"Cheers!" "Cheers!" "Considering it's a drug that's been enjoyed since the dawn of civilisation, the science around alcohol can seem rather vague and conflicting." "We know more about street drugs and how they work than how alcohol works and the effects on our body." "You're not seeing double - we're genetically identical twins." "I don't often get to drink with you." "No, it's nice." "Quite fun." "Get to catch up." "Cheers!" "With the UK drinking guidelines currently under review, we're going to take a look at the evidence on alcohol." "Now, a lot of us think moderate daily drinking doesn't have much effect on our health." "Many believe that a small daily amount of alcohol is actually good for you." "I think a lot of us don't drink like that, that small amount every day." "What we do is we drink very little during the week and then we have two or three big binges at the weekend, whether it's dinner with friends with loads of wine, or we'll drink cocktails or shots out on the town." "So, just how bad is binge drinking for you?" "Well, we're about to find out." "Your good health." "Sante." "As doctors, we want to find out whether the pattern in which we enjoy alcohol really can impact your health." "I feel pretty bad." "As well as looking at the latest science, we'll be using ourselves as guinea pigs." "Really?" "!" "One will be drinking moderately." "That's, for me, a very nice, sociable amount." "And the other having a weekly blow out." "The rest of the week I'm going to feel like a million dollars." "During this month-long test, we'll be looking to see how our livers..." "CHRIS CHUCKLES That's it kicking me, there." "..hearts..." "It's remarkable!" "..and brains cope with two different ways of drinking." "There is evidence that that is impaired." "And the results?" "It's not..." "It's not good." "With the help of some volunteers and the latest scientific research..." "It's this stuff that's doing the damage." "..we discover something so surprising..." "What you don't want is to hear the liver doctor saying "I think that's really interesting."" "Meaning, "I think you're really ill in an interesting way"." "..that it might just change the way in which you enjoy alcohol for ever." "Cheers!" "Cheers, boys!" "Good health." "We all drink in different patterns." "Every Tuesday night we come here after the gym." "Even the instructor comes with us." "Yes." "We drink every day, whether it's a Thursday night, Monday night." "Grant will think nothing of coming home from work and having a glass of wine." "He's more of a home drinker." "Cheers!" "I would go out at least twice a week for something work-related." "I'll have a drink at Christmas and then maybe not again till March." "We're not drinking on a Monday, Wednesday and Thursday." "We can save them up for the weekend." "LAUGHTER" "So, how much does the way we drink alcohol affect our health?" "To find out, Xand and I are going to be delving into the latest research, and will be putting our own bodies to the test." "And rather than looking at the amount of alcohol we drink, we'll be looking at how the pattern of drinking affects us." "So, the Department of Health says that, as a man, you shouldn't regularly drink more than three to four units a day." "So I think that sounds slightly ambiguous, but let's look at what it means." "One unit is 70ml of one of these wines, half a pint of weak lager, or a single shot." "So, in theory, you could drink that amount of alcohol every day and not be over the guideline limit." "Now, for the purposes of our test, we're going to be conservative." "So we're going to take one of them away and I'm going to drink three units every day." "For my bit of the test, I'm going to actually drink the same amount of alcohol per week as Chris." "I'm still going to drink the 21 units, but I'm going to do it all in one night." "Ten and a half pints." "That's what you've got to do in one night." "Or, if you'd rather, you can have it in the form of two bottles of wine, or you could have three quarters of a bottle of whisky." "But what we've got to remember is that Chris is going to be doing exactly the same quantity of alcohol spread out throughout the week." "Right, but there is evidence that drinking small volumes is actually good for you." "You cannot make that claim about getting this drunk." "I don't know." "I think this is how lots of people do really drink." "Including you, on occasion." "And I think, in some ways, it's possible I might be better off because I get a six-day recovery period, and you're aggressively assaulting your body with a bit of alcohol every single day." "You never get a rest." "I think you're being absolutely ludicrous." "I don't drink for the sake of drinking." "Yes, it's a social thing." "Drinking, to me, is actually a way of formal networking now." "I always feel like I can do anything once I've had a few pints." "Invincible." "Having a drink just makes you more chatty, makes you more friendly." "It does, sort of, relax." "Yeah, I won't get up and sing at karaoke unless I've had a drink." "Yeah, it definitely gives confidence." "I don't think alcohol changes me." "I think it probably amplifies me." "HE LAUGHS" "The effect that alcohol has on us depends on a variety of factors." "The smaller we are, the more concentrated the alcohol will be in our system." "Women generally have a higher proportion of body fat than men." "As alcohol is less soluble in fat, they will tend to have a higher blood alcohol than a man drinking the same amount." "Which is why, in the UK, the recommended daily drinking limits are lower for women than for men." "But around the world, drinking guidelines are very different." "In the UK, a woman can have up to this much wine each day." "As a female in Hong Kong, you'd be advised not to go above this amount." "Whereas if you lived in the USA, the daily limit is far higher." "The UK guidelines have changed very little in the past 20 years." "The evidence that moderate daily drinking is good for you is now being questioned." "'We've come for some baseline checks 'so we can track any changes that may take place 'over the next four weeks.'" "Hi, guys." "Hey, good to see you again." "'Dr Gautam Mehta is an academic physician and scientist, 'specialising in alcoholic liver disease." "'To help ensure we're starting from the same place, 'we've both spent the last four weeks completely teetotal.'" "What I find interesting about the month off, I guess, is that I do..." "I feel physically good at any given minute, but actually I feel quite..." "In a way I feel quite miserable." "It's been quite a joyless month, bizarrely." "Really?" "It's been quite noticeable." "When you socialise with people who are drunk, they are extremely boring if you're not drunk, as well." "They're really awful." "I think that's part of it." "I think that is part of it, yeah." "OK." "Thank you very much." "Thank you very much indeed." "That's great." "This morning, I think, when I got up, I thought," ""Oh, it'll be quite interesting and probably quite fun" ""to get drunk tonight."" "Now I'm feeling much more science-y about it." "Like, I think I'm going to look at my hangover very differently tomorrow." "Mm." "Also interested in us is Professor Rajiv Jalan and his team." "Some surprising new research last year showed that the way you drink can really affect your immunity and inflammation levels, so they're going to be looking closely at our blood tests to see if there's any difference caused by our two drinking patterns." "To find genetically identical twins agreeing to do a study such as this is really unique." "Do you want an "I've been brave at the doctor's" sticker?" "Can I have a badge?" "And a lollipop." "'Having braved the blood tests, we're also going to assess 'the state of our livers after four weeks on the wagon.'" "So let's just recline on the couch." "So this is a fibre scan." "This thing sends out sound waves." "It picks up the sound waves going through the liver and bouncing back to the probe to generate a number." "There's a sign of how stiff or how soft and pliable it is." "Here, soft and pliable is actually very good." "OK." "This test is quite funny." "I can feel this pulse going..." "You can literally feel it going right across your tummy, kind of wobbling your liver." "Really?" "Yeah." "So what are my numbers?" "So your median liver stiffness is 3.9 kilopascals." "That means nothing." "Which is very good." "OK." "So it's..." "It's less than mine." "Great stuff." "I think it's worse to go second." "Chris did so well." "Yeah, that's right." "Pressure." "The pressure has mounted." "It's really weird having this done, because I am now thinking about all the drinks I've ever had." "Yeah, so my bet is you will have a slightly firmer, more fibrosed liver than me." "Well..." "You have exactly the same number." "Ah!" "It's interesting how relieved I am by that, actually." "So whatever we've been doing, we've got away with it." "XAND LAUGHS" "So far so good, which is the perfect place to start." "OK, that's great." "And from here on, we see how things change." "'Obviously, we're a tiny sample of just two, 'which means this doesn't qualify as a scientific study, 'but as genetically identical twins 'starting from the same liver stiffness, 'we can see if our test supports the new evidence that's out there.'" "Science has progressed exponentially over the last 20 years since the guidelines were first written." "There's lots more we know about the immune system, about alcohol and about the liver." "I personally love the taste of champagne." "I think it's always a great treat to have it." "Any time of the day or night." "I do like a snowball at Christmas." "Gin and tonic's the way forward for those wishing to diet." "Whatever I've got left in the fridge, basically." "Beer is thirst-quenching." "So many different flavours." "It's wonderful." "Wonderful." "Very nice." "Splendid." "Cheers." "When we say alcohol, we're actually talking about ethanol." "It's ethanol which gives us the buzz we experience when we drink booze." "Chris and I will be drinking exactly the same amount as each other each week, and we'll also be drinking the same type of alcohol." "That way, we should see the effect of how we drink rather than what we drink." "The reason I've chosen vodka is because I don't think I can drink ten and a half pints in an evening." "Nor do I. Now the scientist we spoke to to design the test said if we can start with three shots, that's you done, that's me started, and then I can do the rest with mixers." "So that's the plan." "All right?" "Good." "All right, well..." "How are you feeling about this?" "Are you looking forward to this?" "I don't often get to drink with you." "No, it's nice." "It's fun to catch up." "Cheers." "Neat, warm vodka isn't really my tipple of choice." "My last one." "Cheers." "It's your last drink of the evening." "Really enjoy it." "Three shots is perfect for me." "That's, for me, a very nice, sociable amount." "There you go." "Can you feel it?" "Yeah, I feel great, because I know I don't have to do any more." "When alcohol reaches your stomach, a small amount is absorbed into the bloodstream." "However, the majority will only enter the blood when it exits the stomach and reaches the small intestine." "Once in the circulation, it is taken to the liver, where it will start to be metabolised." "'We know how alcohol is broken down and absorbed by the body, 'but we still don't really know why we get hangovers." "'Lots of us think it's because alcohol makes us dehydrated, 'so I've got an idea.'" "So here's what we're going to do this evening." "You are going to drink the same amount of liquid as me." "For every vodka and orange I have, you're going to have an orange topped up with a shot of water." "So through the evening and all through the night, we're going to collect our urine, and I reckon we'll pee exactly the same amount." "OK." "How are we going to collect the urine?" "Well, funny you should ask." "Funny you should ask." "We're going to use these." "'Something we can resolve even faster 'is the impact of how we drink on our hearts." "'Consultant cardiologist Dr Gerry Carr-White 'is going to show us.'" "So, what I do..." "This is quite safe." "It's just an ultrasound, just like looking at babies and things." "What we'll do is just see if we can get a little picture of your hearts." "This is remarkable." "'Alcohol dilates the blood vessels near the skin." "'As the blood volume spreads, 'the heart beats faster to keep oxygen flowing to our vital organs.'" "What you can see is on the right-hand side of the screen, you can see the main pumping chamber." "Then, can you see that little flappy thing halfway down?" "The thing flapping there, the white flap." "So that's one of the heart valves." "Then the little chamber at the bottom, that's the chamber that tends to speed up or change rhythm when people like you guys have a little too much to drink." "So you've got a normal heart, normal size." "It's functioning perfectly well." "'That's probably because Chris finished his three units 'over two hours ago." "'As the liver can process one to two units of alcohol an hour, 'he'll be almost sober again by now." "'I've had triple that amount, and so my body is struggling to cope.'" "That's your heart." "I don't know if you can see - do you see...?" "It's different to Chris's, right?" "It looks a little bit more enthusiastic." "Yeah, it's very interesting, actually." "I don't echo many drunken people." "But I think I can see a clear difference here." "It's going quicker." "The actual electrics are normal, it hasn't changed rhythm." "It's certainly pumping a lot more vigorously than your brother." "I think, even at this stage, we can see a clear difference in what's happening." "Why is it pumping harder, then?" "I'm still sitting in my chair, doing nothing." "I think what we're seeing is the direct effects of alcohol on your heart." "It's increasing the amount of blood the heart's trying to pump out." "It's probably putting your blood pressure up a little bit and it's making the heart go quicker." "'In the year 2000, 'the results of a ten-year study carried out in Scotland 'suggested that up to 20% more people die 'from heart attacks on a Monday than any other day." "'The authors concluded that this was linked 'to heavy drinking at the weekend.'" "You're probably feeling a bit less enthused about this now." "'Time for a pee." "'And the first chance to see if I'm right about our hydration levels.'" "So, there you go, that's the difference." "If you said, "Oh, I'm dehydrated by that much" - not enough to give you a hangover, by a long way." "But we are nine shots in." "In fact, the paper that's often quoted for the source formula for the diuretic effects of alcohol in the lab dates back to 1942 and was based on only one subject." "'We'll see if our results replicate those at noon tomorrow.'" "All right, well, we'll see." "You can't bet on a horse before it's finished the race." "What?" "You always bet on a horse before it finishes the race." "What I mean is..." "You can't bet on the horse after it finishes the race." "..you can't bet on a horse in the middle of a race." "You can." "You don't win your bet on a horse when it's ahead halfway through the race." "'Monitoring just how high my blood alcohol level will get 'might be beyond me, given I'm already impaired..." "'..so I have a little technical help.'" "This device is measuring, through my sweat, the concentration of alcohol in my blood every ten seconds." "It's a very accurate measure." "I think the interesting thing about that is you're going to continue to get drunk for quite a long time tonight." "XAND GIGGLES" "'By the end of the evening, Chris has had three units of alcohol 'and I've had 21.'" "Yeah, there you go." "It's not that bad, you know." "I think I could do that every Saturday and I..." "See, I've only got to do it in a week." "I've got a week until I have to do it again." "I don't feel that bad." "I feel pretty bad." "'After each binge, I will be supervised 'by the most dedicated medical care available - my brother.'" "I suffer badly in the morning." "I don't do hangovers really too well at all." "I've had hangovers that have lasted three days before." "I still never thought to myself, "Well, I'm not doing that again."" "My solution is usually just lie in bed and pull the blinds down." "I just have a massive fry-up." "There is only one real cure for a hangover... ..death." "'Most of us would recognise the short-term effects 'that follow the morning after a binge-drinking session.'" "Oh, I feel awful." "OK, so we're 8am." "So what do you remember of last night?" "I don't remember exactly." "I wish I'd brushed my teeth." "My mouth feels disgusting." "You did brush your teeth." "Did I?" "Yeah, yeah, you brushed your teeth." "'Alcohol interacts with specific neurotransmitter receptors 'in the brain that are involved in laying down long-term memories." "'During a binge, the big rise in blood alcohol concentration 'leads to high levels of ethanol building up in the brain, 'blocking the normal activity of these receptors, 'which stops memories from being formed.'" "What's your last memory?" "I don't remember leaving." "How was the taxi ride home?" "I think I just slept through it, probably." "I was so tired." "Yeah." "You had a nap in the taxi ride, did you?" "That's what I think." "OK." "# Tambourine" "# With a... #" "Oh..." "We should go dancing." "We could go for a little dance." "You don't remember any of this?" "XAND LAUGHS" "We could do some karaoke with some country songs." "OK, so that's in the taxi." "Now we're at home." "Standing at the top of the stairs." "Why are you feeling so tearful?" "XAND SOBS" "You were really jolly a second ago." "Oh, no." "What's the matter?" "You were singing and everything." "Oh, my God." "This is awful." "Five minutes earlier, you wanted to go dancing." "What was I so upset about?" "It's not embarrassing to watch, actually, it's worrying." "You go, "Wow, I don't remember any of this at all."" "The second thing is this is a graph of your drunkenness." "'Clearly, Xand's blood alcohol was high enough to impair his memory, 'but his tag will reveal exactly how far it went.'" "So this is the driving limit, this green line here." "This is when you started drinking at six, this is when I measured it this morning at almost noon." "You can see this..." "You stopped drinking, your last drink here was about 11 o'clock at night." "You were at your most drunk about 1.30 in the morning." "So you can see your blood was a third of a percentage alcohol." "That's very bad." "Mm." "Do you know what that means in terms of..." "If we looked that up...?" "Yeah, no, I do, I do." "I mean, it's danger of death, isn't it?" "Danger of death." "Not by being hit by a truck, but by just dying because you've had too much alcohol - choking on your own vomit, stopping breathing, having a fit, your heart stopping working, all these different ways that alcohol's bad for you." "'Xand's blood alcohol spiked whilst he was asleep, 'two and a half hours after his last drink.'" "It's shocking, but many of us who have overindulged will have, at some point, been at the same level of risk without ever knowing it." "'What more can we learn from last night?" "'Xander was sure that binging wouldn't dehydrate him 'more than me.'" "I feel like a real idiot." "I was certain that I was going to be, "I'm not dehydrated at all."" "And how do you feel today?" "Dry as a bone." "'As a simple test, we've both drunk the same total amount of liquid 'for the last 24 hours and kept our urine for comparison.'" "So what do you think?" "XAND LAUGHS" "The same." "I mean, that..." "Wait for it to steady down." "Really?" "!" "Really?" "!" "Really?" "!" "What, really that you managed to get it all in the bottle?" "I mean, they look exactly the same." "Have you weighed them?" "In fact, 2.8 litres for me and 2.7 litres for you, so I'm more dehydrated." "'This surprising result was supported by blood tests," ""confirming almost identical hydration levels 'in our blood plasma.'" "That is absolutely astounding." "I feel incredibly dehydrated." "I feel like that's my problem." "And I'm wrong." "'Whilst drinking water can only be a good idea 'the morning after the night before..." "'..there seems to be another culprit that accounts for Xand's suffering.'" "If we find that the blood test from the binge show that there is a lot of inflammation in the blood, then that would be a bit like having a very mild cold or a flu." "I think when people think about it, when you have a very mild flu, it feels a bit like a hangover." "That inflammation can affect the brain and make you feel slow, have a headache, and all the symptoms of a hangover." "The key to that inflammation lies in a chemical that's affected by genetics." "We've taken cheek swabs from three volunteers who are each affected by alcohol in very different ways, to see if their genes can explain why." "So how would you be feeling after drinking that glass?" "Pretty sleepy." "I'd be ready to go to bed, even with my boyfriend kicking me under the table." "Really, it's like an anaesthetic?" "Yep, yep." "After a half pint, I'll start to feel the effect kicking in." "My eyes get red." "My arms, my neck gets red, too." "How bad are your hangovers?" "Oh, it's a continuous headache throughout the day." "Really?" "On any social event, I'll go out and I will have easily four, five, six, seven, eight, nine pints." "No real hangover, no ill effects." "'Helping us to understand these differences 'is Dr Ashley Brown from Imperial College London.'" "Hi, guys." "'Dr Brown studies the genetics of alcoholic liver disease.'" "We can clearly explain these three different experiences with alcohol on the basis of genetic variation." "'That's because the enzymes that break down alcohol 'in our bodies are determined by our genes.'" "Alcohol is first converted into a chemical called acetaldehyde, which becomes toxic at high concentrations." "The acetaldehyde is then broken down - mainly in the liver - by a second enzyme, into carbon dioxide and water." "These can be eliminated from the body." "So we've got the results." "Alice and Joe, you guys have the same variant, and you're different to Glen." "You guys do not get rid of alcohol as quickly." "'65% of Eastern Asians and 5% of Europeans 'have the genes that code for the slow-metabolising enzyme 'at this first stage, 'meaning that alcohol stays in their system for longer.'" "But then we do see a difference in this second enzyme that gets rid of the toxic by-product of alcohol, the acetaldehyde." "Alice, you have a typical genetic profile for this, so you get rid of it as fast as anyone else." "But, Joe, this is where you have a variation in your genes that means that you don't get rid of the acetaldehyde, which is what we're seeing right now looking at you." "This is living genetics." "This is a great example." "I think, you know, what Joe's body is doing is telling him to stop drinking." "What we see in people with that slow gene is that if they carry on drinking through it for social pressures, despite the side effects, then they are putting themselves more at risk of liver disease." "'And it's thought that it's this toxin, this acetaldehyde, 'produced as we break down alcohol, 'which makes Joe's hangovers worse than most." "'But in Glen's case, his enzymes work normally, 'so he breaks down both the alcohol and the acetaldehyde 'at the typical rate." "'So if his enzymes are normal, 'how come he can drink much more alcohol than most people 'without feeling it?" "'" "There is an alternative pathway, which actually breaks down alcohol via a different method." "What's different about this pathway is that it's inducible." "There's no limit to the amount of alcohol that you can carry on passing down that pathway." "This secondary metabolising pathway can be switched on when we drink faster or in larger amounts than the body can cope with." "It works like an overflow system." "This allows the additional alcohol to still pass through the liver." "So Glen has induced or switched on this second way of dealing with alcohol." "Correct." "It goes from the gut to the liver, it's broken down." "It never gets into the bloodstream so it never has that effect on the brain, which is effectively where we feel drunk." "Does this mean that the alcohol is less dangerous in terms of the effects on Glen's liver than it would be for someone who doesn't drink that often or that regularly?" "Absolutely not." "OK, the alcohol is still being broken down by the liver and the breakdown products of the alcohol are what's causing the damage to the liver tissue." "So having got these results, I think the thing" "I really want to know is, where does it leave us with our experiment?" "Xand's been binging, a huge binge once a week." "I've been drinking a little bit every day." "Does this give us any view on who's going to win the argument?" "Binge drinking is really not a good idea." "You're far more likely to be inducing that alternative pathway, which is going to have the damaging effects." "'And my brother is certainly feeling the impact of drinking 21 units.'" "The shoes are like the thing." "Why you can't get to bed if you're drunk - it's cos you've got these shoes on." "This is no thing to be doing at midnight with your 36-year-old twin brother who's a doctor." "Poor guy." "I mean, he's definitely got the bum deal." "Now you might wonder why I believe that" "I can bounce back from a binge in just six alcohol-free days." "The reason I have so much faith in my ability to recover from these binges is the human liver." "It has an amazing capacity to regenerate after it's injured or after bits of it are removed from surgery." "Unless it's irreparably damaged, it can simply grow back." "The liver's unique ability to regenerate itself, combined with advances in medicine, means that we can now remove a portion of liver from a healthy donor and give it to someone who needs it." "Professor Nigel Heaton has performed over 1,000 transplants in his career." "So the live donor programme builds on the idea that the liver can regenerate and regrow." "For an adult-to-adult transfer, 50% of the donor's liver is removed and transplanted into the recipient." "The donor is left with half a liver, the recipient is getting half a liver." "Both livers regenerate over the course of about six to eight weeks." "It's a very rapid process." "It starts within 12 hours of the surgery." "The younger you are, the more rapid." "But even if you're 60 or 70, the liver continues to retain that ability to regenerate." "Today, Professor Heaton and his team are taking 20% of a healthy woman's liver to transplant to her child with liver disease." "Incredibly, Mum's liver will be back to its original size in just over a month." "The liver is a truly remarkable organ." "But there's a limit to how much abuse it can take." "If you go out and you have a binge and if you don't drink for a week, the liver will recover." "The question, though, is whether repeated episodes like that will produce longer-term injury that doesn't recover and leaves scarring." "This is what a cirrhotic liver looks like - scarred by the repeated damage caused by alcohol." "People are suggesting that significant binge drinking contributes more to damage of the liver than steady drinking, but I would say it's the overall amount of alcohol people are drinking." "So I guess I wasn't expecting Professor Heaton to fully endorse me drinking 21 units every Saturday night, but he did say a few interesting things - my liver does benefit from having a few days off, it probably IS important - the total amount of alcohol" "I'm drinking in the week, compared to just how much I'm drinking on any given day, and my liver can recover from binges, but it still doesn't seem like what I'm doing is a very good idea." "In the long term, it'll be causing me harm, but I might not be as wrong as Chris thinks I am." "It's the third week of our test." "This is like a typical night that I've got to come in and drink my three units." "Chris' routine is unchanging, but I've decided to adjust mine." "So rather than finishing everything in four hours, which is what I did last week," "I spread it over a day today, almost 12 hours." "'A few beers at lunch, couple of drinks mid afternoon 'and a bottle of wine for dinner." "Basically, I feel OK.'" "The 21-unit day is very different to the 21-unit evening." "'Even though I spread the units out, it's still a binge.'" "Cheers." "I don't think of us as binge drinkers because we don't go out to get drunk." "If you just go out and drink too much that you stumble home, that's the sign of a good night out, isn't it?" "I think a binge drinker is someone who goes out on a Saturday night and gets absolutely wasted." "You're talking about neat spirits, shots, going crazy." "Throws up in the bush on the way home." "That is the aim - to get completely legless." "Be in a gutter somewhere." "Talking of binge drinking, do you want another one?" "Yeah." "In fact, the Department of Health defines a binge like this - for a woman, it's six units." "That's just two large glasses of wine, or just over 2½ pints." "For a man, a binge is eight units - that's 3½ pints or nearly three large glasses of wine." "What, in one day?" "If you drink beyond that, you're binging." "Is that all?" "I didn't realise that such a small amount of alcohol, technically, was the most that you're allowed." "How many times do you listen to what the government's saying?" "I just don't agree with it at all." "Another thing that many of us don't realise is that the risks associated with drinking change as we age." "Modern science has shown us the most complex organ in our body, the brain, is most vulnerable to binge drinking right at the time when most of us first experience high levels of alcohol." "So it's autumn, and all over the country - all over the world, I guess - students are going to university for the first time." "I mean, I remember it." "It's a weird mixture of excitement, but intense social anxiety." "This felt like the most important friend-making occasion of my life." "Xander and I, like a lot of people, leaned heavily on alcohol as a lubricant to get us through those first few weeks." "The striking thing is how little I remember of that time other than from photographs taken... in many of which, I seem to be wearing women's underwear or lipstick." "That was a typical first-year party." "Everyone around the table, medical students." "We must have 30 bottles of alcohol on that table, empty, and there's only ten of us there." "What a bunch of idiots." "At this age, we have an incredible capacity for learning - an expanding social life, a taste for exploration and testing the limits." "Modern technology has revealed our brains are still developing significantly up until our mid-20s." "Dr Valerie Voon is a consultant neuropsychiatrist." "She's researching the affects of binge drinking on the reward centres in the young adult brain." "There's greater activity when we're exposed to rewards as an adolescent." "That all decreases over time as an adult." "So as an adult, there's a double effect that not only are we able to resist the temptation of having a drink, but the drink itself is less of a temptation." "We just get less of a reward from that drink." "Yes." "There's two components." "So one in terms of what we call "bottom up"" "so what you experience in terms of the reward or the emotion." "That itself blends over time." "The other component, in terms of your frontal cortex being able to put the brakes on to change your behaviours to say," ""No, you can't do this because you have to wake up the next morning", that itself doesn't come online until your mid-20s." "So what you'll see is this imbalance, but as you age it then changes, it then shifts." "So, as we get older, it's not just that life feels less fun, it actually is less fun and we're more able to resist the decreased fun." "You may be OK with it." "To assess the effects of binge drinking on the developing brain," "Dr Voon gives a battery of tests to her volunteers, including cognitive tests to measure their risk taking." "Beth has recently finished her degree at Cambridge." "I thought that I'd be one of the controls, one of the people that they were comparing the binge drinkers to." "I have two things I do every week." "I drink with my brass band friends on the Thursday, have about three pints in the pub with them, and on Friday I'll also have two or three pints." "But because I'm having two or three pints within two hours regularly, that makes me count as a binge drinker." "Dr Voon uses an MRI scanner to examine the brains of young people to search for differences between the binge-drinking group and the other volunteers." "Are you all right there?" "This is actually Beth's brain." "You can see that's actually her facial features." "I can see that." "You can see all the different parts of her anatomy here." "It's like she's made of wood." "Yeah, exactly." "You can start to see this grey area coming into view." "This is an area called the ventral striatum." "Right bang in the middle of the brain." "Yes." "It's involved in motivation and reward processing." "The striatal region is involved in translating motivation into action." "That desire to do something, turning that desire into actually getting the thing that you want." "Yes." "OK." "What we see is that this particular region seems to have increased volume, or increase in size in the binge drinkers, compared to the healthy volunteers." "Dr Voon is now expanding her research to discover if certain people are born with brains predisposed to becoming bingers, or whether binging itself causes the change, or perhaps a combination of the two." "As we work our way further back, this is the hippocampus." "That particular region is involved in longer-term encoding of memory." "This is the stuff that's very important for students at university to have the lay-down facts and recall them in exams." "Yes, exactly." "If you have greater alcohol severity, you also have decreased hippocampal volume." "So if you do test binge drinkers on memory tests, there is evidence that that is impaired." "Really, even when they're sober?" "Even when they're sober." "But I think one of the key things is that once they stop drinking, much of the function can be recovered and then a large proportion go on to lead very regular, healthy, normal lives and, in fact, do very well." "So all is not lost." "All is not lost." "So much like the liver, given the chance, the young adult brain can also recover." "'But alcohol can be addictive, and after four weeks of our test, 'both Xander and I are starting to crave it.'" "How are you feeling?" "I mean, what's striking is that immediately after the binge" "I think I never want to drink again, and by now it's Saturday afternoon, I'm ready for a drink." "You're well up for it." "Yeah." "All right." "What's going to happen to me is what's happened to me every single day for the last four weeks is that I'm going to finish this and then want another one." "That's all you get, isn't it?" "'So far, I've seen that binge drinking 'increases your risk of accident or choking on your own vomit." "'It puts your heart under stress 'and doing it repeatedly means your liver can be scarred." "'But is Chris right to believe that daily drinking within the guidelines 'can be good for your health?" "'" "Research has suggested that red wine may contain an active ingredient that makes it better for us than other booze." "But before you rush off to the off-licence, let's have a look at some of this research." "Phenolic compounds in the grapes, which are responsible for things like their taste and colour, have certain cardioprotective properties that can help prevent bad cholesterol from clogging our arteries." "These polyphenols act as a natural blood thinner, which can fight off heart disease." "This is red wine just as it's starting to ferment." "It smells fantastic." "Now red wine like this can have up to 12 times as many of these polyphenols as white wine, and that's because it's fermented with the skins." "One of these polyphenols, resveratrol, works as a natural fungicide, and it's been touted as a possible wonder drug." "I'm here to harvest pinot noir with Fred Frank, whose grapes have been found to contain high levels of this celebrated compound." "You want to be careful you don't snip your fingers, OK?" "How close am I getting to the...?" "How much stem do I want?" "Does it matter?" "Is that OK?" "It doesn't matter." "That's fine." "So you can actually see that the skin is much thinner than a normal table grape." "It's one of the most fragile grapes that we have." "Very thin-skinned, very tightly bunched, and for this reason it has to produce more resveratrol to protect itself." "They're all touching." "Exactly." "If a fungus gets started in the cluster, because they're so compact, it will easily spread." "That is why pinot noir from the Finger Lakes had the highest levels of resveratrol, according to Cornell University, and they tested wines from all over the world." "So how many bottles of wine have we got in this tub now?" "Probably a couple bottles." "We've been picking for 20 minutes, and this is..." "We've picked, like, two or three bottles." "We've been talking, too." "Yeah, that's true." "I could have gone faster." "If you hadn't been talking to me, I would have..." "It's my fault." "The scientific community began to wonder." "Could this naturally produced defence created by the grapes hold the key?" "Having been tested on body cells in the lab, and then on animals, 'it appeared to have a cardioprotective effect." "'Resveratrol was even shown to inhibit the growth 'of some tumour types, and in yeast and some animals 'it was capable of extending lifespan itself.'" "In 2006, a group of Italian scientists found that if they fed fish food supplemented with resveratrol, they could increase the lifespan of those fish by up to 59%." "That would get me to around 150 years old, which sounds great for red wine." "Except that in order to get the same dose as the fish, you'd need to drink this much red wine every single day." "Even with the higher resveratrol levels in the local pinot noir, you'd still need around 30 bottles, and supplements have yet to be proven to work for us." "The trouble with alcohol is that the difference between medicine and poison is dose." "While red wine and other kinds of alcoholic drinks can have some health benefits, there's a problem." "the problem is that even as the wine is protecting your heart, it's increasing your risks of certain kinds of cancers and liver cirrhosis." "In 2006, a meta analysis of more than a million people was published in an American journal which did show a benefit for a small, daily amount of alcohol." "But this was the amount - one to two units a day." "Now Chris is drinking more than double this." "Other research has shown that that benefit really only occurs in men between the ages of 50 and 60." "Chris is 36." "In 2011, an American study looked at the effect of alcohol on mice genetically engineered to be vulnerable to heart attack and stroke, much like a 50-to-60-year-old man." "Dr John Cullen looked at the impact of the pattern in which the alcohol was consumed as well as the amount." "To navigate this maze of complex information, he divided the mice into three groups - teetotal, moderate and binge drinking." "He then analysed the affects on their blood vessels." "This is the no-alcohol group." "As you can see, we have significant plaque development within the vessel." "It's probably about 50% occluded." "This is just after four weeks." "Plaque is the accumulation of substances such as fat, cholesterol and inflammatory cells along the inside of arteries." "So the teetotal mice have some disease." "Yes, they do." "OK." "So if we move along to mice who had two drinks per day, seven days a week, you can see here we have significantly less plaque development within the vessel and there's more open room so that the blood can flow freely." "Wow, so the mice that are drinking regularly everyday, a normal amount." "Yeah." "For a person, not a mouse, that's significantly less blockage in their blood vessels." "Yes, it is." "These mice were basically doing what Chris is doing, drinking a little bit every day." "Yep, in moderation." "Finally, if we look at our binge group." "Wow!" "So this is 14 drinks over 2 days." "You can see we have much more plaque formation within the vessel and it's almost occluded." "These mice are basically doing what I'm doing." "In a sense, yes." "That blockage, I mean, that's really visible to me." "That blood vessel, which is the blood vessel going to their brain, that's getting blocked, and that's a blood vessel you really don't want to have blocked." "Yeah, cos you could end up having a stroke." "Wow, I mean, it's just..." "It's so clear." "But bear in mind that this is an accelerated model we're using as far as disease process goes." "OK, so these mice are more likely to develop a blockage anyway." "Correct." "That's how it is." "Wow." "So in this study, at two drinks a day, pure alcohol had cardioprotective effects for the mice." "What's striking, though, is that the blood vessels in the binge mice were drastically damaged." "'But why does simply altering the drinking pattern 'cause such a vast difference?" "'" "When we look at the effects on immune cells, alcohol would actually prevent white blood cells from sticking to the vessel wall, and theoretically, if this was in the body, would prevent the initiation of heart disease." "On the other hand, acetaldehyde promotes the stickiness or the adhesion of these immune cells to the vessel wall." "So at low levels, alcohol helps, but at high levels, its by-product - acetaldehyde - is damaging." "We actually have a bottle here." "It looks harmless, but I advise you not to open it." "Why's that?" "Because what we experienced when we first used it, we didn't do it in a fume cupboard and we opened it, and after we were exposed to the fumes, myself and my lab tech both experienced headaches" "like we were having a hangover." "Instant hangover..." "Instant hangover... ..in a bottle." "..without all the fun of drinking." "Looking at the bottle, this is actually quite terrifying because it has three symbols." "It has a flammable symbol, a skull and crossbones, and what appears to be a picture of a human body exploding." "Yeah." "And it says, "Danger."" "Yeah, it is extremely dangerous." "We learnt our lesson the hard way." "Wow." "What's amazing to me is that your body makes this stuff." "Correct." "Your best guess is it's this stuff that's doing the damage to your blood vessels." "That's..." "We think that that might be playing a role." "It's still a mystery to many scientists and researchers, and that's why we continue doing what we do." "'So if binge drinking causes our bodies to be poisoned 'by the high amount of acetaldehyde we produce 'while breaking down the extra alcohol..." "'..then perhaps this is the route of our hangovers...'" "If I stay very still, I'm OK." "'..rather than dehydration.'" "Wow." "'And the effect of that poisoning... 'may linger well beyond the morning after." "'For the past month, 'we've both been drinking 21 units of alcohol a week, 'but Chris has been spreading his units out, 'having three a night, while I have been consuming mine in one day 'and then having the rest of the week alcohol free." "'Now we're back at the Royal Free Hospital 'to see how it's affected us.'" "OK, well, we've got some evidence." "How am I doing?" "Er..." "I must say, your liver stiffness has gone up in a month." "Has it?" "It's gone up, yeah, to 4.9 from 3.9." "That's really..." "I mean, that's quite shocking to me, actually." "He's only been doing it four weeks." "He's only had four drinking sessions in one month." "Yeah." "That's what's striking to me." "I've changed it dramatically without doing something that felt very strange to me." "Right, let's see what the affect of it on me is." "That'll be super interesting." "Let's switch it up." "Thanks." "'It's still within normal limits, 'but that's a 25% increase in liver inflammation." "'Will Chris with his daily three units have fared any better?" "'" "I've got a measurement for you." "It's actually also gone up by about the same amount." "So it does seem that 21 units for a week for a month does seem to change - at least in you two over four weeks - change your liver stiffness." "To me, it's extraordinary." "You wouldn't..." "We have not done something very extreme here." "I was simply drinking the lower end of the guidelines." "I think I was probably drinking less than I would normally have drunk." "Right." "I think this has gone back to normal, probably." "Yeah." "It's not good." "Liver inflammation is what we think as the precursor to what leads to the fibrosis and the chronic liver disease and then the problems." "It makes me think significantly differently about what we've been doing." "'We can't say if these results are relevant to the wider population, 'but in us, the two different drinking patterns 'inflamed our livers to almost the same extent.'" "The lab at the Royal Free has also analysed the blood samples taken during the first and final binge." "We're looking at inflammatory markers called cytokines." "A cytokine is a small chemical released by cells of the body to signal inflammation or infection somewhere, so these might be things that occur when you have an infection like a cold, but also when some of the organs of your body are damaged." "Liver expert Professor Rajiv Jalan has the results." "Hi." "Thank you so much for seeing us." "Thank you." "It's wonderful to meet you guys, finally." "This is what happens to you." "Ooh." "OK." "The left-hand graph shows our results as the test began after four weeks being teetotal." "The graph on the right illustrates before and after our final drinking session." "I mean, that is very dramatic." "That is very dramatic." "So this is Chris, here." "It is the same for Xand." "Your body is manifesting systemic inflammation, which is significantly worse than a healthy individual." "Here, we're looking at tumour necrosis factor alpha." "this is a cytokine that signals inflammation in the body." "It's commonly elevated in patients who are extremely unwell." "Just to be clear, this has changed from week zero to week four - our levels are massively up." "Absolutely right." "You've both got increased systemic inflammation by a similar amount." "This is all over our body." "All over your body, yeah." "These are big changes in cytokines for both of you." "I think that's really interesting." "So just to summarise, so far..." "What you don't want is to hear the liver doctors saying," ""I think that's really interesting."" "Meaning, "I think you're really ill in an interesting way."" "You never want anyone like these guys going," ""I think it's really interesting."" ""It's fascinating and we must study you more."" ""Would you mind seeing some medical students?"" "In 2014, a study at the University of Massachusetts showed an increase in these same inflammatory markers in healthy volunteers after just a single binge." "'The same tests are yet to be performed 'on daily moderate drinkers like me, but three units affected me, too." "'And we saw this surprising result 'in a further five inflammatory markers." "'It seems both of our bodies were responding to alcohol 'as if to injury and infection.'" "Although Xand does seem to be having a bigger change in his inflammatory markers," "I do seem to be quite inflamed at the end of this." "I haven't got away from this scot-free." "I feel like we both lost this argument." "So far, we're both losing, which is what I said at the beginning." "Let me show you now..." "Oh, here we go." "This is looking at the toxin levels." "Ooh." "Ooh." "Endotoxin is a part of many of the bacteria that are resident in our gut." "The presence of endotoxin in our blood samples indicates that pieces of bacteria have somehow escaped from the gut." "In your case, Xand, as you can see, the levels of endotoxin was very different to the endotoxin levels that we see in Chris's blood." "When you're drinking large amounts of alcohol, it produces a particularly deleterious effect on the gut." "At binge-drinking levels, acetaldehyde damages the gut lining, which leads to bacteria leaking into the blood and being circulated around the body." "It's this that causes an increase in inflammatory cytokines which are trying to fight what they perceive to be a bacterial infection." "So, ordinarily, my gut, my intestines, are keeping all of these bacteria out of my bloodstream, right?" "Absolutely." "The problem with the alcohol is it gets broken down into this nasty chemical, the acetaldehyde, and that makes my gut leak it." "It separates the cells and it means the bacterial poisons, effectively, are getting into my bloodstream." "Absolutely." "And that gets my whole immune system going, creates inflammation everywhere, it's damaging my organs." "So this is..." "I mean, I'm literally being poisoned by the bacteria in my own intestines." "Absolutely right." "The scientists in Massachusetts also found these elevated endotoxin levels in the blood of their binge volunteers, confirming the link between systemic inflammation and endotoxin leakage from the gut at binge levels." "By week four, Xand's bloods show that his immune system was already hugely inflamed, even before he's started the final binge." "Maybe the most terrifying bit of this graph for me is that on week four, I've had seven days off, haven't had a drink for seven days, and before I have that first drink" "I've got double the concentration of endotoxin that Chris has got." "So what you're seeing there is the damage to my gut from the previous binging." "Yes." "With that sort of level of binging, six days is not enough to get you back to a healthy base." "It probably takes a month or two." "So it seems like a slam dunk for me, doesn't it, if we have to call it?" "No, it doesn't." "Oh." "There you go." "Listen to the Professor, OK?" "Binging is significantly worse than drinking sensibly 21 units, but I think it's very clear that with the data we have seen," "21 units is certainly not safe for either of you, because these tests are changing to levels that we see in cirrhotic patients... after a month of drinking, to what's called sensible limits." "I'm completely flabbergasted, because this is completely beyond my expectations, so when I saw these results, we went and rechecked them to make sure that these are correct." "Whether 14 units is safe or not, I cannot tell, or whether the safe limit for you is ten units, I cannot tell." "But I think, probably, in the future we will reset the sensible drinking limit to perhaps a little bit lower." "OK." "The government advice on alcohol is currently under review since the House of Commons Science and Technology committee found that there was sufficient concerns about the guidelines to warrant a thorough review of the evidence." "It'll be interesting to see what the new guidelines are when they finish trawling through the latest research." "But whatever they say, will we listen?" "I don't think I've ever considered beer or wine as far as," ""Oh, crikey, I must make sure I'm aware" ""of how many units I'm drinking."" "I would judge my alcohol consumption by what is socially acceptable rather than a chief medical bloke." "Cheers." "Cheers." "We don't drink big amounts on a regular enough basis," "I think, to worry about damage." "At my age, I look forward to my dinner with my glass of wine." "I'm not going to stop that, why should I?" "The government guidelines are a good recommendation, but...they are guidelines." "So we've just got back from Professor Jalan's clinic." "You've got all your bad news and you're feeling miserable and hungover, so you're in quite a good place, I think, to consider your future life with alcohol." "Yeah, I mean, I think I have to dramatically alter every aspect of the way I drink from the binging to the everyday drink." "You're feeling exactly the same as everyone who's ever had a hangover." "Except that I do have new information, which is the binges are very much worse from me than I thought." "They're really bad." "I think, for me, the unexpected thing was how bad moderate drinking can be for you." "That would be if you could stick to a little bit, which, of course, most people can't." "For most of us, one drink leads, inevitably, to another." "That's the thing I learned." "It's not the fourth pint or the fifth pint you've got to worry about." "It's the first." "MUSIC:" "Y'all Come Back Saloon by Oak Ridge Boys" "Xander, Xander, are you having a good time?" "# Tambourine" "# With a silver jingle" "# And she must have known the words" "# To at least a million tunes... #" "Xander, how are you feeling?" "We should go dancing." "We could go for a little dance." "If we could find..." "We could do some karaoke with some country songs..."