High dose folic acid with OH B12 (Dr. V protocol)

[JanisB]

Since the thread on Dr. Vinitisky's protocol has gotten derailed, I am starting this thread to explore

1] PWC responses to taking Folic acid (Folirinse) together with OH B-12 (Perque) in a 5:2 ratio, or other products

AND

2] issues relating to this therapy, such as why it works to balance the ANS and what the risks are,

The responses of 3 of us who have tried it so far.

• almost immediate calming of agitation/palpitations/anxiety
  JanisB: after several days on anywhere from 6 - 10 daily doses, I started to feel jittery and had difficulty sleeping. I cut back, slept, and now take it when symptomatic
  Patient A: after several weeks on the protocol, blood pressure is normalizing and high pulse is coming down
  Patient B: tried for first time during a crash and found it rapidly calmed down system

 

[JanisB]

Concerns with 5:2 Folirinse:B12 Calling all pharmacists and biochemists to take a look and help us resolve this! :worried:

While the doctor who devised and patented this protocol at http://www.freepatentsonline.com/y2008/0045448.html has written that all of his patients with chronic diseases have high serum folic acid, a spate of recent research articles have been looking at the relationship between high serum folic acid and cancer, questioning whether folic acid fortification is beneficial or puts individuals at a greater risk of cancer. Abstract of these articles follow

Note, I am using the term 'folic acid' specifically to refer to pteromonoglutamic acid or PGA, the form called folic acid in supplements and not to folates found in foods.

One issue is whether the association between high serum folic acid and cancer is causal, or whether it might be a consequence of impaired methylation leading to the increased risk for cancer.

Have any of you been tested for serum folic acid and found to be high?
I know my levels were quite high the first time I ran the Vit Diag methylation panel, and after a year of avoiding folic acid but taking the active folates, they were still high.

Abstracts:
[1] Br J Nutr. 2005 Nov;94(5):727-30.
Evidence of unmetabolised folic acid in cord blood of newborn and serum of 4-day-old infants.
Sweeney MR, McPartlin J, Weir DG, Daly S, Pentieva K, Daly L, Scott JM.
Department of Clinical Medicine, University of Dublin, Trinity College, Dublin, Ireland. maryrose.sweeney@ucd.ie

Oral folic acid above certain threshold doses results in unmetabolised folic acid in serum. This raises a number of public health safety issues, principally the potential to mask pernicious anaemia; more recently the theoretical potential for high-dose folic acid to promote cancer has been highlighted. In this paper we set out to examine the appearance of unmetabolised folic acid both in cord blood from newborn full-term and premature infants and serum from 4-d-old infants post-formula feeding. Blood was collected from the umbilical cord of eleven infants in the delivery room immediately after birth. A follow-up serum sample (n 9) was collected 4 d later from infants post-formula feeding. We detected unmetabolised folic acid in cord blood from all infants at birth. In addition, unmetabolised folic acid was present in serum of seven infants post-formula feeding, six of which had increased from birth. Our results imply that infants in Ireland, which does not yet have mandatory fortification, could potentially have circulatory unmetabolised folic acid at the time of birth. We do not know if the presence of folic acid in cord blood will have any adverse consequences. However, if theoretical safety concerns are borne out by future research, the likelihood is that the longer the exposure the more likely the potential for harm. This would also be the case in infants exposed to unmetabolised folic acid as a result of formula feeding.
PMID: 16277775

[2] Nutr Rev. 2006 Oct;64(10 Pt 1):468-75.
Does a high folate intake increase the risk of breast cancer?
Kim YI.

Department of Medicine and Nutritional Sciences, University of Toronto, Division of Gastroenterology, St. Michael's Hospital, Toronto, Canada. youngin.kim@utoronto.ca
Abstract
Although not uniformly consistent, epidemiologic studies generally suggest an inverse association between dietary intake and blood measurements of folate and breast cancer risk. However, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial has recently reported for the first time a potential harmful effect of high folate intake on breast cancer risk. In this study, the risk of developing breast cancer was significantly increased by 20% in women reporting supplemental folic acid intake > or = 400 microg/d compared with those reporting no supplemental intake. Furthermore, although food folate intake was not significantly related to breast cancer risk, total folate intake, mainly from folic acid supplementation, significantly increased breast cancer risk by 32%. The data from the PLCO trial support prior observations made in epidemiologic, clinical, and animal studies suggesting that folate possesses dual modulatory effects on the development and progression of cancer depending on the timing and dose of folate intervention. Based on the lack of compelling supportive evidence, routine folic acid supplementation should not be recommended as a chemopreventive measure against breast cancer at present.
PMID: 17063929

[3] Mol Nutr Food Res. 2007 Mar;51(3):267-92.
Folate and colorectal cancer: an evidence-based critical review.
Kim YI.

Department of Medicine and Nutritional Sciences, Medical Sciences Building, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada. youngin.kim@utoronto.ca
Abstract
Currently available evidence from epidemiologic, animal, and intervention studies does not unequivocally support the role of folate, a water-soluble B vitamin and important cofactor in one-carbon transfer, in the development and progression of colorectal cancer (CRC). However, when the portfolio of evidence from these studies is analyzed critically, the overall conclusion supports the inverse association between folate status and CRC risk. It is becoming increasingly evident that folate possesses dual modulatory effects on colorectal carcinogenesis depending on the timing and dose of folate intervention. Folate deficiency has an inhibitory effect whereas folate supplementation has a promoting effect on the progression of established colorectal neoplasms. In contrast, folate deficiency in normal colorectal mucosa appears to predispose it to neoplastic transformation, and modest levels of folic acid supplementation suppress, whereas supraphysiologic supplemental doses enhance, the development of cancer in normal colorectal mucosa. Several potential mechanisms relating to the disruption of one-carbon transfer reactions exist to support the dual modulatory role of folate in colorectal carcinogenesis. Based on the lack of compelling supportive evidence and on the potential tumor-promoting effect, routine folic acid supplementation should not be recommended as a chemopreventive measure against CRC at present.
PMID: 17295418

[4] BMC Public Health. 2009 Aug 18;9:295.
Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification?
Sweeney MR, Staines A, Daly L, Traynor A, Daly S, Bailey SW, Alverson PB, Ayling JE, Scott JM.
UCD School of Public Health and Population Science, University College Dublin, and Coombe Women's and Infant's Hospital, Dublin, Ireland. maryrose.sweeney@dcu.ie
Abstract
BACKGROUND: Ireland is an example of a country that has extensive voluntary fortification with folic acid. After a public consultation process, in 2006, the Food Safety Authority in Ireland FSAI 1 recommended mandatory fortification. However due to safety considerations this decision is now on hold. Before mandatory fortification goes ahead, existing levels of unmetabolised folic acid and their anticipated increase after fortification needs investigation because of the potential of folic acid to mask pernicious anaemia and possibly accelerate the growth of existing cancers. The aim of this study was to examine the levels of circulatory unmetabolised folic acid in Irish adults (both fasted and un-fasted) and new-born infants (fasted) before the proposed implementation of mandatory folic acid fortification. A secondary aim was to predict the increase in circulatory unmetabolised folic acid levels after fortification. METHODS: Study 1. Setting: Irish Blood Transfusion Service (IBTS). Whole blood samples were collected from blood donors (n=50) attending for routine blood donation sessions (representing the general population). Subjects were not fasted prior to sampling. Study 2. Setting: Coombe Women's and Infant's University Hospital, Dublin. Whole blood samples were collected by venipuncture from mothers (n=20), and from their infant's umbilical-cords (n=20) immediately after caesarean section. All women had been fasted for at least 8 hours prior to the surgery. A questionnaire on habitual and recent dietary intakes of folic acid was administered by an interviewer to all subjects. The data collection period was February to April 2006. Serum samples were analysed for plasma folate, plasma folic acid and red cell folate. RESULTS: Blood Donor Group: Circulatory unmetabolised folic acid was present in 18 out of 20 mothers (fasted) (CI: 68.3%-99.8%) comprising 1.31% of total plasma folate, 17 out of 20 babies (fasted) (CI: 62.1%-96.8%), and 49 out of 50 blood donors (unfasted) (CI: 88.0%-99.9%), comprising 2.25% of total plasma folate, CONCLUSION: While the levels of circulatory unmetabolised folic acid reported are low, it is persistently present in women immediately after caesarean section who were fasting indicating that there would be a constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth. Mandatory fortification might exacerbate this. This has implications for those with responsibility for drafting legislating in this area.
PMID: 19689788

Comment: This is a not a complete list of articles. It's quite long and I have neither the patience, brain power, training, or time to read them all! But it would seem to me, that a high folate diet, consisting largely of greens, would be typical of all hunter-and-gatherer diets. Given what Weston Price and other researchers have found, these diets were healthy for humans. So the issue then boils down to the chemical vitamin PGA = folic acid.

My questions are: How is folic acid/PGA eliminated from the body?
When levels are high, is there evidence that it inhibits methylation?

All contributing questions and opinions welcome.:Retro smile:

 

[Dreambirdie]

Hi Janis--

I'm hoping Rich chimes in with his thoughts about this. I have no idea.

I am in the throes of a nasty allergic response to oaks (spring sucks!) and have been so wired from this, that I've barely slept for the past three nights. When I hear that the folic acid can calm agitation in the nervous system, I am SO tempted to try... yet fear that it will cause a detox of heavy metals, which I can't handle at all right now.

A few questions for you:

Have you tried Rich's/Yasko's Simplified Protocol as well?
If so, how did that compare to Vinitsky's?
and... Are folic acid and perque the only supp's on the Vinitsky protocol?

thanks, DB

 

[JanisB]

When I hear that the folic acid can calm agitation in the nervous system, I am SO tempted to try... yet fear that it will cause a detox of heavy metals, which I can't handle at all right now.

Understandable. I don't know how if this will work the same way. If you want to try 1 or 2 doses, I could send them to you (if I ever find my Perque B12 which seems to have disappeared this morning).

Have you tried Rich's/Yasko's Simplified Protocol as well?

Yes, tried it for a year and am still on the supps, but I also added in some other things per Yasko's advice on tests. Got improvement on VD methylation panel, but very little substantive improvement in symptom reduction and no improvement on UAA or MAP tests. I did find it mildly calming; however, I was not having palpitations when I started.

If so, how did that compare to Vinitsky's?
and... Are folic acid and perque the only supp's on the Vinitsky protocol?

NO, he includes Vit C, Mg, taurine, B6, and glutathione for people who are low. Yasko discourages taurine and B6 for CBS+, but since I've been low on tests, I may start both.
How the two compare? V emphasizes ANS balance. He has you self-test by recording blood pressure and pulse 3x a day and looks for changes in a positive direction. He also does in-office testing with HRV (ANSAR). That's all I know. I'm going to see him June 30, but decided to explore the 5:2 Folirinse B12 beforehand because I got very symptomatic.

 

[JanisB]

Abstract on high folic acid supplementation: Does this alleviate our concerns? The amount was only 1.2 mg daily (v. >30 mg on V's protocol) and the duration was only 12 weeks. Still, looks as if it had lots of benefits and no ill effects. Bolding mine.
J Proteome Res. 2010 Apr 5;9(4):1941-50.

Blood folate status and expression of proteins involved in immune function,
inflammation, and coagulation: biochemical and proteomic changes in the plasma of
humans in response to long-term synthetic folic acid supplementation.

Duthie SJ, Horgan G, de Roos B, Rucklidge G, Reid M, Duncan G, Pirie L, Basten GP, Powers HJ.
Aberdeen University Rowett Institute of Nutrition and Health, Aberdeen, U.K.
sd@rri.sari.ac.uk

We used plasma proteomics to identify human proteins responsive to folate status. Plasma was collected from subjects treated with placebo or 1.2 mg of folic acid daily for 12 weeks in a randomized controlled trial. Homocysteine and folate were measured by immunoassay and uracil misincorporation by electrophoresis. The plasma proteome was assessed by 2-D gel electrophoresis, and proteins were identified by LC MS/MS. 5-methylTHF increased 5-fold (P = 0.000003) in response to intervention. Red cell folate doubled (P = 0.013), and lymphocyte folate increased 44% (P = 0.0001). Hcy and uracil dropped 22% (P = 0.0005) and 25% (P = 0.05), respectively. ApoE A-1, alpha-1-antichymotrypsin, antithrombin, and serum amyloid P were downregulated, while albumin, IgM C, and complement C3 wereupregulated (P < 0.05). More than 60 proteins were significantly associated with folate pre- and postintervention (P < 0.01). These were categorized into metabolic pathways related to complement fixation (e.g., C1, C3, C4, Factor H, Factor 1, Factor B, clusterin), coagulation (e.g., antithrombin, alpha-1-antitrypsin, kininogen) and mineral transport (e.g., transthyretin, haptoglobin, ceruloplasmin). Low folate status pre- and post-treatment were associated with lower levels of proteins involved in activation and regulation of immune function and coagulation. Supplementation with synthetic folic acid increased expression of these proteins but did not substantially disrupt the balance of these pathways.

PMID: 20143872

 

[JanisB]

first article that explains why V's protocol might work so quickly!! (Sorry folks for all the posts)

Gynecol Endocrinol. 2010 Mar 16. [Epub ahead of print]

Folic acid supplementation may cure hot flushes in postmenopausal women: a prospective cohort study.

Gaweesh SS, Abdel-Gawad MM, Nagaty AM, Ewies AA.

Department of Obstetrics and Gynaecology, Shatby Maternity University Hospital, University of Alexandria, Egypt.

Background. Neurotransmitter norepinephrine seems to be involved in the pathophysiology of hot flushes in postmenopausal women, and folic acid was found to interact with its receptors. Objectives. To examine the effect of folic acid supplementation on the occurrence of hot flushes and the plasma level of 3-methoxy 4-hydroxy phenyl glycol (MHPG, the main metabolite of brain norepinephrine). Method. Forty-six postmenopausal women were allocated (by alternation) into 2 groups (n = 23 each); Group 1 received folic acid 5mg tablets daily for 4 weeks and group 2 received placebo tablets. Four women in group 2 discontinued the study. Results. The number of women who reported improvement in hot flushes was significantly higher in the treatment group. On comparing the mean plasma levels of MHPG before and after treatment, a significant lowering was found in the treatment group (mean % change =-24.1 +/- 17.9, p < 0.001) when compared with the placebo-control group (mean % change =-5.59 +/- 16.4, p =0.10). In the treatment group, there was a significant negative correlation between improvement in hot flushes and the plasma level of MHPG (r =-0.453, p =0.03). Conclusion. Folic acid supplementation may cause subjective improvement of hot flushes by lowering the increased central noradrenergic activity.

PMID: 20230331

This study supports Dr. V's experience of using folic acid/B12 combined to lower SNS activity and raise PNS activity.

 

[dannybex]

The responses of 3 of us who have tried it so far.

• almost immediate calming of agitation/palpitations/anxiety
  JanisB: after several days on anywhere from 6 - 10 daily doses, I started to feel jittery and had difficulty sleeping. I cut back, slept, and now take it when symptomatic
  Patient A: after several weeks on the protocol, blood pressure is normalizing and high pulse is coming down
  Patient B: tried for first time during a crash and found it rapidly calmed down system

Damn, I would LOVE to have an almost immediate calming of agitation & anxiety. And come to think of it, have had a few palps in the last few days...

I guess my question is...how long has Vinitsky been using this combo, and has he seen an increase in cancers in his practice?

I would love to hear from Rich too...but wonder what Dr. V himself would say about these concerns.

Thanks Janis!

 

[dannybex]

Janis -- did you see this thread that Rich started a couple weeks back?:

http://www.forums.aboutmecfs.org/showthread.php?1201-Folic-acid-B12-and-cancer-risk

 

[soulfeast]

Here's what I found about the formaldehydes:
http://www.defeatautismyesterday.com...itskypaper.htm


The PSNS is regulated by another neurotransmitter Acetylcholine (ACh). The neurotransmitter is recycled for continuous functioning of the nerve. In this hypothesis, compensatory increase of PSNS is necessary to down regulate SNS activity. However, incomplete recycling of ACh may lead to its increased metabolism. Choline which has 3 methyl groups on a glycine skeleton, is the first byproduct. One methyl group then becomes formaldehyde.







Formaldehyde is a simple one carbon molecule, oxidized from methane via methanol. Formaldehyde can then be oxidized to formic acid. Inherently toxic, it is remarkable that the body actually generates formaldehyde. The concept, however, is no different from the body’s production of carbon monoxide.







Formaldehyde is known to cause increased sympathetic activity. If left uncorrected, this sequence can result in the vicious downward spiral of increased sympathetic activity.







MUSCLE FUNCTION







In the simplest expression of muscle contraction, the motor unit is regulated by a nerve that depends on Acetylcholine to fire. While this nerve function is not a part of the ANS, it nevertheless is potentially subject to the same metabolic dysregulation. Thus, excess formaldehyde production in muscles could increase sympathetic activity, reduce blood flow, reduce proper utilization of glucose for muscle energy and cause increased lactic acid production. The result would be increased insulin production, increased fat deposition, lower blood sugar, and so on. This would form the basis for the insulin resistance or metabolic syndrome precursor to diabetes.







FOLIC ACID







A large complex vitamin, folic acid has an almost obligatory infinity for formaldehyde. Perhaps it is this vitamin that is the ultimate protector of the human body. However, it is also known that too much folic acid is not good. By trapping all the formaldehyde (or methyl groups), proper building, repairing and healing cannot occur.

 

[soulfeast]

I have high serum and low RBC.

http://en.wikipedia.org/wiki/Folic_acid

Unmetabolized folic acid is associated with a reduction in natural killer cell cytotoxicity which reduces the immune system's ability to defend against malignant cells.[78] However, the study also showed that dietary baseline intake of folate may have inverse effects of prostate cancer.

Folic acid supplements stimulate the PI3k/Akt signaling cascade which leads to improved cell survival but this could be beneficial or harmful for the body because cancer cells may use this pathway to survive.[82] Folic acid may also reduce the levels of PTEN (a tumor suppressor gene), making this relationship even more controversial.[82]

 

[soulfeast]

Interesting role for FA that might effect OI???

http://www.sciencedaily.com/releases/2008/03/080327092140.htm

Science News Share Blog Cite Print Email BookmarkBrief, High Doses Of Folate -- B Vitamin -- Blunt Damage From Heart Attack
ScienceDaily (Mar. 28, 2008) — Long known for its role in preventing anemia in expectant mothers and spinal birth defects in newborns, the B vitamin folate, found in leafy green vegetables, beans and nuts has now been shown to blunt the damaging effects of heart attack when given in short-term, high doses to test animals.


In a new study, an international team of heart experts at Johns Hopkins and elsewhere report that rats fed 10 milligrams daily of folate, also known as folic acid or vitamin B9, for a week prior to heart attack had smaller infarcts than rats who took no supplements. On average, researchers say, the amount of muscle tissue exposed to damage and scarred by the arterial blockage was shrunk to less than a tenth.

The team's findings, set for publication in the April 8 edition of the journal Circulation, come just weeks after other international studies in humans suggested that low-dose folic acid supplements may prevent dementia in the elderly and premature births.

"We want to emphasize that it is premature for people to begin taking high doses of folic acid," says senior study investigator David Kass, M.D., a professor at The Johns Hopkins University School of Medicine and its Heart Institute.

"But if human studies prove equally effective, then high-dose folate could be given to high-risk groups to guard against possible heart attack or to people while they are having one," says Kass.

The more likely and most practical advantage to ingesting supplements, he says, lies in folic acid's potential to act as a short-term buffer for people who may be having a heart attack and who rush to their local emergency room complaining of chest pain.

Clinical trials are expected in the near future, although Kass says a major challenge in testing is that a high dose of folic acid for humans comparable to that given the rats would require an average-size adult to swallow more than 200 one-milligram pills per day, "an impractical and unrealistic regimen, even if the body excretes the excess."

In addition, he cautions, "we do not yet know if folate is safe to consume in this high a dose, or how much or how little of it is needed to be effective," citing 25 milligrams per day as the highest dose previously tested safe to consume in adults as.

Kass says that such large amount of folate may also yield unpredictable side effects. Some studies have linked the nutrient supplement to increased rates of colon and prostate cancer.

Each year, an estimated 565,000 first-time heart attacks occur in the United States, with an additional 300,000 recurrent heart attacks.

Results from the new study, conducted in rats - dozens were fed supplements and dozens more did not receive any - showed that overall pumping function during heart attack remained strong in vitamin B9-fortified animals.


In a new study, an international team of heart experts at Johns Hopkins and elsewhere report that rats fed 10 milligrams daily of folate, also known as folic acid or vitamin B9, for a week prior to heart attack had smaller infarcts than rats who took no supplements. On average, researchers say, the amount of muscle tissue exposed to damage and scarred by the arterial blockage was shrunk to less than a tenth.....

The amount of blood pumped by the treated hearts during a 30-minute window when blood flow to the heart was restricted to simulate a heart attack stayed near normal for rodents, at an average ejection fraction of 73 percent. Meanwhile, it fell in the untreated group to 27 percent.

Similarly, the muscle wall at the front of the heart kept contracting during heartbeats, thickening by 37 percent in the supplement-fed group, but the muscle could barely compress, thickening by 5 percent, in the untreated group. (Sixty percent would be the normal amount of thickening in a healthy rat heart.)

Moreover, researchers found that an injection of folic acid into the bloodstream of rats that had never before taken supplements, within the first 10 minutes of a heart attack, was almost equally as effective as preventive therapy in reversing muscle damage, and in lowering infarct size by a factor of 10.

"Folic acid is already well known to be safe to consume in high doses in the short term, and it is very inexpensive, costing pennies per milligram, so its prospects look promising," says Kass.

Researchers plan further tests to determine precisely why folate protects the heart, and to determine how effective it is in not-as-high doses. But they point out that it has long been known for its role in the normal workings of the cell's principal energy source, the mitochondria, whose function is essential to maintaining healthy blood vessels.

It was this evidence that led to the latest study, which, says lead investigator An Moens, M.D., suggests that folate acts as an energy reserve in the heart, "providing much needed energy for muscle contraction, in the form of ATP, at the same time the heart is being starved for oxygen-carrying blood by a blocked artery."

According to Moens, a postdoctoral cardiology research fellow at Johns Hopkins, study results showed that high-energy phosphate levels went down 43 percent in the blood of treated rats, but levels dropped by one-third more (by 66 percent) in untreated rats.

"With more fuel, the heart kept pumping even though its blood flow was reduced," says Moens, now a cardiologist at the University of Antwerp in Belgium. "The smaller heart attacks seemed related to this better energy balance in the heart produced by the folate."

 

[JanisB]

Damn, I would LOVE to have an almost immediate calming of agitation & anxiety. And come to think of it, have had a few palps in the last few days...

I guess my question is...how long has Vinitsky been using this combo, and has he seen an increase in cancers in his practice?

I haven't talked to him. Wait until July. Another patient has told me privately that he says no. Some new research, I will post soon, showed less cancer with folic acid. So the jury is not out yet on this relationship.

 

[JanisB]

Janis -- did you see this thread that Rich started a couple weeks back?:

http://www.forums.aboutmecfs.org/showthread.php?1201-Folic-acid-B12-and-cancer-risk

I just reread that link. I have been worried about folic acid (PGA) v. natural folates. But I have a different opinion from Rich about the dosing. Here's what they gave in the study:

INTERVENTIONS: Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721).

Those are very low doses. Since there is no folic acid supplementation and, since people in Norway do not have lots of leafy greens in their diet (sources of folates), there is a very good possibility that most of them were deficient when the study started. If there is not enough B12 available, folates back up and cannot be used. (This is called the folate trap). The study should have looked at RBC folate as well to see if the supplementation was raising what was actually needed to support methylation.

Per V's theory of the priorities of methylation, the first priority is to make adrenaline. It stands to reason then, that if people start out deficient (which is pretty much the case with everyone with heart disease), then taking a small amount will merely increase their adrenaline levels, adding more stress and imbalancing them further. The stress to cancer connection is well established.

 

[soulfeast]

Why RBC levels are low? I think? Also explains why nerve repair is low on the list of methylation priority.. well, not sure what this is saying.

Methyl FA need to react with homocysteine (mine is low) to be retained by the cell. Methionine deficiency (which i have as well) as well as B12 deficiency will cause this reaction. Cell misinterprets low b12 as low methionine?

Oh.. so these folks are saying that FA without proper levels of b12 (and methionine?) is not good.. sorry my brain is shot tonight.

Oh I think FA deficiency causes low methionine which in turn cases FA to be shuttled away in the methylation cycle. I give up. Sorry if irrelevant.

http://www.ncbi.nlm.nih.gov/pubmed/6115113

The methyl folate trap. A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia.
Scott JM, Weir DG.

Abstract
"It is suggested that in man the methyl folate trap is a normal physiological response to impending methyl group deficiency resulting from a very low supply of methionine. This decreases cellular S-adenosyl-methionine (SAM), which puts at risk important methylation reactions, including those required to maintain myelin. In order to protect these methylation reactions, the cell has evolved two mechanisms to maintain supplies of methionine and SAM as a first priority. (a) Decreased SAM causes the folate co-factors to be directed through the cycle involving 5-methyl-tetrahydrofolate (5-methyl-THF) and methionine synthetase and away from the cycles that produce purines and pyrimidines for DNA synthesis. This enhances the remethylation of homocysteine to methionine and SAM. In addition, by restricting DNA biosynthesis and with it cell, division, competition for methionine for protein synthesis is reduced. Thus, whatever methionine is available is conserved for the vital methylation reactions in the nerves, brain, and elsewhere. (b) 5-methyl-THF, the form in which almost all folate is transported in human plasma, must react with intracellular homocysteine before it can be retained by the cell as a polyglutamate. Since homocysteine is derived entirely from methionine, methionine deficiency will cause intracellular folate deficiency, and the rate of mitosis of rapidly dividing cells will be reduced. although these two processes have evolved as a response to methionine deficiency, they also occur in B12 deficiency, which the cell mistakenly interprets as lack of methionine. the resulting response is inappropriate and gives rise to a potentially lethal anaemia. In these circumstances the methylation reactions are also partly protected by the reduced rate of cell division. This explains why administration of folic acid, which induces cell division and use of methionine in protein synthesis, impairs methylation of myelin and precipitates or exacerbates subacute combined degeneration (SCD). During folate deficiency methionine biosynthesis is also diminished. As in methionine deficiency, the body responds to decreasing availability of SAM by diverting folate away from DNA biosynthesis towards the remethylation of homocysteine to methionine and SAM. The selective use pf available folate to conserve methionine, together with the ability of nerve tissue to concentrate folate form the plasma, explains the absence of SCD in folate deficiency."

I am very confused about polygluatmates in cells. As long as they are attached to the FA its OK?

 

[soulfeast]

I dont understand how unmetabolized FA can cause cancer. Does unmetabolized FA do anything to support cell division?

 

[JanisB]

Why RBC levels are low?

In the book published by Metametrix Labs by Lord and Bralley (Functional Medicine), the section on folic acid says that RBC folic acid goes down
after 123 days of folate inadequacy. Dr. Yasko says that rebuilding RBC folate involves improving membrane health.

on a webpage by Dr. Herbert (Mt. Sinai), at http://www.victorherbert.com/Conn'sCurrentTherapy2003.htm he wrote:

, Caveat: serum folate levels can be normal in the presence of low red cell folate stores immediately after a high dietary folate intake; this is why red blood cell folate is more sensitive for assessment of chronic folic acid deficiency. Serum folate represents folate intake in the last 24 hours; red cell folate reflects folate intake over the last 4 months (the red cell life span).

This was actually an interesting article as I've had borderline high MCV for most of my adult life, but in 2005-2006 when I was talking high doses of Folixor (5 mg folinic acid), I had several CBC's with complete normal MCV levels.

If I don't get improved MCV or RBC folate within 4 months of doing the Folirinse:OHB12 dosing, I'll have to assume I have a problem converting PGA to the active forms, Folinic and 5-MTHF.

 

[JanisB]

Another warning about high folic acid intake by Dr. Victor Herbert

Folate absorption occurs primarily in the upper half of the small intestine. Megaloblastic anemia from folic acid deficiency responds readily to daily oral folate doses as low as 100 to 200 μg of PGA (pteroylglutamic acid). In general, however, 400 μg to 1000μg (1mg) is administered and is usually sufficient to correct deficiency, even in malabsorption states. My general approach is to give 1 mg daily for the first week, except in situations of severe malabsorption, when I administer 2 to 5 mg daily for the first week. I ensure that cobalamin deficiency is not coexistent and may initially co-administer 100 μg of cobalamin. After the first week, I treat with 100 μg orally daily. Full replenishment of folate stores can be achieved within several weeks of oral therapy. Maintenance should be with 400μg folic acid orally daily. If the underlying cause can be reversed, maintenance therapy can be stopped.
Adverse effects can occur from folate treatment with 1 or more mg of PGA daily. This is because at such doses substantial amounts of PGA, which is an oxidized, shelf-stable and thus preferred pharmaceutical form of folic acid, are absorbed by diffusion without being first reduced as is desirable by alimentary tract enzymes to human-cell-usable tetrahydrofolic acid. This absorbed unreduced PGA then blocks cell uptake of tetrahydrofolate, and can actually produce folate deficiency, as Prof. John Scotts group at Trinity Medical College in Dublin, Ireland showed in a large and excellent study of fertile Irish females. Also, giving folic acid to cobalamin-deficient patients will conceal the hematologic abnormalities of the B12 deficiency while allowing subacute combined degeneration of the spinal cord to proceed untreated to irreversibility. One must therefore always look for coexistent vitamin B12 deficiency in all patients for whom folate therapy is proposed.

:worried: This is what concerns me about Dr. V's protocol: I get benefits in terms of calming, but I don't want to get even more folate deficient!

 

[soulfeast]

(b) 5-methyl-THF, the form in which almost all folate is transported in human plasma, must react with intracellular homocysteine before it can be retained by the cell as a polyglutamate. Since homocysteine is derived entirely from methionine, methionine deficiency will cause intracellular folate deficiency, and the rate of mitosis of rapidly dividing cells will be reduced. although these two processes have evolved as a response to methionine deficiency, they also occur in B12 deficiency, which the cell mistakenly interprets as lack of methionine.

I am reading this to say that low methionine which may actually be at least partially caused by low FA to begin with will result in low homocysteine which 5 methyl needs to be retained by the cell. So low RBC FA could be caused by low FA which causes or helps cause lw methionine which causes low homocysteine which FA needs to stay in the cell.

If this is the case, and I am reading this right, then wouldnt it be helpful to also supplement with methionine?

I am also wondering about folks who are MTR ++ (like me). I think this means I guzzle up B12 too fast. Would I need a higher ratio of B12 to FA than the 5:2 calls for? ??

 

[soulfeast]

Another warning about high folic acid intake by Dr. Victor Herbert

Folate absorption occurs primarily in the upper half of the small intestine. Megaloblastic anemia from folic acid deficiency responds readily to daily oral folate doses as low as 100 to 200 μg of PGA (pteroylglutamic acid). In general, however, 400 μg to 1000μg (1mg) is administered and is usually sufficient to correct deficiency, even in malabsorption states. My general approach is to give 1 mg daily for the first week, except in situations of severe malabsorption, when I administer 2 to 5 mg daily for the first week. I ensure that cobalamin deficiency is not coexistent and may initially co-administer 100 μg of cobalamin. After the first week, I treat with 100 μg orally daily. Full replenishment of folate stores can be achieved within several weeks of oral therapy. Maintenance should be with 400μg folic acid orally daily. If the underlying cause can be reversed, maintenance therapy can be stopped.
Adverse effects can occur from folate treatment with 1 or more mg of PGA daily. This is because at such doses substantial amounts of PGA, which is an oxidized, shelf-stable and thus preferred pharmaceutical form of folic acid, are absorbed by diffusion without being first reduced as is desirable by alimentary tract enzymes to human-cell-usable tetrahydrofolic acid. This absorbed unreduced PGA then blocks cell uptake of tetrahydrofolate, and can actually produce folate deficiency, as Prof. John Scotts group at Trinity Medical College in Dublin, Ireland showed in a large and excellent study of fertile Irish females. Also, giving folic acid to cobalamin-deficient patients will conceal the hematologic abnormalities of the B12 deficiency while allowing subacute combined degeneration of the spinal cord to proceed untreated to irreversibility. One must therefore always look for coexistent vitamin B12 deficiency in all patients for whom folate therapy is proposed.

:worried: This is what concerns me about Dr. V's protocol: I get benefits in terms of calming, but I don't want to get even more folate deficient!

so dihydrofolate is still unreduced? would then 5:2 be too heavy on the FA as well, not even considering the PGA blocking the reduced form out of cells.. if thats what this is saying..

 

[dmholmes]

Interesting role for FA that might effect OI???

http://www.sciencedaily.com/releases/2008/03/080327092140.htm

I was taking 2,400 mcg of methylfolate for several months, didn't do a think for my OI. 50 mg of a good magnesium and my OI was barely noticeable after a few days. Doubled the dosage and the OI is pretty much gone. Very odd at first when I am so used to experiencing it every time I stand up.

I was obviously deficient in magnesium, not sure if that would work for most.

David