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Essential Fatty Acids
DHA (Docosohexaenoic Acid)
Nutrition

definition

DHA (Docosohexaenoic Acid):

» overview:

• DHA is the building block of human brain tissue and is particularly abundant in the grey matter of the brain and the retina. Low levels of DHA have recently been associated with depression, memory loss, dementia, and visual problems. Optimal levels of DHA are therefore crucial for pregnant and lactating mothers.

» chemistry:

• Docosahexaenoic acid is a polyunsaturated omega-3 fatty acid, an essential building block of brain tissue that is critical.

» metabolism:

• DHA is particularly important for fetuses and infants; the DHA content of the infant's brain triples during the first three months of life.

• Linolenic acid is a precursor to DHA.

» function:

• DHA plays a vital role in brain development in infants and children.

• Brain cell membrane fluidity is essential for communication between neurons.

• DHA helps keep cell membranes fluid, and also helps to replenish brain tissue.

• DHA is abundant in the grey matter and retina.

» requirements:

RDA: None established.

Optimal daily intake: 100-200 mg (Levine, Barbara S. Nutrition Today, Vol. 32, Nov/Dec 1997, pp. 248-49)

» food sources:

• Ideally, mothers milk. United States is the only country in the world where infant formulas are not fortified with DHA. This despite a 1995 recommendation by the World Health Organization that all baby formulas should provide 40 mg of DHA per kilogram of infant body weight. (Levine, Barbara S. Nutrition Today, Vol. 32, November/December 1997, pp. 248-49)

• Menhaden oil.

• Marine phytoplankton and oil-rich cold-water fish, such as salmon and tuna, are highest sources.

• Available as algae-derived capsules which contain pure DHA

• Difficult to obtain adequate direct sources from vegetarian diet. Flaxseed oil is a good source of linolenic acid, a precursor to DHA.

• Average DHA content of breast milk in the United States is the lowest in the world. (Levine, Barbara S. Nutrition Today, Vol. 32, November/December 1997, pp. 248-49)

» deficiency:

• Poor neurological development.

• Low DHA levels have been linked to low brain serotonin levels which again are connected to an increased tendency to depression, suicide, and violence. (Levine, Barbara S. Nutrition Today, Vol. 32, November/December 1997, pp. 248-49)

• Decreased concentration.

• Memory loss

• Excessive thirst and dry skin are common indicators of an omega-3 fatty acid deficiency.

• Depression, esp. postpartum depression

• Dementia

• Visual problems

» therapeutics:

Dyslexia: (Stordy BJ. Letter, Lancet 1995 Aug 5;346(8971):385)

Alzheimers: DHA reported to improve memory in Alzheimers patients. (Prasad MR, et al. Neurochem Res 1998 Jan;23(1):81-88.)

Attention-deficit Hyperactivity disorder: (Levine, Barbara S. Nutrition Today, Vol. 32, November/December 1997, pp. 248-49; Mitchell EA, et al. Clin Pediatr (Phila) 1987 Aug;26(8):406-411; Stevens LJ, et al. Am J Clin Nutr. 1995 Oct;62(4):761-768)

Stress tolerance and agression: In two sequential studies on the effects of stress on college students researchers found that those using 1.5-1.8 g of DHA daily experiences fewer ill effects of stress, especoially agressive behavior towards others, than did the control group; further they determined that in non-stress situations the two groups showed no significant difference.

(Hamazaki T, et al. J Clin Invest 1996 Feb 15;97(4):1129-1133; Hamazaki T, et al. Lipids 1998 Jul;33(7):663-667)

Depression

Memory loss

Dementia

Visual problems

» dosage:

• Maintenance dose: 100-200 mg per day

• Therapeutic dose: Pregnant and lactating women: 200 mg per day (Kyle)

» toxicity:

• None known to date

• Some fish oil-based supplements may contain Mercury or other toxins in concentrated forms.

» contraindications:

• None known to date

footnotes

Bondia-Martinez E, Lopez-Sabater MC, Castellote-Bargallo AI, Rodriguez-Palmero M, Gonzalez-Corbella MJ, Rivero-Urgell M, Campoy-Folgoso C, Bayes-Garcia R. Fatty acid composition of plasma and erythrocytes in term infants fed human milk and formulae with and without docosahexaenoic and arachidonic acids from egg yolk lecithin. Early Hum Dev 1998 Dec;53 Suppl:S109-119.

Abstract: Human milk contains small but nutritionally significant amounts of long-chain polyunsaturated fatty acids (LCP), such as arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-3) acids, which are not present in most infant formulae. In the present study, the fatty acid composition of plasma and erythrocytes was determined at birth and again at 7 days, 1 and 3 months in 49 healthy full-term infants (37-42 week's gestation). One group of infants was fed exclusively with human milk (n=16) and the others were randomly assigned to a standard term formula (F) (n=15) or the same formula with egg yolk lecithin providing DHA (0.15%) and AA (0.30%) (LCP-F) (n=18). Plasma and erythrocyte LCP values of the three dietary groups did not differ at 7 days of age, but the contents of DHA and AA in plasma and erythrocytes at 1 and 3 months were significantly lower (P<0.05) in infants fed non supplemented formula than in infants fed breast milk and supplemented formula. There were no differences in plasma or erythrocyte AA or DHA concentrations between the group fed breast milk and the group fed supplemented formula during the period studied.

Crawford MA, Costeloe K, Ghebremeskel K, Phylactos A. The inadequacy of the essential fatty acid content of present preterm feeds. Eur J Pediatr 1998 Jan;157 Suppl 1:S23-S27.

Abstract: Arachidonic (AA) and docosahexaenoic (DHA) acids are major components of endothelial, pulmonary and neuro-visual cell membranes. Preterm babies may be born with deficits of both AA and DHA. There is evidence that their endogenous anti-oxidant enzymes defence systems have only reached half the activity expected at term. Yet they are exposed to an oxygen tension greater than physiologically anticipated at this time, and the superoxide dismutase shows no evidence of significant catch-up. After birth, present enteral and parenteral feeds for the preterm baby result in a further drop of AA and DHA plasma proportions to a quarter or third of the intra-uterine expectation. At the same time, the proportion of linoleic acid (LA), the precursor for AA, rises in the plasma phosphoglycerides four-fold, thus denying the preterm infant the provision with which the placenta would have perfused the fetus to meet the very rapid demand for endothelial and neural growth. From the biochemistry it is predictable that this situation could lead to fragile cell membranes, leakage, rupture with peroxidation resulting in the formation of inflammatory and vasoconstrictive agents. CONCLUSION: The essential fatty acid content of current enteral and parenteral feeds for preterm infants is incorrectly formulated.

Francois CA, Connor SL, Wander RC, Connor WE. Acute effects of dietary fatty acids on the fatty acids of human milk. Am J Clin Nutr 1998 Feb;67(2):301-308.

Genzel-Boroviczeny O, Hrboticky N. Plasma values of polyunsaturated fatty acids in extremely low birth weight (ELBW) infants fed breast milk or formula very early in life. Eur J Med Res 1996 Jul 25;1(10):495-498.

Gibson RA, Makrides M. The role of long chain polyunsaturated fatty acids (LCPUFA) in neonatal nutrition. Acta Paediatr 1998 Oct;87(10):1017-1022.

Abstract: Exciting new research has shown that both preterm and term infants can actively convert the essential fatty acids linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3) to long chain polyunsaturated fatty acids (LCPUFA). However, the amount of LCPUFA being produced, particularly of docosahexaenoic acid (DHA, 22:6n-3), may not be sufficient to meet the developmental requirement of the infant. Because DHA is a major component of retinal and brain tissues, a number of studies have been initiated to test the effect of dietary LCPUFA on neural outcomes in infants. These studies have largely involved a comparison of neural responses from infants fed standard infant formula (no LCPUFA) with infants receiving LCPUFA from either supplemented formula or breast milk. The results have been equivocal and may be due to the variety of LCPUFA supplements and formula fat blends used, differing testing techniques as well as variations in clinical trial conduct, but are clearer in preterm than term infants. Overall the results indicate a possible role for LCPUFA in neurodevelopment.

Hamazaki T, Sawazaki S, Nagao Y, Kuwamori T, Yazawa K, Mizushima Y, Kobayashi M. Docosahexaenoic acid does not affect aggression of normal volunteers under nonstressful conditions. A randomized, placebo-controlled, double-blind study. Lipids 1998 Jul;33(7):663-667.

Abstract: We previously found that docosahexaenoic acid (DHA) intake prevents aggression enhancement at times of mental stress. In the present study we investigated changes in aggression under nonstressful conditions. Forty-six students of two universities took either DHA-rich fish oil capsules containing 1.5 g DHA (DHA group: 13 males and 9 females) or control oil capsules containing 97% soybean oil plus 3% of another fish oil (control group: 11 males and 13 females) for 3 mon in a double-blind fashion. At the start and end of the study they took an aggression-estimating test (P-F Study) without a stressor component. DHA (5.9 to 8.5%, P < 0.001) and eicosapentaenoic acid (0.7 to 1.5%, P < 0.001) increased in red blood cell phospholipids in the DHA group, while linoleic acid increased slightly (8.3 to 9.1%, P < 0.002) in the soybean oil control group. In the control group, measured aggression levels decreased from 34.8 to 29.4% (P < 0.005), whereas they remained stable in the DHA group (33.5 to 33.8%). The intergroup differences (-5.4 vs. 0.3%) were marginally significant (P < or = 0.05). Aggression levels were stable in the DHA group whether there was stressor (as previously shown) or not. This effect of DHA appears to be interesting, considering the reported association between a low intake of n-3 fatty acids and depression.

Hamazaki T, Sawazaki S, Itomura M, Asaoka E, Nagao Y, Nishimura N, Yazawa K, Kuwamori T, Kobayashi M. The effect of docosahexaenoic acid on aggression in young adults. A

placebo-controlled double-blind study. J Clin Invest 1996 Feb 15;97(4):1129-1133.

Abstract: 41 students took either docosahexaenoic acid (DHA)-rich oil capsules containing 1.5-1.8 grams DHA/day (17 females and 5 males) or control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and 7 males) for 3 mo in a double-blind fashion. They took a psychological test (P-F Study) and Stroop and dementia-detecting tests at the start and end of the study. The present study started at the end of summer vacation and ended in the middle of mental stress such as final exams. In the control group extraggression (aggression against others) in P-F Study was significantly increased at the end of the study as compared with that measured at the start (delta = +8.9%, P = 0.0022), whereas it was not significantly changed in the DHA group (delta = -1.0%). The 95% CI of differences between the DHA and control groups were -16.8 to -3.0%. DHA supplementation did not affect the Stroop and dementia-detecting tests. Thus, DHA intake prevented extraggression from increasing at times of mental stress. This finding might help understand how fish oils prevent disease like coronary heart disease.

Ikemoto A, Kobayashi T, Emoto K, Umeda M, Watanabe S, Okuyama H. Effects of Docosahexaenoic and Arachidonic Acids on the Synthesis and Distribution of Aminophospholipids during Neuronal Differentiation of PC12 Cells. Arch Biochem Biophys 1999 Apr 1;364(1):67-74.

Kyle, David. Martek Biosciences, Baltimore, MD. October 1997.

Levine, Barbara S. Most frequently asked questions about DHA. Nutrition Today, Vol. 32, November/December 1997, pp. 248-249.

Mitchell EA, Aman MG, Turbott SH, Manku M. Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr (Phila) 1987 Aug;26(8):406-411.

Abstract: This study compared 48 hyperactive children with 49 age-and-sex-matched controls. Significantly more hyperactive children had auditory, visual, language, reading, and learning difficulties, and the birth weight of hyperactive children was significantly lower than that of controls. In addition, significantly more hyperactive children had frequent coughs and colds, polydypsia, polyuria, and a serious illness or accident in the past year than controls, but there was no increase in asthma, eczema, or other allergies. Serum essential fatty acid (EFA) levels were measured in 44 hyperactive subjects and 45 controls. The levels of docasahexaenoic, dihomogammalinolenic, and arachidonic acids were significantly lower in hyperactive children than controls.

Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR. Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem Res 1998 Jan;23(1):81-88.

Abstract: Regional levels of membrane phospholipids were measured in the brain of Alzheimer's disease (AD) and control subjects. The levels of PE-derived and PI-derived total fatty acids were significantly decreased in the hippocampus of AD subjects. Here significant decreases were found in PE-derived stearic, oleic and arachidonic and docosahexaenoic acids, and in PI-derived oleic and arachidonic acids. In the inferior parietal lobule of AD subjects, significant decreases were found only in PE and those decreases were contributed by stearic, oleic and arachidonic acids. In the superior and middle temporal gyri and cerebellum of AD subjects, no significant decreases were found in PC-, PE- and PI-derived fatty acids. The decrease of PE and PI, which are rich in oxidizable arachidonic and docosahexaenoic acids, but not of PC, which contains lesser amounts of these fatty acids, suggests a role for oxidative stress in the increased degradation of brain phospholipids in AD.

Sanchez-Muniz FJ, Bastida S, Viejo JM, Terpstra AH. Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholid and apolipoprotein B concentrations in young adult women. Z Ernahrungswiss 1999 Feb;38(1):20-27.

Abstract: In order to investigate the effect of a short-term application of marine n-3 polyunsaturated fatty acids on the composition of serum very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL), nine women aged 29 +/- 4.2 years, following a diet with a SFA/MUFA/PUFA profile of 2.4/3/1, received supplements of six capsules daily, each capsule containing 0.137 g of n-3 fatty acids (14.5% eicosapentaenoic acid (EPA) and 8.9% docosahexaenoic acid (DHA)) for 10 d. Food consumption, assessed during two 10-days periods indicates that percentage contribution of SFA, MUFA, and PUFA to the daily energy intake did not change through the fish-oil supplementation period, but the daily consumption of n-3 fatty acids increased 2.3 times. N-3 fatty supplementation increased EPA and DHA percentages in serum phospholipids, but failed to decrease (p > 0.05) the cholesterol and triglyceride concentration in serum LDL and HDL, although it did so in VLDL. In contrast, the lipoprotein-phospholipid and lipoprotein-protein concentrations were markedly affected, mainly in LDL and HDL (at least p < 0.01). HDL and VLDL compositions were not affected but the total mass (lipid + protein in mg/dl) concentration of these lipoproteins significantly decreased (p < 0.05), suggesting a lower number of these particles in circulating blood after the n-3 treatment. The LDL-cholesterol/LDL-apolipoprotein B ratio increased (p < 0.01) reflecting a probable increase in LDL size. Following fish oil supplementation, LDL particles contained a significantly lower amount of phospholipids, which also suggests changes in the surface/core ratio of the average LDL. Changes in serum lipoprotein lipids did not significantly correlate with any dietary change other than the n-3 fatty acid increase. The results indicate that a 10-day application of a small supplement of n-3 change the LDL composition leading to less atherogenic LDL particles with lower phospholipid and apolipoprotein (Apo) B concentrations.

Stevens LJ, Zentall SS, Deck JL, Abate ML, Watkins BA, Lipp SR, Burgess JR. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr. 1995 Oct;62(4):761-768.

Abstract: Study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids and in red blood cell total lipids than did the 43 control subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of essential fatty acid (EFA) deficiency had significantly lower plasma concentrations than did 32 subjects with ADHD with few EFA-deficiency symptoms.

Stordy BJ. Benefit of docosahexaenoic acid supplements to dark adaptation in dyslexics. Lancet 1995 Aug 5;346(8971):385. (Letter)

Werkman SH, Carlson SE. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until nine months. Lipids 1996 Jan;31(1):91-97

Abstract: This randomized, double-blind trial tested the hypothesis that the addition of 0.2% docosahexaenoic acid from marine oil to commercially-available preterm and term formulas with > or = 3% linolenic acid would enhance novelty preference and visual attention of preterm infants. Among preterm infants cared for in our center, study infants were a select group considered to be at lower risk for developmental delay. After receiving their assigned diet, they were tested for visual recognition memory and attention with the Fagan Test of Infant Intelligence. The effects of DHA supplementation were analyzed by repeated measures analysis of variance. In paired comparisons of novel and familiar stimuli, DHA-supplemented and control infants had the same novelty preference, but supplemented infants had more discrete looks to both novel (P < 0.03) and familiar (P < 0.02) stimuli and a shorter overall look duration (P < 0.03). Because shorter look duration has been associated with more rapid information processing, preterm infants fed formulas with only linolenic acid may have had slower information processing than those fed DHA.

Xiang M, Lei S, Li T, Zetterstrom R. Composition of long chain polyunsaturated fatty acids in human milk and growth of young infants in rural areas of northern China. Acta Paediatr 1999 Feb;88(2):126-131.

Abstract: The main source of fat in the diet in rural areas of northern China is soybean oil, therefore the pattern of essential fatty acids in human milk may be assumed to differ from that in milk from women in Western countries and to be similar to that of vegans. The concentrations of long chain polyunsaturated fatty acids in human milk and information on diet were analysed for 41 lactating women in rural areas of north China, and the growth of their infants was measured. The subjects were divided into two groups (group I, 1 mo postpartum; group II, 3 mo postpartum). The dietary intake of the mothers was high in carbohydrate and low in fat, protein and energy. The concentrations of linoleic acid (LA) and alpha-linolenic acid (LNA) were high. The ratio of LA to LNA, (21.6), was higher than has been reported from other countries. The concentration of docosa-hexaenoic acid (DHA) was low and the ratio of arachidonic acid (AA) to DHA was much higher (2.8) than recommended and similar to that found in vegans. The concentrations of AA and DHA in the milk correlated positively with the infants' weight gain at the third month (p<0.05) and of DHA with length gain at the first and third months (p<0.01). Since the concentration of AA and, particularly, DHA in the milk declined during lactation, DHA deficiency may appear after 3-4 mo of age in breastfed Chinese rural infants. Further studies of Chinese rural mother-infant pairs are necessary to prove whether supplementation with suitable sources of AA and DHA, such as fish oil, should be recommended as lactation is lengthened to ensure optimal infant growth and development.