One of the things that I truly appreciate about your channel is that you take incredibly complicated scientific studies and concepts and translate them in to simple language for the rest of us. I want to know about all of the scientific research going on out there, but there is no way that I could read and understand it myself.
Eat carnivore omad walking fasting ice bading zeolith sun d3 NAC msm borax dmso never ever take the clot shot seed oils sugar and carbs oxalates processed food pestozides
Here's my recall from a single watch-through: 1) Brain has neurons 2) They need lots of energy 3) They are sorta like octopi...octopuses?.. - they have a large main mass which had many "arms". 4) For some reason they need mitochondria at the end of the arms to "turn over" at a specific time and not all the time. 5) Insulin triggers the "turnover" somehow 6) Insulin resistance can f•ck up the ability for the mitochobdria to get the memo from insulin 7) This means the mitochondria don't "turn over" at the right time and get old or something In other words, insulin resistance can negatively effect brain health.
Yes! Both and! Always appreciate your approach and good to hear "another side" to what "experts" in the HC industry have spouted as "known and settled science" for decades.
I really enjoyed the presentation style / approach: it was refreshing and engaging. The graphics were really good! Pace of delivery was just fine. I found the subject really interesting, particularly as my own background is in physiology / pathology. Definitely subscribing 😀.
For me personally, I love the deep dense dives, but the "baity" videos are fun and are more helpful for the ketovore support group I lead. I think you are striking an excellent balance and I really enjoy the content you are bringing to the table. So, Thank you!!
@00:29 "This creates a spatial problem..." A lot of my friends say _I'm_ spatial. At least I think that's what they're saying. Does that mean I'm brainy, or nervy? *@**4:19** NOTE: AMPK can be disabled by polyol, one of the intermediate metabolic steps of the break-down of fructose. Fructose levels in the brain and spinal cord are the CNS's response to osmotic pressure generated by sugar levels in the rest of the body, outside the blood-brain-spinal cord barrier. Motto of the story: cut out all sugars, and all carbs possible.*
Sounds great, but not always possible. In the beginning, 120 hr work week plus classes. Then supervision of others and 24 hr on call, then private practice with a whole new set of problems. Or the ones that dedicate their life to science, studies ,...Sacrificing everything for their passion. Think of an Albert Einstein or a Tesla. Think of a Walter Willett....many examples. Not an easy path. Stress, job demands....then if a wife or kids involved, never seen a ripped / jacked +200 lbs physician or professor that wasn't divorced. Lots of trade offs. Something has to give.
@@DrAJ_LatinAmerica I agree... and medicine and healthcare are changing... I'm in the process if figuring out my priorities and what will give. But you're right... can't be a researcher, physician, public educator, healthy, and a good partner and parent...
As a physician with a degree in nutrition, I am amazed and joy filled being educated and entertained by your channel. Great balance and remember…..Stay Curious!
@@supercal333I don't think you necessarily want to increase insulin but you do want to increase insulin sensitivity. This is a highly debated topic. The low carb people will tell you that reducing carbs will increase sensitivity but the plant based people will tell you fat reduces sensitivity and that you need to eat very low fat high carb. Who do we believe. But I think that intermittent fasting is universally agreed to help insulin sensitivity so, if nothing else, just extending your overnight fast is going to help. As for which dietary interventions you take, you need to do lots of research and decide for yourself what you think makes the most sense.
I thought Alzheimer’s Disease was thought to be a disease of insulin resistance of the brain? And that a diet that decreases circulating insulin levels promotes mitochondrial health in general, especially in the brain. So are these benefits of PINK1 decreased in those of us following a low carb lifestyle?
There's a relationship between IR and AD, but it's not quite so linear. I think engaging in a lifestyle that improves metabolic health will overall serve one well in preventing AD
What I appreciate about your science communication is that you’re not looking to take findings from papers and use them to assign “good” and “bad” labels to various things. I think I have a tendency to do that when I’m reading papers on my own, just as a means of simplification.
I think this video was very well done with a breakdown and explanation that I can understand. I thought the graphics were well-matched to the narrative. Also, I appreciated your recognition of your tendency to speak rapidly. You then slowed down which resulted in my being able to more easily follow what you were saying. I enjoy all your videos, tho must admit a few have been way over my head. But please, keep putting out your content. I’m always learning something from you. Thank you!!
As a person who is approaching 50 years of living with type 1 diabetes, who is working hard at understanding his health and hopes for a good long life, and whose father suffered severe mental degradation at the end of his life, I both love this type of content and enormously benefited from this specific video. Thanks!
Thank you for these vids. Mitochondria are so basic we must get our understanding of them right. A video that addresses the uncoupling of mitochondria would be a good follow-up.
I'm sure you have considered what the IQ needed is to be able to, at least in basic terms, understand your content. If you want a broader range, you will have to to dumb down a little bit. I don't believe that's what you want. The "less intelectual" videos are still aimed at the same audience. You use those to reach more people, but they don't broaden your audience all that much. You are good at simplifying things, mostly by removing all the jargon or at least explain what it all means. That's what makes it possible for people like myself, that aren't in medicine, to understand what you are talking about. 36K followers however is just a small percentage of your potential audience. If you want to reach more of your audience, the solution is in optimization of your channel. This includes learning to write optimized descriptions for your videos, and using playlists better than you are now. You have only 3 playlists. You need to organize all your videos by different themes and create a playlist for each one. You can add a video to multiple playlists if it makes sense to do so. You can also order them in a playlist so they make logical sense to watch in series. It doesn't have to be by publishing dates. And last but not least,... identify keywords/themes that are popular and find out if any of those you can use on your channel. There may be new ideas there that fit your goals for your channel.
Hi from Japan! Thank you for sharing such interesting studies on your channel! In this video, the study says that Mitophagy occurs when AMPK is off due to insulin signalling. Would that mean that most mitophagy occurs postprandially? It challenges the common idea that mitophagy happens during prolonged fasting states. Please elaborate.
Watch the video again -- carefully -- yes there is a counterintuitive aspect that you're keenly picking up on... one of the things in this paper that struck me... good catch!
@@nicknorwitzPhD Thank you for your reply. Are you pointing out at the ebbs and flows section of the video? In other words, fasting will improve insulin sensitivity which may in turn increase mitophagy postprandially. It would be interesting to see how strong and how long the insulin signal needs to be in order to initiate mitophagy…one possible question: are slow long meals better than short ones or vice versa?
Studies into APOE4 in 3rd world countries show it drives cognitive fortitude to adverse environments. Prevents cognitive decline from starvation or toxic exposures.
You must be getting the content right. Every time I see a new one I make time to watch it. I often spend time afterwards looking up more details on the complex things you cover. I like the graphics & charts you add. These are very helpful for me to understand.
Would LOVE to hear your opinion on the study finding that: The authors of this study write, "...the lowest risk for long-term mortality appears to exist in the wide LDL-C range of 100-189 mg/dL, which is much higher than current recommendations." Mike Mutzel is presenting the study here: ua-cam.com/video/4nm-xIq7I2Q/v-deo.html
This video was great thank you. It was really cool to have a breakdown of a recent paper in biology and understand most of what was going on. I don't think you talk too fast. Apart from when you read out the title of the paper which you obviously did fast intentionally, but that's a bit like "I'm assuming you won't be able to understand this". I think if you had read it out slowly then I would have been able to understand it
Do a mix. We also want to see “normal Nick”… everyday Nick like if you go to your mothers house do you eat the food she gives you or are you a total OCD foodie? I do like your science ones but as we all know scientists are sometimes looking into the black hole but never pull their heads out to see the bigger picture and sometimes miss the truth
Ironically I just closed a recording video talking about my (our) summer projects of making cheesecakes with my girlfriend, who is not keto. At my mother's house, I do the cooking ;). And, yes, I'm very happy to make normal desserts and sweet potato side dishes for those who enjoy them. I "do me" so to speak as I use a KD therapeutically.
I’m now confused. I thought that autophagy, which I assume includes mitophagy, is turned on after prolonged fasting, which turns insulin off, and now you are saying that insulin through inhibiting ampk turns mitophagy ON. Where have I gone wrong?
Nope... you caught the counterintuitive aspect of this paper... which they in fact point out and which captured me. The body is complex and different spaces, organs, cells and sub compartment in cells can operate in different ways. COOL RIGHT?!
I love that you break it all down, I definitely appreciate the slightly slower pace of this video. I also really appreciate yours and Dave's approach as curious scientists willing to follow where the science leads and not just trying to make it say what you want it to. I can't stand the aragance of some of your detractors. Keep up the good work!
so whats the best way to check on whether YOUR own, MY own mitocohondria are pink and healthy? I know brown fat is different colour due to the mitochondria concentrations. The tissue is darker. How can I monitor my MITOCHONDRIA mr Ralph Macchio? Andre
identifying physiological mechanism is powerful and important, not least because it illustrates how much is not known. I think it's critical to keep learning and refining the understanding while not being too dogmatic about macroscopic conclusions and proclamations related to the general population.
This was super hard to follow while having my eggs bene 😂 which probably didnt help, im usually always multitasking (working out, chores, driving etc) when watching or listening to YT. The animation is always improving so youre nailing that part, and it helped to keep me locked in (compared to Laynes latest vid on protein which just showed a diagram 😂). I'm wondering whether you might consider simple analogies if possible to help simplify the logic. There was so much jargon, id probably have to rewatch it 3x with a notepad, and a laptop to lookup definitions etc, which realistically probably wont happen. I appreciate you doing the work to explain complex science, hopefully my attention span and intellect can keep up. Good work Nick 👊😎
You said ORTHOGONAL! Right there you made this a dense one... That said any experiment where you tag stuff and can SEE with your very own eyes the co-location of action is just plain science porn! This made me orthogonal too...
1) Great video as always Nick! You continue to open my eyes to neuronced (6/10 pun?) areas of science and such a wide variety of fascinating literature! 2)If I am interpreting this correctly the production of insulin (Presumably bolus insulin) inhibits AMPK and turns on necessary mitophagy. However the frequency of these insulin spikes may lead to unbalanced mitochondrial turnover and eventually reduced ability to turnover when necessary. 3) Do you think perhaps it occurs post prandially as there is readily available energy coming in for the body and cells to use to breakdown and build new mitochondria? 4) Do we know if all mitochondria in neurons undergo mitophagy every time in the presence of insulin or are there other signaling molecules or mechanisms that prevent every mitochondria from being turned over if they have recently been created? Would love to know your thoughts and no stress if you don't have the time to answer! I will keep learning!
I might need that shirt. I can't tell you how many people I've told about the Oreo Cookie Experiment. I love seeing people's reaction. Of course, I say the same thing Nick does, this DOES NOT mean Oreos are healthy, LOL, but it's meant to be provocative and encourage more studies.
Interesting - Could this be the mechanism by which glucose breaks down mitochondrial networks - triggering mitoptosis? Further, you need cycles of insulin to keep mitochondria pink1 (ahem), but if there are too frequent cycles it can lead to inefficiencies (or perhaps the short chains are good for glucose metabolism), or perhaps cells that are constantly in a state of building mitochondria themselves much less their networks. Insulin resistance would lead to mitochondria becoming old, and perhaps less efficient.. perhaps leading to similar issues. Nick, bring it all together!
All this is fascinating. If you could zoom out and speculate at the disease level, could this be why diabetics have a higher rate of Alzheimer's? I've often heard that APOE4 is the wild type, the one most of our hunter-gatherer ancestors would have had? So, fasting which would mimic their feast and famine cycles in nature, would be advantageous. Then my question is there must be some instances when not having efficient mitophagy is an advantage in nature?
Another vote for maintaining your mixture of “baity” and more rigorous videos. It’s impossible to grow/maintain your audience if every video is at a high-technical level, and if you aren’t able to grow/maintain your numbers you will not be achieving a core mission of educating the masses. Educating and engaging other PhDs is nice, but you can do better than that. Among your gifts is the ability to educate and engage thoughtful people who are not at your scientific level. Plus, even your more “baity” videos have more substance than most other channels. I think you’re doing great; stay on the path. There’s still plenty to learn and share.
Your sincerity is your greatest gift. I still have a hard time following some of your stuff, but I enjoy watching it. This video I'm left with 1. does everyone have apoe4 and 3 cause it sounds like yes. 2. If it is yes how do you know you "turned it on." 3. So is insulin the bad guy in this or the good guy? It sounds like the good guy if we need it for mitophagy? I'll watch it again, but I'm left a little overwhelmed.
Love the videos, regarding the styles, just keep doing what you're doing, the only issue with the ones like Celery has more calories, is that you will get some vegan who uses that title to 'debunk' you, like one did recently with Dr Anthony Chaffee. Love the work you're doing with regards to LMHR, please keep it up.
Hi doctor thanks a lot for the videos, I really appreciate the content. I would like to ask you a question. Do slightly over-physiological doses of testosterone interfere with the process of autophagy and mitophagy? I ask because insulin is an anabolic hormone and so is testosterone. I ask my doctor but he doesn't know. Thanks again.
This is one of a myriad of pathways thought to affect Alzheimer's generation (I think I saw a claim of 27 different associations ... rather than 'risk factors'). The other question isn't asked that even with the turnover is that a good thing that insulin essentially accelerates such a process? From what I had remembered early on in my learning of low carb some people talked about IDE or insulin degrading enzymes being part of the process of clearing young plaques from the brain and with elevated insulin this does not happen, I believe much of this has now fallen by the wayside but it does beg the question is insulin really a good thing and did they try other substrates like Ketones to see if this process happens by other means etc.
4 місяці тому
I think you should offer yourself as a speaker on the Low Carb Cruise. Next one goes to Alaska next year. I am about to go on this years cruise tomorrow. Feldman will be there. You should be on the 2025.
Interesting but that would suggest that IR, consistently high Insulin, would trigger consistent mitochondrial turnover.. which would tend to reduce things like Altzhimers, but the data shows that IR increases risk. Makes me wonder if there is a habituation or other effect that eventually reduces the effectiveness of the pink turnover for chronic high insulin....
I have a question. I am a bit late, so I hope it still gets answered. If I am on a keto diet and my insuline is most of the time low. Does it mean mitophagy isn't happening? And this also a risk factor for Alzheimers? Should I sometimes raise my insulin with a little bit of carbs? Or is there a different mechanism at work? From what I gathered a ketogenic diet would not be ideal, which I am not sure I want to believe. 😊
Spending a little more time explaining the relationships between the enzymes in the core mechanism would help lay people understand what is doing what, where. Knowing your audience is important as you traverse this journey. I appreciate the video, and will share it on social media. Subscribed for more Biochemistry research discussion.
I like when you explain the science. You make it understandable. Most of the time when I have to rewind is when I get distracted and not because you’ve lost me with your explanation. I enjoy all of your videos and appreciate the education. I also appreciate the respectful presentation of the information.
Thank you, Nick! I am very interested in mitochondria since taking and discontinuing a statin. It was bad for my brain and body. Recovery has been slow.
Can you research exercise intolerance and give us a video to help those with chronic illness, please? Post exertional malaise PEM has many root causes.
1) I don’t see the relationship between the first part of the video with cycling on and off eating. 10:45 2) We are told we need to lower our insulin to get into autophagy. This Petri dish study says insulin triggers mitochondria autophagy. ??
Dude had to comment again. Tooo many sound effects! If you need somethung in the background, use a drone sound. Your content isnt a fast paced tiktok video! Its a magnificent educational video, and we are here to learn because we like to learn, not get overstimulated by the sound effects and visuals! The visuals are fine, they dont really interrupt your message
I'm fine with the clickbait even if I prefer more formal titles. Those shenanigans with sound I can't approve however. I won't finish the video if only one ear hears what's being said.
One thing you could add is information at the end of each video that is actionable for people trying to optimize their health. Tie the topic to practicle changes in behavior that would be beneficial. It's a stretch I know but could be very useful.
Am i right to say that this applies most to neuron cells? Mitophagy in other cells in the body may behave differently? Since its counter intuitive that keep insulin low is good for health but at the same tiem bad as it suppression mitophagy?
Love your content so thought id share my opinion on the sound effects you decided to use for thisvideo. They are a bit disturbing as what you say really demands our attention for it to have meaning. What im trying to say is your content is so easy to pay attention to that you dont need sound effects all over the place 😊
I like your variety of approaches to engage your audience. This video is by far the most interesting lead in to intermittent fasting that I have seen. You show the biochemistry of why you should do it. I like your intellectual approach even if I have to watch it five times to understand it. Thanks for sharing.
When we fast, insulin levels are low, it spikes when we eat, especially carbs. So, does that mean there is no mitophagy when we fast and it only activates when we eat? The current view is that fasting promotes mitophagy. Could you clarify? Thank you. Love your channel, btw.
No b/c cell and spatially specific. Autophagy can happen at different times in different places in the body + & you're always producing insulin, so a function of insulin and sensitivity + you release some insulin in response to food even if there aren't carbs (assuming not T1D)
Thank you, for being such a good teacher, one who is passionate about sharing the knowledge, and treats us as companions in the journey, not followers...
One of the things that I truly appreciate about your channel is that you take incredibly complicated scientific studies and concepts and translate them in to simple language for the rest of us. I want to know about all of the scientific research going on out there, but there is no way that I could read and understand it myself.
Thank you! That means a lot!
Eat carnivore omad walking fasting ice bading zeolith sun d3 NAC msm borax dmso never ever take the clot shot seed oils sugar and carbs oxalates processed food pestozides
I don't listen to intellectuals unless they can credibly wear a sleeveless shirt.
This. Thanks for that!
No, same here!
Here's my recall from a single watch-through:
1) Brain has neurons
2) They need lots of energy
3) They are sorta like octopi...octopuses?.. - they have a large main mass which had many "arms".
4) For some reason they need mitochondria at the end of the arms to "turn over" at a specific time and not all the time.
5) Insulin triggers the "turnover" somehow
6) Insulin resistance can f•ck up the ability for the mitochobdria to get the memo from insulin
7) This means the mitochondria don't "turn over" at the right time and get old or something
In other words, insulin resistance can negatively effect brain health.
❤
Long story short….pretty much
further simplifying the simplified 👍
So go on a ketogenic diet.
@@calebrobinson7277 No not ketogenic, time restricted eating, its the cycle that counts, not constant keto
Yes! Both and! Always appreciate your approach and good to hear "another side" to what "experts" in the HC industry have spouted as "known and settled science" for decades.
Definitely not settled science! Science that's settled is boring anyway
I really enjoyed the presentation style / approach: it was refreshing and engaging. The graphics were really good! Pace of delivery was just fine. I found the subject really interesting, particularly as my own background is in physiology / pathology. Definitely subscribing 😀.
My dad died of dementia two years ago. Great content, great presentation. Thank you!
Sorry about your dad. That’s really hard. Glad you enjoyed the video
For me personally, I love the deep dense dives, but the "baity" videos are fun and are more helpful for the ketovore support group I lead. I think you are striking an excellent balance and I really enjoy the content you are bringing to the table. So, Thank you!!
*keto
@00:29 "This creates a spatial problem..." A lot of my friends say _I'm_ spatial. At least I think that's what they're saying. Does that mean I'm brainy, or nervy?
*@**4:19** NOTE: AMPK can be disabled by polyol, one of the intermediate metabolic steps of the break-down of fructose. Fructose levels in the brain and spinal cord are the CNS's response to osmotic pressure generated by sugar levels in the rest of the body, outside the blood-brain-spinal cord barrier. Motto of the story: cut out all sugars, and all carbs possible.*
MORE! WE WANT MORE! I actually started making notes
Yay!!!!
Personally, I enjoy both of your approaches
Awesome, thank you!
Am I the only one who thinks that a fit intellectual in a sleeveless cut off shirt is awesome?
I like you!
@@nicknorwitzPhD The feeling is mutual!
Sounds great, but not always possible. In the beginning, 120 hr work week plus classes. Then supervision of others and 24 hr on call, then private practice with a whole new set of problems. Or the ones that dedicate their life to science, studies ,...Sacrificing everything for their passion. Think of an Albert Einstein or a Tesla. Think of a Walter Willett....many examples. Not an easy path. Stress, job demands....then if a wife or kids involved, never seen a ripped / jacked +200 lbs physician or professor that wasn't divorced. Lots of trade offs. Something has to give.
@@DrAJ_LatinAmerica I agree... and medicine and healthcare are changing... I'm in the process if figuring out my priorities and what will give. But you're right... can't be a researcher, physician, public educator, healthy, and a good partner and parent...
It makes me want to give him a hug
Such a excellent level of detail. Thank you for doing these types of educational videos!!!
Thank you very much!
Impressive unpacking of complex studies in just a few minutes...graphics & reading very supportive. Speed is good...don't slow it down.
I don't have a "slow" button... ask anyone who knows me. And THANKS!
We can adjust the YT speed of the video though 😂
As a physician with a degree in nutrition, I am amazed and joy filled being educated and entertained by your channel. Great balance and remember…..Stay Curious!
I appreciate that! Thank you kindly!
I think you need to simplify it a bit more. Young and pink means nothing to me. Is it good or bad - that means something.
Love your research and willingness to share! Keep up the great work, and Stay Curious!
Stay Curious!!!
I love your approach and your sense of humour. Keep up the good work and please keep being your authentic self.
Appreciate you :)
My father and I have ApoE3/4 and my grandfather had Alzheimers. I find this EXTREMELY critical information for my father and I!
Sorry about your father. I'm ApoE4/4... but I think gene editing is very promising ... MIT doing some AMAZING stuff...
How does it help? Is there any preventative action he can take with this info? Should he be doing things to increase his insulin?
@@supercal333intermittent fasting helps
@@supercal333the idea is to increase sensitivity
@@supercal333I don't think you necessarily want to increase insulin but you do want to increase insulin sensitivity. This is a highly debated topic. The low carb people will tell you that reducing carbs will increase sensitivity but the plant based people will tell you fat reduces sensitivity and that you need to eat very low fat high carb. Who do we believe. But I think that intermittent fasting is universally agreed to help insulin sensitivity so, if nothing else, just extending your overnight fast is going to help. As for which dietary interventions you take, you need to do lots of research and decide for yourself what you think makes the most sense.
I think the speed, animation, etc, are all really good.
Cheers man!
Thank you Nick for continuing to educate all of us as to how the human body metabolism actually works. Bravo! 🙂
You're welcome!
I thought Alzheimer’s Disease was thought to be a disease of insulin resistance of the brain? And that a diet that decreases circulating insulin levels promotes mitochondrial health in general, especially in the brain. So are these benefits of PINK1 decreased in those of us following a low carb lifestyle?
It almost sounds opposite of what we've been talk recently about insulin, so maybe i'm not understanding
There's a relationship between IR and AD, but it's not quite so linear. I think engaging in a lifestyle that improves metabolic health will overall serve one well in preventing AD
I appreciate your gifts of these well-paced, tight explanations. Your curiosity and enthusiasm shine!
What I appreciate about your science communication is that you’re not looking to take findings from papers and use them to assign “good” and “bad” labels to various things. I think I have a tendency to do that when I’m reading papers on my own, just as a means of simplification.
You get me!
please keep talking fast. I have a back button and a replay button
Ha! Noted.
And.. Playback speed control in the settings
I think this video was very well done with a breakdown and explanation that I can understand. I thought the graphics were well-matched to the narrative. Also, I appreciated your recognition of your tendency to speak rapidly. You then slowed down which resulted in my being able to more easily follow what you were saying. I enjoy all your videos, tho must admit a few have been way over my head. But please, keep putting out your content. I’m always learning something from you. Thank you!!
Thank you!
As a person who is approaching 50 years of living with type 1 diabetes, who is working hard at understanding his health and hopes for a good long life, and whose father suffered severe mental degradation at the end of his life, I both love this type of content and enormously benefited from this specific video. Thanks!
Thank you. This really helped me understand why Dr Dale Bredesen recommends intermittent fasting along with ketosis for an APOE4/4.
Thank you for these vids. Mitochondria are so basic we must get our understanding of them right. A video that addresses the uncoupling of mitochondria would be a good follow-up.
I'm sure you have considered what the IQ needed is to be able to, at least in basic terms, understand your content. If you want a broader range, you will have to to dumb down a little bit. I don't believe that's what you want. The "less intelectual" videos are still aimed at the same audience. You use those to reach more people, but they don't broaden your audience all that much.
You are good at simplifying things, mostly by removing all the jargon or at least explain what it all means. That's what makes it possible for people like myself, that aren't in medicine, to understand what you are talking about.
36K followers however is just a small percentage of your potential audience. If you want to reach more of your audience, the solution is in optimization of your channel. This includes learning to write optimized descriptions for your videos, and using playlists better than you are now. You have only 3 playlists. You need to organize all your videos by different themes and create a playlist for each one. You can add a video to multiple playlists if it makes sense to do so. You can also order them in a playlist so they make logical sense to watch in series. It doesn't have to be by publishing dates.
And last but not least,... identify keywords/themes that are popular and find out if any of those you can use on your channel. There may be new ideas there that fit your goals for your channel.
Hi from Japan!
Thank you for sharing such interesting studies on your channel!
In this video, the study says that Mitophagy occurs when AMPK is off due to insulin signalling. Would that mean that most mitophagy occurs postprandially?
It challenges the common idea that mitophagy happens during prolonged fasting states. Please elaborate.
Watch the video again -- carefully -- yes there is a counterintuitive aspect that you're keenly picking up on... one of the things in this paper that struck me... good catch!
@@nicknorwitzPhD Thank you for your reply. Are you pointing out at the ebbs and flows section of the video?
In other words, fasting will improve insulin sensitivity which may in turn increase mitophagy postprandially.
It would be interesting to see how strong and how long the insulin signal needs to be in order to initiate mitophagy…one possible question: are slow long meals better than short ones or vice versa?
Studies into APOE4 in 3rd world countries show it drives cognitive fortitude to adverse environments.
Prevents cognitive decline from starvation or toxic exposures.
You must be getting the content right. Every time I see a new one I make time to watch it.
I often spend time afterwards looking up more details on the complex things you cover.
I like the graphics & charts you add. These are very helpful for me to understand.
Would LOVE to hear your opinion on the study finding that: The authors of this study write, "...the lowest risk for long-term mortality appears to exist in the wide LDL-C range of 100-189 mg/dL, which is much higher than current recommendations."
Mike Mutzel is presenting the study here: ua-cam.com/video/4nm-xIq7I2Q/v-deo.html
I have a video on ApoB and All Cause Mortality in production
Every time you speak, you say something interesting, whether using celery, Oreos, AMPK, or mitocondria. I love it all! Keep it going.
Thanks! 😃
This video was great thank you. It was really cool to have a breakdown of a recent paper in biology and understand most of what was going on. I don't think you talk too fast. Apart from when you read out the title of the paper which you obviously did fast intentionally, but that's a bit like "I'm assuming you won't be able to understand this". I think if you had read it out slowly then I would have been able to understand it
Glad it was helpful!
Getting people to think! How dare you! (Yes, I'm joking)
I dare!
Listening to this makes me realise how limited my brain is!
Do a mix. We also want to see “normal Nick”… everyday Nick like if you go to your mothers house do you eat the food she gives you or are you a total OCD foodie? I do like your science ones but as we all know scientists are sometimes looking into the black hole but never pull their heads out to see the bigger picture and sometimes miss the truth
Ironically I just closed a recording video talking about my (our) summer projects of making cheesecakes with my girlfriend, who is not keto. At my mother's house, I do the cooking ;). And, yes, I'm very happy to make normal desserts and sweet potato side dishes for those who enjoy them. I "do me" so to speak as I use a KD therapeutically.
I’m now confused. I thought that autophagy, which I assume includes mitophagy, is turned on after prolonged fasting, which turns insulin off, and now you are saying that insulin through inhibiting ampk turns mitophagy ON. Where have I gone wrong?
Nope... you caught the counterintuitive aspect of this paper... which they in fact point out and which captured me. The body is complex and different spaces, organs, cells and sub compartment in cells can operate in different ways. COOL RIGHT?!
@@nicknorwitzPhD Yes, that is cool, explaining why, as you said, cerebral insulin resistance can have such a devastating effect
I love that you break it all down, I definitely appreciate the slightly slower pace of this video.
I also really appreciate yours and Dave's approach as curious scientists willing to follow where the science leads and not just trying to make it say what you want it to.
I can't stand the aragance of some of your detractors.
Keep up the good work!
If your going to wear a shirt with no sleeves it should say hulkamania on it.
I’m pretty far from the Hulk 😂… I’m not exactly Liver King nor have Thomas DeLauer arms. Oh well
so whats the best way to check on whether YOUR own, MY own mitocohondria are pink and healthy? I know brown fat is different colour due to the mitochondria concentrations. The tissue is darker. How can I monitor my MITOCHONDRIA mr Ralph Macchio? Andre
identifying physiological mechanism is powerful and important, not least because it illustrates how much is not known. I think it's critical to keep learning and refining the understanding while not being too dogmatic about macroscopic conclusions and proclamations related to the general population.
Amazing video! Really easy to understand all the information.
OK so what should us that have the ApoE4 ultimately be doing beyond LC/Keto/Carni/IF & healthy metabolism??? I actually have 2 copies of ApoE4 😟.
I don’t understand what this means I have to do as a low insulin key compliant keto diabetic?
This was super hard to follow while having my eggs bene 😂 which probably didnt help, im usually always multitasking (working out, chores, driving etc) when watching or listening to YT.
The animation is always improving so youre nailing that part, and it helped to keep me locked in (compared to Laynes latest vid on protein which just showed a diagram 😂).
I'm wondering whether you might consider simple analogies if possible to help simplify the logic. There was so much jargon, id probably have to rewatch it 3x with a notepad, and a laptop to lookup definitions etc, which realistically probably wont happen.
I appreciate you doing the work to explain complex science, hopefully my attention span and intellect can keep up.
Good work Nick 👊😎
You said ORTHOGONAL! Right there you made this a dense one... That said any experiment where you tag stuff and can SEE with your very own eyes the co-location of action is just plain science porn! This made me orthogonal too...
1) Great video as always Nick! You continue to open my eyes to neuronced (6/10 pun?) areas of science and such a wide variety of fascinating literature!
2)If I am interpreting this correctly the production of insulin (Presumably bolus insulin) inhibits AMPK and turns on necessary mitophagy. However the frequency of these insulin spikes may lead to unbalanced mitochondrial turnover and eventually reduced ability to turnover when necessary.
3) Do you think perhaps it occurs post prandially as there is readily available energy coming in for the body and cells to use to breakdown and build new mitochondria?
4) Do we know if all mitochondria in neurons undergo mitophagy every time in the presence of insulin or are there other signaling molecules or mechanisms that prevent every mitochondria from being turned over if they have recently been created?
Would love to know your thoughts and no stress if you don't have the time to answer! I will keep learning!
I might need that shirt. I can't tell you how many people I've told about the Oreo Cookie Experiment. I love seeing people's reaction. Of course, I say the same thing Nick does, this DOES NOT mean Oreos are healthy, LOL, but it's meant to be provocative and encourage more studies.
Interesting - Could this be the mechanism by which glucose breaks down mitochondrial networks - triggering mitoptosis? Further, you need cycles of insulin to keep mitochondria pink1 (ahem), but if there are too frequent cycles it can lead to inefficiencies (or perhaps the short chains are good for glucose metabolism), or perhaps cells that are constantly in a state of building mitochondria themselves much less their networks. Insulin resistance would lead to mitochondria becoming old, and perhaps less efficient.. perhaps leading to similar issues. Nick, bring it all together!
AMPK blocks mitophagy , counter-intuitive !
Like most of the good thing out of AMPK is delayed until the ATP is back.
All this is fascinating. If you could zoom out and speculate at the disease level, could this be why diabetics have a higher rate of Alzheimer's? I've often heard that APOE4 is the wild type, the one most of our hunter-gatherer ancestors would have had? So, fasting which would mimic their feast and famine cycles in nature, would be advantageous. Then my question is there must be some instances when not having efficient mitophagy is an advantage in nature?
Another vote for maintaining your mixture of “baity” and more rigorous videos. It’s impossible to grow/maintain your audience if every video is at a high-technical level, and if you aren’t able to grow/maintain your numbers you will not be achieving a core mission of educating the masses. Educating and engaging other PhDs is nice, but you can do better than that. Among your gifts is the ability to educate and engage thoughtful people who are not at your scientific level. Plus, even your more “baity” videos have more substance than most other channels. I think you’re doing great; stay on the path. There’s still plenty to learn and share.
I like your videos, no matter the style.
Thanks :)
Your sincerity is your greatest gift. I still have a hard time following some of your stuff, but I enjoy watching it. This video I'm left with 1. does everyone have apoe4 and 3 cause it sounds like yes. 2. If it is yes how do you know you "turned it on." 3. So is insulin the bad guy in this or the good guy? It sounds like the good guy if we need it for mitophagy? I'll watch it again, but I'm left a little overwhelmed.
Love the videos, regarding the styles, just keep doing what you're doing, the only issue with the ones like Celery has more calories, is that you will get some vegan who uses that title to 'debunk' you, like one did recently with Dr Anthony Chaffee.
Love the work you're doing with regards to LMHR, please keep it up.
Hi doctor thanks a lot for the videos, I really appreciate the content. I would like to ask you a question. Do slightly over-physiological doses of testosterone interfere with the process of autophagy and mitophagy? I ask because insulin is an anabolic hormone and so is testosterone. I ask my doctor but he doesn't know. Thanks again.
This is one of a myriad of pathways thought to affect Alzheimer's generation (I think I saw a claim of 27 different associations ... rather than 'risk factors'). The other question isn't asked that even with the turnover is that a good thing that insulin essentially accelerates such a process? From what I had remembered early on in my learning of low carb some people talked about IDE or insulin degrading enzymes being part of the process of clearing young plaques from the brain and with elevated insulin this does not happen, I believe much of this has now fallen by the wayside but it does beg the question is insulin really a good thing and did they try other substrates like Ketones to see if this process happens by other means etc.
I think you should offer yourself as a speaker on the Low Carb Cruise. Next one goes to Alaska next year. I am about to go on this years cruise tomorrow. Feldman will be there. You should be on the 2025.
Interesting but that would suggest that IR, consistently high Insulin, would trigger consistent mitochondrial turnover.. which would tend to reduce things like Altzhimers, but the data shows that IR increases risk. Makes me wonder if there is a habituation or other effect that eventually reduces the effectiveness of the pink turnover for chronic high insulin....
Can you address Neuropathy? Sounds like you are addressing the diabetic side effect of nerve damage due to diet.
I have a question. I am a bit late, so I hope it still gets answered.
If I am on a keto diet and my insuline is most of the time low. Does it mean mitophagy isn't happening? And this also a risk factor for Alzheimers? Should I sometimes raise my insulin with a little bit of carbs? Or is there a different mechanism at work?
From what I gathered a ketogenic diet would not be ideal, which I am not sure I want to believe. 😊
Spending a little more time explaining the relationships between the enzymes in the core mechanism would help lay people understand what is doing what, where. Knowing your audience is important as you traverse this journey. I appreciate the video, and will share it on social media. Subscribed for more Biochemistry research discussion.
awesome video. thanks so much
Glad you liked it!
I like when you explain the science. You make it understandable. Most of the time when I have to rewind is when I get distracted and not because you’ve lost me with your explanation. I enjoy all of your videos and appreciate the education. I also appreciate the respectful presentation of the information.
Thanks so much for the kind words and feedback
Thank you, Nick! I am very interested in mitochondria since taking and discontinuing a statin. It was bad for my brain and body. Recovery has been slow.
Can you research exercise intolerance and give us a video to help those with chronic illness, please? Post exertional malaise PEM has many root causes.
1) I don’t see the relationship between the first part of the video with cycling on and off eating. 10:45
2) We are told we need to lower our insulin to get into autophagy. This Petri dish study says insulin triggers mitochondria autophagy. ??
Dude had to comment again. Tooo many sound effects! If you need somethung in the background, use a drone sound. Your content isnt a fast paced tiktok video! Its a magnificent educational video, and we are here to learn because we like to learn, not get overstimulated by the sound effects and visuals! The visuals are fine, they dont really interrupt your message
I heard switching to ketones for energy (fasting, ketogenic diet, exercise etc.) your brain works much more efficiently.
I'm fine with the clickbait even if I prefer more formal titles. Those shenanigans with sound I can't approve however. I won't finish the video if only one ear hears what's being said.
One thing you could add is information at the end of each video that is actionable for people trying to optimize their health. Tie the topic to practicle changes in behavior that would be beneficial. It's a stretch I know but could be very useful.
KEEP DOING WHAT YOU ARE DOING.
Cheers! Will do
IMO You have a good blend of content. Prob something like a 3:1 ratio of dense to the celery type.
I have 2 copies of APOe4. I started keto a few months ago. So does this mean I need a longer fasting window to increase mitophagy.
So, I don't think you said it, but insulin resistance plays into this, right? So perpetually high insulin affects dysfunction in this context?
Am i right to say that this applies most to neuron cells? Mitophagy in other cells in the body may behave differently? Since its counter intuitive that keep insulin low is good for health but at the same tiem bad as it suppression mitophagy?
You have zero empathy for our private linigacy. You got clicks, got me
I like both of your content.
But don't be sad if your try to win vs natural selection ends out of the expectation.
Great video again. So fascinating
You're very welcome!
Nick , that was awesome. Can you go over the Randal cycle?
Love your content so thought id share my opinion on the sound effects you decided to use for thisvideo. They are a bit disturbing as what you say really demands our attention for it to have meaning. What im trying to say is your content is so easy to pay attention to that you dont need sound effects all over the place 😊
I'm in awe of the science 🤗
Yas 👏
So if insulin is patologic high..... = mitochondria goes in to constant mitophagy.... = not so good for metabolic rate ..
So what's the action to be taken here. Should we be trying to increase our insulin to prevent neurodegenerative diseases as we age?
So if Insulin is good for your brain, does that mean we should eat more carbs to get more insulin?
Love this delivery and graphics. I think visibly seeing the connection points and written captions helps me understand better.
Happy you're happy :)
When you feel sleepy after a meal, you are turning over mitochondria in the brain.
I like your variety of approaches to engage your audience. This video is by far the most interesting lead in to intermittent fasting that I have seen. You show the biochemistry of why you should do it. I like your intellectual approach even if I have to watch it five times to understand it. Thanks for sharing.
I appreciate that!
Your balance is fine, and very much appreciated. I get a strong sense of honesty from you, and I really enjoy your self experimentation. Kudos.
I appreciate that!
When we fast, insulin levels are low, it spikes when we eat, especially carbs. So, does that mean there is no mitophagy when we fast and it only activates when we eat? The current view is that fasting promotes mitophagy. Could you clarify? Thank you. Love your channel, btw.
No b/c cell and spatially specific. Autophagy can happen at different times in different places in the body + & you're always producing insulin, so a function of insulin and sensitivity + you release some insulin in response to food even if there aren't carbs (assuming not T1D)
I was searching NN’s store for a Dayspring t-shirt.
Love this video, but also enjoy your humor...
I like the variety. Good work and very thoughtful design.
What are the times you fast? Are you skipping breakfast if so are you aware of the studies that say this might increase LDL?
I usually practice 16-8 with my first meal around 1030 am and dinner around 6 pm if I have my choice.
Thank you, for being such a good teacher, one who is passionate about sharing the knowledge, and treats us as companions in the journey, not followers...
Wow, thank you! Means a lot 🥹
I enjoy the balance!! Love the science but also love the practical ideas! you explain complex science in easy to understand terms!! 💕💕
Thank you very much :).
UA-camrs need to learn to use the settings button to change the speed to suit themselves.
Wondering if you'd be up for addressing / weaving in an axiom I ran into : "insulin suppresses autophagy."
Sure: “simplicity is the death of nuance” is my answer
Btw Nick, they have play speed settings on YT, so just speak normally and viewers can just adjust the speed up or down to suit 👊😎
(That’s my inside thought!)
makes sense, it's cool when when there is no pollitics injected or industry related zig-zags of information and you say things straight :D
I try my best :)