216 - Metabolomics, NAD+, and cancer metabolism | Josh Rabinowitz, M.D., Ph.D.
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- เผยแพร่เมื่อ 25 มิ.ย. 2024
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Josh Rabinowitz is a Professor of Chemistry and Integrative Genomics at Princeton University, where his research focuses on developing a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. In this episode, Josh focuses the discussion on three main topics: metabolomics, NAD (and its precursors), and cancer metabolism. The metabolomics discussion starts with a broad definition of metabolism, metabolites, and fluxomics before diving deep into glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. He then gives a detailed explanation of the electron transport chain and Krebs cycle and their implications with respect to both drugs and nutrition while also explaining how NAD is central to the process of energy generation. He then discusses the age-related decline in NAD and what current literature says about efforts to increase NAD through intravenous or oral supplementation with the precursors NMN and NR, including whether doing so provides any advantage to lifespan or healthspan. Finally, Josh ends the conversation talking about cancer metabolism and how one particular intersection between cancer metabolism and immunotherapy might provide a hopeful outlook on the future of cancer treatment.
We discuss:
0:00:00 - Intro
0:00:08 - Josh’s background and unique path to becoming a research scientist at Princeton
0:09:11 - What sparked Josh’s early interest in metabolism
0:14:59 - Metabolomics 101: defining metabolites and how they are regulated
0:25:42 - Fluxomics: Metabolism as a system in action
0:34:43 - The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation
0:37:44 - The important role of lactate as an alternate fuel
0:50:09 - Fasting lactate levels as a potential early indicator of metabolic dysfunction
0:57:17 - The beauty of the Krebs cycle and the role of NAD in energy production
1:10:46 - How the drug metformin acts on complex I of the electron transport chain
1:15:30 - The difference between NADH and NADPH
1:17:45 - NAD levels with age, and the efficacy of supplementing with intravenous NAD
1:31:44 - The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN
1:43:59 - Exploring the hypothesis that boosting NAD levels is beneficial
1:51:25 - Cancer metabolism and the intersection with immunotherapy
2:00:17 - Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more
2:05:06 - The challenge of treating pancreatic cancer
2:12:07 - Epithelial cancers that might respond to metabolic approaches to therapy
2:14:50 - Josh’s hopeful outlook on the future of cancer treatment
2:16:39 - Nutritional approaches to cancer attenuation
2:23:26 - What makes Princeton University special
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About:
The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 45 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.
Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life).
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In this episode, we discuss:
0:00:00 - Intro
0:00:08 - Josh’s background and unique path to becoming a research scientist at Princeton
0:09:11 - What sparked Josh’s early interest in metabolism
0:14:59 - Metabolomics 101: defining metabolites and how they are regulated
0:25:42 - Fluxomics: Metabolism as a system in action
0:34:43 - The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation
0:37:44 - The important role of lactate as an alternate fuel
0:50:09 - Fasting lactate levels as a potential early indicator of metabolic dysfunction
0:57:17 - The beauty of the Krebs cycle and the role of NAD in energy production
1:10:46 - How the drug metformin acts on complex I of the electron transport chain
1:15:30 - The difference between NADH and NADPH
1:17:45 - NAD levels with age, and the efficacy of supplementing with intravenous NAD
1:31:44 - The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN
1:43:59 - Exploring the hypothesis that boosting NAD levels is beneficial
1:51:25 - Cancer metabolism and the intersection with immunotherapy
2:00:17 - Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more
2:05:06 - The challenge of treating pancreatic cancer
2:12:07 - Epithelial cancers that might respond to metabolic approaches to therapy
2:14:50 - Josh’s hopeful outlook on the future of cancer treatment
2:16:39 - Nutritional approaches to cancer attenuation
2:23:26 - What makes Princeton University special
Olllo9
😅yaatyaud7syf
To your last point, I am admittedly a biohacker. But as a recent cancer patient as well, I can tell you that adherence would be great for cancer patients IF mainstream medicine endorses it. The problem is mainstream medicine across the board doesn't believe in any type of diet or exercise interventions for anyone with cancer. It's not cancer patient's adherence that needs to change, it's doctor's education and beliefs, and the whole medical system that need to change.
💯 ‼️
abso fuckin' lutely!!!!
Absolutely…..
Agree. But we do not see any discussion re Thomas Seyfrieds (cell biologist's ie. not a MD's) metabolic aproach to cancer even here. US insurance driven business model is a huge problem to the ROW countries with more public (w/h)ealthcare.
True statement. Mainstream medicine needs to incorporate dietary and nutritional supplement changes in their protocol. Now, they refuse to advocate for anything not approved effective by FDA. Problem with that is multi dimensional since some dietary and nutritional supplements help some patients and not others. Still, it would be helpful if the medical, provider gave the cancer dietary options they could try rather than forcing the patient to wander alone in the cancer studies wilderness with NO backup.
My personal experience with NAD+ subcutaneous injections and NMN orally has been incredible. I'm a hobby farmer and semi-retired pharmacist. Before taking them, I could do a half day of work on the farm and be wrecked. The rest of the day and the day after. Now, I can do strenuous manual labor all day long and get up and do it again the following day!
Nianicimide (flushing) boosts NAD+. Should I look into subq?
Great episode! I'm a master's student of biomedicine and nutrition at TUM and I can tell that, unfortunately, the lactate topic is still taught in the old way. Nobody is talking about lactate as a key metabolite and intermediate in glucose metabolism outside the Kori cycle. :( Honestly, the level of depth and knowledge that I find in these podcasts is way beyond what universities offer.
it is the same as 'standard care' in treating patient.
Great talk 🙏🖖My father is a pancreatic cancer survivor and it has been 5.5 years. No signs of cancer have returned. Therapy was: surgery, chemotherapy and meanwhile (until today) sulforaphane (broccoli sprouts/capsules with both precursors).
Congrats to your dad on beating pancreatic cancer ..
I adore Josh's scientific reservation and his healthy common sense approach. Absolutely ethical, humble and genius researcher. I wish more scientists could try to be like him, and DO their science instead of SELL their science. Awesome podcast! Thanks!
But does he endorse the jab!?
Dr. Attia delivers yet another mind blowing interview. I’m so grateful.
Great discussion. I love learning about metabolism especially as it relates to insulin. I think that Dr. Ben Bikman would be a great person to have on the show in regards to metabolomics of diabetes and insulin specifically.
I had mucosal melanoma. The genetics of my tumor suggested that reducing insulin and glucose would help. I had Opdivo and Yervoy neoadjuvantly and take metformin and eat low carb. Mucosal melanoma has a very low level of mutations; pretty cold tumor. I am currently in remission.
Thank you so much for making this video, I never get notices when you post a new one and I double checked and Yep I forgot to click the bell so I should be receiving them I hope. I really enjoy your topics I’m sure you know David Sinclair I’ve learned a lot from him also but this lactic acid Not too much about that I haven’t really watch the whole video yet I am right at the point where I start to talk about that and it really concerns me about my muscles I am 86 years old as of July 10, 2022 and I had that virus four years ago so now I’m on oxygen and I walk with a walker I guess I passed out and fell on the kitchen floor and broke my humerus bone, it’s hard to really remember what happened to me I managed to call my daughter and she came over and she thought I was in heaven with the Lord that I was still alive anyway three months in the ICU and all the toxic chemicals I put in my body they didn’t expect me to make it at all but I’m a fighter and I knew that I needed to fight to live because I already have congenital scoliosis which has progressed a lot and other things wrong with me I don’t wanna mention them all but they were giving me insulin shots and I don’t understand why because I didn’t have type two diabetes ever in my life and I ended up getting 200 pounds on top of my 180 I didn’t like this much because then I go home they can’t do surgery on my arm it’s in this weird cast it stuck on there the fuse together and I’m right handed I have to learn how to do everything left-handed I live alone I don’t have any family members to help me here when I moved here I moved on the second floor but I have a oxygen tank and a walker now and I have been in this apartment now 24 seven except for two visits a year to my regular doctor so high thank you so much for any information that you put on here
Thanks for the best explanation 😊
Great interview
As a neurologist, I wholeheartedly concur!!
Please don't ever stop 😊
Thanks Peter 💓 very interesting and love the conversational tone of this interview. Would love to know what both of you eat every day and avoid. I recently heard you say you hate talking about nutrition 😢
He hates it because it's so muddy. Also I assume one of the main reasons Peter doesn't advertise his diet or pharma regime is because he doesn't believe in a one size fits all approach for a raft of different reasons.
Thanks a lot!!! JR is great. DS started to act as a celebrity recently. JR is way smarter Imao.
Recently? He's a prima donna on an endless loop.
what should one do about mantle cell lymphoma in 80+ yr old male, diabetic, 2nd go with MCL???
I’ve been reading his work for years, and this is my first time seeing a face to his name
I wonder if certain health issues can cause older folks to have much lower NAD. I have celiac and using NAD had seemed to be very helpful
Love it 🔥
Taking nmn put my intracellular nad up quite a lot. Tested by Jinfiniti
Peter , for NMN it could be beneficial to take it if you are at risk for non melanoma skin cancers . 500 mg x 2 / day .
NR doesn't raise circulating levels of NAD+??? Martens et. al 2018: "Oral NR supplementation effectively elevated levels of NAD+ in PBMCs by ~60% compared with placebo". Takashi 2021: "Oral supplementation of 500 mg nicotinamide led to a significant increase in blood NAD+ after 12 h "
Iv ONLY
Understanding that they are not able to get the body to show level increases in the organs especially the brain? Blood serum yes but organs with the exception of the liver no
What happened to the carb-glucose-insulin secretion-muscle glucose uptake-etc pathway? What about insulin resistance?
What about SCOT inhibitors? Do you know about that?
Wish you would have talked about Berberine
Niacin is much cheaper than nmn or nr. Yes, you get a flush which lasts 10 or 15 minutes. I don't see any problem with that
What is a flush I didn’t get that. I’m not native English speaker
@@yowandbm your skin turns red and you feel a tingling
@@berdi4berdi4 oh, thanks. I thought it is more serious issue.
Take magnesium and you won’t get flush
@@yowandbm No, it isn't. It's just uncomfortable for some people.
That made me point that i do not understand high glucose level in diabetes. It is said that the reason is when cells are insulin resistant then they do not take glucose untill insulin is high. But what causes that something knows that glucose should be taken by cells? If i was liver that see high glucose i would simply stop putting it into blood, then of course cells would starve if they are insulin resistant, but they must some how communicate it by blood - what is it?
Does the Randle hypothesis imply that low fat diet is better for allowing the body to burn glucose? And how does it explain why some people can eat a mixed diet and never get diabetes?
Genetic lottery of all nondiabetic DNA snps.
People with addiction, namely substance abuse, can use NAD IV infusions to aid with reduction of the withdrawal symptoms. Any validity to the idea that it may restore the dopamine pathways, neurologically speaking, causing a return to what could be considered baseline?
Are there any papers showing why addicts have specific benefit from this type of profitable supplementation service or is this just fad science?
Attia needs to talk to Sinclair, his co chair in the Angermeyer SPAC.
They’ve got to be talking to each other sometimes. No?
@@maxsmart99 they
might be frenemies in the sense that they both to agree on the acquisition project. Attia certainly isn’t quoting the Sinclair copybook on NMN.
He already has on 2 occasions but Sinclair is controversial
th-cam.com/video/T1ACcAwn18Q/w-d-xo.html
In opposition to Peter, Sinclair has a proven track record of being far less interested in letting the prevention of *conflicts of interest* get in the way of accruing mega bucks from companies and the gullible supplement thirsty book buying general public.
Can you do a podcast with Ph.D David Sinclair?
What about IPT?
Photobiomodulation with magnets reduced lactate. Research articles out there 😊
"The cancer cannot make essential polyunsaturates from saturated fats". No mammalian cell can make essential fatty acids. Perhaps cancer cannot make monounsaturated fatty acid and this monounsaturate is needed by all cells, but normal cells can make it, so it is not considered an essential fatty acid.......Thanks for the interesting talk..
Amerika in is a cataclysmic decline in medicine science n technology Much Blessings To All Viewers Worldwide Yuliya ♥️♥️♥️
So NR and NMN pills are waste of money. Got it.
Thomas seyfried is who Peter should get on to talk about this, he's having bat shit crazy results.
Are you guys still using the words "spontaneous remission?
Niacin can flush people on wayyyyy lower doses than "grams". I've seen people flush at 100mg.
I don't see any problem with the flushing
@@berdi4berdi4 I don't either - some people find it very uncomfortable. That said, I was just pointing out the flaw in what was stated in the video.
I think your dose of niacin to cause flush is far too high. I get a very uncomfortable flush at 100mg.
Anyway, the flush lasts for a few minutes. I don't see problem with that. You just feel a bit hot on your skin
@@berdi4berdi4 no it last probably 30 mins and is very uncomfortable for me. Starting low with slow increase helps but I've never been convinced there's any reason to bother.
@@Clem62 Strange. For me its not such a issue. I even find it pleasurable. I usually have around 250mg. I guess it depends on the organism.
why do people do Niacin flushes?
NAD is the key, to reverse aging
“All that economic incentive is great at driving science and clinical answers”. Why not remove the patents & financial incentives of drug companies penetrating the NIH
Genomics is all very interesting. But since you die with the same genome you were born with, the chance of having a great impact on your life with knowledge of genomics is always going to be limited. And whilst gene therapy and epigenetic studies can have an impact that are necessarily limited and very expensive. But by simply knowing the effects of food on genetics we have is massive. Food can kill or cure, enable and disable. And there is so much more to learn than Creb's cycle.
That doesn't follow. Whether you die with your genome or not is irrelevant to whether genomic knowledge can leverage significant life decisions and improvements.
This was pretty depressing to listen too. All the billions of tax payer dollar and the billions more paid by private sector and they basically still don't have squat for a handle on it.
Did you seriously study get the statistics from those who have much much higher success rates? Dr. Nick Gonzales, Dr. James Forsythe, Dr. Thomas Lodi?
Looks like Ryan renolds
Good to hear that these very expensive NAD+ supplements to be taken orally are absolute BS!
Don't waste your $, iv ONLY
How do you feel about taking niacin? I have not yet purchased NR or NMN because I wanted to do some research before I spent my hard earned cash! I do however take resveratrol daily
@@healthhollow7218 I take niacin daily.
I would have done better with estrogen. I have osteoporosis.
There are different reasons for osteoporosis.
Ya know? Ya know? Ya know? Oof
AMAZING talk but why does Josh have a major vocal fry
Will drinking beer 🍺🍺🍺 break my fast?
Why did Attia keep talking over his guest? Did it numerous times at key moments. Not good!
Ok already! Stop scaring the pancreatic cancer patients!
Extremely boring I'll stick with Dr Ford Brewer and I can't take this guy's voice