Effect of Regular Consumption of a Miraculin-Based Food Supplement on Taste Perception and Nutritional Status in Malnourished Cancer Patients: A Triple-Blind, Randomized, Placebo-Controlled Clinical Trial-CLINMIR Pilot Protocol

Abstract

Taste disorders are common among cancer patients undergoing chemotherapy, with a prevalence ranging from 20% to 86%, persisting throughout treatment. This condition leads to reduced food consumption, increasing the risk of malnutrition. Malnutrition is associated not only with worse treatment efficacy and poor disease prognosis but also with reduced functional status and quality of life. The fruit of Synsepalum dulcificum (Daniell), commonly known as miracle berry or miracle fruit, contains miraculin, a taste-modifying protein with profound effects on taste perception. The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled clinical trial designed to evaluate the regular consumption of a food supplement containing a miraculin-based novel food, dried miracle berry (DMB), on the taste perception (measured through electrogustometry) and nutritional status (evaluated through the GLIM Criteria) of malnourished cancer patients under active antineoplastic treatment. To this end, a pilot study was designed with 30 randomized patients divided into three study arms (150 mg DMB + 150 mg freeze-dried strawberries, 300 mg DMB, or placebo) for three months. Throughout the five main visits, an exhaustive assessment of different parameters susceptible to improvement through regular consumption of the miraculin-based food supplement will be conducted, including electrical and chemical taste perception, smell perception, nutritional and morphofunctional assessment, diet, quality of life, the fatty acid profile of erythrocytes, levels of inflammatory and cancer-associated cytokines, oxidative stress, antioxidant defense system, plasma metabolomics, and saliva and stool microbiota. The primary anticipated result is that malnourished cancer patients with taste distortion who consume the miraculin-based food supplement will report an improvement in food taste perception. This improvement translates into increased food intake, thereby ameliorating their nutritional status and mitigating associated risks. Additionally, the study aims to pinpoint the optimal dosage that provides maximal benefits. The protocol adheres to the SPIRIT 2013 Statement, which provides evidence-based recommendations and is widely endorsed as an international standard for trial protocols. The clinical trial protocol has been registered at the platform for Clinical Trials (NCT05486260).

The Regular Consumption of a Food Supplement Containing Miraculin Can Contribute to Reducing Biomarkers of Inflammation and Cachexia in Malnourished Patients with Cancer and Taste Disorders: The CLINMIR Pilot Study

“…Recently, we reported that regular consumption of DMB improved energy intake, fat quantity and quality, fat-free mass, and quality of life in malnourished cancer patients receiving antineoplastic treatment (16). Considering these results, a logical approach is to discern whether this improvement is reflected in the cachexia status.…”

“…The pilot CLINMIR study was designed to evaluate the efficacy and safety of the DMB food supplement on sensory function, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes in adult malnourished cancer patients with taste disorders undergoing active antineoplastic therapy (17). The complete protocol as well as the results of the major characteristics of patients and main outcomes, as well as the DMB composition, have been reported elsewhere (16,17).…”

“…In this sense, Synsepalum dulcificum (Daniell) is a plant whose berries contain miraculin, a glycoprotein that transforms sour flavors into sweet ones and limits bitter and metallic off-flavors, making food more palatable. In December 2021, the European Commission authorized the dried fruits of S. dulcificum (also known as DMB), which naturally contain the taste-modifying protein miraculin as a novel food (16). Recently, our group reported that regular consumption of DMB before each main meal for three months improved taste acuity and salty taste, leading to greater dietary intake (energy intake, fat quantity and quality), and ameliorated nutritional status (fat-free mass) and erythrocyte polyunsaturated fatty acid (PUFA) status (16).…”

“…In December 2021, the European Commission authorized the dried fruits of S. dulcificum (also known as DMB), which naturally contain the taste-modifying protein miraculin as a novel food (16). Recently, our group reported that regular consumption of DMB before each main meal for three months improved taste acuity and salty taste, leading to greater dietary intake (energy intake, fat quantity and quality), and ameliorated nutritional status (fat-free mass) and erythrocyte polyunsaturated fatty acid (PUFA) status (16). Indeed, an improvement in nutritional status could have a positive impact on inflammatory and cachexia states.…”

Efficacy and Safety of Habitual Consumption of a Food Supplement Containing Miraculin in Malnourished Cancer Patients: The CLINMIR Pilot Study

“…A detailed description of the CLINMIR study protocol has recently been published elsewhere [ 40 ]. Below is a summary of the clinical trial.…”