u/dan_in_ca

I have been on LDN for a while now for severe autoimmune issues and it has helped me significantly. I thought I had a reasonable understanding of how it works but this review filled in some gaps.

I guess I didn't realize that the form mattered (I just get it in a pill form). The troche absorbs through the mouth lining and skips over the liver, which makes the absorption more predictable than a capsule going through the GI. Has anyone found that the troche had a better outcome?

Interesting discussion. It seems like a lot of the zone 2 conversation on its mitochondrial benefits has been dominated by correlation data from elite athletes. Elite athletes do enormous volumes of zone 2, and they also have exceptional mitochondrial health. What comes out of the discussion is that in that 40+ hours a week of training, their 20% high intensity work is more absolute high intensity volume than most recreational athletes accumulate in total. We may be attributing adaptations to the 80% that are actually coming from the 20%.

Basically a lot of the research cited in support of zone 2 actually studied moderate intensity continuous training above zone 2. Those findings cannot be straightforwardly attributed to true zone 2.

A disclaimer, they do not say that Zone 2 is worthless. A threshold around 65% of work rate maximum above which mitochondrial adaptation reliably occurs. Zone 2 falls below this for most people. Would be interesting to see a follow up that looks at zone 2 specifically in the context of different aging populations and whether the threshold argument holds across age groups.

Interesting discussion. I think the longevity implications are still being worked out. The video did an analysis of the SELECT trial and other GLP-1 trials of other future indications for the drug class outside of diabetes and weight loss (which we are pretty attuned to at this point). The cardiovascular data in the SELECT trial was interesting.

Semaglutide produced a 20% reduction in major adverse cardiovascular events. The most compelling aspect of this is the timing. Cardiovascular benefits were measurable at six weeks, before meaningful weight loss had occurred in most participants. If the protection were simply downstream of a lighter body it should not appear that early. The signal suggests GLP-1 medications are engaging vascular biology directly, independently of weight loss. Whether that translates into meaningful longevity outcomes over longer timeframes I am not sure of. Is it just the downstream effects of caloric restriction?

GLP-1 receptors are present in cardiac tissue and endothelial cells lining blood vessel walls, which may help explain the early cardiovascular signal and not just caloric restriction.

They talked about muscle loss. The comparative data does not support disproportionate lean mass loss relative to other weight loss approaches. They make the point that GLP-1 therapy has the same amount of muscle mass loss than any other weight loss program.

Still early days but the signal about longevity benefits is pretty fascinating. It would be good if they covered triple g dynamics with retatrutide.