Stress Makes Sugar (Literally!) - New Study Blew my Mind...(🔗 at the end)

1/8) Groundbreaking research just published in @Nature shows that stress can trigger brain circuits with a direct hotline to the liver to make new sugar.

🚨TL; DR Stress can Make Sugar, even independent of eating carbs.

This newly discovered brain-liver axis bypasses the usual hormonal regulators of blood sugar—like cortisol, adrenaline, insulin—and instead sends a direct signal that forces the liver to make and dump sugar into the bloodstream.

Let’s break it down… 2/8) Let me start with an analogy: Imagine if I told you that I could instantly communicate with a friend on the other side of the world. You wouldn’t be shocked—you know I have access to email and a phone. But if I clarified, “No, I’ve invented telepathy,” and could somehow prove it to you, is it fair to say you’d be impressed? That’s analogous to distinction we’re dealing with here: an entirely new and direct line of communication between the brain and liver to influence blood sugar.

Four Subtypes of Diabetes: Groundbreaking Research Out of Stanford (🔗in 7/8 and 8/8)

1/8) Overview:
👉New technologies reveal four subtypes of diabetes
👉Knowing your ‘flavor’ of diabetes (or prediabetes) can guide lifestyle and medical treatment
👉Combining bio-monitoring with big data and machine learning will bring forth a revolution in diabetes care and personalized medicine

*I’m releasing this letter early because the data it covers was conducted by one of my scientific heroes, Stanford’s Professor Michael Snyder @SnyderShot, who happens to be the guest on today’s @hubermanlab podcast episode.

*In fact, Professor Snyder is the only person I’ve pestered Andrew to have on his show, although I suspect the conversation would have happened anyway.

*My two-part interview with Professor Snyder, where we dig into some of his specific studies (Sub-phenotypes of diabetes, personalized medicine, and the famous two peaks of aging) will release part one later this week.

But first, let’s dig into these data! 2/8) The most common form of diabetes — Type 2, often associated with obesity and adult onset — isn’t one disease. It’s actually four different underlying pathologies, showing up in different proportions in different people.

Here’s a metaphor that might help: Imagine a dish made from bread, vegetables, and cheese. The general ingredients stay the same — but their ratios define what you’re eating.

Pile on the vegetables, go easy on the bread, toss in some protein — and you’ve got a Caesar salad with croutons. Flip the script: make bread the base, add a smear of sauce and some melted cheese — and now you’ve got a pizza.

Now imagine if we called both dishes the same thing. That’s what we’ve been doing with Type 2 diabetes.

Can Visceral Fat Cause Depression? (🔗at the end)

1/7) New data reveals how molecular packages called extracellular vesicles (EVs) can travel from visceral fat in the abdominal cavity, through the bloodstream, and into the brain, where they alter the function of specific brain areas and promote depression.

This is no joke. It's (literally) mind-bending science. Let's dig in... 2/7) First, some human context: depression and obesity are highly 'co-morbid'—meaning they often occur together.

Individuals with obesity are twice as likely to experience depression as those with a healthy weight.

Moreover, those diagnosed with depression are similarly at (58%) higher risk of developing obesity down the line, in part due to the adverse effects of certain antidepressant medications.

This can establish a vicious cycle between obesity and depression—a descending spiral with social, psychological, pharmacological, and metabolic components.

But one big question remains unanswered: How does fat tissue contribute to depression?

This is a very difficult question to answer in humans. You can’t perform controlled trials, and the social baggage of living with obesity introduces many psychosocial confounders. So, we turn to animal models.

We return to the human story in the letter—but first, let’s get murine and mechanistic.

Causality is Overrated” – A Respectful Rebuttal to Dr @PeterAttiaMD cc @hubermanlab (🔗at the end)

This thread is about one word: causality.

1/8) People are obsessed with it. But first, let me identify the causal stimulus for this nibble: the quotes Huberman podcast clip @HLPClips (posted yesterday on X) in which Peter Attia expounds upon his “obsession” with causality.

To quote Peter: “Causality is an obsession of mine. Most of the day, on some level, I sit around thinking about causality.”

In this thread I’m going to make the case, respectfully, that Peter misses a big-picture point. This isn’t to ‘mic drop’ or puts points up on some imagined. This is not to end a discussion – it’s to reopen one that is desperately needed.

cc @realDaveFeldman @AdrianSotoMota 2/8) The first three minutes of the clip are devoted to lung cancer, where Peter uses the Socratic method with Andrew to examine the causal relationship between smoking and lung cancer. He ultimately lands on the point:

“If you believe smoking is causally related to lung cancer, then smoking cessation reduces the probability of lung cancer. That is a logical equivalency. There can be no debate about that.”

He then pivots, replacing smoking with ApoB and lung cancer with atherosclerosis, stating: “There is no ambiguity that ApoB is causally related to atherosclerosis.”

Peter even goes so far as to argue that not treating elevated ApoB—even if the a person’s overall major adverse cardiovascular event score is low—is “as idiotic” as permitting someone to smoke.

But here’s where I think Peter is wrong because causality is not the same as importance.

The Molecular Gym: How Your Heart Trains from the Inside Out (🔗in 4/4)

1/4) Every time you exercise, you're not just straining a muscle — you're triggering molecular rewiring in your heart.

The truth is your heart is not “just a pump” — your heart is an endocrine organ, a nucleus of signaling, and a complex communication network... 2/4) But let’s ‘warm-up’ with an intellectually light fact that I bet you didn’t know: Exercise remains the only known physiological stimulus that promotes the generation of new heart muscle cells.

Let’s double-click on this: of all the environmental stressors and physical inputs into our body, only exercise causes the growth and development of new heart muscle cells in adult mammals.

This matters because the adult heart is known for being notoriously resistant to regeneration. Yet with exercise, that rule is bent, if not broken.

Seed Oils: A Provocatively Reasonable Take
*In anticipation of a 3.5hr debate between me and @paulsaladinomd 👉🔗to full letter at the end

1/10) I’m fascinated by the seed oil debate for two reasons:
(1) The data are complex and often contradictory
(2) It’s surprisingly hard to get people to hear what I’m actually saying—rather than what they assume from a headline, thumbnail, or opening remark.

Sometimes those assumptions are shaped simply by the framework of the conversation, such as the debate partner sitting across from me.

But in today’s newsletter, I’m taking a different approach:
🔥I’ll start by outlining, in broad strokes, what I believe and what I do.
🔥Then we will walk through arguments commonly made against seed oils and evaluate each.
🔥Finally, we will end with a set of questions I want you to ask yourself to help you decide what makes the most sense for your own and how to better assess such claims and arguments made about health and nutrition.

All the references are hyperlinked in the letter linked in 10/10 2/10) At a High Level: My Stance on Seed Oils

In short, I believe seed oils—here defined as highly industrialized and processed oils extracted from plants using “harsh” chemical and heating methods—are unnecessary at best and harmful at worst.

I personally avoid sunflower, safflower, corn, and canola oil in my diet (with the sole exception of one brand of salt-and-vinegar pistachios containing a light dusting of sunflower oil—an indulgence I admit in the spirit of transparency).

My decision follows the “precautionary principle.”
We still don’t fully understand these industrialized seed oils, but the balance of probability suggests they’re more likely to be harmful than beneficial—at least compared to more natural fat sources such as extra-virgin olive oil, unprocessed nuts and seeds, and, yes, animal-based fats like ghee or tallow.

Statins Slash GLP-1 Levels - Human Controlled Trial
(🔗 at the end)
1/9) Usually, scientific research excites me. But the paper I just read? It both excited and annoyed me.

It explores how statins – the most profitable drug in history, with annual sales exceeding $20 billion – contribute to insulin resistance, increase diabetes risk, and significantly lower GLP-1 levels in humans.

These findings were published over a year ago – February 6th, 2024 – in @Cell_Metabolism, a highly respected scientific journal.

This should have been headline news. But not a word.

I’ll return to my commentary on the silence around these data. But first, let’s make sure you understand more than most doctors about this overlooked finding. 2/9) In the first experiment, researchers enrolled 30 patients who were starting atorvastatin (20 mg) and 10 control patients who weren’t taking statins. They followed both groups for 16 weeks.

The results?

Statin use led to significant increases in HbA1c, insulin levels, and insulin resistance (HOMA-IR). At the same time, it caused a sharp drop in GLP-1 – ~50% by the end of the four-month trial, with a continued downward trend still clearly visible.

In my opinion, just that one panel – Figure 1H from the paper – should’ve made headlines. Newspapers should’ve been shouting: “Statins cut GLP-1 levels by half! Here's what it could mean for your health.”

1/9) In the most gentlemanly manner possible, @realDaveFeldman just released the lipid-nerd equivalent of “Here, hold my beer”on the KETO-CTA study.

Drawing from his slide deck and some new reveals, I’m going to summarize what you need to know.

First big question: Why have we been quiet and apparently disengaged on the KETO-CTA matter?

After the April 7th paper, “oddities” were noted in the Cleerly data. I can attest that Dave had flagged these well before publication (see ~3:36–5:25 in Dave’s lecture, linked at the end).

However, given his position as the study’s funder, he (and I by proxy) felt it was “inappropriate” to push for additional review analyses at that time. Furthermore, (i) there were robust and novel findings we could (and did) publish, and (ii) Dave et al. knew we’d eventually have all the raw data in hand to review and assess.

So, we published the data we had—knowing there would be more papers from this dataset, including plaque progression metrics with the pre-specified QAngio methodology (Cleerly was not the pre-specified methodology; QAngio was, it just takes longer to process).

We published the data we had with emphasis on the novel finding that: Plaque Predicts Plaque Progression, but ApoB does not. 2/9) Now, the pushback we received on this emphasized novel finding (“Plaque Predicts Plaque Progression, but ApoB does Not”) is perhaps one of the silliest arguments I’ve observed in the metabolic health space.

Critics argued that because “all of these people had high LDL and high ApoB,” there wasn’t a sufficiently “varying dosage.”

The reason this is such a—pardon my directness—stupid argument is because our cohort had the widest dosage variability of any prospective cardiac imaging study ever published.

Can this Little-Known Hormone Can Rejuvenate Your Heart? (🔗 at the end)

1/9) We tend to think of heart aging as inevitable — a slow, steady decline baked into the passage of time. But emerging research suggests that a fat-derived hormone might hold the key to reversing age-related decline in cardiac function. Not with drugs or supplements, but with a simple intervention you can access today. And I’m going to prove it to you.

Perhaps you’ve heard of brown fat—a type of fat tissue that is specialized to produce heat, i.e., “thermogenesis.” It protects against the cold and is often discussed in nutrition, metabolism, and biohacker circles because of its impressive ability to burn calories.

But that simplistic view of brown fat has led many to overlook its more important role: brown fat is an endocrine organ, secreting hormones that alter metabolism and physiology in meaningful ways.

One class of hormones that’s particularly interesting are the oxylipins—metabolites of polyunsaturated fats like omega-3 and omega-6. 2/9) One specific oxylipin that’s gaining attention is 12,13-diHOME, a derivative of the Omega-6 fat linoleic acid.

In a nutshell, a new study in Nature Communications found that 12,13-diHOME levels decrease with age in both humans and animals, alongside a decline in brown fat activity. This decline is associated with decreased cardiovascular function, as 12,13-diHOME acts on the heart to keep it functioning optimally.

But transplanting brown fat from young animals into old animals or directly treating old animals with 12,13-diHOME restores youthful cardiovascular function. This suggests that this special lipid could serve as an anti-aging hormone.

Intermittent Fasting Reprograms the Alzheimer’s Brain (🔗 at the end)

1/5) Emerging research suggests that intermittent fasting — also known as time-restricted feeding (TRF) — may slow the progression of Alzheimer’s disease by altering the rhythmic expression of genes in the brain.
That might sound like an extraordinary claim — maybe even too good to be true. But consider this: Alzheimer’s disease is already closely linked to circadian disruptions — including difficulty falling asleep, staying asleep, and excessive daytime drowsiness.

What’s more, poor sleep impairs the brain’s ability to clear metabolic waste, contributing to the buildup of misfolded proteins associated with Alzheimer’s and other neurodegenerative diseases.

This sets the stage for a vicious cycle: Alzheimer's pathology disrupts the circadian rhythm, which then worsens the disease. 2/5) Now, let’s turn to the study that inspired this newsletter, published in @Cell_Metabolism. Researchers used a mouse model of Alzheimer’s disease. While not a perfect analog for sporadic human Alzheimer’s, these models offer key advantages:
👉The disease progresses rapidly enough to study in real time
👉Interventions can be tightly controlled
👉And crucially, brain tissue can be harvested for molecular analysis

First, researchers observed that the Alzheimer’s mice—like humans with the disease—exhibited altered and fragmented sleep that worsened with age. This led to decreased total sleep time and disrupted patterns of activity across daily cycles. Interestingly, TRF improved these disrupted patterns, restoring them to the level seen in control mice without Alzheimer’s.

Perhaps this isn’t surprising, as food can be a very strong zeitgeber (circadian cue). However, that’s only a superficial understanding. Let’s look under the hood—i.e., under the skull.

1/7) I keep getting pinged about a rather viral reel by @drmarkhyman on Instagram from his interview with @hubermanlab on Seed Oils and the Minnesota Coronary Experiment. I’ve gotten a few questions, so I thought I’d break it down quickly.

Mark was referring was Ramsden et al., 2016 in the BMJ, which presented 'new' data from Minnesota Coronary Experiment — a multi-center, double-blinded, randomized controlled trial conducted between 1968 and 1973... 2/7) The intervention was a corn oil diet versus a control diet relatively higher in saturated fat.

The corn oil diet included 13.2% of calories from linoleic acid (a 280% increase in linoleic acid and a 51% reduction in saturated fat from the baseline diet)

The control diet, which had 4.7% of calories from linoleic acid.

The Hard Truth: Viagra Could Prevent Alzheimer’s Disease (🔗 in 5/5)

1/5) The talk of the town this last week has been the Nature paper showing that Lithium may help prevent Alzheimer’s disease. But what if another common (bedroom) compound could reduce Alzheimer’s risk by 69%? …

Viagra might prevent Alzheimer’s disease. And yes, I am serious. The paper I want to talk about was published in @NatureAging. The researchers began with an exploratory analysis, looking for predicted molecular interactions between existing drugs and pathways involved in Alzheimer’s disease.

Viagra (Sildenafil) stood up — darn it! — I meant, stood out. 2/5) Now, if Viagra truly reduces the risk of Alzheimer’s, we should expect to see that effect in large population datasets. And we do. The researchers performed multiple analyses on over 7 million individuals enrolled in Medicare Advantage insurance plans and found that Viagra use was associated with a 69% reduced risk of Alzheimer’s disease compared to non-users.

The Lithium for Alzheimer’s Paper Everyone is Talking About (🔗 in 8/8)

1/8) A major new paper published in @Nature from researchers at Harvard reinvigorated scientific interest in lithium for Alzheimer’s disease.

We will dive into the new data and end with practical takeaways that could change your daily routine to protect your brain.

And I promise to tell you what I’m doing personally, and what I’m and recommending for my family. But first, let’s lay the groundwork…

cc' @ChrisPalmerMD @janellison @louisanicola_ @Metabolic_Mind @hubermanlab 2/8) Lithium: The Simplest Metal with Mysterious Power

Common and trace metals play critical roles in biology — think about zinc or iron. They’re essential for cell signaling, enzyme activation, and altering biochemical pathways. But the simplest metal of all, and one of the smallest elements on the periodic table, is lithium.

Despite its simplicity, lithium is biologically potent and mysterious.

At very high doses, lithium is a mood stabilizer commonly prescribed for bipolar disorder.

Fascinating, isn’t it? One of the simplest elements in the universe is a frontline treatment for severe mental illness.

Over the years, signals have emerged in the literature suggesting that lithium may protect against Alzheimer’s disease. For example, population studies have found that regions with higher levels of trace lithium in drinking water tend to have lower rates of Alzheimer’s.

Quoting from JAMA Psychiatry: “Exposure to higher long-term lithium levels in drinking water may be associated with a lower incidence of dementia.”

Coincidence? I doubt it.

Obesity Rewires Your Brain, Your Kidneys, and Your Blood Pressure (Full content🔗in 5/5; And 3/5 will freak you out 🫣)

1/5) For decades, we’ve been told to cut back on salt to control blood pressure.

The U.S. Dietary Guidelines still recommend limiting sodium intake to 2.3 grams per day.

But the science behind this advice is far from settled.

In fact, some long-term studies suggest the opposite: that lower sodium intake associates with higher blood pressure. (reference in letter, linked at the end).

And—curiously—people with obesity tend to be more salt-sensitive than lean individuals.

Why?

I promise, we’re going to unpack these questions today in the letter, and give you enough knowledge to terrify your cardiologist and woo your nephrologist.

#salt #bloodpressure #hearthealth #electrolytes @robbwolf @realDaveFeldman 2/5) Body Fat and Blood Pressure: A Complex Connection

Emerging research points to obesity as one culprit causing high blood pressure. Not just because of the extra weight, but because of what fat tissue does behind the scenes.

Let’s look at one such study—a remarkable tour de force published in @Cell_Metabolism ... In this study, researchers fed mice a high-sugar, high-fat, obesogenic diet. Blood pressure didn’t rise right away; it only increased after the mice had become obese. But something else happened first…

GLP-1 vs Alzheimer’s: New Insights (Link in 5/5)

1/5) Look at the graph and brain images below. Let’s start with the graph, which represents the relationship between levels of the hormone GLP-1 circulating in the blood and levels of amyloid in the human brain. Clearly, there’s an inverse relationship: Lower GLP-1 levels associate with more amyloid; higher GLP-1 levels associate with less amyloid.

🧠The brain images reinforce the point: more yellow and red tones indicate more amyloid, whereas more green and blue tones suggest less amyloid. The brain on the left is the scan from the patient with the lowest GLP-1 levels of the twelve represented in the graph; the brain on the right is the scan from the patient with the highest GLP-1 level.

There’s unmistakably an antagonistic relationship between GLP-1 levels and amyloid. Let’s delve into new data to explain why this pattern exists — and what it might mean for your brain health. 2/5) The New Paper in Nature Aging Piqued my Curiosity

These data come from a new paper in Nature Aging, in which researchers set out to study the mechanism by which GLP-1 receptor agonist (GLP-1RA) medications might protect against Alzheimer’s disease.

There are already promising signals in the data, including results from a large cohort study and a Phase II randomized trial in adults with mild cognitive impairment. But the evidence is still early, and the mechanism murky. So, the researchers asked — in very technical terms — “What’s up doc?”

A New Perspective on Sleep: Mitochondria Dance to the Rhythm of the Sun (🔗 in 6/6)
🚨Q&A with the first author of the new @Nature paper
🚨Book Giveaway (@hubermanlab) in 5/6

1/6) The sun—our oldest biological partner—does more than warm our skin or grow our food. Light is the literal foundation of the food chain, yes—but its relationship to metabolism goes far deeper.

Light doesn’t just hit your skin or enter your eyes. It interacts with the trillions of mitochondria scattered throughout your body. And when it does, it sets into motion a metabolic dance—a rhythm of fusion and fragmentation that underlies everything from energy production to sleep regulation.

Get the timing right? The dance flows.

Get it wrong? You’re stepping on your own metabolic toes.

Today, we’re exploring how light influences mitochondrial behavior—starting deep in the brain and extending into your eyes.

cc @R_Mohr @RafSarnataro 2/6) The Brain: Light and the Sleep Drive

A recent paper in @Nature reframes how we understand sleep pressure—the biological drive to sleep that builds the longer we’re awake—not through melatonin, but through mitochondrial choreography.

The researchers found that waking and sleeping drive opposite mitochondrial behaviors: an epic dance between fragmentation and fusion events that ebb and flow with day-night cycles.

This isn’t passive biology. It’s active regulation of sleep itself. When researchers manipulated these mitochondrial states in animals, they were able to alter sleep patterns.

This could be the root cause of why we sleep…

Two Waves of Aging: Molecular Shifts at 44 and 60
(🔗 at the end)

1/4) Aging is not a linear process. Intuitively, maybe you’ve sensed this. But researchers at @Stanford has now revealed—at an astonishing level of molecular detail—how aging unfolds.

Their key finding: aging shows at least two major molecular crests, around age 44 and age 60, when molecules across multiple biological systems shift dramatically.

These molecular “hotspots” may directly influence disease risk (and how we look) with age. I know what you might be feeling. But instead of fear, let’s channel that into curiosity—because these data are profound.

*Note: This paper was the #1 most viral study ever published in @NatureAging (this can be tracked with something called an Altmetric score, which for this paper is 5,453 ). In my opinion, the paper does deserve this honor! 2/4) The research was conducted by the world-renowned Snyder Lab at Stanford, pioneers in “longitudinal multiomics.” This approach combines various “omes”—like the genome, proteome, transcriptome, and microbiome—to form a detailed picture of how an organism functions at the deepest levels.

“Longitudinal” means this wasn’t a snapshot study. Each of the 108 participants (aged 25–75, about half female) was followed over an average of 1.7 years. Researchers collected 5,405 biological samples including blood, stool, nasal secretions, and skin swabs. These yielded 135,239 molecular features, which were analyzed through advanced machine learning.

Interestingly only 6.6% of the molecules exhibited linear aging patterns. The vast majority changed in nonlinear waves—with two major crests of change at ~44 and ~60-year marks.

5 Facts to Know About Fructose vs Fruit

1. Fructose isn’t just “empty calories,” but a biochemically active molecule that can negatively impact your liver and mitochondria. But does that mean fruit is bad? No. (🔗 in 5/5)
2. The small intestine acts as a “fructose filter,” where moderate-dose fructose is bioconverted and “detoxed” before it reaches the portal vein heading to the liver. This system can handle a handful of blueberries but gets saturated and overwhelmed if you smash a large bowl of cereal and a tall glass of OJ.

The Ketogenic Diet and the End of OCD Suffering
(🔗to full letter in 5/6)

1/6) Patient: “I used to tell myself in the depths of OCD, ‘The only way out is death,’ as a kind of mantra to put things into perspective. I’m happy to say I found another way. It would make me really happy if others knew about ketosis as a way to end their suffering.”

This dramatic quote, drawn from a new medical case series, describes one patient’s experience whereby they completely resolved their symptoms of debilitating obsessive-compulsive disorder (OCD) with a ketogenic diet. People with OCD can suffer terribly, sometimes to the point that death may appear a reasonable therapeutic, as was the case with this patient.

In today’s Newsletter, we discuss the case series at hand and why you should care, whether or not you or a loved one suffer with OCD. This is important for everyone to hear. 2/6) Patient A: Early Onset, Harvard Student

Patient 1 was a 22-year-old student at Harvard College, who first started exhibiting symptoms of OCD at 18 months. What began as consistent object alignment evolved into cleaning his friends’ toys, excessive handwashing, balanced twirling (if he spun twice clockwise, he’d need to spin twice counterclockwise to “balance things out”), balanced hugging and kissing, and exclusively symmetrical works of art. He was formally diagnosed with OCD at age 4.

The path that led this young boy to a ketogenic diet, like many others, was unexpected. Noting concerns about his weight, his parents supported him in removing grains from his diet, “unexpectedly noticing a dramatic reduction in his OCD symptoms.” Intensifying his dietary regimen towards a ketogenic diet at age 15 resulted in a “complete cessation of ritualistic behaviors” within two weeks.

Also, of note—and a key element in any ‘case experiment’—reintroduction of the independent variable (dietary carbohydrates sufficient to knock him out of ketosis) results in a change in the dependent variable (OCD symptoms). Indeed, excursions from the ketogenic diet consistently result in a return of symptoms for this patient (and for the others, as we will see). For instance, once while on vacation he indulged in a carbohydrate-rich meal. Shortly thereafter, he was found in his hotel room, late at night, organizing shampoo and conditioner bottles into neat rows.

Patient Perspective:
“The ketogenic diet was transformative for resolving my OCD, mood disorders, and focus issues. Without making the changes to my diet that I did, I would not have had the mental wherewithal to perform well enough in high school to get into Harvard, much less college.”

The Sugar Diet, Protein Restriction, and Longevity: How It All Weirdly Connects (🔗 to full letter in 6/6)

Typically, my posts have twists and turns. I always aim to break expectations in some way, shape, or form.

But today I have a unique challenge: I’m going to try to thread together three seemingly unrelated topics — (1) the Sugar Diet, (2) protein restriction, and (3) longevity. We’ll work through each in turn, citing data from Nature Metabolism, Cell Metabolism and an N = 1 experiment. 2/6) The Sugar Diet: Absurd or Insightful? 🍭

To recap, if you missed my prior coverage on this topic, the Sugar Diet is a rising trend in the nutrition world that is exactly what it sounds like — a diet rich in sugar (candy, soda, fruit, fruit juices, honey, syrups) that supposedly helps you lose fat and boosts exercise performance.

When I first heard about the Sugar Diet, I had the reaction you might expect: assuming its practitioners were headed straight for diabetes and fatty liver disease and possibly had a pre-existing psychiatric disorder if they were willing to try something so absurd.

But biology has a way of humbling and mystifying — if you're open to the data.

The study that changed my perspective was published in Nature Metabolism (see links at the end). Briefly, it included three studies where young men followed a low-protein diet (9% of calories from protein), resulting in approximately a ⚡20% increase in energy expenditure⚡ — around 600 extra Calories burned per day — without any change in physical activity.
The effect appeared to be mediated by a hormone called FGF-21.

Based on these and other data, it appears that protein restriction — rather than sugar itself — increases FGF-21, which in turn ramps up energy expenditure and calorie burning. This helps explain how the Sugar Diet can work, operating in a subset of protein-restriction diets.

The NEW Microbial Molecule Linking Diabetes and Heart Disease (🔗 in 7/7)

1/7) What if one molecule, made by the bacteria in your gut, could quietly sabotage your blood sugar and clog your arteries?

Meet “imidazole propionate” (ImP) a microbial molecule made by gut that is now metabolically linked to both diabetes and heart disease. 2/7) Let’s start with the most recent findings: a paper published in Nature just four days ago found that ImP was associated with atherosclerosis in two independent human cohorts (PESA and IGT) and was shown to cause atherosclerosis in an animal model.

Looking first at the human data: in both cohorts, higher ImP levels correlated with higher fasting glucose, increased markers of inflammation (such as hsCRP), more visceral fat, and lower HDL cholesterol—all signs of metabolic dysfunction.

What’s more, ImP levels directly correlated with the degree of atherosclerosis, as measured by vascular ultrasounds and coronary artery calcium (CAC) scores.

These are interesting associations. But—of course—we must ask: what came first, the chicken or the egg? In this case: the ImP or the metabolic dysfunction?