Miracle Fruit Comprehensive Notes

Miracle Fruit: A Potential Taste-Modifier

Abstract

  • Miracle fruit contains miraculin, a glycoprotein that modifies taste perception at low pH, altering food preferences.

  • This review evaluates evidence on miracle fruit/miraculin, taste modification, and its potential in improving food preferences.

  • Miracle fruit suppresses sourness and induces sweetness in acidic foods/beverages.

  • It enhances sweet taste and reduces salty/bitter tastes in solutions at low pH.

  • The impact on sweet, salty, and bitter foods is not well-studied.

  • Miracle fruit alters food-liking scores in individual foods and mixed diets.

  • Miracle fruit is a pH-dependent taste modifier with potential food applications for improving consumer food preferences.

  • Future research should focus on changes in food preferences with optimal miraculin dose, food type, and individual taste sensitivity variations.

Introduction

  • Miracle fruit (Synsepalum dulcificum) is an evergreen shrub native to West Africa.

  • The red berry weighs about 1.11±0.171.11 \pm 0.17 g and consists of skin, pulp, shell, and seed.

  • It is highly perishable and can be freeze-dried at -20°F for six months.

  • "Miracle fruit" and "miracle berry" are used interchangeably; this paper uses "miracle fruit."

  • Miracle fruit contains miraculin, a glycoprotein with taste-modifying properties.

  • Miraculin is a homodimer composed of 191 amino acids, nitrogen, carbohydrates, and sugars (glucosamine, mannose, fructose, xylose, and galactose).

  • It has a molecular weight of 24,000 to 45,000 Da.

  • Miraculin activates human sweet taste receptors at pH below 6.5, converting sour foods into a sweet taste comparable to sucrose.

  • Miraculin is thermolabile (inactivated above 100 °C) and gets inactivated at pH below 3 and above 12.

  • Miracle fruit pulp, with a pH of 3.3±0.143.3 \pm 0.14, is the only part containing miraculin.

  • Miraculin content in the pulp varies from 0.07 to 1.30 mg/g of juice.

Mechanism of Action

  • The pH-dependent taste modification of miraculin has drawn research attention.

  • Consuming miracle fruit before an acidic fruit like lime can mask the sour taste and induce sweetness.

  • Early explanations included paralysis of tongue papillae, blocking of sour receptors, or adding sweetness to sour acids.

  • Current understanding suggests miraculin changes taste receptors at low pH, inducing sweetness rather than suppressing sourness.

  • Human sweet taste receptors consist of two proteins: taste receptor type 1 membrane 2 (T1R2) and taste receptor type 1 membrane 3 (T1R3).

  • T1R2 responds to small, sweet molecules, while T1R3 responds to large ones.

  • The human sweet taste receptor has three parts: the transmembrane domain, the N-terminal segment Venus Flytrap Domain (VFD), and the cysteine-rich domain.

  • The transmembrane domain is involved in signal transduction.

  • VFD is responsible for ligand binding.

  • The cysteine-rich domain maintains structural stability.

  • VFD has two forms: free form I (resting state) and free form II (resting state), in dynamic equilibrium.

  • Ligand binding to free form II stabilizes the receptor.

Three Steps of Miraculin's Action:
  1. Coating the mouth: Chewing miracle fruit coats taste buds with miraculin.

    • Miraculin interacts with VFD, form II of sweet taste receptors.

  2. Activating the taste receptor: Extracellular acidification protonates T1R2 and miraculin, leading to activation.

    • Full receptor activation occurs with intracellular acidification.

    • The epithelial plasma membrane changes conformation at acidic pH (e.g., 4.8–6.5).

    • The carbohydrate part of miraculin binds to the sweet taste receptor, resulting in pH-dependent receptor activation.

    • Histidine residues in the miraculin polypeptide chain play a key role in the conformational change.

  3. Neuronal signalling: S-fibres convey taste from T1R2/T1R3 receptors, responding to acids after miraculin administration.

    • The sour taste disappears when the sweet taste neuronal signal reaches the brain cortex.

  • The presence of H+ ions is essential; miracle fruit alone does not produce sweetness.

  • The action lasts from 30 seconds to 2 hours after consumption, producing sweetness each time a sour food/drink is tasted until salivary amylase dissociates miraculin from taste receptors.

  • Magnetoencephalography (MEG) studies suggest that after chewing miracle fruit, the sourness component from citric acid diminishes, and sweetness information reaches the primary taste area of the cerebral cortex.

Miracle Fruit Explored As A Taste Modifier

  • Miraculin’s taste modification mechanism makes it a useful taste modifier.

  • Basic taste qualities (sweet, sour, bitter, salty, umami, and fat) affect food liking.

  • Humans prefer sweet, fatty, and salty foods while disliking bitter and sour foods, with individual variations.

  • Bitter taste is associated with isothiocyanates from glucosinolates in brassica vegetables, which have antioxidant, anti-inflammatory, anti-diabetic, and chemoprotective effects.

  • Masking bitterness can facilitate vegetable consumption due to health benefits of phytochemicals.

  • Sour taste is associated with organic acids in fruits, which prevent osteoporosis, inhibit platelet aggregation, produce intestinal hormones, and provide anti-inflammatory and anti-obesity effects.

  • Miracle fruit can sweeten food by masking sour and bitter tastes, improving fruit and vegetable consumption.

Research Aspects

  • Miracle fruit is researched for health applications and taste modification.

  • Health applications (antidiabetic, anticancer, antioxidant, hepatoprotective, anti-hyperlipidemic, and anti-hyperuricemia) have been extensively reviewed.

  • These health benefits are mainly provided by phytochemicals (flavonoids, tannins, alkaloids saponin, etc.) rather than taste modification.

  • Taste modification indirectly encourages healthy eating.

  • Taste modification by miraculin is researched on sour, sweet, bitter, salty tastes, and their combinations in solutions, selected food, and mixed diets.

  • This review compiles available scientific evidence on taste modification studies with miracle fruit/miraculin.

  • It synthesizes and analyzes these studies and discusses the potential role of using miracle fruit to alter taste perception and improve preferences/intake of healthy food (fruits, vegetables, and yogurt).

  • The review identifies research methodologies that yield positive results and any limitations.

Methodology

  • The review adopted both systematic and narrative review methodologies.

  • Studies on taste modification effects of miracle fruit on sour, bitter, sweet, salty, or mixed taste qualities were predominantly quasi-experimental with quantitative outcomes.

  • A systematic search strategy was used to critically evaluate and select relevant original research evidence.

  • A narrative approach was used in synthesis due to the heterogeneity of independent, dependent variables, and outcome measurements. Also, because of unavailability of statistical approaches in some studies, to theoretically interpret the reasons for significant and non-significant results, and to narratively outline the future directions

  • As this was the first review of taste modification studies, a narrative synthesis was appropriate.

Data Sources and Search Strategies:
  • Literature search was performed from June 2023 to September 2023 in MEDLINE (Ovid), CINAHL, Scopus, and Web of Science.

  • Boolean operators (AND/OR) and truncations were used.

  • The Population, Intervention, Comparison, Outcome (PICO) framework defined the research question.

  • Humans (P) received miracle fruit/miraculin (I) compared with pre-test or placebo (C) on perceived taste quality, taste intensity, food preferences/liking, dietary intake, and diet quality (O).

  • Keywords for the exposure variable included miracle fruit, miracle berry, Synsepalum dulcificum, Richadella, and miraculin.

  • Keywords for the outcome variable included taste, taste perception, taste modification, taste sensitivity, food preference, food liking, diet, and diet quality.

  • Reference lists of selected articles were also checked.

  • The PRISMA flowchart was used.

  • Sixteen articles with original research work were included.

Selection Criteria
  • Only publications in English were included.

  • Publications from all years were considered due to the limited research in this area.

  • Animal studies, in-vitro studies, unpublished reports, conference abstracts, letters to the editors, editorials, and commentaries were excluded.

  • Two researchers (SD and GM) independently reviewed abstracts and full texts using Covidence software.

  • Disagreements were addressed by a third reviewer (RJ).

  • Cohen's kappa (κ) inter-rater agreement was calculated as κ=0.911,95%CI:0.789–1.000κ=0.911, 95\% CI: 0.789–1.000, indicating perfect agreement.

Results and Discussion

  • A total of 16 studies on the effect of miracle fruit/miraculin on taste perception and food preferences in human participants were included.

  • More than half (n=13/16) of the studies were conducted after 2011, mostly in Caucasian populations from Western nations (e.g., United States, Brazil, Italy, Lebanon), involving healthy adults (n=14/16), diabetes/pre-diabetes (n=1/16), chemotherapy patients (n=1/16), and patients with inborn errors of metabolism (n=1/16).

  • Sample sizes ranged from 6 to 200 including participants of age ranging from 18–65 years and both genders.

  • Perceived taste intensities were measured on scales ranging from 0–100 (n=2), 0–200 (n=1), 0–10 (n=1), and other line scales such as Just-about-right-scale (9 cm scale) (n=1), 100 mm visual analogue scale (n=1), and 15 cm line scale (n=1).

  • Food preferences were measured on 9-point hedonic scales (ranging from 1-extremely disliked to 9-extremely liked) in n=3 studies and 5-point hedonic scales in n=1 studies.

  • The effect of miracle fruit was experimented in sour (n=15/16), sweet (n=3/16), bitter (n=3/16), salty (n=2/16) tastes, and combinations of two or more tastes (n=3/16).

Sour Taste
  • The majority of studies (n = 15/16) examined the effect of miracle fruit on sour taste using sour acids (n = 5/15), juices/beverages (n=4/15), and food (n=6/15).

  • Miracle fruit significantly decreased sourness, increased sweetness, or improved food liking in n=13/15 studies, agreeing with the mechanism of action.

  • Effectiveness depends on the specific pH of the acid.

  • In vitro study by Sanematsu et al. (2016): Stronger response to miraculin when pH decreased from 6.5 to 4.8, attributed to increased protonation of taste receptor.

  • Minimal response at neutral pH levels (6.5 to 7.4) due to minimal protonation.

  • Perceived sweetness intensity varies with the type of acid.

  • The acidity created by citric acid-containing solutions is more effective for miraculin activity compared to that of acetic acid-containing solutions.

  • Weak acids produce a more undissociated form which enters the intracellular spaces of receptor cell membrane inducing intracellular acidification. Intracellular pH is associated more closely with miraculin activity. Therefore, weak acids are more effective than strong acids in producing taste-modifying effects with miraculin

  • Miracle fruit is a potential sugar substitute in lemonade and lemon juice-based popsicles.

  • Miracle fruit should be coated on the tongue before consumption, generating sweetening effects.

  • Miraculin is deactivated by heat, making it unsuitable as a cooked food ingredient.

Sweet Taste
  • n = 3 studies conducted on sweet taste using sucrose solutions (n=1/3) and sweet food (n=2/3).

  • At neutral pH, miraculin did not alter the perceived sweetness intensity of 0.037 M sucrose solution, jellybeans, dark chocolate, and maple syrup.

  • Miraculin increased the perceived sweetness of the binary mixture containing sucrose and citric acid.

  • The elevated sweetness of sucrose solutions is caused by the additive effect of the sweet taste of sucrose and the sweet taste induced by miraculin’s action on human sweet taste receptors.

  • In-vitro cell-assay by Koizumi et al. (2011): When a sweet-tasting substance was administered at a neutral pH to the receptor cells pre-incubated with miraculin, the activity of the newly administered sweet-tasting substance was inhibited.

Salty Taste
  • n = 2 studies conducted on salty taste using sodium chloride (NaCl) (n = 1/2) and salty crackers (n = 1/2), which claim the requirement of a low pH condition to decrease the perceived salty taste intensity.

  • Miraculin did not alter the perceived saltiness in solutions or food

  • Significant decrease in salty taste in a binary solution containing NaCl and citric acid.

  • The sweetness elicited by miraculin lowered the salt taste perception, under the acidic environment inside the mouth.

Bitter Taste
  • n = 3 studies were conducted with miraculin/miracle fruit on bitter taste.

  • No significant changes in bitterness were observed in caffeine, green tea, or broccoli.

  • Significant decrease in bitterness of the binary mixture containing caffeine and citric acid.

  • Miraculin may decrease perceived bitterness in the presence of low pH conditions.

Combination of Tastes
  • n = 3 studies using solutions on healthy adults (n = 1/3) and mixed diets on diabetes/pre-diabetes and chemotherapy patients (n = 2/3).

  • Positive changes such as the increase in overall food liking and improvement in food intake were observed with mixed diets while the effect of miraculin on solutions provided variable results.

  • Enhancement of sweetness and suppression of sourness at different degrees was observed in solutions containing combinations of two or more tastes.

  • A significant reduction in sourness was observed only in the citric acid+caffeine+sucrose mixture.

  • The observations of miraculin on bitter taste were inconsistent in solutions

Role of Miracle Fruit on Food Preference and Intake

  • The effects of miracle fruit on food preferences were observed in n=3 studies conducted with selected individual sour food/beverages (n=3/3) and mixed diets (n=1/3) claiming the possibility of miracle fruit to alter food liking.

  • Miracle fruit increased the liking of unsweetened lemonade.

  • miracle fruit enhanced the overall liking of yoghurt, goat cheese, and apple while decreasing the liking of lemonade and cucumber pickle in healthy adults

  • In diabetic/pre-diabetic adults miracle fruit has improved the liking towards yoghurt, goat cheese, apple, lemonade, and cucumber pickle compared to a placebo.

  • In terms of food intake, miracle fruit facilitated the food intake in chemotherapy patients and helped the diabetes patients to replace sugar, reducing calorie intake.

  • Taste alterations can either enhance or suppress the liking/intake of food depending on the dose of miraculin, type of food, gender, and interpersonal differences in taste and aroma.

Toxicity and Side Effects of Miracle Fruit

  • No adverse effects reported by the US FDA Adverse Event Reporting System (FAERS) or the Centre for Food Safety and Applied Nutrition (CFSAN) Adverse Event Reporting System (CAERS).

  • Acute toxicity study demonstrated that oral administration of miracle fruit pulp extract, up to a dose of 5000 mg/kg was not toxic enough to cause death of the albino rats. Synsepalum dulcificum seed extract caused death of mice at doses of 5, 10, 20, 100, and 1000 mg/kg, while the dose of 2.5 mg/kg did not cause death.

  • LD50LD_{50} (the dose that causes the death of 50% of animals) for the Synsepalum dulcificum seed extract was calculated as 3.54 mg/kg

  • Miraculin did not demonstrate allergenicity or toxigenicity risks to humans in silico.

  • Absence of cross-allergy between miracle fruit and peanut.

  • Sensory evaluation indicated rapid commencement and disappearance of taste-modifying effects without causing desensitization effect.

Future Directions

  • Future research should determine the effect of miracle fruit on sweet, bitter, and salty food items in pre-post quasi-experimental studies with administration of an acid such as lime juice.

  • Systematic dose–response studies should be conducted with miracle fruit to observe whether the change in dose can increase or decrease the perceived intensities of individual tastes and during the data collection, a low pH condition should essentially be maintained in the mouth to activate miraculin

  • The role of miracle fruit on dietary management should be researched further such as long or short-term interventions can be conducted in participants with other chronic disease conditions such as obesity and cardiovascular diseases to determine the efficacy of miracle fruit in improving food preferences and diet quality. etc.

  • Explore the potential of miracle fruit to improve the preferences for nutritious food and diet quality in healthy populations as an approach to prevent the chronic diseases.

  • Coating the mouth with miracle fruit may play a potential role in the food product development in future food industry as a sugar substitute in confectionary items, mask sour/bitter tastes of fruits and vegetables, and create novel flavour profiles

  • Miracle fruit may play a role in the dietary management of obesity, diabetes, and cancer in future.

Conclusions

  • Miracle fruit can decrease perceived sourness and increase sweetness in acidic food/beverages.

  • It alters the perception of sweet, bitter, and salty tastes only at low pH conditions.

  • Alterations in food liking/preferences depend on the dose of miraculin, food type, and individual taste sensitivity variations.

  • Miracle fruit is a pH-dependent taste modifier with the potential to improve food preferences.