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DHA -a precursor to geniuses? (Journal Review)

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1 DHA -a precursor to geniuses? (Journal Review)
DOCOSAHEXAENOIC ACID DHA -a precursor to geniuses? (Journal Review) Annaliza Chandrasegar 13 –

2 Omega 3 Fatty Acids (PUFS)
There are three major omega-3 fatty acids: Alpha-linolenic acid (ALA) Eicosaentaenoic acid (EPA) Docosahexaenoic acid (DHA) ALA parent omega-3 cannot be produced by the body. ALA supplementation has been considered an effective way to ensure the synthesis of EPA and DHA, A study that examined this issue, however, found that ALA intake increased EPA somewhat while producing virtually no increase in DHA levels.1 Mantzioris E, et al. Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites. Am J Clin Nutr. 1995;61: Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations, Philippe Guesnett and Jean-Marc Alessandri

3 Adults (some DHA from Diet) 100mg daily Pregnant & Breast-feeding
Recommended Dosages Adults (some DHA from Diet) 100mg daily Pregnant & Breast-feeding 200mg daily Children Adults (little DHA from Diet) 200mg Daily

4 Importance of DHA DHA highly unsaturated LCP - Missing Hydrogen atoms -Lots of gaps gaps make DHA very flexible Synapses - membranes surrounding each synapse – Fluid state Brain cells rich in DHA communicate quickly When DHA is in short supply nerve cell membranes become less flexible and less efficient in passing on electrical and chemical messages speed of communication between one brain cell and another is slowed DHA is a highly unsaturated, long-chain polyunsaturated fatty acid (LCP). In chemical terms, this means there are lots of gaps in its molecular structure where hydrogen atoms are missing. These gaps make DHA very flexible and, when optimum amounts are present in cell membranes, it allows electrical signals to pass more easily from one brain cell to another. Because of its structure, DHA also keeps the membranes surrounding each synapse - the communication gap between two nerve cells - in a more fluid state. This helps nerve cells release chemicals into the gap more quickly, and for the detector sites (receptors) on the other side of the gap to recognise messenger chemicals more readily. Brain cells whose membranes are rich in DHA therefore seem to communicate more quickly with each other. When DHA is in short supply, other fatty acids - especially saturated fats - are incorporated into the nerve cell membranes instead. As these are more rigid, however, nerve cell membranes become less flexible and less efficient in passing on electrical and chemical messages. As a result, the speed of communication between one brain cell and another is slowed.

5 Importance of DHA in Pregnancy
development of a baby’s eyes and brain last three months of pregnancy placenta extracts it from the mother’s own blood baby’s levels of DHA are twice as high as his mother’s If maternal levels of DHA are low obtained from the mother’s richest store - her own brain slight shrinkage (2% - 3%) in maternal brain size poor concentration, forgetfulness and vagueness newborn baby is unable to produce DHA from essential fatty acids until he is at least 4 months old DHA is vital for development of a baby’s eyes and brain, especially during the last three months of pregnancy. DHA is so important to a developing baby that, during late pregnancy, the placenta extracts it from the mother’s own blood and concentrates them in her baby’s circulation. As a result, a baby’s levels of DHA are twice as high as his mother’s. If maternal levels of DHA are low, some DHA is also obtained from the mother’s richest store - her own brain. This may account for the slight shrinkage (2% - 3%) in maternal brain size seen in some pregnant women, and account for the poor concentration, forgetfulness and vagueness that many women experience during the last few months of pregnancy. A newborn baby is unable to produce DHA from essential fatty acids until he is at least 4 months old. He therefore depends on what he can obtain from breast milk or enriched formulas.

6 Deposition of DHA in early development
Why DHA for Infants? Deposition of DHA in early development Retinal Health Neuro-Development Respiratory Health

7 Why DHA? DHA, the end-product of the -3 series, is the predominant fatty acid of membrane phospholipids in the brain grey matter and in the retina of mammals 1,2 DHA takes account for about 25% (wt%) of total fatty acids in the human cerebral cortex. for more than 30% in the whole retina, and up to 60% in the discs of the rod photoreceptor cells. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations, Philippe Guesnett and Jean-Marc Alessandri [1] L.Lauritzen, H.S.Hansen, M.H.Jørgensen, K.F.Michaelsen, The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina.Prog.LipidRes.40(2001)1-94. [2] J.M.Alessandri, P.Guesnet, S.Vancassel et al., Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life.Reprod.Nutr.Dev.44(2004)

8 Why DHA? Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens.[1] Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body.[2] The important functioning of BMP signals in physiology is emphasized by the multitude of roles for dysregulated BMP signalling in pathological processes.  Glial cell-derived neurotrophic factor, also known as GDNF is a protein that, in humans, is encoded by the GDNF gene.[1]GDNF is a small protein that potently promotes the survival of many types of neurons.[2] Long-Chain Polyunsaturated Fatty Acids in the Growth and Development of the Brain and Memory, U. N. Das, MD, FAMS, Nutrition 19:62– 65, 2003

9 Long Chain Polyunsaturated Fatty Acids
LCPUFA supplemented infants tend to maintain their plasma and erythrocyte phospholipid DHA concentrations at birth levels 1 ,and show improved visual2,3 and developmental outcomes (mental and psychomotor)4. L.G. Smithers et al. DINO trial/ Prostaglandins, Leukotrienes and Essential Fatty Acids 79 (2008) 141–146 [1] G. Boehm, M. Borte, H.J. Bohles, H. Muller, G. Kohn, G. Moro, Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk, standard formula or formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids, Eur. J. Pediatr. 155 (1996) 410–416. [2] E. Birch, D. Birch, D.R. Hoffman, R. Uauy, Dietary essential fatty acid supply and visual acuity development, Invest. Ophthalmol. Vis. Sci. 33 (1992) 3242–3253. [3] D.L. O’Connor, R. Hall, D. Adamkin, et al., Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective randomized controlled trial, Pediatrics 108 (2001) 359–371. [4] M.T. Clandinin, J.E. Van Aerde, K.L. Merkel, et al., Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid, J. Pediatr. 146 (2005) 461–468.

10 Brain Development Stages

11 Why DHA for Infants? A large corpus of data is in favor of the recommendation of regular dietary intakes of DHA(during at least the first 6 months of life) and suggest that DHA should be added in formulas at the level generally found in human milk ( wt% of total fatty acids) P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous system(CNS) Implications for dietary...,Biochimie (2010),doi: /j.biochi

12 Why DHA for Infants? The deposition of DHA in human brain phospholipids occurs primarily during the foetal period of active neurogenesis and cell maturation(from the sixth month of pregnancy/third trimester) and the early post- natal period of development of intense synaptogenesis, and continues during at least the first two years of life. It has been estimated that DHA accumulates in the brain at a rate of 3mg/d and 5 mg/d during the last trimester of pregnancy and the post-natal period of suckling, respectively 1,2. The major part of brain DHA accumulation occurs post-natally ,during the suckling period(first 6 month of post-natal life). After birth and until 6 months of age, breast milk and/or milk replacers are the sole sources of n-3 and n-6 fatty acids. P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous system(CNS) Implications for dietary...,Biochimie (2010),doi: /j.biochi

13 Why DHA for Infants? The prenatal period represents a critical window for brain membrane biogenesis and for neurodevelopment. Dietary -3 PUFA, supplied in adequate proportion with  -6 PUFA, are thus crucial throughout the pre- and post-natal periods for the cerebral accretion of DHA, and are determining for early neurodevelopment. P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous system(CNS) Implications for dietary...,Biochimie (2010),doi: /j.biochi

14 Why DHA for Infants? RETINAL FUNCTION
Deficiency of PUFA : Based on a clinical trial, Significant abnormalities In the development of visual functions were observed in formula-fed(low PUFA) premature infants comparatively to breast-fed premature infants. The electro-retinogram thresholds of rod cells was increased after 6 wk of feeding (i.e.36 wk post conception) and were normalized 20 wk later (57 wk post conception) indicating a delay in photo-receptor maturation 1,2 More over, lower visual acuities measured by visual-evoked potential(VEP) and by the preferential-looking methods were detected 3 Similar abnormalities in visual acuities measured at 57 wk post-conception were also reported in full-term infants fed during 4 months of formula low in n-3 PUFA 3. Results/ conclusion : In preterm infants, feeding with DHA-enriched formulas resulted (in most cases) In better early visual development outcomes than feeding with standard formulas containing only a-LNA 4 Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations, Philippe Guesnett and Jean-Marc Alessandri [1] R.D.Uauy, D.G.Birch, E.E.Birch, J.E.Tyson, D.R.Hoffman, Effect of dietary omega-3 fatty acids on retinal function of very-low-birth-weight neonates. Pediatr. Res.28(1990) [2] D.G.Birch, E.E.Birch, D.R.Hoffman, R.D.Uauy, Retinal development in very- low-birth-weight infants fed diets differing in omega-3fattya cids.Invest. Ophthalmol. Vis.Sci.33(1992) [3] E.E.Birch, D.G.Birch, D.R.Hoffman, R.Uauy, Dietary essential fatty acid supply and visual acuity development.Invest.Ophthalmol.Vis.Sci.33(1992) [4] J.P.SanGiovanni, S.Parra-Cabrera, G.A.Colditz, C.S.Berkey, J.T.Dwyer, Meta- analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants. Pediatrics 105(2000)

15 Why DHA for Infants? RESPIRATORY HEALTH
The objectives of this double-blind, randomized study among US toddlers below age of 3 were to: (A)Determine usual DHA intakes, (B)Measure the effect of consuming formulas with DHA on red blood cell(rbc)and plasma DHA and (C)Record adverse events in US children between 18 and 36months of age. Children aged 18–36months were provided 237-ml formula with 0, 43, or 130mg DHA per day for 60days. Blood was obtained at 0and 60days and24-hour dietary recalls at 0, 30 and 60days. Usual median daily DHA intake was13.3mg. RBC DHA increased in a dose-dependent manner with increasing DHA intake(p=0.05). Toddlers consuming the formula with 130mg DHA per day have fewer adverse events (p=0.007) and a lower incidence of respiratory illness(p=0.024), compared to the formula without DHA. Modest increases in DHA intake in toddlers might improve development, including respiratory health. Laura M. Minns et al, Toddler formula supplemented with docosahexaenoic acid (DHA) improves DHA status and respiratory health in a randomized, double-blind, controlled trial of US children less than 3 years of age, Prostaglandins, Leukotrienes and Essential Fatty Acids 82 (2010) 287–293 .

16 Why DHA for Infants? NEURODEVELOPMENT
Some clinical studies have also evidenced lower performance on mental development(Bayley MDI score) at 12months of age in preterm infants fed standard formulas compared to infants fed DHA- supplemented formulas. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations, Philippe Guesnett and Jean-Marc Alessandri: S.E.Carlson, S.H.Werkman, J.M.Peeples, W.M.Wilson, Long-chain fatty acids and early visual and cognitive development of preterm infants. Eur.J.Clin. Nutr. 48(1994)S27-S30.

17 How can taking DHA during pregnancy affect infant development?
 Some studies suggest that babies of women with higher DHA consumption during pregnancy may have better mental, visual, social and motor development than babies of women with lower DHA consumption (2). A Norwegian study 4-year-old children of women who received DHA supplements during pregnancy and lactation scored higher on tests of intelligence than babies of un- supplemented women (6).

18 How can taking DHA during pregnancy affect infant development?
A study in Great Britain women who didn’t eat any fish during pregnancy were 48 percent more likely than women who ate at least 12 ounces of fish a week to have a child with low verbal IQ scores (7). However, it is unclear whether the benefits of eating more than 12 ounces of fish a week (which exceeds the current U.S. recommendations) outweighs the potential risks of higher levels of mercury exposure. One recent study also found that children of women who took fish oil supplements during pregnancy were less likely to have developed asthma by age 16, possibly due to the effect of omega-3s on the immune system (8).   1 ounce = 28.35 grams  12 ounces =  grams 12 ounces =  grams

19 Do infants benefit from DHA after birth?
Studies show that premature infants (<37 weeks) -> addition of omega-3s in formula -> improvements in visual function and mental development (9, 10). The American Dietetic Association recommends full-term and premature infants who are not breastfed be fed a formula containing DHA and other omega-3s for at least the first year of life (10).  -Rapid brain growth continues after birth. Breastfeeding women pass on DHA to their infants in breast milk. Breastfeeding women should consume at least 200 milligrams of DHA each day to support the baby’s brain growth(2).  -Many infant formulas contain DHA and other omega-3s. Studies show that premature infants (those born before 37 completed weeks of pregnancy) benefit from the addition of omega-3s in formula with improvements in visual function and mental development (9, 10). -The addition of omega-3s to formula also may benefit term infants. The American Dietetic Association recommends that full-term and premature infants who are not breastfed be fed a formula containing DHA and other omega-3s for at least the first year of life (10). 

20 How much DHA does a pregnant woman need every day?
Pregnant and breastfeeding women :200 mg DHA OD(2). 2 servings of fish, including fatty fish, per week (2). Fish are good sources of DHA because of what they eat in the wild. Farm-raised fish may not contain DHA unless they are fed foods rich in DHA. 

21 How much DHA does a pregnant woman need every day?
Pregnant women should avoid fish that can be high in mercury, shark, swordfish, king mackerel and tilefish (5). Women can safely eat up to 12 ounces of fish that have small amounts of mercury (5). Women who do not want to eat fish can look for other sources of DHA, such as fortified foods. Daily supplements of DHA. A pregnant woman, however, should always check with her health care provider before taking any supplements.  High levels of mercury can harm the baby’s developing central nervous system.

22 Natural Sources of DHA Flaxseed Walnuts Soybeans Canola oil
Pumpkin seeds Dark green leafy vegetables, like spinach and salad greens Cold water fish/fatty fish (such as salmon, herring, sardines and fresh-water trout, tuna, anchovies ) Organ meats (such as calf’s liver). Fortified foods (such as milk, juice, bread and yogurt) Supplements containing fish oil or algae oil.

23 Quantities of EPA and DHA in Fish
The "Alternative Medicine Review" journal outlines the dosage of DHA per 100gm of fish or seafood. Mackerel contains 2,500mg. Herring supplies 1,700mg. Chinook salmon and anchovy provide 1,400mg. Rainbow trout furnishes 500mg. Pacific halibut contains 400mg. Cod, shrimp and catfish supply 300mg. Researchers found that intake of olive oil with omega- 3 fatty acids in fish oil increases the amount supplied to tissues in the body, according to the journal "Poultry Science.”

24 DHA Deficiency (Murine study)
It has been shown that alterations in dopamine neurotransmission, spatial learning memory performance and electro-retinograms in the offspring, which result from n-3 deficiency in mothers, maybe irreversible even though an n-3 fatty acid diet is given to deficient animals at weaning, and even though the DHA content in brain and retina is totally recovered 1,2 P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous system(CNS) Implications for dietary...,Biochimie (2010),doi: /j.biochi [1] E.Kodas,S.Vancassel,B.Lejeune,D.Guilloteau,S.Chalon,Reversibilityofn-3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats: critical role of developmentalstage.J.LipidRes.43(2002)1209e1219. [2] W.L.Chung, J.J.Chen,H.M.Su,Fish oil supplementation of control and(n-3) fatty acid-deficient male rats enhances reference and working memory performance and increases brain regional docosahexaenoic acid levels.J.Nutr. 138 (2008)1165e1171.

25 MOTHER’S MILK vs. FORMULA MILK SUPPLEMENTED WITH DHA
Post-mortem analysis showed that the DHA concentration regularly increased in the cerebral cortex of breast-fed infants, but not in formula-fed infants, its concentration after 48 wk was 30% lower in the formula- fed infants compared to those who had been breast-fed. Brain of the formula-fed infant consuming adequate intake of a-LNA(and no DHA)during the first 6 months of life accumulates DHA at half the rate of the breast-fed infant’s brain (450mgvs.905mg) More over in formula-fed infants, the other organs (liver, adipose and lean tissues) lost about 1g of DHA, whereas the same amount of body DHA is gained in breast-fed infants. P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous system(CNS) Implications for dietary...,Biochimie (2010),doi: /j.biochi

26 Did Einstein’s mother eat fish?
The size of a baby’s brain, and its head circumference are linked to its blood levels of DHA during the first year of life. By the age of nine months after birth, babies fed on mother’s milk (which contains DHA) or formula enriched with DHA seem to have significantly better visual acuity /cognition/respiratory health than baby’s receiving formula that does not contain DHA. So yeah!..maybe 

27 References U.S. Departments of Health and Human Services and Agriculture. The Report of the Dietary Guidelines Advisory Committee on Dietary Guidelines for Americans, 2005. Koletzko, B., et al., for the Perinatal Lipid Intake Working Group. Consensus Statement: Dietary Fat Intakes for Pregnant and Lactating Women. British Journal of Nutrition, volume 98, 2007, pages Office of Dietary Supplements, National Institutes of Health. Omega-3 Fatty Acids and Health. Last updated, 10/28/05, accessed 3/30/09. American Dietetic Association. DHA: A Good Fat. Nutrition Fact Sheet, accessed 3/30/09. U.S. Department of Health and Human Services and U.S. Environmental Protection Agency. What You Need to Know About Mercury in Fish and Shellfish. Accessed 4/2/09. Helland, I.B., et al. Maternal Supplementation with Very-Long-Chain n-3 Fatty Acids During Pregnancy and Lactation Augments Children’s IQ at 4 Years of Age. Pediatrics, volume 111, number 1, January 2003, pages e39-e44. Hibbeln, J.R., et al. Maternal Seafood Consumption in Pregnancy and Neurodevelopmental Outcomes in Childhood (ALSPAC Study): An Observational Cohort Study. The Lancet, volume 369, February 17, 2007, pages Olsen, S.F. Fish Oil Intake Compared to Olive Oil Intake in Late Pregnancy and Asthma in the Offspring: 16 Years of Registry-Based Follow-Up from a Randomized Trial. American Journal of Clinical Nutrition, volume 88, 2008, pages Makrides, M. Outcomes for Mothers and Their Babies: Do n-3 Long-Chain Polyunsaturated Fatty Acids and Seafoods Make a Difference? Journal of the American Dietetic Association, volume 108, number 10, October 2008, pages American Dietetic Association. Position of the American Dietetic Association and Dietitians of Canada: Dietary Fatty Acids. Journal of the American Dietetic Association, volume 107, number 9, September 2007, pages American Heart Association. Fish and Omega-3 Fatty Acids: AHA Recommendations. Accessed 3/30/09. Olsen, S.F., et al. Duration of Pregnancy in Relation to Seafood Intake During Early and Mid Pregnancy: Prospective Cohort. European Journal of Epidemiology, volume 21, 2006, pages Oken, E., et al. Associations of Maternal Fish Intake During Pregnancy and Breastfeeding Duration with Attainment of Developmental Milestones in Early Childhood: A Study from the Danish National Birth Cohort. American Journal of Clinical Nutrition, volume 88, 2008, pages

28 THANK YOU Annaliza A.C


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