Methyl consumption by niacine/niacinamide

[PeterPositive]

Hello,
maybe I am flogging a dead horse here... But I have never gone into the details of the subject in the title.

One fundamental question I have had for quite some time is, how so many people take long term (relatively) high doses of B3 (in the range of at least 250-1500mg) without apparent methylation issues.

Dr Lynch briefly discusses the topic in this short podcast:
http://www.seekinghealth.com/natural-health-podcasts/podcast-5-niacin-and-its-use-safely.html

And provides a link to a study:
http://www.ncbi.nlm.nih.gov/pubmed/11895163

where rats were given a dose of (1,000 mg/kg diet) niacin for 3 months which depleted B6 and B12 and caused a raise in homocysteine. (As Lynch proposes, they mechanism is probably the "stealing" of a methyl group to produce methyl-nicotinamide)

Also this study:
http://www.ncbi.nlm.nih.gov/pubmed/22971213
clearly suggests that high dose niacin/niacinamide cause methyl consumption.
Again they tested humongous dosages ( 0,5-2,4g / kg ) on rats.

I have no idea how this applies to humans. Even at the lowest dosage they used (500mg/kg) we're talking about 35 grams of B3 for a 70Kg man/woman. It's unthinkable.

Bottom line... it seems that niacin/niacinamide could be dosed in the range of 100-500mg, or more when needed, even in people with methylation issues without causing problems. Naturally, people with methylation deficiencies should already be supporting the problem with adequate amounts of methyl donors.

Also this is a generalization and it will always miss specific exceptions. I've read several people in here reporting methylation-related issues with relatively low doses of B3. Experimentation is usually required.

Personally I have always been "scared" of taking more than 50mg of B3 as it seemed some sort of dangerous threshold. Since early 2015 I have started taking more and it seems to be helping without noticeable downsides.

What do you think?

 

[Crux]

I've been taking niacinamide for about 7 yrs. It's calming. I take it with dinner. It helps with sleep, to an extent.

I'm intolerant to niacin...tried repeatedly for decades.

Usually, I take 250 mgs., but more sometimes. More than 500mg. at one time, and I get nauseous. ( weak liver?)

 

[adreno]

I have no idea how this applies to humans. Even at the lowest dosage they used (500mg/kg) we're talking about 35 grams of B3 for a 70Kg man/woman. It's unthinkable.

No, it isn't. You need to read up on converting between rodent and human dosages. It's more like 3.5 grams, which isn't unthinkable.

 

[adreno]

This study shows that 100mg is enough to decrease methyl groups in humans:

http://www.ncbi.nlm.nih.gov/pubmed/23426511

 

[PeterPositive]

No, it isn't. You need to read up on converting between rodent and human dosages. It's more like 3.5 grams, which isn't unthinkable.

Thanks

 

[PeterPositive]

This study shows that 100mg is enough to decrease methyl groups in humans:

http://www.ncbi.nlm.nih.gov/pubmed/23426511

This Is expected, methyl groups are definitely used to create methyl-nicotinamide. The question is if 100mg, for example, is stealing enough methyl groups to cause problems in someone who is already supplementing with methyl donors.

Dr. Lynch suggests that a few hundreds mg of niacin are probably ok. I guess the problem is to be analyzed on per case basis.

 

[PeterPositive]

I've been taking niacinamide for about 7 yrs. It's calming. I take it with dinner. It helps with sleep, to an extent.

I'm intolerant to niacin...tried repeatedly for decades.

Usually, I take 250 mgs., but more sometimes. More than 500mg. at one time, and I get nauseous. ( weak liver?)

Do you also supplement with methyl donors? (Folate,B12 etc)

 

[Crux]

I do take methylcobalamin. Lately, I've tried to reintroduce folate, but I seem to be reacting negatively to it. ( I've been battling bacterial overgrowth, and produced ( in the gut) extremely high amounts of folate in the past.)

I don't supplement any other methyl donors that I know, but I do have some coffee, green tea, and moderate protein.
( there are methyl groups in many foods and drinks.)

 

[adreno]

The question is if 100mg, for example, is stealing enough methyl groups to cause problems in someone who is already supplementing with methyl donors.

That would depend on the amount of methyl donors people are taking, and how undermethylated they are to begin with. I don't think any hard and fast rule can be made about this.

 

[picante]

That would depend on the amount of methyl donors people are taking, and how undermethylated they are to begin with. I don't think any hard and fast rule can be made about this.

I have been taking powdered niacinamide since July and experimenting with the dose, taking about 85 mg at a time, starting with once a day, then trying twice a day. A reeeeally teeny tiny measuring spoon I have (labeled "smidgen") = 85 mg.

Recently I began studying redox problems (glutathione and thioredoxin), and hoping to amp up both glutathione and thioredoxin reductase, I increased my niacinamide to 3 doses a day. That was Sept. 19th.

Well, Saturday the 26th (yesterday) I woke up with the most obvious undermethylation symptom I have: severe low-back inflammation and a jammed-up S-I joint. It hasn't been this bad for a year: when I started trying methylation protocols a year ago, the arthritis in my lower back was the first thing to go (and good riddance!).

The bizarre thing is that since January I haven't been tolerating any but the tiniest dose of MeB12/Mefolate about once a week. Was that because of niacin deficiency?

And then after a week of 255 mg/day (in 3 doses), BLAM, I'm screaming in pain and running for the B12 & folate. Was I really overmethylated all those months?? I don't see how; I was barely taking any methylB12/methylfolate!

Note that I've been working to build my B2 levels as well, over the last several months, and have had to take it really slow (I'm up to 5 mg TID now.)

Going to put my aching back to bed now. Buenas noches.

 

[dannybex]

This Is expected, methyl groups are definitely used to create methyl-nicotinamide. The question is if 100mg, for example, is stealing enough methyl groups to cause problems in someone who is already supplementing with methyl donors.

Dr. Lynch suggests that a few hundreds mg of niacin are probably ok. I guess the problem is to be analyzed on per case basis.

Timely topic -- thanks for starting this discussion @PeterPositive and for posting the studies, links (thanks too @adreno).

I too cannot seem to tolerate hardly ANY niacin or (especially) niacinamide. Been trying for the last four years, and every time within a day or so I become agitated, depressed, irritable, etc., even at doses of less than 100 mgs -- just like @picante.

But I'm probably not taking the same doses of methyl-supps that many of you are. Yet at the same time, Lynch often says to start out with small amounts of methylfolate, and even that can cause problems which (he proposes) can be remedied with 50 mgs of niacin. This has never worked for me, and especially after reading @picante's post, makes me wonder about his hypothesis that methylfolate will increase inflammation unless inflammation is controlled first.

???

Nevertheless, even though we're all different, and there are a multitude of different co-factors and inhibitors of the krebs cycle (and methylation), I think it would be really helpful if everyone posted the amounts of methyl-donors they're taking, along with the amount of niacin(amide).

I'm currently taking 800-1200 mcgs of methylfolate, 2,500 mcgs methyl-b12 and 1,500 mcgs of ad-b12 per day.

 

[dannybex]

This study shows that 100mg is enough to decrease methyl groups in humans:

http://www.ncbi.nlm.nih.gov/pubmed/23426511

I knew that it increased histamine, but not serotonin. That might explain negative reactions, especially in folks with MAO snp issues…?

 

[ahmo]

2.4mg Mfolate;
approx 2 mg MB12;
50 mg niacin;
once a week, 40mg AdB12

 

[picante]

I too cannot seem to tolerate hardly ANY niacin or (especially) niacinamide. Been trying for the last four years, and every time within a day or so I become agitated, depressed, irritable, etc., even at doses of less than 100 mgs -- just like @picante.

Hi, dannybex, I'd better try to make myself clearer. I was taking:
1 drop liquid MeB12 once a week transdermally (probably less than 100 mcg)
With about 250 mcg AdB12 sublingual (about 1/12 of a 3000 mcg tab)
And about 250 mcg Mefolate

In July I started: 85 mg niacinamine/day
In Aug/Sept I alternated between: 85 and 170 mg niacinamide/day
Then titrated to a consistent: 170 mg/day
Followed by: 255 mg/day (for a week)

So unlike you, I was tolerating quite a lot of niacin, and seemed to need it -- my cognitive function went back to normal. The last titration was clearly an overdose, but it took a week to feel the effect, which was inflammation, and for me, that is associated with undermethylation. And in Freddd's list of methylfolate deficiency symptoms, you will find inflammation.

The end of this post may shed some light, too.

 

[Tunguska]

These days any form of niacin > 500mg alone induces fatigue of all sorts, inconsistently. Betaine/TMG appears to help tolerance the best and sometimes could take 1500mg niacins with no problem (taken because I've noticed positives from each). I've taken up to 10 grams of TMG in a day. (http://www.ncbi.nlm.nih.gov/pubmed/10985907 and sure it's not its first time quoted)

 

[dannybex]

Hi, dannybex, I'd better try to make myself clearer. I was taking:
1 drop liquid MeB12 once a week transdermally (probably less than 100 mcg)
With about 250 mcg AdB12 sublingual (about 1/12 of a 3000 mcg tab)
And about 250 mcg Mefolate

In July I started: 85 mg niacinamine/day
In Aug/Sept I alternated between: 85 and 170 mg niacinamide/day
Then titrated to a consistent: 170 mg/day
Followed by: 255 mg/day (for a week)

So unlike you, I was tolerating quite a lot of niacin, and seemed to need it -- my cognitive function went back to normal. The last titration was clearly an overdose, but it took a week to feel the effect, which was inflammation, and for me, that is associated with undermethylation. And in Freddd's list of methylfolate deficiency symptoms, you will find inflammation.

Okay, thanks @picante. Very interesting. That suggests that you were had enough methylation going overall, even with just weekly doses of the b12 and m-folate (and possibly diet-produced methyl-groups) so that that high-ish dose of niacinamide worked for you, until that last week.

A perfect example of how we're all different. Fred, (who I respect a lot, but who also attributes almost everything to a deficiency of methylfolate(!), needs massive doses of b12 and even higher amounts methylfolate yet doesn't tolerate more than (I think) 50 mgs of niacin(amide) a day. Same with thiamine and B2.

But that was interesting re his comments on not only inflammation (which again kind of counter Lynch's), but also increased itching, allergies (or 'atopy'), asthma…which is indeed associated with low folate levels:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693474/

Thanks again. Will be interesting to see what other's methylsupp/niacin(amide) ratios are.

 

[picante]

From your link, @dannybex:

On the one hand, the concomitant rise in allergic diseases(31;32) and serum folate levels in the United States(33) suggests that the relatively recent enrichment of the US diet with folic acid may be a risk factor for allergic disease, an observation that would be consistent with the findings in mice. On the other hand, lower folic acid levels have been implicated in a variety of inflammation-mediated diseases such as cardiovascular disease(34–37) and rheumatoid arthritis(38;39), so it is possible that folate may mitigate against, rather than promote, allergic diseases, which are also inflammation-mediated.

These authors are not distinguishing between "folic acid" and "folate". In light of what Freddd and others say about the folic acid used to "enrich" processed foods, this finding makes perfect sense. Supplemental folic acid causes "paradoxical folate deficiency". It's #9 on his list of "The 95% Reasons Methylation Therapies Fail":

9) Paradoxical Folate Deficiency - Folic acid is taken, which can block at least 10 times as much methylfolate from being active inducing folate deficiency even if methylfolate is also taken. These induced deficiency symptoms are often called "detox" symptoms. Folinic acid is taken which can block at least 10-20 times as much methylfolate from being active inducing folate deficiency even if methylfolate is also taken. These induced deficiency symptoms are often called "detox" symptoms.

 

[dannybex]

Good catch on that study @picante. So frustrating that folate and folic acid are so often used interchangeably.

I guess then one must assume that they probably measured serum folic acid, and not broken down folate, but if it's 'higher folic acid', then doesn't their study instead contradict what Fred has found? They're saying high folic acid levels are associated with less allergies, etc., and Fred is saying high methylfolate does the same.

It sure would be great to know if they measured folic acid or fully metabolized folate. Does anyone (hint, hint) want to email the authors?

Regarding folinic -- it's my understanding that folinic can block methylfolate to the degree Fred suggests only in those with a problem in the MTHFS enzyme. That was RIch's suggestion to Fred anyway, something I don't think Fred had an interest in following up on, but anyway, here's his explanation/theory:

http://forums.phoenixrising.me/index.php?threads/attention-freddd-mthfs-deficiency.11524/

Many take both folinic and methylfolate without any problem, in fact with benefit, and this study showed that folinic was metabolized to methylfolate. It's an ancient study (from 1972) and only three patients, and also not sure how folinic was 'fed' to the patients, but FWIW here it is:

http://onlinelibrary.wiley.com/doi/...ionid=1919BF71ABE7D41CF56153A9A4AF72D8.f04t01

 

[ahmo]

I don't appear to have MTHFS (rs6495446(C;T). 37% frequency). But folinic blocks folate for me.

 

[PeterPositive]

But I'm probably not taking the same doses of methyl-supps that many of you are. Yet at the same time, Lynch often says to start out with small amounts of methylfolate, and even that can cause problems which (he proposes) can be remedied with 50 mgs of niacin. This has never worked for me, and especially after reading @picante's post, makes me wonder about his hypothesis that methylfolate will increase inflammation unless inflammation is controlled first.

Just to clear, Lynch suggests to use 50mg of niacin every 30, or so, minutes. So you should keep taking it until the symptoms calm down. For some people 100mg may be enough, others may need to go way higher than that, depending on how strong is the reaction.

Unfortunately when I had my first bad reactions to methyl supplements I didn't know about this "trick"... eventually the symptoms went away anyways, but I wished I knew that.

cheers