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.

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).

Circulating sestrins and force velocity profiling in older adults with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) in old age affects the musculoskeletal system causing loss of muscle mass, strength, and physical function. Stress-inducible proteins named sestrins are potential novel biomarkers of muscle function due to their ability to suppress oxidative stress and prevent muscle degeneration. Our aim was to determine the association between different force-velocity (F-V) profiles with body composition, physical performance, and glucose control in older adults with T2DM. We also intended to determine the potential utility of sestrin 1 (Sesn1) and 2 (Sesn2) as biomarkers of physical functionality. Fifty-nine participants (69-79 years) were classified in 3 groups according to their F-V profile based on the leg press exercise: nondeficit (NDEF = 40.7%), force deficit (FDEF = 28.8%), and velocity deficit (VDEF = 30.5%). Both VDEF and FDEF groups showed lower muscle power than NDEF (Cohen's d 0.87 and 0.75 for effect size, respectively). Serum Sesn2 levels, maximal dynamic strength, arms and legs fat-free mass were reduced in FDEF compared to the NDEF group (p < 0.05), whereas glycated haemoglobin (HbA1c) and fasting glucose levels were similar among groups. ROC analysis revealed the distinction between the NDEF and FDEF group based on Sesn2 concentrations (<0.72 ng/mL), suggesting their potential use as functional biomarkers for early intervention through exercise. Older adults with T2DM show different F-V profiles, related to low levels of Sesn2, impaired body composition and physical performance, and may be taken into consideration to target exercise training in this specific population.Highlights The influence of different F-V deficit profiles on body composition, physical function and circulating sestrins in older adults with type 2 diabetes were studied.Both force and velocity deficits negatively affected muscle power.Force deficits are associated to low circulating sestrin 2 levels and regional fat-free mass.Basal serum sestrin 2 levels are potential biomarkers to characterise F-V profiles.

Implication of Different Tumor Biomarkers in Drug Resistance and Invasiveness in Primary and Metastatic Colorectal Cancer Cell Lines.

Protein expression profiles are directly related to the different properties of cells and are conditioned by the cellular niche. As an example, they are the cause of the characteristic cell plasticity, epithelium-mesenchymal transition (EMT), and drug resistance of cancer cells. This article characterizes ten biomarkers related to these features in three human colorectal cancer cell lines: SW-480, SW-620, and DLD-1, evaluated by flow cytometry; and in turn, resistance to oxaliplatin is studied through dose-response trials. The main biomarkers present in the three studied lines correspond to EpCAM, CD-133, and AC-133, with the latter two in low proportions in the DLD-1 line. The biomarker CD166 is present in greater amounts in SW-620 and DLD-1 compared to SW-480. Finally, DLD-1 shows high values of Trop2, which may explain the aggressiveness and resistance of these cells to oxaliplatin treatments, as EpCAM is also highly expressed. Exposure to oxaliplatin slows cell growth but also helps generate resistance to the treatment. In conclusion, the response of the cell lines is variable, due to their genetic variability, which will condition protein expression and cell growth. Further analyses in this area will provide important information for better understanding of patients' cellular response and how to prevent resistance.

Quantification of lectins in Synsepalum dulcificum and comparison with reference foods.

A healthy life means a balance between physical activity and a diet rich in fruits and vegetables, however, some plant-based foods can have certain adverse effects due to the presence of anti-nutritional factors, such as lectins, capable of binding molecules and preventing their normal assimilation. The level of lectins in Synsepalum dulcificum fruit was determined by hemagglutination assays in human blood, and its comparison with foods characterized as having high and low lectin content. The relative hemagglutinating activity of berries from Synsepalum dulcificum compared to our positive high lectin content food reference (Pinto bean) corresponds to 3.13-6.25%, representing safe levels for nutritional food.

Miracle Berry as a Potential Supplement in the Control of Metabolic Risk Factors in Cancer.

The increased incidence of chronic diseases related to altered metabolism has become a social and medical concern worldwide. Cancer is a chronic and multifactorial disease for which, together with genetic factors, environmental factors are crucial. According to the World Health Organization (WHO), up to one third of cancer-related deaths could be prevented by modifying risk factors associated with lifestyle, including diet and exercise. Obesity increases the risk of cancer due to the promotion of low-grade chronic inflammation and systemic metabolic oxidative stress. The effective control of metabolic parameters, for example, controlling glucose, lipid levels, and blood pressure, and maintaining a low grade of chronic inflammation and oxidative stress might represent a specific and mechanistic approach against cancer initiation and progression. Miracle berry (MB) (Synsepalum dulcificum) is an indigenous fruit whose small, ellipsoid, and bright red berries have been described to transform a sour taste into a sweet one. MB is rich in terpenoids, phenolic compounds, and flavonoids, which are responsible for their described antioxidant activities. Moreover, MB has been reported to ameliorate insulin resistance and inhibit cancer cell proliferation and malignant transformation in vitro. Herein, we briefly summarize the current knowledge of MB to provide a scientific basis for its potential use as a supplement in the management of chronic diseases related to altered metabolism, including obesity and insulin resistance, which are well-known risk factors in cancer. First, we introduce cancer as a metabolic disease, highlighting the impact of systemic metabolic alterations, such as obesity and insulin resistance, in cancer initiation and progression. Next, as oxidative stress is closely associated with metabolic stress, we also evaluate the effect of phytochemicals in managing oxidative stress and its relationship with cancer. Finally, we summarize the main biological activities described for MB-derived extracts with a special focus on the ability of miraculin to transform a sour taste into a sweet one through its interaction with the sweet taste receptors. The identification of sweet taste receptors at the gastrointestinal level, with effects on the secretion of enterohormones, may provide an additional tool for managing chronic diseases, including cancer.