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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.

Read 9 tweets

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…

Read 9 tweets

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.

Read 6 tweets

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?

Read 6 tweets

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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