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Burn Ketones or Use Steroids for Inflammation Relief: You Choose.

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If you are using steroids you can trick your body with ketosis to begin burning ketones to relieve inflammation. With the cost of healthcare topping record highs, patients come to the clinic with a list of concerns for each visit.  Seventy-five percent of the time pain ranks first or second in their rankings

When helping patients deal with pain, I can always pull out the big hammer for cutting through a patient’s pain.  The big, in this case, refers to narcotics like morphine or Oxycontin. This hammer comes with the severe drawback of addiction. Patients surrender years of their lives to the setbacks of chronic pain.

Opiate treatment provides relief of their distress but can coax their brain into the swamp of addiction. This sets patients and their families back many years. To avoid this possibility, physicians prescribe anti-inflammatory medications instead.

Anti-inflammatory medications do just what their name says: they work against inflammation.  The most potent medicines to remove inflammation: STEROIDS.

Yes.

Steroids win the medication contest to reverse inflammation. Got a lousy knee filled with arthritis?  Nothing changes that chronic inflammation better than a shot of steroids into the knee joint. Got a hot and angry looking rash? Nothing cools down the flames bubbling inside your skin better than a cream filled with steroids.

Doctors use the power of steroids to put out the flames of many medical problems. These medications arrive onto the scene of inflammation like a bucket of water to a firepit. Splash! The jobs’ done. As with most miracle cures, there’s a catch. These medications work great for the “flash and dash.”  

But if you use steroids for too long, you will weaken your immune system, increase your blood sugars, thin your skin, soften your bones and hijack your mood with a surge of hormones.

The substitute medications for steroids when fighting inflammation: Non-Steroid Anti-Inflammatory medications. You have seen this abbreviated as NSAID–Non-Steroidal Anti-Inflammatory Drugs. Typical examples of NSAIDs are ibuprofen, naproxen, or aspirin.

You don’t need my prescription pad to get these medications. Just hop over to your local pharmacy or gas station and find these on the shelves. These medicines are safe enough to use without the close monitoring of a doctor.

NSAIDs won’t shut down your inflammation as fast or as powerfully as steroids, but they are cheap and readily available.

When I instruct someone to take ibuprofen for an ache or a pain, I teach them that the medication will help their pain for eight hours. When setting expectations about how much improvement they should expect, I tell them it’s like a nickel. Yep – a coin.

They can use that ibuprofen every eight hours and expect a nickel’s worth of improvement. If they need more help than ibuprofen can deliver, we prescribe a steroid such as prednisone. Prednisone lasts for twenty-four hours, and it’s worth fifty cents.

Steroids are ten times more potent than NSAIDs like ibuprofen. NSAIDS wear out after 8 hours and steroids last a whole day.  If you take that prednisone several days in a row, it increases in value.

The first day it helps the inflammation by fifty cents. The second day it helps a little more, about fifty-two cents. If you stack prednisone day, after day the power to reduce inflammation keeps rising until about day 10. After that, it steadily sinks back to about twenty-five cents.

The moral of this story is that ibuprofen is a safe, yet mild anti-inflammatory. Prescription steroids are much more powerful, but after time they lose much of their power and have massive consequences on your body.  

Interestingly enough, ketones are estimated to be ten times more powerful than steroid medications. Produce ketones for a month, and the anti-inflammatory effect is worth nearly $5.00!! Let’s put it this way, going keto is 100 times more effective in reducing inflammation than using ibuprofen.  Produce ketones for a year, and estimated that it’s worth $25.00!!

How is this possible?

When your body has excess water, your cells get inflamed they balloon up. On a carb-heavy diet, your system fills up with lots of water molecules. The carb-derived glucose molecules in your system naturally grab onto water molecules. Just how much water are we talking about here? Hundreds of water molecules per glucose molecule!

Think of each glucose molecule as a sponge bouncing down the stream of blood coursing through your veins.  Before starting keto, it’s not uncommon to find an average blood sugar to be 105 mg/dl. Within two weeks their average sugars are in the 90s, and they are down over ten pounds. Much of that initial weight loss is from the extra water hanging onto those additional glucose molecules.

That’s a lot of water. Where did they put it all? Squeezed into many cracks and crevices.  

No wonder, arthritis patients tell me that once they’ve gone keto, they would never go back.  

When your system stops carrying around extra glucose, it let’s go of the water too. Remove that water in someone with arthritis and their joints hurt less. Stiffness is reduced.

Additionally, steroids are naturally made within your body. Steroid prescriptions remove inflammation because they mimic the steroids your body produces. Cortisol is one of your self-made-steroid hormones that eliminates inflammation.

Your cortisol hormones began as fat. Nutritional ketosis boosts hormone production overall. Sustained ketosis improves your body’s production of fat-based hormones across the board, including testosterone, estrogen, cortisol, and aldosterone.  

 

INSULIN INFLAMES

Today if you present to my clinic with chronic pain, I will look to find the source.  Quite often the pain comes from some part of your body that holds onto extra water. Could be a strained back muscle, a bulging disc, arthritis in your back, a kidney stone, a tumor, a pinched nerve or a list of other options.

The one thing all of those concerns have in common: they all hold onto extra water.  While I try to figure out the exact cause of that pain, I tell patients to pee ketones. By the time we get two weeks into the testing and imaging, they are two weeks into ketosis.

That is when most pain patients turn the corner. They are amazed at how much better they feel with this new bath of chemistry.

Now, no matter what the cause of their back pain, I have the best chemistry set present to fix the problem.  

To learn more about the ketogenic diet, check out the book I wrote ANYWAY YOU CAN.

RESOURCES:

  1. Cassiday, Laura. “Big Fat Controversy: Changing Opinions about Saturated Fats.” INFORM: International News on Fats, Oils, and Related Materials, Jun. 2015, pp. 342–377.
  2. Castaldo, Giuseppe, et al. “Very Low-Calorie Ketogenic Diet May Allow Restoring Response to Systemic Therapy in Relapsing Plaque Psoriasis.” Obesity Research & Clinical Practice, vol. 10, no. 3, 2016, pp. 348–352., doi:10.1016/j.orcp.2015.10.008
  3. Feinman, Richard David PhD. The World Turned Upside down: the Second Low-Carbohydrate Revolution. Nutrition & Metabolism Press, 2014
  4. Forsythe, Cassandra E., et al. “Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation.” Lipids, vol. 43, no. 1, 2007, pp. 65–77., doi:10.1007/s11745-007-3132-7

 

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Keto 101

Keto Diet 101: What Can Possibly Go Wrong? KETO FLU.

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If you are peeing ketones and feeling fine, skip these next four  parts of this articles reviewing what can go wrong when you start a keto diet.

However, if you tried to make ketones and you never turned your strip pink, read these posts.  Or maybe you succeeded for a time, but then something went wrong.

If you are a worrier and you read on the internet all the ways this ‘crazy’ diet supposedly messes up your body, read this.   

Keto-recap: A body fueled by sugar is chronically inflamed and in crisis. It is impossible to drip in the exact amount of carb fuel needed without going over or under your requirements. More than a teaspoon of carbs pushes your body into releasing insulin. When glucose is your fuel, eating too little leads to a steady decrease in your metabolism. Conversely, extra, unused glucose, rings your ‘insulin alarm’ triggering a spike of this hormone and continuing the cycle of inflammation.

Fueling your body with fat means no insulin. You rid yourself of the crisis. Your body produces ketones from fat when the glucose falls low enough. Ketones slip through your system and body putting out fires of inflammation the longer the ketones are around. A state of ketosis reverses inflammation caused by chronic high insulin levels.

As an internal medicine doctor, my job is helping with your health’s ‘long game.’ In other words, chronic disease management. When your body swells on the inside, that inflammation causes trouble. Chronic, slow-growing inflammation creeps into more and more areas of your body.  

After years of too many carbohydrates, your system gets really messy on the inside. But it is stable. Your cell walls become stiff and inflexible. The ‘hoses’ that carry your blood are crusty and can’t be easily stretched or relaxed. Reversing this chronic problem is tricky. The day you flip your energy source from carbs to fat, your body chemistry changes. This sends your crusty, stiff-albeit stable-system into flux.

What can go wrong when a carb addict switches to ketones?

KETO FLU

  • THIS PROBLEM AFFECTS PATIENTS: On Day 2 of producing ketones
  • THIS PROBLEM LASTS UNTIL: Lasts for up to a week.

If you Google any side effects of the Keto Diet, keto-flu tops the list of search results.

This condition got its name because chronically inflamed patients experience flu-like symptoms as they transition. Yep, give up those tasty, sweet carbs, and you will feel like you have the flu. When you get the flu, a ‘bug’ sets up a colony or home inside your body and messes with your system. Those critters invading your body cause lots of symptoms. The invading infection steals your water, drinks your salts, and eats up your sugar. Your tummy aches, in part, because the bugs selected your guts as their new home.

Flu symptoms include a headache, tiredness, dizziness when you stand up, racing heart, nausea, loss of appetite, and feeling rather irritable. When you get the flu, you get dehydrated. That dehydration causes all those symptoms. A body switching from sugar to fat also gets dehydrated. Dehydration causes the symptoms collectively called ‘keto flu.’

What’s so dehydrating about producing ketones? Ketones aren’t the cause. Instead, it’s the lack of all those glucose molecules circulating in your system. Glucose is a large, monster-sized molecule that flows through your veins.

Glucose acts like a sponge and holds onto water as it percolates throughout the body. Each glucose molecule holds onto hundreds of water molecules. Excess bloodstream glucose translates to thousands – even millions – of extra water molecules.

Do the math.  

Check your blood sugar. Is it above 100? For every point above 100, you added thousands of extra monster-sized glucose molecules to the 7 liters of blood you hold. Now, multiply that by the hundreds of water particles clinging to each glucose.

Twenty carbs per day lead to way less glucose in your bloodstream. Less glucose holding onto that circulating water causes you to flush that extra fluid out. Over the course of the first week, I have had patients lose 20 pounds. That’s nearly three gallons of excess water.  

Removing the extra water causes significant weight loss. KETO or the ATKINS diet gets picked on through statements like this: ‘The only way you lose weight on a high-fat diet or Atkins-like diet is because you lose water weight.’ That’s exactly what happens….at first.

Millions of water particles lost their chemical sponges and are gone. Without that sugar, the water flows right out the kidneys. Dehydration is defined by the rapid loss of water. All that extra water inflames or irritates your body. Removing it is the right answer.  

Your ‘flu’ or dehydration symptoms appear when you are caught unprepared for ketosis’ water loss.

This water loss hits your kidneys like a tidal wave. Your kidneys remove water from your blood by adding it to your urine. They ‘steal’ salts from your bloodstream to make this happen.    

Before long, you get a headache and feel really tired. You try to stand up only to suffer sudden dizziness and a pounding heart. Oftentimes, you get crabby. Welcome to the keto flu.

The antidote is simple: eat SALT, drink water and slow down.

Let’s start with salt. Yes, I mean salt. Like the white stuff in the shaker on your table. I prefer pink Himalayan salt or sea salt, but common table salt will do. Salt, like fat, is an overly demonized compound.

Fat and salt are essential to the Keto diet. You need to replace the fluid that belongs in your body. Knowing that keto transition sucks salt and water into your urine should motivate you to add salt to anything you eat or drink. You get dizzy because there’s not enough fluid in circulation. Replace that fluid by eating and drinking with salt.

If you add plain water back to your system, you will not fix the flu-like symptoms. The water will go in and flush right back out. The salt holds the proper amount of water in your circulation and corrects the dehydration.  Drink salty broth to keep the keto flu away!

The next step is to slow down.

If you are reading this and considering fueling your body with fat, GREAT. Let me help you succeed. If you are a carb addict with a daily intake of more than 300 carb gram, start slowly.  

Begin with zero calories in your drinks for the first week. Once you are successful with that for seven consecutive days, then remove all white foods: No bread, no rice, not pasta, no pastries.  Follow that rule in addition to the no-calories in your drink for seven straight days as you prepare for ‘transition day.’ This plan gives you the space to allow a gentle shift in your body chemistry to prevent the keto flu. This schedule also gives you enough time to clean out your cupboards.

WARNING: BE CAREFUL IF YOU TAKE HIGH BLOOD PRESSURE MEDICATIONS

  • THIS PROBLEM AFFECTS PATIENTS: On Day 2-3 of producing ketones
  • THIS PROBLEM LASTS: up to a week.

If you are on blood pressure medication and you want to get off them, the keto lifestyle is the answer. However, the transition can be dangerous. Prepare yourself.

My patients taking high blood pressure meds must check their own blood pressure at home. Without all those large glucose molecules loaded with hundreds of additional water particles, your body’s circulation volume drops. Not because of blood loss; because of water lost. Lower volume means less pressure! It takes far less medication to control blood pressure when all that water is gone.   

Thanks to the Keto diet, helping patients get off blood pressure medication has never been easier. You must use a home blood pressure monitor though. Check your blood pressure 2-3 times a day when transitioning. As you reduce and remove carbohydrates from your diet, your blood pressure will drop quickly. Be careful. Let your doctor help you remove those blood pressure medicines as quickly as you remove the carbohydrates. In a matter of five days, I got one patient off of five of his blood pressure meds! This, of course, all depends on how strict you are at following the less-than-20-carbs-a-day rule and how long you have been a carb addict.  

POUNDING HEART

When your heart races inside your chest, a feeling of terror takes over your mind – even if you are a doctor. Your fear is justified. A pounding heart can be a warning of impending death. It signals us to pay attention. If your heart begins to thump inside your chest during ketosis transition, pay attention. Your body is warning you of something.

The most common reason for this symptom is the dehydration mentioned above. Dehydration forces your heart to pump fast and strong. Fix this problem quickly by drinking salted water! Keep doing this until the heart-pounding goes away.

If you have a history of heart arrhythmia or heart failure, you must consult your doctor before you go on a keto diet. If your heart is pounding because of an abnormal rhythm, you can drown yourself in salted water only to make things worse for your heart.

Check out the book ANYWAY YOU CAN on Amazon or Audible by Annette Bosworth, MD for more keto information.

RESOURCES:

  1. Seyfried, Thomas N. Cancer as a Metabolic Disease: on the Origin, Management, and Prevention of Cancer. Wiley-Blackwell, 2012
  2. Siri-Tarino, P. W, et al. “Meta-Analysis of Prospective Cohort Studies Evaluating the Association of Saturated Fat with Cardiovascular Disease.” American Journal of Clinical Nutrition, vol. 91, no. 3, 2010, pp. 535–546., doi:10.3945/ajcn.2009.27725. 
  3. Effect of exercise intensity and starvation on activation of branched-chain keto acid dehydrogenase by exercise; G. J. Kasperek, and R. D. Snider; 01 JAN 1987. https://doi.org/10.1152/ajpendo.1987.252.1.E33
  4. Scott AR1; Joint British Diabetes Societies (JBDS) for Inpatient Care; JBDS;Management of hyperosmolar hyperglycemic state in adults with diabetes; Diabet Med. 2015 Jun;32(6):714-24.   DOI:10.1111/dme.12757

 

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Keto 101

Keto Diet 101: Ketosis and Bad Breath.

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ketosis and bad breath

THIS PROBLEM AFFECTS PATIENTS: When you begin making ketones.

The problem of ketosis and bad breath lasts until the patient is Keto-Adapted (up to 6 weeks). When your body uses ketones, it releases extra units of ketone compounds. Unused ketones flush out of the body as acetoacetate in the urine or acetone through your breath.

Acetone breath is a dead giveaway you’re burning fat for fuel. Acetone smells weird causing metallic- or fruity-scented breath. Surprisingly, many don’t experience this problem at all. Others only have acetone breath for a few days while others can smell the ketones coming out of their sweat and their breath for months on end.

For most people, bad breath lasts for about a month as they adapt to ketosis. The odor usually improves over time as blood ketone levels stabilize in the second or third week.  

Remember: acetone ends up in your breath when lots of extra ketones circulate in your blood. When first transitioning to ketosis, your blood can fill with a whole bunch of ketones waiting their turn to be used as fuel. As your cells ‘remember’ how to use this kind of fuel, more and more cells turn on their ketone-burning parts. At first, only a few cells burned ketones, but by the end of the third or fourth week, many cells throughout the body can burn either ketones or glucose.  

With that improved army of ketone-furnaces inside your mitochondria, less excess compounds float around and in turn fewer acetone fumes out of your mouth. Gradually, your body burns ketones as fast as you make them. With less excess ketones, your breath won’t stink of acetone.

To Deal With Acetone Breath, Try The Following:

#1: GET YOUR TEETH CHECKED. I found it helpful to remind patients that we evolved using ketones. The human race did not evolve eating starches and sugars. Today’s diet fills your mouth with a sugar-bath. It leaves your teeth with tiny pockets where sugar feeds bacteria and other microbes. These hidden cavities allow smelly bacteria to flourish. Cavities and their bacteria are the sources of the long-standing bad breath associated with ketosis.

Please note that the longer you bathe your teeth in ketones, the stronger and healthier your teeth get. Your ancestors kept their teeth for a lifetime by constantly circulating ketones in their blood and spit. Thanks to their high-fat diet, this continued exposure to ketones strengthened their teeth while fighting the bacteria living in their mouths.

#2: DRINK ENOUGH WATER:  Dehydration leaves your mouth dry. Mouth dryness concentrates the power of the bacteria living in your oral cavity. Proper hydration flushes and continually washes your mouth while also diluting the places where bacteria live.

Also, when you drink enough water, you flush ketones from your blood into your urine. You only breathe out acetone when your blood is overflowing with extra ketones. Staying properly hydrated allows your body to get rid of excess ketones through your kidneys. It takes the pressure off your lungs to process ketones and breathes them off as acetone.  

#3: STAY THE COURSE. The best way to keep that acetone fuming out of your mouth is to go in and out of ketosis. Steady ketone production allows the system to adapt and stabilize fully.  Stabilize in this context means that the production of ketones matches the burning of ketones. There will never be a perfect match between these two parts of the equation, but they should get rather close once you have hit your keto-rhythm. The way to mess up this equation is to go in and out of ketosis. That leaves the extra acetone molecules stinking up your breath.  

Hungry for more information on the ketogenic diet? Check out the book ANYWAY YOU CAN on Amazon or Audible by Annette Bosworth, MD.

RESOURCES:

  1. Anderson JC, Measuring breath acetone for monitoring fat loss: Review. Obesity (Silver Spring). 2015 Dec;23(12):2327-34. doi: 10.1002/oby.21242.PMID: 26524104
  2. Toth, Csaba, and Maria Schimmer Zsofia Clemens. “Complete Cessation of Recurrent Cervical Intraepithelial Neoplasia (CIN) by the Paleolithic Ketogenic Diet: A Case Report.” Journal of Cancer Research and Treatment, vol. 6, no. 1, Apr. 2018, pp. 1–5., doi:10.12691/jcrt-6-1-1

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Ketosis vs Ketoacidosis: Separating Benefits from Danger.

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keto diet and cancer

Ketosis vs Ketoacidosis is only a great discussion because they are two separate things. Gives you a chance to kill two birds with one stone! 

“Isn’t Ketosis the same as Ketoacidosis?”

No. Truth be told, I only hear this question from healthcare professionals that didn’t slow down enough to carefully think about that question. Like me, their brain jumped to the near-death scenario of ketoacidosis when they heard the word ketosis. Most of my patients have never heard of either of these words.

Before you present this idea to your doctor, read this blog.  Print it out and take it along on your doctor visit. 

Ketosis vs Ketoacidosis

Ketoacidosis = DANGEROUS

This is a life-threatening condition. This deadly chemistry shift happens to Type 1 diabetics.  Remember, Type 1 Diabetics are those people who cannot produce insulin. Their pancreas does not squirt out this sugar-handling hormone when their blood sugars rise.  

Since 1922, these patients have the privilege of surviving without a functional pancreas because of insulin. Insulin injections allow the entrance of those glucose molecules into the cell.  Once inside, they are burned as fuel.

Without the injection of insulin, Type 1 diabetics can’t use blood sugar as fuel.

Insulin triggers your body’s cells to capture the sugar in the blood and deliver it to your furnaces. Only then can your cells burn it as fuel. Without insulin, sugars circulate continually and never enter cells. Insulin is the chemical key that allows glucose to enter your cells. Once inside, mitochondria burn this sugar compound for energy.

Without insulin, the sugar in your bloodstream rises and rises.  It entered the system and there is no way to get rid of it as fuel.  

What Happens When Mitochondriaa Don’t Get What They Want?

When mitochondria can’t access sugar fuel from your bloodstream, your body switches over to ketones. As previously stated, the enemy of ketones is insulin. When there is no insulin in your body, ketone production has no limit.  

Ketosis vs KetoacidosisKetones, as fuel, work just dandy for Type 1 diabetics. Unlike glucose, ketones need no help getting from your blood to the furnaces insides of your cells. Ketones slip right through your cell walls and straight to your mitochondria for energy production. Ketones ARE usable to a diabetic. Without insulin shots, Type I diabetics switch each and every cell to a ketone-burning furnace.

Before long all furnaces are churning through the ketones. Massive ketones churn out of their liver. Excessive ketones burn within their mitochondria in their tissues. With every cell in the body burning ketones for fuel, a tremendous amount of energy swelters the system.  Remember that each ketone delivers 32 units of energy as compared to 2 units produced by each glucose molecule. While all the engines burn through ketones, the glucose molecules are stuck outside the cell and walled off from the furnaces. This causes the blood sugars to rise and rise while the system burns more and more fuel.

With every cell glowing hot with ketone fuel, what is the problem?  

As the Type 1 diabetic fuels the whole system on ketones, their body’s chemistry becomes overheated and acidic. Couple the intense energy production with the very high blood sugars and these patients can die from this situation. Heavy ketone buildup creates an acidic environment: ketoACIDosis.

Ketosis vs Ketoacidosis

For those of us that normally produce insulin, even after months of cranking out ketones, we will never have 100% of our furnaces burning ketones. Many of our cells use ketones for fuel, but some cells still use glucose. Glucose always outranks fats for fuel, as long as the fuel can get to the furnaces.  

Insulin assists the glucose with entrance into the cell. If glucose floats by, insulin triggers the cell to grab glucose and pull it in. In that situation, the cell burns glucose while ketone fuel is halted. Normally cells constantly change back and forth between using ketones and glucose.

If you look at 100 cells you will find the ratio of those using glucose versus ketones will fluctuation based on how much glucose gets funneled into the furnaces. Once all the glucose is used up, the furnaces switch back to ketones.  If you spread a sprinkle of glucose, a few cells with gobble up that glucose and flip back the other way.

 

Ketosis =  NOT DANGEROUS  

Nutritional ketosis refers to the steady production of ketones which are then converted by your mitochondria into energy. Ketosis is triggered by a sharp drop in blood sugar inside the cell.

This low glucose is made possible by fasting or cutting out your carbs. Without insulin, Type 1 diabetics have low blood glucose inside the cells because they have no insulin ‘keys’ that allow entrance.

Here’s how it normally plays out: once you stop eating so many carbs, your body uses up its stored sugar.

Ketosis vs Ketoacidosis

For those of us with insulin, our body burns the glucose fuel circulating in your blood. Next, it empties your stored fuel in your liver. When all that‘s used up, your insulin and sugars drop continuously. Finally, insulin all but disappears.  

One by one, your mitochondria switch from glucose to ketones for fuel. They keep the fire burning, but transition from the fast-burning sugars to slow-burning fat. Not every mitochondrion makes the switch, but more and more of them transition to burning fat. A few sugars enter your system and quickly get burned as the mitochondria switch back and forth.

When you eat mostly fats, your mitochondria become efficient at using either option for energy. A few are switching over to sugar and back again to fat when all the sugar is gone. This fat/sugar blend keeps ketone levels within a safe range. Without insulin, close to 100% of your cells burn ketones. This creates the life-threatening situation of KetoACIDosis.

For further information about this check out the book, ANYWAY YOU CAN: A Beginners Guide to Ketosis. Visit our site bozmd.com today!

RESOURCES:

  1. Kelley, Sarah Aminoff, and Eric Heath Kossoff. “How Effective Is the Ketogenic Diet for Electrical Status Epilepticus of Sleep?” Epilepsy Research, vol. 127, 2016, pp. 339–343., doi:10.1016/j.eplepsyres.2016.09.018.
  2. Nuttall, F. Q., and M. C. Gannon. “Plasma Glucose and Insulin Response to Macronutrients in Nondiabetic and NIDDM Subjects.” Diabetes Care, vol. 14, no. 9, Jan. 1991, pp. 824–838., doi:10.2337/diacare.14.9.824
  3. Scott AR1; Joint British Diabetes Societies (JBDS) for Inpatient Care; JBDS hyperosmolar hyperglycaemic guidelines group; Management of hyperosmolar hyperglycaemic state in adults with diabetes; Diabet Med. 2015 Jun;32(6):714-24. PMID:25980647  DOI:10.1111/dme.12757

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