Iron deficiency and anemia…haven’t we been down this road before? By this modern era, should we not be able to avoid such a seemingly obvious and directly influenced nutritional deficiency? In less developed countries with more infectious disease exposure, parasitic infections and malnutrition, the rates of anemia range from 30 to 40 percent; mostly in children, pregnant women, elderly and vegetarians.1 Shockingly, iron deficiency is still the most common nutrient deficiency and the most common cause of anemia even in developed countries with higher socioeconomic populations.2 Worse, so many medications, fortifications, and supplements worldwide still use outdated and less than ideal forms of iron, usually with no cofactors, to try to remedy the deficiencies and improve symptoms. Although this may be redundant for many practitioners, let us reexamine anemia so that we are all on the same page. Sometimes it is easy to miss the obvious.
Our patients and clients come to us with their “subjective” symptoms. Unusual pallor of the skin, hair loss, weakness in the muscles, easily fatigued, diminished cognition and mental function, decreased mental or physical work performance, and pregnancy are all symptoms that should alert us to the possibility of anemia. In athletes, we must add to this list an inability to achieve the goals that were once attainable: endurance, duration, speed, strength, frequency of workout and recovery all can be affected by insufficient iron availability relative to blood volume and energy demands. These reported symptoms would lead us to request blood tests, and the objective findings may include low ferritin, low total iron or iron binding capacity, and low RBC (red blood cell) count and poor morphology visible in the CBC (complete blood count) with differential and platelets. Additionally, we must rule out other nutrient deficiencies that are easily measurable such as vitamin B12 and folate.2
There are many reasons we might still see anemia, even in our practices in developed countries. The most obvious cause would be frank blood loss from trauma, surgery and even heavy menses in reproductive aged women. Additionally, illnesses such as ulcers, celiac sprue, diverticulitis and perforation, and hemorrhoids may be more hidden factors. The least obvious is the rate of destruction of old RBCs outpacing the manufacture or maturation rate of new RBCs. Usually an RBC lives about 100 days, and in humans it has no nucleus and does not replicate. Poorly shaped and dysfunctional RBCs may be destroyed earlier. Deficiencies in iron, B12, folate and genetic issues like sickle cell anemia and enzyme defects can contribute to overly large, overly small and strangely shaped RBCs that the spleen will eliminate.2
Iron is the central element in the hemoglobin molecule, and hemoglobin replaces the mitochondria in a matured RBC and thus must contribute to energy production for the cell. We should see upwards of 250 million molecules of hemoglobin per RBC. Each molecule can carry 4 molecules of oxygen, transporting 1 billion molecules of oxygen per RBC!3 We cannot forget that CO2 is also transported by hemoglobin, away from the venous blood and back to the lungs. Copper is another important element for proper RBC morphology. Contained in ceruloplasmin, copper releases iron from storage sites to be incorporated into hemoglobin in the RBCs. Additionally, zinc increases the oxygen-carrying capacity in RBCs.4 We now have iron, zinc, copper, B12, folate, and possibly even molybdenum and B6, as the nutrients playing crucial roles in RBC production, morphology, and O2 and CO2 carrying capacity.
There are many potential single-point failures possible for our clients and patients, depending upon their diets and lifestyles, and also their other health issues. Malabsorption has become a common first-world health concern due to dramatic devastation in microbiome diversity. Diets high in dairy and cereals, vegan or vegetarian diets with few iron-containing plants, and diets of low-income elderly all tend to result in suboptimal iron intake. There are also subgroups of a healthy population who might need higher iron stores—ferritin—than the average person due to their increased requirements for energy. These include heavily-training athletes of all ages but especially reproductive-age females, and anyone training to increase muscle mass which also increases blood volume. Note that pregnancy increases blood volume especially in the second and third trimesters, as can obesity, and these are common populations at risk. Obesity also increases multiple inflammation-related compounds in the body, including hepcidin which acts as a signal to uptake less iron, thus leading to potential iron deficiency.5
It is very important to note that anemia is a final stage of iron deficiency and function. This makes iron deficiency a huge player in a number of early indicators such as quality of life, energy levels, and performance. Iron is utilized as a co-factor in enzymes that drive energy production and metabolism, and these are the first areas to have their “iron funding withdrawn” when there is a shortage. It has been clearly demonstrated at a clinical level that even slight deficiencies or suboptimal storage ferritin levels can be experienced by the patient or client as low energy, low physical performance, poor recovery, lowered work capacity and cognitive function, and lowered productivity. Additionally, minor deficiencies in the pregnant mother have dire consequences for the fetus. Conservative estimates suggest 2 to 4 billion people on our planet today—that is one-quarter to one-half of the population—are iron deficient with none of the typical symptoms diagnosable as anemia. This is non-anemic iron deficiency.5 This means the cells cannot “breathe” properly. Cellular replication can be affected, DNA can be damaged, and as Dr. Otto Warburg showed decades ago, in an O2 depleted environment malignant cells acquire the upper hand as they require less oxygen than normal cells.6
Now let’s discuss iron supplementation. Strangely, still to this day, prescription iron and food fortification come in inexpensive and poorly tolerated forms. These include but are not limited to ferrous sulfate, ferrous fumarate, ferrous pyrophosphate, ferrous gluconate and ferrous ammonium citrate. These are ferrous salts that are “redox active” and can irritate a singular location of the GI (gastrointestinal) tract, possibly generating DNA damage, and certainly imbalancing the microbiome, while upregulating pathogenic microorganism activity. These actions in the gut cause a range of digestive discomforts, compounded by the fact that high levels of supplementation are required to move the needle on iron deficiency both subjectively and objectively. Many of the studies on the benefits of iron supplementation in athletes were conducted with 100 mg doses of ferrous salts. Doses in pregnancy studies were equally high. That’s enough to make anyone have morning sickness! While there have been some interesting formulas created for food fortification and supplements, such as bis-glycinates, iron-enriched yeast7 or Aspergillus oryzae,8 and galacto-oligosaccharides,9 these fail to meet the mark of true sustainability which would require that we accomplish more while using less. Anything we cannot absorb or assimilate winds up in our waste; why not reduce waste whenever possible?
This brings us to organ complexes containing heme iron, and non-heme iron chelatable protein hydrolysates, both of which the digestive system treats more like real food. Organ complexes can be great for patients and clients who choose animal products, so long as the source provides consistent nutritional analyses. For vegan and vegetarian options we turn to plant protein hydrolysates. Among these, the double amino acid chelates are popular in supplements and do use the amino acid pathways for bioavailability in the body. However, the real shining light for effective and safe supplementation, behaving more like nutrient dense food in our bodies, is the Multi-Amino-Acid-Chelate where elemental iron is enzymatically bound to a plant protein. In this type of chelate the element is binding at the amino and carboxyl terminus of peptides composed of any of the 18 or so amino acids present in that plant protein. Common sources of protein used over the years have been soy, corn, pea and rice.10 Now we also have an incredible option of mineral-enhanced spirulina. Spirulina is special because it contains 50 to 70 percent protein, contains all the essential amino acids, is full of antioxidants, and has binding sites for innate mineral content including ample iron.11 It is a perfect candidate for mineral chelation. Spirulina alone, without mineral enhancement, is already so rich in bioavailable iron that it has been demonstrated to improve iron status in pregnant women in a national study in Indonesia better than the ferrous salts previously used, with none of the usual gastrointestinal side effects.12 Spirulina can also now be cultivated by Certified Organic Standards,13 something much less available in the amino acid chelates from typical agricultural products often driven by conventional farming practices. Multi-Amino-Acid-Chelates are powered by peptides, but we must take care to choose nature’s peptides rather than those isolated or synthesized on laboratory benches.
We have been taught to use extreme caution supplementing iron. These precautions are largely based upon ferrous salts, which are poorly representative of how iron enters our bodies as food and how it is processed as food in our GI tract, bloodstream and cellular membranes. In subclinical iron deficiency, with no measurable signs of frank anemia, we must largely rely upon our observations of the patient or client, our intake protocol for gathering information, and begin a well-documented regimen using the most effective form of iron at the lowest effective dose. Food-like supplemental forms are most ideal for this. Multi-Amino-Acid-Chelate forms of iron have shown significant results in days and weeks in doses ranging from 15-60 mg elemental iron daily, in comparison to months on 100 mg doses of ferrous salts or single amino acid chelates. Clinical outcomes reported in case studies included a significant rise in ferritin levels, patient-reported improvements in all symptoms of concern, and none of the usual iron-related digestive disturbances that interfere with compliance and duration of treatment.14
As practitioners, our primary objective is to do our best to help our clients and patients, and do no harm. With all the options available for correction of nutrient deficiencies, we also have the obligation to choose the most sustainable options for a bright future. We must make the effort when possible to choose supplements made from raw materials that can be grown organically and regeneratively and can be produced cleanly with little to no waste, made by companies who are finding ways to reduce their environmental impact with innovations in their operations. As we recommend highly effective supplements that normalize an ethical and environmentally sustainable supply chain, we help build a better future globally, even for those who may not have the choices of food diversity, dietary fortification and supplementation such as we have.
References:
1 www.who.int/health-topics/anaemia#tab=tab.
2 Murray, N.D. Michael, Pizzorno, N.D. Joseph. Encyclopedia of Natural Medicine 3rd Edition. New York Simon and Schuster; 2012:292-299.
3 40.5: Components of the Blood – Red Blood Cells – Biology LibreTexts.
4 Marz, N.D. M.Ac.O.M. Russell B. Medical Nutrition 2nd Edition. Portland, OR Omni-Press; 1997:325-330.
5 Georgieff MK, Krebs NF, Cusick SE. The Benefits and Risks of Iron Supplementation in Pregnancy and Childhood, Annu Rev Nutr. 2019 May 15;39:121–146. doi: 10.1146/annurev-nutr-082018-124213 https://pmc.ncbi.nlm.nih.gov/articles/PMC7173188/.
6 www.britannica.com/biography/Otto-Warburg.
7 Sabatier M, et al. Iron bioavailability from fresh cheese fortified with iron-enriched yeast. Eur. J. Nutr. 2017;56:1551–1560. doi: 10.1007/s00394-016-1200-6.
8 Reddy MB, Armah SM, Stewart JW, O’Brien KO. Iron Absorption from Iron-Enriched Aspergillus oryzae Is Similar to Ferrous Sulfate in Healthy Female Subjects. Curr. Dev. Nutr. 2018;2:nzy004. doi: 10.1093/cdn/nzy004.
9 Jeroense FMD, Michel L, Zeder C, Herter-Aeberli I, Zimmermann MB. Consumption of Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate: A Stable Iron Isotope Study in Iron-Depleted Young Women. J. Nutr. 2019;149:738–746. doi: 10.1093/jn/nxy327.
10 Li Y, Jiang H, Huang G. Protein Hydrolysates as Promoters of Non-Haem Iron Absorption. Nutrients. 2017 Jun 15;9(6):609. doi: 10.3390/nu9060609. PMID: 28617327; PMCID: PMC5490588.https://pmc.ncbi.nlm.nih.gov/articles/PMC5490588/#nutrients-09-00609-t001.
11 Spínola MP, Mendes AR, Prates JAM. Chemical Composition, Bioactivities, and Applications of Spirulina (Limnospira platensis) in Food, Feed, and Medicine. Foods. 2024 Nov 17;13(22):3656. doi: 10.3390/foods13223656. PMID: 39594071; PMCID: PMC11593816. Chemical Composition, Bioactivities, and Applications of Spirulina (Limnospira platensis) in Food, Feed, and Medicine – PMC.
12 Marlina D, Nurhyati F. The Effectiveness of Spirulina Compared with Iron Supplement on Anemia among Pregnant Women in Indonesia, International Journal of Caring September -December Volume 13 | Issue 3| Page 1783-1787. www.internationaljournalofcaringsciences.org/docs/28_nurhayiati_original_13_3.pdf.
13 VerdeMins view.monday.com/5378650213-92b29159f397-48ec4383223e6c939ea3?r=use1.
14 Angrove, N.D., Matt. One Month Blood Vitality® Observational Study in Athletes and Active Adults with persistently low ferritin levels: White Paper https://d2saw6je89goi1.cloudfront.net/uploads/digital_asset/file/867553/Blood_Vitality_AFM_Clinical_White_Paper_2018.pdf.
Amber Lynn Vitale, CN, ACC is Board Certified in Holistic Nutrition® and is a Certified Dietary Supplement Professional™ under the oversight of the National Association of Nutrition Professionals. She is also an Ayurvedic Clinical Consultant and has produced an online course in Traditional Ayurvedic Medicine for the Wild Rose College of Herbal Medicine. Much of her nutrition practice has been in collaboration with Functional Medicine doctors and other Integrative Practitioners. By 2012, she had realized that raw materials sourcing, labeling transparency, legitimate certifications, and educational support were the criteria that would set quality natural products brands apart from the rest; and she made it her mission to educate both the practitioner and public about the standards that ensure a reliable product. She continues to write, lecture and produce online content on health and wellness topics important to the brand and the consumer alike.
