Metabolism is the most complex system in the body because it controls your healthspan.  Healthspan is defined as your longevity minus years of disability.  An efficient metabolism increases your healthspan.  On the other hand, an inefficient metabolism decreases your healthspan.  What controls your metabolism (and hence your healthspan) is not a drug but your diet. 

Metabolic Engineering® provides a clinically validated dietary system to reprogram the metabolism in each of your 30 trillion cells to work at peak efficiency.  The benefits are the loss of excess body fat, improved physical and mental performance, and slowing down aging.  All these benefits lead to a longer healthspan.

What does Metabolism Do?

The answer is just about everything to keep you alive.  It converts food into energy, controls the immune system, controls genetic expression, controls the ability to repair damaged tissue, and far more.  However, your metabolism can be disrupted by a pro-inflammatory diet, leading to the development of insulin resistance.

Because metabolism is so complex, no drug can orchestrate it, but Metabolic Engineering® can, as it uses three distinct, interrelated dietary components.  The first is calorie restriction without hunger or fatigue using the Zone diet.  This intervention reduces insulin resistance  The second is the adequate consumption of omega-3 fatty acids to resolve inflammation caused by insulin resistance. Finally, a unique class of polyphenols known as delphinidins, repair the tissue damage caused by insulin resistance. 

Defining Wellness

The goal of medicine should be the maintenance of wellness instead of treating the symptoms of chronic disease.  So, how can you define wellness?  A good definition would be having an efficient metabolism.  Although metabolism is incredibly complex, there is one blood marker that can provide a unique insight into how efficient your current metabolism is.  That marker is insulin resistance

Defining Insulin Resistance

Insulin resistance is a marker of your ability to remove sugar (i.e., glucose) from the blood into target cells for metabolic use.  The more effective that removal is, the lower your insulin resistance.  The term “insulin resistance” is a misnomer as a cell can take up blood glucose in two ways.  One way is using an insulin-stimulated pathway.  However, there is a second pathway that bypasses the need for insulin.  This pathway accounts for about one-half of the removal of blood sugar, and is governed by the master regulator of metabolism, AMPK.     

Role of AMPK in Metabolism

The reason that AMPK is the master regulator of metabolism is because it is an energy sensor in the cell. If calorie intake is high, AMPK activity is inhibited.  If calorie intake is restricted, AMPK activity is increased.  The increase in AMPK activity enhances your metabolism to function more effectively.  How it does this is complex, but here is a summary of the molecular outcomes occurring when increasing AMPK activity.

You burn fat faster.  Excess body fat is a consequence of an inefficient metabolism.  As a result, incoming calories are stored as fat instead of being converted to energy.  Increasing AMPK activity causes this stored fat to be converted into energy faster.

You are activating glucose uptake.  Glucose is a primary fuel for your metabolism, but only if it gets into the cells. Increasing AMPK activity brings more glucose into the cells without the need for insulin.  This extra pathway for increased glucose into the cell increases energy to maintain an efficient metabolism.

You are controlling gene transcription factors.  AMPK acts as a master regulator of gene expression by turning on and off various gene transcription factors that promote the DNA in of the cell to produce new proteins that control complex metabolic pathways within the cell. 

Modifying gene expression by epigenetics.  AMPK also affects the translation of your DNA by epigenetics.  Although your genes can code for more than 20,000 different proteins, at any one time, only about 5-10 percent of those genes are active.  Increased AMPK activity controls which genes are turned off or turned on by epigenetic control of your DNA.  This fine-tuning by AMPKl places chemical marks on your DNA that determine which genes will be expressed.  As a result, your metabolism becomes much more efficient with optimal AMPK activity to control this complex orchestration of your genes.

You are reducing cellular senescence.  The underlying cause of aging is the development of senescent cells. Senescent cells are also termed “zombie cells” because they appear to be immortal.  They don’t die but continue to secrete inflammatory mediators that cause other cells to decrease their metabolic efficiency.  The result is that you age faster. Usually, the immune system can remove such zombie cells before they create extensive acceleration of aging.  However, if AMPK is inhibited, then the ability of the immune system to identify and destroy these zombie cells is compromised.  The result is you age faster.  Since excess body fat is the primary “breeding ground” for new zombie cells, the loss of excess body fat is your first step toward living longer.

Role of AMPK in Obesity, Chronic Disease, Aging

Obesity can be viewed as one consequence of reduced  AMPK activity.  One of the actions of AMPK is to orchestrate the conversion of stored body fat to chemical energy to orchestrate your metabolism.  If the diet inhibits AMPK activity, you store excess incoming calories as fat instead of burning stored fat as a source of energy.   More ominously, stored body fat is a primary breeding ground for new senescent cells that can spread to every organ in the body to accelerate the earlier development of chronic disease.

Many chronic disease conditions are strongly associated with increased insulin resistance.  As you reduce insulin resistance using Metabolic Engineering®, the symptoms of the severity of any chronic disease related to insulin resistance will be reduced.  This means making any drugs you use to treat the symptoms of chronic disease work better at lower concentrations.   It also means your physician can potentially lower the amount of a drug used to treat those symptoms.  Insulin resistance appears years ahead of developing the symptoms associated with chronic disease.  Thus, the sooner you begin using Metabolic Engineering® to decrease insulin resistance, the longer your healthspan can be expanded.

Finally, reducing insulin resistance using Metabolic Engineering™ allows you to delay the accumulation of excess senescence cells and thus slow aging.

How Metabolic Engineering® Works

Metabolic Engineering™ is an integrated dietary system, not a magic bullet.  Metabolism is too complex for a single drug, let alone a single dietary intervention or nutritional supplement, to fine-tune its dynamic nature. 

Drugs work like a light switch.  They either turn on or turn off the activity of a single enzyme.  Metabolic Engineering™ is like a sound mixing board in which the sound engineer balances out incoming signals to get the a perfectly balanced sound.

The three integrated nutritional components of Metabolic Engineering™ are the following:

1. Calorie restriction without hunger or fatigue to reduce insulin resistance.  Calorie restriction is the most powerful dietary technology for activating AMPK.  However, the only way calorie restriction can be continued for a lifetime is to ensure you are never hungry or bored  following it.
   
   The Zone diet was developed and patented to achieve that goal.  This is possible since the Zone diet is based on a constant balance of protein to the glycemic load of a meal to maintain AMPK in a zone where hunger is stopped for five hours, while the repair of damaged tissue continues.  The satiety pathways used by the Zone diet are the same ones used by the new generation of injectable weight-loss drugs. To activate those satiety pathways, you will need about 30 grams of protein at every meal.  Any less will be insufficient to generate the hormonal signals in the gut that reach the brain via the vagal nerve.  Any more protein is likely to inhibit AMPK activity. 
   
   However, that protein intake must be balanced with carbohydrates.  For an intake of 30 grams of protein at a meal, this will require about 40 grams of carbohydrates.  But which ones?  The lower the glycemic load, the better.  Non-starchy vegetables have the lowest glycemic load, whereas fruits and whole grains have the higher level. Refined grains and simple sugars have the highest glycemic loads.
   
   Finally, you need a dash of fat to complete a Zone meal.  A dash would be about 15 grams of fat.  The best sources are those rich in monounsaturated fats.  This includes extra virgin olive oil, nuts, or avocados.   When you have the correct combination of macronutrients, you will get five hours of appetite suppression with an intake of approximately 400 calories. The secret is learning how to repeat this macronutrient balance at every meal. This is why the Zone diet is the foundation of Metabolic Engineering™.
   
2. However, Metabolic Engineering™ is more complex than calorie restriction without hunger or fatigue. You also require adequate levels of omega-3 fatty acids to make the hormones known as resolvins that turn off inflammation.  These are the most powerful hormones known to medical science, yet without adequate levels of omega-3 fatty acids in the diet, resolvins cannot be produced in sufficient levels to resolve inflammation.
   
   Virtually all chronic diseases are associated with chronic low-level inflammation.  Unless this type of inflammation is resolved, you speed up the development of symptoms associated with a chronic disease.  To have adequate levels of omega-3 fatty acids in the body to promote the formation of  resolvins, you will likely need supplementation.  An additional benefit of adequate intake of omega-3 fatty acids is that resolvins indirectly activate AMPK.
   
3. The third dietary component of Metabolic Engineering™ is adequate intake of polyphenols. Polyphenols are chemicals that provide vegetables and fruits with their color.  They also are indirect activators of AMPK that lead to the activation of gene transcription factors such as Nrf2 that cause the expression of anti-oxidative enzymes that reduce oxidative stress.  Unfortunately, most polyphenols are not very bioavailable.  Thus, to get adequate levels will usually require supplementation with purified polyphenol extracts.

Each of the three dietary component of Metabolic Engineering™ is beneficial, but it is only when all three work together will you obtain the full range of metabolic benefits of Metabolic Engineering™ that are needed to reduce the growing population of senescent cells that accelerate the development of a wide variety of chronic diseases and thus the rate of aging.

Personalizing Metabolic Engineering®

The power of Metabolic Engineering™ is that it can be personalized to the individual since not everyone is genetically the same.  There are certain blood tests that can provide such individualization. Here are some of those blood tests you want to have to slow down aging.

HOMA-IR
Medical science is only valid if you have measurable endpoints.  The success of Metabolic Engineering™ can measured by the reduction of HOMA-IR.  If your HOMA-IR is less than one, your health future is bright.  If HOMA-IR is greater than two, your health future is bleaker.  The higher your HOMA-IR levels are in the blood, the faster your organs are aging. How long does it take to reduce HOMA-IR significantly?  The clinical data states that insulin resistance can be significantly reduced in as little as four days.  Of course, once you stop following Metabolic Engineering™, insulin resistance will quickly begin to rise to its original level.  Metabolic Engineering™ should be considered  a lifetime program to achieve a longer healthspan.

Other blood measurements also indicate how to adjust each of the three dietary interventions of Metabolic Engineering™ to get the maximum metabolic benefits.

TG/HDL ratio
To achieve the maximum benefits of following the Zone diet, your goal is to keep your triglyceride/high-density cholesterol (TG/HDL) ratio under one.  That adjustment can be quickly made by reducing the glycemic load of your diet by eating more non-starchy vegetables as your primary source of carbohydrates.   

AA/EPA ratio
The ideal supplementation levels of omega-3 fatty acids are determined by the arachidonic acid (AA)-to eicosapentaenoic acid (EPA) ratio in your blood.  If the AA/EPA ratio is greater than 3, then you should take more omega-3 fatty acids.  If the AA/EPA ratio is less than 1.5, then you should take fewer omega-3 fatty acids. 

HbA1c
Finally, your glycosylated hemoglobin A1c (HbA1c) level is the blood marker for the correct number of polyphenols you should take.  If your HbA1c is greater than 5.1 percent, you should take more polyphenols. If your HbA1c ratio is less than 4.9 percent, then you take fewer polyphenols. 

These blood markers allow you to personalize your Metabolic Engineering™ program for a better quality of life at every stage, starting in the womb to age 100 and beyond.  Opti