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Is Your Body Digital or Analog?

Is Your Body Digital or Analog?

We live in a digital age.  Do you think of your body as digital or analog?  Answer this simple question.  Do you wear a modern digital watch or a traditional analog watch?

classic analog watchcontemporary digital watch with dateWhy do I ask these questions?  Because it shows how you can look at the time and space in different ways.  An analog watch does not need to be exact or precise.  A quick glance and you know exactly where you are in a diurnal 24 hour cycle.  You immediately see a relational picture.  A digital watch simply gives you a notion.  It does not show you a picture of the day.  Your brain takes a few extra steps converting that to a perceived notion.

Similarly, the problem I see constantly, day by day, is labwork with arbitrary lower and upper boundary values.  All my patients asked me, “well, is that value normal?”  To which I frequently say, “there really is no such thing as normal.”  There is only optimal and acceptable.  And normal changes decade by decade.   Normal for an 80-year-old would not be normal for 35-year-old.

Another easy to understand analogy is your car.  When do you decide to pull into your favorite gas station?  When is your panic time to fill up your tank?  Do you wait until it’s ¼ full?  Until it’s 1/8 full?  Or wait until the dire warning light tells you only have 20 more miles left before you run out of gas?   Just how proactive are you with your car?

You can look at your body in the same way as your automobile.  If laboratory values are “low normal” they are low.  As you will see in the graphic illustrations below.  But first, let me expand upon the title of this blog.  Are you digital or analog?

Because of time constraints and poor learning habits, all lab work is conventionally seen as digital or binary.  You are either in the box or out of the box.  It’s a very simple calculation.  It removes all guesswork, estimates, finesse and discretionary thinking from medical lab analysis.  There are capricious cutoff values that are usually set at 1 to 2 standard deviations (σ) above or below the mean value.  The mistake made by virtually every conventional physician is diagnosing health or disease using in range values.

But lab values represent our personal human physiology.  We are all individuals.  And all these optimal values are better represented by skewed binomial distribution curves.  Seen as part of a continuum — all the way from low to optimal to high.  It is far more physiologic and rational to look at all your lab values as a continuum that fall on a distribution curve. And most often the curve is skewed to the left or right.

This is the basis of Functional and Anti-Aging medicine.

So let’s look at these illustrations taken from my own real clinical data spanning 12 years.  Data from 5000 samples of hematocrit as example.  That is the percentage of red blood cells in the serum. It is essential for oxygen carrying capacity.  A low hematocrit is a measure of anemia.  And that is not a healthy state.  Re-read my blogs on iron deficiency anemia.

Hematocrit viewed as a binary solutionHematocrit seen as a continuum of values

Now let’s say your value is just slightly above the lower cut off with the green stars.  But then you rerun the lab today or tomorrow which will always be slightly different and suddenly the value might be just slightly below the lower level cut off with the red stars.  In the first instance you are “in the normal range.”  In the second instance you are now out of range.  What is the difference between these 2 values?  Essentially nothing.  So the entire practice of looking at lab values in range is neither functional nor rational.  You want to be looking at all lab values as an optimized value on a continuum.  Optimal is the “happy face” zone.

So this then is the difference between digital / binary medicine and optimized functional medicine.

Let’s finish with one more example.  Vitamin D is one of the few lab tests where values are denoted in more rational ranges.

  • 15-25 ng/ml is deficient.
  • 25-33 ng/mL is insufficient.
  • 33-100 ng/ml is sufficient.
  • 100-150 ng/mL is considered excess.
  • And >150 is considered toxic.

Although, in reality, vitamin D is never toxic.  Another wild misconception that dates back decades.

You can see how much more rational these multiple discrete quintile ranges are.

So when I speak with my patients, we are always looking for optimal values not lab data points that are necessarily in range or out of range.  And furthermore, I take a Grandmaster view of laboratory.  I look at balances, relationships and longitudinal trends.  I see a picture of overall health or dysfunction.  Not a list of disparate lab values.

So that is your challenge.  Do you see yourself as digital or analog?  Maybe in the next 20-30 years after The Singularity, when we all have various bionic components, the answer to this question might change.  My answer for today is  — your body is analog.

Food for today’s thought.   Now that you have read through today’s blog, go back and read my thoughts on the Tyranny of the TSH.

Write me with any questions, thoughts or comments.

Philip Lee Miller, MD

Carmel, CA 93923

Treat and Prevent Iron Deficiency Anemia

Treat and Prevent Iron Deficiency Anemia

Iron deficiency anemia

This is the last in our series on Iron Deficiency and Iron Deficiency Anemia. In parts I, IIIII, and IV, I talked about all aspects of the essentiality of iron. How to diagnose iron deficiency anemia. Various controversies surrounding iron supplementation. And the relationship of iron to various inflammatory states including cancer.  Let’s recap this series with specific treatment routines.  I encourage you to read this final wrap-up containing new and revolutionary medical paradigms.

[If you want the nitty gritty, scroll down to “treatment.”]

Enter Functional Medicine

I want to introduce one more refining and overriding concept. A new paradigm shift in medicine. Functional Medicine.  We need to rethink the entire subject of iron deficiency and anemia.  How and when do we recognize the condition of iron deficiency and progressive anemia? And then what triggers our decision to treat – or prevent?

Functional Medicine is a systems biology–based approach that focuses on identifying and addressing the root cause of disease. Each symptom or differential diagnosis may be one of many contributing to an individual’s illness.   — from the Institute for Functional Medicine

Binary vs. Optimal Choices

In America I see two competing medical paradigms. Structural pathologic medicine based on illness and disease. And functional medicine which is based on dysfunction, suboptimal values with the goal of restoring health and wellness. The goal is not identical.  It leads to totally different approaches for you, the patient.

The functional approach to iron therapy realizes various degrees of iron deficiency rather than a binary choice.  “In the box” or “out-of-the-box.” You’re either low or you are high. In reality virtually all medical paradigms follow a normalized distribution. A continuum from very low to very high. The goal is always optimal — in the middle — values. This is a concept stressing to all my audiences 20 years.

Fortunately, a new model is proposed and advocated in a major publication in the Austrian literature. This paper lays out guidelines for treating iron deficiency anemia in cancer patients using absolute (AID) and functional (FID) iron deficiency.  Seemingly two sets of criteria.

Anemia is common in cancer patients [2]. From a practical viewpoint, two forms of iron deficiency need to be differentiated: absolute iron deficiency (AID) and functional iron deficiency (FID). AID is defined by a TSAT < 20 % and a serum ferritin level < 30 ng/ml in otherwise normal individuals, while in cancer patients a higher cut off level of ferritin levels should be applied (< 100 ng/ml). FID is defined by a TSAT < 20 % and serum ferritin levels of > 30 ng/ml in normal individuals and of > 100 ng/ml in cancer patients.

Great.  Here is a clear path.  The Austrian literature articulates a major shift in modern medical thought. That is my purpose in writing series for you.  Iron therapy is anti-angiogenesis preventing neo-vascularization.

Challenging Standard Definitions

I see so many patients who are relatively anemic and are symptomatic. But they still fall within the “normal range.” And are therefore dismissed.  Not falling within the treatment guidelines.  Ready for the paradigm shift?

Now remember from the previous blogs that iron deficiency will proceed anemia. So here is the continuum of iron from fully sufficient to deficient that precedes anemia .  This is a functional view.   We want optimal values.

continuum from iron deficiency to iron deficiency anemia

Anemia appears only after more severe iron deficiency progresses.  Once iron falls to more severe levels.

Conventionally, your diagnosis of anemia must meet these standard criteria.  Hematocrit values < 35% (women) or <40% (men).  Or Hemoglobin values <13 in men or <12 in women.  Remembering that hemoglobin is oxygen carrying capacity.

But in reality, you won’t be diagnosed or treated until values fall even much lower.  At that point you are really sick.

See figure 2 for “normal values.”  You want optimal values.

Men Women
RBC Count (million/ug) 4.2 – 5.9 3.6 – 5.5
Hemoglobin gm/dl 13 – 17 11 – 15
Hematocrit % 40-52% 34-46%

Treatment Options

This is a re-cap and wrap-up of the previous blogs. All preceding blogs give you a more in depth look at all the issues of iron therapy.

How do we treat knowing that earlier intervention is essential?   The total daily dose for severe cases is 180 mg of elemental iron.  I usually use lower doses.   You will need increased doses of magnesium to prevent constipation.

Heme vs non-heme iron sources in food.  

  • Heme based sources of iron is the most efficient. Best source is red meat or chicken livers or sardines.   Non-heme sources, plant based is a less efficient source of daily iron.

Iron Salts

  • Ferrous sulfate 325 mg (65 mg elemental iron) three times daily. The preferred form.  This may raise hepcidin levels thereby decreasing efficient absorption.³
  • Ferrous gluconate 325 mg (12 mg elemental iron) three time daily
  • Ferrous fumarate 325 mg (107 mg of elemental iron) three times daily

Iron chelates

  • AminoIron – 18 mg elemental iron as bis-glycinate
  • Reacted Iron – 29 mg elemental iron as ferrous bis-glycinate

Iron Infusions

  • Ferric carboxymaltose (injectafer) — the most potent and effective for severe cases and those not responsive to oral consumption.
  • You will need to find a sympathetic and creative hematologist to administer and infuse parenteral (im or iv) iron.  A hematologist who is willing to treat early and not late in the process.

Philip Lee Miller, MD
Carmel, CA
May 24, 2018

  1. Iron metabolism and iron supplementation in cancer patients: Wien Klin Wochenschr (2015) 127:907–919 DOI 10.1007/s00508-015-0842-3
  2. Ludwig H, Müldür E, Endler G, et al. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol. 2013;24:1886–92.
  3. Iron Dosing for Optimal Absorption:  NEJM Journal Watch Oct 30 2015.
  4. Iron deficiency Anemia  NEJM May 8, 2015 
Iron Deficiency Signs and Symptoms -Part IV

Iron Deficiency Signs and Symptoms -Part IV

Symptoms of Iron Deficiency Anemia:

Iron is essential for oxygen carrying capacity.  Iron deficiency and anemia decreases oxygen delivery to all major organs of the body. Most especially the brain, heart and muscles.   Iron deficiency manifests with easily identified symptoms and conditions.  Here is a quick overview followed by a more detailed description.

 

common symptoms of iron deficiency anemia

Mental Fatigue and Cognitive Impairment.

Iron is an essential cofactor for neurotransmitter and myelin synthesis.  Brain neuronal cells require iron for DNA synthesis, mitochondrial respiration, and other vital processes.  As with each of these conditions, iron deficiency anemia reduces tissue oxygenation.  The brain is vitally dependent on O2 and glucose.

Pale (pallid) or Yellow (sallow) Skin.

Here is a comparison of a well perfused (red blooded) iron sufficient hand with an anemic iron deficient hand.  This is simply a visual sign of arterial oxygenation saturation.  Well oxygenated and perfused blood is red.   Technically, we can measure arterial pO2, pCO2 and pH.   The pO2 is the partial pressure of oxygen.

Pulling the lower eyelid revealing the conjunctival inner surface.  This reveals a lack of normal capillary perfusion.  While I was an Emergency Physician we also used another rapid test.  Pressing a fingernail watching for rapid reperfusion or capillary refilling.

anemia with (pallid) poor conjunctival perfusion pallor of anemia compared to normally perfused hand

Unexplained Fatigue or Lack of Energy

physical and mental fatigue

Heart Failure in Susceptible Individuals with Heart Disease

In individuals with a weak or failing heart, iron deficiency anemia stresses heart function.  Diminished oxygen saturation requires more rapid blood flow to keep up with oxygen requirements.  This increases heart rate.  We call this tachycardia.  This tachycardia in turn stresses an already weakened heart.   The heart is, after all, a large muscular organ.  Lack of oxygen leads to myoglobin deficit.   It is a circular set of reactions as seen in figure 5

iron and heart failure
figure 5

Pagophagia – Craving for Ice or Clay

This is an interesting phenomenon.  And it is not well scientifically explained.  It is possible this increase in alertness is a response to the fatigue of iron deficiency anemia.

pica or pagopahgia is a symptom or iron deficiency

Sore or smooth tongue and cheilitis

A smooth tongue.  The “angles” of the mouth show signs of angular cheilitis.  This appears to be an inflammatory condition.  In the past I thought this was a vitamin deficiency.

glossitis (re tongue) and angular cheilitis are symptoms of iron deficiency

Brittle nails or hair loss

Another interesting phenomenon  indicating the need for iron in hard connective tissue synthesis.  A poorly explained phenomenon.  We think this may be related to injury to the nail plate – the origin of nail growth.  Somehow this may be more susceptible to damage or injury with iron deficiency anemia.

brittle nails are a symptom of iron deficiency

Restless Legs Syndrome

Restless legs is an annoying condition that disturbs healthy and regenerative sleep.  It is nearly synonymous with “periodic limb movement.”  This is an important  observation during a thorough sleep study.  Iron deficiency as a cause is becoming more recognized.  Iron infusions are quite dramatic in their ability to completely resolve this condition.   In the past we have treated this condition with Mirapex, a dopamine agonist, more commonly used to treat Parkinson’s Disease.

restless leg syndrome at night (periodic limb movement)

Additional Symptoms:

Here are further manifestations mostly related to more rapid arterial blood flow in response to diminished oxygen availability:

  • Shortness of breath or chest pain, especially with activity (dyspnea)
  • Unexplained generalized weakness (asthenia)
  • Rapid heartbeat (tachycardia)
  • Pounding or “whooshing” in the ears (pulsatile tinnitis)
  • Headache, especially with activity (exertional headache)

So let’s move on to the final episode: treatment of iron deficiency and anemia.

Previous Pages

 Part I, Part II, Part III

Iron Metabolism Part I: Sources, Transport, Testing

Iron Metabolism Part I: Sources, Transport, Testing

The Essentiality of Elemental iron

Iron is essential for healthy red blood cell hemoglobin levels. Red blood cell hemoglobin is essential for oxygen transport. Oxygen and glucose are absolutely essential for brain function.  The topic of today’s review.

I think iron metabolism, assimilation and transport is highly misunderstood. And the subject of great controversy.  Here is why. Hemoglobin is the essence of red blood cell function. And you can see in figure 1, iron is the essential core of hemoglobin. Healthy red blood cells transport oxygen.  In plants, magnesium is absolutely essential for chlorophyll function.

Hemoglobin is essential for healthy red blood cells (erythrocytes)
fig1

Red blood cells pass through the vasculature of your lungs. Oxygen is inhaled and absorbed by the circulating red blood cells. This is how oxygen is transported to the rest of your body. Your heart, brain and all other vital organs.

red blood cells transport and release oxygen
fig 2

There is a widely held belief that iron supplementation is only essential for younger women especially and not as necessary in postmenopausal women. Similarly iron is believed to be less essential for men as we grow older. This is based on monthly menstrual cycles were iron is shed.   In reality these differences in age are not that significantly different.

Sources of Iron

Iron is ingested in food sources or supplements.   Beef, chicken liver, oysters, sardines, lentils, spinach.

But the plot thickens.

There is an important difference between heme-iron from red meats and seafoods and non-heme sources.  Heme-iron is much more readily and efficiently absorbed.   Non-heme sources are much less efficiently absorbed.  All plant-based sources are non-heme iron.  Additionally many plant based sources contain phytates, polyphenols, or soy that further inhibit efficient iron absorption.

This is why plant based diets so frequently lead to significant iron deficiency anemia.   A source of heated controversy.

Elemental salts are also considered non-heme based.   That would be ferrous sulfate, ferrous gluconate and ferrous fumarate salts.    So simply looking a charts labeling the iron content of each nutrient is not enough.  Chelated iron sources may lie in between.

heme-iron and non-heme-iron sources
fig 5

Now let’s look at the continuum of iron deficiency to iron deficiency anemia.    You can be iron deficient without suffering anemia. But eventually when iron levels are further depleted true iron deficiency anemia occurs.

Lab Testing — Hematology

Iron deficiency anemia is characterized by very small red blood cells – termed microcytosis.  The MCV (the mean corpuscular volume) is a laboratory measure of your red blood cell size. An MCV < 88-90 infers iron deficiency.

Iron deficiency and anemia
fig 3

Figure 3

[The values in the above diagram are Australian values. Divide the hemoglobin values by 10 for American values. ]

Similarly an MCV > 100 (macrocytosis) raises the possibility of B12 or folate deficiency.  .

These are not absolutes. They are general principles. There other conditions that raise the MCV. Alcohol is a major contributor to large (dysfunctional) red blood cells.

In Hematology we measure red blood cells and white blood cells.  In the past a centrifuged (spun down) sample would contain a percentage of red blood cells with a top layer of serum.  The percentage of sampled red blood cells is called the hematocrit (Hct).  Today’s modern labs use flow cytometers so the hematocrit is inferred and not directly measured.

Hematologists have traditionally follow hemoglobin and not hematocrit.  Which is probably more descriptive.  We want to know how much hemoglobin is available.  That is the oxygen carrier or transporter.   In simple terms the hematocrit = 3 x hemoglobin.

Most labs use these ranges:

  • Hct  (women)  34-46%     <34 is anemic    optimal > 38
  • Hct (men)        39-52%     < 39 is anemic   optimal > 44
  • Hgb (women)   11-15         <11 is anemic     optimal > 13
  • Hgb (men)        12-17         < 12 is anemic   optimal > 14

In practice, I use much tighter ranges.   You are relatively anemic well before you reach these critical cutoff values.   I have denote optimal values vs. strict lab cutoff values.

The third measurement is the actual RBC count.  Your red blood cell mass.

  • Hematocrit

  • Hemoglobin

  • RBC count

  • MCV

Iron Metabolism and Transport

Iron transport in various compartments
fig 4

The movement and transport of iron is complex and subject to various controls.  Figure 4 shows the movement of iron through these various “compartments.”

It is transported in the blood by attaching to transferrin.  A large binding protein complex.  It enters cellular storage through the control of ferroportin.

It is stored intracelluarly in the cellular cytosol as ferritin.   The ferritin complex is a stable protective protein that neutralizes the reactive aspects of free ferrous (Fe³) iron.

Ferritin is the primary measure of stored iron. It is also a acute phase reactant.  A biomarker of inflammation.   This confounds ferritin as a simple measure of iron storage because it can also represent an inflammatory process.

Lab Testing — Iron BioMarkers

Now you can see from diagram 3 that measuring or following simple serum iron levels is inadequate.  It is only a partial measure of iron sufficiency or deficiency.  It is variable.  To obtain a more accurate assessment and picture you must obtain:

  • Serum iron

  • Transferrin Iron saturation

  • Ferritin levels

  • TIBC (total iron binding capacity)

  • Serum transferrin receptor (sTfR) (added for subtle early signs of iron deficiency)

Ferritin is a measure of stored iron. Serum iron measures free floating iron. Because of insurance-based cost containment, ferritin is not routinely included in current laboratory testing. You definitely want ferritin levels.

Now the picture is even richer for the transport of iron. It becomes quite complex. Actually, far more complex than even I had ever imagined. I have often wondered about the relationship between ferritin (stored iron) and serum iron (free floating iron). What is the controlling factor or mechanism?

stay tuned for Part II — signals that control iron absorption

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