Omega-3 Fatty Acids and Fecundation, Pregnancy and Breastfeeding

Ácidos graxos ômega 3 e fecundação, gravidez e amamentação

Carlos Alberto Politano Jorge López-Berroa About the authors

Abstract

Long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as the eicosapentaenoic and docosahexaenoic acids, have been linked to human health in all stages of life, from fetal development to aging. These PUFAs act as precursors for various metabolites involved in the prevention of certain diseases. The recognizable effects of these supplements prior to pregnancy (oocyte maturation), during pregnancy (improvement in the risk of premature delivery, among others) and in the offspring (in terms of cognitive function and the approach to neurodevelopmental disorders) are described in the present narrative review. We concluded that the diffusion of these supplements may improve the prognosis of these patients in a simple, effective way, and with high safety rates.

Keywords
omega-3; eicosapentaenoic acid; docosahexaenoic acid; pregnancy; breastfeeding

Resumo

Os ácidos graxos poli-insaturados (AGPIs) ômega-3 (n-3) de cadeia longa, como os ácidos eicosapentaenoico e docosa-hexaenoico, têm sido associados à saúde humana em todas as etapas da vida, do desenvolvimento fetal ao envelhecimento. Esses AGPIs atuam como precursores de vários metabólitos envolvidos na prevenção de algumas doenças. Os efeitos reconhecíveis desses suplementos antes da gravidez (maturação dos oócitos), durante a gravidez (melhora do risco de parto prematuro, entre outros) e nos descendentes (em termos de função cognitiva e abordagem dos distúrbios do neurodesenvolvimento) são apresentados nesta revisão narrativa. Concluiu-se que a difusão desses suplementos pode melhorar o prognóstico desses pacientes de maneira simples, eficaz, e com altas taxas de segurança.

Palavras-chave
ômega 3; ácido eicosapentaenoico; ácido docosa-hexanoico; gravidez; amamentação

Introduction

Long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as the eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) have been linked to human health in all stages of life, from fetal development to physiological aging.11 Swanson D, Block R,Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr. 2012;3(01):1-7. Doi: 10.3945/an.111.000893
https://doi.org/10.3945/an.111.000893...
The DHA is a relevant component of all biological membranes, and both of these PUFAs are precursors for various metabolites involved in the prevention of several diseases.11 Swanson D, Block R,Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr. 2012;3(01):1-7. Doi: 10.3945/an.111.000893
https://doi.org/10.3945/an.111.000893...

However, in many cases, the contribution of a diet rich in fish is not enough to ensure an adequate intake of these PUFAs.11 Swanson D, Block R,Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr. 2012;3(01):1-7. Doi: 10.3945/an.111.000893
https://doi.org/10.3945/an.111.000893...
Human tissues express enzymes that can metabolize the alpha-linolenic acid (ALA) for the synthesis of DHA and EPA, but in a reduced proportion.22 Neff LM, Culiner J, Cunningham-Rundles S, Seidman C, Meehan D, Maturi J, et al. Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. J Nutr. 2011;141(02):207-213. Doi: 10.3945/jn.110.130021
https://doi.org/10.3945/jn.110.130021...
As a consequence, in many occasions supplementation may be necessary.

The objective of the present review is to describe the potential benefits of DHA and EPA supplementation in the context of reproductive medicine.

Before Conception

Oocyte quality is identified as one of the most relevant factors in relation to female fertility, not only for the fertilization process, but also to ensure embryonic implantation and development.33 Rienzi L, Vajta G, Ubaldi F. Predictive value of oocyte morphology in human IVF: a systematic review of the literature. Hum Reprod Update. 2011;17(01):34-45. Doi: 10.1093/humupd/dmq029
https://doi.org/10.1093/humupd/dmq029...
Among the factors related to oocyte quality, maternal diet is highlighted, since obesity and diabetes can alter mitochondrial function and chromosome alignment at the gamete level.44 Zarezadeh R, Mehdizadeh A, Leroy JLMR, Nouri M, Fayezi S, Darabi M. Action mechanisms of n-3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages. J Cell Physiol. 2019;234(02):1016-1029. Doi: 10.1002/jcp.27101
https://doi.org/10.1002/jcp.27101...
Accordingly, the concentration of fatty acids in the ovarian follicular microenvironment is associated with oocyte quality and embryonic development during in vitro fertilization procedures.44 Zarezadeh R, Mehdizadeh A, Leroy JLMR, Nouri M, Fayezi S, Darabi M. Action mechanisms of n-3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages. J Cell Physiol. 2019;234(02):1016-1029. Doi: 10.1002/jcp.27101
https://doi.org/10.1002/jcp.27101...

The follicular levels of n-3 PUFAs are correlated with plasma lipids, which are modified according to diet and body weight.44 Zarezadeh R, Mehdizadeh A, Leroy JLMR, Nouri M, Fayezi S, Darabi M. Action mechanisms of n-3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages. J Cell Physiol. 2019;234(02):1016-1029. Doi: 10.1002/jcp.27101
https://doi.org/10.1002/jcp.27101...
It is hypothesized that n-3 PUFAs can regulate oocyte maturation by mechanisms mediated by functional changes in granulosa cells linked to peroxisome-proliferator-activated receptors (PPARs) and modifications in the biosynthesis of follicular prostaglandins.44 Zarezadeh R, Mehdizadeh A, Leroy JLMR, Nouri M, Fayezi S, Darabi M. Action mechanisms of n-3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages. J Cell Physiol. 2019;234(02):1016-1029. Doi: 10.1002/jcp.27101
https://doi.org/10.1002/jcp.27101...
According to experimental data, PUFAs are potent PPAR ligands and also increase the expression of the steroidogenic acute regulatory protein (STAR). Thus, a correlation between the circulating levels of PUFAs and the concentration of sex hormones is verified in humans.55 Khajeh M, Rahbarghazi R, Nouri M, Darabi M. Potential role of polyunsaturated fatty acids, with particular regard to the signaling pathways of arachidonic acid and its derivatives in the process of maturation of the oocytes: Contemporary review. Biomed Pharmacother. 2017;94:458-467. Doi: 10.1016/j.biopha.2017.07.140
https://doi.org/10.1016/j.biopha.2017.07...
On the other hand, sex steroids can modulate the synthesis of PUFAs by modifying the expression of desaturases (Figure 1).66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...

Fig. 1
Molecular mechanisms and signaling of n-3 P. Source: Adapted and modified from Calder.66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...

These data from preclinical and experimental models were corroborated by clinical studies. In a prospective trial77 Chiu YH, Karmon AE, Gaskins AJ, Arvizu M, Williams PL, Souter I, et al; EARTHStudy Team. Serumomega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction. Hum Reprod. 2018;33(01):156-165. Doi: 10.1093/humrep/dex335
https://doi.org/10.1093/humrep/dex335...
involving 100 women under assisted reproduction treatment (total: 136 cycles), the levels of circulating n-3 PUFAs were associated with a higher probability of clinical pregnancy and a higher number of live births, and PUFA supplementation was also related with a higher probability of births.77 Chiu YH, Karmon AE, Gaskins AJ, Arvizu M, Williams PL, Souter I, et al; EARTHStudy Team. Serumomega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction. Hum Reprod. 2018;33(01):156-165. Doi: 10.1093/humrep/dex335
https://doi.org/10.1093/humrep/dex335...

On the other hand, PUFAs have been linked to an optimization of spermatogenesis. In animal models, it was shown that PUFA supplementation stimulates the development of seminiferous tubules and increases the density of Sertoli cells.88 Li W, Tang D, Li F, Tian H, Yue X, Li F, et al. Supplementation with dietary linseed oil during peri-puberty stimulates steroidogenesis and testis development in rams. Theriogenology. 2017;102:10-15. Doi: 10.1016/j.theriogenology.2017.07.002
https://doi.org/10.1016/j.theriogenology...
An improvement in the quality and quantity of sperm cells was also reported.99 Lorenzetti A, Marotta F, Yadav H, Celep G, Minelli E, Carrera-Bastos P, et al. Improving sperm quality and spermatogenesis through a bioactive marine compound: an experimental study. Acta Biomed. 2012;83(02):108-113

In humans, a high concentration of DHA in the spermatozoon head is recognized; the dietary content of fatty acids appears to modify the profile of these molecules in male gametes.1010 Esmaeili V, Shahverdi AH, Moghadasian MH, Alizadeh AR. Dietary fatty acids affect semen quality: a review. Andrology. 2015;3(03):450-461. Doi: 10.1111/andr.12024
https://doi.org/10.1111/andr.12024...
However, the effects of n-3 PUFA supplementation are described after no less than 4 weeks of administration; in addition, these effects seem dose-dependent.1010 Esmaeili V, Shahverdi AH, Moghadasian MH, Alizadeh AR. Dietary fatty acids affect semen quality: a review. Andrology. 2015;3(03):450-461. Doi: 10.1111/andr.12024
https://doi.org/10.1111/andr.12024...

Use during Pregnancy

It has been shown that the conversion rate of ALA into EPA and DHA in men reaches 8% and less than 1% respectively, while in women the corresponding rates are 21% and 9% respectively.66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...
This difference is attributed to the higher requirements of n-3 PUFAs during pregnancy and breastfeeding.66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...
According to the joint recommendations of the World Association of Perinatal Medicine, the Early Nutrition Academy and the Child Health Foundation, maternal DHA consumption during pregnancy should not be lower than 200 mg/day. Nutritional supplements are one of the suggested sources to achieve this goal.1111 Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I et al; World Association of Perinatal Medicine Dietary Guidelines Working Group. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: reviewof current knowledge and consensus recommendations. J Perinat Med. 2008;36(01):5-14

Even though a diet rich in fish is also a source of DHA/EPA, the potential content of contaminants, such as mercury, is a matter of concern.1212 Jordan RG. Prenatal omega-3 fatty acids: review and recommendations. J Midwifery Womens Health. 2010;55(06):520-528. Doi: 10.1016/j.jmwh.2010.02.018
https://doi.org/10.1016/j.jmwh.2010.02.0...
Thus, supplements with adequate processing quality to avoid impurities and contaminants may play a prominent role.1212 Jordan RG. Prenatal omega-3 fatty acids: review and recommendations. J Midwifery Womens Health. 2010;55(06):520-528. Doi: 10.1016/j.jmwh.2010.02.018
https://doi.org/10.1016/j.jmwh.2010.02.0...
The administration of between 200 mg and 300 mg/day of DHA to this population has been endorsed by the National Institutes of Health and the International Society for the Study of Fatty Acids and Lipids, among other specialized societies.1212 Jordan RG. Prenatal omega-3 fatty acids: review and recommendations. J Midwifery Womens Health. 2010;55(06):520-528. Doi: 10.1016/j.jmwh.2010.02.018
https://doi.org/10.1016/j.jmwh.2010.02.0...

The maximum growth of the human brain occurs from the beginning of the third trimester of intrauterine life until 18 months after birth;66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...
during this period, the concentration of DHA increases significantly from 900 µg/g to 3,000 µg/g.66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...
Therefore, the need for an adequate n-3 PUFA contribution during this period is highlighted, in order to ensure a normal growth and visual and neurological developments.66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...
Although there is a correlation between DHA levels in maternal and fetal blood, this PUFA is concentrated in the circulation and fetal tissues due to a process known as biomagnification, which seems mediated by the placenta.66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...

Another benefit associated with the PUFA n-3 supplement is the prevention of preterm births (PBs). This is highly important, considering that PB accounts for more than 85% of all perinatal mortality and complications,1313 MakridesM, Best K. Docosahexaenoic acid and pretermbirth. Ann Nutr Metab. 2016;69(Suppl 1):29-34. Doi: 10.1159/000448263
https://doi.org/10.1159/000448263...
in addition to accounting for a greater requirement of intensive care unit resources and a higher risk of early comorbidities, with potential consequences throughout life.1313 MakridesM, Best K. Docosahexaenoic acid and pretermbirth. Ann Nutr Metab. 2016;69(Suppl 1):29-34. Doi: 10.1159/000448263
https://doi.org/10.1159/000448263...
Nevertheless, there are no primary prevention strategies frequently used in the daily practice. In a systematic review with meta-analysis1414 Kar S, Wong M, Rogozinska E, Thangaratinam S. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic reviewandmeta-analysis of randomized studies. Eur J Obstet Gynecol Reprod Biol. 2016;198:40-46. Doi: 10.1016/j.ejogrb.2015.11.033
https://doi.org/10.1016/j.ejogrb.2015.11...
in which the risk of PB and extreme PB (less than 34 weeks of gestation) was evaluated among 5,980 women, the authors verified that the n-3 PUFA supplementation during pregnancy significantly reduced the risk of both criteria. Likewise, they confirmed that these supplements were linked to an increase in birth weight of around 122 g when the participants were compared with those who were not submitted to the supplementation.1414 Kar S, Wong M, Rogozinska E, Thangaratinam S. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic reviewandmeta-analysis of randomized studies. Eur J Obstet Gynecol Reprod Biol. 2016;198:40-46. Doi: 10.1016/j.ejogrb.2015.11.033
https://doi.org/10.1016/j.ejogrb.2015.11...

Taking into account its ease of administration and the achieved results, n-3 PUFA supplementation could play a role as a preventive strategy for PB at a population level, independently of the previous risk and of the dose administered.1414 Kar S, Wong M, Rogozinska E, Thangaratinam S. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic reviewandmeta-analysis of randomized studies. Eur J Obstet Gynecol Reprod Biol. 2016;198:40-46. Doi: 10.1016/j.ejogrb.2015.11.033
https://doi.org/10.1016/j.ejogrb.2015.11...

Moreover, it has been reported that n-3 PUFAs have beneficial effects in women with gestational diabetes, which also extend to the fetus.1515 Elshani B, Kotori V, Daci A. Role of omega-3 polyunsaturated fatty acids in gestational diabetes, maternal and fetal insights: current use and future directions. J Matern Fetal Neonatal Med. 2019:1-13. Doi: 10.1080/14767058.2019.1593361
https://doi.org/10.1080/14767058.2019.15...
In cases of gestational diabetes and preeclampsia, transplacental transmission of n-3 PUFAs is reduced, as demonstrated by lower levels of DHA detected in umbilical cord blood, compared to pregnancies without these alterations.1616 Devarshi PP, Grant RW, Ikonte CJ, Hazels Mitmesser S. Maternal omega-3 nutrition, placental transfer and fetal brain development in gestational diabetes and preeclampsia. Nutrients. 2019;11(05):E1107. Doi: 10.3390/nu11051107
https://doi.org/10.3390/nu11051107...
The importance of early DHA supplementation in women with gestational diabetes is evident, since its late administration would not improve fetal circulation levels, due to the already established alterations in the placental transfer (Figure 2).1717 Jones ML, Mark PJ, Waddell BJ. Maternal dietary omega-3 fatty acids and placental function. Reproduction. 2014;147(05):R143-R152. Doi: 10.1530/REP-13-0376
https://doi.org/10.1530/REP-13-0376...

Fig. 2
Mechanisms of transplacental omega-3 (n-3) polyunsaturated fatty acid (PUFA) transport. Source: adapted and modified from Jones et al.1717 Jones ML, Mark PJ, Waddell BJ. Maternal dietary omega-3 fatty acids and placental function. Reproduction. 2014;147(05):R143-R152. Doi: 10.1530/REP-13-0376
https://doi.org/10.1530/REP-13-0376...
Abbreviations: EL, epithelial lipase; FABP, fatty-acid-binding protein; FABPpm, plasma membrane FABP; FAT/CD36, fatty acid translocase; FATPs, fatty acid transport proteins; LPL, lipoprotein lipase; p-FABPpm, placental plasma membrane FABP; PPAR, peroxisome-proliferator-activated receptor; RXR, retinoic-acid-X receptor; TGs, triglycerides.

Therefore, the appropriate approach to gestational diabetes, in association with fatty-acid supplementation, may improve the metabolic and immune functions, and decrease the risk of PB and the likelihood of developing preeclampsia and neonatal and long-term infant complications.1515 Elshani B, Kotori V, Daci A. Role of omega-3 polyunsaturated fatty acids in gestational diabetes, maternal and fetal insights: current use and future directions. J Matern Fetal Neonatal Med. 2019:1-13. Doi: 10.1080/14767058.2019.1593361
https://doi.org/10.1080/14767058.2019.15...

Administration during Breastfeeding: Cognitive Effects

Given the importance of DHA for the development of the neonate and infant brain, the importance of this PUFA during breastfeeding is highlighted. The suggested doses are similar to those proposed during pregnancy.1111 Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I et al; World Association of Perinatal Medicine Dietary Guidelines Working Group. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: reviewof current knowledge and consensus recommendations. J Perinat Med. 2008;36(01):5-14,1212 Jordan RG. Prenatal omega-3 fatty acids: review and recommendations. J Midwifery Womens Health. 2010;55(06):520-528. Doi: 10.1016/j.jmwh.2010.02.018
https://doi.org/10.1016/j.jmwh.2010.02.0...
The levels of DHA in breast milk may be increased by supplementation,66 Calder PC. Docosahexaenoic Acid. Ann Nutr Metab. 2016;69 (Suppl 1):7-21. Doi: 10.1159/000448262
https://doi.org/10.1159/000448262...
and they seem to correlate with cognitive function and language development in infants, as well as with general psychosocial health.1818 Martins BP, Bandarra NM, Figueiredo-Braga M. The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders andAttention-Deficit/HyperactivityDisorder- a review. Crit Rev Food Sci Nutr. 2019:1-16. Doi: 10.1080/10408398.2019.1573800
https://doi.org/10.1080/10408398.2019.15...
The daily intake of DHA by breastfed infants is estimated between 13 mg to 26 mg/day, which is lower than the intrauterine supply (45–50 mg/kg/day).

The clinical evidence available supports that n-3 PUFA supplementation may optimize the neuronal development of term infants.1818 Martins BP, Bandarra NM, Figueiredo-Braga M. The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders andAttention-Deficit/HyperactivityDisorder- a review. Crit Rev Food Sci Nutr. 2019:1-16. Doi: 10.1080/10408398.2019.1573800
https://doi.org/10.1080/10408398.2019.15...
PBs have been linked with deficiencies in the integrity of the connectivity of the myelin and cortical circuitry, among other complications.1818 Martins BP, Bandarra NM, Figueiredo-Braga M. The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders andAttention-Deficit/HyperactivityDisorder- a review. Crit Rev Food Sci Nutr. 2019:1-16. Doi: 10.1080/10408398.2019.1573800
https://doi.org/10.1080/10408398.2019.15...
These neurodevelopmental alterations increase the risk of autism spectrum disorders (ASDs) and attention deficit and hyperactivity disorder (ADHD).1818 Martins BP, Bandarra NM, Figueiredo-Braga M. The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders andAttention-Deficit/HyperactivityDisorder- a review. Crit Rev Food Sci Nutr. 2019:1-16. Doi: 10.1080/10408398.2019.1573800
https://doi.org/10.1080/10408398.2019.15...
Low DHA levels may at least partially explain these outcomes:1818 Martins BP, Bandarra NM, Figueiredo-Braga M. The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders andAttention-Deficit/HyperactivityDisorder- a review. Crit Rev Food Sci Nutr. 2019:1-16. Doi: 10.1080/10408398.2019.1573800
https://doi.org/10.1080/10408398.2019.15...
in a randomized, placebo-controlled study involving 141 infants with birth weight lower than 1,500 g, the addition of 32 mg of DHA and 31 mg of arachidonic acid per 100 ml of human milk from the first week of life, for an average of 9 weeks, was associated with an improvement in recognition memory and ability to solve problems at 6 months.1919 Henriksen C, Haugholt K, Lindgren M, Aurvåg AK, Rønnestad A, Grønn M et al. Improved cognitive development among preterm infants attributable to early supplementation of humanmilk with docosahexaenoic acid and arachidonic acid. Pediatrics. 2008;121(06):1137-1145 It is hypothesized that conventional DHA ingestion may be insufficient in PB children, since these patients are more sensitive to the effects of maternal PUFA intake on milk content.1818 Martins BP, Bandarra NM, Figueiredo-Braga M. The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders andAttention-Deficit/HyperactivityDisorder- a review. Crit Rev Food Sci Nutr. 2019:1-16. Doi: 10.1080/10408398.2019.1573800
https://doi.org/10.1080/10408398.2019.15...

In patients with ASDs, the administration of n-3 PUFAs may be of special importance, due to their role in brain structure and functionality, neurotransmission and biomembranes, among others.2020 Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S et al. The role of omega-3 fatty acids in developmental psychopathology: a systematic review on early psychosis, autism, and ADHD. Int J Mol Sci. 2017;18(12):E2608 Even though limited benefits of n-3 PUFAs are reported for this population in randomized controlled trials, the absence of statistical significance is attributed to the small number of treated patients and the lack of clinical studies.2020 Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S et al. The role of omega-3 fatty acids in developmental psychopathology: a systematic review on early psychosis, autism, and ADHD. Int J Mol Sci. 2017;18(12):E2608 However, PUFA supplementation may be suggested as a complement for other therapeutic approaches.2020 Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S et al. The role of omega-3 fatty acids in developmental psychopathology: a systematic review on early psychosis, autism, and ADHD. Int J Mol Sci. 2017;18(12):E2608

On the other hand, the association between manifestations of ADHD and low circulating levels of n-3 PUFAs has been consistently reported in different observational studies summarized in a systematic review.2020 Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S et al. The role of omega-3 fatty acids in developmental psychopathology: a systematic review on early psychosis, autism, and ADHD. Int J Mol Sci. 2017;18(12):E2608 Alterations in the serum profile of n-3 PUFAs are recognized in children and adults with ADHD, although it has not yet been defined whether these changes are a consequence of an inadequate intake or abnormalities in the metabolism of these fatty acids. In a meta-analysis,2020 Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S et al. The role of omega-3 fatty acids in developmental psychopathology: a systematic review on early psychosis, autism, and ADHD. Int J Mol Sci. 2017;18(12):E2608 a favorable and significant effect of these supplements has been identified; as a consequence, their co-administration with the available pharmacological strategies may be suggested.

Safety

The supplementation with N-3 PUFAs is considered a highly safe intervention, even regarding the maximum daily doses of 3 g to 4.5 g, according to regulatory agencies.2121 Gow RV, Hibbeln JR. Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors. Child Adolesc Psychiatr Clin N Am. 2014;23(03):555-590. Doi: 10.1016/j.chc.2014.02.002
https://doi.org/10.1016/j.chc.2014.02.00...
Between 1% and 10% of the treated patients may report mild adverse events (dyspepsia, nausea, diarrhea, tendency to develop bleeding), while digestive adverse reactions only involve 0.1% to 1% of the treated patients. The gastrointestinal effects are usually improved with the administration with meals or with a gradual increase in dose.2121 Gow RV, Hibbeln JR. Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors. Child Adolesc Psychiatr Clin N Am. 2014;23(03):555-590. Doi: 10.1016/j.chc.2014.02.002
https://doi.org/10.1016/j.chc.2014.02.00...
Even though isolated cases of increased transaminase levels have been reported, n-3 PUFAs appear to be associated with hepatoprotective effects, and their indication for the treatment of non-alcoholic liver steatosis has even been suggested.2121 Gow RV, Hibbeln JR. Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors. Child Adolesc Psychiatr Clin N Am. 2014;23(03):555-590. Doi: 10.1016/j.chc.2014.02.002
https://doi.org/10.1016/j.chc.2014.02.00...

Conclusion

The supplementation with n-3 PUFAs before, during and after pregnancy is linked to numerous maternal, fetal and childhood benefits regarding the reproductive capacity of women and the cognitive functionality of their offspring. The diffusion of the use of these supplements could improve the prognosis of these patients in a simple, effective way, and with high safety rates.

References

  • 1
    Swanson D, Block R,Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr. 2012;3(01):1-7. Doi: 10.3945/an.111.000893
    » https://doi.org/10.3945/an.111.000893
  • 2
    Neff LM, Culiner J, Cunningham-Rundles S, Seidman C, Meehan D, Maturi J, et al. Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. J Nutr. 2011;141(02):207-213. Doi: 10.3945/jn.110.130021
    » https://doi.org/10.3945/jn.110.130021
  • 3
    Rienzi L, Vajta G, Ubaldi F. Predictive value of oocyte morphology in human IVF: a systematic review of the literature. Hum Reprod Update. 2011;17(01):34-45. Doi: 10.1093/humupd/dmq029
    » https://doi.org/10.1093/humupd/dmq029
  • 4
    Zarezadeh R, Mehdizadeh A, Leroy JLMR, Nouri M, Fayezi S, Darabi M. Action mechanisms of n-3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages. J Cell Physiol. 2019;234(02):1016-1029. Doi: 10.1002/jcp.27101
    » https://doi.org/10.1002/jcp.27101
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Publication Dates

  • Publication in this collection
    22 Apr 2020
  • Date of issue
    Mar 2020

History

  • Received
    08 Nov 2019
  • Accepted
    07 Jan 2020
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