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Functional Testing

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The optimizations described on this page require repeated specialized testing and the professional support of a trusted physician trained in functional medicine


Functional testing takes our longevity strategy to the next level by in-depth monitoring and optimizing our health. This involves taking specialized blood, urine, saliva, hair, and other tests and reviewing the results with our physicians and dedicated doctors.

Choosing the right Doctor


For all of this, it is paramount that we have a personal physician and specialized doctors that we trust and that we can talk openly with and discuss our issues and questions. To have a meaningful conversation with our doctors, we need to educate ourselves on what we talk about, and we need a doctor who treats us as a partner in our quest for optimum health—Doctors who treat us top-down as ignorant patients won't help us at all.


Measuring our Well-Being


To get a holistic view of our health, we monitor several biochemical markers and risk factors, most of them by blood, stool, urine, hair, and saliva testing.

These markers indicate if something is wrong with how we treat our body, the external influences we are exposed to, or our genetic programming. Usually, we do not counter imbalances directly with medication like conventional medicine would suggest (e.g., treating high cholesterol with cholesterol-lowering drugs, which, by the way, is useless). Removing the root cause for an elevated risk factor or out-of-range biochemical marker is necessary.

Tracking risk factors and biochemical markers over time gives us an excellent indication of how our measures like nutrition, detox, workout, mental well-being, and supplementation change our body biochemistry for the better and can be a highly motivating progress indicator in our quest for the dramatic extension of our healthy lifespan.



Gut Biome


A stool sample makes it possible to analyze the distribution of the different kinds of bacteria in our gut. Additionally, the test shows the state of the gut's immune system and the condition of its lining by measuring IgA.

Imbalances can be treated with supplementation and change in diet. They usually resolve once we switch to healthy nutrition, detox our body, and consume enough fiber in our food. Adding pre- and probiotics to our supplement regimen assists in regaining a balanced gut biome.

  See more: GI Effects Comprehensive Profile (gdx.net)

A healthy gut is the hidden key to weight loss (chriskresser.com)



Relevant

  • Microorganism Distribution

  • IgA


Chronic Inflammation


Chronic inflammation is an abnormal, long-term activation of our immune system. During a chronic inflammatory response, our immune system unsuccessfully tries to deal with an infection, injury, or other disease processes. Damage to the tissues in our body frequently occurs during this type of inflammation. Chronic, low-level inflammation is associated with common diseases, including cancer, type II diabetes, osteoporosis, cardiovascular diseases, and others. It can be triggered by uric acid crystals, oxidized lipoproteins, homocysteine, mitochondrial dysfunction, food toxins, gluten, and advanced glycation end products (AGEs).

We can use several biomarkers to detect our level of chronic inflammation. The two most common ones are c-reactive protein (CRP) and fibrinogen. We use the high sensitivity test (hsCRP) for CRP in the range of 0 - 10 mg/L.

Optimum hsCRP in men: < 0.55 mg/L 

Optimum hsCRP in women: < 1.0 mg/L

Optimum Fibrinogen: 200 - 300 mg/dL


Implementing the building blocks of the foundation is the key to reducing chronic inflammation. Additionally, supplementation can help in that regard.

See more: Chronic Inflammation (lifeextension.com)



Relevant

  • hs-CRP

  • Fibrinogen


Cortisol


When stressed, the body responds by increasing cortisol output from the adrenal glands. Cortisol is beneficial and protective at normal levels by controlling blood pressure, blood sugar levels, and inflammation and strengthening the cardiac muscle. A normal cortisol rhythm should peak in the morning and steadily decline through the day, with the lowest levels at night.

An acute rise in cortisol is not necessarily unhealthy, as it is the natural adrenal response to stress. However, cortisol is continuously elevated when stress becomes unresolved or chronic, and our body enters a state known as adrenal resistance.

Chronically elevated cortisol levels are both inflammatory and catabolic. 

They cause a myriad of disorders, including: 

  • thyroid and metabolic dysfunction, 

  • cognitive decline

  • low serotonin levels resulting in depression

  • irritability

  • anxiety

  • carb cravings

  • immune suppression

  • altered glucose metabolism

  • elevated lipid levels

  • increased blood pressure

  • low melatonin levels resulting in altered sleep patterns

  • musculoskeletal issues, resulting in difficulty recovering from exercise and possible subsequent injuries

Cortisol levels are also related to mental acuity and can contribute to degenerative diseases such as dementia and Alzheimer's.

DHEA, a precursor to many other hormones, also relates to adrenal function and, unfortunately, can have an inverse relationship to cortisol. Thus, if we have chronically elevated cortisol levels, we may have proportionately low DHEA, resulting in further metabolic disturbances, including weight gain, poor immune function, and hormonal imbalances.

A saliva cortisol test that samples our cortisol levels multiple times throughout the day is the most convenient and accurate way to observe the amount of free cortisol and its daily cycle.

Like other risk factors, cortisol will usually normalize when implementing the foundation of nutrition, detox, exercise, mental well-being, and stress relief. Adrenal balancing supplements like Rhodiola, Ashwagandha, Ginseng, and Holy basil can also help us in that respect.

see more: Cortisol Stress Profile (gdx.net)

Reducing the Risks of High Cortisol (lifeextension.com)

Stress Management (lifeextension.com)



Relevant

  • Cortisol


Glucose Metabolism


Impaired glucose metabolism is a significant risk factor for cardiovascular disease, diabetes, accelerated aging, and other age-related malignancies.

We monitor fasting blood glucose, insulin, HbA1c & fructosamine in our quarterly blood draws to track our glucose metabolism.

However, we must be aware of certain widespread misconceptions and lesser-known facts to make informed decisions.


Monitoring the trend is important

Conventional medicine uses arbitrary thresholds to classify people into healthy, pre-diabetic, and diabetic. This is not helpful. If a fasting blood glucose of 140 makes us diabetic, a level of 139 will not make us any healthier. In addition to the actual levels, we examine whether our values creep upward over time.


HbA1c is not a reliable marker for diabetes

HbA1c is supposed to measure the average blood glucose level over three months by assessing how much of the blood cell's protein hemoglobin has bound to sugar molecules and formed AGEs. Since its value directly relates to the average lifetime of our blood cells, HbA1c can vary vastly from one person to another. On average, the lifetime is 90 days, but the blood cells of diabetics turnover in as few as 80 days, while they live as long as 140 days in non-diabetics. At the same average blood sugar level, a shorter average lifetime of blood cells directly translates to a lower HbA1c since the cells have less time to accumulate glycated hemoglobin proteins.


Fasting glucose goes up low-carb

Restricting carbohydrates results in a natural drop in insulin levels, activating the hormone Lipase. Fat tissue is then broken down and released into the bloodstream. Our muscles take up these fats, which use them as fuel. And since our muscle's need for fuel has been met, it decreases insulin sensitivity.

On a low-carb diet, a borderline high FBG of 90-105 may not cause concern. However, uninformed physicians might diagnose this as pre-diabetic.


Oral Glucose Tolerance Tests (OGTT) can be misleading

OGTTs are supposed to measure the performance of our glucose/insulin metabolism. These are done by measuring baseline glucose and then consuming 75 g of glucose dissolved in water. Blood glucose is then measured every 30 minutes for up to three hours.

Unfortunately, this is an entirely artificial test, stressing the body as no regular meal would. This is especially true if we are on a low-carb diet, where an OGTT, without consuming high amounts of carbohydrates for at least three days before the test, would almost always indicate that we are diabetic, even when in perfect health.


Post Meal Glucose Levels are the most relevant.

Our preferred method of evaluating our glucose metabolism, apart from monitoring absolute values and trends in our regular blood draws, is tracking its operation. At the same time, our body processes food that we regularly consume. This can be done at home using an inexpensive blood glucose meter or a continuous blood glucose monitor.

Using a glucose meter, we sample our glucose levels before lunch and every hour for three hours. A continuous glucose monitor will test glucose levels every five minutes all day long. This is particularly convenient if we want to track our response to certain kinds of food.

This will also help us identify the most damaging situation in our glucose metabolism: blood glucose spikes after consuming high-carb / high-GL foods.

As a rule of thumb, post-meal blood glucose levels should not spike above 140 mg/dl one hour after the meal, should drop below 120 mg/dl after two hours, and return to pre-meal levels after not more than three hours.


When your “normal” blood sugar isn't normal (Part 1 & 2) (chriskresser.com)

Why hemoglobin A1c is not a reliable marker (chriskresser.com)

Physiological insulin resistance (high-fat-nutrition.blogspot.de)

Continuous Glucose Monitoring (freestylelibre.com)

Wavesense Glucometer (amazon.com)



Relevant

  • Fasting Glucose

  • Fasting Insulin

  • Fructosamin

  • HbA1c


Thyroid


The primary function of our thyroid gland and its two hormones, T3 and T4, is to regulate our metabolism by controlling the rate at which our body converts oxygen and calories to energy. The metabolic rate of every cell in our body is regulated by thyroid hormones, primarily T3.

There is a good chance that our thyroid is either over- or under-active due to genetic variations, auto-immune reactions, or our aging process. These imbalances directly impact our metabolism with numerous secondary effects detrimental to our health and well-being.

To verify and ensure proper operation, we measure relevant antibodies and hormones and adjust the hormones accordingly.

Hyperthyroidism - Hypothyroidism  (lifeextension.com)



Relevant

  • TSH

  • free T4

  • free T3

  • Reverse T3

  • TPO Antibodies

  • TG Antibodies

  • TR Antibodies


Vitamin D


Optimum Vitamin D levels promote strong bones and a healthy immune system, offer protection against various types of cancer, protect against heart attacks, and reduce the risk of cardiovascular diseases.

The body produces vitamin D during sun exposure. However, most don't get enough sun exposure, especially during winter.

Vitamin D can be supplemented easily and is relatively inexpensive. Required doses range from 2.000 to 10.000 IU/day. The amount of D3 in conventional multivitamins is usually insufficient to maintain healthy levels of 50 - 60 ng/ml.

Guarding Against the Dangers of Vitamin D Deficiency (lifeextension.com)

Vitamin D: the new super-nutrient? (chriskresser.com)

  

  

Relevant

  • 25-hydroxy vitamin D


Blood Lipids


Imbalanced blood lipids, particularly cholesterol, are major risk factors for our cardiovascular system. However, there are huge misconceptions about blood lipids, especially in the older medical community, that we must be aware of to make informed decisions about our health.


LDL & HDL are not Cholesterol

Both are just transport proteins that the body uses to distribute cholesterol where needed.


Dietary cholesterol has only a minimal impact.

Dietary cholesterol accounts for less than 10-20% of total cholesterol in our body, which manufactures almost all of its cholesterol by itself. The scientific myth of dietary cholesterol influencing the blood levels of cholesterol originates from experimenting with animals with an entirely different lipid metabolism than humans. Nevertheless, these results were applied 1:1 to the human realm.

There is no need at all to cut back on eggs. Quite the contrary: Eggs are among the most healthy foods we can consume.


No healthy level of "Total Cholesterol" has so far been established

It is almost unbelievable, but true nevertheless: There is no scientific proof for the often quoted healthy total cholesterol level < 200. Even one Canadian study places the nutritional level of total cholesterol between 250 and 300.

Studies on cholesterol usually aim at the correlation between the amount of total cholesterol and the occurrence of heart disease. Unfortunately, correlation is not causation. We also need to remember that these relationships are analyzed for an average population living on an entirely unhealthy sugar, wheat, and dairy diet.

Using total cholesterol to make a statement about one's health is about as accurate as determining the health of a car by combining tire pressure, oil pressure, oil temperature, water temperature, and water pressure in a single number and flashing it one on the dashboard.


Conventional LDL & VLDL measurement is no measurement at all.

The LDL values reported by our blood test are almost always only calculated and never actually measured at all. To avoid the much more costly direct LDL measurement values are estimated by one of two formulas:

Friedewald Formula

LDL = Total Cholesterol - HDL - Triglycerides/5.0 (mg/dL)


Iranian Formula

LDL = Total Cholesterol/1.19 + Triglycerides/1.9 – HDL/1.1 – 38 (mg/dL)


VLDL is often not measured but only calculated by dividing triglycerides by 5


Reporting a single number for LDL completely misses the point

LDL comes in three different particle sizes. Unfortunately, there is no distinction between the various LDL particle sizes in traditional reporting. However, only the smallest size, type B LDL, is the real risk factor for heart disease. LDL-B oxidizes quickly and is small enough to get stuck in between cells. Oxidized LDL-B in conjunction with a chronic systemic inflammation (measured by CRP) triggers an immune reaction causing the particles to be eaten by our immune systems macrophages which in turn get bloated. The bloated macrophages start accumulating in the walls of our blood vessels - until the vessel wall ruptures, releasing a blob of excessive macrophages into the bloodstream, blocking the blood vessel, and causing a heart attack or stroke.

Two people with the same calculated LDL can have an entirely different risk profile for heart disease. One might be perfectly healthy, the other one in grave danger.


Calculated LDL can go up on a healthy diet

When we switch from an unhealthy, toxic, carb-loaded diet based on wheat, sugar, and dairy to a healthy, evolutionary diet and implement the other building blocks of the foundation as well, the distribution of our LDL particle size will shift from high-risk factor small particle LDLs to the good large LDLs.

Unfortunately, standard LDL measurement under-represents small LDLs and will mostly show the increased number of large LDLs. This leads to an increased "measured" total LDL despite the decrease in high-risk factor small LDL.

Unaware physicians will diagnose this as a sign of an increased risk factor. Even so, quite the opposite is true. They might even suggest counteracting with medication to lower LDL.


No use for drugs to lower LDL

Imbalanced cholesterol levels are usually not a root cause of heart disease but secondary effects and an indicator of imbalances in the metabolism. In most cases, they are the consequence of an unhealthy lifestyle, with excess carbohydrates, lack of exercise, lousy detox, harmful stress, and, to some extent, our genetics.

Combining this insight with the knowledge of how LDL is "measured," it becomes apparent that using drugs to lower cholesterol makes little sense and could be compared to putting a sticker over a red light on the dashboard.


Markers that matter are LDL-P, Triglycerides, Lp(a), Lp(a2)

Triglycerides are circulating blood fats. Our carbohydrate consumption mainly drives our level.

Optimum triglycerides: 50 - 80 mg/dL


Correlation studies have identified two other lipoprotein sub-classes associated with an increased risk of cardiovascular disease.

Optimum lipoprotein A - Lp(a): < 20 mg / dL

Optimum lipoprotein A2 - Lp(a2): < 235 mg / dL


The foundation is the key

Once we implement the building blocks of the foundation, we see our relevant lipid blood markers normalize to healthy levels. And even if some of them are a bit off compared to the (unhealthy) population average (most probably due to our genetic makeup), we must remember that they are only a subset of the risk factors attributed to lead to heart disease. We still have a lot of control over the other factors as well.


See more: The most important thing you probably don't know about cholesterol (chriskresser.com)


Relevant

  • LDL-P

  • Triglycerides

  • HDL-P

  • VLDL

  • Lp(a)

  • Lp(a2)


Glycation


Advanced glycation end products (AGEs) form when sugar molecules bind to proteins and lipids in the body. This process is called glycation. Glycation, unfortunately, is a normal part of aging; it is far from desirable.


AGEs are one of the major causes why our body ages

AGEs cross-link with themselves and the surrounding tissue, forming unbreakable bonds and stiffening our tissue as we age. Rigid blood vessels due to AGEs lead to age-related high blood pressure since the ship cannot expand anymore when the heart pumps blood. Stiffening of our heart muscle results in a loss of power and volume and thus the ability to pump blood, oxygen, and nutrition through our body. Stiffening of our lungs and the connected muscles leads to loss of lung capacity. Cross-linking of the collagen in our skin leads to wrinkles and age spots. Cross-linking in our eyes' lenses causes clouding and, thus, vision loss. AGEs contribute to cataracts, atherosclerosis, and kidney failure and are a contributing factor in the development of various age-related diseases.


Tracking Glycation

We can track the level of glycation to some extent by monitoring hemoglobin A1c (HbA1c), which measures the percentage of glycated hemoglobin proteins in our blood cells. An elevated or upward-trending HbA1c over time is a severe risk factor.

Healthy HbA1c: < 5.3 %

Optimum HbA1c: < 5 %


We must remember that HbA1c can vary from person to person. Its measurement is about the average lifetime of our blood cells. That is 90 days on average, but it may vary considerably from person to person. With the same rate of glycation, a shorter average lifetime of blood cells directly translates to a lower HbA1c since the cells have less time to accumulate AGEs.


Limiting Glycation

We want to keep the rate of glycation in our body as low as possible. We do this by preventing our blood sugar from spiking, following a proper diet, and exercising regularly. Additionally, we can supplement with Benfotiamine (a form of vitamin B1), pyridoxal 5'-phosphate (a form of vitamin B6), and Carnosine, which all reduce glycation reactions in our body.

We have to be aware that not only do we make our AGEs, but we also consume pre-manufactured AGEs with our food. AGE forms from sugar and fat under excess heat, e.g., in baking or on a BBQ, especially if the food is partly burned.


A Word on Fructose

Fructose (60% of the carbohydrates in fruit) is seven times more reactive than glucose (the primary carbohydrate in rice or sweet potatoes) regarding forming AGEs. 

As opposed to glucose, which can be used by all the cells of our body, fructose can only be processed by our liver. Hence, excess fructose, which our liver cannot immediately handle, floats in our bloodstream, readily forming AGEs until the liver can take care of it.

Additionally, our liver has only a limited capacity to store sugars. Excess fructose that cannot be kept in our liver is converted and directly transferred to our fat cells for storage.

Thus, we want to keep excess fructose, which our liver cannot process and store, to an absolute minimum. If we consume fruits, our primary fructose source, we do so in the morning, when our liver's storage capacity for sugars is still depleted from the night. We always consume the whole fruit, as opposed to fruit juice, since their fiber slows digestion and fructose absorption into the bloodstream. We avoid fruit juices, even freshly squeezed ones, since they lack that fiber.


In the Future

Unfortunately, our body can not break up or eliminate formed AGEs. Right now, we can only try to limit their formation and accumulation.

Scientists are already developing technologies that allow us to break up cross-linked AGEs and return stiffened tissue to its youthful state. This would result in real rejuvenation techniques, undoing one of the leading causes of aging.


See more: Glycation Accelerates Whole-Body Aging (lifeextension.com)

GlycoSENS: Breaking extracellular crosslinks (sens.org)



Relevant

  • HbA1c

  • Fructosamine


Acid Balance


Our body has to keep a very tight regulation of its alkaline-acidic balance. The pH of our blood has to remain within a tiny window of 7.35 - 7.45. Even slight deviations have significant health implications.

Base excess (BE) indicates the amount of bicarbonate used to balance pH in our system. A negative BE reflects a base deficit in our blood and is equivalent to an acid excess. A value outside the normal range (-2 to +2 mEq) suggests a metabolic disorder.

The most common reason for an imbalance is excess acid due to a bad diet, alcohol, coffee, environmental toxins, smoking, stress, or lack of sleep.

See more: The Ultimate pH Solution


Relevant

  • pH

  • Base Excess (BE)


Fatty Acids


We analyze the distribution and possible imbalances of fatty acids in our body on the cellular level — especially Omega 3, 6, 9, and saturated fats. It's motivating to see these values change for the better once we implement a healthy diet, the foundation's other building blocks, and a basic supplementation program.


See more: Essential and Metabolic Fatty Acids Analysis (gdx.net)



Relevant

  • Omega 3s

  • Omega 6s

  • Omega 7s

  • Omega 9s

  • Saturated Fatty Acids

  • Trans Fats

    

Chronic Allergic Reactions


Consuming an unhealthy diet, excess carbohydrates, sugar, bad fats, wheat, gluten, lactose, or casein, and being exposed to environmental toxins will usually cause an allergic reaction in our body. We can partly track this situation by measuring Immunoglobulin E (IgE). Switching to a healthy diet and detoxing our body will most likely dramatically ease the allergic reaction and can return an elevated IgE to optimum levels.

  Optimum IgE: < 100 kIU/L



Relevant

  • IgE


Micronutrients on the Cellular Level


Optimum health requires that all our cells receive adequate nutrients, vitamins, minerals, and other essential compounds.

Due to genetic mutations, we all process food and nutrients with different efficiency, sometimes to an order of a magnitude. A balanced diet and supplements do not necessarily assure that our cells benefit at the optimum levels. Blood levels alone don't provide an accurate picture either since our deficit might be related to inadequate transport or reduced cellular uptake of a particular compound.

Fortunately, a test allows us to measure the levels of the essential micronutrients within the cells, making it possible to detect deficiencies directly at a cellular level - and counter them by supplementing the missing compound.


SpectraCell Micronutrient Testing (spectracell.com)



Relevant

  • Vitamin A

  • Vitamin B1

  • Vitamin B2

  • Vitamin B3

  • Vitamin B6

  • Vitamin B12

  • Biotin

  • Folate

  • Pantothenate

  • Vitamin C

  • Vitamin D

  • Vitamin K

  • Calcium

  • Magnesium

  • Manganese

  • Zinc

  • Copper

  • Asparagine

  • Glutamine

  • Serine

  • Alpha Lipoic Acid

  • Coenzyme Q10

  • Cysteine

  • Glutathione

  • Selenium

  • Vitamin E

  • Chromium

  • Fructose Sensitivity

  • Glucose-Insulin Metabolism

  • Oleic Acid

  • Choline

  • Inositol

  • Carnitine

  • No labels