#805

I’m not immune to scientific data.

Just because an effect wasn’t detected does not mean there was not an effect.
If no spies were detected in an organization, does not mean there aren’t spies in it. Especially if someone’s been copying documents and things have been leaked (high correlation with LDL, lower SFA, higher PUFA).

Absence of evidence is not evidence of absence.

The reason for - I repeat - lack of statistical significance can simply be because there are few studies that measure apoB, a lack of statistical power.

Here’s from Cochrane:

A common mistake made in instances when evidence is inconclusive is the confusion of a lack of evidence of an effect (due to imprecision) with „evidence of no effect‟.2 It is wrong to claim
that inconclusive evidence (when there is a wide confidence interval that includes potentially
important benefits or harms) shows that an intervention has had „no effect‟. „Statistical
significance‟ should not be confused with the size or importance of an effect.
When results are not „statistically significant‟ it cannot be assumed that there was no impact.

#806

You are immune to scientific data. And it’s not even worth explaining where you’re confused.

#807

If you want to troll, that is perfectly fine for me.

#808

Not trolling, the evidence is clearly laid out in this and other threads that you’re incapable of reading and understanding written statements.

#809

I’ll just ask you a simple question.

If X was not detected, does that mean that X does not exist?

#810

Thank you for you work here on the forum.

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#812

Ok, one last time … If you can’t engage with this simple logic there really is no point. You said (my emphasis)

And yet, there is a systematic review, posted by you, of multiple rcts which found NO impact on apoB from Canola oil.

To go from zero evidence, to a “most likely” belief, suggests that you’re immune to scientific data.

That’s fine, but it does mean there’s no point discussing anything with you.

#813

I’ll repeat the question again since you’re dodging.

If X was not detected, does that mean that X does not exist?

#814

No, but it does mean you should not expect that X will “most likely” happen in the future.

#815

If X was not detected, but it is correlated with Y at 0.80, that was detected, then I do think that X will most likely be detected in the future.

#816

OK - you guys have both done a great job of laying out the evidence. Personally, I’ve found it very helpful. At this point I don’t think you’re going to convince each other that your interpretation is right… so I’d just let it go…

duty_calls_2x-2

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#817

Except there’s no statistically significant finding of correlation, no significance means it could simply be random noise. If you think statistical significance doesn’t matter, that would explain why you’re immune to scientific data.

If you toss a coin and it comes up heads. That doesn’t mean it will “most likely” come up heads next time.

#818

Sorry, just saw this. Yes please.

1 Like
#819

That study is not informing me of the correlation between X and Y. I use other studies for that.

#820

Ok, i understand completely

#821

I don’t think so, but I am quite happy with canola reducing LDL. I like lower LDL.

#822

I don’t want to be overly negative about gene therapy, just that it doesn’t seem ready for healthy people looking to have big muscles.

I guess I assumed AAV but minicircle is definitely different but subject to some of the same risks. AAV is a non-integrating vector as well and actually forms circles during transduction. However, I spent a lot of my postdoc cloning integrated copies of AAV. Turns out the vectors get captured in the repair of naturally occurring DNA double strand breaks and … can integrate. Minicircles and “non-integrating” retroviral vectors have the same problem. In the case of AAV, this happens at a very low frequency (~0.1% of the time) but when you give a human 4 x 10^9 vector genomes / kg in a gene therapy 0.1% becomes 4 x 10^6 integration events / kg. Add to that a strong gene promoter next to say folistatin and you have the potential to activate otherwise silent genes. This is the mechanism of cancers that occurred in retroviral based gene therapies in the 80’s.

That said, promoters have been modified to remove strong viral enhancers and reduced this risk significantly. The risks of AAV gene therapy appear to be innate immune reactions to the high viral load. Several Duchenne patients have died receiving gene therapy in recent years. I still think gene therapy has a reasonable risk profile if you have a life threatening disease, I don’t think I’d do it to make my muscles bigger. Go to the gym.

Re longevity of minicircles, I don’t know a lot about how long they persist. With AAV, transducing non-dividing cells (like liver or muscle or neural tissue) is the key. Even though the majority of AAV vectors don’t integrate they persist and are only lost during cell division because they can’t be segregated to daughter cells without centromeres. Interesting your experience with IGF-1 although I might be concerned about unregulated IGF-1 expression, almost sounds precancerous. Was that Helen Blau’s lab?

Interesting summary of deaths in this article from September 2023

5 Likes
#823

Neo, see my response to rapadmin. Basically I think gene therapy is ready for treatment of fatal diseases but I just think it is hard to justify the risk/benefit for using it in healthy people.

Blockquote Is one risk that one will likely create an immune memory for the vehicle and, even if that is not a “safety risk”, basically become vaccinated against it and that vehicle will hence not be effective for that person in the future if any other gene therapy that uses that vector (or if dosing of the same therapy is needed later)

This is certainly one risk but a minor one as different vector “capsids” can be used (and there are many) for subsequent administration. The real immunologic risk comes from the body’s response to 4 x 10^9 vector genomes / kg. Usually the immune system must be suppressed with steroids to allow the transduction to occur and avoid an overwhelming and potentially lethal response. Only some people have that response and it may be due to whether their immune system has previously been exposed to that particular virus before. Jesse Gelsinger’s death (that was Adenovirus, not AAV (Adeno Associated Virus) they are completely different viruses was due to a fulminant immune response to the vector. It appears there have been a few similar responses with AAV therapies in Duchenne patients.

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#824

In case some of you may be interested, there is a Blueprint meet-up happening in many places on Jan 13:

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#825

Dr. Andrew Steele bashes Bryan Johnson’s supplement program. Bryan Johnson blocks him on X/Twitter:

With regard to Steele’s comments about Vitamin E, the Cochrane review didn’t conclude with confidence that it increased mortality risk, it only considered it a possibility. A later 2014 meta-analysis of randomized controlled trials, citing this Cochrane review, concluded that Vitamin E supplementation has shown no effect on mortality at doses ranging from 23–800 IU/day.

Vitamin E is also not limited to alpha-tocopherol. It’s a group of eight compounds. So the effect of taking a full-spectrum tocopherol mix along with a full-spectrum tocotrienol mix may be different.

Also, there was a mouse lifespan study where alpha tocopherol increased median lifespan by 15%.

6 Likes