DHA

AN ANCIENT NUTRIENT FOR

MODERN HUMAN BRAIN
OPTIMIZATION

CONNY TANJUNG, MD, PHD

NUTRITION & METABOLIC WORKING GROUP
INDONESIAN PEDIATRIC SOCIETY
 DISCLOSURE

The Speaker Got Fund From Commission Of The

European Communities, The European Research
Council & Mead Johnson Pediatric Nutrition
Institute

The Funders Have No Influence On The Design,

Implementation, Analysis And Inter pretation Of
The Data
 INTRODUCTION
New picture places DHA in an integral role in the
evolution of human intelligence

DHA + other PUFA modulate fluidity & activity of

proteins and gene transcription modulator

Fossil record  human evolution coincides with

the inclusion of seafood in the diet
 INTRODUCTION
The early modern humans sourced protein from
freshwater or marine (10–50% of the diet)

Crawford, et al : expansion of the diet to include

seafood related to expansion of grey matter

42 modern mammalian species were studied :

similar in brain chemistry, particularly DHA in the
membrane-rich neural tissues at synapses and
in the retina
 INTRODUCTION
 3 mio years little effect on brain capacity of Australopithecus
spp
 Brain capacity doubled between Homo erectus & Homo
sapiens…..Coincides with intelligence
 Absence DHA land-based mammalian brain size

4-2 m y; 1.9-1.6 m y; 1.8-1.5 m y; 0.4 – 0.3 m y;

BRAIN SIZE OF FOSSIL HOMINIS
EVIDENCE-BASED MEDICINE ERA

Omega 3 & 6 have major impact on

health
Clinical trials & meta-analysis of
provision and status LCPUFA show
inconsistent results
LCPUFA & NEURODEVELOPMENTAL OF HEALTHY BABY
(C0CHRANE)

While some studies showed significant benefit, overall no significant effect

LCPUFA & PRETERM BABY
 Recent Findings
FADS1 & FADS2 Genes Polymorphism and
Their Effect on LCPUFA Concentration
 Regulates by FADS 1 and FADS2 Polymorphisms
affect the composition of LCPUFA
 Carrier of minor allele shows decreased enzyme
activity of D5D & D6D show  substrates (LA & ALA)
&  products (AA, EPA,DHA)
 Successfully replicated in several studies involving
from 69-4457 subjects + GWAS

Schaeffer L, et al. Hum Mol Genet. 2006;15:1745-56

Lattka E, et al. Am J Clin Nutr. 2011;93:382-91.
Rzehak P, et al. Br J Nutr. 2009;101:20-26
Koletzko B, et al. Am J Clin Nutr. 2011;93:211-9
Xie L, et al. J Nutr. 2008;138:2222-8.
Molto-Puigmarti C, et al. Am J Clin Nutr. 2010;91:1368-76
Beneficial effects of FADS SNPs- Early LC-PUFA &
later cognition

 IQ test at the age of 8 years Genotyping FADS2 gene of 5,934 children in

the ALSPAC.
 Previously breastfed children had higher IQ scores than previously formula fed
children.
 Causal inferences on the role of human milk LCPUFA beneficial effect of
breastfeeding was much more pronounced (added 4.5 IQ points ) in children
with a genotype of low ability of LCPUFA synthesis
Steer, et al. 2010
 Analysis of FADS1-2 Genetic Variation &
Minor Allele of Different Population

Minor allele of Indonesian more resembles Mexican ( 93.3 %) than European (27.8 %)

Tanjung C, Rzehak P, Supolo H, et al. Am J of Clin Nutr 2018;108:1135-44

Analysis of FADS1-3 Genetic Variation &
Minor Allele of Different Population

“Out of Africa”
Theory

Tanjung C, Rzehak P, Supolo H, et al. Am J of Clin Nutr 2018;108:1135-44

WHAT ABOUT US?

n-3

ALA ERA EPA DPA DHA EPA / ALA

SNP Genotype n 18:3 20:3 20:5 22:5 22:6 20:5 / 18:3

Indonesian
population

rs174548 C/C 211 0.06 ± 0.03 0.13 ± 0.02 0.11 ± 0.06 0.23 ± 0.09 4.99 ± 1.08 2.17 ± 1.18
rs174548 G/C 148 0.05 ± 0.03 0.14 ± 0.02 0.11 ± 0.06 0.23 ± 0.09 5.21 ± 1.16 2.24 ± 1.27
rs174548 G/G 29 0.05 ± 0.02 0.14 ± 0.02 0.13 ± 0.07 0.23 ± 0.11 5.59 ± 1.25 3.03 ± 2.17

Tanjung C, Rzehak P, Supolo H, et al. Am J of Clin Nutr 2018;108:1135-44

INDONESIAN PROSPECTIVE STUDY OF ATOPIC DERMATITIS IN INFANT

 Major allele Indonesian population’s  less effective

metabolizer
 Major allele European population’s  more effective
metabolizer
 Natural selection & human migration effect
 Modern human have 2 haplotypes A & D; D is more effective
(210-300 ,000y.a.)
Tanjung C, Rzehak P, Supolo H, et al. Am J of Clin Nutr 2018;108:1135-44
Majou D. OCL 2018, 25(4), A401
MENTERI KELAUTAN & PERIKANAN
RECOMMENDED DIETARY ALLOWANCES
 Pregnant women: total DHA intake at least 300 mg/day.
 Breast-feeding women: achieve a minimum average daily supply
of 200 mg DHA result in a milk DHA content of 0.3% of fatty
acids
 Term infants – 1 year : 100 mg DHA/day & 140 mg AA/day
 Birth weight <1,500 g :
 DHA18 to 60 mg/kg/day
 AA18 to 45 mg/kg/day
 EPA < 20 mg EPA

The recommendation does

not stated about supplementation
except for infant formula
FOOD SOURCE OF LCPUFA
FOOD SOURCE OF LCPUFA
Fish species DHA EPA DHA + EPA
(mg/100 g wet wt.)
Ailia coila 180.0 ± 5.0 — 180.0 ± 5.0
Amblypharyngodon 133.3 ± 6.8 94.6 ± 5.4 227.9 ± 10.6
mola
Cyprinus carpio 152.1 ± 9.8 — 152.1 ± 9.8
Crassostrea 383.4 ± 3.1 377.9 ± 3.0 761.3 ± 6.9
madrasensis
Epinephelus spp. 107.8 ± 0.8 47.8 ± 0.4 155.7 ± 1.2
Etroplus suratensis 186.6 ± 31.5 115.3 ± 26.5 301.9 ± 45.6
Fenneropenaeus 80.6 ± 12.3 84.5 ± 25.1 165.1 ± 33.2
indicus
Gudusia chapra 342.0 ± 10.2 — 342.0 ± 10.2
Katsuwonus pelamis — 104.8 ± 0.8 104.8 ± 0.8
Lates calcarifer 127.6 ± 15.6 155.2 ± 13.3 282.7 ± 25.5
Leiognathus 226.2 ± 1.8 224.5 ± 1.8 450.7 ± 2.5
splendens
Neolissochilus 210.1 ± 2.3 301.8 ± 6.5 414.2 ± 5.0
hexagonolepis
Oncorhynchus mykiss 224.6 ± 2.2 81.5 ± 1.5 306.1 ± 2.6
Penaeus monodon 54.1 ± 14.9 108.5 ± 17.6 162.6 ± 22.2
Perna viridis 158.9 ± 1.3 169.9 ± 1.4 328.8 ± 3.2
Puntius sophore 161.7 ± 7.6 303.8 ± 8.3 465.5 ± 9.8
Schizothorax 93.3 ± 1.0 235.8 ± 4.0 337.7 ± 3.1
richardsonii
Sardinella longiceps 534.9 ± 4.3 937.9 ± 7.5 1472.9 ± 6.9
Sperata seenghala 49.6 ± 1.5 35.2 ± 1.0 84.8 ± 2.9
Tenualosa ilisha 934.5 ± 37.1 304.5 ± 14.0 1239.0 ± 25.2
Tor putitora 115.5 ± 12.2 201.9 ± 13.1 316.9 ± 13.1
Trichiurus lepturus 567.8 ± 4.5 203.1 ± 1.6 770.9 ± 5.6
Xenentodon cancila 70.0 ± 4.0 — 70.0 ± 4.0
 EPA and DHA concentration of selected marine fish
species

EPA and DHA concentration of selected freshwater fish

species
 SUMMARY
 Sufficient availability LC-PUFA is essential for
brain development
 SNP of FADS genes modify the composition of
fatty acid
 As Indonesian’s major allele is less effective
metabolizer, the supply of preformed LC-PUFA
may be particularly important
 Direct extrapolation from European to
Indonesian population become questionable
as major alleles among different population
are different
 ACKNOWLEDGEMENT
 University of Indonesia : Damayanti R.Sjarif
Herawati S.Sudoyo

• LMU : Berthold Koletzko

Hans Demmelmair
Peter Rzehak

 Helmholtz : Eva Reischl