side effects from Folates supplements

[pattismith]

I tried both MethylF 2 mg/day, Folinic acid 6 mg/day and Acid F 1.2 mg/day, and got very bad reaction to each one, mainly brain related (strong headache with non functionning brain), together with burning thighs' muscles.

I had a look at what we can find about folates toxicity but there is very few studies about it, neurotoxicity is cited but not explained and there's no study about different folate supplements and their side effect, it's a bit frustrating :

TOXICITY OF FOLIC ACID GIVEN IN PHARMACOLOGICAL DOSES TO HEALTHY VOLUNTEERS (1970) on thelancet

"Abstract
A trial to elucidate the effect of folic acid in pharmacological doses (15 mg. daily) on serum-vitamin-B12 levels in a group of fourteen healthy volunteers was abandoned after 1 month of a projected 3-month period because of the unexpected development of increasingly disturbing toxic effects in the majority. Most of the subjects experienced mental changes, sleep disturbance and gastrointestinal symptoms. Possible mechanisms of these effects are discussed."

on cab direct, the same article is differently presented:


Toxicity of folic acid given in pharmacological doses to healthy volunteers.

Author(s) : HUNTER, R.; BARNES, J.; OAKELEY, H. F.; MATTHEWS, D

Journal article : Lancet 1970 Vol.1 pp.61-63

"Abstract : A total of 14 healthy volunteers were given 15 mg folic acid by mouth daily. The trial was abandoned after 1 month because of toxic effects of a gastrointestinal or nervous kind. It is suggested that folic acid may have a specific effect on cerebral metabolism. If values for folacin in cerebrospinal fluid are correlated with serum folacin, then very high values for folacin in cerebrospinal fluid were probably reached because mean serum folacin values rose from 4.5 to 120 ng per ml at the end of the trial.
The symptoms of folic acid intoxication observed may be related to brain-amine change, which would explain the "alerting" effect of folic acid when given to patients on anticonvulsant drugs.-M. J. B."


How Safe Are Folic Acid Supplements?
Article · Literature Review · August 1996 with 38 Reads
DOI: 10.1001/archinte.156.15.1638 · Source: PubMed

• Norman R. C. Campbell

"Abstract
Periconceptual use of folic acid supplements by women is effective in preventing neural tube defects in the fetus. Folic acid supplements also may prevent atherosclerosis and some malignant neoplasms. Nevertheless, safety concerns have delayed recommendations to increase folic acid consumption by the general population. Among the potential safety issues of folic acid supplementation are (1) difficulty identifying cobalamin deficiency, precipitation of neurologic complications of cobalamin deficiency, and lowering of cobalamin levels; (2) folate neurotoxicity; (3) antagonism of drugs that inhibit folate metabolism; (4) reduced zinc absorption; (5) association with malignant neoplasms; (6) hypersensitivity reactions; and (7) increased susceptibility to malaria. The data that suggest that folic acid supplements are unsafe are weak and consist predominantly of case series and reports. Nevertheless, greater difficulty diagnosing cobalamin deficiency due to "masking" of hematologic abnormalities by folic acid is a potential risk. Strict vegetarians need to be informed that they are at risk of cobalamin deficiency. Physicians need to be aware that routine hematologic indexes have a low sensitivity for cobalamin deficiency, especially in patients who are receiving folic acid supplements. Because no high-quality data exclude specific adverse effects, physicians should be vigilant in identifying detrimental effects when patients increase their consumption of folic acid. Arch Intern Med. 1996;156:1638-1644"

 

[rodgergrummidge]

I tried both MethylF 2 mg/day, Folinic acid 6 mg/day and Acid F 1.2 mg/day, and got very bad reaction to each one, mainly brain related (strong headache with non functionning brain), together with burning thighs' muscles.

I had a look at what we can find about folates toxicity but there is very few studies about it, neurotoxicity is cited but not explained and there's no study about different folate supplements and their side effect, it's a bit frustrating :

TOXICITY OF FOLIC ACID GIVEN IN PHARMACOLOGICAL DOSES TO HEALTHY VOLUNTEERS (1970) on thelancet

"Abstract
A trial to elucidate the effect of folic acid in pharmacological doses (15 mg. daily) on serum-vitamin-B12 levels in a group of fourteen healthy volunteers was abandoned after 1 month of a projected 3-month period because of the unexpected development of increasingly disturbing toxic effects in the majority. Most of the subjects experienced mental changes, sleep disturbance and gastrointestinal symptoms. Possible mechanisms of these effects are discussed."

on cab direct, the same article is differently presented:


Toxicity of folic acid given in pharmacological doses to healthy volunteers.

Author(s) : HUNTER, R.; BARNES, J.; OAKELEY, H. F.; MATTHEWS, D

Journal article : Lancet 1970 Vol.1 pp.61-63

"Abstract : A total of 14 healthy volunteers were given 15 mg folic acid by mouth daily. The trial was abandoned after 1 month because of toxic effects of a gastrointestinal or nervous kind. It is suggested that folic acid may have a specific effect on cerebral metabolism. If values for folacin in cerebrospinal fluid are correlated with serum folacin, then very high values for folacin in cerebrospinal fluid were probably reached because mean serum folacin values rose from 4.5 to 120 ng per ml at the end of the trial.
The symptoms of folic acid intoxication observed may be related to brain-amine change, which would explain the "alerting" effect of folic acid when given to patients on anticonvulsant drugs.-M. J. B."


How Safe Are Folic Acid Supplements?
Article · Literature Review · August 1996 with 38 Reads
DOI: 10.1001/archinte.156.15.1638 · Source: PubMed

• Norman R. C. Campbell

"Abstract
Periconceptual use of folic acid supplements by women is effective in preventing neural tube defects in the fetus. Folic acid supplements also may prevent atherosclerosis and some malignant neoplasms. Nevertheless, safety concerns have delayed recommendations to increase folic acid consumption by the general population. Among the potential safety issues of folic acid supplementation are (1) difficulty identifying cobalamin deficiency, precipitation of neurologic complications of cobalamin deficiency, and lowering of cobalamin levels; (2) folate neurotoxicity; (3) antagonism of drugs that inhibit folate metabolism; (4) reduced zinc absorption; (5) association with malignant neoplasms; (6) hypersensitivity reactions; and (7) increased susceptibility to malaria. The data that suggest that folic acid supplements are unsafe are weak and consist predominantly of case series and reports. Nevertheless, greater difficulty diagnosing cobalamin deficiency due to "masking" of hematologic abnormalities by folic acid is a potential risk. Strict vegetarians need to be informed that they are at risk of cobalamin deficiency. Physicians need to be aware that routine hematologic indexes have a low sensitivity for cobalamin deficiency, especially in patients who are receiving folic acid supplements. Because no high-quality data exclude specific adverse effects, physicians should be vigilant in identifying detrimental effects when patients increase their consumption of folic acid. Arch Intern Med. 1996;156:1638-1644"

Thanks for the refs @pattismith I had a quick look. 2 of the papers are >40 years old (1970) and one is >20 years old (1996). Folate research has progressed significantly in the last 20 years. Much of the more recent evidence supports the folate-fortification of some foods in a number of countries. But I'm still curious about potential Folate toxicity. Were you able to find more recent research publications describing folate toxicity in humans?

Rodger

 

[pattismith]

Thanks for the refs @pattismith I had a quick look. 2 of the papers are >40 years old (1970) and one is >20 years old (1996). Folate research has progressed significantly in the last 20 years. Much of the more recent evidence supports the folate-fortification of some foods in a number of countries. But I'm still curious about potential Folate toxicity. Were you able to find more recent research publications describing folate toxicity in humans?

Rodger

Yes, this is exactly what I noticed in my previous post, only old studies (I quoted all the years in my original post), and not any recent study about folates toxicity and mecanisms...

As you saw, all the studies are about neuroprotective effects of Folic acid, with dosage up to 2 mg per day.

Given the fact that many members on PR report Folates side effects at this dosage (and sometimes under this dose), I can't understand why all these studies never report Folates side effects.

I was so tired and non functionning/comatose yesterday, I had to sleep 2.5 hours in the middle of the day. (I would have slept the whole day if I had the ability to do so)

 

[Learner1]

I tried both MethylF 2 mg/day, Folinic acid 6 mg/day and Acid F 1.2 mg/day, and got very bad reaction to each one

Any of the above is quite a lot to be taking as a start. What factors did you consider in giving these a try?

Folate is used in a large process called methylation, responsible for a myriad of tasks in your body.

It's used in the folate cycle, which feeds the methionine cycle to make glutathione which is used from getting toxins out of your body through the transsulfuration process to be excreted through feces, urine, etc.

Think about clearing a traffic jam on the highway... The cars in front have to get out of the way first, then the cars stuck behind them can start to move, and then the cars behind them. You can't just push really hard from the back of the jam, or bad things will happen.

Folate is a ways back in the jam. You need to work backwards, drinking water and eating fiber to keep output working. Transsulfuation uses B1 and molybdenum - do you have enough?

Then, do you have enough amino acids, used in making glutathione? Are you getting adequate protein and digesting it? Do you need to supplement NAC, glycine, or glutamine?

In the methionine cycle, you need adequate methylB12, along with B6, B2, magnesium and potassium. And maybe methionine.

Once these are in place, them you can add folate. For most people, 5-MTHF is the best choice.

Having good nutritional testing would be helpful in sorting out exactly what you need.

One caution - more folate is not better. Too much or too little can promote cancer, so figuring out what you need and getting the entire process working correctly is important for this and many other reasons.

This diagram is a bit complex, but it shows you a map of these processes and how nutrients interact with them. The bubbles in the diagram are your genes, which impact how these processes work, as can environmental factors...

https://goo.gl/images/cXVsRb

 

[pattismith]

@Learner1 , yes I take all the other supplements you are talking about
(The only one I didn't start yet is Methionine, it will be a next step)

 

[alicec]

I tried both MethylF 2 mg/day, Folinic acid 6 mg/day and Acid F 1.2 mg/day, and got very bad reaction to each one, mainly brain related (strong headache with non functionning brain), together with burning thighs' muscles.

I had a look at what we can find about folates toxicity but there is very few studies about it, neurotoxicity is cited but not explained and there's no study about different folate supplements and their side effect, it's a bit frustrating :

Perhaps the reason you found no recent studies of folate toxicity is that there is no evidence for it. Merck did extensive studies of this before introducing Deplin and essentially found methylfolate is non-toxic even at massive doses.

Many people report sensitivity to folate supplements but this is not a toxicity reaction; there are many possible causes but frequently people find if they start with a tiny dose and build up slowly they do eventually tolerate the supplements and gain benefit.

You started with a very high dose.

Folic acid is different from the other two you tried, and I am not surprised that in the study you linked, 15 mg folic acid daily caused problems.

Folic acid is not a natural folate form and while we can process it using the enzyme DHFR, everyone does this slowly (some 1,300 times more slowly) and some do it very slowly (about a 5-fold natural variation). This allows folic acid to accumulate, which acts as an inhibitor of DHFR. This means that its natural substrate, DHF, also accumulates and this in turn acts as an inhibitor of several enzymes in the folate cycle. Too much folic acid interferes with the whole of the folate cycle.

Even small doses of folic acid can be a problem for some people but 15 mg would be a serious problem for everyone.

 

[Learner1]

@Learner1 , yes I take all the other supplements you are talking about
(The only one I didn't start yet is Methionine, it will be a next step)

It's not whether you're taking them. The key is how much of what you're taking when and what your body is doing with them. It's trickier than it seems. I've been repeatedly surprised by what the labs say... Consulting with an expert doctor would help, too.