🚨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.

🚨 New Genetic Discovery: Why Some People Naturally Eat Less Sugar & Stay Lean 🍫➡️🚫 (link at the end)

Scientists may have just uncovered a hidden biological quirk that makes some people naturally eat less sugar, crave less sugar, and stay lean.

1/5) A paper just published in Gastroenterology found that people with mutations in a gene coding for a carbohydrate-digesting protein called “sucrase-isomaltase” had:
✅Lower intake of added sugar
✅Lower BMI
✅Improved metabolic health

But here’s the kicker: there may be a way to hack this system, even if you weren’t born with these lucky genetics 👀…

#SugarCravings #Metabolism #NutritionScience #GLP1 #FunctionalFood #Genetics #HealthHack 2/5) Researchers found that people with a Sucrase-isomaltase mutation that reduces this protein’s function not only consumed less sugar but also experienced better metabolic health overall.

🍭 Voluntarily ate less sugar
🥤 Drank less sugary fluids
🔁 AND released more GLP-1 in response to sugar

'Lettuce' Be Honest: Fiber Isn’t Always the Answer🥬🤥(Refs linked in letter at the end) 🧵

1/6) We’ve been told for years that fiber is a must-have for gut health—that without it, your microbiome will crumble faster than a stale bran muffin.

But what if I told you… you don’t actually "need" fiber?

But before you throw your kale smoothie at the screen, let’s break down the science—because the truth about fiber is way more complex than a simple 'good' or 'bad.'

#fiber #microbiome #guthealth #educational #SCFA #ketodiet #carnivore #plantbased #metabolism #metabolichealth 2/6) Fiber & Inflammation🔥🥬

Some people argue that fiber-rich foods are anti-inflammatory. But that’s not entirely true.

For example, a landmark randomized controlled trial published in Cell found that some people were inflammatory responders to dietary fiber. Reading from the paper, “Taken together, these data suggest divergent immune system responses to the high-fiber intervention, with high-inflammation participants exhibiting broad increases in steady-state immune activation.”

To be clear, this was NOT the majority of participants.

And it's also worth noting that those with lower microbiome diversity tended to be the inflammatory responders, raising the 🤔hypothesis🤔 that there might be protocols by which one could train-up a microbiome such that it responds with a healthier anti-inflammatory response to fiber...

It’s possible.

But the fact remains that some people have a pro-inflammatory response to fiber that could have negative health consequences and contribute to or exacerbate chronic disease.

What if all *autoimmune diseases* were stemming from the same source, from a seed planted 2 Billion years ago that’s just beginning to flower? 🔥🤔🧵

1/6) That might sound wild—but it’s actually the central thesis of a perspectives paper published in @Nature, which proposes that many autoimmune diseases may be driven by the failure of a relationship that began 2 billion years ago: the one between your body and your mitochondria.

For me, this idea carries personal weight since I suffered from debilitating inflammatory bowel disease, which went into remission on a ketogenic diet.

I’ve seen others similarly put IBD, lupus, multiple sclerosis, and rheumatoid arthritis into remission with lifestyle change.

And I desperately want to know how it works.

But enough chit chat, the paper is entitled: “A break in mitochondrial endosymbiosis as a basis for inflammatory diseases.” (PMID: 38326590).

This thread will explain it in simple terms, but with nuance. 🧵👇

(link to more at the end)

Potentially of interest to:
@ChrisPalmerMD #BrainEnergy
@thegarybrecka @joerogan - Discussed Autoimmune Disease on Epi #2304. I agree with Gary, "God [metaphorically or literally speaking, depending on your beliefs], didn't make a mistake." And THIS might be what we are missing
@hubermanlab @R_Mohr @bryan_johnson because of relationship to circadian rhythms
@MitoPsychoBio because #mitochondria
@AdrianSotoMota @drmarkhyman @MatthewNehsMD @drericwestman @JEverettLearned @AKoutnik @lowcarbGP because I know they will
And Ht/ @davidludwigmd who passed me the paper that inspired this thread, newsletter & upcoming video
#autoimmunity #inflammation #mitochondria #metabolichealth #metabolism 2/6) What is "Mitochondrial Endosymbiosis?"

About 2 billion years ago, a cell consumed another, smaller bacteria-like cell (technically it was an Asgard archaeon). That second, smaller cell didn’t get digested and pooped out, but integrated into the larger one.

This is what’s meant by “endosymbiosis.”

And, you guessed it, that smaller cell was the precursor to our very own mitochondria, the engine and the powerhouse of most of the cells in your body and the center of your metabolism.

But your mitochondria are far more than just little engines.

They are also informational hubs and communication stations, signaling all over your body to cue and coordinate near infinite pathways and processes.

And how mitochondria do this derives, at least in part, from their foreign origins. Truly, mitochondria retain many of the signatures of their foreign origins that mark them much like bacteria or viruses and apart from other components of “you.”

The authors write, “we can also consider mitochondria as a pseudobacterium ‘bricked in’ behind the mitochondrial outer membrane.”

🚨FINALLY! The Lean Mass Hyper-Responder 1 Year Data Just Dropped!🚨
jacc.org/doi/10.1016/j.…

🫀Most participants showed NO OR MINIMAL or progression of coronary plaque
🫀Neither ApoB nor LDL exposure predicted plaque progression
🫀But plaque predicted plaque progression, leading to the conclusion and Title:

1/10) 🧵This thread will give you some high-level points, direct you to more information, and tell you how 🫵YOU🫵 can help change “the science”

(🔗 links at the end!)

ht/ @realDaveFeldman @AdrianSotoMota @Metabolic_Mind @janellison @bschermd @BudoffMd @khurramn1 2/10) Necessary Background

Colleagues and I have spent the last several years studying what happens to cholesterol levels in people who adopt very low-carbohydrate ketogenic diets

🤔Most don’t see increases in cholesterol.

🤔Many even see decreases.

👉However, some see their LDL cholesterol (LDL-C) levels rise so high that most doctors think it’s “inconceivable.”

These special individuals are called ‘lean mass hyper-responders’ (LMHR) because they are, as a population, generally lean and healthy.

In fact, our prior meta-analysis of 41 human RCTs (PMID: 38237807) showed that the leaner a person is, the higher their LDL-C tends to rise on a low-carbohydrate diet trials.
🧈🧈🧈🧈This study also showed that having a BMI < 25 kg/m2 was >5X as powerful as being in the top quartile of saturated fat intake for predicting LDL-C change.

So, this is certainly far more interesting than a ‘blame-the-butter’ story …

Why do some people with crazy high LDL-C and ApoB develop no plaque in their arteries, while others – including those with far lower LDL and lower ApoB – do develop plaque? 🫀🤔(link 🔗 at the end) 🧵...

1/6) We know this is a phenomenon. So, let’s tackle one possible explanation centered around the following term: Transcytosis...

#LDL #ApoB #LMHR #LEM #Cholesterol #HeartHealth #CholesterolCode cc @realDaveFeldman @AdrianSotoMota 2/6) Transcytosis, Made Simple🫀🤔
Your arteries are lined by cells called endothelial cells. Endo- means within, as these cells are within the tube that composes your blood vessels. A coronary plaque grows when cholesterol-containing particles, including LDL particles, slip through the endothelial barrier and begin to seed a plaque.

But HOW do cholesterol-containing particles penetrate the endothelial barrier? It’s not like a healthy endothelial barrier is coarse chicken wire. It’s rather tightly knit.
That’s where “transcytosis” comes into the picture.

Transcytosis is the process whereby a cell – in this case, the endothelial cells lining your arteries – sucks up something from outside (here, an LDL particle containing cholesterol), passes that something through its interior, and then out the other side.

By way of analogy, think of your artery wall like an exclusive nightclub. Some particles get waved in VIP-style. Others get stuck outside. But what if LDL wasn’t just passively slipping through a hole in the wall, but was actually being escorted through by a bouncer? That is - more or less - transcytosis.

🧠Saffron for Depression: The Science, the Studies, and the Recipes🧠

1/5) What if I told you that the kitchen spice – Saffron – could treat depression?

It may sound too good to be true, but that claim is supported by a growing pile of human randomized controlled trials (RCTs) and sensible biological mechanisms.

I’m going to share two of these studies, explain the neuroscience, and direct you to more learning.

This golden spice really might be the next big thing in mental health!

References are in the newsletter linked at the end. #saffron #depression #mentalhealth 2/5) Saffron vs SSRI (RCT)
This double-blind randomized controlled trial compared 6 weeks of saffron supplementation (30mg/d) vs Prozac (fluoxetine), a commonly prescribed selective serotonin reuptake inhibitor (SSRI).

Impressively, the saffron performed equal to the fluoxetine!

You can see the results over 6 weeks here, with the Hamilton Rating Scale for Depression dropping in lock step between the treatments.

The absolute decrease in both treatments was >12. What does that number mean?

Well, in clinical trials, there’s a key distinction between a “statistically significant” difference and a “clinically significant” difference. A “statistically significant” difference means there was a detectable numeric difference, as in over time or between groups. Conversely, a “clinically significant” difference means that size of the change was detectable and meaningful for the patient.

Now while it’s somewhat arbitrary, a clinically meaningful change in this depression scale is ~5 points, which means a ~12-point drop is impressive and is clinically substantial!

Note on Side Effects: One presumed advantage of saffron is that it could have fewer side effects than prescription medications. In this first small pilot trial, there is an apparent trend to lower side effects in the saffron group vs SSRI. To see that table, click on the link at the end of this thread.

Cold Exposure❄️, Omega-6 & Omega-3 🐟. Fats-cinating Research! Let’s dive in! (link at end)

1/5) In this study, 64 adults endured 2 hours of cold exposure near their shivering threshold.

🤔Results🤔

Massive changes in signaling lipids, including omega-6 and omega-3 fats and their derivatives, endocannabinoids and specific pro-resolving mediators.

On net, the changes reflected a signature of improved cardiometabolic health 🫀❤️‍🔥 #coldplunge #hearthealth 2/5) 🥶Some specific Omega-6 and 3 Changes🥶

👉39% Increase in the omega-6 oxylipin 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME). This oxylipin has been shown to increase the uptake of
fatty acids by brown fat and skeletal muscle.

🔥But even more impressive than the omega-6 response was the omega-3 response...

👉17 out of 17 omega-3 fats and their derivatives increased in the blood after cold exposure, by an average of 77%

👉The most prominent change, with an increase of 155%, was in 14- hydroxy-docosahexaenoic acid (14-HDoHE), which has been shown to inhibit activation of platelets involved in blood clots, increase blood flow, and inhibit inflammation.

👉And increases were noted in Resolvin D5, a powerful anti-inflammatory compound that inhibits the production of inflammatory molecules, like IL-6, reduces pain and protects various organs from inflammatory challenges.

☕️Coffee for Gut Health?! 🦠 New Research will have you Express-O-ing excitement!

This thread will reveal what new research in Nature Microbiology has discovered, tell you how much coffee to drink to get the health benefits, compare caffeinated vs. decaf, and more. I hope you’ve had a cup or two because you’ll need focus for this. (🔗link at the end)

1/8) Quick Background on the Health Benefits of Coffee

First, coffee intake has already been associated with lower mortality, reduced cardiovascular disease-related death, and a lower risk of type 2 diabetes. But nutritional epidemiology—the study of diet and health outcomes in large populations—has its limitations because it can only look for correlations.

To solidify coffee’s health halo, what we want is a complementary biological mechanism, a physiological story that helps it all make sense. #coffee #microbiome 2/8) Coffee Changes the Microbiome: Lawsonibacter asaccharolyticus

So, let’s introduce the protagonist of this story, a gut bacterium named Lawsonibacter asaccharolyticus. (I know, it sounds kind of like a Harry Potter spell.)

To discover the Lawsonibacter asaccharolyticus–coffee link, the researchers took information on food intake, including > 150 specific foods with associated and microbiome samples, then look for connections between specific foods and microbiome signatures.

☕️Among the >150 foods analyzed; coffee stood out for having the clearest microbiome signature.

Why do we sleep? 😴And what caused “Brain Constipation? 🧠💩 New research in @CellCellPress
(Link at end, w/ exclusive clip from first author 🤓)

1/4) A Key Function of Sleep is to clear metabolic wastes from the brain.

This function is carried out by the “glymphatic system,” a series of channels that expand as blood vessels constrict. Deep non-rapid eye movement (NREM) sleep is prime time for glymphatic systema and brain waste removal. But a key question that has remained unanswered until now is *HOW* is this system regulated?

🧠Norepinephrine Regulates Glymphatic Flow🌊
The researchers find a group of neurons in the brain stem bathes the brain in norepinephrine pulses while we sleep. Norepinephrine is a vasoconstrictor, and these pulses therefore generate waves of blood vessel constriction that enhance glymphatic flow and metabolic waste removal from the brain.

🧠 Brain Constipation?💩
By way of analogy, think about your gastrointestinal system: Your intestines use rhythmic contractions to move waste out. If that process stops—you get constipated. Now imagine your brain has a similar waste-removal system... but instead of food, it’s clearing out toxic metabolic byproducts. If something blocks that process, you get brain constipation.

What causes brain constipation?

* if I do say so, I think this is a video @hubermanlab, cc @IanGMackey @R_Mohr, and @bryan_johnson and @NTFabiano will each enjoy -- ... and if you want more on glymphatics and sleep, let me know
* Don't miss an exclusive clip from the first author of the research in the full video, link at the end. 2/4) The researchers then asked the provocative question: What do certain sleep medications, specifically Zolpidem, do to norepinephrine pulses and glymphatic function?

💩 In brief, they find that the sleep medication impairs the normal oscillations in norepinephrine and decreases glymphatic flow. The implication is that long-term use could contribute to a build-up of metabolic debris in the brain and, possibly, long-term negative consequences like cognitive decline.

Indeed, long-term human studies have linked Zolpidem to higher rates of dementia and Alzheimer’s disease.

Fortunately, this does not appear to be the case for other medications that are often used to help with sleep, like the atypical anti-depressant trazodone. In fact, there are suggestions that this medication might improve sleep architecture and is associated with lower rates of dementia.

1/8) Yesterday @bryan_johnson claimed he's "aging slower than anyone in the world." This is incorrect by his own measurement tool.

But this thread isn't just a fact-check. It's an assessment of the "Pace of Aging Clock," and how I think one should interpret these data.

🔗 to letter and more data at the end🔗
cc @Derek_Fitness @JEverettLearned 2/8) First, what is the DunedInPACE Score?
PACE stands for Pace of Aging Calculated from the Epigenome—and the score is meant to measure the rate of biological change, with a value of 1.0 = 1 year of biological change per calendar year.

As opposed to the other aging clocks, which were developed by comparing people of different ages, DunedinPACE was developed by following a cohort of individuals who were all the same chronological age and measuring changes in biomarkers reflecting the health and integrity of different organ systems (cardiovascular, renal, hepatic, immune, etc.), then normalizing to 1, such that 1.0 indicates 1 year of biological change per 12-month calendar year.

Ketogenic Diet for Parkinson's Disease - Mega Post
(🔗 to Deep Dive Video at the End.)

Let’s cut to the chase: my answer is a cautious but confident “Yes.”

However, it’s not that simple. In this thread, I’ll break down the “what,” “how,” and “why” of a Ketogenic Diet for Parkinson’s Disease.

1/9) First, what is Parkinson’s disease? 🧠

Parkinson’s disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The motor symptoms are what most classically stand out and include cardinal features of:
👉1) Tremor
👉2) Bradykinesia, which means slowness in movement
👉3) Rigidity, that can make it hard to walk, write, speak, or express facial expressions
👉4) Postural instability, which can lead to falls.
In terms of non-motor symptoms, patients often experience issues with smell, gastrointestinal upset, and sometimes mood disturbances like depression.

How common is Parkinson’s disease?

👉Second most common neurodegenerative disease, behind Alzheimer’s.

👉Impacts >10 million people worldwide and is growing in prevalence much faster than Alzheimer’s disease. If it were an infectious disease, Parkinson’s would be labeled a pandemic.

cc @Metabolic_Mind @bschermd @janellison @ChrisPalmerMD 2/9) What causes Parkinson’s disease? 🧠🤔

Parkinson’s disease is caused by the death of dopamine producing neurons in the brain’s “substantia nigra.” This translates to ‘black substance’ and is a little patch of brain in the midbrain motor system in the brain.

Specifically, Parkinson’s disease is characterized by the aggregation of misfolded “alpha synuclein” protein – the hallmark of Parkinson’s disease – leading to the death of these dopamine producing substantia nigra neurons.

As more neurons die… the disease gets worse. And current standard of care is, basically, replacing the missing dopamine with dopamine supplementation of some form. However, as more neurons die, the underlaying disease progresses, the medications become less effective, and the disease typically gets worse until…

👉👉Well, that’s why we really need better treatments.

Science, Sperm & Sabotage: The Hard Truth About Diet Coke 😲🍆

1/9) This one is going to really Piss Off the Diet Soda Defenders. Also, fair warning, there are a lot of adult puns... let's go...

Punch line: Men, aspartame-sweetened diet sodas could be screwing with your swimmers. You know what I mean, your sperm. It’s a hard truth. Do you have the balls to hear it?

I’m going to quickly hit you with some data, before we cuddle up with a broader point about interpreting animal model literature in an intellectually honest way.

@bryan_johnson @GosuGains @Dr_JonesDC @DoctorTro @BrianWiley_ @DrTarekArab @thelowcarb_rd @KenDBerryMD @BenBikmanPhD @AmericanEpilog @PiaJSigler @BiggestComeback @DaveEDanna @realDaveFeldman @AdrianSotoMota @Physionic_PhD @RenaMalikMD @PNASNews 2/9) Low-Dose Aspartame Causes Anxiety in Mice

The paper I want to spend a few minutes exposing you to was published in PNAS (say that out loud fast and you’ll get the irony 🍆).

The researchers gave mice low-dose aspartame, the mouse-to-human adjusted equivalent of 2-4 small (8 oz) cans of aspartame-sweetened diet soda.

Exposure to aspartame caused anxiety in male and female mice over 12 weeks, as measured by validated behavioral tests like this open field test (OFT), where lower on the chart indicates more anxiety behavior.

Diabetes Remission - Present and Future (🧵)
"[Until] Diabetes remission becomes the norm and remission and hope become mutually reinforcing dance partners in a more metabolically healthy society" (🔗at the end of 10/10)

1/10) Medication-free remission from Type 2 Diabetes is possible and sustainable, and there’s no question about it.

Well, that’s not entirely true. We know it’s possible and sustainable, but what are the key ingredients for long-term success?

What does a person need to go from having out of control blood sugar and metabolic dysfunction to getting their blood sugar under control, their metabolic health in order, and off medications?

That’s the core question to which we will build in this thread, after reviewing important data published on a 5-year study from Virta Health assessing diabetes remission among 120 incredible humans.

Without further a-dough-nut, let’s delve into it...
cc @virtahealth 2/10) Diabetes Remission: What Is It?

Diabetes remission is having an HbA1c, a marker of average blood sugar, of <6.5% while off blood-sugar lowering medications. For obvious reasons, diabetes remission is thought to confer protection against the ravages of the disease.

It does not mean that, at some point, you can go back to eating endless breadsticks at the Olive Garden or Munching on Munchkins at Dunkin Donuts.

You do not develop metabolically gifted adipocytes or a superhero pancreas.

But provided you’re happy to stick with the lifestyle that brought you to remission—in this case, a low-carb ketogenic diet—then your organs and overall health are thought to be protected against the devastations of a disease that can otherwise lead to amputations, nephropathy, neuropathy, retinopathy, heart disease, dementia and a multitude of other disastrous consequences.

Aspartame Causes Heart Disease – Bad News for Diet Coke 💔
(🔗 Link at the end)

1/6) A groundbreaking new study reveals that even low doses of aspartame may contribute to heart disease. If you’re serious about your health, it’s worth considering alternatives. I realize this is a big claim—so let’s break it down.

*Background*
Studies have already linked artificial sweeteners, like aspartame, to cardiovascular disease. However, epidemiological studies have limitations and cannot establish a cause-effect relationship. Conducting a long-term human trial to track heart disease progression isn’t feasible, so researchers turned to animal models to better understand how aspartame may contribute to heart disease. This study examined both mice and monkeys.

⚠️Dose⚠️
A common question is: how much aspartame was used? The primary dose in this study was 0.15% aspartame, roughly equivalent to consuming ~3 Diet Cokes per day in humans. 2/6) Aspartame Causes Cardiovascular Disease in Mice

Feeding mice aspartame caused a dose-dependent acceleration of atherosclerotic plaque development.

There was also a higher number of inflammatory cells in the plaques.

Notably, this occurred without an increase in total or LDL cholesterol.

🧬🍩A Mendelian Randomization Study Found that those who tend to have genetics causing them to secrete more insulin in response to carbohydrates had higher BMI

1/6) This is consistent with the Carbohydrate Insulin Model (#CIM), a model of obesity that places “calories” the passenger seat. The “calorie imbalance” most people blame for obesity can be a result of -- rather a cause of -- fat cell growth.

Let’s break it down (link at the end) 👇 2/6) 🩸The CIM posits that a high glycemic load diet, meaning one that tends to spike blood sugar and blood insulin levels more, gives a hormonal signal to the body to store energy as fat tissue.

👉In other words, energy (Calories) come in, and they’re triaged preferentially towards fat, rather than energy expenditure or lean tissue.

👉As a downstream consequence, energy expenditure goes down and hunger increases. Thus, while “calories in – calories out = weight change” and thermodynamics is maintained, the calorie imbalance is the result of a primary hormonal disturbance.

The model is supported by multiple lines of evidence, including everything from pre-clinical mechanistic studies to human randomized controlled trials. (See newsletter for linked references.)

💪Urolithin A & Muscle Health - Interesting RCT 💪

1/6) This study enrolled 88 overweight adults, mean BMI ~29 kg/m2 , who were between the ages of 40 and 64 for a 4 month intervention where they were treated with one of two doses of urolithin A (500 mg or 1000 mg per day) or a placebo.

Strikingly, both doses of Urolithin A improved leg muscle strength by 10-12% as compared to baseline, and improved leg muscle strength as compared to placebo. (Link at the end)

#mitochondria #microbiome #urolithinA 2/6) In terms of endurance performance, peak power output similarly trended upwards in the Urolithin A groups, about ~4% from baseline, with no change from baseline in the placebo group, along with an increase from baseline in peak VO2 in the 1000 mg dose urolithin A group, and improvements in cycling distance and a walking test that passed the threshold of what’s considered clinically significant.

🚨 What if you could get benefits of Caloric Restriction, without Caloric Restriction?

1/5) New research in Nature uncovers a bile acid called Lithocholic Acid (LCA) with incredible effects on muscle, metabolism, and lifespan. Let’s dive in 🧵

Caloric restriction (CR) is one of the most well-studied interventions for longevity.

🪰 In lower organisms, it extends lifespan dramatically.

🐒 In primates, the effects are smaller on lifespan but significant for healthspan—how long you live healthily.

But there’s a tradeoff: CR often causes muscle loss ❌💪

But if you can identify the metabolic mediators of caloric restriction and increase those, you can work smarter with what evolution has afforded us…

(aside: I bet @bryan_johnson does't know about this yet 👉 *poked*) 2/5) LCA & Healthspan

In this study, they fed mice a calorie-restricted diet for 4 months and analyzed their blood. They identified 695 metabolites altered by CR.

Of these, LCA stood out for its ability to activate “anti-aging” proteins AND in that feeding LCA to control mice replicated CR benefits.

LCA…
👉 Lowered blood glucose
👉 Increased GLP-1 levels
👉 Improved muscle function (grip strength, endurance, recovery)
👉 Boosted mitochondrial content & oxidative fibers
❌💪This is huge because CR usually causes muscle loss. 👉🍽️💪🚨🤔

🚨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.

🔵💡🧠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.

"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.