#1

Beta-blockers negatively affect natural melatonin production, which, to my understanding, has been confirmed in several studies. For some reason, Carvedilol and Nebivolol apparently do not have this effect. According to Dr. Oracle AI, it has been speculated that this could be due to their vasodilatory properties, meaning they may improve blood flow to the pineal gland. However, if a younger person without circulation issues takes Carvedilol or Nebivolol, would their melatonin production still decrease overall? Has anyone looked into this in more detail?

“A low level of endogenous melatonin is a risk factor for development of sleep structure and quality disorders, vascular white matter brain damages with a higher risk for metabolic disorders. Long-term beta-blockers administration decrease endogenous melatonin synthesis to 50% increasing the risk for insomnia and vascular brain damage, mostly in patients with lower initial level of 6-SM circadian excretion.: melatonin, 6-sulfatoxymelatonin, beta-blockers, insomnia, vascular white matter brain damage, leptin, adiponectin.”

"Nocturnal melatonin release was decreased by bisoprolol (-44%, p < 0.05) whereas nebivolol and carvedilol had no effect. QOL with carvedilol was slightly but significantly lower than with the other drugs, whereas bisoprolol and nebivolol did not alter QOL. "

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#2

I looked at beta-blockers extensively. I don’t think they’re great drugs. They seem to disrupt melatonin and glucose metabolisms. So sleep and sugar. Probably the two most important things for healthspan and lifespan. They’re consistently associated with a higher risk of Parkinson’s and the association is probably causal (per MR). Carvedilol and nebivolol seem to be less bad or maybe neutral. If alternative exists (e.g; for hypertension) then better not to use them. But if someone needs a beta-blocker (e.g., for tachycardia or heart failure), then carvedilol and nebivolol might be preferable. Still, there’s a lot of heterogeneity among beta-blockers so better to follow what the cardiologist recommends.

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#3

Good points. On the other hand, mice lacking AC5 live longer. Type 5 adenylyl cyclase disruption increases longevity and protects against stress - PubMed Beta adrenergic activation increases AC5 so beta blockers reduce AC5.

Too much beta adrenergic activation shortens lifespan in mice. Sex hormones and cardiomyopathic phenotype induced by cardiac beta 2-adrenergic receptor overexpression - PubMed There is also some weak evidence that lower beta adrenergic activity is beneficial for longevity in humans. A polymorphism in the beta2 adrenergic receptor genes that is associated with lower activity has been found to be associated with longevity in men but not women. Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with human longevity - PubMed

Overall beta-blockers are kind of a mixed bag IMO.

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#4

I think the best reason to use a beta blocker like Nebivolol or Cardevilol (I think the rest of them should be discontinued) is if someone also wants to lower their resting heart rate at the same time as lower their blood pressure, since the other hypertension meds don’t do it as effectively (aside from specific CCB’s like verapamil and diltiazem)

Fun fact: Nebivolol is VERY popular among bodybuilding circles for damage control.

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