Antioxidants and Metabolic Syndrome

While it may be true that an apple a day keeps the doctor away, eating berries, nuts, and other sweet foods won’t hurt either. Some of the latest nutrition research explores the idea that anti­oxidants in fruit may play a role in preventing health problems associated with metabolic syndrome, such as obesity, cardiovascular disease (CVD), and diabetes.

The idea isn’t new. Thousands of years before the Greek physician Hippocrates recommended using food as medicine, ancient Egyptian doctors recorded their knowledge of the therapeutic value of pomegranates, celery, and spices on pieces of papyri, according to researchers at the University of Manchester in the UK.

Today, a wealth of new data on fruit antioxidants is located in the 21st-­century version of papyri-the National Library of Medicine’s (Bethesda, MD) Medline database. Nutrition scientists are increasingly focusing on polyphenols and other antioxidant nutrients in fruits that appear to help maintain a healthy weight, protect the cardiovascular system, and regulate blood sugar levels.

METABOLIC SYNDROME

Nearly 50 million Americans have metabolic syndrome, a collection of risk factors related to obesity, diabetes, and CVD, according to the National Heart, Lung, and Blood Institute (Bethesda, MD). People with metabolic syndrome are twice as likely to develop CVD and five times more likely to develop diabetes than the general population.

The risk factors that lead to metabolic syndrome include: a large waistline, higher-than-normal levels of triglycerides, low levels of high-density lipoprotein (LDL) cholesterol, higher-than-normal blood pressure, and higher-than- normal blood sugar levels.

A growing body of research implies that foods that are high in antioxidants, fiber, and healthy fats may have a positive effect on some of the risk factors associated with metabolic syndrome. While the evidence is not conclusive, many nutrition experts recommend increasing consumption of antioxidant-rich fruits and vegetables.

NUTS, BERRIES, AND OTHER FRUITS

Conventional wisdom suggests that eating high-fat foods like nuts could lead to obesity. However, new data indicate that may not be the case. In fact, nuts contain significant amounts of healthy fats and fiber that may offset their high energy content. Similarly, berries and other fruits provide nutrients that may fight inflammation, promote a healthy cardiovascular system, and perform a host of other useful bodily functions. Thus, many foods associated with the so-called Mediterranean diet, which draws heavily from plant-based foods, appear to have a positive influence on metabolic syndrome.

For instance, early results from the Prevención con Dieta Mediterranea (PREDIMED) study, a Spanish multi­center trial involving 9000 participants, indicate that the Mediterranean diet protects against CVD by inhibiting oxidative damage to LDL cholesterol.

In the PREDIMED study, researchers assigned one of three diets to a subgroup of 772 volunteers at risk of developing CVD. The participants followed either a Mediterranean diet enriched with 30 g of mixed nuts (15 g of walnuts, 7.5 g of hazelnuts, and 7.5 g of almonds) per day; a Mediterranean diet enriched with 1 L of olive oil per week; or a standard low-fat diet. During the three-month trial, the researchers measured several variables associated with cardiovascular health.

Ancient Man, Professional Botanist

At this year’s International Berry Health Benefits Symposium, held June 11–12 in Corvallis, OR, nu­trition experts gathered to share the latest scientific data on the antioxidant properties of berry fruits. During his keynote address, David Heber, MD, director of UCLA’s Center for Human Nutrition (Los Angeles), took a few moments to acknowledge an early trailblazer in the field of phytonutrition: ancient man.

Modern man’s hunter-gatherer ancestors were “the real professional botanists,” Heber said, noting that they knew more about plants and plant reproduction than most of today’s educated urban population.

“Ancient man lived in equilibrium with plants,” Heber explained. “In the old days, he would eat about 800 varieties of plant foods. Modern Americans eat only three, and if you take out French fries and potato chips, you’re down to one and a half.” According to Heber, today’s diets contain an excess of calories, fat, and sugar, and not enough vitamins, minerals, and plant nutrients. “Our junk diets are out of balance,” he said, adding that “we spend less on our food supply than most other countries do.”

According to Heber, berry phytochemicals play an essential role in human health. “It’s amazing to look at these structures,” he said. “There are simple, active compounds in these plants, and then there are these amazing arrays of chemicals that are produced by plants for their own purposes, but then by a coevolution, we need these substances.”

One reason why berry antioxidants are so important is that they interact with human genes that influence many health conditions. Estimating that genes influence about 30% of a person’s health, Heber said environment, diet, life­style, and other factors account for the other 70%. “Genes are like a blueprint of a house,” he said. “Just because you have a blueprint, you don’t know what kinds of appliances are in the kitchen.”

As an example, Heber noted that while the BRAC1 gene is associated with a 90% lifetime risk of developing breast cancer, only about 10% of women who get breast cancer have a genetic abnormality. “Let’s say you find a gene that causes a 50% increase,” he said. “That sounds really scary and substantial. But if a woman’s risk is 3% and a variant is found that makes her 1.6 times more likely, now she’s just got a 4% risk, and it’s unclear how life-style modification might influence the expression of that gene. Gene-nutrient interactions are much more important than isolated genomics, and that’s where the berries come in.”

Because the list of America’s most commonly eaten fruits and vegetables includes mostly bananas, potatoes, corn, apples, iceberg lettuce, and tomatoes, Heber developed a color-coded diet plan for consumers that classifies fruits and vegetables on the basis of their phytochemical content.

But he also pointed out that consumer education is only part of the solution. Manufacturers can also promote consumer interest in fruit-based products by funding more research into the health benefits of antioxidants, he said, offering pomegranates as an example. “There are currently more than 20 medical publications to date on pomegranates, there are 20 medical publications targeted this year for pomegranate research, and there are more than 30 medical research projects on pomegranates in the works,” he said.

“There are no evil people in the big food industries conspiring against you,” he added. “If you get the public interested in eating the foods you are researching and they start buying them in grocery stores, the grocery stores will stock those products.” Because Americans spend about $130 billion per year fighting obesity, Heber predicted that berries represent a potential “gold mine” of products for health-conscious consumers.

According to PREDIMED general coordinator Ramon Estruch, MD, volunteers who followed the two Mediterranean diets experienced lower blood pressure, blood glucose levels, cholesterol, triglycerides, and less inflammation. The Mediterranean diet volunteers also had elevated levels of high-density lipoprotein (HDL) cholesterol and, most notably, did not gain additional weight. In addition, while the olive oil– supplemented diet had a positive effect on C-reactive protein, the PREDIMED team noted that high levels of antioxidants in the walnuts contributed to the other Medi­terranean diet’s cardiovascular effects, particularly its beneficial effects on triglycerides.

“It’s easy to foresee that the participants who follow the Mediterranean diet supplemented with olive oil or nuts will show in the long run a 50% reduction in the risk of cardiovascular complications,” Estruch said on June 27. The researchers published the results in the July 4, 2007, issue of the Archives of Internal Medicine.

Walnuts aren’t the only nuts with antioxidant effects, however. In the April 27, 2007, issue of the Journal of the American College of Nutrition, George Mason University (Fairfax, VA) researchers reported that pistachios appear to have a favorable impact on blood lipid levels. To test the theory that pistachios, which consist of about 55% mono­unsaturated fat and 32% polyunsaturated fat, can protect the heart, the researchers instructed volunteers in a small, randomized, crossover trial to supplement their regular diet with 2–3 oz of pistachios per day for four weeks and follow a normal pistachio-free diet for another four weeks.

The George Mason University researchers found that when the volunteers supplemented their diet with pistachio nuts, they experienced statistically significant drops in the ratios of total cholesterol (TC) to HDL, LDL to HDL, and apolipoproteins B-100 to A-1. Additionally, the volunteers had higher HDL levels. Overall, the volunteers consumed less saturated fat and more fiber when following the diet.

“These results are exciting because the research indicates that adding pistachios to the daily diet can help protect the heart without a dramatic life-style change,” said James Cooper, MD, the study’s lead author, on June 11. “This research challenges the previously held belief that a low-fat diet is best for heart health. Studies now show that a diet with a moderate amount of healthful monounsaturated fat, like the kind found in pistachios, is a more effective way to prevent heart disease than reducing overall fat intake.”

The study may confirm earlier data presented by different researchers at the Experimental Biology meeting in Washington, DC, last April. In that presentation, data gleaned from a similar crossover trial involving pistachios showed that the nuts also had positive effects on cardiovascular health, possibly via their high lutein content, which appeared to inhibit LDL oxidation.

Berries and other fruits also offer health benefits that are relevant to metabolic syndrome. Fruits contain hundreds of different types of antioxidants, which are often concentrated in brightly colored pigments. While berries are frequently praised for their high antioxidant content, many other types of fruits also contain antioxidants, such as flavonoids, tannins, anthocyanins, and carotenoids.

In the March 2007 issue of the American Journal of Clinical Nutrition, researchers who analyzed data from more than 34,000 postmenopausal women reported an association between flavonoid-rich fruits and a reduced incidence of CVD, coronary heart disease, and stroke over a 16-year period. The list of flavonoid-rich foods identified by the researchers included apples, pears, strawberries, grapefruit, wine, and chocolate.

Chocolate, in fact, may have effects that are similar to those of pistachios and walnuts. According to researchers from the University of Cologne in Germany, eating small amounts of dark chocolate seems to help lower blood pressure without causing significant weight gain.

Reporting in the July 4, 2007, issue of the Journal of the American Medical Association, the University of Cologne researchers randomly gave 44 adults with early-stage hypertension either 6.3 g of dark chocolate per day or an equivalent amount of white chocolate for 18 weeks. The dark chocolate contained approximately 30 mg of cocoa flavonoids per serving, while the white chocolate did not contain any flavonoids.

By the end of the trial, the researchers found that the average systolic and diastolic blood pressure of the volunteers who received the dark chocolate dropped by 2.9 (1.6) mmHg and 1.9 (1.0) mmHg, respectively, but the blood pressure of the white chocolate group did not change. Moreover, in the dark chocolate group, the average prevalence of hypertension decreased from 86% to 68%. According to the researchers, each 3-mmHg drop in systolic blood pressure translates into an 8% reduction in the risk of stroke mortality, a 5% reduction in the risk of coronary artery disease mortality, and a 4% reduction in all-causes mortality. “Although the magnitude of the blood pressure reduction was small,” wrote the researchers, “the effects are clinically noteworthy.”

Ancient Man, Professional Botanist

One of the first things many consumers do when they wake up is reach for coffee. Steifel Laboratories Inc. (Coral Gables, FL) hopes that when they do, it will be as part of their morning skin-care routine.

In June, Steifel Laboratories introduced Revaléskin, a line of cosmeceutical skin-care products formulated with Coffee­Berry, a coffee extract supplied by VDF FutureCeuticals Inc. (Momence, IL).

“Revaléskin can improve the skin’s appearance so quickly because its primary ingredient, CoffeeBerry, is abundant in four powerful polyphenol antioxidants that help prevent and reduce superficial damage from sun exposure and free radicals,” Steifel Laboratories senior vice president of sales and marketing Jim Hartman said on June 26.

Extracted from subripe coffee beans, CoffeeBerry contains a number of compounds, including chlorogenic acid, condensed proanthocyanidins, quinic acid, and ferulic acid. “It’s having four polyphenols that makes CoffeeBerry even more potent than such robust antioxidants as green tea, pomegranates, blueberries, vitamin C, and vitamin E,” Hartman said.

CONSIDER THE SOURCE

Despite the promising new data, the field of antioxidant research has its share of uncertainty. Many of the latest studies are small in scale and short in duration. Moreover, some in vitro and animal research may not be applicable to people. Also, researchers are increasingly discovering that the antioxidant compounds in fruits may rely on complex interactions with genes or other phytonutrients to produce their beneficial effects.

Two different researchers recently pointed out some areas of nutrition research where more data are needed. In the December 2006 issue of Free Radical Biology and Medicine, Linus Pauling Institute (Corvallis, OR) director Balz Frei, PhD, noted that the metabolism of flavonoids within the human body may interfere with their ability to function as antioxidants. And USDA (Washington, DC) scientist Ronald Prior, PhD, reported in the June 2007 issue of the Journal of the American College of Nutrition that the human body’s ability to absorb antioxidants from fruit can vary significantly, depending on the source of the antioxidants.

“If you measure the activity of flavonoids in a test tube, they are indeed strong antioxidants,” according to Frei. “Based on laboratory tests of their ability to scavenge free radicals, it appears they have three to five times more antioxidant capacity than vitamins C or E. But, with flavo­noids in particular, what goes on in a test tube is not what’s happening in the body.”

Similarly, Prior noted that in a series of experiments involving volunteers who ingested various types of fruits, some antioxidant-rich foods like plums did not raise plasma antioxidant capacity (AOC) because they contained other phytochemicals that are difficult for the body to absorb. Other fruits like blueberries did raise plasma AOC, but only after the volunteers ingested higher-than-normal amounts. “Without further long-term clinical studies, one cannot necessarily translate increased plasma AOC into a potential decreased risk of chronic degenerative disease,” he wrote.

New Pomegranate Reference Standards Available

Reference standards have always been an important aspect of natural products manufacturing. Now that the official good manufacturing practices (GMPs) for supplements mandate ingredient testing, they are about to become even more important.

On June 14, Chromadex Inc. (Irvine, CA) unveiled new reference standards for punicalagins A and B, compounds associated with the antioxidant activity of pomegranates. Intended to help manufacturers accurately quantify pomegranate ingredients, the standards are available as part of an HPLC testing kit that includes an HPLC column and testing method, or through contract testing services.

EAT LIKE AN ARTIST

To combat obesity, it helps to eat like an artist. Colorful foods contain the largest share of antioxidant pigments, and fruits are superstars in that regard. Future studies involving fruit antioxidants should further elucidate the connection between flavonoids, other phytonutrient compounds, and metabolic syndrome. Until then, manufac­turers of healthy foods and health-conscious consumers may want to keep both palette and palate in mind.