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The Melanie Avalon Biohacking Podcast Episode #117 - Tim Spector

Tim Spector is a Professor of Genetic Epidemiology at Kings College London and honorary consultant Physician at Guys and St Thomas’ Hospitals. He is also an expert in personalised medicine and the gut microbiome and started the famous UK Twin Registry in 1993. He is the lead researcher behind the world’s biggest citizen science health project – the Covid Symptom study app for which he was awarded an OBE.
Through his work he has been given many awards and prizes and is a Fellow of the Royal Society of Biology and the Academy of Medical Sciences. He has published over 900 scientific papers and is ranked by Google as being in the top 100 most cited scientists in the world. He has published four popular books- including the best-selling Diet Myth and more recently, Spoon-Fed, a Sunday Times bestseller. He writes health blogs, which have been read by more than ten million people and appears regularly in the media all around the world.

Instagram: @tim.spector


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3:30 - IF Biohackers: Intermittent Fasting + Real Foods + Life: Join Melanie's Facebook Group For A Weekly Episode GIVEAWAY, And To Discuss And Learn About All Things Biohacking! All Conversations Welcome!

3:55 - Follow Melanie On Instagram To See The Latest Moments, Products, And #AllTheThings! @MelanieAvalon

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Spoon-Fed: Why Almost Everything We’ve Been Told About Food Is Wrong

The Diet Myth

12:40 - Tim's Personal Story

16:25 - When Does The Difference In Microbiome Occur In Twins?

19:00 - what is the capacity to change the microbiome?

20:50 - the supersize microbiome diet

22:15 - Blastocystis

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26:35 - germ free mice

28:10 - anxiety & depression

28:35 - does every animal have a microbiome?

28:55 - Parasites, Fungi, Bacteria & viruses

29:30 - the layers of the microbiome

30:45 - the microbiome and diet

32:15 - 30 plants a week

33:30 - low carb, keto, and carnivore diets and gut diversity

35:20 - what about people with digestive issues?

38:15 - is the problem with the lack of carbs or the increase in fat?

40:50 - do spices or herbs count toward the 30 plants?

42:45 - fasting and changes in the biome

45:30 - circadian rhythms and chronotypes

46:45 - how zoe works

50:40 - BLUBLOX: Blue-light Blocking Glasses For Sleep, Stress, And Health! Go To BluBlox.com And Use The Code melanieavalon For 15% Off!

53:35 - the macronutrient breakdown of the zoe muffins

57:15 - blood sugar spikes and dips, is it reactive hypoglycemia?

1:01:00 - night time hypoglycemia

1:01:30 - what about muffins that are HFLC or LFHC?

1:04:45 - food myths

1:06:00 - poor fat clearance, and good vs bad fat

1:09:40 - c8 research

1:12:30 - being on keto and having a carb challenge meal

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1:15:15 - what has been the most surprising finding from Zoe and the PREDICT studies?

1:16:30 - the blue poop challenge

1:19:15 - CGMs, accuracy vs precision


Melanie Avalon: Hi, friends, welcome back to the show. I am so incredibly excited about the conversation that I am about to have and not only am I excited, I know that you guys are super excited because you have been begging for this episode for probably over a year now. So, the history on the conversation--, the history of what led up to today, I don't know when it was probably a year ago or so, my cohost, Gin Stephens, on the Intermittent Fasting Podcast did a program called ZOE with the PREDICT studies, and it was so cool, basically, and we're going to dive deep into what it is today. But it's an entire program that analyzes your gut microbiome, and your blood sugar, and fat clearance response, and creates a personalized profile for how you process food. She loved it and was raving about it. I started getting questions all the time from my audience about it and I was like, I haven't actually done it. So, I couldn't really speak to it. So, I decided to do the program myself and also read the work, which I had seen but I haven't actually read yet, and so that is Tim Spector, who created all of this. I read his two most recent books. The first one is The Diet Myth: Why the Secret to Health and Weight Loss Is Already in Your Gut, and his second book, Spoon-Fed: Why Almost Everything We’ve Been Told about Food is Wrong. Well, he does have four books, but those are the two that I read.  

And friends, oh, my goodness, those books were incredible. They are up there, and my favorites books ever, and I honestly, actually mean that they dive so deep into diet from a perspective that I feel is so overwhelmingly not cherry picked. It's refreshing. It basically just really looks at what does food do in our body, what is the history of our genetics with that, how does our gut microbiome play a role, what are the lies, and the myths, and the misconceptions told to us through diet culture, and the processed food industry, and even scientific studies? On top of that, I am now actually currently doing the ZOE program. I think I'm on day eight or so. The whole thing has been amazing. Oh, and then on top of that, Tim is writing the foreword to Gin's new book, Clean(ish). So, that was a really lengthy introduction. But just to say, I am so, so excited about this conversation. Tim, thank you so much for being here. 

Tim Spector: It's a great pleasure. Looking forward to a chat. 

Melanie Avalon: I am as well. So, for listeners, I do think a lot of them are probably pretty familiar with your work, but I will let them know that you are a Professor of Genetic Epidemiology at King's College London. You are a fellow of the Royal Society of Biology and the Academy of Medical Sciences. You've published over 900 scientific papers, which is insane, and this is super cool. You're actually ranked by Google as being in the top 100 most cited scientists in the world. I mean, just let that fact land. That is a very big accomplishment. But yeah, so, to start things off, we were just talking before this, there's so many things that we could talk about. I would just love to know a little bit about your personal story and what led you to where you are today with your fascination with the gut microbiome, and also studying our personalized responses to food? 

Tim Spector: Okay. Well, the story goes way back actually to when I started studying twins 28 years ago, and I set up the UK's twin registry, which now has 14,000 twins in it, which basically the most well studied people on the planet. Most of the early years were spent looking at how fascinating the similar identical twins were compared to their fraternal twins. We made lots of discoveries and interesting things both about diseases, obesity, diabetes, but also things like personality, and even genetics or religion, whatever. You can study anything in these, guys. But after about 10 years, I got to be thinking, "Well, why Siamese identical twins are different? Why do they get, you know, one gets cancer and the other one doesn't?" That seems to happen quite a lot. One gets an autoimmune disease and the other one doesn't, why? Sometimes and not always, but sometimes one is overweight, and the other one's skinny. It started to play on my mind that I've been doing genetics, obviously, I was telling everybody that genes were the only thing that matters, and suddenly I was having a bit of doubt, because these are-- identical twins have identical genes in every cell in their bodies. So, I was looking then for things that might be different in these identical twins and it turned out, the one thing that was most different about them were their gut microbes. That really was that aha moment when we actually tested this in 2013 and came up with a result one of the very early studies, the gut microbiome that actually, they're hardly more similar than your eye. That was pretty amazing and it really led to everything else.  

To me, talking about how-- and thinking about how if our gut microbes are different, then they eat our food, and they produce all these amazing chemicals from our food, and that's probably why we're so different, and why we all react differently, and why we have to look at nutrition in a totally different way to what-- I was taught at medical school, and it's still taught in mainstream nutrition, and to doctors, and health professionals. So really, that's an insight using identical twins, saying, "Well, if identical twins are different from their microbes, that means that a lot of these things we've taken for granted just aren't true." Then when often really got into nutrition in a big way and did a lot of research my books, which is how I caught up on the field, and there we are. This is really why the last 10 years having studied hundreds of different diseases and things and look to genetics, epigenetics, and all kinds of other fascinating scientific areas that I've decided this is the most exciting area of science today. Not only that, I'm not interested in publishing another hundred papers, I'm interested in actually doing something that-- creating science that changes people's lives and that's really where I am today. 

Melanie Avalon: I love that so much and I will say definitely reading your books, definitely the most nuanced and eye-opening view I've seen of the microbiome. So, with the twins, where along the line of their personal timelines does that difference in the gut microbiome occur? Is it at birth or somewhere along the line of their lifestyles or is it different for each individual twin? 

Tim Spector: Well, we haven't been following the twins with collecting that poop for 30 years. Unfortunately, people thought we were crazy when we started 10 years ago. But putting our freezers full of poop samples, most people are happy with blood and urine at a stretch. So, we don't know exactly, but there have been some studies of young twins, they're no different really to unrelated twins in the first three years of life, it's a bit of a lottery, which microbes you get and how you start life, and that depends whether you've had a cesarean section birth, who delivered you, whether you've been given antibiotics, whether you had the infections, whether you're breastfed, which part of the country you lived in, whether you had a smelly dog that used to lick you, all this kind of stuff has a big effect on your startup cultures if you like in your gut. So, we're not sure exactly when these differences occur, but it doesn't look like at any point in life, even identical twins are really the same.  

I think there's so many life events that change the early structure of your microbes, that only means that we're always going to be unique, and that there's so much randomness in it much more so than we ever believed. But that uniqueness actually, although, it's annoying for scientists is actually a great boon for us as individuals, because it means we can work out our own path too and we must-- we can't just depend on other people's answers to things. But it means what didn't work for someone else can work for us. Different diets can work for one person and not another, different medications can work for some people not to others. So, it makes life, on the one end, a bit more complicated, but also, I think is quite empowering. It means that we will have to become our own scientists in a way to understand our own bodies and I think that's an exciting finding. We can't just take it all for granted and assume that some doctor or specialist knows all about us, because they've studied all the people. 

Melanie Avalon: That actually leads really-- well, into one of the biggest questions I have about the microbiome that has haunted me for honestly years, and it has to do with the role of the potential for change in your personal gut microbiome. So, it seems like on the one hand, well, backtracking a little bit, something I never thought about before was you talked in your book about how, you know, there are bacteria everywhere, but there's only certain species that specifically are specialized to colonize the human gut. So, it seems to me that there's certain species that you would get from birth, and if you don't have that natural birth like, can you get them back? Then when people do rounds of antibiotics, can you get them back? How does that compare to the gut bacteria that you can change through diet and lifestyle? Are there certain species that when wiped out, you can just never get back compared to some that you can, "grow" if you follow a certain diet? 

Tim Spector: The truthful answer is nobody knows, but we can speculate. Because we just haven't done these experiments in humans by which you wipe out all their gut bugs and then reintroduce others. We do know from mice that you can grow in sterile environments that you can start reintroducing some, and there's no doubt, some are much harder to grow and others are very easy and there's a spectrum of these microbes. We're seeing in these early studies that, it's actually easier to influence your bad microbes, get them down than is to improve your good ones. And that's an interesting observation we haven't really sorted out it yet. So, once you've wiped out all your good microbes, it does seem hard to grow them back. I've got the story of my son in McDonald's too as anecdote on that, which I do discuss in the book that I wanted to do is a microbiome supersize me experiment, and chose my son, Tom, because he was willing to do it, though, no money as long as I paid for eating all his meals for 10 days in McDonald's. He was a student, and he actually liked McDonald's at the time, and he was very skinny. So, I did this and he lost about 30% or 40% of his gut diversity. So, he lost quite a few species according to our tests at the time.  

Although, I sent him packs of salads and fruit and veg, two to three years later, he still hadn't regained that diversity. So, I think, you can knock off good bugs and find it hard to get them back whereas if you change from a bad diet to a good diet, you can see a reduction in the bad microbes, the inflammatory ones, the ones that come out when you eat lots of fats and processed foods, and you can get rid of them. So, this is all very new. No one's really doing these long-term intervention experiments. So, we're having to guess a lot of it. This is the current view of where we are. There are some species that may be hard to grow and others easier. It's quite interesting. When I tested myself recently, and you'll get your result, there's one of the bugs that the ZOE looks at is called blastocystis. This is a parasite that you really wouldn't want in your gut. Because it's associated with travel diarrhea, and other things, you say, "Oh, I don't want this bug in me." But 30% of British people have it.  

It turns out that it's associated with being thinner and digesting your fats better. So, actually, it's a good parasite to have and people in general way less than they have less internal fat. One in 10 Americans has this parasite go into our latest data, and we've been trying to work out how we can boost it if you'd like and we haven't yet come up with an easy answer. But we know much better how to suppress the bad guys that cause inflammation and mess up your metabolism, So, I think, it's going to be possible but I think it's going to be much more complex in how we deal with these problems. But I think the case of my son is interesting, because it just shows you the small amounts of junk food for a while isn't a real problem, but if you go for a long time without fiber and just eating all these chemicals, you can do some permanent damage to your microbes' community. I'm not saying impossible, but much harder to get back to normal. 

Melanie Avalon: Is that blastocystis hominis? 

Tim Spector: Yes.  

Melanie Avalon: Oh, that's so interesting. Yeah, because when I hear that, I think parasite bad but not. 

Tim Spector: No. People have asked me if I'll sell mine to them. So, yeah, a good deal on the internet  wants my blastocystis.  

Melanie Avalon: Super curious speaking of the germ-free mice, because you talk in your book about how they're expensive to maintain because they require so much more food, because they naturally are thinner. Do they have the health benefits of, we typically see with being underweight or do the germ-free mice that are thinner have other health conditions, there might be a problem. I'm just wondering if that speaks to the potential benefits of a sterile gut. 

Tim Spector: It's interesting, they don't seem to have any anxiety. So, if you wipe out all your gut microbes, you can sort out anxiety level. So, that gets stressed. But they don't really do much either. They're not very interested. They are not interested in-- particularly interested in eating, or having sex, or doing all the fun things in life, but they don't get stressed out. So, they're in this neutral environment where nothing much happens, they don't get particular allergies or anything else like this. So, they're in a strange state, but they do need much more food to stay alive. But I think they have a very dull life. [laughs] So, I wouldn't recommend it for anyone else. It's hard to know, you know, how natural it is comparing them directly, because it's a bit of an artificial experiment. But it's certainly interesting the extremes to see how different they are, and particularly, the effects on the brain. I think that really is really interesting. I think, a real growing area about how important gut microbes are for things like anxiety and depression in humans, and by implication, how important our diet is, and studies have shown it's just as important to--, you can get the same results with a good diet as you can with antidepressant tablets. 

Melanie Avalon: That is fascinating. So, that really does speak to the role of the gut microbiome and creating different neurotransmitters for better or for worse affecting our mental state. Are there any animals that have a GI system that is not colonized by gut bacteria or is every animal have some gut microbiome? 

Tim Spector: Everyone that I know of has some form of gut microbiome. Even fish and other animals, they're everywhere. You remember that these gut microbes, we have the large ones like parasites in our guts, and then we got fungi in there, we've got bacteria, and then actually feeding off the bacteria, we've got parasites on them, which are these virus phages to little viruses, actually feed off our bacteria. So, like a Russian doll, everyone's in a way part of this ecosystem. But that is nearly never ending and who knows, we might find something that's even smaller that's feeding off the viruses, we just haven't found that yet. so, the ecosystem of a jungle, there's always something in there in that hierarchy that's changing it. That's why it's important to think of microbes not. I mean, it's fun to talk about Blastocystis and these other ones, but I think you've got to start seeing them as this community of bugs that like a guild, and they work together as chemical factories.  

I think that's the way to view them. You give them fuel in the form of food, and they convert that to key chemicals that go around your body in those vitamins, either as brain chemicals to keep you happy, as immune regulators to stop you getting autoimmune disease or food allergy, or to fight COVID, or they change your metabolism and your appetite levels, and the rate at which you're burning fat and things. If you think of it in that way, then you got to realize that it isn't just one bug that's important. It is trying to get that the right community, the right team working together to get those chemicals produced in the right balance for you. As many different microbes you've got, the better though your range of defensive chemicals. I think that's the way I've evolved into thinking about the gut microbiome. 

Melanie Avalon: Where are you now with the gut microbiome and diet? So, people who are on extreme approaches to diet veganism or carnivore, and if they do or do not thrive on such approaches, do you think that's chicken or egg like people who do really well on a vegan diet, do you think it's because they had a gut microbiome that is suited well to a vegan diet, or did a vegan diet create a microbiome that can digest a vegan diet? I'm just curious about the chicken and egg between the diet and the microbiome relationship. 

Tim Spector: Yeah, great point. But I'm not sure veganism is the best example because vegan diet really is a plant-based diversity, and probably, a third of the planet have a vegan diet more or less. Clearly, we've evolved to eat like that in many parts of the world. Eating fish, and meat, and eggs isn't crucial to our survival. We know that we've done studies. We compared to the big study with a British gut project, American gut project a few years ago, 11,000 people, we look to see what element of diet gives you the healthiest gut microbes? It was not whether you're vegan, not whether you're a carnivore, fish eater, not whether you drink alcohol or whatever. It was how many plants a week you ate. The optimum was 30 plants. Anyway, this is now a theme that runs through my books and my talks that this is the magic number that makes sense. A plant being any nut, or seed, or herb, or spice, or whatever it is, it's fairly loose term. But it means that if you're  me, a plant-based person but occasionally eats a bit of meat and fish, it doesn't really matter the day as long as I've got enough different plants in my diet, what else I eat. So, it's in a way not about that rather limited description of the diet, it's because there are some very good vegan diets and some very bad vegan diets. 

There are some vegans who just eat cupcakes and sugary mixes without any real food and are highly processed. Other vegans are super healthy. Similarly, you can be a meat eater, but as long as you've got enough plants in your plate, you're going to have the same microbes as a vegan. So, I think that's true. But I think your point was maybe to something like a keto diet or a carnivore diet, where actually you're focusing on meats, proteins, and fats, and a very low carb diet. Again, our data suggests that whereas that for-- some people is fine short-term. For long-term, all our data suggests that that will reduce your diversity of gut microbes. For most people, it leads to long-term problems. Clearly, there's a huge variation within that in some people. We now know are more suited to eating high fat diets rather than high carb diets. That's really what the ZOE program shows you. It really separates those groups. So, you get an understanding of does your body overreact to sugar or does it overreact to fat? Can you rebalance your diet on that basis? We know that microbes are responsible for that.  

As you probably know, some people when they try keto diet immediately say, "Yes, this suits me." and others say, "Oh, this is terrible. I can't bear it." We think it's likely that the makeup of the gut microbes determines how easy it is to adapt to those diets, so that I think there's a short-term answer not a long-term one. I probably confused you on that, but it's not about the labeling of the diet. It's like saying, "Well, what else do you have?" Because I'm sure there are some people on keto who'll say actually have lots of plants as well, and others who sticked strictly to trying to get their 70% fat levels and then neglect that variety that I think is crucial. But if people understand the gut microbiome more I think you can probably modify all these diets, but still help the gut microbiome if you understand that the gut microbiome is actually crucial for your long-term sustainable health. 

Melanie Avalon: If variety in the diet, is it causational or correlational? Is it possible that people who have the gut microbiome to digest a wide variety of plants self-select to that diet and that people who-- Because a lot of people, especially, my audience have digestive issues and they feel like, if they were to go on a whole foods plant-based vegan diet with a ton of different plants that they would experience a lot of digestive distress? So, I wonder if their microbiome is not a "healthy microbiome." So, they automatically are self-selecting to not follow that diet. Does that make sense? 

Tim Spector: Yeah.  it's chicken and egg. I think it comes back to the idea of, you've got diet and you've got the microbiome, and on the one hand, I'm saying to you that diet influences your microbiome, but also your microbiome influences your diet. So, it's a two-way process. If you've got an inflammatory microbiome that's used to having high sugars, fats, processed foods, then it is going to be seeking those kinds of foods in a way, and there's some fascinating animal experiments thinking that you can actually modify your food choices by fiddling with your microbes. Your actual microbes are like, "Give me more burgers," because that's what the microbes are doing well on and they're sending out signals indicating appetite. So, we don't know this is true in humans, but it's certainly true in little small animals. So, I think it is a bit of both, and there is a slight catch 22 that I know a lot of patients get upset when you tell someone with IBS. Just eat lots more vegetables and you'll be fine, because I said, "Well, actually, the vegetables that set me off, so I avoid them."  

I think we have to find that balance and understand there is a two-way relationship. But long-term you have to work out, there are 30,000 edible plants they reckon in the world. So, I think we have plenty of time to try and find ones that we can eat that will be okay for us. I think what I worry about is many of the modern diets and fads don't include this long-term plan to increase your plant diversity. So, they might work short-term, but they might be self-defeating because of this other problem. So, all of these ideas to get you through that short-term need to have some long-term plan. It's a bit like fodmaps diet. They come to an end, and then you said, "Yes, so, it's great. I've avoided all these foods." But then what do you do? You've got a very restricted diet, your microbiome is going to get worse. So, these problems are going to recur unless you find some longer-term solution, which is actually a longer journey. 

Melanie Avalon: Are the potential long-term issues from that from the low carb or are they from the high fat? Because you could be low carb-high fat or you could be low carb, not high fat? 

Tim Spector: I think this all depends, and this comes back to in a way that the idea behind the ZOE program of testing people to look and see what's your standardized response to a muffin loaded with sugar and fat? Is it mainly that you react with a big sugar peak or is it mainly that you react with a big blood fat peak at six hours, which suggests you're not really getting rid of the blood fats as efficiently as you should, which could lead to long-term inflammation problems? We're finding that there's huge variation, and this is what we saw in the ZOE, PREDICT studies, eight-fold differences in how people respond to an identical muffin. So, I think these questions are very hard to answer as a global level because everyone's going to respond differently to whether they're going to respond better to fats, or better to sugars, or well to both, or not well to both.  

So, this probably explains why it's-- We found it hard to tailor diets to people just by dogma of saying all keto diets work or all low-fat diets work, and the trials that have been done have always been inconclusive between the two, because on average some people respond to some or not the other. I think that's where we need to be thinking about is, what diet is right for me? There isn't necessarily a global diet that's going to be perfect for everyone with the caveat that, "Yeah, everyone needs to look after their gut microbes in some way." 

Melanie Avalon: I don't want to have an agenda, and I don't want to have one idea. But if I had one idea, there's not one diet for everybody. I really feel like with the low-carb keto world, I feel like it's sort of like what we're talking about earlier with veganism and you can have plant-based whole foods veganism or you can have processed veganism, and those are two entirely different things. I just wonder how often the difference in with the keto world the actual fat levels. Because I personally tend to follow a higher protein-low fat approach actually with intermittent fasting. But when I do even keto, I don't go crazy high fat. Question about the plant variety, does that include spices? So, if you did a spice blend that had 10 different spices would that count as 10 different things in your diet? 

Tim Spector: It depends on you are an optimist or a pessimist, I think. We don't really know is the answer. What the minimum amount of food is that really counts. I think that's pushing it a bit to be honest to just have a few grains of something. 

Melanie Avalon: Oh man, [laughs] how can I get my 30?  

Tim Spector: But I find it pretty easy, just say, how I changed my diet. I used to have a granola or muesli, low-fat milk and orange juice in the morning and I did my tests worked out that was probably the worst thing I could possibly have. I have yogurt, kefir, mixed fruits, and mixed nuts and seeds, and that gives me like eight plants just on that one meal. So, it's thinking like that and then you can sprinkle others on your salads and whatever. So, it's not as hard as you think. But you know always adding some coriander-- some cilantro, some parsley, these are obviously plants that make sense. Basil, this kind of stuff all counts. Clearly things like turmeric, ginger, yes, they definitely count. Some industrially made spice mix made in China, I'm not sure I'd really go out and claim that's 10 ingredients. Therefore, I'm fine. You got to work out for yourself or you're going to count. It's a bit like intermittent fasting. We don't know what the minimum amount is to break a fast and the same time we don't know what the minimum amount is that's going to stimulate your gut microbes. So, we're revolving our advice as we go along. 

Melanie Avalon: What have you found on fasting and the gut microbiome? I know you talked about Akkermansia. Do you find changes in the gut microbiome with fasting? 

Tim Spector: Well, certainly, we do see changes. Generally, the longer the fast, the less you get inflammatory microbes and the more you get the good guys out, because we know that if you do have a long period of fasting, it allows your microbiome to rest-- A clean up team comes out and basically tidies up your gut lining, and this seems to improve both the quality of the gut lining, but also your general metabolism. We've also seen that meal timings also influence your spikes of your gut, your blood glucose and your blood fats. So, we know that they're crucial factors, but there's many factors involved like circadian rhythms and whether it's morning or evening also makes a difference, which can vary between people as well. But in general, all our data is pointing out at intermittent fasting, or restricted time eating, perhaps more, particularly, which I think is becoming more common than intermittent fasting is beneficial for both your blood sugar responses and your gut microbes. We're still working on this in the analytics, in the ZOE programs, as we find that more and more people who're taking the program, and also do some restricted time eating anyway. So, we are seeing this--  

Interestingly from our first data, we showed that the idea and I mentioned this in the books that skipping breakfast was actually a good idea for many people. It does seem to be backed up by our data, but it's really not true for everybody, and it might change with age as well. So, you might be someone who's always had breakfast, but it might be worthwhile switching to avoid it as you get over 50 or something to see if it's changed. Because you might metabolize food like I do better in the evenings, in the mornings now whereas perhaps when I was 20, it was completely different. So, as always, these things just get more complex, but we're fairly sure that fasting is going to be a major part of our advice going forward and we want to start collecting enough data, so we can be able to tell people whether they're predominant morning person or an evening person and trying to work out based on the science of the testing when they should be doing their fasting period. I think, it's here to stay that, I don't think it's a fad. I think that's something you can do long-term and it suits many people. 

Melanie Avalon: I'm so glad you brought up the circadian rhythm nature. Recently, I've been diving deep into chronotypes because I'm going to interview Dr. Michael Breus, who wrote The Power of When. Also, in the circadian rhythm world, I recently interviewed [unintelligible [00:33:43] Grant. She's a researcher at UCSF and she works with Oura ring. One of her studies, this blew my mind. This made me just rethink blood tests altogether. They had people check their cholesterol panel basically like their Trigs, their HDL, their LDL, and their total cholesterol all day just constantly, and every single person at some point during the day, their markers went into the risk category and the triglycerides, LDL, and total cholesterol I believe all fluctuated significantly. HDL stayed more similar, which I found really interesting. But I don't know. That really blew my mind because it made me realize that I think we often do a snapshot of blood tests and we make a lot of assumptions, but it can really be hard to know what's going on. Have you seen with-- ZOE with the muffins, what role does the timing play in the fat clearance after eating the muffins? Maybe we should backtrack about the setup of how it works. 

Tim Spector: Okay, so, basically what we do this big science experiment a couple of years ago, where we got 1,100 people, mostly twins to do the standardized studies per day in the clinic, and then, two weeks at home. Basically, recreating this as a home kit, this experiment in slightly less detail, but we know what goes on in several thousand people now. We did follow-up studies, and basically, it's giving people set meals, getting to log all their foods, getting to log their energy levels, their appetite, and at the same time, and their sleep and exercise or with wearables, etc. At the same time, logging their continuous glucose levels with a glucose monitor which lasts for two weeks, and I can read on that every five minutes from their phone, also doing a few tests where you see what your six-hour post-meal blood fat level is. We also measure inflammation markers and other things like this and then as well as your microbiome.  

So, basically, you get this rather comprehensive test to look at how you're responding to food in different ways, that allows us then to put all that together in algorithms that gives you scores for all your common foods and ranks them in order for you in person, how you responded in terms of your glucose, how you responded in terms of fat, and how it's going to affect your gut microbes. That way everyone gets a personalized score on an app that they can use to then go on a three-month program of choosing their meals based on what scores they are going to give them, the least peaks, therefore, the least stress and inflammation on their body without restricting calories, without doing things that most diets do. Because we just believe it's just a question of swapping choices and thinking more diversely about what you want to eat. Just thinking more intelligently about food choices. So, that's the basis of it. Clearly to get that information we got to do a bit of-- Basically, you do a home science experiment and share it with tens of thousands of other Americans. So, we get these amazing results which get better all the time.  

As well as being told about the foods, you also get certain gut boosters to say which foods you need to eat to reduce your nasty bugs, and which foods you should eat to boost your good ones even further to improve that ratio which we think is crucial so far. So, that's in essence that what's going on, and we also as part of this, we measure-- and the results so far really show that nearly everyone loses weight without say, calorie counting which I think is a nonsense and six to eight pounds in a month is the average. But I think even more important is actually everyone reports better energy levels and lower appetite signals. So, the less hungry just by switching the foods to something where maybe doesn't give them those spikes, and that's really the essence of where we are. So, we started a few months ago but that's essentially what it is. It's a totally another way of thinking about food that tailors it for you in a way that is sustainable for years rather than just the usual one-month quick diet. 

Melanie Avalon: With the muffins that you use, what is the macronutrient breakdown? So, I'm currently in the process, and for listeners the setup of it right now is that you do one day where you have breakfast and lunch muffins, which I did them in my intermittent fasting window. So, I follow a one-meal-a-day evening. The process for the breakfast and lunch takes about six hours. So, I did it from 7 PM. I was taking my finger prick test at 1 AM or 2 AM. What is the macronutrient breakdown of those muffins, what are you actually testing from them? Then the next day you do another set of breakfast muffins, which I actually haven't done yet because they said I could do it on a different day. But what are you testing from that? 

Tim Spector: Okay, so, I can tell you didn't really like the muffins.  

Melanie Avalon: Sorry to interrupt. It's so funny. So, Gin, my co-host, she was like, "You're not going to like the muffins because there's this idea out there that they don't--" I don't know. People were saying that they don't like the way they taste. I knew, I was like, '"This is going to be--" because I haven't had processed sugar or flour--. It's gluten free flour or vegetable oils in years and I just knew, I was like, "This muffin is going to taste like the most amazing thing I've ever tasted and it did." Then I was ravenously hungry and I was like, I fast every day for 16 to 20 hours, but you have to fast for four hours after it, and it's like I was starving. I was like, "This is awful. [laughs] But it tasted amazing and it made me feel so hungry after." 

Tim Spector: Yeah, most of it is vegetable fat and sugar. So, what we're doing is, the aim is not to give you a muffin that is amazing and a bestselling muffin. It's basically based on our work in the thousand people, what stimulates the blood sugar enough and the fat levels enough to get a response and difference between people without making them sick. So, I can't remember the exact percentages of both, but you can probably tell they're fairly greasy and they leave a stain on the-- on the paper showing that there plenty of fat in them. They also got plenty of sugar that gets released, and it's getting that balance right. So, there's not too much fat to suppress the sugar, etc., etc. What we find is, yeah, that we get a good reading on someone's response to both sugar and fat with that single muffin. That's why we ended up with what it is. So, I think there's only-- there's just the 8% percent protein I think from the flour, but the rest of it is trans sugars. No miracle other ingredient, unfortunately, and not much fiber. So, you wouldn't want to be on that continuously, but you think you did badly with that. I had to do an experiment where I had to eat them continuously every 4 hours for 24 hours to look at my circadian rhythms. I've never felt so ill in my life. I was spiking, I was doing these massive sugar spikes and then dips, and I couldn't concentrate, I couldn't work, I couldn't do anything. It was really horrible. So, I'm not doing that one again. That's the one-- I do lots of experiments, but that was probably the worst [laughs] thing I've done. So, having a one off with a black coffee in the morning, that's probably okay. But having it as every meal is different. But some people do that naturally, in the US that's quite common. People just go from one massive fatty carb to another, and go from one sugar spike to sugar dips. Do you get sugar dips at all? 

Melanie Avalon: I wear CGMs a lot. In general, with the pattern that I do, I'm pretty consistent during the day. I don't really get crazy dips. My blood sugar does lower consistently from breakfast until dinner. Then, when I have dinner, it usually spikes to about 120 max, and then it goes back down, and this is eating. I eat an insane amount of fruit actually, but I do low fat. So, I never like to combine for me personally fat and carbs. So, I either do high carb-low fat or low fat-high carb. But it seems to work pretty well, and I see that on my CGM. The thought I had doing the muffin experiment was I had flashbacks to when I used to eat a typical standard American diet, and having those blood sugar swings and I was just thinking I can't believe I used to do this like this is so miserable. I'm grateful to not be doing that. 

Tim Spector: About six months ago, we published a paper about sugar dips. But one in four people after having a peak, three hours later, which is much longer than anyone ever looks, most people have given up and gone home by then. One in four people have quite a marked sugar dip. Those people are known to them actually reported more hunger, and loss of energy, and ended up eating 10% more calories that day than people who didn't have a dip. So, that to me was really amazing showing that with this new technology and these big numbers, we can find these new facts about people, so the people eating identical muffin, you react very differently. You'll actually eat more or less in that day depending on whether you dipped or not. That really rams home the idea that calories are complete rubbish, the idea that calorie is always equal is complete nonsense. I think, the science is now actually proving it.  

So, I think we're hoping to go on and try and work out how we can tell if someone's a dipper or not and warn them about the starting the day with too many carbs, with other people might be fine on it and never dip, maybe that sounds like you that you know, you're safe. But I think that was a lovely lesson that we mustn't assume we know enough about sugar and insulin, and sometimes you just got to look. Most people stop at two hours, but let's look and see what happens later on. This is what this new technology allows us. It's opening our minds to all these new suggestions, but explains why many-- one in four people do end up with a feeling of low energy midday, needing a cookie or pick me up or something they feel, because they've had that sugar surge and then a three-hour later dip. I thought that was nonsense. I thought people were just hysterical, but they are completely wrong and the science is proving it. It's fascinating stuff. 

Melanie Avalon: So, are those dips reactive hypoglycemia, specifically or is it more related to the fasting? Is it specifically to the food? 

Tim Spector: We don't know. We haven't been able to separate that out because this is just 1,000 people's readings against. So, we've just got the observation. We don't know the exact cause and whether its insulin driven or it's-- These were eating the same foods. So, we can't say that it was a difference in the food. I think it sees a difference in the person. I think we found that everyone can dip at some point. You know what I mean? Everyone's got a threshold that you can dip, but some people dip more than others. 

Melanie Avalon: Before I was ever wearing a CGM, I intuitively felt like I was dipping. I wasn't calling it dipping, but that I was dipping during sleep, after eating, I do see that I on my CGM, but I feel like I sleep through it, and then by the time I'm awake, it resolved itself. Yeah, it's really interesting. 

Tim Spector: You feel tired, so, you don't mind having lots of energy while you're asleep. That's good. 

Melanie Avalon: Right. The reason though I identified it is, it used to be worse in the past, so it would wake me up, but now it doesn't seem to be as much of an issue. I'm super curious, have you considered-- so the muffins, one is a lower fat than the other and lower carb, I believe. Would you be curious to see what would happen if you did two sets of muffins, where one was high carb-super low fat, and one was high fat-super low carb? I just really wonder about the context of processing fats and sugar when they're the only substrate being processed. Because maybe some people do process carbs better, but only in the context of low fat, and maybe some people process fat in the context of low carb. 

Tim Spector: Yeah, well, we did lots of different combinations in the-- both the pilot studies and the actual ZOE clinical trials. So, we did use, I think, five different muffin combinations. The problem is that, you got to use something that people can actually eat in a short time, and many people found that if the muffins was too fatty, and didn't have enough carb, they couldn't actually eat it or they were sick. So, you do have this limitation that if you're developing a commercial product, you want everyone to use, you've got to in a way make sure that it isn't too extreme. So, I think they're interesting experiments to do, but we couldn't really push it to the extremes, and we have to just go by what most people will eat without making themselves sick. So, people are actually very sensitive to fats or sugars more than you might think, and everyone's different on that. So, that's the other parameter that slightly limits us to do this.  

But in the end, we're trying to be pragmatic. We're not necessarily trying to answer all the physiology questions. We're trying to just use this as a base to categorize people as to know which way their metabolism is pointing. But as we get bigger numbers, I think we will be able to start dissecting out these more detailed questions, which also not just carbs and fat, but remember, we've got proteins, we've got fiber, and whether you have a high fiber meal the night before, how much sleep you had the night before, all these other-- There's so many factors that it's very hard to isolate individual ones. So, I think we're probably going to move to this model of really multifactorial design and be pragmatic, because there are so many things that do affect your metabolism. I think in the past, we've been very focused on individual dietary items to extreme. It's a reductionist idea that it's all due to this particular type of carbohydrate, or this particular sugar, or it's all down to fructose, or it's down to this particular fat, or it's down to lectins, or whatever it is. I think we just got to move away from that and realize why it's much more complicated. We may just have to assume we'll never fully understand it, but we can at least process it and use it to our advantage. 

Melanie Avalon: Yeah, actually, to that point, and again, I just encourage the listeners to read your books because they are, like I said, mind blowing. But two of the facts that I wrote down from your books that speak to what you just spoke about, one was you've mentioned basically, if you isolate any compound from food, so, fat, carbs, sugar, whatever it may be, if you isolate it enough, you can create toxicity in a lab trial. Then the second thing was that, you've mentioned a meta-analysis of the 12 major food groups, and every single food group could be connected to increased or decreased risk of death. So, it's basically like, it just goes out the window. I just thought that was so fascinating. 

Tim Spector: Yeah, it's a bit depressing, Mel. But instead of means, yeah, well, when you see a headline about a specific food group causing cancer, or saving you, or being a cure for dementia, just take a raincheck. [laughs]  

Melanie Avalon: Yeah. [laughs] I know. Yeah, so, listeners definitely get the books because he dives deep into all of those "myths." Just a little background on why I was asking the question about the different setup for muffins. One of the questions, because a lot of my audience is low carb or keto, and a lot of them seem to be following a low carb or keto diet. What I wonder is, if a person does the muffins and it comes back with bad fat clearance, so fat is not you know, they don't clear it so well. The assumption-- and I haven't gotten to the recommendations yet for myself personally, but from what my audience is saying, it seems to be the recommendation is to go lower fat. My question is, I wonder if people are bad fat clearers, could the solution or the answer for them, be go lower fat or ironically could it be the complete opposite in that, in order for them to process fats, they need to be devoid of sugar? So, you know, they need to switch to a metabolic state to process fats. So, ironically, another diet that might work for them, might actually be high fat if it's low carb, I just wonder about the implications of people who receive a "bad fat clearance score" for an audience that naturally gravitates towards keto or low carb. 

Tim Spector: Yeah, that's a great question. So, I think the first thing to realize is that, we don't regard all fats as equal. There are fats like high quality extra virgin olive oil that really-- we don't have any upper ceiling on because it's so full of other good things like polyphenols, which are good for your microbes, and etc. Whereas, if you're having saturated fats from say processed meats, then they would be seen as bad fats, and you really want to limit those. So, we do make distinctions between good fats and bad fats for someone who has ended up with a bad fat test. I don't think we know the answer to whether you went on a less than 20% carb diet, whether you'd be able to process your fats better. I simply don't have the data to show that. But it may or may not be true, but it would be risky, partly because I think it might make it harder to keep that diversity we talked about in the gut microbes. Because again, you're slowly switching your diet in a big way. So, it might be hard to get those plants on your plate. That would be my worry.  

But I certainly not against people experimenting themselves to see how they feel, and there always will be exceptions. When we give this individual advice, there might be some people that don't like the advice because they might feel good on a keto diet and get the advice, "Oh, gosh, you know what, I feel good. I'm not clearing this fat." I think at least people have some data to go on and say, "Well, actually, okay. I need to be careful which fats I'm having and I need to pay much more attention to having good fats and maybe just restrict the bad ones." That's generally our philosophy. So, we're not going to say don't eat avocados or extra virgin olive oil, for example, even on someone who has very bad fat profiles. 

Melanie Avalon: Yeah, I'm sure my listeners will love hearing that because that seems to be the biggest question that I was getting from everybody. Have you done much research on MCT, specifically C8 fatty acids? When I do a high fat low carb approach, I don't think people need to be slathering their foods and fat. People might find that surprising because I think people associate me with a low carb or keto approach, or "paleo." I'm suspicious about the role of excess fat in the diet. But I'm fascinated by C8 MCT oil, since it's processed so differently. It's shuttled straight by the portal vein to the liver and doesn't even--, goes a completely different route. I'm just wondering if you've done research on that fat. 

Tim Spector: No, we haven't got enough data really to gauge how that works and it's quite hard to separate out those effects from all the other things you might be eating with that meal. In general, we take a view that food is made up of a composite. Even fatty foods are made up of a whole combination of different fats. So, only the highly processed ones are single fat types. That for us is a problem. There's lots of theoretical reasons that's people quote for this particular fat being better than another, but often, it's the whole food that matters, not the individual ingredients. We still know relatively little about all these fats. But we do know is that, some people when they intake too many fats, whichever fats they are, but particularly some of the stuff from processed foods, it will be hanging around in their body for six to 12 hours, and that causes inflammation in the vessels and all kinds of other metabolic problems. So, just knowing whether you have that susceptibility, I think is a useful guide to which route you should be going. 

Melanie Avalon: What have you seen in general from your studies with the people on the muffins? Do most people, is it usually that they process either carbs or fat better or do some people do great with both, do some people do not so great with both? [giggles] What are the trends? 

Tim Spector: they're not really linked interestingly. You get all of the above. You get people, there's annoying people that process both fantastically, which I hate. Others that process them both badly, and then you got all the others in the middle and good for fat, bad for carbs. So, until you do it, you don't really know. Of course, you've got the third element. Like me, I actually process both pretty fairly badly. I've got bad scores for my sugars and my fats. But my only saving grace is I've got great microbiome scores, which perhaps keeps me alive. 

Melanie Avalon: Is there a worry that people who have been following a keto diet?-- Because a lot of people who follow keto diets, I think there's an idea that when they do have a carb challenge meal that there's a temporary glucose resistance, could that create a false positive for processing carbs? 

Tim Spector: I think it could do.  

Melanie Avalon: Or a false negative?  

Tim Spector: It could do and we're just gathering this data now to see whether we need to tell people to have a few days of other diet first before they take the ZOE challenge. But we don't just have enough data at the moment. So, far, it doesn't look like it. Does affect it, but we don't have a definitive answer at present. In a way, people need to ask themselves, "Well, do I want to test myself for in a way the diet that I want to carry on with or do I want to try and get myself back to where I was in some neutral position to see how generalizable I am? In a way people will have their own questions.  

I think we don't quite know what most people whether they want to test whether their diet they're currently on is healthy, and this would give us the answer, or they want to switch to a neutral diet and then look at their general state of health, but then go back to their other ways. So, I think you need to ask your listeners really what they'd want. I suspect that people already doing intermittent fasting in keto probably want to know how their body is responding to that particular diet, and therefore probably shouldn't change too much about it. Just accept the results as being relevant for them. 

Melanie Avalon: Yeah, now, I'm just thinking yeah, it'd be so cool like in brainstorming mode, if there was another arm or an option for people following low carb keto, where the muffins are tailored to that and they see what happens.  

Tim Spector: Well, I'm sure as we progress, we'll be able to add in these extras and things in particular groups who are interested in doing some extra experiments or tests. We're now offering retesting and so that could also be done at the retest. You could do it in a different way, request different test kits and things. 

Melanie Avalon: Awesome. Well, so I will just do super encourage my listeners, I've been loving the ZOE process. I'm so excited to get back my results. Hopefully, my listeners can all try it if they haven't yet. A lot of them have, but if they haven't yet, definitely try it, and I will let them know that the code MELANIEAVALON10 will get them 10% off. So, that is super amazing. Well, I want to be super respectful of your time. Two more questions before we go. One is, what has been the most surprising thing from everything you've been doing with ZOE and the PREDICT studies? 

Tim Spector: I still get amazed when I look at that first graph we saw from the first ZOE clinical study of this 8- to 10-fold variation in blood sugar and blood fat responses to the same muffin. I still look at that and say wow. Because as you were saying earlier, when you take a fasting blood and you go to your normal clinic, there's actually very little difference and change. So, summating this dynamic difference between healthy people to me was this knockout result, which if you link that with the microbes was also fairly amazing. So, every time we look at the data, there's something else fascinating coming up. That the amount of sleep you get the night before influences your sugar levels and your energy levels, that's pretty amazing.  

The meal before, so sometimes, you need to be looking at maybe 48 hours windows of our food to realize what our metabolic responses are. I think they're cool. Finally, I don't know whether your listeners have done-- heard the blue poop challenge. So, as part of the ZOE studies, we looked at transit time and got everyone to eat a bright blue-flavored muffin, a blood-colored muffin you get with a food dye and you can get instructions on the joinzoe.com website on this. Workout your transit time, which is a cheap way of getting a microbiome tested, which gives you a snapshot of what's going on inside your gut. So, I recommend everyone give that a go, and it's great fun, if you got kids, they love talking about poo anyway, and playing with blue dye although, this can be messy. So, you count how long it takes until you see that in the toilet from the time you eat it and we've done these studies across the world and the average American was about 28 hours, the range was between about 10 hours and six days.  

Melanie Avalon: Six days? Oh, my goodness. That stresses me out so much. 

Tim Spector: But most people have no idea and it will vary a lot. So, these are things that haven't been ever looked at before, an idea that as we're getting to know our bodies more, there are some very simple things we could all do and have fun with. We don't know where the sweet spot is. But yeah, as your diet, we do know that the longer your transit time, the worse your gut microbes look. So, again, people doing keto high fat ones just maybe need to keep a check on that transit times as well as a way of getting an idea what's happening to their microbes in it before they might get them tested formally. We were amazed how well this was performed. I did it as a bit of a joke. But it turns out-- is better than any other medical tests on the market. It's going to be used in all future studies. So, a bit of a fun tip for the family. So, next time we speak, we can compare our transit times, Melanie. 

Melanie Avalon: This probably TMI. I'm a little bit obsessive about monitoring my transit times. [laughs] I just feel like it's so important that things are moving through and I'm always making notes subconsciously. Although, I don't think the blue muffins would show up for me because I ate so many blueberries. I just I don't know if I would-- 

Tim Spector: These are bright luminous. You can't miss these guys. Anyway, if you have to share it, [unintelligible [01:04:07], you can do it in secret, I don't mind. 

Melanie Avalon: Oh, I don't mind sharing them [giggles] open book. Oh, that actually reminded me really quick question. When you're looking at the CGM response to the muffins, is it based on-- does accuracy versus precision matter? Because I wear a CGM often. So, I can check it against a glucometer. Like the one I'm wearing right now I think is off by 10 points. Does that matter or do you just look at the changes? 

Tim Spector: We look at the changes are on the absolutes, and so, we look at the pattern. Yeah, if the baselines are off which they often are a little bit, it doesn't really affect our result. So, they're actually better than people think. They're not very good at low levels, but they're pretty good at the peaks and that's probably the most important. So, the shape of the curve is pretty accurate in these things. They're pretty amazing really considering how new the technology is. Yeah, I think, they're great. 

Melanie Avalon: Do you wear one all the time or how often do you wear one, out of curiosity? 

Tim Spector: I went through a year of wearing them all the time, and I got a bit fed up. So, I've given it a break, but I'm just about-- I've forgotten how I respond to food. So, I'm going to start tomorrow now and get back into it. 

Melanie Avalon: Yeah, I go through waves. I wear one for a few months, and then I'm like, "I can't do this anymore." [laughs] Then I take a break, and then I jump back on the train. But yeah, CGMs are amazing. Well, thank you. This has been so, so incredible. The last question I asked every single guest on this show, and it's just because I realized more and more each day how important mindset is. So, what is something that you're grateful for? 

Tim Spector: I'm grateful that I'm still alive, and I absolutely love my job. I love finding out more and more every day about food, nutrition, being the cutting edge of this science is just the most exciting thing I could have. So, it just gets me up every day and I'm happy to be alive. 

Melanie Avalon: That is so wonderful to hear, and I am so grateful for the work that you're doing. Like I said, your books are incredible. Listeners, you've got to read them, and this ZOE program is just the most eye-opening, incredible thing. I can't thank you enough for bridging the gap between science and scientists in research, and then just the normal people, and especially people who are interested in really taking charge of your health, you're really providing a very practical tool to do that and an agency to you're making a huge impact on our world, and I can't thank you enough. Are there any other links you would like to put out there for listeners, so that they can best follow your work? 

Tim Spector: Well, they can follow me on Instagram, which is mainly about the nutrition side on at a handle @tim.spector. Twitter is more about more of a detailed science and also my deviation into COVID, which also has a link with nutrition, which we've just published, because we have about 4 million people who downloaded our COVID app during the pandemic, join zoe.com website. It has really all the details that we've been discussing. Of course, my books, you can find pretty much anywhere online. Fantastic talking to you and great questions. 

Melanie Avalon: This has been incredible, and hopefully, we can talk again in the future. I really, really appreciate your time and everything that you're doing. 

Tim Spector: Been fascinated to see your results. That'd be great.  

Melanie Avalon: I know. I am so excited. All right, thanks, Tim.  

Tim Spector: Bye.  

Melanie Avalon: Bye. 

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