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Global Functional Ingredients R&D Trends

This article compiles the R&D dynamics of the new functional ingredients for food supplements. The new functional food ingredients include Catechins, Broccoli, Spirulina, and Nettle.

Keeping up with the latest R&D results of functional food materials is one of the most significant actions for the food supplement industry. On November 24, 2022, the Ministry of Agriculture, Food and Rural Affairs (MAFRA)1 and FoodPolis2 jointly published a report on the Global Functional Ingredients Trends3, which introduces the R&D dynamics of the new functional ingredients for food supplements. ChemLinked compiles the key points of these researches for enterprises' reference. 

 1. Catechins

(1) Prevention of Acute Upper Respiratory Infections


Academic article: Prevention of Acute Upper Respiratory Infections by Consumption of Catechins in Healthcare Workers: A Randomized, Placebo-Controlled Trial4


The researchers performed a placebo-controlled, single-blind, randomized control trial to evaluate the clinical effectiveness of the consumption of catechins-containing beverages for preventing acute upper respiratory tract infections (URTIs).


A total of 255 subjects were analyzed (placebo group n =86, low-catechin group n = 85, high-catechin group n = 84). The URTI incidence rate was 26.7% in the placebo group, 28.2% in the low-catechin group, and 13.1% in the high-catechin group (log rank test, p = 0.042). The hazard ratio (95% confidence interval (CI)) with reference to the placebo group was 1.09 (0.61–1.92) in the low-catechin group and 0.46 (0.23–0.95) in the high-catechin group. These findings suggest that catechins combined with xanthan gum protect against URTIs.

(2) Energy Expenditure 


Academic article: Effect of tea catechins with caffeine on energy expenditure in middle-aged men and women: a randomized, double-blind, placebo-controlled, cross-over trial5


The researchers conducted a study aiming to examine the effect of repeated intake of tea catechins on energy metabolism in the resting state in middle-aged men and women.

A total of 30 middle-aged men and women were recruited. A randomized, double-blind, cross-over study was conducted using a tea catechin-enriched beverage (611 mg catechins, 88 mg caffeine) and a placebo beverage (0 mg catechins, 81 mg caffeine) as test beverages. After 2 weeks of continuous test beverage intake, fasting resting metabolic rate and energy expenditure after the ingestion of test beverage were measured.


Among participants, 26 were analyzed. The energy expenditure increased significantly after ingestion of the tea catechin beverage compared with the placebo beverage. This study revealed that continuous intake of tea catechins with caffeine for two weeks significantly increased energy expenditure after ingestion of the tea catechin

(3) Gut Health


Academic article: Intestinal-Level Anti-Inflammatory Bioactivities of Catechin-Rich Green Tea: Rationale, Design, and Methods of a Double-Blind, Randomized, Placebo-Controlled Crossover Trial in Metabolic Syndrome and Healthy Adult6


This clinical trial aims to establish the efficacy of green tea extract to alleviate metabolic endotoxemia-associated inflammation in persons with metabolic syndrome (MetS) by improving gut barrier function.


The researchers planned a double-blind, placebo-controlled cross-over trial in persons with MetS and age- and gender-matched healthy persons, who will receive a low-energy GTE-rich (1 g/day; 890 mg total catechins) confection snack food while following a low-polyphenol diet for 28 days. Assessments will include measures of circulating endotoxin (primary outcome) and secondary outcomes, including biomarkers of endotoxin exposure, region-specific measurements of intestinal permeability, gut microbiota composition, diversity, and functions, intestinal and systemic inflammatory responses, and catechins and microbiota-derived catechin metabolites.


The study result confirmed that Catechins could help reduce the circulating endotoxin. However, not as expected, there is no significant difference between the persons with MetS and healthy persons. Despite of result, according to the article's conclusion, the outcomes could provide foundation for mechanistic studies in vitro examining prebiotic and antimicrobial activities of green tea extract catechins relative to gut barrier function, and help to establish evidence-based dietary recommendations for a health-promoting, commercially translatable, catechin-rich food that can potentially reduce cardiometabolic morbidity, as metabolic endotoxemia initiates low-grade chronic inflammation in metabolic syndrome and provokes the progression towards more advanced cardiometabolic disorders.

2. Broccoli

Effective for Symptoms of COVID-19


Academic article: Efficacy of Broccoli and Glucoraphanin in COVID-19: From Hypothesis to Proof-of-Concept with Three Experimental Clinical Cases7


COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms.


Broccoli was chosen because it contains rich glucoraphanin which is obtained from cruciferous vegetables. The most potent Nrf2 natural activator is sulforaphane,4, 5, 6, 7, 8, 9, 10, but it is difficult to deliver in an enriched and stable form for direct human consumption. Thus, glucoraphanin, the precursor of sulforaphane, is administered orally with myrosinase, the enzyme that transforms glucoraphanin into sulforaphane.


Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6–12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules. A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms.


These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2-interacting nutrients are effective in COVID-19. However, according to the researchers, confirmation is necessary through proper trials on efficacy and safety before the ingredient is used in practice.

3. Spirulina

(1) Weight Loss


Academic article: Effects of Spirulina Supplementation on Obesity: A Systematic Review and Meta-Analysis of Randomized Clinical Trials8

Evidence has suggested that Spirulina supplementation may affect anthropometric indices. Therefore, the researchers performed a systematic review and meta-analysis to summarize published randomized clinical trials which assess the effect of Spirulina supplementation on obesity.


Pertinent studies were identified using Embase, Scopus, ISI Web of Science, PubMed and Cochrane library databases up to May 2019. Mean Differences (MD) were pooled using a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods.


Results of 5 studies showed a significant reduction in weight (MD: -1.56 Kg, 95% CI: -1.98 to -1.14) after Spirulina supplementation. Subgroup analysis based on health status revealed that weight change in obese subjects (MD: -2.06 Kg, 95% CI: -2.45 to -1.68) was greater than overweight participants (MD: -1.28 Kg, 95% CI: -1.62 to -0.93) following Spirulina supplementation. Also, pooled analysis showed that Spirulina supplementation led to a significant reduction in body fat percent (MD: -1.02, 95% CI: -1.49 to -0.54) and waist circumference (MD: -1.40, 95% CI: -1.40 to -1.39), but not in body mass index and waist to hip ratio.


The findings of the present study suggest that Spirulina supplementation significantly reduces body weight, body fat percentage and waist circumference but has no effect on BMI and waist-to-hip ratio. Subgroup analyses indicate that the impact may be more pronounced on obese subjects than overweight individuals. For future studies conducting more specific interventions according to a different age or gender groups is suggested.

(2) Memory Improvement


Academic article: The Effects of Spirulina maxima Extract on Memory Improvement in Those with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial9


Spirulina maxima is a marine microalga that has been promoted worldwide as a superfood. The researchers conducted a study to evaluate its ability to improve memory in older adults using Spirulina maxima 70% ethanol extract (SM70EE). This randomized, double-blind, placebo-controlled clinical trial comprised 80 volunteers who were randomly assigned to two groups. The participants received either 1 g/day of SM70EE or a placebo without changing their diet or physical activity. The participants were examined at baseline and after a 12-week interval to determine whether there were changes in their results for visual learning, visual working memory, and verbal learning tests from the Korean version of the Montreal Cognitive Assessment, brain-derived neurotrophic factor and beta-amyloid levels, and total antioxidant capacity. Compared to the placebo group, the treatment group showed a significant improvement in visual learning and working memory test results and enhanced vocabulary.


SM70EE was shown to improve memory with no adverse effects. Its efficacy in alleviating Alzheimer's disease symptoms was verified for the first time through this clinical trial. SM70EE could play a role in the management of patients with dementia.

4. Nettle

(1) Improvement of Urinary Problems in Older Men


Academic article: The Effect of Nettle Root Extract on Urinary Problems in Older Men with Benign Prostatic Hyperplasia: A Randomized Clinical Trial10


Benign prostatic hyperplasia is one of the most common benign tumors in men. Due to frequent side effects associated with medications used to treat prostatic hyperplasia, the use of herbal plants such as nettle has increased to manage this ailment.


The researchers conducted a study to determine the effect of nettle root extract on urinary problems, prostatic-specific antigen level, and prostate volume in older men with benign prostatic hyperplasia.


Eighty participants were involved in the study and randomly assigned into experimental (n = 40) and control (n = 40) groups. The participants received a tablet containing 300 mg of nettle root extract or a placebo (starch) twice a day for eight weeks. Before and after the intervention, the participants were assessed regarding their prostatic specific antigen level, prostate volume, and the American Urological Association Symptoms Scores associated with urinary problems. Data were analyzed using the Fisher's exact test, the Chi-square test, the Paired t-test, and the independent samples t-test.


After the intervention, there were significant differences between the groups in terms of urinary frequency (control: −0.17 ± 0.74 versus experimental: −0.5 ± 0.67; p = 0.04), urinary urgency (control: 0.12 ± 0.91 versus experimental: −0.32 ± 0.69; p = 0.01), and nocturia (control: 0.0 ± 0.65 versus experimental: −0.28 ± 0.64; p =0.05). The group comparisons showed that there was no significant difference between the groups in terms of changes in the prostate-specific antigen level (p = 0.44), prostate volume (p = 0.22), feeling of incomplete emptying (p =0.72), intermittency (p = 0.26), weak urine stream (p = 0.44), straining (p = 0.85), and quality of life (p = 0.91) associated with urinary problems.


The use of nettle root extract in combination with conventional medical treatment of BPH was effective in decreasing the severity of urinary problems, including urinary frequency, urgency, and nocturia in participants. However, the nettle extract was not effective in modifying prostate-specific antigen level, prostate volume, feeling of incomplete emptying, intermittency, urine stream, straining, and quality of life associated with urinary problems. Nettle extract is recommended for use as a complementary intervention along with traditional medical treatments of benign prostatic hyperplasia.

(2) Improvement of Sleep Quality 


Academic article: Effect of Urtica Dioica (Nettle) on Quality of Sleep in Hemodialysis Patients: A Randomized Clinical Trial10


Sleep disorders are common in patients with end-stage renal disease. The present study aimed to examine the effect of Nettle on sleep quality in hemodialysis patients.


The researchers conducted a randomized clinical trial on 90 hemodialysis patients. Using the convenience sampling method, the participants were selected and then randomly assigned to intervention and control groups. The intervention group was provided with 400-mg Urtica dioica tablets three times a day for three consecutive months. The control group did not receive any intervention.


However, the study's results were indicative of no statistically significant difference between the two groups in terms of sleep quality before and after the intervention (P = 0.09). Moreover, the effect of Urtica dioica on sleep quality was not significantly different at the end of the first (P = 0.14), second (P = 0.34), and third (P = 0.97) months.


As evidenced by the obtained results, Urtica dioica did not significantly improve sleep quality in hemodialysis patients. Despite the use of hypnotics, poor sleep quality is common among hemodialysis patients. Nonetheless, Urtica dioica along with hypnotics, helped maintain the stability of sleep quality in the present study. Urtica dioica tablets in hemodialysis patients decreased sleep latency and increased sleep duration.

(3) Protective Effect on Allergic Asthma


Academic article: Effect of nettle seed on immune response in a murine model of allergic asthma


Asthma is regarded as an inflammatory disease of the lung characterized by inflammatory mediator release, eosinophil recruitment, mucus hypersecretion and bronchoconstriction. The researchers conducted the study to evaluate the protective effect of Urtica dioica seeds on allergic asthma. Mice were sensitized via intraperitoneal injection of ovalbumin (OVA) containing aluminum hydroxide on days 1 and 14. On days 24, 26, 28 and 30, the mice underwent challenges through inhalation of 1% OVA aerosolized using an ultrasonic nebulizer. Animals sensitized and challenged with OVA were treated with theophylline 1% while the other asthmatic group received 3.3−1 nettle seed extract by gavage 15 min after each challenge for eight consecutive days (days 23–30). At the end of this period, the mice were euthanized on day 31 for analysis of lung tissue, bronchoalveolar lavage fluid (BALF) and blood. The results showed that nettle seed significantly (P< 0.05) decreased the following in lung tissue: percentage number of eosinophils in the blood (1.4 ± 0.3%) and BALF (22 ± 5%); Th2 cytokines including IL-5, IL-13, and IL-33 (43.12 ± 3.5, 63.76 ± 3.3 pg/ml, 10.40 ± 0.81 ng/ml respectively); mRNA expression of IL-4 (1.56 ± 0.3), IL-5 (1.42 ± 0.1), IL-13 (1.58 ± 0.04) and Muc5 (1.83 ± 0.2); inflammatory cell infiltration (perivascular inflammation: 1 ± 0.3; peribronchial inflammation: 1.5 ± 0.2); goblet-cell hyperplasia (1.5 ± 0.2); and mucus hypersecretion (25 ± 10%).


The findings demonstrated a protective effect of nettle seed on OVA-induced allergic asthma in mice.

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