Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ [...]

[sb4]

@Learner1 What doses are you taking and did you previously take niacin, where you noticed different effects to the new type?

I remember doing some rough calculations and working out that for 500mg Niacin, the methyl groups used up to metabolise it where pretty small. Maybe if you were already struggling with methylation or used bigger doses it would become an issue.

I guess I am just trying to work out if I should add this to my list of things to try. I have tried both Niacinamide and Niacin over the years without much effect. However I think it would be a reasonable assumption that my NAD/NADH ratio is low considering the lactic acid problems and glucose tolerance issues I have.

 

[Learner1]

I stay away from niacin and niacinamide. Ive taken niacinamide with no effect. I supplement all cofactors as I tend to run short. B6 will convert to niacin if needed.

I take 125mg of sublingual NMN each morning, and get 100mg of NAD+ in a weekly mito cocktail IV. It makes an immediate difference in either form.

Niacin and niacinamide have to go through more conversions. From what I understand, NAD+ is one step from converting to ATP and NMN is two steps away.

A lot of cheap "NAD" supplements are just niacin or niacinamide - read labels carefully.

 

[olegsel]

weekly mito cocktail IV

What is the composition of the cocktail?

 

[Learner1]

B1, B2, B5, B6, 5-MTHF, B12, manganese, magnesium, calcium, molybdenum, glutathione, PolyMVA, and phosphatidyl choline. Divided into 3 IV bags.

 

[pamojja]

B1, B2, B5, B6, 5-MTHF, B12, manganese, magnesium, calcium, molybdenum, glutathione, PolyMVA, and phosphatidyl choline. Divided into 3 IV bags.

I get magnesium-sulfate IVs. The packet-insert says with overdose symptoms, calcium-gluconate IV should be given as antidote. Therefore I guess the magnsium and calcium is divited in 2 different IV bags?

 

[Learner1]

Calcium chloride and MgSO4 are given together. Alao, I forgot carnitine in the list above.

 

[pamojja]

Probably not enough to antagonize the Mg. From the packet-insert:

If you have used a larger amount of Magnesium Verla® i.v. 50% than you should:

Main symptoms and general signs of overdose are muscle weakness, disappearance of deep tendon reflexes, drop in blood pressure and heart rate, increase in skin circulation, ECG changes, vomiting, sedation and confusion.

If the plasma-magnesium concentration exceeds 2 mmol/l, the deep tendon reflexes are weakened, at about 5 mmol/l they are no longer present and respiratory depression occurs. At 6.0-7.5 mmol/l a coma occurs and from
8 mmol/l for respiratory paralysis and diastolic cardiac arrest.

Magnesium intoxication should be treated with intravenous calcium intake - as an antidote (e.g. slow i.v. administration of 10 ml of a 10 % calcium gluconate solution). In addition, the cholinesterase blocker Neostigmine should be administered as it increases the acetylcholine concentration and antagonizes the muscle relaxant effect of magnesium.

 

[Mary]

Calcium chloride and MgSO4 are given together. Alao, I forgot carnitine in the list above.

@Learner1 - please PM me (see PM I sent you)

 

[olegsel]

I never take niacin or niacinamide. They reverse methylation and I need methyl groups too much. My doctors think any of the niacin family supplements, like NAD+, will also affect methylation so good to be aware of thid snd be ready to support methylation.

can you explain this?
I have been taking niacin for a long time. He helps me a little.

 

[Learner1]

Need for nutrients is individual. If you are fiing well with that dose of niacin, great. Thevisdue is suddenly adding a dose when not adjusting everything else. Over time, the methylation balance might change.

Niacin uses up methylation groups, particularly SAMe. So, you could end up undermethylating.

 

[pattismith]

Dysfunctional T Cell Mitochondria Lead to Premature Aging
Author links open overlay panelGuyLenaers12DominiqueBonneau123YvesDelneste245NicolasPapon26
Show more
https://doi.org/10.1016/j.molmed.2020.07.001Get rights and content

Desdín-Micó et al. have shown that Tfam specific knockout in mouse T cells disrupts mitochondrial genome integrity and induces a burst of inflammatory cytokines and tumor necrosis factor (TNF)-α production, resulting in increased senescence, neuromuscular and vascular dysfunction, and molecular features that recapitulate premature aging.

Interestingly, treatment with nicotinamide riboside (NR) alleviates this phenotype by reducing senescence and systemic inflammation.

 

[Learner1]

Better to take NMN. Nicotinamide riboside will not work if one has mutations of these genes...

https://www.uniprot.org/uniprot/Q9NWW6

https://www.uniprot.org/uniprot/Q9NPI5

 

[pattismith]

Better to take NMN. Nicotinamide riboside will not work if one has mutations of these genes...

do you take NMN with caffeine?

I found that Nicotinamide Riboside works for me if taken with caffeine (caffeine alone doesn't work).

And Caffeine seems to be a NMNAT inducer:

Mammalian NAD metabolic pathways. Nicotinic acid (Na), nicotinamide (Nam), and nicotinamide riboside (NmR) serve as precursors for the synthesis of nicotinamide adenine dinucleotide (NAD + ). NAD + can be used in various cellular processes both as a coenzyme in metabolic pathways. as a substrate for covalent protein modifications, and for generation of signaling nucleotides. Nicotinamide phosphoribosyltransferase (NamPRT), nicotinamide mononucleotide adenylyl transferase (NMNAT), nicotinic acid mononucleotide adenylyl transferase (NaMNAT), nicotinic acid phosphoribosyltransferase (NaPRT), NAD synthetase (NADS), NAD kinase (NADK), quinolinic acid transferase (QPRT), ADP ribose (ADPR), cyclic ADP ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), 2'- phospho-cyclic ADP-ribose (P-cADPR), poly-ADP ribose polymerase (PARP), poly-ADP ribose glycohydrolase (PARG).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346375/
Caffeine and NAD+ Improve Motor Neural Integrity of Dissociated Wobbler Cells In Vitro june 2020
Mareike Zwilling, Carsten Theiss,† and Veronika Matschke*†

Abstract

Amyotrophic lateral sclerosis (ALS) is a common degenerative disease of the central nervous system concerning a progressive loss of upper and lower motor neurons.

While 5%–10% of patients are diagnosed with the inherited form of the disease, the vast majority of patients suffer from the less characterized sporadic form of ALS (sALS).

As the wobbler mouse and the ALS show striking similarities in view of phenotypical attributes, the mouse is rated as an animal model for the disease.

Recent investigations show the importance of nicotinamide adenine dinucleotide (NAD+) and its producing enzyme nicotinic acid mononucleotide transferase 2 (Nmnat2) for neurodegeneration as well as for the preservation of health of the neuronal cells.

Furthermore, it is newly determined that these molecules show significant downregulations in the spinal cord of wobbler mice in the stable phase of disease development.

Here, we were able to prove a positive benefit on affected motor neurons from an additional NAD+ supply as well as an increase in the Nmnat2 level through caffeine treatment in cells in vitro.

In addition, first assumptions about the importance of endogenous and exogenous factors that have an influence on the wellbeing of motor nerve cells in the model of ALS can be considered.

 

[Learner1]

Yes, I drink coffee immediately after taking NMN or NAD+ sublingually. I have found caffeine helps dissipate adenosine buildup due to my AMPD1 SNPS that other patients here have also reported having.

I've done two 2 month trials of 1g NR and it does absolutely nothing for me, except waste money. I believe it's due to my NMRK1 and 2 SNPs. Naturally, d-ribose was an ineffective waste of money, too.

NMN and NAD+ are a more direct route to increase NAD+ and readily available.

 

[pattismith]

Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice

Cheng‐Cheng Li

Wei‐Xiang Chen

2020

Abstract

Aims

Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated.

Méthode

To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated.
Results

Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration.

Moreover, NR administration significantly reduced glial activation around the Vessels.

Conclusion

Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.

 

[Learner1]

Though these folks don't seem to have a conflict of interest, many of the papers on nicotinamide riboside are by people trying to sell it.

Again, nicotinamide riboside must be converted to be used, and genetically, many if us cannot make this conversion. I wasted several hundred $$ figuring that out with no benefit.

Taking NAD+ or NADH directly, or NMN, which has fewer steps to convert has been more effective. There are a lot of benefits to to taking NAD and its precursors...

 

[Mr. Cat]

I have looked online for NAD+, but all I seem to find is products that have NMN or NR. Is NAD+ sold by itself OTC, and if so, could someone point me toward a good brand?

 

[Learner1]

I have looked online for NAD+, but all I seem to find is products that have NMN or NR. Is NAD+ sold by itself OTC, and if so, could someone point me toward a good brand?

LIAS Research or Alive by Nature. All the other so-called NAD products aren't. (They might eventually convert to it, but it's not a given.)