How to Tell If Diet Mismatches Genetic Determined Metabolic Ability

Part 4 of “What Six Months of Soup Can Teach Me”

A few practical tips on doing this modified fasting diet are in order.  Timing this around what is going on in life can be helpful.  It gets harder during stressful times.  This made me appreciate how “stress eating” is a problem in the first place.  In contrast, this gets easier during times of high constructive activity.  It seems if we are meaningfully engaged, we don’t get as preoccupied with eating.  The moral is that controlling stress and being busy with meaningful activity is a poorly appreciated part of good dietary behavior.

On to the issues of what is happening with our eating behavior and why a modified fasting diet can be so helpful.  The real issue with the current Western diet for the majority of the U.S. population is that its composition places maximum stress on the portion of our metabolic machinery that is least adept at handling it.  Maximum stress on a weak area typically will cause failure, which in this case, is chronic metabolic disease.

That weak area is the broad group of enzymes used to manage a main end product of carbohydrate digestion - sugars.  There are many dozens of different enzymes involved in the process of trying to convert sugars into energy.  As we previously discussed, when the amounts of sugars exceed the need at the moment, it goes to the liver to be converted to the fat, triglyceride.  The triglycerides are then circulated destined for fat storage in the central (abdomen) portion of the body.  If carbohydrate/sugar intake chronically exceeds the need of the moment, triglyceride is increasingly produced and fat stores increase.

One of the primary features of the Paleo period genetic pattern is multiple SNPs of the genes involved in processing sugars to energy.  The 75-80% of westerners who have this pattern just cannot manage high amounts of carbohydrate/sugar under normal circumstances.

A great question to answer might be how much carbohydrate/sugar does one consume? 

The chart shows estimates of both the amount of energy or calories from carbohydrate as well as the factors regarding its quality.  The more refined the carbohydrate, the faster the sugars become available generating more metabolic stress.  Added refined sugars require no digestion before absorption so all of their energy is immediately available whether it is needed at that instant or not.

By all measures the amount of carbohydrate in the western diet has increased from 200-600%, yet the genetic ability to manage it has literally not changed.  The second and equally troublesome factor is the “glycemic load” of the western diet.  Glycemic load is a combination of how much and how fast a given carbohydrate will raise blood sugar.  Not all carbs are created equal.  Simple sugars and grains have a disproportionately high glycemic load compared to fruits and vegetables.  Simply put, they generate far more stress per gram on metabolism than other carb sources.

A great analogy might be a worker who can process 50 files very accurately in a 40-hour work week.  If you want to make this good worker make a lot of mistakes you can do it one or both of two ways. Have them try to process 200 files in the same week (increased amount of carbohydrate), or have them try to process the same 50 files but only working 2 hours a day for the 5 days (high glycemic load).  The western diet is like having that worker try to do both!

So how do we tell if we are in metabolic stress trying to manage carbohydrates?  The first sign is white adipose tissue or belly fat which is stored triglyceride. 

Typically, when triglyceride production stays high, more will be produced in the liver than can be quickly transferred to belly fat causing blood triglyceride levels to rise.  As fat stores become high, belly fat begins to produce inflammation which begins to injure insulin receptors which are needed to signal cells to take in and use blood sugar.  This fuels the whole triglyceride production cycle even further.

Additionally, when liver triglyceride production is high,  the production of HDL or “good cholesterol” drops and the production of a very small cholesterol molecule, VLDL, increases.  These VLDL particles are particularly worrisome as they become very small dense LDL which is the most dangerous regarding vascular disease risk.

The last step in this metabolic dysfunction cascade is that the insulin resistance so impairs the ability of cells to take in sugars to burn or convert to triglyceride that blood sugar rises.  At the first sign of this the diagnosis of “pre-diabetes” is made, and as it progresses it is eventually called diabetes.  Pre-diabetes is like calling the first trimester of pregnancy “pre-pregnancy”.  I think it should more appropriately be called simply early diabetes.

That was a lot so I’ll summarize.  The common order of problems showing up suggesting metabolic distress in handling carbohydrates is:

1)    Belly fat – excess triglyceride

2)    Increasing blood triglyceride - >125 mild concern, >150 real concern

3)    Decreased HDL - < 40-50.  A triglyceride/HDL >3 is a real concern

4)    VLDL cholesterol >30

5)    Increased small LDL particles – requires specialized testing called an NMR profile

6)    Increased blood sugar

The small LDL particle size needs a little explanation.  We generally make two sizes of LDL or “bad cholesterol”.  The size of the particles determines their ability to cause vascular disease with small, dense particles being more dangerous than large, fluffy ones.  We all make some of each but in varying ratios.  Genetics influence this ratio some, but diet also highly affects it.

The diagram shows 2 persons (“S” and “L”) with an identical LDL cholesterol value of 130 mg/dL.  This is the total weight of LDL in a fixed volume of blood. The small, dense particles are called apo B and the large, fluffy ones are apo A. 

While person “S” and person “L” have the same total weight of LDL, person “S” on the left side has many more small particles and therefore greater risk.

Some persons with “normal” LDL cholesterol levels develop vascular disease while others with relatively high LDL cholesterol never will.  The particle size and number variable is thought to be an important determinant of this contradictory risk.

The point of all of this is that before blood sugar inches up into abnormal range, the body has been firing warning shots across the bow for many years with the above changes in body and blood profile.  Diabetes is a late effect of chronic metabolic chaos. 

A minority in western populations can tolerate a greater percentage of carbohydrate and a somewhat higher glycemic load.  This is like the uncle someone has who smoked a pack of cigarettes and drank a quart of whiskey each day living to be relatively healthy until killed in a skydiving accident on his 90^th birthday.  We all assume we are “that guy”, but they are very rare.  Most of us will need to give careful attention to matching our diet chemistry to our true metabolic ability.  Not doing so has led to the epidemic of metabolic disease which we are trying to beat down with drugs.  The food got us there, and it is the foundation for an effective solution.

So I continue with the modified, intermittent fasting to help reset my metabolism.  Starting with a normal body fat I still lost 7 lbs the first 2 weeks and 1 inch off my waist.  If you take the list of the problems that show up early indicating some metabolic stress, the modified, intermittent fasting does a “system restore” on it all.  The first indicator that that is happening is pulling triglycerides out of belly fat to burn for energy.  I choose not to curse my genetics but rather cheer the knowledge of a solution.

What Six Months of Soup Can Teach Me

Part 3 – How Genetics and Lifestyle Interact, Good or Bad

The big question for all of us to address is how much of our health and disease outcomes will be determined by genetics and how much will be determined by lifestyle, particularly diet.  If you accept that genetics is largely responsible, you will be absolved of most responsibility for the outcome.  Your only hope is medical breakthroughs if you drew poor genetic cards.

If you accept that lifestyle is primarily determinant, it puts the control of your health fate squarely on you.  To my thinking, this is the best case scenario.  What science has shown us since the completion of the analysis of the entire human genome in 2000, the reality is that our health fate is a mixture of both genetics and lifestyle. 

There are approximately 23,000 genes in each of us that our responsible for the design of the proteins, enzymes and other things that form are makeup and function.  Each gene can have many little variations called single nucleotide polymorphisms, or SNPs, with “many” being defined as 40-60.  Some 3.5 million SNPs have been identified in the human genome so we all have thousands of them.

A SNP is a variation of just one nucleotide in a long genetic chain of code.  This is shown here in two variations where “G” or “T” are substituted for the more ideal “A”.

If a polymorphism of a gene that makes an important enzyme in carbohydrate and sugar management exists, the resulting enzyme will function more weakly than normal rendering that person less carbohydrate and sugar tolerant.  Another way of saying that is that they will get in metabolic trouble more quickly eating a higher carb/sugar diet. 

The reason I choose this example is that this pattern seems to exist in about 75-80% of the U.S. population including me.  My dominant genetic pattern comes from my mother’s side of the family, Irish transplants from the earlier 1900’s.  Diabetes and heart disease were the norm in the preceding two generations I knew.  A favorite uncle died of a second heart attack before the age of 40.

So what difference would this Irish/Western European genetic background have to do with carbohydrate tolerance?  It seems when our ancestors left Africa way back, they came to a fork in the road.  They must have listened to one of my favorite philosophers, Yogi Berra who was quoted saying, “if you come to a fork in the road, take it!”  My group turned left up into Europe, while others went to the middle east and beyond.

The theory goes that in Europe there were more animals which led to hunter- gathering type survival.  For those who took the right fork to the middle east, animals were more scarce so they ate more what they could gather which was more dominantly carbohydrate.  Once they figured out how to domesticate grain in Turkey in 9000 B.C., modern plant agriculture was born further increasing the percentage of dietary carbohydrate for those folks.

Two dominant gene patterns naturally occurred in these populations with implications about carbohydrate tolerance.  Those in the middle eastern group who genetically were favored to handle larger amounts of carbohydrate tended to be much healthier, while those who had the less able carbohydrate genetic pattern struggled.  One of the early victims of metabolic stress is fertility so each population became fairly uniform in genetic pattern suited to the food supply of the area. 

My tribe was Paleo-type diet suited.  Migrate us again to the U.S and put our genetic pattern into a 55% carbohydrate, refined sugar and high grain dietary environment and metabolic chaos has ensued.

Fortunately, those who have genetic mediated difficulty in managing carbs/sugars problems can largely be prevented with parts of two different strategies.  The first is keep yourself in a dietary environment that does not stress your metabolic weaknesses.  This is the lower carbohydrate (<40% of energy), very low sugar eating pattern.  Carbs should also come only from whole, complex carbohydrates and are dominantly from vegetables rather than grains.  Grains have a glycemic load (they raise blood sugar and sugar management stress) 8-10 times higher than the same grams of carbs from vegetables.

The second part to managing genetic weaknesses is a targeted nutrient program. 

The diagram shows an important enzyme reaction in converting a breakdown product of sugar, pyruvate, to acetyl CoA which becomes energy. 

The conversion of pyruvate to energy is begun by the enzyme, pyruvate dehydrogenase, When the gene responsible makes a copy of the enzyme, it is inactive.  It is activated by “cofactor” which in this case is vitamin B1 or thiamine.  Those with a gene pattern that causes them to make a weak version of the enzyme can increase its activity by adding higher amounts of co-factor or vitamin B1.

The best approach to our genetic weaknesses is to consume a diet that is compatible with our strengths and places little stress on the weaknesses as well as supplementing extra nutrients known to increase weak enzyme activities. 

But how can one tell what their pattern is?  There are a few ways.  First is family history, although that is not foolproof.  A lot of processed carbohydrate products didn’t exist when grandma was a kid, sugar wasn’t added to everything, nor was processed grain a staple as it is now.  She could have had a subtler carbohydrate intolerance that her diet didn’t not exploit, but ours will.

The second is “wait and see” which many are doing.  If we end up at 55 years old with diabetes and 2 or 3 other related diseases, it tells us more about our intolerances. I don’t think this “wish I had known sooner” approach is the right way to go for me.

The third approach is that different tests such as blood chemistry profiles show the stress of an imbalance between genetic mediated metabolic ability and our diet.  This allows the pre-empting of the potential bad outcome before it has done the damage.  I will talk about how to do that in the next post.

So what does all of this have to do with modified fasting and the chicken soup?  Everything!  If the body is saying we have a metabolic mismatch between fuel and the ability to manage it, modified fasting periodically helps perform a “system restore”.  I do it every so often to keep my computer healthy, why not for my health?

What Six Months of Soup Can Teach Me

Part 2 – The Fed Versus Fasting State

A word of caution is needed here.  There are some health problems that may be helped by this intermittent modified fasting dietary pattern but it should only be done with the agreement of your doctor and with some professional monitoring during the process.  More severe diabetes controlled with medication is an example.  Reducing medication levels under supervision may be needed.  While this is an objective of the dietary pattern it must be done carefully with supervision.  Kidney disease may be another precaution.  So any doubt, coordinate any large dietary change with your treating physician.

So, how am I doing at this?  I am a couple of days into the 5:2 dietary pattern and no body parts have fallen off yet.  I didn’t expect any to but thought I should reassure everyone about that. 

This dietary plan uses a modified fasting pattern of 2 days per week to “reboot” a more normalized metabolic pattern.  On the two days of the modified fasting, 1-1.5 cups of soup is consumed twice at 12-hour intervals.  Tea or black coffee can be consumed as well as water.  The idea is to switch our metabolism from the fed state to one of fasting.  But just “what does that do?” seems to be the question.

As I have a higher genetic risk pattern (I will explain that in a later post), and I tend to do things “the best they can be done”, I am actually doing the 3:4 version which is 4 days of modified fasting and 3 normal dietary days.  Dr. Mosley’s 5:2 version works, but I am doing it a little more aggressively – an affliction I have!

In the fed state dietary energy (calories) is used to provide immediate energy to cells.  All excess is then sent to the liver for conversion to a storage fat, triglyceride.  If fed state occupies too much of our day, we are in a fat production and storage mode increasing all of the diseases that are associated with it.  Carbohydrates especially accelerate the production of triglycerides, thus the high protein/low carb content or Paleo-esque nature of the soup.  The increase in carbohydrate in the western diet over the past 200-300 years from 30% to about 55% of energy has been particularly contributory to the overweight and obesity epidemic as well as its associated chronic disease epidemic.

An additional problem from the constant fed state that upregulates triglyceride production is that some persons have difficulty transporting all of the triglyceride out of the liver to fat storage.  This causes these fats to build up in the liver itself creating non-alcoholic fatty liver disease (NAFLD).  A recent study reported that the number of male teens with NAFLD doubled over the past several decades with 1 in 10 affected by the disease and 1 of every 2 obese teens affected.

In contrast when we are in the fasted state, triglyceride is pulled out of fat storage and burned for energy directly as triglyceride and as ketones which are made in the liver from triglyceride.  The reason the liver turns some of the triglyceride into ketones is that the brain can only burn glucose and ketones but not fat.  We can exploit that in some individuals with cognitive decline or mild dementia using a modified fasting to improve brain function, but more about that in another post.

There are many other positive benefits to spending some time in the fasting state.  It lowers blood sugar and insulin levels which lowers diabetes risk and the risks of many other associated diseases such as arterial disease (heart, stroke, etc), dementia/Alzhiemer’s disease, kidney disease, neuropathy and others.

The metabolic changes during the fasting state were thought to impart an advantage to the success of finding subsequent food either through hunting of gathering.  It appears this fasting state increases mental alertness that would be needed pursuing wild game.  This interesting video is about how mice who have an increased genetic pattern towards developing memory impairment and dementia can greatly reduce this tendency with periodic fasting.

One of the other convincing pieces of evidence for periodic fasting comes from studies about the effect of caloric restriction on healthy longevity.  It seems restricting overall energy consumption in mammals results in important increases in healthy longevity.  This is defined as not simply living longer but being free of chronic disease for a greater portion of this longevity as well, which I think is an objective of almost all of us.

The picture shows the measured effects of caloric restriction in laboratory animals.  The RER is resting energy reserves or stored fat, while WAT is white adipose tissue, the belly fat most associated with disease risk.  Notice the survival age with caloric restriction increases about 15-20% over the ad libitum, or free eating group.

The difficulty with caloric restriction is that it requires constant reductions in caloric intake of 60% for several decades, an ongoing lifestyle few would undertake.  Intermittent fasting, however, can induce a disproportionate amount of the benefit of ongoing caloric restriction but in a much more tolerated way for most persons. 

I guess the other alternative is to live in the wilderness and only eat what you catch or find as did our ancient ancestors who were the origins of our genetic machinery.  This is a trait I learned from parenting.  If they don’t like option “A”, make it look better by giving them a less appealing option “B”!

Not everyone has the same urgency for avoiding the constant fed state and not everyone requires such strict adherence to the Paleo dietary pattern of only 35% of energy from carbohydrate, very low grain, no added sugars.  We are not all genetically wired the same.  There appears to be 2 dominant genetic patterns that most humans have which govern the urgency/intensity of dietary behavior.  I will discuss these 2 patterns in the next post, how they appeared to have originated and how to tell which you may have.  In the meantime, I continue to explore what six months of soup can teach me.  The first few days have been easier than I expected.

What Six Months of Soup Can Teach Me

Part 1 – What is This Journey About and Why Do It?

Welcome to this blog series on the beginning of my adventure with several days each week of semi-fasting.  This journey begins after an encounter with a patient who I suggested make this specific lifestyle change.  The same question that I have answered many times  – “Do you do this?” – was their immediate response.  In the past I have always answered that I largely follow what I am asking them to do in my own ongoing lifestyle.  That response has been honest but left me feeling as if it were an evasive one.

I am not sure what struck me to respond differently this time, but here I am beginning the same journey that I suggested to my patient would be the ideal one for them to resolve several health issues.  I had suggested that this patient begin a 5:2 dietary pattern, a modified Paleo pattern that is perhaps more palatable and yet effective in the right circumstances.

The 5:2 dietary pattern was developed by Dr. Michael Mosley, although the credit for the scientific basis really should go back to our Paleolithic period ancestors.  Of course their contribution came out of survival rather than scientific curiosity concerning health issues.  These distant relatives survived by basically eating what they could find or catch only when they could find or catch it.  This led to a diet with the following characteristics:

• ·         Animal based protein and fat
• ·         Plants that grew naturally without agriculture
• ·         No grain or dairy
• ·         Periods of eating interspersed with long periods without eating
• ·         Fairly intense physical activity in pursuit of food

In an interesting video about this eating pattern.

Dr. Mosley explains some of the rationale from the scientific perspective as well as his personal perspective.  I disagree with him somewhat on the exercise portion and will discuss this later in this series.

Currently it is estimated that 80% of all chronic health problems are the long-term effects of lifestyle related factors with diet and exercise being foremost.  Back to the Paleo diet characteristics; it seems that the long periods where humans were without food (fasting) but pursuing food required a specific genetically determined metabolic efficiency that helped the body function optimally.  These periods of shifted metabolism actually help the body over the long-term and not just during fasting.  If we fast some, we appear to benefit all of the time.

As fertility is one of the first victims of a mismatch between metabolism (one’s chemical functioning) and diet (the fuel provided), the early population became fairly uniform in genetically determined metabolism as the dietary pattern was fixed and uniform.  We are thought to be over 99% genetically identical to these distant relatives who thrived in this dietary environment. 

The reality is that we are wired to thrive in the above lifestyle pattern and, unfortunately destined to be ill in the environment of constant availability of high amounts of refined grain, added simple sugars, higher amounts of carbohydrates and no energy expenditure to obtain food.

So this is the background with which I approach this six months of soup.  I am committed for the rest of the year which is actually 5, months but that title has no rhythm so we will use “6”.  The 5:2 dietary pattern suggests only a cup of soup (grain-less) twice a day at 12-hour intervals.  The soup meets the above food criteria and provides enough energy to function yet induces the positive benefits at 12 hour intervals of fasting. (refer to the cup of soup recipe at the bottom of the post)

The idea is that it is a simple plan that closely mimics the Paleo metabolic state.  This is done on two non-consecutive days with 5 days of one’s typical eating pattern.  Complete overhaul of lifestyle 7-days each week is difficult for most leading to long-term failure, but most can comply with a couple of days each week.  This begins to induce positive metabolic changes; and between the results and progressive reality that good lifestyle is not that difficult, progressive improvements to the daily diet become doable.

Plain tea or coffee is allowed as is water.  Exercise and activity is also needed.  The whole goal is to exploit the beneficial effects of a dietary pattern that maximizes the positive aspects of our genetically determined metabolism and minimizes the negative side.

The real essence of this lifestyle pattern is that it is supported by broad scientific research suggesting that it can prevent or help lower metabolic disease risks such as the current diabetes epidemic, improve and maintain cognitive function, reduce the epidemic of affect disorders (anxiety, depression) as well as other benefits.  In this series I will share the ups and downs, ins and outs and lessons of this journey.  I will also share the extensive science behind all of this and how it applies to my life.  

More about what happens is “fasting” mode in the next report and, of course, how I am doing with all of that.  Soup for breakfast at 5 AM and a little coffee and water today until soup between 5 and 6 PM tonight. So far so good!