Inflammation, ketones and depression


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 a persistent feeling of sadness, loss of interest and hopelessness. Is it estimated that >16 million people in the 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 increased risk of 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 of 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 number 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 breakdown 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 a treatment for neurological disorders such as hard to treat seizures. Many believe that is the benefits of the ketogenic diet are due to the neuroprotective 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 has 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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Ari, C. (2016). Exogenous 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 mice possibly by increasing 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 product is not intended to are not intended to diagnose prevent treat or cure any disease



Got ketones drdebbrain

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


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.
tip for healthy brain

Tips to keeping your brain healthy

8 ways to keep your brain healthy

As  Neurologist I am frequently asked, “what can I take to keep my brain healthy to help prevent Alzheimer’s dementia”.  My answer is that there is no simple pill to keep your brain healthy, but these 8 tips are a great place to start.

  1. Exercise your body: More and more studies are coming out which reinforces what I have long believed, that exercise is the best prescription I can give to prevent Alzheimer’s dementia.
  1. Exercise your brain: Your brain is the most powerful ‘muscle’ of all. If you don’t use it you will lose it!
  1. Keep blood sugars under control: Diabetes increases your risk for Alzheimer’s dementia, as does having high blood sugar levels, in general, even without diabetes.
  1. Consider changing your diet to low carbohydrate high fat diet: A ketogenic diet has been shown to improve brain function, (and it will decrease your risk for diabetes). If you are not ready for that significant of a change, at least start adding more healthier fats into your diet such as: olive oil, DHE, Omega 3 fatty acids and coconut oil.
  1. Keep hydrated, drink more water: You should be drinking half your body weight in ounces of water each day. Example: if you weigh 150 pounds, you should drink 75 ounces of water each day.
  1. Increase your daily intake of antioxidants: Antioxidants help protect your brain from damaging free radicals.  Some common antioxidants include Vitamin C and E along with selenium and flavonoids. The best sources of natural antioxidants are fruits and vegetables.
  1. Decrease stress: If you are unable to limit the amount of stress you have in your life, at least find a healthy way to deal with it. My personal favorite is exercise!
  1. Get more sleep:  Preferably between 7-8 hours per night.



Where is Gluten found? | Food and non-food sources of gluten

Where is GLUTEN found?

Gluten is a protein that is found in wheat, it is the components of wheat that makes it doughy. It is often added to foods to help foods maintain their shape. It is found in many foods but also in some other unexpected places.

Gluten is found in grains such as:

Barley, bulgur, Brewer’s yeast, couscous, farina, graham flour, kamut, matzo, rye, semolina, spelt, triticale, wheat, wheat berries, and wheat germ

There are some grains that are free of gluten:

Amaranth, arrowroot, buckwheat, corn, millet, potato, quinoa, rice, sorghum, soy, tapioca, and teff

Other Foods that contain gluten:

  • Breads:
    • White, wheat, rye, 7 grain, Italian, French, bagels and rolls
  • Pastas:
    • Spaghetti, lasagna, penne, raviolis, dumplings, couscous, and gnocchi
  • Noodles
    • Ramen, soba, chow mein, egg noodles
  • Pastries
    • Croissants, muffins, donuts
  • Crackers
    • Pretzels, goldfish, graham crackers
  • Baked Goods:
    • Cakes, cookies, pie crusts, brownies
  • Cereal & Granola:
  • Breakfast Foods:
    • Pancakes, waffles, French toast, crepes, and biscuits.
  • Breading & croutons:
    • Panko breadcrumbs, stuffing, dressings
  • Sauces & Gravies
    • Traditional soy sauce
    • Cream sauces made with a roux
  • Flour tortillas
  • Beer and other Malt beverages
  • Brewer’s Yeast

Foods that MAY contain gluten:

  • Candy
  • Cheeses
    • Blue Cheese
    • Processed cheese (velveeta)
  • Condiments
    • Salad dressings
    • Marinades
    • Mayonnaise
    • Ketchup
  • Cream filling etc
    • Cheesecake filling
    • Fruit fillings
    • Puddings
  • Dairy products
    • Non dairy creamers
    • Ice cream
  • Drinks
    • Chocolate milk
    • Flavored coffees and teas
    • Instant hot drinks
    • Root beer
    • Vodka
  • Eggs
    • Eggs served at restaurants – some restaurants put pancake batter in their scrambled eggs and omelets. Eggs are naturally gluten-free
    • Egg substitutes
  • Energy bars/granola bars – some bars may contain wheat as an ingredient, and most use oats that are not gluten-free
  • French fries and fried vegetables– be careful of batter containing wheat flour or cross-contamination from fryers
  • Meats
    • Imitation crabmeat
    • Meat substitutes such as vegetarian burgers
    • Meatballs and meat loafs
    • Pre-seasoned meats
    • Processed lunch meats and hot dogs
    • Sausage
    • Self-basting poultry
  • Potato chips
    • Some potato chip seasonings
    • Multi-grain or “artisan” tortilla chips or tortillas
  • Soups, bouillons and broths
  • Starch or dextrin
  • Syrups

Gluten can also be found in nonfood items such as:

  • Cosmetics
  • Lip balm and lip sticks
  • Medications,
  • Non-self-adhesive stamps and envelopes,
  • Play-doh
  • Shampoos/conditioners
  • Toothpastes
  • Vitamins and supplements

Non-Caloric Sweeteners

Non-Caloric Sweeteners,

Friend or Foe?


More and more people have turned to non-caloric sweeteners, in attempts to lose weight or at least, help prevent further weight gains. Questions have been raised about whether or not we are, instead, doing our bodies a disservice?

1.  Can non-caloric sweeteners cause weight gain?

Counterintuitive to what we might think, there is evidence that the use of non-caloric sweeteners may actually be associated with weight gain.  This was first shown in the San Antonio Heart Study. This study-documented weight changes over a 7-8 year period in people who drank beverages sweetened with non-caloric sweeteners compared to those who did not.  They found that those who drank on average 21 beverages sweetened with non-caloric sweeteners per week had about double the risk of being obese.  This was true regardless of the weight of the person at the start of the study.

Another study published in the January 2013 issue of the journal Appetite, found similar findings in rats. In this12 week study rats were fed plain yogurt sweetened with aspartame, saccharin, or sugar in addition to their regular rat chow.  What they found was that the rats that were given either saccharin or aspartame in their yogurt had an increased weight gain compared to rats that were given only sucrose in their yogurt.

2.  Can non-caloric sweeteners increase you risk for type 2 diabetes?

There have been multiple studies that have shown that the consumption of beverages sweetened with non-caloric sweeteners increased the risk for type 2 diabetes compared to non-consumers of beverages sweetened with non-caloric sweeteners.  This was seen even in participants who were of normal weight at baseline.

3.  Can non-caloric sweeteners cause an increase your appetite?

It is unclear why non-caloric sweeteners would cause weight gain and/or increase your risk for diabetes.  One of the theories is that non-caloric sweeteners are felt to increase your appetite.  Experiments have found that the sweet taste, regardless of its caloric content, increases your appetite.  Real sugar tells your brain that it has received enough calories, thus activating satiety signaling and telling your body that you are full.  Non-caloric sweeteners stimulate your appetite by the sweet taste, but your body keeps waiting for the calories to come. When the calories do not come, the sensations of hunger remain.

4.  Are non-caloric sweeteners associated with any side effects?

a. Sucralose (Splenda): has been shown to trigger migraine headaches. It has also showed to increase the incidence of inflammatory bowel diseases possibly due to the decrease in the amount of beneficial gut bacteria as the result of Sucralose consumption.

b.  Saccharin (Sweet’N Low):  has been reported to cause cancers at very high doses.  Between the years 1981 and 2000 the FDA required labeling to warn about possible carcinogenic effects.  Those warnings have since been removed.

c.  Aspartame (NutraSweet and Equal): has possible side effects including dizziness, headaches, GI issues and mood changes.

Aspartame is broken down into phenylalanine (50%), aspartic acid (40%) and methanol (10%) in the body. The excess of phenylalanine from the breakdown of aspartame blocks the transport of important amino acids in the brain contributing to reduced levels of dopamine and serotonin.  Aspartic acid is the precursor to an excitatory amino acid glutamate.  Increased amounts of this and other excitatory amino acids results in increased free radical formations, increased oxidative stress and increased inflammation in the brain. This results in cell death.  These alterations seen are similar to those occurring in neurodegenerative diseases such as Alzheimer’s disease.  Increased inflammation also linked to diseases such as fibromyalgia and other chronic pain syndromes.

It has also been reported that, if stored too long in high temperatures and in a pH above 6, aspartame produces a carcinogenic metabolite – diketopiperazine.  This breakdown product has been reported to cause tumors in the brain including gliomas, medulloblastomas, and meningiomas.

5.  Do ALL non-caloric sweeteners have potential side effects?

Stevia is a natural non-caloric sweetener that is isolated from the plant Stevia Rebaudiana Bertoni.  So far no negative side effects have been reported with its use. Additionally, a study has found that participants who consumed products made with Stevia had lower total caloric intake compared to those consuming sucrose.  Consumption of stevia also lowered postprandial insulin and glucose levels compared to consumption of aspartame and sucrose.

The FDA and most industry-funded studies endorse the safety of these additives. I however have formed my opinion based on these and other studies that I have read.  Based on these studies I have come to the realization that non-caloric sweeteners may not be the best things to be putting into our bodies but if I were going to reach for one maybe a better alternative would be Stevia.


Anton, S. E. (2010). Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite , 55, 37-43.

Fowler, S. P. (2008). Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long-tem Weight Gain. Obesity , 16 (8), 1894-1900.

Rycerz, K. e. (2013). Effects of aspartame metabolites on astrocytes and neurons. Folia Neuropathologica , 51 (1), 10-17.

Shankar, P. P. (2013). Non-nutritive sweeteners: Review and update. Nutrition , 29, 1293-1299.

Swithers, S. (2013). Artifical sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends in Endocrinology and Metabolism , 24 (9), 431-441.


The best foods to eat to prevent dementia

The best foods to eat to prevent Dementia

Unfortunately, there is no pill to prevent Alzheimer’s dementia (AD).  Even the medication that is available for AD does not prevent it or help improve your memory.  The medications just slow down the natural progression of decline in your memory.  So what can you do to help keep your brain healthy?  Well as discussed in an prior post Alzheimer’s Dementia, the best way is a combination of increase physical and mental activity along with healthy eating.  This blog is going to focus on the foods that have been shown to help keep your brain healthy.

It is now known that as your belly grows; your brain tends to shrink.  There is a direct correlation between obesity and the shrinking of the area of the brain that is responsible for memory and recall; the hippocampus.  It has also been found that being overweight doubles your risk of developing Alzheimer’s dementia and being obese will quadruple that risk. So an important goal of eating healthy is for weight loss.  However, being on a brain healthy diet is more than just going on a weight lose diet. It is also about choosing foods that can help keep our brains healthy.

There is scientific evidence that points to certain foods that may promote brain health while others may cause damage and thus should be avoided.

Foods to eat:

  1. Eat foods that are a good source of B and D vitamins.  It has long been recognized that some nutritional deficiencies can cause dementia, specifically, Vitamin B12, thiamine, folate, and most recently Vitamin D
  2. Consume omega 3 fatty acids. Low levels of omega 3 fatty acids have been associated with depression, anxiety, obesity, attention deficit disorder, suicide, and increase risk of Alzheimer’s dementia.  There are three omega 3 fatty acids.  Docosahexaenoic acid (DHA) and eicospentaenoic acid (EPA) which come from fish oils and alpha linolenic acid (ALA) which comes from plant sources.  DHA is the main component of brain synapse and makes up a large portion of the gray matter in the brain. Lower DHA levels are associated with a smaller brain size.  Omega 3 fatty acids reduces inflammation, combats the plaque buildup associated with Alzheimer’s and increases the blood flow to your brain.  Boosting omega 3 fatty acids in your diet is one of the best things that you can do for your weight, mood, brainpower and longevity.
  3. Consume dietary antioxidants.  Antioxidants such as vitamin E, vitamin C, and beta-carotene protect the body and the brain against the destructive effects of free radicals.  Excessive free radical formation causes cell death and tissue damage.  A study done in rats showed that rats who ate a diet rich in blueberries showed better ability to learn new motor skills and gain protection against strokes. There is evidence that that these natural antioxidants activate the brains natural house cleaning mechanisms to clean up the toxic proteins that are linked to age related memory loss and mental decline.
  4. Eat balance portions of protein, carbohydrates, and good fats at each meal.  Having protein at each meal helps to balance blood sugar levels, which can cause “brain fog” from eating simple carbohydrates. Or recently more evidence points to eating a low carb high fat diet.  See more in recent blog post.

One simple way that I am able to get in my all that I need to fuel my body and my brain is by drinking Shakeology.  Besides the benefits of helping you lose weight and reduce craving, Shakeology is also packed with more than 70 of the most nutritious whole food ingredients that your body needs.

  1. There are a total of 13 vitamins that are considered essential for proper body function and Shakeology has them all including Vitamin B1, B12, folic acid, and Vitamin D.
  2. Shakeology also includes short chain omega fatty acids ALA from natural plant based sources of the sachi inchi, chia seed, and flax seed.  However, it is unclear if the ALA gets converted to EPA or DHA so supplementing it with DHA and EPA is still recommended.
  3. It contains some of the most potent antioxidants to help protect the body from free radicals from oxidizing and destroying cells. It also helps support your body’s immune function and promote healthy aging.  The antioxidants in Shakeology include, acai berry, acerola cherry, bilberry, blueberries, cacao, camu-camu, coconut flower nectar, goji berries, pomegranate, rose hips, luo han guo, grape seed, and green tea. Did you know that the American Heart Association and the American Cancer Society recommend eating between 5 and 9 serving of antioxidant rich fruits and vegetables a day; Shakeology meets this recommendation with just one serving.
  4. Shakeology contains about 16 grams of protein and 20 grams of total carbohydrates of which 5 grams is fiber to give you a balanced meal.  Even though it seems to have a high ratio of carbohydrate, it has a low glycemic index averaging 24 (13-46 depending on formulation), which is lower than most fruits and vegetables.  This help to stabilize your sugar and insulin levels and give you the energy your body and your brain needs throughout the day.

“So why can’t I just take a multivitamin that gives some of those nutrients that I need?”  You may ask, well you can. However, unlike some multivitamin pills, Shakeology uses whole food sources of nutrients.  The benefits of using whole food is that the nutrients are preserved as close to their natural state as possible.  This allows your body to better absorb and more efficiently use these nutrients, as intended in nature.

Now I am not saying that drinking Shakeology is going to prevent you from having Alzhemier’s dementia.  Just like the label says: “these statements have not been evaluated by the FDA.”  “This product (Shakeology) is not intended to diagnosis, treat, cure, or prevent and disease”.  However, as a Neurologist I personally drink Shakeology on a daily basis for many reasons, just one of which is to help keep my brain healthy.



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.