Andrew Rosenblum
One of us knows that carbonated drinks are delicious but not good for health. People who drink more than one sweet 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 over $11 billion worth of diet soda to Americans in 2020.
Controversy over sugar-free soda is growing. In May, the World Health Organization (WHO) warned against 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 said than done when faced with a cold, bubbly can of yum. Respect to those who use water, quinoa, and orange.
At the University of California, Davis, a startup called Oobli is one of several companies pitching sweet protein alternatives as a substitute for sugar and non-caloric sweeteners, slipping a sweet protein called Brazzein into an iced tea blend. Brazzein, found in the bright red or mottled gray fruit of the Oubli fruit tree, is 500 to 5,000 times sweeter than sugar. It contains no carbohydrates, so it does not have the metabolic complications of non-caloric sweeteners like insulin spikes.
However, with a steep price of $15 for a 6-pack of iced tea, the company must convince nutritionists and consumers that Brazzein cannot be another disappointing fad sweetener. The company must acknowledge that the sweet protein was grown in a 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 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.)
The typical American consumes about 60 pounds of added sugar a year, with almost half of it coming from beverages.
Oobli's CEO Ali Wing 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 hasn't gone well. They look at updates every 6 weeks on another sugar alternative that could actually be worse for you than we thought. Consumers are skeptical."
But chocolate is just the beginning of the company's ambition. Oobli sees sugar drinks as a very promising niche market. The typical 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 bioengineering, says, "This is the 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."
More Sweeteners Than Meets the Tongue
Due to decades of marketing, these zero-calorie drinks have come to be believed to taste like flavored water.
Ryder says artificial sweeteners trick the body into thinking it's sugar. Recent studies have found that diet soda is not good for health because it can stimulate food cravings or confuse the body. Obese women and people ate more in response to sucralose-sweetened drinks compared to a control group that drank regular sugar soda.
"Sugar and alternative sweeteners are in the same class, they 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 system, which was rarely consumed but is now ubiquitous.
Ryder says taste receptors in the mouth and gut not only detect sweetness 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 the sugar into the bloodstream so we can send it to the cells that need it.'"
Ryder said this sensitivity to sugar evolution is due to a relatively poor diet thousands of years ago. In the summer, our ancestors in the Stone Age derived sugar not only from fruits but also from honey, 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 mouth and gut. Non-caloric sweeteners like aspartame in diet cola play a deceptive role in triggering insulin responses even though these molecules are not actually composed of real sugar.
Ryder says, "Things like aspartame can't 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 problems. This includes a potential association between long-term non-caloric sweetener consumption and cardiovascular disease, the destruction of gut microbiota, colonization of beneficial bacteria, and other organisms in the gut.
Brazzein avoids these metabolic confusions 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.
"They start to break down into peptides and amino acids," he says. "So while sugar and sucralose and aspartame continue to ban insulin responses to all taste receptors in the gut, proteins are already done."
Nutritionists Need More Data But It's Intriguing
Nutrition experts discussing with Proto.Life have provided support for Oobli's Brazzein as a qualified alternative to reducing the calories Americans get from sugary drinks, but expressed a desire for additional research before fully endorsing each 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 William Li, author of this book. He also added that preliminary studies suggest that proteins have antioxidant and anti-inflammatory properties, but research on how much is needed in humans has not been conducted. "So it's premature to speculate on the benefits or potential long-term side effects," he says.
Christina Fasulo, Senior Gastrointestinal Nutritionist at UCLA, sees Brazzein as a promising alternative to excessive sugar in the American diet. She also notes the attractive lab and animal results showing the antioxidant and anti-inflammatory effects of Brazzein, 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 have been found to help with weight loss and fat reduction.
Danica Cowan, a nutritionist at the University of San Francisco, agrees that sugary drinks are a particular concern. Because our bodies process liquid calories faster and can drink sugary drinks much faster. "Most people won't eat 5 cakes a day," she says. "But people can have 5 cans a day."
Cowan strives to reduce the sweetness of the typical Western diet rather than find sugar substitutes for her patients. This way, they become accustomed to lower levels of sweetness in food. If they can't completely cut out added sugar, 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 on "Eat to Beat" is to give willpower a chance. It's about sipping juice with water, tea, and sometimes fruit juice on the list.
The Future of Sweeteners?
But for those who can't quit afternoon sugary drinks, Oobli is one of many companies worldwide.
Oobli CEO Ali Wing says, "The last thing we want is for people to feel bad about eating sweet things."
In addition to Oobli, there are other competitors in the mix. Sweegen in Irvine, California, recently received GRAS (Generally Recognized as Safe) certification to sell Brazzein as an industrial additive. Sweegen has been promoting its sweet protein portfolio with Brazzein's "sweet synergy" and another sweet protein called Thaumatin alongside Stevia products while performing overdrive operations.
"Every time we try to find the silver bullet of perfect low-calorie, non-nutritive sweeteners, we fall short."
An Israeli company based in Rehovot called Amai Proteins has created a "designer" version of the naturally occurring sweet protein Monellin and started testing it with Ocean Spray cranberry juice in 2020. A startup in Santa Monica recently called Nature's Wild Berry. The winning product was a freeze-dried "Miracle Berry" grown in Florida by the company. The key ingredient is a sweet protein called miraculin that coats the tongue and makes tart foods taste abnormally sweet. From what was called a "palate trick" on the show, even lemons, regular cranberry juice, and cider vinegar tasted sweet without any added calories.
The excessive sweetness of guilt-free proteins that are hard to find in nature worries nutritionist Danica Cowan. She says the sweet taste of non-nutritive sweeteners that don't actually deliver sugar can trigger more cravings. "Every time we try to find the silver bullet of perfect low-calorie, non-nutritive sweeteners, 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 is no definitive evidence that long-term side effects, such as sweet cravings, come from simply tasting sweet things," he says. Known side effects stem from the excessive consumption of too many things themselves.
This certainly sounds plausible. However, as nutrition experts have said, we cannot be sure how regularly consuming cans of Brazzein-sweeted drinks over time will affect the complex metabolic system without additional research.
Ecological Justification
Ryder and Wing also create an environmental pitch for sweet proteins over sugar or non-nutritive sweeteners. Brazzein is found in small amounts in Oubli Berries of Pentadiplandra Brazzeana. A tree that extends from the Congo Basin to northern Angola and eastern Nigeria in the tropical Saharan sub-Saharan Africa belt on the edge of the forest. The abundance of this tree would make agriculture incredibly expensive. And even if Oubli fruit trees could be grown in orchards, large-scale agriculture would cause the same deforestation problem as palm oil production in Indonesia or Madagascar. Ryder notes that farmers have planted 6.5 million acres of sugar worldwide, much of it in sensitive tropical regions.
"For every 1% reduction in sugar, we can replace 650,000 acres of sugar cane land, where we've lost more nutrients or grown tropical forests," he says.
So Oobli has turned to biotechnology and genetically modified yeast to produce Brazzein, the same sweet protein naturally grown in trees. According to Ryder, the company has developed a scalable fermentation process that has been proven in commercial-scale sweet protein production in three countries. This allows the company to supply an economic source of sweet protein, allowing forests to grow instead of crops.
And to the palate of this reporter, Oobli's tea tastes sweet without the strange "off" taste that Stevia and synthetic sweeteners can have. I bought a 6-pack and the dessert-loving kids drank the rest. While a sip of Snapple or Arizona Iced Tea Wallop has a sweet palate, Oobli is smooth and balanced, with hints of lemon or peach tea.
In essence, Brazzein behaves differently in the mouth than sugar. There is a slight delay from when you taste sweetness to when it hits the tongue. So Oobli uses a small amount of sugar derived from yolks in tea to avoid confusing the palate. However, the amount of added sugar is minimal. Oobli's iced tea can contains 7 grams of sugar, while a sweet Snapple bottle contains about 46 grams.
Making protein in the lab that is hard to find in nature may feel contrary to all things "natural" behind the organic food movement. Why show restraint and not accept a fig cookie or a flavorful pie? Why can't they just accept a fig cookie or a flavorful pie instead of, say, waiting in line for a calorie-free drink like coffee, tea, or water?
But in a country where 40% of adults are obese, appeals to individual responsibility and dietary morality feel grandiose and inappropriate. Many Americans lack the limits to say they will 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 route. Making hyper-sweet proteins in the lab to kick off the calorie drinking problem could be the best way.
Originally posted on https://proto.life.