Docosahexaenoic Acid Explains the Unexplained in Visual Transduction.

In George Wald's Nobel Prize acceptance speech for "discoveries concerning the primary physiological and chemical visual processes in the eye", he noted that events after the activation of rhodopsin are too slow to explain visual reception. Photoreceptor membrane phosphoglycerides contain near-saturation amounts of the omega-3 fatty acid docosahexaenoic acid (DHA). The visual response to a photon is a retinal cis-trans isomerization. The trans-state is lower in energy; hence, a quantum of energy is released equivalent to the sum of the photon and cis-trans difference. We hypothesize that DHA traps this energy, and the resulting hyperpolarization extracts the energized electron, which depolarizes the membrane and carries a function of the photon's energy (wavelength) to the brain. There, it contributes to the creation of the vivid images of our world that we see in our consciousness. This proposed revision to the visual process provides an explanation for these previously unresolved issues around the speed of information transfer and the purity of conservation of a photon's wavelength and supports observations of the unique and indispensable role of DHA in the visual process.

Past and Present Insights on Alpha-linolenic Acid and the Omega-3 Fatty Acid Family.

Alpha-linolenic acid (ALA) is the parent essential fatty acid of the omega-3 family. This family includes docosahexaenoic acid (DHA), which has been conserved in neural signaling systems in the cephalopods, fish, amphibian, reptiles, birds, mammals, primates, and humans. This extreme conservation, in spite of wide genomic changes of over 500 million years, testifies to the uniqueness of this molecule in the brain and affirms the importance of omega-3 fatty acids. While DHA and its close precursor, eicosapentaenoic acids (EPA), have received much attention by the research community, ALA, as the precursor of both, has been considered of little interest. There are many papers on ALA requirements in experimental animals. Unlike humans, rats and mice can readily convert ALA to EPA and DHA, so it is unclear whether the effect is solely due to the conversion products or to ALA itself. The intrinsic role of ALA has yet to be defined. This paper will discuss both recent and historical findings related to this distinctive group of fatty acids, and will highlight the physiological significance of the omega-3 family.

Erythrocyte phospholipid molecular species and fatty acids of Down syndrome children compared with non-affected siblings.

The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their non-affected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0-16 : 0, 16 : 0-18 : 1 and 16 : 0-18 : 2n-6, with reduced levels of 16 : 0-20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0-18 : 2n-6 and nearly half the proportion of 16 : 0-20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD.

Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development.

NGF blocks polyunsaturated fatty acids biosynthesis in n-3 fatty acid-supplemented PC12 cells.

Regulation of polyunsaturated fatty acid (PUFA) biosynthesis in proliferating and NGF-differentiated PC12 pheochromocytoma cells deficient in n-3 docosahexaenoic acid (DHA 22:6n-3) was studied. A dose- and time-dependent increase in eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3) and DHA in phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer) glycerophospholipids (GPL) via the elongation/desaturation pathway following alpha-linolenic acid (ALA, 18:3n-3) supplements was observed. That was accompanied by a marked reduction of eicosatrienoic acid (Mead acid 20:3n-9), an index of PUFA deficiency. EPA supplements were equally effective converted to 22:5n-3 and 22:6n-3. On the other hand, supplements of linoleic acid (LNA, 18:2n-6) were not effectively converted into higher n-6 PUFA intermediates nor did they impair elongation/desaturation of ALA. Co-supplements of DHA along with ALA did not interfere with 20:5n-3 biosynthesis but reduced further elongation to 22-hydrocarbon PUFA intermediates. A marked decrease in the newly synthesized 22:5n-3 and 22:6n-3 following ALA or EPA supplements was observed after nerve growth factor (NGF)-induced differentiation. NGF also inhibited the last step in 22:5n-6 formation from LNA. These results emphasize the importance of overcoming n-3 PUFA deficiency and raise the possibility that growth factor regulation of the last step in PUFA biosynthesis may constitute an important feature of neuronal phenotype acquisition.

Diet and cancer and heart disease.

The modern Western diet bears little resemblance to the diet which forged the human genome over many million years. The change in basic food structure is operating to distort biology even before conception and into late years, with the epidemic of obesity and diabetes likely to lead to stroke, heart disease, and now dementia, being flagged as a consequence. In addition, mental ill health is overtaking all other burdens of ill health, and almost certainly has its roots in early disturbance of brain development. Whilst lifestyle will be playing its part, there can be little doubt that the common denominator is the aberrations in food development, predominantly in the last century. It seems it is time to reassess food policy. The principle of food production should be nutrition and human health. The globalisation of a food structure linked to such disorders and their appearance globally in response asks that steps be taken to protect other countries from making the same mistakes.

New European Food Safety Authority recommendation for infant formulae contradicts the physiology of human milk and infant development.

The European Food Safety Authority (EFSA) has concluded from a limited review of the literature that although docosahexaenoic acid (DHA) was required for infant formula, arachidonic acid was not 'even in the presence of DHA'. The EFSA report mistakes a nutrient ubiquitous in the diets of infants, and with wide-ranging effects, for an optional drug targeted to a particular outcome that is properly excluded when no benefit is found for that particular outcome. The EFSA's conclusion is not evidence-based. Its conclusions are grounded in trials which tested functionality of DHA, not arachidonic acid. Arachidonic acid has very different biological functions, for instance, in the vasculature and in specific aspects of immunity. None of the trials cited tested any property specific to arachidonic acid. The test of time through natural selection and human evolution has resulted in milk composition in which arachidonic acid and its long-chain polyenoic family members are conserved and occupy a prominent position. As DHA suppresses arachidonic acid, an infant formula with DHA and no arachidonic acid runs the risk of cardio- and cerebrovascular morbidity through suppression of the favourable eicosanoid derivatives of arachidonic acid and cell structural integrity. The EFSA recommendation should be rejected forthwith as unsafe and risking lifelong disability.

The imperative of arachidonic acid in early human development.

This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA into the developing brain of rat pups, its conservation as a principal component in the brains of 32 mammalian species and the high proportion delivered by the human placenta for foetal nutrition, compared to its parent linoleic acid (LA). ArA is quantitatively the principal acyl component of membrane lipids from foetal red cells, mononuclear cells, astrocytes, endothelium, and placenta. Functionally, we present evidence that ArA, but not DHA, relaxes the foetal mesenteric arteries. The placenta biomagnifies ArA, doubling the proportion of the maternal level in cord blood. The proportions of ArA and its allies (di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid) are similar or higher than the total of ω3 fatty acids in human milk, maintaining the abundant supply to the developing infant. Despite the evidence of the importance of ArA, the European Food Standard Agency, in 2014 rejected the joint FAO and WHO recommendation on the inclusion of ArA in infant formula, although they recommended DHA. The almost universal dominance of ArA in the membrane phosphoglycerides during human organogenesis and prenatal growth suggests that the importance of ArA and its allies in reproductive biology needs to be re-evaluated urgently.

Net effects explains the benefits to children from maternal fish consumption despite methylmercury in fish.

In 2001 the U.S. Food and Drug Administration (FDA) issued precautionary advice to pregnant women to limit fish consumption over concern that the methylmercury content might harm their children's neurodevelopment. This concern was based largely on results from an epidemiological study of mothers primarily exposed to methylmercury from consuming pilot whale. Subsequently, FDA and the World Health Organization/Food and Agriculture Organization (WHO/FAO) undertook independent assessments of fish consumption that considered net effects from both fish nutrients, primarily omega-3 fatty acids, as beneficial and methylmercury as harmful. Both assessments estimated that when mothers regularly consume fish during pregnancy, their children are likely to have improved neurodevelopment compared to children of non-fish eaters despite their exposure to methylmercury. These estimated improvements included gains of two to over five full scale IQ points from levels of maternal consumption that are achievable in most of the world. Consistent with those estimates, human research on fish consumption and child neurodevelopment from more than 200,000 mother-child pairs now collectively reports 51 beneficial associations with neurodevelopmental outcomes and three adverse associations, the latter with no discernable pattern. These associations include full scale IQ gains similar to, or somewhat higher than, those estimated by FDA and FAO/WHO. Also consistent with the FDA and FAO/WHO estimates, research has reported beneficial associations with fish consumption when pregnant women are exposed to methylmercury from fish in excess of the U.S. Environmental Protection Agency's (EPA) Reference Dose (RfD). Our analysis evaluates how the net effects approach as utilized by FDA and FAO/WHO provides a holistic explanation for these results with implications for public health policy. This concordance of net effects modeling and empirical scientific evidence supports a clarification of current public health recommendations to focus on greater fish consumption by pregnant women for their children's neurodevelopment.

The role of docosahexaenoic and the marine food web as determinants of evolution and hominid brain development: the challenge for human sustainability.

Life originated on this planet about 3 billion years ago. For the first 2.5 billion years of life there was ample opportunity for DNA modification. Yet there is no evidence of significant change in life forms during that time. It was not until about 600 million years ago, when the oxygen tension rose to a point where air-breathing life forms became thermodynamically possible, that a major change can be abruptly seen in the fossil record. The sudden appearance of the 32 phyla in the Cambrian fossil record was also associated with the appearance of intracellular detail not seen in previous life forms. That detail was provided by cell membranes made with lipids (membrane fats) as structural essentials. Lipids thus played a major, as yet unrecognised, role as determinants in evolution. The compartmentalisation of intracellular, specialist functions as in the nucleus, mitochondria, reticulo-endothelial system and plasma membrane led to cellular specialisation and then speciation. Thus, not only oxygen but also the marine lipids were drivers in the Cambrian explosion. Docosahexaenoic acid (DHA) (all-cis-docosa-4,7,10,13,16,19-hexaenoic acid, C22:6ω3 or C22:6, n-3, DHA) is a major feature of marine lipids. It requires six oxygen atoms to insert its six double bonds, so it would not have been abundant before oxidative metabolism became plentiful. DHA provided the membrane backbone for the emergence of new photoreceptors that converted photons into electricity, laying the foundation for the evolution of other signalling systems, the nervous system and the brain. Hence, the ω3 DHA from the marine food web must have played a critical role in human evolution. There is also clear evidence from molecular biology that DHA is a determinant of neuronal migration, neurogenesis and the expression of several genes involved in brain growth and function. That same process was essential to the ultimate cerebral expansion in human evolution. There is now incontrovertible support of this hypothesis from fossil evidence of human evolution taking advantage of the marine food web. Lipids are still modifying the present evolutionary phase of our species; their signature is evident in the changing panorama of non-communicable diseases. The most worrying change in disease pattern is the sharp rise in brain disorders, which, in the European Union, has overtaken the cost of all other burdens of ill health at €386 billion for the 25 member states at 2004 prices. In 2007, the UK cost was estimated at £77 billion and confirmed in 2010 at £105 billion - greater than heart disease and cancer combined. The rise in mental ill health is now being globalised. The solution to the rising vascular disorders in the last century and now brain disorders in this century lies in a radical reappraisal of the food system, which last century was focussed on protein and calories, with little attention paid to the requirements of the brain - the very organ that was the determinant of human evolution. With the marine fish catch having plateaued 20 years ago and its sustainability now under threat, a critical aspect of this revision is the development of marine agriculture from estuarine, coastal and oceanic resources. Such action is likely to play a key role in future health and intelligence.

Sudanese women's and neonates' vitamin A status.

We have determined and compared the concentration levels of retinol and ß-carotene in the plasma of three Sudanese women groups (displaced southern Sudanese women (DSSW), non-displaced southern Sudanese (NDSSW) and northern Sudanese women (NSW)), who were either pregnant or non-pregnant; and in their neonates (cord plasma). Plasma samples were analysed by high-performance liquid chromatography using reversed-phase column and diode-array detectors. The results revealed that retinol and ß-carotene in the plasma of non-pregnant and pregnant women in the three groups were very low compared with studies reported elsewhere. Over 50% of pregnant DSSW and NDSSW had a low concentration of retinol plasma (< 0.70 µmol/L), and about 15-20% were deficient (< 0.35 µmol/L) according to World Health Organization criteria. Although the average retinol concentration in the plasma of pregnant NSW was > 0.70 µmol/L, which suggests sufficiency status, 32% showed lower levels and 10% were deficient. Plasma retinol ß-carotene levels in the neonates' cords were also lower than their mothers and in comparison with other studies. These findings are in agreement with previous survey data and clinical reports, which also suggest that vitamin A deficiency is of great concern in the country. We concluded that insufficient intake of food of animal origin and repeated malarial and other parasitic diseases are the most likely causes of vitamin A deficiency.

Dietary intake of Sudanese women: a comparative assessment of nutrient intake of displaced and non-displaced women.

OBJECTIVES: To determine the daily intake of essential micro- and macronutrients in Sudanese women, with specific focus on dietary fat and essential fatty acids, and compare the dietary intakes of internally displaced women with those of the non-displaced population. METHODS: Dietary intakes of displaced southern (n=44) and non-displaced southern (n=30) and northern (n=39) Sudanese women were obtained by single 24-hour recall method, and daily nutrient intakes were calculated using 'Foodbase' nutritional software. The displaced women were recruited from Mayo and Soba Aradi camps, south of Khartoum city; and non-displaced southern and northern Sudanese women were recruited from antenatal clinics, universities, hospitals and the community in Khartoum city and Omdurman, Sudan. RESULTS: Carbohydrates provided over 60% of dietary energy for all the Sudanese women groups. The displaced women had significantly lower intake of energy (1744 ± 344 kcal/d), starch (p<0.001) and carbohydrates (312 ± 11 g/d, p<0.01) than both non-displaced southern (1972 ± 229 kcal/d energy, 358 ± 56 g/d carbohydrates) and northern Sudanese women (1988 ± 226 kcal/d energy, 357 ± 56g/d carbohydrates). Fat intake was also lower in the displaced group (34.1 ± 11.9 g/d) than in the non-displaced counterpart (38.5 ± 10.2 g/d) (p<0.05), but was not significantly different from northern Sudanese women (37.6 ± 10.6, p>0.05). Intakes of iodine (33.60-56.96 µg/d), zinc (7.12-9.92 mg/d), retinol (226.1-349.7 µg/d), riboflavin (0.44-0.70 mg/d) and docosahexaenoic acid (11.70-33.49 mg/d) amongst Sudanese women were very low compared with recommendations. CONCLUSION: The Sudanese diet was less diverse and differences in energy and nutrients intakes between groups were due to the amounts of food consumed. This view is supported by a lack of significant differences when intakes were expressed as proportion of whole energy between all groups of women.

Dietary fat intake, body composition and blood lipids of university men and women.

BACKGROUND: Cardiovascular disease rates are high in the U.K., particular in men, and are related to dietary fat intake. We conducted a pilot study to investigate relationships between saturated and unsaturated dietary fat intakes, body composition and blood lipid parameters in Caucasian men and women at university. METHODS: Volunteers (52 men and 52 women; age range 20-50 years) were recruited from staff and students of London Metropolitan University. Dietary intake, body composition, blood pressure and fasting blood glucose and lipids were assessed. Gender differences between the measured variables and their relationships were assessed by Mann-Whitney U-test, and by multi-linear (stepwise) regression, respectively. RESULTS: Men consumed more saturated fat (29.5 vs. 20.5 g/day, p < 0.001), and had elevated levels of glucose (5.34 + 0.74 vs. 4.85 + 0.49 mmol/l, p < 0.001), low-density lipoprotein (LDL) cholesterol (2.99 + 1.5 vs. 2.62+ 0.74 mmol/l, p < 0.05), systolic blood pressure (126.4 + 11.0 vs. 112.6 + 17.2 mm/Hg, p < 0.001), and lower high-density lipoprotein (HDL) cholesterol (1.41 ± 0.34 vs. 1.83 ± 0.43, p < 0.001). Saturated fat was positively associated with total body fat ( p < 0.05), trunk fat ( p < 0.001), HDL cholesterol ( p < 0.05) and systolic blood pressure ( p < 0.001) in women, while in men docosahexaenoic acid and total cholesterol ( p < 0.05), total omega-3 fatty acids and LDL cholesterol ( p < 0.001), total omega-3 fatty acids and triglycerides ( p < 0.01) were positively related. Similar n-3 fatty acid intakes were reported in nutritionally aware students and other university subjects. CONCLUSIONS: The data of this study indicate gender-related differences in response to dietary fat, and widespread low compliance with n-3 fatty acid recommendations. Although the men are highly health conscious and physically active, their blood lipid levels are indicative of a risk of cardiovascular disease. In addition to enhanced nutritional education to increase seafood intakes in this age group of men and women, customised dietary and lifestyle advice may be required in the men.

Neurodevelopment, nutrition and genetics. A contemporary retrospective on neurocognitive health on the occasion of the 100th anniversary of the National Institute of Nutrition, Hyderabad, India.

In celebration of the centenary of the National Institute of Nutrition (NIN), Hyderabad, India (1918-2018), a symposium highlighted the progress in nutrition knowledge made over the century, as well as major gaps in implementation of that knowledge. Brain famine caused by a shortage of nutrients required for perinatal brain development has unfortunately become a global reality, even as protein-calorie famine was largely averted by the development of high yield crops. While malnutrition remains widespread, the neglect of global food policies that support brain development and maintenance are most alarming. Brain disorders now top the list of the global burden of disease, even with obesity rising throughout the world. Neurocognitive health, remarkably, is seldom listed among the non-communicable diseases (NCDs) and is therefore seldom considered as a component of food policy. Most notably, the health of mothers before conception and through pregnancy as mediated by proper nutrition has been neglected by the current focus on early death in non-neurocognitive NCDs, thereby compromising intellectual development of the ensuing generations. Foods with balanced essential fatty acids and ample absorbable micronutrients are plentiful for populations with access to shore-based foods, but deficient only a few kilometres away from the sea. Sustained access to brain supportive foods is a priority for India and throughout the world to enable each child to develop to their intellectual potential, and support a prosperous, just, and peaceful world. Nutrition education and food policy should place the nutritional requirements for the brain on top of the list of priorities.

Lipids in the origin of intracellular detail and speciation in the Cambrian epoch and the significance of the last double bond of docosahexaenoic acid in cell signaling.

One of the great unanswered biological questions is the absolute necessity of the polyunsaturated lipid docosahexaenoic acid (DHA; 22:6n-3) in retinal and neural tissues. Everything from the simple eye spot of dinoflagellates to cephalopods to every class of vertebrates uses DHA, yet it is abundant only in cold water marine food chains. Docosapentaenoic acids (DPAs; 22:5n-6 and especially 22:5n-3) are fairly plentiful in food chains yet cannot substitute for DHA. About 600 million years ago, multi-cellular, air breathing systems evolved rapidly and 32 phyla came into existence in a short geological time span; the "Cambrian Explosion". Eukaryotic intracellular detail requires cell membranes, which are constructed of complex lipids, and proteins. Proteins and nucleic acids would have been abundant during the first 2.5-5 billion years of anaerobic life but lipids, especially unsaturated fatty acids, would not. We hypothesize lipid biology was a key driver of the Cambrian Explosion, because it alone provides for compartmentalization and specialization within cells DHA has six methylene interrupted double bonds providing controlled electron flow at precise energy levels; this is essential for visual acuity and truthful execution of the neural pathways which make up our recollections, information processing and consciousness. The last double bond is critical for the evolution and function of the photoreceptor and neuronal and synaptic signaling systems. It completes a quantum mechanical device for the regulation of current flow with absolute signal precision based on electron tunneling (ET). DHA's methylene interruption distance is < 6 Å, making ET transfer between the π-orbitals feasible throughout the molecule. The possibility fails if one double bond is removed and replaced by a saturated bond as in the DPAs. The molecular biophysical foundation of neural signaling can also include the discrete pattern of paired spin states that arise in the DHA double bond and methylene regions. The complexity depends upon the number of C13 and H1 molecular sites in which spin states are coupled. Electron wave harmonics with entanglement and cohesion provide a mechanism for learning and memory, and power cognition and complex human brain functions.

Retailoring docosahexaenoic acid-containing phospholipid species during impaired neurogenesis following omega-3 alpha-linolenic acid deprivation.

Diminished levels of docosahexaenoic acid (22:6n-3), the major fatty acid (FA) synthesized from alpha-linolenic acid (18:3n-3), have been implicated in functional impairment in the developing and adult brain. We have now examined the changes in phospholipid (PL) molecular species in the developing postnatal cortex, a region recently shown to be affected by a robust aberration in neuronal cell migration, after maternal diet alpha-linolenic acid deprivation (Yavin et al. (2009)Neuroscience162(4),1011). The frontal cortex PL composition of 1- to 4-week-old rats was analyzed by gas chromatography and electrospray ionization/tandem mass spectrometry. Changes in the cortical PL molecular species profile by dietary means appear very specific as 22:6n-3 was exclusively substituted by docosapentaenoic acid (22:5n-6). However, molecular species were conserved with respect to the combination of specific polar head groups (i.e. ethanolamine and serine) in sn-3 and defined saturated/mono-unsaturated FA in sn-1 position even when the sn-2 FA moiety underwent diet-induced changes. Our results suggest that substitution of docosahexaenoic acid by docosapentaenoic acid is tightly regulated presumably to maintain a proper biophysical characteristic of membrane PL molecular species. The importance of this conservation may underscore the possible biochemical consequences of this substitution in regulating certain functions in the developing brain.

Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population.

Poor nutrient intake during pregnancy can adversely affect both infant and maternal health. The aim was to investigate the efficacy of multiple-micronutrient supplementation during pregnancy in a socially deprived population in the developed world. We conducted a randomised, double-blind, placebo-controlled trial of multiple-micronutrient supplementation including 20 mg Fe and 400 microg folic acid, from the first trimester of pregnancy in 402 mothers, in East London, UK. Nutrient status was measured at recruitment, and at 26 and 34 weeks of gestation. Infants were weighed at birth. At recruitment the prevalence of anaemia was 13 %, vitamin D insufficiency 72 %, thiamin deficiency 12 % and folate deficiency 5 %, with no differences between groups. Only 39 % of women completed the study; rates of non-compliance were similar in both groups. Intention-to-treat analysis showed that participants receiving treatment had higher mean Hb at 26 weeks of gestation (110 (sd 10) v.108 (sd 10) g/l; P = 0.041) and 34 weeks of gestation (113 (sd 12) v.109 (sd 10) g/l; P = 0.003) and packed cell volume concentrations at 26 weeks of gestation (0.330 (sd 0.025) v. 0.323 (sd 0.026) l/l; P = 0.011) and 34 weeks of gestation (0.338 (sd 0.029) v. 0.330 (sd 0.028) l/l; P = 0.014) compared with controls. Analysis of compliant women showed supplemented women had higher median concentrations of serum ferritin, erythrocyte folate and 25-hydroxyvitamin D later in gestation than controls. In the compliant subset (n 149), placebo mothers had more small-for-gestational age (SGA) infants (eight SGA v. thirteen; P = 0.042) than treatment mothers. Baseline micronutrient deficiencies were common; the multiple-micronutrient supplement was well-tolerated and improved nutrient status. Multiple-micronutrient supplements from early pregnancy may be beneficial and larger studies are required to assess impact on birth outcomes and infant development.

Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet.

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.

Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein.

OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.

Gestational diabetes mellitus prediction? A unique fatty acid profile study.

OBJECTIVE: To elucidate whether women at risk of gestational diabetes mellitus (GDM) have a unique fatty acid profile compared to women considered normal healthy controls (NHC). METHODS: Three hundred pregnant women were randomized to a control group (NHC) (n = 50) and to one of three high risk groups (n = 250), one of which was GDM (n = 50). At recruitment participants' booking bloods were taken and analyzed for lipid profiles. The GDM group's fatty acid profile is reported here. RESULTS: GDM women compared to NHC had elevated levels of omega 6 (n-6) fatty acids compared to omega 3 (n-3) fatty acids (p = 0.01), of linoleic acid (LA) to docosahexaenoic acid (DHA) p = 0.001, sequentially distorted levels of n-6 fatty acids LA and arachidonic acid (ArA) p = 0.035, as well as significantly depressed levels of n-3 DHA (p = 0.01). CONCLUSION: This paper shows that GDM women have a unique fatty acid profile with elevated levels of n-6 fats, depressed levels of n-3 fats and an abnormal pattern of sequential n-6 metabolism. This profile probably results from a combination of factors including underexpression and or poor utilization of desaturase enzymes, suboptimal dietary fatty acids intake, poor micronutrient status or dysbiosis of the microbiome. These results help inform development of a clinical predictive tool.