Ketosis and PPAR alpha rs1800206(C;G)

[vegarejuvinated]

Hi All,

I have been lurking and reading for a few weeks but this is my first post. So first a big thank you for all of the rich content on this site. A quick bit of background on me. i accidently found out i have two versions of the APOE4 alelle when i did a 23 and me test to try and get some insight into my autoimmune/gut/fatigue issues that i am being treated for by a functional medicine doctor. It wasnt what i was expecting to find but there we are and my attitude is that i would rather know so i can act now.

I have been experimenting with a ketogenic diet since Feb this year and during the times i have succeeded i have quite frankly felt amazing, like I have taken the pill that Bradly Cooper took in Limitless. However its been really hard for me to achieve and maintain ketosis and even after 3/4 day water fasts im only getting low ketone readings (6-8 green flashes on my ketonix breath meter).

In my 23 and me results i also found out that i have a PPAR polymorphism that means i have a problem with fat metabolism and im wondering a few things.

Is this why im finding it difficult to achieve and maintain ketosis?
Should i give up on this idea of ketosis aS I have read its not recommended for this PPAR polymorphism?
Should i try taking a PPAR agonist and if so which one?

I would greatly appreciate any help advice or pointers to more reading. THANK YOU

https://selfhacked.com/blog/about-ppar- ... tivate-it/

[Sara]

Greetings vegarejuvinated and welcome to the apoe4.info website. Congratulations on making so many healthy changes and for already finding and working with a functional medicine doctor. I will leave your question to our more clinically oriented members but just wanted to welcome you and point you in the direction of our primer, viewtopic.php?f=33&t=1418, which contains some excellent information about nutrition, exercise, stress management, sleep and then some. Wishing you the very best on your journey! Sara

[cdamaden]

Hi vegarejuvinated,
I too have the same SNP: rs1800206(C;G). I am mildly ketogenic by eating a 60-70% fat, 15-20% protein, and 15-20% carbs. I can't explain why you aren't in full ketosis but I recall reading other posters (Tincup?) that the breath meter is not a reliable means of determining whether you're in ketosis or not. Take a look at this posting by Theresa:
viewtopic.php?f=16&t=3790&p=44998&hilit ... ath#p44998
Have you explored the use of blood test instead?

As to the impact of the SNP, I ran my raw numbers through Dr. Rhonda Patrick's Genome Analysis Tool
https://www.foundmyfitness.com/genetics
and this is what her report has for this SNP:
This genotype (C;G) has been associated with a lower PPAR-alpha activity and may cause these individuals to have a 2-fold higher risk of type 2 diabetes, increased levels of triglycerides, total cholesterol, LDL cholesterol, small-dense LDL particles, apolipoprotein B, and increased risk for non- fatal heart attack particularly when saturated fat intake is higher than polyunsaturated fat (PUFA) intake. The negative effects on triglycerides, lipids, and cholesterol are more pronounced in men compared to women.

There is a significant gene-diet interaction between carriers of the G allele (such as this genotype) and dietary fat. Those individuals carrying a G allele have greater plasma concentrations of triglycerides and apoC3 when consuming a diet low in PUFAs (<6% of energy), whereas when PUFA intake was high, carriers of the G allele had lower triglycerides and apoC3. Additionally, carriers of the G allele had an increased amount of small, dense LDL particles (a risk factor for cardiovascular disease) when saturated fat intake was high compared to those with a lower saturated fat intake.

These data suggest that carriers of the G allele may have improved triglycerides and cholesterol when saturated fat intake is lower and polyunsaturated fat intake is higher. Polyunsaturated fats are found in foods like fatty fish such as salmon, herring, and polyunsaturated fat is also found in nuts. Saturated fat is found in fatty beef, pork, coconut oil, butter, cheese, and other dairy products.

Since this gene is activated by PUFAs and plays a major role in lipid metabolism including fat oxidation, a ketogenic diet that is high in saturated fat and low in polyunsaturated fats may be detrimental to health.(emphasis added) It may be best to make sure that the majority of dietary fat intake has a higher polyunsaturated fat to saturated fat ratio.

The way I read this is that I can have a ketogenic diet but I need to eat more PUFAs (keeping a good Omega 3 to Omega 6 balance) than saturated fats. My biggest challenge is that I like to keep liver products in my diet because of its micronutrient profile.

I'm keen on learning more about this SNP, so please post anything you learn or contact me directly.
Regards,
Chris

[pharmacydoc]

Thanks for the info! After I read your post, I looked up the gene on my Promethease report. Interestingly, I am homozygous for rs4253778(G;G). Some of the pieces are starting to come together now.

In trying to get into ketosis, I was eating high amounts of saturated fat and coconut oil. However, my recent Cardio IQ showed LDL particle number of 1946, LDL small of 267, and LDL medium of 355. These numbers frankly frightened me! I have cut out the coconut oil completely and cut the animal protein to 2-3 servings per week.

I am almost never in ketosis even though my only carbs are 1/2 cup of berries, 1 small apple, and sometimes 2 cups of beans in a day. I have a sensitivity to nuts and need to eat something for protein. In fact, I have just given up on the ketosis because it doesn't seem to work for me.

[KatieS]

Thanks for the info! After I read your post, I looked up the gene on my Promethease report. Interestingly, I am homozygous for rs4253778(G;G). Some of the pieces are starting to come together now.

In trying to get into ketosis, I was eating high amounts of saturated fat and coconut oil. However, my recent Cardio IQ showed LDL particle number of 1946, LDL small of 267, and LDL medium of 355. These numbers frankly frightened me! I have cut out the coconut oil completely and cut the animal protein to 2-3 servings per week.

I am almost never in ketosis even though my only carbs are 1/2 cup of berries, 1 small apple, and sometimes 2 cups of beans in a day. I have a sensitivity to nuts and need to eat something for protein. In fact, I have just given up on the ketosis because it doesn't seem to work for me.

Like you I had to cut the coconut oil and milk out entirely. What are you using to test for ketosis? Although I'm a CC, I seem to never register much on my Mojo ketone meter, but have repeatedly tested moderate on the urine ketone sticks.

[pharmacydoc]

I just use the urine ketone sticks because I don't need an accurate reading. But, even then, I'm rarely in ketosis. I can sometimes see a moderate ketosis when I take a tablespoonful of MCT oil, but not always.

[vegarejuvinated]

I have just bought myself a keto mojo meter so that I can test my blood ketones and I'm going to begin with a three day fast so that I can be sure that I am in ketosis. My plan is to experiment with a lot less animal and coconut fats and test regularly over a couple of weeks to see what happens. I haven't had a detailed cholesterol test so I actually don't know what the impact of my high fat diet is my stats but I will ask my doctor to run the test when I see her in January.

I have been following the Whals protocol to address my auto immune condition which is very high in coconut fat and I have been consuming a couple of tablespoons of brain octane oil every day. I've also started experimenting with a supplement called TTA and r-alpha lipoic acid as they are both supposed to be PPAR agonists. I'm not really clear on how I will assess if they are effective though.... I guess I should see higher readings on my ketone meter. I'll post back with the self experimentation results.

[vegarejuvinated]

Here is a bit of reading I found from someone who posted on Reddit

https://www.google.com.au/amp/s/amp.red ... my_weight/

[cdamaden]

Please keep us posted on how the keto mojo compares to your other ketone measurements.


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[viaswiss]

I also have the PPAR-a polymorphism and it makes me wonder if intermittant fasting or ketosis is worth it. I've had some but not great luck with it in the past.. I was also using lots of saturatedfats at the time. Currently I am just making sure to get 4-5 grams of Fish Oil daily which is supposed to help activate the PPAR-a gene. The reddit post above also has good info but I have not tried those supplements.

Currently I am just making sure to eat only slow digesting carbs and take my fish oil and olive oil, its what seems to work best for me at least body composition wise. I plan to follow this thread though to figure out what is best for us.