iron deficiency & Vitamin D
Anaemia is the most common haematological disorder affecting humanity (Madu & Ughasoro, 2017). Anaemia is a condition in which you lack enough healthy red blood cells to carry adequate oxygen to your body's tissues. Having anemia can make you feel tired and weak. There are many forms of anemia, each with its own cause. Anemia can be temporary or long term, and it can range from mild to severe.
Iron deficient anaemia (IDA) is the most common type of anaemia.
And, iron deficiency (ID) is the most common nutritional deficiency in Australia and significantly under-diagnosed (RCPA, 2017). It is in fact the most prevalent worldwide nutrient deficiency (Kim & Wessling-Resnick, 2015) and it can cause iron deficient anaemia when the deficiency is sufficiently severe enough to reduce erythropoiesis (production of red blood cells) (Bermejo & Garcia- Lopez, 2009).
Anaemia of chronic disease (ACD) or anaemia of chronic inflammation is the second most prevalent cause of anaemia, after IDA. It is usually observed as a mild to moderate anaemia in patients diagnosed with other chronic disease conditions, such as malignancies, chronic infections and auto-immune diseases (Madu & Ughasoro, 2017).
Other common types of anaemia include:
Pernicious anaemia: caused by a lack of vitamin B12 in the diet, or inhibited absorption.
Aplastic anaemia: a condition in which the bone marrow doesn’t make enough new red blood cells, white blood cells, and platelets because the bone marrow’s stem cells are damaged.
Hemolytic anaemia: a condition in which red blood cells are destroyed earlier than normal.
Back to iron deficiency, whereby the blood is lacking adequate levels of healthy red blood cells. As iron is needed to make haemoglobin (a protein in red blood cells that allows the transportation of oxygen from the lungs to all the body’s tissues) haemoglobin can also reduce when iron is deficient. Other functions of iron physiologically include cellular respiration, immune function, nitric oxide metabolism and DNA synthesis.
Based on the lack of oxygen supply to the body and tissues in iron deficiency (and lack of haemoglobin), symptoms include; extreme fatigue, weakness, pale skin, chest pain, fast heartbeat, shortness of breath, headache, dizziness, light-headedness, cold hands and feet, inflammation or soreness of tongue, brittle nails, unusual cravings for non-nutritive substances, poor appetite, poor attention span and mental function. Initially symptoms may be mild but as the deficiency worsens, these can intensify.
The causes of iron deficiency include blood loss (menstruating women, peptic ulcer, hiatal hernia, corelactal cancer), a lack of iron in the diet, an inability to absorb iron (from insufficient stomach acid, lack of intrinsic factor, coeliac disease, other GIT inflammatory conditions like Chron’s, in autoimmune disease or hormonal imbalance) or during pregnancy.
To assist IDA, intake of iron needs to increase, but simply prescribing iron supplements or increasing dietary intake is only partially addressing the issue. As mentioned, the inability to absorb iron once ingested is part of the problem. Phytic acid (found in foods like whole grains, cereals, soy, nuts and legumes), polyphenols (coffee and tea have a high content) and calcium- rich foods (milk, cheese or a supplement) can severely hinder the absorption of iron.
Conversely, vitamin A and beta-caretone (good food sources include carrots, sweet potatoes, spinach, kale, squash, red peppers, cantaloupe, apricots, oranges and peaches) along with Vitamin C (foods high in this nutrient include citrus fruits, kiwi fruit, passionfruit, dark green leafy vegetables, capsicum melons and berries) greatly assist the absorption.
Even so, instruction to avoid or add these mentioned substrates with iron intake may still not be getting at the root cause of the iron deficiency. It has been hypothesized that Vitamin D may affect iron regulation and erythropoiesis (red blood cell production) by its influence on hepcidin, an amino acid peptide, via inflammatory cytokines. Iron deficiency, in turn, was identified as one of the factors for vitamin D deficiency. The mechanism underlying this association involves the reduction of pro-inflammatory cytokines by vitamin D as well as the direct suppression of hepcidin mRNA transcription. There is also evidence that vitamin D may be protective against anaemia by supporting erythropoiesis (Smith & Tangpricha, 2016).
Vitamin D is both a hormone nutrient and fat soluble vitamin, this pleiotropic nature has influence on health through calcium absorption, along with significant involvement in gene expression processes and calcium/ phosphate metabolism influencing a multitude of physiological and pathophysiological mechanisms (Malczewska-Lenczowska et al., 2018).
As mentioned, optimal levels of vitamin D may improve iron recycling and serum levels through down-regulatory effects on hepcidin and pro-inflammatory cytokines (Smith & Tangpricha, 2016). This is due to the conversion of cholecalciferol (inactive Vitamin D) to the biologically active form, calcitriol (1,25-dihydroxyvitamin D3) requiring two steps of hydroxylation—the first in the liver and the second in the kidney—which depend on enzymes containing heme.
Lack of iron > Iron deficiency > Reduction of erythropoiesis (production of red blood cells) and therefore lack of hemoglobin > Reduced heme enzyme lowers synthesis of the biologically active form, Vitamin D3 > Disturb synthesis of vitamin D3 leads to deficiency > Further reduction of erythropoiesis (cycle starts again….)
Hepcidin inhibits and ultimately degrades ferroportin, the transmembrane protein that transports iron and therefore controls the amount of iron absorbed in the intestine and released from cellular storage (Braithwaite et al., 2019).
Normally, hepcidin is suppressed in iron deficiency, allowing increased absorption of dietary iron and replenishment of iron stores through a feedback loop. Increased erythropoietic activity also suppresses hepcidin production (Nemmeth & Ganz, 2009). However, inflammation can cause an increase in hepcidin concentration that reduces dietary iron absorption and the capacity for iron to migrate from cells, resulting in decreased hemoglobin concentrations (Braithwaite et al., 2019).
Inflammation > Hepcidin increase > Inhibits ferroportin, the protein that transports iron > Reduction in absorption of iron from intestine and cellular stores > Iron deficiency
Understanding that there may be a multi-pronged etiology to iron deficiency will be especially beneficial when trying to treat the root cause, as herbalists, nutritionists and naturopaths.
Using myself as an example; I have two auto-immune conditions, one relating to the GIT (Coeliac disease) and intestinal damage/ inflammation most likely affecting the ability to absorb iron (along with other nutrients). Coupling this with a Vitamin D deficiency (and for anyone living in Melbourne, studies have been done which highlight we are not getting adequate amounts of UVA during winter due to the changes of the angle of the sun, affecting the skin’s ability to produce Vitamin D) then it’s no wonder my iron stores (ferritin) are at 16 (range should be between 30-200ug/L) and Vitamin D dropped over Winter from 57 to 46 (range should be between 50-200mmol/L) despite supplementing 1000IU/ day.
Treatment for me is increased Vitamin D supplementation (to 4000IU/ day), iron supplementing following the guidelines of avoid/ addition elements and anti-inflammatory actions. Solely taking iron supplements was not enough to combat my deficiency and I will be working hard to take on board all the factors and remedies.
I hope that this may shed some light on the underlying causation of iron deficiency and give some understanding that there is more than one type of anaemia, and these varieties could in fact overlap and co-exist. Understanding the root cause of the iron deficiency (ie. absorption, inflammation, intestinal damage, hepcidin increase, vitamin D deficiency, inhibited heamoglobin synthesis) gives more scope in treating the condition successfully and over a longer term.