Andrew Rosenblum

One of us likes carbonated drinks, but knows they are not good for health. People who drink more than one sugary drink a day tend to gain weight and are 26% more likely to develop type 2 diabetes than those who do not. That's one reason why food companies sold more than $11 billion worth of diet sodas to Americans in 2020.

The controversy over sugar-free soda is growing. In May, the World Health Organization (WHO) warned about consuming artificial sweeteners for weight loss. Worse, the organization also found that long-term consumption of non-caloric sweeteners can actually contribute to type 2 diabetes, cardiovascular disease, and premature death. WHO recommends that people make an effort to reduce sugar intake instead.

But it's easier to look at the colorful can of yum with lots of cold foam than to say. I respect everything about people who use water, quinoa, and oranges.

Oobli, a startup in California, is one of several companies touting sugar and non-caloric sweeteners as alternatives, and has slipped a sweet protein called Brazzein into an iced tea blend. Originally found in the bright red or mottled gray fruit of the Oubli fruit tree, Brazzein is 500 to 5,000 times sweeter than sugar. It contains no carbohydrates, so it does not cause metabolic complications such as insulin spikes associated with non-caloric sweeteners.

However, for the 6-pack of iced tea sold for $15, the company needs to convince nutritionists and consumers that Brazzein cannot be another disappointing fad sweetener. The company must acknowledge that the sweet protein was grown in the lab through fermentation with the help of genetically modified yeast for economic and ecological reasons. And there is an issue of safety confirmation from the U.S. Food and Drug Administration (FDA). (The company announced peer-reviewed studies confirming the safety of the sweet protein through fermentation with genetically modified yeast in collaboration with third-party labs, allowing the product to be sold in the U.S. until the FDA issues a letter agreeing with these conclusions. However, some retailers do not carry it.)

The average American consumes about 60 pounds of added sugar a year, with almost half of it coming from beverages.

Ali Wing, CEO of Oobli, says, "Today, 75% of American consumers are actively trying to reduce sugar. Chocolate bar. "There are 50 forms of sugar, and we've been trying for the past 20 years, and it's not going well. They update every 6 weeks on another alternative sugar that can actually be worse for you than we thought. Consumers are skeptical."

But chocolate is just the beginning of the company's ambition. Oobli sees sugary drinks as a really promising niche market. The average American consumes about 60 pounds of added sugar a year, with almost half of it coming from beverages. Jason Ryder, CTO of the University of California, Berkeley, and adjunct professor of chemistry and bio-molecular engineering, says, "This is a sugar delivery mechanism."

Wing says, "Beverages are the 800-pound gorilla of the problem. And that's why so many people switched to diet soda or unsweetened tea from the start."

More than meeting the tongue

Due to decades of marketing, zero-calorie drinks have been believed to be as flavorful as water.

Ryder says artificial sweeteners deceive the body into thinking it's sugar. Recent studies suggest that diet soda is not good for health because it can stimulate appetite or confuse the body. Obese women and people ate more in response to the taste of sucralose sweetened drinks compared to the control group who drank regular soda.

"Sugar and alternative sweeteners are in the same class, they are both small molecules, and they both fundamentally do the same thing," he says. "They bombard your T1R2 and T1R3 taste receptors." These molecules essentially bombard our system, which was almost never consumed, but is now ubiquitous.

Ryder says these molecules not only detect sweetness in taste receptors on the tongue and in the gastrointestinal tract, but also perform important signaling functions. "They tell your brain, 'Hey, we have sugar coming! It's time to make insulin. We need to bring sugar into the bloodstream so we can send it to the cells that need it.'"

Ryder said this sensitivity to sugar evolved because our ancestors thousands of years ago relied solely on sugar derived from fruits in the summer, in addition to honey, other starches, and complex carbohydrates. In contrast, the modern food system is so full of simple sugars and sweeteners that it effectively overwhelms taste receptors in the mouth and gut. Non-caloric sweeteners like aspartame in diet cola play a role in tricking the body into an insulin response even though these molecules are not actually composed of real sugar to be collected.

Contrastingly, modern food systems are filled with simple sugars and sweeteners that effectively overwhelm taste receptors in the mouth and gut. Artificial sweeteners like aspartame in diet sodas play a deceptive role in triggering insulin responses even though these molecules are not actually composed of real sugar to be metabolized.

Ryder says, "Things like aspartame cannot be metabolized properly, so they continue to trigger insulin responses." But there's no sugar to go in."

So our repeated insulin trips can lead to type 2 diabetes and many other issues. This includes a potential link between long-term non-nutritive sweetener consumption and cardiovascular disease, disruption of gut microbiota, colonization of beneficial bacteria, and other organisms in the gastrointestinal tract.

Brazzein avoids these metabolic disruptions because our bodies process proteins differently. It tastes sweet in the mouth but does not trigger insulin responses and is broken down in our gut.

Ryder says, "They start to break down into peptides and amino acids. So while sugars and sucralose and aspartame continue to banish insulin responses to all taste receptors in the gut, the proteins are already done."

Nutritionists wanted more data, but it's intriguing

Nutrition experts discussing with Proto.Life offered qualified support for Oobli's Brazzein as a way to reduce the calories Americans get from sugary drinks, but expressed a desire for additional research before fully endorsing the product.

"Are there health benefits to Brazzein-sweeted drinks? Yes. They have fewer calories than regular sugar, so they have a lower blood sugar load," says author William Li in Eat to Beat. He also added that preliminary studies suggest that proteins have antioxidant and anti-inflammatory properties, but research on how much is needed for humans has not been conducted. "So it's premature to speculate on the benefits or potential long-term side effects," he says.

UCLA senior gastrointestinal nutritionist Christina Fasulo sees Brazzein as a promising alternative to excessive amounts of sugar in the American diet. She also notes the antioxidant and anti-inflammatory effects of Brazzein shown in compelling lab and animal results, but wants to see human studies before recommending the substance to patients.

Fasulo also points out that the evidence for diet soda is not entirely conclusive. According to a meta-analysis of 20 recent randomized controlled trials, non-nutritive sweeteners actually help induce weight loss and fat reduction.

Danica Cowan, a nutritionist at the University of California, San Francisco, agrees that sugary drinks are a particular concern. Because our bodies process liquid calories more quickly and can consume sugary drinks much faster. "Most people wouldn't eat 5 cakes in a day," she says. "But they could have 5 cans in a day."

Cowan strives to reduce the sweetness of the typical diet rather than find sugar substitutes for patients. This way, they become accustomed to lower levels of sweetness in food. If they can't completely cut out added sugars, she recommends naturally occurring sweeteners like stevia or monk fruit, but with the long-term goal of cutting out those substitutes entirely. She advises patients to get used to the natural sweetness of food rather than using the distorted sweetness of the current food system as a baseline. And part of William Li's advice in Eat to Beat is to give Willpower a chance. It's drinking small juices with water, tea, and occasionally fruit juice from the juice list.

The Sweetener of the Future?

For those who can't quit afternoon sugary drinks, Oobli is one of several companies worldwide.

Oobli CEO Ali Wing says, "The last thing we want is for people to feel bad about enjoying a sweet treat."

In addition to Oobli, there are other competitors in the mix. Sweegen in Irvine, California, recently received GRAS ( Gras ) certification to sell Brazzein as an industrial additive. Sweegen has been touting its protein sweetener portfolio as "Sweetensify" with Brazzein's " sweet synergy " and another sweet protein called Thaumatin alongside Stevia products while performing overdrive operations.

"Every time we tried to find the silver bullet of perfect low-calorie, non-nutritive sweeteners, we fell short."

An Israeli company based in Rehovot called Amai Proteins has created a "designer" version of naturally occurring sweet proteins like Monellin and started testing it with Ocean Spray cranberry juice in 2020. A Santa Monica startup called Nature's Wild Berry recently won $80,000 investment from Mark Cuban and Lori Grenier on the pitch show Shark Tank. The winning product was freeze-dried "Miracle Berry" grown by the company in Florida. The key ingredient is a sweet protein called miraculin that coats the tongue and makes tart foods taste unusually sweet. In what one judge called a "parlor trick," lemons, regular cranberry juice, and even cider vinegar tasted sweet despite having no sweet calories.

The excessive sweetness of guilt-free proteins is a concern for nutritionist Danica Cowan. She says that the sweet taste of non-nutritive sweeteners that do not actually deliver sugar actually triggers more cravings. "Every time we tried to find the silver bullet of perfect low-calorie, non-nutritive sweeteners, we fell short."

But Ryder says that because the body metabolizes Brazzein as a protein, it won't trigger cravings when tasting sweetness. "As far as I know, there is no definitive evidence that simply tasting sweet things like sweet cravings and other long-term side effects come from simply tasting sweet things. Known side effects come from the metabolic processes of too many things themselves."

That sounds plausible. But as nutrition experts have said, we can't know for sure how regularly consuming a Brazzein-sweeted drink will affect the complex metabolic system over time without additional research.

Ecological Justification

Ryder and Wing also make an environmental pitch for sweet proteins over sugar or non-nutritive sweeteners. Brazzein is naturally occurring in Oubli Berries of Pentadiplandra Brazzeana. A tree found on the forest edge of the tropical Sahel belt stretching from the Upper Nile Valley and Angola to eastern Nigeria. The abundance of this tree would make agriculture incredibly expensive. And even if Oubli fruit trees could be cultivated in orchards, large-scale agriculture would cause the same deforestation problem as palm oil production in Indonesia or Madagascar. Ryder says farmers have planted 6.5 million acres of sugar worldwide, much of it in sensitive tropical areas.

"For every 1% reduction in sugar, we can either lose 650,000 acres of sugar cane land, or we can replace growing tropical forests."

So Oobli has transitioned to biotechnology and genetically modified yeast to produce the same Brazzein naturally grown in trees. According to Ryder, the company has developed a scalable fermentation process that has been proven in commercial-scale production of sweet proteins in three countries. This allows the company to supply economically sweet proteins without the need for forests to grow crops.

And to this reporter's palate, Oobli's tea tastes sweet without the odd "off" taste that Stevia and synthetic sweeteners can have. I bought a 6-pack and the dessert-loving kids drank the rest. While there's a sweet aftertaste with a Snapple or Arizona Iced Tea Wallop, Oobli has a smooth balance and comes in various lemon or peach tea flavors.

In essence, Brazzein behaves differently in the mouth compared to sugar. There's a slight delay from when the sweet taste is perceived to when it hits the tongue. So Oobli uses a small amount of sugar derived from sucrose in tea to not confuse the tongue. But the amount of added sugar is minimal. Oobli's iced tea can has 7 grams of sugar, while a sweet Snapple bottle has about 46 grams.

Making proteins in the lab that are hard to find in nature can feel like the antithesis of everything behind the organic food movement. Why show restraint and not cut back on diet soda? Why can't people just accept a fig cookie or a flavorful pie instead, or hold out for drinks like coffee, tea, and water?

But in a country where 40% of adults are obese, appeals to individual responsibility and dietary morality feel grandiose and inappropriate. Many of us lack the restraint to cut back. Or we simply don't care. We suck down soda as if there's no tomorrow. And let's face it. There are millions of us. Synthetic biology may offer an escape. Making hyper-sweet proteins in the lab could be the best way to start addressing the calorie drinking problem.

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