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Nick Norwitz

@nicknorwitz

Mar 7

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.

3/4) The Good News: With advancements in technology, maybe we will soon be able to enhance glymphatics efficiency and ‘brain cleaning,’ including during sleep and perhaps even during waking hours. In my biomedical fantasy, I could rinse my brain between blocks of work while watching a Marvel Movie, or Harry Potter, Game of Thrones. What a dream!

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Nick Norwitz

@nicknorwitz

Mar 6

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.

3/8) Bryan Johnson previously boasted a value of to 0.66 as his DunedinPACE rate of aging score, suggesting that he’s biologically aging at ~66% or ab out 2/3rd of the average person. Then, around this past New Year's, he reported a DunedinPACE score of 0.57, a ‘personal best’ according to Bryan, claiming that his birthday is every 21 months (12 / 0.57). Yesterday, he claimed a score of 0.48.

Nuance Note: It’s not clear to me if this is a result of:

1. an actual downward trend in his score reflecting true slowed pace of aging

2. a function of test variability and the fact he just has more measures from which to choose and report

3. if he’s modifying his protocols to ‘optimize’ his metric, but without translation to bona fide slowing of biological age. More on this in a moment…

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Nick Norwitz

@nicknorwitz

Mar 2

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.

3/9) But here’s something interesting about these dopamine neurons in the midbrain that die off in Parkinson’s disease: They are huge with many branches (this is called arborization), are relatively few, and are very energy hungry. ⚡️⚡️⚡️

They also have a calcium-pacemaking activity that gobbles up energy like a hungry teenager.

All this means, these substantia nigra neurons are particularly metabolically active cells and are, therefore, especially susceptible to energy deprivation. And when the neurons are starved of energy, they die.

But what if we could rescue energy metabolism in substantia nigra neurons? Could we slow or stop Parkinson’s disease?

In theory, yes.

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Nick Norwitz

@nicknorwitz

Mar 1

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.

3/9) The mechanism likely had to do with changes in levels of receptors for key neurotransmitters, glutamate and GABA, in the emotional center of the brain.

Now, I know what you’re thinking: “Wow, this research deeper goes than a prostate exam from an overenthusiastic urologist.” But we’re not even at the interesting part…

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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...

Read 10 tweets

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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