ActiFolate
Complete Folate Nutrition Dietary Supplement
-800 mcg. pharmaceutical grade Folic Acid, 5-Formyl Tertahydrofolate, and L-5-methyl tetrahydrofolate
-60 vegetarian tablets (two month supply) -- $12.99 per bottle
-Recommended one tablet daily after breakfast for maintenance
-FDA approved to be exclusively sold as a dietary supplement by Metagenics
-Ingredients:
Folic Acid, 5-Formyl Tertahydrofolate, and L-5-methyl tetrahydrofolate, microsrystalline cellulose,
stearic acid, silica, and modified cellulose coating.
What is it?
Folic Acid, 5-Formyl Tertahydrofolate, and L-5-methyl tetrahydrofolate
are needed for folate to be metabolized.
Folic Acid needs to be converted to 5-Formyl Tertahydrofolate, which
needs to converted to L-5-methyl tetrahydrofolate, the
active and isomeric form of folate in the blood. Have a complete folate
nutritional supplement is especially important for
those individuals (roughly 25% of humans) who do not have the ability to activate folic acid due to
genetic variability (what is called a MTHFR enzyme deficiency).
What Does it Do?
Folates are essential
water-soluble vitamins that are involved in DNA synthesis and have a high
potential for normalizing homocysteine plasma levels.
Humans cannot
synthesize folates in the body and must thus obtain them from dietary sources.
Green vegetables in particular are rich in folate but otherwise hard to find in
nature. During processing and cooking, significant amounts of food folate are
lost.
According to the
foremost researchers on genetically inherited folate enzyme insufficiency,
Professor Rowena Matthews at University of Michigan, “About 15 percent of all
Americans may be particularly vulnerable to folic acid deficiency.”
A 1997 The Lancet study echoes this statement.
Who Should Take it?
Low folate has been
associated with various disorders such as:
§
Cardiovascular
Disease
§
Alzheimer’s
disease
§
Neural tube
defects
§
Megaloblastic
anemia
§
Colon Cancer
In some cases, these
disorders could be linked to inefficient MTHFR enzyme activity. ActiFolateä
assures that each folate cycle is accounted for.
Actifolateä is suggested for the following (or have in family
history):
§
Cardiovascular
Disease
§
Homocysteinemia
(mild, moderate, or severe)
§
Neural tube
defects
§
Prenatal,
Pregnant, or Lactating
§
Megaloblastic
anemia
§
Smoking
§
Salicylate
Sensitivity
§
Dementia or
Alzheimer’s disease
§
Cancer
(especially colon)
§
Depression
§
Serotonin
deficiency
§
Stress-related
conditions
§
Support
growth in children
§
Age-related
conditions
§
Chronic
alcoholism
§
Coeliac
disease
§
Anticonvulsant,
Corticosteroid, NSAIDs, Oral Contraceptive, Metformin, Methotrexate,
Trimethoprim-containing antibiotics, and/or Sulfasalazine
consumption
§
Synthetic
estrogen consumption
How Does it Compare to Other Folic Acid Products?
Folic Acid supplements are
the most common form used for supplementation. They are synthetic and virtually
unknown in nature. It only becomes biologically active by enzymatic conversion
steps (must be reduced and methylated during and after absorption). It
is believed that up to 25% of human beings do not have the ability to make the
conversion. ActiFolateä
is an exclusive, patented formula made for Metagenics which accounts for all steps
in the folate cycle to assure the natural form of folate is directly taken up by
the cell.
When Can I Take it?
One tablet daily after
breakfast for maintenance. Please refer to your licensed health professional for
therapeutic dose.
References
1.
Matthews
EG, Vanoni MA, Hainfeld JF, Wall J. Methylenetetrahydrofolate reductase.
Evidence for spatially distinct subunit domains obtained by scanning
transmission electron microscopy and limited proteolysis.
J. Biol. Chem. 259:11647-1640, 1984.
2. Mudd SH, Levy HL, Skovby B. Disorders of transsulfuration. In “The
metabolic and molecular bases of inherited disease” (Scriver CR, Beaudet AL,
Sly WS, Valle D, Eds.), 7th ed., pp. 1279-1327. McGRaw-Hill, New York, 1995.
3. Katzen HM, Buchanan JM. Enzymatic synthesis of the methyl group of
methionine VIII. Repression-depression, purification and properties of
5,10-methylenetetrahydrofolate reductase form Escherichia coli. J. Biol. Chem.
240:825-835, 1965.
4. Saint-Girons I, Duchange N, Zakin MM, Park I, Margarita D, Ferrara P,
Cohen GN. Nucleotide sequence of metF, the E. coli structural gene for 5-10
methylene tetrahydrofolate reductase and of its control region. Nucleic Acid.
Res. 11:6723-6732, 1983.
5. Sheppard CA, Summer JS, Goyette P, Frosst P, Rozen R, Matthews RG.
Methylenetetrahydrofolate reductase: Comparison of the enzyme from mammalian and
bacterial sources. In: Homocysteine Metabolism: From Basic Science to Clinical
Medicine (editors: Graham I, Refsum H, Rosenberg IH, Ueland PM), 31-35, Kluwer
Academic Publishers, Norwell, Ma, 1997).
6. Goyette P, Summer JS, Milos R, Duncan AMV, Rosenblatt DS, Matthews RG,
Rozen R. Human methylenetetrahydrofolate reductase: isolation od cDNA, mapping
and mutation identification. Nat. Genet. 7:195-200, 1994.
7. Frosst P, Bolm HJ, Mils R, Goyette P, Sheppard CA, Matthews RG, Boers
GJH, den Heijer M, Kluijtmans LAJ, van der Heuvel LP, Rozen R. A candidate
genetic risk factor for vascular disease: a common mutation in
methylenetetrahydrofolate reductase. Nat. Genet. 10:111-113, 1995.
8. Fross P, Zhang Z-X, Pai A, Rozen R. The methylenetetrahydrofolate
reductase (MTHFR) gene maps to distal mouse chromosome 4. Mamm. Genome
7:864-865, 1996.
9. Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, Chan M, Rozen R.
Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR).
Mammalian Genome, in press.
10. Rosenblatt DS. Inherent disorders of folate transport and metabolism.
In The metabolic and molecular bases of inherited disease (Scriver CR, Beaudet
AL, Sly WS, Valle D, Eds.), 7 th ed., pp. 3111-3129. McGraw-Hill, New York, 1995
11. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in
the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations
in severe MTHFR deficiency. Am. J. Hum. Genet. 56:1052-1059, 1995.
12. Goyette P, Christensen B, Rosenblatt DS, Rozen R. Severe and mild
mutations in cis for the methylenetetrahydrofolate reductase (MTHFR0 gene, and
description of 5 novel mutations in MTHFR. Am. J. Hum. Genet. 59:1268-1275,
1996.
13. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE.
Plasma homocysteine levels and mortality in patients with coronary artery
disease. N. Engl. J. Med. 337:230-236, 1997.
14. Boushey C, Beresford SAA, Omenn GS, Motulsky AG. A quantitative
assessment of plasma homocysteine as a risk factor for vascular disease JAMA
274:1049-1057, 1995.
15. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B,
Graham I. Hyperhomocysteinemia: an independent risk factor for vascular disease.
N. Engl. J. Med. 324:1149-1155, 1991.
16. Kozich V, Kraus E, De Franchis R, Fowler B, Boers GHJ, Graham I,
Kraus JP. Hyperhomocysteinemia in premature arterial disease: examination of
cystathionine b-synthase alleles at the molecular level. Hum. Mol. Genet.
4:623-629, 1995.
17. Kluijtmans LAJ, van den Heuvel LP, Boers GHJ, Frosst P, Stevens EMB,
van Oost BA, den Heijer M, Trijbels FJM, Rozen R, Blom HJ. Molecular genetic
analysis in mild hyperhomocysteinemia: A common mutation in the
methylenetetrahydrofolate reductase gene is a genetic risk factor for
cardivascular disease. Am. J. Hum. Genet. 58:35-41, 1996.
18. Kang S-S, Wong PWK, Susmano A, Sora J, Norusis M, Ruggie N.
Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for
coronary disease. Am. J. Hum. Genet. 48:536-545, 1991.
19. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH,
Rosenberg IH, Selhub J, Rozen R. Relation between folate status, a common
mutation in methylenetetrahydrofolate reductase, and plasma homocysteine
concentrations. Circulation. 93:7-9, 1996.
20. Christensen B, Frosst P, Lussier-Cacan S, Selhub J, Goyette P,
Rosenblatt DS, Genest Jr J, Rozen R. Correlation of a common mutation in the
methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine in
patients with premature coronary artery disease. Arterioscler. Thromb. Vasc.
Biol. 17:569-573, 1997.
21. Gallagher P, Meleady R, Shields D, Tan KS, McMaster D, Rozen R, Evans
A, Graham I, Whitehead AS. Homocysteine and risk of coronary herat disease:
evidence for a common gene mutation. Circulation 94:2154-2158, 1996.
22. Izumi M, Iwai N, Ohmichi N, Nakamura Y, Shimoike H, Kinoshita M.
Molecular variant of 5,10-methylenetetrahydrofolate reductase is a risk factor
of ischemic heart disease in the Japanese population. Artherosclerosis
121:293-294, 1996.
23. Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y,
Maemura K, Shindo T, Minamino T, Ohno M, Yamaoki K, Ogasawara K, Aizawa T,
Suzuki S, Yakazi Y. Genetic polymorphism of 5,10-methylenetetrahydrofolate
reductase (MTHFR) as a risk factor of coronary artery disease. Circulation
95:2032-2036, 1997.
24. Arruda VR, von Zuben PM, Chiaparini LC, Annichino-Bizzacchi HM, Costa
FF. The mutation Ala677– Val in the methylene tetrahydrofolate reductase gene:
a risk factor for arterial disease and venous thrombosis. Thromb. Haemostasis
77:818-821, 1997
25. Deloughery TG, Evans A, Sadeghi A, McWilliams J, Henner WD, Taylor
LM, Press RD. Common mutation in methylenetetrahydrofolate reductase. Circulación
94:3074-3078, 1996.
26. Schwartz SM, Siscovick DS, Malinow MR, Rosendaal FR, Beverly RK, Hess
DL, Psaty BM, Longstreth Jr WT, Koepsell TD, Raghunathan TE, Reitsma PH.
Myocardial infarction in young women in relation to plasma total homocysteine,
folate, and a common variant in the methylenetetrahydrofolate reductase gene.
Circulation 96:412-417, 1997.
27. van Bockxmeer FM, Mamotte CDS, Vasikaran SD, Taylor RR.
Methylenetetrahydrofolase reductase gene and coronary artery disease.
Circulation 95:21-23, 1997.
28. Viel A. Dall’Agnese L, Simone F Canzonieri V, Capozzi E, Visentin
MC, Valle R, Boiocchi M. Loss of heterozygosity at the
5,10-,ethylenetetrahydrofolase reductase locus in human ovarian carcinomas.
Brit. J. Cancer 75:1105-1110, 1997.
29. Weisberg I, Tran P,Christensen B, Sibani S, Rozen R. A second genetic
polymorphism in methylenetetrahydrofolate (MTHFR) associated with decreased
enzyme activity. Molec. Genet. Metab., in press.
30. MRC Vitamin Study Research Group. Prevention of neural-tube defects:
results of the Medical Research Council Vitamin Study. Lancet 338:181-137, 1991.
31. Czeizel AE, Dudas I. Prevention of the first occurrence of
neural-tube defects by periconceptional vitamin supplementation. N. Engl. J.
Med. 327:1832-1835, 1992.
32. Steegers-Theunissen RPM, Boers GHJ, Trijbels FJM, Finkelstein JD,
Blom HJ, Thomas CMG, Borm GF, Wouters MGAJ, Eskes TKAB. Maternal
hyperhomocysteinemia: a risk factor for neural-tube defects? Metabolism
43:1475-1480, 1994.
33. Mills JL, McPartlin JM, Kirke PN, Lee YJ, Conley MR, Weir DG, Scott
JH. Homocysteine metabolism in pregnancies complicated by neural-tube defects.
Lancet 345:149-151, 1995.
34. van der Put NMJ, Steegers-Theunissen RPM, Frosst P, Trijbels FJM,
Eskes TKAB, van den Heuvel LP, Mariman ECM, den Heyer M, Rozen R, Blom HJ.
Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida.
Lancet 346:1070-1071, 1995.
35. Whitehead AS, Gallagher P, Mills JL, Kirke PN, Burke H, Molloy AM,
Weir DG, Shields DC, Scott JM. A genetic defect in 5,10
methylenetetrahydrofolate reductase in neural tube defects. Q. J. Med.
88:763-766, 1995.
36. Ou CY, Stevenson RE, Brown VK, Schwartz CE, Allen WP, Khoury MJ,
Rozen R, Oakley Jr. GP, Adams Jr. MJ. 5,10-methylenetetrahydrofolate reductase
genetic polymorphism as a risk factor for neural tube defects. Am. J. Med.
Genet. 63:610-614, 1996.
37. Kirke PN, Mills JL, Whitehead AS, Molloy A, Scott JM.
Methylenetetrahydrofolate reductase mutation and neural tube defects. Lancet
348:1037-1038, 1996.
38. Christensen B, Arbour L, Tran P, Sabbaghian N, Platt R, Gilfix B,
Rosenblatt DS, Forbes P, Rozen R. Relation between the C677T polymorphism in the
MTHFR gene, the folate levels in red blood cells, and risk for neural tube
defects. Presented to the American Society for Human Genetics, Baltimore,
Maryland, USA. October, 1997.
39. Shaw GM, Rozen R, Finnell RH, Wasserman CR, Lammer EJ. Maternal
vitamin use, genetic variation of infant methylenetetrahydrofolate reductase and
risk for spina bifida. Am. J. Epidemiol, in press.
40. Giovannucci E, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, Willett
WC. Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men.
J. Natl. Cancer. Inst. 87:265-273, 1995.
41. Ma J, Stampfer MJ, Giovannucci E, Artigas C, Hunter D, Fuchs C,
Willet W, Selhub J, Hennekens CH, Rozen R. Methylenetetrahydrofolate reductase
polimorphism, reduced risk of colorectal cancer and dietary in teractions.
Cancer Res. 57:1098-1102, 1997.
42. Chen J, Giovannucci E, Kelsey K, Rimm EB, Stampfer MJ, Colditz GA,
Spiegelman D, Willett WC, Hunter DJ. A methylenetetrahydrofolate reductase
polimorphism and the risk of colorectal cancer. Cancer Res. 56:4862-4864, 1996.
43. Jones PA. DNA methylation errors and cancer. Cancer Res.
56:1463-1467, 1996.
44. Blount BC, Ames BN. Development of a sensitive assay for detection of
uracil in DNA. In Chemistry and Biology of Pteridines and Folates (Ayling JE et
al. Eds.), pp. 741-744. Plenum Press, New York, 1993.
45. Report on the Rare Diseases and Conditions Research
Activites of the National Institutes of Health 1999: Neural Tube Defects. Office of
Rare Diseases, National Institute of Child Health and Development (NICHD)
46. Morris, Jill, Phd., Office of Genomics and Disease Prevention, Centers
for Disease Control. Smoking, folate and methylenetetrahydrofolate reductase
status as interactive determinants of adenomatoous and hyperplastic polyps of
colorectum. Aug 14, 2001
47. National Institutes of Health News Release. Currently Recommended
Folate Intake May be Insufficient for Large Group of People. May 30, 1997
48. Homocysteine, Folate, vitamin B6, and Cardiovascular Disease. JAMA
Feb 4 (1998)-Vol279, No.5
(see
another full set of references attached)