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My latest publication in the Australian Veterinary Journal.
Researched natural agents can provide efficacy
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Peter J Anderson
15.7K posts
Peter J Anderson
@PeterJAnderson_
Published Researcher. Conduct Clinical Trials. Research nitric oxide, ASCVD and endothelium chemistry. BlackBelt Fudoshin Bujutsu. Port Adelaide FC .
New South Wales, Australia Katılım Mart 2020
3.1K Takip Edilen1.8K Takipçiler
@lipo_fan Missed the ‘and fat’ part which steers away from phosphorus
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@lipo_fan Wow this is ‘crazy’
Imagine the effects of being an athlete and LCD on CAC
-maybe it’s the ‘good’ CAC like athletes have that comes with less MACE
Could it be higher phosphorus to calcium ratio in ( bone free ) meats - especially organ meats ?
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"LCD in young adults were associated with a higher risk of coronary artery calcium progression in middle age"
🤨"Replacement of carbohydrates with predominantly animal but not plant protein or fat in low-carbohydrate diets has the potential of enhancing CAC progression"
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The shared mechanisms of all cardio metabolic risk factors on atherosclerosis via the eNOS ‘bank ‘
Peter J Anderson@PeterJAnderson_
This paper helps explains the shared mechanisms of all risk factors They can all-singularly or in sum -uncouple eNOS-reducing nitric oxide to a level that enables lipoprotein retention chemistry - in particular low NO then disinhibiting PDGF and TGF-b to allow GAG elongation and binding with LDL ( let alone NO also inhibiting VSMC proliferation, adhesion factors ICAM and VCAM , platelet aggregation etc) If one looks at eNOS as a ‘bank’ of function , then sometimes one risk factor ( LDL in FH for example) can uncouple enough ( not binary) to reduce NO to that critical level of retention initiation and proliferation. Other times with low LDL one or the sum of the other risk factors can uncouple eNOS to this level Sometimes the sum of all the risk factors still isn’t high enough to critically uncouple “You can have many of them and do fine” as you said It should be noted that even aging eventually can uncouple eNOS (Aging risk factor should be on pic from this paper) When eNOS is uncoupled upstream then it doesn’t take much LDL midstream to be retained to make atherosclerotic plaque ( why we see plaque even at low LDL) ahajournals.org/doi/10.1161/ci…
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Looking closer at clotting anomalies in FH cohorts…
Is this simply explained by the reduced nitric oxide ?
FH cohorts have increased markers of platelet activation and coagulation (fibrinogen, factor VIII, PAI-1, etc.)
But does NO deficiency directly create a pro-thrombotic endothelium by removing NO’s natural inhibitory effects on:
-Platelet adhesion and aggregation.
-Tissue factor expression.
-Coagulation cascade activation.
-Fibrinolysis ?
The same low-NO state also promotes inflammation, smooth muscle proliferation, and LDL retention (via GAG changes), linking the “clotting”
strongly with the degree of endothelial dysfunction (low NO).
@_earthling74
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Peter J Anderson retweetledi
FH cohorts shown to have serious endothelial dysfunction ( lack of nitric oxide - confirmed by greatly reduced FMD assays) from 10 yo
Nitric oxide is also one of the body’s most potent anti thrombotic agents
Endothelial dysfunction precedes the first signs of atherosclerosis but more importantly sets up retention of the high LDL
High LDL is one of 7 risk factors ( singularly or in sum) that can uncouple the enzyme that makes nitric oxide ( eNOS)
Basic and proven science - but no one seems to discuss
researchgate.net/publication/24…
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This paper helps explains the shared mechanisms of all risk factors
They can all-singularly or in sum -uncouple eNOS-reducing nitric oxide to a level that enables lipoprotein retention chemistry - in particular low NO then disinhibiting PDGF and TGF-b to allow GAG elongation and binding with LDL ( let alone NO also inhibiting VSMC proliferation, adhesion factors ICAM and VCAM , platelet aggregation etc)
If one looks at eNOS as a ‘bank’ of function , then sometimes one risk factor ( LDL in FH for example) can uncouple enough ( not binary) to reduce NO to that critical level of retention initiation and proliferation.
Other times with low LDL one or the sum of the other risk factors can uncouple eNOS to this level
Sometimes the sum of all the risk factors still isn’t high enough to critically uncouple
“You can have many of them and do fine” as you said
It should be noted that even aging eventually can uncouple eNOS
(Aging risk factor should be on pic from this paper)
When eNOS is uncoupled upstream then it doesn’t take much LDL midstream to be retained to make atherosclerotic plaque ( why we see plaque even at low LDL)
ahajournals.org/doi/10.1161/ci…
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Good thread. Risk factors are just what the name implies: factors associated with risk. You can have many of them and do fine. And you can have none of them and have an event. They are modifiers of odds, not guarantees of events or safety.
Andrew Scott@ScottAppliedSci
“Half of heart-attack patients have normal cholesterol!” This is a favourite anti-LDL slogan. It sounds devastating. Unless you know basic high school statistics! If someone says it, they just announced they are embarrassingly out of their depth. Here's exactly why 🧵
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Pls feel free to use glass flow chart ( I was honoured years ago when President of European Dermatologists Association asked to adopt it)
Yes Type 4 is great fun detective work- consort dermatitis from hubbys cosmetics-positive patch test to hair dyes “I don’t dye my hair “ ( but does a lot of photocopying)-
Weed pollen in wind giving sunburn pattern where no clothes etc
It’s a fascinating and rewarding vocation you have
This app is great for patients to get exacerbating secondary Histamine triggers in diet down
Very user friendly like traffic lights
( even notes DAO)
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@PeterJAnderson_ Now you're speaking my language. Type IV contact allergy.
And I like the glass device, a lot.
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Eczema went from rare to common starting in the 1960s.
For 50 years, smart people came up with smart explanations.
Genes. Diet. Stress. Allergens. Not enough exposure to dirt. Not enough exposure to animal poop (real theory). Too many cleaning products. Not enough moisturizer. Too many antibiotics. Not enough breastfeeding.
None of them held up.
A new theory dropped in 2023. I didn't believe it.
I was wrong.
Thanks to one researcher at the NIH who kept an open mind and followed the evidence, we now understand one of the biggest medical mysteries of the last half century.
If you wonder how chemicals are affecting us in the modern world, this is going to kind of blow your mind.
And no, it's not an "all chemicals are bad" hit piece.
It's specific chemicals coming from places you wouldn't expect.
I'll lay out all the evidence on Saturday morning including what I'd probably do if I was worried about me or my kids getting eczema.
Most of it's cheap and easy.
Nothing to sell. No regimen I'm pushing. No affiliate links.
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@SomerwilTara @EstebanDL I think they are both are great contributors to the nitric oxide journey via their polyphenols constituents
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@PeterJAnderson_ @EstebanDL Please be kind and tell me what you think about Aronia berry powder and blueberry powder. 🙏
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@SomerwilTara @EstebanDL Hi Tara
This is the last of the 500 classics ( I snapped it up 2 years ago when they were changing to a 350)
Do you like the fish tail muffler ( I thought it’s a 50s thing and would suit the retro look)
I ride it daily which keeps me young
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@PeterJAnderson_ @EstebanDL Wow that is some Enfield .
Is it 500 classic or 350 ?
Are you kidding me , how can U say U are older in the context of a great bike.The Brits created some nice ones this is one of them .When I was younger & wiser I rode a Triumph.
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Yes no histamine =no eczema/ asthma/ hayfever
( the manifestation of where histamine arrives in skin/ lungs or nasal pharynx is the genetic influence)
The Histamine glass emphasises the role of histamine and importantly shows one doesn’t have to avoid all allergens all the time- just enough to lower histamine below symptom activation level.
This is assisted by the ( temporary) reduction of secondary triggers which alone can’t make it to symptom activation level ( sometimes with a low level allergy- say IGE of 95 ku/L - one can go into remission just by reducing secondary triggers)
The patients love the Histamine Glass - demystifies allergies
It can explain how a food or beverage can cause itching wheezing or sneezing that they have no allergy to because it’s high in histamine and is just maxing out their glass ( when they avoid enough allergens then they won’t react to those items)
… and then there is the wonderful world of type 4 contact allergens
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@PeterJAnderson_ That's actually pretty good.
The major driver is in one of the general categories you've got covered.
And I'd say we think of mast cells, the main source of histamine, as a bigger driver than the histamine itself, but histamine is in the game.
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@lipo_fan Fantastic paper mate
Proteoglycan binding is where all the action is -
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K.J.WILLIAMS
"2 studies that until now had remained largely overlooked one of them is not even in PubMed,suggest a protective role for HDL right FROM THE START OF ATHEROGENESIS: HDL interferes with the irreversible binding of plasma LDL to proteoglycans obtained from arteries"
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@PeterJAnderson_ @EstebanDL Thank you so much for your speedy response. I take already for 6 yrs L citrulline 3 g morning 3 g evening.Also beetroot 3 g . I'll look to buy the powders I mention.
You really are a great and helpful person not only a guy who has great taste in bikes .😉👍🙏🤗
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@IvicaMaslaceti @AmmousMD @Chainsaw59598 Interesting paper
Whilst this is not the same as UV rays known to activate dermal nitric oxide - there is still a few enzymatic pathways that it could occur
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@PeterJAnderson_ @AmmousMD @Chainsaw59598 NO story reminds me of the study from 2021:
pubmed.ncbi.nlm.nih.gov/33951300/
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@AmmousMD @IvicaMaslaceti @Chainsaw59598 Mechanism of all risk factors uncoupling eNOS
ahajournals.org/doi/10.1161/ci…
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Hi Tara
L-Citrulline is actually more efficient at creating arginine and then nitric oxide than straight arginine is.
There is also some great dietary nitrate powders that also boost nitric oxide ( and don’t need eNOS enzyme)
I’m in Aus but I see over your way there are red spinach powders ( 9% nitrates) and arugula powder( 10% nitrates) that don’t have the added unwanted oxalates that beetroot does ( beetroot powder much lower in nitrates also)
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@PeterJAnderson_ @EstebanDL Great Post Peter .
I am really working hard to increase and improve my NO . I wonder if taking L arginine would be a solution for me since my LPa doesn't respond to any statin ?
Thank you for this post .🤗👍🙏
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Apart from, or on top of LLT , noting its retention (not concentration or trancytosis ) that seems to be the rate limiter of atherosclerosis…
How can we switch off retention ?
Theoretically if we could maintain or regain great coupled eNOS and great ensuing physiological endothelial nitric oxide levels…
….PDGF and TGF-b would remain tonically inhibited enough to prevent proteoglycan GAG chain elongation which would greatly inhibit LDL binding and retention ( regardless of concentration or trancytosis rates )
( let alone adequate nitric oxide’s inhibiting and controlling actions on VSMC proliferation, ICAM and VCAM adhesion factors , MCP-1, platelet aggregation, thrombosis , LDL oxidation, NF-kB etc etc )
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Something new: A Cardio Case Study 🫀
In the wake of a viral cholesterol article in @Telegraph, I thought I’d walk through a case study to show how to think about a deceptively simple question:
How should we manage high LDL and ApoB?
Here: staycuriousmetabolism.substack.com/p/apob-alice-a…
The conventional approach is algorithmic:
“If level is above X, do Y.” But humans are not simple linear systems. We are complex biological machines, metabolic webs, shaped by context, history, physiology, and tradeoffs.
That’s the challenge this article raises: can we see the nuance behind individual care and elevate our thinking beyond harmful platitudes like “lower is always better”?
Medicine should treat humans as complex biological individuals, not as lab values on an algorithm.
See if you can keep up...
Nick Norwitz MD PhD@nicknorwitz
This article came out in @Telegraph this morning, and it’s already gaining significant traction, apparently reaching top three on the site within hours or release. telegraph.co.uk/health-fitness… There’s clearly a lot of engagement, so since I won’t be able to respond to every comment, I want to clarify a few things upfront. First, I am not, nor have I ever been, anti-pharmacotherapy. What I am against is a lack of nuance. I don’t believe it’s my place to say something as simplistic as “X drug is overprescribed,” (some editorial liberties were taken). However, my concern is that they are prescribed without sufficient individualization and thoughtfulness. My critique is not of pharmaceuticals themselves, but of a system that too often operates algorithmically, rather than with the precision each patient deserves. Having personally experienced the downsides of that kind of care (multiple times), I feel comfortable speaking to it with the authority of a patient, MD PhD or not. Second, I did not request, solicit, or pay for this article in any way. I was approached for it just as I was for an upcoming lecture at the @UniofOxford Longevity Summit, hosted at Rhodes House this weekend. I did no approaching, nor do I get any sort of kickbacks. Third, this is not an article I wrote, nor is it intended to be an academic dissertation. If you’re looking for deeper nuance, I’d encourage you to explore my broader body of work, on YouTube or through my Substack, which covers dozens of articles on heart health and synthesizes hundreds of studies and human trials. staycuriousmetabolism.substack.com/p/hearthealth And thanks for making is #2 Overall Best-Selling in Science on Substack, Globally. That's heartening :). But I’ll leave you with this: What is a consensus worth… when the status quo it represents has failed to meaningfully improve public health?
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To clarify yes ApoB risk factor in this paper appears before endothelial dysfunction
High ApoB uncouples eNOS which causes endothelial dysfunction which then disinhibits PDGF and TGF-b enabling GAG elongation and LDL binding
This paper confirms this hierarchical order -high LDL creating endothelial dysfunction ( via uncoupling ) BEFORE plaque appearance
It doesn’t show LDL retention before endothelial dysfunction?
I agree it doesn’t require a dysfunctional endothelium to cross and enter but again entry doesn’t guarantee retention
…as we have discussed high concentration can mean linear high trancytosis entry but retention rates can be estranged from retention
I have no doubt those hypercholesterolemiac cohorts I quoted still had the high concentrations upregulating CAV-1 to increase trancytosis entry but what happened to retention? ( influenced by multiple factors independent of concentration and trancytosis)
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Poor metabolic health is upstream of heart disease. ApoB is the road.
"Metabolic health is the root cause" is one of the most effective framings in wellness misinformation. Not because it is wrong. Because it is incomplete in exactly the right way.
Here is what it leaves out.
Insulin resistance, visceral fat, and poor glucose control all raise cardiovascular risk. CTT, Mendelian randomization, and 50 years of lipid research confirm it. But they raise it primarily by raising ApoB particle burden.
Chronically elevated insulin drives hepatic VLDL production. VLDL converts to LDL. ApoB rises. ApoB-containing particles accumulate in the arterial wall.
Remove the ApoB step and you have a mechanism with no road.
The clinical implication is direct. A patient who improves metabolic markers but whose ApoB remains elevated is not protected. The particle burden is still loading the arterial wall.
The surrogate won. The outcome did not.
The clinical implication is direct. A patient who improves metabolic markers but whose ApoB remains elevated is not protected. The particle burden is still loading the arterial wall.
The surrogate won. The outcome did not.
This is why ApoB measurement is not optional when someone tells you their metabolic health "improved." TG came down. HDL went up. Blood sugar normalized.
ApoB is the question a cardiac surgeon sees answered on the operating table. Not in the bloodwork from three years ago.
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