Why are Mitochondria Important? 

Mitochondria are organelles that are present in every cell of the body except red blood cells. Probably everyone reading this learned about these little guys in high sch­ool biology, where they were described as "the energy packs of the cells."

About 20% of our body weight is mitochondria. This translates to about 250 quadrillion of these organelles. There are 37.2 trillion body cells with an average of 1 to 2000 mitochondria per cell. Sperm each have about 16 mitochondria and oocytes have 100,000 (which shows you where the power is).

The accepted theory is that mitochondria were once bacterial cells that created a commensal relationship with eukaryotic cells, and gave the eukaryotic cells the energy to become multicellular. The eukaryotes gave mitochondria more machinery and structure. Working together, multicellular organisms were able to evolve.

What Are the Mental Health Manifestations of Mitochondrial Function?

I became interested in mitochondria a few years back, for I had noticed that a certain percentage of patients with depression were quite treatment resistant. They seemed to actually get worse with conventional psychiatric medications. And they did not really respond that well to the naturopathic lifestyle and natural remedies that I commonly prescribed. These patients often complained of physical exhaustion, great difficulty with exercise, headaches, brain fog and sensitivity to noise and lights. Most upsetting, these patients would tell me that their doctors had said their feelings were ‘all in their head’ and just a part of being depressed. Interested in looking for the underlying cause, I started reading research suggesting mitochondrial dysfunction could play a role in mental health.

I found very strong evidence demonstrating that many mental health conditions, including bipolar disorder, depression psychosis, personality challenges, OCD, anxiety, autism and even dementia, may have roots in mitochondrial dysfunction [1]. This makes sense, for the mitochondria’s main job is to produce far greater amounts of ATP (36 molecules to be exact) from one molecule of glucose by using the cells Krebs cycle to perform oxidative phosphorylation. This is in contrast to the paltry 2 ATP molecules our cells could otherwise make via the glycolytic pathway, which doesn’t use mitochondrial help.

Neurons have a greater number of mitochondria per cell than most other cells, so it is no wonder that brain and mood will be greatly affected by a dampened mitochondrial function. As an example, it has been shown that there is greatly decreased ATP production and many increased mitochondrial DNA deletions in major depression [2]  [3]. Additionally, altered calcium sequestration in the mitochondria seems to play a role in functional mitochondrial changes that affect the pathophysiology of anxiety [4].

How Can Mitochondrial Function Become Compromised?

A number of issues will affect mitochondrial function: stress, hyperglycemia, dysinsulinemia, inflammation, iron and metal toxicity, and lipid peroxidation. Another major player is stress. These issues will combine to increase mitochondrial DNA damage, changing the ability of the mitochondria to form the proper antiporters and ion pumps needed to create concentration gradients to keep up energy production. Once energy production ceases, these gradients start to fall apart. Like a leaky dam, ions, minerals and inflammatory molecules start moving into parts of the mitochondria, jamming up the works and encouraging mitochondrial swelling. As this takes place, the whole cell itself starts to ‘blow up’ with inflammatory reactions. B vitamins and NADH are used up trying to keep DNA structures intact, contributing to further mitochondrial destruction. As mitochondria get destroyed at a faster rate than they can heal, the cell becomes at risk of apoptosis. As more cells die, more inflammation occurs, keeping the downward spiral of destruction going.

What Are Some Ways to Test the Mitochondria?

If you are practitioner interested in looking further at mitochondria, unfortunately there is no one test to check on this. However, if your patient presents with the above concerns, you can run serum carnitine, iron levels, CoQ10, lactic and pyruvic acid, glutathione, hormonal levels, zinc, insulin, the MTHFR gene, and vitamin D. Then, depending on the particular case, you may want to look at organic acid testing, mold issues and oxalate overload. ATP profiles are also performed in medical research. Muscle biopsies are the gold standard to confirm certain types of mitochondrial problems.

I also like to look at adrenal stress tests to test the function of the Hypothalamic Pituitary Adrenal axis. ZRT's heavy metal testing can look for toxins, while dried urine and saliva testing can help check into reasons for an imbalanced stress system which leads to mitochondria-damaging excess catecholamines. ZRT's hormone and neurotransmitter testing can also be a key to understanding which neurotransmitters need support while working on the underlying mitochondrial dysfunction. 

How to Help Repair the Mitochondria

While there is no one treatment to heal mitochondrial dysfunction, I have learned that the body typically knows how to heal. When given the right supports, it will move in the right direction. In that spirit, I strongly recommend a comprehensive 5-step plan designed to address the contributing multifactorial issues:

1 – Sleep: obtaining 8 hours a night, with consistency and getting to bed before 11pm. If the patient has insomnia, then this needs to be addressed. Slumber is when the mitochondria clean themselves up and rebuild, and the brain de-inflames. There is no substitute for sleep.

2 – Exercise: if a patient is tired, then exercise should be gentle. Moving the body is important for detoxification, cleaning up inflammation, and catalyzing mitochondrial biogenesis [5].

3 – Healthy diet: eating a mitochondria-building diet including whole foods, with plenty of healthy protein, vegetables, and healthy oils, will provide the nutrients and anti-inflammatory molecules needed for mitochondria to clean, rebalance and rebuild. Avoid sugary foods, simple carbs, fried foods and excess fats, as well as processed foods and foods with dyes and preservatives. If I do not know a patient’s sensitivities and want to start a general dietary plan, I find the Mediterranean Diet is often the best place to start, and I include green tea, berries, and apples, for these have mitochondria-building phytonutrients.

4 – Relaxation work: minimizing the sympathetic load will lower catecholamine production and signal the body to rebuild. Meditation, yoga, acupuncture, and massage are wonderful choices. Talk therapy and Cognitive Behavioral Therapy (CBT) may be needed if anxiety and stress are promoted by thoughts.

5 – Avoiding toxins: checking for mold toxicity, oxalates, metal exposures, and any other chemical exposure that might be present in the home or work environment. Also, for some people who have a genetic tendency to not break down toxins effectively due to liver cytochrome P450 genetic SNPs, even common household exposures from rugs, cleaners, perfumes, shampoos, lotions, and inorganic food might be enough to jeopardize their mitochondrial function.

6 – Supplementation: there are some supplements that can be indirectly and directly supportive of mitochondrial health. For example, B complexes will help Krebs cycle function, and fish oil is shown to positively support mitochondrial dynamics [6]. Foods and supplements that support phase I and II liver detoxification can help when there’s a strong toxicity picture. And direct mitochondrial supports may include carnitine, lipoic acid, and nicotinamide. I often prescribe N-Acetyl Cysteine (NAC), for it encourages oxidative phosphorylation, mitochondrial membrane integrity and homeostasis of the mitochondrial milieu. These supplements are only a partial list, for there are many other evidenced-based supplements I might use depending on the particulars of a patient’s case.

I will also recommend Hypericum (St. John’s wort) for mitochondria-related depression. Besides being the most well-studied herb and recognized as a bona fide treatment for mild to moderate depression, research suggests it can help neuronal mitochondria regenerate [7].

Conclusion

For mental health disorders, there is no one answer. Using a multifactorial approach that is individualized may have the best results. Please feel free to refer to my textbook on the subject for more details on how to create a plan for your patient [8].

Hippocrates recommended healthy food, sunlight, exercise, and herbs like St. John’s wort. Although this was 2500 years ago, and mitochondria were not discovered at that time, I think the father of medicine had a pretty solid plan for mitochondrial dysfunction. Since practitioners today have a great deal of new information about psychiatric illness, we can build upon Hippocrates’ plan to help our patients with mental illness.

Related Resources

• Blog: Neurotransmitters, Mood & the Perception of Stress
• Provider Datasheet: Neurotransmitters Testing
• Webpage: Neurotransmitters

Bio

Dr. Peter Bongiorno co-medical director of Inner Source Health, with thriving practices in New York City and Long Island. He is immediate past president of the New York Association of Naturopathic Physicians.  He authored, How Come They’re Happy and I’m Not? The Complete Natural Guide to Healing Depression for Good (Red Wheel), the practitioner-guide Holistic Therapies for Anxiety and Depression (WW Norton). His newest book is, Put Anxiety Behind You: The Complete Drug-Free Program. Visit InnerSourceHealth.com and www.3UNeed.com, and join him on Facebook and twitter @drbongiorno for updates on naturopathic mental health.

References

[1] Scaglia,F. The role of mitochondrial dysfunction in psychiatric disease. Dev Disabil Res Rev 2010;16:136–143.

[2] Gardner A, et al. Gardner respo A, et al. CNS Spectr. 2008;13:805-14 CNS Spectr. 2008;13:805-14.

[3] Rezin et al. Acute administration of ketamine reverses the inhibition of mitochondrial respiratory chain induced by chronic mild stress. Brain Res Bull. 2009;79:418-21. 

[4] Schweitzer N. Pegging pathology on mitochondrial dysfunction. Scientist. 2004;18:28. 

[5] Lumini JA et al. Beneficial effects of exercise on muscle mitochondrial function in diabetes mellitus. Sports Med. 2008;38(9):735-50. 

[6] Sun R. Dietary supplementation with fish oil alters the expression levels of proteins governing mitochondrial dynamics and prevents high-fat diet-induced endothelial dysfunction. Br J Nutr. 2014 Jul;112(2):145-53.

[7] Wang et al. Hyperforin promotes mitochondrial function and development of oligodendrocytes. J Neurochem 2011. Nov.119(3):555-68.

[8] Bongiorno PB. Holistic Solutions for Anxiety & Depression: Combining Natural Remedies with Conventional Care a therapist's guide. W.W. Norton, New York (March 2015): 244-261.