Genetic Testing for Personalized Nutrition. Podcast with Alon Keinan

Personalized nutrition is a hot topic. Various media outlets recently reported that people might be able to use a specific genetic test to determine whether they would thrive on a “paleo” or a vegetarian diet. Unfortunately, it’s not quite that simple. Here is my take on this subject and how you can use testing to make more informed dietary choices.

One of the fundamental tenets of the Paleo diet is that dietary changes associated with the introduction of agriculture and animal husbandry (about 10,000 years ago) occurred too recently for our genomes to have fully adapted. This is likely true, but we also know that the ability to digest lactose into adulthood (lactase persistence) is more prevalent in parts of the world where people domesticated animals and relied upon milk as a source of nutrition. Among other factors, this is probably because there was selection pressure for increased frequency of the gene mutation that enabled people to consume milk in those areas. This is evident today when you look at the global distribution of the lactase persistence genotype (people who continue to be able to digest the sugar in milk into adulthood).

In the latest episode of humanOS Radio (see episode below), I discuss another adaptation that has emerged relatively recently (on an evolutionary timescale) that relates to how people respond to consuming polyunsaturated fatty acids (PUFAs). First, let’s quickly go over how PUFAs act inside the body and why this matters.

Personalized Nutrition: A Simplistic Primer on Essential Fatty Acids

As you probably know, omega-3 and omega-6 are essential fatty acids – our bodies can’t make them themselves but need them to function, so we need a certain amount in our diets. Fortunately, α-linolenic acid (omega-3) and linoleic acid (omega-6) are quite common in plants and animals alike, so deficiency is not likely in a diet with enough calories.

However, we also need certain long-chain omega-3 and omega-6 fatty acids. These are more complex PUFAs that have many important functions – they are required for healthy brain development, for instance. These long-chain PUFAs include arachidonic acid, docosapentaenoic acid (DHA), and eicosapentaenoic acid (EPA).

Importantly, consuming enough of these in the diet is trickier for some people. We can get these in two different ways. One is to eat a diet that is rich in preformed long-chain fatty acids. Oily fish is an abundant source of DHA and EPA. Meat and fish are higher in arachidonic acid.

As you can see, most of the best sources are animal products. So does this mean that vegetarians and vegans are out of luck? Fortunately, the body can biosynthesize the long-chain fatty acids from α-linolenic acid and linoleic acid. This “desaturation” process is mediated by enzymes called fatty acid desaturases, which insert double bonds at specific locations on the fatty acids to change their shape and function. However, this is obviously extra work for the body, and we now realize that people naturally vary in how efficiently they handle this conversion process.

Why are some people better at converting long-chain fatty acids than others?

And what implications might this have for our diets?

These questions bring us to my guest today.

Guest

In this episode of humanOS Radio, I interview Dr. Alon Keinan, Professor at the Department of Biological Statistics & Computational Biology at Cornell University. His lab investigates the evolutionary origin of genetic variation in human populations, and his team has been looking into what factors may have shaped genetic variation in ability to synthesize long-chain fatty acids.

In a recent study, researchers examined variants of the genes(the FADS genes) that code for fatty acid desaturase. This mutation consists of an insertion or a deletion of some DNA base pairs, each of which affects the expression of the FADS genes.

The team looked at ancient DNA samples and found that different versions of the FADS2 gene emerged and predominated in different populations around the world. This variation corresponded to the types of diets that these groups adopted. After the advent of farming in Europe, for instance, the insertion mutation became much more prevalent, which also coincided with a more plant-based diet. This makes sense because the insertion mutation enables people to more efficiently process omega-3 and omega-6 fatty acids and convert them into DHA, EPA, and arachidonic acid.

Genetic variation has carried over into modern populations. In a prior study, Dr. Keinan’s lab found that populations around the world that historically ate a predominantly vegetarian diet (India, Africa, parts of East Asia) were more likely to have the so-called “vegetarian” gene variant than those of European heritage. When comparing samples around the globe, they found that 68% of Indians had the insertion mutation versus just 18% of Americans, suggesting that selection pressure from diet may have played a role in shaping differences in gene frequencies.

Like I said earlier, we do need those long-chain fatty acids. So, at first you’d probably think that being able to easily convert them is an advantage, right? The problem is that you don’t want too much of them. What if, for instance, someone with the insertion mutation eats a diet high in meat and eggs, thus making a surplus preformed long-chain fatty acids? As just one possible consequence, such a person might generate excess arachidonic acid. High levels of arachidonic acid may increase systemic inflammation, and this could lead to greater long-term risk of diseases such as cancer and atherosclerosis. So, if you happen to have the insertion mutation, you probably want to consider how your dietary choices are affecting your inflammatory status.

Personalized Nutrition: Testing for Variation in This Gene

The findings from Dr. Keinan’s lab add to a growing mass of evidence suggesting that people may benefit from using genetic testing to achieve personalized nutrition, instead of relying on one-size-fits-all nutritional recommendations. The problem is that most of us don’t know enough about our own genes to benefit from personalized nutrition. However, this is starting to change.

After talking to Dr. Keinan, I wondered if there was an easy way for a consumer – like me – to find out whether they had the so-called vegetarian mutation in this gene, without having to involve a physician or insurance. That’s how I found out about Insito.me. They make it simple to learn more about a wide range of genetic traits, and they recently added a test so you can determine your FADS gene variant to get a better understanding of your own fatty acid metabolism profile. Here’s how it works.

(Below I describe the process I went through to get my test done, but please note that humanOS.me has no financial relationship with Helix or Insito.me.)

First, get your DNA sequenced – head over to the Helix Store!

At this screen, you can purchase one of a wide array of different genetic testing products. If you want to learn about the genes relevant to fatty acid desaturation, order the Metabolism kit by Insito.me (shown above on the right hand side). Go ahead and create your account at Insito.me so you can view the analysis later.

They will send you a kit with everything you need to collect a small saliva sample, plus a pre-paid shipping box to send the sample over to the lab. Once the analysis is complete, Helix will notify you via email.

Now, the fun part: viewing your results. Log in to your account at the insito.me website. Up in the right hand corner of the website, click on your name – you can see it next to the box that says Get Traits. (You can also access your trait bundles via the iOS app if you prefer).

You’ll be brought to a screen showing a list of products. Any that you’ve purchased and that have results ready should be shown as available. Assuming you got the Metabolism bundle like I did, click there.

As you can see here from my results, the metabolism bundle breaks down eight different tested traits, including alcohol tolerance, caffeine metabolism, and lactose tolerance. The traits are characterized simply as either “Hunter” or “Farmer” versions to give you a quick idea of how old your trait variations are on the timescale of human evolution and how they express themselves.

You can click on any of the listed traits to learn more. Let’s check out Fat Synthesis (the subject of Dr. Keinan’s work).

As you can see, I have the “Farmer” version of this trait, meaning that my body more efficiently synthesizes long-chain polysaturated fatty acids.

Personalized Nutrition: What can you do about it?

As I discussed earlier, individuals with the plant-based diet haplotype (like me) have a greater propensity to synthesize arachidonic acid from linoleic acid in the diet. This can be a problem because arachidonic acid is a precursor for molecules that increase inflammation and clotting. These are both important processes, but you don’t want too much of either, especially as you get older.

So why has this become an issue?

Partially because the fatty acid composition of the typical modern Western diet is strongly shifted toward omega-6 – far more so than that of our ancient ancestors. Anthropological evidence suggests that humans evolved on diets with a roughly 1:1 ratio of omega-6 to omega-3 fatty acids. Now, most of us are eating a diet that is closer to 15:1… or more!

Furthermore, you could be getting a double whammy if you are also eating a lot of foods that are rich in preformed arachidonic acid (like meat, poultry, and eggs). So, if you’re going to be eating animal products like I listed while eating a paleo diet, I recommend minding the sources of your animal products as the diets of the animals will significantly impact the fatty acid profile of their meat. Also, be mindful of the other sources of short-chain PUFAs – like seeds and nuts.

Finally, if we look at the dominant sources of arachidonic acid and linoleic acid in the American diet, ultra-processed foods are significant offenders: sausages, fries, pasta dishes, pizza, breads, grain-based desserts, cold cuts, and so on. No big surprise there.

We don’t know enough yet to give prescriptions for personalized nutrition, but I think we can glean a few broad guidelines to moderate arachidonic acid levels:

1. Try to limit intake of linoleic acid in the diet, which is abundant in certain nuts and seeds, as well as oils pressed from nuts and seeds. For most people, the easiest way to do this will be to swap out industrially processed seed oils (sunflower, corn, peanut, soy, and so on) for fruit oils like olive or avocado. You can also find high-oleic versions nowadays that are lower in linoleic acid.
2. Rein in consumption of meat and eggs, especially if you consume a lot of calories from nuts and seeds. If you aren’t taking in a lot of linoleic acid, this may be a less pressing concern.
3. Ultra-processed foods and restaurant dishes tend to be high in both arachidonic acid and linoleic acid, for a multitude of reasons. It would be wise to limit these types of food if you have the insertion mutation. Okay, let’s be honest, it would probably be wise for everyone to do this.

For more of my thoughts on dietary fat, check out this blog. If you want to learn more about Dr. Keinan’s research, and how it might affect your ability to make smart personalized nutrition choices, check out the interview below!

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Transcript

Alon Keinan - 00:06: I'm not saying that, that's the only reason, but if your ancestors have been following almost a purely plant based diet for hundreds of generations, and then in the last two generations, they've started consuming a very different diet, one of the effects, they would have too much Omega 6 which has been associated directly with risk of cardiovascular disease with higher cholesterol and so on.

Kendall Kendrick - 00:35: Human OS. Learn, Master, Achieve.

Dan Pardi - 00:45: Dr Alon Keinan, welcome to Human OS Radio.

Alon Keinan - 00:48: Thanks for having me, Dan.

Dan Pardi - 00:50: To start off, please tell us about where you work, and the type of work you do in your lab.

Alon Keinan - 00:55: I work at Cornell University, in Inthica. Generally my lab covers a range of topics [inaudible 00:01:02] that covers human population genomics, and the effect of genetic variance on complex disease. We are a computational lab for the most part, meaning most of our background is in Computer Science, statistics, maths, physics, and so on, as well as some genetics.

01:20: What we do best is develop new methods or new approaches to examine genetic data in order to make new discoveries based on the huge amounts of genetic data that is, thanks to advancement in technology, is being generated. Recently we became very interested in the combination of nutrition and how it falls in this spectrum, both in the context of signatures of natural selection, how different diets have led to different populations being different genetically, as well as the implications it has on complex disease in the field that some call in Nutrigenomics.

Dan Pardi - 01:58: Tell us about some of the work that's relevant to the most recent article in Nature that serves as a background for the discussion on the most recent findings.

Alon Keinan - 02:07: We'll have to start with a bit of general introduction of some pretty exciting results will follow.

Dan Pardi - 02:12: Please yeah.

Alon Keinan - 02:15: Our work involves how innate humans and other animals in omega 3 and omega 6 and their effect. In general why omega 3 is rightly referred to as anti-inflammatory, and omega 6 as pro-inflammatory. That's contrary to common knowledge. It is important to have both of them. They are involved in many other vehicles of functions such as brain development, cognitive function, immune response and the list goes on and on.

02:43: For the sake of the discussion today, just need to remember that we need certain levels of both of them, but then again not too much.

Dan Pardi - 02:50: Right so these fatty acids we don't synthesize them, so we need to consume them.

Alon Keinan - 02:54: That's a good point. So, for both of them the function of versions come in the form of what is known as long chain polyunsaturated fatty acids. I emphasized the long chain part as this is key in the total results as well, but what we're saying, there are many fatty acids and one of the characteristics is simply the length of the molecule, with shorter versions not carrying out the many functions that I describe.

03:18: So we can get the long chain versions in one of two ways. First, consuming what we call animal based foods can provide these directly. Animal based include of course, meat that is richer in omega 6, as well as fish and other seafood, which are richer in omega 3, but also animal products such as egg and milk.

03:37: Now, shorter chain polyunsaturated fatty acids are the target to consume from any plant based foods including fruits, vegetables, seeds, can be converted in our body if that's what you were referring to, to longer form. A gene family called FADS, F-A-D, for fatty acids desaturisers is involved in this biosynthesis, and again, just for the sake of the the work they should know that the enzyme encoded by FADS, one, the first of three genes in the family, facilitates the transition from short to long, in this biosynthesis.

Dan Pardi - 04:10: So in human health it is critical that we have access to these long chain polyunsaturated fatty acids for human brain development and controlling information, and the omega 3 is considered generally to be anti-inflammatory, and the omega 6 is considered to be more inflammatory, but both are critical for human health?

Alon Keinan - 04:31: Now we mentioned the rate of their relation specifically of the variant that we find there to dozens of their diseases for instance. So that's where we start. The previous study that you mentioned that has been published last year, and some of your listeners might well have read or heard about it since it has been all over the media, mostly dubbed as the vegetarian gene, and often is misrepresented I'm afraid.

Dan Pardi - 04:58: That's not uncommon.

Alon Keinan - 04:59: So, in that study from last year, we studied mostly Indian populations, that is a South Asian population, not Native Americans. Most Indian populations traditionally practiced a diet that is mostly plant based. And we discovered that genetic variant in the regions of the FADS genes that I mentioned, have been adaptive in their populations, but not in all other populations.

05:26: In other words, some genetic variants have been targeted by natural selection in the evolutionary history of Indian populations, which in turn lead to these variants having high frequencies in these populations today. And together with our collaborators from the group of [inaudible 00:05:46], in the Department of Nutrition here in Cornell University, they have show that this variance increased the efficiency of the biosynthesis of long chain Polyunsaturated Fatty Acid from shorter ones, which we further observed to be at least in part, by increasing the expression of FADS1, the amount of how much enzyme is being expressed in our cells, which result in being more efficient biosynthesis.

Dan Pardi - 06:15: What are the dietary sources of the short chain fatty acids that are then converted by the FADS1 enzyme into the longer chain?

Alon Keinan - 06:22: All plant based fatty acids are all short chain of several types actually, and all of them can be converted by the same biosynthesis, whether it's all kind of seeds and foods, and vegetables. So it seems that this plant based diet over hundreds of generations of course, which entailed little direct consumption of the active from, the long forms of omega 3 and omega 6, have led to a very strong selective pressure for the more efficient biosynthesis because that's the only way of obtaining them in that case.

Dan Pardi - 06:59: Right. As humans moved from eating a more hunter gatherer diet in certain parts of the world the selection pressure of eating more plants caused this alterations in the expression of the F-A-D-S gene, so the fatty acid desaturation gene, and that enabled humans to produce these necessary fatty acids for our health from plant seeds and non-animal sources?

Alon Keinan - 07:22: Indeed. That's in Indian populations that have been vegetarian, or actually vegan for a long, long time. We immediately thought about why aren't we seeing the same thing for Europeans? There have been a few related studies as well that also have not seen any result for Europeans. When we studied the Indian populations, we just applied the same methodology and did not detect any strong signals for this natural selection. Indeed, we hypothesized that the reason for that, is that while Europeans have indeed follow a mostly plant based diet for most of their history, since they become founders, since the neolithic evolution in each region, in each part of Europe, their Paleolithic ancestors were hunter gatherers and practiced different diets.

08:12: I'm talking about the neolithic evolution, this is something that took place after the advent of agriculture, anywhere between six to ten thousand years ago, depending on when we're talking about. So, we decided to try and distinguish the genetic signature left by each of these two epochs of evolution before and after the neolithical evolution, where the environment and specifically, the diet has been very different.

08:37: To do that, we have resorted to what is called ancient DNA. There have been incredible recent technological advancement that allowed to extract DNA from fossils and sequence it. That way, beyond getting a window as we usually do into evolution by studying genetic diversity that the past has left on extinct populations, we can now also directly study the genetics of either extinct populations, or the ancestors of some populations to date.

09:10: What we have done, we mined and put together the data published by all ancient DNA studies, most of them are in Europe, and we put these also side by side with many contemporary populations. One of these studies from David Reick school led by Matthew Simons has already examined instances of the natural selection since about the neolithic evolution, by comparing the prediction of genetic variance, but then insert our populations and comparing it to the frequency of genetic variance in respect to populations today.

09:48: They did a Genome Wide on the entire genome and they reported many instances of selection, one of them indeed that around these FADS genes. One of the things that our study has done though for the first time is that, instead of just considering differences in frequencies between ancient populations and modern populations, we also compared frequencies between several ancient populations from different periods since we realized that the potential effect of natural selection is not necessary lasted to the present because of the changing environment, change in diet in this case right.

10:23: With that, I will quickly summarize three results concerning the natural selection that we observe, generalizing. On this study I just mentioned, but also using other data and tests for natural selection that focus only on recent periods, we found a long region of many genetic variants that are being targeted by positive selection that are adaptive recently in European populations. And much like in the same case of Indian populations, the variant that is being targeted by selection in each of them is in the direction of increasing the expression of FADS1, which as we know, increases the efficiency of the biosynthesis. And the rationale is the same as in India, we're seeing these populations recently, meaning after the neolithic evolution have mostly consumed [inaudible 00:11:15], with little meat, or little sea-based diet, hence they need an efficient biosynthesis. And there's been very strong selection for such biosynthesis.

Dan Pardi - 11:25: Right.

Alon Keinan - 11:25: Second, we could partition Europe to several geographical regions both historically and in its present, and compared between them and these alleles that are, let's say associated with a plant based diet, are of much higher frequency in Southern Europeans and seem to have been under stronger selections in Southern European farmers than northern Europeans, which after long discussion and reading the papers, especially help with our new anthropologies collaborator, also by research Professor [inaudible 00:11:58] from Harvard University.

12:00: We assume is also in line with diet since northern European farmers still had access to some seafood sources, and they also drank more milk and did so earlier. So once there's domesticated animals, cows specifically, they started consuming their milk and from the milk you get the long form already. While in the South the Mediterranean has not been [inaudible 00:12:26] very useful for having a real sea food based diet, hence the difference anthropologically between the diets of northern and southern Europeans, and we actually see this gradient of more and more selection for efficient biosynthesis as we travel from north to south Europe.

Dan Pardi - 12:44: So these genetic adaptations that took place enabling European farmers to be better adapted for the shift in their diet from hunter gatherer dietary patterns and adaptation, clearly caused identifiable biological consequences that enabled these European ancestors to be better suited for greater dietary plant volume.

13:04: Did those adaptations only allow for these humans to thrive on a wider breath of food proportions? Or did these adaptations simultaneously make previous food proportions like high meat and seafood less healthy for this specific population?

Alon Keinan - 13:18: A good question there. We'll answer it first by describing the last result, an equivalent in populations that still rely on different diets.

Dan Pardi - 13:26: Great.

Alon Keinan - 13:26: Essentially you say that once this biosynthesis is more efficient, they do not necessarily have to consume other foods that are not just plant based.

13:39: So when we look now, only at paleolithic populations based on ancient DNA only, and we have such populations, which were hunter gatherers in several points in time, and we look at the same genetic variance at the same region we see that there is very, very strong positive natural selection adaptation on the very same genetic variance that are targeted by selection recently. All of them with one notable exception that the selection is in the opposite variance, on the opposite alleles what we called. So each genetic variant is two alleles, let's say an A allele and a G alleles. So the G alleles has been targeted by very strong natural selection, pre- neolithic, hence increasing in frequency, the G allele. Then, all of a sudden, as somebody has turned a switch, not only that it stopped increasing in frequency because selection has stopped, but rather selection on the alternate, the A allele started a very strong selection as well, and the A allele instead started increasing in frequency, from the neolithic and the G alleles started decreasing in frequency.

14:54: So there are selection on opposite alleles before and after the neolithic, which is selection essentially on the opposite function, meaning that Paleolithic, there is selection for that use in the reducing the expression of FADS1 and making the biosynthesis less efficient, as opposed to what we have seen in farmers.

15:17: The amazing thing is that it happens via the exact same genetic variance, which was already in existence. As far as I know, it's the only example where this has happened in natural populations in general, and the question is why is it so important to make that biosynthesis less efficient?

15:35: Evolution is trying to stop it, which is going back to your question and to the fact that having too much omega 3 or omega 6 is actually dangerous. And if you have too much, the ratio between the two is also important, but let's not get into that, and since this hunter gatherers rely heavily on a very healthy dose of sea-based diets and some meat as well, in those times they were eating not only the fish and the seafood that we're used today, but actually small the sea-based mammals as well, such as seals with blubber and all. So the level that they received of omega 3, omega 6 was so high presumably that if their biosynthesis was efficient as well it would just mean they would likely have too much, hence the selection for stopping it.

Dan Pardi - 16:26: That has interesting implications for today perhaps.

Alon Keinan - 16:29: Yeah. You see, today, by the way, populations are still practicing this kind of diet, so there's been a study showed a certain variant in Greenlandan Inuit. And we see some of this variancy in a different Eskimo population that we studied, but Greenlandan Inuit still consumed the diet that I described, mostly in sea-based and so on, and they report the variant that is under natural selection in the fat region and we do see that it's one of those variants and the [inaudible 00:17:00] has indeed been under natural selection in hunter gatherers. Paleolithic but, the opposite variance has been under selection recently in Europeans, which effectively leads to this variant being [inaudible 00:17:13] today in Europeans. But not before it increase in frequency during tens of thousands of years Paleolithic.

Dan Pardi - 17:20: Okay, so this plant adaptation enabled this group of people to thrive off of a much more heavy plant based diet because of the frequency of this allele that occurred that enabled the conversion of the short chain to the long chain poly-unsaturated fats that we need.

Alon Keinan - 17:34: Um hmm.

Dan Pardi - 17:35: Was there a simultaneous adaptation that made the heretofore previous diets of hunter gatherer based less healthy for humans, or did it just widen the breadth of what these humans could consume and thrive?

Alon Keinan - 17:46: Um Hmm.

Dan Pardi - 17:46: It not as though now humans were only able to eat a plant based diet but, then maybe that is the case because if you do carry the FADS1 gene, which means that you can convert more the short chain to the long chain, but you're also eating a high meat diet that contains a lot of these long chain fatty acids there could be the problem of too high levels in the body. So, that is a risk.

Alon Keinan - 18:08: Exactly. And that is the theory at least. Once the population has evolved to eat a plant based diet. Having too much meat in your diet can lead to high levels of omega 3 and omega 6 and of course it has implications for specialized diet and so on.

18:23: But even on the population level, I'm not claiming that's the only reason, but to go back to Indian populations people might find it surprising, but the risk of cardiovascular disease in Indian today, especially in the big cities where you now have essentially a McDonald's or similar on every street corner, might be different types of meat but many populations have completely changed their diet.

18:48: What some [inaudible 00:18:50] cardiovascular disease is actually two fold in India than in any other place in the world, including even the US. So everybody thinks that we are eating too much red meat and we as Americans and have a heart attack today as a consequence. So the risk has actually doubled in India and a different way to look at it is that about 50% of the overall global risk and cause of cardiovascular disease is in India. While they are representing about less than quarter of the world's population.

19:19: Now I'm not claiming that's the only reason but definitely if your ancestors have been following almost a purely plant based diet for hundreds of generations and then in the last two generations they've started consuming a very different diet, one of the effects is there's too much omega 6 which has been associated directly with risk of cardiovascular disease with higher cholesterol and so on.

19:43: In fact in Europeans the recent study is and where most Genome Wide Association studies have been, unfortunately, but most Genome Association studies, that's the disassociation of genetic variance with disease, they've been mostly in individuals of, let's say, northwestern European ancestry and mostly US and UK and so on. We see that just the variance that we have seen is under strong selection has been associated, altogether two hundred different associations with forty-five different diseases and traits, including several that we found, and they all work in the direction that you would predict based on knowing if it's the plant based allele or the meat based allele.

20:31: Specifically we see that it's associated with the biosynthesis of frequency by seeing that they are associated with more long chain and lower levels of the petal cells. Now I'm focusing on the plant based variance and the plant based one also says with lower risk of systemic inflammation and cardiac death and we decrease resting [inaudible 00:20:55] which reduced risk of cardiovascular disease with lower levels of tri-glycerides and with lower risk of inflammatory diseases, specifically inflammatory bowel diseases. Crohn's disease and also diverticulitis and so on and so forth and even with a lower risk of bi-polar disorder.

21:12: Now I should mention that these are Gnome Wide Association studies and when I say low-risk these only effect the risk by a fraction of a percent for the most part because these are very complex diseases that they have many risk factors associated with them. But the direction is always the one that makes sense in regards to what we have seen from the evolutionary standpoint. And this is of course in European's that consume today's diet.

Dan Pardi - 21:36: Interpreting this, you can see how the guidance to put somebody on a mostly plant based diet if they have one version of the FAD's gene could be deleterious to their health because they won't be converting it into enough of these primary substances that are needed. And conversely.

21:53: So this then set's the stage for that, instead of generalized dietary guidance, personalized genetic based nutrition programs. And this is a lot of talk about that these days, what do you think about the field. What its promises what are its drawbacks?

Alon Keinan - 22:09: So the drawback first is that there are many people and companies out there that make claims that they can design a personalized diet while few of these are really rooted in any science, since it doesn't require any FDA approvals or such that is pretty wide open for charlatan's. But, at the same time I think it's a very promising field. Because, as I would exemplify first in these results, and it's actually about to be incorporated into a director to consume a Genomics programs. One of the services is that in some cases these types of nurtigenomic insights can lead to recommendations that only require very small changes on the side of the individual and that they can quite reliably and quickly feel whether anything is wrong, or test whether anything is wrong, which is often not the case for complex diseases.

23:02: Somebody, like myself, who carry two copies of the meat based appetite. So of course we all should ideally eat what our ancestors have eaten and the same type of diet, but I do not even hope to be able to interest anybody of changing their diet completely, especially if they are vegetarians or vegan you do specific reasons. So if somebody like that let say wants to be vegetarian then you're right, then they will be exposed of not getting enough omega 3, omega 6, presumably. Then actually one recommendation is that they can still consume directly the long form of omega 3, omega 6 from meat based products like eggs and milk.

23:45: But if you are totally vegan and you are not willing to do even that then there are still a few recommendations that I could make. One of them for instance involves plant based oils. So we consume oils, by the way, that are very unhealthy, that is always a ratio of omega 6 to omega 3 associated with them. I don't know, Canola oil, it's about 16 to 1. Olive oil it's a ratio about 12 to 1. So you would like to lower this ratio and there are some new seed based oils that you can consume, like chia seed and so on. And the thing is that the oil is [inaudible 00:24:24] huge amounts of the seeds, lets say, and still they do not have any of the end product, but even if the biosynthesis is not as efficient, assuming of course it's not shut down completely, which is not the case.

24:37: You consume so much of the petal cells of the starting point fatty acids for the biosynthesis that the body can still produce enough omega 3 and omega 6 and there are some things that most vegan's agree with me that they eat, which is all types of algae for instance. Many of them would eat the vegetarian sushi and they actually do carry long form omega 3 and omega 6, they actually play out the biosynthesis themselves. So that will do it for you. And this is something that even vegans will consume and if they don't it's the simplest thing to add to the diet.

25:18: And impact can be very quick and could also be tested in the blood. They don't measure omega 3, omega 6 in a standard blood test but it can be tested, so it is an available process.

Dan Pardi - 25:30: Yeah, so that was one of my next questions. What can people who are interested in their health do today to try to figure some of this stuff out? It sounds like one thing is to understand if you have copy number and variant you have of the genes. Secondly can you do an assessment of your omega 3 and omega 6 ratio to then try to understand at least what your diet has been like and at least the result of it.

Alon Keinan - 25:52: Okay, so like I said, there is test, which is becoming cheaper and cheaper. It still involves a quite sophisticated technology but standard companies offer the simple test at least of the main forms of omega 3 and omega 6 for something like a hundred bucks so even if the insurance companies don't yet cover it, that's an investment into one's self that might be worth making. Maybe, you might have to insist with your physician to allow you to have one of these tests but it's doable. And you can do of course before and after making a dietary change.

26:22: But even without a test of cells there are something that many vegans find themselves suffering from, some very mild medical issues like re-currant inflammations or these sores in the mouth, which has been associated with B-12 vitamin but, we also know it's a reflective of not having enough omega 3. So if you make one of these small changes to your diet and you quite quickly see improvement in any of these types of symptoms that shows that you are into the right direction and that you have been lacking specifically in omega 3.

Dan Pardi - 26:58: Good. I think you mentioned that there was one genomic test that you felt was valid, that's available today?

Alon Keinan - 27:05: There are two ways of moving this towards [inaudible 00:27:07] it. To practice is ideally would go through the physician office or at least the nutritionist office, but the other route nowadays with direct to consumer type of platforms and specifically one of these platforms have been in touch with us about incorporating these specific results into their platform, such as they can test indeed what types of variance you have, might ask you a couple of questions about your diet, make some very cautionary, for now, recommendation based on that. Because obviously this whole story's part of the effective diet on your well being. It's not just about omega 3 and omega 6, even though they are important components.

27:48: I think in the grand scheme and talking about specialized diet in Nutrigenomics, I think that the main thing to take from this study is just how important overall diet has played in our evolution. And changes in diet instantaneously change the way that selection is involved. It's inescapable that our diet today is interacting with our genetic in the way that it affects our well being. And we are just starting to figure out this interaction. This is one result. We have a couple of other results in this realm as well. And for now we can make some recommendations, but we still have to be taken with at least moderate pinch of salt.

Dan Pardi - 28:27: Well, thank you for coming on to HumanOS radio, describing the research that you do, your recent study, the implications of your findings, the state of personalized nutrition or nutrigenomics and some of the possibilities that this field will yield to help us have better information on ourself to guide our health behavior towards optimal outcomes. So, appreciate the work you do and for spending the time with us.

Alon Keinan - 28:55: Thanks very much and thanks for having me then.

Kendall Kendrick - 29:01: Thanks for listening and come visit us soon at HumanOS.me