32 Comments
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Filip Ainouz's avatar

Brilliant as usual Nick! And what a great conclusion. You are a real metabolism guru.

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Nick Norwitz MD PhD's avatar

Thank you Filip. So kind!

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Rebekah Bavry, RN, CPHC, CKNS's avatar

*fight with my kids ensues as I tell them no more diet soda at restaurants* sigh.

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Nick Norwitz MD PhD's avatar

Lol... how about a goat milk kefir... doesn't AppleBee's serve that?

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Rebekah Bavry, RN, CPHC, CKNS's avatar

Ew. lol. My kids are 17, almost 18, so they are at that age where soon they will be going out and eating whatever the heck that they want no matter what Momma says 😂 right now mom buys the groceries so they will eat whatever I tell them to

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Austin's avatar

So, absent an insulin response, there would be no mechanism? E.g. if a person were drinking diet Cokes and fasting insulin levels were < 5.

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Nick Norwitz MD PhD's avatar

It's unclear whether these data would translate to someone in good metabolic health. The mechanism described might not be the whole story. So, while the axis in question wouldn't work without an insulin response (acute or chronic), it's still a gamble. Also, while we have CGM, we don't have continuous insulin meters for public or clincal use.

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Murphmitch's avatar

My fasting insulin levels are 5 or less. Drink 1 Coke Zero a day. Used to drink 5 or more daily for years. CAC & CT angio no evidence of disease.

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Nick Norwitz MD PhD's avatar

CAC & CCTA on your N = 1 trump biomarkers and animal studies, I'll give you that. But... CVD is only only disease... https://www.pnas.org/doi/10.1073/pnas.2213120119

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Murphmitch's avatar

Interesting! Thanks!

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Vince Sortman's avatar

How was the aspartame delivered to the animals in the study? I ask because I drink a diet soday now and then, but it is diluted with ice and it will take me 30 - 40 minutes to drink it. I'm assuming ingesting .05% aspartame over 30 minutes has a different biological effect than ingesting the same amount in 30 seconds.

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Nick Norwitz MD PhD's avatar

In the long-term trials, it was provided in the drinking water. I assume freely available. For the acute treatment study, each mouse was orally fed with 200mL of distilled water containing vehicle or different concentrations of aspartame by drop-

ping the solution onto the mouse’s face. A precise duration isn't given.

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Andrew's avatar

Interesting. The most compelling things I had heard previous to this was "it might make you crave more sweets." Since I went Ketovore I decided to abstain from diet coke as my experience is it's harder to lose weight drinking diet coke and now I believe I won't ever be going back.

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Charlotteleclerc's avatar

@dr_idz

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Matt Staton's avatar

Does this likely apply to allulose?

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Nick Norwitz MD PhD's avatar

I don't think so. Allulose lowers insulin, if anything.

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Adam Vossen's avatar

Any thought on why cutting the vagus nerve disrupted plaque formation? If aspartame triggers insulin release and can lead to insulin resistance which is a known inflammatory state that can damage endothelium, the absence of vagal nerve function must change pancreas function even in the setting of a stimulus. Interesting

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sams's avatar

what exactly does .15 apm mean as the .15 percent of the recommended dose for humans adjusted in mice, .15 percent of thier daily liquid intake or .15 percent of an average apm content in human soda adjusted for mice size

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Nick Norwitz MD PhD's avatar

Dose this look right to you? -- To calculate a % solution in science, you use the formula, mass of solute / mass of solution; where "mass of solute" is aspartame, and "mass of solution" is the total mass of the solution (aspartame + water).

If a mouse drinks 2 mL water per day on average and water is 1 g/mL, that’s 2g, or 2000 mg. So, one can solve for 0.00015 = X / (X+2000 mg). You can simplify the denominator to about 2000 and solve for X as 0.3 mg aspartame.

If a C57BL/6J mouse weighs 30g, that’s a dose of 0.3mg/0.03kg = 10mg/kg. According to the Joint FAO/WHO Expert Committee on Food Additives, the upper tolerable limit for aspartame is 40 mg/kg per day.

I Diet Coke has 200 mg aspartame. 600 mg / 70 kg human = 8 mg/kg.

*A key assumption in this calculation included how much the mice drank per day. If they drank more, say 3 mL, the daily aspartame dose would be 15mg/kg, etc. Regardless, the dose was very likely below the UTL for humans.

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sams's avatar

Yes, this helps, thank you. I was calculating 15% instead of .15 %. However .15 percent is .0015 not .00015 which would give us 99mg/kg which is more than double the UTL, However I do now see that the lowest dose .05 percent/.0005 would be a little below the UTL. although I think your calculations might be off as I think you now have the lowest dose at 8.3mg/kg when I think it should be 33mg/kg.

Math:

.15% = .0015

2ml water per = 2g which is 2000mg water per day

.0015=x/(x+2000mg) simplified to 2000mg*.0015 = 3mg

30g mouse reference would give us 3mg/.03kg = 99mg/kg

.05% = .0005

2ml water per = 2g which is 2000mg water per day

.0005=x/(x+2000mg) simplified to 2000mg*.0005 = 1mg

30g mouse reference would give us 1mg/.03kg = 33mg/kg

Using a 5 '9 male with a BMI of 22 / 68kg for reference I think it would be more accurate to describe the study as feeding the mice between 11 and 33 cans of diet coke per day.

Furthermore as far as I can tell c57bl/6j mice have an estimated water intake of 5.7ml per day almost triple what is in your calculations

Figure 2: https://policies.unc.edu/TDClient/2833/Portal/KB/ArticleDet?ID=132199#:~:text=The%20estimated%20daily%20water%20intake,highly%20correlated%20with%20food%20consumption.

Although this study suggests it could be as high as 8ml per 30g bodyweight per day

https://pmc.ncbi.nlm.nih.gov/articles/PMC1397713/

Which would give us a much larger estimated AMPmg/kg intake

.05% = .0005

5.7ml water per = 5.7g which is 5700mg water per day

.0005=x/(x+5700mg) simplified to 5700mg*.0005 = 2.85mg

30g mouse reference would give us 2.85mg/.03kg = 94mg/kg

If we use the c57bl/6j mice with a body weight of 30g and and a daily water intake of around 5.7ml per day I do not think it would be inaccurate to say that the human adjusted dose was roughly 33 to 99 cans of diet coke per day

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Nick Norwitz MD PhD's avatar

Actually .15% is .00015. I think you missed a 0.

.15% = .00015

2ml water per = 2g which is 2000mg water per day

.00015=x/(x+2000mg) simplified to 2000mg*.00015 = 0.3mg

30g mouse reference would give us 0.3mg/.03kg = 10mg/kg

This is what I have as well. See above. So we have consensus?

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sams's avatar

dude did you seriously edit this comment to double down on ur blatant mistake?

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Nick Norwitz MD PhD's avatar

I said there was a mistake. I'm not hiding that. There are actually several ways to do the math but my initial one did have a genuine error. That was acknowledged and I've updated the text above. The conclusions did not change.

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sams's avatar

i think your math might be a little off. to convert a decimal to a percent you have to multiply the decimal by 100, in the same vain to convert a percent to a decimal you divide the percent by 100. I have attached some resources so you can check my work.

https://wagner.nyu.edu/files/students/Math_Review_-_Review_topics_-_Percents.pdf

https://txwes.edu/media/twu/content-assets/images/academics/academic-success-center/Quick-Guide-to-Percentages-and-Decimals.pdf

https://www.calculatorsoup.com/calculators/math/decimal-to-percent-calculator.php

you also did not address my issue with number you chose for the daily water intake of rats.

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Feb 22
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sams's avatar

if i were to a do a study with the percent solution for humans it wouldnt it work out to to , 3000ml of water per day, 1g/ml,3000g times 1000 to get 3000000mg of water for humans daily, * .15 = 450000mg of apm which is a hundred and 160 times the upper tolerable limit for humans. meaning you would need to drink 2045 cans of diet coke to get the same amount of aspartame as the mice. unless my math is wildy off doesnt this discrepancy in size adjusted apm dose kind if render the study not very useful

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Nick Norwitz MD PhD's avatar

See above, again. I'm pretty sure present math (with Feb 23 correction) is correct.

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Terry Boult's avatar

To me, the most interesting part of this article is the mechanics of the action of Insulin on plaque. Noting in the paper suggests the that mechanism is restricted to aspartame as its not part of the mechanism. This suggests that high-carb diets may be directly causal for atherosclerotic development.

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Nick Norwitz MD PhD's avatar

They certainly did not restrict the mechanism to aspartame. So my best guess is that a pack of skittles also doesn't do your heart's blood vessels any favors.

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buddhi's avatar

Does this study mean that aspartame providers who keep selling the stuff now have liability? Is it dispositive?

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Nick Norwitz MD PhD's avatar

Liability? There's tons of junk we know contributes to chronic disease. Big food isn't held liable. People are left to make their "informed" choices.

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buddhi's avatar

Seems like a good study pointing to a causal inference (dose-dependence plus mechanism plus not LDL confounded).

Coke can't now say that did not know. That's liability. All the other junk, who knows what it directly does, so no direct liability.

If information is not available or is distorted or inadequate there can be no informed choice, or consent, as with vaccinations and the other junk. Luckily for Pharma, the MD is their cut-out - they can lay off liability to the MD, though not entirely, due to the "learned intermediary doctrine." The food industry (the right arm of healthcare) has no arm's length liability protection, except for incorporation. RFK Jr would know about this.

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Alan's avatar

"informed" choices - That's where you come into the picture. Thanks for your review/translation into something I can understand..

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