NPC1L1 and Ketone Diarrhea

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
SarahB
Contributor
Contributor
Posts: 20
Joined: Wed Apr 24, 2019 3:02 pm

NPC1L1 and Ketone Diarrhea

Postby SarahB » Wed Jun 12, 2019 4:15 am

Okay - just throwing out hypotheses here. NPC1L1 is a gene that codes for an intestinal cholesterol transporter. Multiple variations in NPC1L1 have been reported that vary in their efficacy, such that some people with mutant NPC1L1 transport cholesterol poorly. These people have low serum cholesterol and a lower risk of cardiovascular disease.

Naturally, this gene has been targeted by drug companies. The drug Ezetimibe blocks the NPC1L1 receptor. A side effect of ezetimibe is sudden severe bursts of diarrhea, all that unabsorbed cholesterol shooting out the other side. Some of us have a similar reaction to a ketone diet. The episodes of keto-diarrhea are intermittent and do not seem to clear with time.

I suggest that the high cholesterol on a ketone diet is a problem for some people with a low uptake variant of NPC1L1, hence the reason some people get diarrhea on a ketone diet. The occasional high cholesterol meal triggers a bout of nasty diarrhea as the cholesterol passes through. It is also possible that one's microbiome normally clears up a lot of the excess cholesterol in poor absorbers. The low carb starvation of the microbiome along with a low amount of fiber makes the situation worse. A similar scenario could apply to other lipid molecules with special transporters, if those special transporters were also subject to variation in efficacy.

I came up with this theory, because in addition to ketone diarrhea, I also have a low serum LDL. In fact, I have to work to get my LDL up into the normal range, despite having a crap lipid transport situation internally. I should have cholesterol problems, but I do not. I have even worried about the actuarial consequences of low LDL.

So...I'm just saying. Wish I could figure out the snps to see if I have a variant, but the naming is too variable between 23andMe and the relevant papers. Anybody out there a scientist?

User avatar
CarrieS
Support Team
Support Team
Posts: 402
Joined: Thu Jun 22, 2017 12:21 pm

Re: NPC1L1 and Ketone Diarrhea

Postby CarrieS » Wed Jun 12, 2019 8:00 am

SarahB wrote:So...I'm just saying. Wish I could figure out the snps to see if I have a variant, but the naming is too variable between 23andMe and the relevant papers. Anybody out there a scientist?

Hi SarahB,
I'm wondering if running your genetic report through an engine like StrateGene (Dr. Ben Lynch) http://go.strategene.org/genetic-analysis/ or Found My Fitness https://www.foundmyfitness.com/genetics (Dr. Rhonda Patrick) might provide you with some of the insights you are seeking. No guarantees, just a thought.
APOe4/4
Functional Medicine Certified Health Coach
National Board Certified Health & Wellness Coach
Certificate for Reversing Cognitive Decline for Coaches (FMCA)
Certified Fermentationist

BrianR
Senior Contributor
Senior Contributor
Posts: 206
Joined: Tue Oct 02, 2018 12:32 pm
Location: Southeastern Michigan

Re: NPC1L1 and Ketone Diarrhea

Postby BrianR » Wed Jun 12, 2019 4:06 pm

SarahB wrote:So...I'm just saying. Wish I could figure out the snps to see if I have a variant, but the naming is too variable between 23andMe and the relevant papers. Anybody out there a scientist?

Sarah, you could search snpedia, e.g.: https://www.snpedia.com/index.php/NPC1L1, note that not all the SNPs listed in the lower right seem to have research information.

When I search for NPC1L1 in my promethease report, I see the following SNPs rs217434, rs17655652, rs2072183, rs52815063 - none of which seems particularly interesting, but at least some of those pages have studies cited.

User avatar
floramaria
Support Team
Support Team
Posts: 811
Joined: Tue Jul 04, 2017 11:22 am
Location: Northern New Mexico

Re: NPC1L1 and Ketone Diarrhea

Postby floramaria » Thu Jun 13, 2019 12:06 pm

SarahB wrote: The low carb starvation of the microbiome along with a low amount of fiber makes the situation worse.


Hi SarahB,

Your whole post is very interesting but I am going to respond to just this element, your comment regarding the microbiome.
Safeguarding a healthy microbiome is a challenge in a traditional paleo-ketogenic diet, but the microbiome does not need to be starved in low carb ketogenic diet as long as it includes a large quantity and wide variety of vegetables . This also creates a high fiber intake. I checked this out with a microbiologist after hearing him say in a webinar that a high fat diet is bad for the microbiome. My understanding is that a healthy microbiome is crucial for overall good health, so I was upset. In my message to him, I told him that as a carier of the ApoE4 allele, I am eating a plant based ketogenic diet to support my brain health, but hoped I did not have to choose between my brain and my microbiome. My lunch salad that day had 18 different botanicals.
His response, was that he had never heard of someone eating a lot of vegetables while being on a ketogenic diet. He said that his comment about the high fat diet being damaging to the microbiome was based on the assumption that it was a meat based diet since his experience with keto has been with people who severely limit vegetable intake and thereby do in fact starve their microbiomes.
Functional Medicine Certified Health Coach
IFM/ Bredesen Training in Reversing Cognitive Decline (March 2017)

thjj
Contributor
Contributor
Posts: 86
Joined: Thu Nov 15, 2018 7:48 pm

Re: NPC1L1 and Ketone Diarrhea

Postby thjj » Thu Jun 27, 2019 10:49 pm

I just ordered ox bile. Hopefully it will help with my digestion of fats and cholesterol. There is a theory that poor digestion of fats may cause the keto rash.
· • She/her · • ·
ApoE4/4 status known: 2018 | Born: 1969 | Cognitive Impairment: none

thjj
Contributor
Contributor
Posts: 86
Joined: Thu Nov 15, 2018 7:48 pm

Re: NPC1L1 and Ketone Diarrhea

Postby thjj » Mon Jul 08, 2019 10:07 pm

update on the ox bile―I've taken it for about a week & I don't notice any difference.
· • She/her · • ·
ApoE4/4 status known: 2018 | Born: 1969 | Cognitive Impairment: none

thjj
Contributor
Contributor
Posts: 86
Joined: Thu Nov 15, 2018 7:48 pm

Re: NPC1L1 and Ketone Diarrhea

Postby thjj » Mon Jul 08, 2019 10:29 pm

...I also started taking Activated Charcoal, and although it's not helping w the actual keto rash, it appears to help with the itching. It works as an Adsorbent (unwanted proteins bind to it and they're whisked away out of the digestive tract, so to speak).
· • She/her · • ·
ApoE4/4 status known: 2018 | Born: 1969 | Cognitive Impairment: none


Return to “Science and Research”

Who is online

Users browsing this forum: No registered users and 14 guests