Personalize Your Nutrition Based On Genetics

Dr. Rhonda Patrick here. Today we're going to discuss a few consumer-available tools that allow you to learn a little bit more about your genes and also how specific nutrients interact with your genes. This field of study is known as nutrigenomics. In addition, we're going to look at how this affects metabolism and how you age in general. We'll also be discussing a few specific gene polymorphisms that can be readily genotyped, including MTHFR, FADS2, FUT2, APOE, FOXO3, and more. The first step is a relatively inexpensive $99 23andMe test. You may be thinking to yourself, wait a minute, I thought 23andMe stopped generating health reports. You'd be correct, they did. However, they still give you the raw data, and this can still be very useful.

The second step is a tool that's $5 called Promethease. Promethease will take your 23andMe raw data and match it to a very large database consisting of over 57,000 published single nucleotide polymorphisms. It'll then tell you what diseases you may be predisposed to, as well as how different micronutrients may, may have different absorptions and bioavailabilities, et cetera. My goal here is to discuss some of the more meaningful of the 57,000 gene polymorphisms, particularly those that may be influenced by modest dietary and lifestyle changes. For my own life, I've already found this information to be particularly useful. and helping me and my family lower some of our disease risk to diseases that we may have been otherwise predisposed to.

But before we get started, I want to cover a few of the basics, like what are gene polymorphisms? Gene polymorphisms are variations in the sequence of DNA of a gene that alters the function in a gene, either in a good or a bad way. This is very different from mutations, which occur randomly, because gene polymorphisms occur in a sizable percentage of the population, and they're thought to have been selected for, for a reason. Gene polymorphisms can lead to diseases like Alzheimer's disease, and also can lead to different phenotypes like eye color. For every gene that you have, you have 2 copies of it, one from mom and one from dad. These are called alleles.

In fact, if you were to look at your 23andMe raw data, you would see 2 letters which correspond to DNA nucleotides for that gene, one from mom and one from dad. In some cases, maybe only one of your parents has a specific gene polymorphism, and they pass that on to you. In that case, you would be heterozygous for that gene polymorphism, which may or may not have any measurable effect. In other cases, maybe both of your parents have a specific gene polymorphism which they pass on to you. In that case, you would be homozygous for that gene polymorphism, and that does have a measurable effect. Now that we have all the basics out of the way, let's dive into a few of the genes of interest today.

The first gene polymorphism that I want to discuss isn't actually a gene polymorphism, it's a cluster of gene polymorphisms in the folate metabolism pathway. Folate, or vitamin B9, serves 2 very important functions. First, it serves as a precursor for the DNA nucleotide thymine, which means it's essential to make all new cells in the body, whether we're talking about new gut cells or new brain cells. The second important function is folate serves as a precursor to methyl groups, which are important for turning genes on or turning genes off. Most of the time, they're important for turning genes off. And this is known as epigenetics.

This specific cluster of polymorphisms are associated with the gene 5'-10'-methylenetetrahydrofolate reductase, also known as MTHFR, and is associated with the reduced capacity to convert 5'-10'-methylenetetrahydrofolate into 5-methylfolate. 5-methylfolate plays a very important role for making those methyl groups that turn genes off and turn genes on. In addition, it also reconverts homocysteine into the amino acid methionine. This means that while people with these gene polymorphisms are able to make the DNA nucleotide thymine, they aren't able to efficiently convert dietary folate or supplemental folic acid into 5-methylfolate.

For this reason, it's often associated with higher levels of homocysteine, which have also been associated with a whole host of vascular diseases, including coronary artery disease, stroke, and vascular dementia. Due to one or more combination of these polymorphisms in the MTHFR gene, approximately 40% of the population has 40% reduced functional efficiency of MTHFR enzyme. Approximately 20% of the population has a 70% reduction in functional efficiency of the enzyme, and approximately 10% of the population has between an 80 to 90% reduction in functional efficiency of the MTHFR enzyme.

Despite the fact that there are a large percentage of the population has one or more of the combinations of this gene polymorphism, studies have shown that supplementing with 5-methyltetrahydrofolate and methylcobalamin Vitamin B12 can successfully circumvent some of the shortcomings of these gene polymorphisms and lower homocysteine levels. Another common gene polymorphism affecting approximately 46% of the population is in the NBPF3 gene, and this affects vitamin B6 levels. People with this gene polymorphism have slightly lower vitamin B6 levels and may require that people increase their dietary intake of B6 and/or also supplement with vitamin B6. Since we're talking about B vitamins, another gene polymorphism in the FUT2 gene affects the way vitamin B12 is absorbed in the intestines.

People with this specific gene polymorphism need to take a sublingual vitamin B12 to ensure that they're getting enough vitamin B12. Let's move on to vitamin A, also known as retinol. We can convert carotenoids such as beta-carotene into provitamin A, also known as retinal. However, there are a cluster of gene polymorphisms associated with the BCMO1 gene that affect the ability of our gut cells to convert beta-carotene into retinal and reduce its ability between 30 to 70%. In fact, around 42% of the population has one gene polymorphism associated with this reduced efficiency, and approximately 24% of the population has another polymorphism also associated with reduced efficiency.

People that have this, these cluster of gene polymorphisms in the BCMO1 gene can increase their dietary intake of animal products, which are high in vitamin A, or can supplement with the active form of vitamin A, not beta-carotene. But be careful not to take too much vitamin A as it can be toxic at high doses. How about those omega-3 fatty acids? There are common gene polymorphisms in the delta desaturase gene, FADS, that affect the ability to convert the plant omega-3 fatty acid alpha-linolenic acid, ALA, into eicosapentaenoic acid, EPA, which is often found in marine sources. This polymorphism can either increase or decrease the efficiency to convert ALA into EPA.

Because this conversion efficiency is already so low, having the polymorphism that decreases efficiency even further is not a good thing and may affect how much fish people consume as well as what you supplement with. This is particularly relevant for vegetarians that often take ALA as their primary source of omega-3 fatty acids and may want to consider supplementing with another option such as microalgae oil, which has more EPA and DHA and doesn't rely on having to convert it from ALA. Let's move on to one of my personal favorites, vitamin D. There are a couple of common polymorphisms in the CYP2R1 gene, which encodes for the vitamin D 25-hydroxylase, the enzyme that is responsible for converting vitamin D3 into 25-hydroxyvitamin D, which is the major circulating form of vitamin D, which goes on to be converted into the active steroid hormone.

People with these specific polymorphisms have a lower circulating 25-hydroxyvitamin D level and also have reduced enzymatic activity of the 25-hydroxylase. This has been associated with a higher all-cause mortality. Other studies have shown that people that have serum levels of 25-hydroxyvitamin D between 40 and 60 nanograms per milliliter have the lowest all-cause mortality and also have the longest telomere length. It's generally known that supplementing with around 1,000 IUs of vitamin D3 a day can raise serum 25-hydroxy vitamin D levels by around 5 nanograms per milliliter. This may not be the case for people with these gene polymorphisms, and other lifestyle factors may also play a role. What about choline?

Choline also is a very important precursor, much like folate, to make methyl groups, which turn genes Off or on? Well, we can make choline from phosphatidylcholine. However, 44% of women have a gene polymorphism in the PEMT gene, which does not allow them to make choline from phosphatidylcholine. This specific polymorphism does not respond to estrogen, which is known to activate the PEMT gene. For this reason, women with this polymorphism have to increase their dietary intake of choline. Egg yolk is a great source of choline. Let's move on to ApoE.

There are a series of polymorphisms that make 4 different forms of ApoE, which encodes a lipoprotein that's made in the liver, which binds to cholesterol, transports the cholesterol throughout the bloodstream, brings it to tissues, and recycles it back to the liver. It's also made in the astrocytes of the brain, where it transports fatty acids and cholesterol to neurons. Approximately 25% of the population have a specific form of ApoE called ApoE4. which is associated with higher circulating levels of LDL and also is associated with a 2 to 3-fold increased risk for Alzheimer's disease. I'm currently researching ApoE biology, both in the brain and in the liver, and I'm writing a paper on it right now for publication.

I will be covering this topic in depth and comprehensively in a future video. And last but not least, let's talk about the longevity gene FOXO3. FOXO3 is associated with longevity for several reasons. Flies and worms that have an equivalent of FOXO3, or the homolog, have a 100% increase in lifespan. So worms go from living 15 days to 30 days. Mice that have the equivalent of FOXO3 experience a 30% increase in lifespan. And humans that have polymorphisms associated with making more FOXO3 have an increased chance of living to be 100 or being a centenarian. The reason FOXO3 is associated with longevity is because it turns on a whole host of genes that make you more resilient to stress. It turns on antioxidant genes. It turns on genes that repair DNA damage.

It turns on genes that kill tumor cells, and it turns on genes that make sure proteins don't aggregate and clump inside of your cells. To sum it up, having more FOXO3 is pretty awesome. if you're lucky. In summary, knowing which gene polymorphisms you have is very useful, and that's why tools like 23andMe and Promethease are a great combination. Having this knowledge allows you to tailor your diet and lifestyle to your own genes and to optimize your micronutrient and macronutrient intake such that you may extend your lifespan when applicable. I'm Dr. Rhonda Patrick, and I'll catch you next time.