Andrew Rosenblum
One of us knows that carbonated drinks are delicious but not good for health. People who drink more than one sugary beverage a day tend to gain weight and have a 26% higher chance of developing type 2 diabetes compared to those who do not. And that is one of the reasons why food companies sold over $11 billion worth of diet soft drinks to Americans in 2020.
Skepticism about sugar-free soda is growing. In May, the World Health Organization (WHO) warned against consuming artificial sweeteners for weight loss. Worse, the agency also found that long-term consumption of non-sugar sweeteners could actually contribute to type 2 diabetes, cardiovascular disease, and early death. The WHO recommended that people instead work to reduce their sugar intake.
However, it is easier said than done when a cold, bubbly can of yum stares you in the face. I respect everyone who uses water, quinoa, and oranges.
In California Davis, a startup called Oobli is one of several companies pitching sweet protein alternatives as substitutes for sugar and non-sugar sweeteners, sliding a sweet protein called brazzein into iced tea blends. Brazzein, found in the bright red or speckled gray fruit of the original Oubli fruit tree, is 500 to 5,000 times sweeter than sugar. It contains no carbohydrates, so it has none of the metabolic complications of non-sugar sweeteners like insulin spikes.
However, for iced tea sold at a fairly steep price of $15 per six-pack, the company has to convince nutritionists and consumers that brazzein cannot be just another fad sweetener. The company acknowledges that consumers must accept that it is grown in a lab through fermentation, courtesy of gene-edited yeast, for economic and ecological reasons. And there is the issue of safety confirmation from the U.S. Food and Drug Administration (FDA). (The company has published peer-reviewed studies confirming that the sweet protein is safe in collaboration with third-party labs, allowing it to sell the product in the U.S., but some retailers do not carry it until the FDA issues a letter agreeing with these conclusions.)
The typical American consumes about 60 pounds of added sugar a year, nearly half of which comes from beverages.
Oobli's CEO, Ali Wing, says, “Today, 75% of American consumers are actively trying to reduce sugar. Chocolate bars. “There are 50 forms of sugar, and we’ve been working on it for the last 20 years, and it’s not going well. They see updates every six weeks on another sugar alternative that can actually be worse for you than we thought. Consumers are skeptical.”
But chocolate is just the beginning of the company’s ambitions. Oobli sees sugary beverages as a really promising niche market. The typical American consumes about 60 pounds of added sugar a year, nearly half of which comes from beverages. Jason Ryder, CTO at the University of California, Berkeley, and an adjunct professor of chemical and biomolecular engineering, says, “This is the 800-pound gorilla of sugar delivery mechanisms.
Wing says, “Beverages are the 800-pound gorilla of the problem. And that’s why so many people switched to diet soda or sugar-free tea in the first place.
More than sweeteners meet the tongue
Decades of marketing have led to these zero-calorie drinks being believed to be the same as flavored water.
Ryder says artificial sweeteners trick the body into thinking it’s sugar. Recent studies suggest that diet soda can stimulate food cravings or confuse the body, making it unhealthy. Obese women and people ate more in response to sucralose-sweetened beverages compared to a control group that drank regular sugar sweetened soda.
“Sugar and alternative sweeteners are all small molecules, and they all fundamentally do the same thing,” he says. “They bombard your T1R2 and T1R3 taste receptors.” These molecules essentially overstimulate our systems, which have barely been consumed but are now ubiquitous.
Ryder says that taste receptors on the tongue and in the gastrointestinal tract not only detect sweetness but also perform important signaling functions. “They tell your brain, ‘Hey, sugar is coming! It’s time to make insulin now. We need to get sugar into the bloodstream so we can send it to the cells that need it.’”
Ryder says this sensitivity to the presence of sugar evolved because, for thousands of years, it was relatively scarce. In the summer, aside from fruit, our Paleolithic ancestors derived sugar only from tubers, other starches, and complex carbohydrates.
In contrast, the modern food system is filled with simple sugars and sweeteners that effectively overload taste receptors in the tongue and gut. Non-sugar sweeteners like aspartame in diet cola act as a trick to trigger an insulin response even though these molecules do not actually consist of real sugar that the body can collect.
Ryder says, “Things like aspartame can’t be metabolized properly, so they keep hitting the insulin response. “But there’s no sugar coming 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-sugar sweetener consumption and cardiovascular disease, disruption of gut microbiota, and 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 on the tongue but does not trigger an insulin response and is broken down in our gut.
Ryder says, “They start breaking down into peptides and amino acids. “So while sugar and sucralose and aspartame continue to trigger insulin responses across all the taste receptors in the gut, proteins are already done.”
Nutritionists need more data but are intrigued
Nutrition experts in conversations with Proto.Life have expressed qualified support for Oobli’s Brazzein as a way for Americans to reduce calories from sugary beverages, but they have expressed a desire to see more research before fully endorsing each product.
“Are there health benefits to Brazzein-sweetened beverages? Yes. They have fewer calories than regular sugar and a lower glycemic load,” says William Li, author of Eat to Beat Disease. He also added that preliminary studies suggest that the protein has antioxidant and anti-inflammatory properties, but research to determine what dosage is needed in humans has not been conducted. “So it’s premature to speculate about benefits or potential long-term side effects,” he says.
Christina Fasulo, a senior clinical dietitian at UCLA, notes that Brazzein appears promising as an alternative to excessive sugar in the American diet. She also points out intriguing lab and animal results showing Brazzein’s antioxidant and anti-inflammatory effects but says she would like to see human studies before recommending the substance to patients.
Fasulo also notes that the evidence regarding diet soda is inconsistent without fully dismissing it. A recent meta-analysis of 20 randomized controlled trials found that non-sugar sweeteners actually help induce weight loss and fat reduction.
Danica Cowan, a dietitian at the University of California, San Francisco, agrees that sugary sweetened beverages are a particular concern. This is because our bodies process liquid calories much faster and can drink sugary beverages much more quickly. “Most people wouldn’t eat five cakes in a day,” she says. “But people can have five cans in a day.”
Cowan encourages patients to work on reducing the sweetness of their diets generally rather than seeking sugar substitutes. This way, they become accustomed to lower levels of sweetness in food. If they cannot completely cut out added sugars, she recommends naturally occurring sweeteners like stevia or monk fruit, but she also has a long-term goal of completely cutting those substitutes out. She advises patients to get used to the natural sweetness of foods rather than using the distorted fructose content of the current food system as a baseline. And part of William Li’s advice in Eat to Beat Disease is to give willpower a chance. It’s about drinking water, tea, and sometimes fruit juice instead of sugary drinks.
The future of sweeteners?
But for those who can’t quit sugary drinks in the afternoon, Oobli is one of several companies worldwide.
Oobli CEO Ali Wing says, “The last thing we want is for people to feel bad about having a sweet tooth.”
In addition to Oobli, there are other competitors in the mix. Sweegen, based in Irvine, California, recently received “GRAS” (Generally Recognized As Safe) certification to sell Brazzein as an industrial additive. Sweegen is promoting its protein sweetener portfolio called “Sweetensify” alongside Brazzein’s “sweet synergy” and another sweet protein called Thaumatin while performing overdrive work.
"Every time we try to find the perfect low-calorie, non-effective sweetener, we fall short."
An Israeli company based in Rehovot called Amai Proteins has created a “designer” version of a naturally occurring sweet protein called Monellin and began trials with Ocean Spray cranberry juice in 2020. A startup in Santa Monica recently called Nature's Wild Berry received an $80,000 investment from Mark Cuban and Lori Grenier on the startup pitch meeting game show Shark Tank. The winning product was a freeze-dried “Miracle Berry” grown in Florida. The key ingredient is a sweet protein called miraculin that coats the tongue and makes tart foods taste unusually sweet. One judge on the show called it “palate trickery,” where even lemon, plain cranberry juice, and apple cider vinegar tasted sweet despite having no sweet calories.
The excessive sweetness of this seemingly guilt-free protein worries dietitian Danica Cowan. She says that the sweet taste of non-sugar sweeteners that do not actually deliver sugar can lead to more cravings. “Every time we try to find the perfect low-calorie, non-effective sweetener, we fall short.”
However, Ryder says that because the body metabolizes brazzein as a protein, tasting sweetness will not trigger cravings. “As far as I know, there’s no definitive evidence that simply tasting sweet things leads to cravings like simple sugars do. The known side effects come from the metabolism of too many things themselves.”
This certainly sounds plausible. But as nutrition experts have said, we cannot be sure how regularly consuming cans of Brazzein-sweetened drinks will affect our complex metabolic systems over time without further research.
Ecological justification
Ryder and Wing also make an environmental pitch for sweet proteins over sugar or non-sugar sweeteners. Brazzein occurs only in small amounts in the Oubli Berries of Pentadiplandra Brazzeana, a tree found on the forest edges of the tropical sub-Saharan African belt stretching from the Congo River basin and northern Angola to eastern Nigeria. The abundance of this tree makes agriculture incredibly expensive. And even if the Oubli fruit tree can be cultivated in orchards, large-scale agriculture would cause the same deforestation issues as palm oil production in Indonesia or Madagascar. Ryder notes that farmers have planted 65 million acres of sugar worldwide, a significant portion of which is in sensitive tropical areas.
“For every 1% reduction in sugar, we could replace 650,000 acres of sugar cane land, which could either lose more nutrition or replace growing tropical rainforests.”
Thus, Oobli has turned to biotechnology and genetically modified yeast to produce brazzein, the same protein that grows naturally on trees. According to Ryder, the company has developed a scalable fermentation process. “We have developed a proven fermentation process for sweet protein manufacturing at commercial scale in three countries.” This allows the company to provide an economical source of sweet protein, allowing forests to grow instead of crops.
And in this reporter's palate, Oobli's tea is subtly sweet without the strange “off” taste that stevia and synthetic sweeteners can have. I bought a six-pack, and my dessert-oriented sons drank the rest. While Snapple or Arizona Iced Tea Wallop has a sweetness that hits the palate, Oobli is smoothly balanced with various lemon or peach tea flavors.
That said, brazzein behaves differently in the mouth than sugar. There is a slight delay when it hits the tongue and is recognized as sweet. Thus, Oobli uses a small amount of sugar derived from agave in the tea to avoid confusing the tongue. However, the amount of added sugar is minimal. Oobli iced tea cans contain 7 grams of sugar, while a sweet Snapple bottle contains about 46 grams.
Making proteins in a lab that are hard to find in nature can feel like the opposite of everything behind the organic food movement’s “natural.” Why can’t people show restraint and cut back on diet cola? Why can’t they just accept fig cookies or flavored pies instead, or have a caloric beverage atmosphere with coffee, tea, and water?
But in a country where 40% of adults are obese, appeals to personal responsibility and dietary morality feel flashy and inappropriate. Many of us Americans 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, that’s millions of us. Synthetic biology may offer an escape. Making hyper-sweet proteins in a lab may be the best way to start addressing the calorie-drinking problem.
Originally published on https://proto.life.