The fatty acid amide ingredient studied is oleoylethanolamide (OEA) which Gencor has launched under the brand name Trpti - meaning satisfaction in Hindi - at Expo West held earlier in March this year at Anaheim, California.
Gencor’s managing director and founder Ramasamy Venkatesh first revealed to NutraIngredients-Asia last September that the company has been researching on an ingredient which could potentially serve as an alternative to GLP-1 or glucagon-like peptide-1 drugs.
In a follow-up interview at Vitafoods Europe held at Barcelona during May 20 to 22, Venkatesh said that Gencor has embarked on its second clinical trial on the ingredient, following positive pilot study findings.
“In the first clinical study which was 12-week long, our primarily objective was to find out changes in the microbiome.
“The pilot study which followed after was to look at GLP-1 production and we saw an increase in GLP-1 in the subjects immediately after they started eating.
“That is very interesting for us - the effects are acute, which is why we decided to look into the acute effects of GLP-1 through the current 120 participants study,” he said.
The ongoing second clinical trial, which is taking place in Australia and run by RDC Clinical, will examine changes in serum GLP-1 levels as the primary outcome, said Venkatesh.
“OEA is a fatty acid amide produced by the body. It controls your microbiome health, inflammation, glucose and lipid synthesis, satiety, and weight management.
“It acts through multiple mechanism of actions. The key one is potentiating the release of GLP-1.
“GLP-1 is produced in the body in response to food, as your body sends a signal to your intestine which leads the intestine to convert the fatty acid oleic acid - also a source of energy - into OEA.
“OEA then binds to a receptor call GPR119 that potentiates the release of GLP-1,” explained Venkatesh.
GLP-1 medications and supplements has been in the spotlight for its effects on weight loss in the recent year.
However, there are concerns around GLP-1 medication use, as it could cause side effects such as muscle loss and the “Ozempic skin” where the skin turns saggy or wrinkly.
The secondary outcomes will assess other biomarkers linked to insulin transportation, such as changes in serum GIP (gastric inhibitory polypeptide), DPP-4, glucagon, glucose, and insulin levels.
Dipeptidyl peptidase-4 (DPP-4), in particular, is an enzyme that degrades GLP-1.
Therefore, it is of interest to see whether Trpti could reduce DPP-4 levels during the second clinical trial.
“When DPP4 levels come down, then GLP-1 will act better and insulin transportation will be better. As such, we are looking at multiple biomarkers.”
According to information listed on the US Clinical Trials registry, this is a placebo-controlled, single blind, cross-over study.
It will compare the metabolic effects of two different doses of OEA at 150mg, 300mg and placebos in study participants over an eight-hour period.
This means that all participants will complete all three arms of the study - taking OEA at two different doses and the placebo as well.
Study participants have to be aged 30 and above and are generally healthy with a BMI of 25 to 34.9 kg/m2.
The OEA studied are made with LipiSperse - a cold water dispersion technology developed by Pharmako Biotechnologies.
The technology is said to allow solid or powder form of lipophilic active ingredients such as curcumin, resveratrol, and OEA, which have relatively low bioavailability and poor solubility in water to be easily dispersed in cold water.
It therefore helps to increase the bioavailability of uptake of these active ingredients in the body.
The study is expected to complete by July, said Venkatesh.
Existing findings
The pilot study on TRPTI have showed an increase in GLP-1 levels, while its first clinical study has shown an upregulation of beneficial bacteria.
Findings of the clinical study are in the process of being written for journal publication.
However, top line results have reported an increase in two key beneficial bacteria Akkermansia Muciniphila and Faecalibacterium Prausnitzii.
The former has been found to be inversely associated with obesity, diabetes, inflammation, and metabolic disorders. It is also involved in mucus layer integrity.
On the other hand, the latter is said to produce butyrate and bioactive anti-inflammatory molecules such as shikimic and salicylic acids.
Other bacteria that were upregulated include Parasutterella excrementihominis, Clostridium sp AM49 4BH, Parabacteroides johnsonii, and Desulfovibrio fairfieldensis.
Parasutterella excrementihominis, for example, is also associated with beneficial effects on metabolic conditions, including obesity and inflammatory bowel disease, due to their involvement in carbohydrate metabolism and production of short-chain fatty acids.
Desulfovibrio fairfieldensis, on the other hand, is a sulfate-reducing bacterium that can produce hydrogen sulfide, which has potential effects on gut barrier function.
Gut microbiome health is important in this case as this could affect GLP-1 production in the body, said Venkatesh.
“For GLP-1 to be produced, your body should be producing the right amounts of OEA and that is dependent upon your intestinal health and your microbiome.
“This is because intestinal inflammation and poor microbiome health can affect the production of OEA in the body.
“OEA, on the other hand, also maintains the amount of good bacteria in the body as it has the property to upregulate the amount of good bacteria.
“It is a two-way street. A good microbiome helps OEA production and at the same time, OEA can increase the amount of good bacteria,” he explained.
He added that by producing short-chain fatty-acids that play a role in lipids and glucose metabolism, these bacteria are also said to be important for weight and fat management.
There was also a reduction in intestinal inflammation markers, like IL-1β and IL-2.
“With all these benefits, Trpti could be a fantastic product for the gut health and microbiome segment of the market, in addition to it’s metabolic benefits through GLP-1,” he said.