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Nick Norwitz

@nicknorwitz

Feb 14

🚨Keto vs GLP-1: New Study Reveals Advantages of Lifestyle

👉Is the Keto diet Unsustainable?
👉Are GLP-1s ushering in a new era for Obesity Medicine?
👉Which is a more powerful weight loss intervention?

1/8) 🧵 A new paper answers these questions in a powerful, provocative way. Let’s break it down…

Ht/ @DoctorTro @lowcarbGP @bigfatsurprise et al.

2/8) Our story centers on a new paper that colleagues and I recently published covering a 1-year study in which a self-insured manufacturing company approached a metabolic health clinic in seek of support for their employees.

The metabolic health clinic enrolled 50 employees, selected based on “greatest medical need,” factoring in the presence of metabolic syndrome, diabetes, obesity and the number of medications patients were taking.

The average starting BMI of the 50 enrolled subject was 43.2 kg/m2 (or 271 pounds) and 64% had type 2 diabetes or prediabetes.

3/8) These patients had near universally tried and failed lifestyle treatments and diets before, a common plight for middle-aged Americans that often leads to learned helplessness and a disheartening resolution that, ‘this is just how it is.’

🤔Pause and consider if you or someone you know has ever found themselves in this valley of diet despair.

But the metabolic health clinic took on the challenge and enrolled 50 participants in an intense multi-modal lifestyle change program, abbreviated TOWARD that centered on patients consuming a ketogenic diet of fewer than 30 grams of total carbs per day.

❌And patients were explicitly not told to attempt caloric restriction and instead eat according to their subjective hunger.

In summary, this wasn’t just an isolated dietary intervention insofar as people weren’t just given instructions and let off into the world. It was a dietary intervention buffered by education and community support. I’ll get to the pros and cons of this when I discuss limitations. But let’s first reveal the stunning results...

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Nick Norwitz

@nicknorwitz

Feb 13

🔵💡🧠What if a specific form of light therapy could help clean your brain and hopefully protect against Alzheimer’s disease? (🔗at the end)

New 2025 research reveals how this might work, and how you can take advantage of breaking science today.

1/7) Brain Biology Background🧠
But first, I need to arm you with brain biology background about the brain’s cleaning system: the glymphatic system.

The glymphatic system is a set of channels that expand as blood vessels constrict. Imagine you have a blood vessel running through brain tissue, all bathed in cerebrospinal fluid.

When the blood vessel constricts and shrinks in diameter, it creates space between the vessel and brain tissue, allowing more cerebrospinal fluid to flow through and wash away waste.

🚨But a big question remains, “How do you increase glymphatic flow and clearance of metabolic waste?”

🔵💡Now… Let there be light! 40 Hertz blue light, to be more specific.

One Hertz equals one cycle per second. So, 40 Hertz just means 40 flickers per second."

Prior work has shown that 40-Hertz light flickers can improve cognition in Alzheimer’s patients and animal models.

🤔But how? ...

cc neuronerds 🤓 @hubermanlab @ChrisPalmerMD @NTFabiano @TuitNutrition @NeuroWoodworks

2/7) Well, returning to glymphatics—this waste removal system is impaired in Alzheimer’s disease, which means metabolic junk accumulates in the brain, including soluble amyloid particles. This can lead to a cascade of events, precipitating cognitive decline and dementia.

Now, there’s one more nibble of neuronal knowledge I need to give you before we get to the results. The glymphatic flow is regulated, in part by water channels on brain support cells called astrocytes around blood vessels in the brain.

These water channels are called aquaporin 4 (AQP4) and, to put it simply, more water flow through aquaporin 4 channels allows for better flow and more rinsing of metabolic debris from the brain.

🔵40 Hz Blue Light Enhances Cognition💡
3/7) The researchers exposed one group of Alzheimer’s mice to 40 Hertz blue light for 1 hour per day for 2 weeks, then testing their cognition on validated cognitive tests like a Y-maze and novel object recognition tests.

They found the blue light treatment improved memory performance closer to that of non-Alzheimer’s mice.

Shown are Figures 1C and 1E from the paper. “WT-Con” are non-Alzheimer’s control mice. “AD-Con” are Alzheimer’s mice that did not receive 40 Hz blue light treatment, and “AD-BLUE” are Alzheimer’s mice that did receive 40 Hz blue light treatment. As you ca see, 40 hz blue light treatment restores performance in Alzheimer’s mice to levels comparable with non-Alzheimer’s mice.

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Nick Norwitz

@nicknorwitz

Feb 12

"It's not how old you are. It's how you are old." 💪

1/4) I can’t think of a better quote to encapsulate the results of the brand new study that included 139 adults spanning ages 20 to 93, including active and inactive participants across the age spectrum, and asked the question: What are the relative effects of aging and exercise on body composition and muscle function?

The results: Surprisingly uplifting. (link at the end)
#exercise #longevity #muscle #healthyaging

Ref: PMID: 39933528. Cell Reports Medicine. Feb 6, 2025

💪Results: Body Composition💪
2/4) One of the most fascinating findings was how closely the profile of the oldest active group mirrored that of the youngest inactive group.

For example, comparing active individuals over 70 (mean age: 76) with inactive individuals in their 20s and 30s (mean age: 30), their body compositions were nearly identical. They were within 0.1% body fat of each other (27.2% vs 27.11%), and within 0.2% lean mass of each other (69.7% vs 69.9%).

It’s rather eerie how closely matched in body composition an active 76-year-old is compared to an inactive 30-year-old.

💪Importance of Muscle (Endocrine Organ)💪
3/4) Muscle mass is, in fact, one of the greatest predictors of longevity and health span.

Not only does muscle tissue combat frailty, but muscle is a critical endocrine organ, secreting hormones into the blood like irisin, which protects against neuro-inflammation, increases brain-derived neurotrophic factor (BDNF) – which is key for the effects of exercise on neurogenesis and cognition – and may reduce your risk of cognitive decline and dementia.

Indeed, having more muscle increases irisin, as well other muscle-derived hormones broadly classes as “myokines” (muscle hormones) that can signal to the brain to improve brain health.

So, in a nutshell, your muscle literally signals to your brain with chemicals that protect it.

💪Think about that next time you’re doing a squat – a butt exercise that’s also a brain exercise.

Muscle is also your biggest sink for blood glucose, helping to maintain healthy blood sugar levels – which has positive knock-on effects for your blood vessels and brain.

The keep it simple, stupid line here is don’t forget resistance training as you age.

💪Your future self is spotting you—don’t let them down.

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Nick Norwitz

@nicknorwitz

Feb 6

A Big Congratulations to my friend Ben Bikman for his wonderful appearance on Diary of a CEO podcast. Out there educating the masses about Metabolic Health!

Here are 5 Fast Facts about Insulin Resistance, Calories & Fat to whet your appetite. Then, check out the episode with @BenBikmanPhD and @StevenBartlett.

1. Erectile Dysfunction (ED) may be a ‘canary in the condom.’ Ben cites this paper (PMID: 23681359) ~12 min into the podcast, which concludes:

“ED may be the first clinical sign of endothelial dysfunction and a clinical marker of cardiovascular and metabolic diseases. Subclinical endothelial dysfunction and insulin resistance may be the underlying pathogenesis of ED”

2. Not all tissues and pathways become insulin resistant equally.
Insulin Resistance refers to a pathological state that tends to occur when fat cells get too big. In response, they stop ‘listening’ to insulin. The pancreas compensates by increasing insulin production, leading to “hyperinsulinemia” (high insulin). But here’s the catch…

Not all tissues and pathways become insulin resistant equally. Thus, you end up with dual pathologies, where some tissues aren’t getting enough insulin signal and others are getting too much.

This is why high insulin in insulin resistance can lead to more new fat generation in the liver, while at the same time insulin can’t suppress the generation of glucose by the liver (gluconeogenesis) as well and brain glucose metabolism becomes impaired.

3. The more insulin resistant you are, the more you benefit from carbohydrate restriction.

This has been demonstrated in multiple randomized controlled trials. For example, in one recent 2025 study (PMID: 39756404), among insulin resistant women put on low-fat vs low-carb diets, the women on the low-carb diet lost more weight and – despite losing more weight – maintained higher resting energy expenditure and total energy expenditure.

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Nick Norwitz

@nicknorwitz

Feb 6

Dopamine, Fat Loss, and Inflammation: The Science of Cold Plunging 🥶🧠🔥

Cold showers and cold plunging are a rising health trend (ht/ @hubermanlab @joerogan). I have to ask: Is there solid science to back up this practice?

Let’s review 3 papers on why you shouldn't cold plunge… and why you should... (Links at the end)

1/4) 🔥You shouldn’t cold plunge to burn calories and lose body fat

Truthfully, it’s not efficient. Take, for example, a recent interventional trial in 15 overweight adults who were exposed to a cold-water suit for 10 consecutive days for 1 hour per day to induce shivering.

😢And, at the end of the treatment period there was no change in fat mass.

Now, during cold exposure it’s true your body increases energy output to maintain body temperature. And that did happen. But it’s not efficient.

Think about this: you could get more bang for your “calorie” buck by just walking. Even light walking at 3 mile per hour uses 3 METs, which is usually more than typical cold exposure, and less painful.

So, from this new paper – and the balance of other literature – cold exposure is not efficient for increasing calorie burning and losing fat.

But does that mean you shouldn’t cold plunge or cold shower? ...

ref. Sellers A.J. et al. Cold acclimation with shivering improves metabolic health in adults with overweight or obesity. Nature Metabolism. 2024. PMID: 39643644

#coldplunge #inflammation #Dopamine

2/4) 🧠Cold Exposure and Dopamine/Mental Health

In a famous study from 2000, researchers immersed subjects in water of different temperatures, 32, 20 and 14 degrees Celsius for 1 hour each in a crossover. And they found that the cold water (14C) increased dopamine concentrations by > 250%

Importantly, this rise was slow and steady, and dopamine was still elevated well into the recovery period.

They only measured up to 1 hour after the cold-water immersion; but, based on the shape of the curve, I’d be surprised if the dopamine rise didn’t last for at least several hours.

Granted, I’ll caveat and clarify, these are dopamine levels from the blood, not the brain. And dopamine doesn’t cross the blood brain barrier. However, it’s clear there is a robust activation of the central nervous system with a dramatic change in neurochemicals and a commonly reported “post-cold high” that is robust and stable for many people.

So, while there is a lot we don’t know, I still think the mental health boost is one big reason to consider cold plunging.

Ref. Sramek P. et al. Human physiological responses to immersion into water of different temperatures. Eur J Appl Physiol. 2000. PMID: 10751106

3/4) 🔥Cold Plunge & Reducing Inflammation

In a 2022 study in Nature Metabolism researchers looked at a hormone called "Maresin" - a hormone made by brown fat.

They found that cold via activation of the sympathetic ‘fight-or-flight’ branch of the nervous system causes brown fat to release more Maresin, which decreases inflammation in the liver and the whole body, independent of any weight loss

This speaks to how cold exposure can change the hormonal landscape of our bodies by altering how fat tissue, and also other tissue like muscles, secrete different hormones.

Ref. Sugimoto S. et al. Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation. Nature Metabolism. 2022. PMID: 35760872

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Nick Norwitz

@nicknorwitz

Feb 3

🍇The Grape Debate🍇: Is fruit healthy? And how much is too much?

1/10) These aren’t easy questions to answer. In this thread and associated with video, we will dissect these questions with the critical thought they deserve, in a manner you’ll hopefully a-peach-ciate🍑.

We will review why fructose in fruit is contextually different than fructose in many processed foods. We will then review why the scientific literature can be misleading.
Finally, will end with the practical guide, helping you to rank fruits based on various parameters.

🥭Fructose vs Fruit

Fructose is a metabolically harmful molecule beyond just being “empty calories.” Fructose can act in the liver to promote metabolic syndrome, depleting cells of energy and harming mitochondria, and potentially even enhancing the growth of certain cancers. (references in newsletter and video)

But does that mean fruit is bad?

Perhaps counterintuitively: Not necessarily, no. Let’s reconcile…

2/10) The negative effects of fructose depend on its metabolism in the body, starting with the liver.

However, the intestines transform fructose into other molecules, glucose and organic acids before fructose gets to the liver.

The image shown is what happens when the researchers gave animals an equal combination of radio-labeled (C13) glucose and fructose, and then collect samples from the portal vein going from the intestines to the liver. Either fructose OR glucose is labeled at any one time. (Note, need to use animals for ethical reasons, but process is conserved in humans. More on. This below)

You can see, glucose (black) passes right through the intestines en route to the liver, but fructose (blue) does not. It gets transformed, leaving very little fructose going to the liver.

On the right is a breakdown of the specific molecules into which fructose is transformed.

3/10) However, and here’s the catch: higher doses of fructose doses as in a sugar sweetened beverages can be harmful, since they exceed the capacity of the body to filter and transform the fructose, leading to spillover to the liver.

The authors of a seminal paper on the topic based on tracer studies write, “the balance between fructose consumption and intestinal fructose clearance capacity determines liver exposure to dietary fructose and thereby fructose toxicity.”

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