There is a lot of information about the importance of iron. Information about oxidative stress is also easily available. However, not much is brought out about iron supplements and oxidative stress linked to supplementation. What does oxidative stress anyway mean?
In nutrition science oxidative stress is explained as follows: Our bodies continuously produce reactive oxygen species. Some of those species are oxygen radicals, which react fast with other substances. Our bodies need reactive oxygen species – for instance to regulate certain functions of growth factors and infections. However, such oxygen species can also damage our bodies – react with fatty acids, proteins, carbohydrate chains, DNA and RNA and thus, significantly damage cells and intercellular structures .
Our bodies have strong defense systems that protect us daily from oxidative stress. Such systems (e.g. enzymes such as superoxide dismutase SOD, catalase KAT, glutathione peroxidase GPx) form the body´s antioxidant protection. Oxidative stress is therefore a situation, where antioxidant protection is not enough to fight against cellular damage . Long lasting oxidative stress is the cause of different diseases and can also speed up the process of aging .
How are iron supplements and oxidative stress linked to each other?
Iron is a a reactive metal. Iron is non-toxic, when it is bound in our bodies and there is no free iron. Free iron causes powerful oxidative stress. In order to prevent the formation of free iron, our bodies have different iron transporting and storage systems . For instance, a protein called ferroportin transports iron out of cells, which we shortly covered in this blog. Iron is bound to a protein called transferrin in blood. Usually transferrin is saturated 15–55% with iron. A protein called ferritin is used for iron storage  . In order to check body´s iron stores, ferritin level is checked.
What happens when we supplement with iron?
Different iron salts are used in iron supplements, mainly non-heme divalent iron salts in oral supplements, which we covered in our blog in co-operation with Rando Tuvikene, senior researcher and associate professor of chemistry at the University of Tallinn. Divalent iron salts are absorbed by active and passive mechanisms. Vitamin C releases non-heme iron from its carrier and free iron is formed. Vitamin C increases the bioavailability of non-heme iron, which is the reason, why it is often added to iron supplements under the name ascorbic acid. The higher the amount of iron administered, the more iron is absorbed via the passive route. This increases the saturation of transferrin up to 100%. The rest of the iron is left as free iron, which is not bound to transferrin. In some research papers, the amount of free iron not bound to transferrin is used as the basis for calculating the level of oxidative stress . According to new iron administration guidelines, iron can be administered every second day and smaller amounts of elemental iron can be used. Old guidelines suggested taking iron daily and higher doses of elemental iron. Read more about taking iron every second day from here.
The higher the molecular weight of an iron salt, less free iron is released from such an iron complex. For example, in intravenous iron supplementation, trivalent iron salts are used, which have very high molecular weight. Intravenous iron administration is linked to many different risks, because intravenously bioavailability of a substance is 100% as the substance is injected straight to the vein. Such medicine can only be purchased with doctor´s prescription and iron injections are performed by medical personnel. When iron is absorbed by intestine, there is no need to get iron injections. As trivalent iron salts have very high molecular weight, such iron forms are not well absorbed by the intestine. Therefore, divalent iron salts are used in oral supplements that are more effective in increasing iron stores.
In a research paper from 2018, anemic children aged 1–13 were examined and two different iron salts, trivalent polymaltose complex (Ferrum Lek drug in Estonia) and divalent iron bisglycinate (Nôgel´s iron food supplements) were compared. Children were divided into two groups: the first group was administered polymaltose complex and the second group was adminstered iron bisglycinate in same amounts. Both iron salts significantly increased the hemoglobin level and decreased the level of transferrin, but iron bisglycinate significantly increased iron stores, i.e. ferritin. There was no remarkable differenc in iron stores between the beginning and the end of the trial in terms of polymaltose complex . Although trivalent iron salts cause minimum oxidative stress, these are not often used in oral iron supplements as the absorption through intestine is weak (high molecular weight).
In case of iron deficiency anemia (low hemoglobin and ferritin levels), it is important that iron stores, i.e. ferritin, is sufficiently filled. During the iron supplementation period, hemoglobin reacts first and increases, because iron stores (ferritin) are filled up very slowly. When iron stores are not sufficiently filled up and supplementation is discontinued, there is a high risk that anemia develops again. For a successful iron cure, an iron salt with high bioavailability and low reactivity is needed that effectively increases iron stores and irritates the stomach as less as possible.
Latent (hidden) iron deficiency can be diagnosed with ferritin levels <20–30 μg/l according to different research, but cases, where ferritin is below 50 μg/l and a person has some chronic infection, iron deficiency cannot be excluded. For such patients, iron deficiency is normally excluded when ferritin level is at least 100 μg/l .
Ferritin level at least 50 μg/l can be regarded sufficient for healthy individuals, but the optimal level depends on an individual. In a reasearch paper, where ferritin as an indicator for general health was examined, it was found that formation of red blood cells at bone marrow level was not sufficient with ferritin level below 50 μg/l , this was the case even with values over 70 μg/l. The optimal level of ferritin in that particular research was estimated to be 100–150 μg/l. The level of ferritin for diagnosing latent (hidden) iron deficiency was <40 μg/l and transferrin saturation less than 12% in that research paper . There are also people, who suffer from iron deficiency symptoms and get help from iron supplementation with ferritin level of 50 μg/l and over.
Did you know that…
According to 2016 guidelines of iron supplementation for adult women and adolescent girls by World Health Organization (WHO), it is recommended to take iron supplements 30–60 mg daily continuously for 3 months during a year in such areas, where iron deficiency anemia occurs for more than 40% of cases among girls and adult women . Here it should be taken into account that not all girls and women have heavy menstruation. Also there is no statistics gathered for anemia incidents among girls and adult women e.g. in Estonia. However, menstruation blood and lost iron are one of the most common reason for suffering iron deficiency at fertile age. Read more about menstruation and iron deficiency from here.
Among divalent irons salts, iron bisglycinate iron supplements with as small amounts of vitamin C as possible should be preferred. Nôgel´s iron food supplements contain natural form of vitamin C only about twenty milligrams for daily dosage, which is enough to increase the bioavailability of divalent iron salts. When an iron supplement already contains vitamin C, do not take additional vitamin C supplements in order to minimize the level of oxidative stress.
In experimental studies it has been found that already 20–60 mg of vitamin C is enough to increase the absorption of inorganic iron multiple times . Senior researcher and associate professor of chemistry at the University of Tallinn, Rando Tuvikene: ”Divalent iron has high reactivity and can thus cause oxidative stress and damage cells in its free form. Ferrous ion charge in iron bisglycinate is neutralized by two ligands (glycine), meaning this kind of iron complex´s (i.e. chelate) reactivity is lower, oxidative effect smaller and the effect on the gastric mucosa milder (less likely to irritate the gut). Strong connections between glycine and iron ions avoid iron´s reaction with many substances found in food that would considerably weaken iron absorption when using other iron salts . Such substances are, for example, polyphenols, phytates and oxalic acid.
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