Menstrual Iron Loss Research Articles

Nutritional Iron Requirements and Deficiency

Deficiency of iron is a major cause for disability and mortality globally and it occurs due to non-absorption of iron from diet. Hence, the physiological requirements of human body cannot be met leading to various conditions of health concern such as gestational complications, poor pregnancy outcome, decreased educational and occupational performance. Usually, the dietary iron bioavailability is low in populations consuming vegetarian diet. This iron deficiency can cause several health and economic losses. At large, whole nation and country suffers as a consequence.
 Iron requirements are at specified upward extent in adolescents, particularly during the rapid growth period [1]. Overweight children and adolescents are at higher risk of iron deficiency due to insufficient dietary intake of iron and use of those foods which are unbalance in nutrition [2]. Menstrual blood iron losses varies markedly from one woman to another but these losses are very constant for an individual from month to month [3]. Even in geographically widely separated populations of the world, the central part of the variation of menstrual blood losses is controlled genetically by fibrinolytic activators in the uterine mucosa. The variations in iron contents in different populations are related to a variation in the absorption of iron from the diets but not related to a variation in iron requirements [4,5].
 Iron supplementation and flour fortification can control iron deficiency in populations. Governments should take initiatives by monitoring the health status of populations by adopting various methodologies and conducting surveys, follow ups and then providing fortified foods to deficient populations, taking special care of pregnant anemic women and devising a proper policy and guidelines in this regard.

Efficacy of a High-Iron Dietary Intervention in Women with Celiac Disease and Iron Deficiency without Anemia: A Clinical Trial.

Background and Aim. Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing age in whom the imbalance between menstrual iron loss and inadequate iron intake from their diet plays the major role. A recommended approach to this condition is yet to be established. This study aimed to compare, in this subset of patients, the efficacy of a dietary approach consisting of an iron-rich diet against the traditional pharmacological oral-replacement therapy. Material and Methods. Between February and December 2016, consecutive CD female patients of child-bearing age as referred to our outpatient center with evidence of IDWA (ferritin <15 ng/mL or 15–20 ng/L with transferrin saturation <15%) were enrolled. After the completion of a 7-day weighed food intake recording to assess the usual iron dietary intake, the patients were randomized in two arms to receive a 12-week iron-rich diet (iron intake >20 mg/die) versus oral iron supplementation with ferrous sulfate (FS) (105 mg/day). Blood tests and dietary assessments were repeated at the end of treatment. The degree of compliance and tolerability to the treatments were assessed every month by means of specific questionnaires and symptoms evaluation. Results. A total of 22 women were enrolled and divided in the diet group (n = 10, age 37 ± 8 years) and in the FS group (n = 12, age 38 ± 10 years). The food intake records demonstrated an inadequate daily intake of iron in all the enrolled subjects. At the end of the treatments, ferritin levels were higher in the FS group (8.5 (5) versus 34 (30.8), p = 0.002). Compliance and tolerability were similar in both treatment groups (89% versus 87%, p = ns). Conclusions. These findings did not support any equivalent efficacy of an iron-rich diet compared to a FS supplementation in non-anemic iron-deficient women affected by CD. However, the diet appeared a well-tolerated approach, and adequate dietary instructions could effectively increase the daily iron consumption, suggesting a role in the long-term management of IDWA, especially in patients who do not tolerate pharmacological supplementation.

Simplified population data analysis using gamma distribution for nutritional requirements and its application to the estimation of iron requirements for women of child-bearing age

BackgroundEstimation of nutritional requirements is a difficult task, especially for nutrients whose requirements have skewed distribution like iron in menstruating women. ObjectiveTo mathematically develop a simplified population data analysis using gamma distribution for the estimation of nutritional requirements, not depending on extensive numerical calculation. MethodsThe required equations for the estimation of requirements were devised and solved. Existing data of iron intakes and iron losses in literature were fitted to cumulative distribution curves including gamma distribution. The proposed method was applied to the estimation of iron requirements in women using the National Health and Nutrition Survey data from 2003 to 2007 in Japan. ResultsThe type 2 equation of nutritional state is first introduced: prevalence of inadequate nutritional state = Σ(individuals with intake/requirement <1)/(total number of individuals). The prevalence of inadequate nutritional status is determined by F-distribution with positive real number parameters, if the intake and the requirement have independent gamma distributions. The sum of basal and menstrual iron losses is well approximated by gamma distribution, if the basal and menstrual iron losses have independent gamma distributions. Using these relationships, an approximate estimate of iron requirements was determined. Iron intakes and losses were found to be well approximated by gamma distribution. The median of the coefficient of variation (CV) of basal iron loss was 34 %. A new correction method for intra-individual variation in gamma distribution under constant CV is presented also. The median of the estimated median iron requirement was 8.12 mg, 8.15 mg and 8.18 mg for women aged 18−29 years, respectively, as the exact numerical estimate, the approximate estimate using BETA.INV in Excel and the approximate estimate using F.INV in Excel. For women aged 30−49 years, it was 9.15 mg, 9.17 mg and 9.14 mg. The intake covering the needs of 97.7 % women was 14.55 mg, 14.44 mg and 14.49 mg for women aged 18−29 years, and 15.70 mg, 15.77 mg and 15.60 mg for women aged 30−49 years. ConclusionThe approximate estimates of iron requirements agreed well with the exact numerical estimate. The proposed method is useful for the estimation of iron requirements in menstruating women that usually requires extensive numerical calculations.

Investigating the Essentiality and Requirements of Iron from the Ancient to the Present.

This review discusses the development of studies that evaluated the essentiality and requirements of iron from the ancient to the present. The therapeutic effects of iron compounds were recognized by the ancient Greeks and Romans. The earliest recognition of the essentiality of iron was stated by Paracelsus, a distinguished physician alchemist, in the sixteenth century. Iron was included in the earliest nutritional standard prepared for the Royal Army by E. A. Parkes, the first professor of hygiene. The League of Nations Health Organisation determined average iron requirements based on literature review. In the first US Recommended Dietary Allowances (RDA), the RDA of iron was determined from the results of iron balance studies. In the current Dietary Reference Intakes, iron requirements were determined based on the factorial method with the aid of Monte Carlo simulation for combining basal and menstrual iron losses. Population data analysis is a recently developed alternative that does not use the pre-estimated iron absorption rate and requires the prevalence of inadequacy instead. Population data analysis uses the convolution integral for combining basal and menstrual iron losses to ensure the required accuracy. This review also provides new estimates of hair and nail iron losses.

Kosttilskudd med jern ved jernmangel

A low supply of iron in the diet may result in iron deficiency and mild iron-deficiency anaemia in healthy individuals. Women are more susceptible than men because of menstrual iron loss. We compared the effect of a low dose of iron, administered as a dietary supplement, with a high pharmacological dose of iron to otherwise healthy individuals with iron deficiency and mild iron deficiency anaemia. In a randomised, double-blind trial conducted in 2000-2001, 73 women and three men with iron deficiency received either 27.6 mg of iron consisting of ferrous fumarate enriched with 13% haem iron, or 100 mg ferrosulphate daily for 12 weeks. Blood samples were analysed four times in the course of the treatment. The median ferritin value rose by 13 and 7 μg/l in the high-dose and low-dose group, respectively. The increase in ferritin was significantly higher in the high-dose than in the low dose group ( < 0.001). There was no statistically significant difference between the groups in the change in Hb, serum-iron or serum-iron binding capacity. The median haemoglobin value increased by 0.4 g/100 ml in both groups. Gastrointestinal side effects were experienced by 58% in the high-dose group and 35% in the low-dose group. Four subjects in the high-dose group and one in the low-dose group broke off the treatment because of side effects. A supplement of low-dose iron is enough to increase iron stores in cases of nutritional iron deficiency in healthy individuals and to optimise haemoglobin. High-dose iron caused the largest increase in iron stores. Low-dose iron resulted in the least side effects.

Blood donation, blood supply, iron deficiency and anemia - It is time to shift attention back to donor health

Since the 1980s blood collectors worldwide have focused on two central themes: blood product safety and an adequate blood supply. From the standpoint of safety, specifically the reduction of transfusion-transmitted diseases, the achievements over the past quarter century are remarkable. With respect to the adequacy of the blood supply, the past decade has witnessed major gains in some countries of Europe, Canada and the US and less than had been expected in others, including Brazil, where the challenge of having a more stable blood supply, in which supply and demand are in better balance remains an important issue(1). On the other hand, the aforementioned achievement has come at a price: iron depletion of the repeat blood donor. Blood centers have long recognized that it is more effective and less expensive to collect blood from existing donors than to recruit new donors. While first-time donors, particularly the young and minorities, have been more successfully recruited, 70% of US and 40-70% (depending on the region) of Brazilian donors are repeat donors(1,2). The only known significant disadvantage of blood donation is the potential risk of iron deficiency (ID). Iron is a vitally important element in the human metabolism. It plays a central role in erythropoiesis and is also involved in many other intracellular processes in all the tissues of the body. The potentiality of the individual donor to give blood without developing ID and iron deficiency anemia (IDA) varies widely, probably due to differences in nutritional iron intake, the differences in prevalences of ID in each study population, menstrual iron loss in females, the frequency of blood donation and the use of supplemental iron(2). The frequency of ID is high in blood donors (1.8% to 8.4% in males and 4.5% to 34.8% in females), and more dependent on the frequency of donations than on the cumulated number of donations(2,4). In addition to this, ID is a significant problem and its prevalence is increasing in many countries around the world. The prevalence has been reported to be 9-40% in women, depending on age and menstrual status and 2-5% in men(1,2). Because menstruating females begin their blood donation careers from a lower starting point, subsequent donations pose a risk for greater clinical harm. Females have much higher rates of both ID and IDA.The clinical implications of ID and IDA are not insignificant, including fatigue, reduced work performance and intellectual capacity, reduced endurance, restless leg syndrome, pica, and cognitive and immune function changes. The degree of symptomatology is proportionate to the severity of the anemia(1,2). Moreover, low hemoglobin (Hb) accounts for 4-10% of total deferrals, with the vast majority occurring in women. Therefore it seems reasonable to secure adequate iron reserves in the donor population in order to maintain an appropriate donation potentiality and to avoid possible hematological and non-hematological complications related to ID(1,2). The question that arises is whether this practice is in the best interest of donor health. In this issue of Revista Brasileira de Hematologia e Hemoterapia, Silva et al., representing the Hemocentro Regional de Uberaba, Minas Gerais, Brazil, have brought this issue to light(5). Given the findings in this and other studies, what measures can blood collectors pursue to address iron depletion? There is no single answer, but several approaches should be considered: 1) modifying the donor Hb requirements and measurement of Hb, 2) changing the interdonation interval, 3) testing for serum ferritin, and 4) iron supplementation.

Do changes in iron metabolism contribute to the acceleration of the atherosclerosis process?

There are several risk factors whose association with atherosclerosis, a chronic disease with complicated etiology, is well established, including age, gender, smoking, lipids metabolism disorders, diabetes mellitus, obesity and reduced physical activity. Surprisingly, many cardiovascular related deaths occur in individuals without standard risk factors, so it has been suggested that these cases must be the result of other factors, previously not taken into account. This phenomenon resulted in the development of research focused on finding new risk factors. In 1981, Sullivan first postulated the so-called “iron hypothesis”, suggesting that the regular menstrual iron loss, rather than other known effects of estrogen, protects women against coronary heart disease. It is widely believed at present, that iron is an essential catalyst in the oxidation and oxidative modification of low-density lipoprotein cholesterol which appears to be one of the pivotal steps in the early phase of the formation of the atherosclerotic plaque. Thus, iron depletion through menstrual loss might reduce oxidative stress and beneficially affect atherogenesis. Stored iron appears to be essential in the process of atherogenesis which is strictly required for normal cellular metabolism but also serves as a reservoir from which toxic-active iron can be liberated under atherogenic stimuli and result in lipid peroxidation. In this process, two pathways i.e., iron homeostasis metabolic pathway and metabolic pathways involving proinflammatory cytokines are closely interconnected. In human monocytes, these cytokines also increase the uptake of non-transferrin-bound iron, via the stimulation of divalent metal transporter-1 synthesis and cause iron retention by down-regulating ferroportin synthesis. It has been found recently that iron depositions are prominent in human atherosclerosis lesions. It can therefore be concluded that the results of scientific research, particularly those of the last ten years, provide a strong pathological basis to support the role of iron metabolism alterations in vascular damage and in the progression of atherosclerosis process.

Numerical methods for estimating iron requirements from population data.

The estimation of iron requirements is crucial for nutrition and food policy. The traditional methods for estimating iron requirements are balance methods based on iron intakes and excretions and factorial methods based on estimated iron absorption rates and estimated iron losses from body compartments. As an alternative, numerical methods for estimating iron requirements from population data of iron status were developed. The iron status data reported by Satoh (1991) were used in the sixth edition of Recommended Dietary Allowances for Japanese. The menstrual iron losses in Japanese premenopausal women were estimated from the literature to calculate total iron losses as the sum of basal iron losses and menstrual iron losses. The use of this alternative method is illustrated by analyzing the same population data comprising the prevalence of iron deficiency and the distribution of iron intake. The estimated average requirements were affected by the form of distribution function, the relative standard deviation of requirements, and the correlation coefficient between iron intakes and requirements. We conclude that numerical methods can be very useful for estimating iron requirements and to elucidate dietary recommendations of iron. These methods may contribute to determining requirements of other nutrients as well as iron.

Advantages and disadvantages of an iron-rich diet.

A review by invitation about advantages and disadvantages of an iron-rich diet by analyzing physiological iron requirements, dietary factors influencing iron absorption and the regulatory systems available to control iron absorption according to needs. The control to prevent iron deficiency is good but not perfect, as observed in previously described studies on relationships between individual iron requirements and the probability of iron deficiency developing in relation to diet. The control to prevent iron overload seems to be perfect except in the few subjects being homozygotes for hereditary hemochromatosis. A diet rich in easily available iron is important for covering basal iron losses, menstrual iron losses and the high iron requirements for growth from infancy to adolescence and for pregnancy.

Iron absorption from the whole diet: comparison of the effect of two different distributions of daily calcium intake

The possibility of reducing calcium inhibition of iron absorption by decreasing calcium intake in lunch and dinner meals, which provided the most dietary iron, was examined in 21 healthy female volunteers. During a 10-d period, nonheme iron in all meals was extrinsically labeled with radioisotopic iron to a uniform specific activity. Iron absorption from two identical 10-d periods was compared when meals were labeled with two different iron radioisotopes and when the same amount of calcium (937 mg) was distributed in two ways, in either mainly breakfast and late evening meals or more evenly in all meals. About 30-50% more iron was absorbed when no milk or cheese was served with lunch or dinner. The difference was statistically significant. Median iron requirements (1.61 mg/d) calculated from body weight and menstrual iron losses agreed with the mean value of median iron absorption in the two 10-d periods (1.54 mg/d), which supports the validity of the present method. A reasonable separation of calcium and iron intakes would improve iron nutrition.

3 Prevention of iron deficiency

This chapter discusses different methods to prevent iron deficiency--to reduce iron losses (e.g. reducing menstrual iron losses by using a contraceptive pill or combating of hookworm infestation) or to increase iron absorption. Iron absorption can be increased (1) by modifying the composition of meals--increasing the content of dietary factors enhancing iron absorption (e.g. meat and ascorbic acid) or reducing the content of factors inhibiting iron absorption such as phytate and iron-binding phenolic compounds, (2) by increasing the iron content of the diet by fortification with iron, or by (3) supplementation with iron tablets. Several factors to consider in the choice of strategy are discussed such as the importance of the bioavailability of the diet for the efficacy of iron fortification, the choice of vehicle for iron fortification that is compatible with the iron compound used, the feasibility to increase the bioavailability of the dietary iron by modification of the composition of the diet and the short time available in pregnancy to ensure a sufficient supply of the extra iron needed limiting the effective measures available to supplementation with iron tablets.

The cost of successful adolescent growth and development In girls in relation to iron and vitamin A status

The role of iron and vitamin A in adolescent growth and development is not well described. During adolescence iron requirements are increased, reaching a maximum at peak growth, but after menarche, menstrual iron loss must also be replaced. An observed rise in retinol-binding protein concentrations at puberty level 4 indicates a role for vitamin A in sexual maturation. Iron and vitamin A deficiencies may slow the tempo of growth. Conversely, for girls on marginal diets, an extended catch-up growth period may lead to depletion of these nutrients. The costs of achieving growth may also include cephalopelvic disproportion in girls becoming pregnant and increased risk of menorrhagia.

Management of IUD-associated menorrhagia in female rhesus monkeys (Macaca mulatta)

The study was undertaken to evaluate the effect of antifibrinolytic agents (epsilon-aminocaproic acid, EACA; tranexamic acid, AMCA), anti-inflammatory drugs (indomethacin, IND; ibuprofen, IBU; naproxen, NAP) and root extract of the plant Boerhaavia diffusa (BD) on menstrual cycle length (MCL), duration of menstrual flow (DMF), menstrual iron loss (MIL) and activity of uterine tissue plasminogen activator (tPA) in IUD-fitted monkeys. Premature onset of menstruation was observed in IUD-fitted monkeys (26.0 +/- 0.7 days, mean +/- SE) as compared to controls (28.7 +/- 0.4 days). No noteworthy change was observed in the MCL of drug treated monkeys as compared to IUD-fitted monkeys. An increase of 155%, 123.2%, and 288% was observed in the DMF, MIL and tPA activity after IUD insertion as compared to controls. Antifibrinolytic agents reduced the DMF, MIL and activity of tPA in IUD-fitted monkeys up to 117.4%, 116.4%, and 254%, whereas anti-inflammatory drugs caused a decrease only up to 69%, 95.1%, and 138%, respectively. Conclusively, root extract of B. diffusa treated IUD-fitted monkeys showed noticeable reduction in their DMF (124%), MIL (120.8%) and tPA activity (272%).

Anemia in adolescence. 1. Disturbances of iron balance.

The primary cause of anemia in adolescents is negative iron balance. This is primarily due to menstrual iron loss in females and growth demands plus borderline diets in males. Normal blood indexes for this age group are proposed. Low values cannot be attributed to simple iron deficiency without a thorough search for occult blood loss or other underlying illness.

Anemia in adolescence. 2. Hemoglobinopathies and other causes.

Many complex forces are at work during adolescence which can contribute to the occurrence of anemia. Careful consideration of the entire patient should enable a physician to identify the unusual as well as the more common causes of anemia in this age group. Anemia in teenage girls is primarily due to menstrual iron loss. In boys, borderline diets and the demands of rapid growth predominate as causative factors. Hemoglobinopathies (thalassemia, sickle cell disease), G6PD deficiency, infectious mononucleosis, and illicit drug use account for small proportions of cases.

The determination of menstrual iron loss

A procedure involving dry ashing and spectrophotometry with thioglycollic acid is described for the determination of iron loss during menstruation. In its development the nonvolatility of iron was checked and wet-oxidation and dry-ashing methods of destroying organic matter compared with special reference to citrated whole blood. For the level of iron characteristic of whole blood and two methods were found to give similar results with a precision of better than 2.4% with the component attributable to the method being rather less that 1%; the remainder is thought to arise mainly from sample heterogeneity.

Community study of menstrual iron loss and its association with iron deficiency anaemia.

Although anaemia, as conventionally defined, appears to be common in Great Britain (Kilpatrick, 1961; Elwood, 1964), little is known about the factors which are likely to cause a negative iron balance and eventually lead to iron deficiency anaemia. The main loss of iron from the body in females is by menstruation, but the relative impor tance of menstrual loss and dietary intake of iron in the determination of the level of circulating haemoglobin does not seem to have been examined in a representative sample of the community. A series of epidemiological studies was conducted recently to investigate a variety of aspects of iron deficiency. The basic study is described in Elwood, Waters, Greene, and Wood (1967). In the study reported here, the association between haemato logical state and menstrual loss of iron is examined in a representative sample drawn from a total community. Details of the dietary intake of iron in these women will be presented elsewhere but the relevance to iron balance of both menstrual loss and dietary intake is examined. Method An area in the Rhondda Fawr was selected and the 1,005 female residents aged 20 to 64 years we e invited to co-operate in a haematological survey. Women who were pregnant were omitted. The 355 women who were between 20 and 39 years inclusive were stratified by haemoglobin level at intervals of 1 g./lOO ml. blood, and within these groups sub-samples of up to eleven subjects were chosen at random to give a total sample of 59 (Table I). Of these, four who had become pregnant since the initial survey were excluded, as were a fu ther six whose menstrual periods occurred at such irregular intervals that estimates of the iron lost in one or two menstrual periods could not be used as guide to the loss over long periods of time. Each woman was visited by a doctor and asked co-operate in the present study. Those who agreed were visited by a health visitor (G.R.) and the method for collection of the menstrual loss was explained. Soluble pads or tampons of a single make were supplied throughout the study.