High dose Niacinamide causes strong anhedonia and muscle twitches

[Candeias]

Does anyone know why when I reach aprox 3 grams of Niacinamide I get a strong anhedonia and constant muscle twitches from one day to the next? It's frustrating because I'm getting the intended effects and then everything falls apart..

I'm following Kaufman and Hoffer's work, but they don't report these side effects. I have supp a B complex, TMG too because of the homocysteine and 250mg of TUDCA.
I would like to understand what goes wrong..

 

[redsun]

Does anyone know why when I reach aprox 3 grams of Niacinamide I get a strong anhedonia and constant muscle twitches from one day to the next? It's frustrating because I'm getting the intended effects and then everything falls apart..

I'm following Kaufman and Hoffer's work, but they don't report these side effects. I have supp a B complex, TMG too because of the homocysteine and 250mg of TUDCA.
I would like to understand what goes wrong..

Niacinamide in high doses has a tranquilizing effect (it agonizes GABA receptors). High GABA can promote anhedonia. Muscle twitching could be due to the acute reduction in catecholamine degradation since COMT needs SAM-e which is getting used up for niacinamide excretion. Thus you will have more norepinephrine and epinephrine in blood which signals acetylcholine release in skeletal muscles, contributing to muscle twitch, which are simply spontaneous muscle contractions. Sudden elevation in catecholamines can also make you feel anhedonic.

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives - PubMed

Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and...

pubmed.ncbi.nlm.nih.gov

"This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease."

 

[Candeias]

Niacinamide in high doses has a tranquilizing effect (it agonizes GABA receptors). High GABA can promote anhedonia. Muscle twitching could be due to the acute reduction in catecholamine degradation since COMT needs SAM-e which is getting used up for niacinamide excretion. Thus you will have more norepinephrine and epinephrine in blood which signals acetylcholine release in skeletal muscles, contributing to muscle twitch, which are simply spontaneous muscle contractions. Sudden elevation in catecholamines can also make you feel anhedonic.

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives - PubMed

Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and...

pubmed.ncbi.nlm.nih.gov

"This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease."

Yes, I believe it is something related, as both symptoms come together. I will increase the dose more slowly, and the methyl groups to see

 

[Vileplume]

Any isolated nutrient (supplement) is likely to cause some intestinal irritation, which can lead to anhedonia

 

[Candeias]

Any isolated nutrient (supplement) is likely to cause some intestinal irritation, which can lead to anhedonia

I don't think this is the case though, as I was at 2 grams with no problems and the problems started when I went up suddenly. But it was something that happened in the near past only with 1.5 grams, so it must be some catecholamine/homocysteine imbalance and/or liver. But I don't really know for sure

 

[Dapose]

The dose makes the poison is what I always thought. But I wish you luck! Also, are there additional ingredients in your supplemental niacinamide or are you taking pharmaceutical grade? Just curious cuz alot of the brands I use to look at in health stores all had weird additives like magnesium stearate Silica, etc and if you were taking 6 of those pills you might be getting shity effects from poorly made pills. Idk. Ray talks about this. B complex’s like you mentioned a lot of times have goofy additional ingredients.
Peace.