Publications
339 results found
Crawford MA, Sinclair AJ, Wang Y, et al., 2023, Docosahexaenoic acid explains the unexplained in visual transduction, Entropy: international and interdisciplinary journal of entropy and information studies, Vol: 25, ISSN: 1099-4300
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.
Crawford MA, Sinclair AJ, Hall B, et al., 2023, The imperative of arachidonic acid in human reproduction, Progress in Lipid Research, Vol: 91, Pages: 1-22, ISSN: 0163-7827
We are presenting new evidence on essential fatty acids (EFA) in prenatal human development. We have demonstrated, for the first time, the detailed process of active selection of some fatty acids by the placenta (biomagnification) and rejection of others (bioreduction) and how this strategy is of supreme importance for understanding of the biology of human reproduction. The biomagnification process by the placenta is dominated by arachidonic acid (ArA) and its allies: di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid. Stearic acid is similarly bio-magnified which is likely to provide for the sn-1 position in membrane synthesis. In contrast there is a bioreduction of oleic, linoleic and all ω3 precursors for docosahexaenoic acid (DHA), including eicosapentaenoic acid (EPA). Although DHA is biomagnified, the amplification from mother to fetus is small compared to ArA. We report on the dominant compartmentalisation of ArA from mother to fetal plasma, cell membranes of red cells, mono-nuclear cells, endothelium and the placenta. We conclude that ArA and its allies, play a paramount role in the development of the products of conception. It is plausible that inadequate provision of ArA may be relevant to the neuro-vascular complications of prematurity and neurodevelopmental disorders associated with premature birth. We present evidence of ArA's universal role from an identical arachidonic acid-based strategy observed in contrasting cultures. The dominance of ArA in the prenatal and in post-natal nutritional provision by human milk makes a compelling case for re-evaluation of its role, especially in reproductive biology.
Schmidt WF, Chen F, Broadhurst CL, et al., 2022, Unique and redundant spectral fingerprints of docosahexaenoic, alpha-linolenic and gamma-linolenic acids in binary mixtures, JOURNAL OF MOLECULAR LIQUIDS, Vol: 358, ISSN: 0167-7322
Wang Y, Johnson M, Crawford M, et al., 2022, On COVID-19 and membrane lipids and public health, Science and Technology of Cereals, Oils and Foods, Vol: 30, Pages: 55-58
Coronavirus has a lipid membrane. Whist replication requires hijacking the RNA tools of the host to synthesize virion protein, that then has to be wrapped in a lipid membrane to enable the budding off which extends the infection. Recent studies implicate certain essential fatty acids with replication suppression properties. The lipid membrane is commonly thought of as a fatty barrier to water solubles. It is however highly ordered and compositionally specific to cellular and sub cellular functions. There will likely also be an optimum specificity for the viral coat. Whist DNA, RNA and protein compositions are not affected by diet, the lipid membrane is. Moreover, the greater sensitivity of males over females to inadequacy of these essential fatty acids and membrane integrity has been known since the 1960s. With evidence that arachidonic and docosahexaenoic acids exhibiting anti-viral, immune, anti-inflammatory, blood pressure control and resolvin activity, their status needs to be urgently examined in relation to the prevention and therapy for Covid-19. It would also be advisable to re-assess food policy. The lipid requirements for the membrane rich systems as in the brain, nervous, vascular and immune systems have not been considered. There is little doubt these were significant in shaping the human genome over several million years. Departure from such conditions would be predicted to put populations at risk to disorder and infection, with males being more at risk than females.
Crawford M, 2022, A study of severe malnutrition in Malawian children illustrates the need for appropriate lipid nutrition to protect the brain, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 115, Pages: 1257-1258, ISSN: 0002-9165
Crawford MA, Wang Y, Marsh DE, et al., 2022, 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, Prostaglandins, Leukotrienes and Essential Fatty Acids, Vol: 180, Pages: 1-16, ISSN: 0952-3278
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.
Crawford MA, Schmidt WF, Broadhurst CL, et al., 2021, 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, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 166, ISSN: 0952-3278
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- Citations: 6
Ogundipe E, Samuelson S, Crawford MA, 2020, Gestational diabetes mellitus prediction? A unique fatty acid profile study, Nutrition and Diabetes, Vol: 10, ISSN: 2044-4052
ObjectiveTo elucidate whether women at risk of gestational diabetes mellitus (GDM) have a unique fatty acid profile compared to women considered normal healthy controls (NHC).MethodsThree 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.ResultsGDM 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).ConclusionThis 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.
Ogundipe E, 2020, Gestational diabetes mellitus prediction? A unique fatty acid profile study, Nature Diabetes
Hibbeln JR, Spiller P, Brenna JT, et al., 2019, Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 151, Pages: 14-36, ISSN: 0952-3278
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- Citations: 57
Spiller P, Hibbeln JR, Myers G, et al., 2019, An abundance of seafood consumption studies presents new opportunities to evaluate effects on neurocognitive development, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 151, Pages: 8-13, ISSN: 0952-3278
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- Citations: 8
Charani E, Cunnington AJ, Yousif AHA, et al., 2019, In transition: current health challenges and priorities in Sudan, BMJ Global Health, Vol: 4:e001723, ISSN: 2059-7908
A recent symposium and workshop in Khartoum, the capital of the Republic of Sudan, brought together broad expertise from three universities to address the current burden of communicable and non-communicable diseases facing the Sudanese healthcare system. These meetings identified common challenges that impact the burden of diseases in the country, most notably gaps in data and infrastructure which are essential to inform and deliver effective interventions. Non-communicable diseases, including obesity, type 2 diabetes, renal disease and cancer are increasing dramatically, contributing to multimorbidity. At the same time, progress against communicable diseases has been slow, and the burden of chronic and endemic infections remains considerable, with parasitic diseases (such as malaria, leishmaniasis and schistosomiasis) causing substantial morbidity and mortality. Antimicrobial resistance has become a major threat throughout the healthcare system, with an emerging impact on maternal, neonatal, and paediatric populations. Meanwhile, malnutrition, micronutrient deficiency, and poor perinatal outcomes remain common and contribute to a lifelong burden of disease. These challenges echo the UN sustainable development goals and concentrating on them in a unified strategy will be necessary to address the national burden of disease. At a time when the country is going through societal and political transition, we draw focus on the country and the need for resolution of its healthcare needs.
Ogundipe E, Tusor N, Wang Y, et al., 2018, Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 138, Pages: 6-13, ISSN: 0952-3278
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- Citations: 21
Crawford MA, Thabet M, Wang Y, 2018, An introduction to a theory on the role of pi-electrons of docosahexaenoic acid in brain function - The Quantum Brain, OCL - Oilseeds and fats, crops and lipids, Vol: 25, ISSN: 1258-8210
In Part I, we discuss the background to views on brain function and our thesis that it is conducted by π-electrons which perform sensory reception, memory, action, cognition and consciousness. Our thesis is consistent with the classical views of ion movement and synaptic protein strengthening. However, protein based views contain no element of precision for the signal. Precision is essential for true signal transduction of sensory input and the faithful execution of learnt neural pathways. In Part II, we incorporate these principles to discuss the mechanism whereby electron function adds precision of signal energy to the process through the Pauli Exclusion Principle. The Huxley-Hodgkin (HH) account of neural function describes the movement of sodium, potassium and calcium ions to create electrochemical potentials across membranes with well-established mathematical and experimental support. To explain learning, consciousness and perception, others have claimed brain function depends on protein synthesis or RNA coding. Some consider super position and collapse as the computational mechanism. This however is fragile with no mechanism described to protect from natural collapse and decoherence at the temperatures of the brain. A novel approach was adopted by Penrose and Hammeroff who describe consciousness as a function of ʻobjective reduction’ (ʻOR’) of the quantum state. This orchestrated OR activity (ʻOrch OR’) is taken to result in moments of conscious awareness and/or choice (Hameroff S, Penrose R. 2014 Consciousness in the universe: a review of the ʻOrch OR’ theory. Phys Life Rev 11(1): 39–78. Doi: 10.1016/j.plrev.2013.08.002. Epub 2013 Aug 20). Orch-OR operates in principle in protein tubules of neurons. This concept is non-computational and has received much attention with a convincing advocacy and its share of criticism. The advocacy includes the fossil record of organisms that emerged throughout the first Cambrian period with on
Crawford MA, Thabet M, Wang Y, et al., 2018, A theory on the role of π-electrons of docosahexaenoic acid in brain function. The six methylene-interrupted double bonds and the precision of neural signaling, OCL-OILSEEDS AND FATS CROPS AND LIPIDS, Vol: 25, ISSN: 1258-8210
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- Citations: 3
Sassine AJ, Sivarajasingam SP, Cocker ATH, et al., 2018, Erythrocyte oleic acid is correlated with increasing natural killer cells in maternal blood, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Elsevier, Pages: 319A-319A, ISSN: 1933-7191
Sassine AJ, Wang Y, Singh N, et al., 2018, Fatty Acid Composition in the Preterm and Term Human Placentae., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 302A-302A, ISSN: 1933-7191
Sassine AJ, Sooranna GR, Singh N, et al., 2017, Placental Fatty Acid Translocase (FAT/CD36) and Tranport Protein-4 (FATP-4) Are Less Expressed in the Human Preterm Than Term Placenta., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 280A-280A, ISSN: 1933-7191
Stark AH, Reifen R, Crawford MA, 2016, Past and Present Insights on Alpha-linolenic Acid and the Omega-3 Fatty Acid Family., Crit Rev Food Sci Nutr, Vol: 56, Pages: 2261-2267
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.
Ogundipe E, Johnson MR, Wang Y, et al., 2016, Peri-conception maternal lipid profiles predict pregnancy outcomes, Prostaglandins, Leukotrienes and Essential Fatty Acids, Vol: 114, Pages: 35-43, ISSN: 0952-3278
In this study, healthy women and those at high-risk of adverse pregnancy outcomes (pre-eclampsia, fetal growth restriction, gestational diabetes) were selected to assess the effect of fatty acid supplementation. The purpose of this paper is to report two novel findings (i) at recruitment the receiver operating characteristic (ROC) for erythrocyte oleic acid predicted spontaneous delivery at 34 weeks gestation (ROC=0.926 n=296) for all women entering the study. Further analysis revealed oleic and all monounsaturated fatty acids were similarly predictive with or without a supplement during the pregnancy. (ii) At delivery, we observed a biomagnification of saturated fatty acids from mother to fetus with the reverse for monounsaturates. The major conclusions are (i) the status of the mother in the months prior to conception is a stronger predictor of preterm delivery than the events during the pregnancy. (ii) Saturated fats may be playing an important function in supporting fetal membrane growth.
Crawford MA, Wang Y, Forsyth S, et al., 2015, The European Food Safety Authority recommendation for polyunsaturated fatty acid composition of infant formula overrules breast milk, puts infants at risk, and should be revised, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 102, Pages: 1-3, ISSN: 0952-3278
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- Citations: 37
Matsudaira T, Gow RV, Kelly J, et al., 2015, Biochemical and Psychological Effects of Omega-3/6 Supplements in Male Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized, Placebo-Controlled, Clinical Trial., J Child Adolesc Psychopharmacol, Vol: 25, Pages: 775-782
BACKGROUND: An abnormality in long chain-polyunsaturated fatty acid (LC-PUFA) levels has been implicated in attention-deficit/hyperactivity disorder (ADHD). Studies evaluating LC-PUFA supplementation for therapeutic efficacy in ADHD have shown mixed and, therefore, inconclusive results. METHODS: Seventy-six male adolescents (age 12-16 years, mean = 13.7) with ADHD were assessed for the effects of 12 weeks omega-3 and omega-6 supplements on biochemical and psychological outcomes in a randomized, placebo-controlled, clinical trial. The primary outcome measure was change in the Conners' Teacher Rating Scales (CTRS) following 12 weeks of supplementation of LC-PUFA or placebo. At baseline, the placebo and treatment groups had comparable levels of LC-PUFA as measured by red blood cell phosphatidylcholine. In the treatment group, supplementation enhanced eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total omega-3 fatty acid levels. RESULTS: No superiority of LC-PUFAs to placebo was observed on the primary outcome. Further, there were no reliable treatment effects on aggression, impulsivity, depression, and anxiety. CONCLUSIONS: Future studies should use larger sample sizes and longer supplementation period to detect small-modest effects for clinical recommendations in ADHD.
Patrikios IS, Loucaides GN, Pantzaris M, et al., 2015, Omega-3, Omega-6 PUFA and γ-Tocopherol in multiple sclerosis: PLP10 intervention efficacy and red blood cells' membrane lipids composition, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 323-323, ISSN: 1352-4585
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- Citations: 1
Bueno AA, Brand A, Neville MM, et al., 2015, Erythrocyte phospholipid molecular species and fatty acids of Down syndrome children compared with non-affected siblings, BRITISH JOURNAL OF NUTRITION, Vol: 113, Pages: 72-81, ISSN: 0007-1145
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- Citations: 13
Cunnane SC, Crawford MA, 2014, Energetic and nutritional constraints on infant brain development: Implications for brain expansion during human evolution, JOURNAL OF HUMAN EVOLUTION, Vol: 77, Pages: 88-98, ISSN: 0047-2484
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- Citations: 86
Crawford MA, Broadhurst CL, Cunnane S, et al., 2014, Nutritional Armor in Evolution: Docosahexaenoic Acid as a Determinant of Neural, Evolution and Hominid Brain Development, Military Medicine, Vol: 179, Pages: 61-75, ISSN: 1930-613X
Crawford MA, Broadhurst CL, Guest M, et al., 2014, A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution (vol 88, pg 5, 2013), PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 91, Pages: 233-233, ISSN: 0952-3278
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- Citations: 1
Brenna JT, Burdge GC, Crawford MA, et al., 2014, RE: Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 106, ISSN: 0027-8874
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- Citations: 5
Crawford MA, Hussein I, Nyuar KB, et al., 2014, The global crisis in brain nutrition and the rise in mental-ill health, Human Evolution, Vol: 29, Pages: 207-227, ISSN: 0393-9375
H. sapiens is defined by a large, complex brain. Our genome is 96% identical to that of the chimpanzee, yet our behavior is 96% different. Cerebral expansion cannot be explained by an origin on the African savannah, as expansion requires docosahexaenoic acid (DHA) and trace elements such as iodine, selenium, copper, zinc and manganese, all of which are concentrated in the aquatic food webs. These brain-specific nutrients are in poor supply inland, as witnessed by the 2 billion today at risk of iodine deficiency and mental retardation. This century we are seeing a rise in obesity, metabolic syndrome and mental ill-health, especially amongst young people. The rise in mental ill-health is closely following the previous trend for increased cardiovascular disease, moving from the US and EU towards developing countries. The health audits in the EU and UK have put the cost of brain disorders and mental illhealth higher than any other burden of ill health. In the UK, the Department of Health has estimated the cost to be greater than heart disease and cancer combined. Mental ill-health is now predicted to reach the top three in the ranking of the worldwide burdens of ill-health in 6 years' time. This trend cannot be reversed unless the amount of specialist lipid nutrients, especially required by the brain for its growth, structure and function, is increased in global diets. Similarly, reversing poverty and malnutrition requires more attention on increasing brain-specific nutrients, than protein and calories. Evolution does not stand still. The rise in mental ill-health is related to intensive land agriculture and highly processed foods, providing diets nearly devoid of DHA and its accessory micronutrients. If the upward trend in mental ill health continues throughout this century then prosperous, peaceful, cooperative societies will become unreachable for most humans. Increasing mental ill-health represents a serious threat to humanity because it amounts to human de-evolutio
Sumich AL, Matsudaira T, Heasman B, et al., 2013, Fatty acid correlates of temperament in adolescent boys with attention deficit hyperactivity disorder., Prostaglandins Leukot Essent Fatty Acids, Vol: 88, Pages: 431-436
Atypical fatty acid metabolism has been reported in attention deficit hyperactivity disorder (ADHD), however, its relationship with temperament in this population is unclear. The current study investigated the association between blood levels of fatty acids implicated in brain structure and function (omega-3, omega-6, omega-9) and personality traits of stability (neuroticism, conscientiousness and agreeableness) and plasticity (extraversion and openness). Twenty right-handed adolescent boys with ADHD completed a self-report NEO-FFI personality questionnaire, and had fatty acid content assessed from red blood using gas chromatography. Pearson's correlations showed no significant associations between omega-3 levels and personality. After correction for multiple comparisons, Adrenic Acid (C22:4n6) was inversely associated with stability. Oleic acid (C18:1n9) was positively associated with plasticity. Results are in line with a role of fatty acids in brain function. They suggest that those fatty acids that are involved in myelination (Adrenic, Oleic) have the strongest associations with temperament in adolescents with ADHD.
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