6. Homocysteine levels in vegetarian and non
vegetarian life style – Epidemiology in India
India predominantly
follows vegetarian food
habits
Higher levels of
homocysteine due to
Vitamin B12 deficiency
www.veganhealth.org as accessed on 28th April 2012 Homocysteine Levels
7. Homocysteine and Pregnancy
Homocysteine conc. decreased in pregnancy due to
Hemodilution
Raised GFR
Hormonal changes of pregnancy
Increased fetal uptake
Hague WM Best Practice & Research Clinical Obstetrics & Gynaecology 2003;17(3):459–469, 2003
8. Indian Study
2010
Hyperhomocysteinemia in Pregnancy
In an Indian maternal nutrition study, two thirds of
pregnant mothers had low levels of vitamin B12
Only an occasional mother had low folate concentration.
Vitamin B12 and folate play vital role in one carbon (1-C)
metabolism, crucial for fetal growth
This study showed that the plasma tHcy concentration at
34 weeks gestation was lower in those who received
vitamin B12 supplementation compared to those who
received only folic acid or no supplementation
Katre P et al. Vitamin B12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12
and high folate status Asia Pac J Clin Nutr 2010;19 (3):335-343
9. Hyperhomocysteinemia is an independent causal factor
in pregnancy complications
……..Current Drug Metabol 2007 Jan;8(1):17-31
10. Clinical outcomes in Pregnancy
Approximately 2-fold to 3-fold increased risk for :
• Pregnancy-induced hypertension
• Abruptio placentae
• Intrauterine growth restriction
Cobalamine deficiency :
• HELLP syndrome
• Abruptio placentae
• Intrauterine growth restriction
• Intrauterine fetal death
Pyridoxal 5-phosphate deficiency
• Increased risk for pregnancy-induced hypertension 4-fold
Hyperhomocysteinemia, Pregnancy Complications and the Timing of Investigation
Re´gine P. Steegers-Theunissen,et al. VOL. 104, NO. 2, AUGUST 2004
The American College of Obstetricians and Gynecologists as accessed on 29 th April 2012
11. Other congenital defects
spontaneous
miscarriage recurrent abortion
NTDs
IUGR
Hyperhomocysteinemia
Pre-term labour
Intrauterine fetal death Pre-eclampsia
placental abruption
Hyperhomocysteinemia, Pregnancy Complications and the Timing of Investigation
Re´gine P. Steegers-Theunissen,et al. VOL. 104, NO. 2, AUGUST 2004
The American College of Obstetricians and Gynecologists as accessed on 29 th April 2012
13. J Nutr. 2006 Jun;136(6 Suppl):1731S-1740S
Women with hyperhomocysteinemia have
increased risk of pregnancy complications
and adverse pregnancy outcome
14. BJOG. 2006 Dec;113(12):1412-8
Maternal hyperhomocysteinemia is a risk factor for
Congenital Heart Disease
Clin Chem Lab Med 2005; 43(10): 1052-7
Early abortion, pregnancy complications and poor
pregnancy outcomes have been linked to
hyperhomocysteinemia
15. American Journal of Perinatology. January 2006; 23(1):31-35
Hyperhomocysteinemia during pregnancy is a risk
factor for development of preeclampsia and its
complications
Eur J. of Obs & Gynae & Reprod Biol 2003
Numerous studies have demonstrated association
between increased levels of homocysteine and
spontaneous miscarriages, IUGR, preeclampsia
and fetal death
16. Pregnancy outcomes are multi-factorial
Sundrani D.P. et al. / Medical Hypotheses 77 (2011) 878–883
17. Hyperhomocysteinemia as risk factor
Pregnant women with hyperhomocysteinemia have a 7.7-fold
risk for preeclampsia
Hyperhomocysteinemia associated with recurrent pregnancy
loss
MHTFR mutation in 16% cases
López-Quesada E, Vilaseca MA, Lailla JM. Eur J Obstet Gynecol Reprod
Biol. 2003 May 1;108(1):45-9.
18. Diagnostic Measures
When to Screen ?
Values in early pregnancy are more reliable
Second-trimester plasma homocysteine concentrations do not
predict the subsequent development of pregnancy-induced
hypertension, preeclampsia, and intrauterine growth
restriction
Hogg BB, Tamura T, Johnston KE, Dubard MB, Goldenberg RL. Am J Obstet Gynecol. 2000 Oct;183(4):805-9
Zeeman GG, Alexander JM, McIntire DD, Devaraj S, Leveno KJ. Am J Obstet Gynecol. 2003 Aug;189(2):574-6 as accessed
on 28th April 2012
20. Treatment
Dietary modification
Folate supplementation[500-5000microgram/day]
Vitamin B12 supplementation
particulary for indian population due to high prevalance of
vegeterian diet
Supplementation of pyridoxine[B6]
Sundrani D.P. et al. / Medical Hypotheses 77 (2011) 878–883
Hague WM Best Practice & Research Clinical Obstetrics & Gynaecology 2003;17(3):459–469, 2003
21. Role of vitamin B6, B9 and B12 in management
Methionine is an essential amino acid obtained from
protein in the diet
Some methionine is turned into homocysteine
The body turns much of this homocysteine back into
methionine with the help of vitamin B12
Low vitamin B6 status can also cause elevated
homocysteine in some people
www.brewboost.com as accessed on 1st May 2012
22. Role of vitamin B6, B9 and B12 in management
Demethylation
Methionine synthase
Cystathionine beta
synthase
Transsulfuration
Available at www.medscape.com as accessed on Aug 2012
MTHFR- methyl tetrahydrofolate reductase
23. FOLIC ACID
Important cofactor in the Remethylation of Homocysteine
Making of new cells and cell replicatio n
Folic acid-vitamin B supplementation significantly
reduce total Hcy levels
Low conc associated with risk of preterm delivery,
Low birth weight infants and IUGR
AJCN. 2000; 71: 1295S-1303S,
Am J Obstet Gynecol. 2004 Dec;191(6):1851-7.
Bostom et al, 2002
24. VITAMIN B12
A cofactor, Methionine Synthetase (MS) in methylation
Enzyme, catalyses the transfer of CH3 group from
MethylTetrahydrofolate Homocysteine
In Vit. B12 def, folate is trapped as unusable MTHF,
causing functional folate deficiency.
Thus plays a key role in the remethylation of
Homocysteine to Methionine.
25. VITAMIN B6
A cofactor, Pyridoxal Phosphate in methylation
Reduces the level of homocysteine by the process of
transulfuration to cysteine & hence related
pregnancy complications are reduced
Vitamin B6 levels of mothers at the onset of
pregnancy have a positive correlation with birth
weight of newborns
Effective in the treatment of nausea and vomiting of
pregnancy
Int J Vitam Nutr Res. 1978;48(4):341-7
27. Folate, Vitamin B12 & B6 - effective & safe to
reduce homocysteine levels
The relationship between serum homocysteine (hcy)
levels and pregnancy complications was studied
Homocysteine lowering effects of folate, vitamin B12 and
Vitamin B6
332 pregnant women
They were given-
folate- 5 mg/day, vitamin B12- 1000 mcg/day for 6 weeks
and of vitamin B6- 1000 mcg/day
Quereshi S et al. JPMA 60:741; 2010
28. Folate, Vitamin B12 & B6 - effective & safe to
reduce homocysteine levels
Quereshi S et al. JPMA 60:741; 2010
29. Conclusion
Folate, Vitamin B12 & B6 supplementation is effective & safe to reduce
homocysteine levels
Quereshi S et al. JPMA 60:741; 2010
30. Conclusion
Vitamins (folate, B6, B12) play important role in metabolism
of homocysteine
Deficiency of vitamins (folate, B6, B12) is associated with
hyperhomocysteinemia
Hyperhomocysteinemia may be associated with some of the
complications in preganancy
Supplementation of Folic acid, B6 and B12 is effective and safe
in reducing homocysteine levels
31. Prophylaxis
Folic acid and vitamins B6 and B12 are necessary in metabolism
of Hcys; therefore they can be used for both treatment and
prophylaxis of hyperhomocysteinemia
Proper diet
Abstaining from tobacco or smoking
Optimal physical activity
http://www.czytelniamedyczna.pl/3431,prophylaxis-and-treatment-of-hyperhomocysteinemia.html
32. Top Three “Best Practices” to Improve Birth
Outcomes & Reduce High Risk Births (NGA, June
2004)
Improve access to medical care and health care
services
Encourage good nutrition and healthy lifestyles
Eating healthy foods
Taking folic acid (Methylating agents)
Reduce use of harmful substances
Available at http://www.nga.org/cms/home/nga-center-for-best-practices/ as accessed on Aug 2012
33. Summary
Hyperhomocysteinemia is independent causal factor
for pregnancy complications
Folic acid, methylcobalamin and pyridoxine
deficiencies lead to hyperhomocysteinemia and are
prevalent in pregnant women
Supplementation of folic acid, methylcobalamin and
pyridoxine helps in management of
hyperhomocysteinemia
Levels of homocysteine are closely related to B vitamins; the conversion of homocysteine to methionine in the remethylation pathway requires folic acid and B12. The conversion of homocysteine to cystathionine and cysteine through transsulfation necessitates B6. Therefore, lowered levels of B12 or B6 can be associated with elevated homocysteine concentrations. Folic acid deficiency or methylenetetrahydrofolate reductase (MTHFR) deficiency are also causes of hyperhomocysteinemia. The recognition that homocysteine may play a role in hypercoagulability should raise consideration of nutritional replacement in patients with malignancy or pregnancy. Similarly, patients with known hypercoagulability due to inherited defects of the APC pathway should maintain adequate stores of folic acid, B12, and B6.