HOMOCYSTEINE

FOLIC ACID

1. Intravenous treatment with folinic acid (0.9 mg), vitamin B12 (cyanocobalamine 1.5 mg and hydroxycobalamine 1.5 mg) 3 times/week after dialysis significantly reduced homocysteine levels in hemodialysis patients compared to untreated patients.

G Ital Nefrol. 2002 May-Jun;19(3):301-7.
[Intravenous folinic acid and vitamin B12 supplementation and homocysteine concentration in hemodialysis patients]
[Article in Italian]
Corghi E, Patrosso C, Bamonti F, Baragetti I, Novembrino C, Lando G, De Franceschi M, Buccianti G.
PMID: 12195398

2. Treatment with folic acid (oral 15 mg/day) combined with intravenous methylcobalamin (500 mg after each hemodialysis) normalized homocysteine levels in hemodialysis patients compared to the control group. The addition of vitamin B6 did not alter the effectiveness of treatment. This treatment could be of benefit to patients with renal failure who are at risk for developing atherosclerosis and cardiovascular disease.

Nephrol Dial Transplant. 2002 May;17(5):916-22.
Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation.
Koyama K, Usami T, Takeuchi O, Morozumi K, Kimura G.
PMID: 11981084

3. Treatment with folic acid (intravenous 45 mg/week) for 10 weeks adding vitamin B12 (injected 500 micrograms) in the last 2 weeks, reduced homocysteine levels and improved endothelial functioning in hemodialysis patients with renal failure.

Nephrol Dial Transplant. 2002 May;17(5):857-64.
5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.
Buccianti G, Raselli S, Baragetti I, Bamonti F, Corghi E, Novembrino C, Patrosso C, Maggi FM, Catapano AL.
PMID: 11981074

4. Different dosing methods of folic acid: 1) calcium folinate (50 mg/week intravenous), 2) calcium folinate (50 mg/week oral), 3) folic acid (45 mg/week oral) combined with intravenous vitamin B6 (750 mg/week) and oral vitamin B12 (3 mg/week) for 6 months all had similar and significant effect on reducing homocysteine levels in hemodialysis patients.

Nephrol Dial Transplant. 2002 May;17(5):865-70.
Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.
Ducloux D, Aboubakr A, Motte G, Toubin G, Fournier V, Chalopin JM, Drueke T, Massy ZA.
PMID: 11981075

5. Treatment with folic acid (5 mg for two 8 week periods) reduced homocysteine levels in children with chronic renal failure. This may reduce risk of vascular disease associated with chronic renal failure.

Circulation. 2002 Apr 16;105(15):1810-5.
Comment in:
Circulation. 2003 Jan 7;107(1):e6-7; author reply e6-7.
Does oral folic acid lower total homocysteine levels and improve endothelial function in children with chronic renal failure?
Bennett-Richards K, Kattenhorn M, Donald A, Oakley G, Varghese Z, Rees L, Deanfield JE.
PMID: 11956124

(1 microgram = 0.001 milligrams)

6. A combination of folic acid (1 mg/day), vitamin B12 (6 micrograms/day) and vitamin B6 (6 mg/day) was effective in lowering homocysteine levels and potential risk for endothelial damage in children with sickle cell disease.

Am J Hematol. 2002 Apr;69(4):239-46.
Optimization of folic acid, vitamin B(12), and vitamin B(6) supplements in pediatric patients with sickle cell disease.
van der Dijs FP, Fokkema MR, Dijck-Brouwer DA, Niessink B, van der Wal TI, Schnog JJ, Duits AJ, Muskiet FD, Muskiet FA.
PMID: 11921017

7. Daily treatment with folate (10 mg for 2 months) significantly reduced homocysteine levels and improved endothelial dysfunction, oxidative stress and hypercoagulation in patients at risk for coronary artery disease or atherosclerosis.

Eur J Clin Pharmacol. 2002 Apr;58(1):1-5. Epub 2002 Feb 19.
The effects of folate supplementation on some coagulation parameters and oxidative status surrogates.
Mayer O Jr, Simon J, Rosolova H, Hromadka M, Subrt I, Vobrubova I.
PMID: 11956665

8. Doses of folic acid (15 mg/day for 2 months) reduced homocysteine levels in hemodialysis patients. When the folic acid therapy was followed by the addition of vitamin B12 (1 mg/day for another 2 months), there was no significant change to homocysteine levels.

Nephrol Dial Transplant. 2002 Mar;17(3):455-61.
Hyperhomocysteinaemia, folate and vitamin B12 in unsupplemented haemodialysis patients: effect of oral therapy with folic acid and vitamin B12.
Billion S, Tribout B, Cadet E, Queinnec C, Rochette J, Wheatley P, Bataille P.
PMID: 11865092

9. Treatment with folic acid (5 mg/day) reduced oxidative stress and homocysteine levels in renal transplant recipients.

Transplantation. 2002 Feb 27;73(4):663-5.
Treatment of hyperhomocysteinemia with folic acid reduces oxidative stress in renal transplant recipients.
Abdelfatah A, Ducloux D, Toubin G, Motte G, Alber D, Chalopin JM.
PMID: 11889451

10. Treatment with folic acid (5 mg/day for 6 weeks) improved endothelial function and reduced homocysteine levels in patients with coronary artery disease.

Circulation. 2002 Jan 1;105(1):22-6.
Comment in:
Circulation. 2002 Aug 13;106(7):e33.
Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering.
Doshi SN, McDowell IF, Moat SJ, Payne N, Durrant HJ, Lewis MJ, Goodfellow J.
PMID: 11772871

11. Doses of folate (5 – 15 mg/day) reduce homocysteine levels in patients with renal failure.

Nephrol Dial Transplant. 2002;17 Suppl 5:24-7.
Erratum in:
Nephrol Dial Transplant. 2002 Oct;17(10):1862.
Folate metabolism in renal failure.
Teschner M, Kosch M, Schaefer RM.
PMID: 12091603

12. A daily supplement of folic acid (926 micrograms) is required to maintain low levels of homocysteine and protect elderly people from cardiovascular disease.

QJM. 2002 Jan;95(1):27-35.
Comment in:
QJM. 2002 Jul;95(7):485.
The effect of folic acid supplementation on plasma homocysteine in an elderly population.
Rydlewicz A, Simpson JA, Taylor RJ, Bond CM, Golden MH.
PMID: 11834770

13. Treatment with folic acid (5 mg/day) plus pyridoxine (250 mg/day) lowered systolic and diastolic blood pressure, reduced homocysteine levels and had positive vascular effects in those with potential risk for atherothrombotic disease.

Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2072-9.
Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebo-controlled trial.
van Dijk RA, Rauwerda JA, Steyn M, Twisk JW, Stehouwer CD.
PMID: 11742887

14. Doses of folic acid (400 micrograms/day) lowered homocysteine levels in healthy adults.

J Am Coll Cardiol. 2001 Dec;38(7):1799-805.
Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype.
Pullin CH, Ashfield-Watt PA, Burr ML, Clark ZE, Lewis MJ, Moat SJ, Newcombe RG, Powers HJ, Whiting JM, McDowell IF.
PMID: 11738277

15. Doses of folic acid (1 mg), vitamin B12 (400 micrograms/day) and pyridoxine (10 mg/day) for 6 months after coronary angioplasty reduced homocysteine levels and decreased restenosis and thus should be considered in angioplasty patients.

N Engl J Med. 2001 Nov 29;345(22):1593-600.
Decreased rate of coronary restenosis after lowering of plasma homocysteine levels.
Schnyder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FR, Meier B, Turi ZG, Hess OM.
PMID: 11757505

16. Hemodialysis patients received vitamin E (400 mg after each session) for 3 months. After 1 month, they received folic acid (10 mg intravenously after hemodialysis). The folic acid reduced homocysteine levels and prevents lipid peroxidation, which can reduce risk of atherosclerosis and cardiovascular disease in hemodialysis patients.

Nephrol Dial Transplant. 2001 Nov;16(11):2172-5.
Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E.
Bayes B, Pastor MC, Bonal J, Junca J, Romero R.
PMID: 11682663

17. Compared to placebo, treatment with folic acid (5 mg/day for 12 weeks) reduced homocysteine levels and improved endothelial function in patients with coronary artery disease.

J Am Coll Cardiol. 2001 Jun 1;37(7):1858-63.
A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease.
Thambyrajah J, Landray MJ, Jones HJ, McGlynnFJ, Wheeler DC, Townend JN.
PMID: 11401123

18. Oral doses of calcium folinate (30 mg/3 times/week), vitamin B12 (500 mg/3 times/week) and vitamin B6 (200 mg/3 times/week) after hemodialysis sessions, reduced homocysteine levels in patients on hemodialysis.

Minerva Urol Nefrol. 2001 Jun;53(2):57-9.
[Effectiveness of oral supplements of folates, vitamins B12 and B6 in hemodialysed patients. Preliminary results after 5 months of follow-up]
[Article in Italian]
Sepe V, Ottone S, Patrucco G, Cecere P, Colombo P, Cagna G, Costantini L, Piccini G, Filiberti O, Peona C.
PMID: 11455311

19. This review indicates that doses of folate (from 0.2 – 10 mg/day) reduces homocysteine levels in patients with homocysteinemia and in healthy subjects. Folate may also prevent cardiovascular disease.

Int J Vitam Nutr Res. 2001 May;71(3):173-8.
Homocysteine, folate, and cardiovascular disease.
Ward M.
PMID: 11582839

20. Doses of minerals and vitamins: folic acid (800 micrograms), vitamin B12 (6 micrograms), vitamin B6 (10 mg) 3 times/week for 12 weeks decreased homocysteine levels to a greater degree than did folic acid alone.

J Ren Nutr. 2001 Apr;11(2):67-72.
Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.
Dierkes J, Domrose U, Bosselmann KP, Neumann KH, Luley C.
PMID: 11295026

21. A daily dose of folic acid (0.8 mg) is necessary to lower homocysteine levels, which is not readily available in a normal daily diet. Lowered homocysteine is linked to lower mortality from ischemic heart disease.

Arch Intern Med. 2001 Mar 12;161(5):695-700.
Comment in:
Arch Intern Med. 2002 Mar 11;162(5):608-9.
Randomized trial of folic acid supplementation and serum homocysteine levels.
Wald DS, Bishop L, Wald NJ, Law M, Hennessy E, Weir D, McPartlin J, Scott J.
PMID: 11231701

22. A daily dose of folic acid (1 mg) and vitamin B12 (1 mg/day) for 4 weeks lowered homocysteine levels in patients with renal disease.

Kidney Int. 2001 Mar;59(3):1103-9.
Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia.
Manns B, Hyndman E, Burgess E, Parsons H, Schaefer J, Snyder F, Scott-Douglas N.
PMID: 11231366

23. An injection of folate (1.1 mg), vitamin B12 (1 mg), and vitamin B6 (5 mg) 8 times in 21 days reduced homocysteine, methylmalonic acid and methylcitric acid levels in elderly patients. As high homocysteine levels may affect mental performance, supplementation is recommended.

Gerontology. 2001 Jan-Feb;47(1):30-5.
Long-term effects of vitamin B(12), folate, and vitamin B(6) supplements in elderly people with normal serum vitamin B(12) concentrations.
Henning BF, Tepel M, Riezler R, Naurath HJ.
PMID: 11244289

24. A daily dose of folic acid (1 or 2 mg) for 3 weeks reduced homocysteine levels in men and women.

Lipids. 2001;36 Suppl:S27-32.
Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations.
Malinow MR, Duell PB, Williams MA, Kruger WD, Evans AA, Anderson PH, Block PC, Hess DL, Upson BM, Graf EE, Irvin-Jones A, Wang L.
PMID: 11837988

25. Supplementation with folic acid (400 micrograms) and vitamin B12 (500 micrograms) lowers homocysteine and could result in reduced risk from coronary heart disease and therefore reduce economic costs associated with coronary heart disease.

Arch Intern Med. 2000 Dec 11-25;160(22):3406-12.
Potential clinical and economic effects of homocyst(e)ine lowering.
Nallamothu BK, Fendrick AM, Rubenfire M, Saint S, Bandekar RR, Omenn GS.
PMID: 11112233

26. Daily supplementation with folic acid (5 mg) and vitamin B12 (1 mg) improved flow-mediated dilatation and endothelial function, and reduced homocysteine levels in patients with coronary heart disease.

Circulation. 2000 Nov 14;102(20):2479-83.
Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine.
Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, Kooner JS.
PMID: 11076820

27. A daily dose of folic acid (either 250 micrograms or 500 micrograms) for 4 weeks significantly reduced homocysteine levels in women.

Indian Heart J. 2000 Nov-Dec;52(7 Suppl):S53-58.
Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial.
Brouwer IA, van Dusseldorp M, Thomas CMG, Duran M, Hautvast JGAJ, Eskes TKAB, Steegers-Theunissen RP.
PMID: 11339442

28. Compared to placebo, daily doses of folic acid (500 micrograms) reduced homocysteine levels in postmenopausal women.

Am J Obstet Gynecol. 2000 Oct;183(4):945-7.
Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women.
De Leo V, La Marca A, Morgante G, Ciani F, Zammarchi E, Setacci C.
PMID: 11035344

29. Daily supplements of folate (427 micrograms) and folate enriched breakfast cereal (to increase folate to 600 micrograms/day) resulted in a decrease in plasma homocysteine levels in adults 36 – 71 years of age.

Am J Clin Nutr. 2000 Jun;71(6):1448-54.
Dietary strategies for lowering homocysteine concentrations.
Riddell LJ, Chisholm A, Williams S, Mann JI.
PMID: 10837284

30. Daily doses of folate (1 mg), vitamin B12 (0.2 mg), and vitamin B6 (100 mg) for 6 weeks reduced homocysteine in patients with venous thromboembolism.

Med Clin (Barc). 2000 Jan 15;114(1):7-12.
[Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype]
[Article in Spanish]
Gonzalez Ordonez AJ, Medina Rodriguez JM, Fernandez Alvarez CR, Sanchez Garcia
J, Fernandez Carreira JM, Alvarez Martinez MV, Coto Garcia E.
PMID: 10782453

31. A daily dose of folic acid (250 micrograms) is more effective than 500 micrograms/day in reducing homocysteine levels in healthy women.

Ann Nutr Metab. 2000;44(5-6):194-7.
Homocysteine-lowering effect of 500 microg folic acid every other day versus 250 microg/day.
Brouwer IA, van Rooij IA, van Dusseldorp M, Thomas CM, Blom HJ, Hautvast JG, Eskes TK, Steegers-Theunissen RP.
PMID: 11146323

32. Supplementation with folic acid (10 mg/day for 8 weeks) improved homocysteine levels and endothelial functioning in healthy adults compared to placebo.

J Am Coll Cardiol. 1999 Dec;34(7):2002-6.
Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.
Woo KS, Chook P, Lolin YI, Sanderson JE, Metreweli C, Celermajer DS.
PMID: 10588216

33. Daily doses of folic acid (2.15 mg) significantly reduced homocysteine levels for up to 6 years without side effect.

Nephrol Dial Transplant. 1999 Dec;14(12):2903-6.
Sustained reduction of hyperhomocysteinaemia with folic acid supplementation in predialysis patients.
Jungers P, Joly D, Massy Z, Chauveau P, Nguyen AT, Aupetit J, Chadefaux B.
PMID: 10570095

34. Daily doses of folic acid (5 mg), vitamin B6 (300 mg) and vitamin B12 (1000 micrograms injected/week), for 8 weeks reduced homocysteine levels and the amount of thrombin produced.

Thromb Res. 1999 Sep 15;95(6):281-8.
Treatment of hyperhomocysteinemia with folic acid and vitamins B12 and B6 attenuates thrombin generation.
Undas A, Domagala TB, Jankowski M, Szczeklik A.
PMID: 10527405

35. Daily doses of folic acid (5 mg) for 6 weeks reduced homocysteine levels and improved endothelial function in patients with hyperhomocysteinaemia.

Eur J Clin Invest. 1999 Aug;29(8):659-62.
Comment in:
Eur J Clin Invest. 1999 Aug;29(8):657-8.
Oral folate enhances endothelial function in hyperhomocysteinaemic subjects.
Bellamy MF, McDowell IF, Ramsey MW, Brownlee M, Newcombe RG, Lewis MJ.
PMID: 10457148

36. Patients with normal homocysteine levels had similar incidence of cardiovascular events as patients with hyperhomocysteinaemia taking supplements of folic acid (5 mg/day) and vitamin B6 (250 mg/day).

J Intern Med. 1999 Jul;246(1):87-96.
Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature peripheral arterial occlusive disease. A prospective cohort study.
de Jong SC, Stehouwer CD, van den Berg M, Geurts TW, Bouter LM, Rauwerda JA.
PMID: 10447230

37. Daily doses of folic acid (400 micrograms/day), vitamin B6 (12.5 mg) and vitamin B12 (500 micrograms) reduced homocysteine levels to the same degree as 1 mg or 5 mg folic acid/day

Am J Cardiol. 1999 Mar 15;83(6):821-5.
Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12.
Lobo A, Naso A, Arheart K, Kruger WD, Abou-Ghazala T, Alsous F, Nahlawi M, Gupta A, Moustapha A, van Lente F, Jacobsen DW, Robinson K.
PMID: 10190392

38. Daily doses of folic acid (0.5 mg) and pyridoxine (100 mg) for 8 weeks reduced homocysteine levels in patients with premature arterial disease and their at-risk relatives.

Atherosclerosis. 1999 Mar;143(1):177-83.
Combination of low-dose folic acid and pyridoxine for treatment of hyperhomocysteinaemia in patients with premature arterial disease and their relatives.
van der Griend R, Haas FJ, Biesma DH, Duran M, Meuwissen OJ, Banga JD.
PMID: 10208493

39. Compared to placebo, doses of folic acid (either 250 micrograms/day or 500 micrograms/day) reduced homocysteine levels in healthy women.

Am J Clin Nutr. 1999 Jan;69(1):99-104.
Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial.
Brouwer IA, van Dusseldorp M, Thomas CM, Duran M, Hautvast JG, Eskes TK, Steegers-Theunissen RP.
PMID: 9925130

40. Doses of folate (2 mg/day) reduce homocysteine levels but may not be enough to reduce homocysteine in patients with renal failure.

Am J Nephrol. 1999;19(3):405-10.
Effect of usual doses of folate supplementation on elevated plasma homocyst(e)ine in hemodialysis patients: no difference between 1 and 5 mg daily.
Spence JD, Cordy P, Kortas C, Freeman D.
PMID: 10393379

41. This review suggests that folic acid at a dose of 200 micrograms may be the minimum required to maintain homocysteine levels and prevent neural tube defects.

Ann Pharmacother. 1998 Oct;32(10):1087-95.
Drug and environmental factors associated with adverse pregnancy outcomes. Part III: Folic acid: pharmacology, therapeutic recommendations, and economics.
Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ.
PMID: 9793602

42. The recommended daily allowance of folate (180 micrograms/day) is reported to be insufficient to maintain low homocysteine levels in postmenopausal women.

J Nutr. 1998 Jul;128(7):1204-12.
Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women.
Jacob RA, Gretz DM, Taylor PC, James SJ, Pogribny IP, Miller BJ, Henning SM, Swendseid ME.
PMID: 9649607

43. A diet including cereal enriched with folic acid (200 micrograms) reduced homocysteine levels compared to an unenriched diet. Those with the highest homocysteine levels had the greatest reduction in homocysteine.

Eur J Clin Nutr. 1998 Jun;52(6):407-11.
The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study.
Schorah CJ, Devitt H, Lucock M, Dowell AC.
PMID: 9683392

44. Supplementation with vitamins (1 mg folic acid, 7.2 mg pyridoxine, and 0.02 mg vitamin B12) was more effective at reducing homocysteine in healthy males than supplementation with antioxidants (150 mg ascorbic acid, 67 mg vitamin E and 9 mg beta-carotene).

Am J Clin Nutr. 1998 May;67(5):858-66.
Erratum in:
Am J Clin Nutr 1998 Sep;68(3):758.
Comment in:
Am J Clin Nutr. 1999 Jun;69(6):1287-9.
Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial.
Woodside JV, Yarnell JW, McMaster D, Young IS, Harmon DL, McCrum EE, Patterson CC, Gey KF, Whitehead AS, Evans A.
PMID: 9583842

45. A daily dose of folic acid (5 mg) maintained low homocysteine levels in healthy volunteers. The recommendation is that the recommended daily allowance of folic acid is not sufficient to maintain low homocysteine levels and therefore lower the risk of atherosclerosis.

Ned Tijdschr Geneeskd. 1998 Apr 4;142(14):782-6.
[Recommended dietary allowance of folic acid is insufficient for optimal homocysteine levels]
[Article in Dutch]
Brouwer DA, Welten HT, van Doormaal JJ, Reijngoud DJ, Muskiet FA.
PMID: 9646611

46. Daily doses of folic acid (0.5 – 5 mg) and vitamin B12 (0.5 mg) can lower homocysteine levels by a third or a quarter.

BMJ. 1998 Mar 21;316(7135):894-8.
Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration.
[No authors listed]
PMID: 9569395

47. Daily doses of folic acid (5 mg), pyridoxine (50 mg) and vitamin B12 (0.4 mg) reduced homocysteine levels in subjects with high and with normal homocysteine. In addition, different daily doses of folic acid alone (0.5 mg or 5 mg) both reduced homocysteine levels in subjects with normal homocysteine.

Arterioscler Thromb Vasc Biol. 1998 Mar;18(3):356-61.
Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers.
den Heijer M, Brouwer IA, Bos GM, Blom HJ, van der Put NM, Spaans AP, Rosendaal FR, Thomas CM, Haak HL, Wijermans PW, Gerrits WB.
PMID: 9514403

48. Supplementation with folic acid alone (400 micrograms/day) was as effective as adding vitamin B6 (2 mg/day) and more effective that vitamin B6 alone in reducing homocysteine levels in healthy women.

Int J Vitam Nutr Res. 1998;68(2):98-103.
Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women.
Dierkes J, Kroesen M, Pietrzik K.
PMID: 9565824

49. Daily doses of folic acid (5 mg) for 4 weeks significantly lowered homocysteine levels in patients on dialysis with renal disease.

Nippon Jinzo Gakkai Shi. 1998 Jan;40(1):8-16.
[Effects of folic acid supplementation on hyperhomocysteinemia in CAPD patients: effects on unsaturated fatty acids]
[Article in Japanese]
Hirose S, Kim S, Matsuda A, Itakura Y, Matsumura O, Tamura H, Nagasawa R, Mitarai T, Isoda K.
PMID: 9513377

50. A daily intake of folate (350 micrograms) is required to prevent increases in plasma homocysteine levels in the general population.

Eur J Clin Nutr. 1997 Oct;51(10):643-60.
Folate intake in Europe: recommended, actual and desired intake.
de Bree A, van Dusseldorp M, Brouwer IA, van het Hof KH, Steegers-Theunissen RP.
PMID: 9347284

51. Doses of folic acid (10 mg 3 times/week) corrected the low plasma folic acid levels that were present in 80% of all hemodialysis patients. It also corrected elevated homocysteine levels.

Clin Nephrol. 2000 Jan;53(1):48-54.
Erythropoietin, folic acid deficiency and hyperhomocysteinemia: is there a possible relationship in chronically hemodialyzed patients?
Korzets A, Ori Y, Chagnac A, Weinstein T, Herman M, Zevin D, Malachi T, Gafter U.
PMID: 10661482

52. Daily doses of folic acid (0.5 – 5 mg) and vitamin B12 (0.5 mg) lowered homocysteine levels while vitamin B6 had no effect. Thus, the risk is lowered for coronary, cerebral, and peripheral vascular disease.

Semin Thromb Hemost. 2000;26(3):341-8.
Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements.
Clarke R, Armitage J.
PMID: 11011852

53. Folic acid at a dose of 2.4 mg/day is superior to a dose of 0.4 mg/day folic acid in reducing homocysteine levels in renal transplant recipients. All subjects were also supplemented with vitamin B6 (50 mg/day) and vitamin B12 (0.4 mg/day).

Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):2918-21.
Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients.
Beaulieu AJ, Gohh RY, Han H, Hakas D, Jacques PF, Selhub J, Bostom AG.
PMID: 10591669

TMG BETAINE
(1 gram = 1000 milligrams)

54. Compared to placebo, a daily dose of either betaine (6 grams) or folic acid (800 micrograms – 0.8 mg) for 6 weeks both reduced homocysteine levels to a similar degree after a methionine-loading test.

J Nutr. 2003 May;133(5):1291-5.

Betaine supplementation lowers plasma homocysteine in healthy men and women.

Steenge GR, Verhoef P, Katan MB.

55. A daily dose of betaine (6 grams) for 12 weeks with a hypoenergetic diet decreased homocysteine levels compared to the group not receiving supplementation.

Am J Clin Nutr. 2002 Nov;76(5):961-7.

Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects.

Schwab U, Torronen A, Toppinen L, Alfthan G, Saarinen M, Aro A, Uusitupa M.

56. Supplementation with betaine (3 grams/day from months 3 - 15) reduced homocysteine and homocystinuria in an infant and improved neurological development and growth.

An Esp Pediatr. 2002 Apr;56(4):337-41.

[Neonatal onset methylmalonic aciduria and homocystinuria:Biochemical and clinical improvement with betaine therapy]

[Article in Spanish]

Urbon Artero A, Aldana Gomez J, Reig Del Moral C, Nieto Conde C, Merinero Cortes B.

57. A daily dose of betaine (6 – 9 grams/day) lowered homocysteine levels in patients with homocystinuria who did not respond to therapy with pyridoxine, folic acid and vitamin B12. This is a safe and effective dosage for up to 16 years.

J Inherit Metab Dis. 1997 Jun;20(2):295-300.

The natural history of vascular disease in homocystinuria and the effects of treatment.

Wilcken DE, Wilcken B.

58. A d aily dose of betaine (3 grams/day) lowered homocysteine levels without side effects in patients with homocystinuria who did not respond to therapy with pyridoxine.

J Inherit Metab Dis. 1988;11(3):291-8.

The effect of oral betaine on vertebral body bone density in pyridoxine-non-responsive homocystinuria.

Gahl WA, Bernardini I, Chen S, Kurtz D, Horvath K.

59. A dose of betaine (6 grams/day) added to pyridoxine and folic acid reduced homocysteine levels to normal after a methionine-loading test.

Metabolism. 1985 Dec;34(12):1115-21.

Homocystinuria due to cystathionine beta-synthase deficiency--the effects of betaine treatment in pyridoxine-responsive patients.

Wilcken DE, Dudman NP, Tyrrell PA.

60. Doses of betaine (15 – 20 grams/day) improved homocysteine remethylation, reducing homocysteine levels in a patient with homocystinuria.

Eur J Pediatr. 1984 Jun;142(2):147-50.

Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.

Wendel U, Bremer HJ.

61. Patients taking antiepileptic drugs are prone to high homocysteine levels, which were lowered with daily doses of folic acid (0.4 mg), pyridoxine (120 mg) and riboflavin (75 mg) for 30 days. The supplements also improved endothelial function.

Epilepsy Res. 2002 Oct;51(3):237-47.
The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs.
Apeland T, Mansoor MA, Pentieva K, McNulty H, Seljeflot I, Strandjord RE.
PMID: 12399074

62. Daily doses of folic acid (2.5 mg), riboflavin (5 mg), vitamin B12 (0.4 mg) for 12 weeks lowered homocysteine levels in patients with coronary artery disease compared to placebo or to subjects consuming cereals fortified with folic acid.

Arterioscler Thromb Vasc Biol. 2002 Mar 1;22(3):488-91.
Total homocysteine lowering treatment among coronary artery disease patients in the era of folic acid-fortified cereal grain flour.
Bostom AG, Jacques PF, Liaugaudas G, Rogers G, Rosenberg IH, Selhub J.
PMID: 11884295

VITAMIN B6/PYRIDOXINE

63. Daily doses of vitamin B6 (1.6 mg/day for 12 weeks) were given to subjects who had been given folic acid (400 micrograms/day) and riboflavin (1.6 mg/day) for 18 weeks and were therefore replete with these supplements. The vitamin B6 supplementation lowered homocysteine levels.

Am J Clin Nutr. 2001 Apr;73(4):759-64.
Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete.
McKinley MC, McNulty H, McPartlin J, Strain JJ, Pentieva K, Ward M, Weir DG, Scott JM.
PMID: 11273851

64. Doses of pyridoxine ((240 mg/day) and folic acid (10 mg/day) reduced homocysteine levels without side effect in patients with early onset vascular disease.

Atherosclerosis. 1990 Feb;81(1):51-60.
Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment.
Brattstrom L, Israelsson B, Norrving B, Bergqvist D, Thorne J, Hultberg B, Hamfelt A.
PMID: 2407253

65. A combination of vitamin B6 (120 mg/day) and folic acid (0.3 mg/day) reduced homocysteine levels to a greater degree than folic acid alone.

Scand J Clin Lab Invest. 1999 Apr;59(2):139-46.
Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6 ) in healthy individuals. Oral doses of vitamin B6 reduce concentrations of serum folate.
Mansoor MA, Kristensen O, Hervig T, Bates CJ, Pentieva K, Vefring H, Osland A, Berge T, Drablos PA, Hetland O, Rolfsen S.
PMID: 10353328

66. Doses of folic acid (0.2 mg), vitamin B6 (8.0 mg) and vitamin B12 (0.010 mg) 3 times/day prevented increases in homocysteine levels in slightly overweight subject on a weight reduction program.

Res Exp Med (Berl). 1998 Jul;198(1):37-42.
Vitamin supplementation during weight reduction--favourable effect on homocysteine metabolism.
Henning BF, Tepel M, Riezler R, Gillessen A, Doberauer C
PMID: 9706668

VITAMIN B12/COBALAMIN
(1 microgram = 0.001 milligrams)

67. Daily doses of vitamin B12 (100 micrograms) reduced homocysteine levels in patients with hyperhomocysteinemia.

Mo Med. 2003 Mar-Apr;100(2):155-8.
Interrelationship of homocysteine-cobalamin-folate indices in human subjects of various ages: can hyper-homocyteinemia be relieved with B-12 supplementation?
Flynn MA, Singh A, Slaughter J, King P, Krause G, Herbert V, Thomas W.
PMID: 12710169

68. Hemodialysis patients taking folic acid (1 mg/day) were given a multivitamin containing folic acid (1 mg/day) and vitamin B12 (1 mg/day) for 4 weeks after which they were given either placebo of folic acid (1 mg/day) for another 4 weeks. Supplementation with folic acid and B12 reduced homocysteine levels more than folic acid alone.

Metabolism. 2003 Feb;52(2):168-72.
Vitamin B12 decreases, but does not normalize, homocysteine and methylmalonic acid in end-stage renal disease: a link with glycine metabolism and possible explanation of hyperhomocysteinemia in end-stage renal disease.
Hyndman ME, Manns BJ, Snyder FF, Bridge PJ, Scott-Douglas NW, Fung E, Parsons HG.
PMID: 12601627

69. Five injections of vitamin B12 (2200 micrograms) over 2 weeks reduced homocysteine levels in vegans and vegetarians who were deficient in vitamin B12 and had elevated homocysteine levels.

Ceska Slov Farm. 2002 Nov;51(6):310-2.
[Therapy of hyperhomocysteinemia with vitamin B12]
[Article in Slovak]
Krajcovicova-Kudlackova M, Blazicek P, Sebekova K, Valachovicova M.
PMID: 12501494

70. Daily doses of vitamin B12 (1500 micrograms) and folic acid (5 mg) given to patients with ischemic stroke reduced homocysteine levels to a greater degree than either supplement individually.

J Neurol Sci. 2002 Oct 15;202(1-2):65-8.
Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic stroke: effect of combined therapy with folic acid and mecobalamine.
Sato Y, Kaji M, Kondo I, Yoshida H, Satoh K, Metoki N.
PMID: 12220694

71. Daily doses of vitamin B12 (400 micrograms), folic acid (1 mg) and pyridoxine (10 mg), given to patients with recent angioplasty reduced homocysteine and the number of coronary incidence after surgery.

JAMA. 2002 Aug 28;288(8):973-9.
Comment in:
ACP J Club. 2003 Mar-Apr;138(2):33.
J Fam Pract. 2003 Jan;52(1):16-8.
Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial.
Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM.
PMID: 12190367

72. Daily oral doses of folic acid (5 - 6 mg) and pyridoxine (5 - 10 mg) more effectively reduced homocysteine levels in patients with renal failure when combined with injected vitamin B12 (1 mg/week after dialysis) than when oral vitamin B12 (10 micrograms) was added to the supplements.

Metabolism. 2002 Jul;51(7):881-6.
Hydroxocobalamin reduces hyperhomocysteinemia in end-stage renal disease.
Elian KM, Hoffer LJ.
PMID: 12077735

73. Intravenous treatment with folinic acid (0.9 mg) and vitamin B12 (1.5 mg cyanocobalamine and 1.5 mg hydroxycobalamine) significantly lowered homocysteine levels in hemodialysis patients following dialysis compared to no treatment.

74. Nitrous oxide anesthesia increases homocysteine levels and therefore can increase myocardial ischemia following surgery. A daily dose of folate (2.5 mg), vitamin B6 (25 mg), vitamin B12 (500 micrograms) for 1 week before surgery prevented the increase in homocysteine levels and the associated myocardial ischemia compared to placebo.

Anesth Analg. 2001 Dec;93(6):1507-10, table of contents.
Comment in:
Anesth Analg. 2002 Sep;95(3):787.
Preoperative oral B vitamins prevent nitrous oxide-induced postoperative plasma homocysteine increases.
Badner NH, Freeman D, Spence JD.
PMID: 11726432

75. Injected doses of vitamin B12 (1 mg/month) for 3 months reduced homocysteine levels in hemodialysis patients with renal disease.

Clin Invest Med. 2001 Feb;24(1):5-11.
Parenteral vitamin B12 reduces hyperhomocysteinemia in end-stage renal disease.
Kaplan LN, Mamer OA, Hoffer LJ.
PMID: 11266032

76. Injected vitamin B12 (1 mg/month) with oral folic acid (1 mg/day) was more effective than folic acid (6 mg/day) homocysteine in patients with renal failure on hemodialysis.

Metabolism. 2000 Feb;49(2):215-9.
A tale of two homocysteines--and two hemodialysis units.
Hoffer LJ, Bank I, Hongsprabhas P, Shrier I, Saboohi F, Davidman M, Bercovitch DD, Barre PE.
PMID: 10690947

77. Injected vitamin B12 (1 mg/week for 4 weeks) reduced homocysteine in renal disease patients with low levels of vitamin B12.

Metabolism. 1999 May;48(5):631-5.
Supplementation with vitamin B12 decreases homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease.
Dierkes J, Domrose U, Ambrosch A, Schneede J, Guttormsen AB, Neumann KH, Luley C.
PMID: 10337865

78. Daily oral doses of folic acid (1 mg) and pyridoxine (10 mg) and vitamin B12 (0.05 mg) for 6 weeks reduced homocysteine levels 54% in men with hyperhomocysteinemia. When supplementation ended, some homocysteine levels rose again after 18 weeks indicating that supplementation may be required long term to avoid hyperhomocysteinemia.

Clin Investig. 1993 Dec;71(12):993-8.
Hyperhomocysteinemia and the response to vitamin supplementation.
Ubbink JB, van der Merwe A, Vermaak WJ, Delport R.
PMID: 8124058

79. Doses of vitamin B12 (1 mg/day for 12 weeks) reduced plasma homocysteine levels in patients with dementia.

J Intern Med. 2003 Jul;254(1):67-75.
Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia.
Clarke R, Harrison G, Richards S; Vital Trial Collaborative Group.

VITAMIN C/ASCORBIC ACID

80. Different doses of vitamin C (2 gram single dose) or (1 gram/day for 6 months) each improved endothelial function in patients with high levels of homocysteine.

J Inherit Metab Dis. 2002 May;25(2):107-18.
Vitamin C therapy ameliorates vascular endothelial dysfunction in treated patients with homocystinuria.
Pullin CH, Bonham JR, McDowell IF, Lee PJ, Powers HJ, Wilson JF, Lewis MJ, Moat SJ.