The implication seems to be that over ingestion of certain synthetic B properties isn't actually such a good thing. B1 isn't really the issue but certain others can be difficult if you have specific genes that impede processing of them.
I'm told that Dr Constantini only advises the B complex (as support for Thiamine) in cases whereby PWPs aren't getting relief from Thiamine alone. I was wondering if anybody could confirm this please?
Thanks for your time.
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jeeves19
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Wow! Interesting and concerning, my take on the article is folate is natural and folic acid is synthetic and used to fortify foods and supplements. The article seems to make a correlation between folic acid and an increase in cancer rates? Should we avoid folic acid all together ?
" there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid [1 mg/day], the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). "
From the full text:
"Folic acid is more bioavailable than natural sources ... There are plausible biological reasons why high levels of folate may promote carcinogenesis. Folates have a key role in the synthesis of nucleotides ( 1 , 2 ) that are needed for proliferating neoplastic cells, and there is an increase in the expression of folate receptors in several cancer types"
So the carcinogenic effect of folic acid may only be because it is better absorbed. I am going to take a break from my high dose folinic acid pending further clarification.
1 mg/day is a high dose and should only be taken when taking folate depleting drugs like methotrexate or if you have a MTHFR mutation. (If I got to choose which ever genetic mutation I wanted it would be this one because of the name....I have the MTHFR mutation!)
"Those affected by the MTHFR mutation are unable to process folic acid in a healthy manner, and as such, they are encouraged to incorporate supplements of active folate into their dietary habits."
Really, 5-methyltetrahydrofolic acid (Methyl folate) is the only type to take because it is immediately bio-available thus a lower dose can be used, say 400 mcg/day. People with MTHFR mutations take high doses of Methyl folate and this brand has a 10 mg/day dose:
High dose folic acid is problematic because of the following.
High folic acid intake in aged mice causes a lowered immune response
"Previous studies have shown an association between high folic acid intake and a reduction in the immune system defenses needed to fight viral infections and cancer."
Unsurprisingly, 'antifolate' drugs are effective in targeting pathogens.
"Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi."
On the Action of Methotrexate and 6-Mercaptopurine on M. avium Subspecies paratuberculosis
(M. avium subspecies paratuberculosis (MAP) is the putative cause of Crohn's disease.)
"Methotrexate acts by inhibiting dihydrofolate reductase, folate generation and the consequent production of adenine."
"We show that methotrexate and 6-MP inhibit MAP growth in vitro. Each of the four isolates manifests different % −ΔcGI. These data are compatible with the hypothesis that the clinical improvement in patients with IBD treated with methotrexate and 6-MP could be due to treating a MAP infection."
The second line TB antibiotic, PAS (a potential PD therapy):
Mycobacterium tuberculosis Folate Metabolism and the Mechanistic Basis for para-Aminosalicylic Acid Susceptibility and Resistance
"Herein, we discuss previous studies that demonstrate PAS-mediated disruption of iron acquisition, as well as recent genetic, biochemical, and metabolomic studies that have revealed that PAS is a prodrug that ultimately corrupts one-carbon metabolism through inhibition of the formation of reduced folate species."
I do not need blood transfusions but I cannot give blood either.
And finally, anemia is associated with PD so, and if anemic, these 2 supplements are a must:
"Anemia was more common in the history of cases than of controls (odds ratio 2.00, 95% confidence interval 1.31–3.06, p = 0.001). The association remained significant after adjustment for cigarette smoking, exposure to pesticides, or hysterectomy (in women). The association was not significantly different between men and women, or between PD patients with or without rest tremor. Analyses stratified by time of onset of anemia showed a greater association for anemia that started 20 to 29 years before the onset of PD. Hemoglobin levels were slightly but consistently lower in cases than in controls across all ages."
No I do not blame my father. My mother has anemia and my father had PD. My brother also has the trait of Type 2 anemia but no PD. I acquired a PD-like syndrome after being exposed to excessive chemicals (and was able to reverse it). No one to blame there.
My multivitamin has .8 mg of folic acid, plus each packet of Emergen-C has .1 mg of folic acid. I take several of those daily, so I have been over 1 mg/day. Plus I was taking 8 mg folinic acid daily. Plus my B- complex has 5-methyltetrahydrofolic acid (Methyl folate) which adds another 400 mcg/day. So I have been way overdosed by accident.
As I understand it, all the different forms count when it comes to overadosage. Is that not so?
Yes I think you are correct. Though without testing serum folate/foic acid/cobalamin levels in conjunction with homocysteine/meltylmalonic acid level(s), your true needs for folate may not be known. Since you take L-dopa your B vitamin (folate/cobalamin/pyridoxine) requirements are greater than an untreated individual. Your body may (or may not) be using all of the folic acid to convert homocysteine into methionine???
It occurred to me that there may be a B complex that does not include folic acid and I found one:
I've been also concerned about MTHFR which runs in my family. However, according to Dr. Ben Lynch "To convert folic acid into methylated folate requires a) multiple functional genes producing b) functional enzymes which requires c) adequate cofactors." So there are more genetic factors to consider.
One of the required "functional genes" is DHFR, which is supposedly to be the only enzyme that reduces folic acid to dihydrofolate which has physiological benefits. "Only 200 mcg of folic acid can move through a human enzyme called DHFR. This is in humans who have a functional DHFR gene. There are known DHFR variants which lead to a further significant reduction in function." Unmetabolized folic acid can bind to folate receptors, block them from metabolizing folate and lead to a functional folate deficiency.
So, we need to avoid folic acid supplements and processed foods fortified with folic acid. Reading products' ingredients is a good hobby to have these days.
For my money folic acid (FA), along with cyanocobalamin (C) and pyridoxine hydrochloride (PH) are the junk food of vitamins. Sure if you are deficient of B9/folate, cobalamin/B12 or pyridoxine/B6, then FA, C and PH will help the average (non-MTHFR) person. But given a choice one should choose Methyl folate, methylcobalamin and pyridoxyl 5 phosphate. over the above vitamins. Thiamine, niacin, biotin and riboflavin are fine in their standard forms and are good therapy.
Your first line is a statement you post as is if you are a doctor.
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People Richard Melvin is an art grad from a no name school. Stop treating him like a source of knowledge.
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Rich I don't doubt your intentions are the best, but I wish you could do a little introspection and realize you are not smart enough to be making statements like: "1 mg/day is a high dose and should only be taken when taking folate depleting drugs . . ."
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You are neither a doctor nor a scientist nor even smart. Please stop doling out advice to people that would eat dirt if they thought it would cure their disease.
Here in the US you can test for MTHFR by a blood test (on doctors prescription) in any diagnostic lab or by sending a saliva sample to 23&me for genetic testing which currently costs $199.
Since MTHFR variants have tendency to raise blood homocysteine (Hcy) which in the mainstream medicine is considered to be increasing risk for cardiovascular disease (in reality elevated Hcy is a risk factor for many degenerative diseases including PD) you can ask your physician to test for Hcy which can be indirect indicator of MTHFR variants. The normal range of Hcy is quite wide and varies from lab to lab, the optimal value would be around 7-9 mcmol/L even though some labs consider normal range to be up to 15.
I understand that US has mandatory fortification of flour with folic acid. It's important that we do not go down this path in the UK - we have been on the verge of it for some time. I avoid North American bread flour as I assume it has folic acid in it. If you live there, you are presumably getting folic acid every time you eat bread, cakes, biscuits etc
I have one copy of the mthfr gene and was unaware of it for a long time. My first pregnancy I lost the baby at 30 weeks gestation. For the next 6 pregnancies I was treated with heparin (blood thinner injections) , folic acid (methylated I think, it was a prescription), and baby aspirin daily . All thankfully went full term. For my final pregnancy (9 yrs ago)the dr tested me for mthfr, apparently it was a test that wasn’t available previously. Since I tested positive to only one copy of the gene instead of 2, for my last pregnancy I only took the prescription methyl folate and baby aspirin , no injections of blood thinners (heparin) . At the time the dr. said it was something I only needed to worry about when pregnant. I’ve asked every dr since and not one has been able to advise me. Ive heard that 50 percent of the population are carriers of one or both genes. I don’t think most drs are well versed in this area and my question is should I be on a prescription for methyl folate, should I have my homocysteine levels checked?? Thanks for any info
While pregnant my mother was visiting Cuba, in long ago revolutionary days. The woman at the boarding house fed her a diet of sauteed liver, everyday, a natural source of folate. Based on this discussion I will consider if my near weekly pot of spinach and lentil soup is enough folate, and cut out the folic acid supplement. Thank you.
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looking for the best B-complex to take along with additional B1 Hcl
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