point the evidence is really mounting that a multivitamin may be worth seriously considering just as a form of insurance and to hedge your bets.

I would say the second would be a vitamin D supplement, 1000 to 2000 IU a day, a small to moderate dose, no mega dosing, not taking doses of 6,000, 10,000 IU a day, small to moderate dose. 

[00:05:51] Jonathan Wolf: So why don't we start at the very beginning, JoAnn, like, what are dietary supplements and vitamins? 

[00:05:57] JoAnn Manson: So think of vitamins as organic compounds or substances that our bodies usually do not make.

But are essential for our metabolism and for good health. In fact, we do synthesize vitamin D through the skin when exposed to ultraviolet B light. But otherwise, vitamins and minerals are not made by the body. They're essential to function, and we need to get them from food or from supplements. 

[00:06:29] Sarah Berry: I think though JoAnn, a lot of people use the word supplements not just for essential components.

So out on the market at the moment, there are so many supplements out there that might be, you know, beta-glucans. So a kind of fiber or polyphenols, for example, that actually they're not essential. And so I think this is something really important to clarify, the difference between essential supplements versus these emerging new supplements that aren't essential in the way vitamins are.

[00:06:58] JoAnn Manson: That is absolutely correct. There are more than 90,000 dietary supplements on the market. 

[00:07:06] Jonathan Wolf: 90,000? That's crazy. 

[00:07:09] JoAnn Manson: A dizzying array of supplements on the market in the US and I imagine it's not too different in the UK and most of these dietary supplements have not been well studied. My comments were limited to the essential vitamins and minerals, but even there, the supplements are usually not really necessary if you follow a healthy diet, and that's what we encourage as the number one guideline, not to take supplements for that purpose, but certainly, for many of the other tens of thousands of dietary supplements, there's very little research about efficacy or safety. And in fact, these supplements can get on the market without testing for either efficacy or safety.

But if problems are found, they can be withdrawn from the market. So it's a real problem. It's buyer beware. Consumers beware, and many people are spending a lot of money on dietary supplements that are not only of no value to their health, but actually can be harmful, especially when taken in high doses. So we have to be very careful about safety issues and avoid mega dosing.

[00:08:27] Sarah Berry: I think that's a huge problem. There are so many of these mega-dose vitamins out there, but there's reasonable evidence, I think, to show that there's a certain dose at which we have the maximum health benefits, a dose at which it becomes harmful, or a dose at which actually you are just peeing it all down the toilet.

[00:08:45] JoAnn Manson: For essential vitamins and minerals, the Institute of Medicine, National Academy of Medicine, and professional organizations in different countries do provide guidelines but for many of the dietary supplements out there, there are no guidelines even in terms of the doses that would be appropriate. 

[00:09:04] Jonathan Wolf: So, just to make sure I've got this, there's a sort of wild west here, so there's this small number of essential vitamins.

Maybe you could tell us in a minute what those are and the key ones. And then there's this, just this vast mass of things over which you are saying there's really no scientific evidence at all that should take them, and quite a lot of concern that you might just be taking stuff that is bad for you. Is that right?

[00:09:23] JoAnn Manson: Absolutely true. We have very, very little research on benefits, and risk safety issues for the vast majority of the supplements that are on the market. 

[00:09:33] Jonathan Wolf: And why do you think there is all of this advertising that's suggesting that we should be taking all these supplements and, and vitamins? How have we ended up here?

[00:09:41] JoAnn Manson: I think because it's possible to get them on the market and to promote them and you know, sell them. And many people are just looking for magic bullets, for popping a pill that they think will benefit their health. And I think it's really unfair to the public to mislead them into thinking that there's research and evidence that most of these dietary supplements will be of benefit to their health.

In fact, there's very little evidence for that. But there are some vitamins and minerals that are really important for health, and it's essentially what's in your multivitamin pills. You know, if you look at any generic multivitamin, it will have vitamin A, a number of B vitamins like folic acid and B6, B12, vitamin C, vitamin D, vitamin E, and vitamin K. These are the really essential vitamins. And then you will also see calcium, magnesium, selenium, a number of minerals as well. 

[00:10:46] Jonathan Wolf: So that's interesting, right? So you suddenly struck to a much smaller set of things versus the 90,000 that you've been talking about. Now, you've done, just as Sarah was saying before, some of the biggest research studies in the world, full stop.

And then specifically into a number of these dietary supplements. Could you maybe just start by telling us about your own research, like why you did this and what it tells us today and what is still, I guess, open and uncertain?

[00:11:11] JoAnn Manson: We've been doing large-scale randomized clinical trials. These are relatively pragmatic, low-cost trials with very large numbers, often more than 20,000 participants nationwide in the US. For close to 30 years, we started with some antioxidant vitamins. We studied beta carotene, vitamin C, and vitamin E, and overall we did not see clear benefits of these antioxidant vitamins.

And over time there were several randomized clinical trials as actually suggested some risks of beta carotene, especially in smokers, an increased risk of lung cancer and vitamin E, and an increased risk of hemorrhagic stroke, the bleeding type of stroke. And there are now recommendations, at least in the U.S., the U.S. Preventive Services task force saying, do not take beta carotene or vitamin E supplements.

We started with some of these, what looked like very promising antioxidant supplements. We did not see the benefits of vitamin C for the prevention of cancer and cardiovascular disease. And then since the year 2009, we've moved into large-scale trials, testing vitamin D and the marine omega-3s, which are basically fish oil and EPA, DHA, in the prevention of cancer, cardiovascular disease, autoimmune diseases, mood, depression changes, cognition changes, very extensive art research on vitamin D and the marine omega-3s. And then even more recently, we have been testing the multivitamins as well as the cocoa flavanol supplements.

In the physician's health study II, which began well 20 years ago, we were also testing multivitamins, and so we have now two large-scale trials of multivitamins in physician's health study II, we did see a significant reduction in total cancers and 8% reduction, but the trial went on for 11 years. It took a very long time to adequately test the multivitamins in terms of cancer prevention.

So these are long-term effects. And in the more recent trial of multivitamins, we're seeing a very exciting finding over only three years for slowing cognitive decline. We're actually seeing a 60% reduction over the three years in the rate of cognitive decline in the multivitamin group versus the placebo group in some research we're doing in collaboration with Wake Forest School of Medicine.

[00:14:07] Jonathan Wolf: And I think you said vitamin C, which I think lots of people will still associate with something they should take when they've got a sore throat like me today. 

[00:14:14] JoAnn Manson: Mm-hmm. 

[00:14:14] Jonathan Wolf: Sounds like I should be throwing that out the window. Is that right JoAnn? 

[00:14:17] JoAnn Manson: The research on its value for shortening upper respiratory infection duration has been actually controversial. Some studies do show a little bit of benefit. Taking it for the short term during an upper respiratory infection is still reasonable. But for prevention of cancer, cardiovascular disease, diabetes, and chronic disease outcomes, it has not been shown to be a benefit in large-scale randomized clinical trials.

[00:14:46] Jonathan Wolf: I think you went further than that, at least for some of these, and said it might actually be harmful. 

[00:14:50] JoAnn Manson: So for vitamin C, we didn't see clear harm or risk, but we did see for vitamin E in the physician's health study II, we saw an increased risk of hemorrhagic stroke, the bleeding type of stroke. And we also saw that all-cause mortality was slightly bit higher in the vitamin E group compared to the placebo group.

[00:15:15] Jonathan Wolf: Would that cause you to be cautious about very high dosing of anything unless there was like really good evidence for it? Or would you say in most cases, Hey, don't worry, your body's just going to deal with any of these things, so don't really worry? It might be wasted, but there's no harm. Because that sounds quite scary that I've always sort of thought of these things as being basically inert if you took more than you needed, but here you're seeing real harm. That's like a negative impact, like a drug. Does that really reset the way we should think about supplements or vitamins?

[00:15:47] JoAnn Manson: Yes. I think we should avoid megadosing because these micronutrients and these dietary supplements are not inert.

And in fact, even among the vitamins, you have the fat-soluble and water-soluble vitamins. So with fat-soluble, they get stored in the fat tissue. Some get stored in the liver, and you can become toxic with vitamin A, vitamin D, vitamin K, and vitamin E, you know, these are fat-soluble vitamins. The B vitamins are water-soluble.

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You have a little more latitude in terms of dosing, but even with mega doses of water-soluble vitamins you can get - there are some neuropathy symptoms that can occur. You can get a problem with masking, you know, for example, if you take too many certain D vitamins, it can mask a problem with B12, which, if you have a deficiency of B12, can be associated with an increased risk of cognitive decline.

So there are risks also very, very high doses of an isolated micronutrient that can interfere with the absorption of other similar micronutrients. For example, it's one of the concerns about beta carotene that if you take it in very high doses, it might interfere with the absorption of other carotenoids, of which there are hundreds, and it may also interfere with the bioavailability of some of the other carotenoids.

[00:17:24] Jonathan Wolf: I think the message I'm taking is throw away all of the things I have, which are like in mega doses there's no upside, and there might be some real downsides. 

[00:17:34] JoAnn Manson: I would look at whether there is a recommended dietary allowance or a daily intake. Look at the label. Look for several things on the label. If you take any sort of dietary supplement, first, look at the percent of the dosing in that pill relative to the dietary intake or the recommended dietary allowance.

Sometimes you will see 500% a 1000%. many folds higher than what's needed. I generally avoid that unless I've been prescribed it by a clinician. And there are sometimes, like with B12, some people with pernicious anemia and other conditions may need quite a high intake of B12. So if you're not under the supervision of a doctor or clinician for the purpose of taking higher doses, generally avoid this general principle. Don't take more than the recommended dietary allowance or the daily intake, and also look on the label at a seal for quality control assessment because there are many dietary supplements out there that don't undergo adequate quality control testing. And they can have contamination with heavy metals, and contamination with microbes.

And often the dose that's listed on the label is not what you're getting because it's not really confirmed to have that content.

[00:19:01] Sarah Berry: I think there are a lot of people who think, you know, more is better. And so often I look in people's cupboards because I'm nosy and I see the kind of supplements they're taking and it worries me this mismarketing, but it worries me also the mega dosing.

And often I say, Oh you know, you don't actually need that much. But people think, oh, the more is better. And I try and simply explain to them, well actually, If your body doesn't need it, your body then has to just work harder in order to process it or excrete it or get rid of it some way. And I think that's a really simple way of explaining to people that actually, you know, it might not be doing really serious damage, but you are actually, you know, adding to the work that your body has to do.

And JoAnn, one thing that I was particularly interested to be able to talk to you about when Jonathan allowed me to gatecrash, his podcast, are the two big trials that I know have just recently come out. VITAL and COSMOS and Jonathan, I wonder if we can spend a few minutes going through these because I think they're both covering supplements that even in the field of nutritional research is really contentious, so vitamin D, which I know you mentioned at the beginning, Omega-3, and then also the polyphenols from the COSMOS. And so Vitamin D's been a really hot topic. it's contested a lot, whether we should be taking it as a supplement. And I think during Covid it really came to a head and, actually I don't think there's a clear consensus.

And so I wonder if you can tell us your perspective on this and also the findings from your vital trial where I know you looked at vitamin D. 

[00:20:33] JoAnn Manson: So the VITAL trial, which is the vitamin D and Omega-3 trial, was conducted in more than 25,000 US men and women across the entire country. 

[00:20:45] Jonathan Wolf: I don't want to cut across, but I just wanna emphasize 25,000 is an enormous study, right?

Like we are used in nutritional science. We're looking at studies of 25 people or 30 people for three months. Is that a fair contrast? I just want to make sure that listeners understand before you just glide on.

[00:21:03] JoAnn Manson: It was an enormous study and the reason it was so large was to be able to look at clinical events such as heart attacks, strokes, cancer, diabetes a wide range of clinical outcomes as opposed to just looking at changes in cholesterol levels or a biomarker or a blood pressure change. We wanted to see if there were actual effects on clinical events, and it takes a study that large, a randomized trial that large, over 5.3 years. So we reported the results in 2019, that Vitamin D and Omega-3s, and we looked at the independent as well as the joint effect of these supplements did not prevent our primary endpoints, which were major cardiovascular events, a combination of heart attack, stroke, and death from cardiovascular disease. For the Omega-3s, there was a modest 8% reduction that was not statistically significant for CVD events, and for the omega-3s, we did see a significant reduction in the secondary outcome of heart attack, a 28% reduction in a heart attack. I'll come back to that, but our other major primary endpoint was cancer and total invasive cancer.

We did not see a benefit of either the vitamin D or the omega-3s in reducing the cancer endpoint over 5.3 years. Now, of course, for cancer, it may take longer. We're continuing to follow the participants. We're now at an additional three years of follow-up, and four years of follow-up, and we hope to follow over at least a decade for cancer endpoints as well as cardiovascular endpoints.

But we did not see for those primary endpoints, a reduction with either supplement. With vitamin D, however, we did see with a secondary endpoint of cancer death, that there was a borderline reduction, a 17% reduction. And then when we accounted for, you know, there's a latency period for cancer and we had pre-specified that we would look at people who were taking the vitamin D for at least two years, we did see a statistically significant 25% reduction in cancer death. And then when we looked at advanced cancer as an endpoint, metastatic or fatal cancer, in the overall follow-up period, we did see a statistically significant 17% reduction in advanced cancer.

Now, there are some other randomized trials that also suggest that Vitamin D doesn't prevent the first diagnosis of cancer, first occurrence of cancer, but it may affect tumor biology, make tumors less invasive, and less likely to metastasize, and therefore there may be a reduction in cancer, death, or advanced such as metastatic cancer.

This requires further study. Not ready to make general public health recommendations that everyone take vitamin D for this purpose, but there's some exciting research in that area. Another finding we had for Vitamin D was a significant reduction in autoimmune diseases such as rheumatoid arthritis, and psoriasis.

And this may be because vitamin D has been shown to have some benefits for the immune system to boost immune function, but to tamp down inflammation. Both of these would be relevant to reducing the risk of autoimmune diseases as well as potentially reducing the severity of Covid illness, which is why I said during the pandemic it would be reasonable to take 1000 to 2000 IU a day. Vitamin D, although not essential. 

[00:25:13] Jonathan Wolf: Can I ask a question, JoAnn? Because I think if our listeners were listening to this, you're listening to all of these things when you take vitamin D that are like a statistically significant reduction in cancer. And I think they're all going to be like, Oh, I'm, I'm gonna go out and do that tomorrow for certain, for every day for the rest of my life.

Like, that sounds incredibly important, but actually, we're sounding quite cautious about your advice on Vitamin D. Can you help everybody listening to understand that? 

[00:25:35] JoAnn Manson: I realize that it may not come across clearly whether or not to take these supplements. I think the main point, after all these years of testing vitamin D and seeing these results, we recently published that Vitamin D did not prevent fractures, bone fractures, and osteoporotic fractures, and that was very surprising to people.

[00:25:59] Jonathan Wolf: And that's because there've been a lot of people who have historically thought that it was really important against fractures and something that after menopause, you should therefore take. Is that right JoAnn?

[00:26:07] JoAnn Manson: It was believed that if vitamin D had any role, it was for bone health and preventing fractures preventing osteoporosis.

Now, the findings don't mean that Vitamin D has no role in maintaining bone health. What it means is that we need only small to moderate amounts of vitamin D for bone health, cardiovascular disease, and many of these other health outcomes. The reason is probably that evolutionarily because vitamin D is so essential to health, we evolve to be able to regulate the metabolism of vitamin D very tightly so that in terms of the biologically active form of vitamin D enough is getting into the tissues, is getting to the vitamin D receptor.

We don't need large amounts. The amount we can get from food sources and from incidental sun exposure. As I mentioned, we synthesize, vitamin D, a precursor vitamin D in the skin from ultraviolet B light exposure. So just being outdoors 15 minutes, a few times a week, you know, running errands, taking walks, being physically active will provide some incidental sun exposure, not during winter months, but you know, during, let's say six months of the year. And some of that vitamin D is then stored and there are food sources of vitamin D.

[00:27:37] Sarah Berry: JoAnn, can I jump for a minute from vitamin D over to Omega-3? Because I know you looked at that in the same study. And this is something that I've been interested in my own research and we know as nutritional scientists, you know, all Omega-3 is not the same. That there are different types of omega-3 fats, and I think this is somewhere again, where it'd be really good to be able to inform people on what to look at on the back of the pack of their supplements in relation to omega-3, because there's the kind of omega-3 that we know, which we call EPA and DHA, Jonathan, I know you don't like me to do long names, so I'm not gonna give you the long name. Which actually comes from fish oil and then there's the more plant-based.

It's not quite as big, an omega-3 fat that I won't, again, give you the fatty acid name, but, it'd be really good, JoAnn, if you could point listeners in the direction of what to look for and what you think based on your research and what we know in nutritional research has greater efficacy in health outcomes. 

[00:28:39] JoAnn Manson: I think that's a really good point. We really should separate and make clear whether we're talking about marine fish, or oil-based omega-3s, which are EPA plus DHA.

We tested the marine omega-3s in a dose of 1.2 to 1 of the EPA to DHA. So it was a combination, a little more EPA than DHA in the VITAL trial. There are also plant-based, such as alpha-linolenic acid, and some of the plant-based omega-3s and three fatty acids do get converted to EPA, DHA, and EPA. So you know, you do get some of that marine-based omega-3s from the plant conversion plant-based, but it's at a relatively low level.

There have been some trials of plant-based omega-3s. Been inconsistent in terms of the clear benefits. Overall for the marine fish-based omega-3s, there's work on an algae-based form of this, which may be more environmentally sustainable long term. But anyway, for the EPA, and DHA, the evidence overall is that there's a small reduction in heart disease, but no clear reduction in stroke or in the major cardiovascular events when you're looking at heart disease and stroke, it may be only a modest, if any, reduction because stroke is generally not reduced.

[00:30:18] Sarah Berry: Yeah. In, summary, Joan, when people ask me, if should I have fish oil-based omega-3 or if can I have any old omega-3? I always suggest to people that they should have fish oil omega-3.

Would you agree with that? 

[00:30:34] JoAnn Manson: I would agree that there's much more evidence for the fish-based omega-3s in terms of reduction in cardiovascular outcomes, especially heart disease and heart attack. 

[00:30:46] Jonathan Wolf: Listening to that, it didn't sound like you were pushing very hard that I should be taking omega-3 every day. This sounded like these were quite small impacts, which after all we know that if you just taught me to improve the quality of my diet, I would also probably have a very big impact on all of these things. So it sounded like you were much softer than on vitamin D is that a misunderstanding?

[00:31:06] JoAnn Manson: Well, I think that we're not quite ready to make public health recommendations that everyone takes a fish oil supplement. What we found in VITAL was that in people who had low fish consumption in their diet, low dietary intake of fish at baseline, fish being the major, the primary source of the marine omega-3s, they benefited more from the one gram a day.

We tested. In fact, that group did have a reduction in the primary endpoint of major cardiovascular events, close to a 20% reduction, and those who were already getting one and a half servings per week of fish did not benefit. So if you have very low fish consumption, if you're vegetarian or you don't like fish, you know, you may wanna talk with your healthcare provider about whether you should take a fish oil supplement or even a prescription omega-3, because that's where the benefit was.

We also, surprisingly, found a very large benefit among African Americans. For the heart attack endpoint. We saw a 77% reduction in heart attacks with the omega-3s. And this was not due to low fish consumption at baseline because consumption was not lower in the African American participants.

So we want to look further at this finding to see if it can be replicated and if so, it may actually be an important approach to reducing health disparities. Of course, it's only, you know, one aspect of many health disparities out there, but it may actually make a difference in terms of heart disease if it can be replicated.

[00:32:48] Sarah Berry: And I think that's a really important point that builds on all of the work that we are doing at ZOE, which is trying to look at what works in terms of food intake for each individual's biology because we know that we all respond differently to food. And just in the way that you've said that some people benefited more than other people with the omega-3. Is this something that you've looked at?

Because I should imagine that you have huge variability in the effectiveness of the supplements across individuals where it's more useful for some individuals than it is for other individuals. 

[00:33:22] JoAnn Manson: Yes, we've looked at these questions in a number of different ways. So in our first randomized trial of the physician of the multivitamins, the physician's health study II, we looked by age group at whether there were differences across age in benefits for the cancer reduction that was seen overall.

And we saw that older participants who were above the age of 70, tended to have a greater reduction in cancer with the multivitamin assignment compared to the placebo group. Now, this may be because the diet for many seniors, will be a little poorer.

There may be poor absorption of vitamins and minerals, and so this is a group that seems to benefit more, an 18% reduction in cancer, one 8% reduction in the older age group compared to overall an 8% percent reduction and very little reduction in cancer in the younger age groups. So it may be that if you are already getting these vitamins and minerals, this is not gonna help to take a multivitamin. That would be very, very plausible. And, you know, rational that it's gonna benefit the people who have lower, you know, intake, more than the people who are already adequate or replete in that micronutrient.

But another point I want to make is that dietary supplements will never be a substitute for a healthy diet. If you have a diet that is high in red meat, saturated fat, processed foods, and all of these unhealthy sugar, refined carbs, very unhealthy foods, and you just throw a multivitamin at that and you know, start to pop a multivitamin that's not going to make you healthier. I mean, you're still going to have health problems related to that very unhealthy diet. When you are following a healthy diet, such as a high intake of fruits, vegetables, whole grains, fish, unprocessed, whole foods, you are going to - you're that diet, those foods will be replacing unhealthy foods such as red meat and you know the processed foods.

And if you're just taking a dietary supplement, you're not going to be replacing anything that's in your usual diet. This is another reason why it's so important to be encouraging first, the healthy diet, which will naturally, you know, these foods will be replacing unhealthy foods and also this very complex matrix of vitamins, minerals, polyphenols and phytochemicals.

And we've talked about, you know, the fiber and all the other benefits that you get from fruits, vegetables, whole grains, and a diet that's healthy like that. You just can't replace it. You can't package that into a pill and, you know, get those benefits by popping a pill. I know people love to, you know, think of a pill as a panacea and a magic, you know, bullet, but it's really not possible and there is no pill like that.

[00:36:52] Sarah Berry: And so JoAnn, what would be one piece of actionable advice that you could give to listeners of the show regarding taking supplements? And you can break this down if you want to, kind of different subgroups of people that may benefit. 

[00:37:07] JoAnn Manson: Yes, I think that the focus should be on a healthy diet, a healthy balanced diet, and try to get the vitamins, minerals, and phytochemicals whenever possible from food.

And again, the vitamins, and minerals, will be better absorbed from food than when taken as a supplement. And you get all these other benefits of, you know, this matrix. And you also will replace unhelpful foods. Buy healthy food. So I think that that's a really important principle. Try to get it from food.

Now there is the appropriate targeted use of certain dietary supplements for pregnant women or women who are planning a pregnancy, it is extremely important to think about taking a multivitamin, and taking a prenatal vitamin during the pregnancy and even prior to conception. That is really essential to healthy pregnancy preventing, you know, the neural tube defects.

That's been well demonstrated, but also a recent study in China just suggested that congenital heart defects are reduced through folic acid as well. So I think that is really important in that high-risk group. There are some recommendations by pediatric societies, and organizations about the infants who are breastfed, maybe take vitamin D, take iron, you know, I won't go into a lot of details about that, but of course, if you have an infant, discuss that with your pediatrician. 

[00:38:43] Jonathan Wolf: But just very high level actually, because I, I'm very interested in this, like, let's say for kids under five, just broadly do you think actually we should be giving them vitamins?

And I think about this with my own three-year-old, as I push quite hard trying to get good food. My 14-year-old actually eats pretty well now. My three-year-old. It's incredibly hard to get her to eat anything that isn't beige and we do give her vitamins I was curious what your take would be on that.

[00:39:10] Sarah Berry: Jonathan, that's the same for my 10-year-old as well, not just your three-year-old. So what should we do, JoAnn? 

[00:39:18] JoAnn Manson: Yes. The American Academy of Pediatrics does have certain recommendations that are more for the infant, especially the infant that's breastfed because the formulas do have vitamin D and some have iron.

And so, you know, you get some of those micronutrients there in the formula. But of course, we encourage breastfeeding. But taking vitamin D, supplemental vitamin D, and iron, there are recommendations from the academy. For older children such as your own? I think it depends on really the quality of their diet.

Most children do not really require multivitamins or dietary supplements. If you can get them to have some fruits, vegetables, and fish and some, you know, poultry, even a reasonably healthy diet is probably enough. And if they can be physically active and spend time outdoors, being physically active, they probably will be able to do quite well.

So I generally haven't recommended that routinely parents should give their children multivitamins or any dietary supplements after that infancy period that the pediatric societies do have recommendations for. Then when you talk about other high-risk groups, people with macular degeneration, there is some evidence that they will benefit from a formulation that is antioxidant vitamins and copper and zinc.

That was shown in the AREDS trial, and the AREDS 2 trial, and there are formulations. I don't want to get into specific brand names, but you know, certainly, if you have macular degeneration, discuss this with your clinician. And there are some products of vitamins and minerals that have been found to be a benefit in slowing the progression of macular degeneration.

So that's a high-risk group. Then there are older adults who are in nursing homes or have osteoporosis bone health problems. Probably should be taking calcium and vitamin D supplementation.

Our findings, In VITAL, were not targeted to high-risk groups who already have osteoporosis. It was a usual risk, generally healthy, midlife, older adult population who don't seem to need the supplement for bone health purposes, but older adults may. And then there are people, as I mentioned, the male absorption conditions.

You know, if you have Crohn's disease, ulcerative colitis, or Celiac disease is another one. For severe lactose intolerance, it may be a benefit to take these vitamin-mineral supplements. And I think that there are some other groups that would benefit those who take medications like metformin, proton pump inhibitors, these medications that could interfere with the absorption of some of these vitamins and minerals.

[00:42:13] Sarah Berry: So JoAnn, you've highlighted all of these different people that for different reasons would benefit from supplements. Obviously, you know, some of these only apply to maybe 1% of people or even less than that. And so my take home from listening to you talk through all of that is that given that there's no harmful effect of taking a standard dose multivitamin, maybe the outcome is, is that actually we would all benefit from taking a standard dose multivitamin.

[00:42:46] JoAnn Manson: You know, again, I don't want to make a public health recommendation that everyone takes multivitamins. The US Preventive Services Task Force just weighed in on this and made the recommendation that it was not indicated. You know, that everyone takes multivitamins.

However, at the same time, their meta-analysis showed a 7% statistically significant reduction in cancer, taking all of the trials of multivitamins, including the physician's health study II. And they looked at all of the trials that had been done on multivitamins and said there was a significant reduction, but they're still not recommending it. So I think I'm going to leave those guidelines to professional organizations and societies because generally, as a researcher, I'm trying to provide evidence and data that can be used by these professional societies and organizations, synthesize the evidence and come to the public health recommendations.

When you asked me what I thought was reasonable, I do think, especially during this pandemic period, taking the vitamin D 1000 to 2000 IU a day and just hedging your bets and also a multivitamin is quite reasonable, if you have concerns about having this really healthy, well-balanced diet.

I think it's very reasonable because these specific supplements have been so well tested and they have been shown to have some benefits, and they're also very importantly, safe, with long-term use, and I think that can't be said about so many of the other dietary supplements on the market. Of the more than 90,000 plus supplements out there, most have not been well tested at all and don't have a clear efficacy for any outcome, and also haven't been clearly shown to be safe, and some of them haven't been shown at all to be safe, even with short-term use.

[00:44:52] Jonathan Wolf: Amazing. JoAnn, I'm going try and do something we always try and do at the end of this podcast, which is for me to try and summarize, you know, what we've just covered. And this time both you and Sarah can keep me honest. So I think we started by saying that most people can probably get all the vitamins and nutrients they need from a healthy, varied diet.

We also said that actually taking too many of these vitamins can be toxic. So these sorts of mega doses aren't just neutral, they could really be a problem. Then we talked about multivitamins and there's this new really exciting evidence from your latest study. On vitamin D, I think on balance, the evidence suggests there is some impact on our health and that many of us may get enough from our food and sun.

And then I think the final thing we talked about again, was sort of specific groups. So for example, omega-3, you've seen this impact, but it looks like, it's really impacting if you're not eating these fish, if your kid's fish consumption is there, it probably doesn't have much impact. And then I think picking out some specific groups.

So interestingly with children, you were saying after infancy probably doesn't require it, but in pregnancy or prior to conception, incredibly important. And this is where you were, was strongest in the entire discussion. As we get towards older adults, there's potentially a lot more value and we may see more of this.

And I think this is, again, this general view. There's not just one feedback for everybody. Your own personal situation is very important. And so it sounds like particularly as we're thinking about ourselves or other people we know who may be a bit older, really thinking there might be some value there.

[00:46:20] JoAnn Manson: Superb summary, Jonathan. 

[00:46:22] Jonathan Wolf: Oh, well that's my one point in doing this.

JoAnn, thank you so much. I, I would say just at the end of this, that the other big area of research that you've been covering is about everything to do with women's health, and I do hope that we can tempt you back for a whole podcast just on this topic.

[00:46:38] JoAnn Manson: Yes, absolutely. I'd love to do that. 

[00:46:41] Jonathan Wolf: Wonderful. Thank you so much, and thank you, Sarah, for helping to keep this podcast on track. 

[00:46:46] Sarah Berry: Thank you, thank you for letting me gate crash, and great to chat with you, JoAnn. 

[00:46:51] JoAnn Manson: Yes, thank you so much, Jonathan, Sarah, I actually really enjoyed it. 

[00:46:55] Jonathan Wolf: Wonderful. 

Thank you to JoAnn and Sarah for joining me on ZOE Science and Nutrition today.

We hope you enjoyed today's episode. If you did, please be sure to subscribe and leave us a review. If this episode left with questions. Please send them in on Instagram or Facebook, and we'll try to answer them in a future episode. If you'd like to present more about how to get the vitamins you need from whole foods that are right for you, then you can try ZOE's personalized nutrition program.

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As always, I'm your host, Jonathan Wolf. ZOE Science and Nutrition are produced by Fascinate Productions with support from Sharon Feder, Yella Hewings-Martin, and Alex Jones here at ZOE. See you next time.

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