Post

@ketochow

@Elinav_Lab

More from @nicknorwitz

Nick Norwitz

@nicknorwitz

May 17

The Power of CAC = 0: When Does LDL Matter?
(🔗to full letter at the end)
1/7) One landmark study published in the journal Circulation in 2023 followed 23,132 middle-aged people (median age 57) from the Western Denmark Heart Registry for a median follow-up of 4.3 years.

Over this time, 552 had cardiovascular events. And the researchers sought to answer the question: What predicted who would have a cardiovascular event?
But there’s more…

They broke those 23,132 participants into those who had a positive Coronary Artery Calcium (CAC) scan and those who had a CAC of 0.

🫀Among those with CAC > 0, LDL-C did predict who would have a cardiovascular event.
🫀Among those with CAC = 0, there was no association between LDL-C and cardiovascular disease events.

2/7) Here are data from Figure 1.

If CAC > 0: As LDL-C rises, the adjusted Hazard Ratio (aHR) increases. aHR is a ratio of how likely an event is to occur in one group compared to another over time.

Here, we are comparing people across LDL-C spectrum. Among those with CAC > 0, higher LDL-C has an aHR > 1 meaning higher risk of heart events and cardiovascular disease in those with higher versus those with lower LDL-C.
* “adjusted” for age, sex, smoking status and diabetes.

If CAC = 0: What you can clearly see is a flat red line at 1. This suggests higher LDL-C does not associate with higher risk of heart events and cardiovascular disease in those with CAC = 0. It provides some warranty.

What’s more, even when they took those with very high LDL-C > 193 mg/dl vs LDL-C <116 mg/dl, when CAC = 0 there was no observed benefit of having lower cholesterol (aHR = 0.95).

Ref, PMID: 36621817

3/7) The researchers also replicated these findings in an entirely separate cohort, the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Notably, in this study, the median age = 62 years and median follow-up = 16.6 years.

Despite the older age and longer timeframe, the results remained the same: higher LDL-C was not associated with heart attacks or cardiovascular disease when CAC = 0.

Zooming out and summarizing: Among those with CAC = 0 in the initial population of >23,000 middle-aged adults, there was no significant association between LDL-C and heart attacks or atherosclerotic cardiovascular disease. These results were replicated in another cohort with a 16.6-year follow-up period.

Read 7 tweets

Nick Norwitz

@nicknorwitz

May 16

1/4) Today’s Video (just released) is a Microbiome Masterclass! (link at the end)
I’ll review

1️. Why your microbiome is CRUCIAL to your health

2️. How to tell if your microbiome is OUT OF BALANCE, scientifically this is called “microbiome dysbiosis,” although the answer might not be what you expect.

3️. What all those gut health BUZZWORDS actually mean—like prebiotics, probiotics, postbiotics, fermented foods, and more

4️. How to TAKE CARE OF your microbiome—including surprising ways your mind can directly influence your gut.

5️. Where THE FUTURE of microbiome science is headed…

2/4) As a teaser, in this thread, let me give you a peek from part 4, subsection 6 (How to TAKE CARE OF your microbiome: Your Mental Health Changes Your Gut Health)

While we all intuitively know our gut feeling can impact our mood, our guts and brains have a bidirectional relationship.

What I’m really trying to say is that your mind and brain can talk to your gut and influence gut and microbiome health. Let me give you 2 examples:

A recent study showed that the brain can alter levels of a molecule, indole-3-acetate (IAA), that can effectively poison stem cells in the lining of the intestines, contributing to poor gut health and gastrointestinal symptoms.

👉 Specifically, psychological stress, via activation of the fight-or-flight branch of the nervous system, causes changes in microbiome function…
👉 This increases levels of the indole-3-acetate molecule in the gut
👉 IAA harms the energy producing mitochondria in intestinal stem cells, leading to stem cell failure and contributing to poor gut health.

3/4) Another recent study found that Stress changes activity in the central amygdala which signal via the Vagus nerve from the brain to glands in the intestines called Brunner’s Glands.

Brunner’s glands secrete mucin to feed gut bacteria. And stress, via this brain-to-gut axis, inhibits Bruner’s glands starving specific gut bacteria, altering the microbiome, leading to bloating and other unfortunate symptoms.

But what does this mean practically?

Relaxation techniques, light breathing exercises, yoga, mediation, sex, and “user-specific relaxation techniques” can be a gut health hacks!

Read 4 tweets

Nick Norwitz

@nicknorwitz

May 13

Is eating keto all the time really optimal? Or should you Carb Cycle? 🥯🔄🥯

1/4) Let’s discuss “Cyclic Metabolic Switching” (CMS) Theory

The CMS posits that extended fasting (or carbohydrate restriction) sufficient to trigger the metabolic state of ketosis leads to the activation of adaptive cellular stress response pathways.

During this time, cell growth pathways—including those stimulated by the hormone insulin, and a key metabolic regulator called mTOR—are inhibited. Then, during refeeding, pathways that promote cell growth (like those downstream of insulin and mTOR) are activated

🔄This creates cycles of activation between stress response pathways and growth and development pathways.

2/4) Analogy: It’s the metabolic equivalent of a good weightlifting program: you stress your muscles to trigger adaptation. Then, you need to rest and recover—and it’s during that rest (when you eat and sleep that growth occurs.

But if you spend too much time in either phase—too much exercise with too little recovery, or too much eating and sleeping with not enough stress—your health will suffer.

🌊In general, and as a high-level truth, biology and physiology operate in ebbs and flows

3/4) That said, if you want candid my opinion: I don’t think Carb Cycling is necessary.

There aren’t conclusive data, but I strongly believe you can “hack” the Cyclic Metabolic Switch

Remember, refeeding refers to giving your body a “growth” stimulus. While the “growth” pathways are complex, one could argue that insulin is the most relevant hormone for signaling growth. And you don’t need carbs to spike insulin. Protein also spikes insulin. In fact, some proteins, like whey protein, can spike insulin quite a lot.

But don’t expect to see the same jump in blood sugar. Protein doesn’t have sugar, and protein also increases other counterbalancing hormones, like glucagon.

Still, you get a “growth” signal and insulin spike from protein. Having large enough protein can spike insulin and signal growth pathways. This is why I don’t this you need to carb cycle to activate Cyclic Metabolic Switching.

Read 4 tweets

Nick Norwitz

@nicknorwitz

May 8

1/11) Since our KETO-CTA paper was published on April 7, 2025 there has been an undeniable and conspicuous spiral of events, leading to a strong diverse set of opinions on the data.

It’s also been noted that since around April 18th, my co-authors and I have been quiet regarding criticisms rendered. I’ll speak for myself when I say this wasn’t personal my preferred approach.

However, it was the strong preference of JACC Advances that we work through the preferred academic channels – namely, by responding to Letters to the Editors passed to us from the journal. Now that we’ve done so (links at the end), I’m pleased to break my silence and speak more freely.

2/11) First and foremost, I encourage everyone to listen to this recent hour-long conversation between Dave Feldman and Chris MacAskill about the controversy.

Truthfully, I think it was among the most honest, humble, and sincere conversations my ears have ever had the pleasure of capturing.

Please start there if you’ve been following the controversy and want a grounding perspective.
youtu.be/cM0KaSp5IIE?si…

3/11) The April 7th Paper was Fully Peer-Reviewed. But it Wasn’t Perfect

Now, here are some points I’d like to make to begin to reanimate productive discussion and resolve confusions.

First, let’s get this straight, the April 7th published paper was fully peer-reviewed and approved by all the authors. That’s not in question and was previously clarified in a joint statement.

Read 11 tweets

Nick Norwitz

@nicknorwitz

May 7

How to Start a Mediterranean Ketogenic Diet: A Step-by-Step Guide (Link to more🔗 in 5/5)

1/6) I started a ketogenic diet on June 1, 2019, and it saved me from debilitating inflammatory bowel disease.

But here’s a hard fact: despite its many benefits—including for obesity, diabetes, mental health, autoimmune and inflammatory conditions—ketogenic diets are still grossly misunderstood. Many people assume keto is all about bacon, butter, and steak, low in fiber, and at odds with what most have been taught, and internalized over their life courses, is “healthy.”

🚨That’s a huge misconception!🚨

Ketosis isn’t about specific foods—it’s about a metabolic state, where you’re producing ketone bodies. You can be keto while eating anything from a fully #vegan diet to a fully #carnivore one.

There is not one ketogenic diet. There are infinite.

And a Mediterranean ketogenic diet is an excellent entry point for many people because it balances the perceived health benefits of Mediterranean eating with the metabolic advantages of keto

Simply put, Medi-Keto is a low-friction dietary entry point to low-carb diets for many people.

Today’s Newsletter breaks down the how-to of Medi-Keto, including:

👉 4 ‘musts’ for preparing to start on your ketogenic lifestyle.
👉 My 9 favorite Medi-Keto foods and help flesh out your shopping list.
👉Common Q&A

In this thread, I’ll tease you with a few highlights…

2/6) Fatty Fish

Fatty Fish are a great source of protein, healthy fats, and micronutrients to support muscle growth, brain health, healthspan and even longevity.

Remember the acronym “SMASH” for Salmon, Mackerel, Anchovies, Sardines and Herring.

For salmon, I’d give Wild Alaskan Sockeye the edge of health and for Sardines, I suggest getting whole sardines (skin and bone) packed in BPA-free tins with water or brine, rather than with oil. (My personal go-to is Wild Planet)

3/6) Extra Virgin Olive Oil

If I were to do a video on all the health benefits of a good, true extra virgin olive oil it would be longer than the entire Lord of the Rings Saga (aside: Gollum was definitely oxidized).

But, practically speaking, what you need to know is how to pick a real extra virgin olive oil, as many bottles labeled “extra virgin” aren’t actually extra virgin and aren’t as healthy.

My top 3 tips for choosing a real extra virgin olive oil are:
(i) Dark glass or metal bottle, not plastic or clear
(ii) “Pressed” or “Harvest” date within the last 2 year
(iii) Look for a bottle that’s transparent about where the olives come from, ideally single source.

*What's the photo?

That's the TRPA1 receptor. The natural compound "oleocanthal" binds to this receptor in the back of the throat, and - if present in good amounts - should cause a burning sensation, and even make you cough. So, to really test for a good high polyphenol EVOO, take a shot and hope for a burning, stinging KICK in the back of your throat

Read 6 tweets

Nick Norwitz

@nicknorwitz

May 3

🚨How Chronic Stress Causes Depression🧠
(Link to Letter 🔗 at the end)

1/8) A new paper about the neuroscience of depression is the most fascinating mental health papers I’ve read in 2025!

It reveals a possible central biological mechanism by which chronic stress can contribute to depression and opens doors to innovative solutions for improving mental health. (link at the end)

Let’s get into it…
#depression #mentalhealthmatters #autophagy
cc/of interest @janellison @ChrisPalmerMD @NTFabiano @KetoCounselor @TuitNutrition @hubermanlab @AllyTransforms @bschermd @Metabolic_Mind

2/8) Background to Know: Lateral Habenula 🌶️ & Autophagy♻️

The habenula is a region in the middle of the brain important in processing
aversive and unpleasant stimuli and in the stress response.

🌶️Because I love memory tricks, the way I remember this is: habenula sounds like habanero, the spicy pepper that can be 100x hotter than a jalapeño — and is therefore an aversive and unpleasant stimulus for most people. So now you won’t forget it! Specifically, the lateral habenula is important in processing responses to unpleasant stimuli and stress.

♻️Think of autophagy as your brain’s janitor crew. It’s a built-in cleanup and recycling system within cells. When proteins get old or broken, a membrane wraps around them like a trash bag, isolating the waste from the rest of the cell. That bag — called an autophagosome — then fuses with the cell’s digestive center and breaks the waste down into reusable parts.

But here’s the catch: under chronic stress, it’s like the janitors go on strike. The trash piles up, the system clogs, and neurons start to malfunction. That’s where things start to go wrong — and potentially spiral toward depression.

And that’s what they show in this paper — at a high level — autophagy within the lateral habenula is impaired, contributing to depression.

3/8) Chronic Stress Inhibits Autophagy in the Lateral Habenula

First, it’s important to note that there are already data suggesting autophagy markers are impaired in people with mental health disorders, including depression.

To demonstrate a causal relationship, the researchers subjected mice to various chronic stress protocols designed to model depression. This decreased autophagy, specifically in the lateral habenula.

You can see that here (Figure 1G): the result of an experiment where they exposed mice to acute or chronic stress and measured levels of a protein called p62, which is normally broken down by autophagy.

👉Taller bars = less autophagy👈

And you can see taller bars in the chronic stress condition — meaning autophagy is inhibited by chronic stress.

Read 8 tweets

Share this page!

Enter URL or ID to Unroll

Nick Norwitz

Try unrolling a thread yourself!

More from @nicknorwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Did Thread Reader help you today?

Don't want to be a Premium member but still want to support us?

Send Email!