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@KenDBerryMD

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Nick Norwitz

@nicknorwitz

Feb 26

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.

3/10) What is the Virta Health Model?
The Virta Health model, at a high level, is a continuous remote care app that can be now accessed commercially through direct payment or insurance coverage.

There is a telemedicine care team that advises participants on nutrition therapy and manages diabetes medication.

👉The dietary therapy includes advising patients to consume < 30 g carbohydrates per day, 1.5 g protein per kg body weight, and fat intake to satiety.

Otherwise, the diet plan is individually tailored—be your personal preference a tomahawk in tallow or tarragon tofu...

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Nick Norwitz

@nicknorwitz

Feb 21

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.

3/6) Aspartame Increases Insulin and Causes Insulin Resistance 🙊🙈

Researchers found that aspartame increased insulin levels in a dose-dependent manner and increased insulin resistance, as measured by glucose and insulin tolerance tests.
Remarkably, the effects of aspartame on insulin resistance were even greater than those of sucrose (table sugar).

Similar results were observed in monkeys, where aspartame consumption led to a significant spike in insulin levels, suggesting these effects generalize to primates.

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Nick Norwitz

@nicknorwitz

Feb 20

🧬🍩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.)

3/6) In this paper, researchers used a complementary approach (🧬Mendelian randomization🧬) to assess the #CIM.

Mendelian randomization is a method scientists use to study whether a certain factor (like insulin secretion in response to carbs) causes a particular outcome (in this case, obesity).

It relies on genetic variations -- nature’s random experiment -- to uncover possible cause-and-effect relationships.

So, in this study, the researchers asked the question: Does genetically determined carbohydrate-stimulated insulin secretion predict obesity?

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Nick Norwitz

@nicknorwitz

Feb 17

💪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.

3/6) How do the metabolic changes stack up? The researchers observed decreases in acylcarnitines, a metabolic change that suggests increased fat burning by mitochondria, and decreased inflammation, as measured by CRP and a cytokine panel. I won’t pretend these data strike me with shock and awe. However, I can see a clear signal and personally consider this a meaningful finding.

Additionally, they measured levels and markers of proteins related to mitophagy, which is the process by which old-damaged mitochondria are removed. Mitophagy is important for maintaining muscle and organ health. Interestingly, the researchers found increases in components of the Parkin system that regulates mitophagy, at least at the 500 mg dose.

Urolithin A treatment in this study also increased levels of key components of the mitochondrial electron transport chain (complexes I - III).

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Nick Norwitz

@nicknorwitz

Feb 16

🚨 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. 👉🍽️💪🚨🤔

3/5) LCA & Lifespan

LCA…
👉Increased fly lifespan by 11% 🪰
👉Increased worm lifespan by 23% 🪱
👉In mice, LCA showed trends for lifespan increases (5% in males, 10% in females), though not statistically significant.

For details... obviously see full video, linked at the end...

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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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