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Why would Niacin cause depression?

Messages
7
This has happened for a second time recently. About 3 weeks ago after supplementing methylfolate 300mcg/day for 2 weeks with no b12 I was feeling a bit agitated so I took 20mg of Niacin and felt it took the edge off, I wanted to see how I reacted to more Niacin and took 150mg spread out through the next day. I ended up feeling severely depressed for days with low energy.

OK, I understand the part of soaking up methyl donors, but why would I be plunged into a deep depression? I couldn't find any information of this happening to anyone else. And I have never experienced this before with Niacin. I cycled through a bunch of supplements zinc, magnesium and eventually when I tried b12 it completely stopped the depression, I didn't feel great but was relieved that I felt neutral.

So fast forward two weeks, I was introducing methylfolate slowly, taking about 200mcg for a few days while taking 3mg mb12 and 3mg ab12. Until yesterday when I took 300mg around midday followed by another 200mg at night. Later that night I was very anxious and agitated, had a restless nights sleep and also head pressure. It lasted through to today when I decided to take 25mg of Niacin, those symptoms mostly subsided but was again replace with a depression.... from 25mg of Niacin. That's only slightly more than the RDA!

What's going on here? Is it straight up b12 deficiency? methyl trapping? Maybe B out of balance? Or did the Niacin use up Sam-e?

Let's say for example I had b12 deficiency and taking folate and niacin was exacerbating the problem. Wouldnt the 25mg of mB12 + 20mg of aB12 I have been taking over the last 2 weeks take on the miniscule amount of folate in comparison?

Also for the last 3 weeks I have been experiencing waking up with very dry eyes and completely dry mouth. How does this fit in, in terms of methylation?
 

SJB944

Senior Member
Messages
178
Not sure if this helps, but I found taking even small amounts of niacin ramps up my need for mfolate and potassium -- that is while also taking MB12 and ADb12. By small amounts I mean 25mg, broken up into two lots taken morning and lunchtime.

It is almost a cliche, but after taking mb12 and adb12, my symptoms have most often been related back to taking either not enough folate (methylfolate) or potassium, or both.

To make things clearer, I actually stopped taking just about everything but mb12, and kept taking it until I produced folate deficiency symptoms, that way I could get some clarity. I then took enough folate to those symptoms abated and went from there.

Fred says the following: "With 1mg of AdoCbl and 1mg of MeCbl each held for 1-2 hours against oral mucosa, one could end up with 200-400 mcg or more absorbed. This is enough to turn on all layers of healing except CNS for many of us. A start of methylfolate of 800mcg or less will usually produce a burst of healing on a couple of layers that then demands more folate than the body has easily available and so shorts other layers to supply the ones that are healing causing paradoxical folate insufficiency. So one titrates methylfolate until the insufficiency symptoms go away. This is usually between 1600mcg and 20-30mg depending upon how one reacts to other folates and B1, b2, b3.

While this is happening there is also usually a need for potassium of which needs to be titrated to the level of no symptoms. This usually happens in the range of 1200-3000mg daily in 4-6 divided doses. Again, this is dependent upon how fast cells are being formed and if too much b1, b2, and/or b3 can also be insatiable."

At: http://forums.phoenixrising.me/index.php?threads/active-b12-protocol-basics.10138/page-8#post-413853

Question is do your symptoms fit into either those of potassium or folate deficiency?
 
Messages
7
Unfortunately, last year I tried ramping up methylfolate up to 2-3mg a day for a couple days without a good result. I then tried upping my potassium intake by a lot and that ultimately made me feel worse.

I dont think I have potassium deficiency as I did increase my potassium after the first depressive episode with no improvement. And since methylfolate has been the best supplement for alleviating depression in the past you could say it makes sense that it was a folate deficiency. Kind of a scary thought though, being caught between anxiety, panic, insomnia when methylfolate "goes wrong" or the severe depression of the Niacin. Talk about a rock and a hard place.
 

Violeta

Senior Member
Messages
2,895
I was thinking it might be a B2 deficiency symptom, and when I saw the dry I thought so even more. Also, for some reason, B2 and B3 can sometimes be antagonistic. Do you take B2?
 

SJB944

Senior Member
Messages
178
@hansieg Yep, so often this illness is about being stuck between a rock and a hard place -- also difficult to think logically when pushed into anxiety or depression! Hope someone else here can shed some light.
 
Messages
20
Hey yes this exact same thing happens to me. Every time I take niacin, even when not taking any other supplements, I become depressed for several days and sometimes a full week or more. Niacin in supplemental doses can increase serotonin levels which, contrary to popular belief, actually can make a lot of people depressed. Serotonin itself is usually a sedative and it certainly can cause depression. Vitamin B6 can do the same thing. Niacin in very high doses has been used to "treat" schizophrenia. In my personal opinion, the fact that niacin makes you depressed is a good sign. The depression continues even after the niacin should be out of your system because it takes time for the body to reset. Just curious - do you have seasonal depression as well?
 
Messages
20
To clarify the above - its a good sign because it means your rejecting the higher levels of serotonin because you don't want to succumb to the "relax, be happy, give up" signals of serotonin. If niacin makes you "happy" then it means you've embraced the feeling of helplessness.
 
Messages
7
Violeta, I have taken B2 in the past but not currently taking it. Something must have changed since last year where I was in a similar situation with overmethylation and taking niacin stopped the symptoms but didnt cause a depression.

User, maybe you are right, have you found a way to combat it? I mean other than avoiding niacin.

I just watched in a recent methylation video by bill walsh that niacin acts as a dopamine uptake enhancer. So maybe my issue is with low dopamine.
 
Messages
20
Net-net niacin will decrease dopamine but it will increase it slightly in a particular area (I forget which area). Net-net yes you will have less dopamine. Niacin can also reduce epinephrine (adrenaline) and norepinephrine. Niacin causing depression doesn't mean you necessarily have low dopamine - it could mean you brain is used to more dopamine and when dopamine is lowered (by niacin) you become depressed. Someone who is more serotonin-focused wouldn't become depressed from niacin. Last time you took niacin and it didn't affect you. what time of the year was it? Was it in like February? To clarify - you do not have seasonal depression?

I don't think there is anything you can do but wait a couple of days and then drink coffee. I never drink caffeine but half a cup of coffee seems to combat the negative effects of the niacin for me. I think its more a symptomatic solution.
 
Messages
7
I meant more like if niacin is taking my body in one direction, what supplement/s can I take to go in the other direction?

I dont think I have seasonal issues. It was about August when I took it last year, so around the same time.
 
Messages
7
Ok, I'm feeling severely depressed and anxious today. Like I am seriously considering checking into a mental health clinic if it continues..

Does anyone else have an opinion of went went wrong? I have never had depression this bad. Timeline:

- 3 weeks of methylfolate 300mcg/day and felt good initially
- After experiencing agitation/anxiety and panic one day about 3 weeks in, I took 25mg followed by 150mg Niacin
and felt very depressed and wiped out for a week. It was around here I started waking up every morning with very dry eyes and dry mouth.
- After a week of cycling supplements to try address the depression (zinc, copper, magnesium, and I think i tried a few B's) I felt that my depression lifted after taking dibencozide. I continued taking that along with mb12 for about a week(about 3mg a day of each).
- I came to the conclusion I may have experiencd methyl trapping and decided to reintroduce metafolin. I was taking 200mcg of it for a few days. I recall that I felt "pretty good" that day and decided to add another 300mcg. Late into the night I woke up feeling anxious and decided to take another 25mg of Niacin and got another depressed feeling.

I really dont know what to make of this. I'm still feeling depressed 1 week after the 25mg of Niacin, and about a month from the 150mg of Niacin which makes the Niacin directly as the cause seem unlikely. So I'm guessing it must be a methylation issue or deficiency of something else? I have tried other things in the meantime that could have exacerbated the problem. Zinc, copper, magnesium, b1, b2 and a small amount of b12 are all supplements I tried in the last few days. What could the very dry eyes and completely dry mouth every morning mean? I've read of a conditon called sjogrens which I could have. While depression is a symptom of it, it doesnt seem like people with it are having severe cases of it.
 

caledonia

Senior Member
@hansieg

Check out Ben Lynch's info on what to do if you have methylfolate side effects. Feeling good for awhile, but then starting to feel bad is classic.

http://mthfr.net/methylfolate-side-effects/2012/03/01/

http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/

Another thing to consider is that according Walsh's theory for methylation and mental illness, you may be an undermethylator. In this case, methylfolate acts as the opposite of an SSRI and is counterproductive mentally.

In this case, you would avoid all forms of folate, and support methylation with other supps such as SAMe, methionine, and/or TMG.
 
Messages
20
Try drinking some coffee, especially if you don't normally drink it. Did you make any major lifestyle changes from last year to this year (lose weight, increase exercise, change sleep schedule, etc)?

I would bet a lot of money that the depression is a result of the niacin trying to raise your serotonin levels. Or, it could also be toxins - niacin causes fat cells to rupture and toxins to flow out for detox, but if something else is blocked they just recirculate. Lastly - separate note - one time I had what I thought was a methyl block and I spent months trying to correct it but it turned out I had been bit by a tick and developed lyme disease and that was causing all the problems. So, be on the look out for other variables that may be at play.
 

TheChosenOne

Senior Member
Messages
209
I have the exact same problem. I've used niacin in the past to lower my anxiety levels. It triggered a depressive episode. Today, the only niacin I take (modarate amount - 50 mg) comes from a B complex and it doesn't give me any problems.
I see no one recommending things that can lower anxiety without lowering methylation.

What works excellent for me are:
Lithium orotate (10 mg). This is probably my most important supplement. Lithium is given to people that have bipolar, so I tried it. It helps dramatically. Even in this low dose. It makes me more resistant to stress (and hence lowers anxiety). Highly recommended if you have COMT++.
Magnesium (500 mg). Increases COMT activity.
HydroxyB12 (1000 mcg). A precursor of methylB12.
GABA (500 mg). GABA inhibits the firing of neurons, while glutamate does the opposite. Although, it doesn't cross the blood-brain barrier, a lot of people report positive effects.
B6 (10 mg). B6 is a cofactor in the conversion of glutamate to GABA. I use this at night.
B complex. Probably not for everyone, but it contains all the B vitamins. I use this in the morning.
Tyrosine (500 mg). Useful if you want to bypass methylation and increase dopamine levels. This gives me more motivation and lessens depression.
Phosphatidylcholine (210 mg). Stimulates BHMT. Phosphatidylcholine is one of the things that are made from SAMe (about 1/3). This means that if you take this, you can save some SAMe. SAMe is needed for COMT to work.

All these supplements individually may have only a minor effect (except for lithium in my case). But combined it works very well.

The result is that both depression and anxiety have improved severely.

Please note that I have some form of bipolar.

If you can't handle methyl supplements that well, you might be better off using supplements that increase methylation without necessarily increasing the total amount of methyl donors.

Something else that might be worth trying is theanine. It is a building block for GABA. There are other supplements that are GABA derivatives and can cross the blood-brain barrier. That might be interesting too.
Also, there is a whole thread about anxiety that might be worth investigating.
 
Messages
7
I'm back, still experiencing anxiety and depression, although not as severe as a week ago. I found that drinking a whole litre of coconut water a day reduced my depression by 50-70%. Which I started on the day of my last post. I was able to tolerate 1 l of coconut a day for 6 days. But yesterday I felt symptoms of what I assume are high potassium( head pressure, spacey feeling). I didnt drink any coconut water today, and my mood is feeling a little lower again. So now it seems like im damned if i do, damned if i dont.

I have a few questions. Considering my significant improvement with coconut water would you say this was a straight up potassium deficiency? I didnt/dont have most of the potassium deficiency symptoms which are:

Weakness tiredness, or cramping in arm or leg muscles, sometimes severe enough to cause inability to move arms or legs due to weakness (much like a paralysis) NO
Tingling or numbness NO
Nausea or vomiting NO
Abdominal cramping, bloating YES (bloating)
Constipation NO
Palpitations YES(nothing severe though)
Passing large amounts of urine or feeling very thirsty most of the time NO
Fainting due to low blood pressure NO
Abnormal psychological behaviour:depression, psychosis, delirium, confusion or hallucinations. YES (Depression)

Though I improved significantly with increasing potassium, I'm wondering if it is more complex than that. Maybe it worked by antagonizing one of the B vitamins(b12?) or something else? Or maybe I do have potassium deficiency but a the same time also a deficiency in something else that potassium antagonizes? B12 or b1. Hence why its a double edge sword.

I'm wondering if its thiamine, as I know its a potassium antagonist. And I also found out earlier this year that I was able to tolerate zinc better when I took thiamine. B12 is something to consider too. I wonder if even my low dose of folate 300mcg per day was enough to use up and deplete b12.

Problem with being in such a state is that you have very little room for error to try things. Feel like im walking on a tight rope with my sanity atm.
 

Oci

Senior Member
Messages
261
I have the exact same problem. I've used niacin in the past to lower my anxiety levels. It triggered a depressive episode. Today, the only niacin I take (modarate amount - 50 mg) comes from a B complex and it doesn't give me any problems.
I see no one recommending things that can lower anxiety without lowering methylation.

What works excellent for me are:
Lithium orotate (10 mg). This is probably my most important supplement. Lithium is given to people that have bipolar, so I tried it. It helps dramatically. Even in this low dose. It makes me more resistant to stress (and hence lowers anxiety). Highly recommended if you have COMT++.
Magnesium (500 mg). Increases COMT activity.
HydroxyB12 (1000 mcg). A precursor of methylB12.
GABA (500 mg). GABA inhibits the firing of neurons, while glutamate does the opposite. Although, it doesn't cross the blood-brain barrier, a lot of people report positive effects.
B6 (10 mg). B6 is a cofactor in the conversion of glutamate to GABA. I use this at night.
B complex. Probably not for everyone, but it contains all the B vitamins. I use this in the morning.
Tyrosine (500 mg). Useful if you want to bypass methylation and increase dopamine levels. This gives me more motivation and lessens depression.
Phosphatidylcholine (210 mg). Stimulates BHMT. Phosphatidylcholine is one of the things that are made from SAMe (about 1/3). This means that if you take this, you can save some SAMe. SAMe is needed for COMT to work.

All these supplements individually may have only a minor effect (except for lithium in my case). But combined it works very well.

The result is that both depression and anxiety have improved severely.

Please note that I have some form of bipolar.

If you can't handle methyl supplements that well, you might be better off using supplements that increase methylation without necessarily increasing the total amount of methyl donors.

Something else that might be worth trying is theanine. It is a building block for GABA. There are other supplements that are GABA derivatives and can cross the blood-brain barrier. That might be interesting too.
Also, there is a whole thread about anxiety that might be worth investigating.

Thanks for the information. I have COMT++ and some similar snps too and so it gives me ideas to try out. I am wondering what B Complex you are using? One without methylated B12?
Thanks, Ann
 

TheChosenOne

Senior Member
Messages
209
Thanks for the information. I have COMT++ and some similar snps too and so it gives me ideas to try out. I am wondering what B Complex you are using? One without methylated B12?
Thanks, Ann
I'm using a wrong one. It contains folic acid, which is bad. But I'm almost through it. It does not contain methylB12. I was able to up my methylB12 dose to 500 mcg, since I've switched to 2x120 mg lithium orotate (which is 9 mg lithium). I hope this helps.
 
Messages
40
This is a very old post. But since I have a very similar experience to which I didn't find a solution, I want to add my experience.

One possible explanation could be the effect nicotinic acid has on cholesterole.

I also noted that as much as I enjoy the niacin flush and also as much as it can improve some health issues, I also get severely depressed, in the days following. I am just leaving a terrible week behind me where I was next to unable to have any clear thought and was basically unable to eat or do anything due to an extreme lack of motivation. It already happened repeatedly quite similarly in the past, so I was already wary of the consequences. However awareness that the depressive symptoms could be due to the niacin did not help very much. I was trapped in an endless train of dark thoughts, self-criticism/hate and tiredness.

So serotonine might be involved as well, but rather a lack of it, instead of a too much of it.

I am starting to giving credibility to the Cholesterol-hypothesis since I started to feel much better after eating three large eggs this afternoon and also lots of pork fat and butter the last two days.

I am just adding this in case it might help someone on the journey and also since maybe there is someone with a more complete picture of the metabolic processes that might be involved.

For some time I could not believe that it is due to the nictotinic acid, since nictotinic acid is actually also used to ease depression and panic.

https://www.greenmedinfo.health/blog/underreported-dangers-low-cholesterol
  • Cholesterol Is Needed To Prevent Aggression: It has been known for almost 30 years that low serum cholesterol levels are associated with habitually violent tendencies of homicidal offenders under the influence of alcohol.https://www.greenmedinfo.health/blog/underreported-dangers-low-cholesterol#_edn1 Since then, there are at least 8 other studies that have either confirmed or explored the cholesterol-violence link, including both violence towards self and other. One of the possible explanations for this association was discussed in an article published in the British Journal of Psychiatry in 1993: "One of the functions of serotonin in the central nervous system is the suppression of harmful behaviour impulses...Low membrane cholesterol decreases the number of serotonin receptors. Since membrane cholesterol exchanges freely with cholesterol in the surrounding medium, a lowered serum cholesterol concentration may contribute to a decrease in brain serotonin, with poorer suppression of aggressive behaviour".[ii] Not surprisingly, several reports have now surfaced on cholesterol-lowering statin drugs contributing to irritability and/or aggression.
 
Messages
40
Another thing just came to my mind; I just remembered that cholesterol is the precursor to pregnenolone and progesterone and the depression felt very similar to my worst premenstrual syndrome experiences.

So there is actually a link between cholesterol levels and the female cycle.

In the second half of the cycle, when progesterone levels rise, also cholesterol levels fall! Of course they do, when cholesterol is needed to synthesize progesterone!

What we generally observe is the rise in progesterone and therefore PMS has been interpreted as a consequence of the rise in progesterone. But maybe it is in fact the fall in cholesterol and the resulting desensibilisation of serotonin receptors in the brain.