2017 Cranberry Update: Should We Focus on PACs or on the Whole Fruit?

Photo © Shutterstock.com/DMITRIY NOSYREV

Judging by the massive turnout at Women’s Marches around the world this past January, women’s liberation is clearly back in style. (The movement even has its own signature headgear: those très chic pink caps.) And while it’s gratifying to stand back and marvel at all the oppressions the distaff sex has liberated itself from-the patriarchy, household drudgery, shoulder pads-to tweak a certain marketing slogan from feminism’s second wave, “You’ve got a long way to go, baby.”

Case in point: Women have yet to liberate themselves from urinary tract infections (UTIs), or from the endless courses of antibiotics needed to treat them. But they’re making progress, thanks to research into the cranberry, which has long been something of a folk remedy for when urinary health falters.

Notes Christina Khoo, PhD, director, global research sciences, Ocean Spray Cranberries (Lakeville-Middleboro, MA), “For generations, women have passed down their belief in cranberry’s ability to help prevent urinary tract infections based on their own positive experiences.” What’s different now, she says, is that “more than 50 years of well-documented research has turned this folklore into fact.”

What’s also different is that the cranberry is proving to be an equal-opportunity defender, its functional phenolics and chemical constituents conferring a wide range of health benefits beyond the urinary tract alone. So maybe we can have it all? Cranberry supporters are keen to find out.

UTIs and You

Whether they affect you or not-and if you’re a woman, they probably do-urinary tract infections are serious business. “UTIs are among the most common bacterial infections treated in women, which is why they garner so much interest,” says Cindy Taccini, director of global health communications at Ocean Spray.

According to statistics from the National Institute of Diabetes and Digestive and Kidney Diseases, UTIs are the second-most common type of infection in humans, triggering roughly 8.1 million doctor visits per year. Women are particularly susceptible-thanks in part to their shorter urethras, which hasten bacteria’s trip to the bladder-putting their lifetime risk of getting a UTI north of 50%. Moreover, says Dean Mosca, president, Proprietary Nutritionals Inc. (Kearny, NJ), “Once an individual has had a UTI, the likelihood of having another escalates.”

Prevention is key, he emphasizes, as “antibiotics aren’t a long-term solution, due to the possible development of antibiotic resistance and detrimental effects on good gut bacteria.” A 2014 World Health Organization report on global antibiotic resistance noted that resistance to one of the drug classes most widely used to treat Escherichia coli–caused UTIs-the fluoroquinolones-was already so widespread that, in some parts of the world, the drugs are ineffective in more than 50% of patients. No wonder, Taccini says, that WHO considers antibiotic resistance “one of the greatest challenges to public health today, and one that makes leveraging cranberry’s benefits important.”

Resistance Fighters

That the humble cranberry might bend this curve seems a stretch. But, says Mosca, “Unlike antibiotics, which kill bacteria, cranberry works by changing bacterial structure and preventing adhesion to tissues, providing for effective prevention without the risk of developing antibiotic resistance.”

We know this now, but it took the research community a while to figure out. As far back as the 1700s and 1800s, Mosca says, researchers were already investigating cranberry and seized upon its ability to acidify urine as a possible mode of action-although further research failed to support it. So while cranberry stayed popular for urinary health, “its true mechanism remained a mystery.”

That changed in the early 1980s when research appeared in the Journal of Urology showing that cranberry inhibited E. coli adherence to urinary-tract epithelial cells by 80%, a finding that human clinical trials later confirmed. Subsequent research then focused on cranberry’s condensed tannins- antioxidant flavonoids known as proanthocyanidins, or PACs-as the source of the anti-adhesive effect. “These compounds adhere to the fimbriae of the bacterial surface,” Mosca explains, “thus preventing adhesion to the mucosal lining of the bladder.” And that makes it easier to flush bacteria out with urination. “In 1991,” he says, “this finding was duplicated by Israeli researchers and published in the prestigious New England Journal of Medicine.”

Studies continue to support cranberry’s effectiveness. “The largest clinical trial¹ of its kind, published last year in The American Journal of Clinical Nutrition, showed that drinking an 8-oz, or 240-ml, glass of cranberry juice a day reduces symptomatic UTIs by nearly 40% in women with recurrent UTIs, reducing the burden of UTIs and the antibiotic use associated with treating recurrent UTIs,” Khoo notes. “The study showed that 30 courses of antibiotics were avoided in women with symptomatic UTI during the course of the six-month study period.”

Go Whole

And though cranberry PACs “have taken center stage as the cranberry component responsible for its bacteria-blocking benefits,” Khoo continues, scientists are gaining “exciting insights” into other cranberry constituents that contribute to the bacteria-blocking effect, including flavonols and “newly discovered” xyloglucan oligosaccharides. “Researchers now believe cranberry’s ability to block bacteria is due more to its combination of compounds working together than to a single component,” she says. “This unique blend of bioactive components is what makes the cranberry such a powerful fruit.”

And the idea of delivering cranberry’s whole spectrum of benefits via whole-berry ingredients is increasingly popular with cranberry processors and brands, too. Notes Dan Souza, vice president, sales and marketing, and category manager for urinary, cardiovascular, and cognitive health, Naturex-DBS (Sagamore, MA), “What we’ve found is that Nature knows more than we do.” The main lesson he thinks researchers learned in teasing apart different fractions’ benefits is that “the more parts of the cranberry we use in these models, the better results we see. So let’s not try to reinvent the cranberry here. Let’s optimize what Nature made for us.”

Beyond UTIs

When we do, we realize that cranberry’s benefits go beyond the bladder-or the entire urinary tract. Indeed, says Mosca, “Any common pathogenic bacteria that can colonize through adhesion is definitely a target for either prevention or eradication.” In fact, “some general studies on cranberries suggest that they may tackle more than just the one pathogen that causes urinary-tract and bladder infections.”

For example, the bacteria that causes stomach ulcers, Helicobacter pylori, infects about half the world’s population, according to the World Organization of Gastroenterology, and “research suggests that cranberry’s antibacterial properties may help promote stomach health in certain adult populations by suppressing H. pylori,” Khoo says.

Cranberries are even good for the mouth-and not just because they taste great. “Emerging studies suggest that cranberry can help promote oral health by reducing the activity of cavity-forming bacteria,” Khoo says. “Specifically, cranberry extracts reduced inflammatory responses to oral bacteria and/or bacterial growth.”

Khoo adds that research has expanded to encompass more of the fruit’s antimicrobial effects, including its action against bacterial aggregation, growth, and biofilm formation. “Emerging data also suggest that cranberries have prebiotic properties that promote ‘good-bacteria’ growth and activity,” she says.

Gut Instincts

As a foil to the antibiotics that often do the exact opposite, the notion that cranberries might actually promote gut health is encouraging. And here again, Khoo says, the main player appears to be PACs, “as these large polymeric compounds can be metabolized by gut flora to yield bioactive components that can impact the immune system in the gut and confer anti-inflammatory properties or provide food for the gut biome.” An “elegant” review on the subject by Cires et al. appeared in Frontiers in Nutrition in 2016, she says.²

Stephen Lukawski BA, M.Ed, director of business development and global sales, Fruit d’Or Nutraceuticals (Notre-Dame-de-Lourdes, QC, Canada), notes that his company teamed with UAS Labs (Wausau, WI) to conduct a cranberry-probiotics study³, now published in the Journal of Functional Foods. The results held that the pairing of whole-fruit cranberry with probiotics inhibits in vitro invasion of gut epithelial cells by extra-intestinal pathogenic bacteria (ExPEC). “The standardization of soluble and insoluble PACs derived from whole-fruit cranberries reduces the invasiveness of ExPEC,” he says, “and c-PAC inhibition of ExPEC invasion was not hindered by the probiotic component.”

The company also partnered with Sabinsa (East Windsor, NJ) to show that Fruit d’Or’s organic cranberry-seed powder, standardized to a minimum 3% PACs and combined with Sabinsa’s LactoSpore Bacillus coagulans probiotic, acted prebiotically and “was more effective by 200% than fructooligosaccharide or inulin,” Lukawski says. The cranberry-seed powder, with its protein and fiber, provided handy nitrogen and carbon fuel for the Bacillus coagulans strain, it appears. Lukawski’s conclusion: “Cranberry juice plus probiotics plus prebiotics equals a great synbiotic gut formulation.”

Measuring Progress

While research credits cranberry’s panoply of bioactives for making it so effective in these conditions, it’s still the fruit’s PACs that garner the most attention-from scientists, brands, and consumers. And as consumers get savvier about cranberry’s benefits, they’ll start scanning product labels for PACs specifically, and at specific levels.

And yet, says Cal Bewicke, president, Ethical Naturals (San Anselmo, CA), “Many types of cranberry extract and concentrate products are offered with specifications according to ratios or other methods, which can be very confusing to a consumer trying to find a good source of material to use.” Further, accurately measuring cranberry’s A-type PACs, which he says are those linked to improved urinary, oral, and gut health, “has always presented a challenge due to their structural complexity and degree of polymerization.” Methods ranging from colorimetry, chromatography, and mass spectrometry all aim at a correct true analysis, but their results can vary, are often hard to reproduce, and may fail to distinguish cranberry PACs from those from other sources, he says.

The 2010 emergence of the DMAC (or BL-DMAC, after its initial developers at Brunswick Labs) method “has allowed manufacturers to develop and verify highly concentrated cranberry extracts from whole fruit,” Bewicke says, leveling the playing field for manufacturers and providing “a product that the consumer can clearly evaluate with respect to potency.” The test also allows brands to make claims that correspond more accurately to specific amounts of cranberry PACs-an advantage that he says wasn’t possible before the consistency and reliability that he says DMAC now supplies.

Lukawski also praises improved means of measuring the fruit’s key actives, and hopes the industry goes further. “We need higher-quality testing for the standardization of bioactive markers, such as PACs, to stop companies from selling inferior cranberry ingredients and so consumers can identify quality.” He even thinks DNA authentication “to prevent adulteration” is a good idea. Simply relying on cranberries’ healthy halo alone “hurts us all,” he says.

It’s All in the Ingredient

By contrast, Souza thinks companies should “stay away from the standardization game” and just show that a cost-effective amount of cranberry delivers strong activity, as demonstrated in clinical trials. “Depending on the application we’re going for,” he says, “we’ll use different ratios of the different parts of the cranberry. So there are certain applications where maximum PACs are the best solution because you might need something that’s water soluble and has quick uptake-say, for oral health.” Other applications will require a different blend.

Ultimately, he says, “We continue to try to make it easier for customers by giving them efficacy, traceability, identification, non-adulteration, and safety data-all the checkmarks you need as a sourcing manager.”

And because today’s cranberry ingredients come in everything from concentrates and extracts to powders and dried berries themselves, they let brands “take advantage of opportunities for product innovation,” Taccini says. One of the assets of powders and berries “is that they can be incorporated into a variety of products like baked goods, cereals, and waters while maintaining the cranberry components that are important for health and functionality,” she adds. “They also contribute great taste.”

And they’re recognizable as real, whole fruits-perhaps even “superfruits.” At a time when “consumers simply want more fruit in their diets,” Taccini says, this alone puts the berry steps ahead. Yet, she says, “It’s the unique benefits of the cranberry that differentiate us from other fruits and help us live up to the broader idea of being a superfruit.”

Also read:

UTIs: They’re Not Just for Women Anymore

Talk about gender equality! Yes, urinary tract infections are practically synonymous with “women’s health,” and women suffer from them at rates about four times those of men. Even so, men still get ’em.

This fact did not escape Dan Souza, vice president, sales and marketing, and category manager for urinary, cardiovascular, and cognitive health, Naturex-DBS (Sagamore, MA), who realized that treating urinary health solely as a women’s issue left half the population-and half the potential market for cranberry-based remedies-unaddressed.

“So we did a lot of digging to see what other applications we could find for cranberry,” he says, “and we saw that it actually works well for men’s urinary symptoms.” When men hit their 40s and 50s, age-related prostate enlargement produces lower urinary tract symptoms-“think frequency of having to go to the bathroom, waking up to have to go to the bathroom or, on the other end of the spectrum, a hesitancy to go to the bathroom, or not being able to get started,” Souza says.

Clinical trials on his company’s standardized cranberry ingredient yielded evidence of symptom relief, including “great data on men’s overactive and underactive bladder symptoms.” There’s a $5 billion per-year market for the drugs in that space, he says, but the drugs induce side effects that no one-male or female-likes. Cranberries, refreshingly, have no known side effects. Having started clinical trials in women, too, the company’s “hoping that the mechanism is similar in men and women and that we’ll be able to get some good clinical results there, as well,” he says.

Also read:

Cranberry Industry Skewers JAMA Editorial Proposing No UTI Benefits

How Should We Market the Cranberry?

Cranberry Plus Probiotics Defends against E. Coli in Preclinical Study

Cranberry Plus Probiotic Tackles First Gummy

References:

1. Maki KC et al., “Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection,” American Journal of Clinical Nutrition, vol. 103, no. 6 (June 2016): 1434-1442
2. Cires MJ et al., “The gastrointestinal tract as a key target organ for the health-promoting effects of dietary proanthocyanidins.” Frontiers in Nutrition. Published online January 3, 2017.
3. Polewski MA et al., “Ability of cranberry proanthocyanidins in combination with a probiotic formulation to inhibit in vitro invasion of gut epithelial cells by extra-intestinal pathogenic E. coli,” Journal of Functional Foods, vol. 25 (August 2016): 123-134