Microalga extract shows promise for fatigue through mitochondrial function

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Astaxanthin-rich Haematococcus pluvialis extract may reduce exercise fatigue by activating AMPK, enhancing antioxidant defences and supporting mitochondrial biogenesis. (Getty Images/iStockphoto)

Freshwater microalga extract shows anti-fatigue effects by boosting antioxidant defences and mitochondrial function in new animal research published in Frontiers in Nutrition. 

Researchers in South Korea reported positive results after testing Haematococcus pluvialis extract (YHC-T-2414) in muscle cells and mice to see whether it reduced oxidative stress, improved mitochondrial function, increased exercise performance, and reduced fatigue through specific pathways.

“YHC-T-2414 may have potential as a natural functional ingredient for alleviating exercise-induced fatigue,” wrote the authors, some of whom were employed by Yuhan Care Co., the supplier behind the ingredient used in the study.

Combating fatigue through antioxidant and mitochondrial pathways

Fatigue is characterized by physical and mental exhaustion caused by prolonged exercise and daily stress. One cause of fatigue is oxidative stress, which happens when too many reactive oxygen species (ROS) build up and damage muscles and mitochondria, reducing energy production.

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AMP-activated protein kinase (AMPK) helps cells manage energy and protect themselves from ROS, activating the NRF2-KEAP1 pathway, which increases antioxidant protection, and the SIRT1-PGC-1α pathway, which improves mitochondrial function and energy production.

H. pluvialis contains astaxanthin, a strong antioxidant, and previous studies suggest that it can reduce fatigue. However, the researchers in the current study noted that most studies have focused on pure astaxanthin rather than the whole H. pluvialis extract.

H. pluvialis extract contains other natural compounds such as carotenoids like lutein, β-carotene, zeaxanthin, canthaxanthin and violaxanthin, as well as fatty acids, proteins, amino acids, carbohydrates, and polysaccharides, which the researchers suggest may work together to provide stronger and broader antioxidant and anti-fatigue effects than astaxanthin alone.

Astaxanthin-rich extract may reduce exercise fatigue

The researchers prepared YHC-T-2414 from dried H. pluvialis and measured its astaxanthin content (the final extract contained about 100 mg of astaxanthin per gram).

They tested the extract in muscle cells to make sure it was not toxic, then exposed the cells to H₂O₂ to create oxidative stress and tested whether YHC-T-2414 could protect them, measuring cell damage, antioxidant activity, ROS levels, and proteins involved in the AMPK pathways using different laboratory tests.

They also tested the extract in 40 male mice divided into four groups: untreated control, creatine, and two YHC-T-2414 doses (12.5 and 25 mg/kg/day). The mice received the treatments daily for 21 days.

The researchers then performed a weight-loaded swimming test to measure how long the mice could swim before exhaustion. Finally, they collected blood and muscle samples to measure LDH, CK, lactate, MDA, inflammatory markers, and other fatigue-related indicators.

In cell tests, YHC-T-2414 protected muscle cells from oxidative damage. It did not harm normal C2C12 muscle cells and protected them from H₂O₂-induced damage. It also reduced LDH and CK, which are markers of muscle damage. The extract showed antioxidant activity and reduced ROS levels by approximately 55% at the highest dose tested.

YHC-T-2414 also activated AMPK in stressed muscle cells, helped the cells increase their antioxidant defenses, reduce harmful ROS, and protect them from oxidative damage. YHC-T-2414 was also found to activate the SIRT1-PGC-1α pathway, which potentially helped the cells make and maintain healthy mitochondria.

“These findings suggest that the potential anti-fatigue effects of YHC-T-2414 may be associated with modulation of the AMPK-NRF2-KEAP1 pathway involved in antioxidant defense and the AMPK-SIRT1-PGC-1α pathway associated with mitochondrial biogenesis,” the researchers wrote.

However, they noted that as they only tested these pathways in muscle cells and further research is needed to confirm the same effects in animal muscle tissue.

Results from the mouse experiments found that after 21 days of treatment, those given YHC-T-2414 swam for much longer before becoming exhausted, with the 25 mg/kg dose producing the greatest improvement. The supplement also lowered blood lactate, CK, and LDH, which the authors noted suggested less muscle stress and fatigue. It also reduced MDA, a marker of oxidative stress, and the higher dose also reduced the inflammatory markers TNF-α and IL-6.

“Overall, YHC-T-2414 may alleviate fatigue by enhancing antioxidant responses and supporting mitochondrial biogenesis-related signaling pathways,” the researchers concluded.

They added that the results provide “mechanistic evidence for the anti-fatigue activity of the whole H. pluvialis extract, rather than that of a purified single component.”

Further studies are needed to confirm whether these signaling pathways are similarly regulated in skeletal muscle following YHC-T-2414 administration, they concluded.


Source: Frontiers in Nutrition; doi: 10.3389/fnut.2026.1906109; “Haematococcus pluvialis extract YHC-T-2414 mitigates exercise- induced fatigue by promoting antioxidant defense and mitochondrial biogenesis.” Authors: Jeong, J. et al.