Dear all,

Apologies if I don't engage every time I am tagged. This month, I'm overseeing hospital care, and I'm very busy.

Thank you all for your interest in our work! Your support keeps us motivated and your questions & criticism keep us improving.

I'll address them here 🧵 Some have pointed out that SuppTable1 shows that people with ⬆️CAC (>100) had 2.4 annual PAV change. Is this too fast?

Sure! Many have defined fast plaque progression as a yearly change >1% (i.e. PARADIGM reg).

Is the keto-induced ⬆️ApoB to blame for their plaque progression?

⚠️📣NEW PAPER📣⚠️
@JACCJournals
with @nicknorwitz, @realDaveFeldman,
@DrRagnar, Venkat Manubolu, April Kinninger, @jayearls &
@BudoffMd

(URL🔗 at the end of this 🧵)

Longitudinal CCTA-LMHR data is HERE!!!

And...

YES!!!
It's awesome!!!

But, first... Those who know me, know, that the hill I'll die defending is "Mount Nuance."

I'm an internist. I'm physiologically incapable of making straightforward statements.

Don't take my word, ask @DGlaucomflecken about my kind.

If you expect to hear "X is Good" & "Y is Bad," well...

⚠️📣NEW PAPER🔔‼️
@AJCNutrition
(link at the end👇🏼🧵)

With Yusceli Flores, @nicknorwitz, @realDaveFeldman, Mark Pereira, Goodarz Danaei, and @davidludwigmd

A meta-analysis (MAA) + individual participant data (IPD) analysis of 41 RCTs entailing the #LEM and the #LMHR phenotype. In 2022, we published an observational study suggesting BMI was a mayor player in LDL-C changes during carbohydrate restriction:

However, we didn't have dietary intake reports, all data was self-reported, and all participants self-selected their diet. doi.org/10.1093/cdn/nz…

What do the liver, the thyroid, 🩸phosphorus & your 🩸glucose have to do with migraine?

⚠️🚨NEW PUBLICATION 🚨⚠️
@SciReports with @DrElenaGross

nature.com/articles/s4159…

Many don't think about migraine (or most chronic 🧠conditions) as metabolic diseases.

But they are! 🧵 The human 🧠 is the most amazing thing around. Intuitively, this amazingness does not come cheap!!!

The human 🧠 is exceptionally expensive to sustain energetically.

Compared to other primates, we have the most expensive 🧠👇🏼

doi.org/10.1038/nature…

2nd erythritol 🧵.
(Shorter than the 1st one I✋️)

Given that some of the pieces of evidence are "similar" and some of the researchers are the same?

Is erythritol the new TMAO?

Why I'd advise avoiding erythritol but not choline (TMAO)?

First 🧵
threadreaderapp.com/thread/1630971… TMAO = Trimethylamine N-oxide.

After we eat choline-rich foods, SOME gut🦠 produce TMA (Trimethylamine) which is then transported to the liver and converted into TMAO.

Not mutually exclusive, but most people said they'd prefer seeing rather than joining a discussion to analyze THAT erythritol paper, and I have some airport hours ahead...

Here go🧵.

In case you've been living under a rock, this is the paper:

nature.com/articles/s4159… Relevant disclosures for interpreting my interpretation?

I'll speak more as a clinician clinician who sees many ⬆️CVDrisk patients following a low-carb diet than as a healthy adult who follows a low-carb diet and occasionally consumes erythritol.

A wonderful conversation with @CaseyRuff convinced me of joining a bit late the satiety-scores debate.

This 🧵 has my two cents about it and the story of a short and weird experiment @castanedaprado and I carried out a six years ago.

🪙🪙 If we are as strict as possible (in a real world setting) about our energy balance, and eat the same food every day, the order of ingredients shouldn't change our weight loss or our satiety, right?

A short 🧵on:

Is 🧬 the #1 cause of obesity?

I thought this was worth doing because at least one of the experts on the new committee Dietary Guidelines for Americans (which are followed by many other countries in the🗺️) thinks it is 👇

https://twitter.com/DrEenfeldt/status/1617577340942286888?s=20&t=Ue1pxTb1-ZXq4mt1HHaA_w

First and foremost (as with most things in Medicine)

THIS IS A MULTIFACTORIAL PHENOMENON INVOLVING DIFFERENT AND INTERACTING BIOLOGICAL AND SOCIAL FACTORS WITH VARYING DEGREES OF RELEVANCE

⚠️NEW PAPER⚠️
@AJCNutrition with: Mark Pereria, Cara Ebbeling, @LuciaAronica & @davidludwigmd

doi.org/10.1016/j.ajcn…

With many of my favorite things:
1) Open Science.
2)Critical analysis of high quality research.
3) Causal inference.
4) #CiCo vs #CIM
5) 1600 lines of R code. This is a post-hoc analysis of the DIETFITS, a high-quality RCT from @StanfordMed lead by @GardnerPhD (who kindly reviewed an earlier version of our manuscript) which compared carbohydrate vs fat restriction to achieve weight-loss during one year.

jamanetwork.com/journals/jama/…

⚠️🚨 NEW PUBLICATION ⚠️🚨

This very cool project was lead by the amazing Dr @David_Dearlove

It's one of the few direct comparisons between endogenous vs exogenous ketosis.

How are they similar?
How are they different?

physoc.onlinelibrary.wiley.com/doi/full/10.14… Not all forms of ketosis are created equal and most ketogenic interventions do more than just raising the concentration of blood BHB (i.e. they also change insulin, cortisol and/or amino acid metabolism).

These differences and these simultaneous effects are frequently overlooked

My favourite PhD Thesis experiment was published today:

doi.org/10.1002/edm2.3…

This study has a very simple experimental design but comes with an enthralling story about integrated metabolism.

It also comes with beautiful Sci-Art from the amazingly multi-talented @nicknorwitz Featuring:
ketone bodies (BHB), aminoacids (a.a.), Krebs' 🔃, Cahill's 🔃, Randle's 🔃, Cori's 🔃, anaplerosis & ⬆️⬆️ gluconeogenesis (GNG) and diabetes (DM).

Why ⚡ ketosis ⬇️ blood glucose (Glu)?

Why this effect seems to be ⬆️⬆️ in people living with DM?

Why it matters?

😃🚨NEW PAPER🚨😃

dx.doi.org/10.1136/jim-20…

@JIM_AFMR

There are way too many mortality scores for COVID-19. Do we still need them?

But more than that...

There are way too many scores in Medicine. The use and abuse of predictive scores is a Hallmark of current medical care. This was a battle of 🧠 vs 💻, a real 🌎 comparison of human learning vs machine learning.

🥊STATISTICAL MODELS🥊
VS
🥊 CLINICAL GESTALT🥊

I see this COVID-19 example as a proof of concept for the need to re-evaluate the clinical value of the zillion scores we use everyday.

Our systematic review is finally online!

You can learn more about it in the 🧵 below.

Why we needed another SR about low carb interventions for people with diabetes?

What we learned from it?

(Relevant insights for EBM vs CIM!)
@nicknorwitz, @DaveKeto , @davidludwigmd

https://twitter.com/annapnicholas/status/1437815945695834112

You can find, read for free and compare our pre print here:

medrxiv.org/content/10.110…

Ya está disponible en YouTube la sesión 9 del curso de Metodología y Estadística de la @uiem2017

Hablamos sobre correlación y, sobre todo, de causalidad.

(Link al final del 🧵) Una correlación puede ser perfecta y de todos modos ser inútil.

Por ejemplo, un reloj con la hora de 🇪🇸 tendría una correlación perfecta con la hora de 🇲🇽 pero me haría llegar temprano a mis citas.

Estoy obsesionado con el metabolismo humano, los modelos biológicos de envejecimiento y con la datos (Mido todo lo que puedo y hasta tengo todo mi 🧬 secuenciado).

Hace poco concluí que tengo ~10 años menos.

🧵sobre ¿Cómo ser un evidence-based chavo-ruco? Primero hay que dejar claro que NO HAY NADA DE MALO CON ENVEJECER.

¡Al contrario! Es prueba de nuestra fortuna y buenas decisiones.

Les tengo mucho más respeto a las canas y a las arrugas que fobia.

El objetivo es otro:

1/ ¡POR FIN!

El curso de conceptos estadísticos indispensables para profesionales de la salud que le di a los residentes del @incmnszmx ya está en Youtube.

Busquen el link a la playlist en el 🧵
(quiero que sí lean el 🧵 😉) @doctormacias RT🙏 2/ No podemos practicar Medicina Basada en la Evidencia, si no le entendemos a la evidencia... 🤦‍♂️

Pues bien... Desde hace décadas, muchos estudios han mostrado que la mayoría de los profesionales de la salud tiene problemas utilizando conceptos estadísticos básicos 😟