Got Brain Fog?

woman chooses her cloud to hide his face

What is brain fog and how do you treat it?

A question, “how do you treat brain fog?” was asked to a group of headache specialists.  The question was about a patient who suffers from frequent migraine headaches who had also has been experiencing brain fog.  The patient felt like this brain fog was almost as disabling as his migraines.  The brain fog which occurred during and outside of his migraine headaches was limiting his ability to work as a professor at a medical school.  The question posed was how to best treat his brain fog.

The answers from the group of varied from recommending better treatment of his migraines to medical treatment of the underlying depression that he MUST have.  Thinking about it, I realized that this would be what I would have recommended as little as a couple of years ago when someone would come see me with the complaint of brain fog.

Based on my last two years of research into the underlying causes of many neurological symptoms and diseases along with the many benefits of being in ketosis, my treatment recommendations are now different.

So what is brain fog?

Brain fog is not currently recognized as a medical diagnosis.  It, however, is a symptom that is frequently reported in many different medical disorders.  Depending on its severity it can be very disabling, sometimes more disabling than their underlying medical diagnosis.  A precise definition of brain fog also has not been established.

People who suffer from brain fog describe their symptoms as:

  • Difficult focusing
  • Mental fatigue
  • Cloudy or hazy thinking
  • Slow thinking
  • Difficulty concentrating
  • Inability to multitask
  • Forgetfulness

Brain fog has been reported in a variety of medical disorders including:

  • Chronic fatigue syndrome
  • Fibromyalgia “fibro fog”
  • Postural tachycardia syndrome
  • Lupus
  • Multiple sclerosis
  • Celiac disease
  • Autism spectrum disorders
  • From chemotherapy “chemo fog”

I like many people have experienced some of these symptoms transiently related the side effects of from medications, specifically the antihistamines that I take for my cedar allergies.  (I had a pretty severe episode yesterday.)  The difference, however, is when it is due to an underlying medical condition such as fibromyalgia the brain fog is a continuous symptom. The brain fog often does not improve even after treatment or control of their disease.  For example brain fog related to chemotherapy has been reported to last up to 15 years after completion of chemotherapy. (Orchard, 2017) This is in contrast to when it is from the “transient” causes listed below, which is typically resolved when you remove the cause.

The potentially “treatable” or “transient” causes of brain fog symptoms:

  •  Thyroid problems (both hypo and hyperthyroid)
  • Anemia (low red blood cell count)
  • Hypoglycemia (low blood sugar)
  • Vitamin deficiencies (Vit. B12, Vit. D, magnesium, etc.)
  • Food allergies/sensitivities (gluten, wheat, dairy, casein, etc.)
  • Chronic infections/molds/toxins
  • Gut dysfunction (leaky gut)
  • Medication side effects
  • Sleep problems (insomnia, obstructive sleep apnea)

Things that can worsen the symptoms of brain fog include:

  • Stress
  • Difficult mental tasks
  • Exercise
  • Fatigue
  • Lack of sleep

What is the underlying cause of brain fog?

The short answer is no one knows for sure.  Two potential causes that I discovered thru my review of the literature are neurogenic inflammation and mitochondrial dysfunction.

Neurogenic inflammation:

Inflammation of the brain (neurogenic inflammation) has been implicated in many neuropsychiatric diseases including migraine headaches, fibromyalgia, chronic fatigue syndrome, depression and multiple sclerosis.  Neurogenic inflammation is also thought to be involved in the pathogenesis of brain fog. (Theohariedes, 2016) (Orchard, 2017) A simplistic way to think about this inflammation in the brain is that it causes slowing of the neurons in the brain, kinda like potholes in the road would cause.  When there are a lot of potholes on the road, you have to slow down, and you are not able to go as fast as the speed limit.  When there is too much inflammation in the brain, the brain is not able to go full speed, and the symptoms that you might experience is brain fog.

Dysfunctional Mitochondria:

The function of the mitochondria is to produce energy (ATP) for the body.  Many chronic degenerative neurological diseases have abnormalities in the mitochondrial functional as an underlying cause. This includes migraine headaches, Alzheimer’s dementia, Parkinson’s disease, multiple sclerosis and chronic fatigue syndrome. Research indicates that mitochondria dysfunction may not only be an underlying cause of these diseases but also may be the cause of the fatigue that is also seen these disorders.  When the mitochondria are not functioning well, they will produce decreased amounts of ATP.  It is believed that this lack of ATP in the muscles, from the dysfunctional mitochondria, is the cause of the generalized fatigue.  Just as the fatigue in the muscles is due to dysfunction of the mitochondria in the muscles, the brain fatigue or fog may be due to the dysfunction of the mitochondria in the brain.  (Myhill, 2009) 

Treatment options:

Currently, there are not any recommended treatment guidelines for brain fog.

Standard medical treatment typically starts with medications:

1.    Often medications are tried to optimize the treatment of the underlying medical condition that it is associated with.  Such that patients that have migraine headaches; the treatment approach would be to optimize the treatment to help prevent headaches or treated the migraines more effectively.

2.    The use of stimulants and antidepressants

Conservative treatment

  1. Remove any underlying causes of  the “treatable causes” listed above
  2. Improve sleep
  3. Vitamin supplementation (Vit B12, thiamine, magnesium, Vit D, omega-3 fatty acids, exogenous ketone supplement)
  4. Dietary changes:
    1. Increase healthy fats such as omega-3 fatty acids and decrease sugars: Based on research in cancer patients and animal models it has been shown that increasing omega-3 fatty acids during chemotherapy decreases neuroinflammation and improves the complaints of brain fog.  Eating a diet high in sugars however caused increased inflammation and worsened cognitive function.  Thus increasing Omega-3 fatty acids (both EPA and DHA) and eating a low carb diet may be beneficial.(Orchard, 2017)
    2. If those treatments have not helped then the next step, I would recommend is not only eating low carb but also considering being on a ketogenic diet or taking exogenous ketone supplements*.  Ketones have not only been shown to decrease inflammation but also improve mitochondria function.(Achanta, 2017) Clinically people who are in ketosis (either nutritionally from diet or from taking supplements) have reported less brain fog, better mental focus, and increased energy.

Bibliography

Achanta, L. (2017). Beta-hydroxybutyrate in the brain: One molecule, multiple mechanisms. Neurochemical Research, 42, 35-49.

Myhill, S. (2009). Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med, 2, 1-16.

Ocon, A. (2013). Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome. Frontiers in Physiology, 4 (63), 1-8.

Orchard, T. (2017). Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits. Breast Cancer Res Treat, 161, 391-398.

Raffa, R. (2011). A proposed mechanism for chemotherapy-related cognitive impairment (‘chemo-fog’). Journal of Clinical Pharmacy and Therapeutics, 36, 257-259.

Ross, A. (2013). What is brain fog? An evaluation of the symptoms of tachycardia syndrome. Clin Auton Res, 23, 305-311.

Theohariedes, T. C. (2016). Mast cells, brain inflammation, and autism. European Journal of Pharmacology, 778, 96-102.

*The Food and Drug Administration has not evaluated these statements.  These products are not intended to are not intended to diagnose prevent treat or cure any disease.  If you are under medical supervision for any allergy, disease, taking prescription medications or you are breastfeeding contact your medical provider before adding any new supplements to your daily regimen.

The medical information on this site is provided as an information resource only. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.

AAIC breaking news

The Ketogenic Diet Improves Cognitive Function

AAIC breaking news

Breaking NEWS!

The Ketogenic Diet Improves Cognitive Function

The first trial using the ketogenic diet (KD) in patients with Alzheimer’s disease was presented at the 2017 Alzheimer’s Association International Conference. It was presented in a session of the Conference that was dedicated to the potential benefits of ketones called: Brain Ketone Metabolism, Ketogenic Interventions, and Alzheimer’s disease.

As discussed in another blog post, it is known that in Alzheimer’s disease, the brain loses its ability to uptake and use glucose. This decreased glucose utilization results in decrease energy (ATP) production, causing an energy deficit in the brain. It is believed that this energy deficit then increases the risk of neuronal dysfunction and cognitive decline. Specifically, it has been shown that patients with early Alzheimer’s disease have 20-30% less glucose uptake and utilization in certain areas of the brains compared to cognitively normal older adults. Research by Dr. Cunnane has shown that the uptake and utilization of ketones are the same in brains of patients with Alzheimer’s disease compared to the brains of cognitively normal older adults. (Cunnane, 2016)

This research by Dr. Cunnane shows that the even the areas of the Alzheimer’s brains that had decreased uptake of glucose had normal uptake of ketones. The implication of this is that the neurons themselves are not dead just not able to use glucose. The hope is that ketones can help improve cognition by improving this brain energy deficit. This was the basis of the KU Alzheimer’s Disease Ketogenic Diet study. The objection of the study was to see if by changing the fuel source from glucose to ketones thru the KD, would result in improvement of cognitive symptoms in patients with Alzheimer’s disease.

The KU Alzheimer’s Disease Ketogenic Diet Feasibility and Retention Trial

The KU Alzheimer’s Disease Ketogenic Diet Feasibility and Retention Trial involved 15 patients with a diagnosis of mild Alzheimer’s disease. The 15 patients were placed on the KD and an additional triglyceride supplement for 3 months. The degree of ketosis was measured thru urine and plasma ketone levels. Cognitive function tests were assessed at baseline, at the end of the 3 months, and then a month later after back on a regular diet.

Out of the 15 patients, 5 were able to unable to achieve ketosis and dropped out of the study. The 10 that were able to get into ketosis and remain on the diet for 3 months, showed an improvement in cognitive function of 4.1 points on the Alzheimer’s Disease Assessment Scale-Cog (ADAS Cog) score. After returning back to a standard diet, the scores then dropped back down to their baselines values.

The author of the study, Dr. Swerdlow, was noted to say: “As far as Alzheimer’s studies go, a 4 point improvement in the ADAS Cog score is fairly robust.” “It suggests a meaningful improvement in cognition.” “It is greater than that seen in the cholinesterase inhibitors studies.” (Hughes, 2017)

Data from this study support the need for further studies of KD in Alzheimer’s disease. The intervention was well tolerated without serious adverse event. The main limitation of the study was adhering to the KD. (Swerdlow, 2017)   Dr. Swerdlow noted that the KD is not an easy diet to be on, and potentially an easier way to get ketones to the brain may be with supplements, which does not require such a strict low carbohydrate diet.

 

Bibliography

Cunnane, S. C. (2016). Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health During Aging and the Treatment of Alzheimer’s Disease. Frontiers in Molecular Neuroscience, 9, 1-21.

Hughes, S. (2017, August 03). Boosting Brain Ketones Metabolism: A New Approach to Alzheimer’s. Medscape Medical News.

Swerdlow, R. (2017). The KU Alzheimer’s Disease Ketogenic Diet Feasibility and Retention Trial: Results from a Pilot Study. Alzheimer’s Association International Conference.

 

The medical information on this site is provided as an information resource only. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.

 

Are you ready to experience BETTER?

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Ketones are the preferred fuel source for our brains

What is Ketosis?

Like most people, I did not know what ketosis was or whether having ketones in the body was a good thing or not. Ketosis by definition is the just the state of having ketones in our body. Since most of us have always eaten a carbohydrate-based diet, which uses glucose as the main fuel for our brains to run on, we did not know there was anything different. However, recently I have done a lot of research and found a huge body literature supporting the multiple benefits of having ketones in our bodies and using it for fuel instead of glucose.

I recently had the honor to listen to Dr. Stephen Cunnane, one of the leading researchers on nutrition and brain development, speak on his research about ketones as fuel for the brain. I have a few takeaways from that talk and from his recent article, published in Frontiers in Molecular Neuroscience that I would like to share to, hopefully, help show that having ketones in our bodies is indeed a good thing

Ketones are the preferred fuel source for the brain

It has been known since the 1960s, that ketones are the alternative fuel source, instead of glucose, for the brain. Dr. Cahill at that time showed that the liver would produce ketones when glucose levels were low, as a way of survival during times of fasting or starvation.

The amount of ketones that are taken up into the cells of the brain is directly related to the number of ketones that are present in the blood. Such that, the more ketones that are present in the blood, the more ketones will be taken up into the brain to be used. This is different than glucose, which is pulled into the brain cells based on the brain’s energy needs. Glucose also requires the presence of insulin to open the door for glucose to get into the cells (which is an issue in some neurological disorders such as Alzheimer’s Dementia).

In adults, the liver only produces ketones when glucose supplies are low, so ketones and glucose have not been available at the same time. Now that exogenous therapeutic ketones have been developed, your body can actually have ketones present even when glucose is also around. Thus, the body potentially now can have two different fuel sources in the body at the same time. So which one does the brain prefer? Dr. Cunnane researched just that question, and with the use of PET scans to show the amount uptake of glucose and ketones in the brain. He found that that amount of glucose utilization in the brain decreases as the availability of ketones to the brain increases. I.e. if the energy needs of the brain are being meet by ketones, glucose uptake decreases. Thus when ketones are around, they are actually the preferred energy substrate for the brain.

Ketones are essential to the developing infant’s brain

Ketones are essential to the developing infant. In the neonatal brain, there is insufficient glucose available to meet the very high-energy needs of the growing brain thus; it must rely heavily on ketones for fuel. Ketones are not only needed as a fuel but they are also the main substrate needed for brain lipid synthesis (brain development). Even after the infant is born the infant’s brain relies on ketones for fuel. Thus, the infant remains in a sustained state of ketosis. This ketosis is not a function of food restriction (or low glucose levels) but is due to the medium chain fatty acids (MCFAs) that are supplied from the breast milk (and some formulas). The MCFAs are then stored in the infant’s adipose tissue. After breastfeeding ends, the adipose tissues provide will enough fats for ketones to be produced for many months.

So, in summary, being in ketosis is very natural. It is the body’s way to be protective of our brain during times of starvation or fasting. It is also probably also the diet of our ancestors. It is also a very natural state since we are born in ketosis and with breast milk stay in ketosis throughout infancy. Lastly, our brain actually prefers ketones over glucose. Are you ready to see how good your brain feels with it is fueled with ketones?

Got ketones drdebbrain

Bibliography

Cunnane, S. C. (2016). Can Ketones Help Rescue Brain Fuel Supply in Later life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease. Frontiers in Molecular Neuroscience , 9, 1-21.
The medical information on this site is provided as an information resource only. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.
PET_Normal_brain

Can ketones be used as an alternative fuel source in the Alzheimer’s brain?

Can ketones be used as an alternative fuel source in the Alzheimer’s brain?

Dementia is a progressive neurological disorder resulting in a decline in cognitive function that interferes with daily activities. The most common cause of dementia is Alzheimer’s Dementia (AD). There is currently no treatment for AD and the cause of AD is still unknown. One thing that is well established, is that there is deteriorating brain glucose utilization, both uptake and metabolism, in the Alzheimer’s brain. This is based on decades of research looking at glucose uptake in brains using PET scans. These studies have shown a 20-25% global decreased brain glucose utilization compared to normal age related controls. (See picture below) This decreased glucose utilization is localized regionally in the parietal, posterior cingulate and temporal cortex of the brain. This pattern of decreased utilization is relatively specific to AD compared to other forms of dementia and normal aging itself and is used to help diagnose people who have AD. In the past this pattern of decreased glucose utilization seen in patients with AD, generally, was believed to be a consequence of neuronal cell death.

alzheimers-PET ok

Recent evidence now reveals that this brain energy deficit is present long before the clinical diagnosis or even before the symptoms of AD start. Specifically, glucose utilization has been shown to be 9% lower in cognitively normal individuals older than 65 years of age compared to younger cognitively normal individuals. The glucose deficit is also present in adults who are less than 40 years of age who have genetic or lifestyle risk factors for AD, even before having cognitive symptoms. For example young women who have polycystic ovarian syndrome (PCOS) have been shown to have decreased brain glucose utilization deficit similar to what would be seen in people in their 70s and 80s. PCOS patients have mild insulin resistance, which is associated with an increased risk of AD. Is it plausible then that this deficit of brain glucose utilization may exacerbate or may even be the cause of, instead of the consequence of neuronal loss in AD. One theory proposed is that it is a vicious cycle in decreased glucose utilization that then causes deteriorating neuronal function, which then results in a higher demand for glucose, with the eventual emergence of cognitive decline.

So what if there is another fuel that the brain can use other than glucose?

Dr. Cahill showed in the 1960s that ketones are the main alternative fuel source/energy supply for the brain as a way to protect the brain in times of starvation. It is also known that  infant rely on ketones as the main fuel source due to the metabolic stresses that occur with the rapidly growing infant brain. (see prior blog post) So if the human species relies on ketones to confront these energy challenges why couldn’t it work for the aging or Alzheimer’s brain?

It is has been shown that the brain uptake of ketones is proportional to the plasma ketone levels, but does this change in the aging brain or AD brain? Dr Cunnane looked at just this question. He used PET studies to show that the brain uptake of ketones is the same in patients with AD as compared to age matched cognitively healthy controls. The brain ketone utilization in AD was proportional to the plasma concentration and was the same as age matched controls. I repeat, the areas of the brain that showed decreased glucose utilization in the Alzheimer’s brain had normal uptake and utilization of ketones. This, to me is very exciting! As a neurologist I have always believed that decreased glucose utilizations in patients with AD, was a sign that those brain cells were dead. This data by Dr. Cunnane, however, shows that those cells are just not able to use glucose but can use ketones, thus are NOT dead.

So then would fueling the body with ketones be a potential treatment option of AD?

Babies are born into ketosis and stay in ketosis because the breast milk contains medium chain fatty acids which are rapidly absorbed and transformed quickly into ketones.  Coconut oil is another medium chain fatty acids. When medium chain fatty acids such as coconut oil are added to the diet in patients with AD, cognitive benefits have been shown. Clinical trials using ketogenic interventions in AD have also shown improvement with cognitive function. (see prior blog post) This suggests that interventions that increase ketone levels may have beneficial therapeutics in patients with AD and deserve further study.

The take home message, to me is: there is an impairment of glucose uptake and metabolism in the brain in patients with Alzheimer disease (AD). However, the brain uptake of ketones remains the same in AD as compared to healthy controls. There for interventions that increase ketones availability, either with a ketogenic diet or ketone supplements may help improve the energy deficits seen in the AD and aging brain. Though we do not know if there will be clinical benefits without further study.  Isn’t worth a try?

 

Bibliography

Cunnane, S. (2011). Brain fuel metabolism, aging, and Alzheimer’s disease. Nutrition, 27, 3-20.
Cunnane, S. C. (2016). Can Ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease. Annuals of the New York Academy of Science, 1367, 12-20.
Cunnane, S. C. (2016). Can Ketones Help Rescue Brain Fuel Supply in Later life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease. Frontiers in Molecular Neuroscience, 9, 1-21.
The medical information on this site is provided as an information resource only. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.
broken-brain

Treating Concussions with Ketones

broken-brain

What is a Concussion?

Head injury, whether it is from a concussion or a severe traumatic brain injury, can have long term and serious consequences. Concussions are typically described as mild traumatic brain injury. Concussions are most commonly occur from sports related injuries, such as from being tackled in football, to hitting a soccer ball off of head, or falling off a bicycle. In the US, there is estimated between 1.6 to 3.8 million sports related concussions that occur every year. The rates for concussion are highest in pediatric and adolescent age ranges. Even though concussions often do not cause structural damage to the brain, they still can causes significant symptoms. Headaches are the most common symptom seen with a concussion, but other post concussion symptoms include problems sleeping, impaired memory, dizziness, balance problems, attention problems and depression. These symptoms can last from weeks to months and in some cases even longer. (Giza, 2014)

Concussions have come to the forefront of pubic awareness with the recently discovered disease, chronic traumatic encephalopathy, which was the topic of the movie ‘Concussion’. Chronic traumatic encephalopathy (CTE) is the neurodegenerative changes that occur in the brains of individuals who have sustain multiple concussions earlier in their lives. CTE results in long-term neurological symptoms including behavioral, cognitive and motor symptoms.   The behavioral symptoms include depression, mood swings, aggression and possibly suicide. The cognitive deficits can range from memory problems to dementia. The motor symptoms vary from parkinsonian tremors to ataxia and even possibly a motor neuron disease. (Jordan, 2014)

What is the treatment of concussion?

Currently, there is no medical treatment for concussion except supportive measures. Other than the prevention of concussion in the first place, there is no medical ways to prevent it from progressing into CTE.

What is the pathobiology of concussion?

The underlying pathobiology of concussion has been well described. The shaken brain causes a disruption of the cellular membranes. This then causes a release of chemicals; potassium to flow out of the cells and calcium to flow into the cells. This triggers a cortical spreading depression of the neurons, which then results in the release of glutamate from the cells. The brain needs energy, or ATP to reestablish a balance or homeostasis of these chemicals. ATP is produced in the mitochondria of the cell after the uptake of glucose thru the process of glycolysis.(Giza, 2014)

Immediately after the brain injury there is then a transient increase in glucose uptake, followed by a prolonged decreased in glucose uptake and decrease glycolysis. This impairment in glucose uptake and glycolysis results in an over decreased in ATP production. This time of energy crisis or metabolic dysfunction of the brain is variable, ranging from days to months, depending on severity of injury and age of the brain.(Prins, 2104) Other changes that are occurring in the brain during this time include; increased glutamate excitotoxic damage and increased free radical production. During this time of metabolic dysfunction the brain is felt to be more vulnerable to a second injury. (Giza, 2014)

Is there an alternate fuel source that can be used?

Ketones are the only known natural alternative of glucose that can be used for cerebral energy metabolism. The advantage of using ketones is that they produce ATP thru beta- oxidation not thru glycolysis. Thus ketones are able to bypass the glucose metabolic derangements that are seen associated with brain injuries. ATP supply is also increased from mitochondria biogenesis that is seen with ketones. (Streijger, 2016) In the injured brain, ATP stores have been to be restored after administration of a ketone, beta-hydroxybutyate. (Prins, 2004) Ketones may also benefit the injured brain by their antioxidant effect, ability to increase the antioxidant glutathione and reduce free radical production. (Gano, 2014) Ketones also have been shown to protect cells against glutamate-induced neurotoxicity. (Ziegler, 2003) Hence, using Ketones as an as alternate fuel source instead of glucose, as therapeutic treatment of head injury is appealing.

How does this translate clinically?

There have not been any trials, as of yet, in humans. In studies using adolescent rats, the ketogenic diet has been shown to improve outcomes both with cognitive and motor function, following traumatic brain injury.   When the rats are pretreated with ketogenic diet they were found to have 58% less cortical injury volumes and better neuronal preservation. (Streijger, 2016)

For maximum neuroprotective effects, it is best to be in a state of ketosis (a state where the body is producing ketones) prior to any brain injury. The next best is to start it as soon as possible after the injury. Typically, if you start a ketogenic diet, it may take a while, up to several days, before you will be in ketosis. Another option, which can be used either in place of, or in addition to a ketogenic diet, is to use a ketone supplement. This supplement will get your body in the state of ketosis in less than 60 minutes. This supplement is not currently FDA approved for the treatment of concussion or other diseases. However, the researchers, who are currently using this supplement in research studies for concussion and head injury, are very excited about its potential. They currently recommended it for anyone who plays contact sports and are discussing potential uses in college and profession sports.

protect-brain-football

Bibliography

Gano, L. (2014). Ketogenic Diet, mitochondria, and neurological diesases. Journal Lipid Research, 55, 2211-2228.
Giza, C. C. (2014). An Introduction to Sports Concussions. Continuum Lifelong learning in Neurology, 20 (6), 1545-1551.
Jordan, B. (2014). Chronic Traumatic Encephalopathy and other long-term sequelae. Continuum, lifelong learning in Neurology, 20 (6)1588-1604.
Prins, M. (2004). Increased cerebral uptake and oxidation of exogenous BHB improves ATP following traumatice brain injury in adult rats. Journal of Neurochemistry, 90, 666-672.
Prins, M. M. (2014). The collective therapeutic potential of cerebralketone metabolism in traumatic brain injury. Journal of Lipid Research, 55, 2450-2457.
Streijger, F. (2016). Ketogenic Diet and Ketones for the Treatment of Traumatic Brain and Spinal Cord Injury. In S. Masino (Ed.), Ketogenic Diet and Metabolic Therapies (pp. 133-146). Oxford.
Ziegler, D. (2003). Ketogenic diet increases glutathion peroxidase activity in rat hippocampus. Neurochem Res, 28, 1793-1797.
parkinsons-word-brain-get-fit

Ketones and Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Parkinson’s disease is a progressive neurodegenerative disorder, characterized by tremors, slowness of movement, rigidity and problems with balance. These symptoms are believed to be due to the degeneration of the dopaminergic neurons in the substantia nigra. The mechanism of this neurodegeneration in PD remains unclear. (Masino, 2016) Currently, there is only symptomatic treatment.  There are no treatments available currently for delaying or preventing this neuronal damage that causes PD.

parkinsons-word-brain-get-fit

One of the potential theories of what causes this degeneration of the substantia nigra, is from mitochondrial dysfunction, specifically, impaired complex I activity of the electron transport chain.(VanItallie, 2005) Impairment of the mitochondrial results in decreased energy (ATP) production. As with most neuro-degenerative disorders there is probably also a component of  increased inflammation. (Masino, 2016) Another theory is that there is increased oxidative stress. (Shaafi, 2015) This increased oxidative stress is from increased levels of reactive oxygen species.  The antioxidant Glutathione is also decreased levels in patients with PD.(Cheng, 2009)

The ketogenic diet (KD) has been used for treatment for drug resistant epilepsy since the 1920s. There is  mounting research that ketones are neuroprotective thus ketones and the KD are increasingly being studied in a number of other neurological disorders; including Alzheimer’s dementia, ALS, autism, cancer, stroke, traumatic brain injury and even Parkinson’s disease. (Gano, 2014)   Ketones are produced naturally from the liver under conditions of sustained low glucose levels, such as times of starvation or when on a ketogenic diet. The ketogenic diet is a high fat, low carbohydrate diet that metabolically shifts the body from using glucose to ketones as it main source of fuel. When present, ketones are the preferred fuel source for the brain. (Cunnane, 2011)

Ketones have several benefits that are potentially neuroprotective.  One of the potential neuroprotective benefit of ketones in PD is from the improved energy (ATP) production. There are three different ways that using ketones instead of glucose as a fuel result in more ATP. First of all ketones have been shown to bypass the blocked pathway in the mitochondria that is damaged in PD, thus the previously damaged mitochondria are now able to produce ATP. (Gano, 2014) Secondly, ketones have also been shown to actually stimulate new mitochondrial to form.  (Gasior, 2006)  Lastly, ketones are a more efficient source of energy (produce more ATP) per unit of oxygen compared to glucose.

Another potential neuroprotective benefit of ketones is from the anti-inflammation and anti-oxidant effects of ketones. This has been shown in several different animal model of PD. One study looked at mice, which were treated with the neurotoxin MPTP. MTPT causes a neurodegeneration of the dopamine neurons similar to what is seen in PD. The mice which were treated with KD prior to injection with MPTP, were shown to have had decreased pro-inflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) levels in the substantia nigra. Importantly, this resulted in preserved levels of dopamine and protection against the motor dysfunction typically caused my MPTP. (Yang, 2010)

In another study using the rat model of PD induced by 6-OHDA also showed neuroprotective effects of ketones. The KD pretreated rats were found to have the dopaminergic neurons of the substantia nigra protected from the neurotoxicity of the 6-OHDA. The researchers felt that this was possibly due to decrease oxidative stress. They found less ROS and increased level of the antioxidant glutathione in the rats on the KD compared to those on normal diet. (Cheng, 2009)

So does this improved ATP production, decrease inflammation and decreased oxidative stress correlate with clinical improvement? A recent study looked just at that. In the PD model of rats, the rats feed a KD had improved motor function compared to rats feed a normal diet. (Shaafi, 2016)

So the next question then is, how does this translate clinically in humans with PD? To date there is only one small human study, that I am aware of. This study placed 7 PD patients on a KD, 5 of which remained on the KD for 28 days. Those 5 patients had on average a 43% reduction of their Unified Parkinson’s Diseases Rating scale. The clinically improved symptoms included: resting tremor, freezing, balance, gait, mood and energy level.(VanItallie, 2005)

In summary, animal studies, when exposed to neurotoxins that would typically cause PD, showed that ketones resulted in decrease inflammation, decrease ROS, and increase ATP production compared to animals on standard diets.  These findings correlated with improved dopamine levels and improved motor function.   There, however is limited data on how this translates to clinical benefits in PD patients.  The one study using the KD in PD patients has encouraging results, but more studies are needed.

Currently one of the limitation is that the KD is very hard to stick with.  Luckily there is another way to get into ketosis;  the use of *ketone supplement.   This supplement, which is a blend of ketone salts, that puts your body into a state of therapeutic ketosis within 60 minutes of drinking it without having to be on a strict ketogenic diet. Now, this ketone supplement is not an approved treatment by the FDA for treatment of PD or any other disease. However, based on what the research suggests for PD and other neurological conditions, if something as simple as drinking this supplement could help, why not give it a try?

a-new-fuel

Bibliography

Cheng, B. (2009). Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson’s disease. Brain Research , 1286, 25-31.
Cunnane, S. E. (2011). Brain fuel metabolism, aging and Alzheimer’s disease. Nutrition (27), 3-20.
Gano, L. (2014). Ketogenic diets, mitochondria, and neurological diseases. Journal of Lipid Research , 55, 2211-2228.
Gasior, M. (2006). Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioral Pharmacology , 17, 431-439.
Masino, S. A. (2016). Ketogenic Diet and Metabolic Therapies. (S. A. Masino, Ed.) Oxford.
Shaafi, S. (2015). Modulatory role of ketogenic diet on neuroinflammation; a possible drug naive strategy to treatment of Parkinson’s disease. Advances in Bioscience and Clinical Medicine , 3 (4), 43-47.
Shaafi, S. (2016). The efficacy of the ketogenic diet on motor functions in Parkinson’s disease: A rat model. Iranian Journal of Neurology , 15 (2), 63-69.
VanItallie, T. (2005). Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study. Neurology , 65, 728-730.
Yang, X. (2010). Neuroprotective and Anti-inflammatory Activities of Ketogenic Diet on MPTP-induced Neurotoxicity. Journal of Molecular Neuroscience , 42, 145–153.
*These products are not intended to are not intended to diagnose prevent treat or cure any disease. If you are under medical supervision for any allergy, disease, taking prescription medications or you are breastfeeding contact your medical provider before adding any new supplements to your daily regimen.
The medical information on this site is provided as an information resource only. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.

Exercise to prevent Alzehimer’s dementia

Dementia is a defined as a cognitive decline resulting in a decline in daily function. The most common cause of dementia is Alzheimer’s Dementia (AD). In the United States there are over 5.3 million people in the United States who have AD. This number is estimated to triple by 2050. The main risk factor for developing AD is aging. The majority of other major risk factors including diabetes, obesity, and physical inactivity, are potentially modifiable thus we have control over. (Barnes, 2011)

Out of all the risk factors physical inactivity may have the largest impact on prevention of AD. It has been estimated that over 1.1 million cases of AD are potentially attributable to physical inactivity.(Barnes, 2011) Such that those who engage in the highest physical activity have been estimated to have a decreased risk of AD by 45% compared to lowest physical activity category. (Hamer, 2009)

Exercise has indirect effects of improving your brain by improving health conditions that are also risk factors for AD. Specifically exercise results in weight loss that then decreases risk of obesity. Diabetes and hypertension are also improved with exercise. Improvement in these health conditions, then, potentially may result in a decrease risk of strokes.

Epidemiological studies have shown that increased lifetime engagement in physical activity can reduce the risk of developing dementia in cognitively normal elderly persons. (Taafee, 2007) Specially, moderate activity during mid-life is associated with 39% decreased risk of developing mild cognitive impairment (which is one of first stage of AD). The good new is that even starting an exercise program later in life is also associated with a 32% lower risk for mild cognitive impairment. (Bherer, 2013).

Evidence is also growing that exercise may not only reduce the risk of dementia but also have some benefit in improving memory as we age and if you already have dementia. Exercise has been shown to preserves memory, processing speed, and executive function that typically decline with age. (Bherer, 2013) Exercise in patients with dementia overall has a positive effect on cognitive function based on a meta- analysis of 18 randomized studies. (Groot, 2016) Exercise also improves balance, mobility and thus reduced the risk of falls.

The beneficial effects of exercise are supportive by the brain imaging research that has been done. These studies have noted a decrease rate of the shrinking of brain in those who have higher aerobic fitness levels. Also shown is that the area involved in memory, the hippocampus, has a larger volume with exercise. (Kelly, 2014)

How exercise is believed to result in these changes are of course not completely know. Things that are believed is that exercise has neuro-protective effects on the brain. One of the main factors believed to be contributive to age related diseases and AD is oxidative stress mediated by reactive oxygen species. Exercise has been shown to decreases reactive oxygen species and increases the activity of antioxidant systems.   Exercise also increases a neuropeptide, brain derived neurotropic factor (BDNF) that helps to promote neurogenesis in the hippocampus. (Radak, 2010) (Bherer, 2013)

How much exercise is needed? To reduce risk of cognitive decline in cognitively normal persons over the age of 65 the World Health Organization recommends: A weekly minimum of 150 minutes of moderate intensity aerobic activity or 75 minutes of vigorous intensity aerobic activity. (Groot, 2016) I would also recommend adding some muscle strengthening exercises to help improve strength. To help prevent falls consider adding in some yoga or Tai Chi to help with balance.

 

Bibliography

 

Barnes, D. Y. (2011). The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurology, 10, 819-828.

Bherer, L. E. (2013). A Review of the Effects of Physical Activity and Exercise on Cognitive and Brain Functions in Older Adults. Journal of Aging Research, 1-8.

Erickson, E. E. (2011). Exercise training increases size of hippocampus and improves memory. Proceeding of the National Academy of Sciences of the United States of America , 108 (7), 3017-3022.

Groot, C. E. (2016). The effect of physical activity of cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing Research Reviews , 25, 13-23.

Hamer, M. C. (2009). Physical activity and risk of neurodegenerative disease: a systemic review of prospective evidence. Psychol. Med , 39, 3-11.

Kelly, M. E. (2014). The impact of exercise on the cognitive functioning of healthy older adults: A systemic review and meta-analysis. Aging Research Reviews , 16, 12-31.

Radak, Z. E. (2010). Exercise Plays a Preventive Role Against Alzhemier’s Diease. Journal of Alzheimer’s Diease , 20, 777-783.

Soli, F. (2011). Physical activity and risk of cognitive decline: a meta- analysis of prospective studies. Journal of Internal Medicine, 269, 107-117.

Taafee, D. e. (2007). Physical activity, physical function, and incident dementia in elderly men: the Honolulu-Asia Aging Study. Journal Gerontology , 63 (5), 529-535.

 

 

Ketones as a treatment for seizures

The treatment of recurrent seizures (epilepsy) thru the use of dietary changes, specifically starvation, has been reported since Biblical times. The metabolic benefits of starvation are due to the shift to fat metabolism resulting in ketone body production. Since the ketogenic diet has the same metabolic effects of starvation, it has been used for the treatment of epilepsy first by Dr. Russell M. Wilder from Mayo Clinic, in the 1920s. Dr. Wilder observed a reduction of seizures by 50%. (Keene, 2006)

The diet fell out of favor as anti-seizure medications were developed. Since 1994 there has been a renewed interest in the ketogenic diet after the publicity of a young boy named Charlie who was treated very successfully with the ketogenic diet. He remains seizure free today off medications despite now being off the ketogenic diet.

The anti-epileptic effects of the ketogenic diet have been well studied. It is most commonly used kids with medically intractable seizures. A meta-analysis of the studies that have been performed since 1990 was published in Pediatric Neurology in 2006. This study found 15.6% of the children who were treated with the ketogenic diet for 6 months became seizure free and a third had greater than 50% reduction of seizures. Of significance, is that these patients were intractable, meaning they continued to have frequent seizures despite being on multiple antiepileptic medications before starting the diet.(Keene, 2006) The ketogenic diet is has been shown to be effective for all types of seizure disorders both in kids and adults. What is amazing is that some of the patients treated with ketogenic diet can actually maintain a significant reduction in seizures frequency or remain seizure free even after discontinuing the diet. (Baranano, 2008)

The difficulty with this treatment is not whether the ketogenic diet works but keeping people compliant with it. It is a very rigid diet composed of eating very high fats (as high as 80- 90% fats) and very low carbohydrates (5%). This requires detailed meal planning, prepping, and weighing of foods. If this is not maintained, such that amount of carbohydrates are increased even a slight amount (such as by eating a half of a banana), they will be kicked out of ketosis. Thus losing the anti-epileptic benefits of the ketones until they get back into ketosis, which may take several days.

The anti-epileptic effect of the ketogenic diet is believed to be from the ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) that are produced by the body when on ketogenic diet. Thus the next question is if giving the ketones exogenously, as an oral ketone supplement, would it have the same benefits as the ketogenic diet?

There have been 3 studies using different animal models of seizures. They have all shown that the use of exogenously given ketone bodies has an anti-epileptic effect. One study looked at preventing grand-mal seizures induced by central nervous system oxygen toxicity. (D’Agostino, 2013) Another looked at rats treated with a pro-convulsant agent PTZ. (Viggiano, 2015) The third study used a mouse model that represents human temporal lobe epilepsy. Importantly, this study also documented that the administration of ketone bodies has a direct positive effect, independent of the hypoglycemia. (Kim, 2015)

The mechanisms underlying the anticonvulsant effects of ketone bodies are not completely clear. Research indicates multiple possible mechanisms including thru the neuroprotective properties of ketones. Ketone bodies also have been shown to decrease the release of the excitatory neurotransmitter glutamate and increase the inhibitory neurotransmitter GABA. Others potential benefits include increasing intracellular ATP levels, decreasing reactive oxygen species, and improvement of mitochondrial function.

For more information about the ketogenic diet check out my other blog posts including potential benefits of Alzheimer’s dementia. For more information on a commercially available exogenous ketone supplement click this link.

Please, if you do want to use the ketogenic diet for treatment of your epilepsy make sure you are under medical supervision and do not stop or alter your anti-epileptic medication without the approval of your Neurologist.

Bibliography

Baranano, K. W. (2008). The Ketogenic Diet: Uses in Epilepsy and Other Neurologic Illness. Current Treatment Options Neurology, 10 (6), 410-419.

D’Agostino, D. E. (2013). Therapeutic ketosis with ketone esters delays central nervous oxygen toxicity seizures in rats. Am J Physiol Regul Integr Comp Physiol, 304, R829-R836.

Keene, D. (2006). A Systemic Review of the USe of the Ketogenic Diet in Childhood Epilepsy. Pediatric Neurology (35), 1-5.

Kim, D. Y. (2015). Ketone Bodies Mediate Antiseizure Effects through Mitochondrial Permeability Transition. Annals of Neurology (78), 77-87.

Stafstrom, C. E. (2012). The ketogenic diet as a treatment paradigm for diverse neurological disorders. Frontiers in Pharmacology, 3, 1-8.

Viggiano, A. D. (2015). Anticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure. Brain Research , 50-54.

 

The medical information on this site is provided as an information resource only. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.

Fuel your body with the power of ketones

Ketones are an alternative fuel source for our brain and body.

Our bodies need energy to preform our daily activities. This energy is at the molecular level is called ATP. ATP is produced in the mitochondria of all cells. It however also takes energy to produce ATP. This energy comes from the break down of one of two different fuel sources, glucose or ketones.

  1. Glucose is the broken down to produce ATP by the process called glycolysis
    1. Glucose comes from
      1. Carbohydrates that we eat
      2. The break down of the stored glucose in the form of glycogen
      3. Protein from our diet that break down into amino acids into glycogen then into glucose
  2. Ketones are broken down to produce ATP thru the process called Beta- oxidation
    1. Ketones are formed by the break down of fats.
      1. There are 3 different ketones (ketone bodies):
        1. Acetoacetate
        2. Beta-hydroxybutyrate
        3. Acetone

How can I get into ketosis?

  1. Starvation
  2. Intense exercise
  3. Eating ketogenic diet (70% fats, 20% proteins and 5% carbohydrates)
  4. Adding endogenous ketone supplement

The majority of the US population is currently only fueled by glucose, since the body is not able to tap into the second fuel source of ketones until it has run out of glucose. Our bodies however are designed to use either ketones or glucose as a mechanism to protect our species in times of starvation. Just think about how we lived in the caveman days when there was not any grocery stores or McDonalds on every block.  In the summer and spring when food was plentiful, cavemen would eat more food and pack on and store the extra as fat.  Then in the fall and winter when food was scarce, the cavemen would live off that extra stored fat by switch over from using glucose to ketones as primary fuel source.

The brain actually prefers to use ketones as a fuel when it is available.

There are 3 main reasons why ketones are a better source of energy for your brain.

  1. Ketones produce more ATP than glucose.
  2. Ketones are a cleaner less toxic source of energy since they produce less carbon dioxide and free radicals than when the body uses glucose as a fuel source
  3. Unlike glucose, ketones do not depend on insulin to get into the cells for use.

Are you often fatigued in the middle of the day? Do you have a hard time and need more energy to get thru a busy day at work, a long workout or just for a day of play? If so, instead of reaching for a high calorie candy bar, soda or energy drink, which will cause you to crash in a couple of hours, consider changing your fuel source to ketone based instead of glucose.

 

Hello from Dr. Deb

 

An alternative approach to Neurology

Hello Dr. Deb here. I just wanted to say thanks for liking my Facebook page @ https://www.facebook.com/BrainBodyFitness/. I also wanted to introduce myself to those who do not know me. I am currently 48 years old. I am a wife and a mom of wonderful 2 young girls. I have been practicing neurology for over 18 years. I specialize in headache medicine but still manage all types of neurological diseases including Alzheimer’s dementia, seizures, strokes, multiple sclerosis and Parkinson’s disease. However pain and migraines are the conditions I see the most.

I started this website and my Facebook page because over the years my approach to the practice of medicine and specifically neurology has changed. I previously believed that my job was just to find the right pill for your symptoms. I since have come to the conclusion that sometimes the best medicine is not a pill that I can give, but a healthy life style that you choose for yourself. I have discovered this both thru my patients but also with my personal experience. I too suffer from migraines and depression but since making some changes with exercise and changes my diet to include ketosis I have had significant improvement in my symptoms.

Over the last couple of years I have been doing more and more research on the powers of exercise, nutrition and most recently the benefits of ketones. I will be making a series of videos over the next several of weeks so that I can share with some of what I have learned.  I hope that you will find some value in these videos.

Sincerely,

Dr. Deb