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#06 – The latest science on MTHFR, dosing B vitamin supplements, APOE4 and more with Dr. Aaron Gardner

MTHFR is a gene that has generated a ton of interest in the health and wellness world, but many remain skeptical. A few years ago at SXSW in Austin I was practically laughed out of the room for asking a question about MTHFR to a panel of genetics experts. However, what are common mutations in these genes have been blamed on everything from autism to breast cancer to heart disease, but is there good science to back up these claims? We brought back Gene Food’s resident geneticist, Dr. Aaron Gardner to go over the latest research on MTHFR. We cover the lab tests that can help determine how well MTHFR and other methylation genes are functioning, ideal dosing for B vitamins, other genes that impact the methylation cycle and why an amino acid metabolite called homocysteine is a problem for many with MTHFR SNPs. The episode also touches on other genetic markers such as APOE4 and whether a high fat diet is a good idea for carriers of this much-discussed genetic marker. At the end of the show, we get into omega-3 fatty acid metabolism and the histamine genes.

Listen on Google Play Music


This Episode Covers:

  • Basics of MTHFR [7:45];
  • MTHFR, lab tests and homocysteine [12:00];
  • B vitamin supplements, methylation and dosing [18:00];
  • CBS genes and other genes that impact methylation [27:46];
  • APOE4 and high fat diets [40:00];
  • FADS1, omega-3 fatty acid metabolism and DHA deficiency in Vegans [49:49];
  • Dangers of vegetable oil [1:00];

Discussion and Show Notes:

We’ve gotten into the basics of MTHFR in a number of blog posts:

And of course, we have the dedicated MTHFR page listed in our Guide to Nutrigenomics.

We touched on in the show, but providers like 23andme have taken a position that is “anti-MTHFR.”

One of the tips we give in the show to determine whether MTHFR and other methylation SNPs are “working” is to have homocysteine tested. This blog post also gives 7 genes linked to high homocysteine and how to lower that metric.

Boston Heart and Cleveland Heart Labs definitely test for homocysteine.

This is the blog post we referenced listing the various studies that looked at increased cancer risk when supplementing with B vitamins. This post also contains Aaron’s chart: B vitamins and cancer risk: what you need to know

Spectra Cell is a lab I mentioned that offers micro-nutrient testing.

MTRRone of the methylation genes Aaron mentions in the show.

CBS genes and sulfur metabolism. Here is a blog post I wrote on the CBS genes as well as our CBS gene page.

This is the Pure B vitamin product I discussed on the podcast with fairly conservative dosing of the various B vitamins. The good news is the product comes in capsule form and therefore it’s easy to adjust dosing.

As we get into APOE4, it may be helpful for some to take a look at our first podcast episode covering Ketogenic diets. Aaron references some promising studies in mice looking at ketogenic diets and APOE4. Those studies can be found here and here.

We also wrote this blog post titled Can a ketogenic diet prevent Alzheimer’s in APOE4 carriers?

As we go through the APOE4 discussion, I mention the “Retterstol study.” Here is a link. Retterstol is important because it shows wild differences in lipids when different people go on a high fat diet.

The discussion of Vegan diets and omega-3 fatty acid metabolism centers around FADS1 and this paper, which highlights the major differences in PUFA metabolism based on genetic variants and how minority populations are more likely to convert more omega-g fats into inflammatory bi-products like arachidonic acid.

Here is a link to the Nutrition Facts video recommending an algal oil supplement for Vegans.

I mentioned a study that looked at men with low EPA/DHA and how feeding them a diet high in plant sources of omega-3 actually caused DHA to go down. Here is the study.

These Algal oil brands are made with sunflower oil! what?

Here is a post I wrote titled Why I don’t eat vegetable oil.

And here is the NEJM study on Lp(a) which shows that Lp(a) binds preferentially to oxidized phospholipids.

I have been using the Cronometer app lately to track both macros and micronutrient intake.

AOC1 genes or as we called them, the “histamine genes.”

Zonulin and histamine – is there a link?

John O'Connor

John O'Connor is the founder of Gene Food. He is passionate about nutrition, genetics, and wellness and uses this blog to publish self experiments as well as some of the research that the Gene Food team does internally to highlight stories of bio-individuality.

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  1. Angela Rooney says:

    I was wondering if a whole food IF eating plan, as opposed to ketogenic diet with or without fasting is a good plan to ward off, or assist in cognitive decline. And it’s relationship to the APO 3&4 genes. Also it’s relationship to mthfr c677t snps

  2. Markus says:

    I’ve been into this field of health for more than 10 years and have seen many trends come and go. During this time, I’ve done a couple of stupid mistakes, but have learned many valuable lessons along the way. Specifically, the years of high-fat paleo didn’t go well with my APOE4/4-genotype.

    With that said, I truly believe that the future of health lies in developing a better understanding of the interaction between our genetics and the environment around us. For instance, being homozygous FADS1 would’ve been very beneficial in the past, but in the modern world with the ubiquitous use of vegetable oil, it can be very detrimental if one isn’t careful about eating out and avoiding processed food in general.

    Btw, regarding methylation and MTHFR, you should have Chris Masterjohn on the podcast.

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