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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.

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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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Got Stress?!?

Got Stress?!?

Here something you can do to help!

Now days, who doesn’t? So many things in life can cause stress including work, traffic, kids, family, bills, taxes and watching the news just to name a few. Stress is often sited as a cause of many medical illnesses such as migraine headaches, stomach problems, depression, suppressed immune system, hypertension and heart disease.

It is how you deal with that stress is the important thing. Many people deal with stress by drinking, smoking and overeating thus also increasing the risk of alcohol abuse, lung cancer and obesity. As a physician I encourage my patients to find ways to deal with stress in a non-destructive way. Personally I use exercise to help me deal with my stress. Recently I discovered I had been drinking some natural stress reducers in my health shake, Shakeology.

Shakeology is all natural whole food shake. It contains 70 different super foods, some of which are considered to be adaptogens. Adaptogens are herbs or compounds found in nature that naturally helps your body cope with stress. These adaptogens help maintain balance in your body. For example if you are wired from stress, adaptogens will calm you down. If you are too depleted and lack energy, an adaptogen will lift you back up. Adaptogens also promote a strong immune function by modulating or stabilizing your immune system. If you are sick it will improve your immune response, if you have an autoimmune problem they may help decrease that response. Last but not least, adaptogens naturally help increase your energy.

There are nine different adaptogens blended in Shakeology including; Ashwagandha, Astragalus, Cordyceps, Ginkgo, Maca Root, Maitake, Reishe, Schisandra, and Holy Basil.

Here is some more information on a couple of the adaptogens that are found in Shakeology.

Astragalus root is one of the most potent adaptogen. It is an ancient Chinese herb that has been used for thousands of years for natural therapeutic healing. As an adaptogen, Astragalus root protects the body against physical, mental, emotional stress and promotes a healthy immune system. It is felt to help fight viral & bacteria infections, inflammation, and may even fight cancer. Astragalus is good for people with diabetes since it has also been shown to help maintain normal blood sugar levels. Because it contains high amounts of antioxidants, Astragalus can protect cells against free radical damage. Astragalus also boosts metabolism, endurance and increase energy, which ultimately can lead to weight loss.

Maca Root has been used for centuries to help combat stress and fatigue and increase stamina. As an adaptogen, it may also help support a healthy immune system. Maca root is a nutrient-dense whole food packed with vitamins, plant sterols, dietary fiber, essential fatty acids, minerals (including calcium, magnesium, and iron), as well as 19 of the 22 essential amino acids. Maca Root has a higher amount of calcium than is in milk. The omega acids found in Maca root helps support brain function. Maca root has even been reported to boost libido, improve fertility and decrease menopause symptoms- BONUS!!

So if you also have a life full of stress, put down that margarita and give Shakeology a try. I challenge you to try for a month and find out just how well your body can feel when it is fueled with what it truly needs.

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This information is not intended to replace the advice of a doctor. Shakeology is not intended to diagnose, treat, cure, or prevent any disease or been evaluated by theFood and Drug Administration.