Need To Figure Out Niacin and NAC Curing Me

basebolt

I've had severe fatigue/depression and insomnia for a while. Tried lots of things for it. A few months back I was trying high dose niacin and it totally resolved my issues. Like life-changing effects were felt, almost like hypomania but it wasn't because my mind was calm and I had a desire to sleep. The niacin had this effect many times during a two-day period. Then it stopped. Strangely an l-arginine supplement brought it back but then it stopped too.

Since that experience, I've tried very high doses and consistently taking the niacin for weeks. Also I've tried oral NAD powder, NADH, nicotinamide, and NR. Nothing.

My second experience with the problems going away was from an IV administration of n-acetylcysteine. It nearly had the same effect as the niacin did back then. Oral NAC doesn't do this, but l-cystine does to a certain degree. It is toxic in high doses though, causing a waxy build-up in the liver among other issues.

If any bioenergetic experts know what could potentially be going on please let me know

Ismail

@basebolt Did you ever figure out what was going on? Perhaps the high dose B3 was utilising other co-factor nutrients (which may have been needed to be replaced/replenished etc.)?

LucH

@basebolt said in Need To Figure Out Niacin and NAC Curing Me:

Since that experience, I've tried very high doses and consistently taking the niacin for weeks. Also I've tried oral NAD powder, NADH, nicotinamide, and NR. Nothing.

Negative interaction with NAC
*) Treatment with NAC may strengthen the effects of some medications that suppress the immune system, such as azathioprine (Imuran), cyclophosphamide (Cytoxan), or prednisone (Deltasone). Do not take NAC with these medications without talking to your doctor first.
*) NAC may not be safe for people who bleed easily. NAC may raise your odds of bleeding problems if you have a bleeding disorder such as hemophilia or you take blood-thinning drugs.
=> Prolonged dose NAC interfere with platelet aggregation.
*) NAC can widen your blood vessels. This may further lower your blood pressure and cause serious headaches if you take nitroglycerin regularly.
*) NAC supplements may ease symptoms of mental health conditions such as depression, schizophrenia, and substance use disorders. There’s ongoing research in this area.
https://www.webmd.com/diet/health-benefits-nac

*) When Niacin (or vitamin B3) and NAC (N-acetyl cysteine) are combined, especially under specific pH and concentration conditions, a chemical reaction may occur that forms pyrazinic acid (pyrazine).
Most sources specify that no interaction has been found between NAC and niacinamide (or nicotinamide). This is incorrect when there is prolonged concomitant use with a high dosage of NAC.
The toxic effects of pyrazinic acid may include cellular damage and oxidative stress, which is of particular concern for people with predispositions to oxidative stress-related diseases.
Sources and References

Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management
https://doi.org/10.1016/j.jceh.2012.12.001 2013.
The toxicity of pyrazinamide is both dose dependent with a higher dose at 40–50 mg/kg, with NAC combination. (2 800 to 3 500 mg NAC for 70 Kg/weight, or +/ 170 Lb).
Unproven (questionable) cancer therapies.
ML Brigden - Western Journal of Medicine, 1995 - ncbi.nlm.nih.gov
Mega-doses of vitamin B3 (niacin) have liver toxicity and have produced acid peptic disease,
myocardial infarct, gouty arthritis, glucose intolerance, hyperkeratosis, and skin rashes."

LucH

@Ismail said in Need To Figure Out Niacin and NAC Curing Me:

Perhaps the high dose B3 was utilising other co-factor nutrients (which may have been needed to be replaced/replenished etc.)?

Well seen.
Need TMG 500 mg 2x/d. (methyl bonds).
Make a pause. Excess methyl is not advised but the lack of methylation is going to set havoc on metabolism.
High dose B3 has an impact on several enzymes from the detox pathway (Cyp450).
There is interaction between B1 B2 B3 and B8 in the energy process. Not only. When I supplement high dose of one of B1 B3 B6, I always take a B complex 2X/wk.
*) Energy and nutrients needed for metabolism

Carbs => Pyruvic acid => Acetyl CoA: Mg, B1 B2 (FAD) B3 (NAD) + B5
Required nutrients to extract energy in the form of electrons (electrons in the transport chain) (= oxidative phosphorylation => oxidation-reduction reactions are vital for ATP synthesis)
Acetyl CoA => Citric Acid Circle (Krebs circle): B1, B2 (FAD), B3 (NAD), Mg, Mn, Fe, GSH + B5

jamezb46

@LucH

Do you think TMG is necessary if eating 4 eggs + 1 oz liver per day + meat (methionine) totaling around 1000 mg choline per day?

LucH

@jamezb46 said in Need To Figure Out Niacin and NAC Curing Me:

Do you think TMG is necessary [with]1000 mg choline per day?

Probably not but there are 2 ways (with niacin and niacinamide) when taking HD supplement.
Need to find the info back.
Edit: I find the source back (Amazoniac, citing studies):
I try to summarize. Note I don't manage the whole stuff: too long; I need more brain energy
We should not supplement with high dose niacin or niacinamide, on a long term. Better taking co-factors from whole food.
One step: Choline is a well-known methyl donor, but it cannot play a methyl-donor role until it is converted to betaine in the liver and kidneys [23].
Source: Posted on RPF
https://raypeatforum.com/community/threads/niacinamide-or-just-plain-niacin.1104/post-354409
(Same post, from the post titled “Niacinamide or Just Plain Niacin?” – DMF member – Start date Jan 26, 2013. See Page 2, Amazoniac).
Note: The_one_I_mustn't_pronounce_the_name is asking the "permission" to target you (cookie) and you have to accept the politics of the Lion, which I didn't, of course. So, if you want to come back, delete the trace (cookie) before the second time or you'll probably be offside / forbidden of access.

Excerpt (from page 3, Amazoniac, same post):
"Niacin is the precursor of the important coenzymes NAD and NADP. NAD levels are dramatically altered by dietary levels of niacin. [59] Since NAD and NADP are crucial in redox reactions,[59] excessive niacin may lead to significant impacts on the redox status of the body by affecting NAD contents. Our recent study demonstrated that excessive nicotinamide might increase the generation of hydrogen peroxide, a highly ROS, and have a role in the development of insulin resistance.[35,60]"

jamezb46

@LucH

Interesting take. Thanks for the info. But what about nicotine then? I found a company selling wood toothpicks soaked in 3mg nicotine. Could be interesting.

Can you link to any studies showing that 500-600mg Niacinamide daily caused any insulin resistance? IIRC that amount of niacinamide can increase NAD+ levels by up to 24x, which I think you're suggesting might be excessive.

LucH

@jamezb46 said in Need To Figure Out Niacin and NAC Curing Me:

Can you link to any studies showing that 500-600mg Niacinamide daily caused any insulin resistance?

I'm not going to make this search for 3 reasons:

Need time and much energy.
The excerpts from the study given by Amazoniac have already given 2 sources on excess B3. You could have been first trying to reach them.

Note that the excess B3 must be understood on the long term, not in cure.

The studies are not all clear (different conclusions).

B3 supplement has an impact on lipogenesis. The time period impact is said to be only for 2 hours. I don't feel it so (I took Kg / Lb weight when taking niacinamide 100 mg).
Niacin and niacinamide are said to affect lipolysis differently. In theory.

Examples of studies:
*) From “Long-term Treatment With Nicotinamide Induces Glucose Intolerance and Skeletal Muscle Lipotoxicity” p4
https://raypeatforum.com/community/threads/long-term-treatment-with-nicotinamide-induces-glucose-intolerance-and-skeletal-muscle-lipotoxicity.15393/post-211103
=> It is shown that nicotinamide and oxythiamine inhibit inclusion of C from glucose into free fatty acids, antivitamin intensifies lipolysis in the fatty tissue of the diseased animals."
*) Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277745/
NB: Possible adverse effect when taking B3 longer than 1 month.

Study Link (given by Amazoniac): https://doi.org/10.1038/hr.2011.133
https://www.nature.com/articles/hr2011133
35. Li D, Sun WP, Zhou YM, Liu QG, Zhou SS, Luo N, Bian FN, Zhao ZG, Guo M . Chronic niacin overload may be involved in the increased prevalence of obesity in US children. World J Gastroenterol 2010; 16: 2378–2387.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20480523
Conclusion: The appetite-stimulating effect of nicotinamide appears to involve oxidative stress. Excess niacin consumption may be a major factor in the increased obesity prevalence in US children.
=> A 3-h blood glucose was significantly lower after co-administration of glucose and 300 mg nicotinamide. The obesity prevalence among American children increased with the increasing per capita niacin consumption, the increasing grain contribution to niacin due to niacin-fortification, and the increasing niacin-fortified ready-to-eat cereal consumption, with a 10-year lag. The regression analyses showed that the obesity prevalence in the US children of all age groups was determined by niacin consumption.
60. Zhou SS, Li D, Sun WP, Guo M, Lun YZ, Zhou YM, Xiao FC, Jing LX, Sun SX, Zhang LB, Luo N, Bian FN, Zou W, Dong LB, Zhao ZG, Li SF, Gong XJ, Yu ZG, Sun CB, Zheng CL, Jiang DJ, Li ZN . Nicotinamide overload may play a role in the development of type 2 diabetes. World J Gastroenterol 2009; 15: 5674–5684.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19960564
Conclusion: These findings suggest that nicotinamide overload, which induced an increase in plasma N(1)-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.
=> Results: Diabetic subjects had significantly higher plasma N(1)-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects.
Decrease in NAD/NADH ratio and increase in H(2)O(2) generation were also observed in human erythrocytes after exposure to N(1)-methylnicotinamide in vitro.
Note (LucH): increase in H(2)O(2) = Hydrogen peroxide => ROS = oxidative stress.