Research Updates: Active Aging, Migraines, Sleep & More

PEA Shown to Ease Migraines

Gencor shared the news of a double-blind, placebo-controlled human clinical trial demonstrating that its palmitoylethanolamide (PEA) ingredient, Levagen+, is a safe and effective supplement for reducing discomfort and duration of migraines in healthy participants. Published in the journal Pharmaceuticals, the study investigated the effectiveness of pain reduction, duration, and medication use during a migraine. Gencor gave an overview of the study: Upon the commencing of migraine symptoms, study participants were either given 600mg of PEA (Levagen+) or a placebo (maltodextrin). Once the dose was taken, participants recorded a visual analog scale (VAS) for pain every 30 minutes for 4 hours or until the migraine resolved. If the migraine had not resolved 2 hours post-dose, study participants were instructed to take a second supplement.

The findings: Levagen+ resolved more headaches than the placebo after 2 and 8 hours, and the Levagen+ participants also had a lower VAS for pain score at 1.5 and 4 hours and significantly reduced rescue medication compared to the placebo.

“The results of this study further back PEA’s clinically validated benefits for its analgesic and inflammatory properties in addition to its neuroprotective effects,” said R.V. Venkatesh, Co-founder and Managing Director at Gencor, in a press release. “We are thrilled about the promising results and potential of Levagen+ to support those who suffer from migraine.”

Levagen+ is powered by LipiSperse delivery technology developed by Pharmako Biotechnologies and is applicable for dietary supplements, food and beverages, and cosmeceuticals. . It is a self-affirmed GRAS ingredient clinically tested to support joint health, sleep, recovery, immunity, discomforts, and inflammation.

CoQ10 Phytosome Shown to Improve Physical Performance

Indena shared the news that supplementation with CoQ10 Phytosome (Indena’s UBIQSOME) has been shown to improve physical performance in older adults with statin-associated asthenia, according to a independent double-blind, randomized, placebo-controlled study. In the study, 60 subjects were randomized to receive daily supplementation either with placebo or 150 mg CoQ10 Phytosome for 8 weeks. After the first 4 weeks of supplementation, both groups significantly improved in asthenia compared to baseline; 4 weeks later, the effect on asthenia was maintained, versus placebo and baseline, only in the supplemented group (statistical significance was reached both versus baseline and versus placebo).

“We’re very proud that UBIQSOME, our coenzyme Q10 formulated with Phytosome, the proprietary Technology Platform developed by Indena, has been useful for the trial," said Serena Tongiani, Chief Product Officer at Indena. "And of course we’re very happy that this preliminary clinical evidences confirm the values of our product in the field of cardiovascular health. We’ve been working to confirm our UBIQSOME as the leader in muscle uptake CoQ10 supplementation. This independent study is consistent with the capacity of UBIQSOME to reach the right biological target, and indicates its potential in case of asthenia in statin-users. Another important result for our portfolio.”

Indena noted that, thanks to its Phytosome formulation, UBIQSOME is a food-grade highly absorbable form, standardized in coenzyme Q10 (18-22% by HPLC), which optimizes coenzyme Q10 levels not only in blood but also in muscles.

"Longevity Vitamin" Ergothioneine Supports Cognitive Health

Blue California announced the completion of a double-blind, placebo-controlled clinical trial showing its ingredeints ErgoActive ergothioneine supports aspects of cognitive function, memory, and sleep in healthy elderly subjects with subjective memory complaints. The company explained: "Despite decades of preclinical research, association studies, and clinical studies conducted with mushrooms, it remained untested whether supplementation with pure ergothioneine can improve cognitive outcomes. Rigorous clinical studies were lacking. Today, Blue California has made a substantial advancement by sponsoring a double-blinded, placebo-controlled clinical study conducted at a national research institution."

Robert B. Beelman, Ph.D., Professor Emeritus of Food Science and Director of the Center for Plant and Mushroom Foods for Health at Pennsylvania State University, said in a press release, "The results of this study provide important clinical evidence supporting the idea that ergothioneine is a ‘longevity vitamin’ that can help mitigate cognitive decline and sleep issues commonly associated with aging."

Linda May-Zhang, Ph.D., VP of Science and Innovation, Blue California, added, "Blue California is proud to have sponsored such an important human study. We are pleased by the results showing improvements of cognitive function and ability to get to sleep in subjects consuming ErgoActive for four months.”

Ayurvedic Blend Improves Muscle Health, Strength, Endurance

In a randomized, double-blind, placebo-controlled study, the branded ingredient Strengthera, which is a synergistic blend of extracts from botanicals from the Ayurvedic medicine tradition, was shown to improve strength and endurance in older adults. The 12-week study involved 92 healthy women and men ages 55-70 who took 650 mg of the ingredient once per day in conjunction with an at home exercise program designed for older subjects. Testing was conducted at baseline, 4, 8, and 12 weeks. Researchers measured muscle strength, muscle endurance, functional mobility, lean mass, and muscle quality.

The findings, as outlined in a press release from PLT Health Solutions, Inc.: Statistically significant results started at four weeks; at 12 weeks, the Strengthera cohort showed a 4.2x improvement in lower body strength, a 4.5x improvement in grip strength, and a 1.5x improvement in muscle endurance over what was seen with placebo plus exercise program. In the walking test, Strengthera subjects showed a 1.9x greater improvement in walking capacity based on distance and speed over placebo. In lean muscle mass, the Strengthera group increased their total lean mass relative to baseline. Improvements were also seen in energy and vitality.

Jennifer Murphy, Director of Innovation & Clinical Development for PLT, said the findings are important for anyone who wants to remain active and vital as they age. "Muscle health and mobility are important for quality of life at every age, but they are especially critical as we get older," Murphy noted. "The ability to maintain strength is essential for remaining active and independent, which are key factors in good health. Grip strength, in particular, is not only considered an accurate indicator of vitality and overall muscle strength, but also a biomarker of longevity and a strong predictor of future health. Another important differentiator of this new study is that it included women. Too often muscle ingredients focus studies on men only, but of course, we know that due to physiological differences, benefits should be illustrated in both populations."

Multi-Strain Probiotic May Improve Sleep Quality

Research published in Beneficial Microbes has found that the multi-strain probiotic branded as Probiotical’s Bifizen may improve multiple indicators of sleep quality. The study began in early 2020, just before the announcement of COVID-19, then restarted in September 2020. As Probiotical noted in a press release, "the influence of this background phenomenon on the anxiety and sleep physiology of the subjects is unknown yet likely not inconsequential."

The randomized, double-blind, placebo-controlled study involved 70 healthy men and women who complete a nine-week protocol: six weeks of supplementation with Bifizen or a matched placebo, followed by a three-week “washout” period. The Bifizen group reported a significant reduction in time to fall asleep after six and nine weeks of supplementation, compared to baseline. Data indicated strong trends toward greater sleep duration and total time in bed for the supplemented group, and researchers speculated that Bifizen altered the composition of the intestinal microbiota, which in turn impacted various biomarkers affecting sleep.

“Lack of quality sleep affects health, mood, and overall well-being,” said Probiotical SpA CEO Vera Mogna. “These results represent an encouraging solution and represent an exciting direction for the probiotics industry. Probiotical remains committed to studying the gut-brain axis and investigating the positive impact of beneficial probiotics on quality of life.”

Probiotical added that previous published research found Bifizen has a significant effect on measures of minor depression, anxiety, and mood.

Squalene Shows Promise in Reducing COVID-19 Mortality

Sublingual squalene may play a role in decreasing mortality rates and preventing re-hospitalization among subjects with COVID-19, according to a new study published in Nature, titled Utilizing the Sublingual Form of Squalene in COVID-19 Patients: A Randomized Clinical Trial. Researchers investigated the impact of sublingual squalene on patient outcomes during the critical period of the pandemic.

The clinical trial spanned from November 2021 to January 2022 and involved 602 eligible COVID-19 subjects, divided into a control group and a treatment group, both of which were statistically similar in terms of various demographic and clinical parameters. Subjects in the treatment group received a regimen of five drops of sublingual squalene every 4 hours for 5 days in addition to standard treatment; the control group received standard treatment alone. Patients were monitored for 30 days following discharge from the hospital.

The findings, as outlined in a press release from PhytoGaia: The treatment group experienced a significant decrease in mortality rates; after one month, 94.7% of the patients in the treatment group were alive, compared to 81.4% in the control group. Sublingual squalene also showed effectiveness in preventing re-hospitalization due to COVID-19, with 19.3% of the patients in the treatment group requiring re-hospitalization, in contrast to 46.8% in the control group.

"These findings suggest that squalene administered sublingually holds promise as an effective intervention for reducing mortality and re-hospitalization rates among COVID-19 patients," said Dr. Ariati Aris, Scientific Affairs Specialist at PhytoGaia. "This represents a significant step forward and opportunity in our fight against the pandemic, offering a potential lifeline especially for those COVID-19 patients with severe symptoms."

Bryan See, Vice President of PhytoGaia, added, “The role of squalene as an anti-inflammatory, immune-modulatory and antioxidant drug offers promise for COVID-19 patients. PhytoGaia offers a novel combination of natural plant squalene + tocotrienol complex (STGaia) which may provide impressive synergistic health benefits.”

PhytoGaia added that the results underscore the importance of continued research and innovation in identifying novel therapeutic approaches to combating COVID-19, and further study into the potential of sublingual squalene is warranted to unlock its full therapeutic benefits.

Lutein, Zeaxanthin Deliver Eye Health & Cognitive Benefits for Kids

OmniActive Health Technologies shared the results of study published in Advances in Therapy that looked at Lutemax Kids, a proprietary, low-dose extract of lutein and zeaxanthin isomers. The randomized, double-blind, placebo-controlled trial included 60 healthy male and female children given either a daily dose of Lutemax Kids, containing 10 mg lutein and 2 mg zeaxanthin isomers in a gummy format, or placebo.

The finding: Supplementation with Lutemax Kids resulted in significant improvements in aspects of vision performance and cognition. Over time, supplementation with Lutemax Kids:

Significantly increased blood levels of lutein and zeaxanthin
Increased macular pigment optical density (M.P.O.D.) levels
Increased visual processing speed
Decreased eye strain and fatigue attributed to digital device usage
Significantly improved aspects of cognitive health, including attention, focus, episodic memory, visuospatial memory, and visuospatial processing speed

“The study results demonstrated that Lutemax Kids supplementation contributes positively to aspects of eye health and cognitive performance in school-aged children, echoing the well-documented benefits observed in adults,” said Dr. Billy Hammond, Professor (Behavioral and Brain Sciences Program) at the University of Georgia and lead researcher in the study. “From improved visual processing speed to eye strain that may result from digital device use, these outcomes serve as a foundation for tailored supplementation in children. It also emphasizes the potential to help meet specific needs of children during a critical developmental phase."

OmniActive said this research expands upon earlier published research on adults, including the LAMA I & LAMA II (Lutein, Vision and Mental Acuity), and B.L.U.E. (Blue Light User Exposure) studies.

Dr. Arun Balakrishnan, Chief Innovation Officer at OmniActive, added, “Understanding the profound impact of these vital nutrients on young eyes and minds is a game changer, shedding light on their role in fostering well-being from an early age. Our pioneering efforts with this study come at a critical time when supplement brands are looking to cater to children’s health and wellness needs with safe, plant-based, and efficacious ingredients. As we continue to see the benefits of lutein and zeaxanthin across all life stages, we're reaffirming lutein and zeaxanthin’s significance in promoting a healthier future for our younger generation across the globe."

Pomegranate Extract May Support Gut Microbiome & More

In a four-week, double-blind, placebo-controlled, randomized clinical trial, the branded ingredient Pomella, a patented pomegranate extract, was evaluated for its impact on gut microbiome, short chain fatty acids (SCFA), and mitochondrial health. Researchers looked at the effects of 250mg/day of Pomella in healthy adults 25-55yrs for beneficial effects on the gut microbiome, circulating short-chain fatty acids and gut-microbial derived ellagitannin metabolites, namely urolithins, using whole genome sequencing for gut microbial analysis.

The findings, according to a press release from Verdure Sciences: Gut functional analyses are consistent with circulating short-chain fatty acids (SCFAs), reinforcing the idea that Pomella supplementation improves SCFA levels by influencing the gut microbiome. The company said the results imply that consuming Pomella promotes a healthier gut and improves gut-body communication.

Researchers highlighted significant changes in SCFAs pre and post Pomella extract supplementation, and also noted an increase in certain species such as Coprococcus eutectus, Roseburia faecis, Roseburia inulinivorans, Ruminococcus bicirculans, Ruminococcus calidus, Faecalibacterium prausnitzii, Methanobrevibacter smithii, and Collinsella aerofaciens within the Pomella group. This, the release said, suggests that ellagitannins from pomegranate may trigger changes in these bacteria, potentially influencing overall health by affecting short-chain fatty acids, secondary metabolites, and the synthesis of urolithin A.

“The support for the gut microbiome, short chain fatty acids, metabolic health, mitochondrial and cellular support are all areas we have seen previous data support," said Kristen Marshall, Digital Marketing Manager, Verdure Sciences. "This study helps bolster an already interesting story—making it much more compelling now. Tremendous interest continues to build for gut and digestive health, skin support and beauty from within as well as specific gut and skin microbiota and we are honoured that Pomella is so well poised to tackle this category’s needs.”

“It is interesting to see how science around Pomella over the last 10 years have shifted focus from demonstrating important results on the role of Pomella as a bioavailable, powerful antioxidant with several benefits to human health to new exciting findings on gut microbiome support and the link with skin health and overall health,” added Teresita Ruda, Head of Brands and Marketing at LEHVOSS Nutrition, which distributes the ingredient across Europe.

Pomegranate Extract Promotes Healthy Aging

Euromed’s branded pomegranate extract Pomanox has been shown to promote healthy aging in mice, including preventing frailty, improving motor skills, and reducing oxidative stress in the cerebellum (responsible for coordination, motor learning, and cognitive tasks). According to a press release, the researchers looked at how to overcome the problem of falling and subsequent bone fractures in the elderly by addressing balance and stance, which are controlled by the cerebellum.

Pomanox also was shown to maintain antioxidant levels in elderly mice after four months of supplementation. This effect was particularly evident in the cerebellum, Euromed reported. The extract also influenced gene expression related to the apoptosis pathway, suggesting support for healthy aging. Euromed also shared that, although no changes in grip strength and endurance were found, the results showed that pomegranate extract supplementation improved the motor skills in terms of coordination and neuromuscular function, and helped prevent age-related weight loss.

“Pomanox is already well known to provide benefits for cardiovascular and metabolic health, satiety, sports performance, mood, skin and cognitive health," said Andrea Zangara, Head of Scientific Communication and Medical Affairs at Euromed. "The novelty of this work focuses on the fact that the pomegranate extract could be used to help prevent deterioration associated with normal aging. The authors of this independently conducted study have observed for the first time that the cerebellum is the area where aging is first noticed in a model without pathology. As Pomanox acted efficiently here, it could be a helpful tool to reduce the risk of falls so common in aging, and other functional impairments.”

Euromed also noted that pomegranate’s health benefits come from punicalagins, and Pomanox contains up to 30% punicalagins.

Precision Prebiotic Reshapes Microbiota Composition for Consistent Gut Health Benefits

NutriLeads shared the news of a study, published in Food Hydrocolloids, that provides insights into the fermentation mechanisms that enable its ingredient BeniCaros to overcome differences in individual gut microbiota composition to consistently increase beneficial bacteria present in the gut of most people. BeniCaros is a precision prebiotic fiber identified as rhamnogalacturonan-I (carrot RG-I, cRG-I); it is sourced from upcycled carrot pomace.

The study utilized SIFR technology and found that BeniCaros consistently had positive effects across all individuals despite initial differences in their gut microbiota composition. The research employed the in vitro intestinal model, the M-SHIME, which was adapted to study the fermentation kinetics of BeniCaros by the gut microbiota of four healthy donors in parallel.

NutriLeads reports: BeniCaros underwent rapid fermentation in the proximal colon compartment by a consortium of gut microorganisms. The initial fermentation pattern varied among donors and was influenced by the individual baseline microbiota. However, after daily supplementation of cRG-I- for three weeks, the final fermentation characteristics became consistent across all four donors. The fermentation of BeniCaros resulted in an increased production of short-chain fatty acids, especially propionate, known to confer beneficial health effects on the host.

“The study results provide further evidence on how complex prebiotic fibers, such as BeniCaros, can reliably deliver health benefits,” said Joana Carneiro, Ph.D., NutriLeads Chief Executive Officer. “These findings are especially interesting for manufacturers of prebiotic health products aiming to deliver more effective propositions with predictable, consistent gut health benefits.”