7.3: Blood

Blood is made up of red blood cells, white blood cells, and platelets suspended in a fluid called plasma. Blood is about one-half cells and one-half plasma. Blood continually mixes as it moves through the heart and blood vessels. If a blood sample is put in a tube with an anticoagulant (a substance that prevents clotting), the red blood cells settle to form the bottom half of the blood sample. On top of the red blood cell layer is a thin layer of white blood cells.

The upper half of the blood sample is the plasma, a clear, yellowish fluid. If the plasma has a lot of fat (e.g., after a high-fat meal), it’s cloudy and the fat might even rise to form a layer of fat.

Red Blood Cells

Red blood cells are made in bone marrow, and make up most of the blood cells. Their job is to carry oxygen and carbon dioxide. Men normally have a higher concentration of red blood cells than women (about 5.4 vs. 4.8 million per microliter of blood).

Hemoglobin in red blood cells is what actually carries oxygen (O₂) and carbon dioxide (CO₂). It has an iron-containing part (heme) and a protein part (globin). Heme is red, giving red blood cells (and blood) their color. When carrying oxygen, blood is bright red; it’s dark and purplish when carrying carbon dioxide. Routine blood samples taken from arm veins are dark—blood is on its way back to the heart and is carrying mostly carbon dioxide.

Without hemoglobin, the 5 quarts of blood of an average adult would carry only about 1 tablespoon of oxygen. Hemoglobin increases the oxygen‑carrying capacity by about 70-fold, to about 1 quart of oxygen.

Hemoglobin can also carry carbon monoxide (CO), and binds even tighter to carbon monoxide than to oxygen (or carbon dioxide). Thus, carbon monoxide can displace oxygen in blood. You can die from lack of oxygen when breathing carbon monoxide coming from the deliberate or accidental venting of exhaust fumes into a car, even though there’s still a lot of oxygen in the car.†

Tobacco smoke also has carbon monoxide. Smokers can’t carry as much oxygen in their blood because some of their hemoglobin is tied up with carbon monoxide. As a result, smokers run out of breath sooner when exercising. This may be why many people quit smoking soon after starting an exercise program or taking up a sport. Smokers are also more prone to heart attacks (Chap. 8). Carbon monoxide adds to this risk, especially when oxygen delivery to the heart muscle is barely adequate due to narrowed coronary arteries.

A red blood cell lasts about four months. Its protein is then broken down to amino acids for reuse; the iron in heme is reused to make more hemoglobin; and the rest of the heme is made into bile pigments and excreted as part of bile. If these bile pigments build up in the blood and tissues, the skin looks yellow (jaundice).

This abnormal buildup can be from less excretion of bile pigments due to a diseased liver or gallbladder, or a defective bile duct. Accelerated destruction of abnormal red blood cells can also cause bile pigments to build up.

Athletic Competition: A limiting factor in endurance events is how fast blood can deliver oxygen to muscles. Some athletes try to increase blood’s oxygen‑carrying capacity by increasing the number of red blood cells. One way is “blood doping:” about 2 units (almost a quart) of the athlete’s blood is drawn about 2 months before competition and then stored. Meanwhile, the body replenishes the blood cells. A few days before competition, the athlete gets a transfusion of the stored blood (extra red blood cells).

Another way is injecting erythropoetin, a human protein (made for medical use by biotechnology) that increases the body’s production of red blood cells. The use of either of these methods is against the rules of the International Olympic Committee.

A legitimate way is to train at high altitude before competition at sea level. At high altitude, the body responds by making more red blood cells (and hemoglobin) to compensate for the lower oxygen pressure of the atmosphere.

^{†Dr. Jack Kevorkian (the “suicide doctor”) often used a canister of carbon monoxide attached to a gas mask to help people commit suicide.}

Anemia

The word anemia is from the Greek, meaning without blood. Anemic people have fewer red blood cells or less hemoglobin in their red blood cells from blood loss, impaired production of red blood cells or hemoglobin, or increased destruction of red blood cells. Despite the many causes of anemia, the end result is that blood can’t carry as much oxygen.

An anemic person tires easily and often has such symptoms as weakness, dizziness, headache, drowsiness, and irritability. In short, there’s less physical and mental capacity for work and productivity. Also, anemia can lessen the body’s ability to warm itself in response to cold (cold intolerance). Severe anemia can cause cessation of menstrual periods, loss of sexual desire, heart failure, and shock.

Anemia can be diagnosed from a blood sample by measuring the volume of red blood cells (Figure 7.4), measuring hemoglobin concentration, or examining and counting the number of red blood cells (Table 7-1). Several nutritional deficiencies can cause anemia. The most common ones are deficiencies of iron, folate, and vitamin B₁₂.

Figure 7.4: Hematocrit

Iron-Deficiency Anemia

Iron deficiency is the most common cause of anemia. Iron is an essential part of hemoglobin, so not enough iron means not enough hemoglobin. In iron-deficiency anemia, red blood cells are small and pale because they have less hemoglobin.

Iron deficiency can be from needing more iron (as when growing or pregnant), not getting enough in the diet, less of it being absorbed, or a combination of these. This occurs mainly in children and women of childbearing age. Children need more iron for their increasing blood volume and growing bodies.

Women lose iron in menstrual blood. Blood losses vary, so women vary in the amount of iron needed for replacement. It follows that any condition that changes the amount of menstrual blood also changes iron needs, e.g., oral contraceptives lessen menstrual blood losses.

Menstruation can stop entirely with extreme thinness, as can happen with anorexia nervosa or among ballet dancers. Although menstruation stops during pregnancy, more iron is needed for the growing fetus and the woman’s larger blood volume.

Iron deficiency is unusual among men and postmenopausal women because they have minimal iron losses. Blood donors are, of course, an exception. Blood banks check for anemia, and don’t allow donations of more than a pint about every 2 months. Men and postmenopausal women with iron-deficiency anemia are checked for chronic bleeding, especially in the digestive tract, e.g., an undiagnosed bleeding ulcer.

Iron deficiency is usually corrected by getting more iron in the diet or in supplements. Compared to other nutrients, iron is poorly absorbed from the intestine. This is an important safeguard, because excessive iron in the body can be toxic. Aside from blood losses, very little iron is lost from the body once it’s absorbed. The intestine serves as a gatekeeper by adjusting the amount absorbed. Absorption is normally low, but more iron is absorbed when the body needs more.

Iron in foods: The two main forms of dietary iron are heme iron—iron that’s ingested as a part of heme (e.g., the iron-containing part of hemoglobin)—and non-heme iron (inorganic iron). Heme iron is absorbed better than non-heme iron.

Heme iron is found in animal tissue, mainly in hemoglobin and myoglobin (an oxygen-carrying molecule similar to hemoglobin, but found in muscle). Most of the iron in animal tissue is heme iron, but some—such as iron in egg yolk—is non-heme. About 25% of heme iron is, absorbed, whether or not a person is iron-deficient.

Because of the telltale “bloody” color of heme, we can figure that red meat (e.g., beef) has more heme iron than light meat (e.g., chicken, fish), and that the darker meat of a chicken leg has more heme iron than the lighter meat of the breast.

Red blood cells are made in the bone marrow and broken down in the liver, making bone marrow and liver rich dietary sources of heme iron. (Eating bone marrow is more common in Europe than in the U.S.)

Amounts of iron in about 3 oz of lean, cooked portions of animal tissues are: beef liver (7.5 mg); hamburger (3.9); lamb (2.6); skinless dark chicken meat (1.4); skinless light chicken meat (1.1) salmon, swordfish, or trout (1.0). (The RDA is 18 mg iron for menstruating women, and 8 mg for men and postmenopausal women.)

We eat a lot of heme iron in meat, but we eat more non-heme iron (e.g., from fortified breakfast cereals and enriched bread). Plants have non-heme iron, which is more poorly absorbed than heme iron. But the absorption of non-heme iron varies from about 2% to 45%, depending on whether you’re deficient in iron, the amount of iron in the meal, and what else is in the meal. Thus, unlike sources of heme iron, it’s hard to evaluate dietary sources of non-heme iron.

One can’t say that we absorb more iron from ½ cup cooked spinach (2 mg iron) than from an egg (1 mg iron), because other substances in the meals can affect the amount absorbed. For example, meat, fish, or foods having vitamin C, eaten in the same meal increase absorption of non-heme iron. Conversely, substances such as tannins (as in tea), phytic acid (as in wheat bran), and oxalic acid (as in spinach) in the meal can combine with non-heme iron, preventing its absorption.

We get more iron from an egg if the breakfast also includes sausage and orange juice, and less iron from a spinach salad served with a whole wheat roll and tea. The meat in sausage and the vitamin C in orange juice increases iron absorption, whereas oxalic acid in spinach, phytic acid in the whole wheat roll, and tannins in tea all bind to iron and prevent its absorption.*

As mentioned in Chapter 4, Recommended Dietary Allowances (RDAs) take into account differences in absorption. Only a small amount of the iron ingested is actually absorbed, so the amount recommended (RDAs for iron) is about ten times more than what the body actually needs.

Food rich in non-heme iron (in portions with 1 to 2 mg iron) include: ¼ cup peanut butter, raisins, bran breakfast cereal, or cooked cream of wheat; ½ cup cooked spinach, chard, lima beans, or peas; 2 slices enriched or whole wheat bread; 1 egg yolk; 3 dried apricot halves; and 5 prunes. Other foods included in the same meal increase the absorption of non-heme iron, e.g., a small amount of meat or fish, and especially foods rich in vitamin C (e.g., oranges, grapefruit, strawberries, melon, broccoli, green peppers).

Milk has very little iron (only about 0.1 mg per cup; the RDA for children, ages one to ten, is 10 mg), and milk is typically a big part of a child’s diet. When the diet is top-heavy in milk and milk products, there’s a risk of iron deficiency. (Newborns normally have about a 6-month supply of iron stored in their liver, to “hold them over” until they get other foods besides milk.)

Iron supplements: Iron fortification of many breakfast cereals and enrichment of white flour with iron have lessened iron deficiency in the U.S. Also, many people take iron supplements. Absorption of iron in these supplements varies.

Iron supplements are easily available and inexpensive, but it’s still a good idea for those at risk of deficiency to work on eating more iron-rich foods. Improving the diet in one nutrient—iron in this case—tends to improve the diet in other nutrients as well. Also, iron supplements can cause side effects, such as constipation, nausea, and stomach cramps.

You can also supplement your diet without iron pills—by cooking acid foods (foods containing vinegar, lemon juice, wine, tomato sauce, etc.) in cast iron pots and pans. Acid dissolves some of the iron in the cookware, putting it in the food. You can increase the iron content of tomato-based (acidic) spaghetti sauce, for instance, by simmering it in a cast iron pot. An old folk-remedy for anemia is to put a long iron nail in an apple overnight and then eat the apple— after removing the nail, of course!

Iron toxicity: Our intestines normally protect us from absorbing excess iron, but massive amounts of iron can overwhelm this safeguard and cause acute iron poisoning—an emergency. A typical victim is a child who accidentally ingests the mother’s iron pills. Acute iron poisoning also occurs with food or beverages heavily contaminated with iron, e.g., acidic drinks brewed or stored in iron vats.

Because iron-deficiency anemia is common among children and young women, it’s been suggested that more foods be fortified with iron. But it’s argued that this might cause more cases of hemochromatosis. In this disease, excessive amounts of iron are absorbed from normal diets because of a genetic error that impairs the intestine’s ability to keep it out. The danger is an accumulation of iron to toxic levels in the body.

Hemochromatosis is mostly a man’s disease.** Women also have this genetic error, but lose iron in menstruation and pregnancy. Men don’t have a regular outlet for iron unless they are regular blood donors.

Hemochromatosis rarely is found before middle age. It’s apparent only after many years of accumulating excess iron in various tissues. It isn’t localized to any one part of the body and can be fatal. Iron deposits can, for example, cause liver damage (e.g., cirrhosis) and heart damage (e.g., irregular rhythms). About 1 of 10 in the U.S. has inherited the abnormal gene from one parent, and 1 of 300 from both parents.

This is why it’s worrisome for men to take self-prescribed iron supplements. Men and postmenopausal women generally don’t need them except, perhaps, if they’re regular blood donors. Even without genetically increased iron absorption, men taking big doses of iron might, over the years, put themselves at risk for toxicity.

Heavily fortified breakfast cereals often have lots of iron—good for children and young women who need more iron, but not so good for many adult men (especially those who eat several bowls a day) and postmenopausal women.

The story of Jim Becker, named at age 79 to the Green Bay Packers Fan Hall of Fame in 2010, tells of a fortunate combination of genes and environment. At age 21, money was tight, so this devoted fan started selling his blood to pay for game tickets. By age 44, he had given 145 pints of blood. At age 44, he was diagnosed with hemochromatosis when a doctor noted that Jim’s father had died of hemochromatosis at age 43 and had Jim tested. All those blood donations literally saved his life.

Sweden used to heavily fortify food with iron but stopped in 1995. It had helped the problem of iron-deficiency anemia, but it also appears to have caused more hemochromatosis. This reminds us that there can be problems with too much of an essential nutrient.

^{*Iron absorption from this salad lunch may not be as good as from the egg-and-sausage breakfast, but it’s more in line with the advice to eat less fat and cholesterol and more fiber. A breakfast of orange juice and either peanut butter on toast, or cream of wheat cereal mixed with fat-free milk is good, in terms of both iron absorption and dietary recommendations.
**Jim Clark, founder of Silicon Graphics and Netscape, was treated for hemochromatosis. His experiences with the health care system led him to create his third billion-dollar company, Healtheon, which merged with WebMD in 1999.}

Folate-Deficiency Anemia

Folate (or folic acid) is a B-vitamin needed to make DNA, the genetic material in our cells. Folate has a key role in cell division because DNA must be made before a cell divides. Folate deficiency hampers cell division, most of all in cells that divide fast.*

Cells that become red blood cells divide fast, so folate deficiency causes an anemia in which red blood cells are bigger (getting ready to divide) and fewer (less able to divide). The usual remedy is more folate by diet or supplement.

Rich sources of folate include liver (where folate is stored in the body) and leafy, dark-green vegetables. Folate/folic acid was, in fact, first isolated from spinach, and its name comes from the Latin word meaning foliage. Other good sources of folate are asparagus, artichokes, brussels sprouts, beans (lentils, lima beans, green beans, peas, etc.), broccoli, avocado, and oranges.

Folate is fragile and can be damaged, especially by heat and acid conditions. Some folate is lost with cooking and processing—good reason for including dark green salads of romaine lettuce or spinach in the diet. The RDA for folate allows for expected losses in food preparation. Also, the liver can store about a three-month supply, which acts as a buffer against short-term deficiencies in the diet.

Folate deficiency is most common when there is both a greater need and low body stores from a long-term dietary deficiency. Pregnant teenagers from low-income families are of particular concern. The RDA for folate goes up during pregnancy—cells divide fast in the growing fetus, and teenagers often have a poor diet (thus marginal stores of vitamins), and many don’t get prenatal care or prenatal vitamins.

Folate deficiency can increase the risk of spontaneous abortion and neural tube defects (the neural tube is a structure in the embryo that becomes the brain and spinal cord). Some of these defects occur during the first month of pregnancy, before most women get prenatal care or take prenatal vitamins, so women who can get pregnant are advised to take folate/folic acid in a vitamin pill or in a fortified food (e.g., fortified breakfast cereal).

Folate deficiency is common among alcoholics, who often have poor diets. Their folate deficiency is made worse because alcohol itself hampers folate’s activity in the body. Also, excessive alcohol intake increases the need for folate, hampers its absorption, and increases its excretion. Alcoholics also often have damaged livers that hampers their storing folate.

Some people are deficient but don’t have folate-deficiency anemia, because it generally occurs only in the late stages of deficiency. One way of detecting milder deficiency is to measure blood-homocysteine, which goes up when folate is low.* (High blood-homocysteine also raises the risk of atherosclerosis; see Chap. 8.) As of 1998, folate has been included with some other B-vitamins that are added, by law, to enrich staple grains like white flour, so folate deficiency and related birth defects are now less common in the U.S.

^{*Cells divide rapidly in the lining of the small intestine—they’re continually being replenished (Chap. 6). Folate deficiency impairs this cell division. This, in turn, impairs the small intestine’s lining and the absorption of nutrients, making a dietary deficiency of folate worse. Also, as discussed in Chap. 12, cell division is rapid and out of control in cancer; drugs that interfere with folate can be effective in treating cancer.
*Vitamins B₆ or B₁₂ deficiency can also cause high blood-homocysteine, but folate deficiency is the most common cause.}

Pernicious Anemia

Pernicious anemia is caused by a vitamin B₁₂ deficiency, almost always due to a lack of intrinsic factor, rather than a deficiency of B₁₂ in the diet. As discussed in Chapter 6, intrinsic factor is made in the stomach and is needed to absorb B₁₂ in the small intestine.

Pernicious anemia seems to be an autoimmune disease in which the body mistakenly makes antibodies against its own intrinsic-factor-producing stomach cells, and destroys them as if they were foreign invaders. So, people with this disease can’t absorb B₁₂ in their food and must get B₁₂ another way, usually by injection.

The liver can store enough B₁₂ for about four years. Thus, an actual deficiency may not occur for several years after the loss of the stomach cells that make intrinsic factor, and the symptoms often appear gradually. Pernicious anemia mostly occurs after age 50.

B₁₂ deficiency also hampers cell division and causes anemia. The anemia is indistinguishable from that caused by folate deficiency—red blood cells are larger and fewer. The crucial difference is that B₁₂ deficiency can also cause permanent nerve damage. B₁₂ is needed to make myelin, a crucial component of nerve cells (Chap. 15), so it’s very important to detect and treat the deficiency early to prevent permanent nerve damage. Often, the first sign of B₁₂ deficiency is the anemia.

The anemia of B₁₂ deficiency can be cured by large amounts of folate. This can be a problem, because folate won’t do anything about the damage to the nerve tissue from B₁₂ deficiency, and can, in fact, make the damage worse. In other words, large amounts of folate can delay the diagnosis of a B₁₂ deficiency by curing its telltale anemia. This delay increases the risk of permanent nerve damage.

Pernicious means deadly. In late stages of this disease, the nerves and spinal cord degenerate. Pernicious anemia was a fatal disease until 1926, when two physicians found effective treatment in a dietary regimen that included about a half pound of liver a day. They didn’t know what caused pernicious anemia nor what was in the dietary regimen that was effective.† For discovering an effective treatment (and discovering that the disease had something to do with nutrition), George Minot and William Murphy won the Nobel Prize in 1934.

Liver is a rich source of B₁₂** because it’s stored there. By eating all that liver, a small amount of B₁₂ is absorbed, despite the absence of intrinsic factor. In 1948, B₁₂ was isolated from liver (it was the last vitamin discovered). In 1955, Dorothy Hodgkins determined the complex structure of B₁₂, and won the Nobel Prize in 1964.

B₁₂ is an unusual vitamin because it’s made only by microbes. It is, in fact, the only vitamin that plants can’t make. B₁₂ found in animal tissues and animal products comes from that made by microbes, e.g., microbes in a cow’s rumen make B₁₂, which the cow absorbs—and we get in beef and milk.

We need very little B₁₂; the adult RDA is 2.4 micrograms (less than 1/10,000,000 of an ounce). People who eat meat, fish, milk, or eggs get enough B₁₂.

Because B₁₂ isn’t found in plants, vegans (who don’t eat any animal food) are at risk of deficiency. They can get B₁₂ from several sources: sometimes, they inadvertently ingest B₁₂ when their food or water is contaminated with microbes that make this vitamin. Microbes in soil might be enriched further by the use of bacteria-containing manure as fertilizer.

These bacteria can be a source of B₁₂ if food grown in this soil isn’t thoroughly washed (B₁₂ isn’t easily destroyed by cooking). B₁₂-synthesizing microbes in the root nodules of some legumes (beans) can also be a source. Other sources include plant foods fortified with B₁₂ (e.g., some breakfast cereals or soy milk) and special yeast grown in a B₁₂-enriched broth.

Vegans develop a B₁₂ deficiency only after a severe and long-term shortage (the body can store enough to last several years, and very little is needed). But, one concern is a delayed diagnosis—a strictly vegetarian diet often has a lot of folate, which can cure the telltale anemia of B₁₂ deficiency without protecting against nerve damage.

Infants born of mothers who have been vegans for a long time are especially vulnerable. They’re born with low body stores of B₁₂, and are commonly fed only breast milk during early infancy. As might be expected, the breast milk of a longtime vegan mother has very little B₁₂. Sometimes, the infant’s nervous system is damaged.

^{†The role of an intrinsic factor was discovered a few years later. (It’s made in the stomach, so it’s intrinsic to the body; required nutrients are extrinsic.) The enlightening—and unappetizing—experiment: the discoverer (Dr. William Castle) ate some beef (which has B12), and then used a stomach tube to bring up the meat/stomach-juice mixture, which was then fed to patients with pernicious anemia.
**Liver is also a rich source of folate, and the prescribed diet also included a lot of fruits and vegetables (including spinach), many of which are rich in folate. All this folate certainly must have helped remedy the anemia of B12 deficiency..}​​​​​​​