“Fish Oils–Adjuvant Therapy in Chronic Heart Failure?”

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Heart Failure and Fish Oils

http://www.vitasearch.com/CP/experts/KWitteAT09-12-06.htm

Dr Klaus Witte MD, MRCP (UK)

SpR and Lecturer in Cardiology,

Castle Hill Hospital

Castle Road, Cottingham,

Hull HU16 5JQ, UK

klauswitte@...

(+44) 7768 254073

“Fish Oils–Adjuvant Therapy in Chronic Heart Failure?”

Eur J Cardiovasc Prev Rehabil, 2004 Aug;11(4):267-74. 44924 (9/2006)

Kirk Hamilton: Can you please share with us your educational

background and current position?

Klaus Witte: I did my undergraduate medical training at King’s College

Hospital in London, UK. In order to gain a good background in other

fields I spent time in emergency medicine, nephrology and respiratory

medicine before starting my training in cardiology. After two years in

South Wales, I accepted a research fellowship in Hull with Drs.

Cleland and . It was during this time that I became

interested in nutrition in patients with severe heart failure (my other

research interests included exercise physiology). After writing my MD

thesis (Exercise Limitation in Chronic Heart Failure – University of

London 2004), I carried on with clinical training in Leeds (UK) and

spent 18 months at Mount Sinai Hospital, Toronto (Canada) expanding my

skills and a developing a research interest in device therapy for heart

failure. I currently am in my final year of training in cardiology in

Leeds. I continue to perform mechanistic studies exploring both the

cause of breathlessness in CHF and the impact of therapies on exercise

limitation.

KH: What got you interested in studying the role of fish oil and

heart failure? Do you think heart failure is an inflammatory condition?

KW: Increasingly we are recognizing that heart failure is an

inflammatory condition – or at least has a large inflammatory component.

C-reactive protein (CRP) and other markers of inflammation along with

cytokines are raised in CHF and correlate with prognosis. Many of the

inflammatory derangements and the aggressive weight loss that

characterize severe CHF are also found in patients with cancer cachexia.

It was during a conversation with a dietician colleague whose main

interest was the anti-inflammatory effects of fatty acid supplementation

in patients with pancreatic cancer cachexia that I decided to

investigate the possible effects in CHF patients.

KH: Why consider only fish oil as your omega-3 source? Why not use

alpha-linolenic acid from flaxseed oil?

KW: Alpha linolenic acid is a source of n-3 fatty acids, and is

converted in vivo to eicosapentaenoic acid (EPA) relatively

inefficiently. Most work has been performed on the effects of EPA and

docosahexaenoic acid (DHA). However, one could use ALA as a source of

n-3. In addition to flaxseed oil, walnuts have a particularly high

concentration. The large doses needed for investigation of the

physiological effects in small studies are only available by direct

ingestion of the fish oils. However, since fish stocks are running low,

increasing population consumption of the most potent source might be

difficult. Hence, the increasing importance of other less investigated

sources of n-3 oils (such as flaxseed oil and walnuts) which might

provide adequate amounts.

KH: What is fish oil’s effect on endothelial function and how does

that relate to heart failure?

KW: There are a number of potential mechanisms by which fish oils

might improve endothelial function. Firstly, they might increase nitric

oxide release, and they also reduce the production of proinflammatory

cytokines from the endothelium and lead to reduced production of other

endothelial based mediators such as endothelin-1 which is a powerful

vasoconstrictor. In addition, they reduce the production of vascular

adhesion molecules and the adherence of monocytes to endothelial cells.

KH: How does fish oil reduce vascular tone? And how does that help

heart failure?

KW: Heart failure is a condition where the chronic activation of

compensatory vasoconstrictive mechanisms normally employed to restore

some haemodynamic derangement (such as bleeding) lead to increased

myocardial work (afterload). Many contemporary therapies aim to reduce

this vasoconstriction. Fish oils reduce vascular tone by a number of

mechanisms including endothelial effects as above and altered calcium

signaling in the vascular smooth muscle. They also have chronic effects

including the reduction of vascular smooth muscle cell proliferation and

migration through their anti-cytokine effects. There are also

suggestions that they can reduce rennin-angiotensin system activation.

KH: What is fish oil’s role with regards to platelet aggregation, and

subsequently heart failure?

KW: Fish oils reduce platelet aggregation, by reducing the production

of the pro-coagulant thromboxane A2. Heart failure is a condition where

there is low level activation of haemostatic mechanisms. Patients are at

higher risk of thrombotic and embolic events and are often prescribed

aspirin which may have additional disadvantages in this population.

KH: What does the term “myocardial relaxation” mean (diastole?)? And

how does that relate to heart failure? What is fish oil’s role?

KW: Myocardial relaxation (diastolic function) is a term used to

describe how well the heart relaxes between each beat. If the heart

relaxes poorly, blood cannot flow in easily to fill it before the next

beat. Fish oils can lead to improved myocardial relaxation. This might

be a direct effect on myocardial cells either through improved calcium

handling (the flow of calcium in and out of cells determines both

contraction and relaxation), increased nitric oxide release (to help the

heart relax) or a consequence of reduced afterload.

KH: What is the benefit of stabilizing myocardial cells and

prolonging the refractory period in heart failure patients? What is fish

oil’s function in this?

KW: After each electrical event (depolarization), a myocardial cell

has pumps to move salt ions (Na+, K+, Ca2+) across it in order to

recharge the electrical gradient across the membrane ready for the next

stimulated activation (depolarization). However, the cellular membrane

is slightly ‘leaky’. Once the pumps stop, the ions leak back at a given

rate. Once a certain amount of charge has leaked back, past a given

threshold, the cell can discharge if a normal wave of heart activation

has not yet occurred. This unique feature of cardiac cells is known as

automaticity. It is of benefit in some circumstances, but can in

conditions of stress, ischaemia or cell death, also lead to an abnormal

beat. Fish oils alter the lipid profile of cellular membranes possibly

reducing the rate of repolarization and the ‘leak’, but also increasing

the threshold at which the automatic depolarization occurs, thereby

reducing the chances of an extra beat. By increasing the proportion of

fish oil lipids in the membrane, thereby increasing the rate at which

sodium travel across the membrane during a depolarization, the recovery

time, during which no other beats can be supported, is relatively

longer. This is of benefit on avoiding the initiation and prolongation

of abnormal heart rhythms.

KH: How does fish oil increase appetite?

KW: They reduce the production of proinflammatory cytokines which

suppress appetite.

KH: How does fish oil’s ability to modulating immune function by

altering prostaglandin formation and inflammatory mediators affect heart

failure?

KW: The inflammatory processes adversely affect vasomotor function,

renal function, muscle loss, appetite, and haemostasis. Fish oils

suppress the inflammatory response.

KH: What dose range of eicosapentaenoic acid (EPA) and

docosahexaenoic acid (DHA) is recommended or has been used in heart

failure patients?

KW: The only ongoing randomized morbidity and mortality outcome study

in patients with CHF is the GISSI

Heart Failure project which is using 1g fish oils per day, but other

groups have used far higher doses, up to 8g per day. Endothelial

benefits can be seen with 1.8g EPA and 1.2g DHA.

KH: Are there potential side effects of fish oil supplementation in

heart failure patients? What heart failure patients should take fish oil

and who shouldn’t?

KW: There are no suggestions of serious side effects. One will have to

wait for the randomized study to identify whether the purported

reduction in T-cell mediated immunity has any clinical effects.

KH: How do you assess the need for fish oil supplementation in heart

failure patients? Do you do fatty acid assessment?

KW: Not currently. One might at present have some hesitation in

individuals with a history of ventricular tachycardia (VT) who do not

yet have a defibrillator (ICD). These data are based on a study in 200

patients with ICD in whom those with a history of VT had more VT and

those with ventricular fibrillation (VF) as their ICD indication had

fewer arrhythmias at follow up. There was a strong trend to overall

reduced mortality in the group randomized to fish oils who had more VT.

In contrast however, those patients with VF as their ICD indication

randomized to fish oils had fewer arrhythmias at follow up. There was a

strong trend to overall reduced mortality in the fish oil group in this

small study.

KH: Do you have any further comments on the role of fish oil and

heart failure?

KW: We await eagerly the results of the GISSI-HF project.

--

ne Holden, MS, RD < fivestar@... >

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