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One of the fastest moving trends in the "high end" health space at present is IV infusion therapy of various types, be it vitamins, methylene blue, or more recently, NAD+
There is certainly research claiming that IV doses are absorbed well. eg: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751327/&source=gmail&ust=1658958798077000&usg=AOvVaw1mmn45j0gMFp-xZ0W9CeX w"> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751327/ , but this paper also notes that the researchers did no analysis on the fate of the NAD+ infused.
Regarding that fate, I reproduce a hyperlipid comment in full here
> Adding extra NAD+ should increase the NAD+/NADH ratio, making it easier to put an electron back through complex I without transferring it to oxygen, it just regenerates NADH.
> ROS generation occurs during RET when the NAD+/NADH ratio is low. Whether this is a good or a bad thing depends on how you view ROS and how pathological a person's core food choices have been.
> Certainly niacin is also a ketone mimetic and a FFA release inhibitor so there is a lot going on with this particular precursor.
Of course, Petro is biased, in that "pathological" usually revolves around insulin.
A relevant post here. Quotes below.
> The correct pathway for the metabolism of glucose without insulin is to lactate without any overall depletion of cytoplasmic NAD+
> Lactate can then be taken up by mitochondria exactly as ketones are. Lactate will, in the mitochondria, be reconverted to pyruvate, depleting mitochondrial NAD+ in exactly the same way as the conversion of BHB to AcAc does. Equally this happen right next door to complex I, just waiting to regenerate NAD+ and keep that NAD+:NADH ratio nice and high.
> The whole point of the glycerophosphate shuttle (in Protons terms) is to facilitate insulin signalling.
> Loss of the four pumped protons due to bypassing complex I and using mtG3Pdh instead as part of insulin signalling appears perfectly reasonable under conditions of active caloric ingress.
> Sustained insulin signalling causes sustained loss of cytoplasmic NADH, which generates NAD+. Once this has happened there is no longer the surfeit of cytoplasmic NADH over NAD+ from glycolysis, which is essential to drive lactate formation. Glycolysis must therefore stop at pyruvate under insulin.
This is complicated, and more complicated when considering how the two G3P dehydrogenases work together in concordance with NAD+ and NADH levels. See wiki -- https://en.wikipedia.org/wiki/Glycerol-3-phosphate_dehydrogenase&source=gmail&ust=1658958798077000&usg=AOvVaw24EG2T4Ty3Qp-cAm40rLW T"> https://en.wikipedia.org/wiki/Glycerol-3-phosphate_dehydrogenase , and note that Petro always uses the term 'mtG3Pdh', instead of 'GPD2'.
SIDENOTE: highlight the note about Metformin inhibiting GPD2. Another paper describing this -- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074244/&source=gmail&ust=1658958798077000&usg=AOvVaw2151MqbWnsCSKpFcYlo2o U"> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074244/ and also note this paper -- https://www.frontiersin.org/articles/10.3389/fimmu.2018.01605/full&source=gmail&ust=1658958798077000&usg=AOvVaw2UCFRNvvVAcgeIEE-nV_k f"> https://www.frontiersin.org/articles/10.3389/fimmu.2018.01605/full
> mtROS Are Important for T Cell Activation
> Stimulation of the T cell receptor (TCR) drives T cells into rapid proliferation and differentiation. T cell activation induces a rapid increase in mtROS production (18). Sena et al. also found that mtROS from complex III are required for CD4+ T cell activation and mitochondrial targeted antioxidant mitovitamin E attenuates IL-2 production.
> An alternative source of mtROS in mitochondria is mitochondrial glycerol-3-phosphate dehydrogenase 2 (GPD2). GPD2 oxidizes glycerol-3-phosphate to dihydroxyacetone phosphate leading to a hyper-reduced state of ubiquinone called ubiquinol in the inner mitochondrial membrane.
> Kamiński et al. found that GPD2 could directly produce ROS and accumulating ubiquinol could support ROS production at other ETC sites such as complex I (64). GPD2 depletion has been shown to inhibit mtROS production during T cell activation and decrease IL-2 expression. Mitochondrial and GPD2 induced ROS are important for T cell activation.
ie: localised loss of inflammatory response, which is charge driven (inflammation is "positive charge", or more accurately, "lack of charge motion"). Possible lack of proper immune response as a result.
Brute force addition of exogenous NAD+ will flood the cytoplasm of whatever cell manages to uptake the compound. What happens then is literally anyone's guess, given the above complications.
Personally, I cannot test nor predict any particular lasting benefit from these compounds. My current opinion is thus that it is a waste of money at best (or an opportunistic money maker!) with low dosages doing nothing to change normal metabolic function anyway, and the fate of super high doses not yet fully studied.
It should also be obvious that this is a classic "treat the symptom" move. Something goes wrong first, and thus NAD+ is depleted (proponents will cause this "normal aging process," and is only relative to NADH, which Petro notes you can also work to reduce.)
Adding more NAD+ likely does not fix the cause of relative low NAD+ to NADH.
And, of course, whilst the Niacin-type compounds have to undergo specific processing, and have vastly different effects from a straight shot of NAD+, they also have a longer history of use, so if anything, are preferred...and inexpensive.
This topic was modified 1 year ago by Josh Lamaro
Topic starter
Posted : 27/07/2022 6:25 am
