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

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 = 39

48 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the pharmacist Volunteers were withdrawn if less than 90% of the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) 62.58 ± 10.95 64.89 ± 8.29

Male/Female

(n/n)

12/7 10/8

Diabetes (n (%)) 6 (31.6%) 7 (38.9%)

Dialysis Duration

(months)

27.00 ± 17.75 27.33 ± 38.09

BMI (kg/m2) 27.08 ± 6.43 26.29 ± 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>0.0001

*

Figure 2. % Response to Intervention

% R

esp

onse

((post-intervention - pre-intervention value)/pre-intervention)*100Values 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

Supplement Prescription: Patent Protected

Supplement Dose Vitamin C (ascorbate) 60mg Vitamin E (tocopherol) 10mg Vitamin K 65g Folic acid (mg) 800g B2 Riboflavin (mg) 1.6mg *B6 (mg) 10mg *B12 (g) 12 g B5 (Pantothenic acid, mg) 1mg B1 Thiamin (mg) 1mg Zinc 15mg Copper 1.5mg Selenium 75g