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Omega-3s Yield Heart-Saving Effects Even in Small Amounts
5/29/2006
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Small controlled trial confirms protective heart-rate benefits of omega-3s and shows that low doses work as well as high doses

by Craig Weatherby


If one thing is clear about omega-3s, it is that they reduce the risk of heart attack, stroke, and sudden cardiac death. We know this because of a huge amount of research data from animal studies, epidemiologic studies, and controlled clinical trials.


Omega-3s produce these risk reductions primarily via their effects on heart rhythms, platelet aggregation (the blood’s “stickiness”) and inflammation, but also through minor decreases in blood pressure and minor but significant modifications to blood lipids (fats and cholesterol).


Key Points

  • Results of a clinical trial in heart attack survivors show that relatively low doses of omega-3s yield the same life-saving heart-rate changes seen in studies that tested much higher doses.
  • The observed heart-rate changes are associated with a reduced risk of the ventricular arrhythmias (erratic heartbeats) that cause about half of all cardiac fatalities.
  • The new results confirm earlier findings that the ability of omega-3s to protect healthy people and heart attack survivors against Sudden Cardiac Death flows from their ability to enhance the tone of the vagus nerve, reduce heart rate, and increase heart rate variability.

But until the release of new clinical results last month, the heart-risk reduction benefits of omega-3s had only been documented in clinical studies where people were taking doses three to five times higher than the one gram per day currently recommended by the American Heart Association.


Researchers tend to use large doses of omega-3s in epidemiological and clinical studies because most do not last very long, and the scientists want to ensure that the doses are high enough to allow them to detect any benefits that omega-3s might confer.


However, people can only obtain these relatively large doses by taking several fish oil capsules every day, or by eating fatty fish such as salmon for breakfast, lunch, and dinner.


While either dietary approach—or, more practically, a combination of fish meals and omega-3 supplements—would provide these high experimentally successful doses, it seems unlikely that a majority of Americans would actually achieve those high doses. Accordingly, researchers have wondered whether lower doses would yield similarly strong protection against premature heart-related deaths.


Before delving into the encouraging results of the new clinical study from Kansas City, let’s quickly review the critical connections between heart rate, heart rhythms, sudden cardiac death, and the marine omega-3s found in abundance only in fatty fish and fish oil supplements.


Why omega-3s help prevent sudden cardiac death

The protective powers of fish and fish oil stem in large part from the normalizing effects of marine omega-3s (DHA and EPA) on the heart’s electrical impulses, which act as a natural pacemaker.


Most instances of cardiac arrest and ensuing Sudden Cardiac Death (SCD) are caused by erratic heart rhythms called arrhythmias. When cardiac electrical impulses go awry the result can be an extremely dangerous kind of arrhythmia affecting the heart’s ventricular (lower) chambers, which do the hard work of pumping blood into the lungs to pick up oxygen, and pumping that oxygen-rich blood through the body.


Ventricular arrhythmias can take one or both of two forms: ventricular tachycardia, in which electrical impulses in the heart become rapid, or ventricular fibrillation, in which electrical impulses become chaotic and fluttery (Doctors and fans of TV medical shows will know ventricular fibrillation as “v-fib”).


Either form of ventricular arrhythmia can cause the heart to stop beating (cardiac arrest) and can be triggered by any form of heart disease. Unless a cardiac defibrillator is applied to the victim’s chest very quickly, he or she will suffer Sudden Cardiac Death, which accounts for about half of all annual deaths related to coronary heart disease.


SCD is often confused with death from a heart attack (myocardial infarction), which occurs when heart muscles become too weakened by years of inadequate blood supply (thanks to clogged arteries) to keep working. People confuse SCD and heart attack in part because a heart attack can cause the fatal sequence of arrhythmia, cardiac arrest, and SCD.


In contrast to the ventricular chambers, where the arrhythmias that typically cause SCD arise, the heart’s atrial (upper) chambers only need to perform the easy task of pumping blood down into the heart’s workhorse ventricular chambers. While atrial fibrillations can allow blood to pool and form stroke-inducing clots, a large body of evidence demonstrates that fish-rich diets reduce the risk of stroke.


The critical distinction between atrial and ventricular fibrillations explains why the authors of the Physicians' Health Study analysis we examined last week (see “Omega-3s and heart rhythms: media reports on recent study sowed confusion”, below) emphasized that the protective benefits of fish consumption against sudden cardiac death far outweigh the minor, theoretical risks posed by the increased incidence of atrial fibrillation found among the middle-aged male participants who ate two-to-five fish meals per week.


New study is first to confirm heart-benefits of modest omega-3 intake

As we’ve said, health authorities agree that the marine omega-3s in fish and fish oil (EPA and DHA) reduce the risk of Sudden Cardiac Death. And the ability of these fatty acids to prevent ventricular fibrillation explains much of the reduction in SCD risk attributed to eating fish.


Now, the results of a new study from St. Luke's Hospital in Kansas City (O'Keefe JH Jr. 2006) indicate that after just four months, men taking low doses of omega-3s showed beneficial increases in heart rate variability: an effect known to reduce the risk of dangerous ventricular arrhythmias and ensuing cardiac arrest and SCD.


The Kansas City team wanted to test whether a daily dose of omega-3s totaling only 810 mg—which is substantially lower than the one gram per day recommended by the American Heart Association—would produce the kinds of heart rate changes associated with a reduced risk of ventricular arrhythmia and resulting death (Control over heart rate is a critical factor in preventing arrhythmic fibrillation in the heart’s ventricular chambers).


To that end, they recruited 18 white men (average age 67.8) with a history of heart attack and relatively weak blood-pumping force. The men were told to eat no more than one fish meal per month, and were randomly assigned to take either placebo capsules (50:50 mix of corn and olive oils) or omega-3 capsules three times a day for four months, after which the two groups switched pill regimens (unbeknownst to them) and continued the trial for another four months.


At the end of each period, the Kansas City team measured the participants’ heart rate, heart rate, variability and the speed with which their heart rate recovered after exercise, as well as effects on blood pressure, heart function and fasting blood levels of lipids (fatty acids and cholesterol), markers of inflammation, and the arteries’ ability to dilate when the heart needs to pump more blood through the body (“arterial compliance”).


The results showed that omega-3 supplements lowered average heart rate from 73 beats per minute to 68 beats per minute, improved heart rate variability in the “high frequency band” and significantly improved post-exercise heart rate recovery. (Arrhythmias are also less likely to occur if your heart rate returns to its normal “resting rate” quickly after you exercise.)


The notion that an increase in the variability of your heart rate would reduce your risk of dangerous ventricular arrhythmias seems counterintuitive, since doctors’ goal is to prevent erratic heart rhythms.


However, heart rhythm and heart rate are distinctly different things. Heart rate variability refers to beat-to-beat alterations in heart rate. At rest, the hearts of healthy people exhibit periodic variations in the time intervals between consecutive heart beats, and it turns out that arrhythmias are less likely to occur if the time intervals between beats vary within a safe range


The interest in measuring heart rate variability (HRV) stems from its ability to predict survival after heart attack. The results of several prospective studies demonstrate that reduced HRV predicts fatal ventricular arrhythmia, and raises the risk of sudden death in heart attack survivors, independent of other prognostic indicators.


In addition, the findings from a small number of studies suggest that reduced heart rate variability may predict risk of survival among people free of symptomatic heart disease.


Multiple studies have also shown that the faster heart-rate recovery seen for the first time in the Kansas City trial predicts a reduced risk of adverse cardiovascular events, including cardiac arrest and SCD. And the decrease in heart rate seen in this study approximated the drop produced by beta-blocker drugs, which, like omega-3s, have been shown to decrease the risk of SCD.


The authors concluded that the positive effects of omega-3s on heart rate and heart rate recovery were consistent with an increase in vagus nerve activity: an effect that may explain the decrease in risk for sudden cardiac death documented in epidemiologic studies and randomized, controlled clinical trials.


As the Kansas City researchers said, there findings prove that relatively low doses of omega-3s can confer big cardiac benefits in only four months: “Our observations … suggest that modulation of HR [heart rate] can be achieved in patients with known coronary heart disease who consume recommended amounts [1,000 mg per day] of EPA plus DHA.”


Kansas City results expand on earlier Danish research

In a clinical study published in 2003, Danish researchers were the first to report that supplemental omega-3s increased heart rate variability significantly, both in men at high risk of SCD and in healthy men (Christensen JH 2003). The Danes also found that the male participants’ tissue levels of omega-3s correlated closely with the degree of heart rate variability.


Highlighting the differences between genders, the beneficial heart rate variability effect was not seen in the participating women.


Sudden cardiac death vs. heart attack: not synonymous, despite similarities


Sudden Cardiac Death (SCD)—which accounts for about half of all annual deaths related to coronary heart disease—is often confused with death from a heart attack (myocardial infarction).


Heart attacks result when clogged arteries reduce the heart’s blood supply and atrophy heart muscle, and most do not yield a cardiac arrest and Sudden Cardiac Death.


For reasons that remain uncertain, but likely relate to genetics and lifestyle, people’s cardiovascular systems react differently to gradual clogging of arteries. Some suffer a slow atrophying of their heart muscles and resulting heart attacks, while others die suddenly when a ventricular arrhythmia stops their heart, often before they’ve experienced or shown any symptoms of heart disease.


However, like the victims of heart attacks, 90 percent of adult victims of SCD have two or more major coronary arteries narrowed by fatty buildups, while scarring from a prior heart attack is found in two-thirds of victims.


Typically, SCD occurs when the electrical impulses in the heart become rapid, chaotic or both and cause the heart to suddenly stop beating.  Any of the several forms of cardiovascular disease can lead to cardiac arrest and sudden cardiac death.

Like the Kansas City trial, the Danish clinical study ran for four months, so the broader heart-rate variability benefit seen in the Danes’ investigation may have been due to the higher dose used, which ranged from 2.0 to 6.6 grams (2,000 to 6,600 mg) of omega-3s, or three to eight times the dose used in the Kansas City trial.


The Danes concluded that the ability of omega-3s to protect heart attack survivors against Sudden Cardiac Death is a beneficial byproduct of these nutrients’ ability to enhance the tone of the heart-rate controlling vagus nerve, and that omega-3s increase heart rate variability by acting both in the brain and heart.


Omega-3s and heart rhythms: media reports on recent study sowed confusion

Last week, we critiqued media reports on a new analysis of data from the Physicians' Health Study, most of which bore highly misleading headlines that implied the study’s results call into question the life-saving effects of omega-3 fatty acids on certain heart rhythms (See “Misleading Headlines Distort Meaning of Research on Fish and Heart Rhythms”).


It’s true that one of the authors’ findings was a correlation between frequent fish consumption among some of the participating male doctors (two-to-five or more meals per week) and a 41-55 percent increase in their incidence of diagnosed atrial fibrillation, compared with the participating men who only ate fish only once a month.


But the authors of the data analysis emphasized that their finding, if confirmed, does not call into question the life-saving powers of fish consumption.


In fact, they noted that the life-saving benefits of eating fish frequently—or taking fish oil supplements—far outweigh the risks stemming from the possibility that it might yield increased rates of atrial fibrillation.


The researchers said this because atrial fibrillation is considered much less life-threatening than ventricular fibrillation, which causes cardiac arrest and ensuing Sudden Cardiac Death, the risk of which marine omega-3s are proven to cut by 40-50 percent.



Sources

  • O'Keefe JH Jr, Abuissa H, Sastre A, Steinhaus DM, Harris WS. Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions. Am J Cardiol. 2006 Apr 15;97(8):1127-30. Epub 2006 Mar 3.
  • Christensen JH. n-3 fatty acids and the risk of sudden cardiac death. Emphasis on heart rate variability. Dan Med Bull. 2003 Nov;50(4):347-67. Review.
  • Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans. A meta-analysis of randomized controlled trials. Circulation 2005;112:1945-1952.
  • Leaf A, Xiao YF, Kang JX, Billman GE. Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids. Pharmacol Ther. 2003;98(3):355-377. Albert CM, Hennekens CH, O'Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998;279(1):23-28.
  • Billman GE, Kukielka M. Effects of endurance exercise training on heart rate variability and susceptibility to sudden cardiac death: protection is not due to enhanced cardiac vagal regulation. J Appl Physiol. 2006 Mar;100(3):896-906. Epub 2005 Dec 1.
  • Smith LL, Kukielka M, Billman GE. Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction. Am J Physiol Heart Circ Physiol. 2005 Apr;288(4):H1763-9. Epub 2004 Nov 24.
  • Routledge HC, Chowdhary S, Townend JN. Heart rate variability--a therapeutic target? J Clin Pharm Ther. 2002 Apr;27(2):85-92. Review.
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