Breaking new IHC 2017

Ketone supplements prevent migraine headaches

Breaking new IHC 2017

Supplementation with BHB salts can decrease migraine frequency by 51%

That was the conclusion of a pilot study presented at the 18th Congress of the International Headache Society. The study looked migraine frequency after a month of supplementation with the ketone body, beta –hydroxybutyrate (BHB).   The participants consisted of four females and one male who had refractory migraines, defined as having an average pretreatment migraine frequency between 6-24 migraines a month.

The BHB supplement, in salt form, was given at a dose of 10 mg twice a day on top of a normal diet. During the one month on the supplement, there was an average reduction of 51% in migraine days compared to baseline. The migraine days per month went from a pretreatment an average of 16.25 day down to 8 migraine days during the month.

Granted this was a small study with only five participants, but the 51% reduction in only one month is impressive. Especially since Topiramate, probably the most prescribed medication for migraine prevention, also showed about a 50% reduction in migraine frequency.

The good news is that there is a BHB salt supplement that is commercially available without a physician’s prescription. Click here to find out more about the ketone supplement.*  For more information on why ketones may be beneficial in patients with migraines please see prior blogs.

Bibliography

Gross, E. (2017). Preliminary Data on Exogenous Ketone Bodies in Migraine Prevention. 18th Congress of the Internation Headache Society, (PO-01-069).

Silberstein SD, (2004). Topiramate in migraine prevention, results of a large controlled trial. Arch Neurol. 61:490–5.

 

*These statements have not been evaluated by the Food and Drug Administration. 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

 

 

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Inflammation, ketones and depression

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New theories on how inflammation may be a cause of depression, and how the ketogenic diet may be a novel treatment option

Depression is the most commonly diagnosed neuropsychiatric disorder, (Chen, 2017) characterized by persistent feeling of sadness, loss of interest and hopelessness. Is it estimated that >16 million people in US have suffered from a depressive episode in the past year, which represents 6.7% of all American adults.

The cause of depression has typically been blamed on a chemical imbalance in the brain, specifically a decrease in the monoamine neurotransmitters (serotonin, noradrenaline and dopamine). Most of the anti-depressant medications work by increasing the levels of these monoamines neurotransmitters. It is estimated that a third of depressed patients treated with these anti-depressant medications however, do not improve. (Miller, 2016) (Yamanashi, 2017) So maybe the pathophysiology of depression is not that simple.

Scientific evidence now suggests that inflammation plays a role in the pathophysiology of depression.

Psychosocial stress is a very common risk factor for the development of depression. Studies have shown that stress, especially early life-trauma, is associated with an increase risk for developing depression. (Miller, 2016) Stress has been shown to cause many pathological changes in the body including increased inflammation. When the body is stressed, the NLRP3 inflammasome is activated. When activated the NLRP3 inflammasome causes the release of the pro-inflammatory cytokines (interleukin 1 beta, interleukin -6 and tumor necrosis factor alpha). These pro-inflammatory cytokines, which are markers for inflammation, have been noted to be significantly higher in the brains of patients with depression and in people who have committed suicide. The amount of inflammatory present correlates to the amount of life stressors that one experiences. This then directly correlates to a higher risk of developing depression. (Miller, 2016)

It is this increased amount of inflammation in the brain that is believed to be the underlying cause of depression. (Yamanashi, 2017) Inflammation may cause depression thru several different mechanisms. First of all, studies have indicated that the inflammatory in the brain causes a decrease in the amount of the anti-depressant monoamines neurotransmitters. Next, high level of inflammatory also results in the increase the amount of glutamate in the brain. Elevated glutamate level in the brain has also been correlated with causing depressive symptoms. (Miller, 2016) Not only does having increased inflammation increase depressive symptoms but also may limit the antidepressant medications from working as well. (Miller, 2016)

So does decreasing the levels of this inflammation result in improvement in the depression symptoms?

The answer is yes. Studies have indeed shown that blocking the release of these inflammatory cytokines can reverse the depressive behaviors induced by stress and the levels of inflammation in the brain. (Yamanashi, 2017) (Miller, 2016) Since the NLRP3 inflammasome is such a critical factor in the development of this inflammation, blocking of this inflammasome is a potential target. Ketones, specifically Beta-hydroxybutyrate (BHB) has been shown to have to exert an anti-inflammatory effect via inhibition of the NLRP3 inflammasome. (Yamanashi, 2017) Ketones are the break down products of fats. They are produced naturally in your liver during times of starvation or while on a ketogenic diet. The ketogenic diet has been used since the 1920s as treatment for neurological disorders such as hard to treat seizures. Many believe that is the benefits of the ketogenic diet are due to the neuro-protective and anti-inflammatory properties of ketones.

To date the benefits of ketones or a ketogenic diet in depression have only been studied in animal models. The first study showed that rats that were pretreated with a ketogenic diet showed less depressive activities compared to the rats on a standard diet. (Murphy, 2004) In 2017, two studies were published using ketone supplementation in animal models of depression. One study by Chen showed that exogenous BHB improved depressive behaviors in mouse models. This improvement was similar to the benefits seen with treatment of the anti-depressant medication imipramine. (Chen, 2017) Another study, using rat models of stress, looked the anti- inflammatory and antidepressant effects of ketone supplementation with BHB. They found that the rats that were pretreated with BHB had less depressive and anxiety behaviors than would typically be seen with stress. Also the amount of inflammation in the brains of the stressed rats was decreased in the BHB treated rats. (Yamanashi, 2017)

Ketones have also been shown to have other benefits that may also help with depression symptoms. The ketone BHB has been shown to increase the levels of brain derived neurotrophic factor (BDNF), which has been shown to be decreased in psychiatric diseases including depression. (Chen, 2017) Additionally, BHB has been shown to decrease the excitatory neurotransmitter glutamate and increase the levels of the calming neurotransmitter GABA. This increased ratio of GABA to glutamate also reduces anxiety. (Ari, 2016)

These animal studies and research suggest that the ketone, beta-hydroxybutyrate, may have an antidepressant effect. So can something as simple as changing your diet, or using a ketone supplement* improve depression? That question in humans has not been formally studied. However wouldn’t it be worth a try? If you would like to give it a try, I will be happy to help.

Your Name: *

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What interests you the most about the ketogenic lifestyle?:

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Bibliography

Ari, C. (2016). Exogneous Ketone Supplements Reduces Anxiety-Related Behaviors in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats. Frontiers in Molecular Neuroscience, 9, 1-10.

Chen, L. (2017). Beta-hydroxybutyrate alleviates depressive behaviors in micepossibly by increaseing the histone3-lysine9-Beta-hydroxybutyrylation. Biochemical and Biophysical Research Communications, 490, 117-122.

Miller, A. H. (2016). The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature, 16, 22-34.

Murphy, P. (2004). The Antidepressant Properties of the Ketogenic Diet. Biological Psychiatry, 56, 981-983.

Yamanashi, T. (2017). Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses. Nature, 7, 1-10.

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.

These statements have not been evaluated by the Food and Drug Administration.  This products is not intended to are not intended to diagnose prevent treat or cure any disease

 

 

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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.
diabetes

Type 2 Diabetes and the ketogenic diet

diabetes

Scope of problem:

The rate of diabetes has been increasing at an alarming rate. In the United States it is estimated that 29.1 million people currently have diabetes. World wide this number is approximately 170 million people, which is expected to reach 366 million by the year 2030. Diabetes is a serious chronic health problem. Having diabetes increases your risk for multiple other medical conditions such as peripheral neuropathy, visual loss, kidney damage, limb amputation, high blood pressure, heart disease, strokes and even Alzheimer’s dementia. People who have diabetes can also have up to 10 years shorter life span than individuals without diabetes. (Westman E. , 2016)

Diabetes 101:

There are two types of diabetes.

  1. Type 1 diabetes, which is also called: insulin dependent or juvenile diabetes. The onset is typically seen in kids. In type 1 diabetes, the body is not able to produce enough insulin.
  2. Type 2 diabetes, which is also called: adult onset or insulin resistant diabetes. Type 2 diabetes is more common, accounting for approximately 90-95% of all cases of diabetes. In type 2 diabetes, the insulin that is present does not function as well. (Al-Khalifa, 2009)

The carbohydrates and sugars that we eat are broken down into glucose causing a raise in blood glucose. When blood glucose increases it causes insulin to be released. Insulin is needed to transport the glucose into the cells so that it can be used. If there is not enough insulin around, or if it does works properly, the body is unable to utilize the glucose as fuel. If the cells are unable to take in the glucose, glucose will build up in the blood or stored as fat. Having high levels of glucose in the blood then can cause damage to the tiny blood vessels in your eyes, kidneys, and nerves.

believe that this rise in obesity and thus diabetes is the direct result of the change in the dietary guidelines that came out in 1977. (DiNicolantonio, 2014) These dietary recommendations, which are still in place today, recommend the Americans should eat less saturated fat along increasing the amount of carbohydrates that we eat. When dietary fats are removed from foods, to improve taste, the fats are replaced with added sugars. Unfortunately this resulted in a huge increase in the amount of sugars that Americans were eating. Which then results in increase risk of obesity. Since obesity is the main risk factor for developing Type 2 Diabetes, the rates of diabetes has also increased. (Westman E. , 2016)

obesity graphDM rates CDC

Treatment of diabetes:

Managing carbohydrate/glucose levels and weight loss is the recommended treatment goal of diabetes. The debate, however, is which diet is the best to do that. A low fat/ low calorie diet is what is most often recommended for patients with diabetes. However, this diet has not been as successful as we would have hoped. Other dietary options include a low carbohydrate/high fat diet, which has been used since the early 1900’s for the treatment of diabetes. The low carbohydrate/high fat diet recently has become more popular since it often associated improved weight loss. (Feinman, 2015) Dating back as far as 1863, Dr. William Banting has been advocating a low carbohydrate/high fat diet has been used for weight loss. (Westman E. , 2016) More recently, studies comparing eating a low carbohydrate diet to low fat diet have shown greater improvements with the low carbohydrate diets on numerous endpoints including, weight loss, abdominal fat loss, glucose levels along insulin levels and insulin resistance. (Volek 2008)

Based on these and other studies showing benefit with a low carbohydrate/high fat diet, a study in 2012 came out comparing a low carbohydrate/high fat ketogenic diet (LCKD) to a low calorie diet in patients with type 2 diabetes. This study showed a beneficial effect of the LCKD over the conventional low calorie diet in patients with diabetes. Specifically they found that those on LCKD had significantly more weight loss and greater improvement in the blood glucose levels and HbA1c levels. The LCKD group also had improvements in the cardiovascular profiles of the cholesterol with significant decrease in triglycerides, total cholesterol and LDL levels whereas the HDL levels were increased. (Hussain, 2012)

Studies have also shown that those eating low carbohydrate ketogenic diet were able to decrease the doses of their anti-diabetic medications. Some were even able to taper off as much as 10 units of insulin per day in eight days, still with maintaining normalization of glucose levels. (Westman, 2008) In some individuals actually able to “reverse” their type 2 diabetes. (Westman E. , 2016)

Thus, as a summary, lifestyle modification that includes reducing carbohydrate intake such as by eating a low carbohydrate/ high fat, ketogenic diet is an effective treatment option in patients with diabetes with the added bonus of weight loss. These changes have also been associated with decreasing the amounts of anti-diabetic medication and insulin, and in some cases being able to get off and medications altogether.   If you have type 2 diabetes and are not currently happy with your control, the fact that you are always hungry and continue to gain weight despite eating a low calorie/high carbohydrate diet, then consider trying a low carbohydrate/high fat diet. What do you have to lose, except some extra weight and possible some medications?

For more information about a ketogenic diet, read my recent blog on ketogenic basics. If you are concerned about what eating ‘all those fats’ might do to your heart, check out my blog on whether a ketogenic diet is safe for your heart. Lastly if you would like some help with the ketogenic diet just fill out the below form and I will try to help.

Your Name: *

Email Address: *

What interests you the most about the ketogenic lifestyle?:

Please leave this field empty.

 

Bibliography

Al-Khalifa, A. (2009). Therapeutic role of low-carbohydrate ketogenic diet in diabetes. Nutrition, 25, 1177-1185.
DiNicolantonio, J. (2014). The cardiometabolic consequences of replacing saturated fats with carbohydrates or omega 6 polyunsaturated fats: Do the dietary guidelines have it wrong? Open Heart, 1-3.
Feinman, R. (2015). Dietary carbohydrate restriction as the first approach in diabetes managment: Critical review and evidence based. Nutrition, 31, 1-13.
Hussain, T. (2012). Effects of low-carie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition, 28, 1016-1021.
Volek, J. (2008). Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Progress in lipid research, 43, 307-318.
Westman, E. (2008). Has carbohydrate-restiction been forgotten as a treatment for diabetes mellitus? A perspective on the ACCORD study design. Nutritional Metabolism, 5, 10, 1-2.
Westman, E. (2016). Ketogenic diets as highly effective treatments for diabetes mellitus and obesity. In S. Masino (Ed.), Ketogenic diet and metabolic therapies (pp. 362-375).

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.

 

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Treating Concussions with Ketones

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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.

Kick Start to a Ketogenic Lifestyle

Are you ready to try a ketogenic lifestyle but do not know where to start? Then it is time for you to join my next “Kick Start to a Ketogenic Lifestyle” private Facebook group.

The research surrounding the medical benefits of a ketogenic lifestyle is impressive including epilepsy, Alzheimer’s dementia, cancer, diabetes and as a natural treatment for inflammation.

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Brain aging and memory loss due to Dementia and Alzheimer's disease with the medical icon of a group of color changing autumn fall trees in the shape of a human head losing leaves as a loss of thoughts and intelligence function.

Can Alzheimer’s disease be treated with ketones?

Brain aging and memory loss due to Dementia and Alzheimer's disease with the medical icon of a group of color changing autumn fall trees in the shape of a human head losing leaves as a loss of thoughts and intelligence function.

The brain’s main fuel source is glucose. However, it has been shown that the brains of people who have Alzheimer dementia (AD) are not able to utilize glucose as well as normal people. When there is not enough glucose to meet it’s metabolic needs, the neurons that work the hardest, i.e. those involved with memory and cognition are the first ones to be compromised and thus show impairment. So the question is: is there another fuel that the brain can use?

The answer luckily is yes! Ketone bodies (KB) or ketones are another fuel source for the brain and the body. Acetoacetate and Beta-hydroxybutrate are collectively known as ketone bodies (KB). KB are normal metabolites that are manufactured by the liver as an alternative fuel for the body and the brain when dietary sources of carbohydrates are in short supply, a process called ketosis. Ketone bodies can be produced in healthy individuals either during times of fasting or by eating a ketogenic diet. The ketogenic diet was first introduced, over 80 years ago, as a dietary treatment of uncontrolled epilepsy in children. The ketogenic diet is diet consisting of high amounts of fat and low amounts of carbohydrates. Other ways of producing ketones nutritionally are by eating high amounts of medium chain triglycerides (MCTG) such as coconut oil repetitively throughout the day.

When ketones are available they are a better fuel source for the brain in patients with AD for several reasons. First of all ketones do not need insulin for uptake into the cell, so it is easier for the brain to get this fuel source compared to glucose. This decrease usage of glucose is visible on brain PET scans, which look at the uptake of glucose. In patients with early AD, there is a 14% overall decrease in the uptake of glucose compared to normal controls. In contrast, when these same patient are placed in brain PET scans looking at the uptake of ketones, the uptake is the same both in the patients with early AD and normal controls.

Other possible theories on way ketones are a better source of fuel for patients with AD is that they are a more efficient source of energy. First of all ketones produce more energy (ATP) compared to glucose. Secondly, the mitochondria, the cells that produce the body’s energy, are believed to be impaired in patients with AD. Ketones, however, are able to bypass the blocked site of the energy pathway, the Krebs cycle, in the mitochondria. This allows the mitochondria to produce energy more efficiently when it is fueled with ketones.

There have been several published clinical studies looking at the effects of ketosis in patients with mild cognitive impairment and AD. The results have shown improved cognitive performance in patients who are in ketosis either from eating a ketogenic diet or from a diet consisting of very high dose of MCTG oils (20- 70 g/day). This improvement in memory was positively correlated the urinary ketone levels, i.e. the higher the level of ketones in the body, the better the cognitive effect.

Even more exciting than the fact that the ketogenic diet has been shown to help memory in people with AD, is that there is also evidence that being in ketosis might also have some disease modifying benefits in AD. In mouse models of AD, a ketogenic diet has been shown to actually improve the pathology associated with AD. Specifically, the mouse brains were found to have less beta- amyloid formation and less phospholated tau protein formation, the neuropathology associated with AD. Ketones have also been shown to have a neuro-protective effect on the hippocampal neurons from both glutamate and amyloid beta toxicity. The hippocampi in rats that are fed a ketogenic diet have also have an increase amount of mitochondria. The neuro-protective effect thus may result from enhanced energy reserves, which improves the ability of the neurons to resist metabolic challenges. Another possibility is that ketone metabolism as compared to glucose metabolism generates less free radicals and lower oxidative stress, thus resulting in improved antioxidant capacity, decrease CNS inflammation, and thus less cell death.

There are potentially 2 problems associated with the ketogenic diet. 1) It is very difficult to adhere to, especially in people who have dementia, who are not self motivated to stick with the diet. 2) Eating a high carbohydrate meal while on the ketogenic diet would potentially throw the person out of therapeutic ketosis and it   may take a day or two to get back in, thus taking several days before seeing any benefits again. Up until now the only other alternative to the ketogenic diet to produce therapeutic ketosis is the repetitive ingestion of high does of MCTG. The problem with it is: the doses high enough to produce therapeutic ketosis are often associated with significant GI side effects. Additionally, taste of MCTG is often difficult to swallow.

Luckily now there is a better way. There is a now a ketone supplement available to the public. This supplement, which is a proprietary blend of ketone mineral salts, 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 AD or any other disease for that matter. However, I am so convinced, based on what the research suggests on what the Alzheimer’s brain needs to function at its optimal level. Along with what the potential benefits of being in the state of ketosis offers, including how it could work for the Alzheimer’s brain that I personally drink it myself and have also recommended it to my parents. Since there is no known cure for AD or proven treatment yet available, if something as simple as drinking this supplement twice a day would help with your memory would you give it a try?

Bibliography

Cunnane, S. C. (2016). Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease. Annals of the New York Academy of Sciences, 1367, 12-20.

Cunnane, S. e. (2011). Brain fuel metabolism, aging and Alzheimer’s disease. Nutrition (27), 3-20.

Gano, L. B. (2014). Ketogenic diets, mitochondria, and neurological diseases. Journal of Lipid Research, 55, 2211-2228.

Gasior, M. e. (2006). Neuroprotective and disease modifying effects of the ketogenic diet. Behavoral Pharmacology (17), 431-439.

Hashim, S. W. (2014). Ketone body therapy: from the ketogenic diet to the oral administartion of ketone ester. Journal of Lipid Research, 55, 1818-1826.

Krikorian, R. E. (2012). Dietary ketosis enhances memory in mild cognitive impairment. Neurobiology of Aging, 425 (e19).

Newport, M. T. (2015). A new way to produce hyperketonemia: Use of ketone ester in a case of Alzheimer’s disease. Alzheimer’s & Dementia, 11, 99-103.

 

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.