Mary Hannon-Fletcher

1. Micronutrient supplementation in haemodialysis patient enhances folate levels and reduces homocysteine Mary Hannon-Fletcher 4th Annual Translational Medicine Conference City Hotel, Derry/Londonderry, Northern Ireland 10-11 May 2012

2. Background • Cardiovascular diseases (CVD) are the leading cause of death in HD patients • 40-50% of the mortality • In addition to the traditional risk factors for CVD • Patients undergoing haemodialysis (HD) have additional cardiovascular risk factors: • hyperhomocysteinaemia • <15µmol/L, increased risk of cardiovascular disease < 10µmol/L • increased vascular oxidative stress • HD enhances this metabolic disorder

3. Hyperhomocysteinaemia

4. Oxidative Stress • Imbalance in the pro-oxidant : antioxidant. • overproduction of the precursors of reactive oxygen species (ROS) • decreased efficiency of inhibitory and scavenging systems • Antioxidants defences compromised in HD patients • ROS are well known to be capable of causing cellular and tissue damage

5. Diet in HD patients • Malnutrition is prevalent in 40-50% • Very restricted diets resulting in regulation of certain nutrients such as: • sodium, potassium, phosphate, protein & fluids • Reduction or exclusion of certain foods increases the risk of inadequate intakes • Under-nutrition exacerbates oxidative stress • Together with the increased losses of essential minerals and water-soluble vitamins via HD • Many studies have reported HD patients deficient in several important vitamins

6. Aims • To examine the effect of a 12 month placebo controlled micronutrient supplement (containing folic acid, B vitamins, antioxidant vitamins and trace elements) on folate and homocysteine (tHcy) levels in HD patients

7. Study Design Recruited n = 39 Baseline clinical history: blood Treatment n =18 Placebo n=19 Randomised to treatment on baseline tHcy 48 week intervention n=16 n = 14 Post Intervention clinical history: blood

8. Participants and Methods • Ethical permission was obtained from ORECNI and Governance was obtained from the WHSCT • tHcy was measured using an immunoassay • Plasma folate and whole blood folate were measured by a microbiological assay • Supplements were provided monthly in a bottle by the pharmacist • Volunteers were withdrawn if less than 90% of the supplements were taken

9. Table 1: Volunteer Baseline Characteristics Values are presented as mean ± SD

10. Figure 1. Changes in plasma folate, whole blood folate and tHcy post a 12 month placebo controlled multivitamin supplement in HD patients. Plasma Folateng/ml WBF ng/ml tHcymmol/l * Values mean ± standard deviation. * p>0.05; **p>0.002; *** p>0.0001

11. Figure 2. % Response to Intervention % Response Values mean ± standard deviation. * p>0.05; **p>0.002; *** p>0.0001 ((post-intervention - pre-intervention value)/pre-intervention)*100

12. Summary • Plasma and whole blood folate increased significantly in the treatment group • tHcy significantly decreased in the treatment group • Such that post intervention we report a 20% reduction in tHcy in the treatment group • tHcy post (20.5 ± 9.4 mmol/l), while levels remained high in the placebo group (25.3 ± 5.4 mmol/l)

13. Conclusion • The improvement in folate status suggests a benefit of this type of intervention in the treatment of the oxidative damage in HD patients • The significant decrease in tHcy has a beneficial effect on these patients • This provides evidence that this type of treatment should be introduce into clinical care in HD patients • However, not all patients respond well i.e. no or little change in tHcy • Further research is required to investigate these non responders

14. Acknowledgements • Supported by grant from WHCST • Amgen / Irish Nephrological Society Research Award • Thanks to the research group: • Dr Peter Garrett • Ms Twyla Moffitt • Dr Ann Molloy

15. Supplement Prescription: Patent Protected