3M-Brazzein as a Natural Sugar Substitute Attenuates Obesity, Metabolic Disorder, and Inflammation

Kim, Hansaem; Kang, Jihun; Hong, Seungwoo; Jo, Seon-Yeong; Noh, Hyangsoon; Kang, Byung-Ha; Park, Suhyun; Seo, Young-­Jin; Kong, Kwang-Hoon; Hong, Sungguan

doi:10.1021/acs.jafc.0c00317

Cited by 10 publications

(8 citation statements)

References 46 publications

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“…Nothing from this study suggests toxic potential of brazzein. The results of Kim et al 62 are consistent with the lack of effect of brazzein on body weight gain, and overall lack of adverse effects, noted in our 90-day study of brazzein.…”

Section: Discussionsupporting

confidence: 91%

“…One study has been conducted with mice to assess the potential antiobesity effects of brazzein. 62 In this study, groups of seven male C57BL/6 J mice (7 weeks old) were exposed to brazzein containing mutations 31 R/E36D/E41 A (i.e., "3Mbrazzein") produced from Kluyveromyces lactis or aqueous solutions of 10% sucrose equivalents in their drinking water for a period of 15 weeks. A group of six control mice received water.…”

Section: Discussionmentioning

confidence: 99%

“…The authors reported that relative to sucrose, body weight gain and fat accumulation were reduced. Moreover, Kim et al 62 reported that administration of brazzein did not affect glucose homeostasis or indices of insulin resistance and inflammation. Nothing from this study suggests toxic potential of brazzein.…”

Section: Discussionmentioning

confidence: 99%

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Safety evaluation of oubli fruit sweet protein (brazzein) derived from Komagataella phaffii, intended for use as a sweetener in food and beverages

Lynch

Wang²,

et al. 2023

Toxicology Research and Application

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Naturally sweet proteins have no glycemic effect and offer a fundamentally new approach to sweetness and health for individuals seeking to reduce their added sugar intake. However, unlike many commercial sweeteners, little research has been performed on the potential safety implications of adding these uniquely sweet proteins to food and beverages. In this study, a naturally sweet protein found in the West African Oubli plant ( Pentadiplandra brazzeana), referred to as Oubli fruit sweet protein or brazzein, was expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation, and a safety and risk assessment was undertaken for its use as a sweetener in food and beverages. Potential consumption levels of brazzein were estimated to be 3 mg/kg body weight/day based on the National Health and Nutrition Examination Survey. The safety of brazzein derived from K. phaffii was evaluated through in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and a 90-day dietary oral toxicity study in rats. There was no indication of allergenicity in the in silico analyses. Brazzein was non-genotoxic in the in vitro assays and showed no adverse effects in the 90-day oral toxicity study up to the highest dose tested, where the no-observed-adverse-effect level (NOAEL) was 978 and 985 mg/kg body weight/day in males and females, respectively. The totality of evidence in the in silico allergenicity, in vitro genotoxicity, and 90-day dietary toxicity studies demonstrates that brazzein derived from K. phaffii is considered safe for use as a sweetener in food and beverages.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Safety evaluation of oubli fruit sweet protein (brazzein) derived from Komagataella phaffii, intended for use as a sweetener in food and beverages

Lynch

Wang²,

et al. 2023

Toxicology Research and Application

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“…Kim. H, et al, (2020) [34] investigated the use of brazzein as a possible natural sugar substitute and its link with obesity, metabolic disorder and inflammation. They reported lack of adiposity hypertrophy and no disruption of glucose homeostasis or insulin resistance and inflammation.…”

Section: Metabolism and Health Aspectsmentioning

confidence: 99%

Naturally occurring non-nutritive sweeteners: A review

Rao¹,

Rizwana²,

Lalmuanpuia³

et al. 2021

Int. J. Appl. Res.

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Today's well-informed consumer is demanding health promoting foods which not only have natural ingredients and are additive free, but also offer functional properties without compromising on the taste. Excessive consumption of sugar is a leading cause of non-communicable diseases, globally. Not more than 10% of the calories should be derived from sugar for optimal health. This has led to the increase in demand of food products containing sugar free alternatives. Therefore, naturally occurring non-nutritive sweeteners that have positive effects on the body weight as well as metabolism may facilitate in limiting the sugar intake and accomplishing the present recommendations. They are also an excellent alternative both for the consumers as well as the food industry in place of artificial sweeteners. These natural sweeteners are extracted from indigenous plants, provide insignificant calories, taste like sucrose, do not exhibit metallic after taste, and moreover, offer significant health benefits. The steviol glycosides and Luo Han Guo fruit (Monk fruit) are the natural extracts of plants, which are commercialized. In addition, numerous plant proteins such as thaumatin, brazzein, miraculin and several carbohydrates as rare sugars such as D-tagatose, D-allulose, D-sorbose and D-allose are being explored as potential substitutes to intense sweeteners which are reviewed in this paper. These are being extensively studied by the researchers for their physicochemical and functional properties and their possible use in low-calorie food formulations. They have a history of safe consumption by the natives of the country of their origin and have a generally recognized as safe (GRAS) or a novel food status.

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“…In order to meet the needs for sweet food from people who should reduce their sugar intake, it is urgently needed to develop natural and noncaloric sweeteners with good taste characteristics. An ideal solution is to commercialize sweet‐tasting proteins that do not adversely affect health [ 4 , 5 , 6 , 7 ].…”

mentioning

confidence: 99%

Expression of a triple mutational des‐pGlu brazzein in transgenic mouse milk

Lü

et al. 2022

FEBS Open Bio

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Brazzein has excellent potential for use as a sweetener because of its high level of sweetening potency and stability against extreme temperature and pH. It is extracted from the tropical and difficult—to‐cultivate African plant Pentadiplandra brazzeana , which hampers its commercial viability. Here we report the mammary‐specific expression of wildtype or triple mutational (H31R/E36D/E41A) des ‐pGlu brazzeins in the milk of transgenic mice. Using enzyme‐linked immunoassay (ELISA), western blot, and sweetness intensity testing, we confirmed that the triple mutation made the des ‐pGlu brazzein molecule 10,000 times sweeter than sucrose in a weight base, even after 10 min of incubation at 100 °C; in addition, the triple mutant was also significantly sweeter than the wildtype des ‐pGlu brazzein. This study provides new insights for producing brazzein or brazzein‐sweetened milk from animals for use in food and healthcare applications.

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3M-Brazzein as a Natural Sugar Substitute Attenuates Obesity, Metabolic Disorder, and Inflammation

Cited by 10 publications

References 46 publications

Safety evaluation of oubli fruit sweet protein (brazzein) derived from Komagataella phaffii, intended for use as a sweetener in food and beverages

Safety evaluation of oubli fruit sweet protein (brazzein) derived from Komagataella phaffii, intended for use as a sweetener in food and beverages

Naturally occurring non-nutritive sweeteners: A review

Expression of a triple mutational des‐pGlu brazzein in transgenic mouse milk

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