If I was smarter, I might not be so excited about Niacin. I am pretty excited.
Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications 2019 ncbi.nlm.nih.gov/pmc/articl...
"Parkinson’s disease (PD) is a progressive disorder characterized by degeneration of dopaminergic neurons within the substantia nigra, whose main hallmarks are abnormal aggregation of the α-synuclein protein, inhibition of mitochondrial respiratory complex 1, oxidative stress and neuroinflammation. Because only 5–10% of PD cases can be ascribed to genetic predisposition, several environmental factors may play a role in sporadic forms of PD [149]. Among them, vitamin B3 is a promising preventive and therapeutic factor (Table 1), as it can alleviate certain types of early-onset PD symptoms. NAD+ levels, indeed, fall in patients with PD and, conversely, increasing niacin intake can increase dopamine synthesis in the striatum and restore optimal NAD+/NADH ratio needed for the activity of mitochondrial complex 1 [148]. High niacin levels can also sequester transition metal ions (including iron) that usually accumulate together with the occurrence of aggregated misfolded proteins [149,150]. Furthermore, optimal levels of vitamin B3 are needed for reducing oxidative stress and neuroinflammation, also implicated in PD pathogenesis: low doses of niacin alter macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenothype, while exogenous NADPH suppresses oxidative stress and glia-mediated neuroinflammation [151,152].
Neurons are the only cells of the brain expressing NNMT that seems to play an important role in sustaining neuron homeostasis [153]. Despite numerous investigations, the exact cause-effect relationship between NNMT and PD neuropathogenesis remains unclear. Some authors refer to NNMT as a risk factor for PD, since its levels are elevated in the cerebrospinal fluid and midbrain dopamine neurons of PD patients [153,154]. High NNMT activity is associated with low activity of mitochondrial complex 1, thus providing a link with mitochondrial dysfunction triggering neurodegeneration [154,155]. It is noteworthy that N1-methylnicotinamide (the metabolite generated by the action of NNMT) is structurally similar to N-methy-l-4-phenylpyridinium (MPP+), a toxin damaging dopamine neurons [168]. Conversely, other studies have demonstrated that the enzyme is able to (i) counteract the MPP+-mediated toxicity on mitochondrial complex 1, (ii) activate neuronal autophagy for balancing energy sources and cell homeostasis, and (iii) modulate neuron morphology and differentiation, by inducing neurite branching, synaptophysin expression and dopamine accumulation and release [156]. Likewise, NAD supplementation or inactivation of NAD-consuming enzymes [like PARP-1, a poly(ADP-ribose) polymerase involved in DNA repair] rescue mitochondrial defects and protect neurons against degeneration, in familial forms of PD characterized by mutations in the pink1 gene; this finding suggests that neurotoxicity associated with mitochondrial defects may be prevented by modulating NAD+ salvage metabolism in order to enhance NAD availability [169]."
Which brand do you use and how are you handling the flush feeling? I have my husband taking the no flush Life Extension Niacin 640mg but I think I need to switch him to the one you are speaking of.
Now that I went to 1000 mg twice a day, WHICH I HAVE NOT SEEN ANYBODY RECOMMEND, I use these Rugby tablets: amazon.com/dp/B003H5SXDQ?ps...
I do think flush is better. Take with food, that will take an edge off the flush. And start low and work your way up. Those Carlson tablets are 50 mg, so it takes 5 to get 250 mg, but gives you a chance to work your way up. The Rugby tablets are 500 mg, so you could cut those in half to get 250 mg. There are 1000 500 mg tablets, so cut in half would last 2000 days at 250 mg a day.
”NAD+ levels, indeed, fall in patients with PD and, conversely, increasing niacin intake can increase dopamine synthesis in the striatum and restore optimal NAD+/NADH ratio needed for the activity of mitochondrial complex 1 [148].”
IMO I would try to understand how ‘optimal NAD+/NADH ratio’ works before changing doses overnight, but I might be wrong I'm not a biochemist. 😔
Today Saffron rice, Carnaroli rice, Tre Cuochi saffron, delicious.
Lou T's comments are at the bottom of the article. This comment with Simon's answer is, in my opinion, enlightening about the NAD. Does it show us how to best use niacin? The key is in the gradual, not steep, of dose increase? Would it be better with the addition of other vitamins and minerals without exaggerating? Would it be better if done cyclically in a occasional way ?. These are the questions that I ask myself, but I'm not a biologist or a doctor,
I am trying to understand the context of this chemical reaction in cellular life.
Thank you Gioc, I really appreciate your taking the time to make sense of this.
I read through those the best I could. Some points from my not very sharp mind:
1: I don't understand why they focus on NR and Niagen and seemingly everything else but Nicotinic Acid. NA is the only B3 that binds with GPR109A and the only one that causes a flush. I have written off the fake Niacin's as distractions.
2: I think you raise a good point about how fast to raise the dosage. I jumped from 250 mg to 1000 mg to 1000 mg within 4 days. I may go higher.
3: Another good point about co-vitamins. I was watching some videos of Dr. Hoffer, the father of high dose Niacin, and he mentioned including vitamin C. Dr' Hoffer successfully treated schizophrenia with Niacin. A lot of Niacin. One thing I will always err on is the side of action. This may be because I have poor impulse control or I might not care that much about what happens to me. I might start adding vitamin C, but I am really trying to cut my stack.
4: I can't find the paper, but I swear I saw some study that showed the benefits of Niacin disappeared quickly once Niacin was discontinued.
New Year, but the story remains the same: individual variability in response to drugs and supplements.
Case in point, my spouse use 500mg Sustained Release Niacin from Doctor’s Best. She will not be at work without it. Takes away the tiredness.
I do however skip over to a B-Complex over the weekend for balance.
Would not labor the point, but GPR109A binding that Bolt emphasizes, is what got me interested. Saw a response in hours.
And this could not be a ‘placebo effect’: she has no idea what she is taking. Found this attitude infuriating at first, but I have accepted it, as I can better judge the effect that supplements have.
We take a lot of stuff, for which there are good theoretical reasons for their use. But for most we can never be sure, because their is no easily discernible benefit.
In this instance, she took an immediate interest in her kitchen, and begin to wash dishes. This was quite dramatic as she did not have any energy or interest in such activity. It may seem small but she fancies herself as a dominant force in the kitchen.
Additionally the constant complaints of being tired and not knowing if she could make it to retirement ceased.
With four months to go, the complaints are coming back. May need to pull off another miracle. 🌴🍻🌺
P.S: Niacin in use since September 2020. Used ‘ATP Co-Factors’ for a two years before. This product is combination of no-flush Niacin and Riboflavin (B2).
Very interesting CaseyInsights, as always. Thank you for taking the time to respond. The sense of duty is the highest motivation, in that you are an example for all of us Pwp and caregivers.
One thing to dig is an absorbable appropriate level of B3, and what forms of B3 are not proper, and whether B3 included in vitamin pills or other forms of pills compromises that good B3.
Happy New Year to you, bolt! ... Sadly my "internal" tremors this past month have become "external" as my fingers are now visibly moving several times a day. This is despite my tackling PD from the very first day I had the very first recognizable symptom, June 20, 2021.
GREAT NEWS! 95% of my internal tremors have disappeared... and 99% of the (very few in number) finger/hand/ankle/ EXTERNAL tremors have also disappeared ... This happened over the last 10 days or so... when I have time I'll explain more because there are LOTS of details!
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Could the NAD+ precursor, Niagen, be the best supplement ever? 
