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Fish and Veggies Bring Complementary Benefits
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Omega-3s seen to improve heart rates and rhythms and suppress heart-unhealthful protein; mouse study illuminates heart-health attributes of common veggies
by Craig Weatherby

If we're to believe Nat King Cole’s golden oldie, the days of summer are lazy, hazy, and crazy. But the sober-minded publishers of bio-medical journals paid Cole’s 1963 pop hit no heed. In fact, they released so many studies on omega-3s and heart-health this summer that we couldn’t fit them all in one issue of “Vital Choices”!

So, we’ve spread these encouraging findings across a three-part “Heart-Health Harvest” series. Part I features the revealing studies summarized below (see links in box below), Part II will appear next week, and Part III is slated for our September 25 issue.

We hope that our special series will help clarify matters for the many consumers left confused by a series of dismaying research results.

Good news follows mixed messages
Starting in September of 2005 and ending this past spring, marine omega-3s took a one-two combination of scientific punches that tarnished—only slightly and temporarily, as it turned out—their heart-healthy image.

The first blow was scientifically sound but very limited in scope. There’s no question that for most people, omega-3s exert beneficial effects on heart rates and rhythms (see “More heart rhythm benefits,” below). But a series of studies published over the past 12 months uncovered an important exception to this general rule.

These unexpected findings demonstrated that omega-3s can be unsafe for the small subset of cardiac patients so sick that they require an implanted cardiac defibrillator (ICD) to keep their heart rhythms regular (See “Fish Oil Can't Rescue the Sickest Cardiac Patients' Heart Rhythms”).

The second blow came from a “meta-analysis” published last March in the British Medical Journal (BMJ). And its’ fundamental flaws—which were obvious even to astute amateurs—came under immediate fire from the vast majority of experts who submitted comments to the journal’s Web site.

The BMJ review’s authors analyzed evidence from selected human studies and concluded that omega-3s offer do not clear cardiac benefits (Hooper L et al 2006). However, the authors’ peculiar study-selection decisions presented a distorted picture of the overwhelmingly positive clinical evidence.

And within three months, a group of leading cardiac researchers published another meta-analysis that avoided these study-selection errors. Unsurprisingly, this better-designed evidence review reaffirmed the value of omega-3s in preventive heart health (Wang C et al 2006; see “Omega-3 Heart Benefits Affirmed by U.S.-Japan Study”).

Its authors concluded, based on the best, most relevant human evidence, that omega-3s help prevent heart problems in two ways:
  • Omega-3s provide substantial “secondary prevention”: This simply means that in people who’ve already suffered a heart attack, stroke, or other adverse cardiac event, omega-3s help prevent a second occurrence.
  • Omega-3s provide a modest level of “primary prevention": In other words, omega-3s help prevent an adverse cardiac diagnosis and the first occurrence of a heart attack or other adverse cardiac event. (The evidence for these benefits is substantial, but weaker than for secondary prevention.)
And a stream of positive research results that followed over the summer months further support or expand on the clear cardiac benefits offered by marine omega-3s.

These three installments constitute Part I of our Heart-Health Harvest series:

Marine Omega-3s Suppress Heart-Attacking Protein
Homocysteine is an amino acid (protein fragment) that, among other things, plays a role in the body’s metabolism of B-vitamins like folic acid (folate) and vitamin B-12.

Elevated homocysteine levels are closely associated with increased risk of dying from cardiovascular disease and other causes, and people with high blood levels of the amino acid are more likely to suffer from depression and age-related cognitive decline.

Among women, elevated homocysteine levels are also associated with decreased bone mineral density, increased risk of osteoporosis, and increased risk of pregnancy complications and adverse pregnancy outcomes (Refsum H et al 2006).

(In recent years, researchers have recommended supplemental folic acid as a way to reduce homocysteine levels. Coincidentally, the FDA ordered bread makers to start adding that same B-vitamin to their products a few years back, to reduce the risk of birth defects.)

But it remains unclear whether excess blood homocysteine is the primary perpetrator in heart and other health problems, or a red flag that indicates ill health caused by other factors.

As the author of a recent evidence review (Selhub J 2006) put it, “…[the] multitude of relationships between elevated… [blood levels of] homocysteine and diseases that afflict the elderly point to the existence of a common denominator that may be responsible for these diseases. Whether this denominator is homocysteine itself or whether homocysteine is merely a marker remains to be determined.”

Since human health declines as homocysteine levels rise, any generally beneficial food factor that inhibits production of this red-flag protein is likely to improve health. In the case of omega-3s, it seems reasonable to hypothesize that they lower high homocysteine levels by improving the negative underlying conditions that cause them in the first place.

And recent research results prove that dietary omega-3s lower homocysteine levels. This is especially true of omega-3 DHA, which raises blood levels of homocysteine-lowering folic acid (and vice versa).

Chinese study finds omega-3s lower homocysteine levels.

Early this year, a joint Chinese-Australian research team reported that higher blood levels of omega-3s yield lower blood levels of homocysteine (Li D et al 2006). They also found that high blood levels of omega-6 arachidonic acid were associated with high levels of homocysteine: findings that support the idea that Americans’ excess consumption of omega-6 fatty acids is just as unhealthful as their generally low intake of omega-3s.

Dr. Hibbeln’s DHA-folate finding:

Renowned omega-3 researcher and psychiatrist Joe Hibbeln, M.D. directs the outpatient clinic at the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Last March he co-authored an intriguing study, whose results support the Chinese-Australian teams' finding that omega-3s lower homocysteine levels.

Dr. Hibbeln's NIAAA team tested blood samples taken from 15 normal and 22 hostile and aggressive men (average age 38) obtained prior to 1996, when the FDA ordered routine enrichment of American flour with folic acid.

They found that the men with low blood levels of DHA also had low blood levels of folic acid (folate). As they said, “Our findings present one explanation why some conditions associated with hostility and low DHA status, such as cardiovascular disease and emotional disorders, are also associated with low folate status.”

Taken together, these findings on omega-3s, folic acid, and homocysteine indicate that fish and fish oil might enhance heart and emotional/mental health in previously unsuspected ways.

Big Harvard Study Bolsters Omega-3s’ Heart-Rhythm Benefits
In the late 1990, doctors across the United States started the Cardiovascular Health Study (CHS): a series of observational studies funded by the National Heart, Lung and Blood Institute. CHS researchers recruited 5,888 volunteers aged 65 or older, and the project, based at the University of Washington in Seattle, has produced more than 400 published research papers to date, with many more in progress.

Our omega-3-research radar picked up a recently published arm of the CHS study, led by famed cardiac researcher Darius Mozaffarian M.D., MPH of Harvard Medical School.

Last month, Dr. Mozaffarian’s team reported finding that CHS participants who consume higher amounts of fish enjoy a reduced risk of developing the especially dangerous abnormal heart beats called ventricular arrhythmias. And they traced this benefit to omega-3-induced improvements in the electrical properties of people’s heart-muscle cells (Mozaffarian D et al 2006).

The Harvard/Brigham group analyzed data collected from 5,096 older men and women (average age 73) in the four CHS-study cities. Over a one-year period, the average fish consumption reported by study participants ranged from less than four times a year to more than five portions every week: a 65-fold difference.

The 5,096 subjects in the study also received electrocardiographs to measure their heart rates and rhythms.

And, in an unusual step, blood levels of omega-3s (EPA and DHA) were measured in a subset of 56 participants, to detect any relationship between participants’ fish intake, the levels of omega-3s in their tissues, and measured heart-health effects.

Dr. Mozaffarian’s team found that the resting heart rates of the volunteers who reported eating the most fish averaged 3.2 fewer beats per minute lower than the heart rates of those who reported eating less than one portion of fish per month. (Higher resting heart rates increase the risk of sudden cardiac death.)

The Harvard/Brigham group also found that the study participants who reported higher intakes of tuna and other broiled or baked fish had less risk of “extended ventricular repolarization” (EVP): an electrical property of the heart that promotes arrhythmias in the heart’s ventricular chambers (a location that pose particular dangers).

And when they looked at the 56 participants who underwent blood tests, those whose omega-3 blood levels indicated that they normally consumed amounts of fish comparable to the five-meals-per-week subjects had comparably low (healthy) heart rates.

As Dr. Mozaffarian said, “A one-gram-per-day higher intake [of EPA and DHA from fish] was associated with a 2.3 beats per minute lower heart rate and a 46 percent lower likelihood of prolonged ventricular repolarization … the observed differences in HR [heart rate] and ventricular repolarization may, in part, account for the lower incidence of arrhythmic events [dangerously abnormal rhythms] seen with fish and fish oil intake.”

He and his colleagues hypothesized that the known effects of omega-3s on the chemistry of “ion channels” in heart-muscle cells, which are associated with the heart’s electrical signals, probably account for the lower risk of rhythm-risking EVP seen in their study.

Common Veggies Enhance Animals’ Artery Health

Most Americans seem aware of the “Five-a-Day” message from US health authorities, which urges people to eat five servings of fruits and vegetables per day.

This advice flows from a substantial body of evidence indicating that diets high in fruits and vegetables may reduce consumers’ risks of cardiovascular disease and stroke. Produce-rich diets also appear to reduce the risk of gastric, lung, colon, and oral cancers, but not breast or prostate cancers.

The government’s “Five-a-Day” advice goes largely unheeded. Recent studies show that the average American consumes about three portions of fruits and vegetables a day, with some 40 percent of their intake consisting of starchy, relatively "empty-calorie" vegetables such as peeled potatoes (often fried in unhealthful fats).

Scientists who’ve examined the many human studies conducted to date say that vegetable-rich diets seem to reduce the risk of cardiovascular disease, lower blood pressure and levels of “bad” (LDL, ILDL, VLDL) cholesterol, and boost blood levels of “good” (HDL) cholesterol.

For example, the findings from a recent meta-analysis of human evidence indicate that eating five or more portions of fruit and vegetables per day could cut the risk of stroke by 26 percent (He FJ et al 2006).

Surprisingly, the animal study summarized below was the first to scrutinize the effect of increased vegetable consumption on the development or progression of atherosclerosis.

Atherosclerosis is defined by formation of fatty plaques on blood vessel walls, which eventually protrude into the vessel’s opening and can reduce blood flow, or burst and block blood flow entirely, causing a heart attack, stroke, or sudden cardiac death.

Mouse study supports vascular benefits of common vegetables.

The new findings come from a team at Wake Forest University School of Medicine (Adams MR et al 2006). Their work was funded by General Mills, which supplied the freeze-dried vegetables used in the investigation.

Michael Adams, D.V.M. led the study, which involved mice with elevated blood levels of low-density lipoprotein (LDL or “bad”) cholesterol: a well-known risk factor for atherosclerosis and cardiovascular disease in humans.

Half of the mice were fed a vegetable-free diet and half got 30 percent of their calories from a mixture of freeze-dried broccoli, green beans, corn, peas and carrots. (These rank among the 10 vegetables consumed most frequently in the United States.)

After four months had passed, the researchers measured two forms of cholesterol (free and ester) to estimate the extent of atherosclerosis. As they’d hypothesized, the arterial plaques in the vegetable-fortified-diet group were 38 percent smaller than the plaques in the mice fed vegetable-free diets.

The veggie-fed mice also showed significant reductions in body weight (seven percent) and cholesterol levels. (Total cholesterol levels dropped 12 percent while levels of especially dangerous VLDL and ILDL cholesterol fell by 32 percent.)

Dr. Adams admitted that it remains unclear exactly how the high-vegetable diet reduced accumulation of plaques in the rodents’ artery walls: “Although the pathways involved remain uncertain, the results indicate that a diet rich in green and yellow vegetables inhibits the development of hardening of the arteries and may reduce the risk of heart disease.”

Anti-inflammatory action of veggies seen vital to artery effects.

Echoing the inflammation-threat theme of last week’s lead “Vital Choices” article (here), Dr. Adams said that a 37 percent reduction in a key marker of inflammation in mice and humans (serum amyloid A) dropped 37 percent in the veggie-diet mice. This result suggests that vegetable consumption may inhibit inflammation, thanks most likely to the antioxidant phenols and sulfur compounds in the five vegetables added to the mouse feed.

As Dr. Adams said, “It is well known that atherosclerosis progression is intimately linked with inflammation in the arteries. Our results, combined with other studies, support the idea that increased vegetable consumption inhibits atherosclerosis progression through antioxidant and anti-inflammatory pathways.”

The results of this landmark animal study help explain why fruits and vegetables help prevent cardiovascular disease and stroke, and should stimulate human research on this critical topic.

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