Researchers from Australia conducted the double-blind, randomised, placebo-controlled trial with 426 participants, finding that 300 mg of Gencor's Levagen+ consumed twice daily for 12 weeks “may be an effective treatment option for the prevention of URTIs and cold and flu symptoms.”
The study, funded by Pharmako Biotechnologies, manufacturer of the supplement, concludes: “Overall, Levagen+ was found to be a safe and effective treatment option for those with URTI symptoms, with results indicating that it can decrease the total number of URTI episodes and the symptoms of scratchy throats and coughing.”
R.V. Venkatesh, co-founder at Gencor, states: "Along with a healthy diet and exercise, Levagen+ can be a strong ingredient to support immune health.”
URTIs are caused by an infection of the mucosal lining of the upper airway, typically originating from either bacteria or viruses.
On average, adults have between two and four episodes of the common cold per year, and due to the frequency of occurrence, URTIs require prophylactic and/or treatment options for symptoms that have minimal to no side effects.
Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive signalling lipid that is part of the N-acylethanolamine (NAE) family. In the case of cold and flu infections where there is an increase in inflammatory cytokine production, PEA has been proposed to work to modulate interleukins and downregulate mast cell production at inflammation sites.
PEA initiates NF-κB pathways via the activation of PPAR receptors, with a high affinity for PPAR-α, and works in a concentration-dependent manner to decrease NLRP3 and inflammasome activation. The anti-inflammatory effects of PEA reportedly allow it to reduce the expression of cytokines released from macrophages. Overall, the known mechanisms of action of PEA support the observation that it can decrease the symptoms associated with URTIs.
According to the authors, the current efficacy of PEA on cold and flu symptoms is based on theoretical evidence or animal studies, and while some human clinical studies have indicated that PEA is an effective treatment in reducing cold and flu symptoms, these studies are almost 50 years old, indicating a need for new studies to investigate the effects of modern PEA formulations on cold and flu symptoms.
Recent human clinical studies have focused more on the potential effects of PEA on inflammation associated with COVID-19, where PEA has been shown to be effective against respiratory symptoms caused by increased inflammation associated with COVID-19.
One study showed that supplementation with ultra-micronised PEA reduced markers of inflammation, and another showed that PEA could bind to the SARS-CoV-2 protein, causing a decrease in viral infection by approximately 70%.
However, the authors state: “It is important to note that both endogenous levels of PEA and exogenous PEA administration have previously been reported to be insufficient in mitigating a significant clinical response due to poor absorption, resulting in low plasma concentrations.”
They suggest that when PEA is combined with dispersion technology (i.e., Levagen+), PEA absorption is significantly increased, leading to higher plasma concentration levels that may enable a therapeutic effect, but that further research is needed to establish its effectiveness and safety concerning applications on cold and flu symptoms.
Therefore, the new study aimed to explore the efficacy of Levagen+ on the incidence, severity, and duration of URTIs compared to a placebo in otherwise healthy adults.
The trial utilised an active group and a placebo group, where participants (n = 426) consumed either 300 mg of Levagen+ or a placebo (maltodextrin) twice daily for 12 weeks.
Participants completed a questionnaire daily upon the commencement of symptoms until symptoms subsided.
A total of 87 participants experienced at least one URTI during the study, with a total of 103 URTI episodes recorded. The Levagen+ group reported significantly fewer URTI episodes (39 and 64, respectively; p = 0.0056) and fewer participants were sick at least once during the study (32 and 55, respectively; p = 0.0116) compared to the placebo group.
The Levagen+ group also reported a significant reduction in the median severity score of URTI symptoms for scratchy throat (3 vs. 7) and cough (2 vs. 7) compared to the placebo group.
Overall, the results suggest that the total number of URTI episodes was significantly lower in the Levagen+ group when compared with the placebo group.
The authors do note however that in the present study only 21 participants (16 in the placebo and 5 in the Levagen+) reported fever, and this number may be too low to determine an effect. They suggest that the issue could be in the self-reporting style of the study.
They add: “Future studies into the efficacy of PEA would benefit from looking at specific etiologies and severity within URTIs. Further research on the effect of PEA on fever would require larger numbers that focus specifically on the temperature development of participants during an illness.”
“The Efficacy of Palmitoylethanolamide (Levagen+) on the Incidence and Symptoms of Upper Respiratory Tract Infection—A Double Blind, Randomised, Placebo-Controlled Trial.”