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DHA and arachidonic acid (AA) are important for neurodevelopment. A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants. Mildly abnormal general movements at 3 months have been associated with a non-optimal current brain condition. We investigated whether supplementation of DHA during pregnancy and lactation influences the infant's brain development and whether additional AA modulates this effect. Healthy women were randomly assigned to DHA (220 mg/d, n 42), DHA+AA (220 mg each/d, n 41) or control (n 36), from about week 17 (range 14-20 weeks) of pregnancy until 12 weeks postpartum. The control and the DHA+AA groups had approximately comparable dietary DHA/AA ratios. The standardised neonatal neurological examination was carried out at 2 weeks. General movement quality was assessed at 2 and 12 weeks. Neither DHA alone nor DHA+AA influenced outcomes in the traditional examination. General movement quality of infants in the DHA group was lower than that of infants in the other two groups, especially at 12 weeks: 61% of the infants in the DHA group showed mildly abnormal general movements compared with 31% in the control group (P = 0.008) and 34% in the DHA+AA group (P = 0.015). We conclude that general movement quality at 12 weeks is sensitive to the maternal dietary DHA/AA balance. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation. We studied 98 CFS patients (21-69 years, 21 males) and 99 age- and sex-matched controls (19-65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation. Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3) (13.3%). FT3 below the reference range, consistent with the "low T3 syndrome," was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% confidence interval = 1.00-6.54). Most observations persisted in two sensitivity analyses with more stringent cutoff values for body mass index, high-sensitive C-reactive protein (hsCRP), and WBC. We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of "non-thyroidal illness syndrome" and "low T3 syndrome" experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with, e.g., T3 and iodide supplements might be indicated.

The mantra that dietary (saturated) fat must be minimized to reduce cardiovascular disease (CVD) risk has dominated nutritional guidelines for decades. Parallel to decreasing intakes of fat and saturated fatty acids (SFA), there have been increases in carbohydrate and sugar intakes, overweight, obesity and type 2 diabetes mellitus. The "lipid hypothesis" coined the concept that fat, especially SFA, raises blood low-density lipoprotein-cholesterol and thereby CVD risk. In view of current controversies regarding their adequate intakes and effects, this review aims to summarize research regarding this heterogenic group of fatty acids and the mechanisms relating them to (chronic) systemic low-grade inflammation, insulin resistance, metabolic syndrome and notably CVD. The intimate relationship between inflammation and metabolism, including glucose, fat and cholesterol metabolism, revealed that the dyslipidemia in Western societies, notably increased triglycerides, "small dense" low-density lipoprotein and "dysfunctional" high-density lipoprotein, is influenced by many unfavorable lifestyle factors. Dietary SFA is only one of these, not necessarily the most important, in healthy, insulin-sensitive people. The environment provides us not only with many other proinflammatory stimuli than SFA but also with many antiinflammatory counterparts. Resolution of the conflict between our self-designed environment and ancient genome may rather rely on returning to the proinflammatory/antiinflammatory balance of the Paleolithic era in consonance with the 21st century culture. Accordingly, dietary guidelines might reconsider recommendations for SFA replacement and investigate diet in a broader context, together with nondietary lifestyle factors. This should be a clear priority, opposed to the reductionist approach of studying the effects of single nutrients, such as SFA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

CHD may ensue from chronic systemic low-grade inflammation. Diet is a modifiable risk factor for both, and its optimisation may reduce post-operative mortality, atrial fibrillation and cognitive decline. In the present study, we investigated the usual dietary intakes of patients undergoing elective coronary artery bypass grafting (CABG), emphasising on food groups and nutrients with putative roles in the inflammatory/anti-inflammatory balance. From November 2012 to April 2013, we approached ninety-three consecutive patients (80% men) undergoing elective CABG. Of these, fifty-five were finally included (84% men, median age 69 years; range 46-84 years). The median BMI was 27 (range 18-36) kg/m(2). The dietary intake items were fruits (median 181 g/d; range 0-433 g/d), vegetables (median 115 g/d; range 0-303 g/d), dietary fibre (median 22 g/d; range 9-45 g/d), EPA+DHA (median 0.14 g/d; range 0.01-1.06 g/d), vitamin D (median 4.9 μg/d; range 1.9-11.2 μg/d), saturated fat (median 13.1% of energy (E%); range 9-23 E%) and linoleic acid (LA; median 6.3 E%; range 1.9-11.3 E%). The percentages of patients with dietary intakes below recommendations were 62% (fruits; recommendation 200 g/d), 87 % (vegetables; recommendation 150-200 g/d), 73% (dietary fibre; recommendation 30-45 g/d), 91% (EPA+DHA; recommendation 0.45 g/d), 98% (vitamin D; recommendation 10-20 μg/d) and 13% (LA; recommendation 5-10 E%). The percentages of patients with dietary intakes above recommendations were 95% (saturated fat; recommendation < 10 E%) and 7% (LA). The dietary intakes of patients proved comparable with the average nutritional intake of the age- and sex-matched healthy Dutch population. These unbalanced pre-operative diets may put them at risk of unfavourable surgical outcomes, since they promote a pro-inflammatory state. We conclude that there is an urgent need for intervention trials aiming at rapid improvement of their diets to reduce peri-operative risks.

In the present study we evaluate the feasibility of gene expression in white blood cells as a peripheral marker for winter depression. Sixteen patients with winter type seasonal affective disorder were included in the study. Blood was taken by venous puncture at three time points; in winter prior and following bright light therapy and in summer. RNA was isolated, converted into cRNA, amplified and hybridized on Illumina® gene expression arrays. The raw optical array data were quantile normalized and thereafter analyzed using a metagene approach, based on previously published Affymetrix gene array data. The raw data were also subjected to a secondary analysis focusing on circadian genes and genes involved in serotonergic neurotransmission. Differences between the conditions were analyzed, using analysis of variance on the principal components of the metagene score matrix. After correction for multiple testing no statistically significant differences were found. Another approach uses the correlation between metagene factor weights and the actual expression values, averaged over conditions. When comparing the correlations of winter vs. summer and bright light therapy vs. summer significant changes for several metagenes were found. Subsequent gene ontology analyses (DAVID and GeneTrail) of 5 major metagenes suggest an interaction between brain and white blood cells. The hypothesis driven analysis with a smaller group of genes failed to demonstrate any significant effects. The results from the combined metagene and gene ontology analyses support the idea of communication between brain and white blood cells. Future studies will need a much larger sample size to obtain information at the level of single genes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Docosahexaenoic (DHA) and arachidonic (AA) acids are important for neurodevelopment. We investigated the relation between erythrocyte (RBC) DHA and AA contents and neurological development, by assessment of General Movements (GMs), in populations with substantial differences in fish intakes., Methods: We included 3-month-old breastfed infants of three Tanzanian tribes: Maasai (low fish, n = 5), Pare (intermediate fish, n = 32), and Sengerema (high fish, n = 60); and a Dutch population (low-intermediate, fish, n = 15). GMs were assessed by motor optimality score (MOS) and the number of observed movement patterns (OMP; an MOS sub-score). RBC-DHA and AA contents were determined by capillary gas chromatography., Results: We found no between-population differences in MOS. OMP of Sengerema infants (high fish) was higher than OMP of Dutch infants (low-intermediate fish). MOS related to age. OMP related positively to infant age (P < 0.001) and RBC-DHA (P = 0.015), and was unrelated to ethnicity and RBC-AA., Discussion: The positive relation between RBC-DHA and the number of observed movement patterns of 3-month old infants might reflect the connection of DHA with motor development.

Little is known about the interrelationships between maternal and infant erythrocyte-DHA, milk-DHA and maternal adipose tissue (AT)-DHA contents. We studied these relationships in four tribes in Tanzania (Maasai, Pare, Sengerema and Ukerewe) differing in their lifetime intakes of fish. Cross-sectional samples were collected at delivery and after 3 d and 3 months of exclusive breast-feeding. We found that intra-uterine biomagnification is a sign of low maternal DHA status, that genuine biomagnification occurs during lactation, that lactating mothers with low DHA status cannot augment their infants' DHA status, and that lactating mothers lose DHA independent of their DHA status. A maternal erythrocyte-DHA content of 8 wt% was found to correspond with a mature milk-DHA content of 1·0 wt% and with subcutaneous and abdominal (omentum) AT-DHA contents of about 0·39 and 0·52 wt%, respectively. Consequently, 1 wt% DHA might be a target for Western human milk and infant formula that has milk arachidonic acid, EPA and linoleic acid contents of 0·55, 0·22 and 9·32 wt%, respectively. With increasing DHA status, the erythrocyte-DHA content reaches a plateau of about 9 wt%, and it plateaus more readily than milk-DHA and AT-DHA contents. Compared with the average Tanzanian-Ukerewe woman, the average US woman has four times lower AT-DHA content (0·4 v. 0·1 wt%) and five times lower mature milk-DHA output (301 v. 60 mg/d), which contrasts with her estimated 1·8-2·6 times lower mobilisable AT-DHA content (19 v. 35-50 g).

We investigated the relations between fatty acid status and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol ratio in five Tanzanian ethnic groups and one Dutch group. Total cholesterol/HDL cholesterol ratio is a widely used coronary artery disease (CAD) risk factor. Fatty acid status was determined by measurement of fatty acids in serum cholesterol esters and erythrocytes. Data reflecting the influence of fatty acid intakes on serum total cholesterol and lipoprotein cholesterol were obtained from documented intervention studies. We found that 14:0, 16:0 and saturated fatty acid (SFA) status correlates positively with total cholesterol/HDL cholesterol ratio, while their intakes were unrelated. Linoleic acid and polyunsaturated fatty acid (PUFA) status and PUFA intake exhibited negative relations with the total cholesterol/HDL cholesterol ratio. These data suggest that a high SFA status, not a high SFA intake, is associated with increased CAD risk, while both high linoleic acid status and PUFA status are associated with reduced CAD risk. Consequently, the total cholesterol/HDL cholesterol ratio is a questionable risk marker since meta-analyses of randomized controlled trials show that partial dietary replacement of SFA for linoleic acid, the dominating dietary PUFA, does not change CAD risk. We conclude that many lifestyle factors, not SFA intake alone, determine SFA status, and suggest that interaction with many other lifestyle factors determines whether SFA status has a relevant contributing effect in low-grade inflammation, lipoprotein changes and CAD risk. The present outcome may teach us to consider the health effects of the entire diet together with many nondietary lifestyle factors, opposite to the reductionist approach of studying the effects of single nutrients, SFA and PUFA included., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this review, we focus on lifestyle changes, especially dietary habits, that are at the basis of chronic systemic low grade inflammation, insulin resistance and Western diseases. Our sensitivity to develop insulin resistance traces back to our rapid brain growth in the past 2.5 million years. An inflammatory reaction jeopardizes the high glucose needs of our brain, causing various adaptations, including insulin resistance, functional reallocation of energy-rich nutrients and changing serum lipoprotein composition. The latter aims at redistribution of lipids, modulation of the immune reaction, and active inhibition of reverse cholesterol transport for damage repair. With the advent of the agricultural and industrial revolutions, we have introduced numerous false inflammatory triggers in our lifestyle, driving us to a state of chronic systemic low grade inflammation that eventually leads to typically Western diseases via an evolutionary conserved interaction between our immune system and metabolism. The underlying triggers are an abnormal dietary composition and microbial flora, insufficient physical activity and sleep, chronic stress and environmental pollution. The disturbance of our inflammatory/anti-inflammatory balance is illustrated by dietary fatty acids and antioxidants. The current decrease in years without chronic disease is rather due to "nurture" than "nature," since less than 5% of the typically Western diseases are primary attributable to genetic factors. Resolution of the conflict between environment and our ancient genome might be the only effective manner for "healthy aging," and to achieve this we might have to return to the lifestyle of the Paleolithic era as translated to the 21st century culture., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Sufficient vitamin D status may be defined as the evolutionary established circulating 25-hydroxyvitamin D [25(OH)D] matching our Paleolithic genome., Methods: We studied serum 25(OH)D [defined as 25(OH)D₂ + 25(OH)D₃] and its determinants in 5 East African ethnical groups across the life cycle: Maasai (MA) and Hadzabe (HA) with traditional life styles and low fish intakes, and people from Same (SA; intermediate fish), Sengerema (SE; high fish), and Ukerewe (UK; high fish). Samples derived from non-pregnant adults (MA, HA, SE), pregnant women (MA, SA, SE), mother-infant couples at delivery (UK), infants at delivery and their lactating mothers at 3 days (MA, SA, SE), and lactating mothers at 3 months postpartum (SA, SE). Erythrocyte docosahexaenoic acid (RBC-DHA) was determined as a proxy for fish intake., Results: The mean ± SD 25(OH)D of non-pregnant adults and cord serum were 106.8 ± 28.4 and 79.9 ± 26.4 nmol/L, respectively. Pregnancy, delivery, ethnicity (which we used as a proxy for sunlight exposure), RBC-DHA, and age were the determinants of 25(OH)D. 25(OH)D increased slightly with age. RBC-DHA was positively related to 25(OH)D, notably 25(OH)D₂. Pregnant MA (147.7 vs. 118.3) and SE (141.9 vs. 89.0) had higher 25(OH)D than non-pregnant counterparts (MA, SE). Infant 25(OH)D at delivery in Ukerewe was about 65 % of maternal 25(OH)D., Conclusions: Our ancient 25(OH)D amounted to about 115 nmol/L and sunlight exposure, rather than fish intake, was the principal determinant. The fetoplacental unit was exposed to high 25(OH)D, possibly by maternal vitamin D mobilization from adipose tissue, reduced insulin sensitivity, trapping by vitamin D-binding protein, diminished deactivation, or some combination.

Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D₂ and D₃ (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (SD 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (SD 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.

Purpose: Higher long-chain polyunsaturated fatty acids (LCP) in infant compared with maternal lipids at delivery is named biomagnification. The decline of infant and maternal docosahexaenoic acid (DHA) status during lactation in Western countries suggests maternal depletion. We investigated whether biomagnification persists at lifelong high fish intakes and whether the latter prevents a postpartum decline of infant and/or maternal DHA status., Methods: We studied 3 Tanzanian tribes with low (Maasai: 0/week), intermediate (Pare: 2-3/week), and high (Sengerema: 4-5/week) fish intakes. DHA and arachidonic acid (AA) were determined in maternal (m) and infant (i) erythrocytes (RBC) during pregnancy (1st trimester n = 14, 2nd = 103, 3rd = 88), and in mother-infant pairs at delivery (n = 63) and at 3 months postpartum (n = 104)., Results: At delivery, infants of all tribes had similar iRBC-AA which was higher than, and unrelated to, mRBC-AA. Transplacental DHA biomagnification occurred up to 5.6 g% mRBC-DHA; higher mRBC-DHA was associated with "bioattenuation" (i.e., iRBC-DHA < mRBC-DHA). Compared to delivery, mRBC-AA after 3 months was higher, while iRBC-AA was lower. mRBC-DHA after 3 months was lower, while iRBC-DHA was lower (low fish intake), equal (intermediate fish intake), and higher (high fish intake) compared to delivery. We estimated that postpartum iRBC-DHA equilibrium is reached at 5.9 g%, which corresponds to a mRBC-DHA of 6.1 g% throughout pregnancy., Conclusion: Uniform high iRBC-AA at delivery might indicate the importance of intrauterine infant AA status. Biomagnification reflects low maternal DHA status, and bioattenuation may prevent intrauterine competition of DHA with AA. A mRBC-DHA of about 6 g% during pregnancy predicts maternal-fetal equilibrium at delivery, postnatal iRBC-DHA equilibrium, but is unable to prevent a postnatal mRBC-DHA decline.

Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes., Subjects and Methods: We analyzed the brain (n=18), liver (n=14) and adipose tissue (n=11) FA compositions of 20 stillborn infants with different gestational ages (range 8-38 weeks) born to Tanzanian women with low linoleic acid (LA) intakes and high intakes of docosahexaenoic (DHA) and arachidonic (AA) acids from local fish., Results and Discussion: With advancing gestation, brain saturated-FA (SAFA; in g/100g FA), polyunsaturated-FA (PUFA), DHA, 20:3ω6, 22:4ω6 and 22:5ω6 increased, while monounsaturated-FA (MUFA), 20:3ω9, 22:3ω9 and AA decreased. Decreasing brain AA might be caused by increasing AA-metabolism to 20:3ω6, 22:4ω6 and 22:5ω6. In the liver, SAFA, PUFA and LA increased, while MUFA decreased with gestation. The steep increase of (mostly de novo synthesized) SAFA in adipose tissue coincided with relative decreases of MUFA, PUFA, DHA, LA and AA with advancing gestation. Compared to Western infants, the currently studied African infants had higher DHA, lower AA, and a higher DHA/AA-ratio in brain and adipose tissue, while the LA content of adipose tissue was lower., Conclusion: The low LA and high DHA and AA intakes by the mothers of these infants might support optimal α-linolenic (ALA) vs. LA competition for Δ5D and Δ6D-activities and DHA vs. AA antagonism. Conversely, the Western diet, characterized by high LA and lower DHA and AA intakes, might disturb these evolutionary conserved mechanisms aiming at an optimal ω3/ω6-balance., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: There are no data on the fatty acid (FA) compositions of preterm and term milks for sub-Saharan African populations with advancing lactation. However, it is generally acknowledged that our ancestors evolved in sub-Saharan East-Africa, where they inhabited the land-water ecosystems., Methods: We compared the FA-compositions of preterm (28-36 weeks) and term (37-42) colostrum (2-5 day), transitional (6-15) and mature (16-56) milks in rural African women with stable dietary habits and lifelong high freshwater fish intakes., Results: From colostrum to mature milk: the median docosahexaenoic acid (DHA) content decreased from 1.11 to 0.75; and arachidonic acid (AA) from 0.93 to 0.69 g% in preterm milk. In term milk, DHA decreased from 0.81 to 0.53 and AA from 1.08 to 0.55 g%. Medium-chain saturated-FA (MCSAFA) increased from 16.9 to 33.7, and 7.92-29.0 g%, while mono-unsaturated FA (MUFA) decreased from 32.5 to 22.6, and 40.0-26.5 g%, in preterm and term milk, respectively. Consistent with the literature, preterm colostrum contained higher DHA and MCSAFA, and lower MUFA compared to term colostrum. These differences vanished rapidly with advancing lactation. MUFA and MCSAFA were inversely related., Conclusions: The presently found DHA in preterm colostrum and mature milks and AA in premature mature milk proved the highest reported in the literature so far, as derived from analysis with capillary GC-columns. We confirmed the much higher MCSAFA and lower MUFA contents in milk of rural African, compared to Westernized women. The milk FA composition of this traditional population might show us the FA composition on which our species evolved and consequently to which our genome has become adapted to optimally support (infant) health., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

There is great variability in the degree to which children with attention deficit/hyperactivity disorder (ADHD) improve through behavioral treatments. This study investigates the influence of the dopamine transporter gene (SCL6A3/DAT1) on outcome of behavioral parent training (BPT). Study subjects were a subsample (n = 50, for whom DAT1 genotypes were available) of a randomized controlled BPT effectiveness study (N = 94) comparing BPT plus ongoing routine clinical care (RCC) versus RCC alone in referred children (4-12 years old) with ADHD. Treatment outcome was based on parent-reported ADHD symptoms and behavioral problems. Presence of 2 versus no or 1 DAT1 10-repeat allele served as moderator variable. Time × Treatment × Genotype effect was analyzed with repeated-measures analysis of variance, controlling for baseline medication status. Results indicate that DAT1 moderated treatment response (p = .009). In children with no or 1 DAT1 10-repeat allele, superior treatment effects of BPT + RCC compared with RCC alone were present (p = .005), which was not the case in children with 2 DAT1 10-repeat alleles (p = .57). Our findings suggest that genetic differences in DAT1 in children with ADHD influence their susceptibility to a behavioral intervention directed at shaping their environment through their parents. The role of the dopamine system in motivation and learning and in the aberrant sensitivity to reinforcement in children with ADHD may explain this moderating effect, given that the management of contingencies is typically addressed in BPT., (PsycINFO Database Record (c) 2012 APA, all rights reserved.)

Introduction: There is no information on the whole body fatty acid (FA) contents of preterm or term infants, although scattered information on the FA-composition of many organs is available., Material and Methods: We collected data on the weights, lipid contents and FA-compositions of the quantitatively most important fetal organs of appropriate for gestational age (AGA) Western infants. From these we estimated the total body contents of linoleic (LA), arachidonic (AA) and docosahexaenoic (DHA) acids at 25, 35 and 40 weeks of gestation., Results: Western infants accrete FA in the order of LA>AA>DHA at all stages during pregnancy and the highest accretion rates are reached in the last 5 weeks of gestation, i.e. 342 mg LA, 95 mg AA and 42 mg DHA/day. At term, most of the infant's LA, AA and DHA is located in adipose tissue (68, 44 and 50%, respectively), with substantial amounts of LA also located in skeletal muscle (17%) and skin (13%); of AA in skeletal muscle (40%) and brain (11%); and of DHA in brain (23%) and skeletal muscle (21%). The term AGA infant has accreted about 21 g LA, 7.5 g AA and 3 g DHA, which constitutes a gap of 12 g LA, 3.3 g AA and 1.5 g DHA compared to a 35 weeks old AGA infant., Conclusion: The current fetal LA, AA and DHA pool sizes and accretion rates may especially be useful to estimate the preterm infant's requirements and the maternal LCP needs during pregnancy. Since they derive from populations with typically Western diets they do not necessarily reflect 'optimality' or 'health'., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Little is known about the gestational age (GA) dependent content, composition and intrauterine accretion rates of fatty acids (FA) in fetal white adipose tissue (WAT)., Objective & Design: To acquire this information, we collected abdominal subcutaneous WAT samples from 40 preterm and term fetuses. Their GA ranged from 22 to 43 weeks. FA were expressed as mg/g wet WAT and g/100g FA (g%). Intrauterine WAT FA accretion rates were estimated for appropriate (AGA) and large (LGA) for gestational age infants., Results: From 25 to 40 weeks gestation, saturated-FA (SAFA) increased from 83 to 298 mg/g WAT and monounsaturated-FA (MUFA) from 83 to 226 mg/g WAT, while polyunsaturated-FA (PUFA) increased insignificantly from 18.0 to 23.2 mg/g WAT. As percentages of total FA, SAFA increased from 46 to 55 g%, MUFA decreased from 44 to 41 g%, and PUFA from 10.3 to 4.26 g%. Docosahexaenoic (DHA) and arachidonic acid (AA) accretion rates in WAT during the 3rd trimester for AGA infants were 88 and 193 mg/week, respectively. Contemporaneous DHA and AA accretion rates for 4500 g LGA infants were 184 and 402 mg/week, respectively. Compared to the whole 3rd trimester, increment rates during the last 5 weeks of gestation were about 2-fold higher., Conclusion: FA accretion rates, notably those of DHA and AA, may be important for designing nutritional regiments for preterm infants. The current WAT-DHA and WAT-AA accretion rates are considerably lower than previously reported in the literature., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: Long-chain polyunsaturated (LCP) fatty acids (FA) are important during infant development. Mother-to-infant FA-transport occurs at the expense of the maternal status. Maternal and infant FA-status change rapidly after delivery., Methods: Comparison of maternal (mRBC) and infant erythrocyte (iRBC)-FA-profiles at delivery and after 3 months exclusive breastfeeding in relation to freshwater-fish intakes. Approximation of de-novo-lipogenesis (DNL), stearoyl-CoA-desaturase (SCD), elongation-of-very-long-chain-FA-family-member-6 (Elovl-6), delta-5-desaturase (D5D) and delta-6-desaturase (D6D)-enzymatic activities from their product/essential-FA and product/substrate-ratios., Results and Discussion: Increasing iRBC-14:0 derived from mammary-gland DNL. Decreasing mRBC-ω9, but increasing iRBC-ω9, suggest high ω9-FA-transfer via breastmilk. Decreasing (m+i)RBC-16:0, DNL- and SCD-activities, but increasing (m+i)RBC-18:0 and Elovl-6-activity suggest more pronounced postpartum decreases in DNL- and SCD-activities, compared to Elovl-6-activity. Increasing (m+i)RBC-18:3ω3, 20:5ω3, 22:5ω3, 18:2ω6, mRBC-20:4ω6 and (m+i)D5D-activity, but decreasing mRBC-22:6ω3 and (m+i)D6D-activity and dose-dependent changes in iRBC-22:6ω3 confirm that D6D-activity is rate-limiting and 22:6ω3 is important during lactation. Fish-intake related magnitudes of postpartum FA-changes suggest that LCPω3 influence DNL-, SCD- and desaturase-activities., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The hormonal milieus of pregnancy and lactation are driving forces of nutrient fluxes supporting infant growth and development. The decrease of insulin sensitivity with compensatory hyperinsulinemia with advancing gestation, causes adipose tissue lipolysis and hepatic de novo lipogenesis (DNL)., Subjects and Methods: We compared fatty acid (FA) contents and FA-indices for enzyme activities between preterm (28-36 weeks) and term (37-42) milks, and between colostrum (2-5 days), transitional (6-15) and mature (16-56) milks. We interpreted FA differences between preterm and term milks, and their changes with lactation, in terms of the well known decrease of insulin sensitivity during gestation and its subsequent postpartum restoration, respectively., Results: Compared with term colostrum, preterm colostrum contained higher indices of DNL in the breast (DNL-breast) and medium chain saturated-FA (MCSAFA), and lower DNL-liver and monounsaturated-FA (MUFA). Preterm milk also had higher docosahexaenoic acid (DHA) in colostrum and transitional milk and higher arachidonic acid (AA) in mature milk. Most preterm-term differences vanished with advancing lactation. In both preterm and term milks, DNL-breast and MCSAFA increased with advancing lactation, while DNL-liver, MUFA, long chain SAFA and AA decreased. DHA decreased in term milk. MUFA was inversely related to MCSAFA in all samples, correlated inversely with PUFA in colostrum and transitional milks, but positively in mature milk. MCSAFA correlated inversely with PUFA in mature milk., Conclusion: Higher maternal insulin sensitivity at preterm birth may be the cause of lower MUFA (a proxy for DNL-liver) and higher MCSAFA (a proxy for DNL-breast) in preterm colostrum, compared with term colostrum. Restoring insulin sensitivity after delivery may be an important driving force for milk FA-changes in early lactation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Erythrocyte (RBC) fatty acid compositions from populations with stable dietary habits but large variations in RBC-arachidonic (AA) and RBC-docosahexaenoic acid (DHA) provided us with insight into relationships between DHA and AA. It also enabled us to estimate the maternal RBC-DHA (mRBC-DHA) status that corresponded with no decrease in mRBC-DHA during pregnancy, or in infant (i) RBC-DHA or mRBC-DHA during the first 3 months postpartum (DHA-equilibrium) while exclusively breastfeeding. At delivery, iRBC-AA is uniformly high and independent of mRBC-AA. Infants born to mothers with low RBC-DHA exhibit higher, but infants born to mothers with high RBC-DHA exhibit lower RBC-DHA than their mothers. This switch from 'biomagnification' into 'bioattenuation' occurs at 6g% mRBC-DHA. At 6g%, mRBC-DHA is stable throughout pregnancy, corresponds with postpartum infant DHA-equilibrium of 6 and 0.4g% DHA in mature milk, but results in postpartum depletion of mRBC-DHA to 5g%. Postpartum maternal DHA-equilibrium is reached at 8g% mRBC-DHA, corresponding with 1g% DHA in mature milk and 7g% iRBC-DHA at delivery that increases to 8g% during lactation. This 8g% RBC-DHA concurs with the lowest risks of cardiovascular and psychiatric diseases in adults. RBC-data from 1866 infants, males and (non-)pregnant females indicated AA vs. DHA synergism at low RBC-DHA, but antagonism at high RBC-DHA. These data, together with high intakes of AA and DHA from our Paleolithic diet, suggest that bioattenuation of DHA during pregnancy and postnatal antagonism between AA and DHA are the physiological standard for humans across the life cycle., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The relation between docosahexaenoic (DHA) and eicosapentaenoic (EPA) vs. arachidonic acid (AA) seems characterized by both synergism and antagonism., Materials and Methods: Investigate the relation between EPA+DHA and AA in populations with a wide range of EPA+DHA status and across the life cycle. EPA+DHA and AA were determined in erythrocytes (RBC; n=1979), umbilical arteries (UA; n=789) and umbilical veins (UV; n=785)., Results: In all compartments, notably RBC, the relation between EPA+DHA and AA appeared bell-shaped. Populations with low RBC-EPA+DHA (<2g%) exhibited positive relationships; those with high RBC-EPA+DHA (>8g%) negative relationships. Antagonism in UA and UV could not be demonstrated., Conclusion: Both synergism and antagonism might aim at a balance between ω6 and ω3 long-chain polyunsaturated fatty acid (LCP) to maintain homeostasis. Synergism might be a feature of low LCPω3 status. AA becomes suppressed by antagonism from an RBC-EPA+DHA >8g%., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The dietary intake of saturated fatty acids (SAFA) is associated with a modest increase in serum total cholesterol, but not with cardiovascular disease (CVD). Replacing dietary SAFA with carbohydrates (CHO), notably those with a high glycaemic index, is associated with an increase in CVD risk in observational cohorts, while replacing SAFA with polyunsaturated fatty acids (PUFA) is associated with reduced CVD risk. However, replacing a combination of SAFA and trans-fatty acids with n-6 PUFA (notably linoleic acid) in controlled trials showed no indication of benefit and a signal toward increased coronary heart disease risk, suggesting that n-3 PUFA may be responsible for the protective association between total PUFA and CVD. High CHO intakes stimulate hepatic SAFA synthesis and conservation of dietary SAFA . Hepatic de novo lipogenesis from CHO is also stimulated during eucaloric dietary substitution of SAFA by CHO with high glycaemic index in normo-insulinaemic subjects and during hypocaloric high-CHO/low-fat diets in subjects with the metabolic syndrome. The accumulation of SAFA stimulates chronic systemic low-grade inflammation through its mimicking of bacterial lipopolysaccharides and÷or the induction of other pro-inflammatory stimuli. The resulting systemic low-grade inflammation promotes insulin resistance, reallocation of energy-rich substrates and atherogenic dyslipidaemia that concertedly give rise to increased CVD risk. We conclude that avoidance of SAFA accumulation by reducing the intake of CHO with high glycaemic index is more effective in the prevention of CVD than reducing SAFA intake per se.

Introduction: Perinatal changes in maternal glucose and lipid fluxes and de novo lipogenesis (DNL) are driven by hormones and nutrients. Docosahexaenoic acid (DHA) reduces, whereas insulin augments, nuclear abundance of sterol-regulatory-element-binding-protein-1 (SREBP-1), which promotes DNL, stearoyl-CoA-desaturase (SCD, also Δ9-desaturase), fatty acid-(FA)-elongation (Elovl) and FA-desaturation (FADS). Decreasing maternal insulin sensitivity with advancing gestation and compensatory hyperinsulinemia cause augmented postprandial glucose levels, adipose tissue lipolysis and hepatic glucose- and VLDL-production. Hepatic VLDL is composed of dietary, body store and DNL derived FA. Decreasing insulin sensitivity increases the contribution of FA from hepatic-DNL in VLDL-triacylglycerols, and consequently saturated-FA and monounsaturated-FA (MUFA) in maternal serum lipids increase during pregnancy. Although other authors described changes in maternal serum and RBC essential-FA (EFA) after delivery, none went into detail about the changes in non-EFA and the mechanisms behind -and/or functions of- the observed changes., Hypothesis: Postpartum FA-changes result from changing enzymatic activities that are influenced by the changing hormonal milieu after delivery and DHA-status., Empirical Data: We studied FA-profiles and FA-ratios (as indices for enzymatic activities) of maternal and infant RBC at delivery and after 3 months exclusive breastfeeding in three populations with increasing freshwater-fish intakes. DNL-, SCD- and FADS2-activities decreased after delivery. Elongation-6 (Elovl-6)- and FADS1-activities increased. The most pronounced postpartum changes for mothers were increases in 18:0, linoleic (LA), arachidonic acid (AA) and decreases in 16:0, 18:1ω9 and DHA; and for infants increases in 18:1ω9, 22:5ω3, LA and decreases in 16:0 and AA. Changes were in line with the literature., Discussion: Postpartum increases in 18:0, and decreases in 16:0 and 18:1ω9, might derive from reduced insulin-promoted DNL-activity, with more reduced SCD- than Elovl-activity that leaves more 16:0 to be converted to 18:0 (Elovl-activity) than to MUFA (SCD-activity). Postpartum changes in ΣDNL, saturated-FA and MUFA related negatively to RBC-DHA. This concurs with suppression of both SCD- and Elovl-6 activities by DHA, through its influence on SREBP. Infant MUFA and LA increased at expense of their mothers. Sustained transport might be important for myelination (MUFA) and skin barrier development (LA). Maternal postpartum decreases in FADS2-, and apparent increases in FADS1-activity, together with increases in LA, AA, and 22:5ω3, but decrease in DHA, confirm that FADS2 is rate limiting in EFA-desaturation. Maternal LA and AA increases might be the result of rerouting from transplacental transfer to the incorporation into milk lipids and discontinued placental AA-utilization., Implications: Perinatal changes in maternal and infant FA status may be strongly driven by changing insulin sensitivity and DHA status., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. The effects of DHA (220 mg/day, n=41), DHA+AA (220 mg/day, n=39) or placebo (n=34) during pregnancy and lactation on neurodevelopment at 18 months, and the relations between umbilical cord DHA, AA and Mead acid and neurodevelopment were studied. An age-specific, standardized neurological assessment for the evaluation of minor neurological dysfunction (MND), and the Bayley Scales of Infant Development (BSID) were used. The intervention did not influence any of the outcomes. Umbilical venous (UV) Mead acid was negatively and n-6 fatty acids were weakly positively associated to the BSID mental developmental index. Children with simple MND had lower UV DHA compared to normally classified children. We conclude that relatively short-term maternal DHA or DHA+AA supplementation does not influence neurodevelopment at toddler age, although some parameters of brain development are related to perinatal DHA and AA status., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Low long-chain PUFA (LC-PUFA, or LCP) consumption relates to suboptimal neurodevelopment, coronary artery disease, and [postpartum (PP)] depression. Maternal-to-infant LCP transport during pregnancy and lactation is at the expense of maternal status, a process known as biomagnification. Despite biomagnification, maternal and infant LCP status generally declines during lactation. To assess the 1) turning point of biomagnification [level from which maternal (m)LCP status exceeds infant (i)LCP status]; 2) LCP equilibrium (steady-state-level from which mRBC-LCP stop declining during lactation); 3) corresponding iLCP-status; and 4) the relationship between RBC-DHA and RBC-arachidonic acid (AA), we measured RBC-fatty acids in 193 Tanzanian mother-infant pairs with no, intermediate (2-3 times/wk), and high (4-5 times/wk) freshwater fish consumption at delivery and after 3 mo of exclusive breast-feeding. At 3 mo, mRBC-DHA was lower than the corresponding iRBC-DHA up to a mRBC-DHA of 7.9 g%. mRBC-DHA equilibrium, with equivalent mRBC-DHA at both delivery and at 3 mo PP, occurred at 8.1 g%. This mRBC-DHA equilibrium of 8.1 g% corresponded with an iRBC-DHA of 7.1-7.2 g% at delivery that increased to 8.0 g% at 3 mo. We found between-group differences in mRBC-AA; however, no differences in iRBC-AA were observed at delivery or 3 mo. Relations between RBC-DHA and RBC-AA were bell-shaped. We conclude that, at steady-state LCP intakes during lactation: 1) biomagnification occurs up to 8 g% mRBC-DHA; 2) mRBC-DHA equilibrium is reached at 8 g%; 3) mRBC-DHA equilibrium corresponds with an iRBC-DHA of 7 g% at delivery and 8 g% after 3 mo; 4) unlike RBC-DHA, mRBC-AA and iRBC-AA are independently regulated in these populations; and 5) bell-shaped RBC-DHA vs. RBC-AA-relations might support uniform iRBC-AA. A (maternal) RBC-DHA of 8 g% might be optimal for infant neurodevelopment and adult cardiovascular disease incidence.

Our genome adapts slowly to changing conditions of existence. Many diseases of civilisation result from mismatches between our Paleolithic genome and the rapidly changing environment, including our diet. The objective of the present study was to reconstruct multiple Paleolithic diets to estimate the ranges of nutrient intakes upon which humanity evolved. A database of, predominantly East African, plant and animal foods (meat/fish) was used to model multiple Paleolithic diets, using two pathophysiological constraints (i.e. protein < 35 energy % (en%) and linoleic acid (LA) >1.0 en%), at known hunter-gatherer plant/animal food intake ratios (range 70/30-30/70 en%/en%). We investigated selective and non-selective savannah, savannah/aquatic and aquatic hunter-gatherer/scavenger foraging strategies. We found (range of medians in en%) intakes of moderate-to-high protein (25-29), moderate-to-high fat (30-39) and moderate carbohydrates (39-40). The fatty acid composition was SFA (11.4-12.0), MUFA (5.6-18.5) and PUFA (8.6-15.2). The latter was high in α-linolenic acid (ALA) (3.7-4.7 en%), low in LA (2.3-3.6 en%), and high in long-chain PUFA (LCP; 4.75-25.8 g/d), LCP n-3 (2.26-17.0 g/d), LCP n-6 (2.54-8.84 g/d), ALA/LA ratio (1.12-1.64 g/g) and LCP n-3/LCP n-6 ratio (0.84-1.92 g/g). Consistent with the wide range of employed variables, nutrient intakes showed wide ranges. We conclude that compared with Western diets, Paleolithic diets contained consistently higher protein and LCP, and lower LA. These are likely to contribute to the known beneficial effects of Paleolithic-like diets, e.g. through increased satiety/satiation. Disparities between Paleolithic, contemporary and recommended intakes might be important factors underlying the aetiology of common Western diseases. Data on Paleolithic diets and lifestyle, rather than the investigation of single nutrients, might be useful for the rational design of clinical trials.

We showed that docosahexaenoic acid (DHA) supplementation during pregnancy and lactation was associated with more mildly abnormal (MA) general movements (GMs) in the infants. Since this finding was unexpected and inter-individual DHA intakes are highly variable, we explored the relationship between GM quality and erythrocyte DHA, arachidonic acid (AA), DHA/AA and Mead acid in 57 infants of this trial. MA GMs were inversely related to AA, associated with Mead acid, and associated with DHA/AA in a U-shaped manner. These relationships may indicate dependence of newborn AA status on synthesis from linoleic acid. This becomes restricted during the intrauterine period by abundant de novo synthesis of oleic and Mead acids from glucose, consistent with reduced insulin sensitivity during the third trimester. The descending part of the U-shaped relation between MA GMs and DHA/AA probably indicates DHA shortage next to AA shortage. The ascending part may reflect a different developmental trajectory that is not necessarily unfavorable., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Polymorphisms of monoamine-related genes have been associated with depression following life events. The peripartum is a physiologically and psychologically challenging period, characterized by fluctuations in depressive symptoms, therefore facilitating prospective investigations in this gene x environment (G x E) interaction., Methods: Eighty nine pregnant women filled in two Edinburgh Postpartum Depression Scale (EPDS) questionnaires during pregnancy and two in the postpartum period. MAOA, COMT and 5-HTT polymorphisms were analyzed., Results: We found a significant interaction between the development of depressive symptoms in the course of pregnancy and polymorphisms in 5-HTT (p=0.019); MAOA (p=0.044) and COMT (p=0.026), and MAOA x COMT (p<0.001). Particularly, women carrying the combination of low activity variants of MAOA and COMT showed increased EPDS scores at week 36 of pregnancy and 6 weeks postpartum, but not during early pregnancy or 12 weeks postpartum., Conclusion: We found that MAOA in combination with COMT appears to regulate not only the stress response in laboratory experiments, but also seems to influence the stress-evoked onset of mood during normal, mild, stressful events, such as experienced in the peripartum period. These findings support the GxE concept for depression, but they underline the complexity of this concept, as the cumulating effects of these polymorphic genes (i.e. MAOA+COMT) might be needed and the effects of these polymorphic genes becomes apparent in special environmental or physiological conditions (i.e. the peripartum period). We therefore suggest that G x E interactions become especially noticeable from longitudinal study designs in specific physiological or social challenging periods.

Objective: To estimate the incidence of Sickle-Cell Disease (SCD) in Aruba and St. Maarten and to determine whether universal screening would be cost-effective according to United Kingdom criteria., Methods: Consecutive cord blood samples were collected in Aruba and the Dutch part of St. Maarten during 3 and 4 months, respectively. Samples were subjected to High Performance Liquid Chromatography (HPLC) screening of haemoglobin variants., Results: Of the 368 samples (87.6% of all registered births) collected in Aruba, 10 (2.72%; CI 1.3, 4.9%) tested heterozygous for the Sickle-cell gene (HbAS) and 7 (1.90%; CI 0.8, 3.9%) for the haemoglobin C gene (HbAC). Of the 193 samples (83.5%) collected in St. Maarten, 14 (7.25%; CI 4.0, 11.9%) contained HbAS and 10 (5.18%; CI 2.5, 9.3%) HbAC. Hardy-Weinberg equilibrium predicted an incidence of 2.65% for HbAS and 1.86% for HbAC in Aruba and 6.80% for HbAS and 4.86% for HbAC in St. Maarten. These figures imply a newborn rate of about 2 SCD patients per 3 years in Aruba and 2 SCD patients per year in St. Maarten., Conclusions: Universal screening of newborns for SCD seems cost-effective for St. Maarten.

Umbilical veins (UV) and arteries (UA) of preeclamptic women in Curaçao harbor lower long-chain polyunsaturated fatty acids (LCP). The present aim was to test these findings in Mwanza (Tanzania), whose inhabitants have high LCPomega3 and LCPomega6 intakes from Lake Victoria fish. Women with preeclampsia (n=28) in Mwanza had lower PUFA and higher 20:0 in UV and UA, compared with normotensive/non-proteinuric controls (n=31). Their UV 22:6omega3, 22:4omega6, LCPomega6, omega6, and LCPomega3+omega6 were lower, while saturated FA, potentially de novo synthesized FA (Sigmade novo) and (Sigmade novo)/(LCPomega3+omega6) ratio were higher. Their UA had higher 16:1omega7, omega7, 18:0, and 16:1omega7/16:0. Umbilical vessels in Mwanza had higher 22:6omega3, LCPomega3, omega3, and 16:0, and lower 22:5omega6, 20:2omega6, 18:1omega9, and omega9, compared to those in Curaçao. Preeclampsia in both Mwanza and Curaçao is characterized by lower LCP and higher Sigmade novo. An explanation of this might be placental dysfunction, while the similarity of umbilical vessel FA-abnormalities in preeclamptic and diabetic pregnancies suggests insulin resistance as a common denominator.

Background: The decrease of maternal docosahexaenoic (DHA) status during pregnancy has been associated with postpartum depression, especially in women with a low intake of DHA. Since the DHA intake in the Netherlands is low, we investigated whether supplementation of low doses of DHA or DHA plus arachidonic acid (AA) during pregnancy and lactation could prevent depressive symptoms and sleep disturbances in this period., Methods: Women were supplemented daily with placebo, DHA (220 mg) or DHA+AA (220 mg each) from week 16 of pregnancy till three months postpartum. Fatty acid analyses were performed in the available plasma samples at 16 and 36 weeks of pregnancy. Depressive symptoms were measured in weeks 16 and 36 of pregnancy and six weeks postpartum using EPDS and within one week postpartum using a blues questionnaire., Results: 119 women completed the study. The average frequency of fish intake was low, 0.94 times per week, and did not differ between the groups. The supplementation groups did not differ in mean EPDS scores or changes in EPDS scores, nor in incidence or severity of postpartum blues. Red blood cell DHA, AA and DHA/AA ratio did not correlate with EPDS or blues scores. Indices of sleep quality did not differ between the groups., Conclusion: Supplementation of 220 mg/day DHA or DHA+AA (220 mg/day each) does not prevent peri-partum depressive symptoms, in a population based sample with low background DHA intake., Trial Registration: ISRCTN Register nr. ISRCTN58176213.

Introduction: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. Maternal diet influences milk DHA, whereas milk AA seems rather constant. We investigated milk AA, DHA and DHA/AA after supplementation of AA plus DHA, or DHA alone during pregnancy and lactation., Subjects and Methods: Women were supplemented with AA+DHA (220mg each/day), DHA (220mg/day) or placebo during pregnancy and lactation. Milk samples were collected at 2 (n=86) and 12 weeks (n=69) postpartum., Results: Supplementation of AA+DHA elevated milk AA (week 2, 14%; week 12, 23%) and DHA (43% and 52%) as compared to placebo. DHA tended to decrease milk AA and vice versa. Milk AA, DHA and DHA/AA decreased from 2 to 12 weeks postpartum., Conclusions: Milk AA and in particular DHA are sensitive to maternal supplementation. It seems that maternal AA and notably DHA status decline with advancing lactation.

We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from day 3 prior to conception till day 15 of pregnancy. We concentrated on DHA, AA, Mead acid, and EFA-index [(omega-3+omega-6)/(omega-7+omega-9)] in maternal erythrocytes, maternal brain, and fetal brain. It was found that erythrocyte EFA/LCP sensitively reflects declining EFA/LCP status in pregnancy, although this decline was not apparent in maternal brain. Differences in erythrocyte EFA/LCP coincided with larger differences in fetal brain EFA/LCP as compared to EFA/LCP in maternal brain. Both maternal and fetal brains were affected by short-term EFA/LCP intake, but the developing fetal brain proved most sensitive. The inverse relationship between fetal brain AA and DHA suggests the need of a maternal dietary DHA/AA balance, at least in mice.

Background: We need information on the diet on which our genes evolved., Objective: We studied the milk fatty acid [FA] composition of mothers living in the island of Chole [Tanzania, Indian Ocean]. These mothers have high intakes of boiled marine fish and coconut, and consume plenty amount of fruits and vegetables., Design: The outcome was compared with three fish-eating tribes living along Tanzanian freshwater lakes [Kerewe, Nyakius, Nyiramba], four tribes living in the Tanzanian inland [Hadzabe, Maasai, Sonjo, Iraqw] and our milk FA database., Results: Milk from Chole contained high levels of 12:0 [20.17 g%], 14:0 [21.19], 12:0/14:0 ratio [0.92 g/g], arachidonic acid [AA, 0.50 g%] and docosahexaenoic acid [DHA, 0.73], but low levels of linoleic acid [LA, 4.23]. The combination of a high medium chain fatty acid [MCFA;

The present review addresses the effect of pre- and postnatal supplementation of nutrition with long-chain polyunsaturated fatty acids (LCPUFA) on neurodevelopmental outcome. The few studies which addressed the effect of prenatal LCPUFA status or prenatal LCPUFA supplementation suggest that a better prenatal arachidonic acid (AA) and doxosahexaenoic acid (DHA) status might be related to a better neurodevelopmental outcome until at least 18 months of age. A review of the few randomized controlled trials on formula supplementation with LCPUFA in preterm infants did not provide evidence for a significant beneficial effect of LCPUFA on developmental outcome. A review of the trials on formula supplementation with LCPUFA in term infants revealed that supplementation with LCPUFA, in particularly supplementation with >or=0.30% DHA, has a beneficial effect on neurodevelopmental outcome until 4 months. The studies could not demonstrate a consistent positive effect beyond that age. It was concluded that the relatively subtle effects of LCPUFA supplementation on neurodevelopmental outcome do not only depend on dosage but also on the gestational period during which the nutritional components are supplied: supplementation prior to term seems to have more effect than that after term.

Homo sapiens has evolved on a diet rich in alpha-linolenic acid and long chain polyunsaturated fatty acids (LCP). We have, however, gradually changed our diet from about 10,000 years ago and accelerated this change from about 100 to 200 years ago. The many dietary changes, including lower intake of omega3-fatty acids, are related to 'typically Western' diseases. After a brief introduction in essential fatty acids (EFA), LCP and their functions, this contribution discusses our present low status of notably LCPomega3 in the context of our rapidly changing diet within an evolutionary short time frame. It then focuses on the consequences in pregnancy, lactation and neonatal nutrition, as illustrated by some recent data from our group. We discuss the concept of a 'relative' EFA/LCP deficiency in the fetus as the outcome of high transplacental glucose flux. This flux may in the fetus augment de novo synthesis of fatty acids, which not only dilutes transplacentally transported EFA/LCP, but also causes competition of de novo synthesized oleic acid with linoleic acid for delta-6 desaturation. Such conditions were encountered by us in mothers with high body mass indices, diabetes mellitus and preeclampsia. The unifying factor might be compromised glucose homeostasis. In search of the milk arachidonic acid (AA) and docosahexaenoic acid (DHA) contents of our African ancestors, we investigated women in Tanzania with high intakes of freshwater fish as only animal lipid source. These women had milk AA and DHA contents that were well above present recommendations for infant formulae. Both studies stimulate rethinking of 'optimal homeostasis'. Subtle signs of dysbalanced maternal glucose homeostasis may be important and observations from current Western societies may not provide us with an adequate basis for dietary recommendations.

Low status of long-chain polyunsaturated fatty acids (LCP) and essential fatty acids (EFA) in the fetus is associated with less favorable neonatal neurological condition. A 'relative', rather than 'absolute' EFA deficiency might explain this finding. A relative EFA deficiency may derive from impaired maternal glucose homeostasis. We measured fatty acids in umbilical vessels of infants born to 7 mothers with (gestational) diabetes mellitus and of 258 infants born to healthy mothers. Umbilical veins of infants of diabetic mothers had higher omega7 and omega9 fatty acids and DHA deficiency index and lower 20:4omega6 and EFA index. Their umbilical arteries had higher omega7 and omega9 fatty acids, and lower 20:4omega6, LCP and EFA index. We conclude that children born to mothers with poor glucose homeostasis have lower EFA and LCP status, which is consistent with a 'relative deficiency' deriving from augmented de novo fatty acid synthesis from the abundant glucose.

Background: We found an unexplained, persistent discrepancy between the outcomes of two apolipoprotein-E (apo-E) genotyping methods for a patient with features of familial dysbetalipoproteinaemia (FD). Polymerase chain reaction - restriction fragment length polymorphism resulted in the apo-epsilon(2)/epsilon(2) genotype, whereas minisequencing indicated apo-epsilon(2)/epsilon(3). The discrepancy was predicted to derive from a novel mutation., Methods: Sequencing of patient DNA, set-up of a mutation analysis method and establishment of mutation occurrence in 19 family members of the proband and investigation of its association with serum lipid indices., Results: Sequencing demonstrated a G-insertion in codon 95 or 96 ((95)AAG-(96-)GAG-->(95)AAG-(96)GGA-G) of the apo-epsilon(3) allele. The mutation, designated apo-epsilon(3Groningen), was predicted to cause a frameshift, a premature stop codon at codon 146 (AAG-->TAA) and the expression of a truncated apo-E protein, if any. Four family members with the apo-epsilon(3Groningen) were identified. Two family members with apo-epsilon(3)/epsilon(3Groningen) had serum lipid indices within reference ranges but low-serum apo-E. Three subjects with apo-epsilon(2)/epsilon(3Groningen), proband included, had serum cholesterol, triglycerides and calculated low-density lipoprotein-cholesterol levels above the reference ranges. Their electrophoresis pattern showed the classical broad-beta band, indicative of FD., Conclusion: Apo-epsilon(3Groningen) heterozygosity is unlikely to precipitate FD, unless provoked by compound apo-epsilon(2) heterozygosity or other FD precipitating factors.

Aim: Previously, we found a beneficial effect of 2 mo supplementation of infant formula with long-chain polyunsaturated fatty acids (LC-PUFA) on neurological condition at 3 mo in healthy term infants. The aim of the present follow-up study was to evaluate whether the effect on neurological condition persists until 18 mo., Methods: A prospective, double-blind, randomized control study was conducted. Three groups were formed: a control (CF; n = 169), an LC-PUFA-supplemented (LF; n = 146) and a breastfed (BF; n = 159) group. Information on potential confounders was collected at enrolment. At the age of 18 mo, neurodevelopmental condition was assessed by the age-specific neurological examination of Hempel and the Bayley scales. The Hempel assessment resulted in a clinical neurological diagnosis, a total optimality score and a score on the fluency of motility. The Bayley scales resulted in mental and psychomotor developmental indices. Attrition at 18 mo was 5.5% and non-selective. Multivariate regression analyses were carried out to evaluate the effect of type of feeding while adjusting for confounders., Results: None of the children had developed cerebral palsy and 23 (CF: n = 8; LF: n = 10; BF: n = 5) showed minor neurological dysfunction. The groups did not show statistically significant differences in clinical neurological condition, neurological optimality score, fluency score, and the psychomotor and mental development indices. Multivariate analysis confirmed that there was no effect of type of feeding on neurological condition., Conclusion: This study indicates that the beneficial neurodevelopmental effect of 2 mo LC-PUFA supplementation in healthy term infants can not be detected at the age of 18 mo.

Long-chain polyunsaturated fatty acids, notably arachidonic (AA) and docosahexaenoic (DHA) acids are abundant in brain and may be conditionally essential in fetal life. We investigated umbilical artery (UA) and vein (UV) fatty acid compositions and early neonatal neurological condition in 317 term infants. Neurological condition was summarized as a clinical classification and a 'neurological optimality score' (NOS). Neurologically abnormal infants (n=27) had lower UV DHA and essential fatty acid (EFA) status. NOS correlated positively with AA (UV), and EFA (UV) and DHA status (UV and UA) and negatively with 18:2omega6 and omega9 (UV), and 20:3omega9, omega7 and C18 trans fatty acids (UV and UA). UV DHA, AA, saturated fatty acids, gestational age and obstetrical optimality score explained 16.2% of the NOS variance. Early postnatal neurological condition seems negatively influenced by lower fetal DHA, AA and EFA status. C18 trans fatty acids and 18:2omega6 may exert negative effects by impairment of LCP status.

Epidemiological studies indicate a positive relation between iron status and coronary artery disease (CAD) risk The HFE C282Y allele is associated with increased iron status and higher CAD risk. We investigated whether HFE C282Ymight be a CAD risk factor in Curaçao in a case-control study design. The patient group comprised 42 men and 10 women. Fifty-four men and 30 women without history of CAD served as age and gender matched controls. HFE C282Y genotypes were established using sequence-specific priming polymerase chain reaction. None of the investigated subjects were homozygous for HFE C282Y, whereas 5/52 (9.6%) CAD patients and 1/84 controls (1.2%) were heterozygous for HFE C282Y (p = 0.03). The HFE C282Y mutation was 8.8 fold (95% CI 1.001, 77.8; p = 0.049) more prevalent in CAD patients than in controls. The HFE C282Y allele frequency in Curaçao is higher than that of African populations, but comparable with that of Jamaica. We conclude that Curaçao CAD patients have somewhat higher frequency of HFE C282Y heterozygosity than controls, and that the HFE C282Y allele frequency in the Curaçao population is higher than might be expected in persons of African descent. The consequences of HFE C282Y heterozygosity as CAD risk factor are as yet uncertain, since there is no proof that iron lowering reduces CAD risk.

To investigate the minimal duration of exclusive breastfeeding for optimal neurological outcome, we assessed the quality of general movements (GM) at 3 mo of 147 breastfed healthy term infants that were followed from birth. The quality of GM is a sensitive marker of neurological condition. The quality of GM was classified as normal-optimal, normal-suboptimal, mildly abnormal and definitely abnormal. Information on social and pre- and perinatal conditions and the duration of breastfeeding was collected prospectively. Logistical regression analyses were used to adjust for confounders. There was a positive association between breastfeeding duration and movement quality, with a saturation effect at the age of approximately 6 wk. In the group of infants breastfed for < or = 6 wk (n = 55), 18% exhibited normal-optimal GM, 47% normal-suboptimal GM, and 47% mildly abnormal GM. In contrast, in the group of infants breastfed for > 6 wk (n = 92), 43% exhibited normal-optimal GM, 45% normal-suboptimal GM, and 12% mildly abnormal GM. Exclusive breastfeeding for >6 wk was therefore associated with markedly less abnormal and more normal-optimal GM. Thus, we conclude that breastfeeding for > 6 wk might improve the neurological condition in infants.

Background: Homocysteine is a cardiovascular disease risk factor. We investigated, both in subjects with past plasma total homocysteine (tHcy) test indications and healthy adults, the diagnostic value of a fasting (tHcy) (f-tHcy) and the added value of a post-methionine-load tHcy (postload-tHcy)., Methods: Plasma homocysteine cut-off values were retrospectively used for hyperhomocysteinemia assessment in 3477 subjects with past tHcy test indications and 177 apparently healthy subjects. Cut-off values were based on reference limits (f-tHcy < or = 15.0; postload-tHcy < or = 50.0 micro mol/l), relative risk (f-tHcy < or = 12.0, postload-tHcy < or = 38.0; or f-tHcy < or = 10.0 micro mol/l) and vitamin-optimized reference limits (f-tHcy < or = 9.3; postload-tHcy < or = 35.1 micro mol/l)., Results: Use of the American Heart Association 10 micro mol/l f-tHcy cut-off value gave hyperhomocysteinemia prevalences of 65% in subjects with past tHcy test indications and 50% in healthy subjects. The combination of the vitamin-optimized reference limits for f-tHcy and postload-tHcy gave a hyperhomocysteinemia prevalence of 79% in subjects with tHcy test indications, of which only 5% was on account of increased postload-tHcy. Corresponding values for healthy subjects were 68% and 3%, respectively., Conclusions: Employment of a 10 micro mol/l (American Heart Association) or 9.3 micro mol/l (vitamin-optimized reference) cut-off value leaves no indications for tHcy testing from an evidence-based point-of-view.

Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1-15 yr as well as in venous cord blood lipids of full-term infants. Here we report FA compositional data of cord blood vessel wall lipids in 308 healthy, full-term infants (gestational age: 39.7 +/- 1.2 wk, birth weight: 3528 +/- 429 g, mean +/- SD). The median (interquartile range) of the sum of 18-carbon trans FA was 0.22 (0.13) % w/w in umbilical artery and 0.16 (0.10) % w/w in umbilical vein lipids. Nonparametric correlation analysis showed significant inverse correlations between the sum of 18-carbon trans FA and both arachidonic acid and DHA in artery (r = -0.38, P < 0.01, and r = -0.20, P < 0.01) and vein (r = -0.36, P < 0.01, and -0.17, P < 0.01) wall lipids. In addition, the sum of 18-carbon trans FA was significantly positively correlated to Mead acid, a general indicator of EFA deficiency, in both artery (r = +0.35, P < 0.01) and vein (r = +0.31, P< 0.01) wall lipids. The present results obtained in a large group of full-term infants suggest that maternal trans FA intake is inversely associated with long-chain PUFA status of the infant at birth.