Eggs DO NOT Increase Cholesterol: NEW Mechanism!

Paper: www.cell.com/cell/pdf/S0092-8...
Some people were wondering about human RCTs on egg intake and cholesterol. This is from the most recent (n = 140) RCT, showing no impact of egg intake on LDL cholesterol: “Changes in HDL- and LDL levels were similar for Fortified Egg (FE) compared with Non-Egg (NE). Subgroup analyses revealed increased HDL and decreased LDL in patients ≥65 years for FE compared with NE, though not statistically significant.” www.jacc.org/doi/10.1016/S073...
Prior video on manipulating LDL levels on a ketogenic diet: • How to LOWER LDL on Ke...
Thumbnail created using meal photo from @ZackStrength on Twitter, with permission.
Chapters
0:00 - Intro, Cholesin
1:00 - Cholesterol Inhibitor Mechanism
3:36 - Relevance in humans
4:36 - Medications and Mechanism
8:01 - Disclaimer
#RxMetabolism University Project
I hope you’re all appreciating the improvement in my channels’ production quality. My earlier videos were all recorded on an iPhone, with minimal editing, and I have since transitioned to 4K filming on a Sony alpha 6700 camera, coupled with crisp audio on Rode microphones and topped off with outsourced professional video editing.
These improvements in your educational experience would not be possible without the extremely generous support of RxSugar (rxsugar.com, discount code NICK20), and company CEO Steve Hanley. I am NOT paid to explicitly promote their product, NOR given profits on sales, NOR otherwise incentivized to try to exploit you for my own gain. No, this is a different!
My friend Steve, and by extension his company, are devoted to promoting population metabolic health, as a mission I share! To that end, WE feel compelled to provide free education on metabolic health you all of you via KZbin. I do my part by generating video content, but I require support, especially as a busy PhD and MD trainee. (I’m not a career influencer). To amplify the message and enhance the lessons, Steve and RxSugar are supporting video editing fees.
Perhaps this will build brand trust and in that way work into the business model? Or maybe not. But I share this with you in the spirit of openness and transparency. And if you can believe me, I feel the strength of our movement comes from the fact that all of us, from me to Steve to you, are bonded by a deep desire and passion to Make Metabolic Health Mainstream!
For more on the science of allulose, see this video: • Allulose: Healthiest S...

[@tlewis5901]

Dr. Nick one of the MOST helpful 10 minutes on Cholesterol ever. Thanks this was great

[@nicknorwitzPhD]

You're very welcome! But you could have called it "egg-cellent" ;)

[@jamesalles139]

@@nicknorwitzPhD I see what you did there LoL thanks

[@nicknorwitzPhD]

@@jamesalles139 And I'm glad the video didn't "scramble" your brain, nor do you feel I'm the "deviled" for implying eggs are healthy... although I know some extremists who probably want to "poach" me for my positive position on eggs. They can "fry" but they will finds it's "hard" (boiled) to take me (sunny side) down...

[@jamesalles139]

@@nicknorwitzPhD 🥚An egg a day keeps the doctor away, but that might have been a bit egg-cessive. 😜

[@cyberfunk3793]

@@nicknorwitzPhD Isn't this all very well known already? There is an adaptation but it can't actually compensate for the dietary cholesterol consumed, so indeed eating eggs raises cholesterol in subjects with healthy LDL baseline. The studies (sometimes funded by lobbies) that seem to show no raised levels are done on people with already elevated cholesterol, where they are replacing something else with the eggs. If you gave vegans the eggs, the difference would be much clearer. ""Association between Egg Consumption and Cholesterol Concentration: A Systematic Review and Meta-Analysis of Randomized Controlled Trials": "Based on available evidence, this is the largest meta-analysis in exploring the impact of egg consumption on LDL-c/HDL-c ratio among healthy subjects and reveals that more eggs consumed per day may influence cardiovascular disease risks by increasing LDL-c and the LDL-c/HDL-c ratio. Notably, longer-term high egg-consumption may lead to higher LDL-c/HDL-c ratio and LDL-c. However, RCTs with long tern follow-up are needed to guarantee the association between egg consumption and human health"

[@wendycarter5718]

I eat 4 eggs (cooked in butter) for breakfast and 6 eggs (cooked in butter) in the evening !! Done it for years , feeling great at 76 years old !😊

[@robertobiagio8226]

Hi Nic, thank you for bringing this to our attention! I have been following your channel because you are a disruptor and lateral thinker - more of you in this world! I am a clinical physiologist and have been in private medical practice for over 40 years. Yes, way past my sell by date! I know that our clinical colleagues have no clue about basic physiology/biochemistry and how to interrogate published literature. They accept any finding in a peer reviewed study without asking “stupid” questions! “Western” Medicine is in a mess because of my generation of “learned” clinicians. I realise though, we are now in the terminal phase of this cycle because a new generation, like you, are not accepting any garbage dished up by biased scientists, clinicians and big pharma. With the help of all the new technology, of which I cannot keep up, I am of the opinion that the ills of the last 50 odd years will be corrected. Please continue on your present path because you are rocking the boat which is desperately needed. You will knock heads with the professors/deans of my generation but do not flinch - I hold them accountable for the mess our medical science is in. They are the watch dogs but have totally failed us. But the future is bright with people like you and your generational colleagues.

[@nicknorwitzPhD]

Love THIS: "we are now in the terminal phase of this cycle because a new generation"... I hope you're right!?

[@dennisward43]

@@nicknorwitzPhD It's all about getting the message out to more people until the truth that science counts for much more than scientific consensus reaches a tipping point. Keep up the good work.

[@user-el4xs2yb6d]

" I am of the opinion that the ills of the last 50 + years will be corrected". You are a sanguine soul! Big food, big pharma, big agri have heavily invented in the food pyramid with the ADA, AHA and the government on board. It is the food pyramid that's killing people. Will they allow all the $$$ investment headed to drains?

[@terriem3922]

Yes, how many people have suffered health problems because of lack of knowledge? I am going back to eating eggs from happy chickens. They are expensive eggs, but the guilt and karma from eating eggs from hens suffering affects me.

[@user-el4xs2yb6d]

@@terriem3922 "The karma from eating eggs affects me". Did you know that more than a few dozen plants eat animals? Please search KZbin for "plants that eat animals" Some plants even eat tiny monkeys. Did you ask the plant if it knows karma?

[@anomarnamloh7444]

Interesting. A KZbin content creater just released a video on, What Happens if you eat 4 eggs a day. The study you referenced wasn't mentioned but I love when folks are on the same wavelength. The creator is Sten Ekberg a former decathelete and noe a Chiropractor

[@LowHangingFruitForest]

I love Sten, but he spends an hour telling you sobering her could in 18 minutes and I don’t have time for that. He talks slow and repeats himself constantly.

[@anomarnamloh7444]

@KidAnarky11631 some of us who are not too bright or scientifically or medically trained need that slow deliberate pace. You can always go into the video's settings and increase the speed.

[@PardieDiem]

I just watched it!

[@carolj.3175]

Thanks, my Dr fixates on cholesterol which I don't think is bad at 278 overall. Least he wants me on is ZETIA. Seems counter to me?

[@kenadams5504]

​@@carolj.3175If you exercise ,you could eat a sweet potatoe each day for less ldl , and it will not affect your ketogenesis very much.

[@upduhwhazoo6438]

Good editing. Great pacing. You got this channel dialed in. You explain complex things so we can better navigate our health journeys. You are not telling me what to do - instead, you add clarity. Perfect.

[@nicknorwitzPhD]

Thanks! That's what I aim to do!

[@davidgrimes4726]

If only humans could learn from the hubris of this whole egg episode that it took 60+ years to understand the mechanism of cholesterol homeostasis. Yet very firm guidelines were introduced by the AHA around egg consumption (

[@nicknorwitzPhD]

Don't blame young Dr. Nick... I'm not responsible for mistakes made 3 decades prior to my birth ;) ... since my mom was burn in 1965, I suppose the "egg" of me was ~3 then... ;)

[@cyberfunk3793]

There is no revalations here. It's been know for a while that body can compensate for dietary cholesterol partly, but it's also known that this mechanism is nowhere near adequate enough to compensate fully for it and even modest amounts of for example eggs raise LDL in people who start at low healthy levels. "Based on available evidence, this is the largest meta-analysis in exploring the impact of egg consumption on LDL-c/HDL-c ratio among healthy subjects and reveals that more eggs consumed per day may influence cardiovascular disease risks by increasing LDL-c and the LDL-c/HDL-c ratio. Notably, longer-term high egg-consumption may lead to higher LDL-c/HDL-c ratio and LDL-c. However, RCTs with long tern follow-up are needed to guarantee the association between egg consumption and human health"

[@Bashkir097]

Fascinating! Thank you, I love a paper like this with my morning tea.

[@nicknorwitzPhD]

Yes! Me too!

[@PudgyCurmudgeon]

That was "eggcellent"! Thanks!

[@nicknorwitzPhD]

Glad it didn’t scramble your brain

[@frankenz66]

​@@nicknorwitzPhDToo late, my brain is already scrambled, but I try to keep a "sunny side up" attitude. 😂

[@nicknorwitzPhD]

@@frankenz66 lol

[@tammyellison735]

Fascinating, my husband is an Osteopathic physician who believes the body tries to find homeostasis. This is why many fads don't work like changing your Ph through diet

[@btudrus]

This even applies to blood pressure or blood sugar. If parameters like BP or BS are off it means the regulation is dysfunctional...

[@nicknorwitzPhD]

Perhaps... but the word "fad" may be tossed around too liberally for my taste... e.g. Keto is often called a fad. I argue it's a metabolic state, separate from Quest Bars ;)

[@rlwings]

Dietary cholesterol does not increase blood levels of cholesterol. (Any food, not just eggs).

[@nicknorwitzPhD]

Ya, but eggs have better SEO

[@cyberfunk3793]

Dietary cholesterol obviously raises LDL in most people when they start with healthy baseline. If you start at LDL 200, your LDL isn't going to go up due to eggs. That is why eggs lobby funds studies, where the study subjects already have a high LDL to begin with, so no difference is seen. It's cholesterol and saturated fat that as a combination raises LDL. "Based on available evidence, this is the largest meta-analysis in exploring the impact of egg consumption on LDL-c/HDL-c ratio among healthy subjects and reveals that more eggs consumed per day may influence cardiovascular disease risks by increasing LDL-c and the LDL-c/HDL-c ratio. Notably, longer-term high egg-consumption may lead to higher LDL-c/HDL-c ratio and LDL-c. However, RCTs with long tern follow-up are needed to guarantee the association between egg consumption and human health"

[@LawrenceAugust_]

@@cyberfunk3793 Tell us you didn't bother to watch the video.

[@cyberfunk3793]

@@LawrenceAugust_ I did and the exact gene that affects the mechanism is irrelevant to the bigger picture that has been known for a long time. The claim made in the title is simply false and refuted for example in the meta-analysis of clinical trials I quoted. It's a typical claim made by the eggs lobby.

[@cyberfunk3793]

@@LawrenceAugust_ Again as my previous reply was deleted: I watched it, but the exact mechanism is irrelevant because the claim in the title is simply false.

[@Deborah-dv3iw]

Brilliant Nick. Thanks for sharing.

[@nicknorwitzPhD]

You're welcome!

[@trentriver]

Amazing overview of the new science. Nick - please just keep being Nick!

[@nicknorwitzPhD]

I don't think I have a choice! That's great news to some people... but not all 😉

[@trentriver]

@@nicknorwitzPhD LOL!

[@judyanderson4766]

Great delivery Nick, for those of us not scientifically trained, but seeking answers. Your 'pause, rewind' advice works so well! I feel I now have an understanding of the complexity of the process as well as the simplicity of how our own biology optimises our cholesterol levels. One of your best ever! Bravo, please keep doing what you are doing.

[@nicknorwitzPhD]

Thank you! Deeply appreciate this!

[@donaldmcpherson3226]

I learn something new every day. Thank you.

[@nicknorwitzPhD]

You're welcome!!!

[@JesusMartinez-mk6fc]

Great video Nic! It's amazing that this new hormone (Cholesin) has just been discovered within the last year or so considering all the research that's been conducted on cholesterol over the last two centuries since its discovery. This could be a Nobel prize in medicine worthy discovery. I remember clipping a newspaper article from about 20 years ago, about a study that came out of Iowa State University if memory serves, where they empirically demonstrated that eating large quantities of eggs didn't raise cholesterol.

[@annchenweidemann5694]

Thank you, Nick. Fabulous info!!!

[@nicknorwitzPhD]

you're very welcome!

[@robyn3349]

Thank you, Nick!

[@nicknorwitzPhD]

You are very welcome Robyn

[@iainneilson1453]

It seems to me that the more we learn, the more questions we need to ask about the basic mechanisms and what changes in lifestyle might help avoid or resolve issues with metabolism, rather than what medication can be developed to address the symptoms. If the money put into pharmaceutical development were invested in basic science, maybe we wouldn't be where we are, in terms of public health. On the flip side, I don't imagine the pharmaceutical industry would be interested in funding research which eliminates the need for their products.

[@nicknorwitzPhD]

We can dream, can't we? "If the money put into pharmaceutical development were invested in basic science, maybe we wouldn't be where we are, in terms of public health"

[@iainneilson1453]

I look forward to that day.

[@mbrochh82]

Here's a ChatGPT summary: - Eating eggs does not increase cholesterol levels. - The mechanism involves a newly discovered hormone called colescent. - Colescent inhibits cholesterol production in the liver. - When dietary cholesterol is consumed, colescent levels rise, inhibiting liver cholesterol synthesis. - If no dietary cholesterol is consumed, colescent levels remain low, and the liver increases cholesterol synthesis. - Cholesterol binds to the Neiman Pick type C1 like one transporter, triggering colescent release. - Colescent binds to the GPR-146 protein on liver cells, inhibiting the S-R-E-B-P-2 pathway, which controls cholesterol synthesis. - Variations in the colescent gene and its receptor correlate with changes in cholesterol levels in humans. - Pharmacotherapy implications: Statins, PCSK9 inhibitors, and ezetimibe (Zedia) affect cholesterol levels through different mechanisms. - Ezetimibe blocks cholesterol absorption but also reduces colescent release, leading to compensatory cholesterol synthesis in the liver. - Combining ezetimibe with colescent could potentially provide a more effective reduction in cholesterol levels. - Main message: The hormone colescent plays a crucial role in regulating cholesterol levels by inhibiting liver cholesterol synthesis in response to dietary cholesterol, explaining why eating eggs does not increase cholesterol levels.

[@jobrown8146]

Thank you. Another great explanation that I can understand. I wouldn't want to be tested on it, but my knowledge is increasing bit by bit.

[@hpb19]

Thank you for this one. The cholesterol debate won't go quietly. My first thought was that using medication to block a natural process is playing with fire, but at the same time, I had to check myself. All medications do that. It can be a life-saving difference.

[@rongqut7576]

Love your diagram

[@nicknorwitzPhD]

Thanks. The figure in the video is from the paper. The thumbnail was made by a friend, Andrew, and using a Zack S. Photo, with permission from Zack

[@terriem3922]

My Grandma ate 2 eggs a day and had low cholesterol. She didn't pig out, ate moderately. I have higher cholesterol no matter what I eat, and have avoided eggs for years. Genetics.

[@susanbeever5708]

Nice. Along with demonstrating reverse cholesterol synthesis: TG decrease as HDL increases-or lack of it depending on the individual, fasting shows how cholesterol syntheses increases.

[@mikewalkow1860]

Hearing you on Stemtalk gave you ALOT of credibility in my book! I wish some of the more well know " experts" would have you on their shows.

[@nicknorwitzPhD]

Thanks! Was a fun time... in due time I'm sure...

[@monnoo8221]

yep, completely agree, mechanisms explaining the whole context end to end are cool. would be interesting to see how that chol receptor is being regulated, also pathologically, eg in IBS, or under gluten load. etc.

[@llnow1237]

Thank you for this excellent summary. I’m new to your channel and I completely understood your explanation. Question- if LDL was an issue, could they just give you the hormone in order to down regulate your liver - why would they need to also give you the drug to control absorption ? I am on the carnivore diet and my LDL has skyrocketed- but every other marker is great. My Dr wants me on a statin and so far I’ve been able to say no. Disregarding hyper-responders, now I am wondering if those of us who react to carnivore diets this way may just have a hormone issue or a liver issue. You definitely have me thinking and thanks to your great video I can head down the rabbit hole-of other KZbin videos better prepared.

[@cobbrg]

Definitely interested to hear your thoughts on LMHR and Ezetimibe.

[@nicknorwitzPhD]

Hypothesis: will punch above it's weight in terms or LDL-C reduction vs general population

[@richardb8267]

Great content as always! Could you please look into Citrus Bergamot as claimed by some people to be one of the best natural way to decrease LDL and Trig while raising HDL? Thanks.

[@chrisbrowning3313]

this is great Nick... love your work (and eggs!!) so a double whammy. I just wondered if you a a tendency towards a diet outline for someone with APOE4 polymorphism (so a tendency for super High T Chol and LDL)?

[@nicknorwitzPhD]

pubmed.ncbi.nlm.nih.gov/33921683/

[@RobertWells1]

I like how when you said "take a step back", you took a step back...😊

[@scotchbarrel4429]

I appreciate your take on it. My only concern is whether it would be neccessary for most people to get exogenous medication for these ptoblems in the first place. Im guessing the need to speculate on these mechanisms will help those who are severely in need. Also, i love the way your illustrations have improved, now youve got the circles indicating individual parts of the diagram as youre explaining it. I hope Huberman watches your channel, coz this level of detail would of been handy in his latest vid on back pain, and explaining the McGill exercises, which luckily i stumbled across on his other channel, of him physically doing it. Still, your method is far superior, the diagrams and the anonymous guy evolving his skills on this detail is very appreciated, give him a hi five for me 👊😎

[@nicknorwitzPhD]

"I hope Huberman watches your channel" ... hey me too ;). We've chatted. From all our interactions, he's a really nice guy. I hope we get to interaction more, but I think my academic career will have to mature a bit more...

[@thecarpenter645]

Thank you for your inquiry into all these topics and the way you put things across, I understand you a whole lot more than my GP as they are some what conditioned by “ big Pharama” and not science. Don’t get me wrong I don’t believe you just like I don’t believe my GP I just understand you a hell of a lot more than my GP. Sorry for the comparison but the topics you are mentioning are a big help to my health and my standard of living. Thank you once again.

[@nicknorwitzPhD]

I’m glad you feel my content is helpful and easy to understand:)

[@michaelhegarty788]

Many thanks Nick ,interesting. I think not vilifying Ldl or putting Ldl on a pedestal is to be considered. Stay curious

[@bjmsamrlm]

Great content. Any thoughts on CETP inhibitors (e.g.- obicetrapib), particularly in the context of ApoE4?

[@homomorphic]

Very cool. Any time a new hormone is identified it is very cool. Given the subjects that interest you most, I am surprised you aren't planning on specializing in endocrinology.

[@nicknorwitzPhD]

I am...

[@IQTech61]

Yes, this information is very cool because eggs are one of the best foods for us to eat. Thank you. :)

[@nicknorwitzPhD]

They are egg-cellent!

[@AliceFarmer-bg4dw]

Nick that was awesome. That just proves we don’t know much. How about quantum biology?

[@nicknorwitzPhD]

I think I might be quantum entangled with Dave Feldman and Adrian Soto Mota in a nerd trio

[@AliceFarmer-bg4dw]

@@nicknorwitzPhD Mitochondrial Energy and hormone changes with light. Sunlight and artificial light. Deuterium, water and grounding to the earth providing electron balance for the mitochondria. Have you heard of this?

[@Classicontento]

would be interesting to have you on Huberman

[@nicknorwitzPhD]

I mean... I'd say yes...

[@btudrus]

BTW, the MAPK/ERK pathway is linked to tumorigenesis as well. Does it mean that eating cholesterol would suppress cancer?

[@activeintech]

I did an experiment where I ate a dozen eggs a day for one month in addition to my normal diet (but only a slight caloric surplus). I ate other foods as well, including some carbs, and my cholesterol shot way up. I sort of had a LMHR response. My HDL and LDL went way up, and my triglycerides way down. Could this have been due to the saturated fat content, or a slight increase in calories and weight gain (~+3 pounds), or a LMHR type response? Inhibited Cholesin hormone?

[@SimonHealthAction]

You're probably a lean mass hyper-sterol absorber (LMHSA) meaning you probably over-absorb cholesterol. Take a cholesterol balance blood test to find out. Don't forget to get an ApoE genotype test done too. Nick wants to talk about the cholesterol balance test in his next video since he loves us LMHSAs almost as much as LMHRs. Alas, my sense of humor is an acquired test!

[@proper2979]

Eating eggs increases your cholesterol that is why your cholesterol shot up. The extent of the increase depends on the rest lf your diet beforehand obviously. Someone on keto would likely not notice that much of a different. But if you were low fat before youd likely see your cholesterol double.

[@activeintech]

@@SimonHealthAction thank you for the reply!

[@gailm.8190]

Question: do you think plant sterols may act as an agonist to release cholesin and that’s how they reduce cholesterol levels? I did the n=1 eggsperiment a long time ago: totally removed eggs (~6/day) from my diet and my LMHR-high cholesterol didn’t budge (I didn’t know I was a LMHR at the time). I brought them back in with confidence and have never looked back, and am trying to raise carbs a bit and reduce saturated fat and that has worked for ~150 points. Thank you for a great and very informative video!!

[@dennisward43]

Definitely cool, Nic. It poses many more questions. Cholesin works with eggs to inhibit blood cholesterol so can we assume it will work for all dietary cholesterol? And what % of dietary cholesterol is inhibited? 100%? 50%? Is all dietary cholesterol the same? And what other factors - such as weight, stress, lack of sufficient sleep , exercise, genes, etc - may be factors in making blood cholesterol and ldl rise?

[@nicknorwitzPhD]

"Cholesin works with eggs to inhibit blood cholesterol so can we assume it will work for all dietary cholesterol?" - Yes. Was just using eggs and an example food and for SEO. In terms of %, I think there is near complete compensation, although may differ by individual.

[@jaro6985]

@@nicknorwitzPhD Super interesting, but, your liver maxes out at producing around 1g of cholesterol per day. So if you exceed 1g of cholesterol intake via the diet (5 eggs), then cholesin presumably can't limit any more than that 1g. What happens to the cholesterol then?

[@jimo559]

The human body is a Complex Adaptive System and yet….as you describe….supremely intelligent. As Donald Rumsfeld was fond of saying, there are “Unknown, Unknowns” whenever you attempt to intervene in a complex adaptive system whether it is political or biological (like homeostasis) In a nutshell, Rumsfeld wisdom almost ALWAYS means that the end result of screwing around with a complex adaptive system puts your self-interest in a worse position than before. Attempting to pharmacologically intervene in the LDL of an LMHR is case in point. Just too many Unknown Unknowns like the role LDL plays in the immune system.

[@Youtuberr44]

Well stated!

[@ArcoZakus]

The perfect example from history is bloodletting. Of course, I would guess that the doctors who performed it at the time did not give their patients (or their survivors) refunds. That pattern will probably repeat if someday it is found that cholesterol lowering drugs have been more harmful than helpful overall.

[@proper2979]

Makes no sense. Human diets inherently mess with that "complex adaptive system." Everytime you eat your messing with it. Sounds super pretentious.

[@agfairfield8575]

@@ArcoZakus I predict that PCSK9 inhibitors that DRAMATICALLY reduce cholesterol by irreversibly altering the liver will be shown to be much more harmful than helpful [See already: "The systematic review of RCTs of PCSK9 antibodies challenges their "efficacy breakthrough and the "lower, the better" theory" Current Medical Research and Opinion Vol 34 Issue 10 2018]

[@jimo559]

@@proper2979 No argument there. Diets do impact how your health emerges. And “emergence” is the hallmark of a CAS. When Ancel Keyes “messed” with the American Diet WHAT emerged was not what everyone involved had hoped for. What emerges from a keto diet is generally good for many sick people who try it. The emergence of sky high LDLin LMHRs in the presence of amazing health seems counter-intuitive for reasons like unknown-unknowns. Drs trying to medicate what could be a natural and beneficial phenomena in an LMHR is pretentious, IMO. We just don’t know.

[@melissawitherspoon9094]

Thank you

[@nicknorwitzPhD]

You are welcome!

[@manitikman]

This prompts the question why, if the body is working hard to maintain cholesterol in a certain range, we think it would be a good idea to take drugs designed to push the body out of that range, without fully understanding the mechanisms. Shouldn't we be working on understanding why the body sees that range as optimal before we start tinkering?

[@carolj.3175]

Fabulous point!

[@matthewtrout1440]

It's not very good at maintaining a tight range. I can alter my diet a bit and shift my TC by a hundred points in a few months using nothing but whole foods. Does it matter? Some argue it's the end all be all, others argue it doesn't matter at all.

[@annettestephens5337]

Too right

[@manitikman]

@matthewtrout1440 I've been on Keto, Atkins, carnivore and the SAD during the past 20+ years, and my LDL has stubbornly maintained the same range. I know you can alter it substantially in the short-term, the Oreo experiment demonstrates that, but at least for me, diet doesn't alter it long-term.

[@nicknorwitzPhD]

Depends... are we optimizing for the same outcomes that natural selection optimized for?

[@CAM89583]

That's why I won't take cholesterol meds now. When Crestor first came out my Dr. put me on it. It lowered it, then about 3 years later it started climbing again. In my mind that says my level is where my body wants it. Felt better after I quit taking it too. Didn't realize all the side effects it was giving me. Sigh.

[@anielyantra1]

good job! keep the bar high. Here's a mechanism for you; If you treat people like they are stupid then they will respond that way.

[@nicknorwitzPhD]

Good one! Really... love this... I'm "borrowing" it

[@GameofTrees]

That was awesome, my cardiologist tried to prescribe Zedia 😃 now I know why I declined 😃

[@nicknorwitzPhD]

Umm... you may be getting something from this video that wasn't said... please work with your physician. This is a mechanistic explanation. Also, to be crystal clear, the compensation to Zetia re cholesin/endogenous synthesis is not complete.

[@GameofTrees]

@@nicknorwitzPhD fair enough, I will listen again, of course I declined before you made the video so you didn’t influence the decision, she is uncomfortable with my 388 LDL amongst otherwise perfect numbers and sees no need for a CT angiogram. I scored a 16 on my CAC so I am curious, but curiosity was not valid in her opinion. I am in search of other opinions 😃 Thanks for the clarification 👍🏻

[@allisonal]

Interesting! I’m curious if dietary phytosterols (from plants) stimulate the same pathway. Which have been touted to decrease LDL, but which the body has mechanisms to pump back into the GI tract.

[@ematise]

I saw a video on KZbin about how bad phytosterols are for metabolism, being able to block the animal fat cholesterol absorption.

[@nastaranashoori]

Hi Nick, What is high cholesterol in your knowledge? LDL and HDL

[@AliceFarmer-bg4dw]

Nick , your work is awesome. I am very interested in the lipid energy model. However, I want to know the full spectrum. Not just how carbohydrates and fats change it, but how carbohydrates fats, sunlight, hormones, water, and magnetism, change the lipids in the body. I have seen evidence that sunlight increases vitamin D and decreases lipids. This would play a role in different diets. And we know that people live in different latitudes for diurnal sun angle. We know that indigenous tribes typically spend more time in sunlight. And most of the time they have lower lipid levels. Even though that are on a carnivore diet. Why?

[@spacejaime]

Dr. Nicholas - I took Zetia for two months and asked my Dr. for a lipid panel as I was curious how the lipids where at. I suffer from high trigs, not high total cholesterol. Anyway, the results came in, and sure, my LDL was lower, but also my HDL went from 48 DOWN to 36. I quit the drug immediately and went back to fenofibrate. Could you explain this effect on HDL?

[@BARBELLS-AND-BUDS]

I switched to a Keto then carnivore diet. My cholesterol definitely went up. But the type(s) that went up arent necessarily bad, LDL and HDL, while Trig went DOWN. Then in subsequent testing cholesterol LDL has been declining over time, while HDL went up further, then leveled off. SO... I went from 234lbs 39.5" waist 26%BF to 178lbs 15%bf 32" waist. Whos healthier the lower cholesterol obese me, or the higher (LDL) cholesterol me? I can workout again because autoimmune issues are at bay, and fatty liver and anemia etc are resolved. Did I mention my testosterone almost doubled, my thyroid level increased? EVERY marker across the board in improved unless you count LDL as a negative

[@Damcarnivore]

That’s cool I thought we didn’t know. I would ask so tell the system that shows eating unsaturated fats increases cholesterol.

[@apriljohnson6191]

So, considering this information, how does this model describe the situation when familial hypercholesterolemia occurs? Is it a cholesin deficit that is the proposed cause given this model? Also, do I understand that the CPC1L1 receptor is on the PSCK9 protein? Do I have the correct? Thank you for explaining this research. 🙂

[@btudrus]

"So, considering this information, how does this model describe the situation when familial hypercholesterolemia occurs?" In most cases it doesn't describe FH at all. The mechanism how FH (which is a set of very different genetic mutations) cause high LDL is the same how eating sugar causes high LDL: It is all mediated by mitochondrial dysfunction. The inability of mitochondria to fully "burn" the substrate for energy leads to the activation of the citrate shuttle by which the mitochondria tries to protect itself. A large amount of citrate is pushed out of the mitochondria and converted to AcetylCoa in the cytosol. Coseqeuntly, AcetylCoa is converted either into fatty acids (triglycerides) and mostly exported out of the liver in a VLDL particle - or converted through the HMGCoa-pathway all down into cholesterol and also mostly pushed out of the liver as again VLDL. VLDL then looses it's TG cargo and is converted into LDL...

[@dogphlap6749]

Interesting (but it was a Nic Norwitz video so that is hardly a surprise).

[@nicknorwitzPhD]

AWEEE!

[@shanebaird543]

One of the things I hear the vegan docs say is that the studies that show animal fat doesn’t raise cholesterol are taking diets they consider high in fat already and add a little more so the raise in cholesterol isn’t statistically significant. If you take some eating plant based low to no fat adding eggs will raise cholesterol. I don’t know what the truth is. What I do know is I ate a proper “healthy “ vegan diet and my physical health slowly declined. Eating high meat carnivore/ketovore has restored my physical health very quickly and I feel the best I have in decades. I feel like a healthy 20 year old at 47.

[@ImNoclue]

So when’s the egg & Oreo study coming out?

[@nicknorwitzPhD]

Icky... I had one Oreo omelette during that expt and that gave my tongue PTSD

[@doejohn8674]

I see a multi billion dollar market opening up: cholesin 'enhancer' or something like that, new patents combining it with existing cholesterol medications...

[@hkgonra]

I’m really curious now about all this. Had a heart attack in November with mildly elevated LDL, put me on ezetimibe since and just took me off because my latest bloodwork 2 weeks ago showed LDL at 33.

[@nicknorwitzPhD]

Sorry about your medical history. Please work with your doctor and stay safe.

[@snakeace0]

Another great point i can rais when cardiologists try to tell my clients that they need to eat less cholesterol heavy foods in order to decrease harmless LDL levels. It doesnt help that tests for actual oxidated-vLDL´s have to be financed privately in our already heavily taxed state healthcare system in germany. You wouldnt believe just how many Cardiologists dont even know about OX-LDL at all...

[@skc-wg2yq]

i love "the how"

[@nicknorwitzPhD]

As do I... ;)

[@RebootCongress]

Is that NPC1L1 enzyme (?) related to Niemann-Pick Disease?

[@nicknorwitzPhD]

Annoyingly, not really: Niemann-Pick disease types A and B are caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene

[@zealman79]

Though for some people, i'm guessing they will synthesize cholesterol even if their intake is moderately high due to an error in the process somewhere down the line...hence high LDL numbers regardless of intake. but for the majority this process works well? also love the karate kid reference hehe...'Sweep the leg' 'BUT SENSEI'

[@robz.3225]

Nick, do you think this might work for other foods that are high cholesterol?

[@nicknorwitzPhD]

Absolutely... it's not egg specific... that was just an example food

[@northerncowboy8409]

You mentioned Cholesin down-regulating cholesterol synthesis. Got it. Then you said if you're not eating cholesterol, Cholesin will remain low, and cholesterol synthesis would be up-regulated. There's a difference between up-regulating and not down-regulating. Does Cholesin also inhibit release of cholesterol up-regulators? Will the liver produce cholesterol without any hormonal signaling?

[@nicknorwitzPhD]

Timestamp? Either I made a verbal error or you heard wrong…

[@scottshort262]

Hey Nick fellow LMHR here. If body wants cholesterol homeostasis, then why is our cholesterol so high while general population is normal or low? how are differences in LMHRs explained given this new information?

[@machietheapachie7214]

Question! If cholesterol is 15% of diet and 85% internally generated, and the body will intelligently self-regulate into a state of homeostasis...am i correct in presuming that the body simply doesn't deduct the points of cholesterol from the body that have been added from the diet? Otherwise that's just the same homeostatic outcome, right? But rather (and I hope), it treats the impact of each source of cholesterol as percentage (i.e.: a 50% increase in dietary cholesterol = 7.5% more, which ideally has a 50% decrease in bodily cholesterol = - 42.5%)? That would be a better homeostasis and therefore a greater incentive, right?

[@christopherroberts27]

So is the absorption of exogenous cholesterol vs synthesis of endogenous cholesterol 1-to-1 relation? Seems like eggs or any exogenous source could potentially create a surplus that exceeds whatever your homeostatic baseline would be if you don’t have a good understanding of what your body would naturally synthesize if exogenous sources were completely eliminated. Just curious if that was considered.

[@darylfortney8081]

So could we just take Cholesin directly instead of statins if we need to lower cholesterol in people who's 'cholesterol balancing' mechanism obviously errors on the high side? Or maybe a gut probiotic that generates more Cholesin per gram of dietary cholesterol absorbed?

[@hanko5750]

I believed that babbling BS for DECADES about eggs .. then as I changed my life style (what some call diet) I had the wakeup call that eggs are really, really good for you. Thanks for this ... love the details, i.e. FACTS

[@Sunweaver593]

Eggs are so packed with nutrients, they’re like nature’s vitamin pills

[@martinklawinski2933]

I wonder if phytosterols also aktivate cholesin release.

[@erikvosenmd676]

Thanks GREAT information!!! Also I am thinking some cholesterol must be good considering the centenarian swedish cohort study (2024, citation below), showing higher total cholesterol in those over 100yrs old, so overall balanced cholesterol is our friend :) Thanks cholesin! Murata S, Ebeling M, Meyer AC, Schmidt-Mende K, Hammar N, Modig K. Blood biomarker profiles and exceptional longevity: comparison of centenarians and non-centenarians in a 35-year follow-up of the Swedish AMORIS cohort. Geroscience. 2024 Apr;46(2):1693-1702. doi: 10.1007/s11357-023-00936-w. Epub 2023 Sep 19. Erratum in: Geroscience. 2023 Nov 4;: PMID: 37726432; PMCID: PMC10828184.

[@jamesasimmons]

Ah, another biochemistry fix. Thanks Nic.

[@nicknorwitzPhD]

Thank you for your thank you!

[@fiddlestyx21]

Hey nick. What did your apo b do with the oreo experiment?

[@nicknorwitzPhD]

Drop like a rock through air

[@fiddlestyx21]

I was curious. Mine went up to 198 latest profile. My lp(a) went from 41 to 78.8 also. Thanks for all you are doing in the world of lipids.

[@user-gb4wp4bg3h]

My friend Dr Nick, do you know what the real problem is? I will tell you. They say that In order to have a Coronary Disease you have to have over a 50% stenosis. Then probably you should follow guidelines. Most of us perform a CT Coronary angiography and find that there are plaques around 30% to 40% infarction to two or three arteries without having any other serious problems (HOMA IR = 1 , Triglycerides to HDL ratio 1 ...etc). AND the serious decision arises: should we take a Lowering LDL Drug or not , since we are on keto diet and we have Total Cholesterol around 250 and LDL around 180. I would appreciate your thoughts on this topic (without ofcourse taking them as a medical advice).

[@alexd7466]

One problem however: FHC is often about cleaning up 'old' cholesterol , not about how much is created (from food or liver). Where it comes from isn't that relevant.

[@freddygoulet6101]

What about those with hypercholesterolimia? I have been told dietary cholesterol does affect those people negatively.

[@chrisbeerad8835]

i read an article in T NATION nearly 10 years ago that said dietary cholesterol doesnt directly effect blood levels . it never mentioned this hormone though

[@KenJackson_US]

Is there any acronym registry board or authority? Suppose some researcher finds a new protein and decides to name it GPR, PKA or ERK? How can they check to see if those are already taken?

[@nicknorwitzPhD]

They don't... there are many acronyms with several meanings. You need to figure it out based on context.

[@tspicks4360]

The mechanism you describe is interesting. Your title might be better put to say "Dietary cholesterol does not cause serum cholesterol increase". There are numerous studies showing an increase in serum cholesterol from eating eggs. How? Sat fat? A 2020 meta-analysis by Mah-Yun Li et al, "Consumption and Cholesterol Concentration: A Systematic Review and Meta-Analysis of RCT's" shows this.

[@billdublewhopper3064]

If you are a vegan, eating eggs raises cholesterol. If you are a carnivore or omnivore then eating eggs will not significantly rise. Simple explanation

[@tspicks4360]

@@billdublewhopper3064 The meta-analysis I mention above was not based on studies of vegans, so a carnivore/vegan interpretation doesn't really apply there. They simply found that in these various randomized controlled trials, eating eggs raised cholesterol significantly. As I said, a likely mechanism is saturated fat, known to raise serum cholesterol.

[@thetweakjunkie1576]

It's always the SREBP2 regulator, never trusted that thing from day 1 🤔😂 But seriously Doc, thanks for the details.

[@nicknorwitzPhD]

Glad to help

[@btudrus]

@@nicknorwitzPhD all SREBP are suspicious.... and these are connected. it's because cholesterol synthesis and DNL are connected in function and regulation and of course a dyslipidaemia comes usually with both, high LDL-C and TG rich VLDL....

[@skysurferboy]

I guess I ll have to watch that again a few times.

[@FoodPornNetwork]

Yes my little brain stops listening right away lol I dont know why I watch these videos haha I dont need to know why, just the good news lmao

[@nicknorwitzPhD]

Do it! Do it now!

[@billtrudell1636]

It’s interesting but I’m not a fan of trying to bypass your system. I try to find ways to increase health within the system. If there was a dietary pattern to follow to get results that has more value to me. But it is valuable to understand the mechanisms.

[@Appleblade]

Should we intervene to remove toxins (chelate, sweat out, etc) and to repair damaged cells (provide nutrients), but not to 'improve' regulation? In basic physics, chemistry, biology, sociology... negative feedback regulation abounds. Can anyone think of illnesses of disregulation that aren't caused by toxins or cell damage?

[@KenJackson_US]

Yes. Genetic diseases are from mutations you're born with.

[@jillengland3277]

Cholesterol is not LDL …. So lowering actual cholesterol production might not actually reduce lipids. Perhaps the cholesterol molecules carried by those lipids. I admit I don’t know if they actually test LDL for total part cholesterol/sterol. I am interested if they test for this.

[@KarlKrassnitzer-mm8wb]

So there could be an evolutionary sense to keep cholesterol in a specific range.

[@btudrus]

But there are other pathways which have an effect on cholesterol synthesis

[@nuvamusic]

Then of course there are tons of people with this homeostatic/ self-compensatory mechanism all screwed up from the get go. So unless they have constant steatorrhea as means of getting rid of excess dietary fats/cholesterol, their excess dietary cholesterol WILL increase their blood cholesterol levels eventually, and cause the myriad of vascular problems (atherosclerosis). Therefore, I think it is wrong to interpret these new studies by generalizing and promoting the “it’s fine to keep eating food high in cholesterol because it’s not the cause of your high cholesterol” when over the years we’ve seen the majority of patients with moderate high chol levels can and will lower them by just modifying the diet. No medication involved. So yes, generalization via sensationalism is bad.

[@stellat2405]

However the danger from increased cholesterole is not the Chol per se, but the debris in the damaged epithelium. So cholesin or not the issue is not that

[@GlueTubber]

I think there needs to be a big rethink in public health - the body needs to be studied as a system of systems, rather than a collection of isolated parts. Cholesterol is used to produce other hormones, so how can it be bad for the body? When cholesterol is out of whack, why? That points to a problem in the feedback mechanism, but not a why.

[@desmomotodesmomoto2033]

But if they are on high carbs diet, what happens? The study was done on people on keto about eggs and cholesterol?

[@nicknorwitzPhD]

No it was not done on keto people

[@kbkesq]

My 21yo son is vegan and has total cholesterol of 95. If he eats 3-4eggs a day he will double his cholesterol and you know this. The question is what is the risk of elevated cholesterol.

[@nicknorwitzPhD]

Eating 4 eggs will change his cholesterol from 95 to 190? Really? That’s unusual

[@yavor_zlatanov]

Is cholesin available as a standalone drug or supplement?

[@nicknorwitzPhD]

Not to my awareness, no.

[@btudrus]

So, and yet another consequence: PKA a) inhibits glycolysis and b) activates gluconeogesis in hepatocytes. Which means eating cholesterol does the exact opposite. In other words makes you more insulin sensitive...

[@btudrus]

BUT that would also mean that eating cholesterol supresses de novo lipogenesis WHICH WOULD BE A REALLY GOOD THING!

[@btudrus]

Ok, so there are 3 forms of SREBP: "SREBP-1c regulates transcription of genes involved in FAs, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), two crucial DNL regulation enzymes, and triacylglycerol synthesis, whereas SREBP-1a stimulates both FAs and cholesterol synthesis. SREBP-2 regulates transcription of genes that control cholesterol synthesis. All these pathways interact and overlap in a complicated fashion" (Na Li et al. "SREBP Regulation of Lipid Metabolism in Liver Disease, and Therapeutic Strategies" ...) So SREBP2 is indeed different from SREBP1-c - BUT I think it would really be worth it looking at what Cholesin doesn to the other SREBP variants and how it affects de novo lipogenesis (DNL). I would bet that Cholesin would suppress DNL as well which would mean that EATING cholesterol is beneficial from a metabolical point of view (you don't really want your DNL upregulated!)...

[@WA4OSH]

I asked ChatGPT this: Where are GPR146 receptors found in the human body? ChatGPT: GPR146 receptors, also known as G-protein coupled receptor 146, are primarily found in the central nervous system (CNS) of humans. They are particularly abundant in the brain, including regions such as the hypothalamus, which plays a key role in regulating various physiological functions like appetite, sleep, and hormone secretion. These receptors may also be present in other tissues and organs, but their functions outside the CNS are less understood. ...So the stomach talks to the hypothalamus via #Cholesin about eating cholesterol?

[@nicknorwitzPhD]

Interesting hypothesis... not sure how much, if any, cholesin gets into the CNS.

[@WA4OSH]

@@nicknorwitzPhD Ahhh yes. Does GPR146 easily cross BBB? They've eaten 8 eggs and liver again, Get going it's party time? Eg is caviar really physiologically an aphrodisiac?

[@shiplesp]

It just goes to show us that we have a long way to go before we are smarter than evolution.

[@StyzeSoulmaker]

Help me understand why this means eating eggs doesn't increase cholesterol. This hormone regulates cholesterol produced by the liver, but surely cholesterol from eggs also gets absorbed. If you eat enough eggs surely that will outweigh the reduced cholesterol production by the liver

[@user-nz4un6se7y]

How many eggs that would be? The title is phrased that way because that's what's practical. People are worried about eating eggs because they think they will overflow on cholesterol.

[@chargermopar]

So you are telling me that my eating a dozen eggs a day for decades did not make me more likely to have a heart attack? That's too bad!

[@nicknorwitzPhD]

Sorry to disappoint

[@ilmostro16]

@@nicknorwitzPhDCould eating too many eggs, like going overboard, simply push this system beyond its ability to maintain homeostasis? It was a joke, but in all seriousness, what if someone did eat 12 eggs a day for 10 years. Wouldn’t that just be too much cholesterol? Not that any sane person would eat that many eggs a day, but I would think that there would be some number of eggs that you’d overwhelm this mechanism, like anything else, there’s always a tipping point. For myself, I eat 3 eggs a day, every day, for breakfast. Sometimes with half an avocado, and/or half a cup of full fat cottage cheese.