The most common complaint that I get in my office when someone has started a ketogenic diet is, “Doc, I feel fatigued. Will this ever go away?”
That feeling of fatigue, some refer to as the “keto-flu,” is usually due to a couple of things. First, you may not be eating enough fat (I recommend a 1 gram to 1 gram ratio of protein to fat when getting started). Second, you’re not taking in enough salt (specifically sodium, potassium, magnesium and/or zinc). These four salts are essential electrolytes our body requires for proper function.
If salt is the problem, the you will be experiencing leg cramps. Cramps during daytime activity are usually due to low sodium or potassium levels. Cramps that wake you up at night are usually due to low magnesium or zinc. Leg cramps can also be due to hypothyroidism or significant blood sugar swings. Dr. Nally will usually check for this during your visit with him.
“But isn’t too much salt bad for you?” I am frequently asked.
Too much salt is only bad for you if you’re eating a “low-fat” diet.
What if increasing salt intake actually lowered your blood pressure?
Did you know that increasing your salt intake can actually improve your diabetic blood sugar if you are following a correct diet? Could it be that easy?
Almost every patient that I see in the office has a significant worry about salt intake, some greater than others. In fact, some people are so fearful about salt that when I initially began encouraging its use, they told me that I was crazy, and they left my practice.
Has restricting salt over the last 50 years really worked, or is it doing more damage than we think?
That was the question that was asked by Dr. Ames in the American Journal of Hypertension 17 years ago. However, his answer never got a mention. In fact, I’ve been in practice for almost 20 years, and incidentally stumbled upon this article when it was mentioned by a colleague of mine. Granted, the study is a small sample size of people, only twenty-one. However, the results are profound.
Twenty-one patients with hypertension were randomized to periods of no salt (placebo) and periods of 2 grams (2000 mg) of sodium chloride four times a day (a total of 8 grams of salt per day). Glucose tolerance tests were completed with insulin levels at the end of each intervention period.
Insulin Resistance and Hypertension Improve by Adding Salt
Three very noteworthy results happened. First, those patients with insulin resistance and diabetes had improvement in their glucose levels while on 2 grams of sodium supplementation.
Second, those with hypertension also, shockingly, showed improvement in their blood pressure while on the 2 grams of sodium supplementation.
Third, those with insulin resistance had a lowering of their insulin levels during the period of increased sodium intake. These findings fly in the face of the dogma that’s been drilled into our heads that “salt is bad!”
“But, Dr. Nally, you can’t base your findings on a small group of 21 people,” the experts say.
Yes, it is a small study group. However, these findings are identical to what I, also, see clinically every day in my practice for over 20 years.
We know that the average human needs at a minimum 3 grams of sodium per day and 3 grams of potassium per day. The standard American diet (SAD diet) including processed foods contains 2-3 grams per day of sodium and potassium. In fact, the CDC claims the worst salt containing meals for you are:
Bread
Processed chicken dinners
Pizza
Pasta
Insulin also stimulates additional retention of sodium at the kidney level. If you are insulin resistant, producing excess insulin in response to starches or sugars, you retain notably larger amounts of salt when eating the standard American diet (SAD diet) or a “low-fat” diet. However, if your following a low-carbohydrate or ketogenic lifestyle, you won’t be eating the meals above and you’re probably not getting near enough salt.
Salts, or electrolytes, are essential in normal cellular function. Low salt in the body is like running your car without oil. It will run, but not very efficiently and over the long term will cause problems. This is the cause of the keto-flu I wrote about previously. And, according to the study above, it is a potential driver of our persisting insulin resistance, diabetes and hypertension.
How Much Salt Should I Use?
In my office, I encourage use of 3-4 grams of sodium and 3-4 grams of potassium daily when using a ketogenic lifestyle. That’s approximately 1 ½ – 2 teaspoons of salt per day. I like the Redmond’s RealSalt or pink Himalayan salt because these products contains all four types of salt (sodium, potassium, magnesium and zinc).
It is probably that your salt restrictions is making your insulin resistance and blood pressure worse. That’s what the clinical evidences are pointing toward, and it is what I see every day in my office.
Want to know more about a ketogenic life-style? Click the KetoLife link to get some basics.
If you’re already following a ketogenic lifestyle, then let me help you navigate the bumps and turns by going to the KetoKart and checking out the products I recommend to jump-start ketosis DocMuscles-style!
Until then, I’ll have another piece of bacon, please . . . and, oh, pass the salt!
I get asked this question all the time. And, my answer is that 85% of the people that walk through the doors of my clinic will not be fully successful in weight loss, reversal of diabetes, normalization of blood pressure and reversal of heart disease and/or vascular disease without it.
I am frequently asked, “Is Keto for everyone?” Does everyone need to follow a ketogenic lifestyle? The answer is “No.” 15% of the population will be able to maintain great health with calorie restriction and exercise. However, the principles that provide a successful ketogenic lifestyle are easily understood and incorporated by anyone looking for improved health, energy and weight control.
Principle #1 – Insulin is the Master Hormone
Insulin is the master hormone when it comes to weight loss and the diseases of civilization. Whether you are insulin resistant or not, insulin is essential for life and proper function of the cells of the body, but too much insulin production in response to sugars, starches or complex carbohydrates causes disease.
How do you know if you are insulin resistant (producing too much insulin)?
Skin tags are pathognomonic (a characteristic indicative of the presence of disease) for insulin resistance. If you have skin tags, you may want to focus your diet on increased carbohydrate restriction.
You may not need to completely remove carbohydrate from your diet, however, recognizing that not all carbohydrates are created equal and avoiding those with higher carbohydrate content will help many improve weight and halt the progression of disease. I have many patients that with just partial carbohydrate restriction they are able to lose 20-30 lbs, improve their cholesterol profiles and improve their blood pressure.
There are sixteen different diseases that respond very effectively to carbohydrate restriction. You can read about them and how the ketogenic lifestyle effectively reverses them in The Keto Cure.
Principle #2 – Saturated Fat & Cholesterol Aren’t the Demons We’ve Made Them Out to Be
Saturated Fat and cholesterol aren’t the demons we’ve made them out to be. Another way to put it is: “Don’t blame the butter for what the bread did.”
Since 1984, nutrition experts treat fat and cholesterol containing foods like the witches of Salem. Experts castigate their use as if they were the “Avada Kedavra“ curse of the fantasy world.
As an example, eggs, specifically the egg yolk (the part of the egg containing all the cholesterol and saturated fat), have been demonized by just about every health magazine I’ve ever read. (To this day, the chef at every breakfast bar I’ve ever visited asks if I want an ‘egg white only’ omelet.) Interestingly, there is actually no scientific data association between whole egg consumption and heart disease. The science simply does not exist. Seriously, check for yourself.
I personally eat 6-8 eggs a day and my cholesterol is perfect. Back 1000 years ago, only the aristocrats at the chickens. All laborers and serfs ate the eggs . . . who would be dumb enough to eat your food source? (Don’t answer that.)
For example, the MR-FIT study, the largest cholesterol study ever completed, is incessantly quoted as the study that demonstrates reduction in cholesterol leads to reduction in cardiovascular disease, but this trial was actually a failure and did not demonstrate improved risk by lowering cholesterol. In fact, the Director of the study, Dr. William Castelli stated, “. . . the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower people’s serum cholesterol…”
Researchers found that people who ate the most cholesterol, including the most saturated fat, weighed the least. They were also the most physically active. In fact, the British Medical Journal published a 2015 study demonstrating that saturated fat is NOT linked to vascular disease, diabetes or increased mortality (de Souza RJ et al., BMJ 2015,351:h3978).
In my clinic, the basis of appetite suppression is eating adequate protein that includes saturated fat and cholesterol. This is the most powerful tool in my clinical approach to the treatment of weight loss. I can use foods like red meat, bacon, butter and coconut oil without concern or worry of heart disease as long as you are keeping your carbohydrate intake less than 20 grams per day.
Baseline insulin levels allow for peace of mind about heart disease risk. Heart disease risk goes down when insulin levels are maintained at normal baseline levels. Increasing saturated fat, while at the same time lowering carbohydrate intake has been demonstrated to shift the cholesterol to a more heart protective form (Griffin BA et al., Clin Sci [Lond], 1999 Sep).
Principle #3 – Nutritional Ketosis Has Anti-Inflammatory & Age Slowing Effects On the Body
Ketones in the blood at a nutritional level (0.5-4 mmol/L) have tremendous anti-inflammatory and age slowing effects on the body. Even having them present intermittently has dramatic improvement on overall inflammatory changes and disease in the body.
Ketones are the usable fuel of the body when the liver breaks down fat for energy. They suppress the NLRP3 inflammasome in every cell in the body. This is important because it allows for more rapid recovery from exercise. It also dramatically decreases pain and fatigue that comes from diseases like arthritis, rheumatoid arthritis, multiple sclerosis and auto-immune disease (Y.H. Youm, et al., Nature Medicine, vol. 21, no. 3, pp. 263–269, 2015.)
If full blown ketosis isn’t for you, partially restrict starch and carbohydrates for a mild to moderate benefit. Even small amounts of ketones in the blood are helpful. This provides increased recovery time, and improved inflammation control.
So, even if you don’t follow a strict ketogenic lifestyle, the principles above are powerful. These three principles make this dietary approach universally effective for weight loss. They are also very powerful for disease management. Even partial application of carbohydrate restriction can benefit just about everyone.
You can learn much much more about the Ketogenic Lifestyle as a member of DocMuscles.com. Click the link and sign up now.
And, don’t forget to get your signed copy of my book, The Keto Cure.
Lock-boxes have always fascinated me. Lock-boxes with special keys are even more fascinating. The more I’ve learned about fat cells (adipocytes), the more I think about them as special fuel depositories or fat lock-boxes. Before the invention of refrigerators, fast-food, Bisquick and beer, our bodies preserved and reserved fat as a precious commodity.
The body, when given fat with carbohydrates or excess protein, quickly places the fat into a lock-box for safe keeping. It does this for two reasons. First, the body can store fat very efficiently. Second, hormone signals stimulate fat storage when other fuel sources (carbohydrate & protein) are present in excess. The body can access this stored fuel only when the right presentation of hormonal keys are present. Fascinatingly, we now know from recent research, there are actually three types of lock-boxes for fat in the human body (white adipose tissue, brown adipose tissue, and tan adipose tissue).
The greatest challenge for the obesity doctor is getting into the fat lock-box. Some people’s boxes are like the “Jack-in-the-Box” you had as a child – just add a little exercise spinning the handle and the box pops open (These are those people that say, “Oh, just eat less and exercise and you’ll lose weight.”) For the majority of the people I see, it’s more like the lock above with a four or five part key required to turn the gears just right. (And, that key often only seems available on a quarter moon at midnight when the temperature is 72 degrees.) Fat cells, called adipocytes, require four, and possibly more, keys to open them up and access the fuel inside. Exercise is only one of those keys. However, exercise alone often fails.
Over the last 18 months, I have been surprisingly impressed with the results patients have by the addition of both medium chain triglycerides and exogenous ketones. A number of people have asked me, “Why do you encourage the addition of exogenous ketones to a person already following a ketogenic diet?”
Others just accuse me of self promotion, saying, “You’re just trying to sell a product!”
Or they exclaim, “Giving more ketones is just a waste of time and money.”
A few of the uneducated holler from across cyberspace, “You’re just going to cause ketoacidosis!”
Believe me, I’ve heard it all. And, the skepticism is understandable. I work with people every day, looking closely at weight gain/loss, metabolism, cholesterol, blood pressure, inflammation, etc. With any “low-carb” or “ketogenic product,” I test it out on myself and my family, before I offer it to my patients or even consider encouraging its use in my practice. I have this desire to understand “the how” and “the why” before I prescribe the who and when.
The Fat Lock-Box Keys
First , let’s talk about the adipocyte as a fat lock-box – and where you find the keys. Then, we’ll discuss how products may or may not help.
Insulin
There is only one door INTO the adipocyte for the fat, and the key to that door is insulin. Insulin stimulates an enzyme called lipoprotein lipase that essentially pulls the fat from the cholesterol molecule into the fat cell. Without insulin, fat doesn’t enter the fat cell. As a result, type I diabetics (those that make absolutely no insulin) look anorexic if they don’t take their needed insulin. Insulin is also the first key to the back door on the adipocyte. Actually, if there is too much insulin in the system, fat enters easily through the front door but cannot exit the back door (Picture 1). Insulin seals up the back door so that fat cannot exit very effectively.
That’s why insulin is the master hormone when it comes to obesity. You’ve got to lower the over-all insulin load to get the adipocyte slowing fat entry and increasing fat exit. If you don’t do that, I don’t care how much you exercise, 85% of the population will struggle with weight loss. Hmmm, seems kind a familiar to the last 50 years of our obesity epidemic, No?
Picture 1 – Four Key Pathways to Adipocyte Stimulation of Lipolysis
Catecholamines
The second key to the back door of the fat cells are the catecholamines. These are adrenaline (epinephrine), norepinephrine, adrenocorticotropic hormone (ACTH) and even serotonin. These hormones are produced in the adrenal glands through exercise, fear and even recollection of powerful memories. Medications can also stimulate production of these hormones. The catecholamines stimulate cAMP. cAMP opens the fat cell, releasing fatty acids for fuel.
The thyroid hormone conversion of T4 to T3 also plays a role in uptake of the catecholamines by adnylyl cyclase (AC). Low levels of T3 (like those seen in hypothyroidism or in cases of thyroiditis) also inhibit unlocking of the fat lock-box. Conversion of T4 to T3 is driven by the presence of bile salts in the gut. Increase fat intake increases the presence of the bile salts which naturally leads to better T3 conversion. Hence my constant references to eating more fat and bacon. .
Inflammation & Medications
The third key is an inhibitory effect on adenylyl cyclase (AC) activity by alpha and beta adrenoreceptors, adenosine, prostaglandins, neuropeptide Y, peptide YY, HM74-R & nicotinic acid. These inhibitory and inflammatory hormones produced in the brain, gut and other areas decrease cAMP activity in the fat cell and slow fat loss. The fancy long names are all hormones causing inflammation. Of note, many are also stimulated by medications including blood pressure lowering drugs. Check with your doctor if the medications you are taking may be causing weight gain, or halting your weight loss.
Please note that the first three keys have effect on the cAMP pathway for release of fat from the adipocyte. These three keys turn on or off effective function of cAMP leading release of fatty acids from the fat cell.
Naturitic Peptides
The fourth key follows a separate pathway. This is why I’ve clinically seen patients experience weight loss even in the presence of higher insulin, inflammatory disease or hypothyroidism. This key activates release of the naturitic peptides (ANP, BNP). These hormones are released from the heart when it squeezes more powerfully. As the cardiac muscle contracts, it releases ANP & BNP hormones. These hormones stimulate the cGMP pathway in the adipocyte. It then activates hormone sensitive lipase (HSL) and perilipin to release free fatty acids. Again, this pathway is separate from the pathway by which the first three keys released fat. Exercise increases heart contractility, but is inhibited by high insulin levels. However, ketones themselves also stimulate this increased contractile effect.
There actually is a fifth key not referenced above. The fifth key to the fat lock-box amplifies testosterone’s presence through the HPG axis. Insulin resistance and leptin resistance lower testosterone in men and raise it in women, causing poly-cystic ovarian syndrome (PCOS). Normalizing insulin levels (with a ketogenic diet) while at the same time increasing ketones as the primary fuel powerfully resets the HPG axis through a complex series of hormonal reactions. Growth hormone is balanced and testosterone returns to a normal range.
Clinically, 60% of the people I see in the office have abnormal testosterone due to insulin resistance. This leads to hypogonadism in men and PCOS (abnormal periods, facial hair growth and/or infertility) in women. Restricting carbohydrates and maintaining nutritional ketosis by diet and/or addition of exogenous ketones has a powerful corrective factor in these people.
Testosterone influences the up-regulation of the alpha & beta adrenergic receptors (the 2nd & 3rd key above). Hence, if your testosterone is low, it has a suppression on the way that the catecholamines influence fatty acid release from the fat cells. If your testosterone and growth hormone are normal, muscle development and adrenaline stimulus from exercise helps amplify the use and mobilization of fat from the fat cell. In people with insulin resistance and leptin resistance, exercise and the catecholamines don’t have the same fat burning effect.
What Does This Actually Mean?
Yes, I have greatly simplified a series of very complex hormonal pathways in the explanation of the keys above. Why do you think understanding obesity has been so difficult? Think of your adipocytes as a fat lock-box.
What’s even more important is the knowledge that the fat cell DOES NOT open or close because of calories. There is no dogmatic calorie-meter on the wall of the fat cell. There is no calorie key to the fat lock-box. Really, . . . in the 50 years of studying fat, researchers haven’t found one. (Prove me wrong when you show me an electron micro-graph of a calorie-meter in the wall of a cell). Science has demonstrated multiple times that the lack of food from starvation or excessive fasting suppresses thyroid function (an inhibitory effect on key #3). Restricting calories actually inhibits fat loss in many people.
The fat lock-box keys I refer to above are hormone responses to the presence of macro-nutrients (food). That means, first reduce your carbohydrate intake by eating real food from good sources. You can learn how to get started by registering for my FREE six part weight loss mini-course. Second, be as active as you can. Third, reduce stress and medications that have inhibitory effect on catacholamines. Fourth, balance your thyroid. And, fifth, get into ketosis and consider adding exogenous ketones to your dietary regimen. It really is that simple.
References
(For those of you that still believe there is a calorie key – or just need something to do while in the bathroom):
Lafontan et al. Arterioscler Thromb Vasc Biol. 2005
This week on Episode #50 of KetoTalk.com we talked about those proteins highest in arginine and lysine with the greatest potential for spiking your insulin and kicking you out of ketosis. Here is a Graphic to give you a little help:
Tune in for KetoTalk Epsiode #50 on iTunes where it is now available or go to KetoTalk.com on the computer and listen there. We talk about the insulin response from proteins; What is Lipedema and does a ketogenic diet help?; Muscle burning; Dehydration; and can Phentermine be used with a ketogenic lifestyle?
Ketosis plays a major role in lowering blood glucose, insulin and notably improving memory in those with Mild Cognitive Impairment and risk for Alzheimer’s Disease (1). Watch this short 5 minute segment on how a ketogenic lifestyle helps. You can learn about a Ketogenic Lifestyle by reading my blog post: A Principle Based Ketogenic Lifestyle. And you can ramp up your blood ketones in less than 30 minutes by getting exogenous ketones at DynamicKetones.com.
Enjoy!!
References:
Krikoria R et al. “Dietary ketosis enhances memory in mild cognitive impairment.” Neurobiology of Aging. Feb 2012, Vol 33:2 p 419-425.
Why should you consider using a ketogenic lifestyle? There are many reasons. This is part 8 of a 25 part series and this one focuses on how ketosis improves testosterone in men and estrogen in women.
I had the chance to appear for an interview on Vicki Fitch’s podcast last night: A Fresh Perspective. We talked about bacon, ketogenic diets, hypoglycemia, sweeteners, food cravings, #FitchSlaps, exogenous ketones and we answered a bunch of great questions from the Facebook Live audience. You can see video of the show below:
Had a great time. Let me know what you think. Thanks, Vicki!!
Stomach Pain & Swelling with Hereditary Angio-Edema (HAE)
Listen to KetoTalk Podcast #32 where we talk about hereditary angio-edema, adequate ketone ranges, statin use while in ketosis and healthy keto questions. You can listen in by going to KetoTalk.com or you can listen in on iTunes.
“About 40 percent of my older patient population who take statins while eating ketogenic experience some form of myalgia they didn’t have before. And there’s an amplified side effect profile: muscle ache, joint pain, generalized fatigue, liver enzyme elevation, and cloudy headed.” — Dr. Adam Nally
KEY QUOTE: “Children are born in ketosis, so ketones are perfect for babies. The level of fat in breast-milk is essential for them to maintain their health and their growth.” — Dr. Adam Nally
Here’s are the 12 questions Jimmy and Adam answered in this special Keto Talk Mailbox Blitz extended podcast today:
– Testimonial from someone who learned his lesson why it’s important to stay ketogenic all the time
– Three-decade study confirms saturated fats are bad for health
– Is increased testosterone from a ketogenic diet a bad thing for women?
– Why am I still struggling with low energy and low ketones after months of being in ketosis?
– Can being in nutritional ketosis above 1.0 mmol cause painful headaches?
– Do artificial sweeteners and stevia raise insulin?
– Is my ketogenic diet causing me to cramp up before and during my half marathon racing?
– Is MCT oil a better fat to use on a ketogenic diet than other fats like coconut oil, cream, or butter?
– Why do I have a constant stomachache while I’m on a ketogenic diet?
– Do you have to be in ketosis to burn fat?
– Does being in ketosis lead to daily spotting and extended periods?
– Are ketones in my baby’s breastmilk safe for her to consume? And why did my milk supply drop when I went keto?
– What is the impact of the supplement creatine on ketones, blood sugar, and insulin levels?
– Can I ease into ketosis as a way to avoid the dreaded “keto flu?”
KEY QUOTE: “If you’re not feeling energy after that adaptation period of 2-4 weeks at the very most, then you’re doing something wrong. Let that be your wakeup call to change something.” — Jimmy Moore
Hypertension (elevated blood pressure) is one of the triad symptoms of metabolic syndrome. Most of the hypertension that I see clinically is driven by insulin resistance as the underlying cause. I see this problem in a very large majority of the people in my office and I am seeing people younger and younger show up with continually increasing blood pressure.
In medical school, we were taught to treat “borderline” or “slightly elevated blood pressure,” through “lifestyle changes” which was another way of saying exercise, caloric restriction & hold the salt. But most physicians today will tell you that exercise, salt & caloric restriction doesn’t work. When asked why the 34 year old male in my office suddenly has elevated blood pressure, the only explanation we had was it is a “genetic problem,” or “blood pressure naturally goes up as we get older,” or “you’ve been eating too much salt,” and they are started on blood pressure medication and sent on their way. But, as time went on, I found that I had to keep adding more and more blood pressure medication to control the continually rising blood pressure of the patients in my practice.
Most of these people will have a progressive elevation in blood pressure over time, and these blood pressure (anti-hypertensive) medications are/were continually raised until the person is on four or five different blood pressure pills at maximal doses. Again, when questioned why, their genetics are blamed and that is the end of it. Or is it?!
What shocked me was that when I took patients off of salt & caloric restriction, and placed them on low carbohydrate high fat diets (and yes, I gave them back their salt), their blood pressure normalized. I noticed that as their fasting insulin levels began to fall, their blood pressure began to return to normal.
What?! Blood pressure rise is caused by insulin?!
Ummm . . . Yes!
I am a prime example. During the first few years of my medical practice and reserve military service, we had routine vitals checkups. I was working out 3-5 days a week with weights and running 3-5 miles 2-3 times a week and restricting my calories to 1500 per day. So, I thought I was in pretty good shape. However, it was not uncommon for for the nurse to raise her eyebrows at my blood pressure readings in the 140-160 systolic and 85-98 range diastolic. “Oh, it’s the lack of sleep last night,” or “it’s the caffeine I had this morning,” would be my excuse. But I was making a lot of excuses, and in light of those excuses, my caloric restriction, exercise and salt restriction, I was also still gaining weight.
By the 5th year of my medical practice, I weighed 60 lbs heavier than I do today and I struggled to keep my blood pressure under 150/95. I was violating my own counsel . . . don’t trust a fat doctor for nutritional advise. (Or, was that advise from Dr.House?)
A much slimmer, healthier and happier Dr. Nally (center) in 2016
After cutting out the carbohydrates (I’ve kept my carbohydrate intake < 20 grams per day), moderating my protein intake and eating all the fat I am hungry for each day, my recent physical examination at the beginning of June 2016 revealed my blood pressure at 112/64. I don’t remember ever having blood pressure that low. And to be honest, I didn’t sleep well the night before my exam due to a number of middle of the night patient calls.
When I first started treating the insulin resistance problem in the human, rather than the blood pressure problem, I began to see immediate reductions in blood pressure within one to two weeks. So much of a reduction that if I didn’t warn the patient that they should begin to back down their blood pressure medications, they would experience symptoms of dizziness, light-headedness, headache and a few patient’s nearly passing out. On a low-carbohydrate, high-fat (ketogenic) diet you need salt (sodium, potassium, & magnesium). The process of burning fat as fuel causes you to lose increased amounts of sodium & potassium, and you have to replace these electrolytes. A number of my patients begin a low-carbohydrate, high-fat diet and are afraid of increasing their salt intake. Not replacing these electrolytes while on a ketogenic diet can also lead to low blood pressure, dehydrate and dizziness.
I often wondered why applying a ketogenic diet had such a profound effect on blood pressure so quickly. Dr. Robert Lustig helped answer that question for me.
In order to understand how the Standard American Diet (we call it the SAD diet in my office) raises your blood pressure, it is important to understand how the body processes the basic sugar molecule. Sugar is one glucose molecule bound to a fructose molecule. This is broken down in the body and 20% of the glucose is metabolized in the liver, the other 80% is sent on to be used as fuel throughout the body. Fructose, however, is where the problems arise. 100% of the fructose is metabolized in the liver, and the by product of fructose metabolism is increasing the liver’s production of MORE glucose and the byproduct of uric acid. Uric acid is produced and this inhibits the production of nitric oxide. The diminished nitric oxide in the presence of an increased level of glucose (stimulating increased insulin production due to eating starches) constricts the blood vessels and raises blood pressure. Yes, that donut you just ate raised your blood pressure for the next 12 hours.
The mechanism that fructose containing carbohydrates, sugars and starches raise blood pressure, cholesterol and cause weight gain can be seen in the really complex diagram found in Dr. Lustig’s 2010 article:
So, how do you lower your blood pressure through diet?
First, cut out all the simple sugars. These include anything with table sugar, high fructose corn syrup and corn syrup. (This is why people with any change in diet see some improvement in weight and blood pressure as they remove the simple sugars like candy, sugared drinks and pastries from their diet.)
Second, limit your overall intake of other sources of carbohydrates including any type of bread, rice, pasta, tortilla, potato, corn and carrots. Realize that carbohydrate in fruit is fructose, and when taken with other forms of glucose can have the same effect as table sugar – it can and will raise your blood pressure, as well as halt or cause weight gain.
Third, if you are taking blood pressure medications for hypertension, see your doctor about close monitoring of your blood pressure as it can and will drop within 2-4 weeks of making these dietary changes.
Maintaining ketosis is really important for weight loss and blood pressure or hypertension control. I am very much an advocate of using real food for this process, but I have also found that the use of exogenous ketone salts aid significantly in maintaining ketosis. I have found that exogenous ketones are the next step in bridging the difficulty of day to day maintenance of ketosis.
It isn’t making the mistakes that’s critical; it’s correcting them and getting on with the task that’s important. If you’ve been calorie restricting and exercising to lower you blood pressure, don’t fret. A simple change in your diet focused on restricting starches and carbohydrates has been demonstrated in my office to be more powerful than many of the blood pressure medications we’ve used for years.
Dr. Nally recently spoke about Low-Carbohydrate/Ketogenic Diets on the 2016 Low Carb Cruise to the Eastern Caribbean. While there, he and Jimmy Moore recorded another episode of KetoTalk with Jimmy and the Doc.
Here’s what Jimmy and Dr. Nally talked about in Episode 20:
– We are in front of a LIVE audience of Ketonians
– How long will you experience hair loss when you go ketogenic?
– What role does resistant starch have on the keto diet?
– Is eating high-fat with high-carb harming my boyfriend?
– How does intermittent fasting help with keto?
– Whether to count total vs. net carbohydrates
– Whether you need to cycle carbs when building muscle
– What the best way to test your ketones is
– How to test blood ketones on a budget
– What the difference is between an NMR and basic lipid panel
– The dramatic changes in your cholesterol when going keto
– How long should you be on keto before running blood tests?
– Whether you should cut fat lower on keto to speed up weight loss
– Is having a lower body temperature a bad thing when eating keto?
You can listen at the iTunes page here, or download it for free to your favorite iTunes player.
How do you know if you're insulin resistant? What questions need to be asked? What should your numbers be? And, many other great ketosis questions. Also, why does Dr. Nally look like he has dirt on his chin? See it here . . .
Diseases seem to arrive in three’s each day in my office. Today I had three different patients with cholesterol concerns who were notably confused about what actually makes the cholesterol worse, and what causes weight gain. Each of them, like many patients that I see, were stuck in a state of confusion between low fat and low carbohydrate lifestyle change. My hope is to give my patients and anyone reading this blog a little more clarity regarding what cholesterol is, how it is influenced and how it affect our individual health.
First, the standard cholesterol profile does not give us a true picture of what is occurring at a cellular level. The standard cholesterol panel includes: total cholesterol (all the forms of cholesterol), HDL (the good stuff), LDL-C (the “bad” stuff) and triglycerides. It is important to recognize that the “-C” in these measurements stands for “a calculation” usually completed by the lab, and not an actual measurement. Total cholesterol, HDL-C and triglycerides are usually measured and LDL-C is calculated using the Friedewald equation [LDL = total cholesterol – HDL – (triglycerides/5)]. (No, there won’t be a quiz on this at the end . . . so relax.)
However, an ever increasing body evidence reveals that the concentration and size of the LDL particles correlates much more powerfully to the degree of atherosclerosis progression (arterial blockage) than the calculated LDL concentration or weight (1, 2, 3).
There are three sub-types of LDL that we each need to be aware of: Large “fluffy” LDL particles (type I), medium LDL particles (type II & III), and small dense LDL particles (type IV).
Weight & Size of VLDL, LDL & HDL
Why LDL-C is misleading: Identical LDL-C of 130 mg/dL can have a low risk (Pattern A) with a few “big fluffy LDL particles or high risk (Pattern B) with many small dense LDL particles.
Second, it is important to realize that HDL and LDL types are actually transport molecules for triglyceride – they are essentially buses for the triglycerides (the passengers). HDL can be simplistically thought of as taking triglycerides to the fat cells and LDL can be thought of as taking triglycerides from the fat cells to the muscles and other organs for use as fuel.
Third, it is the small dense LDL particles that are more easily oxidized and because of their size, are more likely to cause damage to the lining of the blood vessel leading to damage and blockage. The large boyant LDL (“big fluffy LDL particles”) contain more Vitamin E and are much less susceptible to oxidation and vascular wall damage.
Eating more fat or cholesterol DOES NOT raise small dense LDL particle number. Eating eggs, bacon and cheese does not raise your cholesterol! What increases small dense LDL particles then? It is the presence of higher levels of insulin. Insulin is increased because of carbohydrate (sugars, starches or fruits) ingestion. It is the bread or the oatmeal you eat with the bacon that is the culprit. The bread or starch stimulates and insulin response. Insulin stimulates the production of triglycerides and “calls out more small buses” to transport the increased triglyceride to the fat cells (4, 5, 6, 7).
Fourth, following a very low carbohydrate diet or ketogenic diet has been demonstrated to decreased small dense LDL particle number and correlates with a regression in vascular blockage (8, 9). So, what does this really mean to you and me? It means that the low-fat diet dogma that that has been touted from the rooftops and plastered across the cover of every magazine and health journal for the last 50 years is wrong. . . absolutely wrong.
I talk about this and answers questions on today’s Periscope. You can see the recording on Katch.me with the comments in real time here:
Superko HR, Gadesam RR. Is it LDL particle size or number that correlates with risk for cardiovascular disease? Curr Atheroscler Rep. 2008 Oct;10(5):377-85. PMID: 18706278
Rizzo M, Berneis K. Low-density lipoprotein size and cardiovascular risk assessment. QJM. 2006 Jan;99(1):1-14. PMID: 16371404
Rizzo M, Berneis K, Corrado E, Novo S. The significance of low-density-lipoproteins size in vascular diseases. Int Angiol. 2006 Mar;25(1):4-9. PMID:16520717
Howard BV, Wylie-Rosett J. Sugar and cardiovascular disease: A statement for healthcare professionals from the Committee on Nutrition of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. Circulation. 2002 Jul 23;106(4):523-7. PMID: 12135957
Elkeles RS. Blood glucose and coronary heart disease. European Heart Journal (2000) 21, 1735–1737 doi:10.1053/euhj.2000.2331
Stanhope KL, Bremer AA, Medici V, et al. Consumption of Fructose and High Fructose Corn Syrup Increase Postprandial Triglycerides, LDL-Cholesterol, and Apolipoprotein-B in Young Men and Women. The Journal of Clinical Endocrinology and Metabolism. 2011;96(10):E1596-E1605.
Shai I et al. Cirulation. 2010; 121:1200-1208
Krauss RM, et al. Prevalence of LDL subclass pattern B as a function of dietary carbohydrate content for each experimental diet before and after weight loss and stabilization with the diets. American Journal of Clinical Nutrition. 2006; 83:1025-1031
Gentile M, Panico S, et al., Clinica Chimica Acta, 2013, Association between small dense LDL and early atherosclerosis in a sample of menopausal women, Department of Clinical Medicine and Surgery, University “Federico II” Medical School, Naples, Italy Division of Cardiology, Moscati Hospital, Aversa, Italy A. Cardarelli Hospital, Naples, Italy
This week I had the pleasure of seeing a really nice 46 year old Hispanic male who is fairly new to the office. He came back in to see me in follow up on his diabetes. To give you a bit of background history, the patient came to see me about 6 months ago, just not feeling very well. Based on his symptoms of fatigue, history of elevated blood sugar and family history, lab work was completed.He saw us initially with a Hemoglobin A1c of 12.3% in June (normal should be 4.9%-5.6%). This means he had an average blood sugar over the previous three months of about 310 mg/dL (normal should be < 110 mg/dL).
Past Medical History include: Diabetes Mellitus – type II (not on any medications when initially seen), Hypertension (high blood pressure), Dyslipidemia (elevated cholesterol) and a non-specific heart arrhythmia.
Medications: None
Surgeries: Knee & shoulder arthroscopies
Family History: Father Diabetes, Stroke, Heart Disease, Hypertension, Elevated Cholesterol
After getting his labs back, we had a very long conversation about the need to either fix his diet dramatically, or he may be looking at using 3-4 oral medications or even insulin to control his blood sugar.
When I see average blood sugars (HbA1c) stay over 6.5% (or greater than 140 mg/dL), the risk for retinal, kidney and nerve damage is significant and often irreversible after 4-5 years. Most physican’s are affraid to lower the HbA1c to less than 7.0% with medications due to low blood sugar events, and so the diabetes community has “settled” with 7.0% as being effective. However, it still isn’t low enough. I saw this happen with my father and with other members of me family. I’ve seen it happen over and over with my patients over the last 15 years when they have not lowered their blood sugar and reduced the high insulin loads that occur in response to those high blood sugar levels. It has been my experience that HbA1c can be very safely lowered to the normal range, as low as 5.2-5.6% without symptomatic low blood sugars, with the correct diet and careful use of medications.
As you can see, a dramatic change in his blood sugar has occurred in a three month interval. Not only that, we see a significant change in his cholesterol profile.
Previously, we looked at LDL-C for heart disease risk, however, I have multiple patients that have had heart disease with normal LDL-C ( <100 mg/dL). LDL-C is just a summation of all the particles. The LDL particle is actually made up of three sub-types and it is specifically the small dense particle that causes the vascular risk. You can see a dramatic normalization of the small dense particle LDL with no change in LDL-C and minimal change in Total Cholesterol in the patient’s labs when he reduces his carbohydrate intake. This is a pattern I see every single day. When serial carotid ultrasound studies are completed, I see reduction in blockage and reduction in the vascular wall thickening. I will be very interested to see the vascular studies on this patient and I will await his results as he tightens up his diet even further.
All in all, he has dramatically brought his diabetes under control with carbohydrate restriction and if he continues this lifestyle, he has reduced his risk for retinal damage, reduced his risk for kidney damage, reduced his risk for nerve damage and essentially added 20 years to his life.
(Disclosures: Dr. Nally has no vested interest, monitary or otherwise, in Novo Nordisc or it’s products including liraglutide.)
I can’t help myself. Some days I enjoy a good murder mystery, but on others, I enjoy a good journal article elucidating our understanding of leptin. No, leptin is not a tiny Irish folk character or even a superhero. Leptin is a hormone. It’s made by fat cells. Anything made by fat cells becomes fascinating to a “fat doctor.”
Why is learning about leptin illuminating?
Well, if Sir Arthur Conan Doyle was an Obesity Specialist, the mystery would have been that Mr. Plump was killed by the wrench in the kitchen, but the wrench seems to have never left tool case in the garage. No one has been able to figure out how leptin, the allegorical wrench, plays its roll in lepin resistance. We know that a lack of leptin allows hunger to persist and a person without leptin will continue to eat without the sensation of feeling full – leading to obesity. What we haven’t understood is – what causes the brain to no longer sense larger and larger amounts of leptin being produced by those who are obese.
That is . . . we haven’t understood it until now. . .
We have known for some time that the hormone leptin is a key hormone produced by the adipose (fat) cells that suppresses hunger. A majority of obese patients in my clinic have elevated circulating leptin levels 2-10 times the normal levels. We know that a lack of leptin leads to obesity, but the patients that I see in the office are producing an over abundance consistent with leptin resistance. The leptin signal is not being recognized by the brain. This is very similar to type II diabetes and insulin resistance. The pancreas is producing an over abundance of insulin, but the cells are recognizing the signal to let the glucose in through the door way.
Three recent and very interesting studies have pointed to the probable cause. First, one of the most common genetic disorders causing human obesity is loss of function of the melanocortin receptor.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
If the MC-4R receptor is broken, suppression of appetite is limited, continued eating occurs and weight gain continues. Leptin, produced by every adipose cell in the body, is carried in the blood stream to the brain and must pass through the blood-brain barrier. Once it crosses the blood-brain barrier and enters the hypothalamus, it has a stimulatory effect on the MC-3R receptor in the Arcuate Nucleus of the hypothalamus causing stimulation of the MC-4R receptor in the Parventricular Nucleus and Lateral Hypothalamus to turn off hunger.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
However, if leptin cannot cross the blood brain barrier, the signal is never received from the adipose cells and continued eating without satiation (feeling full) persists. Studies have shown that dietary fructose ingestion alone or in combination with diets high in fat suppress the transmission of leptin across the blood-brain barrier.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
Fructose is the primary component of high-fructose corn syrup, and makes up 45-50% of every other type of natural form of sugar (sucrose). Yes, it’s the major component found in table sugar, brown sugar, honey, agave, molasses and maple syrup. This is why a Paleolithic Diet isn’t fully effective for people with leptin resistance.
Lastly, anything that raises triglycerides inhibits leptin from crossing the blood-brain barrier.
Image adapted from 2011 “The Skinny About Fat” presentation – Adam Nally, D.O.
Insulin has a direct effect on triglycerides. (See the articles “Insulin Resistance & The Horse,” “Fat Thoughts on Cholesterol,” “Ketogenic Living” and “So, What is this Ketogenic Thing?“). If your insulin levels go up, triglyceride production goes up. The patient with insulin resistance, pre-diabetes, impaired fasting glucose or type II diabetes produces between two to ten times the normal amount of insulin when eating the standard American diet (SAD diet). These patients have significant triglyceride elevation because of the high insulin response to carbohydrates in their diet. (Many of them were told by their doctor that “It’s just genetic so take your Lipitor.”) Statin drugs lower the LDL-C (calculated “bad cholesterol” level), but don’t reduce triglycerides effectively. Inadequate treatment of high triglycerides allows poor blood-brain barrier transmission of leptin and worsening leptin resistance.
In fact, this is the challenge and problem with the “frequent fasting” or “intermittent fasting” fad for weight loss that has been popping up in the blogosphere. If fasting reaches a state of starvation (which is a very fine line metabolically), it stimulates a stress response . . . causing a spike in cortisol, release of glycogen (a form of sugar), a compensatory release of insulin and a spike in triglycerides. If you have tried intermittent fasting and you’ve gained weight, you are probably not “fasting,” your probably “starving.” We’ve known for years that triglycerides are elevated in starvation. This diminishes leptin’s ability to cross the blood-brain barrier and leads to worsening leptin and insulin resistance.
High leptin levels caused by leptin resistance also seems to play a significant role in the development of diabetic retinopathy – damage to the tiny blood vessels at the back of the eye feeding the retina. Diabetic retinopathy starts insidiously without any symptoms initially and can lead to eventual blindness if not treated. Leptin seems to upregulate vascular endothelial growth factor (VEGF) which leads to narrowing of the blood vessels called “ischemia.” Chronic ischemia of the retinal vessels leads to damage to the delicate retinal cells of the eye.
So what do you do if you have leptin resistance. First, eliminate carbohydrates from your diet, especially sugars, high fructose corn syrup and any other form of simple sugar. This is why I am such a big fan of low carbohydrate, high fat diets.
Third, use a supplement containing alpha-lipoic acid, carnosine high gamma vitamin E and benfothiamin (derivative of Vitamin B1). These have been demonstrated to decrease inflammation and render protection to the blood vessels.
The use of Epigallocatechin gallate (EGCg), a derivative extract of green tea, has been shown to repress hepatic glucose production, one of the insidious factors of insulin resistance, and may play a role in stabilizing the effect insulin has on production of triglycerides. You should consider using KetoEssentials. It is my specially formulated multivitamin that contains all of the above supplements, and includes methylated folic acid (B9), the necessary vitamin B6 & B12, chromium, vandium & zinc that help to further stabilize insulin resistance.
Fourth, get a good night’s sleep. Lack of sleep causes a stress response, increases cortisol, raises blood sugar and insulin leading to further leptin resistance.
Fifth, mild to moderate resistance exercise has been shown for years to improve insulin resistance significantly. If you’re not exercising, take a 20 minute walk 2-3 times per week, ride a bike for 20 minutes, start a weight lifting program, consider yoga or Pilates, Remember, jumping to conclusions, flying off the handle, carrying things too far, dodging responsibility and pushing your luck don’t qualify as resistance exercise.
Above all, if you’re having trouble losing weight, controlling insulin or leptin, see your doctor. He or she can really help.
References:
Ray F. Gariano, Anjali K. Nath, Donald J. D’Amico, Thomas Lee, and M. Rocio Sierra–Honigmann. “Elevation of Vitreous Leptin in Diabetic Retinopathy and Retinal Detachment.” Invest Ophthalmol Vis Sci. 2000;41:3576–3581
Hammes HP, Du X . “Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.” Nat Med. 2003 Mar;9(3):294-9. Epub 2003 Feb 18.
Hipkiss AR, Brownson . “Reaction of carnosine with aged proteins: another protective process?” Ann N Y Acad Sci. 2002 Apr;959:285-94.
Zachary A. Knight, K. Schot Hannan, Matthew L. Greenberg, Jeffrey M. Friedman. “Hyperleptinemia Is Required for the Development of Leptin Resistance.” PLoS ONE 5(6): e11376. doi:10.1371/journal.pone.0011376.
Min-Diane Li. “Leptin and Beyond: An Odyssey to the Central Control of Body Weight.” The Yale Journal of Biology and Medicine. 2011;84(1):1-7.
Eri Suganami, Hitoshi Takagi,Hirokazu Ohashi, Kiyoshi Suzuma, Izumi Suzuma, Hideyasu Oh, Daisuke Watanabe, Tomonari Ojimi, Takayoshi Suganami, Yasushi Fujio, Kazuwa Nakao, Yoshihiro Ogawa and Nagahisa Yoshimura. “Leptin Stimulates Ischemia-Induced Retinal Neovascularization: Possible Role of Vascular Endothelial Growth Factor Expressed in Retinal Endothelial Cells.” Diabetes. September, 2004. vol. 53 no. 9 2443-2448
Joseph R. Vasselli, Philip J. Scarpace, Ruth B. S. Harris, and William A. Banks. “Dietary Components in the Development of Leptin Resistance.” Adv. Nutr. 2013: 4: 164–175.
Joseph R. Vasselli. “Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance.” Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1365-9. doi: 10.1152/ajpregu.90674.2008. Epub 2008 Sep 10.
Waltner-Law ME, Wang XL Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem. 2002 Sep 20;277(38):34933-40. Epub 2002 Jul 12.
85% of the people that walk through my office doors have some degree of insulin resistance.
What is “insulin resistance?” It is an over production of insulin in response to ANY form of carbohydrate intake (yes, even the “good carbs” cause an insulin over-response in a person with insulin resistance.)
How do I know this? Because I routinely check insulin levels (I check them every three months) and the down stream markers of insulin on a large number of the patients that I see. I have been fascinated by the fact that a diet high in both sugar and fat [like the Standard American Diet, (SAD) diet] turn on the genetics leading to insulin resistance. Starch and sugar load the genetic gun.
Insulin acts like a key at the glucose doorway of every cell in your body. In many people, the insulin signal is blocked by hormones produced in the fat cell and the the insulin, acting like a “dull or worn out key” – can’t open the glucose doorway as efficiently.
So, the body panics, and releases extra insulin in response to the same load of carbohydrate or glucose. People with insulin resistance will produce between 2-20 times the normal amount of insulin in response to a simple carbohydrate load. Recent studies(1, 2) reveal high cholesterol and diets high in both fat and carbohydrate cause insulin resistance to progress or worsen.
So, instead of producing enough insulin to accommodate the one slice of bread or the one apple that you might eat, the insulin resistant person produces enough insulin for an entire loaf of bread or an entire bushel of apples. This excess insulin then stimulates one or all of the following:
Weight Gain – Insulin directly stimulates weight gain by activating lipoprotein lipase to take up triglycerides into the fat cells. This causes direct storage of fat and increases your waistline. (3)
Elevated Triglycerides – Insulin directly stimulates production of free fatty acids and triglycerides through hepatic gluconeogenesis and is even more notably amplified by the broken signaling mechanism of the FOX-01 phosphorylation mechanism in patients with insulin resistance. (4)
Increased number of Small Dense LDL (sdLDL) particles – Low density lipoprotein (LDL, or “bad cholesterol”) is actually comprised of various sized lipoproteins including small, medium and large. As triglycerides increase, the small dense LDL particle numbers increase. Research points to the fact that it is the small dense particle that is highly atherogenic (leading to the formation of vascular plaques within the arteries). (5, 8)
Elevated Uric Acid – Leptin resistance and insulin resistance syndromes are often found together and are suspected to have significant influence on each other. High insulin loads lead to “sick adipose cells” causing leptin resistance. This has a dramatic effect on hepatic fructose metabolism increasing the production of uric acid. Excess insulin suppresses urinary excretion of uric acid and dramatically increases serum content of uric acid and the risk of kidney stones and gout. (6, 7)
Increased Inflammation – Increased levels of circulating insulin have a direct correlation on raising many of the inflammatory markers and hormones including TNF-alpha and IL-6 in the body (9). Any disease process that is caused by chronic inflammation can be amplified by increased circulating levels of insulin including asthma, acne, eczema, psoriasis, arthritis, inflammatory bowel and celiac disease, etc.
Elevated Blood Pressure – Increased uric acid production from insulin resistance as noted above directly suppresses production of nitric oxide within the vasculature and increases blood pressure (7). This completes the triad of metabolic syndrome (elevated triglycerides & cholesterol, weight gain, and elevated blood pressure) found in patients with insulin resistance.
Water Retention – We have known for many years that insulin affects the way the kidney uses sodium in the distal nephron. Insulin has a direct effect on sodium retention in the kidney. As insulin levels rise, the kidney retains increased levels of sodium (10). Water follows sodium and thereby causes fluid retention. This is the reason that many of my insulin resistant patients who have struggled with leg swelling and edema suddenly improve when they correct their diet and their high circulating insulin levels fall. It is also the reason that many of my patients show up in my office after the holidays with swollen legs and amplified swelling in their varicose veins after cheating on their ketogenic diets.
If you are plagued by any or all of these, my first suggestion is to see your doctor and get screened for insulin resistance. I treat patients with these every day and have reversed these effects in thousands of patients with the correct diet and/or medications. Having seen these signs and patterns over the last 20 years of medical practice, I am still astonished every day by the dramatic effect our diet plays on the hormonal changes within the body. Remember that the food you eat is actually the most powerful form of medicine . . . and the slowest form of pernicious poison.
Cholesterol Elevation Impairs Glucose-Stimulated Ca2+Signaling in Mouse Pancreatic β-Cells, Endocrinology, June 2011, Andy K. Lee, Valerie Yeung-Yam-Wah, Frederick W. Tse, and Amy Tse; DOI: http://dx.doi.org/10.1210/en.2011-0124
Glucose-Stimulated Upregulation of GLUT2 Gene Is Mediated by Sterol Response Element–Binding Protein-1c in the Hepatocytes, DIABETES, VOL. 54, JUNE 2005; Seung-Soon Im, Seung-Youn Kang, So-Youn Kim, Ha-il Kim, Jae-Woo Kim, Kyung-Sup Kim and Yong-Ho Ahn
Selective versus Total Insulin Resistance: A Pathogenic Paradox, Cell Metabolism, Volume 7, Issue 2, 6 February 2008, Pages 95–96, Michael S. Brown, Joseph L. Goldstein
Association between small dense LDL and early atherosclerosis in a sample of menopausal women, Department of Clinical Medicine and Surgery, University “Federico II” Medical School, Naples, Italy Division of Cardiology, Moscati Hospital, Aversa, Italy A. Cardarelli Hospital, Naples, Italy, Gentile M, Panico S, et al., Clinica Chimica Acta, 2013
Sugar, Uric Acid and the Etiology of Diabetes and Obesity. Diabetes. 2013;62(10):3307-3315, Richard J. Johnson; Takahiko Nakagawa; L. Gabriela Sanchez-Lozada; Mohamed Shafiu; Shikha Sundaram; Myphuong Le; Takuji Ishimoto; Yuri Y. Sautin; Miguel A. Lanaspa
Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010 Sep;110(9):1307-21. doi: 10.1016/j.jada.2010.06.008. Lustig RH
Cardiovascular Risk in Patients Achieving Low-Density Lipoprotein Cholesterol and Particle Targets. Atherosclerosis. Vol 235; 585-591, May 2014, Peter P. Toth, Michael Grabner, Rajeshwari S. Punekar, Ralph A. QuimboMark J. Cziraky c, Terry A. Jacobson
Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome The Insulin Resistance Atherosclerosis Study (IRAS), Circulation, July 2000, 102:42-47; Andreas Festa, MD; Ralph D’Agostino, Jr, PhD; George Howard, DrPH; Leena Mykka¨nen, MD, PhD; Russell P. Tracy, PhD; Steven M. Haffner, MD
The Effect of Insulin on Renal Sodium Metabolism. Diabetologia. September 1981, Volume 21, Issue 3, pp 165-171. R. A. DeFronzo
I recently read a blog post decrying anyone that would recommend a low carbohydrate / ketogenic diet to their patients.
What?!
In fact, this particular blog outlined a number of “adverse reactions” to a ketogenic diet, and based upon these perceived reactions, the writer advised severe caution with its use in just about anyone. It is important to note at the outset that most of the data this blogger quotes are from older studies completed in children for the treatment of epilepsy with specific liquid ketogenic dietary meal replacements. (Not what you’d expect in a low-carb / ketogenic diet for the average obese adult today.)
Diet Confusion
Thanks to recent misinformation by a number of medical professionals, including the person writing the blog referenced above, a poor understanding of fatty acid metabolism by the general community, and a distinct lack of understanding of human adaptability recorded over the last 5,000-6,000 years, there is still significant confusion about ketogenic diets.
It is important to recognize the crucial fact that the human body is designed to function quite well when supplied any of three macronutrients: carbohydrates, proteins or fats. It does so through an amazing series of enzymatic reactions referred to as the Krebs (tricarboxylic acid) cycle, producing needed ATP (adenosine triphosphate) required for our muscles to contract, our heart to beat and our diaphragm to expand our lungs. What’s even more amazing that that the body was designed to recognize the season we are in based up on the food we eat. That is, until we invented refrigerators in 1913. (Now our bodies think it’s year round summer time . . . wait . . . I live in Arizona where it is year round summer time.)
No, this is not a post about unplugging your refrigerator, living on solar, getting off the grid and saving energy.
Our bodies recognize the seasons we are in based upon inherent hormone release. The key hormone is insulin. Insulin can be looked at as the seasonal indicator to our bodies. Insulin production rises and falls based on our intake of carbohydrates (sugar, starches, some fibers). Insulin, essentially, tells our bodies when it is a “time of plenty” and when it was a “time of famine.” Why? You ask. We didn’t have refrigerators 100 years ago and you were lucky if you had a root cellar. The body needs to know when to store for the famine (the winter) that was around the corner. Insulin is that signal.
During the summer, potatoes, carrots, corn and other fruits are readily available. These are all starchy carbohydrates and they all require the body to stimulate an insulin response so that they can be absorbed. Insulin stimulates fat storage (J Clin Invest. 2000;106(4):473-481. doi:10.1172/JCI10842). Just like bears, our bodies were designed to store for the winter.
If you think back in history, your grandparents probably used stored meats & cheeses that could be salted or smoked for preserving during this time of year. Those crossing the plains were commonly found with pemmican, a concentration of fat and protein used as a portable nutrition source in the absence of other food. (Chapter VIII. Narrative of the Life of David Crockett, of The State of Tennessee, Written by Himself, Sixth Edition [E.L. Carey and A. Hart:Philadelphia] 1834, 1837; Marcy, The Prairie Traveler, p. 31.) Think about conversations you may have had with your grandmother when she told you that for Christmas, she received an orange. A single orange for a gift?! Many of my patients drink 12-15 of them in a glass every morning. The winter diets of our grandparents were very low in starches and carbohydrates. When carbohydrate intake is low, little insulin is produced.
Again, insulin is the hormone that tells you that you’re in “a time of plenty” and stimulates weight gain and cholesterol production to prepare for winter. Those prescribing the use of ketogenic diets understand this innate human adaptive trait, and use it to effect changes in weight, cholesterol and other desired metabolic changes.
Three types of ketones. Uptodate.com, May 2015
Now, let’s define the difference between ketosis and keto-acidosis and try to clarify the misinformation that is being spread around the blogosphere.
A ketone is a molecule the body produces from the breakdown of fat and some proteins (amino acids). There are specifically three types of ketones: beta-hydroxybutyric acid, acetoacetic acid and acetone. If ketosis was “bad,” then why would our bodies produce these molecules? They are not bad, and in fact, multiple studies show that the body is often more efficient and effective when it functions on ketones rather than glucose as its primary fuel source. The body can only supply a limited amount of sugar or glucose for fuel. If you talk to runners, marathoners or triathletes, they will tell you that after about 45-90 minutes of continuous endurance exercise the glucose supply runs out and they will experience what is termed a “bonk” (have a low-blood sugar or hypoglycemic episode). Unfortunately, our bodies can only store about 18-24 hours of glucose.
Metobolic Changes of Ketogenic Diet (American Journal of Physiology – Endocrinology and Metabolism Published 1 June 2007 Vol. 292 no. 6, E1724-E1739 DOI: 10.1152/ajpendo.00717.2006)
However, the body can store days upon days of fat in the form of triglyceride in the fat cells. Triglyceride is broken down into ketones. If glucose is the “unleaded” fuel, you can think of ketones as the “diesel fuel” that is easier to store and runs longer.
The average body functioning on ketones as the primary fuel will have a ketone level measured in the blood somewhere between 0.4 and 4 mmol/L. Because of a balance that is created by the use of ketones and a feedback mechanism that kicks in when the ketone level rises, the body will maintain a pH of around 7.4.
Ketoacidosis is dramatically different. If you are a type I diabetic, you don’t produce any insulin. The feedback mechanism regulating ketone use is broken and the ketone levels and triglyceride breakdown speeds up because the body can’t access glucose and can’t produce insulin. The ketone levels spike and the level can rise to > 25 mmol/L. In the presence of a high blood sugar and high ketone level, the acid level in the blood shifts to a pH of less than 7.3. This is referred to as metabolic acidosis and can be life threatening as the low pH shuts down the bodies’ enzymatic processes and a person becomes critically ill and without treatment, can die. (Kitabchi AE et al., Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults. www.uptodate.com, May 2015.)
If you’re not a type I diabetic, you have nothing to worry about. Regardless of what the “ketogenic nay-sayers” blog about, your liver makes approximately 240g of glucose per day, this stimulates a basal release of insulin which keeps the pH in check. It’s also what keeps weight loss at a consistent pace of around 2-10 lbs per month.
If you are a type I diabetic, don’t fret. Carbohydrate restriction can still be used very effectively. It just takes some balancing and understanding of your individual metabolism. Talk to your physician and/or medical bariatrician about how to follow a carbohydrate restricted diet while using insulin.
What about all the other “adverse effects” the blogosphere and other so-called experts claim about ketogenic diets?
Let’s take them on one by one. Are you ready?
Gastrointestinal (GI) disturbances – Yes. Any time you change your diet you may experience diarrhea, constipation or gassiness. Most of the time, this is because you are either 1) not eating enough leafy greens (fiber) or 2) you’re using a supplement that contains an artificial sweetener. Most of the studies on ketogenic diets did not incorporate fiber and the studies used to make this point were on children who used a ketogenic fat supplement shake or liquid preparations containing these artificial sweeteners to make them palatable. If you have spoken to any bariatrician, they will tell you, the best way to follow a ketogenic diet is to eat real food. If you want to read about the anecdotal GI effects of sweeteners, read the comment section in Amazon about the Haribo Sugar Free Gummy Bears.
Inflammation Risk – In every patient that I have placed on a ketogenic diet in the last 8 years, all inflammatory markers including CRP, Sedimentation Rate and Uric Acid have all decreased. Inflammation gets better on an appropriately formulated ketogenic diet. The older studies of ketogenic diets in children contain most of their fat from Omega-6 fatty acids from vegetable oil which will increase inflammation and oxidative stress, spike the cortisol levels and have the secondary effect of actually raising the triglycerides. (Simopoulos AP,The importance of the ratio of omega-6/omega-3 essential fatty acids, Biomed Pharmacother., 2002 Oct;56(8):365-79.)
Muscle Cramps/Weakness – The process of weight loss occurs by burning fat into CO2 and water. We breathe the CO2 out, but the water produced has to follow salts out through the kidneys. Hence, we lose salts. This can cause weakness and muscle cramps. The solution? Stop restricting salt on a low carbohydrate diet. We are the only mammal that restricts salt and we do it because low-fat diets cause us to retain water. Low carbohydrate diets do the opposite. Use sea salt or sip beef or chicken bouillon broth with your dinner. The use of yellow mustard also helps (the small amount of quinine in yellow mustard stops the cramping). If you have congestive heart failure, talk to your doctor about monitoring your salt intake in balance with your diuretic or water pill.
Hypoglycemia – If you read the ketogenic diet research, most of it was done on epileptic children. The diets called for a period of starvation, then the use of a ketogenic liquid based on the John’s Hopkin’s protocol. It is a well-known fact in medicine that starvation in children can frequently cause hypoglycemia, especially in children with other genetic or congenital defects leading to forms of epilepsy. In clinical practice, with ketogenic diet use in adults, hypoglycemia is rare.
Low Platelet Count (Thrombocytopenia) – Again, this was seen in the epileptic children who were placed into starvation first, then introduced a liquid fat replacement shake to stop intractable seizures. These liquids or shakes were often nutrient deficient in other essentials. Folic acid, B12 and copper deficiency can occur when not eating “real food.” Low platelet counts are rarely seen on ketogenic diets based around “real food.” Many children in the ketogenic studies had been on or were concomitantly on valproic acid for their seizures. Valproic acid is commonly known to cause thrombocytopenia (Barry-Kravis E et al, Bruising and the ketogenic diet: evidence for diet-induced changes in platelet function. Ann Neurol. 2001 Jan;49(1):98-103.; Kraut E, Easy Bruising, http://www.uptodate.com, May 2015.)
Easy Bruising – This is usually due to inadequate protein supplementation as was the case in much of the ketogenic literature where protein levels were also restricted. (Kraut E, Easy Bruising, http://www.uptodate.com, May 2015.)
Pancreatitis – Patients who are insulin resistant or have impaired fasting glucose commonly have high triglycerides. Elevation in triglycerides itself is a cause of pancreatitis. Ketogenic diets lower the triglycerides. However, if a patient has not been following their diet as directed, spikes in the triglycerides can occur placing the person at risk for pancreatitis.
Long QT Intervals/Heart Arrhythmias – The list of things causing Long QT intervals and abnormal heart rhythms is long and variable (Acquired Long QT Syndrome. Berul C et al. www.uptodate.com, May 2015). It is well know that starvation, rapid weight loss and liquid protein diets can cause a delay in the conduction signal in the heart. Anyone wishing to start any diet should have an electrocardiogram (EKG) through their doctor to ensure that the diet (of any type) doesn’t exacerbate a prolonged QT interval.
Three year weight loss and metabolic improvement in a patient on a Low-Carb / Ketogenic diet. Note: Patient admits to not following ketogenic diet during holidays from Nov 2013 – Feb 2014 (see the dramatic changes to the body when cheating happens)
Cardiomyopathy – Prolonged QT intervals have been associated with cardiomyopathy and the former can stimulate the later. Any diet that has the potential to prolong a QT interval has the potential to cause cardiomyopathy. Hence the need for regular EKG monitoring on any diet (Acquired Long QT Syndrome. Berul C et al. www.uptodate.com, May 2015).
Lipid/Cholesterol Changes – In the 8 years I have been applying ketogenic diets to patients, I have seen dramatic improvement in the triglycerides and HDL levels. The only time triglycerides rise over 100 is if the patient is using artificial sweeteners or is cheating on the carbohydrate restriction. Total cholesterol commonly rises, however, this is indicative of the fact that there is a shift in the LDL particle size and this affects the calculation of both total cholesterol and LDL-C. In light of this, most of my patients have dramatic improvement in triglycerides and small dense LDL particle number. I’ve included the common cholesterol changes I seen in my office as a few case reports to demonstrate the effectiveness of a ketogenic diet:
2 year ketogenic dietary labs and weight loss
Myocardial Infarction – It is interesting that one blogger includes this on the list of adverse reactions, however, when you actually read the study, the author of the paper make an “assumption” that there was potential for heart attack due to an elevated total cholesterol, however, a correlation was never made. Again, in the 8 years I have been using ketogenic diets, I have seen dramatic improvement in cholesterol profiles, inflammatory markers, atherosclerosis and carotid intimal studies (Shai I et al, Circulation 2010; 121:1200-1208).
Three year metabolic history of a Low-Carbohydrate / Ketogenic diet
Menstrual Irregularities / Amenorrhea – It is well known that any diet causing protein or other nutritional deficiency will affect the menstrual cycle first and growth second. The only time menstrual irregularities occur with a ketogenic or Low-Carb diet is when a patient is not taking in enough protein or is not eating real food. What amazes me is that a properly applied ketogenic diet causes normalization of the menstrual cycle, and in my practice, I’ve had a number of women successfully be able to conceive after making a ketogenic dietary change.
For more details on the nutrient content of a ketogenic diet, see the recent article by a friend of mine, Maria Emmerich. She’s been creating ketogenic diets for years and has a number of fantastic books my wife and I have been using in our home over the last nine years. She is one among many that can give you some direction on how to devise a healthy, real food based ketogenic diet. See the page on my website here that will give you some direction in formulating your Ketogenic Lifestyle.
Nally Family Low-Carb / Ketogenic Cheese Cake
So, to celebrate Mother’s Day, today, with my family, I am going to indulge in some Low-Carb / Ketogenic Cheese Cake!! Happy Mother’s Day, to all of you and especially to all you mothers out there making a healthy difference in the lives of your families! (You can find the recipe for this delicious cheese cake here)
In the words of Sir William Ostler, “If it were not for the great variability among individuals, medicine might well be a science and not an art.”
The only way to successfully loose weight is to modify or turn off the mechanisms that stimulate fat storage. For years we have been told that this was just a problem of thermodynamics, meaning the more calories you eat, the more calories you store. The solution was, thereby, eat less calories or exercise more, or both. We are taught in school that a 1 gram of carbohydrate contains 4 kcal, 1 gram of protein contains 4 kcal, and 1 gram of fat contains 9 kcal.
It’s easy to see that if I’m going to limit my calories, cutting out fat is the first step. For the last 65 years, we as a society have been doing just that, cutting out fat, exercising more and eating fewer calories. What has it done for us? It’s made us fatter! (1)
Obesity Rates Around the World
Some may argue that we really aren’t eating fewer calories and exercising more. But most people I have seen in my office have tried and tried and tried and failed and failed and failed to loose weight with this methodology. The definition of insanity is “doing the same thing over and over and expecting a different result.”
Most of my patients are not insane, they recognize this and stop exercising and stop restricting calories . . . ’cause they realized, like I have, that it just doesn’t work! If you’re one that is still preaching caloric restriction and cutting out fat, I refer you to the figure above and the definition of insanity . . .
So, if reducing the calories in our diet and exercising more is not the mechanism for turning on and off the storage of fat, then what is?
Before I can explain this, it is very important that you appreciate the difference between triglycerides and free fatty acids. These are the two forms of fat found in the human body, but they have dramatically different functions. They are tied to how fat is oxidized and stored, and how carbohydrates are regulated.
Fat stored in the adipose cells (fat cells) as well as the fat that is found in our food is found in the form of triglycerides. Each triglyceride molecule is made of a “glyceride” (glycerol backbone) and three fatty acids (hence the “tri”) that look like tails. Some of the fat in our adipose cells come from the food we eat, but interestingly, the rest comes from carbohydrates
(“What! Fat comes from sugar?! How can this be?!!“)
De Novo Lipogenesis
We all know that glucose derived from sugar is taken up by the cells from the blood stream and used for fuel, however, when too much glucose is in the blood stream or the blood sugar increases above the body’s comfort zone (60-100 ng/dl), the body stores the excess. The process is called de novo lipogenesis, occurring in the liver and in the fat cells themselves, fancy Latin words for “new fat.” It occurs with up to 30% (possibly more if you just came from Krispy Kream) of the of the carbohydrates that we eat with each meal. De novo lipogenesis speeds up as we increased the carbohydrate in our meal and slows down as we decrease the carbohydrate in our meal. We’ve known this for over 50 years, since it was published by Dr. Werthemier in the 1965 edition of the Handbook of Physiology (2).
While we know that fat from our diet and fat from our food is stored as triglyceride, it has to enter and exit the fat cell in the form of fatty acids. They are called “free fatty acids” when they aren’t stuck together in a triglyceride. In their unbound state, they can be burned as fuel for the body within the cells. I like to think of the free fatty acids as the body’s “diesel fuel” and of glucose as the body’s version of “unleaded fuel.” The free fatty acids can easily slip in and out of the fat cell, but within the adipose cell, they are locked up as triglycerides and are too big to pass through the cell membranes. Lipolysis is essentially unlocking the glycerol from the free fatty acids and allowing the free fatty acids to pass out of the fat cell. Triglycerides in the blood stream must also be broken down into fatty acids before they can be taken up into the fat cells. The reconstitution of the fatty acids with glycerol is called esterification. Interestingly, the process of lipolysis and esterification is going on continuously, and a ceaseless stream of free fatty acids are flowing in and out of the fat cells. However, the flow of fatty acids in and out of the fat cells depends upon the level of glucose and insulin available. As glucose is burned for fuel (oxidized) in the liver or the fat cell, it produces glycerol phosphate. Glycerol phosphate provides the molecule necessary to bind the glycerol back to the free fatty acids. As carbohydrates are being used as fuel, it stimulates increased triglyceride formation both in the fat cell and in the liver, and the insulin produced by the pancreas stimulates the lipoprotein lipase molecule to increased uptake of the fatty acids into the fat cells (3).
So when carbohydrates increase in the diet, the flow of fat into the fat cell increases, and when carbohydrates are limited in the diet, the flow of fat out of the fat cells increases.
Summarizing the control mechanism for fat entering the fat cell:
The Triglyceride/Fatty Acid cycle is controlled by the amount of glucose present in the fat cells (conversion to glycerol phosphate) and the amount of insulin in the blood stream regulating the flow of fatty acid into the fat cell
Glucose/Fatty Acid cycle or “Randle Cycle” regulates the blood sugar at a healthy level. If the blood glucose goes down, free fatty acids increase in the blood stream, insulin decreases, and glycogen is converted to glucose in the muscle and liver.
These two mechanisms ensure that there is always unleaded (glucose) or diesel fuel (free fatty acids) available for every one of the cells in the body. This provides the flexibility to use glucose in times of plenty, like summer time, and free fatty acids in times of famine or winter when external sources of glucose are unavailable.
The regulation of fat storage, then, is hormonal, not thermodynamic. Unfortunately, we’ve know this for over 65 years and ignored it.
We’ve ignored it for political reasons, but that’s for another blog post . . .
References:
1. James, W. J Intern Med, 2008, 263(4): 336-352
2. Wertheimer, E. “Introduction: A Perspective.” Handbook of Physiology. Renold & Cahill. 1965.
3. Taubs, G. “The Carbohydrate Hypothesis, II” Good Calorie, Bad Calorie. Random House, Inc. 2007, p 376-403.
The FDA approved an intense new artificial sweetener, Advantame. Because of its chemical similarity, Aspartame now has a super sweet cousin. This sweetener, 20,000-37,000 times more sweet than table sugar (sucrose), is found in powder form and dissolves in water. However, it does partially break down when exposed to heat or used in heated drinks, so it may not be that great for cooking.
Similar to Aspartame, one of the breakdown metabolites is phenylalanine, implying that those with sensitivity to phenylalanine or PKU may need to avoid it, however, the amount of phenylalanine produced when ingested was felt to be fairly negligible.
My interest was peaked by the fact that Advantame does not raise blood sugar or insulin levels in the multiple animal and three humans studies reviewed here and here. This implies that it probably won’t cause weight gain and the studies in animals actually revealed some negligible weight loss.
The FDA claims this is a very safe artificial sweetener due to it’s intense sweetness and requirement for only small quantities to be effective. In fact, Josh Bloom from the American Council on Science and Health was quoted saying that, “About the only way this stuff could harm you is if you were run over by a truck that was delivering it.”
From the perspective of weight loss, this may be another sweetener that could be used effectively on a carbohydrate restricted diet.
the underlying cause. I see this problem in a very large majority of the people in my office and I am seeing people younger and younger show up with continually increasing blood pressure.
begin to back down their blood pressure medications, they would experience symptoms of dizziness, light-headedness, headache and a few patient’s nearly passing out. On a low-carbohydrate, high-fat (ketogenic) diet you need salt (sodium, potassium, & magnesium).
as well as the fat that is found in our food is found in the form of triglycerides. Each triglyceride molecule is made of a “glyceride” (glycerol backbone) and three fatty acids (hence the “tri”) that look like tails. Some of the fat in our adipose cells come from the food we eat, but interestingly, the rest comes from carbohydrates
before they can be taken up into the fat cells. The reconstitution of the fatty acids with glycerol is called esterification. Interestingly, the process of lipolysis and esterification is going on continuously, and a ceaseless stream of free fatty acids are flowing in and out of the fat cells. However, the flow of fatty acids in and out of the fat cells depends upon the level of glucose and insulin available. As glucose is burned for fuel (oxidized) in the liver or the fat cell, it produces glycerol phosphate. Glycerol phosphate provides the molecule necessary to bind the glycerol back to the free fatty acids. As carbohydrates are being used as fuel, it stimulates increased triglyceride formation both in the fat cell and in the liver, and the insulin produced by the pancreas stimulates the lipoprotein lipase molecule to increased uptake of the fatty acids into the fat cells (3).
The FDA approved an intense new artificial sweetener, Advantame. Because of its chemical similarity, Aspartame now has a super sweet cousin. This sweetener, 20,000-37,000 times more sweet than table sugar (sucrose), is found in powder form and dissolves in water. However, it does partially break down when exposed to heat or used in heated drinks, so it may not be that great for cooking.