Mitochondria and Mental Health

Brain Energy, Mitochondria, and Mental Health
Dr Chris Palmer, MD, Harvard Psychiatrist

A major change in psychiatry has been going on for awhile now in which more and more clinicians and researchers are recognizing mental health disorders as related to, and sometimes caused by, physical states in the body and therefore using therapies that are meant to address these states.  A primary example of this is looking at brain metabolism (mitochondrial function in the brain).

The Keto diet is a 100 year old, evidence based therapy that can stop seizures that medication can't stop.  This is evidence of how powerful nutrition and diet can be in treating and altering brain function.  Psychiatrists use epilepsy medications to treat people with other mental mental health conditions often, usually off-label, so there's nothing new about using the ketogenic diet to treat other mental health conditions.  Seizure meds are used to treat dementia, eating disorders, anxiety, psychosis, mood disorders, substance use disorders, and others.  

The Brain Energy Theory- Mitochondria do more than just produce energy for cells "mitochondria play a role in directing and allocating resources for cells".  Not all of the food that mitochondria in the brain process is turned into ATP- some is turned into serotonin, dopamine, or cortisol, and they also play a part in regulating those molecules.  Mitochondrial function is one way of understanding the imbalances of the neurotransmitters and hormones in the brain.  They are also involved in regulating inflammation (turning it both on and off) and epigenetics by signaling the nucleus of the cell to regulate the transcription of gene.  They monitor our outer and inner environment; sensing stress levels, food intake, blood sugar levels, and oxygen levels.  

"Mitochondria play a role in our response to trauma- psychological and social stressors."  Trauma and stressors play a role in mental illness, so this connection could be very significant, because while people have known that there is a connection they haven't known exactly what that connection is on a biological level.  He points out that mitochondria seem to be a way to "connect the dots" in the mental health puzzle between factors like trauma, neurotransmitters, sleep, substances like drugs and alcohol (I would add exercise and sunlight too).  These are all things that affect mitochondrial and metabolic health or are affected by it or both.  People with mental health conditions have higher rates of many physical disorders including diabetes, obesity, heart attacks, strokes, and generally have a shorter life expectancy.  This connection also opens up the possibility of more and better treatments.

For people who struggle to believe this connection is real, he explains that mitochondria are what drives metabolism, which is how we take food and oxygen and transform them to keep ourselves alive.  If these processes are disturbed it means illness, and if they are disturbed enough or stop, we die.  Most poisons work by harming mitochondria- that's how they harm or kill you.  Other cellular components can be harmed without nearly as much danger to the organism.  It makes sense that since mitochondria are the most important part of the cell and what keeps it able to perform its function, if they aren't functioning right the cell won't be able to function right.  

Mitochondria can become both under-active AND overactive.  This makes sense because there are mental health disorders involving areas of the brain becoming overactive as well as areas becoming under-active.  If the health of mitochondria impacting the cell's functioning is the cause or major contributing factor to many mental health disorders that would explain why they can be better or worse at different times of day (or different seasons), why they can be worsened by stress and sleep deprivation.  A lot of the details aren't known yet but already the basic insight that mitochondria are central to mental health is transformative of the fields of psychiatry and psychology.

What options are available to support mitochondrial functioning?

There are a huge variety of things available to help mito function including sun exposure, red light therapy, various supplements, glutathione, methylene blue, and more, but these can only help so much if core lifestyle issues aren't addressed.  For example, alcohol is a potent mito toxin so a person drinking a large amount daily is poisoning their mitochondria far beyond what those things can help.  Having healthy mitochondria requires lifestyle changes- eating well and avoiding highly processed foods, sleeping well, exercising, and avoiding excess stress.  

The ketogenic diet and its effect on brain function has been studied for a long time, its known to change neurotransmitter levels, inflammation, the gut microbiome, but Dr Palmer says that he believes the impact it has on mitochondria is its most important therapeutic effect.  The keto diet creates a state in the body similar to fasting, which is known to trigger mitophagy (when the cell breaks down old and defective mitochondria that are replaced by new, healthy ones) and mitogenesis (which is the production of new, healthy mitochondria).  Dr Palmer suggests that these two processes that remove old, defective mitochondria and replace them with more and healthier ones, might lead to long-term healing where a person could potentially go off the keto diet and remain healthy.  People who are on the diet to control seizures will usually be kept on the diet for 2 to 5 years after the point at which their seizures completely stop (some people with seizures must stay on keto for life).  People can experience improvement of mental health symptoms, even very significant improvement or remission in weeks or months.  Psychotic symptoms tend to take weeks if not months to improve especially if severe.  People often wonder if making some changes in their diet, such as eating more fatty fish, will be enough.  Dr Palmer says maybe for people with relatively mild symptoms or conditions, some changes such as eating more fatty fish can help, but he points out that those changes don't stop seizures but the keto diet does, he says  "ketogenic therapy is a unique and powerful intervention".

What about other interventions to support mito health?

Exercise is a really important factor also and should be part of a treatment plan.  The two types of exercise for which there is the most evidence of benefit for mito health are strength training (aka lifting weights, working out to build muscle) and level 2 cardio (which he defines as 3-60 minutes of running, cycling, etc that gets you breathing hard but not out of breath).  Those types of exercise increase the number and health of mitochondria in muscles which then send endocrine signals to your brain that improve brain function.  Exercise alone isn't enough to heal mito, lose weight, or heal type 2 diabetes.  If people exercise more but don't change how they eat they don't get significant or sustained weight loss.  There has been one very well-done study of middle-aged adults who were prescribed exercise.  In addition, half were given the drug metformin to take and the other half were given a placebo.  The group that got metformin didn't get the mito and metabolic benefits of exercise the way the other group did, which is evidence that metformin interferes somehow with mitochondrial biogenesis.  Many other medications, including many psych meds, are known to interfere in mito function and biogenesis, so this should be considered.  Lifestyle behaviors such as drinking alcohol and smoking cigarettes and marijuana are also mito toxins.  

The psych drugs that can do this are mostly the anti-psychotics, which have been known to have metabolic side-effects and neurological side effects.  They can cause significant weight gain (he has seen people gain as much as 100 pounds in 6 months), they can cause type 2 diabetes, they worsen every known risk factor for cardiovascular disease (raise blood pressure, raise triglycerides, worsen LDL levels), and increase inflammatory biomarkers.  

This represents a new way to understand mental illness and what might be happening in the brain, and a new way to treat it.  This is especially important as mental health remains highly stigmatized in the US and research around it receives very little funding in comparison to disorders considered to be physical.  Many mentally ill people are in prisons, shelters, or even on the street.  "There is tremendous injustice, in my mind, in how we treat people with mental illness".  Dr Palmer points out that while psychological and social factors play a role in mental illness, it's no less physical and "real" in that way.  People with mental illness "deserve medically necessary treatment".  If we can get needed care to people in prison or who are homeless and who have mental illness, they won't be in prison or homeless anymore, they can live enjoyable, productive lives. 

 

 

 

 

 

 

Carbon Monoxide Brain Injury

Carbon monoxide is an invisible odorless gas that is a byproduct of burning fuels including auto emissions, lawnmowers, fireplaces, furnaces and other natural gas appliances such as water heaters.  Natural sources include forest fires and a small amount from the breakdown of heme in the body.  Smoking increases CO levels and smokers have increased CO levels to between 5% and 9%, but heavy smokers can have levels up to 15% in the blood.  In the indoor environment, smokers become net contributors to ambient CO levels.  CO can build up in the air inside and reach dangerous levels if there is not proper ventilation or the burning is occurring in a small, confined space.  

Some lesser-known sources of CO include "incomplete combustion and inadequate ventilation of domestic natural gas, indoor burning of charcoal for barbecues, propane gas cylinders (forklift trucks), petrol powered generators, and methylene chloride exposure from spray paint (hepatic conversion to CO)".  Carbon monoxide monitors can be placed near potential sources to alert you if there is a leak.  Many travel experts recommend bringing a carbon monoxide monitor with you when you travel because regulations vary from place to place and are not always fully enforced anyway.

"COHB decreases with a half life of approximately 320 minutes in air. However this half life is further decreased to 80 minutes if 100% oxygen is given to the patient."  Symptoms of carbon monoxide poisoning include headache, dizziness, fatigue, poor tolerance for exercise, weakness, chest pain (also called angina), nausea, vomiting, and confusion.  Acute exposure can lead to confusion, seizure, loss of consciousness, and even death.  The presence of additional stressors, such as low temperatures may increase the effects of CO.  A number of studies have found even small changes in ambient CO levels correlating with cardiac complications and death "levels of CO commonly found in urban outdoor air may induce arrhythmia, angina, and sudden death in people with heart disease." as well as a statistically significant increase in Myocardial Infarction in patients with increased chronic exposure to CO.    

"To make the diagnosis, a blood test with access to a co-oximeter, to measure carboxyhaemoglobin (COHB) levels is required." If a person survives the exposure they may have long-term damage to the brain.  The symptoms of brain injury from carbon monoxide resemble those of brain injury from other sources and can include headaches, dizziness, and difficulties with sleep, mood, balance, vision, movement, memory, and other cognitive problems.  Symptoms may be present right away or can be delayed.  Injury to the brain from acute exposure can often be seen on MRI scans soon after the exposure occurred.

Carbon monoxide exposure can lead to brain injury in several ways.  It can cause hypoxia, a state in which the brain does not receive adequate levels of oxygen, because carbon monoxide binds to the hemoglobin in the bloodstream which limits the amount of oxygen that can be transported to the cells in the brain.  If cells don't receive enough oxygen they are not able to produce enough energy to function properly and can even die, particularly in the brain region called the hippocampus which is important for memory.  Carbon monoxide can also cause injury to the brain from inflammation, from damaging certain proteins that surround neurons, and from causing iron to be released into the brain which is toxic to brain cells.  In some cases, treatment with Hyperbaric Oxygen Therapy can reverse some of this damage.

Carbon Monoxide Brain Injury

Carbon monoxide poisoning mimicking gastroenteritis

Association of the frequency of acute cardiorespiratory complaints with ambient levels of carbon monoxide

Revenge of the barbecue grill. Carbon monoxide poisoning

Occult carbon monoxide poisoning in patients with neurologic illness
"We conclude that unrecognized carbon monoxide poisoning occurs in a small but important fraction of patients with wintertime neurologic illness and can be identified by a characteristic risk factor profile."

Chronic and occult carbon monoxide poisoning: we don’t know what we’re missing
"There is a strong possibility that low level exposure to CO is responsible for widespread and significant morbidity, however the clinical syndrome produced is often overlooked because of a range of presentations, obscure symptoms, and a lack of awareness of the problem.  In the USA, comparatively small changes in ambient levels of CO as a result of pollution have been shown to affect rates of presentation to emergency departments with various complaints."

"“Occult CO poisoning” is used to indicate those cases of CO poisoning that may never come to the attention of a medical practitioner. In most cases, this is as a result of chronic CO poisoning and most frequently the patient will not even ask for a medical opinion. Occasionally acute poisoning as a result of exposure to high concentrations of gas may remain occult, and although the patient presents to a medical practitioner—the diagnosis is missed (at least until the patient re-attends, often with cohabitees with similar symptoms). Occasionally, deaths have occurred."

"Pyramid of disease: CO poisoning can be looked upon as a “disease” with a pyramid of presentation—the tip of the iceberg is overt acute poisoning, while the base is occult, low level exposure. A difficult question to answer is: how big is the base? Even ambient levels of CO in the atmosphere as a result of pollution cause changes in the hospitalization and mortality rates of patients with certain diseases."

"At levels of COHB greater than 10% patients with pre-existing cardiac disease experience increased severity and duration of angina and if levels rise above 15% they are at increased risk of myocardial infarction. If a patient has had an acute myocardial infarction, the threshold for ventricular fibrillation can be reduced to 9% COHB.  Patients with severe chronic bronchitis or emphysema experience a significant reduction in the walking distance when breathing air after exposure to CO and intermittent claudication occurs with less provocation in patients with low levels of COHB. Even in normal subjects a COHB concentration as little as 4.4% has been shown to limit work capacity and maximal oxygen consumption." 

"In patients with acute poisoning, 30% or more may experience delayed onset of neuropsychiatric symptoms. Symptoms include cognitive and personality changes, dementia, psychosis, parkinsonism, amnesia, depression, and incontinence. There is also good evidence that apparently minor low level acute and chronic exposure causes varying degrees of neuropsychological impairment.  It is postulated that CO causes lipid peroxidation of neurological tissues.  Early hyperbaric oxygen therapy decreases the extent of lipid peroxidation and this would explain the decreased incidence of neuropsychiatric sequelae after hyperbaric treatment. The regions of the brain most frequently involved include the globus pallidus and deep white matter.

Epidemiological bases for the current ambient carbon monoxide standards

Ambient carbon monoxide and increased risk of daily hospital outpatient visits for respiratory diseases in Dongguan, China

Systematic review and meta-analysis of studies between short-term exposure to ambient carbon monoxide and non-accidental, cardiovascular, and respiratory mortality in China
"Our meta-analysis demonstrated that exposure to ambient CO was positive with risk of deaths from all non-accidental causes, total cardiovascular, and respiratory diseases. Based on these findings, tougher intervention policies and initiatives to reduce the health effects of CO exposure should be established."

Chronic and occult carbon monoxide poisoning: we don’t know what we’re missing

Carbon monoxide poisoning mimicking gastroenteritis.

Carbon monoxide: not gone, not to be forgotten

Vision and Eye Health

LED light can damage eyes, health authority warns
"The "blue light" in LED lighting can damage the eye's retina and disturb natural sleep rhythms, France's government-run health watchdog said this week.  New findings confirm earlier concerns that "exposure to an intense and powerful [LED] light is 'photo-toxic' and can lead to irreversible loss of retinal cells and diminished sharpness of vision."

While less dangerous, even chronic exposure can "accelerate the ageing of retinal tissue, contributing to a decline in visual acuity and certain degenerative diseases such as age-related macular degeneration," the agency concluded.

LED cellphone, tablet and laptop screens do not pose a risk of eye damage because their luminosity is very low compared to other types of lighting, Francine Behar-Cohen, an ophthalmologist and head of the expert group that conducted the review, told journalists."

Better Vision for Patients with Albinism - Brian Brooks, NIH Clinician Scientist
A study performed on mice showed that if they had albinism and had a little tyrosinase in their blood, administration of the drug nitisinone caused their fur and eyes to become more pigmented.  Improvement in vision can be detected in mice within one month of this treatment. 

Nitisinone increases melanin in people with albinism
"A small pilot clinical study at the National Eye Institute (NEI) suggests that the drug nitisinone increases melanin production in some people with oculocutaneous albinism type 1B (OCA-1B), a rare genetic disease that causes pale skin and hair and poor vision. Increased melanin could help protect people with the condition against the sun’s UV rays and promote the development of normal vision. Study results were published in JCI Insight. NEI is part of the National Institutes of Health (NIH)."

How to Cook Eggs for Maximum Antioxidant Nutrients
In this video by Dr Eric Berg, he discusses how certain antioxidants found in eggs, lutein and zeaxanthin, are important for health- particularly eye health (and liver and brain health as well).  They particularly accumulate in the retina and lens of the eye and protect against Age-Related Macular Degeneration and Cataracts.  They also limit blue light exposure by absorbing that wavelength of light.  Blue lights are also damaging to the eyes.  These two nutrients can also be found in vegetables, shrimp, lobster, salmon, avocado, and egg yolks.  Eggs should be organic and pasture-raised.  They can be damaged or destroyed by excessive heat so it is important to cook the eggs gently and with no excess heat.  Ideally the yolks should be runny, as in poached eggs or fried eggs sunny side up.  Additionally, omega-6 fatty acids are pro-inflammatory and if eaten in excess can contribute significantly to damage to the eyes, so reducing consumption of those oils is also important.  They are found in vegetable oils such as corn oil, soy oil, and canola oil.