I recently started a program with Nutritional Psychiatrist Dr Georgia Ede, Ketogenic Diets for Mental Health. I am fascinated by the brain and how we can get the most out of our one precious life. To me it’s a no ‘brainer’ that what we eat directly impacts our brain. But I don’t really understand how.. and what happens when things go wrong. This is where Dr Ede’s work is hopefully going to help me.

If you haven’t seen this, I recommend you watch this first.

Let’s get in to the first session, entitled The Science and Safety of Ketogenic Diets for Mental Health.

This session was looking at the evidence behind diet and neurological conditions; brain metabolism and when this goes wrong; inflammation and oxidative stress; ketogenic diets and certain psychiatric conditions; and finally looking at the myths about the safety of ketogenic diets.

The Science of Ketogenic Diets and Neurological Disorders

There is extensive research behind ketogenic diets for epilepsy (over 100 years of evidence, research and clinical trials) showing consistently a reduction of seizures in more than 50% of people following a ketogenic diet. There is also emerging evidence for the use of ketogenic diets in other neurological conditions, such as MS, Parkinson’s, ALS (Amyotrophic lateral sclerosis), Huntington’s disease, and traumatic brain injury. Since the brain is not divided into neurology cells and psychiatry cells, it makes sense that an intervention that helps with neurological conditions could also help with psychiatric conditions.

The underlying features common to many psychiatric disorders include:

  • neurotransmitter imbalances
  • excess inflammation and oxidative stress
  • cerebral glucose hypometabolism
  • mitochondrial damage
  • unstable neural networks
  • impaired neuroplasticity
  • low BDNF (Brain-derived neurotrophic factor) activity (helps the brain form new circuits required for learning and memory)
  • sensory gating deficits
  • NMDA receptor dysfunction
  • glutamate excitotoxicity

You don’t need to have an acute understanding of all of this, except to know that high blood sugar and insulin levels can cause every one of these underlying features.

The ketogenic diet has been shown in scientific studies to have the ability to correct all of these problems.

The Psychiatric Dangers of Hyperinsulinemia

You have have heard about the metabolic dangers of hyperinsulinemia. A problem of consistently high levels of circulating insulin levels due to the cells becoming resistant to the effects of insulin and having to push out more and more to lower blood glucose levels. Insulin resistance (IR) is also associated with psychiatric conditions, such as:

  • depression
  • PTSD
  • bipolar disorders
  • schizophrenia
  • children with obesity and psychiatric disorders, particularly anxiety disorders

While there is much to learn about the role IR plays in most psychiatric conditions, there is emerging evidence to suggest that insulin resistance may play a role in the severity and course of certain mental health symptoms in some cases.

How might this be the case?

Decades of Alzheimer’s research has shown that the fundamental problem caused by IR is the restriction of the brain’s access to energy.  Essentially, there is a problem at the blood/brain barrier where it becomes increasingly difficult for insulin to cross into the brain. High blood sugar = high brain sugar, but paradoxically, the higher the blood insulin, the lower the brain insulin. This means that while the brain is swimming in glucose (or energy), it actually cannot process this glucose into energy without adequate insulin, which means it is starving to death.

Studies consistently show that the more insulin resistant a person is, the slower their brain glucose processing. We know very little about how this problem influences psychiatric conditions other than dementia, but it stands to reason that a shortage of brain energy could cause problems for mood, behaviour and cognition.  Studies have found evidence of brain glucose processing problems in depression, bipolar disorder, and schizophrenia.

Inflammation and Oxidative Stress

It is well established that hyperglycemia (high glucose levels ) causes inflammation. For people that eat high sugar foods multiple times a day, the inflammation process never quiets down leading to uncontrolled, chronic inflammation. Chronic inflammation and oxidative stress can also contribute to psychiatric problems by throwing neurotransmitter systems out of balance. The kynurenine pathway is a prime example of this (let’s see if I can explain this in simple terms as this is important).

In normal conditions, tryptophan (an essential amino acid) is used to synthesize the important neurotransmitters serotonin and melatonin (our feel good and sleepy hormones). Most of it travels down the kynurenine pathway where it is used to help regulate the balance between other neurotransmitters (most importantly glutamate and GABA). The balance of these two neurotransmitters largely determine the brains overall activity level. Glutamate is the brains gas pedal, GABA the break pedal.

Under the influence of stress, excess inflammation and/or oxidation, this process goes askew, resulting in less serotonin, less melatonin, more dopamine, less GABA, and far more glutamate (up to 100 times more) creating glutamate excitotoxicity. This eventually leads to the brain being unable to form new circuits and the excess glutamate directly damages proteins, lipids, nucleic acids and mitochondria. All critical brain structures can be compromised and begin to atrophy.

Ketogenic Diets

Canadian neuroscientists Dr Stephen Cunnane describes the brain as a hybrid engine that can run entirely on glucose or on a mixture of glucose and ketones. I found this YouTube video by Dr Cunnane on Brain Glucose and Ketone Metabolism.

Ketones burn more safely, cleanly, and efficiently than glucose molecules – with much less oxidation and inflammation. A great way to think of ketones versus glucose is to think of kindling versus logs. The kindling burns very quickly and needs refuelling often and produces lots of smoke (oxidative damage). The logs are a slow burn, steady energy with very little smoke.

Given a choice, most brain cells will choose to burn ketones over glucose. In fact ketones can satisfy about 75% of the brain’s total energy needs. There are some brain cells that require glucose (of which the body can totally make on demand through a process called gluconeogenesis).

Ketones can easily cross into the brain, even in people with severe insulin resistance. The higher your blood ketones, the higher your brain ketones. In stark contrast to glucose, ketones burn easily in a low insulin environment, making ketones an ideal fuel source for the insulin resistant, insulin deficient brain.

What about the safety of the ketogenic diet?

Let’s look at the myths.

Ketogenic diets raise LDL which increases the risk for heart disease

Low carbohydrate diets can raise LDL levels – on average about 10% but in some cases much higher. However, clinical studies find that this increase is due to a rise in large LDL particles which are not associated with heart disease risk. The vast majority of people on a ketogenic diet see healthy increases in HDL, reduction in inflammation markers and blood pressure, and dramatic reductions in triglycerides. All of these biomarkers are a much stronger predictor of cardiovascular disease than LDL.

Dr Georgia Ede talks about her concern about the risks of cholesterol lowering statin drugs pose to brain health.  Statins work by turning down the activity needed to synthesize new cholesterol molecules. All statin drugs cross the blood/brain barrier, enter brain cells, and reduce the brain’s ability to manufacture vital cholesterol molecules. The brain contains 20% of the body’s cholesterol and is vital to brain function.  If the brain is too low in cholesterol it can’t form or function properly, impacting all critical brain activity, including learning and memory.

The ketogenic diet triggers eating disorders

Any diet can trigger an eating disordered attitudes and behaviours. All eating disorders are not the same. and there is emerging evidence that carbohydrate restriction can help people who struggle with binge eating, overeating or food addiction. Currently, ketogenic diets are not recommended in anorexia.

Ketosis is an unnatural state that will lead to ketoacidosis

Ketosis is a natural metabolic state. Whenever insulin levels are low enough, humans naturally start breaking down fat molecules into fatty acids and ketones. Infants are born in ketosis. People can generate ketones when they are sleeping, fasting, restricting calories, or eating a ketogenic diet. Nutritional ketosis is a healthy metabolic state in which glucose, ketones and pH levels all remain in a healthy range. Ketoacidosis is a life-threatening medical emergency in which ketones rise to such extremely high levels that the blood pH drops to dangerously acidic levels – but this can only happen in people with insulin deficiency (Type 1 diabetes) or people taking certain medicines. Otherwise, there is always enough insulin present to prevent uncontrolled production of ketones.

Too much fat is bad for the heart

The vast majority of RCT (randomised controlled trials) find no connection between total fat or saturated fat and heart disease. Even the USDA dietary guidelines removed its limit on total fat intake back in 2015. It wouldn’t make sense for fat to cause heart disease. All whole plant and animal foods naturally contain a mixture of saturated and unsaturated fat, so we’ve been eating saturated fat for all of human history.

Ketogenic diets cause kidney stones

The only published evidence that this can happen comes from the study of children following specialized, restrictive ketogenic diets for epilepsy, and this risk can be reduced dramatically with potassium citrate supplements. Risk factors of kidney stones include dehydration, magnesium deficiency, high oxalate intake, and certain medications.

Too much protein robs calcium from bones and causes osteoporosis

Protein is very important to the growth and maintenance of bone. While protein metabolism does generate acids that need to be buffered by calcium and eliminated by the kidneys, the body compensates by increasing calcium absorption from the diet, not from the bones. A 2017 USDA review of studies concluded that ‘a high protein diet does not negatively affect calcium homeostasis.’

The brain needs carbohydrates (my favourite one)

Although the brain does need some glucose at all times, that glucose does not have the come from the diet. Through a process called gluconeogenesis as said above, the body can easily generate glucose from fat and protein.

As with all my posts, this is not medical advice. Seek help from your medical practitioner before changing your diet or adjusting medications.