• Dr.Kats posted an update

      8 months ago (edited)

      This applies to all other B-vitamins, and to another so-called "vitamin" too...

      “Niacin activated genes involved in riboflavin metabolism and flavin synthesis”

      Exogenous niacin enhances Cd tolerance in pepper via NADP(H) pool expansion, photosynthetic electron transport recovery and antioxidant system activation

      https://www.sciencedirect.com/science/article/pii/S0304423825004868

      shawndralynn, AJ West and 3 others
      32 Comments
      • “the Cd+NAC1 treatment significantly enhanced the expression level of the gene encoding NAD+ synthase (EC:6.3.1.5). Correspondingly, compared with mono-Cd treatment, the Cd+NAC1 treatment significantly increased the accumulation of nicotinamide adenine dinucleotide (NAD+, NADP+ and NADPH) and its precursor metabolites, including nicotinamide, nicotinamode d-ribonucleotide (NMN), Deamino-NAD+ (NaND).” …

        • In the riboflavin biosynthesis pathway, Cd and exogenous NAC influenced the expression levels of four enzyme-coding genes involved in the biosynthesis of riboflavin and its derivatives. The genes encoding riboflavin synthase (EC:2.5.1.9), riboflavin kinase (EC:2.7.1.26), FMN hydrolase (EC:3.1.3.102), and tartrate-resistant acid phosphatase type 5 (ACP5, EC:3.1.3.2) were significantly down-regulated under mono-Cd treatment, while Cd+NAC1 treatment prevented this negative effect. Correspondingly, mono-Cd treatment significantly reduced the accumulation of reduced riboflavin and flavin adenine dinucleotide (FAD), whereas Cd+NAC1 treatment markedly increased the accumulation of riboflavin, reduced riboflavin, and FAD. Additionally, flavin mononucleotide (FMN) levels were significantly elevated following Cd exposure, regardless of NAC supplementation.

          Oh, and it applies to “C” too.. and pretty much eevrything else too…

          In the glutathione metabolism pathway, three enzyme-coding genes involved in the biosynthesis of glutathione (GSH), such as aminopeptidase N (PepN), leucyl aminopeptidase (PepA), and glutathione S-transferase (GST), were down-regulated under mono-Cd treatment. In contrast, Cd+NAC1 treatment up-regulated the expression of these genes and enhanced the accumulation of ascorbate (ASA) and GSH. l-ascorbate peroxidase (APX) and glutathione peroxidases (GPX) play crucial roles in the ASA-GSH cycle by catalyzing the conversion of H2O2 to H2O. Following Cd exposure, the expression of DEGs encoding APX and GPX was significantly down-regulated, while Cd+NAC1 treatment effectively suppressed this negative effect.

          • Niacin treatment up-regulated the expression of these genes and enhanced the accumulation of ascorbate (ASA) and GSH.

          • Dr.Kats (edited)

            “Vitamin” C:

            Niacin treatment up-regulated the expression of these genes and enhanced the accumulation of ascorbate (ASA) and GSH.

            • THIS IS A VERY THOROUGH, EXCELLENT STUDY. I highly recommend for ALL to read.

              3
              • Clinical Trial
                Vitamin C elevates red blood cell glutathione in healthy adults

                https://doi.org/10.1093/ajcn/58.1.103

              • Plasma glutathione (GSH) increased significantly in all intervention groups, especially in vitamin C (p=0.005). A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects.
                https://www.jstage.jst.go.jp/article/jnsv/62/1/62_54/_article

                • @83377 and what was the clinical significance beyond acute jumps in plasma? Bet they got no improvement to their actual OPD symptoms

                • Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency
                  https://www.sciencedirect.com/science/article/pii/S0002916523055892

                  • Impaired striatal glutathione–ascorbate metabolism induces transient dopamine increase and motor dysfunction.
                    Malik, M.Y., Guo, F., Asif-Malik, A. et al. Nat Metab 6, 2100–2117 (2024).
                    Published 28 October 2024
                    DOI: 10.1038/s42255-024-01155-z (https://doi.org/10.1038/s42255-024-01155-z)

                    • @83377 yes and giving C exogenously doesn’t repair this endogenous system. It just acutely disguises how much worse it was right before in terms of blood metabolites. But the actual metabolism of the system is not impaired because of causally a lack of one of the diminished metabolites as a result being exogenously quenched, but rather the lack of NAD+/NADP+

                    • Hydrogen peroxide, ascorbate, and glutathione: building the Foyer-Halliwell-Asada pathway.
                      Noctor G. (2025). Planta, 261(6), 132.
                      Published: 08 May 2025
                      DOI: 10.1007/s00425-025-04702-4 (https://doi.org/10.1007/s00425-025-04702-4)

                      • @83377 and likely the ascorbic acid exogenously supplemented giving off electrons bootleg is exasperating all this leading to oxidative stress – would surely be the case if we didn’t have niacin in the mix making NAD+

                    • Low Nourishment of Vitamin C Induces Glutathione Depletion and Oxidative Stress in Healthy Young Adults.
                      Waly, M. I., Al-Attabi, Z., & Guizani, N. (2015). Preventive nutrition and food science, 20(3), 198–203.
                      Published online 30 September 2015
                      DOI: 10.3746/pnf.2015.20.3.198 (https://doi.org/10.3746/pnf.2015.20.3.198)

                      • @83377 yea lowly nourished (needing to exogenously supply) if NAD/NADP+ is lowly …

                        • @Dr.Kats Humans cannot synthesize vitamin C – (needing to exogenously supply)

                          • @83377 yes they can’t because they have been niacin and tryptophan deficient their whole anthropology – but now they can … you’re believing authors saying this about C that we must supplement it – who don’t even know the difference between niacin and niacinamide, let alone what I just showed you

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                            • @83377 SAME HUMANS CANT SYNTHESIZE NAD+(without niacin supplemented) … SO ADMINISTER NAD+ and call it a vitamin too???

                              1
                              • @83377 this 10000% happens in humans too … all living things… it’s the electron transport chain.. we just haven’t taken niacin with L-tryptophan enough and properly to manifest it fully yet. There is a reason members are finally all excelling without “vitamin C” and who were suffering in relation just previously if “vitamin C” was included and retained too much/long

                                1
                                • @83377

                                  Humans don’t have this photosynthetic ETC…

                                  …but we do have an almost parallel redox cycle inside mitochondria, cytosol, and peroxisomes using the same cofactors.

                                  In human cells:
                                  • Niacin → NAD⁺ / NADP⁺ → NADH / NADPH
                                  • NADPH is regenerated via:
                                  • Pentose phosphate pathway (G6PD)
                                  • Malic enzyme
                                  • NADP⁺-dependent isocitrate dehydrogenase

                                  How NADPH regenerates ascorbate in humans

                                  This happens through the ascorbate–glutathione cycle, which is functionally identical to the APX/GSH/DHA system in plants.



                                  So in humans, NADPH from niacin indirectly keeps ascorbate (vitamin C) reduced and active via the glutathione–ascorbate coupling system.
                                  So yes — the mechanics are analogous:
                                  • NADP⁺ (from niacin) accepts electrons from metabolism.
                                  • NADPH donates electrons to glutathione reductase.
                                  • GSH then reduces dehydroascorbate → ascorbate, restoring vitamin C.



                                  Simplified summary

                                  In both plants and humans, niacin-derived NADPH is the universal “electron currency” that keeps antioxidants (like ascorbate and glutathione) reduced and active.
                                  Humans don’t use chlorophyll or PSI/PSII for this — we use metabolic dehydrogenases — but the redox logic is identical.the ascorbate–glutathione cycle, which is functionally identical to the APX/GSH/DHA

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                                  • Dr.Kats (edited)

                                    @83377 We have more than enough ascorbate in diet these days.. we are just not regenerating it / keeping it reduced and active at the rate we need to because of not the lack of ascorbate being consumed (then from diet) daily but because of the lack of supplementing sufficient nicotinic acid supplied with free-form L-tryptophan fraction daily to make adequate NAD+ to accomplish such recycling. This applies to pretty much ALL other so-called nutrients that all sorts of investigators and clinicians, “experts” claim we have to supplement too — who are all missing the underlying causality of what niacin making NAD+ (protons) entails combined with the related responsibilities, in coupling to niacin making NAD+, of tryptophan as the other growth factor.

                                    1
                                    • @83377 Tragically, while “overlooking” the causal influence of niacin-NAD/tryp, oblivious to their underlying subclinical pellagra, folks are eager to take whatever alternatives experts misadvise instead, not realizing the level of damage they’re afflicting to themselves in the process.

                                      1
                                • I know the ascorbate–glutathione cycle, but do you think diet has enough ascorbate before it is endogenous and recycled?
                                  Especially being unstable and easily oxidized

                                  • Hydrogen peroxide, ascorbate, and glutathione: building the Foyer-Halliwell-Asada pathway.
                                    Noctor G. (2025). Planta, 261(6), 132.
                                    Published: 08 May 2025
                                    DOI: 10.1007/s00425-025-04702-4 (https://doi.org/10.1007/s00425-025-04702-4)

                                    • Ascorbate and Glutathione: The Heart of the Redox Hub,
                                      Christine H. Foyer, Graham Noctor, Plant Physiology, Volume 155, Issue 1, January 2011, Pages 2–18,
                                      Published: 06 January 2011
                                      DOI: 10.1104/pp.110.167569 (https://doi.org/10.1104/pp.110.167569)

                                      • The ascorbate-glutathione cycle coming of age.
                                        Foyer, C. H., & Kunert, K. (2024). Journal of experimental botany, 75(9), 2682–2699.
                                        2024 May 3
                                        DOI: 10.1093/jxb/erae023 (https://doi.org/10.1093/jxb/erae023)

                                        • “We have more than enough ascorbate in diet these days.”

                                          Does that apply to Triptophan, too?
                                          Tryptophan requirement for man 70Kg is 280mg/day
                                          Estimate consumption of Tryptophan in western diet between 600-800mg/day

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