Post

@LipidJournal

@realDaveFeldman

@MichaelMindrum

@realDaveFeldman

More from @nicknorwitz

Nick Norwitz

@nicknorwitz

Aug 21

1/5) In the Metabolic Health Army, is there Space for Sweets?

🤔A "Case Study" on Brownies! 🍫🧈

🏆Opportunity to "win" a prize (3 winners) for a loved one, if you read to the end and Quote RT thoughtfully 👇

I’m not a sweets guy… anymore. But before I adopted a #ketodiet for treatment of my IBD, I LOVED 💕sweets, especially brownies! And if, pre-keto, you’d told me I needed to give up Brownies for life, I would have tossed marmite in your face!

So, I get that some people feel sweet treats will enhance their life and aren’t ready to give them up. That’s not a judgement, it’s pragmatism.

Consider this: Even if you don’t “do” sweet, do you have a loved one who you wish would take a step towards reducing sugar in their diet?

💔Don’t you want a “foot in the door” for their metabolic health?

I know I have many people like this in my life… which is why I’m a fan of tools -- like the “brownie” I’m going to use as a case study -- that can act like “lifestyle transformation springboards” …

… NOT because I need them myself at this stage of my journey, but because I know people who can and do use these to start/maintain their personal metabolic health journey.

But if you’ve been following me, you know I don’t do empty sales pitches.

I like providing people options and tools, but all I want to buy with my words is your curiosity. #StayCurious

In this thread, I promise:

👉 To Use Brownies as hook to speak to interesting metabolism and physiology

👉 To Emphasize my “why”: why I think there is room for brownies in the ammunition pack of our metabolic health army.

👉 To offer you a tool, either for yourself or a loved one, to consider, and opportunity to win a tool for them.

Let’s start with some DATA and SCIENCE…

cc colleagues @DominicDAgosti2 @BenBikmanPhD @AKoutnik

2/5) “Other” Sweeteners

When it comes to low-carb desserts, the first question that comes to my mind is:

🍩What’s the sweetener?

Sweeteners are a heterogenous group of molecules, and the research on them is fascinating.

Here are two astonishing facts about common artificial sweeteners: Sucralose and Aspartame.

🍩Sucralose has been shown, in human randomized controlled trials, do induce insulin resistance and changes in dopamine activity in the brain when consumed even at low-moderate doses in the context of a mixed macronutrient diet.

The effects are quite profound. So profound, in fact, one sub-study in teenagers needed to be prematurely terminated because of the massive jump in HOMA-IR that occurred with sucralose intake, again when consumed with carbohydrates – as in many common foodstuffs like ‘lower sugar’ yogurts (Cell Metabolism, 2020; PMID: 32130881).

🍩Aspartame is another problem child in the metabolism story.

One of the most fascinating studies, to me, on aspartame showed that aspartame dosed at the mouse equivalent of 2-4 Diet Coke per day not only caused an anxiety phenotype in the mice but also led to trans-generational inherence of this anxiety phenotype for up to 2 generations – even when the children and grandchildren of the mice hadn’t been exposed to aspartame themselves (PNAS, 2022; PMID: 36459641).

🧬There are human data on aspartame and anxiety, irritability and mood changes as well. But I think the ‘transgenerational anxiety’ phenomenon is particularly thought provoking. Not only does it give one pause to think about the metabolic consequences of some “considered safe” ingredients, but it does so framed by the reality that these are data we will never have for humans.

So, we must each ask, what is our risk tolerance and what are we risking when we drink that Diet Coke?

3/5) The Allulose Advantage.

In the world of sweet, allulose has to be my favorite molecule. Allulose is a rare natural sugar and the C-3 epimer of fructose

The human RCT data show that it is non-glycemic and non-insulinogenic. In fact, it attenuates the insulin and glucose impacts of normal sucrose too.

Reflecting back on the sucralose study above, whereas sucralose is a “metabolic partner in crime” with sugar, allulose is a shield against sugar… it’s a sweet anti-sugar.

Allulose has other interesting metabolic properties as well, including inducing GLP-1 production.

Nuance Note: Although there is debate over whether terms like “Nature’s Ozempic” is reasonable, given natural foodstuffs don’t induce endogenous GLP-1 production to levels even close to the supraphysiological doses imposed by exogenous GLP-1RA administration (e.g. Ozempic), one can also argue that GLP-1 inducing functional foods may help to restore normal hormonal physiology where it’s disrupted, as in the GLP-1 deficit that occurs in insulin-resistance disorders.

For more on GLP-1 science, drawn from recent literature in top journals, start with these two breakdowns, below. FWIW, I do not advocate “for” or “against” the use of this and related classes of medications. I just like them as physiology teaching tools. What you decide with your doctor is not my business.

Read 5 tweets

Nick Norwitz

@nicknorwitz

Aug 20

🥩Steaking a Claim: Is Haem Iron the Hidden Culprit in Diabetes?

🧵1/5) A new study asserts “Here we show that haem iron intake but not non-haem iron is associated with a higher T2D risk.”

It concludes, “These findings have important public health implications in shaping guidelines to prevent diabetes by limiting the daily consumption of foods rich in haem iron, particularly red meat.”

Methods
The primary analysis was conducted on 204,615 participants from the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHS2) and the Health Professionals Follow-up Study (HPFS).

The researchers quantified associations between total, haem, and non-haem iron and T2D risk & between iron intake and established metabolic biomarkers.

High-level Questions to Consider
👉 Are there confounders? What are they?

👉 What are the metabolic associations and how can we use these to filter these data for relevance at the individual level?

👉 Is the AI cover image for this 🧵 fun or garish? 😂

2/5) Basic Confounders

Participants with greater haem iron intake were generally less physically active, more likely to smoke and had at least trending higher BMI.

Furthermore, haem iron intake was positively correlated with a Western style-diet, which includes more “sweets and desserts, french fries, and refined grains,” here quoting from reference 31 where Western diet score is characterized.

To their credit, the authors of the current paper note that the association between dietary patterns and T2D risk could “also be partly due to… high added sugar in the Western diet…” seems plausible...

3/5) Metabolomics

Among the most prominent metabolomic findings were that C-peptide (a marker of insulin release), and TG/HDL-C ratio were higher with more haem iron intake.

Given this correlation, and the fact that whatever underlying metabolic dysfunction contributes to T2D risk also likely manifests in worse markers of metabolic health (e.g. high C-peptide/insulin/insulin resistance, high TG and low HDL-C), I’d suggest that if one’s metabolic markers are ‘optimized’ these data have little relevance on the individual level.

🚨The beautiful thing about metabolic health science is that the proof is in the pudding (the markers, both metabolomic and functional).

So, if a study says X-containing food is associated with Y “bad” markers and Z “bad” outcome, but you eat a lot of X-containing food, and your markers are excellent… well… the conclusion should be obvious.

No a double standard please... Of course, this cuts both ways, and I’d never criticize someone for abstaining from red meat or eggs or any food if they are themselves doing well. To each their own. Humans are heterogenous.

Read 5 tweets

Nick Norwitz

@nicknorwitz

Aug 12

1/4) This Thread proceed in 3 Parts:

i) A History
ii) A Social Analysis
iii) A Challenge and Opportunity for @BioLayne to help himself

It will have an unavoidable aura of (mindful) “Functional Drama,” i.e. I will present accusations and accountability statements. They will not be vague, but specific – with examples.

Furthermore, I’ll lead my 3 rules for “Fighting” 🥊

i) It Must Add Value, e.g. correcting misinformation or holding bullies to account

ii) Efforts at Bridge Building Failed.

iii) I Must be Ready for Relationship Repair, turning “Foe to Friend,” provided the other party is willing to meet me with authenticity and good will…

Note: This is a clip a video that May or May Not be released. That will depend on Layne Norton @BioLayne (he’s blocked me, so someone may want to notify him).

And to @hubermanlab. I apologize for bringing drama to your doorstep. If you decide to review the contents of this thread, I think you'll find it purposeful. As I know you to be a man of integrity with a devotion to open dialogue, I think you will appreciate it far more that you would be off-put by it.

2/4) The History.

Layne’s considers himself a “BS Crusher” (in bio) and prides himself on being evidence based. He’s an aggressor. That’s no secret and – honestly – it’s worked for him from a marketing perspective.

No shade. There’s pragmatism there.

However, he often fails to hold himself to a high standard of evidence and reason. And, when he missteps on the data or physiology, he has a pattern of failing to correct the record.

I did promise specifics:

>> In his review of our work, @BioLayne selectively ignores RCT-level evidence. Given the degree to which he professes to love “THE HUMAN RANDOMIZED CONTROLLED TRIAL" I found this 'odd.' This was despite being aware of this work, consuming my time and that of colleagues @AdrianSotoMota @realDaveFeldman @Lipoprotein asking question about our meta-analysis of RCTs, and being given ample opportunity to engage in a public dialogue on the matter on his platform or hosted by a third party.

>> In his review of our work, Layne also misrepresents the physiology. He claims certain data refute the Lipid Energy Model #LEM, where they are consistent with the model. Moreover, this was clarified to him in peer-reviewed text and direct messages prior to his coverage. (

>> When these and other elements of error and hypocrisy were raised by well-meaning third parties, Layne was defensive. Rather than engage on an intellectual level, he tossed around vulgarities, like “Sit down, you’re a fucking eye doctor. Sit down”

There are more examples of his pattern of defensive posturing and frank bullying in the full video linked at the end.

And, for those who haven’t caught on yet, I have a 0-tolerance policy for bullying. ZERO TOLERANCE.

>> Layne failure to correct the record when he’s made errors is a pattern. Recently, @theProof corrected Layne on his analysis of a Protein study. Layne hasn’t defended himself, nor clarified the matter to his large following. He has simply ghosted the (polite and fair) correction.

The below is a short clip from a prior response video to Layne. Forgive the stethoscope… I was in a shirt lunch break at the hospital. Again, links at the end.

3/4) An Analysis.

@BioLayne is interesting to observe and analyze from a branding and marketing perspective. He clearly considers himself the “predator.” Frankly, it’s worked for him. Just look at his cross-platform follower count.

But no predator has a 100% success rate… And what does a lion do when it’s clear he’s chosen the wrong prey and is outmatched. He runs, for who wants to get trampled by a buffalo.

This is adaptive. It’s good for survival.

From this perspective, it makes sense to me why @BioLayne may choose to ignore me.

Some time ago, after he chose to come after me with a tangential remark, citing data he clearly didn’t analyze carefully (Figure 1 in his chosen citation undermined his core point)...

I suggested to him privately that:

“I understand your MO as a self-described BS-crusher. I’m not looking for a fight. But, speaking practically, I warn you I’m not easy prey.”

He replied something to the effect, “Is that a threat?”

At the time I said, “I’m just being pragmatic.”

But I’ve since changed my answer to a simple, “Yes.”

I say this calmly and without malice. I’d prefer not to fight. But if you come looking for a fight, I’m happy to end it.

Given where things stand, it seems maybe I already have? But I hope not. Sincerely...

Read 4 tweets

Nick Norwitz

@nicknorwitz

Aug 9

1/6) Do you want to learn to address the root cause of metabolic syndrome and insulin-resistance disorders?

Of course you do! (links at the end)

🤯And these New Data will Blow your Mind! 🤯

Background
First, for some relevant background: You’ve certainly heard of Ozempic and related obesity medications in the GLP-1 agonist class. This means these drugs mimic a natural hormone (GLP-1) produced by cells in the intestines.

What you may not know is that metabolic syndrome and insulin-resistance disorders, including obesity, diabetes, etc. are associated with a deficiency in natural GLP-1.

So – high-level – “replacing” what’s missing makes sense. BUT, we should also ask “WHY?”

THE QUESTION: Why is there a GLP-1 deficiency in insulin-resistance disorders?

2/6) There have been some hand-wavy answers for a time, e.g. that ‘inflammation’ damages the cells that make GLP-1 in the gut, or that specific inflammatory immune cells “mop up” GLP-1.

But these new data get more specific, more targeted, and provide inroads for practical innovation.

3/6) THE MECHANISM

In brief, researchers discover that an obesogenic Westernized diet, in a mouse model, increases levels of a specific gut bacteria – Desulfovibrio – that produces hydrogen sulfide gas that damages mitochondria in GLP-1 producing cells, leading to a GLP-1 deficit.

In humans too Desulfovibrio levels are increases in insulin resistance disorders and metabolic syndrome in association with a GLP-1 deficit.

Read 6 tweets

Nick Norwitz

@nicknorwitz

Aug 2

Too Cool for Stool! 🧵A Nerdy💩 Thread🧵

1/6) While multiple lines of evidence support a “metabolic advantage” for #ketodiet #lowcarb diets for treatment of #obesity and weight loss, the exact mechanisms remain a mystery

New research in @NatMetabolism shows how #Ketodiets can cause POOPING OF MORE CALORIES. And, surprise (!), the mediating molecules are NOT ketones… but something else…

In this thread & associated video, I'll take about human data, animal model data proving a fascinating causal pathway, and provide practical take-aways

2/6) The causal pathways the researchers dissect in this paper is as follows:

Ketogenic diets alter the #microbiome to decrease levels of certain gut bugs (BSH-enzyme coding bacteria) that modify bile acids, leading to a rise in a subset of taurine-conjugated bile acids.

Two of these, TDCA and TUDCA, proved to be causal for weight loss & improved glucose homeostasis.

3/6) There are also data in humans consistent with the mechanistic/causal data in mice

For example, in an interventional trial a low-carb #ketodiet led to an avg of 5.27 kg lost in 12 weeks associated with decreased levels of gut bacteria encoding for BSH enzyme and increased levels of taurine-conjugated bile acids

(more on human clinical "consistencies" in the full video, linked at the end)

Read 6 tweets

Nick Norwitz

@nicknorwitz

Jun 28

🧵1/5): Artificial Sweeteners are Sold Simply as “Sweet without the Calories.”

🤔But while your tongue may get confused, your “Gut Sense” is harder to deceive!

Brilliant work from Diego Bohorquez featured on @hubermanlab shows HOW your body Outsmarts Sweet!

In this thread (please watch vids!), I will walk you through data from a landmark paper that I found awesome – truly, a moment when I say back and went “WOW, our bodies are AMAZING!”

At the end, find the link to the @hubermanlab episode, paper, and FULL VIDEO (11.5 min) breakdown.

cc @R_Mohr @scicommedia @gutbrains

2/5) In this study, the researchers identify “neuropod cells,” which are gastrointestinal cells with nerve-like properties that can sense sweet in the intestines with specific receptors (we will get to what these are in a moment), and then transmit the signal to the brain via the Vagus nerve. (👇jump to 0:56 if you're impatient, like me)

3/5) At this moment, it’s worth taking a detour to explain a technique called “Optogenetics” that these researchers use and that it is becoming increasingly popular to manipulate neuron (and other cell type) activity to prove causality in a system.

⚡️👀Watch clip plz⚡️
In optogenetics, you force specific cells to express channels/pumps on their membranes. The activities of these channels/pumps can be altered by exposure to different wavelengths of light.

Therefore, you can use expression patterns of these channels/pumps, along with different light wavelengths to turn “on” and “off” different cells and circuits.

It’s literally a light switch!
⚡️👀Watch clip plz⚡️

So, using green light they shut off neuropod cells and found that in so doing they could block the response in the Vagus nerve.

Otherwise put, by cutting out singling at the middleman cell – the neuropod cell – they blocked the signal from sugar or sweetener to the Vagus nerve.

This shows that neuropod cells are essential in sensing sweet in the intestines.

Read 5 tweets

Share this page!

Enter URL or ID to Unroll

Nick Norwitz

Try unrolling a thread yourself!

More from @nicknorwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Nick Norwitz

Did Thread Reader help you today?

Don't want to be a Premium member but still want to support us?

Send Email!