Hesperetin increases mitochondrial ATP content 33% - the most potent compound out of 7949 tested for cellular respiration

[cs3000]

High throughput screening of mitochondrial bioenergetics in human differentiated myotubes identifies novel enhancers of muscle performance in aged mice

Hesperetin (derivative of Hesperidin in orange juice) improves cellular respiration for more ATP which is a key to overall health. increased mitochondria ATP by 33%. and also improved spare capacity by 25%
most potent effect out of 7949 tested compounds

boosts mitochondrial gene expression

Mitochondrial dysfunction is increasingly recognized as a contributor to age-related muscle loss and functional impairment. Therefore, we developed a high throughput screening strategy that enabled the identification of compounds boosting mitochondrial energy production in a human skeletal muscle cell model. Screening of 7949 pure natural products revealed 22 molecules that significantly increased oxygen consumption and ATP levels in myotubes. One of the most potent compounds was the flavanone hesperetin.

Hesperetin (10 µM) increased intracellular ATP by 33% and mitochondrial spare capacity by 25%​

They followed up with an animal study in aged mice.
showing 4mg/kg human dose for 6 weeks completely reversed the muscle fiber size decrease usually seen in aging, & increased running performance

In aged mice administration of hesperetin (50 mg/kg/d) completely reverted the age-related decrease of muscle fiber size and improved running performance of treated animals. These results provide a novel screening platform for the discovery of drugs that can improve skeletal muscle function in patients suffering from sarcopenia or other disorders associated with mitochondria ldysfunction

this series included hesperetin as well as 2 other compounds that signifcantly elevated ATP levels by more than 15% in the primary screen (Fig.2a).
A quantitative comparison of compound activities based on dose-response relationships confirmed hesperetin as one of the most effective natural products tested (Fig.2b). Moreover, evaluation of mitochondria-derived ATP (Fig.2c) and direct measurements of cellular respiration (Fig.2d) verified its mitochondria-targeted mechanism of action. In the latter experiments hesperetin specifcally increased spare capacity (Fig.2d,e) which is considered as an indicator of mitochondrial fitness/flexibility 14–16 and a potential blood biomarker for physical ability that correlated with gait speed in older adults

mitochondrial ATP synthase 6 (Mtatp6) was highest upregulated after hesperetin stimulation

An important transcriptional master regulator of mitochondrial biogenesis is the coactivator Pgc-1alpha which increases mitochondrial biogenesis and improves oxidative capacity in differentiated myotubes. In line with Pgc-1alpha upregulation we detected increased protein levels of the respiratory chain complexes
(Fig.3f,g, Suppl. Fig.1c). Notably, all complexes except complex II were upregulated.

(it improves complex II where there is heavy metal toxicity image)


and has a bunch of broad benefits in animal studies - which likely is further proof of ray peats central idea of correcting cellular energy (mitochondria) to allow corrected structure to rebuild health in self-organising lifeforms

from generative energy

 

[Prota]

High throughput screening of mitochondrial bioenergetics in human differentiated myotubes identifies novel enhancers of muscle performance in aged mice

Hesperetin (derivative of Hesperidin in orange juice) improves cellular respiration for more ATP which is a key to overall health. increased mitochondria ATP by 33%. and also improved spare capacity by 25%
most potent effect out of 7949 tested compounds

boosts mitochondrial gene expression
View attachment 47889


View attachment 47888


They followed up with an animal study in aged mice.
showing 4mg/kg human dose for 6 weeks completely reversed the muscle fiber size decrease usually seen in aging, & increased running performance







(it improves complex II where there is heavy metal toxicity image)


and has a bunch of broad benefits in animal studies - which likely is further proof of ray peats central idea of correcting cellular energy (mitochondria) to allow corrected structure to rebuild health in self-organising lifeforms

from generative energy
View attachment 47884

Very nice! Thank you!

 

[bloooeh]

Thanks @cs3000 . This means I need to juice more often!

 

[Elie]

I wonder how it metabolic effect compare with caffeine...

 

[xeliex]

High throughput screening of mitochondrial bioenergetics in human differentiated myotubes identifies novel enhancers of muscle performance in aged mice

Hesperetin (derivative of Hesperidin in orange juice) improves cellular respiration for more ATP which is a key to overall health. increased mitochondria ATP by 33%. and also improved spare capacity by 25%
most potent effect out of 7949 tested compounds

boosts mitochondrial gene expression
View attachment 47889


View attachment 47888


They followed up with an animal study in aged mice.
showing 4mg/kg human dose for 6 weeks completely reversed the muscle fiber size decrease usually seen in aging, & increased running performance







(it improves complex II where there is heavy metal toxicity image)


and has a bunch of broad benefits in animal studies - which likely is further proof of ray peats central idea of correcting cellular energy (mitochondria) to allow corrected structure to rebuild health in self-organising lifeforms

from generative energy
View attachment 47884

Excellent post.

Some of those quotes hit home for me and help define the pro-metabolic philosophy.

"When energy flows through matter, order accumulates...."

 

[cs3000]

Excellent post.

Some of those quotes hit home for me and help define the pro-metabolic philosophy.

"When energy flows through matter, order accumulates...."