1. Mary Hannon-Fletcher Micronutrient supplementation in haemodialysis patient enhances folate levels and reduces homocysteine 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 Baseline clinical history: blood Treatment n =18 Recruited n = 39 48 week intervention n=16 Placebo n=19 n = 14 Post Intervention clinical history: blood Randomised to treatment on baseline tHcy

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measured by a microbiological assay  Supplements were provided monthly in a bottle by the pharmacist  Volunteers were withdrawn if less than 90% of the supplements were taken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. Characteristic Placebo (n=19) Intervention (n=18) Age (years) 62.58 ± 10.9564.89 ± 8.29 Male/Female (n/n)12/710/8 Diabetes (n (%))6 (31.6%)7 (38.9%) Dialysis Duration (months) 27.00 ± 17.7527.33 ± 38.09 BMI (kg/m 2 )27.08 ± 6.4326.29 ± 4.80 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. Values mean ± standard deviation. * p>0.05; **p>0.002; *** p>0.0001 WBF ng/ml Plasma Folate ng/ml tHcy mmol/l *

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

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  mol/l), while levels remained high in the placebo group (25.3 ± 5.4  mol/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

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