Impact of cod liver oil consumption in infants and children: A systematic review

doi:10.21203/rs.3.rs-2139509/v1

Background

Cod liver oil (CLO) is a nutritional supplement derived from liver of cod fish. It has high level of the omega-3 fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, and very high levels of vitamins A, D, and E. Supplementing cod liver oil for infant and children is associated with many health benefits such as decreased risk of upper respiratory tract infection, better visual development, and decreases chance of developing Type 1 diabetes. The main aim of this review is to assess the impact of codliver oil consumption in children’s and infants.

Methods

We used databases PubMed/MEDLINE, CINHAL and Cochrane library and other sources like Goggle and Goggle scholar. All searches were limited to English language without restriction for publication year. All studies identified through different databases combined, exported and managed using Endnote X9.1 software. Information’s such as Authors, study location, publication year, study design, sample size, comparison group and reported outcomes was extracted.

Result

From the results of this review, we can conclude that Cod liver oil is very important for children in many aspects. It reduces the risk of type 1 diabetes, through the anti-inflammatory effects of long-chain omega 3 fatty acids. It also decreases in upper respiratory tract pediatric visits during the winter and early spring. It also supports normal brain development and functioning and vision during the prenatal period and throughout infancy and childhood. Consumption of codliver oil is also useful in reducing the symptoms of ADHD in children.

Conclusion

As a conclusion, Cod liver oil is very important to health of children since it contains omega-3 fatty acids and vitamins A, D, and E. Cod liver oil is important in reducing risk of type 1 diabetes, upper respiratory tract pediatric visit and ADHD. Cod liver oil is crucial for fetal brain development and enhancement of IQ score, and fetal visual development. More attention to this important nutrient by the concerned body may lead to improved dietary supplements and prevention of many diseases in children.

Cod-liver oil

Cod oil

Infant

Children

Cod liver oil (CLO) is a nutritional supplement derived from liver of cod fish. It has high level of the omega-3 fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, and very high levels of vitamins A, D, and E. High quality CLO is a pale yellow, thin, oily liquid having a slightly fishy and bland taste[1]. CLO has been used for centuries as a food for both animals and human beings. Several fishing companies pooled their resources and began producing CLO for animal feed and eventually highly refined oil of pharmaceutical standards[1].

The earliest recorded medical use of cod-liver oil dates to 1789, and is credited to Dr Darbey of Manchester Infirmary[2] , while he used it for treating rheumatism. Cod Liver oil is high in Vitamins A & D which are natural anti-inflammatory to reduce inflammation of the mucus membranes[3].

CLO, which is obtained from the livers of cod fish, is rich in vitamins (A, D, and E) and in omega-3 fatty acids. As a supplement, in either capsule or liquid form, it supplies the important fatty acids, eicosapentaenoic acid, and docosahexaenoic acid. Eicosapentaenoic acid is used by the body to produce prostaglandins and reduce triglyceride levels. These combined effects can significantly reduce the high blood pressure, risk of heart disease, and the mortality of a heart attack. Believing that CLO has so many benefits has led some lay people to try it for penile augmentation by subcutaneous injection[1].

Omega 3 fatty acids found in cod-liver oil are long chain essential fatty acids (eicosapentaenoic acids) EPA and (docosahexaenoic acid) DHA which are concentrated in synaptic neuronal membrane and regulate vascular and immune function that affects the central nervous system[4], Dietary deficiency of these fatty acids in humans has been associated with bipolar mood disorder and schizophrenia[5]. Intake of omega 3 fatty acids found in the cod liver oil can lower symptoms of depression [6], and could be beneficial in the treatment of some patients with anxiety disorders[7].

Omega-3 fatty acids, in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), play an essential role in maintaining overall health in humans throughout the lifespan[8]

Mechanistically, the beneficial effects of DHA and EPA on health are mediated directly through the alteration of membrane phospholipids and the cellular receptors that influence cellular behavior and response, as well as indirectly through modulation of hormone levels and reduction of oxidative stress, which, in turn, affect the behavior of cells and tissue[8-11]Epidemiological and experimental studies have indicated that consumption of more n-3 long-chain polyunsaturated fatty acids may reduce the risk for a variety of diseases, including cardiovascular, neurological and immunological disorders, diabetes and cancer[12].

Cod liver oil is an important source of both vitamin D and the long-chain n−3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in the Norwegian population. In Norway, dietary vitamin D supplementation is recommended from infancy, preferably in the form of cod liver oil [13, 14].Thus, regular intake of cod liver oil is recommended for several purposes. Since the 1920s, health authorities in several countries have recommended a daily spoonful (5 ml) of cod liver oil during the autumn and winter months as a measure of protection against rickets and vitamin D deficiency [15]. Childhood cod liver oil consumption has recently been linked to decreased forearm bone mineral density in perimenopausal and postmenopausal Norwegian women[16].

The discovery of essential fatty acids omega-6 and omega-3 have shown that deficiencies, mainly of omega-3 long chain polyunsaturated fatty acids, result in visual and cognitive impairment and disturbances in mental functions in infants and also in cognitive function in adults, as fatty acids are beneficial to vascular health and may forestall cerebrovascular disease and thus dementia[17].

Historically, cod liver oil was used to treat rickets in children and ‘‘old pains’’ in adults. It was used by members of fishing communities before it was recognized as medically valuable by physicians[18]. Cod liver oil is a rich source of omega 3 fatty acids and has been widely used as omega 3 fatty acid supplementation[19]. Cod liver oil has a very long history of usage as a medicinal oil, before the advent of synthetic vitamins, cod-liver oil was consumed regularly by the general population for its vitamin A and D supplementation[14]. later on, it has been found that various health benefits of cod liver oil is associated with omega 3 fatty acids[20]. The main objective of the study is to review the health impact of codliver oil in children using a systematic review and meta-analysis.

Data source and Searches

To find potentially relevant studies, we systematically searched two major databases (i.e., PubMed/MEDLINE, CINAHL) and search engines (Google and Google scholar). Additionally, the reference lists of eligible studies were checked for additional articles. The search was conducted by two authors (Sileshi Demelash Sasieand Fantu Mamo Aragaw) independently. Studies identified through the systematic search were retrieved and managed using Endnote X9. The final studies were searched from the above-mentioned databases (Table 1).

Study selection criteria

Inclusion Criteria	Design: all
	Study setting: globally
	Population: children
	Publication status: All published and unpublished articles
	Language: English language

Exclusion criteria	Articles that were not fully accessed after at least two email contacts of the principal investigator were excluded.

Screening process

All titles/abstracts identified in the electronic databases were screened by 2 authors (Sileshi Demelash Sasie,and Aschalew Abayneh) independently of one another. Discrepancies were resolved by discussion. All potentially relevant full texts were screened by 3 authors (Berhanu Wodajo, Muluken Azage, and Fantu Mamo Aragaw) independently of one another. Discrepancies were resolved by discussion. In the case of discrepant judgments, a third author (Sileshi Demelash Sasie) was involved.

Data extraction process and quality assessment

Two authors (Sileshi Demelash Sasie ,and Muluken Azage) independently performed data extraction using a pre-defined eligibility criterion to ensure consistency. The data extraction form was prepared using a Microsoft™ Excel spreadsheet. Disparities between authors were resolved through discussion once the sources of disagreements were identified. The following information was extracted from each primary article: study location, publication year, study design, sample size, comparison group, reported outcomes, and first author.

Characteristics of eligible studies

As presented in Figure 1, four studies met the inclusion criteria and were included. Among the included studies, about half (50%) were from New york[21, 22], one from Norway[23] ,and one from Colorado[24] (Table 2)

Studies suggest that liquid cod liver oil of adequate purity and acceptable taste for infants and young children, as well as a children’s multivitamin/mineral supplement with selenium and other trace metals[25]. Studies suggest that use of cod liver oil during the first year of life was associated with a lower risk of type 1 diabetes [26].

Studies also suggest that cod liver oil supplementation may be one of the complementary treatments for obese children who have low baseline DHA content. Thirty-seven children aged 1-2 years attending a Child Health Panel in Lancashire and who had had little or no cod-liver oil during their lives were compared with 50 controls who had received cod-liver oil regularly. In respect of tooth eruption, radiological appearance of the wrist and serum alkaline phos-phatase there was no difference between the two groups[27]. Liquid cod liver oil intake has been, and still is, a substantial source of vitamin D during the long, dark winter season in Iceland[28].

Cod liver oil is an important source of both vitamin D and the long-chain n3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in the Norwegian population[13, 14]. Long-chain fatty acids have been shown to reduce the risk of chemically induced diabetes in experimental animals[29].

A case-control study from Norway examining the contribution of omega-3 fatty acid intake on type 1 diabetes was showing that children with diabetes were less likely to have been given cod liver oil during infancy than children without diabetes[23].

DHA supports normal brain development and functioning and vision during the prenatal period and throughout infancy and childhood [30-32]. These omega-3 fatty acids must, therefore, need to be consumed directly through the diet from foods that are rich in DHA and EPA, primarily in the form of oily fish[8]

From the 1920s to the 1940s, many children in the United States were given a teaspoon of cod liver oil each day as a source of vitamins A and D[33]. Omega-3 fatty acids present in cod liver oil may help in reducing the symptoms of ADHD in children aged seven to 12 years[34]. However, many regional diets contain limited omega-3 fatty acid content, particularly where seafood consumption is low[35, 36]. Consequently, DHA and EPA are not likely consumed in adequate amounts from the typical diet to accumulate in tissues at sufficient levels to produce their desired effects[8].

As a conclusion, Cod liver oil is very important to health of children since it contains omega-3 fatty acids and vitamins A, D, and E. Cod liver oil is important in reducing risk of type 1 diabetes, upper respiratory tract pediatric visit and ADHD. Cod liver oil is crucial for fetal brain development and enhancement of IQ score, and fetal visual development. More attention to this important nutrient by the concerned body may lead to improved dietary supplements and prevention of many diseases in children.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Availability of data and material

All data analyzed during this study are included in its supplementary information files.

Competing interests

The authors declare that they have no competing interests.

Funding

No funding was obtained for this study

Author Contributions

SDS & FMA originated the research idea. SDS, AA, BW, FMA, and MA contributed to the data synthesis and writing the manuscript. All authors have read and approved the manuscript.

List of abbreviations and acronyms

CLO: Cod liver oil, DHA: Docosahexaenoic acid, EPA: eicosapentaenoic acids, OM: Otitis media, PRISMA: preferred reporting system for systematic review and meta-analysis, USA: United States of America

Acknowledgments

The authors would like to forward a special acknowledgment to the authors of the primary studies.

Al-Ansari AA, Shamsodini A, Talib RA, Gul T, Shokeir AAJU (2010) Subcutaneous cod liver oil injection for penile augmentation: review of literature and report of eight cases. 75:1181–11845
Guy RAJAJoDoC (1923) The history of cod liver oil as a remedy. 26:112–1162
Dhanawat GS (2013) : Rhinitis, sinusitis and ocular disease–2100. New approach to treat allergic rhinitis with Vitamin E, cod liver oil and Vitamin C with use of nasal steroidal spray. In: World Allergy Organization Journal: : BioMed Central; 2013: P175-P175
Salem N, Litman B, Kim H-Y, Gawrisch KJL (2001) Mechanisms of action of docosahexaenoic acid in the nervous system. 36:945–9599
Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB (2003) Mahadik SPJPr: Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. 121:109–1222
Raeder MB, Steen VM, Vollset SE, Bjelland IJJoAD (2007) Associations between cod liver oil use and symptoms of depression: the Hordaland Health Study. 101:245–2491–3
Buydens-Branchey L, Branchey MJPr (2008) Long-chain n-3 polyunsaturated fatty acids decrease feelings of anger in substance abusers. 157:95–1041–3
Calder PCJTJon (2012) Mechanisms of action of (n-3) fatty acids. 142:592S–599S3
Nettleton JA (2005) Katz RJJotADA: n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. 105:428–4403
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Johansson L, Solvoll K, Bjørneboe G-EA (1997) Drevon CJSjon: Dietary habits among Norwegian men and women.
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Rajakumar KJP (2003) Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. 112:e132–e1352
Forsmo S, Fjeldbo SK, Langhammer AJAjoe (2008) Childhood cod liver oil consumption and bone mineral density in a population-based cohort of peri-and postmenopausal women: the Nord-Trøndelag Health Study. 167:406–4114
Caramia, GJMp (2008) Omega-3: from cod-liver oil to nutrigenomics. 60:443–4564
Linday LA (2005) Nutritional Supplements and Upper Respiratory Tract Illnesses in Young Children in the United States. Preventive Nutrition. edn.: Springer, pp 521–549
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Linday LA, Shindledecker RD, Dolitsky JN (2002) Pippenger CJAoO, Rhinology, Laryngology: Lemon-flavored cod liver oil and a multivitamin-mineral supplement for the secondary prevention of otitis media in young children: pilot research. 111:642–6527
Linday LA, Tapia-Mendoza J, Shindledecker RD (2004) Dolitsky JNJAoO, Rhinology, Laryngology: Effect of daily cod liver oil and a multivitamin-mineral supplement with selenium on upper respiratory tract pediatric visits by young, inner-city, Latino children: randomized pediatric sites. 113:891–90111
Stene LC, Joner G (2003) Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. 78:1128–1134nutrition NCDSGJTAjoc6
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Table 1: Search history

	1 PubMed search history
Search	Query	Items found
#3	((((Cod-liver oil) OR (Cod oil)) OR (Cod liver)) OR (Cod-liver oil[MeSH Terms]) AND ((fha[Filter]) AND (fft[Filter]))) AND ((((Children) OR (child)) OR (infant)) OR (infants [MeSH Terms]) AND ((fha[Filter]) AND (fft[Filter])))	*101*
#2	(((Cod-liver oil) OR (Cod oil)) OR (Cod liver)) OR (Cod-liver oil[MeSH Terms])	2,344
#1	(((Children) OR (child)) OR (infants)) OR (infant [MeSH Terms])	3,345,769
	CINHAL search history
Search	Query	Items found
S4	(Children OR child OR infants OR infant) AND (S2 AND S3)	63
S3	Children OR child OR infants OR infant	321,798
S2	Cod liver oil OR Cod oil OR Cod liver OR MW Cod liver oil	9867
	Cochrane library search history
Search	Query	Items found
S1	Cod liver oil OR Cod oil OR Cod liver AND Children OR child OR infants OR infant	35

Table 2: Characteristics of included articles for the review

No	Author, year	country	Aims of the study	Design	Methods of analysis	Sample Characthrstics				Reported outcome
No	Author, year	country	Aims of the study	Design	Methods of analysis	Sample size	Average age (SD)	Control	Sample	Reported outcome
1	Linday, L.A., et al,2004[22]	New York	To study impact of consumption of codliver oil in decreasing URTI in children	Randomized site design	Intention-to-treat efficacy analysis		2.03 years (SD, ±1.04 year	-	children 6 months to 5 years of age	Intake of cod liver oil and was associated with a decrease in upper respiratory tract pediatric visits during the winter and early spring
2	Stene, and N.C.D.S.G.J.T.A.j.o.c,2003[23]	Nor way	To study impact of consumption of codliver oil in decreasing diabetes in children	Case-control study	Logistic regression	801		15 years	All new cases of type 1 diabetes diagnosed in children aged 15 years	Use of cod liver oil during the first year of life was associated with a significantly lower risk of type 1 diabetes
3	Norris, J.M., et al.,2007[24]	Colorado	To examine whether intakes of omega-3 & 6 fatty acids are associated with the development of islet autoimmunity (IA) in children.	An observational study	survival analysis	1770	-----	-----	Children at risk for diabetes for the appearance of islet autoantibodies.	Dietary intake of omega-3 fatty acids is associated with reduced risk of IA in children at increased genetic risk for type 1 diabetes
4	Linday, L.A., et al.2002,[21]	New York	To assess the utility of cod liver oil with other supplements for prevention of Otitis media		ANOVA	28	-----	children undergoing eye ear, nose, and throat procedures	children between 1 - 10 years of age admitted to NYEE	lower levels of EPA(omega 3) and selenium in children, when combined with vitamin A levels in the lower reference range, predispose some children to OM

Impact of cod liver oil consumption in infants and children: A systematic review

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Abstract

Background

Methods

Result

Conclusion

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Introduction

Methods

Discussion

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