351 replies to this topic

[ceridwen]

Actually not sure that it was MitoQ on its own was combined with diet and other supplements

[bosharpe]

Hi there,

 

I'm wondering whether to continue taking MitoQ or switch to NiaCel (A bit cheaper in price) by Thorne Research. I can only afford one but am wondering which one is better for a healthy male in his early 30s. Any recommendation from you guys here? I've not noticed much (if any) difference on Mitoq so far, but realise that doesn't mean it isn't working in some way.

 

 

[gregmacpherson]

Hi All, 

 

An interesting article over at Fightaging.org

 

https://www.fightagi...ted-antioxidant

 

 

[Kalliste]

Some people selling PQQ and CoQ10 are using your recent studies on Arterial relaxation with MitoQ to market their stuff. That's nearly illegal in some countries. Are you aware?

 

Hi All, 

 

An interesting article over at Fightaging.org

 

https://www.fightagi...ted-antioxidant

 

[gregmacpherson]

Some people selling PQQ and CoQ10 are using your recent studies on Arterial relaxation with MitoQ to market their stuff. That's nearly illegal in some countries. Are you aware?

 

Yes, I noticed that in some marketing on twitter yesterday.  I called them out on it.  Feel free to send me examples by direct message and I will do what I can.  

 

It does our industry no favours when we have unscrupulous companies doing this sort of thing - its another reason why consumers need to dig deeper and ask for studies.  Very frustrating!! 

 

Thanks for letting me know. 

 

Greg

[TRUGAN]

In a short clinical study we looked to get the best result in the shortest timeframe - hence the 20mg.   You will see the same benefit over time with the 10mg - it just wont happen quite as quickly.

 

Yes, 20mg dose coming later this year.

 

 

Will the 20mg still come this year?

[John250]

Would it be beneficial to use MitoQ, SkQ1 and Ubiquinol all together?

[gregmacpherson]

Would it be beneficial to use MitoQ, SkQ1 and Ubiquinol all together?

 

There is some benefit to combining MitoQ with low dose ubiquinol if you are on a Statin but otherwise no real benefit.  And no benefit in taking MitoQ with SKQ1. 

Will the 20mg still come this year?

 

Scheduled early next year now. We had to delay due to strong demand on our 5mg product after the Colorado study. 

 

Thanks. 

[Daniel Cooper]

As part of any of the published studies has anyone looked at blood parameters to see if anything changed with mitoq supplementation?  Specifically has anyone done a before/aftter CBC and did it have any effect on hemoglobin/hematocrit levels?

 

 

 

 

[John250]

As part of any of the published studies has anyone looked at blood parameters to see if anything changed with mitoq supplementation? Specifically has anyone done a before/aftter CBC and did it have any effect on hemoglobin/hematocrit levels?

No changes in Hemoglobin before and after use. Why? Is MitoQ supposed to increase hemo? I sure hope not as my levels are already too high.

[gregmacpherson]

No changes in Hemoglobin before and after use. Why? Is MitoQ supposed to increase hemo? I sure hope not as my levels are already too high.

 

This hasn’t really been looked at yet. In the Colorado trial they measured oxLDL levels, and in the Hep C trial they measured liver enzymes (AST, ALT, GGT & ALP) and saw significant changes but no measures of CBC or haem levels, etc in any clinicals to date.  Nothing has been picked up in our monitoring either. 

[Razor444]

@gregmacpherson

 

Is there a timeline for your 20mg product?

 

Thanks.

[OP2040]

Please take this with a grain of salt, but definitely add me to the people with some sort of adverse reaction.  I stopped taking it and the symptom has gone away, but I don't want anyone to overvalue this testimony.  I'm just one person, lots of variables.

 

 

[gregmacpherson]

@gregmacpherson

 

Is there a timeline for your 20mg product?

 

Thanks.

Hi, It will be Feb/March 2019. 

 

Thanks

[Kalliste]

 

The American Journal of Pathology

Available online 22 September 2018

In Press, Uncorrected Proof

What are Uncorrected Proof articles?

 

 

Regular article

Placental Adaptation to Early-Onset Hypoxic Pregnancy and Mitochondria-Targeted Antioxidant Therapy in Rat

Author links open overlay panelAnna M.Nuzzo^∗Emily J.Camm^†‡Amanda N.Sferruzzi-Perri^†‡Thomas J.Ashmore^†Hong-waYung^†‡TerezaCindrova-Davies^†‡Ana-MishelSpiroski^†Megan R.Sutherland^†AngelaLogan^§ShaniAustin-Williams^†Graham J.Burton^†‡AlessandroRolfo^∗TulliaTodros^∗Michael P.Murphy^§Dino A.Giussani^†‡

https://doi.org/10.1...ath.2018.07.027Get rights and content

Under a Creative Commons license

open access

   

The placenta responds to adverse environmental conditions by adapting its capacity for substrate transfer to maintain fetal growth and development. The effects of early-onset hypoxia on placental morphology and activation of the unfolded protein response (UPR) were determined using an established rat model in which fetal growth restriction is minimized. We further established whether maternal treatment with the mitochondria-targeted antioxidant (MitoQ) confers protection during hypoxic pregnancy. Wistar dams were exposed to normoxia (21% O₂) or hypoxia (13% to 14% O₂) from days 6 to 20 of pregnancy with and without MitoQ treatment (500 μmol/L in drinking water). On day 20, animals were euthanized and weighed, and the placentas from male fetuses were processed for stereology to assess morphology. Activation of the UPR in additional cohorts of frozen placentas was determined with Western blot analysis. Neither hypoxic pregnancy nor MitoQ treatment affected fetal growth. Hypoxia increased placental volume and the fetal capillary surface area within the labyrinthine transport zone and induced mitochondrial stress as well as the UPR, as evidenced by up-regulation of glucose-regulated protein 78 and activating transcription factor 4 protein abundance. Treatment with MitoQ in hypoxic pregnancy increased placental maternal blood space surface area and volume and prevented the activation of mitochondrial stress and the activating transcription factor 4 pathway. The data suggest that mitochondria-targeted antioxidants may be beneficial in complicated pregnancy via mechanisms protecting against placental stress and enhancing placental perfusion.

The placenta is the main interface between the mother and fetus, and it regulates intrauterine development by supplying nutrients and oxygen required for fetal growth. There is now clear evidence that the placenta can sense and respond to supply signals arising from the mother and demand signals from the fetus. The organ can adapt morphologically and functionally to these signals (eg, by altering placental and fetal blood flow, fetal nutrient supply, and secretion of signaling molecules, including hormones).¹ To date, most of the research effort on placental adaptation to adverse pregnancy has focused on maternal nutritional challenges or maternal glucocorticoid overexposure and their effects on placental structure and function.2, 3 Chronic fetal hypoxia is one of the most common consequences of complicated pregnancy, and it is associated with a variety of maternal, placental, and fetal conditions, including pregnancy at high altitude, gestational diabetes, preeclampsia, and placental insufficiency.4, 5 Despite this, the effect of hypoxia on the placenta remains relatively unexplored. Decrements in fetal growth have been observed in rodents exposed to hypoxia during mid to late pregnancy.6, 7, 8 Of interest, compared with late-onset hypoxic pregnancy that restricts fetal growth,8, 9, 10 hypoxia exposure earlier in pregnancy does not necessarily reduce fetal or birth weight.11, 12 This suggests that there are adaptations in maternofetal resource allocation during early-onset hypoxia that help to maintain fetal growth and appropriate development. In relation to the effects of hypoxic pregnancy on placental morphology, the available data from studies in rodents are variable. Increases, decreases, or no difference in placental weights; the surface area and volumes of the maternal and/or fetal compartments; barrier thickness; and transfer of glucose and amino acids and their transporters have been reported.7, 13, 14, 15, 16, 17 This variability is most likely attributable to differences in the duration, severity, and mode of induction, and whether exposure to hypoxia is accompanied by reductions in maternal food intake during the challenge.9, 12, 18, 19

Placental oxidative stress is implicated in the pathophysiology of several complications of human pregnancy, including preeclampsia,20, 21 high-altitude pregnancy,22, 23 and cases of intrauterine growth restriction.²⁴ Closely associated to oxidative stress is disruption of endoplasmic reticulum (ER) function. The ER is a site of integration of various stress responses, including hypoxia, mediated principally through the unfolded protein response (UPR), which aims to restore normal ER function.25, 26, 27 The UPR comprises three highly conserved parallel signaling branches: protein kinase RNA–like ER kinase (PERK), inositol-requiring enzyme, and activating transcription factor (ATF) 6α. Activation of these pathways has been reported in placentas from human intrauterine growth restriction infants with or without preeclampsia28, 29, 30 and, to a lesser extent, in healthy pregnancies at high altitude.²³

Recently, the potential use of antioxidant therapies to protect the placenta and fetus against oxidative stress in complications of pregnancy and birth has attracted much attention. We developed a rodent animal model of hypoxic pregnancy that minimizes effects on maternal food intake, thereby helping to isolate the effects of hypoxia on the placenta and offspring.11, 31 Using this model, we have shown that early-onset hypoxia from days 6 to 20 of gestation increases placental size and induces placental oxidative stress and that maternal treatment with the antioxidant vitamin C is protective.11, 31, 32 Although these data provide proof of principle that maternal antioxidant therapy may confer protection to the placenta and offspring in hypoxic pregnancy, in these studies, only high doses of vitamin C were effective. In addition, clinical trials have reported that maternal treatment with vitamin C in human pregnancy complicated by preeclampsia did not prove protective to the mother or baby.33, 34 Therefore, there is increasing interest in alternative maternal antioxidant therapies to protect the placenta and offspring in complicated pregnancy, with greater translational capacity to the human clinical situation.

Mitochondria-targeted antioxidants might offer a plausible alternative, because most endogenous reactive oxygen species are generated within mitochondria.³⁵ The most extensively studied compound of this class is the mitochondria-targeted ubiquinone derivative (MitoQ), which can pass easily through all biological membranes and accumulate several hundredfold within mitochondria, thereby enhancing protection from oxidative damage.36, 37 The use of MitoQ in vivo in several different rodent models of human pathology has shown that MitoQ can protect against oxidative damage in adult offspring.38, 39, 40, 41, 42, 43, 44, 45 Furthermore, long-term oral administration is safe, and unlike other conventional antioxidants, MitoQ does not demonstrate pro-oxidant activity at high doses in vivo.46, 47 An oral preparation of MitoQ has already safely undergone phase 1 and 2 human clinical trials. A study demonstrated that MitoQ can be safely administered for 1 year and is well tolerated by patients.⁴⁸ To date, only one study has investigated the antioxidant benefits of MitoQ in pregnancy, reporting that treatment of the pregnant rat with nanoparticle-bound MitoQ during hypoxic pregnancy could protect fetal brain development.⁴⁹ Therefore, the aim of this study was to investigate the effects of hypoxic pregnancy, with and without maternal treatment with MitoQ, on placental morphologic capacity for substrate transport and to determine whether UPR-sensing mechanisms were affected. https://www.scienced...002944018300191

 

Dont know how this should be interpreted.

 

SKELETAL MUSCLE ATROPHY AND DYSFUNCTION IN BREAST CANCER PATIENTS: ROLE FOR CHEMOTHERAPY-DERIVED OXIDANT STRESS

Blas A. Guigni

,

Damien M. Callahan

,

Timothy W. Tourville

,

Mark S. Miller

,

Brad Fiske

, … Show all Authors

12 Sep 2018https://doi.org/10.1...cell.00002.2018

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Abstract

How breast cancer and its treatments affect skeletal muscle is not well defined. To address this question, we assessed skeletal muscle structure and protein expression in 13 women diagnosed with breast cancer, who were receiving adjuvant chemotherapy following tumor resection, and 12 non-diseased controls. Breast cancer patients showed reduced single muscle fiber cross-sectional area (CSA) and fractional content of both sub-sarcolemmal and intermyofibrillar mitochondria. Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused reductions in myosin expression, mitochondrial loss and increased reactive oxygen species (ROS) production in C2C12 muscle myotube cell cultures, supporting a role for chemotherapeutics in the atrophic and mitochondrial phenotypes. Additionally, concurrent treatment of myotubes with mitochondrial-targeted antioxidant (MitoQ) prevented chemotherapy-induced myosin depletion, mitochondrial loss and ROS production. In patients, reduced mitochondrial content and size, and increased expression and oxidation of peroxiredoxin 3, a mitochondrial peroxidase, were associated with reduced muscle fiber CSA. Our results suggest that chemotherapeutics may adversely affect skeletal muscle in patients and that these effects may be driven through effects of these drugs on mitochondrial content and/or ROS production.

 

 

Molecular and Cellular Biology / Genetics

Abstract 1332: Autophagic clearance of protein aggregates is impaired in cancer cells with dysfunctional mitochondria

Thomas Biel and Ashutosh Rao

DOI: 10.1158/1538-7445.AM2018-1332 Published July 2018

 

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Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL

Abstract

Mitophagy and aggrephagy are selective types of autophagy that degrade damaged mitochondria and protein aggregates, respectively. Dysfunctional mitochondria are known to undergo mitophagy and cause protein aggregation. How a cell can simultaneously coordinate the removal of dysfunctional mitochondria and protein aggregates via autophagy is unknown. Here, two agents, Mitoquinone (MitoQ) and MitoApocynin (MitoApo), known to induce mitochondrial dysfunction and mitophagy in MDA-MB-231 cells were used to investigate the accumulation of protein aggregates and the mechanisms that contribute to selective autophagy. Using a protein aggregate dye and a poly-ubiquitinated antibody, carbonyl cyanide m-chlorophenyl hydrazine (CCCP), MitoQ, and MitoApo were identified as agents that caused an accumulation of poly-ubiquitinated protein aggregates in cancer cells by FACS analysis and confocal imaging. Microflow imaging of the cellular lysates confirmed a relative accumulation of large protein (>460 kDa) complexes. To establish the presence of aggrephagy, the aggregates were colocalized with LC3. Wild type and ATG7 knockout MEF cells were used to test whether protein aggregates accumulated in an autophagy-dependent manner. Our data currently demonstrates the kinetics of autophagic clearance of drug-induced protein aggregation and dysfunctional mitochondria.

http://cancerres.aac...ment/1332.short

 

 

Mitochondrial ROS-derived PTEN oxidation activates PI3K pathway for mTOR-induced myogenic autophagy

• Jin-Hwan Kim,
• Tae Gyu Choi,
• Seolhui Park,
• Hyeong Rok Yun,
• Ngoc Ngo Yen Nguyen,
• Yong Hwa Jo,
• Miran Jang,
• Jieun Kim,
• Joungmok Kim,
• Insug Kang,
• Joohun Ha,
• Michael P. Murphy,
• Dean G. Tang &
• Sung Soo Kim

Cell Death & Differentiation (2018) | Download Citation

Abstract Muscle differentiation is a crucial process controlling muscle development and homeostasis. Mitochondrial reactive oxygen species (mtROS) rapidly increase and function as critical cell signaling intermediates during the muscle differentiation. However, it has not yet been elucidated how they control myogenic signaling. Autophagy, a lysosome-mediated degradation pathway, is importantly recognized as intracellular remodeling mechanism of cellular organelles during muscle differentiation. Here, we demonstrated that the mtROS stimulated phosphatidylinositol 3 kinase/AKT/mammalian target of rapamycin (mTOR) cascade, and the activated mTORC1 subsequently induced autophagic signaling via phosphorylation of uncoordinated-51-like kinase 1 (ULK1) at serine 317 and upregulation of Atg proteins to prompt muscle differentiation. Treatment with MitoQ or rapamycin impaired both phosphorylation of ULK1 and expression of Atg proteins. Therefore, we propose a novel regulatory paradigm in which mtROS are required to initiate autophagic reconstruction of cellular organization through mTOR activation in muscle differentiatio

https://www.nature.c...1418-018-0165-9

[OP2040]

Please take this with a grain of salt, but definitely add me to the people with some sort of adverse reaction.  I stopped taking it and the symptom has gone away, but I don't want anyone to overvalue this testimony.  I'm just one person, lots of variables.

 

Hi Folks,

I'd like to humbly retract the statement above.  I am thinking my symptoms were mostly anxiety-related as they were still there for quite some time after I stopped taking MitoQ.

 

I am adding it back into my regime soon and will report back if I notice anything.

[TRUGAN]

Did they cancel plans for the 20 mg caps?

[timedilation]

Does anyone have any updates to report on mitoQ?  New user experiences?  Recent studies or trials?  Company discounts?

[Mind]

Due to the company sponsoring a lot of research, they raised their prices in the last couple of years. I used some last year. No negative side effects.

[LOOKINGFORTIME]

Share the love - Get 20% off MitoQ here

[Kalliste]

I used to like MitoQ but I have add that it does no good in situations where you feel anger or stress. It seems to make you far more capable of feeling anger and engaging in verbal arguments. I exploded at a lady on a bus who complained about me one time. 

 

 

[aribadabar]

I used to like MitoQ but I have add that it does no good in situations where you feel anger or stress. It seems to make you far more capable of feeling anger and engaging in verbal arguments. I exploded at a lady on a bus who complained about me one time. 

 

MitoQ does not have such a dramatic effect on mood. Look for the cause(s) elsewhere.