Transcript Document

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
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
Recruited n = 39
Baseline
clinical history: blood
Treatment
Randomised to treatment on
Placebo
n =18
baseline tHcy
n=19
48 week intervention
n=16
n = 14
Post Intervention
clinical history: blood
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 Volunteers were withdrawn if less than 90% of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
Table 1: Volunteer Baseline Characteristics
Characteristic
Age (years)
Male/Female (n/n)
Diabetes (n (%))
Dialysis Duration
Placebo
Intervention
(n=19)
(n=18)
62.58 ± 10.95
64.89 ± 8.29
12/7
10/8
6 (31.6%)
7 (38.9%)
27.00 ± 17.75
27.33 ± 38.09
27.08 ± 6.43
26.29 ± 4.80
(months)
BMI (kg/m2)
Values are presented as mean ± SD
tHcy mmol/l
WBF ng/ml
Plasma Folate ng/ml
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
% Response
Figure 2. % Response to Intervention
Values mean ± standard deviation. * p>0.05; **p>0.002; *** p>0.0001
((post-intervention - pre-intervention value)/pre-intervention)*100
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)
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
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Thanks to the research group:
Dr Peter Garrett
Ms Twyla Moffitt
Dr Ann Molloy
Supplement Prescription: Patent Protected
Supplement
Vitamin C (ascorbate)
Vitamin E (tocopherol)
Vitamin K
Folic acid (mg)
B2 Riboflavin (mg)
*B6 (mg)
*B12 (mg)
B5 (Pantothenic acid, mg)
B1 Thiamin (mg)
Zinc
Copper
Selenium
Dose
60mg
10mg
65mg
800mg
1.6mg
10mg
12 mg
1mg
1mg
15mg
1.5mg
75mg