33 new things we've learned about Mitochondria
| Ⓒ By Jonathan Roseland |
I'm not a doctor, medical professional, or trained therapist. I'm a researcher and pragmatic biohacking practitioner exercising free speech to share evidence as I find it. I make no claims. Please practice skepticism and rational critical thinking. You should consult a professional about any serious decisions that you might make about your health. Affiliate links in this article support Limitless Mindset - spend over $150 and you'll be eligible to join the Limitless Mindset Secret Society.
This article will summarize the recent science that’s been done on Mitochondria along with some salient insights and knowledge coming out of the Biohacker community online.
Impressively in the past year, there have been over 230 scientific papers published specifically on Mitochondria, including 11 clinical trials. Mitochondria is a hot area of research, this article will not summarize every single one but some of the more interesting findings of the current year.
If you want to go even deeper into the state of the art of Mitochondrial science and research I'll recommend the new book, Mitochondria and the Future of Medicine: The Key to Understanding Disease, Chronic Illness, Aging, and Life Itself by Lee Know. I also enjoyed Head Strong by Dave Asprey which is full of really actionable lifehacks for optimizing your mitochondria for living the bulletproof life.
Caloric Restriction in Healthy Individuals
A North American study evaluated the effect of caloric restriction over 12 months in 51 people.
It provided yet more evidence that fasting is a really smart idea; there are three types of fasting that I recommend habituating, someone might wonder if decreasing intake of food markedly robs you of crucial fuel that your Mitochondria need...
Some gym bros might be thinking, when I'm hitting the gym frequently I need to eat a lot more. If I starve myself with fasting won't that hurt my gains and performance?
Not really. This study found that fasting will either not affect or improve mitochondrial function in your muscles.
It concluded
In healthy nonobese humans, [caloric restriction] has no effect on muscle mitochondrial function; however, having a "more coupled" (versus "less coupled") phenotype enables [caloric restriction]-induced improvements in muscle mitochondrial function.
Resveratrol
An American placebo-controlled study of 30 older glucose-intolerant adults found after 6 weeks of dosing that...
Mitochondrial number, but not size, was increased.
But...
Resveratrol treatment of older adults with impaired glucose regulation may have beneficial effects on vascular function, but not glucose metabolism or insulin sensitivity. Changes in gene expression suggest effects similar to those observed with caloric restriction
This kind of confirms what I've said elsewhere about Resveratrol; that it does pretty much the same thing as fasting, but its benefit to otherwise healthy people is limited.
A Chinese study implied that resveratrol may be a healthy treatment for depression.
The antidepressant action of resveratrol was accomplished through the interruption of mitochondrial oxidative stress and the prevention of cell apoptosis in the hippocampus. These findings support the potential for resveratrol as a possible pharmacological agent for depression treatment in the future.
Elamipretide
A double-blind placebo-controlled human trial of a new drug, Elamipretide was conducted at Duke University Medical Center. The heart is 25% by weight Mitochondria thus Mitochondrial dysfunction has a lot to do with heart failure and this novel Mitochondria targeting peptide is something to watch.
This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose-effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy.
Mitochondrial Nootropics
There have been at least 3 papers on Mitochondrial Nootropics, performance-enhancing supplements, and drugs, like Memantine and Piracetam.
From a paper on Alzheimer's out of Charles University in Prague.
The direct effect of cognitives and nootropics used in the treatment of [Alzheimer's] on mitochondrial respiration is relatively small. The safest drugs in terms of disturbing mitochondrial function appear to be piracetam and rivastigmine. The MAO-A inhibition by cognitives and nootropics may also participate in mitochondrial neuroprotection.
According to an Indian paper on Piracetam and neurodegenerative diseases:
Piracetam treatment offered significant protection against [Lipopolysaccharide] induced oxidative and inflammatory parameters... [Lipopolysaccharide] administration caused augmented level of reactive oxygen species and depleted mitochondrial membrane potential which were attenuated with piracetam treatment.
A paper out of the University of Erlangen in Germany took a top-down approach by investigating several older antidementia drugs, like Piracetam and Ginkgo Biloba extract, these...
improve experimentally many aspects of mitochondrial dysfunction including mitochondrial dynamics and also improve cognition and impaired neuronal plasticity, the functionally most relevant consequences of mitochondrial dysfunction.
It concluded
Drugs interfering with [mitochondrial permeability transition pore] function will improve not only mitochondrial impairment in aging and [Alzheimer's disease] but also will have beneficial effects on impaired neuronal plasticity, the pathomechanism which correlates best with functional deficits (cognition, behavior) in aging and [Alzheimer's disease].
Mitochondrial Eye Drops?
The eyes may be the windows to the soul because they contain a high density of Mitochondria, thus eye problems and poor vision are consistently symptomatic of Mitochondrial dysfunction.
A 70-patient trial was conducted in Russia which evaluated a product Visomitin which has a restorative effect on vision with the following On-label clinical indications:
- Dry eye syndrome
- Initial stage of age-related cataract
- Cataracts and glaucoma, including their most bad choices
- Uveitis
- Enteral inflammations
- Neurodegeneration
If your eyes, one of the most complex and impressive organs, require quite a lot of Mitochondria it makes sense to stick mitochondrial-targeted antioxidants right in your eyes.
Mito-TEMPO
At least 40 scientific papers discussed a new drug, the Mitochondria-targeting antioxidant Mito-TEMPO. Without getting too hyperbolic Mitochondria-targeting antioxidants are a really exciting new class of drugs that deliver exactly what your mitochondria need to the actual interior of your mitochondria. This is important because (to use a very crude metaphor) your mitochondria poop - they produce waste in the form of reactive oxygen species - and that poop needs to be cleaned up! Imagine that you had a toilet that you pooped in but you never flushed it and your plumbing didn't work, it would eventually get backed up and be quite a problem! The same thing happens to our mitochondria! Thus targetted antioxidants have amazing potential for treating a host of diseases and conditions ultimately caused by mitochondria dysfunction.
According to a study out of Shanghai
Mito-TEMPO ameliorates renal fibrosis by alleviating mitochondrial dysfunction and endoplasmic reticulum stress... which sheds new light on prevention of renal fibrosis in chronic kidney disease.
Its other potential clinical uses are wide-ranging from cancer therapy and neurodegenerative disease pathogenesis to depression and improving post-thaw sperm quality - as in cold sperm? So I'll keep some Mito-TEMPO handy for the next time I'm trying to impregnate an Eskimo in her igloo!
An American study out of Louisiana State University Health Sciences Center in Shreveport found it prevents brain damage and inflammation associated with stroke and Nicotine usage.
Mito-Tempo did not have an effect in control rats, but prevented the chronic nicotine-induced augmentation of ischemic brain damage and post-ischemic inflammation.
This is relevant to those, like obese, elderly smokers, who are at risk for stroke. If they refuse to put down their cigarettes they should at least pick up some Mito-Tempo or even CoQ10 supplements! Speaking of CoQ10...
Coenzyme Q10
CoQ10 is the Nootropic perhaps most well known as the Mitochondrial supplement. Impressively in the past year alone, there have been over 140 papers published specifically about it.
A joint team of Swedish and Norwegian researchers published a very encouraging follow-up to a double-blind, placebo-controlled study conducted 12 years ago.
- The original study gave selenium and CoQ10 to 443 older Swedes for four years.
- None of the elderly Swedes had died of cardiovascular conditions, this is especially impressive considering the large quantity of study subjects.
The study found that more than a whole decade later taking the CoQ10 and Selenium was still helping the Swedes.
Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity...
The protective action was not confined to the intervention period, but persisted during the follow-up period.
This suggests that taking some CoQ10 now will do you good in the years and decades to come, especially if you combine it with selenium.
Dr. Lee Know is a huge fan of CoQ10, he explains its mechanism
Coenzyme Q10 (CoQ10) is an antioxidant, a membrane stabilizer, and a vital component in the mitochondrial ETC. It also regulates gene expression and apoptosis; is an essential cofactor of uncoupling proteins and permeability transition pores; and has anti-inflammatory, redox modulatory, and neuroprotective effects. (2351-2354)
Now there's a catch to CoQ10, it's not very bioavailable, in fact, some forms of it are pretty useless.
Unfortunately, absorption of this rather large fat-soluble molecule is challenging, which is a main factor limiting its therapeutic use. Research has shown that oil-based formulations ( typically softgels ) are much better absorbed, and water-dispersible liposomal or pre - emulsified formulations are even better. Ubiquinol ( reduced CoQ10 ) seems to offer much better absorption than ubiquinone ( oxidized CoQ10 ), and water-soluble ( solubilized ) ubiquinol is even better absorbed. (2364-2368)
Three vendors that meet these high standards for absorption are...
A preliminary Italian study confirmed that water-soluble CoQ10 helps women suffering from fibromyalgia...
Our results show that, compared to a control group, administration of CoQ10 significantly improved most pain-related outcomes by 24-37%, including fatigue... and sleep disturbance... These results confirm the considerable role played by CoQ10 in reducing pain, fatigue, and sleep disturbance in subjects affected by fibromyalgia.
As the research advances more and more scientists and biohackers agree that supplementing a bit of CoQ10 is a smart idea for almost everybody over age 35.
Methylphenidate a Mitochondrial Hack for ADHD?
A Chinese paper noted that the ADHD drug and ostensible smart drug Methylphenidate benefits our Mitochondria:
Our results show that low doses of [Methylphenidate] play protective roles in maintaining mitochondrial homeostasis in response to hypoxia-induced oxidative stress. Our findings may provide novel insight into the mechanisms of MPH in the treatment of ADHD, and shed light on the disease mechanisms of ADHD.
Pyrroloquinoline Quinone
Good luck trying to properly pronounce Pyrroloquinoline Quinone! We'll just call it PQQ. This supplement is worth your attention because it actually stimulates the genesis of new Mitochondria.
Traditionally, it was believed that generating new mitochondria (mitochondrial biogenesis) could only occur as a result of strenuous exercise or extreme calorie restriction, which is why research on PQQ (pyrroloquinoline quinone) is so exciting. Early in 2010, researchers found PQQ not only protected mitochondria from oxidative damage, it also stimulated the growth of new mitochondria! (2274-2277)
A Japanese study concluded
Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.
If you don't have the budget for fancy PQQ supplements, quality dark chocolate is a good supplemental source.
B Vitamins
Are an underrated class of crucial Mitochondrial supporting vitamins. Dr. Know explains...
Of all the nutrients defined as true vitamins, the ones that have the greatest direct impact on cellular metabolism and energy production are collectively known as the B vitamins. This group is made up of numerous distinct nutrients, and each is either a cofactor in an important metabolic process or a precursor of an important energy-related molecule. (2666-2669)
Interestingly, in 2017 a joint team of American, Canadian, Swedish, and Chinese researchers conducted a human cross-over study on air pollution's insidiously toxic effect on our genes and mitochondria.
Air pollution is a major public health concern worldwide. The molecular mechanistic underpinnings of the health effects of air pollution are not fully understood, and the lack of individual-level preventative options represent a critical knowledge gap. Our study demonstrated the epigenetic effects of air pollution and suggested that B vitamins might be used as prevention to complement regulations to attenuate the impact of air pollution on the epigenome.
So check out the air pollution index for your city, if it's bad (don't freak out!) be sure to supplement B Vitamins; folic acid, B6, and B12 especially!
Creatine
Is a well-known supplement that's often unfairly caricatured as something just for gym bros because it helps them get bigger but it's a bonafide Mitochondrial Nootropic...
Because the brain and nervous system require such high amounts of energy, it’s logical to assume the neurological system can benefit greatly from creatine—and this is being corroborated by clinical research. A growing number of studies have found that creatine can protect the brain from neurotoxic agents and certain forms of brain injury. (2650-2652)
A notable human double-blind, placebo-controlled creatine study was completed at the University of São Paulo Medical School in Brazil.
Totaling 18 bipolar patients
Dosed with 6 grams of creatine daily
For 6 weeks
The premise of the study was that...
Novel treatment approaches that target clinical and cognitive aspects of bipolar depression are needed, and research on pathophysiology suggests that mitochondrial modulators such as the nutraceutical creatine monohydrate might have a therapeutic role for this condition.
The notable finding was that
There was a statistically significant difference between the treatment groups of the change on the total scores after 6 weeks in the verbal fluency test...
So it's a biohack for verbal intelligence, at least for those with bipolar depression. It concluded
Our trial, which was the first to investigate the cognitive effects of creatinemonohydrate on bipolar depression, indicates that supplementation with this nutraceutical for 6 weeks is associated with improvement in verbal fluency...
Magnesium
A paper out of the University of Glasgow explores the crucial role magnesium plays in the maintenance of telomere homeostasis
Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease.
Unless you supplement Magnesium regularly you're probably deficient (especially if you drink a lot of coffee)...
Magnesium is likely one of the most underrated minerals and most people are just not consuming enough of it. One reason most are deficient in this mineral is that water softeners, while great for making your faucets shiny, has reduced the water’s hardness by removing minerals such as magnesium...Then there’s our rising caffeine intake, which increases the amount of magnesium we lose through urine... All these factors contribute to the alarming statistic that 70 – 80 percent of the developed world population is deficient in magnesium. (2569-2575)
D-Ribose
Your heart especially requires a lot of Mitochondria and this relatively unknown Mitochondrial supplement optimizes and normalizes cardiac function.
D-ribose is finding utility and acceptance in cardiac surgery; the heart is one of the organs that respond most favorably to D-ribose supplementation. Supporting the heart’s ability to preserve and rebuild its energy pool by supplementing with D-ribose is one of the first steps in restoring energy efficiency in any cardiovascular condition. Studies have shown it is effective in improving cellular energetics in congestive heart failure, coronary artery disease, and angina. (2212-2215)
A 2017 American study identified it as an exercise performance and recovery biohack...
- It was a double-blind, cross-over trial of 26 healthy subjects
- They did 60 minutes of high-intensity exercise and VO2max was quantified
- Dosed 10 grams of D-Ribose daily
It posed
Recovery from these lower ATP levels can take days, which can affect performance on subsequent days of exercise. Untrained individuals often suffer the stress and consequences of acute, repeated bouts of exercise by not having the ability to perform or recovery sufficiently to exercise on subsequent days.
It concluded
[D-Ribose] supplementation in the lower VO2 max group resulted in maintenance in exercise performance, as well as lower levels of [Rate of perceived exertion] and [creatine kinase].
MitoQ
In the past year, there have been over 10 scientific papers published about the branded antioxidant technology MitoQ.
A study of 20 older, healthy Americans done at the University of Colorado found that it's a vascular system hack that outperformed a placebo...
Excess reactive oxygen species production by mitochondria is a key mechanism of age-related vascular dysfunction. Our laboratory has shown that supplementation with the mitochondrial-targeted antioxidant MitoQ improves vascular endothelial function by reducing mitochondrial reactive oxygen species...
These findings in humans extend earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mitochondrial reactive oxygen species may hold promise for treating age-related vascular dysfunction
They must really like to drink at the University of North Carolina because even the mice there get drunk! At least they did in an interesting study that demonstrated that MItoQ is something of a boozing Biohack which mitigates the damage that toxic acetaldehyde does.
MitoQ also reversed alcohol-induced hepatic lipid accumulation through enhancing fatty acid β-oxidation. Alcohol-induced [Endoplasmic reticulum] stress and apoptotic cell death signaling were reversed by MitoQ. This study demonstrated that speeding up acetaldehyde clearance by preserving ALDH2 activity critically mediates the beneficial effect of MitoQ on alcohol-induced pathogenesis at the gut-liver axis.
But MitoQ research is not limited to the anglosphere MitoQ discussed how it regulates healthy autophagy.
Mitochondrial Function and Cramping
A Norwegian trial of 28 patients drew a connection between the Mitochondria and intermittent claudication, which is a painful muscle-cramping condition that makes it difficult or impossible to walk.
It concluded
Changes in walking performance seem to relate to changes in mitochondrial function after exercise...
Furthermore, relationships between changes in peak walking time and mitochondrial respiration seem to exist.
Mitochondrial Nootropics take time
From time to time, frustrated Nootropics users will contact me complaining that they've tried different popular Nootropics like Modafinil, Piracetam, and others BUT they still suffer from debilitating fatigue, anxiety, or memory deficits despite having good lifestyle habits and diet. Maybe the smart drugs worked a little or temporarily but they were far from transformative.
This is likely a case of catastrophic Mitochondrial dysfunction. The studies on the Mitochondrial support supplements indicate that repairing the function of this foundational energy generation system takes time - it could take 6 months or more of dosing something like CoQ10 to turn things around.
mtDNA and Knee Osteoarthritis
There were two meta-analysis papers published in 2017 by the same researchers in Spain on the topic of how mitochondrial DNA (that's the DNA you get from your mother) is implicated in the arduous condition of knee osteoarthritis, which is arthritis of knee bones and joints. A meta-analysis paper is a paper that analyses other studies and research that has been done, so it’s a bigger picture view, this meta-analysis looked at over 3200 cases and drew a connection between a genetic haplogroup with more functional mitochondria and the risk of developing Osteoarthritis.
Vs Leukemia
There were 26 papers published in the last year looking at the connection between the disease Leukemia and Mitochondria.
A study of 26 Australian Leukemia patients identified mtDNA mutations as a major cause of the disease.
Somatic mitochondrial DNA (mtDNA) mutations have been identified in many human cancers, including leukemia...
When patients with leukemia achieve remission, the remission peripheral blood may be a suitable and easily accessible control tissue, but this approach has not previously been applied to the study of mtDNA mutations.
An Argentinean paper comments on autophagy
Autophagy plays different roles depending on the type of pathology. In leukemia cells, it has been demonstrated that autophagy could be either detrimental, leading to an increase of the apoptosis rate, or protective, acting as a key process that augments proliferation and survival of cancer cells.
Lee Know clarifies what apoptosis is...
When executed properly , apoptosis is a well - orchestrated process of cellular self - destruction . Silently , in the human body , about ten billion cells are lost by this process every day. (750-751)
An in vitro Chinese study concluded that Ginsenoside could be a helpful treatment
In conclusion, these findings suggested that GRh2 and GRg3 induce mitochondrial-associated apoptosis by increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more effectively inhibit cell growth and accelerate apoptosis than GRg3. This study provides a potential novel strategy for the treatment of acute lymphoblastic leukemia.
So all the more reason to follow the Chinese grandma's advice and take some Ginseng!
Pharmaceuticals vs Mitochondria
An increasing number of researchers are alarmed that popular Pharmaceuticals have serious side effects on our Mitochondria.
With the increasing use of pharmaceutical medications, there has been a rise in health conditions linked to mitochondrial dysfunction — and mitochondrial dysfunction is increasingly implicated in the etiology of drug-induced toxicities. Despite this, testing for mitochondrial toxicity is still not required by the Food and Drug Administration of the United States, Health Canada, or any other regulatory body responsible for drug approval. Medications can damage the mitochondria both directly and indirectly (1630-1633)
Conclusion
The abundance of MItochondrial science makes me optimistic about medicine reorienting itself away from "bandaid" solutions and half-measures for chronic disease. Cellular and mitochondrial dysfunction are the ultimate source of most chronic diseases. Take care of your mitochondria and your mitochondria will take care of you!
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