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SANTIAGO, CHILE. Oxidative stress has been implicated as a major factor in the development
and promotion of atrial fibrillation (AF). The main reactive oxygen species (ROS) involved
in causing oxidative stress are the superoxide anion, singlet oxygen, nitrogen dioxide
(peroxynitrite) and hydroxyl radicals. They share the dubious distinction of being able
to cause inflammation and inflict considerable damage in tissues, cells and individual DNA strands.
Under normal circumstances any ROS attacking the heart lining or adjacent lung tissue would
quickly be rendered harmless by the body�s own antioxidants or by antioxidants obtained
through the diet. However, if antioxidant defenses are inadequate, the immune system is
compromised, or if the autonomic nervous system is highly dysfunctional or stressed, it
is likely that the ROS could get the upper hand and initiate an inflammatory response
and subsequent arrhythmia.
Inflammation of the heart lining has also been linked to the development and promotion
of AF and a strong association between severity of AF and the level of the inflammation
biomarker CRP (C-reactive protein) has been established. There is also evidence that
omega-3 polyunsaturated fatty acids (fish oils) materially reduce inflammation and CRP level.
A group of Chilean and Greek researchers now reports that pre-procedure supplementation
with a combination of antioxidants (vitamins C and E) and fish oil is effective in reducing
the incidence of post-operative AF in patients undergoing valve surgery or coronary artery
bypass surgery. Their clinical trial involved 203 patients scheduled for on-pump cardiac
surgery. The average age of the patients was 60 years, 86% were male and all were in
normal sinus rhythm and had no previous history of arrhythmia.
The patients were randomized to receive placebo or supplementation with 2 grams/day of
fish oil (DHA:EPA ratio of 2:1), 1 gram/day of vitamin C and 400 IU/day of vitamin E.
Fish oil supplementation was initiated 7 days prior to the procedure and supplementation
with vitamins C and E was started 2 days before. All supplementation was discontinued
upon discharge from hospital. ECG or Holter monitoring was carried out until discharge
with ECG-documented AF for at least 60 seconds being classified as post-operative atrial
fibrillation (POAF). POAF occurred in 9.7% of supplement group members and in 32% of
placebo group members � a statistically highly significant difference. The mean time
to POAF occurrence (from completion of surgery) was 3.3 days in the supplement group
and 2.9 days in the placebo group.
Oxidative stress was assessed as malondialdehyde (MDA) level in blood throughout the trial
and in right atrial tissue during surgery. After 5 days of fish oil supplementation, blood
levels of MDA were an average 59.6% higher than baseline level and 45.6% higher than the
average level in the placebo group. However, after the addition of vitamins C and E there
was no longer any difference in pre-surgery MDA levels. MDA levels, not surprisingly,
increased after surgery, but to a much lesser degree in the supplement group. CRP levels
also increased after surgery but significantly less so in the supplement group than in
the placebo group (2.2-fold vs. 3.6-fold increase).
The researchers also noted a significantly higher activity of the endogenous antioxidant
enzymes catalase, superoxide dismutase and glutathione peroxidase in the atrial tissue of
supplemented patients. They conclude that supplementation with a combination of antioxidants
(vitamins C and E) and fish oils reduces the incidence of post-operative AF in cardiac surgery
patients by about 66%. Supplementation also increases antioxidant potential and decreases
oxidative stress and inflammation. They note that using a fish oil supplement with a ratio
of DHA (docosahexaenoic acid) to EPA (eicosapentaenoic acid) of 2:1 may be important in short
term trials as there is evidence that DHA is incorporated more rapidly into human atrial tissue
than is EPA.
Editor�s comment: This study adds to existing evidence that vitamin C is useful in preventing
postoperative atrial fibrillation in coronary artery bypass surgery[1]. There is also evidence
that vitamin C prevents early recurrence following cardioversion of persistent AF and is
effective in reducing levels of inflammatory markers and fibrinogen[2]. The finding that fish
oil supplementation on its own increases oxidative stress is not surprising and supports my
position that fish oil should always be taken in combination with vitamins C and E.
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