Scientific Studies Backed TetraSOD® Properties
Index of contents:
- Scientific Research on the TetraSOD® ingredient
- Relevant Scientific articles on SOD
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Completed Scientific Research about TetraSOD®
One of our primary goals has always been to support the benefits of TetraSOD® with world-class scientific research. For this reason, we have carried out our studies in the hands of researchers specialized in antioxidant properties and their health benefits.
TetraSOD® Studies Sumary
Improvement of Semen Quality in Idiopathic Infertile Men by Dietary Supplementation with TetraSOD®: A Pilot Clinical Trial
Juan Manuel Corral, Meritxell Jodar, Roger Matheu, Eva González, Enrique Castaño, Carlos Unamunzaga, Lalia Mantecón and Carlos Infante
A randomized double-blind pilot trial was carried out to assess the potential beneficial effects of TetraSOD<sup>®</sup> on the semen quality of idiopathic infertile men. Forty individuals were recruited and divided into two experimental groups, receiving either 25 mg/day or 250 mg/day of TetraSOD<sup>®</sup> for 90 days. Semen volume, sperm concentration, total sperm number, progressive motility, and normal forms were determined both at the commencement (t=0) and the end (t=3 months) of the trial. Statistically significant increases in all parameters but normal forms were induced by the highest dose of TetraSOD<sup>®</sup>, revealing the potential use of this ingredient in the clinical treatment of idiopathic infertility in men.
At t=0, no statistically significant differences were observed for any parameter between individuals targeted to either 25 mg/day or 250 mg/day group, indicating initial homogeneity of the two experimental groups. However, after the supplementation period with TetraSOD®, individuals consuming 250 mg/day exhibited significantly higher values than those receiving 25 mg/day in semen volume (3.09 ml vs 2.45 ml), sperm concentration (17.16 vs 11.63 x 106 sperm/ml), total sperm number (52.75 vs 28.17 x 106 sperm), and progressive motility (32.85 vs 26.10%). Moreover, the 90 days supplementation period with 250 mg/day provoked significant increases in relation to initial values at t=0 in semen volume (34.93%), sperm concentration (86.16%), total sperm number (137.6%), and progressive motility (25.86%). Additionally, supplementation with 250 mg/day allowed sperm concentration, total sperm number, and progressive motility to be over the respective LRL established by the WHO [21]. The group receiving 25 mg/day also exhibited significant increases (although lower compared with 250 mg/day) at t=3 months when compared to t=0 in semen volume (21.29%) and total sperm number (77.74%), but not in sperm concentration and progressive motility. Finally, no significant effect of TetraSOD® supplementation was observed in normal forms.
A 90-day dietary supplementation period with 250 mg/day of TetraSOD® increased semen volume, sperm concentration, total sperm number, and progressive motility in idiopathic infertile men. These results suggest that TetraSOD® may enhance male fertility.
TetraSOD® activates the antioxidant response pathway in human cells
Ramírez, P., Mantecón, L., Unamunzaga, C., Infante, C.
TetraSOD® activates the antioxidant response pathway in human cells: An in vitro approach
In this work, we examined the antioxidant bioactivity of TetraSOD® in muscle cells (Normal Human Skeletal Muscle Myoblasts, HSMMs) using an in vitro approach. We detected an induction of primary antioxidant enzyme activities (SOD, GPx, and CAT) which was further related to gene expression up-regulation of a selected set of genes involved in response against oxidative stress, including NRF2 and HMOX1.
It has been demonstrated that TetraSOD® exerts its antioxidant capacity via the master antioxidant switch NRF2/HMOX-1 pathway, selected genes being additionally regulated at transcriptional level.
TetraSOD® induces the cells endogenous production of SOD, CAT and GPX.
TetraSOD® activates the internal antioxidant system of the organism (indirect antioxidant) in contrast to other antioxidants that exert its antioxidant activity by directly scavenging free radicals (that is, there has been only demonstrated that they have antioxidant capacity in an in vitro test like DPPH or ORAC protocols).
Effects of Tetraselmis chuii Microalgae Supplementation on Anthropometric, Hormonal and Hematological Parameters in Healthy Young Men: A Double-Blind Study
Ángel García, Víctor Toro-Román, Jesús Siquier-Coll, Ignacio Bartolomé , Diego Muñoz
and Marcos Maynar-Mariño
The aim of this study was to evaluate the effects of Tetraselmis chuii (TC) microalgae
supplementation for sixty days on hematological, anthropometric and hormonal parameters in
healthy young men. Forty-six men divided into a placebo group, a group supplemented with 25 mg/day of TC and another group supplemented with 200 mg/day of TC participated in this doubleblind study. PG ingested 200 mg/day of lactose powder.
It has been verified that the walls of the genus Tetraselmis sp. contain acidic and sulfated polysaccharides. Several studies have shown that sulfation of the polysaccharides can enhance detection by TLR4 receptors of macrophages. Upon recognition of the polysaccharides, TLR4 would increase the production of bone marrow-stimulating cytokines and chemokines. This would increase the proliferation of the various immune cells, as well as their extravasation into the bloodstream.
The results obtained in the present work indicate that daily supplementation with 25 mg of TC (TetraSOD®) for sixty days could optimize hematological, hormonal, biochemical and anthropometric parameters in healthy male students.
No additional improvements were observed with the intake of 200 mg of TC. The data obtained provide a physiological approach that could determine the potential use of this microalgae in both the sports and health fields although most of the endocrine-metabolic mechanisms underlying the effects of TC remain unknown at present. Future research is needed to clarify the pathways of action of TC in the human body.
Clinical trial: Effects of TetraSOD® as food supplement in athletes
Rodrigo Bellido, F.J.
Effects of Tetraselmis chuii intake on oxidative stress in athletes. Extremadura University, Thesis, 2017.
Effects of TetraSOD® consumption in a total of 32 male football players with a minimum of 4-year previous experience in football training and subjected to regular training and competition during the span of the study
Supplementation with TetraSOD® provoked the main following effects (Rodrigo Bellido, 2017):
– Decrease in fat body mass (-8,8%)
– Improvement in performance during the effort stress test
HEART RATE ANAEROBIC THRESHOLD: Significant decrease in heart rate during activity (-3,6%)
HEART RATERECOVERY PHASE: Significant decrease in heart rate 3-minutes post activity (-4,2%)
HAEMOGLOBIN O2 CARRYING CAPACITY: Significant increase in haemoglobin levels (+4,9)
– Effect against oxidative stress
VITAMIN E LEVELS OXIDATIVE STRESS: Significant increase in vitamin E levels (+13,4%)
The consumption of TetraSOD® for 1 month obtained similar or higher results in Haemoglobin without and O2 consumption when compared to a high-altitude or high intensity training for at least three months.
TetraSOD®, a Unique Marine Microalgae Ingredient, Promotes an Antioxidant and Anti-Inflammatory Status in a Metabolic Syndrome-Induced Model in Rats
Katherine Gil-Cardoso, Josep M. Del Bas, Antoni Caimari, Carmen Lama, Sonia Torres, Lalia Mantecón and Carlos Infante
In the present study, the potential bioactive effects of three dietary dosages of TetraSOD® in enhancing antioxidant and antiinflammatory mechanisms to combat the metabolic disturbances that compose MetS were assessed in rats given a cafeteria (CAF) diet.
Chronic supplementation with 0.17, 1.7, and 17 mg kg1 day1 of TetraSOD® for 8 weeks ameliorated the abnormalities associated with MetS, including oxidative stress and inflammation, promoting endogenous antioxidant defence mechanisms in the liver (GPx and GSH), modulating oxidative stress and inflammatory markers in plasma (NOx, oxLDL and IL-10), and regulating genes involved in antioxidant, anti-inflammatory and immunomodulatory pathways in the liver, mesenteric white adipose tissue (MWAT), thymus, and spleen. Overall, TetraSOD® appears to be a potential therapeutic option for the management of MetS.
In the present study, our findings show subtle effects of TetraSOD® in metabolic parameters, tending to decrease plasma glucose after 17 mg kg1 bw of TetraSOD® administration and circulating levels of LDL/VLDL-C in the CAF + 0.17 group, compared to the group that received CAF diet and the vehicle. After 8 weeks of nutritional intervention with the CAF diet, clear metabolic alterations that characterize MetS were observed in our rats, including increased body weight and fat mass, hyperglycaemia, hyperinsulinaemia, insulin resistance, hypertriglyceridemia and chronic low-grade systemic inflammation.
Following a corrective therapeutic strategy with these doses of TetraSOD® would not be enough to improve advanced obesity and the metabolic alterations associated with MetS that was achieved after 8 weeks of CAF diet. However, testing these doses in early stages of obesity or following preventive strategies could be considered for future studies.
In summary, chronic supplementation with TetraSOD® ameliorates oxidative stress and inflammation disturbances associated with MetS. Its beneficial effects against this metabolic disorder include (i) the promotion of endogenous antioxidant defence mechanisms in the liver, (ii) the modulation of oxidative stress and inflammatory markers in plasma, and (iii) the positive modulation of genes involved in antioxidant, anti-inflammatory and immune pathways in the liver, MWAT, thymus and spleen. Altogether, TetraSOD® is postulated to be a promising therapeutic strategy for MetS management.
Phytoplankton Supplementation Lowers Muscle Damage and Sustains Performance across Repeated Exercise Bouts in Humans and Improves Antioxidant Capacity in a Mechanistic Animal
Matthew Sharp, Kazim Sahin, Matthew Stefan, Cemal Orhan, Raad Gheith,
Dallen Reber, Nurhan Sahin, Mehmet Tuzcu, Ryan Lowery, Shane Durkee
and Jacob Wilson
The purpose of this study was to investigate the impact of antioxidant-rich marine phytoplankton supplementation (Oceanix, OCX) on performance and muscle damage following a cross-training event in endurance-trained subjects. Additionally, an animal model was carried out to assess the effects of varying dosages of OCX, with exercise, on intramuscular antioxidant capacity. Methods: In the human trial, endurance-trained subjects were randomly divided into placebo (PLA) and OCX (25 mg) conditions for 14 days. The subjects were pre-tested on a one-mile uphill run, maximal isometric strength, countermovement jump (CMJ) and squat jump (SJ) power, and for muscle damage (creatine kinase (CK)).
When observing CMJ power, it was found that performance dropped equally in both groups. Intriguingly, however, SJ power declined more in the PLA compared to the OCX group (15% at 24 h Post). These differences were paralleled by greater increases in muscle damage in the PLA (+14% at 24 h Post) compared to the OCX. The ability of OCX to improve power in the SJ but not the CMJ may be due to the differences in mechanics between the two exercises. Specifically, athletes may be able to better use passive elastic components of connective tissue and tendons to overcome muscle damage in a CMJ relative to a SJ, which removes much of the ability to store and release elastic energy.
Intriguingly, the ability to use elastic energy increases as the stretch-shorten cycle time decreases. Correspondingly, the high intensity run in our study would demonstrate the shortest stretch shortening cycle in all the measures examined. Thus, the lack of differences in endurance between conditions despite greater muscle damage in the PLA may be explained by similar reasons to the CMJ. In support, we found that decrements in our isometric measure of strength from Pre to 48 h Post were greater in the PLA group (12%) than OCX.
We can conclude that the training program was e ective at inducing high levels of neuromuscular fatigue. However, marine phytoplankton supplementation (Oceanix, OCX) was able to improve recovery, sustain power, and prevent declines in strength across repeated endurance and cross-training bouts. Since recovery can be defined as, “returning what was lost due to exercise”, we demonstrated that OCX supplementation can improve recovery from intense competitions. Moreover, we present for the first time mechanistic data, which support the OCX role in improving intramuscular antioxidant capacity when combined with exercise.
TetraSOD® activates the antioxidant response pathway in human cells: An in vitro approach
In this scientific Research, we examined the antioxidant bioactivity of TetraSOD® in muscle cells (Normal Human Skeletal Muscle Myoblasts, HSMMs) using an in vitro approach. We detected an induction of primary antioxidant enzyme activities (SOD, GPx, and CAT) which was further related to gene expression up-regulation of a selected set of genes involved in response against oxidative stress, including NRF2 and HMOX1.
Conclusions:
It has been demonstrated that TetraSOD® exerts its antioxidant capacity via the master antioxidant switch NRF2/HMOX-1 pathway, selected genes being additionally regulated at transcriptional level.
TetraSOD® induces the cellular endogenous production of SOD, CAT and GPx. TetraSOD® activates the internal antioxidant system of the organism (indirect antioxidant) in contrast to other antioxidants that exert its antioxidant activity by directly scavenging free radicals (that is, there has been only demonstrated that they have antioxidant capacity in an in vitro test like DPPH or ORAC).
Authors: Pilar Ramírez, Sonia Torres, Carmen Lama, Lalia Mantecón, Carlos Unamunzaga and Carlos Infante*
Scientific Publication: pdf
Clinical trial: Effects of TetraSOD® as food supplement in athletes
This scientific study on TetraSOD® is framed within the doctoral thesis of Rodrigo Bellido F. J., current professor at the University of Extremadura (department: medical-surgical therapeutics).
In that thesis, Effects of Tetraselmis chuii intake on oxidative stress in athletes, the effects of TetraSOD® consumption were studied in a total of 32 male football players with a minimum of 4-year previous experience in football training and subjected to regular training and competition during the span of the study
Results and conclusions:
The consumption of TetraSOD® for 1 month obtained similar or higher results in Haemoglobin content and O2 consumption when compared to a high-altitude or high intensity training for at least three months.
Supplementation with TetraSOD® provoked the main following effects:
- Decrease in fat body mass (-8,8%)
- Improvement in performance during the effort stress test
- HEART RATE ANAEROBIC THRESHOLD: Significant decrease in heart rate during activity (-3,6%)
- HEART RATE RECOVERY PHASE: Significant decrease in heart rate 3-min post activity (-4,2%)
- HAEMOGLOBIN O2 CARRYING CAPACITY: Significant increase in haemoglobin levels (+4,9)
- Effect against oxidative stress
- VITAMIN E LEVELS: Significant increase in vitamin E levels (+13,4%)
Author: Rodrigo Bellido, Francisco Javier
Thesis directors: Maynar Mariño, Marcos Antonio
Scientific Publication: pdf
Scientific articles of interest about SOD
In the bibliography you can find additional information about other scientific studies on the health benefits of SOD and diets rich in SOD, as well as their applications to mitigate the effects of many health challenges:
- Superoxide dismutase, an updated review on its health benefits and industrial applications: https://doi.org/10.1080/10408398.2021.1913400
- Antioxidant Foods and Cardiometabolic Health: https://doi.org/10.3390/antiox11040746
- Effects of SOD Supplementation on Ergospirometric, Haematological and Biochemical Parameters: https://doi.org/10.3390/ijerph17186885
- Antioxidant-Rich (SOD) Marine Phytoplankton Supplementation Lowers Muscle Damage: https://doi.org/10.3390/nu12071990
- Therapeutic Treatment of Superoxide Dismutase Amyotrophic Lateral Sclerosis Model Mice: https://doi.org/10.3390/ijms23063403
- Effect of Physical Exercise Under Different Intensity and Antioxidative Supplementation for Superoxide Dismutase: https://doi.org/10.3389/fphys.2022.707176
- Health benefits of microalgae and their microbiomes: https://doi.org/10.1111/1751-7915.14082
Science white paper overview
TetraSOD®
evidence summary
A professional HTML summary of the studies included in the Science White Paper, structured by research area, authorship, model, intervention and principal scientific findings.
Evidence matrix
Detailed breakdown provided below.
| Research area | Authors | Model | Dosage / context | Abstract |
|---|---|---|---|---|
| Antioxidant response pathway | Pilar Ramírez, Sonia Torres, Carmen Lama, Lalia Mantecón, Carlos Unamunzaga and Carlos Infante | In vitro | 30, 150 and 1500 U/ml · 24 h | TetraSOD® increased the activity of SOD, GPx and CAT in human skeletal muscle myoblasts and positively regulated genes encoding antioxidant enzymes, including SOD1, SOD2, GPx1 and CAT. |
| Metabolic syndrome model | Katherine Gil-Cardoso, Josep M. Del Bas, Antoni Caimari, Carmen Lama, Sonia Torres, Lalia Mantecón and Carlos Infante | Rats | 0.17, 1.7 and 17 mg/kg/day · 8 weeks | In a rat model of metabolic syndrome, TetraSOD® modulated oxidative-stress and inflammatory markers in serum, liver, adipose tissue and immune tissues. |
| Exercise performance and muscle damage | Matthew Sharp, Kazim Sahin, Matthew Stefan, Cemal Orhan, Raad Gheith, Dallen Reber, Nurhan Sahin, Mehmet Tuzcu, Ryan Lowery, Shane Durkee and Jacob Wilson | Human + rats | Human: 25 mg/day · 14 days | TetraSOD® supported recovery, sustained power and reduced strength decrements across repeated endurance and cross-training bouts. |
| Exercise recovery and repair mechanisms | Matthew H. Sharp, Kazim Sahin, Matt W. Stefan, Raad H. Gheith, Dallen D. Reber, Charlie R. Ottinger, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Ryan P. Lowery, Shane Durkee and Jacob M. Wilson | Human + rats | Human: 25 mg/day · 5-week training programme | TetraSOD® improved long-term recovery, both perceptually and functionally, following a training programme designed to induce neuromuscular fatigue. |
| Exercise recovery and immune function | Matthew Sharp, Jacob Wilson, Matthew Stefan, Raad Gheith, Ryan Lowery, Charlie Ottinger, Dallen Reber, Cemal Orhan, Nurhan Sahin, Mehmet Tuzcu, Shane Durkee, Zainulabedin Saiyed and Kazim Sahin | Human + rats | Human: 25 mg/day · 14 days | TetraSOD® accelerated exercise recovery, supported strength outcomes and helped preserve salivary IgA during and after intensive training. |
| Aerobic performance in soccer players | Víctor Toro, Jesús Siquier-Coll, Ignacio Bartolomé, María C. Robles-Gil, Javier Rodrigo and Marcos Maynar-Mariño | Human | 25 mg/day · 30 days | TetraSOD® showed ergogenic effects in amateur soccer players, including improvements in aerobic-power indicators and selected hematological variables. |
| Body composition and blood markers | Ángel García, Víctor Toro-Román, Jesús Siquier-Coll, Ignacio Bartolomé, Diego Muñoz and Marcos Maynar-Mariño | Human | 25 or 200 mg/day · 60 days | TetraSOD® induced changes in anthropometric and hematological parameters, including increased muscle percentage and reduced fat percentage. |
| NRF2 signalling and VO₂peak | Stuart P. Cocksedge, Carlos Infante, Sonia Torres, Carmen Lama, Lalia Mantecón, Manuel Manchado, Jarred P. Acton, Nehal S. Alsharif, Tom Clifford, Alex J. Wadley, Richard A. Ferguson, Nicolette C. Bishop, Neil R. W. Martin and Stephen J. Bailey | Human | 25 mg/day · 14 days | TetraSOD® improved aerobic capacity, increasing peak oxygen uptake, and activated skeletal-muscle genes involved in antioxidant response. |
| Semen quality pilot study | Juan Manuel Corral, Meritxell Jodar, Roger Matheu, Eva González, Enrique Castaño, Carlos Unamunzaga, Lalia Mantecón and Carlos Infante | Human | 25 or 250 mg/day · 3 months | TetraSOD® improved semen-quality indicators after three months of supplementation in idiopathic infertile men. |
| Neuroprotection and barrier permeability | Melis Cokdinleyen, Alberto Valdés, Huseyin Kara, Elena Ibáñez and Alejandro Cifuentes | In vitro | T. chuii extracts and carotenoid transport assays | T. chuii compounds protected neuronal cells from neurotoxic damage and selected carotenoids showed capacity to cross barrier models relevant to intestinal transport and blood–brain barrier permeability. |
| Gut microbiota and prebiotic function | Magdalena Majchrzak, Stacey Paterson, Jaime Gutiérrez-Corral, Diego Gómez-Garre, Alberto Ortega-Hernández, Miguel Ángel de la Fuente, Blanca Hernández-Ledesma and Pilar Gómez-Cortés | In vitro microbiota model | Gastrointestinal digests · fermentation model | TetraSOD® behaved as a prebiotically functional ingredient, modulating microbial growth patterns and supporting short-chain fatty-acid production. |
| Telomere protection and cellular ageing | Alfonso Blázquez-Moreno, Lorena Orgaz, Estefanía Rodríguez-Moreno, Adrián Asensio, Marta Marsal, Lalia Mantecón, Carlos Infante, Enrique Samper and Emmanouil Flemetakis | In vitro | Human neonatal fibroblasts · standard and oxidative-stress conditions | TetraSOD® showed telomere-protective effects in human neonatal fibroblasts, particularly under oxidative-stress conditions. |
| Male fertility and reproductive outcomes | Marina Leiva, Judit Castillo, Di Wang, Marta Guimerà, Raquel Ferreti, Alicia Diez, Laura Noguera, Lalia Mantecón, Dolors Manau, Rafael Oliva, Carlos Infante, Carlos Unamunzaga, Eva González, Juan Manuel Corral and Meritxell Jodar | Human | 250 mg/day · 3 months | In men with oxidative stress-related idiopathic infertility, TetraSOD® supplementation improved sperm-quality parameters, hormonal markers, sperm DNA integrity and reproductive outcomes. |
| Cellular health review | Stuart P. Cocksedge, Lalia Mantecón, Enrique Castaño, Carlos Infante and Stephen J. Bailey | Review | Integrated evidence review | This review positions SOD-rich T. chuii as a cellular-health promoter through antioxidant-system activation, anti-inflammatory modulation, DNA-damage protection, immune-function support and cellular-signalling regulation. |
Detailed evidence cards
Compact technical cards with authorship, publication data and interpretation.
1TetraSOD® Activates the Antioxidant Response Pathway in Human Cells: An In Vitro Approach›
In vitro
30, 150 and 1500 U/ml · 24 h
NRF2 and HMOX-1 gene expression were upregulated, supporting the involvement of the NRF2 antioxidant and anti-inflammatory pathway.
Mechanistic cellular evidence for direct and indirect antioxidant activity at the ingredient level.
2TetraSOD®, a Unique Marine Microalgae Ingredient, Promotes an Antioxidant and Anti-Inflammatory Status in a Metabolic Syndrome-Induced Model in Rats›
Rats
0.17, 1.7 and 17 mg/kg/day · 8 weeks
Reported effects included lower oxLDL, higher IL-10, increased hepatic glutathione, activation of GPx activity and regulation of antioxidant and inflammatory genes.
Preclinical data indicating antioxidant and anti-inflammatory modulation; not direct human clinical efficacy evidence.
3Phytoplankton Supplementation Lowers Muscle Damage and Sustains Performance across Repeated Exercise Bouts in Humans and Improves Antioxidant Capacity in a Mechanistic Animal›
Human + rats
Human: 25 mg/day · 14 days
Mechanistic data showed increased intramuscular SOD, CAT and GPx activity, reduced serum MDA, and lower markers of muscle damage such as myoglobin and creatine kinase.
Evidence suggests a role in exercise recovery through antioxidant-capacity support and reduced muscle-damage markers.
4Marine Phytoplankton Improves Exercise Recovery in Humans and Activates Repair Mechanisms in Rats›
Human + rats
Human: 25 mg/day · 5-week training programme
Reported mechanisms included increased positive myogenic factors such as NCAM and MyoD, lower myostatin, and reduced MuRF-1 and MAFbx expression.
Data point to recovery support through satellite-cell progression and protein-turnover modulation.
5Marine Phytoplankton Improves Recovery and Sustains Immune Function in Humans and Lowers Proinflammatory Immunoregulatory Cytokines in a Rat Model›
Human + rats
Human: 25 mg/day · 14 days
Mechanistic outcomes were associated with lower intramuscular and serum TNF-α and IL-1β, plus reduced intramuscular MDA.
Findings connect functional recovery with modulation of oxidative-stress and pro-inflammatory cytokine responses.
6Effects of Tetraselmis chuii Microalgae Supplementation on Ergospirometric, Haematological and Biochemical Parameters in Amateur Soccer Players›
Human
25 mg/day · 30 days
Reported changes included improvements in heart-rate variables, absolute and relative VO₂max, oxygen pulse, hemoglobin and mean corpuscular hemoglobin.
Results are consistent with improved aerobic-efficiency indicators under the study conditions.
7Effects of Tetraselmis chuii Microalgae Supplementation on Anthropometric, Hormonal and Hematological Parameters in Healthy Young Men›
Human
25 or 200 mg/day · 60 days
The presentation highlights increases in immune-cell counts, including basophils, monocytes and lymphocytes, alongside changes in hematocrit and mean corpuscular hemoglobin.
The data suggest systemic marker modulation in healthy young men, with dose-specific interpretation requiring context from the full article.
8Tetraselmis chuii Supplementation Increases Skeletal Muscle NRF2 and Antioxidant Enzyme Gene Expression, and Peak Oxygen Uptake in Healthy Adults›
Human
25 mg/day · 14 days
Key genes highlighted include NRF2, SIRT1, GPX7, SOD2, CAT, GSR, PRDX3, PRDX6 and GSTM3, alongside genes linked to host defense, mitochondrial function, differentiation and cellular signalling.
This study links human skeletal-muscle gene expression with a functional oxygen-uptake outcome.
9Improvement of Semen Quality in Idiopathic Infertile Men by Dietary Supplementation with TetraSOD®: A Pilot Clinical Trial›
Human
25 or 250 mg/day · 3 months
The study reported significant increases in semen volume, total sperm number, sperm concentration and progressive motile spermatozoa in ejaculate.
Pilot-level clinical evidence; study design limitations should be clearly acknowledged in external communication.
10Neuroprotective Potential of Tetraselmis chuii Compounds: Insights into Blood–Brain Barrier Permeability and Intestinal Transport›
In vitro
T. chuii extracts and carotenoid transport assays
Protection was reported against L-glutamate- and hydrogen peroxide-induced damage; several carotenoids showed measurable barrier permeability.
Mechanistic evidence for neuroprotective potential of T. chuii-derived compounds, not direct clinical evidence.
11Modulatory Effects of Tetraselmis chuii Gastrointestinal Digests on Human Colonic Microbiota›
In vitro microbiota model
Gastrointestinal digests · fermentation model
The presentation highlights lower growth of bacterial pathogens, higher growth of Akkermansia and Butyricimonas, increased butyrate and improved microbial diversity and resilience.
Evidence supports a microbiota-modulating profile under experimental model conditions.
12An Antiageing Telomere-Protective Effect of Superoxide Dismutase-Rich Tetraselmis chui in Human Cells›
In vitro
Human neonatal fibroblasts · standard and oxidative-stress conditions
Reported outcomes included increased 20th-percentile telomere length, increased median telomere length under oxidative stress, fewer critically short telomeres and a reduced telomere-shortening rate.
Cellular ageing-related evidence; should be framed as in vitro data rather than consumer-level anti-ageing claims.
13Superoxide Dismutase-Rich Tetraselmis chuii Supplementation Improves Semen Quality in Idiopathic Infertile Males: A Double-Blind Randomized Placebo-Controlled Trial›
Human
250 mg/day · 3 months
The presentation highlights normalization of LH and FSH, doubled sperm concentration, higher progressive motility, reduced double-strand sperm DNA breaks, increased live birth rates and a higher rate of spontaneous pregnancies.
The strongest fertility-related study in the set, but claims should still remain within the limits of the study population and design.
14The Potential of Superoxide Dismutase-Rich Tetraselmis chuii as a Promoter of Cellular Health›
Review
Integrated evidence review
NRF2 and SIRT1 are presented as central factors that may mediate cellular homeostasis-related effects.
Useful as a synthesis layer, but it should be separated from primary intervention studies in scientific communication.
Scientific Research on the TetraSOD® Ingredient
Legal Notice:
The information presented below is intended for scientific and technical purposes only, directed exclusively to professionals in the food and research industries, and refers solely to the ingredient, not the finished product. It does not constitute advertising and is not intended for the end consumer.
The studies summarized here are provided for informational purposes and do not constitute authorized health claims under Regulation (EC) No. 1924/2006.
TetraSOD® is a naturally derived ingredient included in certain dietary supplements and foods, and it is not intended for the diagnosis, treatment, cure, or prevention of any disease.
Clarification Note:
The data presented summarize results observed by the authors under the experimental conditions of the studies. These findings should not be interpreted as evidence of clinical efficacy or as health claims applicable to the general consumption of dietary supplements.
Summary of Scientific Studies on the Ingredient TetraSOD®
One of the main objectives of our research has been to scientifically evaluate the biological characteristics of the TetraSOD® ingredient through studies conducted in collaboration with leading universities and research centers. These studies aim to better understand the antioxidant and metabolic mechanisms associated with the ingredient, without implying any health claims or clinical effects on human health.
- Evaluation of Seminal Parameters in a Pilot Clinical Trial
Title
Improvement of Semen Quality in Idiopathic Infertile Men by Dietary Supplementation with TetraSOD® : A Pilot Clinical Trial.
Authors
Juan Manuel Corral, Meritxell Jodar, Roger Matheu, Eva González, Enrique Castaño, Carlos Unamunzaga, Lalia Mantecón, and Carlos Infante
Publication data
Biomedical Journal of Scientific & Technical Research 2023, 50(4):41971-41975; doi:10.26717/BJSTR.2023.50.007999Objetivos
Objectives
This randomized single-blind pilot trial aimed to assess the potential beneficial effects of TetraSOD® (derived from the marine microalga Tetraselmis chuii) on the semen quality of idiopathic infertile men. The study investigated whether TetraSOD® supplementation could improve seminal parameters in men diagnosed with idiopathic infertility, a condition representing approximately 30% of male infertility cases where no obvious cause explains the altered sperm characteristics.[1]
Results
Forty individuals (ages 18-45) diagnosed as infertile were randomly divided into two groups receiving either 25 mg/day or 250 mg/day of TetraSOD® for 90 days (covering a complete spermatogenesis cycle). Semen parameters including ejaculate volume, sperm concentration, total sperm number, progressive motility, and normal forms were evaluated at baseline (t=0) and after treatment (t=3 months).
At baseline, no statistically significant differences were observed between the two groups for any parameter, indicating initial homogeneity. However, after the 90-day supplementation period, individuals consuming 250 mg/day exhibited significantly higher values than those receiving 25 mg/day in multiple parameters: semen volume (3.09 mL vs 2.45 mL), sperm concentration (17.16 vs 11.63 × 10⁶ sperm/mL), total sperm number (52.75 vs 28.17 × 10⁶ sperm), and progressive motility (32.85% vs 26.10%).
The 250 mg/day dose provoked significant increases from baseline values in semen volume (34.93% increase), sperm concentration (86.16% increase), total sperm number (137.6% increase), and progressive motility (25.86% increase). Importantly, supplementation with 250 mg/day allowed sperm concentration, total sperm number, and progressive motility to exceed the respective Lower Reference Limits (LRL) established by the World Health Organization.
The group receiving 25 mg/day also exhibited significant but lower increases at 3 months compared to baseline in semen volume (21.29%) and total sperm number (77.74%), but not in sperm concentration and progressive motility. No significant effect of TetraSOD® supplementation was observed in normal sperm morphology for either dose.
Conclusions
This pilot study provides initial evidence that TetraSOD® supplementation, particularly at 250 mg/day for 90 days, may significantly improve semen quality in men with idiopathic infertility. The dose-dependent effects observed strongly suggest a genuine therapeutic effect rather than placebo. The improvements observed in semen volume, sperm concentration, total sperm number, and progressive motility indicate that TetraSOD® may enhance male fertility through its demonstrated capacity to induce cellular antioxidant mechanisms. The ingredient’s high superoxide dismutase (SOD) activity and balanced nutritional composition (including vitamins, minerals, essential fatty acids, pigments, amino acids, and polyphenols) likely contribute to reducing oxidative stress, which is known to negatively impact spermatogenesis, epididymal maturation, and sperm capacitation. These results suggest TetraSOD® may be a valuable complementary therapy in the clinical treatment of male idiopathic infertility. However, the absence of a placebo control group and the limited sample size recommend validation through a larger double-blind randomized placebo-controlled trial with intermediate dosages to better define the clinically relevant dose range.
3.Activation of the NRF2/HMOX1 Antioxidant Pathway in Human Cells (In Vitro).
Title
TetraSOD® Activates the Antioxidant Response Pathway in Human Cells: An In Vitro Approach
Authors
Pilar Ramírez, Sonia Torres, Carmen Lama, Lalia Mantecón, Carlos Unamunzaga, and Carlos Infante
Publication data
African Journal of Biotechnology 2020, 19(6):367-373; doi:10.5897/AJB2020.17163
Objectives
This study aimed to examine the antioxidant bioactivity of TetraSOD® in human skeletal muscle cells in vitro. The research investigated whether TetraSOD® supplementation could induce primary antioxidant enzyme activities (SOD, glutathione peroxidase, and catalase) and activate genes involved in the cellular response against oxidative stress, including those encoding the transcription factor NRF2 and downstream antioxidant response elements.
Results
Normal Human Skeletal Muscle Myoblasts (HSMMs) were incubated with TetraSOD® extract at three different SOD concentrations: 30, 150, and 1500 U/ml for 24 hours, with phosphate buffer serving as control.
- Antioxidant Enzyme Activities:
The lowest dose (30 U/ml) did not produce statistically significant changes in enzyme activity compared to the control. At both the 150 and 1500 U/ml doses, significant increases were detected in all three antioxidant enzymes:
- SOD activity: increased by approximately 34% at 150 U/ml and 37% at 1500 U/ml
- GPx activity: showed the highest variation, ranging between 72-83% increase at 150 and 1500 U/ml, respectively
- CAT activity: increased by approximately 37-42% at 150 and 1500 U/ml, respectively
- Gene Expression Results:
TetraSOD® treatment significantly upregulated multiple antioxidant response genes in a dose-dependent manner:
- SOD1: showed the highest induction at 30 U/ml (4.49-fold), remaining elevated at 150 U/ml (4.32-fold), and declining to 3.80-fold at 1500 U/ml
- SOD2: was upregulated across all doses, ranging from 2.02-fold to 2.14-fold increase
- SOD3: showed no significant changes between treatments and control
- GPx1: increased significantly at 150 U/ml (2.14-fold) and 1500 U/ml (2.23-fold), with a non-significant 1.85-fold increase at 30 U/ml
- GPx4: exhibited no significant changes across any treatment
- CAT: was significantly increased at 150 U/ml (1.47-fold) and 1500 U/ml (1.55-fold)
- NRF2: showed no significant changes at 30 U/ml, but significant increases at 150 U/ml (2.05-fold) and 1500 U/ml (2.04-fold)
- HMOX1: was significantly upregulated at 30 U/ml (1.69-fold) and 150 U/ml (1.54-fold), but not at the highest dose
Conclusions
TetraSOD® activates the NRF2/HMOX1 antioxidant response pathway in human skeletal muscle cells, resulting in coordinated upregulation of primary antioxidant enzymes and their encoding genes. The ingredient functions as both a “direct” antioxidant through its high endogenous SOD, GPx, and CAT activities, and as an “indirect” antioxidant by inducing cytoprotective proteins through NRF2 pathway activation. The dose-dependent effects observed suggest optimal efficacy in the 150-1500 U/ml range, with coordinated responses between enzyme activity levels and mRNA expression of key antioxidant genes (SOD1, SOD2, GPx1, and CAT). These findings represent an important contribution to understanding the molecular basis of TetraSOD® ‘s cytoprotective effects and suggest that the ingredient may provide cellular protection against oxidative stress through coordinated activation of endogenous antioxidant defense systems. Further in vivo research is necessary to fully elucidate the complete mechanisms underlying the protective and preventive effects of TetraSOD® consumption.
- Hematological and Hormonal Parameters in Healthy Young Men
Title
Effects of Tetraselmis chuii Microalgae Supplementation on Anthropometric, Hormonal and Hematological Parameters in Healthy Young Men: A Double-Blind Study
Authors
Ángel García, Víctor Toro-Román, Jesús Siquier-Coll, Ignacio Bartolomé, Diego Muñoz, and Marcos Maynar-Mariño
Publication data
International Journal of Environmental Research and Public Health 2022, 19, 6060; doi: 10.3390/ijerph19106060
Objectives
This study aimed to evaluate the effects of TetraSOD® supplementation for sixty days on hematological, anthropometric, and hormonal parameters in healthy young men. Specifically, the research investigated whether varying doses of TetraSOD® (25 mg/day versus 200 mg/day) would induce favorable changes in body composition, hormonal profiles, and blood parameters in a double-blind, placebo-controlled design.
Results
Forty-six healthy male participants were divided into three groups: placebo group (PLA; n=16), group supplemented with 25 mg/day of TetraSOD® (SG 25; n=15), and group supplemented with 200 mg/day of TetraSOD® (SG 200; n=15). Assessments were conducted at baseline, month 1, month 2, and after 30 days of supplementation cessation (desadaptation).
- Anthropometric Parameters:
Significant increases in muscle percentage were observed in both SG 25 and SG 200 at month 2 compared to baseline (p < 0.05). Correspondingly, significant decreases in fat percentage occurred in both supplemented groups (p < 0.05), while the PLA group showed no significant changes. In SG 25, significant decreases in sum of six skinfolds were observed at month 2 compared to baseline (p < 0.05).
- Hormonal Parameters:
Significant increases in erythropoietin (EPO) were observed in both supplemented groups at month 2 compared to baseline (p < 0.05). Insulin-like growth factor 1 (IGF-1) increased significantly in SG 25 and SG 200 at month 2 and remained elevated after desadaptation (p < 0.01). Free testosterone increased in SG 25 at both month 2 and desadaptation compared to baseline (p < 0.05). Cortisol levels remained stable in supplemented groups but increased significantly in PLA during desadaptation (p < 0.05). Growth hormone (GH) decreased significantly in both PLA and SG 200 during desadaptation compared to baseline (p < 0.05).
- Hematological Parameters:
In SG 25, significant increases in leukocytes and lymphocytes were observed (p < 0.05). In SG 200, significant increases in lymphocyte concentrations occurred at month 2 compared to baseline (p < 0.05). Platelet levels decreased significantly in both PLA and SG 25 (p < 0.05). Hematocrit and mean corpuscular hemoglobin (MCH) decreased significantly in both supplemented groups during desadaptation compared to previous evaluations (p < 0.05).
Conclusions
Daily supplementation with 25 mg of TetraSOD® for sixty days effectively optimized hematological, hormonal, biochemical, and anthropometric parameters in healthy male students. No additional improvements were observed with the 200 mg dose, suggesting that 25 mg/day represents the most effective dose. TetraSOD® supplementation increased anabolic hormones (free testosterone and IGF-1), enhanced erythropoiesis (through increased EPO), and improved immune function markers (increased leukocytes and lymphocytes). The composition of TetraSOD® , particularly its high superoxide dismutase (SOD) activity, bioactive peptides, polyunsaturated fatty acids (PUFAs), and polysaccharides, appears to mediate these beneficial effects. The improvements in body composition were attributed to combined effects of increased testosterone and IGF-1, which promote muscle protein synthesis and reduce fat accumulation. These findings provide preliminary evidence that TetraSOD® supplementation may be beneficial in both sports and health fields, although further research with larger sample sizes, longer duration, and both male and female participants is needed to fully elucidate the mechanisms of action.
- Preclinical Model of Metabolic Syndrome in Rats
Title
TetraSOD® , a Unique Marine Microalgae Ingredient, Promotes an Antioxidant and Anti-Inflammatory Status in a Metabolic Syndrome-Induced Model in Rats
Authors
Katherine Gil-Cardoso, Josep M. Del Bas, Antoni Caimari, Carmen Lama, Sonia Torres, Lalia Mantecón, and Carlos Infante
Publication data
Nutrients 2022, 14, 4028; doi:10.3390/nu14194028
Objectives
This study aimed to assess the potential bioactive effects of three dietary dosages of TetraSOD® in enhancing antioxidant and anti-inflammatory mechanisms to combat the metabolic disturbances that compose metabolic syndrome (MetS) in rats given a cafeteria (CAF) diet. The research investigated whether TetraSOD® supplementation could ameliorate oxidative stress and inflammation associated with diet-induced obesity and MetS.
Results
Fifty male Sprague-Dawley rats were used in the study. After 8 weeks on a CAF diet to induce MetS, forty rats were randomly divided into four groups receiving vehicle or TetraSOD® at 0.17, 1.7, or 17 mg/kg body weight per day for an additional 8 weeks, while ten control rats continued on standard diet.
- Oxidative Stress and Inflammatory Markers in Plasma:
TetraSOD® supplementation at 17 mg/kg/day significantly decreased oxidized LDL (oxLDL) circulating levels by 11.89% compared to CAF diet controls (p = 0.044). Plasma nitric oxide (NOx) levels were enhanced by 56.67% in the 0.17 mg/kg group compared to control. The highest dose (17 mg/kg) significantly increased anti-inflammatory interleukin-10 (IL-10) levels by 113% compared to CAF control.
- Hepatic Antioxidant Enzymes and Markers:
The CAF diet decreased hepatic glutathione (GSH) levels, but supplementation with 17 mg/kg TetraSOD® increased GSH by 15.21% compared to CAF control (p = 0.018). Glutathione peroxidase (GPx) activity in the liver increased by 12.71% in the 0.17 mg/kg group (p = 0.043).
- Hepatic Gene Expression:
TetraSOD® supplementation significantly upregulated genes involved in GSH metabolism, including glutathione peroxidase 1 (GPX1), glutathione reductase (GR), and glutathione synthetase (GSH-S) in all supplemented groups. Both SOD1 and SOD2 genes showed significant upregulation with TetraSOD® supplementation. Pro-inflammatory pathway genes including TGFβ1 and NFκB1, which were upregulated by the CAF diet, showed significant downregulation with TetraSOD® supplementation.
- Gene Expression in Mesenteric White Adipose Tissue (MWAT):
Adiponectin (ACDC) gene expression increased significantly in the 0.17 and 1.7 mg/kg groups. Pro-inflammatory cytokine genes IL-1β, TNFα, and IFNG were significantly downregulated in all TetraSOD® -supplemented groups compared to CAF control. Anti-inflammatory IL-10 gene expression significantly increased in the 17 mg/kg group.
- Immune Tissue Gene Expression:
In the thymus, TetraSOD® supplementation at all doses significantly downregulated pro-inflammatory genes (TNFα, IL-1β, IFNG, NFκB1) that were upregulated by the CAF diet, while significantly upregulating anti-inflammatory IL-10. Similar patterns were observed in the spleen, with additional upregulation of FOXP3 (a regulatory T cell marker) in the 17 mg/kg group.
Conclusions
Chronic supplementation with TetraSOD® for 8 weeks at doses of 0.17, 1.7, and 17 mg/kg/day ameliorated abnormalities associated with MetS, including oxidative stress and inflammation, in CAF diet-induced obese rats. The ingredient promoted endogenous antioxidant defense mechanisms in the liver by increasing GPx activity and GSH levels, and by upregulating genes encoding key antioxidant enzymes (SOD1, SOD2, GPX1, GR, GSH-S) and GSH synthesis enzymes (GCLm). TetraSOD® modulated oxidative stress and inflammatory markers in plasma by reducing oxLDL, increasing NOx and IL-10 levels, demonstrating both antioxidant and anti-inflammatory properties. The ingredient regulated genes involved in antioxidant, anti-inflammatory, and immunomodulatory pathways across multiple tissues including liver, mesenteric white adipose tissue, thymus, and spleen. Specifically, TetraSOD® downregulated pro-inflammatory cytokines (IL-1β, TNFα, IFNG) and inflammatory pathway genes (NFκB1,) while upregulating anti-inflammatory markers (IL-10, adiponectin, FOXP3). These findings indicate that TetraSOD® operates through multiple mechanisms including enhancement of cellular antioxidant enzyme systems, modulation of the Nrf2/HMOX-1 and NFκB signaling pathways, and regulation of pro- and anti-inflammatory cytokine production. Overall, TetraSOD® appears to be a potential therapeutic option for the management of metabolic syndrome by addressing both oxidative stress and chronic inflammation that characterize this condition.
- Evaluation of Phytoplankton on Exercise-Related Parameters and Biological Response Markers in Humans and an Animal Model
Title
Phytoplankton Supplementation Lowers Muscle Damage and Sustains Performance across Repeated Exercise Bouts in Humans and Improves Antioxidant Capacity in a Mechanistic Animal
Authors
Matthew Sharp, Kazim Sahin, Matthew Stefan, Cemal Orhan, Raad Gheith, Dallen Reber, Nurhan Sahin, Mehmet Tuzcu, Ryan Lowery, Shane Durkee, and Jacob Wilson
Publication data
Nutrients 2020, 12, 1990; doi:10.3390/nu12071990
Objectives
The purpose of this study was to investigate the impact of TetraSOD® on athletic performance and muscle damage following cross-training events in endurance-trained subjects. Additionally, an animal model was conducted to assess the effects of varying dosages of TetraSOD® on intramuscular antioxidant capacity in exercising rats.
Results
- Human Trial:
In the human study involving 18 endurance-trained subjects who underwent a 14-day supplementation protocol (25 mg/day), significant differences were observed between the TetraSOD® and placebo (PLA) groups. Squat jump (SJ) power decreased 15% less in the TetraSOD® group compared to PLA at 24 hours post-exercise. Isometric strength decrements from baseline to 48 hours post-exercise were 12% greater in the PLA group than in the TetraSOD® group. Serum creatine kinase (CK) levels, a marker of muscle damage, were 14% higher in the PLA group compared to TetraSOD® group at 24 hours post-exercise.
- Animal Trial:
In the animal model, Wistar rats performed treadmill exercise five days per week for six weeks while receiving varying doses of TetraSOD® supplementation. Intramuscular antioxidant capacity increased in a dose-dependent manner across groups (Exercise + High Dose TetraSOD® > Exercise + Low Dose TetraSOD® > Exercise Only > Control). Specifically, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all significantly elevated in supplemented groups compared to exercise alone. Markers of muscle damage (CK and myoglobin) were significantly lower in supplemented groups compared to exercise-only groups. Oxidative stress, measured by malonaldehyde (MDA) levels, was reduced in a dose-dependent manner with TetraSOD® supplementation.
Conclusions
TetraSOD® supplementation effectively sustains athletic performance and reduces muscle damage across repeated exercise bouts involving endurance, strength, and power activities. The mechanistic data suggest that TetraSOD® operates by elevating intramuscular antioxidant capacity in skeletal muscle, particularly through increased activity of key antioxidant enzymes such as SOD, CAT, and GSH-Px. These findings indicate that TetraSOD® may be beneficial for athletes competing under high-stress scenarios with limited recovery time between events, potentially improving recovery during demanding training or competition periods.
- Evaluation of Marine Phytoplankton on Exercise-Related Parameters in Humans and Animal Models
Title
Marine Phytoplankton Improves Exercise Recovery in Humans and Activates Repair Mechanisms in Rats
Authors
Matthew H. Sharp, Kazim Sahin, Matt W. Stefan, Raad H. Gheith, Dallen D. Reber, Charlie R. Ottinger, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Ryan P. Lowery, Shane Durkee, and Jacob M. Wilson
Publication data
International Journal of Sports Medicine 2021, 42:1070-1082; doi:10.1055/a-1320-1061
Objectives
The study investigated the effects of TetraSOD® supplementation on: 1) perceived recovery and ground reaction forces in humans following a non-functional overreaching resistance-training program, and 2) myogenic molecular markers associated with muscle cell recovery in a rat model. The research aimed to determine whether TetraSOD® could enhance recovery during periods of intensified training designed to induce overreaching.
Results
- Human Trial:
Twenty-two subjects completed a 5-week resistance training program with intentional overreaching during weeks 2 and 5, receiving either 25 mg/day of TetraSOD® or placebo (PLA). TetraSOD® supplementation produced significant improvements in perceived recovery status at post-testing compared to PLA (TetraSOD® : +1.1 ± 0.4 a.u., +16%; PLA: –0.5 ± 0.9 a.u., –6%). While both groups demonstrated decreased peak and mean rate of force development (RFD) following the overreaching weeks, the PLA group remained significantly decreased at post-testing (67.7% of baseline), whereas the TetraSOD® group returned to baseline levels (98.0% of baseline). The relative change in peak and mean RFD at post-testing was significantly different between groups.
- Animal Trial:
Wistar rats performed treadmill exercise five days per week for six weeks while receiving either PLA, low-dose TetraSOD® (2.55 mg/Kg/day), or high-dose TetraSOD® (5.1 mg/Kg/day). TetraSOD® supplementation in exercising rats significantly increased positive myogenic factors (MyoD and NCAM) that regulate satellite cell proliferation and decreased negative regulators (myostatin, MuRF-1, and MAFbx) in a dose-dependent manner. Serum creatine kinase (CK) levels, a marker of muscle damage, were significantly elevated in the exercise-only group compared to control, but both supplemented groups showed significantly lower CK levels than the exercise-only group, with the high-dose group demonstrating the greatest reduction.
Conclusions
TetraSOD® supplementation (25 mg/day) effectively improves long-term recovery during intensified resistance training that induces non-functional overreaching. The ingredient sustained explosive strength performance and improved perceived recovery status in humans following fatiguing training periods. Mechanistically, these benefits appear to be driven through enhanced cell cycle regulation of satellite cells and improved protein turnover, as evidenced by increased expression of positive myogenic regulators (MyoD and NCAM) and decreased expression of negative regulators (myostatin and its downstream targets MuRF-1 and MAFbx). These findings indicate that TetraSOD® may be beneficial for athletes undergoing high-stress training scenarios with limited recovery time between sessions. No adverse effects or negative changes in blood safety parameters were observed, confirming the safety of the ingredient for human consumption.
- Evaluation of Marine Phytoplankton on Exercise-Associated Parameters and Immune Markers in Humans and a Rat Model
Title
Marine Phytoplankton Improves Recovery and Sustains Immune Function in Humans and Lowers Proinflammatory Immunoregulatory Cytokines in a Rat Model
Authors
Matthew Sharp, Jacob Wilson, Matthew Stefan, Raad Gheith, Ryan Lowery, Charlie Ottinger, Dallen Reber, Cemal Orhan, Nurhan Sahin, Mehmet Tuzcu, Shane Durkee, Zainulabedin Saiyed, and Kazim Sahin
Publication data
Physical Activity and Nutrition 2021, 25(1):042-055; doi:10.20463/pan.2021.0007
Objectives
This study investigated the effects of TetraSOD® on: 1) maximal isometric strength and immune function in healthy humans following a one-week high-intensity resistance-training program, and 2) the proinflammatory cytokine response to exercise in a rat model. The research aimed to determine whether TetraSOD® could prevent decrements in functional exercise recovery and immune function while modulating oxidative stress and proinflammatory cytokine responses.
Results
- Human Trial:
Twenty-two healthy participants completed a study protocol consisting of a 14-day supplementation phase (25 mg/day TetraSOD® or placebo (PLA)) followed by five consecutive days of intense resistance training. TetraSOD® supplementation prevented significant declines in the isometric peak rate of force development (RFD) compared to placebo. Specifically, the PLA group demonstrated significantly decreased peak RFD at 48 hours post-training (67.7% of baseline), while the TetraSOD® group returned to baseline levels (98.0% of baseline). The absolute mean difference in peak RFD from baseline to 48 hours post-testing was significantly different between groups (PLA: -2202 ± 981 vs. TetraSOD® : -949 ± 716 N·s⁻¹). Additionally, salivary immunoglobulin A (sIgA) concentration was significantly lower following the resistance training protocol in the PLA group (202.8 µg/mL decrease) but not in the TetraSOD® group (148.8 µg/mL decrease, not significant).
- Animal Trial:
Twenty-eight Wistar rats were divided into four groups: control, exercise only, exercise + low-dose TetraSOD® (2.55 mg/kg/day), and exercise + high-dose TetraSOD® (5.1 mg/kg/day), performing treadmill exercise five days per week for six weeks. TetraSOD® supplementation in exercising rats decreased intramuscular levels and serum concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in a dose-dependent manner compared to exercise-only and control groups. Both supplemented groups showed significantly lower TNF-α levels than the exercise-only group, with the high-dose group demonstrating the greatest reduction. Intramuscular malondialdehyde (MDA) concentration, a marker of oxidative stress, was significantly reduced in supplemented groups compared to both control and exercise-only groups in a dose-dependent manner.
Conclusions
TetraSOD® supplementation (25 mg/day) effectively prevented decrements in indices of functional exercise recovery and immune function following short-term intensive resistance training in humans. The ingredient sustained explosive strength performance and preserved salivary immunoglobulin A levels, which serve as markers of immune function. Mechanistically, these benefits appear to be mediated by modulating the oxidative stress and proinflammatory cytokine response to exercise, as evidenced by reduced intramuscular oxidative stress (lower MDA levels) and decreased production of proinflammatory cytokines (TNF-α and IL-1β) in the rat model. These findings indicate that TetraSOD® supplementation may be beneficial for individuals undergoing intensive training periods, potentially reducing the risk of immune suppression and infection that can occur during high-stress training scenarios. The study concluded that mitigating proinflammatory cytokines could improve neuromuscular function and the functional capacity of musculature during recovery periods.
- Investigation of Tetraselmis chuii on Antioxidant Enzyme Gene Expression and Oxygen Consumption-Related Variables in Healthy Adults
Title
Tetraselmis chuii Supplementation Increases Skeletal Muscle Nuclear Factor Erythroid 2-Related Factor 2 and Antioxidant Enzyme Gene Expression, and Peak Oxygen Uptake in Healthy Adults: A Randomised Crossover Trial
Authors
Stuart P. Cocksedge, Carlos Infante, Sonia Torres, Carmen Lama, Lalia Mantecón, Manuel Manchado, Jarred P. Acton, Nehal S. Alsharif, Tom Clifford, Alex J. Wadley, Richard A. Ferguson, Nicolette C. Bishop, Neil R. W. Martin, and Stephen J. Bailey
Publication data
Antioxidants 2025, 14, 435; doi:10.3390/antiox14040435
Objectives
This study aimed to assess the effect of supplementation with 25 mg/day superoxide dismutase (SOD)-rich Tetraselmis chuii (T. chuii) for 14 days on high-intensity endurance exercise capacity, peak oxygen uptake (VO₂peak), and numerous genes related to Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) signalling and its downstream effects on antioxidant and inflammatory responses in human skeletal muscle tissue. The research sought to determine whether T. chuii supplementation would increase endurance exercise capacity, VO₂peak, and genes related to NRF2 signalling and antioxidant and anti-inflammatory responses in skeletal muscle tissue of healthy adults.
Results
The study consisted of two separate experiments with independent participant groups. In the gene expression study, 13 healthy male participants completed a randomized, double-blind, crossover design with 14 days of supplementation (T. chuii or placebo) separated by a 2-week washout period. In the exercise performance study, 13 healthy male participants followed the same supplementation protocol with exercise testing before and after each supplementation period.
- Gene Expression Results:
- chuii supplementation significantly increased skeletal muscle gene expression of 15 genes with medium to large effect sizes (p < 0.05). Key upregulated genes included: NRF2 (1.62-fold ± 2.16), glutathione peroxidase 7 (GPX7; 1.26-fold ± 1.37), glutathione-disulfide reductase (GSR; 1.22-fold ± 1.41), glutathione S-transferase Mu 3 (GSTM3; 1.34-fold ± 1.49), peroxiredoxin 6 (PRDX6; 1.36-fold ± 1.57), extracellular signal-regulated kinase 3 (ERK3; 1.92-fold ± 2.42), p38 alpha (p38α; 1.33-fold ± 1.58), and sirtuin 1 (SIRT1; 1.73-fold ± 2.25). Additionally, phospholipase A2 group XIIA (PLA2G12A; 1.63-fold ± 2.05), phospholipase A2 group XVI (PLA2G16; 1.36-fold ± 1.42), JUN proto-oncogene (JUN; 1.53-fold ± 1.89), cullin 3 (CUL3; 1.77-fold ± 2.49), and others showed significant increases. An additional 12 genes showed upregulation with medium effect sizes without reaching statistical significance (p = 0.05-0.10), including catalase (CAT; 1.40-fold ± 1.87) and superoxide dismutase 2 (SOD2; 1.40-fold ± 1.86).
Correlation analyses revealed strong to moderate negative relationships between baseline gene expression and the magnitude of change after T. chuii supplementation in 53 genes (p < 0.05), indicating that individuals with lower baseline expression exhibited greater increases following supplementation.
- Exercise Performance Results:
Compared to pre-supplementation values, VO₂ peak was significantly increased following T. chuii supplementation (p = 0.013) but not placebo (p = 0.66). End-exercise VO₂ was significantly greater after T. chuii supplementation (4.06 ± 0.38 L/min) compared to pre-supplementation (3.92 ± 0.28 L/min; p = 0.013; effect size = 0.8). No significant changes were observed in end-exercise rating of perceived exertion (RPE), blood lactate concentration, or time to exhaustion (Tlim), although Tlim showed a non-significant 17% increase compared to baseline.
Conclusions
Short-term T. chuii supplementation (25 mg/day for 14 days) effectively increased skeletal muscle gene expression of the master antioxidant transcription factor NRF2 and key enzymatic antioxidants (GPX7, GSR, GSTM3, and PRDX6), signalling kinases (ERK3 and p38α), and post-translational regulators (SIRT1) that protect against cellular stress. This represents important evidence that T. chuii can activate NRF2 signalling in human skeletal muscle, unlike many other purported nutritional NRF2 activators that have shown no effect in human trials. The supplement also significantly increased VO₂ peak, a critical determinant of exercise capacity and performance that is inversely associated with ill health and mortality. The molecular mechanisms underlying the improved VO₂ peak may involve enhanced mitochondrial biogenesis through NRF2, SIRT1, and MAPK signalling pathways, though direct assessment of mitochondrial content was not performed. The inverse relationship between baseline gene expression and supplementation-induced changes suggests that individuals with depleted antioxidant status may benefit most from T. chuii supplementation. These findings indicate that SOD-rich T. chuii represents a promising natural supplement with potential to improve skeletal muscle antioxidant responses and systemic oxidative metabolism in healthy adults. The supplement was well tolerated with no reported side effects.
- Evaluation of Tetraselmis chuii Supplementation on Ergoespirometric, Hematological, and Biochemical Parameters in Amateur Soccer Players
Title
Effects of Tetraselmis chuii Microalgae Supplementation on Ergospirometric, Haematological and Biochemical Parameters in Amateur Soccer Players
Authors
Víctor Toro, Jesús Siquier-Coll, Ignacio Bartolomé, María C. Robles-Gil, Javier Rodrigo, and Marcos Maynar-Mariño
Publication data
International Journal of Environmental Research and Public Health 2020, 17, 6885; doi:10.3390/ijerph17186885
Objectives
This study aimed to analyze the effects of TetraSOD® supplementation during thirty days on ergospirometric, haematological, and biochemical parameters in amateur soccer players. The research sought to evaluate whether TetraSOD® supplementation (25 mg/day) would improve athletic performance and aerobic capacity while assessing potential positive or negative effects on blood parameters in a double-blind, placebo-controlled design.
Results
In the study involving thirty-two amateur soccer players randomized into control (PLA; n=16) and TetraSOD® supplemented groups (TetraSOD® ; n=16) who ingested 25 mg of TetraSOD® or lactose placebo (PLA) daily for thirty days, significant improvements were observed in the supplemented group.
- Ergospirometric Parameters:
Heart rate decreased significantly after TetraSOD® supplementation compared to PLA at both aerobic threshold (VT1) and anaerobic threshold (VT2), with reductions at VT1. Maximum heart rate (HRmax) decreased significantly in TetraSOD® post-supplementation (198.43 ± 6.28 to 194.42 ± 4.52 bpm; p < 0.05). Oxygen pulse increased from 19.04 ± 2.53 to 22.08 ± 2.25 mL/beat (p < 0.05). Absolute VO2max increased from 3.72 ± 0.35 to 3.99 ± 0.25 L/min (p < 0.05), and relative VO2max increased from 53.56 ± 3.26 to 56.74 ± 3.43 mL/min/kg (p < 0.05). Heart rate recovery at 3 minutes post-test also decreased significantly in TetraSOD® compared to PLA (p < 0.05).
- Haematological Parameters:
Haemoglobin levels increased significantly in TetraSOD® from 15.12 ± 0.87 to 16.58 ± 0.74 g/dL (p < 0.01), and mean corpuscular haemoglobin (MCH) increased from 28.03 ± 1.57 to 30.82 ± 1.21 Pg (p < 0.05). Conversely, haematocrit decreased from 48.03 ± 2.15 to 46.68 ± 2.05% (p < 0.05), and mean platelet volume (MPV) decreased from 9.02 ± 1.13 to 8.04 ± 1.05 fL (p < 0.05).[1]
- Biochemical Parameters:
Glucose levels increased from 83.01 ± 10.31 to 91.01 ± 5.40 mg/dL (p < 0.01), uric acid increased from 5.76 ± 0.76 to 6.04 ± 0.77 mg/dL (p < 0.05), and creatinine increased from 0.96 ± 0.10 to 1.07 ± 0.12 mg/dL (p < 0.05). All biochemical parameters remained within normal clinical ranges. No changes were observed in the control group.
Conclusions
TetraSOD® supplementation (25 mg/day) for thirty days effectively improved ergospirometric parameters in amateur soccer players, demonstrated by decreased resting heart rate and increased maximum oxygen uptake. The improvements in oxygen pulse and oxygen consumption suggest enhanced oxygen transport and metabolic efficiency during aerobic exercise. The increases in haemoglobin and MCH suggest that TetraSOD® may enhance erythropoiesis through its mineral content, particularly iron and calcium, which support red blood cell function and oxygen delivery. The protective effects on biochemical markers indicate that TetraSOD® supplementation produces no adverse effects on liver or kidney function, with all parameters remaining within normal ranges. Although preliminary, these results suggest that TetraSOD® supplementation could serve as an ergogenic aid for amateur athletes, though further research with larger sample sizes, different populations, and various TetraSOD® concentrations is needed to establish dose-response relationships and elucidate the precise mechanisms of action.
Scientific articles of interest about SOD
Numerous studies in the scientific literature investigate the role of the enzyme superoxide dismutase (SOD) in antioxidant defense mechanisms and its function within cellular redox balance. These studies provide insights into its biological relevance and potential implications in various physiological contexts.
- Superoxide dismutase, an updated review on its health benefits and industrial applications:https://doi.org/10.1080/10408398.2021.1913400
- Antioxidant Foods and Cardiometabolic Health:https://doi.org/10.3390/antiox11040746
- Effects of SOD Supplementation on Ergospirometric, Haematological and Biochemical Parameters:https://doi.org/10.3390/ijerph17186885
- Antioxidant-Rich (SOD) Marine Phytoplankton Supplementation Lowers Muscle Damage:https://doi.org/10.3390/nu12071990
- Therapeutic Treatment of Superoxide Dismutase Amyotrophic Lateral Sclerosis Model Mice:https://doi.org/10.3390/ijms23063403
- Effect of Physical Exercise Under Different Intensity and Antioxidative Supplementation for Superoxide Dismutase:https://doi.org/10.3389/fphys.2022.707176
- Health benefits of microalgae and their microbiomes:https://doi.org/10.1111/1751-7915.14082