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Anemia

Red Blood Cells—Critical For Every Function in Your Body

The human red blood cell (RBC) serves as the ultimate delivery service. Without sufficient quantity and quality of RBCs, optimal health is not achievable. An insufficient supply or poor quality of RBCs puts an individual at risk for a variety of conditions, including anemia, lethargy, cognitive impairment, ADHD, developmental delay, amenorrhea (the absence or suppression of menstruation), hair loss and unexplained fatigue.

RBCs not only deliver life-sustaining oxygen and nutrients to the 75 trillion cells that comprise the human body via the 60,000 miles of blood vessels, they also remove waste products from cellular metabolism.

A healthy adult has approximately 2-3 x 1013 red blood cells at any given moment, made via a process called erythropoiesis in the bone marrow at a rate of about 2 million per second. This means that there are between 4 to 5 million RBCs per microliter (equivalent to a cubic millimeter (mm3). In contrast to red blood cells, there are only 4,000 to 11,000 white blood cells (WBCs) or 150,000–400,000 platelets in each microliter of blood.

A single RBC measuring 6-8 micrometers are significantly smaller than most other human cells and each contain approximately 270 million molecules of hemoglobin, the iron containing component of blood that binds onto oxygen.

In addition to its oxygen carrying capacity, when RBCs are damaged and their cell walls are ruptured by invading pathogens such as bacteria, the iron containing hemoglobin triggers free radical damage to the pathogen’s cell wall thus contributing to its demise.1

By definition anemias are a disease characterized by low oxygen transport capacity of the blood, arising from either low red blood cell count, abnormal size or shape or other abnormality of the RBC. Common nutrients associated with insufficient quantity or quality of red blood cells include: Iron, Vitamin B12 and Folic Acid. It is important to note that as with many health conditions, there are overt cases of anemia and marginal or “subclinical” cases, yet when it comes to healthy aging, barely acceptable does not achieve one’s health goals.

With this appreciation of the sheer quantity of RBCs needed, it is no wonder that sufficient nutritional building blocks are required to nourish and sustain optimal health and healthy aging. This is especially true considering that the average life cycle of a red blood cell is 120 days. Thus the bones are continually producing new blood cells.

Iron

Consuming sufficient non-constipating bioavailable iron is critical to maintaining healthy RBCs, since low iron levels will become a rate-limiting factor in RBC and hemoglobin production, and will also result in small sized RBCs (microcytic). The lab range for RBC size, called MCV (Mean Corpuscular Volume) is between 80 to 100. Nutritionally oriented physicians consider any wavering from 90 to be unacceptable. In the case of iron deficits, size of RBCs will approach 80 or can become lower than 80.

Generalized signs and symptoms of iron deficiency include microcytic anemia (marked by abnormally small red blood cells) and hypochromic anemia (marked by a greater than normal mean corpuscular hemoglobin concentration), lethargy, cognitive impairment, developmental delay, amenorrhea, hair loss and many others.2

Iron deficiency can arise for many reasons including chronic illness, cancer and part of the aging process. Achlorhydria (lack of stomach acidity) can lead to decreased iron absorption and B12.

Vegetarians are at an increased risk of becoming iron deficient since vegetables contain “non-heme”, which is iron that does not coming from an animal, and that is generally less absorbable. Red meat, poultry and fish provide approximately 40 percent heme iron and 60 percent non-heme iron. Heme iron is absorbed at a rate of 23 percent compared to 2 to 20 percent for non-heme iron. The average vegetarian diet is estimated to contain 5 to 10 percent iron bioavailability.  It is possible to be a very healthy vegetarian, yet vigilance is important when it comes to both iron and B12 status.

Iron is found in the body in both its reduced state (ferrous) and oxidized state (ferric). Beyond iron’s role in RBC production, iron plays an important role in the electron transport chain as an electron carrier in cytochromes essential for mitochondrial function. It is also instrumental in the functioning of most enzymes in the Krebs cycle, where energy is created for your cells.3 Brain neurotransmitters also require iron as an essential cofactor in the production of dopamine, norepinephrine, and serotonin. During pregnancy, infancy and early childhood iron deficiency anemia is associated with impaired behavioral and neurological development.4-5

Other therapeutic applications for iron beyond RBC production, mitochondrial, Kreb cycle and generalized brain chemistry production include ADHD. There is growing interest in the role of iron in some cases of attention deficit-hyperactivity disorder (ADHD). Evidence suggests that children with ADHD are more likely to be iron deficient. Furthermore the level of iron deficiency seems to be correlated with the severity of ADHD symptoms.6 Additionally, reaching optimal iron levels appears to improve cognitive function in iron-deficient children and adolescents, including verbal learning and memory even in non-anemic iron-deficient adolescent girls.7 There is also evidence that it can help support the reversal of developmental and learning deficits in iron-deficient children.8

Initial evidence suggests that iron supplementation may help address unexplained fatigue in non-anemic women with borderline or low serum ferritin concentrations.9

It is important to note that iron is the leading cause of fatal childhood poisoning, thus supervised use of iron is important and excess dosages must be avoided. In addition, it is best to take calcium 2-3 hours away from iron, as it appears to inhibit the absorption of dietary heme and non-heme iron. Use of acid blockers can also lessen iron absorption.10

Supplemental doses of iron may lessen zinc absorption, especially when dietary mineral intake is low.11-12 The proposed mechanism is that the carrier molecules for iron and zinc within the GI tract can become saturated at high doses, and there is competition for non-specific carriers.13

Folic Acid

A low folic acid level can serve as an independent risk factor for lower than optimal RBCs and can present with a larger than optimal MCV moving toward or exceeding an MCV of 100. It is important to note that it is not clinically prudent to supplement with folic acid by itself, since it can mask pernicious anemia (B12 deficiency) that if not identified can lead to neurological damage.14-16 This is why consuming folic acid and B12 together is the best approach for supporting healthy RBC production. With less than 11 percent of North Americans consuming the minimalist government recommendations for fresh vegetables and fruit, it is no wonder that folic acid levels are low. In addition, folic acid absorption from the small intestine is optimal at pH 5.5 to 6.17 A higher pH associated with either low stomach acid or the use of acid blockers can contribute to reduce folic acid absorption.

Vitamin B12

Similar to folic acid deficiency, B12 deficits are associated with an increased size of RBCs producing a larger MCV value on lab tests. This increase in RBC size, commonly associated with aging, is counterproductive, since with aging the atherosclerotic narrowing of blood vessels already limits blood flow of normal sized RBCs.

Similar to the dilemma of iron and folic acid absorption, low stomach acid and use of acid blockers contribute to lower B12 absorption. Gastric acid is needed to release vitamin B12 from protein for absorption. Thus a highly bioactive absorbable form of B12 is a must in assuring proper RBC production.18

Vitamin C

Vitamin C improves absorption of supplemental or dietary non-heme (plant-derived) iron consumed at the same time.19-20 Evidence points to the fact that the amount of vitamin C ingested is a factor in iron absorption and iron status.21 Furthermore, vitamin C can help lessen the inhibitory effects of substances that reduce iron absorption such as dietary phytates and tannins. Vitamin C likely accomplishes this by helping generate “reduced iron” and decreasing the formation of the less soluble ferric form.22

Other Nutritional Considerations

Riboflavin is involved in the mobilization of iron for heme synthesis from the iron storage molecule, ferritin.23 Vitamin B6 is another important factor since sufficient levels of vitamin B6 and the B6 co-enzymatic form pyridoxal-5-phosphate are important to support RBC production.

Conclusion

Using a comprehensive iron product that provides the very important “triad” building blocks for RBCs that also include B12 and folic acid in highly bioavailable forms is important to support the billions of microscopic RBCs that nourish the 75 trillion cells of your body that are desperately seeking oxygen and nourishment. By doing so, individuals will be one step farther along in their pursuit of healthy aging, optimal wellness and increased energy levels.

By Chris D. Meletis, ND

References

1. Jiang N, Tan NS, Ho B, Ding JL.Respiratory protein-generated reactive oxygen species as an antimicrobial strategy. Nat Immunol. 2007 Oct;8(10):1114-22.

2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002. Available at: www.nap.edu/books/0309072794/html/.

3. Shils M, Olson A, Shike M. Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea and Febiger, 1994.

4. Sever Y, Ashkenazi A, Tyano S, Weizman A. Iron treatment in children with attention deficit hyperactivity disorder. A preliminary report. Neuropsychobiology 1997;35:178-80.

5. Beard J. Iron deficiency alters brain development and functioning. J Nutr. 2003;133:1468S-72S.

6. Konofal E, Lecendreux M, Arnulf I, Mouren MC. Iron deficiency in children with Attention-Deficit/Hyperactivity Disorder. Arch Pediatr Adolesc Med. 2004;158:1113-15.

7. Bruner AB, Joffe A, Duggan AK, et al. Randomized study of cognitive effects of iron supplementation in non- anaemic iron-deficient adolescent girls. Lancet. 1996;348:992-6.

8. Soewondo S. The effect of iron deficiency and mental stimulation on Indonesian children’s cognitive performance and development. Kobe J Med Sci. 1995;41:1-17.

9. Verdon F, Burnand B, Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003;326:1124.

10. Skikne BS, Lynch SR, Cook JD. Role of gastric acid in food iron absorption. Gastroenterology. 1981;81:1068-71.

11. Donangelo CM, Woodhouse LR, King SM, et al. Supplemental zinc lowers measures of iron status in young women with low iron reserves. J Nutr. 2002;132:1860-4.

12. O’Brien KO, Zavaleta N, Caulfield LE, et al. Prenatal iron supplements impair zinc absorption in pregnant Peruvian women. J Nutr. 2000 130:2251-5.

13. Davidsson L, Almgren A, Sandstrom B, Hurrell RF. Zinc absorption in adult humans: the effect of iron fortification. Br J Nutr. 1995;74:417-25.

14. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc. 2000;100:88-94.

15. Title LM, Cummings PM, Giddens K, et al. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol. 2000;36:758-65.

16. Antony AC. Megaloblastic Anemias. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone 2000: 451-79.

17. Russell RM, Golner BB, Krasinski SD, et al. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med. 1988;112:458-63.

18. Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H2-receptor antagonists. Med Toxicol Adverse Drug Exp. 1988;3:430-48.

19. Fleming DJ, Jacques PF, Dallal GE, et al. Dietary determinants of iron stores in a free-living elderly population: The Framingham Heart Study. Am J Clin Nutr. 1998;67:722-33.

20. Lynch SR. Interaction of iron with other nutrients. Nutr Rev. 1997;55:102-10.

21. Cook JD. Food iron availability: back to the basics. Am J Clin Nutr. 1998;67:593-4.

22. Hallberg L, Hulthen L. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr. 2000;71:1147-60.

23. Fishman SM, Christian P, West KP. The role of vitamins in the prevention and control of anemia. Public Health Nutr 2000;3:125-50.

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