01 May 2019

Personalized Diets

12 1NTR390 13 Personalized Diets video.

module 12 personalized treatment and

prevention the Dietary Guidelines for Americans is a report that's been issued every five years since 1980 and in this report very general guidelines are provided for all Americans for healthy eating in the latest issue of the Dietary Guidelines there was a significant focus on personalization of the diet with words like using an adaptable framework in which individuals can enjoy foods that meet their post personal cultural and traditional preferences and in fact in this document the word personal is mentioned 24 times without knowing anything about genes or metabolites we know that we can personalize diet based on life stage disease status socioeconomic status and culture food preferences aversions and security physical activity levels and athletics timing and shift work and a person's preparation knowledge and skills so all of these things can be used as we learned in the last module to personalize a diet but how do we go beyond these basic notions well there's any number of companies out there that will be happy to personalize your diet for you and the one common

theme as you can see is some very slick marketing and beautiful packaging and in which you send off your samples and get your DNA based diet revealed remember that all of these companies are out to make money and many of them have nobody on staff or and not one person as part of the development of the company that is actually a scientist so what do you send them so most of these companies are Jean based companies and the reason why is because DNA is a very sturdy molecule if you can extract it from fossilized bones you know you can extract it from a fresh sample so it's really really easy to collect samples almost often almost always it's going to be cheek cells that are coming from inside your mouth and these companies use various methods on the left there and the top you can see that this is a little it's a spit cup can take combined with a a tube and basically you spit if to spit about a mil of saliva and then that gets combined with some liquid that's a preservative and you shake that up and send that in you can also slough those cells off the inside of your cheeks using a brush or a swab and again you

put those into tubes and you send them in and because DNA is so sturdy it's really easy to get a good sample from almost everybody and get to get a very robust test buccal cells or cheek cells are also contain RNA and protein in addition to DNA so you can use those cells to characterize the genome the oral transcriptome the oral microbiome and the oral proteome and you need special preservation methods if you're going to do anything besides DNA even DNA requires some kind of preservation but it's a it's a super easy molecule to extract and it's very very sturdy and can travel at room temperature and that's why it's most of these tests are our DNA based they also use a very simple technology this is an example of a bead array reader these readers can use chips which is shown there on the right and companies like DNA 23andme use these DNA chips the more dense ones and then companies many of the basic smaller companies use smaller sets of DNA arrays that have maybe even less than 100 snips on them these services are super cheap and that's why they make their their products based on genotype and that is even though there are other

kinds of technologies for example we learned in the last module how robust the microbiome is to changes in your diet and how important it is it's much more complicated to collect a gut microbiome arrays can be used to characterize gene expression and methylation and the technology is simple and fast so these types of DNA based sample collection is pretty easy whereas other types of sample collection it may be more challenging not very many people feel comfortable collecting feces and so there's some barrier to those individuals who even would pursue a test that required sending in such a sample so what are you getting on these tests so here's an example and this is not from a gene based diet but this is output from 23andme that then can be re-evaluated by a company called Prometheus so they'll take your genotypes which are almost exactly the same genotypes that you're going to get from any other smaller company 23andme is probably a denser array than any other company and they're going to give you a report that looks something like this so the Prometheus reports aren't very

beautiful but here are when I typed in diet here's the output that came up so this says based on my genotype I'm claimed to lose two and a half times as much weight on a low-fat diet and they give you some information here about which snips they're basing this claim on so you can go back and you can look up the snips and see what they're actually saying one of the snips on which this claim is based is a study of four genes fa b p2 leppe are left and FTO in a set of women 105 women following bariatric surgery what this study found was that only leptin genotype at position 222 223 showed any association to weight loss following bariatric surgery and in fact they state twice in the abstract you don't have to even read the whole paper they still state twice that the other genotypes did not present any significant association so while this was part of the report that said that I'm susceptible to resistance to weight loss this this paper doesn't seem to support that another paper on which this genotype based analysis was given is this paper one of the snips is found in the beta-2

adrenergic receptor and in this study of 78 Spanish women what they concluded was that women carrying the glue allele had a greater reduction in body weight the non blue allele carriers and that they claimed in this small sample of Spanish women they end the abstract by saying these findings should be taken as preliminary and be replicated in further energy restriction studies with larger sample sizes so the authors of this paper were cautious in interpreting their findings but Prometheus was pretty in cautious in giving this information about potentially responding to low-fat diets in another part of report of the report it indicated that I'm part of the 88% of the population claimed not to maintain weight loss unless I perform high-energy exercise I looked at the snips to see what they predicted one of the papers the only one that I could really find that related to the interpretation was a paper about the trip 64 arge polymorphism in the beta 3 adrenergic receptor gene and again in this small study of 76 perimenopausal women what they found was that the wild-type which is the trip trip

homozygotes lost significant amounts of weight but if you'll notice there it's point seven four kilograms which is about maybe about a pound and a half maybe two pounds and the other women didn't lose much weight at all again this is a really small study it's very specific to perimenopausal women and to make this interpretation is really really over selling the information so these are two examples and actually I didn't try very hard to find two examples from this report in which the interpretation of the genotypes was very much an over interpretation of the existing literature most of us geneticists who do this work report these associations with caution and these analyses are meant to be interpreted at the level of populations not individuals and that's one of the biggest worries with these gene based dietary programs is that they're taking population reports and turning them into here's how you will respond to a given diet based on your genotype and that is very worrisome for us cautious scientist other ethical issues associated with these tests are that they have the potential to be reveal non-paternity as

you've seen it doesn't take very many markers to show when individuals and families may not be related and so if a family decides to go in and all get genotyped for a diet based test they may find out information that they weren't prepared to eat to hear the tests may also reveal other types of disease risk so this is very true for the apoE gene which you evaluated in an earlier module and which a woman has proposed is the key to creating diets based on a pony genotype back when a pony was first being genotyped quite a lot it was really just to look at risk of atherosclerosis and possibly to inform treatments for lowering lipids much later it was revealed that a bowi genotype is very strongly associated with Alzheimer's disease and finding your apoE genotype and its association with Alzheimer's is much more significant than looking at that gene in the context of whether or not you should eat low or high fat diets so the again that's very specific information that you may not be prepared to hear the tests may reveal confidential information about other family members so if some but not all family members

get genotyped depending upon who gets genotyped you can actually infer genotype to the other members of the family and that may be very worrisome to those other members tests may be misinterpreted and over interpreted as we just saw in these two examples again the companies are generally taking Association reports from the literature and turning them into diagnostic information that they're then passing on to their clients and the tests may not be technically valid so very little information is usually provided from these companies about how exactly they process your DNA how they ensure that it's your DNA how how they ensure that the test runs accurately and how they evaluate the genotypes and so all of those issues may influence validity of the test as you evaluate the validity of a test you can use a methodology called the analytical and clinical validity clinical utility and ethics model and in this model you analyze the analytical validity a measure of the accuracy of a genotyping as we were just talking about in terms of documenting the samples and documenting and verifying the robustness

of the technology itself scientific validity so concerns about the strength of the evidence the misinterpretation or over interpretation of Association studies and the lack of reporting in which associations are observed in specific types of populations and not taking that into account the clinical utility so many of these effects as in the example of a weight loss of 0.76 kilograms may not have any kind of clinical utility in the context of the individual and then of course there are all kinds of ethical legal and social implications as we've discussed so in this module you'll see more information about the strengths and the weaknesses of various types of personalized nutrition and then you'll get the opportunity to apply some of the things that you've learned in this module in your module project