Did you read the "full of citation" monograph I posted? There's data shwoing unique benefits to p5p.
In seriously sick people, as I acknowledged above. The overwhelming majority of supplement users will see no such benefit. It only belongs in things like autism or "My liver! My liver!" formulas, not a mainstream multi.
High dose p5p is not associated with any neuropathy, while pyridoxine is. PN may compete with p5p creating a deficiency or it may be neurotoxic itself if unconverted/excessive.
http://www.ajcn.org/...int/46/1/78.pdf This study discusses the non-linear response even with healthy people suggesting that this competition does take place at higher doses.
This is all correct, but I made those points myself in posts 13 and 24. The overwhelming majority of people need an order of magnitude less than the UL, so they don't need PL.
While it seems to be scoffed at that many may have difficulty with conversion or enzymatic deficiencies, I know there's a plethora of studies regarding another B-vitamin in the methylation pathway, folic acid...many do have trouble hitting 5-mthf.
That problem goes away with a few milligrams of B2. (Unless there's another polymorphism that I'm unaware of.)
Circulation. 2006 Jan 3;113(1):74-80.
Comment in:Circulation. 2006 Jul 25;114(4):e65; author reply e66.
Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism.
McNulty H, Dowey le RC, Strain JJ, Dunne A, Ward M, Molloy AM, McAnena LB, Hughes JP, Hannon-Fletcher M, Scott JM.
Northern Ireland Centre for Food and Health, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland. h.mcnulty@ulster.ac.uk
BACKGROUND: Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status. METHODS AND RESULTS: From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C-->T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, n=26) or wild-type (CC, n=28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in erythrocyte glutathione reductase activation coefficient; P<0.01 in each case). However, homocysteine responded only in the TT group, with levels decreasing by as much as 22% overall (from 16.1+/-1.5 to 12.5+/-0.8 micromol/L; P=0.003; n=32) and markedly so (by 40%) in those with lower riboflavin status at baseline (from 22.0+/-2.9 and 13.2+/-1.0 micromol/L; P=0.010; n=16). No homocysteine response was observed in the CC or CT groups despite being preselected for suboptimal riboflavin status. CONCLUSIONS: Although previously overlooked, homocysteine is highly responsive to riboflavin, specifically in individuals with the MTHFR 677 TT genotype. Our findings might explain why this common polymorphism carries an increased risk of coronary heart disease in Europe but not in North America, where riboflavin fortification has existed for >50 years.
PMID: 16380544
I instinctively distrust B-vitamin megadose advocates. They throw hundreds of milligrams at the problem and then pretend that it's the required dose without doing any dose-finding experiments. Later on they end up with egg on their faces when it turns out that a moderate dose works just as well.
http://www.ajcn.org/...t/full/75/4/616In another study, 3 patients responded to oral vitamin B-6 (600–750 mg/d) with a decrease in serum ornithine and a return to normal of reduced concentrations of serum lysine. Lower doses of vitamin B-6 (18–30 mg/d) appeared to work just as well as the high doses.
Searching PubMed for "migraine riboflavin 400" yields 6 hits. In the most recent one (TEN YEARS after the initial study) they finally figured out that only 25 mg or less is required, but it wasn't even a proper dose-finding experiment. The placebo had 25 mg, worked better than previous placebos, and even worked as well as the megadose.
Headache. 2004 Oct;44(9):885-90.
Comment in: Headache. 2006 Mar;46(3):531.
A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial.
Maizels M, Blumenfeld A, Burchette R.
Kaiser Permanente, Family Practice, Woodland Hills, CA, USA.
OBJECTIVE: To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin, magnesium, and feverfew. BACKGROUND: Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results, and there has been only a single placebo-controlled trial of riboflavin. DESIGN/METHODS: Randomized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo contained 25 mg riboflavin. The study included a 1-month run-in phase and 3-month trial. The protocol allowed for 120 patients to be randomized, with a preplanned interim analysis of the data after 48 patients had completed the trial. RESULTS: Forty-nine patients completed the 3-month trial. For the primary outcome measure, a 50% or greater reduction in migraines, there was no difference between active and "placebo" groups, achieved by 10 (42%) and 11 (44%), respectively (P=.87). Similarly, there was no significant difference in secondary outcome measures, for active versus placebo groups, respectively: 50% or greater reduction in migraine days (33% and 40%, P=.63); or change in mean number of migraines, migraine days, migraine index, or triptan doses. Compared to baseline, however, both groups showed a significant reduction in number of migraines, migraine days, and migraine index. This effect exceeds that reported for placebo agents in previous migraine trials. CONCLUSION: Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis, and suggests that riboflavin 25 mg may be an active comparator. There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis.
PMID: 15447697
