This topic contains 10 replies, has 2 voices, and was last updated by Kim 1 year, 1 month ago.
July 25, 2012 at 4:25 pm #2966
Hello Dr. Ben and all, I am a fairly “healthy” 54 year old woman who has been blessed with 8 healthy children. After our first birth, I was diagnosed with hypothyroidism and have been on 90 mg ARMOUR ever since. In the past few years, I have worked on keeping fatigue at bay and feel I fight brain fog a bit. I exercise and eat fairly well. A year ago my natural doctor put me on bi-identical hormones for my hot flashes and other menopausal symptoms. My regular doctor was concerned about hormone replacement thus wanted me be tested for MTHFR T/T, which resulting in our awareness of this in me. The natural doctor said to stay on my compounded hormone cream and added B12 shots (self-administered) 3 times per week, L-methylfolate 100 mcg 3 times per day, and most recently Niacin time-released 500 mg twice each day. I also take DHEA from compounding pharmacy, Vit D w/ K2, Omega 3’s fish oil, Vit C, Iodine 6 mg day, and Alpha Lipoic Acid 600 mg twice each day.
I hope this regimen cures my brain fog and fatigue. I did have minor flushing with the Niacin but not unbearable. I read on your website film strip presentation you do not recommend Niacin unless to fight symptoms which I don’t have. I am confused now as to whether or not to stay on it. Please comment and know I am very grateful for any insights. CarolJuly 26, 2012 at 2:00 am #2973
Do you know why your doctor recommended niacin? It is something some doctors recommend now for lowering cholesterol levels. But these recommendations don’t take into account whether a person has MTHFR mutations. Niacin uses up methyl groups as it gets metabolized. Time-released niacin causes liver problems and isn’t a good form. Slow-release niacin isn’t as damaging. But 1000 mg is a large dose, especially for someone with MTHFR mutations.
My doctor and I talked about niacin last week. During that appointment, I presented my homo A1298C test results. He disagreed about niacin using up methyl groups and wanted me to take 50 mg. of niacin. I don’t think he’s very knowledgable about MTHFR though. Since niacin is supposed to be a necessary vitamin, I too would like Dr. Ben’s opinion on whether someone with MTHFR without overmethylation symptoms should totally avoid niacin as a supplement. But to backup my contention that niacin could be deleterious to me, I researched for references. Here is what I found:
http://www.heartfixer.com/CHC%20-%20Medical%20Topics%20-%20Niacin.htm – a cardiologist in Ohio. “Homocysteine: Homocysteine levels may increase in relation to Niacin, as Niacin metabolism in the liver places a strain on the Methyl cycle. Specifically, SAMe is used up, methylating Niacin. It appears that the metabolic side effects of Niacin (elevated liver chemistries and blood sugar), and the rise in Homocysteine sometimes observed with Niacin treatment, are related to Methyl group depletion.”
http://www.enzymestuff.com/methylation.htm According to Pfeiffer, “Actually excess niacin (B3) is metabolized by methylation and thus uses up methyl groups.”
http://ajpendo.physiology.org/content/281/5/E1095.full However, niacin is excreted as methylated pyridones, the formation of which uses SAM as the methyl donor. In their study, Basu and Mann maintained rats on diets supplemented with niacin and monitored effects on plasma sulfur amino acids. Their experiments showed that niacin supplementation significantly increased plasma homocysteine levels. These results, and those of Miller et al. (23) and Allain et al. (1), underscore the importance of peripheral methylation reactions, and the consequent effects on methionine metabolism, during the course of drug therapy
http://jn.nutrition.org/content/127/1/117.abstract?ijkey=8b000a08f789696d5077cfa07013b97f64ede4f1&keytype2=tf_ipsecsha, Basu and Mann. “The present study provides evidence that pharmacological levels of niacin interfere with the metabolism of methionine, leading to hyperhomocysteinemia and hypocysteinemia.”
In the abstract: “It is proposed that this heptatotoxicity [of high dose niacin] reflects the high demand for methyl groups imposed by niacin catabolism.”
From page 2 of the text: The catabolic pathways for niacin in humans have been
determined (11–13). A portion of ingested niacin is conjugated
to glycine, in a process involving nicotinyl-coA as
an intermediate, and the resulting conjugate (nicotinuric
acid) is excreted in the urine. This metabolic pathway is
more prominent when niacin is administered in rapid acting
form rather than in time-release preparations
(11). The remaining niacin is used for NAD synthesis;
when this NAD is cahttp://www.freewebs.com/stopped_our_statins/betaine_alleviate_hepatotoxic_risk_niacin_therapy.pdf tabolized, most of the released
free niacinamide is N-methylated, and a portion of this
N-methylnicotinamide is oxidized to form N1-methyl-
2-pyridone-5-carboxamide. These are the major endproducts
of niacin catabolism, and are excreted in the
urine. It appears that NAD synthesis is the primary fate of
niacin in humans; nicotinuric acid synthesis may only
become prominent when high levels of niacin saturate the
capacity for NAD production (11).
It is immediately
apparent that catabolism of NAD places a substantial
strain on the methylating capacity of hepatocytes. If
we assume that 80% of a 2 gram daily dose of timerelease
niacin will be methylated, this will require the
methyl groups from about 2 grams of methionine (in the
form of S-adenosylmethionine). Under ordinary circumstances,
the lion’s share of the liver’s methylating capacity
is used for creatine synthesis (14), since creatine turnover
(in males) is about 2 grams daily (of which the diet provides
a variable quantity, up to 1 gram) (15), it can be estimated
that less than 2 grams of methionine are required
for daily endogenous creatine production. Thus, the
methylation requirements imposed by high daily doses of
niacin are large compared to the liver’s normal methylating
activity. Fortunately, the methionine synthase reaction
(in which 5-methyltetrahydrofolate donates a
serine-derived methyl group to homocysteine with the
assistance of vitamin B12) can ‘recycle’ methionine so
that a limited dietary intake of methionine is often sufficient
to support ordinary methylation requirements.
Theoretically, when methyl group demand is high, upregulated
activity of enzymes required for de-novo serine
synthesis and folate pool turnover might be expected to
maintain adequate methylating capacity; however, it
seems likely that at least in some individuals these adaptive
mechanisms would function suboptimally. Thus, the
additional methyl requirements imposed by high-dose
niacin therapy may have the potential to strain the capacity
of the methionine synthase reaction, such that the
hepatocyte pool of S-adenosylmethionine (SAM) becomes
significantly depleted. As a result, other crucial methylation
reactions in hepatocytes – such as synthesis of
membrane phosphatidylcholine – will be underactive. I
postulate that this is the chief metabolic mechanism
whereby high-dose niacin therapy evokes hepatotoxicity.
Furthermore, inasmuch as S-adenosylmethionine is a
potent allosteric activator of the enzyme cystathioninebeta-
synthase (16), required for the irreversible disposal
of homocysteine, it is reasonable to expect that such therapy
will tend to raise serum levels of homocysteine – a
phenomenon that presumably would have a countervailing
negative impact on the vascular benefits of niacin
This thesis is consistent with the fact that rapid-acting
niacin, which is less prone to damage the liver, is more
likely to be excreted as nicotinuric acid than is timerelease
niacin. Also consistent is the fact that niacinamide,
which lacks the hypolipidemic and flush-inducing effects
of niacin, but which requires methylation for its metabolism,
can induce hepatic damage when administered in
high doses (17–19). In rats consuming choline-deficient
diets, high-dose niacinamide has been reported to diminish
liver SAM levels, induce fatty liver and DNA singlestrand
breaks, and depress creatine synthesis (20–22),
these effects are alleviated by administration of methyl
donors. The absence of comparable reports concerning
niacin may reflect the fact that, in rats, the predominant
metabolite of high-dose niacin is nicotinuric acid (23) – a
fact that may also account for the lack of evidence that
niacin can be hepatotoxic in rats. Swendseid and colleagues
recognized the possible relevance of their rodent
niacinamide research to niacin therapy when, citing the
potential toxicity of high-dose nicotinic acid, they advised
that ‘careful consideration should be given to the state of
methyl pool of such patients…(19)’.August 7, 2012 at 7:20 pm #3080
Lynn and Carol –
Great post and excellent topic.
Great references also Lynn – you rock.
My comment is this:
– Niacin may be very useful for those with MTHFR and COMT variants especially.
1) Because it appears that those with COMT can speed up their COMT enzyme with niacin thereby breaking down the neurotransmitters that tend to accumulate due to excessive methylfolate.
2) If you are taking the right amount of methylfolate and you do not have COMT, then I do not use niacin at all because it uses up SAMe. This is not good because those with MTHFR may already have low SAMe – potentially – so we do not want to lower it further.
The second issue with niacin though is that it is a vasodilator and also helps increase breakdown of fats which lead to further detoxification.
The niacin also may increase nitric oxide so those with A1298C MTHFR variants may have elevated nitric oxide and nitrotyrosine ( I am seeing it more and more ) – so the niacin may be useful initially – it can very quickly begin to cause side effects due to increase production of NO and nitrotyrosine. This can cause all sorts of neurological symptoms.
It gets complicated very quickly – I already am hesitating how much information to put here because I could write all day.
If you experience methylfolate side effects and/or have COMT variants, then niacin may be a life savior for you. I’ve seen it literally turn around many of my clients within an hour. When I mean turn around, I mean they stop breaking things, stop attacking people, anxiety drops immensely and they calm down.
I recommend 50 mg of nicotinic acid every 30 minutes to 1 hr as long as symptoms of anxiety and irritability are present due to excessive methylfolate or excessive neurotransmission – or overmethylation.
Keep in mind that SAMe is also a very potent detoxifier and if we can mobilizing toxins that are stimulating or toxic in any way – and most are – then symptoms may occur. I have a client who has a long history of meth, LSD and other drugs and they have MTHFR C677T homozygous – and if I use ANY form of methyl donors, they get very bad and I suspect it is from detoxing the drugs.
Anyhow – it is all a balance and there is nothing set in stone as methylation is too dynamic.
Niacin is wonderful for some people with MTHFR and others it is not.
The bottom line is this:
– if you suffer from methylfolate side effects, take niacin.
– if you have a COMT variant and you need to speed that mutation up to reduce your risk of anxiety or breast cancer, then a bit of niacin may be useful WHILE you are also supplementing with methyl donors – if needed.August 7, 2012 at 7:48 pm #3081
I tested positive for MTHFR. I have been on the meds for 3 months now. I feel no different. How and/or when will I know that I am on the correct amount of meds?August 7, 2012 at 8:05 pm #3082
I am MTHFR compound hetero. I also have COMT +/+, +/+. I was over methylating. I decreased my folate, changed my methylcobalamin to hydroxy and lowered my P5P because of CBS +/+, +/-. I reacted negatively to the niacin. Awful headache. I know adding NADH d ribose has helped. I go out in the sunshine for no less than 1 hour a day for seratonin. And GABA has turned my life around. I notice if I eat too many leafy greens or get too much folate in me, I go into panic attacks. I put 250mg of GABA on my tongue and the anxiety is gone for me in a few minutes. Since I have lessened my active b\’s because of the COMT and have added the GABA and NADH/dribose, the panic and anxiety is gone,I have lost 15 pounds in 3 weeks, I am smiling every day, sleeping like a baby and my adult acne is fading away.August 7, 2012 at 8:14 pm #3083
Dear Dr Ben
Will you get a reaction if you take B12 ( methyl Cobalamin) similar to the lady above? I am now using the MTHFR protocol on a client with Hetro C677 and she is feeling anxious and having really bad \\\\\\\’hay fever\\\\\\\’ within 2 days of taking the B12. I\\\\\\\’m following your protocol of introducing each of the supplements for a week at a time. Loved your podcast with the presentation by the way. This form of support would be an excellent way to help educate some of my colleagues back in London on how to use this for each MTHFR copy. Great stuff!August 7, 2012 at 9:26 pm #3089
Angela, I am trying to build a list of doctors who are treating methylation and MTHFR. I am looking for some doctors in the UK for family and people that visit my website and page on facebook. My email is email@example.com The only one I am familiar with so far is Patrick Holford.August 9, 2012 at 1:01 pm #3100
Angela, Sorry to get off the topic of this post, but I am also experiencing a sudden onset of hayfever, with runny nose and lots of sneezing. I haven’t started back on the methylfolate after getting severe muscle pain. I’m only on the methyl b12. I’ve been on it for a few weeks, but I do remember having an episode like this that was short lived a few weeks ago. I haven’t had problems with allergies for many years, since stopping gluten and milk products. Now I suddenly am having a coughing fit.August 12, 2012 at 10:40 pm #3130
I’m confused about multivitamins – specifically Seeking Health’s Optimal Multi-vitamin. It contains 400mcg of l-methylfolate and metafolin, which I understand is a good dose for those treating a C677T polymorphism. Yet it also contains 95mg niacin/niacinamide, which is 475% of the RDA. If niacin uses up methyl groups, and your response from Aug 7th says to avoid it unless you’re trying to undo an overmethylation situation, then why would the Seeking Health multi-vitamin contain such a high amount of niacin?
I’m searching for a multivitamin that contains methylfolate (or at least doesn’t contain folic acid) as well as P-5-P yet the niacin has me confused. Thank you.November 8, 2013 at 11:22 pm #378043
“http://jn.nutrition.org/content/127/1/117.abstract?ijkey=8b000a08f789696d5077cfa07013b97f64ede4f1&keytype2=tf_ipsecsha, Basu and Mann. “The present study provides evidence that pharmacological levels of niacin interfere with the metabolism of methionine, leading to hyperhomocysteinemia and hypocysteinemia.”
You don’t mention the part of the study where they say that the rats were fed “400 or 4000 mg niacin/kg (compared with 47 mg/kg diet in the control diet)” This corresponds to 24 to 240 GRAMS of niacin a day for the subjects and 2.8 grams for the controls in a 130 lb person. How could this possibly be relevant for someone trying to decide if they should take a few grams of niacin a day or not? I think the real information we can get from this article is that it is safe to take 2.8 grams a day for a 130 lb person.November 14, 2013 at 10:57 pm #378165
I took a look at another similar study and found out that the mg/kg was the niacin in the food, not the amount of niacin they fed each rat per kg of rat! I take back what I said before.
But I would mention that in the study they said that taking B6 along with the niacin stopped the homocysteine levels from being elevated. I think that if you take high niacin or niacinamide you have to be careful to increase the amounts of the support for the methionine cycle and the CBS pathway because you are upregulating both of them.
I have particular interest in this because I have a son who has schizophrenia and he has doubles on the COMT downregulation mutations and I am trying to figure out how to keep his COMT working as well as possible.