Second Edition Data Networks DIMITRI BERTSEKAS Massachusetts Institute ofTechnology ROBERT GALLAGER Massachusetts Institute ofTechnology PRENTICE HALL, Englewood Cliffs, New Jersey 07632
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Can My Genes Determine the Best,Type of Diet For Me. We all know the story fed up with how you feel you decide to go on a diet So you open up Google and search. for the best fat loss diet But you get a multitude of results some tell you to avoid carbohydrates completely. whilst others tell you to focus on meat and vegetables and avoid dairy You open up your favourite magazine. and see that their favourite celebrity of the moment has got her body bikini ready by eating only grapefruits. before 6pm The health section of your newspaper has a review of a new diet book promising that if you follow. its 9 steps exactly you can lose loads of weight and not worry about calories. SO WHERE DO YOU START, That s the problem isn t it there is just too much information Diet fads come and go and the grass is always. greener on the other side People struggle to make meaningful dietary changes because the next best thing is. always around the corner Part of the problem with fad diets is that people don t seem to be able to adhere to. them due to the more often than not restrictive nature for long enough to see any meaningful changes Here at. DNAFit we want to move away from the idea that a diet should be hard and involve a dramatic reduction in. calories Instead a diet should be a way of life the way you eat to support your health. Think back to a way of eating that worked best for you Did your friends or significant other respond in the same. way Or were there differences between you all The more you think about it the more you realise that your. genes might be playing a role in determining how well you respond or don t to any given diet. All diets are made up of macronutrients of which there are three four if you include alcohol fats. carbohydrates and proteins What we know now is that our genes can impact how well we tolerate both fats. especially saturated fats and carbohydrates the main sources of energy in our diet If we don t tolerate. carbohydrates quite as well perhaps we should consume less of them Similarly if our genes indicate that high. intakes of saturated fat are likely to increase our risk of obesity and cardiovascular disease then it might be. worthwhile consuming less of them, One of the main genes with regards to saturated fats is the FTO gene People with the TT genotype for FTO can. tolerate saturated fats really well and as such can generally stick to the current guidelines However those with. the AT and AA genotypes carry an increased risk of fat gain with higher intakes of saturated fat a risk which isn t. present at lower intakes In fact in a 2009 study it was seen that AA genotypes were three times more likely. to become obese on a low carbohydrate diet than TT genotypes This shows really nicely that a low carb high fat. diet is not appropriate for everyone especially when you consider than almost 20 of people have the AA. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. Another gene that can impact how well we tolerate saturated fats is the APOA2 gene A different study from. 2009 found that when subjects had more than 22g of saturated fat per day those with the APOA2 CC genotype. had a significantly higher body mass index than subjects who consumed less than 22g of saturated fat per day. Again this wasn t seen to the same extent in APOA2 TC and TT genotypes showing that different people. tolerate the same nutrient very differently 22g of saturated fat isn t even that much it s about 10 of the. calories when on a 2000 calorie per day diet,BUT WHAT ABOUT CARBOHYDRATES. There is another gene TCF7L2 which can interact with carbohydrate intake to determine type II diabetes risk. When on a high glycaemic load diet those with the TT genotype of TCF7L2 had about a 2 5 times higher risk of. developing type II diabetes compared to those with the CC genotype However when on a low glycaemic load. diet this risk was much much lower Again same nutrient different response. With the DNAFit diet reports we look at your genotypes for FTO APOA2 TCF7L2 and six other genes to. determine your sensitivity to both carbohydrates and saturated fat Once we have done this we will place you on. a diet matched to your genes,DOES THIS MATTER, The best type of diet is one you can stick to It doesn t matter how good a diet is if you can t continue with it day. in day out then you won t see results Fortunately there is evidence that a genetically matched diet increases. diet adherence and also increases fat loss compared to a standard weight loss diet A 2007 study published in the. aptly titled Nutrition Journal gave 50 people a genetically matched diet and compared them to 43 people who. were just following a standard diet Early on when motivation was high both groups lost weight However after. 300 days those on the genetically matched were much more likely to have maintained weight loss Those in the. genetically matched diet reduced their body mass index by 1 93kg m2 a weight loss of over 6kg for someone. 1 8m tall whilst the standard diet group had gained an average of 0 51kg m2 on their BMI equivalent to a. weight gain of just over 1 5kg for a 1 8m tall individual As you can see the results of this study and others like it. show that a genetically matched diet can increase both weight loss and adherence to a diet. IS IT TIME YOU FOUND OUT WHICH TYPE OF,DIET WORKS BEST FOR YOU. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. How to Take Control of Your Health By,Meeting Your Micronutrient Needs. Whilst macronutrients fats carbohydrates and proteins have a big impact on your levels of body fat it could. be argued that micronutrients are more important for overall health Micronutrients are a group of compounds. that include vitamins and minerals and if we don t get enough of them it can make certain illnesses and. diseases a bit more likely Fortunately we have access to a wide variety of foods which means that a vitamin. and mineral deficiency in the 21st century is very uncommon within the developed world The problem is that. whilst we may be free from deficiency we might not be getting enough to maximise our health When we. consider that polymorphisms in some of our genes could make our requirements even higher it becomes even. more apparent that we might not be getting enough through our diet to truly be at our optimum. WHAT GENES CAN AFFECT,MY MICRONUTRIENT REQUIREMENTS. At DNAFit we look seven different genes that affect your requirements for antioxidants omega 3 vitamin B and. vitamin D Whilst we know that the guideline daily allowances are sufficient for most people small. polymorphisms within these genes can increase the risk of certain health issues which in most cases can be. very easily corrected by just consuming slightly more of a certain nutrient. Let s take vitamin B for example When determining the vitamin B requirements for each person we look at a. gene called MTHFR at a particular site known as C677T MTHFR creates an enzyme called. methylenetetrahydrofolate reductase which plays a role in a complex series of reactions called methylation. What we know is that different people have different genotypes of MTHFR which can make this enzyme work. slightly less well In people with the CC genotype the enzyme works really well and is not associated with any. disease risk However in people with the TT genotype the enzyme activity is reduced working approximately. 35 as well as people with the CC genotype and in CT genotypes the activity is about 75 that of CC. genotypes One thing this enzyme does is covert something called homocysteine to methionine Elevated. homocysteine is associated with an increase in risk of cardiovascular disease hypertension and stroke If the. ability to convert homocysteine to methionine is reduced because of these differences in the MTHFR gene then. homocysteine can accumulate within the blood increasing the risk of those diseases. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. SOUNDS SCARY IS THERE ANYTHING I CAN DO 05, The good news is that whilst this does sound scary and concerning any risk can really easily be reduced by. making some simple dietary changes It turns out that vitamin B9 is really effective at reducing homocysteine. especially in MTHFR CT and TT genotypes You might have heard of vitamin B9 before as folate or folic acid it. tends to be found in green leafy vegetables and in some countries is added to foods through fortification. Whilst the RDA for folate is 400ug per day research indicates that if you have the MTHFR CT and TT genotype. then this likely isn t enough to keep homocysteine at healthy levels A study from 2002 published in the American. Journal of Clinical Nutrition found that at this recommended daily intake homocysteine was much higher in. those with the TT genotype compared to those with the CC genotype. However when the subjects in the study with the TT genotype were put on a high folate diet or took a folic acid supplement. their homocysteine levels dropped to that of the CC genotypes The key here was that the amount of folate or folic acid required. to create this change was at least 600ug per day and as high as 800ug levels 1 5 and two times higher than the current. recommended daily allowance So we can see quite nicely that a one size fits all approach to micronutrients doesn t work. letting people with the CT and TT genotypes of MTHFR down These people need a higher intake of vitamin B9 and also B6 and. B12 which all work together in order to maximize their health which they can do through either having more green leafy. vegetables or use of vitamin supplements,WHAT OTHER GENES WHICH CAN AFFECT. MY MICRONUTRIENT NEED, In our other panels we look at genes that can affect antioxidant requirements SOD2 CAT GPX1 omega 3. requirements IL6 TNF and vitamin D requirements VDR In all these cases people with small changes within. these genes find that the recommended daily allowance is insufficient for their needs and that they are let down. by the one size fits all approach currently used to make dietary recommendations. Looking closer at vitamin D it is estimated that as much as 70 of the population of the UK don t get enough of. it on a regular basis even though the recommended daily allowance is pretty low 600iu Research in. sportspeople shows that a useful intake for them can be as high as 5000iu per day One of the reasons for this is. that vitamin D isn t all that common in high amounts within our diets and the most common way for humans to. get vitamin D is from the sun Now countries like the UK don t get much sun anyway which causes issues but. even in the summer or in hot countries many people still don t go outside that often This is due to an increase. in inside jobs like office work and the fact that inside tends to be cooler and more comfortable in summer. months particularly in more southerly climates, And additional factor is the fact that many people avoid the sun due to worries about skin cancer Whatever the. reason the simple fact remains that most of us don t get enough vitamin D to meet the recommended daily. allowance When you add to the mix that polymorphisms within the VDR gene can further increase the need for. vitamin D you can see that this might be an area of our diet to look more at Hopefully you can see that we are. being let down by a one size fits all approach Knowing which versions of genes that affect your micronutrient. needs can really help you take charge of your health and make meaningful changes in order to live at your best. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. Is Caffeine Bad For Me, I m sure you ve seen the headlines telling us how too much caffeine is bad for our heart And I m sure you ve. seen the articles telling us how coffee can protect our heart Confusing isn t it As with everything how much. caffeine and therefore coffee you can tolerate is dependent not only on your genes but also on environmental. factors We know there is a gene called CYP1A2 which creates an enzyme also called CYP1A2 This enzyme is. involved in many reactions but the one we are interested in pertains to caffeine You see CYP1A2 is responsible. for 95 of all caffeine metabolisation in the body We also know that different people will have different. versions of this gene which means this enzyme may work faster or slower People with the AA genotype are. classed as fast metabolisers of caffeine and those with the AC and CC genotypes are classed as slow. metabolisers,SO WHY DOES THIS MATTER, Well caffeine is one of the most consumed drugs on the planet In the US the average amount of caffeine. consumed per day is around 300mg which is the equivalent to around 5 shots of espresso caffeine content of. coffee can vary greatly or 4 energy drinks In the UK we drink over 70 million cups of coffee per day an average. of more than one per person It is safe to say that most of us consume caffeine on a regular basis If it s going to. potentially cause us some health issues we should know about it. This is where the CYP1A2 gene comes in Research shows that in general the greater the number of cups of. coffee a person has per day the greater their heart attack risk In a 2006 study carried out in Costa Rica the land. of great coffee it was seen that in people consuming 4 or more cups of coffee per day the risk of a heart attack. was about twice as high as consuming no coffee at all Interestingly consuming one cup of coffee per day. reduced the risk of heart attack compared to having no coffee It could be that coffee or caffeine has a. protective effect on the heart or it could be that people who don t consume coffee or caffeine on a regular. basis have an underlying health issue which causes them to avoid caffeine. So far so good High coffee intakes are associated with an increased risk of a heart attack something that we. already know However the researchers went one step further and examined the effect of CYP1A2 genotype on. caffeine intake to see if it had any effect on heart attack risk And what they found could be very important to. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. all In fast metabolisers the risk associated with consuming 4 or more cups of coffee per day was lower than 07. seen in the joint group In slow metabolisers it was higher This illustrates that slow metabolisers are more. likely to have a heart attack from higher caffeine intakes than fast metabolisers. HOW CAN YOU USE THIS INFORMATION,TO MAXIMISE YOUR HEALTH. By knowing your CYP1A2 genotype you can better understand your bodies response to caffeine If you re a slow. metaboliser it makes sense to limit your caffeine intake to less than four cups of coffee per day if you re a fast. metaboliser this is not as important As such at DNAFit we recommend that slow metabolisers limit their. caffeine consumption to about 200mg of caffeine per day whilst fast metabolisers can have up to 300mg per. day Slow metabolisers should also avoid caffeine later on in the day because they metabolise it slower it will. stay in their system for longer increasing their chance of sleep disturbances. It s important to remember that it s not only coffee that contains caffeine Tea does too although again the. amount varies with type and brew time Typically black tea contains around 45mg of caffeine as does green. tea Energy drinks also contain caffeine with an average amount of 30mg per 100ml Soft drinks can also be. caffeinated with most colas having around 35mg per can And it s not just drinks that contain caffeine Dark. chocolate can have up to 30mg per bar and max strength cold remedies and pain relievers also often have. caffeine listed as an ingredient, There s also a second gene which can have implications as to how much caffeine you consume the vitamin D. receptor gene or VDR This gene plays a role in how well your body utilises vitamin D and different genotypes. require different amounts of vitamin D for optimal health From a caffeine standpoint we also know that some. VDR genotypes carry a higher risk for a loss of bone mineral density with high caffeine intakes than others A. loss of bone mineral density is associated with an increased risk of fracture so it really can pay to understand. how your VDR gene can impact how much caffeine you should consume It turns out that individuals with the. CC genotype of VDR are at risk of a significant loss of bone mineral density with higher caffeine intakes and. this effect is not seen in other genotypes or with a lower caffeine intake As such if you have the CC genotype. DNAFit would always recommend that you limit your caffeine intake to 200mg per day regardless of whether. you are a fast or slow metaboliser, As you can see it really can pay to understand how your genes may affect how much caffeine you can consume. on a regular basis and enable you to take charge of your own health and wellbeing. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. SPECIAL REPORT A One Size Fits All,Approach Is Letting You Down. When you re deciding what the healthiest diet is for you what do you do Perhaps you do an online search. engine type in a phrase and look at the top links Perhaps you read a book or a blog post by nutritionists you. like and respect Perhaps you re taking advice from your friends family or other professionals How do you. know that the information you get from these sources is the best for you. You don t What all the advice you re given does is tell you what works either in theory or in practice for a. certain number of people The thing is if you look at research you will see a big difference in how people. respond to a diet or supplement If there is research looking at the use of a high fat low carbohydrate diet for. weight loss the results might show that on average it was effective However if you look closer at each. individual s results you can bet that no one responded exactly the same some people will have lost weight. whilst some would have gained weight, That s because most nutrition research and diet information doesn t look at what actually makes us who we are our genes We. are all different and inherently we know this to be true We all know someone who can eat all the pasta they like without putting. on any weight maybe that s you whilst some people only need to think about bread to put on weight that s me Part of these. differences will be due to small changes in our genes which enable us to tolerate carbohydrates better or worse and knowing. about these differences can be useful when it comes to choosing a diet. The same is true when it comes to vitamins and minerals We are told how much to consume by the government. and medical establishments in the form of guidelines such as the Recommended Daily Allowances RDAs. These are the amount of each nutrient we should take to avoid deficiency but don t look at how to create. optimum health We now know that small changes in our genes can mean that the RDA is woefully inadequate. for us and can leave us at risk of certain health issues For example the MTHFR gene can have a big impact on. how much vitamin B we need and the VDR gene can dictate the optimum amount of vitamin D we require for. optimal health We will examine these micronutrient requirements later in this series. At DNAFit we give you a much better idea of how to personalise your nutrition. and optimise your health, DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. Personalise your nutrition, We do this by giving you the best type of diet for weight management which we arrive at by looking at your. sensitivity to saturated fats and carbohydrates This gives you an idea of how well you tolerate each of these. We then look at detoxification ability This isn t about a detox diet which doesn t work but instead looks at. how well your liver can deal with toxins Do you need to give it a bit of a helping hand by consuming less of. certain types of foods or more cruciferous vegetables Again we will look at this in greater detail later in the. We also look at nutrient needs I ve already mentioned Vitamin B and D but we also look at genes linked to. antioxidant and omega 3 requirements All of this information allows you to create a way of eating in order to. ensure you are performing at your best, Next up we look at food sensitivities How sensitive are you to salt could you afford to cut down on it even. more than the guidelines recommend What about alcohol is it true that a glass of red wine a day is good for. your heart or is this beneficial effect reduced in you This is determined by the ADH1C gene which we test for. as part of our report We also look at caffeine sensitivity in this section. Finally we look at food tolerances About 65 of the world s population are lactose intolerant is this you If it. isn t then there isn t any particular need to avoid milk products but if you are this might explain some. symptoms you haven t quite been able to put your finger on We also look at coeliac disease risk in this section. We know that two genes HLA DQ2 and HLA DQ8 are present in about 95 of people with coeliac disease so if. you have at least one copy of these genes your risk of developing coeliac disease is 1 in 35 If you haven t got. one of these genes then your risk is 1 in 2000 Again all of this is useful information when it comes to optimising. your health, We can therefore see that a one size fits all approach to our health and nutrition is letting us down It s far too. general Instead getting your hands on your genetic information can be a really good way to begin. personalising your diet to your needs allowing you to be healthier throughout. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. Understand Detoxi cation to Take,Control of Your Health. If you ve been interested in health for a period of time you will no doubt have come across the term. detoxification What this word relates to is the removal of toxic substances from the human body a function. which is primarily carried out by the liver This term has been picked up on in the form of detox diets which. become very popular every January as people try to repair the excesses of the festive period These diets whilst. largely harmless actually don t contribute at all to good health as they are an example of fad dieting with little. or no evidence behind them, We shouldn t throw the baby out with the bathwater however Whenever we take on any form of toxin our. body has to work to get rid of it This occurs through a variety of pathways which as already mentioned tend to. focus around the liver This comes primarily in two phases imaginatively called Phase 1 and Phase 2 At the risk. of oversimplifying these pathways Phase 1 converts a toxic substance to a less toxic substance and Phase 2 is. the process by which the body is able to excrete this less toxic substance. Typically the toxins include HCAs and PAHs found in grilled meat medications including paracetamol and. ibuprofen caffeine alcohol and pesticides and herbicides found in food Depending on some polymorphisms. found in specific genes we might be better or less good at both Phase 1 and Phase 2 detoxification and we. might be required to avoid certain types of food or consume more of others in order to support both phases. SO WHAT IS PHASE 1,DETOXIFICATION, In the DNAFit Diet test when we look at Phase 1 detoxification we are specifically looking at how well the body. metabolises two compounds called Heterocyclic Amines HCA and Polycyclic Aromatic Hydrocarbons PAH. These are compounds that form in cooked meat especially meat that has been cooked at a high temperature. for a long period of time or has become blackened or chargrilled When we eat these meats our body begins. to metabolise them and this creates a toxic by product This toxic by product is bad news as it is carcinogenic. and is potentially one of the reasons why there is a link between red meat consumption and cancer There are. two genes that have an impact on how quickly we metabolise HCAs PAHs CYP1A2 which we already met. concerning its relationship with caffeine and EPHX1. DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482. Both these genes create enzymes that are part of the Phase 1 detoxification process and determine whether 11. we are slow or fast metabolisers of these HCAs PAHs If we are a fast metaboliser we get a rapid. accumulation of this toxic by product and our body is a bit overwhelmed and can t deal with it leading to DNA. damage If we are a slow metaboliser then we metabolise these HCAs PAHs much slower meaning that we. get a much gentler increase in the toxic by product and as such our body is much better placed to deal with it. What does this mean for you Well if you are a fast metaboliser we would recommend that you limit your. intake of meat cooked at high temperatures to 1 2 servings per week Generally this means that when you cook. meat you should try to do so at a lower temperature and possibly use a liquid to protect the meat a bit more. think curries stews stir fries etc In our experience the riskiest meats are barbequed meats which are often. blackened and chargrilled crispy bacon which tends to be cooked at a high temperature for a long period of. time and steaks especially if they re well done,WHAT ABOUT PHASE 2. DETOXIFICATION, As mentioned before Phase 2 detoxification is the process by which toxins are prepared for excretion from the. body There are two genes which play a major role in this GSTM1 and GSTT1 These genes are a bit different to. the majority of the other genes in our panel in as much as you either have them in their full form I for insertion. or have them in a shortened form D for deletion It s not at all uncommon to have at least one deleted version. of this gene about 50 of people have the D form of GSTM1 and about 20 of people have the D form of. GSTT1 So whilst it s not uncommon to have the deleted form of at least one of these genes those individuals. will have a reduced Phase 2 detoxification capacity This might sound like bad news but there is a really simple. dietary trick we can use to completely mitigate the loss of these genes and that is to consume more. cruciferous vegetables, Cruciferous vegetables including cabbage broccoli kale Brussels sprouts and cauliflower contain a whole. host of healthful substances of which one isothiocyanates help to support the Phase 2 detoxification pathway. Typical recommendations for cruciferous vegetables are to consume 1 2 servings per week however if we. know you have at least one D form of GSTM1 or GSTT1 DNAFit will recommend that you consume at least 3 4. servings of these vegetables per week in order to support your Phase 2 detoxification. Based on the above it should be clear to see that your genes can play a role in supporting your detoxification. pathways which is important in controlling disease If you have polymorphisms in these genes there isn t. anything to worry about but you should make dietary changes in order offset any risk associated with these. gene variants,CAN YOU AFFORD NOT TO, DNAFit guides Diet V1 Oct 2016 A 1 Fore Street London United Kingdom W www dnafit com 640521 159 482.
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