Mannoheptulose (MH) is a monosaccharide that naturally occurs in unripe avocados. It could potentially be used as a novel calorie restriction (CR) mimetic – a substance that mimics the metabolic and physiological benefits of CR, without the requirement to reduce food.
Writing in Nutrients, researchers from Australia and the US found daily consumption of MH didn’t change glucose tolerance or insulin sensitivity in nondiabetic adults with obesity. But there was preliminary evidence it reduced insulin requirements in a subgroup of participants.
A new tool to fight obesity?
Obesity is a global health challenge associated with cardiovascular diseases, diabetes mellitus and cancer. Moderate calorie restriction reduces people’s risk of chronic diseases – but it can be difficult to maintain long-term.
The current study emerged from interest in developing intracellular glycolysis (a process through which glucose is converted to energy) inhibitors to stimulate CR-like responses.
MH has been proposed by researchers as a CR mimetic since research suggests it increased the median and maximal lifespan of fruit flies. A study showed dogs receiving 2–20 mg/kg of MH through unripe avocados showed reduced fasting insulin. However, a second study couldn’t replicate this result.
So far, human studies describing consumption of MH are extremely limited. To the authors’ knowledge there is only one featuring a sample of just eight men. In it, fasting insulin was reduced in five men, with no discernible change in plasma glucose.
The study used a two-arm, parallel group, double-blinded, randomised controlled trial with 60 participants recruited between 2021 and 2022. The trial lasted 13 weeks. The authors used unripe Hass avocados from an Australian commercial crop. The flesh and peel were shredded by a
disintegrator, then transferred to a freeze-drying machine for 96 hours.
Based on calculations from previous studies on dogs, the authors’ target dose was 2 mg/kg of MH. They originally planned to treat a separate group with a higher dose, but this wasn’t possible.
The study’s primary outcome measure, glucose AUC (the area under the receiver operating characteristic curve), didn’t differ between groups.
However, after adjusting for weight change a subgroup analysis showed reduced insulin AUC.
The authors note that this “provid[ed] preliminary evidence consistent with animal studies that the supplement reduced insulin requirements in those individuals at high risk for cardiometabolic disease.”
“The findings of the current study add to the limited evidence pertaining to the impact of MH on reducing the insulin response after an OGTT [oral glucose tolerance test].”
The authors identify several limitations of the study. The extract featured “lower-than-expected MH enrichment”. This might have introduced “additional compliance issues and the likelihood that some beneficial outcomes may have been attributed to other bioactives in the AvX.”
The study also featured a high proportion of Caucasian women, which might limit its application to other groups. They added that the dose might not have been high enough to impact glycaemia during an OGTT performed the following day.
The researchers were affiliated with the University of Adelaide (Australia), Louisiana State University (USA), Isagenix International LLC (USA), De Paoli Farms (Australia), the University of Western Australia, and Prolongevity Technologies LLC (USA).
2023, 15(22), 4812; doi: 10.3390/nu15224812
“Effects of an Unripe Avocado Extract on Glycaemic Control in Individuals with Obesity: A Double-Blinded, Parallel, Randomised Clinical Trial”
Authors: L. Zhao, D.K. Ingram, E. Gumpricht, et al.