Niacinamide + pyruvate may treat glaucoma (human study)

haidut

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Some excellent results from a human clinical trial. Namely, a combination of 3g niacinamide and 3g (calcium) pyruvate daily demonstrated significant therapeutic effect in patients with already established glaucoma. I can't access to actual study link on JAMA, but I suspect the mechanism of action is, again, improved bioenergetic state with niacinamide raising the NAD/NADH ratio and suppressing excessive lipolysis, while both niacinamide and pyruvate also suppressing excessive fatty acid oxidation (FAO). Pyruvate also has anti-inflammatory effects of its own, as does niacinamide and those effects were probably also involved in the therapeutic mechanism of action. Finally, considering the studies I posted in regards to our product Pyrucet, instead of using 3g calcium pyruvate, one may be able to get away with a much lower dose ethyl pyruvate (found in Pyrucet). Multiple studies have demonstrated ethyl pyruvate can provide the same effects as salts such as calcium pyruvate, but at 100-fold lower doses. So, just to err on the side of caution, that means one may be able to replicate the study dosage of calcium pyruvate by using 50mg-100mg ethyl pyruvate. Now, Pyrucet also contains (ethyl) acetoacetate and that chemical is also capable of raising the NAD/NADH ratio. Thus, by using Pyrucet, one may be able to lower the niacinamide dose as well. In my experience, a dose of 500mg ethyl acetoacetate daily provides similar oxidative boost as a dose of about 2g niacinamide. That means 1g niacinamide and a full dose (24 drops) of Pyrucet may be able to not only replicate the study design but potentially provide additional benefit that the study protocol could not.

Nutritional Supplements and Performance During Visual Field Testing (B3 Vitamin) - Full Text View - ClinicalTrials.gov
Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma
Nicotinamide and pyruvate helps improving vision in glaucoma patients: JAMA

"...A new study reveals that a combination of nicotinamide and pyruvate significantly improved visual function in the short term. The results confirm previous experimental research suggesting a role for these agents in neuroprotection for people with glaucoma and confirming the need for long-term studies to establish their usefulness in slowing progression. The findings of this study were published in the journal JAMA Ophthalmology on 18th November 2021. This study was conducted by Carlos Gustavo De Moraes and the team with the objective to see if a combination of nicotinamide and pyruvate can enhance retinal ganglion cell activity in people with glaucoma, as evaluated by routine automated perimetry. This was a phase 2 randomized, double-blind, placebo-controlled clinical study where 197 participants were evaluated for eligibility at a single academic institution. 42 patients with treated open-angle glaucoma and moderate visual field loss in at least one eye were chosen and randomized. The study included 32 participants who finished it and were included in the final analysis. The average (standard deviation) age was 64.6 (9.8) years. Twenty-one of the twenty-one participants (66%) were female. Data on participant race and ethnicity were acquired by self-report to verify that the distribution mirrored that seen in clinical practice in the United States, but are not disclosed here to safeguard patient privacy. For this work, patients were recruited in April 2019 and were followed up on until December 2020. The data was examined from January through May of 2021. The results were seen as; patients with manifest open-angle glaucoma treated with a combination of nutritional supplements (nicotinamide and pyruvate) experienced a statistically significant improvement in visual function based on the number of improving test locations on SAP compared to the placebo group in this placebo-controlled clinical trial. Furthermore, the rate of change of the visual field PSD was considerably different, indicating that global perimetric sensitivity has improved. In conclusion, nutritional supplementation with high doses of nicotinamide and pyruvate can increase visual field sensitivity in treated glaucoma patients with mild functional loss in the near term. The development of novel neuroprotective medicines for glaucoma patients may be enabled by the selection of drugs targeting NAD and bioenergetic capability to boost cellular resilience. A clustered visual field testing paradigm will most likely be effective for assessing future neuroprotective drugs.
 

David PS

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Thank you for the links related to glaucoma. Here are a few more that you or your readers might find interesting.
 

Tim Lundeen

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@haidut @David PS -- thanks for all the links, great stuff!

Pyruvate lowers glutamate, so raises GABA:glutamate ratio. GABA should be protective because it typically lowers Ca influx into cells. That could be an important factor in the niacinamide+pyruvate study. Oxaloacetate also does this.
 
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@haidut @David PS -- thanks for all the links, great stuff!

Pyruvate lowers glutamate, so raises GABA:glutamate ratio. GABA should be protective because it typically lowers Ca influx into cells. That could be an important factor in the niacinamide+pyruvate study. Oxaloacetate also does this.

@Tim Lundeen I have negative mood/neurological effects with pyruvate. Does it mean that I have low cerebral glutamate and therefore poor energy function within the Krebs cycle?
 

Tim Lundeen

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I have negative mood/neurological effects with pyruvate. Does it mean that I have low cerebral glutamate and therefore poor energy function within the Krebs cycle?
Could well be...
Through the process of glycolysis, one molecule of glucose breaks down to form two molecules of pyruvate. Depending on the microcellular environment (specifically, oxygen availability, energy demand, and the presence or absence of mitochondria), pyruvate has several separate fates:

In mitochondria-containing cells, pyruvate can enter the citric acid cycle within the mitochondrial matrix and undergo oxidative phosphorylation. Aptly named due to its dependence on oxygen as the final electron acceptor, oxidative phosphorylation cannot take place in the absence of oxygen. Moreover, as the enzymes of both the citric acid cycle and electron transport chain are within the mitochondria, cells lacking mitochondria (e.g., erythrocytes) cannot rely on oxidative phosphorylation for energy production.

In erythrocytes and oxygen-deprived tissue, pyruvate remains within the cytoplasm and converts to lactate, a process referred to as anaerobic glycolysis. This final reaction allows for the regeneration of NAD+, a cofactor that must be available in high enough intracellular concentrations for the earlier reactions of glycolysis to remain favorable. Compared to oxidative phosphorylation, however, anaerobic glycolysis is significantly less efficient, providing a net production of only 2 ATP per glucose molecule (versus 32 ATP per glucose molecule produced during oxidative phosphorylation).
So possibly the extra pyruvate is going to lactic acid, which can be problematic. Maybe you need mitochondrial support: thiamin, biotin are often low because they are thiols and destroyed by aldehydes. Or maybe zinc deficiency... Or, I've been taking MitoSynergy copper for the last month, which seems to route copper-I to mitochondria, and it seems to be very helpful.
 
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Could well be...

So possibly the extra pyruvate is going to lactic acid, which can be problematic. Maybe you need mitochondrial support: thiamin, biotin are often low because they are thiols and destroyed by aldehydes. Or maybe zinc deficiency... Or, I've been taking MitoSynergy copper for the last month, which seems to route copper-I to mitochondria, and it seems to be very helpful.

It seems that pyruvate also acts on the methylation cycle in the sulfur pathway ...
 

aliml

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Inaut

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A little off topic but my friends mom was diagnosed with a stage 4 ocular tumour... What would you recommend @haidut for something like this?
 
EMF Mitigation - Flush Niacin - Big 5 Minerals

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