Fish and human brain evolution

Carlson and Kingston ([2007]: Am J Hum Biol 19:132–141) propose that preformed dietary docosahexaenoic acid (an omega-3 fatty acid in fish) did not have a significant role in hominin encephalization. Their position hinges on claiming that humans are able to make sufficient docosahexaenoic acid from the plant-based \parent" omega-3 fatty acid—alinolenic acid. They also suggest that hominin fish consumption occurred too late to have materially influenced encephalization. The authors quantify here a summary of the published data showing that humans cannot make sufficient docosahexaenoic acid to maintain normal infant brain development. The authors also provide evidence that the fossil record shows that some of the earliest hominins were regularly consuming fish. Hence, we reject Carlson and Kingston’s position and reiterate support for the concept that access to shore-based diets containing docosahexaenoic acid was necessary for hominin encephalization beyond the level seen in the great apes. Am. J. Hum. Biol. 19:578–581, 2007

Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements

La communauté scientifique accorde beaucoup d’intérêt à plusieurs acides gras polyinsaturés (PUFA) et à leur atténuation potentielle du taux de mortalité et de morbidité causée par les maladies dégénératives du système cardiovasculaire et du cerveau. Il n’en demeure pas moins que la confusion demeure au sujet du taux de conversion chez l’humain des PUFA en amont – acide linoléique ou α-linolénique (ALA) – en des substances respectives à plus longue chaîne. On ne connaît toujours pas les bienfaits potentiels de l’ALA en amont de l’acide eicosapentaénoïque (EPA) ou de l’acide docosahexaénoïque (DHA). La confusion est en partie née du fait que les mammifères disposent des enzymes nécessaires pour synthétiser les PUFA à chaîne longue à partir des PUFA en amont alors que les études in vivo chez l’humain révèlent que ≈5 % de l’ALA est converti en EPA et moins de 0,5 % de l’ALA est converti en DHA. Du fait de la très faible capacité de cette voie de synthèse chez des humains en bonne santé non végétariens, même un grand apport alimentaire d’ALA a un effet négligeable sur la concentration plasmatique de DHA ; on observe le même phénomène chez les PUFA oméga-6 : l’apport alimentaire d’acide linoléique a peu d’effet sur la concentration plasmatique de l’acide arachidonique. Nonobstant cette conversion à faible rendement, l’ALA et l’EPA ont potentiellement un rôle à jouer au plan de la santé chez l’humain qui n’a rien à voir avec la conversion en DHA dans la voie de désaturation-élongation des acides gras.Abstract: There is considerable interest in the potential impact of several polyunsaturated fatty acids (PUFAs) in mitigating the significant morbidity and mortality caused by degenerative diseases of the cardiovascular system and brain. Despite this interest, confusion surrounds the extent of conversion in humans of the parent PUFA, linoleic acid or alpha-linolenic acid (ALA), to their respective long-chain PUFA products. As a result, there is uncertainty about the potential benefits of ALA versus eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Some of the confusion arises because although mammals have the necessary enzymes to make the long-chain PUFA from the parent PUFA, in vivo studies in humans show that asymptotically equal to 5% of ALA is converted to EPA and <0.5% of ALA is converted to DHA. Because the capacity of this pathway is very low in healthy, nonvegetarian humans, even large amounts of dietary ALA have a negligible effect on plasma DHA, an effect paralleled in the omega6 PUFA by a negligible effect of dietary linoleic acid on plasma arachidonic acid. Despite this inefficient conversion, there are potential roles in human health for ALA and EPA that could be independent of their metabolism to DHA through the desaturation - chain elongation pathway

Survival of the fattest: fat babies were the key to evolution of the large human brain.

Abstract In the past 2 million years, the hominid lineage leading to modern humans evolved significantly larger and more sophisticated brains than other primates. We propose that the modern human brain was a product of having first evolved fat babies. Hence, the fattest (infants) became, mentally, the fittest adults. Human babies have brains and body fat each contributing to 11-14% of body weight, a situation which appears to be unique amongst terrestrial animals. Body fat in human babies provides three forms of insurance for brain development that are not available to other land-based species: (1) a large fuel store in the form of fatty acids in triglycerides; (2) the fatty acid precursors to ketone bodies which are key substrates for brain lipid synthesis; and (3) a store of long chain polyunsaturated fatty acids, particularly docosahexaenoic acid, needed for normal brain development. The triple combination of high fuel demands, inability to import cholesterol or saturated fatty acids, and dependence on docosahexaenoic acid puts the mammalian brain in a uniquely difficult situation compared with other organs and makes its expansion in early humans all the more remarkable. We believe that fresh-and salt-water shorelines provided a uniquely rich, abundant and accessible food supply, and the only viable environment for evolving both body fat and larger brains in human infants.

Plasma Ketone and Medium Chain Fatty Acid Response in Humans Consuming Different Medium Chain Triglycerides During a Metabolic Study Day

Background: Medium chain triglycerides (MCT) are ketogenic but the relationship between the change in plasma ketones and the change plasma medium chain fatty acids (MCFA)—octanoate, decanoate, or dodecanoate—after an oral dose of MCT is not well-known. An 8 h metabolic study day is a suitable model to assess the acute effects on plasma ketones and MCFA after a dose of tricaprylin (C8), tricaprin (C10), trilaurin (C12) or mixed MCT (C8C10).Objective: To assess in healthy humans the relationship between the change in plasma ketones, and octanoate, decanoate and dodecanoate in plasma total lipids during an 8 h metabolic study day in which a first 20 ml dose of the homogenized test oil is taken with breakfast and a second 20 ml dose is taken 4 h later without an accompanying meal.Results: The change in plasma acetoacetate, β-hydroxybutyrate and total ketones was highest after C8 (0.5 to 3 h post-dose) and was lower during tests in which octanoate was absent or was diluted by C10 in the test oil. The plasma ketone response was also about 2 fold higher without an accompanying meal (P = 0.012). However, except during the pure C10 test, the response of octanoate, decanoate or dodecanoate in plasma total lipids to the test oils was not affected by consuming an accompanying meal. Except with C12, the 4 h area-under-the-curve of plasma β-hydroxybutyrate/acetoacetate was 2–3 fold higher when no meal was consumed (P &lt; 0.04).Conclusion: C8 was about three times more ketogenic than C10 and about six times more ketogenic than C12 under these acute metabolic test conditions, an effect related to the post-dose increase in octanoate in plasma total lipids

Plasma n-3 fatty acid response to an n-3 fatty acid supplement is modulated by apoE ɛ4 but not by the common PPAR-α L162V polymorphism in men

The risk of Alzheimer's disease is increased for carriers of apoE4 (E4) or the PPAR-α L162V polymorphism (L162V), but it is decreased in fish and seafood consumers. The link between high fish intake and reduced risk of cognitive decline in the elderly appears not to hold in carriers of E4, possibly because better cognition is linked to EPA+DHA in the blood, but only in non-carriers of E4. As yet, no such studies exist in carriers of L162V. Our objective was to determine whether the plasma fatty acid response to a dietary supplement of EPA+DHA was altered in carriers of L162V and/or E4. This was an add-on project; in the original study, men were selected based on whether or not they were carriers of L162V (n 14 per group). E4 status was determined afterwards. All subjects received an EPA+DHA supplement for 6 weeks. L162V polymorphism did not interact with the supplement in a way to alter EPA and DHA incorporation into plasma lipids. However, when the groups were separated based on the presence of E4, baseline EPA and DHA in plasma TAG were 67 and 60 % higher, respectively, in E4 carriers. After the supplementation, there were significant gene × diet interactions in which only non-carriers had increased EPA and DHA in plasma NEFA and TAG, respectively

Plasma incorporation, apparent retroconversion and β-oxidation of 13C-docosahexaenoic acid in the elderly

<p>Abstract</p> <p>Background</p> <p>Higher fish or higher docosahexaenoic acid (DHA) intake normally correlates positively with higher plasma DHA level, but recent evidence suggests that the positive relationship between intake and plasma levels of DHA is less clear in the elderly.</p> <p>Methods</p> <p>We compared the metabolism of ¹³C-DHA in six healthy elderly (mean - 77 y old) and six young adults (mean - 27 y old). All participants were given a single oral dose of 50 mg of uniformly labelled ¹³C-DHA. Tracer incorporation into fatty acids of plasma triglycerides, free fatty acids, cholesteryl esters and phospholipids, as well as apparent retroconversion and β-oxidation of ¹³C-DHA were evaluated 4 h, 24 h, 7d and 28d later.</p> <p>Results</p> <p>Plasma incorporation and β-oxidation of ¹³C-DHA reached a maximum within 4 h in both groups, but ¹³C-DHA was transiently higher in all plasma lipids of the elderly 4 h to 28d later. At 4 h post-dose, ¹³C-DHA β-oxidation was 1.9 times higher in the elderly, but over 7d, cumulative β-oxidation of ¹³C-DHA was not different in the two groups (35% in the elderly and 38% in the young). Apparent retroconversion of ¹³C-DHA was well below 10% of ¹³C-DHA recovered in plasma at all time points, and was 2.1 times higher in the elderly 24 h and 7d after tracer intake.</p> <p>Conclusions</p> <p>We conclude that ¹³C-DHA metabolism changes significantly during healthy aging. Since DHA is a potentially important molecule in neuro-protection, these changes may be relevant to the higher vulnerability of the elderly to cognitive decline.</p

Eicosapentaenoic acid decreases postprandial beta-hydroxybutyrate and free fatty acid responses in healthy young and elderly

Objectives: We investigated whether a dietary supplement rich in eicosapentaenoic acid (EPA) increases fasting plasma ketones or postprandial ketone responses in healthy young and elderly subjects. Methods: Ten young (22 ± 1 y old) and 10 elderly (75 ± 1 y old) subjects were recruited and participated in two identical study days, one before and one 6 wk after providing an EPA-enriched supplement (1.4 g/d of EPA and 0.2 g/d of docosahexaenoic acid). On the study days, blood samples were collected at fasting and every hour for 6 h after giving a breakfast. Fasting and postprandial plasma β-hydroxybutyrate (β-OHB), free fatty acid (FFA), triacylglycerol, glucose, and insulin responses were measured. Fatty acid profiles were assessed in fasting plasma samples before and after the EPA supplement. Results: After the EPA supplement, postprandial plasma β-OHB responses decreased by 44% in the young and by 24% in the elderly subjects, in addition to 20% and 34% lower FFA responses in the young and elderly adults, respectively. β-OHB and FFAs were positively and significantly correlated in young but not in elderly subjects before and after the EPA supplement. In both groups, postprandial plasma triacylglycerols, glucose, and insulin were not significantly different after the intake of the EPA supplement. Before and after the EPA supplement, fasting plasma EPA was 50% higher in the elderly but increased by about five times in both groups after intake of the EPA supplement. Conclusion: Contrary to our expectations, EPA supplementation lowered postprandial β-OHB response and, in the elderly subjects, the concentration of postprandial β-OHB was not lowered after intake of the EPA supplement

Image-derived input function in dynamic human PET/CT: methodology and validation with 11C-acetate and 18F-fluorothioheptadecanoic acid in muscle and 18F-fluorodeoxyglucose in brain

International audienc

Cardiorenal ketone metabolism: a positron emission tomography study in healthy humans

Ketones are alternative energy substrates for the heart and kidney but no studies have investigated their metabolism simultaneously in both organs in humans. The present double tracer positron emission tomography (PET) study evaluated the organ distribution and basal kinetic rates of the radiolabeled ketone, 11C-acetoacetate (11C-AcAc), in the heart and kidney compared to 11C-acetate (11C-Ac), which is a well-validated metabolic radiotracer. Both tracers were highly metabolized by the left ventricle and the renal cortex. In the heart, kinetic rates were similar for both tracers. But in the renal cortex, uptake of 11C-Ac was higher compared to 11C-AcAc, while the reverse was observed for the clearance. Interestingly, infusion of 11C-AcAc led to a significantly delayed release of radioactivity in the renal medulla and pelvis, a phenomenon not observed with 11C-Ac. This suggests an equilibrium of 11C-AcAc with the other ketone, 11C-D-beta-hydroxybutyrate, and a different clearance profile. Overall, this suggests that in the kidney, the absorption and metabolism of 11C-AcAc is different compared to 11C-Ac. This dual tracer PET protocol provides the opportunity to explore the relative importance of ketone metabolism in cardiac and renal diseases, and to improve our mechanistic understanding of new metabolic interventions targeting these two organs