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 Table of Contents  
Year : 2020  |  Volume : 45  |  Issue : 3  |  Page : 156-159

Serum and salivary ferritin levels in iron-deficiency anemia − is there a difference?

1 Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission07-May-2020
Date of Acceptance27-Jul-2020
Date of Web Publication23-Jun-2021

Correspondence Address:
MD Amr M Gawaly
Department of Internal Medicine, Faculty of Medicine, El Gish Street, Tanta, 9111
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejh.ejh_23_20

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Introduction Iron-deficiency anemia (IDA) is one of the most important nutritional deficiencies in Egypt. The assessment of serum ferritin has been the gold standard method in the detection of this disease However, this involves the drawing of venous blood, which is invasive and is sometimes physically and psychologically traumatic to the patients, and sometimes it is difficult to withdraw blood from hidden veins. This study was done to estimate and correlate serum ferritin levels and saliva ferritin levels of patients with IDA, thus assessing the effectiveness of saliva as an alternative noninvasive diagnostic tool. This study was done to estimate, compare, and correlate the ferritin levels in serum and saliva of patients with IDA, to determine whether saliva can be used as a predictive marker to monitor the iron levels in IDA.
Patients and methods A total of 60 patients with IDA and 20 healthy participants as control were chosen for the study. Quantitative estimation of serum and salivary ferritin levels was performed by solid-phase ELISA. Hemoglobin levels were also estimated to confirm the anemic status of the patient. Data were statistically analyzed using SPSS software version 19.
Results There was increased salivary ferritin level in patients with IDA. A negative significant correlation was found between serum hemoglobin and both salivary ferritin level and salivary/serum ferritin ratio, and a significant negative correlation between serum and salivary ferritin levels.
Conclusion Salivary ferritin is a noninvasive method for the detection of IDA with a good predictive effect.

Keywords: ferritin, iron-deficiency anemia, salivary ferritin

How to cite this article:
Gawaly AM, El-Naby AA, Alghazaly GM. Serum and salivary ferritin levels in iron-deficiency anemia − is there a difference?. Egypt J Haematol 2020;45:156-9

How to cite this URL:
Gawaly AM, El-Naby AA, Alghazaly GM. Serum and salivary ferritin levels in iron-deficiency anemia − is there a difference?. Egypt J Haematol [serial online] 2020 [cited 2021 Sep 23];45:156-9. Available from: http://www.ehj.eg.net/text.asp?2020/45/3/156/319159

  Introduction Top

According to the WHO, two billion people in the world have anemia, and half of them are owing to iron deficiency. Anemia is a serious global public health problem that particularly affects young children and pregnant women. WHO estimates that 42% of children less than 5 years of age and 40% of pregnant women worldwide are anemic [1].

Iron is an essential element for all living organisms. Oxygen transport is the most important function of it in hemoglobin. A broad spectrum of reasons can cause iron-deficiency anemia (IDA); such as malnutrition and bleeding and is largely detected based on different hematological laboratory findings [2].

Analyses of different body fluids are pushing the field of biomedical research forward owing to its reliability to identify biochemical targets [3]. One of the most important diagnostic body fluids is saliva, which has significant biochemical and logistical advantages in comparison with blood [4].

Saliva collection is safe to both patient and health care provider, noninvasive, and relatively simple, and may be done frequently without discomfort to the patient and has low-cost storage [5]. The potential advantage of this diagnostic body fluid could extend to clinical decision making and health care [6].

Ferritin is an omnipresent and highly conserved iron-binding protein. Increasingly, iron and ferritin are emerging as an important element in the pathogenesis of diseases. Ferritin levels seem to reflect the magnitude of iron stores in the body, and decreased serum Ferritin levels are used as an indicator for anemia. The salivary ferritin may be considered as the potential new discriminating index with the advantage of an easy and noninvasive approach [7].

  Aim of the work Top

The objective of this study was to determine the salivary ferritin in patients with IDA and its correlation to serum ferritin and hemoglobin.

  Patients and methods Top

This study was conducted on 60 patients with IDA from the internal medicine department Tanta university and 20 healthy participants as control. All were divided into four groups as follows: group 1 included 20 patients with mild IDA (serum hemoglobin level is 10–12 g/dl), group 2 included 20 patients with moderate IDA (serum hemoglobin is level 7–10 g/dl), group 3 included 20 patients with severe IDA (serum hemoglobin level is <7 g/dl), and group 4 included 20 healthy participants with serum hemoglobin more than 12 g/dl without IDA as a control group. Patients fulfilling the criteria of IDA (microcytic hypochromic anemia, hemoglobin concentration <12 g/dl in females and <13.5 g/dl in males, hematocrit value <35.9% in females and 39.9% in males, and mean corpuscular volume <80 fl, and serum ferritin <12 μg/l). Patients with chronic hepatitis and liver cirrhosis, patients with Hodgkin’s lymphoma, patients with hemolytic anemia, and patients with chronic inflammation and infection were excluded. Detailed history taking and complete clinical examination was done. Complete blood count included the following: hemoglobin level, detected by automated hemoglobin meter; serum total bilirubin; direct bilirubin; erythrocyte sedimentation rate; and lactate dehydrogenase. Serum ferritin and salivary ferritin were tested by solid-phase ELISA using the available commercially kits (provided by Monobind Inc., Lake Forest, California, USA).

The saliva samples were taken within 24 h before sampling at a rate of 2 ml, emphasizing the avoidance of eating food, using toothbrushes, chewing gum, taking beverages or cigarette smoking during the two hours before sampling in the interval of 9–11 a.m., after asking them to rinse the mouth with deionized distilled water and was transferred to the laboratory. The collected data were organized, tabulated, and statistically analyzed using SPSS software (Statistical Package for the Social Sciences, version 19; SPSS Inc., Chicago, Illinois, USA) [8].

A written consent was taken from all the participants in this study after informing them about the study and the possible hazards. This study was approved by the Medical Research Ethics Committee of the Tanta Faculty of Medicine according to the Declaration of Helsinki.

  Results Top

Among the studied groups, comparison between the groups regarding sex had no significant difference (P=0.032). Moreover, comparison between these groups regarding the age had no significant difference (P=0.841) ([Table 1]). Mean salivary ferritin level was statistically significantly higher in all studied groups in comparison with the control group (P˂0.001), and also comparison between the studied groups regarding the serum ferritin showed statistically significant higher levels in the control group rather than other groups (P˂0.001). The studied groups showed that salivary/serum ferritin ratio was statistically significantly higher in the diseased groups compared with the control group, with significant elevation as anemia worsens (P˂0.001) ([Table 2]). The correlation between the hemoglobin and serum ferritin was highly significantly positive, but we noticed a highly statistically significant negative correlation between hemoglobin and both salivary ferritin and salivary/serum ferritin ratio (P˂0.001) ([Table 3] and [Figure 1]). A highly significant negative correlation was observed between the salivary and serum ferritin levels, as well as between the salivary/serum ferritin ratio and serum ferritin level (P˂0.001) ([Table 4] and [Figure 2] and [Figure 3]).
Table 1 Demographic data of the studied groups

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Table 2 Mean salivary ferritin, serum ferritin, and salivary/serum ferritin ratio in the studied groups

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Table 3 Correlations between hemoglobin and serum ferritin, salivary ferritin, and salivary/serum ferritin ratio

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Figure 1 Correlation between hemoglobin and salivary/serum ferritin ratio.

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Table 4 Correlation between the serum ferritin and both salivary ferritin and salivary/serum ferritin ratio

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Figure 2 Correlation between serum ferritin and salivary/serum ferritin ratio.

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Figure 3 Correlation between serum ferritin and salivary ferritin.

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  Discussion Top

Venous blood sampling is the most common method of checking different blood markers in patients with blood disorders; however, sampling of venous blood and carrying it has had the risk of contamination and infection; moreover, this is a relatively invasive and painful procedure and may not be appropriate for younger and older patients, patients with sedentary life, and those have difficulty in finding blood vessels.

Regarding the relationship between the amounts of markers in saliva and serum of the blood and limited and conflicting results of previous studies, this study was conducted to identify the value of a noninvasive method to evaluate the ferritin level in patients with IDA.

In the previous study, there was no statistically significant difference between the studied groups regarding age and sex, and this was in agreement with Canatan et al. [6]. In the previous study, the mean value of the serum ferritin was significantly higher in the control group (117.76±19.50) than the diseased groups. This is expected, as the serum ferritin is an indicator for the iron store status, and this was in agreement with McLean and colleagues, and Grant and colleagues, who considered serum ferritin the most readily available and a useful index of IDA [9].

However, this contrasted with the findings of Kalantar-Zaden [10], and Mc Grath [11], who considered that serum ferritin is an acute-phase reactant that increases with inflammation, infection, hyperthyroidism, malignancies, and liver disease. In our study, we excluded patients with these diseases from the study.

Salivary ferritin levels were significantly higher in patient groups when compared with the control group. The mean values were 6.39±0.27, 6.5±0.33, 9.04±0.74, and 4.2±1 ng/ml in mild, moderate, severe anemia, and control groups. respectively.

This was in agreement with the results of Jagannathan et al. [7], who found that the salivary ferritin was significantly higher in the severe anemia group than the mild and moderate and control groups. The mean value of salivary ferritin in iron-deficiency cases was 153.24±46.58 µg/dl, and the mean ferritin levels in controls were 93.87±30.15 µg/dl.

Moreover, it was in agreement with the study of Aghazadeh et al. [12], who studied the serum and salivary ferritin in 140 patients of IDA and 140 healthy controls. They found that the mean value of salivary ferritin in iron-deficient cases was 111.4 µg/dl and the mean ferritin levels in controls were 94.77 µg/dl. Thus, the salivary ferritin was found to be significantly higher in iron-deficient participants compared with the controls.

The exact mechanism by which anemia caused a rise in salivary ferritin is not exactly known. The levels of salivary ferritin in normal participants is 95–105 µg/dl, whereas the levels increase up to 130–170 µg/dl in IDA. However, it may be speculated that the iron-dependent enzymatic functions of the saliva also help in the conservation of iron through the saliva of iron-deficient patients [13].

Other possibilities include endocytosis of ferritin by the ducts of salivary glands and its excretion into the saliva and presence of high molecular weight iron-binding properties of saliva [14].

Internalization of ferritin in the intercalated ducts in the form of lysosomes in the parotid duct could serve as a possible mechanism for the increased salivary levels. This mechanism hitherto has been established in rats, but the evidence is not conclusive in human beings. This may also be the mechanism for alterations in the proteins in saliva before it reaches the oral cavity [15].

Changes in salivary ferritin occurs even before the hematological changes and hence these measurements are clinically significant in monitoring the iron status [16].

In the present study, there was a highly positive correlation between the serum ferritin and hemoglobin (R=0.803), and a highly significant negative correlation between hemoglobin and both salivary ferritin and salivary/serum ferritin ratio (R=−0.866 and −0.947, respectively).

Moreover, there was a highly significant negative correlation between serum ferritin and both salivary ferritin and salivary/serum ferritin ratio. This agrees with that of Aghazadeh et al. [12], who stated that the increase in serum ferritin decreases the salivary ferritin level.

  Conclusion Top

The expression of ferritin in saliva in patients with IDA may be owing to the enzymatic functions in the saliva and the endocytosis of ferritin, which can possibly elevate the salivary ferritin. Further extensive studies with a larger sample size could open a new horizon in the broad field of IDA, and the salivary ferritin may be used as a reliable diagnostic marker in IDA and may confirm the exact mechanism by which the salivary ferritin was increased.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kodati S. Correlation of serum & salivary ferritin levels in iron deficiency anemia patients. Int J Biol Med Res 2018; 9:6317–6320.  Back to cited text no. 1
Hagve TA, Lilleholt K, Svendsen M. Iron deficiency anaemia − interpretation of biochemical and hematological findings. Tidsskr Nor Laegeforen 2013; 133:161–164.  Back to cited text no. 2
Markopoulou S, Nikolaidis G, Liloglou T. DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer. Clin Chem Lab Med 2012; 50:1723–1731.  Back to cited text no. 3
Bigler LR, Streckfus CF, Dubinsky WP. Salivary biomarkers for the detection of malignant tumors that are remote from the oral cavity. Clin Lab Med 2009; 29:71–85.  Back to cited text no. 4
Rahim F. Salivary ferritin and iron as a marker and new discriminating indices between iron deficiency anemia and thalassemia: a meta-analysis. Russian Open Med J 2017; 6:e0204.  Back to cited text no. 5
Canatan D, Akdeniz SK. Saliva iron and ferritin levels in patients with thalassemia and iron deficiency anemia. Mediterr J Hematol Infectious Dis 2012; 4:e201–e205.  Back to cited text no. 6
Jagannathan N, Neelakantan P, Ramani P, Premkumar P. Salivary ferritin-A concise update on current concepts. Int J Curr Res Rev 2012; 4:60–62.  Back to cited text no. 7
Dawson B, Trapp RG. Basic and Clinical Biostatistics. Chapter 7–9. 3rd ed., Lange Medical Book/McGraw-Hill, Medical Publishing Division. 2001. PP. 161–218.  Back to cited text no. 8
McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr 2009; 12:444–454.  Back to cited text no. 9
Kalantar-Zadeh K, Rodriguez RA, Humphreys MH. Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant 2004; 19:141–149.  Back to cited text no. 10
McGrath HJr, Rigby PG. Hepcidin: inflammation’s iron curtain. Rheumatology (Oxford) 2004; 43:1323–1325.  Back to cited text no. 11
Aghazadeh M, Eslami H, Pirzadeh A. Evaluation of correlation between saliva and serum ferritin level in patients with iron deficiency anemia and comparison group. J Hum Soc Sci 2016; 21:8.  Back to cited text no. 12
Mishra OP, Agarwal KN, Agarwal RM. Salivary iron status in children with iron deficiency and iron overload. J Trop Pediatr 1992; 38:64–67.  Back to cited text no. 13
Lagunoff D, Benditt EP. Proteolytic enzymes of mast cells. Ann N Y Acad Sci 1963; 103:185–198.  Back to cited text no. 14
Hand AR, Coleman R, Mazariegos MR, Lustmann J, Lotti LV. Endocytosis of proteins by salivary gland duct cells. J Dent Res 1987; 66:412–419.  Back to cited text no. 15
Rennie JS, MacDonald DG, Dagg JH. Iron and the oral epithelium: a review. J R Soc Med 1984; 77:602–607.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4]


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