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@KenDBerryMD

@KenDBerryMD

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Nick Norwitz

@nicknorwitz

Jun 1

😰🔥 What causes anxiety?

1/5) Obviously, the answer is many things. But an underappreciated truth is that behavioral states and emotions — including anxiety — can be the consequence of a metabolic state.

New data show how inflammation can act directly on the brain to promote (or soothe) anxiety. (link at the end)

#anxiety #anxietyrelief #mentalhealth #inflammation

2/5) The story of this study begins with an inflammatory molecule called 🔥IL-17🔥

IL-17 levels are increased in inflammatory disorders like psoriasis, inflammatory bowel diseases (ulcerative colitis and Crohn’s disease), rheumatoid arthritis, and ankylosing spondylitis.

👉It’s certainly relevant to humans. But to prove a causal connection between IL-17 and anxiety, researchers turned to animal models. Researchers treated mice with a chemical that increases IL-17 levels.

This made the mice more anxious on three different validated behavioral tests.

3/5) Next, to connect the dots, the researchers looked for IL-17 receptors in the brain.

Indeed, they found that IL-17 receptors were concentrated in the anxiety center of the brain, the basolateral amygdala.

👉And they found that directly administering IL-17 into the brain induced anxiety.

💡Furthermore, chemically turning “on” or “off” the neurons in the basolateral amygdala that harbored IL-17 receptors turned anxiety “on” or “off” in the animals, respectively.

This strongly suggests that neurons in the basolateral amygdala can cause anxiety — and that increasing levels of the inflammatory signaling molecule IL-17 activates these neurons to promote anxiety.

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Nick Norwitz

@nicknorwitz

May 31

🍭The Sugar Diet Works—But Not for the Reason You Think❌ You win comments section.

On (extremely) popular demand, I decided to cover this viral trend #SugarDiet. What I discovered surprised me. You can find a link to a newsletter with more details at the end, but let’s review some of the data. 1/7) What is the Sugar Diet? If you haven’t been following. The sugar diet is defined by eating low-protein, low-fat and lots of carbs.

As an example, @MarkSmellyBell has been on the sugar diet for several weeks and eating ~0.5 grams of protein per pound of body weight (~100 grams at 209 lbs), keeping fat <30 grams and eating as much as 800 grams of sugary carbs per day. If we use the numbers 100g protein, 30g fat and 800g carbs that’s 3,870 Calories, with 83% from carbs.

He’s also including “sugar fasts” on top of his sugar diet, where for days at a time he’ll consume only these six foods: fruit, fruit juice, maple syrup, honey, sugar, and candy But he’s reporting rapid weight loss. And others are reporting similar. So, should you believe them, or are they just lying on behalf of Big Jellybean? Let’s discuss some important data, then you can decide for yourself. #sugardiet #metabolichealth #educational #staycurious #FGF21

cc @hubermanlab + @GardnerPhD re protein requirements. Andrew noted you have different perspectives on optimal protein intake on your recent May 12, 2025 HLP podcast. These Nat Metabolism data may provide an unexpected source of intellectual reconciliation @R_Mohr

@MikeMutzel @Physionic_PhD @drmarkhyman, I figure this is of general interest to you
@drgabriellelyon re protein restriction, invited comment

2/7) The Data

The study that captured my attention was recently published in Nature Metabolism. It investigated the effects of a low-protein, high-carb diet on energy expenditure. The subjects were healthy young men in their mid-20s, mean BMI ~25 kg/m2, who were placed on a diet that was **9% protein and 70% carbs** as percent of calories for five weeks, before reverting to a higher protein diet (18% protein) for the following five weeks.

🔥Remarkably, after about a week on the low-protein, high-carb diet the participants needed to increase their energy intake to maintain body weight.

By week five, they’d increased energy intake by **19% (574 Calories per day)** but had lost 1.0 kg. This 574 Calorie increase in energy intake while losing 1.0 kg occurred without a significant change in muscle mass and without an increase in physical activity.

They also replicated the low-protein, high-carb diet results on another set of young men. Again, energy intake needed to be increased by 20% to maintain weight, without any increase in physical activity.

3/7) High Carbs or Low Protein?

Finally, they asked whether swapping some of the carbs for fat changed the result by conducting a third similar study, but one in which protein was 9% and fat was more than doubled to 50%, while carbs were chopped down to 41%.

✋Pause and make a prediction.

If it was the power of carbs and sugar accounting for the metabolic boost, you’d expect swapping carbs for fat would reduce the benefit. But, if it were the protein restriction that was responsible for the increased energy expenditure, you’d expect the same results as in the other studies.

Question: Can you guess what happened?

Answer: On the protein-restricted higher fat diet, the results were the same, namely that participants needed to eat 21% more Calories per day by the end of week five to maintain their weight. And, again, there was no change in physical activity.

Thus, something about the protein restriction was causing these folks to burn off more energy.

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Nick Norwitz

@nicknorwitz

May 29

🫀New Data! How Heart Diseases Causes Brain Damage🧠 – And How THESE Specific Foods Can Help (🔗 at the end)

1/7) If you have an unhealthy heart, you have an unhealthy brain as well. This is not just an association. Your organs talk to each other. And if you have heart atherosclerosis your heart transforms from a loving spouse into an abusive partner. New research shows HOW this works and how to potentially “intercept” the abusive messages to protect your brain (and your heart) and heal their relationship to support your health.

👉Overview👈
The new research in question was just published in Cell Metabolism and specifically reveals how immune cells in the heart called “foam cells,” in plaques in the heart, release little packages called “exosomes.” These travel to the brain where they cause oxidative stress, impair glucose metabolism, and otherwise cause metabolic dysfunction.

A Quick THANK YOU!
Before you continue through this thread (and hopefully the full letters), I wanted to share today is my graduation from Harvard Medical School. So, inevitably, I’m spending the morning with a Yerba Mate and a new paper to celebrate becoming "Nick Norwitz MD PhD." It’s certainly a time to reflect and be grateful.

And I’m incredibly grateful for all of you and your shared enthusiasm for metabolic health. I’m beyond thrilled to be able to ‘rebound’ what I learn off of all of you. So, a huge THANKS! This is just the beginning of our journey together! Now, today’s metabolic lesson…

2/7) Let’s define these 3 Key buzzwords quickly:
👉Foam cells: Type of immune cell (macrophage) that exist in plaques in coronary arteries and are core to the development of atherosclerotic cardiovascular disease. If macrophages are Bruce Banner, foam cells are little Hulks smashing and damaging all in their path.

👉Exosomes: Small, membrane-bound spherical packages that float around in the blood and carry biological cargo like proteins, lipids, and nucleic acids to other cells.

👉microRNA: In this case, the microRNA are the messages in the exosome packages microRNA are small RNA molecules. RNA is the readout from your genome. While some RNA, called mRNA, is used to make proteins, other RNA has regulatory jobs. microRNA are genetic regulators that change how DNA is read in cells throughout the body.

3/7) Quick Summary: In atherosclerosis, foam cells in plaques in the heart send out exosome packages filled with angry messages (miRNA). These abusive messages go to the brain and change metabolism—for the worse.

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Nick Norwitz

@nicknorwitz

May 27

Can a ketogenic diet reduce your risk of colorectal cancer? 🤔💩 (link to more at end)

1/8) While we will never have long-term human randomized trials for dietary therapy for cancer prevention, animal studies can provide fascinating mechanistic insights.

This research was conducted in microbiome-humanized mice. What this means is that, to make this experiment more relevant to people, researchers created humanized microbiome mice. Specifically, they took stool samples from 5 healthy human beings, mixed them together, and gave that to mice that had no microbiomes of their own.

They then treated these humanized mice with compounds that cause intestinal inflammation and predisposed the mice to develop colon cancer.

After that, the mice were fed either a standard chow diet (with carbohydrates) or a low-carb, high-fat ketogenic diet, which increased circulating levels of ketone bodies.

🚨Impressively, the keto mice exhibited fewer tumors, smaller tumors, and an overall lower tumor burden.

#coloncancer #cancerresearch #ketodiet

2/8) Then, to prove a causal connection between the microbiome shift, via the ketogenic diet, and protection against colon cancer, the researchers did a “Fecal Microbiome Transplant” – they transferred microbiomes from keto-fed mice into other mice who hadn’t eaten a ketogenic diet.

Remarkably, the microbiome transplant transferred the anti-cancer protection to the receipt mice.

3/8) So, the next question is: How?

The ketogenic diet selected for a bacterial community that produced more of a fatty acid called stearic acid, an 18-carbon saturated fatty acid. This stearic acid had 2 main effects:

1. Stearic acid caused tumor cells themselves to die (apoptosis)

2. Stearic acid suppressed inflammation by decreasing levels and activity of inflammatory immune cells (Th17 cells).

It’s this one-two punch—targeting both the cancer cells and the inflammatory tumor microenvironment—that made the stearic acid produced in response to the ketogenic diet such a potent anti-cancer compound.

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Nick Norwitz

@nicknorwitz

May 24

Lp(a) Explained: Genetics, Risk, and What You
Can Actually Do ❤️‍🔥🫀
🔗 all references and more info at the end

1/9) By now, you’ve probably heard the term Lp(a). But to get everyone up to speed, Lp(a) is a major causal risk factor for atherosclerosis. On a per particle basis, it’s thought to be ~6X as atherogenic as LDL particles.

Now, two more things to know about Lp(a):

i) Its levels are largely (~90%) genetically determined
ii) There aren’t many medications or lifestyle treatments to modify Lp(a)

So, what do you do if you’re genetically cursed, like me?

Well, if you read the full letter (🔗 at the end), I promise on my own heart that you'll understand of Lp(a): what it is, why it matters, and what you can do to reduce your risk... and why I'm not panicking, despite my 165 nmol/l.

#hearthealth #lpa #ApoB #LDL #inflammation #IL6 #niacin #cardiovascularhealth #ApoE4 #HRT #oxidation #seedoils #metabolichealth #medicaleducation #meded #atherosclerosis #siRNA #

2/9) The letter will progress in 7 chapters, the first three of which I'll review in this thread:
1. Defining Lp(a)
2. Guidelines on Measuring Lp(a) & Risk Thresholds
3. Medications in Development to Lower Lp(a) 🧪
4. How to Reduce Cardiovascular Risk if you have high Lp(a) 🫀
5. How Statins Increase Lp(a) and What is Means 💊
6. Oxidized Phospholipids: The Cargo of Lp(a)
7. Nuance Notes for the Nerds 🤓: Lp(a) as an acute phase reactant, Menopause, HRT, and ApoE4

3/9) Defining Lp(a)

To understand Lp(a) you first need to understand a better-known lipoprotein particle, the "LDL particle." LDL particles are spheres that carry fat and cholesterol around the bloodstream.

A core feature of both LDL and Lp(a) is an ApoB lipoprotein that gives the particles function. In fact, the broader class of particles floating in the bloodstream that includes both LDL and Lp(a) is called ApoB-associated lipoprotein particles.

That makes sense, right?

🚨Now, here’s the critical difference between LDL and Lp(a): Lp(a) has a “tail.” 🐕

That tail is an additional protein called apolipoprotein(a) -- apo(a) in the graphic -- which is coded in your DNA by the LPA gene.

The apolipoprotein(a) “tail” attaches to the ApoB with a bond (called a “disulfide bridge” for the need-to-know nerds).

So, to quickly review: LDL and Lp(a) are both particles containing ApoB. But Lp(a) has the addition of an apolipoprotein(a) attached to the ApoB.

Terms:
👉ApoB (or ApoB100) - Major lipoprotein defining a class that includes LDL particles and Lp(a) particles
👉apolipoprotein (a) - the "tail" on Lp(a). It attaches on ApoB
👉LPA - the gene that codes for apolipoprotein (a)

Next question: What does the apolipoprotein(a) tail do?

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Nick Norwitz

@nicknorwitz

May 17

"The Science Isn't Settled" - Please read this thread to the end if you've been following the KETO-CTA "drama" ... there's a BIG surprise... 🧵💣

1/6) One thing that's become obvious to me in the past month is that social media is shaped by Selective Attention.

This thought occurred to me this morning as I was composing a reply to the first comment on this morning's #StayCurious Metabolism Newsletter about CAC Scores.

I'll copy that in (2/7) below for easier reading (pictured on the bottom left).

For what it's worth my colleagues and I cc @realDaveFeldman @AdrianSotoMota @khurramn1 et al. are not dogmatic with respect to #statins, keto, etc. nor do we ever discourage anyone #LMHR or otherwise, from thinking critically and responsibly about their own INDIVIDUAL health journey.

You'll note quite clearly that I said in the reply (and/or I've said before) that were I to be over 40 y/o (see letter for why I said 40) with a positive CAC I'd take lipid lowering medications even in the light of the KETO-CTA data where ApoB did not predict progression (rationale, below). That's not news. Now, I wouldn't do it blindly. I have my thoughtful concerns. But I would do it.

One point @PeterAttiaMD has made with which I more-or-less agree (although we certainly don't see eye-to-eye on this topic), is that the buffet of pharmaceutical options for lipid management has grown, providing more choices for patients to fit their preferences and concerns.

2/6) Here's the copy & pasted reply to the first comment. I'd highlight that this is not an outlier reply, but routine. While we are very careful not to give medical advice via social media, we do spend a tremendous amount of time trying to support people (esp #LMHR) 'caught between a rock and a hard place.'

Often, this is in private DMs, or even phone calls. The irony is I've probably spent more time indirectly helping #LMHR individuals lowering LDL/ApoB than almost all of our detractors and - I'll just call a duck a duck - trolls. This is not because I ever push the "you should" do X. But - I think - because I walk people thought the thought processes that would go through my own head.

The Copy & Pasted Reply from this AM (open to critique):

If I were in your shoes, here a few questions I'd ask myself:

1) Did keto change my LDL/ApoB? For most, this is not the case. But, in your case, certainly seems your LDL is higher on keto than vegan.

2) If 'yes' keto did increase your LDL/ApoB what is the relative contribution of fiber vs SAT/UNSAT ratio vs lipid energy model/ #LMHR physiology? You can play with these variables within a ketogenic diet, e.g. swapping butter as a cooking fat for sesame oil or avocado oil, or adding soluble fiber in the form of low-carb whole foods.

3) Do I know if your/my CAC increased on keto, or was 128 at baseline when I started keto?

4) Even if it did, e.g. if you're LMHR, do the data suggest LDL/ApoB lowering would improve risk? I'd say the data aren't clear. In our analyses (KETO-CTA), while NCPV metric specifically increased more in those with positive baseline CAC-- and with a high degree of inter-metric variability (e.g. median TPS score change was 0 -- in both those with positive and negative CAC, ApoB did not predict plaque progression. We will definitely have more to say on this over the summer and I'm sorry academic moves at the pace of a narcoleptic turtle.

5) That said, I'd also ask myself about the additional possible benefits of a given medication, e.g. anti-inflammatory effects of statins, potential effect on MPO (see other letter), etc.

6) On balance, if it were me in your shoes, I would apply the precautionary principle where possible (emphasis on "where possible," as idk if you're using a ketogenic diet therpauetically). That means, if I were >40 and had a positive CAC and was able to add carbs (e.g. going from <20g/d to 150g/d of 'healthy carbs') and/or carb cycle (see prior letter) and/or start pharmacotherapy with careful monitoring of biomarkers of personal interest (e.g. desmosterol levels were I to take a statin) that's what I would do.

3/6) I will caveat that reply, and any of my two cents on lipids and cardiovascular health, with the obvious fact that I am a 29-year-old PhD (MD PhD in 12 days! Sorry, had to drop that in there), and NOT a board certified cardiologist, nor do I have decades of experience treating patients with lipid disorders, like some of my associates from whom I have the pleasure of learning (cc @Lipoprotein @drjohnm - conversion with the latter releasing on @chadinabhan podcast soon).

While I'm certainly "enthusiastic" - @VivaLongevity accurately called me a "good promoter" on his podcast with @realDaveFeldman I hope I've been clear about what I am, and what I am not:

✅I am:
I am curious and relatively sharp, if I do say so myself. (I think I have the receipts to back that.) I also try my best to be honest and transparent (more on that in a moment).

❌I am not:
I am not a cardiologist, nor have I ever pretended to be. I'm not even a listened clinician. So I'm never giving you personal medical advice.

🤔Area of Growth and Reflection:
Another thing I am is impatient. As my mentors and friends can tell you, I sometimes "jump the gun." This had gotten me in trouble my whole life. Only now, with a more public presence (and sorry to those who don't like me, that's only going to become more pronounced with time) the stakes are raised. My actions don't just impact me, and you can choose to believe me or not, but I do spend a lot of time reflecting on how I could do better as a communicator moving forward. I've learned a lot over the past two months alone.

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