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February 4 - April 8, 2025
low levels of these vitamins and other factors may simply be a consequence of mitochondrial dysfunction, not the cause of it. If that’s the case, adding more may not solve the problem. And pills like this don’t automatically stimulate mitochondrial biogenesis or mitophagy. But dietary interventions, good sleep, stress reduction, removing mitochondrially impairing medications, and exercise can!
people who adhere to the Mediterranean diet (MD) are less likely to develop depression. But for people who are already depressed, can adopting this diet improve symptoms? It appears that it can, at least for some people.
The mitochondria in the MD-fed animals maintained normal differences between brain regions, whereas the mitochondria in the Western-fed animals lost these normal distinctions. The brain areas affected are known to play a role in diabetes and Alzheimer’s disease.
fasting, intermittent fasting (IF), and fasting-mimicking diets may play a role in treating mental disorders. They all result in the production of ketone bodies, which are made when fat is being used as an energy source. Fat gets turned into ketones. And, interestingly, this process occurs exclusively in mitochondria,
Ketones are an alternate source of energy to cells. They also serve as important metabolic signaling molecules, resulting in epigenetic changes. Ketones can be a rescue energy source to insulin-resistant brain cells. While glucose might have trouble getting into these cells, ketones can get inside pretty easily.
the hippocampus, a brain region often involved in depression, anxiety, and memory disorders, was largely driving the improvements from IF. It appeared to be due primarily to higher levels of GABA activity, which reduced hyperexcitability.
IF is thought to promote brain health, including reducing oxidative stress and inflammation, improving mitophagy and mitochondrial biogenesis, increasing brain-derived neurotropic factor (BDNF), improving neuroplasticity, and promoting cellular stress resistance.33 These are powerful healing interventions not currently available in a pill.
about 30 percent of patients with epilepsy don’t improve with any of the pills we have to offer, so the ketogenic diet was resurrected in the 1970s at Johns Hopkins for use in treatment-resistant epilepsy. Clinical use of this diet has grown around the world since.
Neurologists, neuroscientists, and pharmaceutical companies have been studying this diet for decades trying to better understand its anticonvulsant effects. It provides an alternate fuel source, which can be a lifeline to insulin-resistant brain cells. It also changes neurotransmitter levels, regulates calcium channels, decreases inflammation, improves the gut microbiome, increases overall metabolic rate, reduces insulin resistance itself, and most importantly, induces both mitophagy and mitochondrial biogenesis.
I have seen people with severe, treatment-resistant psychotic disorders achieve full remission of their symptoms for long periods of time through a ketogenic diet.
The effects of the diet in the first year are just like a medication. People need to remain on the diet religiously. They can’t stop it for “cheat days,” just like they can’t stop their medications for cheat days.
the researchers found that when people were on the ketogenic diet, they had improvement in daily function and quality of life. I should point out that this is one of the few studies to demonstrate improvement in symptoms of Alzheimer’s disease. Most studies, like the intranasal insulin studies I told you about, only prevent progression of the disease.
there is no question that the gut microbiome plays a role in mental and metabolic health. In terms of proven interventions, however, this field is in its infancy.
Avoid antibiotic exposure if possible. Antibiotics are known to disrupt the microbiome, and they can sometimes directly cause mitochondrial dysfunction.
Avoid highly processed foods. Eating foods high in fiber,
Probiotics might play a role for some people, although we don’t have much evidence that they can improve metabolism or mental health.
Fecal microbial transplants are being studied but are experimental at this point.
Strategies to improve gut health may improve mental health.
Mental health and metabolic health are inseparable. This applies to everyone, including those simply trying to lose weight, or manage their diabetes, or prevent a heart attack or Alzheimer’s disease. Diet and exercise are often not enough.
They were using the ketogenic diet as a weight-loss method. She decided to give it a try. Within two weeks, not only did she begin to lose weight, she noticed significant improvement in her psychotic symptoms. She said that for the first time in years, she was able to hear the birds singing outside. The voices in her head were no longer drowning them out. Her mood was also improving,
The brain energy theory offers clear answers: drugs and alcohol converge on metabolism and mitochondria. Most drugs fit into one of two categories—they either stimulate or inhibit cells.
alcohol and marijuana, which I’ll focus on soon, both have broad effects throughout the body. They act through receptors mostly found on the surfaces of cells, which then impact the mitochondria within those cells. However, mitochondria also have their own receptors for marijuana, nicotine, alcohol, and Valium right on their membranes. These drugs directly impact mitochondria.
Drugs and alcohol form a feedback loop with metabolism and mitochondria. People can enter this feedback loop in different ways, but once they get in, it can be difficult to get out.
If people binge drink, these enzyme systems back up, and acetaldehyde levels rise. The first signs of problems are with mitochondria. They swell up, have trouble producing ATP, and create more ROS.
Chronic alcohol consumption leads to chronic oxidative stress, a sign of mitochondrial impairment. This leads to inflammation, which only makes the problems worse. All of this is occurring throughout the body, but particularly in the liver and brain.
When people drink alcohol, their brains use less glucose as an energy source and instead use acetate from alcohol.3 Over time, alcoholics develop a problem with brain glucose metabolism. Their brain cells become energy deprived when they are sober.4 When they drink alcohol again, acetate fuels these struggling brain cells and provides relief. This brain energy deficit may be one of the reasons that alcoholics have trouble staying away from alcohol.
people who got the ketogenic diet needed less detox medication and had fewer withdrawal symptoms. They also reported fewer cravings for alcohol. Brain scans showed improved brain metabolism and reduced levels of brain inflammation compared to those on the standard American diet. This pilot study demonstrated that a dietary intervention, seemingly unrelated to alcoholism, could make a big difference in the brains, and symptoms,
They tested rats on the ketogenic diet and found that their blood alcohol levels increased fivefold compared to rats on a normal diet, even though they all got the same amount of alcohol. This means that if people with alcohol use disorder were to try the ketogenic diet on their own, it could be dangerous if they drink. They could get much more intoxicated than usual.
Marijuana affects the endocannabinoid system in the human body. Receptors for cannabinoids are found throughout the body, but they are highly concentrated in the brain. There are primarily two types of receptors—CB1 and CB2. These are located on cell membranes, but CB1 receptors are also located directly on mitochondria.
the predominant theme in neurons is that marijuana slows the function of mitochondria through CB1 receptors.
the regions of the brain highest in CB1 receptors showed “accelerated age-related cortical thinning” in the marijuana users, meaning that marijuana’s effects on these mitochondrial receptors was likely the cause of these brain areas getting thinner.
CB1 receptors on mitochondria. When these receptors were activated by THC (the active ingredient in marijuana), it led to a reduction in both mitochondrial function and energy sources going to neurons. It also led to social withdrawal behaviors.
brain energy and mitochondria play a primary role in our ability to remember.
A study of 1.2 million Americans found that those who exercised had 43 percent fewer days of poor mental health, even after controlling for physical and sociodemographic characteristics.1 This study found that any type of exercise was better than no exercise, but that the largest benefits were seen for team sports, cycling, and aerobic and gym activities. The optimal “dose” was forty-five minutes, three to five times per week.
the study with 1.2 million people was a correlational study. As you know by now, correlation doesn’t equal causation. It’s possible that people who exercise already have good mental and metabolic health,
Exercise has been studied as a treatment for mental disorders, with depression being the most studied illness. The results are mixed, with some studies showing benefits and others not.
