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Fat Lock Box #DocMuscles #KetonianKing

Ketones – One of the Keys to the Fat Lock-Box

Do you have the keys to your “fat lock-box?”

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?

Stimulation Lipolysis #DocMuscles #KetonianKing
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.

#WhereIsBaconBoy #DocMuscles #KetonianKing

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.

Hypothalamus-Pituitary-Gonadal (HPG) Axis & Testosterone

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):

  1. Lafontan et al. Arterioscler Thromb Vasc Biol. 2005
  2. Lenard NR, Obesity, 2008
  3. Li XF et al, Endo (April 2004) Vol 145
  4. Liu YY& Brent GA, Trends Endocrinol Metab. 2010 Mar; 21(3): 166–173
  5. Max Lafontan et al. Arterioscler Thromb Vasc Biol. 2005;25:2032-2042
  6. Skorupskaite K et al, Hum Rep Update, Mar 2014, vol 20

Dietary Counseling Tantrums

I am a Family Practice Physician.  I spent eleven years of my life training to become a physician certified in Family Medicine.  But, I found this wasn’t enough.  I struggled to treat the “diseases of civilization” that arise from society, our Western diet and lifestyle.

I, also, specialize in dietary weight/obesity management and low-carbohydrate/ketogenic diets.  I actually spent an additional three years obtaining specialized training and board certification in this field.   When you add all the training and my years of experience in practice together, I’ve spent over 25 years perfecting this art of medicine.

Because of this training, I have been very blessed that people from all over the world travel to Surprise, Arizona, to see me for weight management, dietary advise, and counseling on the diseases of civilization.  I’ve been amazed that simple changes in diet halt and reverse obesity, arthritis, diabetes, cholesterol, high blood pressure, etc.  The list goes on and on …

But I find a disturbing mindset pervasive through the community and the nation:

CarbCounseling

After listening to an number of people get angry over this issue in the last few weeks, I began wondering to myself…

“Who ties your shoelaces for you?”

Podcast #32: Hereditary Angioedema, Lower Blood Ketones, Statins, Healthy Keto Lifestyle

Hereditary AngioEdema.jpg
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.

Statin.jpg

“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

 

KetoTalk: Episode 27 -Mailbox Blitz, Low Energy, Headache, Stomach-Ache, Breast-Feeding While On Keto

Mailbox desert

Listen in today as Jimmy and Adam blaze through a bunch of listener questions in Episode 27 of KetoTalk with Jimmy and the Doc!

GetAdaptBars

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

KetonesKETOOS

Listen in here at KetoTalk.com or you can download the episode for free on iTunes.

How Fat Lowers Your Blood Pressure

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 Blood Pressure Surprisethe 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?!Time Changes Everything

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.

Nally 1998 Expanding Waist

 

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?)

Nally 2016
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.

Loegolas Blood Pressure

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 Himalayan Saltbegin 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. GetAdaptBars

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:

Metabolism of Fructose

 

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.

You can find out how to get started on a low carbohydrate, high fat (ketogenic) diet in my recent articles  The Principle Based Ketogenic Lifestyle – Part I and Ketogenic Principles – Part II.