Subclinical Iron Deficiency, Part 3: Causes and Symptoms

Anemia caused by a lack of iron is known as hypochromic microcytic anemia. The reason for this series of articles is that people need not have anemia to suffer from a multitude of symptoms caused by inadequate iron. In part 1, we saw how a typical iron deficiency can mislead a provider and frustrate a patient. In part 2, we reviewed the compensatory cascades leading to vicious cycles that occur when low iron is missed. Now let's look at deficiency and related issues.

To some practitioners, the term subclinical means before symptoms are present. Others were taught that subclinical is a period with varying degrees of symptoms prior to a clinical state. In the case of iron, symptoms are often present, even though the most commonly used indicators on a complete blood count (CBC) with differential - hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (hypochromic when anemic) and mean corpuscular volume (microcytic when anemic) - can be within normal ranges. This is compounded by the incorrect and often repeated assumption that symptoms of iron deficiency will not appear until a person is anemic.

Uptake

Iron is absorbed from food and carried in the blood by a protein made in the liver called transferrin. Iron absorption is affected by both stored levels and food sources. Iron uptake improves when reserves decline. Approximately two-thirds of the iron we absorb ends up in the bone marrow, where it is used for the synthesis of a protein called hemoglobin. Another 10 percent is in the protein myoglobin, and the rest is stored (most of which by a protein called ferritin) in the liver, spleen, bone marrow and muscles.

Dietary iron from animal sources (heme iron) is absorbed 2-15 times better than iron from vegetables (non-heme iron). On average, a diet supplying 10 percent of iron from heme will provide 30 percent of body levels. When heme is 30 percent of dietary iron, it accounts for approximately 70 percent of the 4-5 grams in the body.

Table 1: Digestive IronBinders • Oxalates: in spinach, beets, berries and greens • Phytates: from seeds, beans, nuts, corn, oats • Tannins: in tea, coffee • Calcium carbonate: from antacids and supplements

Not only is the absorption of heme iron superior by itself, but it also improves the uptake of non-heme iron when sources of heme iron (beef, poultry, lamb, pork or fish) are part of the meal that includes non-heme foods. The vitamin C in fruits and vegetables can also improve the absorption of non-heme iron. Conversely, there are many compounds that impede iron absorption. (See Table 1.) Therefore, people who eat little or no animal protein have a much higher risk of deficiency.

The highest sources of iron in animal protein are from organ meats, oysters, beef and dark meat poultry. The best sources of iron in a vegetarian diet comes from fortification (cereals, protein drinks, protein/granola/food bars), beans of all types, spinach, broccoli and molasses.

Deficiency

The number-one mineral deficiency in the world is iron. In general, around 25 percent of the people on the planet lack iron in various degrees. Estimates of iron deficiency in developed nations vary; often it's discussed interchangeably with anemia. This is wrong because a person can be low in iron without having anemia. This adds to the confusion and is why it's not hard to find incorrect statements such as, "People don't notice any signs or symptoms until they become anemic." This is why many with mild to moderate deficiencies are not diagnosed until or unless they develop anemia. Others will get just enough iron to avoid anemia. In both cases, there will be plenty of symptoms. All you need to do is ask.

Table 2: Causes of IronDeficiency • Excessive losses (acute, chronic or episodic bleeding) • Inadequate intake (vegetarians, low animal proteindiets) • Poor absorption (Celiac & Crohn’s diseases, drug& food interactions) • Increased demand (pregnancy, lactation, adolescence,serious disease)

Premenopausal women are affected 10 times as often as men for one obvious reason: blood loss. Bleeding is the primary mechanism for iron loss. The majority comes from menstrual, GI (internal) and/or traumatic bleeding. There are, however, other ways to lose small amounts of iron. Both sexes lose small amounts of iron through sweating, urination, defecation and exfoliation of both skin and mucosal cells. These can amount to approximately 30 mg a month.

Table 3: Other Causes ofIron Loss • Intestinal cell exfoliation • Skin cell exfoliation • Exertional hemolysis • Sweat losses • Urinary losses

Red blood cell hemolysis, which is seen in people who run or march long distances, can also contribute to non-hemorrhagic losses. Iron deficiency due to increased demand (e.g., pregnancy) or decreased ability to absorb (e.g., celiac or Crohn's) can begin even with a macronutrient intake that is considered adequate. It only takes a few questions (what they eat, what (supplements) they take and how they feel) to determine if a person with a GI disorder or a pregnancy has a potential problem. (See Table 2 for the causes of iron deficiency and Table 3 for other ways the body fails to retain iron.)

Functions

Table 4: Signs andSymptoms of Low Iron
Fatigue	Shortness of breath with activity
Sleepy after exercise	Pale skin
Cold hands	Cold feet
Itching	Hair loss
Chest pain	Sore tongue
Cracks at corner of mouth	Abdominal pain
Restless legs syndrome	Restless sleep
Brain fog	Reduced immunity (more colds, infections)
Headache	Cravings for ice and dirt
Dizziness	Tinnitus
History of low iron	Poor wound healing
Lightheadedness (upon standing after sitting)	Palpitations

Iron is best known for its role in energy. As a component of hemoglobin, it enables the transportation of oxygen from the lungs to the cells. Iron is also in the muscle protein myoglobin and proteins known as cytochromes, which are involved in energy synthesis via the electron transport chain. Iron is essential formaking L-carnitine, collagen, and neurotransmitters such as dopamine, noreprinephrine and serotonin. An iron enzyme drives the rate-limiting reaction needed to synthesize DNA. T- lymphocyte levels and natural killer cell activity both decrease when iron levels are low. In fact, between structural, enzymatic and transport functions, there's not a cell in the body that doesn't use iron. And that explains why the symptoms of low iron can be so variable. See table 4.

Once you begin to look for iron deficiency, it won't be long before you find it. In the fourth and final installment of this series, we will review testing for and treatment of iron deficiency.