Dr. Patricia Fitgerald Blog on Nutritional Studies

Eggs as Bad as Smoking? Vitamins Linked to Mortality? Making Sense Out of Nutritional Studies With Expert Dr. Alan Gaby

The abundance of nutritional research available certainly gives us food for thought when making decisions regarding diet and nutritional supplementation. It can also lead to confusion due to misleading headlines and questionable interpretations of studies.

If you've come across headlines such as "Are Eggs As Bad As Smoking?," "Are Our Vitamins Killing Us?" and "Fish Oil No Lifesaver?," you can't but help feeling puzzled as to how to separate the truth from the hype.

The average person who is interested in keeping up with the latest research most likely doesn't have the time or the expertise to weed through the actual studies to determine if the press reports of the research are reliable. Fortunately, a nutritional science expert has taken the time to interpret the studies for us as well as provide takeaways so we can put these studies to practical use for optimal health. Alan Gaby, M.D., is the author of Nutritional Medicine, a comprehensive scientifically-based guide to the use of diet and nutritional supplements to prevent and treat illness. With more than 1,374 pages and over 15,000 references, Dr. Gaby considers Nutritional Medicine the pinnacle of his life's work -- to investigate nutritional medicine and to teach others what he has discovered.

I was fortunate to recently meet up with this brilliant researcher at a medical conference where he was teaching doctors how to interpret nutritional studies.

PF: Dr. Gaby, thanks for taking the time to speak with me and share your wisdom with The Huffington Post audience. It seems that as the volume of nutritional studies and the corresponding media reporting increase, the confusion as to how to make sense of these studies is also on the rise. Not too long ago, we saw eggs being compared to smoking, yet we have also seen other studies demonstrating benefits of eating eggs. How can one interpret these studies to know if eggs are beneficial or harmful to health?

AG: Eggs are a good source of many beneficial nutrients, and they also contain a large amount of cholesterol (all of it in the yolk). Studies in animals have clearly shown that dietary cholesterol in its pure form does not cause atherosclerosis (hardening of the arteries).

However, cholesterol is an unstable molecule that spontaneously oxidizes in the presence of oxygen (room air) to form cholesterol oxides, which are highly toxic to arteries. The oxidation of cholesterol by oxygen is greatly accelerated in the presence of heat. If the yolk of an egg remains intact during cooking (as with boiling or poaching), the cholesterol in the yolk is not exposed to room air, and the formation of cholesterol oxides would be expected to be minimal. In contrast, breaking the yolk during cooking (as with scrambling) would presumably lead to the formation of large amounts of cholesterol oxides. Consequently, the benefits and risks of eating eggs may depend in large part on how they are cooked.

The study you cited showed that eating more eggs was associated with more extensive atherosclerosis in the carotid arteries. However, simply showing an association does not prove cause and effect. There might be fundamental differences in diet, lifestyle, and body chemistry between people who do and do not eat large amounts of eggs, and some of those differences (as opposed to the number of eggs consumed) might explain the observed association. Based on the totality of the evidence, it appears that boiled or poached eggs can be an important part of a healthful diet, whereas consumption of scrambled (and possibly fried) eggs should be kept to a minimum.

PF: The benefits of another popular item, fish oil, have been questioned in a study that recently received a lot of attention in the media. Millions of Americans take fish oil daily. Doctors prescribe it. We have read about so many benefits for cardiovascular health, brain health, and anti-inflammatory benefits. Are there benefits to fish oil, specifically for heart health?

AG: The study you mentioned was a meta-analysis (pooled analysis) of 20 randomized controlled trials (including a total of 68,680 patients) that examined whether supplementing with the omega-3 fatty acids present in fish oil can decrease heart disease-related mortality or deaths due to any cause.

In the pooled analysis, omega-3 fatty acids decreased heart disease-related deaths by 9 percent and deaths due to any cause by 4 percent. Because these decreases were not statistically significant, the researchers concluded (erroneously) that omega-3 fatty acids had no effect on cardiac or all-cause mortality.

The correct conclusion is that omega-3 fatty acids decreased cardiac deaths by 9 percent and all-cause mortality by 4 percent, but because the effects were not statistically significant, we are less than 95 percent certain that the benefits were real (as opposed to being due to chance). Failure to demonstrate that an effect was statistically significant is not the same as demonstrating there was no effect.Furthermore, the potential benefit of taking fish oil might be greater than the results of the meta-analysis suggest. That is because some of the studies that showed a strong positive effect were "diluted" by several flawed studies that found no beneficial effect of fish oil.

One of the negative studies enrolled 18,645 Japanese patients (27.2 percent of all the patients in the meta-analysis), and therefore had a relatively strong influence on the results of the pooled analysis.

The main weakness of that study is that fish consumption is high in Japan. The protective effect of omega-3 fatty acids against heart disease can be obtained with relatively low doses, and little or no additional benefit can be achieved by increasing the dose.

Consequently, one would not expect fish oil supplementation to reduce mortality in this population where fish consumption is high. In another negative study included in the meta-analysis, olive oil was used as the "placebo." Olive oil is a known cardioprotective agent, so the fact that fish oil was not more effective than olive oil does not mean fish oil was ineffective.

A large body of research has shown that fish oil is useful for preventing and treating heart disease. Some experts recommend a dose of approximately 1 gram per day for people who want to reduce their risk of developing heart disease, and about 2 to 6 grams per day for people with existing heart disease. People with heart disease and those taking medications should consult a health care practitioner before supplementing with fish oil.

PF: Millions of Americans take a basic multivitamin, and they believe they are doing something beneficial for their health. They certainly aren't taking them to bring about an earlier death! However, several recent studies have implied that multivitamins do not contribute to a longer life. Is it beneficial to take a multivitamin? Are these studies misleading?

AG: Yes, the studies are misleading. The first study claimed to find that women who took a multivitamin had a 6 percent higher death rate than women who did not take vitamins.

However, nowhere in the study was the actual death rate reported. Rather, the researchers reported "adjusted" death rates. When the data were adjusted only for age and caloric intake, there was no significant difference in mortality between vitamin users and nonusers. It was only after further adjustment for cigarette smoking, body mass index, blood pressure, educational level, diabetes, use of hormone-replacement therapy, physical activity, and intake of fruits and vegetables that the increase in mortality was found.

For each of these factors, the vitamin users were in the "healthier" category when compared with the nonusers (e.g., less diabetes, less obesity, more physical activity).

To compensate for these differences, the researchers artificially adjusted the death rate of the vitamin users upward. No information was provided about how those adjustments were calculated, and it is possible that the researchers over-adjusted the data. In addition, the researchers failed to consider various health characteristics of vitamin users that would have led them to adjust their death rate downward.

Some of the reasons that people take vitamins (for example, they are tired or depressed, their joints hurt, or both of their parents died of heart disease) might predict an increased risk of mortality. Failure to consider those factors might give a skewed picture of the risks and benefits of taking vitamins.

In the more recent study, the incidence of heart disease was not lower in male physicians who took Centrum Silver for 11 years than in those who took a placebo. According to the label, Centrum Silver contains (in addition to vitamins and minerals) crospovidone, butylated hydroxytoluene, FD&C Blue 2 Aluminum Lake, FD&C Red 40 Aluminum Lake, FD&C Yellow 6 Aluminum Lake, polyethylene glycol, polyvinyl alcohol, sodium aluminum silicate, sodium benzoate, talc, and titanium dioxide.

It would be surprising if none of those chemicals were harmful with long-term use. In addition, Centrum Silver provides 15 milligrams of zinc per day. Long-term use of zinc might deplete copper, and copper deficiency may increase the risk of developing heart disease. Centrum Silver does contain copper, but during the study period it was in the form of cupric oxide, which studies have suggested cannot be absorbed by humans.

A number of earlier studies suggested that various vitamins and minerals can, indeed, help prevent heart disease. The new study did not address the question of whether a better-formulated product that is free from extraneous chemicals would be beneficial.

PF: Dr. Gaby, thank you so much for giving us insight to these important nutritional subjects. We'll look forward to your nutritional science expertise in your upcoming blogs at The Huffington Post Healthy Living.

More Omega-3 Fish Oil Syrup for my Waffles, Please

Fish Oil Supplements: Do They Do The Body Any Good?, Scientific American 

by Melinda Wenner Moyer

If you've been following the media trail on fish oil lately, you've probably been tempted to forgo the smelly capsules. A systematic review of 20 studies published last week in JAMA The Journal of the American Medical Association reported that neither eating extra helpings of fish nor taking fish oil supplements reduces the risk of stroke, heart attack or death. In June a review of studies published on behalf of the Cochrane Collaboration, an independent, not-for-profit organization that promotes evidence-based decision-making, concluded that fish oil pills fail to prevent or treat cognitive decline. And a 2011 meta-analysis by Yale University researchers debunked the idea that omega-3s alleviate depression. These proclamations run counter to what we have been told about fish and fish oil for decades. So why is the consensus changing? Is it time for us to toss out our pills for good?

Not necessarily. Although it's true that early research on fish oil seemed far more promising—one 1999 trial, for instance, reported that people who took omega-3 pills were 10 percent less likely to have a heart attack, stroke or die from cardiac disease than people who did not—some researchers think that recent negative findings reveal more about us than they do about fish oil. Omega-3 pills may be beneficial for certain people but not for others, they say, and existing studies may not account for individual differences.

There's no question that polyunsaturated omega-3 fatty acids—the technical name for the good fats found in fish and fish oil—are important parts of a healthy diet. Our bodies can't make them, yet we need them to survive, as they form part of our cell membranes. Although the mechanism by which they might prevent heart disease, cognitive decline and depression isn't well understood, research suggests that they reduce blood pressure and inflammation and that they increase brain blood flow and give neurons structural strength.

And no one questions the World Health Organization's recommendation that pregnant and
nursing women should consume at least 300 milligrams of omega-3s daily to boost fetal brain development. "That [benefit] has been clearly demonstrated in trials," says Dariush Mozaffarian, a cardiologist and epidemiologist at Harvard University, who studies fish oil.

But for other adults, the health benefits of supplementing have become much harder to gauge. That's in part because many of us get lots of these good fats from our diet anyway: According to the United Nations Food and Agriculture Organization, per capita fish consumption has doubled (pdf) since 1961, and "more consumption doesn't really add much bang for your buck," Mozaffarian says. In other words, adding more omega-3s to an already omega-3–rich diet does not do much good, a fact that could help explain why recent studies have been more equivocal than studies from several decades ago, when fish was less popular. "We have no evidence from populations whose dietary intake of omega-3 fatty acids may be low and who may therefore benefit from supplementation," says Alan Dangour, head of the nutrition group at the London School of Hygiene and Tropical Medicine and co-author of the recent Cochrane review. In addition, preliminary research suggests that certain ethnic groups—such as Japanese and Italians—may benefit more from omega-3 supplements than others, perhaps in part because of how well their bodies absorb the fats.

Another potential problem is that most of the research on fish oil and heart health—including all of the trials included in the recent JAMA analysis—have involved subjects who already have heart disease or established risk factors. Whereas this isn't necessarily a problem in itself, it means that very little research has addressed whether fish oil supplements benefit healthy people. "The jury is still out on whether omega-3 supplements can prevent a first cardiovascular event in people at usual risk," says JoAnn Manson, an epidemiologist at Brigham and Women's Hospital in Boston who is conducting a trial to answer this question, which she estimates will be finished in 2016.

Moreover, because so many trials have involved subjects with heart problems, subjects in recent years have been "taking multiple medications, such as aspirin and statins, which can obscure the effects of supplements," Manson says. (Half of the studies included in the JAMA analysis were conducted after statins became commonplace.) This fact could also help explain the outcome discrepancies between recent trials and older ones carried out during the pre-statin era. Indeed, a February 2012 analysis of a large European clinical trial reported that fish oil supplements do not prevent second heart attacks among people taking statins, but that it cuts risk by half among people who don't take the medications. (Because there were so few non-statin users enrolled in the trial, this finding did not quite reach statistical significance.)

People who enroll in and complete omega-3 trials may differ from typical Americans in important ways, too. "Members of the public who volunteer to join randomized controlled studies are frequently healthier and more active than the average for the population," Dangour says, which could affect outcomes in unknown ways. In addition, he adds, people who drop out of trials are often the sickest, and they might be the ones who would most benefit from supplementation.

There's also more than one type of fish oil. Typically, in omega-3 intervention studies, subjects take pills containing a near-equal mixture of two fats, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—but some research suggests that in certain situations and for certain outcomes, one may be better than the other. For instance, a 2011 meta-analysis concluded that fish oil capsules don't help treat depression, but a group of British and Norwegian researchers challenged these findings, citing evidence that pills containing at least 60 percent EPA do seem to provide mood benefits. Another controversial question is whether the omega-3 dose is important in and of itself or whether the ratio of omega-3 to omega-6 fats one consumes is more important. (Although omega-6 fats are important for survival, Americans tend to consume far more of these fats than they need.)

Finally, whereas the recent JAMA analysis concluded that fish oil has no effect on cardiovascular outcomes, the researchers did find that omega-3s reduced the risk of cardiac death by 10 percent, an effect that was statistically significant (having a "p value" of 0.01).

The researchers did not report the finding in their conclusions because they subsequently modified their statistical calculations to account for the fact that they had used the same data set to ask a number of different "exploratory" questions: In this case, does fish oil prevent heart attacks? Strokes? What about sudden cardiac death? The team wanted to tighten their definition of statistical significance to account for the fact that the more questions one asks, the more likely one is to get a positive result by chance. Still, Mozaffarian says, "if you combine all the data and look only at cardiac death, there is a statistically significant benefit. A 10 percent reduction in the number-one cause of death in both men and women in the U.S. is a big deal."

So, should you take fish oil pills or not? Most researchers agree that oily fish such as salmon and mackerel are far better way to get your fill of good fats. Many of the early, promising studies on omega-3s involved fish rather than fish oil pills (in one, men who were advised to eat fish were 29 percent less likely to die in the two years following a heart attack than men who were not), and a 2010 study by Columbia University scientists reported that following a Mediterranean diet—which, among other things, is rich in fatty fish—reduces the risk of Alzheimer's disease by 34 percent. "Not only may people be benefiting from the omega-3 fatty acids in fish, but the fish may be displacing such foods as hamburgers and quiche from the diet, both high in saturated fat," explains Alice Lichtenstein, director of the Cardiovascular Nutrition Laboratory at Tufts University.

If you don't eat fish, then the question of what to do becomes more difficult. Researchers argue that, ultimately, we need more randomized, controlled clinical trials on omega-3 supplements—particularly in healthy people who don't take medications—but these are becoming rare, in part because the supplements will never be big moneymakers. "Generic fish oil is available, so drug companies don't have any strong motivation to fund trials," Mozaffarian says.

But despite the murky science, if you don't get omega-3s from other sources—or if you have heart disease risk factors but aren't taking medications—omega-3 pills may still be a good idea. "There's no harm in taking a fish oil supplement, and there could be benefits," Mozaffarian says. "The bottom line is that getting some [omega-3] is better than getting none."