Pre-DX Ingredients & Science

 

Supplement Facts
Recommended Serving Size: 1 Capsule Daily    
Amount Per Serving Dose % Daily Value
L-Methylfolate (Magnafolate-C®/L-5-MTHF Ca C crystal)  2.5 mg 625
Vitamin C (Ascorbic Acid)  33.3 mg 55
Vitamin D (Cholecalciferol)  2000 IU 500
Vitamin E Natural Tocopherols (Alpha, Beta, Gamma, & Delta)  7.5 IU 25
Vitamin B1 (Thiamine Hydrochloride)  1.5 mg 100
Vitamin B2 (Riboflavin)  10 mg 588
Vitamin B3 Niacin  1.5 mg 7.5
Vitamin B6 (Pyridoxal-5-Phosphate)  3 mg 150
Vitamin B12 (Methylcobalamin) 500 mcg 833
Vitamin B12 (Hydroxocobalamin)  500 mcg 833
Pantothenic Acid (Calcium-D-Pantothenate)  5 mg 50
Zinc (Zinc Oxide)  10 mg 100
Selenium (L- Selenomethionine)  20 mcg 29
Copper (Cupric Oxide)  667 mcg *
N-Acetyl Cysteine (NAC)  300 mg *
Alpha Lipoic Acid  300 mg *
# Percent Daily Values are based on a 2,000 calorie diet    
* Daily Value not established    

Magnafolate-C TM Patent # 9150982

  

These ingredients work synergistically to address the nutritional needs of patients with Auto-Immune Disorders, elevated Inflammation and Oxidative stress, Neuropathies as well as Low Vitamin B12, Vitamin D, Folate and elevated Homocysteine.

Data suggests that small nerve fiber and microvascular damage as well as oxidative stress and inflammation starts well before symptoms occur. Overwhelming evidence recommends that we identify and address these conditions early and optimize nutritional support. 

 

Pre-DX as A Neurotrophic Agent Provides a Novel MOA (Mechanism of Action)

Neurotrophic refers to nutrition for the nerves. The ingredients in Pre-DX provide nutritional management of endothelial dysfunction associated with numbness, tingling, and burning sensations in diabetes patients with neuropathy. It offers a neurotrophic benefit by improving endothelial dysfunction and maintaining blood flow in the vessels that carry important nutrients and oxygen to the peripheral nerves.

Pre-DX is composed of the bioactive forms of essential B vitamins along with other agents that reduce inflammation and oxidative stress and are critical for peripheral nerve health.

 

Science:

  1. Pre-DX helps regenerate BH4, a cofactor for eNOS to convert L-arginine into nitric oxide
  2. Nitric oxide is diffused into the smooth muscle cells
  3. Smooth muscle cells dilate, and blood flow is increased

 

 MOA

Ingredients:

L-methylfolate (folate) Methylcobalamin & Hydroxocobalamin (vitamins B12) Pyridoxal 5’ phosphate (vitamin B6), N-Acetyl Cysteine (NAC), Alpha Lipoic Acid, Vitamins C, D, E, B1, B2, B3, Pantothenic Acid, Zinc, Selenium, Copper.

Benefits:

Nitric oxide synthesis, myelin synthesis, neurotransmitter synthesis

 

Nitric Oxide Benefits 

 

The endothelium (the thin layer of cells that line the interior surface of blood vessels) helps maintain blood flow by producing a substance called nitric oxide. Nitric oxide signals the blood vessels to relax corresponding with improved blood flow to peripheral nerves. Studies have shown that endothelial cells produce twice as much nitric oxide in the presence of L-methylfolate.

Maintaining blood flow in the small blood vessels is critical for peripheral nerves to maintain their normal functions, such as peripheral nerve repair and regeneration. This includes production of the myelin sheath, a fatty substance that protects the nerve fibers. Research has demonstrated a significant increase in epidermal nerve fiber density after 6 months of L-methylfolate compared to baseline; further research is ongoing.

 

Key Ingredients

Magnafolate-CTM [(6S)-5-Methyltetrahydrofolic acid, Calcium salt C Crystal (L-Methylfolate)]

Pre-DX contains a proprietary blend of vitamins and minerals shown to help manage homocysteine levels resulting from metabolic active folate deficiencies caused by certain medical conditions, MTHFR polymorphisms, and/or medications. Individuals with some chronic illnesses, taking certain medications, or who have the genetic MTHFR deficiencies cannot efficiently metabolize dietary folate or folic acid into its bioactive form, L-methylfolate. This step is required for reducing homocysteine levels. 

Clinical studies have concluded that direct supplementation with L-methylfolate reduces homocysteine levels and increases plasma folate levels more effectively than folic acid, especially in those with MTHFR genetic variations.       

B-Vitamins 

Vitamins B6 and B12 status has been associated with elevated homocysteine.  In conjunction with supplemented folate, the addition of Vitamin B12 has been shown to reduce homocysteine more than folic acid alone. Homocysteine levels of individuals with homozygous MTHFR genotype were particularly sensitive to the status of several B vitamins (B2, B12 and B6). An inverse relationship between riboflavin status and plasma homocysteine has also been observed, especially in those with the MTHFR polymorphism. Riboflavin supplementation was shown to lower homocysteine in individuals homozygous for the MTHFR polymorphism. A combination of B vitamins (B2, B6, B12) in addition to folate supplementation has also shown to significantly reduce plasma homocysteine concentrations in older patients.

Vitamin D 

An inverse relationship has been found between homocysteine levels and Vitamin D concentration.  Vitamin D may modulate the expression of genes involved in homocysteine metabolism.  In animal models, Vitamin D deficiency has also been shown to impair the synthesis of folate transport protein necessary for folate absorption across the intestine.

Zinc

A number of the enzymes that are involved in homocysteine and methionine metabolism are zinc metalloenzymes.   Therefore, a serum zinc deficiency can reduce the activity of the enzymes and therefore increase serum homocysteine levels. Zinc supplementation has been shown to reduce plasma homocysteine levels by eliminating zinc deficiency.

 

Other Synergistic Ingredients

Vitamins and N-Acetyl Cysteine

Since homocysteine induces oxidative stress, antioxidants such as Vitamin E, C, and N-Acetylcysteine (NAC, a precursor of the body’s natural glutathione) are important synergistic dietary ingredients for protecting vascular tissue from oxidative damage. NAC, Vitamin C, and Vitamin E have been shown to significantly attenuate homocysteine-induced damage. Pantothenic acid (sometimes referred to as Vitamin B5) is found in the body in the form of Coenzyme A (CoA), which is involved in the synthesis of glutathione. Vitamin B1 (Thiamine) and also indirectly acts as an antioxidant.

Alpha Lipoic Acid

Alpha-lipoic acid is a vitamin-like chemical called an antioxidant.  Alpha-lipoic acid is most commonly taken by mouth for diabetes and nerve-related symptoms of diabetes including burning, pain, and numbness in the legs and arms.  Alpha-lipoic acid seems to help prevent certain kinds of cell damage in the body, and also restores vitamin levels such as vitamin E and vitamin C. There is also evidence that alpha-lipoic acid can improve the function and conduction of neurons in diabetes.

Minerals

Selenium is a trace element that also functions as an antioxidant through the selenium-containing enzyme glutathione peroxidase, a vital antioxidant enzyme found in all cells with specific activity against hydrogen peroxide. Deficiencies in selenium have been associated with lowered activity of this antioxidant enzyme.

 

MTHFR C677T & A1298C

  • Pre-DX is ready for immediate usage by your cells
  • Patients with CT Polymorphism have less than 71% MTHFR enzyme activity available to metabolize folic acid
  • Patients with TT polymorphism have less than 34% MTHFR enzyme activity available to metabolize folic acid
  • Homocysteine is poorly converted
  • Can increase inflammation and free radical damage

What Happens if there is a Mutation? 
C677T

  • Cardiovascular Disease
  • Peripheral Neuropathy
  • Birth Defects
  • Age-Related Macular Degeneration
  • Ischemic Stroke
  • Peripheral Artery Disease

A1298C

  • Migraines
  • Chronic Fatigue
  • Fibromyalgia
  • Dementia
  • Ischemic Stroke
  • Sagittal Sinus Thrombus

The MTHFR A1298C mutation affects the enzyme methylenetetrahydrofolate reductase by inhibiting the utilization of 5-methyltetrahydrofolate (5-MTHF), or methylfolate, in producing an important chemical called tetrahydrobiopterin, or BH4. BH4 is a cofactor in neurotransmitter production, including serotonin, dopamine, melatonin, epinephrine, and norepinephrine. It also plays a role in the production of nitric oxide. If you have the MTHFR A1298C mutation, you may be deficient in BH4, which may cause psychological or neurological problems, as well as cardiovascular disease.

MTHFR participates in a multistep process that converts homocysteine to methionine. A decrease in the function or amount of MTHFR causes increased blood levels of homocysteine. Increased homocysteine blood concentrations are associated with an increased risk for cardiovascular disease including venous thrombosis, atherosclerosis, stroke, and peripheral artery disease. Genetic, environmental (diet) and physiologic factors affect homocysteine levels. Folate, vitamin B6 and vitamin B12 are involved in regulating homocysteine levels; dietary supplementation can decrease blood homocysteine concentrations.

Two mutations of the MTHFR gene, C677T and A1298C, cause decreased enzyme activity and are fairly common. The C677T mutation encodes an alanine to valine substitution at amino acid 223 of the MTHFR enzyme. This mutation results in an enzyme with only 45% – 50% of the normal activity, and the enzyme is inactivated by heat (thermolabile). The A1298C MTHFR variant results in a glutamate to alanine substitution of the MTHFR protein, and the enzyme activity is decreased to 68% of the wild type enzyme.

*Patients diagnosed with MTHFR C677T TT, MTHFR A1298C CC and a combination of the two will may need higher doses of L-Methylfolate.  Please check with your health provider for recommended on dosing.


STUDIES


* The studies listed below DO NOT have Pre-DX in them but use similar ingredients or refer to disease states that the ingredients address. Pre-DX does not make a claim to cure diseases but addresses specific symptoms from the nutritional side.

1. CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, CDC; 2011.

2. Knowler WC, Barrett-Conner E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.

3. Geiss LS, James C, Gregg EW, et al. Diabetes risk reduction behaviors among U.S. adults with prediabetes. Am J Prev Med 2010;38:403–9.

4. CDC. National Health and Nutrition Examination Survey. Atlanta, GA: US Department of Health and Human Services, CDC; 2012.

5. Herman WH, Smith PJ, Thompson TJ, et al. A new and simple questionnaire to identify people at increased risk for undiagnosed diabetes. Diabetes Care 1995;18:382–7.

6. Mayer-Davis EJ, Dabble D, Lawrence JM, et al. Risk factors for type 2 and gestational diabetes. In: Venkat Narayan KM, Williams D, Gregg EW, Cowie C, eds. Diabetes public health: from data to policy. New York, NY: Oxford University Press; 2011:33–63.

7. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013;36:S11–66.

8. Selvin E, Steffes MW, Gregg E, Brancati FL, Coresh J. Performance of A1C for the classification and prediction of diabetes. Diabetes Care 2011;34:84–9.

9. CDC. Increasing prevalence of diagnosed diabetes—United States and Puerto Rico, 1995–2010. MMWR 2012;61:918–21.

10. Clarke, R., Daly, L., Robinson, K., Naughten, E., Cahalane, S., et al. 1991. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 324:1149–1155.

11. Homocysteine Studies Collaboration. 2002. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 288:2015–2022.

12. Guilliams, T.G. 2004. Homocystiene – a risk factor for vascular diseases: Guidelines for Clinical Practices. JANA. 7(1):11-24.

13. Wulffele, M.G., Kooy, A., Hehert, P., Bets, D., Octerop, J.C., Borger van der Burg, B., et al. 2003. Effects of short-term treatment with metformin on serum concentration of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Int Med. 254:455-463.

14. Scaglione, F.1. Panzavolta, G. 2014. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing Xenobiotica. 44(5):480-8.

15. Lambie, D.G., Johnson, R.H. 1985. Drugs and folate metabolism. Drugs. 30(2):145-55.

16. Amilburu, A., Idoate, I., Ponz, F., Larralde, J. 2002. Inhibition of intestinal absorption of 5-methyltetrahydrofolate by fluoxetine. J. Phys. Biochem. 57(2):71-79.

17. Ruscin, J.M., Page, R.L. 2nd, Valuck, R,J, 2002. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother. 36(5):812-6.

18. Cai, W., Yin, L.,Yang, F., Zhang, L., Cheng, J. 2014. Association between Hcy levels and the CBS844ins68 and MTHFR C677T polymorphisms with essential hypertension. Biomed Rep. 2(6):861-868.

19. Heifetz, E.M., Birk, R.Z. 2014. MTHFR C677T Polymorphism Affects Normotensive Diastolic Blood Pressure Independently of Blood Lipids. Am J Hypertens. Aug 27. Epub ahead of print.

20. Nazki, F.H., Sameer, A.S., Ganaie, B.A. 2014. Folate: metabolism, genes, polymorphisms and the associated diseases. Gene. 533(1):1-20.

21. Khandanpour, N., Willis, G., Meyer, F.J., Armon, M.P., Loke, Y.K., Wright, A.J., et al. 2009. Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case-control study and meta-analysis. J Vasc Surg. 49(3):711-8.

22. Yigit, S., Karakus, N., Inanir, A. 2013. Association of MTHFR gene C677T mutation with diabetic peripheral neuropathy and diabetic retinopathy. Mol Vis. 2013 Jul 25;19:1626-30.

23. Niu, W., Qi, Y. 2012. An updated meta-analysis of methylenetetrahydrofolate reductase gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy. Diabetes Res Clin Pract. 95(1):110-8

24. Maeda, M, Fujio, Y., Azuma. J. 2006. MTHFR gene polymorphism and diabetic retinopathy. Curr Diabetes Rev.2(4):467-76.

25. Sun, J., Xu, Y., Zhu, Y., Lu, H., Deng, H., Fan, Y., et al. 2003. The relationship between MTHFR gene polymorphisms, plasma homocysteine levels and diabetic retinopathy in type 2 diabetes mellitus. Chin Med J (Engl). 116(1):145-7.

26. Simões, MJ., Lobo, C., Egas, C., Nunes, S., Carmona, S., Costa, MÂ., et al. 2014. Genetic Variants in ICAM1, PPARGC1A and MTHFR Are Potentially Associated with Different Phenotypes of Diabetic Retinopathy. Ophthalmological. 232(3):156-62.

27. Tanaka, K., Nakayama, T., Yuzawa, M., Wang, Z., Kawamura, A., Mori, R., et al. 2011.

28. Liu, H.H., Shih, T.S., Huang, H.R., Huang, S.C., Lee, L.H., Huang, Y.C. 2013. Plasma homocysteine is associated with increased oxidative stress and antioxidant enzyme activity in welders. Scientific World Journal. 2013:370487.

29. Faraci, F.M., Lentz, S.R. 2003. Hyperhomocysteinemia, oxidative stress and cerebral vascular dysfunction. Stroke. 35:345-347

30. Rodrigo, R., Passalacqua, W., Araya, J., Orellana, M., Rivera, G. 2003. Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension. J Cardiovasc Pharmacol. 2003 Oct;42(4):453-61.

31. Pushpakumar, S., Kundu, S., Sen U. 2014. Endothelial dysfunction: The link between homocysteine and hydrogen sulfide. Curr Med Chem. 21:3662-3672.

32. Fohr, I.P., Prinz-Langenohi, Bronstrup, A., Bohlmann, A.M., Berthoid, H.K., Pietrzik, K. 2002. 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr. 75(2):275-82.

33. Prinz-Langenohl, R., Brämswig, S., Tobolski, O., Smulders, Y.M., Smith, D.E., Finglas, P.M., Pietrzik, K. 2009. [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C–>T polymorphism of methylenetetrahydrofolate reductase. Br J Pharmacol. 158(8):2014-21.

34. Smith, D.E., Hornstra, J.M., Kok, R.M., Blom, H.J., Smulders, Y.M. 2013. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism. Clin Chem Lab Med. 51(8):1643-50.

35. van Guldener, C., Stehouwer, C.D. 2001. Homocysteine-lowering treatment: an overview. Expert Opinion on Pharmacotherapy 2 9):1449–1460.

36. Hustad, S., Midttun, O, Schneede, J., Vollset, S.E., Grotmol, T., Ueland, P.M. 2007. The Methylenetetrahydrofolate reductase 677->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. Am J Hum Genet. 80(5):846-855.

37. García-Minguillán, C.J., Fernandez-Ballart, J.D., Ceruelo, S., Ríos, L., Bueno, O., Berrocal-Zaragoza, M.I., et al. Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine. 2014. Genes Nutr.9(6):435.

38. Hustad, S., Ueland, P.M., Vollset, S.E., Zhang, Y., Bjørke-Monsen, A.L., Schneede, J. 2000. Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem. 46(8 Pt 1):1065-71.

39. McNulty, H., Dowey le, R.C., Strain, J.J., Dunne, A., Ward, M., Molloy, A.M., et al. 2006. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation.113:74-80.

40. Gariballa, S.E, Forster, S.J., Powers, H.J. 2012. Effects of mixed dietary supplements on total plasma homocysteine concentrations (tHcy): a randomized, double-blind, placebo-controlled trial. Int J Vitam Nutr Res.;82(4):260-6.

41. Amer, M., Qayyum, R. 2014. The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults. J Clin Endocrinol Metab. 99(2):633-8.

42. Eloranta, J.J., Zair, Z.M., Hiller, C., Hausler, S., Stieger, B., Kullak-Ublick, G.A. 2009. Vitamin D3 and its nuclear receptor increase the expression and activity of the human proton-coupled folate transponder. Molecular Pharmacology. 76(5):1062-1071.

43. Heidarian, E., Amini, M., Parham, M., Aminorroaya, A. 2009. Effect of zinc supplementation on serum homocysteine in type 2 diabetic patients with microalbuminuria. Rev Diabet Stud. 6(1):64-70.

44. Huang, R.F.S., Huang, S.M., Lin, B.S., Hung C.Y., Lu, H.T. 2002. N-Acetylcysteine, Vitamin C and Vitamin E Diminish Homocysteine Thiolactone-Induced Apoptosis in Human Promyeloid HL-60 Cells. J Nutr. 132(8):2151-2156.

45. Slyshenkov, V.S., Dymkowska, D., Wojtczak, L. 2004. Pantothenic acid and pantothenol increase biosynthesis of glutathione by boosting cell energetics. FEBS Letters 569(1-3):169-172.

46. Lukienko, P.I., Mel’nichenko, N.G., Zverinskii, I.V., Zabrodskaya, S.V. 2000. Antioxidant properties of thiamine, Bulletin of Experimental Biology and Medicine. 130(9);874–876.

47. Takahashi, K., Newburger, P.E., Cohen, H.J. 1986. Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity. J Lin Invest. 77(4):1402-1404.

48. Scaglione, F.1. Panzavolta, G. 2014. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing, Xenobiotica. 44(5):480-8.

49. Lambie, D.G., Johnson, R.H. 1985. Drugs and folate metabolism. Drugs. 30(2):145-55.

50. Amilburu, A., Idoate, I., Ponz, F., Larralde, J. 2002. Inhibition of intestinal absorption of 5-methyltetrahydrofolate by fluoxetine. J. Phys. Biochem. 57(2):71-79.

51. Sobczyńska-Malefora, A., Harrington, D.J., Lomer, M.C., Pettitt, C., Hamilton, S., Rangarajan, S., Shearer, M.J. 2009. Erythrocyte folate and 5-methyltetrahydrofolate levels decline during 6 months of oral anticoagulation with warfarin. Blood Coagul Fibrinolysis. 20(4):297-302.

52. Ruscin, J.M., Page, R.L. 2nd, Valuck, R,J, 2002. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother. 36(5):812-6.

53. Wicken, B., Bamforth, F., Li, Z., Zhu, H., Ritvanen, A., Redlund, M., et al. 2003. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 40:619-625.

54. Jacques, P.F., Bostom, A.G., Williams, R.R., Ellison R.C., Eckfeldt, J.H., Rosenberg, I.H., et al. 1996. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996. 93:7-9.

55. Rosen, R. 2000. Genetic modulation of homocysteinemia. Semin Thromb Hemost. 26(3):255-61.

56. Zittoun, J., Tonetti, C., Bories, D., Pignon, J.M., Tulliez, M. 1998. Plasma homocysteine levels related to interactions between folate status and methylenetetrahydrofolate reductase: a study in 52 healthy subjects. Metabolism. 47(11):1413-8.

57. Faraci, F.M., Lentz, S.R. 2003. Hyperhomocysteinemai, oxidative stress and cerebral vascular dysfunction. Stroke. 35:345-347

58. Rodrigo, R., Passalacqua, W., Araya, J., Orellana, M., Rivera, G. 2003. Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension. J Cardiovasc Pharmacol. 2003 Oct;42(4):453-61.

59. Fohr, I.P., Prinz-Langenohi, Bronstrup, A., Bohlmann, A.M., Berthoid, H.K., Pietrzik, K. 2002. 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr. 75(2):275-82.

60. Prinz-Langenohl, R., Brämswig, S., Tobolski, O., Smulders, Y.M., Smith, D.E., Finglas, P.M., Pietrzik, K. 2009. [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C–>T polymorphism of methylenetetrahydrofolate reductase. Br J Pharmacol. 158(8):2014-21.

61. Smith, D.E., Hornstra, J.M., Kok, R.M., Blom, H.J., Smulders, Y.M. 2013. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism. Clin Chem Lab Med. 51(8):1643-50.

62. Lim, H.S., Heo, Y.R. 2002. Plasma total homocysteine, folate, and vitamin B12 status in Korean adults. J Nutr Sci Vitaminol (Tokyo). 2002. 48(4):290-7.

63. Chen, K.J., Pan, W.H., Yang, F.L., Wei, I.L., Shaw, N.S., Lin, B.F. 2005. Association of B vitamins status and homocysteine levels in elderly Taiwanese. Asia Pac J Clin Nutr. 2005;14(3):250-5.

64. van Guldener, C., Stehouwer, C.D. 2001. Homocysteine-lowering treatment: an overview. Expert Opinion on Pharmacotherapy 2 9):1449–1460.

65. Homocysteine Lowering Trialists’ Collaboration, Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, UK. 2000. Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials. Indian Heart J. 52(7 suppl):S59-S64.

66. Hustad, S., Midttun, O, Schneede, J., Vollset, S.E., Grotmol, T., Ueland, P.M. 2007. The Methylenetetrahydrofolate reductase 677->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. Am J Hum Genet. 80(5):846-855.

67. García-Minguillán, C.J., Fernandez-Ballart, J.D., Ceruelo, S., Ríos, L., Bueno, O., Berrocal-Zaragoza, M.I., et al. Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine. 2014. Genes Nutr.9(6):435.

68. Hustad, S., Ueland, P.M., Vollset, S.E., Zhang, Y., Bjørke-Monsen, A.L., Schneede, J. 2000. Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem. 46(8 Pt 1):1065-71.

69. McNulty, H., Dowey le, R.C., Strain, J.J., Dunne, A., Ward, M., Molloy, A.M., et al. 2006. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation.113:74-80.

70. Gariballa, S.E, Forster, S.J., Powers, H.J. 2012. Effects of mixed dietary supplements on total plasma homocysteine concentrations (tHcy): a randomized, double-blind, placebo-controlled trial. Int J Vitam Nutr Res.;82(4):260-6.

71. Amer, M., Qayyum, R. 2014. The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults. J Clin Endocrinol Metab. 99(2):633-8.

72. Abdel-Azeim, S., Li, X., Chung, L.W., Morokuma, K. 2011. Zinc-homocysteine binding in cobalamin-dependent methionine synthase and its role in the substrate activation: DFT, ONIOM, and QM/MM molecular dynamics studies. J Comput Chem. 32(15):3154-67

73. Heidarian, E., Amini, M., Parham, M., Aminorroaya, A. 2009. Effect of zinc supplementation on serum homocysteine in type 2 diabetic patients with microalbuminuria. Rev Diabet Stud. 6(1):64-70.

74. Huang, R.F.S., Huang, S.M., Lin, B.S., Hung C.Y., Lu, H.T. 2002. N-Acetylcysteine, Vitamin C and Vitamin E Diminish Homocysteine Thiolactone-Induced Apoptosis in Human Promyeloid HL-60 Cells. J Nutr. 132(8):2151-2156.

75. Slyshenkov, V.S., Dymkowska, D., Wojtczak, L. 2004. Pantothenic acid and pantothenol increase biosynthesis of glutathione by boosting cell energetics. FEBS Letters 569(1-3):169-172.

76. Lukienko, P.I., Mel’nichenko, N.G., Zverinskii, I.V., Zabrodskaya, S.V. 2000. Antioxidant properties of thiamine, Bulletin of Experimental Biology and Medicine. 130(9);874–876.

77. Takahashi, K., Newburger, P.E., Cohen, H.J. 1986. Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity. J Lin Invest. 77(4):1402-1404.

78. Scaglione, F.1. Panzavolta, G. 2014. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing, Xenobiotica. 44(5):480-8.

79. Lambie, D.G., Johnson, R.H. 1985. Drugs and folate metabolism. Drugs. 30(2):145-55.

80. Amilburu, A., Idoate, I., Ponz, F., Larralde, J. 2002. Inhibition of intestinal absorption of 5-methyltetrahydrofolate by fluoxetine. J. Phys. Biochem. 57(2):71-79.

81. Sobczyńska-Malefora, A., Harrington, D.J., Lomer, M.C., Pettitt, C., Hamilton, S., Rangarajan, S., Shearer, M.J. 2009. Erythrocyte folate and 5-methyltetrahydrofolate levels decline during 6 months of oral anticoagulation with warfarin. Blood Coagul Fibrinolysis. 20(4):297-302.

82. Ruscin, J.M., Page, R.L. 2nd, Valuck, R,J, 2002. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother. 36(5):812-6.

83. Wicken, B., Bamforth, F., Li, Z., Zhu, H., Ritvanen, A., Redlund, M., et al. 2003. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 40:619-625.

84. Jacques, P.F., Bostom, A.G., Williams, R.R., Ellison R.C., Eckfeldt, J.H., Rosenberg, I.H., et al. 1996. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996. 93:7-9.

85. Rosen, R. 2000. Genetic modulation of homocysteinemia. Semin Thromb Hemost. 26(3):255-61.

86. Zittoun, J., Tonetti, C., Bories, D., Pignon, J.M., Tulliez, M. 1998. Plasma homocysteine levels related to interactions between folate status and methylenetetrahydrofolate reductase: a study in 52 healthy subjects. Metabolism. 47(11):1413-8.

87. Faraci, F.M., Lentz, S.R. 2003. Hyperhomocysteinemai, oxidative stress and cerebral vascular dysfunction. Stroke. 35:345-347

88. Rodrigo, R., Passalacqua, W., Araya, J., Orellana, M., Rivera, G. 2003. Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension. J Cardiovasc Pharmacol. 2003 Oct;42(4):453-61.

89. Fohr, I.P., Prinz-Langenohi, Bronstrup, A., Bohlmann, A.M., Berthoid, H.K., Pietrzik, K. 2002. 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr. 75(2):275-82.

90. Prinz-Langenohl, R., Brämswig, S., Tobolski, O., Smulders, Y.M., Smith, D.E., Finglas, P.M., Pietrzik, K. 2009. [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C–>T polymorphism of methylenetetrahydrofolate reductase. Br J Pharmacol. 158(8):2014-21.

91. Smith, D.E., Hornstra, J.M., Kok, R.M., Blom, H.J., Smulders, Y.M. 2013. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism. Clin Chem Lab Med. 51(8):1643-50.

92. Lim, H.S., Heo, Y.R. 2002. Plasma total homocysteine, folate, and vitamin B12 status in Korean adults. J Nutr Sci Vitaminol (Tokyo). 2002. 48(4):290-7.

93. Chen, K.J., Pan, W.H., Yang, F.L., Wei, I.L., Shaw, N.S., Lin, B.F. 2005. Association of B vitamins status and homocysteine levels in elderly Taiwanese. Asia Pac J Clin Nutr. 2005;14(3):250-5.

94. van Guldener, C., Stehouwer, C.D. 2001. Homocysteine-lowering treatment: an overview. Expert Opinion on Pharmacotherapy 2 9):1449–1460.

95. Homocysteine Lowering Trialists’ Collaboration, Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, UK. 2000. Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials. Indian Heart J. 52(7 suppl):S59-S64.

96. Hustad, S., Midttun, O, Schneede, J., Vollset, S.E., Grotmol, T., Ueland, P.M. 2007. The Methylenetetrahydrofolate reductase 677->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. Am J Hum Genet. 80(5):846-855.

97. García-Minguillán, C.J., Fernandez-Ballart, J.D., Ceruelo, S., Ríos, L., Bueno, O., Berrocal-Zaragoza, M.I., et al. Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine. 2014. Genes Nutr.9(6):435.

98. Hustad, S., Ueland, P.M., Vollset, S.E., Zhang, Y., Bjørke-Monsen, A.L., Schneede, J. 2000. Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem. 46(8 Pt 1):1065-71.

99. McNulty, H., Dowey le, R.C., Strain, J.J., Dunne, A., Ward, M., Molloy, A.M., et al. 2006. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation.113:74-80.

100. Gariballa, S.E, Forster, S.J., Powers, H.J. 2012. Effects of mixed dietary supplements on total plasma homocysteine concentrations (tHcy): a randomized, double-blind, placebo-controlled trial. Int J Vitam Nutr Res.;82(4):260-6.

101. Amer, M., Qayyum, R. 2014. The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults. J Clin Endocrinol Metab. 99(2):633-8.

102. Abdel-Azeim, S., Li, X., Chung, L.W., Morokuma, K. 2011. Zinc-homocysteine binding in cobalamin-dependent methionine synthase and its role in the substrate activation: DFT, ONIOM, and QM/MM molecular dynamics studies. J Comput Chem. 32(15):3154-67

103. Heidarian, E., Amini, M., Parham, M., Aminorroaya, A. 2009. Effect of zinc supplementation on serum homocysteine in type 2 diabetic patients with microalbuminuria. Rev Diabet Stud. 6(1):64-70.

104. Huang, R.F.S., Huang, S.M., Lin, B.S., Hung C.Y., Lu, H.T. 2002. N-Acetylcysteine, Vitamin C and Vitamin E Diminish Homocysteine Thiolactone-Induced Apoptosis in Human Promyeloid HL-60 Cells. J Nutr. 132(8):2151-2156.

105. Slyshenkov, V.S., Dymkowska, D., Wojtczak, L. 2004. Pantothenic acid and pantothenol increase biosynthesis of glutathione by boosting cell energetics. FEBS Letters 569(1-3):169-172.

106. Lukienko, P.I., Mel’nichenko, N.G., Zverinskii, I.V., Zabrodskaya, S.V. 2000. Antioxidant properties of thiamine, Bulletin of Experimental Biology and Medicine. 130(9);874–876.

107. Takahashi, K., Newburger, P.E., Cohen, H.J. 1986. Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity. J Lin Invest. 77(4):1402-1404.



Dosage and Administration

The recommended adult dose is 1 capsule orally per day (with a meal) or as recommended by your health care practitioner.  Pre-DX is not recommended for use with children or during pregnancy.

 

Contraindications

Pre-DX is contraindicated in patients with known hypersensitivity to any of the components contains in this product.  Pre-DX contains folate, which may interact with certain drugs that interfere with folate absorption or metabolism of homocysteine. Consult your healthcare professional (e.g., doctor or pharmacist) for more information.  If you are pregnant or breastfeeding, check with a doctor before using Pre-DX.

 

Adverse Effects

Allergic reactions to 5-MTHF are rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including:  rash, itching/swelling, dizziness or trouble breathing. Nausea, vomiting, headache, other gastrointestinal symptoms, and rash have been associated with NAC.  There are rare reports of renal stone formations with NAC.

 

Pre-DX is a product of Southeast Healthcare Consultants, LLC.

 

For more information: info@pre-dx.com
or call 833-RxPreDX or (833) 797-7339
Southeast Healthcare Consultants, LLC
Franklin, TN 37064

 

Cancellation and Refunds

Subscriptions can be cancelled at any time for any reason.  We will refund 100% of your purchase price with no questions asked.  You do NOT need to return the product.  For a Full Refund please email: info@pre-dx.com

 *These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.