Jade Guest

Relationship between central and peripheral fatty acids in humans

BackgroundIn recent years the physiological and pathological importance of fatty acids in both the periphery and central nervous system (CNS) has become increasingly apparent. However surprisingly limited research has been conducted comparing the fatty acid composition of central and peripheral lipid stores.MethodsThe present study compared the distribution of polyunsaturated (PUFA), as well as specific saturated (SFA) and monounsaturated (MUFA) fatty acids in the whole blood and cerebrospinal fluid (CSF) of humans. Gas chromatography with flame ionization detection was used to determine the fatty acid profiles of twenty-eight matched CSF and whole blood samples. Multiple linear regression modeling, controlling for age, was used to identify significant relationships.ResultsA significant positive relationship was seen between whole blood total omega-3 fatty acids and the CSF omega-3 subfractions, docosapentaenoic acid (DPA) (P = 0.019) and docosahexaenoic acid (DHA) (P = 0.015). A direct association was also observed between the whole blood and CSF omega-6 PUFA, arachidonic acid (AA) (P = 0.045). Interestingly an inverse association between central and peripheral oleic acid was also found (P = 0.045).ConclusionsThese findings indicate a relationship between central and peripheral fatty acids of varying degrees of unsaturation and chain length and support the view that some systemic fatty acids are likely to cross the human blood brain barrier (BBB) and thereby influence central fatty acid concentrations.

Changes in oxidative damage, inflammation and [NAD(H)] with age in cerebrospinal fluid.

An extensive body of evidence indicates that oxidative stress and inflammation play a central role in the degenerative changes of systemic tissues in aging. However a comparatively limited amount of data is available to verify whether these processes also contribute to normal aging within the brain. High levels of oxidative damage results in key cellular changes including a reduction in available nicotinamide adenine dinucleotide (NAD+), an essential molecule required for a number of vital cellular processes including DNA repair, immune signaling and epigenetic processing. In this study we quantified changes in [NAD(H)] and markers of inflammation and oxidative damage (F2-isoprostanes, 8-OHdG, total antioxidant capacity) in the cerebrospinal fluid (CSF) of healthy humans across a wide age range (24–91 years). CSF was collected from consenting patients who required a spinal tap for the administration of anesthetic. CSF of participants aged >45 years was found to contain increased levels of lipid peroxidation (F2-isoprostanes) (p = 0.04) and inflammation (IL-6) (p = 0.00) and decreased levels of both total antioxidant capacity (p = 0.00) and NAD(H) (p = 0.05), compared to their younger counterparts. A positive association was also observed between plasma [NAD(H)] and CSF NAD(H) levels (p = 0.03). Further analysis of the data identified a relationship between alcohol intake and CSF [NAD(H)] and markers of inflammation. The CSF of participants who consumed >1 standard drink of alcohol per day contained lower levels of NAD(H) compared to those who consumed no alcohol (p<0.05). An increase in CSF IL-6 was observed in participants who reported drinking >0–1 (p<0.05) and >1 (p<0.05) standard alcoholic drinks per day compared to those who did not drink alcohol. Taken together these data suggest a progressive age associated increase in oxidative damage, inflammation and reduced [NAD(H)] in the brain which may be exacerbated by alcohol intake.

Effects of dietary derived antioxidants on the central nervous system

Oxidative stress refers to the pathological state in which the production of reactive oxygen and nitrogen species is increased above the bodys antioxidant defense and repair capacity. Functional damage, with subsequent cell death, may occur as a consequence of the oxidization of cellular components, such as, proteins, lipids, and nuclear material. Several features of the brain suggest that it is particularly vulnerable to oxidative stress. The brain possesses the highest oxygen metabolic rate of any organ and is continually exposed to excitatory amino acids and neurotransmitters. The brain also contains a high concentration of oxidizable polyunsaturated fatty acids, but has comparatively limited endogenous antioxidant defense mechanisms. Accumulating evidence indicates that dietary-derived antioxidants may mitigate the development of neurodegenerative diseases, with a number of recent studies focusing on the potential therapeutic benefits of supplementation. This review focuses on our current knowledge of how some of these diet-derived antioxidants may exert their neuroprotective effects.

Central kynurenine pathway shift with age in women.

Age is considered a dominant risk factor in the development of most neurodegenerative disorders. The kynurenine pathway, a major metabolic pathway of tryptophan is altered in the majority of neurodegenerative disorders. In this study, we have analysed CSF samples from 49 healthy women across a wide age range (0–90) for kynurenine pathway metabolites and the inflammatory marker neopterin. Our results show central tryptophan metabolism is increased with age in women, with an apparent shift towards the neurotoxin quinolinic acid. We also observed an increase in central levels of the inflammatory marker neopterin with age and a positive correlation between neopterin and kynurenine pathway activation. We conclude that, the changes that occur in the kynurenine pathway as a result of normal ageing are mechanistically linked to increased inflammatory signalling and have some explanatory potential with regard to age‐associated degenerative diseases in the CNS. Management of health in ageing and (preventative) treatment would do well to look to the kynurenine pathway for potentially novel solutions.

Novel relationships between B12, folate and markers of inflammation, oxidative stress and NAD(H) levels, systemically and in the CNS of a healthy human cohort.

Objective: To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort. Methods: Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F2-isoprostanes, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified. Results: In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P ≤ 0.01; P ≤ 0.01) and plasma NAD(H) (P ≤ 0.05; P ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)]. Within the CNS plasma Hcy correlated positively with CSF IL-6 (P ≤ 0.01) and negatively with CSF NAD(H) (P ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P ≤ 0.01). Discussion: These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS.

Role of Omega-3 PUFAs in Neurobiological Health

The importance of the essential, dietary-derived, polyunsaturated fatty acids (PUFAs) omega-6 and omega-3 to human health was first reported over 85 years ago. Subsequent research has revealed many beneficial effects of the omega-3 PUFAs in particular. This has been linked to their involvement in multiple biochemical functions, including synthesis of inflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. Through these pathways, the omega-3 PUFAs help modulate aspects of inflammation and immunity, cell growth and tissue repair. While a detailed understanding of the mechanisms involved in the role of omega-3 PUFAs to health in the central nervous system (CNS) is still to be elucidated, a role for both inflammatory modulation and a direct impact on neuronal membrane fluidity and receptor function is apparent. At least partially through these mechanisms, low omega-3 levels have been associated with CNS-linked disorders such as poor cognition, depression, anxiety disorders, poor anger control, attention deficit hyperactivity disorder (ADHD) and accelerated neurodegeneration in the elderly.Following a brief introduction to the history and chemistry of the omega-3 family of PUFAs, this chapter will provide an overview of the omega-3 fatty acids and how various members of this PUFA family influence central nervous system function leading towards either health or disease.

Postprandial oxidative stress is increased after a phytonutrient-poor food but not after a kilojoule-matched phytonutrient-rich food.

Research indicates that energy-dense foods increase inflammation and oxidative activity, thereby contributing to the development of vascular disease. However, it is not clear whether the high kilojoule load alone, irrespective of the nutritional content of the ingested food, produces the postprandial oxidative and inflammatory activity. This study investigated the hypothesis that ingestion of a high-fat, high-sugar, phytonutrient-reduced food (ice cream) would increase oxidative and inflammatory activity greater than a kilojoule-equivalent meal of a phytonutrient-rich whole food (avocado). The individual contributions of the fat/protein and sugar components of the ice cream meal to postprandial inflammation and oxidative stress were also quantified. Using a randomized, crossover design, 11 healthy participants ingested 4 test meals: ice cream, avocado, the fat/protein component in ice cream, and the sugar equivalent component in ice cream. Plasma glucose, cholesterol, triglycerides, and inflammatory and oxidative stress markers were measured at baseline and 1, 2, and 4 hours (t1, t2, t4) after ingestion. Lipid peroxidation was increased at 2 hours after eating fat/protein (t0-t2, P < .05) and sugar (t1-t2, P < .05; t1-t4, P < .05). Antioxidant capacity was decreased at 4 hours after eating ice cream (t0-t4, P < .01) and sugar (t0-t4, P < .01). Ingestion of a kilojoule-equivalent avocado meal did not produce any changes in either inflammatory or oxidative stress markers. These data indicate that the ingestion of a phytonutrient-poor food and its individual fat/protein or sugar components increase plasma oxidative activity. This is not observed after ingestion of a kilojoule-equivalent phytonutrient-rich food.

Suboptimal Omega-3 Levels in Australian Adolescents

Objective: To quantitate the omega-3 status in a cohort of Australian adolescents. Design, Setting and Participants: A cross-sectional descriptive study of 251 apparently healthy adolescents (192 female, 59 male) aged 15-17 years, in year 11, from 10 schools within the Northern Sydney and Central Coast areas of New South Wales. Participants provided a morning non-fasting blood sample via finger-prick and written answers to specific demographic and lifestyle questions. Omega-3 index was calculated by adding %EPA and %DHA values in the whole blood. Equivalent erythrocyte omega-3 index values were obtained by using conversion factors (1.33 for EPA and 2.22 for DHA) from published erythrocyte/whole blood values. Main Outcome Measures: Quantitation of the individual, and estimation of the group average, blood omega-3 Index. Results: The blood omega-3 Index for this adolescent cohort ranged from 2.1-22.3 with a mean of 8.3±3.2, and median of 7.8. On average males had a higher omega-3 Index compared to females (10.5±3.7 vs 7.7±2.6, p 8. Three percent had an Index of <4, placing them in the high risk category for disease. On average, adolescents from low or medium socioeconomic communities had a significantly lower omega-3 Index compared to those from higher socioeconomic neighbourhoods (mean difference=1.4, p=0.018). Overall 20% of boys and 17% of girls reported regularly taking omega-3 supplements. Regular use of omega-3 supplements was associated with a higher average omega-3 Index (9.8±3.7, n=44 compared to 8.0±3.0, n=203, p=0.001 in those not taking supplements). Conclusion: This study indicates that Australian adolescents, even when from advantaged homes, have a high probability of below optimum omega-3 levels. As reduced omega-3 levels are linked to conditions of public health concern such as diabetes, asthma and depression, targeted strategies to improve the omega-3 status in the childhood population may be warranted.

Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM) for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose) polymer production. Significant decreases in total NAD(H) and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM) decreased levels of NAD(H) in primary human astrocytes. NAD(H) depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H)]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene.

Carotenoids and Neurobiological Health

The consumption of carotenoid phytonutrients, largely as part of plant tissue, has been associated with a number of health benefits. Epidemiological and other studies support a link between higher dietary intake and tissue concentrations of carotenoids and lower risk of chronic diseases such as heart disease, diabetes, and some cancers. Evidence also suggests that increased levels of carotenoids can help maintain healthy cognitive function, especially into older age. Carotenoids mediate their beneficial effects via several mechanisms including cell growth regulation and modulation of gene expression and immune activity. However their primary protective mechanism is thought to be due to their potent antioxidant properties that effectively scavenge free radicals and reduce the risk of oxidative damage. This chapter discusses the impact of carotenoids on neurological health by first reviewing their chemical characteristics, dietary sources, and general mechanisms of action before examining in some detail the available evidence for a protective role for various carotenoids in neurodegenerative disease.