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 May 2012

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

Hyperhomocysteinaemia

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

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

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

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

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measured by a microbiological assay  Supplements were provided monthly in a bottle by the pharmacist  Volunteers were withdrawn if less than 90% of the supplements were taken

Characteristic Placebo (n=19) Intervention (n=18) Age (years) ± ± 8.29 Male/Female (n/n)12/710/8 Diabetes (n (%))6 (31.6%)7 (38.9%) Dialysis Duration (months) ± ± BMI (kg/m 2 )27.08 ± ± 4.80 Table 1: Volunteer Baseline Characteristics Values are presented as mean ± SD

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> WBF ng/ml Plasma Folate ng/ml tHcy mmol/l *

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

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)

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

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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