Dave Feldman
Is MVX the New Frontier in Predicting All Cause Mortality? – Dr. William Cromwell – #CoSci
updated
Check out Adrian Soto-Mota's original thread here: twitter.com/AdrianSotoMota/status/1747474910165798998
Check out Nick Norwitz's video here: youtube.com/watch?v=FcUUqGJBXFM
- For our published papers, visit https://CholesterolCode.com/papers
- Nick's Oreo vs Statin Experiment: cholesterolcode.com/oreos-versus-statins-an-lmhr-cholesterol-drop-n-1
- The Collaborative Science Conference official site: https://CoSci.org (come join us!)
This video covers my initial self-experiments, the development of the Lipid Energy Model, and the challenges faced in moving this research forward.
Chapters:
0:00 - Introduction: The Year of Change in Cholesterol Research
0:10 - Dave's Transition from Software to Lipidology
0:22 - The Low Carb Diet and Cholesterol Spike
0:44 - The Lipid Energy Model Hypothesis
1:03 - Lean Mass Hyperresponders Phenotype
1:41 - The Citizen Science Foundation & Crowdfunding Research
2:30 - The Llist Institute Study & Key Findings
3:01 - Scientific Publications and Community Impact
4:02 - Upcoming Research and Conferences
5:02 - Conclusion: The Future of Cholesterol Research in 2024
-- You can find Part 1 here: youtube.com/watch?v=QVb1ZKyQ3VQ
For our papers, see:
cholesterolcode.com/papers
Social
x.com/realDaveFeldman
instagram.com/realDaveFeldman
UPDATE: you can see my Part 2 here – youtu.be/whdee7n8DO0
His video: youtube.com/watch?v=rHSnKt5kG3I
Shawn Baker's original video (referenced regarding edit): youtube.com/watch?v=0hYLVF7VY3k
For our papers, see:
cholesterolcode.com/papers
Social
x.com/realDaveFeldman
instagram.com/realDaveFeldman
It's actually a fundraising event to benefit the Citizen Science Foundation, and it's going to be fantastic! We have an incredible slate of featured speakers which include Nadir Ali, Ben Bikman, Ken Berry, Ben Bocchicchio, Dominic D'Agostino, Khurram Nasir, Jaime Seeman -- and we've just added William Cromwell, Nick Norwitz, and Amber O'Hearn.
This video isn’t about our main speakers, it’s about *you*.
We want to also feature fellow "citizen scientists" like myself to share their original story, research, and/or hypothesis in a 14 minute talk.
We'll have nearly two dozen slots for these "Citizen Science Speakers", so there's plenty of room. It can be in the style of a TED talk, or deeply entrenched in data. Let us know what you have in mind.
Go to CoSci.org/apply to apply for your speaker slot at our conference, or refer this to someone you know who might be interested.
Please submit by January 7th – we’ll be choosing candidates by the 14th.
I look forward to seeing you all here in Las Vegas this March. Cheers!
Visit CoSci.org to donate and join us!
KETO (#LMHRstudy) vs Control (#MiHeart)
METHODS – 80 Participants of #LMHRstudy fell within #MiHeart age range and were then matched 1:1 for age, gender, race, diabetes mellitus, hyperlipidemia, hypertension, and past smoking to asymptomatic subjects from the #MiHeart cohort.
PRIMARY ANALYSIS – High resolution heart scans (#CCTA) allowing for primary analysis of Total Plaque Score (TPS), Total Stenosis Score (TSS) and Segment Involvement Score (SIS)
RESULTS
The matched mean age was 55.5 years, with mean #LDL cholesterol of 272 mg/dL (max LDL-C 591) mg/dl and mean 4.7 years duration on a ketogenic diet.
🚨 There was no significant difference in coronary plaque burden of #LMHRstudy (mean LDL-C 272) cohort as compared to #MiHeart controls (mean LDL 123 mg/dl); nb: pre-KETO LDL-C in KETO group was 122 mg/dl
🚨 There was no significant difference in CAC (median and IQR) [0 (0,56)] versus [1 (0, 49)], p = 0.520
🚨 No relationship of LDL-C elevations and plaque
⚠️ is still ongoing for second CCTA completion in our cohort by February of 2024. And as always, please continue to work with your doctor.
- I will have my own video reaction and thoughts in the coming hours.
🙏🙏🙏 to everyone -- and I mean everyone -- who helped us get to this pivotal milestone. 🙏🙏🙏
See @nicknorwitzPhD's companion video on this analysis here: youtu.be/IMkDwtJVeB0
To follow updates on the KETO Study (#LMHRstudy), please follow CitizenScienceFoundation.org
For our papers, see:
cholesterolcode.com/papers
Social
x.com/realDaveFeldman
instagram.com/realdavefeldman
cholesterolcode.com/papers
To follow updates on the LMHRstudy, please follow CitizenScienceFoundation.org
Social
x.com/realDaveFeldman
instagram.com/realdavefeldman
We discuss the present view of modern medicine for high ApoB on cardiovascular disease risk in the context of healthy individuals, featuring clips courtesy of an interview with Dr. William Cromwell on the Nutrition Made Simple YouTube channel (youtube.com/watch?v=pcp_uKo-wwM)
Dr. William Cromwell is the Chief Medical Officer of Precision Health Reports - precisionhealthreports.com/bio/wcromwell
Nutrition Made Simple is hosted by Gil Carvalho MD PhD -youtube.com/c/NutritionMadeSimple
0:00 Introduction to the Controversy
0:53 Insulin Resistance and Heart Disease Risk
2:56 The Debate on ApoB and Other Risk Factors
4:59 Interaction of Inflammation, Insulin Resistance, and High apob
5:41 Rising Cholesterol on a Ketogenic Diet
6:00 Study on High LDL Cholesterol with Low Risk Factors
Highlights
- Lean mass hyper-responders exhibit extreme increases in LDL-c on ketogenic diets.
- LDL-c increases in LMHRs are dependent on carbohydrate restriction.
- Other cardiometabolic risk factors are normal to optimal in LMHRs.
- A prudent clinical approach is required for managing LDL-c in LMHR patients.
- Research is warranted to assess mechanisms and cardiovascular risk of this trait.
LMHR are individuals who exhibit extremely high LDL cholesterol (LDL-C) on a ketogenic diet, along with low triglycerides and high HDL-C, indications of good metabolic health. This prospective study aims to assess atherosclerotic plaque development in 100 LMHR using the most sensitive non-invasive imaging technology available, a coronary artery calcium scan with coronary CT angiography.
In the interview, Dave discusses the findings from the baseline scans of the 64 LMHR recruited to date (August 2022). Highlights include that: Participant a mean age is 53 years; Have been on a ketogenic diet with extremely high LDL-C (mean of 233 mg/dl) for an average of 4 years; And, consistent with prior literature (below), LDL-C levels were normal (mean 135 md/dl) prior to their ketogenic diet, they were negative for monogenetic familial hypercholesterolemia, and were indeed leaner than the average American (mean BMI 22.6 kg/m2).
Given the participants’ age and duration of time with LDL-C levels in the top 0.1% of the population, one might expect a substantial amount of plaque in their coronary arteries. However, about two-thirds of participants have 0 Total Plaque Score; and, across all 64 participants, the highest plaque score was 8, out of a 45 scale. Professor Budoff reports the plaque findings are “much lower than I anticipated” (4:45).
DISCLAIMER: This video is based on unpublished and preliminary data that should not be used for the basis of clinical decision making.
Prior studies:
LMHR cohort, Current Developments in Nutrition:
academic.oup.com/cdn/article/6/1/nzab144/6446805
LMHR case study, low-saturated fat:
frontiersin.org/articles/10.3389/fendo.2022.830325/full
Lipid Energy Model:
mdpi.com/2218-1989/12/5/460
Dave’s cholesterol drop n = 1:
pubmed.ncbi.nlm.nih.gov/35938774
Dr Victor Neel, MD PhD is a medical attending and dermatology at MGH. His interest in LMHR derives from the discovery that he himself is a LMHR -- Yes, we just dropped that bomb!
massgeneral.org/doctors/17391/victor-neel
Dr Albert Sy, MD RN is a medical resident at the MGH. He’s also a certified personal trainer and new father of two! He just started a podcast called Omnipotent Health and Fitness, which you should all check out, and can be found at @Omnipotent_HF and @AlbertSyMD on Twitter.
linkedin.com/in/albert-sy-408b9160
And, of, course, you all know Dr. Nick Norwitz, PhD, who is a medical student doing his clerkship rotations at MGH. He is @nicknorwitz on Twitter. So, we have almost every level of medical hierarchy from Harvard / MGH on this panel: attending, resident, and medical student!
References to our prior papers:
LMHR paper: academic.oup.com/cdn/article/6/1/nzab144/6446805
LMHR case report: frontiersin.org/articles/10.3389/fendo.2022.830325/full
LMHR case report video abstract: youtube.com/watch?v=JSEqIsYBZxU
Lipid Energy Model: mdpi.com/2218-1989/12/5/460
LEM video abstract: youtube.com/watch?v=AkzxESsTJyM
The Lipid Energy Model (LEM) examines the phenomenon of rising cholesterol levels for those on low carbohydrate diets and how this may provide powerful insights into lipid metabolism overall.
The LEM provides a mechanistic explanation for:
(i) the Lean Mass Hyper-Responder (LMHR) phenotype, characterized by the triad of high LDL (at or above 200 mg/dL), high HDL (at or above 80 mg/dL or above), and low triglycerides (at or below 70 mg/dL), as well as for
(ii) the phenomenon that LDL-C change on low-carbohydrate diets tends to associate inversely with BMI.
The LMHR phenotype and observation that leaner people with better metabolic health markers are possibly at greater likelihood for increases in LDL-C were described in our prior observational cohort study: doi.org/10.1093/cdn/nzab144.
We have also recently provided a particularly comprehensive clinical vignette of an LMHR: doi.org/10.3389/fendo.2022.830325.
As a personal aside from the first and last authors (Nick Norwitz and Dave Feldman), while we've longed looked forward to this milestone, we wish to note that this is just the first of many. Interest in LMHR continues to grow, not only within the low-carb community, but within academic medicine. The publication of the LEM hypothesis paper is a landmark, not because it provides a comprehensive theory with rigorous support from human trials assessing the model, but because it presents a concrete hypothesis with direct and testable predictions.
It is our hope that the publication of the LEM paper (version 1.0) will encourage fellow researcher to help us test these ideas in interventional trials and, thereby, advance scientific knowledge regarding LMHR and, perhaps, human lipid metabolism more broadly.
You can also post questions in advanced to our twitter accounts: @realDaveFeldman and @nicknorwitz
Highlights:
- Upon adopting a ketogenic diet relatively low in saturated fat (~18% saturated ~82% unsaturated), the patient’s LDL-C increased from 95 mg/dl to a peak of 545 mg/dl
- Consistent with prior data (doi.org/10.1093/cdn/nzab144) demonstrating an inverse association between BMI and LDL-C on low-carb diets, moderate weight gain contributed to a drop in LDL-C
- Advanced genetic testing, including whole exome and targeting cardiovascular disease panel revealed no genetic variations that could explain his presentation
- Patient underwent a CCTA after 2.5 years at levels comparable to those found in homozygous FH. No detectable plaque was observed.
- Strengths: Patient presents with strong LMHR phenotype despite relatively low sat fat intake, consistent with notation that LMHR phenotype doesn’t require high saturated fat intake; rigorous dietary record keeping and nutrition data extraction; additional exercise and weight tracking; Longitudinal BMI correlates inversely with LDL-C, consistent with prior data; includes advanced genetic testing; includes CCTA at 2.5 years (with time-exposure matched comparison to homozygous FH case)
- Limitations: N = 1. Caution: Should not be generalized to other patient cases. Patient is young and relatively short timespan. Possible or likely patient will develop plaque in coming years and is at increased ASCVD risk. Highlights need for further study on this phenomenon.
For more information and if interested in participating in contributing your anonymized data for citizen science, visit precisionhealthreports.com/oyl
And thanks again to GB for generously contributing their product and services for our LMHR Study.
👇👇👇 Here's a more detailed overview and their contact info 👇👇👇
GBinsight offers advanced genetic testing for high cholesterol, coronary heart disease, type 2 diabetes, obesity and Alzheimer’s disease.
Self-check: Should you take a GBinsight genetic test?
gbhealthwatch.com/gbinsight/patient-overview.php
GBinsight Dyslipidemia and ASCVD Genetic Test
gbhealthwatch.com/gbinsight/gb-panels-info.php?catalog=GB2030
How to Order
gbhealthwatch.com/gbinsight/patient-easy-order-steps.php
Sign up for a Provider Account
gbhealthwatch.com/gbinsight/comboSignup.php
Contact them:
GBinsight
GB HealthWatch
support@gbhealthwatch.com
(858) 224-9879
Highlights:
- Increased LDL-C on Low Carb Diets strongly associate with leanness (low BMI) and low triglyceride/HDL-C ratio
- Modest intervention of added carbs reduced LDL-C in case series
- Further analysis of “Lean Mass Hyper-responder” subcategory
Highlights:
- Increased LDL-C on Low Carb Diets strongly associate with leanness (low BMI) and low triglyceride/HDL-C ratio
- Modest intervention of added carbs reduced LDL-C in case series
- Further analysis of “Lean Mass Hyper-responder” subcategory
Here's their info:
gbhealthwatch.com
Follow them on Twitter & Instagram: @GBHealthWatch
Should you take a GBinsight genetic test?
gbhealthwatch.com/gbinsight/patient-overview.php
How to Order a GBinsight Genetic Test
gbhealthwatch.com/gbinsight/patient-how-to-order.php
GBinsight Dyslipidemia and ASCVD Genetic Test
gbhealthwatch.com/gbinsight/gb-panels-info.php?catalog=GB2030
Contact them: support@gbhealthwatch.com
Own Your Labs is an online service that helps you order your bloodwork privately through LabCorp. It works in three simple steps.
First, go through our site and add blood tests to your cart which you can then pay for at checkout.
Second, after you’ve placed your order, we email you an order sheet for you to print out and bring to your nearest Labcorp to get your bloodwork done.
And third, when Labcorp completes its testing, you can review your results on their patient portal.
There are also other companies like ours that offer this service and we do encourage you to comparison shop.
We even list our favorite choices on the website.
But there is something very unique about Own Your Labs and why we launched it.
Like ourselves, we want to encourage others to share their anonymized data to help our community and advance science.
So when checking out at Own Your Labs, you are given this choice directly.
You can complete your purchase without contribution.
Or you can help out by adding some demographic information and agreeing to submit your anonymized data to our data pool.
As an incentive, we give a special discount for everyone who opts in.
Bear in mind your first and last name, date of birth, city, and any contact information are always withheld from this data pool to help ensure anonymity.
Thank you for watching, and let us know if you have any further questions. ownyourlabs.com/contact-us
If you know little to nothing about cholesterol:
You can check out our Simple Guide to Cholesterol series. It’s full of illustrations and is written for laypeople. cholesterolcode.com/a-simple-guide-to-cholesterol-on-low-carb
You can also enter your cholesterol numbers into our popular Report tool to check them against many risk calculations at the same time – cholesterolcode.com/report
If you’re wanting to learn more about why cholesterol could be higher, particularly on a low carb diet:
You can watch my recent presentation to Stanford University on the Lipid Energy Model – cholesterolcode.com/presenting-the-lipid-energy-model-to-stanford-university
You can check out the Lipid Energy Model poster – cholesterolcode.com/model
Or you can also check out the Frequently Asked Questions (FAQ) page – cholesterolcode.com/hyper-responder-faq
If you’re looking to better understand the risk associated with high cholesterol on a low carb diet:
You can watch my Deep Dive on Cholesterol and Risk presentation for a more optimistic outlook – youtube.com/watch?v=UZv00mMiB9M
Or you can read The Case for Lower LDL on Low Carb by Spencer Nadolsky for the more pessimistic counterpoint – cholesterolcode.com/guest-post-the-case-for-lower-ldl-on-low-carb
If you’d like to understand possible benefits of cholesterol and the immune system:
You can read Siobhan’s overview article on the topic –cholesterolcode.com/lipoprotein-power-ldl-and-the-immune-system
Or watch her presentation – youtube.com/watch?v=c8my6dGwzG4
And if you’d like to learn more about lipoprotein(a), you can check out her presentation on this topic as well – http://cholesterolcode.com/lpa
Lastly — you can always just ask us anything on our Questions Page – cholesterolcode.com/questions
Just be aware our site does not constitute medical advice and we always recommend consulting with your doctor.
Please visit CitizenScienceFoundation.org to contribute – Note this is a public charity with a fully qualified 501(c)(3) status (see your tax preparer for details).
Our companion post for this video can be found here: citizensciencefoundation.org/powering-milestone-and-30000-from-goal-for-travel-and-genetic-testing
Please consider supporting the LMHR study at: CitizenScienceFoundation.org
For a deeper dive into the model, check out my Stanford presentation here: youtube.com/watch?v=ewc7VvbkTTg
For all other questions, visit CholesterolCode.com
Producer Note: Please see the accompanying post on CholesterolCode for the graphics shown.
Site mentioned: Lean Mass Hyper-responders facebook group
facebook.com/groups/LeanMassHyperResponder
1:30 How does Philippa’s view on Lean Mass Hyper-responders differ from Dave’s?
3:11 How Philippa found the Lean Mass Hyper-responders facebook group
6:39 Philippa’s history with Hashimotos and perspective on thyroid function in LMHRs
Producer note: Hashimotos Thyroiditis is an autoimmune condition affecting the thyroid often resulting in an underactive thyroid
7:52 Does Philippa feel Lean Mass Hyper-responders have a thyroid dysfunction?
11:05 In accordance with the lipid energy model, wouldn’t you need lower T3 in order for higher levels of lipolysis to take place?
13:43 Does higher relative delivery of Free Fatty Acids to the liver result in higher production of VLDL? Does it depend on context?
17:31 What is futile cycling of fatty acids? Does it make sense?
21:18 The distributed object network model of energy potential trafficking, and how VLDL and fat tissue repletion, may play a key role.
26:58 Is it possible for someone who has never had hypothyroidism symptoms who went on a low carb diet and developed a Lean Mass Hyper-responder profile to completely erase the profile with medication?
30:35 Example of a Lean Mass Hyper-responder reversing the profile from diet
Producer note: To provide a little additional information, having been in close communication with the LMHR in question, the drop of LDL to 140 mg/dL from 800 mg/dL+ was after increasing weight by ten pounds, increasing meal frequency from one meal a day to two meals a day, decreasing exercise intensity and frequency and including “carb ups”. So macronutrients did change as did multiple other factors. As Philippa said, these are consistent with the lipid energy model, and her thyroid/anabolic signaling model.
33:06 Is the loss of a menstrual cycle in female Lean Mass Hyper-responders a red flag, and/or common?
36:37 Review of triglyceride and fatty acid metabolism in adipose, skeletal muscle, and liver and how it relates to the lipid energy model.
Producer Note: Please see the accompanying post on CholesterolCode for the graphics shown.
Study mentioned: Fatty acid metabolism in adipose tissue, muscle and liver in health and disease - Keith N. Frayn, Peter Arner and Hannele Yki-Järvinen 2006
pubmed.ncbi.nlm.nih.gov/17144882
44:13 What are the commonalities and differences between lipid profiles in people with hypothyroidism and Lean Mass Hyper-responders?
Study mentioned: The effects of thyroid dysfunction on lipid profile – C.V. Rizos, M.S. Elisaf, and E.N. Liberopoulos 2011
ncbi.nlm.nih.gov/pmc/articles/PMC3109527
47:50 Common reasons for high triglycerides in Lean Mass Hyper-responders, and generally for those on a low carb/carnivore diets.
Post mentioned: High triglycerides on low carb and what to do about it.
cholesterolcode.com/high-triglycerides-on-low-carb-and-what-to-do-about-it
Producer note: Going by submitted data on CholesterolCode, triglyceride levels of 200+ are not that uncommon from coffee sensitivity. Although a pull of the data we have would be necessary to see exactly how frequent it is, anywhere between 150-250 is what I most commonly see, from memory.
51:05 HDL and triglyceride inverse correlation and relation to Lean Mass Hyper-responders and the thyroid dysfunction hypothesis
53:11 Are there other things to look out for that may help suggest a non-favorable situation relating to the Lean Mass Hyper-responder profile?
55:40 Dave’s data on IGF-1 and LDL-C compared to predicted correlation
Producer Note: Please see the accompanying post on CholesterolCode for the graphics shown.
58:27 Overview of thyroid markers, their structure, and function
1:02:33 Does Philippa have any additional thoughts to share before wrapping up?
Blood marker changes of interest in Lean Mass Hyper-responders mentioned: MCV (Mean Corpuscular Volume) in 90s-100s, RBC (Red Blood Cell count) decreasing slightly, RDW (Red Blood Cell Distribution Width) increasing slightly
1:05:05 Context of blood markers being studied and how correlation with pathological contexts may be relevant
1:07:29 Leptin levels in the context of low carb, the thyroid dysfunction hypothesis, and the lipid energy model
1:12:50 Will Lean Mass Hyper-responders show signs of insufficient anabolic signaling, such as low bone density, over time?
1:17:37 Dave’s thoughts on investigating potential downsides to the Lean Mass Hyper-responder profile.
Link Mentioned: Philippa’s google doc on the thyroid dysfunction hypothesis
dropbox.com/s/8aqmntirz6t0fat/document%20for%20facebook.docx?dl=0
1:23:08 Outro
Bay of Islands
Tauranga
Napier
Wellington
Dunedin (canceled)
Dubai
London
Wales
Antwerp
Brussels
* Several cities for transfers/layovers not included (like flying Sydney to Perth to ultimately reach Dubai)
You can find more about our research at CholesterolCode.com.
Studies cited for the Triad:
ncbi.nlm.nih.gov/pubmed/27166203
ncbi.nlm.nih.gov/pubmed/11176761
Thanks to everyone who has contributed thus far and helping us to launch this project!
I talk with Nadolsky about the Citizen Science Foundation, LMHR Measurement Project, Q&A and a *VERY BIG ANNOUNCEMENT*!
Please consider supporting this project at CitizenScienceFoundation.org -- thank you!
CitizenScienceFoundation.org
The Lean Mass Hyper-responder (LMHR) phenotype is characterized by LDL cholesterol of 200 mg/dL (5.17 mmol/L) or higher, HDL-C of 80 mg/dL (2.07 mmol/L) or higher, and Triglycerides of 70 mg/dL (0.79 mmol/L) or lower. We are likewise interested in “borderline” LMHRs that are near these same cut points.
We are seeking to help provide wide spectrum blood panels and cardiovascular testing such as CT Angiogram, Carotid Intima Media Thickness (CIMT), and Coronary Artery Calcium (CAC) score to this phenotype of interest.
We further wish to encourage ongoing communication and follow up with participants, including a further set of measurements in five years.
With your support, we hope to gather data for at least 25 of these “hyper-responders”, but hope to meet our stretch goal of 100. We currently estimate costs for these tests to be between $1,000 to $2,000 and will cover wide spectrum blood tests as well as advanced physical testing such as CTA, CIMT, and CAC.
100% of proceeds will go toward testing and service costs for this project.
Again, we’re honored to have your consideration in helping us move this research forward. Thank you!
CitizenScienceFoundation.org
0:00 Intro and Ethan’s background
3:33 Cholesterol Skeptics and Concerned Medical Professionals – meeting in the middle.
( cholesterolcode.com/wp-content/uploads/2019/08/CholesterolScience-with-Ethan-Weiss.png )
8:20 How many patients does Ethan feel reach a decent level of knowledge about lipidology and cardiology?
10:15 Navigating the discussion on the benefits/risks of lipid changes from diet
17:15 When cholesterol is elevated for a metabolic reason alone – does it pose a greater risk?
( cholesterolcode.com/wp-content/uploads/2019/08/CholesterolScience-with-Ethan-Weiss-1.png )
( cholesterolcode.com/wp-content/uploads/2019/08/key-question.png )
23:00 Giving doctors the benefit of the doubt – are doctors just trying to help?
27:10 Dave’s disappointment with perceived lack of curiosity from the medicalsphere.
30:15 The difficulty in discussing possible benefits from lipoproteins and potential influence on all-cause mortality
36:50 Nuances of data collection and statin trials
- Study mentioned: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial thelancet.com/journals/lancet/article/PIIS0140-6736(02)09327-3/fulltext
Note from producer:
In the efficacy and safety statement for the trial mentioned it lists Merck Sharp & Dohme (manufacturers of simvastatin) as well as Hoffmann-La Roche (manufacturers of the vitamins used) as providing partial funding for the study:
-- "The study is being funded by the UK Medical Research Council, the British Heart Foundation, Merck Sharp & Dohme (manufacturers of simvastatin[…]) and Hoffmann-La Roche (manufacturers of the vitamins[…])" doi.org/10.1053/euhj.1998.1350
- However in the published paper of the results it states the following:
-- "The Clinical Trial Service Unit has a staff policy of not accepting honoraria or other payments from the pharmaceutical industry, except for the reimbursement of costs to participate in scientific meetings." doi.org/10.1016/S0140-6736(02)09327-3
44:56 If there were a trial that showed that people with high HDL, high LDL, and low triglycerides didn’t benefit from statins would [Ethan] want to know that information? (twitter.com/erreyedoc/status/1162070100037574656)
- Study mentioned: Influence of Low High-Density Lipoprotein Cholesterol and Elevated Triglyceride on Coronary Heart Disease Events and Response to Simvastatin Therapy in 4S ahajournals.org/doi/full/10.1161/hc5001.100624
52:40 Open data, machine learning, and possibilities moving forward
56:20 Non-HDL and mortality from the NHANES dataset
twitter.com/DaveKeto/status/1133177415486693376?s=20
58:30 Changes in ability to connect with researchers and scientists
1:00:05 What does Dave mean by risk?
1:04:10 Modifications to low carb to achieve lower LDL
1:08:55 What Dave has learned about the importance of rigorousness in self-experimentation
1:13:29 Can self-experiments have benefits applicable to people beyond the person doing them?
1:17:29 Cholesterol biosynthesis
1:18:40 Reverse causality – is there a possibility that the lipoproteins are reflecting a problem and not causing it?
Note from producer: I attempted a follow-up to see if I could find any studies looking at the impact of infusion of native mouse lipoproteins on atherosclerosis development, but I have not found any thus far.
1:24:33 Clotting, vascular injury, and engineering
1:29:55 The impact of placebo
Podcast mentioned: The Hidden Brain: The Untapped Potential of Placebos to Heal (transcript available) npr.org/2019/04/29/718227789/all-the-worlds-a-stage-including-the-doctor-s-office
1:33:23 The impact of seeing lipids change – could this impact the results of the study?
1:35:56 If it were dose dependency would all drugs that lower LDL have a likewise decrease in cardiovascular disease mortality?
1:38:46 Drug trials – ideals, replication, and funding
1:42:35 Wrap up and outro
Ethan Weiss Contact:
Twitter: @ethanjweiss
0:00 Introductions
1:30 The Innate immune system and the adaptive immune system – what’s the difference?
3:25 The innate immune system and bacteria
8:00 How does immunity relate to atherosclerosis?
13:34 A link between atherosclerosis and diabetes/autoimmune diseases?
16:35 Absorption in the gut, and intestinal permeability
22:10 Nick and Nathan’s hypothesis
24:30 Dave’s thoughts on the hypothesis – is there anything to support or contradict the hypothesis?
28:24 The nuance of atherosclerotic plaque progression
Book mentioned: Natural History of Coronary Atherosclerosis by Constantin Velican
31:16 Multiple initiators of atherosclerosis – do they all have the same root cause?
33:00 Does atherosclerosis progression and regression come down to gateway keeping?
35:00 High frequency testing to challenge the hypothesis – Dave’s proposal
36:45 Atherosclerosis as a post-prandial phenomenon and ‘binge-ury’
40:00 Proposed testing of the hypothesis and follow-up questions regarding intestinal permeability
43:20 Learning from high carb experiments and aftereffects
49:10 The impact of the microbiome, and issues with testing in humans
51:00 Devil’s advocate – what about LDL?
1:00:00 Drugs used to prevent heart disease, lipoproteins, and how they relate to the endotoxin hypothesis
1:03:39 The disconnect in research on lipoproteins and immunity
1:08:34 How drugs relate to the endotoxin theory (cont)
1:10:04 If the drugs impact disease progression and all-cause mortality – why not take them?
1:11:32 Lean Mass Hyper-responders – do Nick and Nathan feel caution is needed to lower their LDL?
Term used: For more information on Lean Mass Hyper-responders see the page on CholesterolCode.
1:13:53 The importance of a long-term follow-up study on Lean Mass Hyper-responders
1:19:05 Outro0
Nick/Nathan’s Patreon: patreon.com/rootcausinghealth
Twitter: twitter.com/rootcausing
Website: rootcausinghealth.com
YouTube: youtube.com/channel/UCR5qmqb8ydX8rmBRwEUXJHg


