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Volunteers were withdrawn if less than 90% of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
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