Nutritional modulation of cognitive function and mental health Natalie Parletta, Catherine M. Milte, Barbara J. Meyer  Journal of Nutritional Biochemistry  Volume 24, Issue 5, Pages 725-743 (May 2013) DOI: 10.1016/j.jnutbio.2013.01.002 Copyright © 2013 Elsevier Inc. Terms and Conditions

Fig. 1 Overview of links between Mediterranean-style diet and healthy brain function via plant compounds/nutrients. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Fig. 2 Antioxidant and brain overview. ROS = reactive oxygen species. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Fig. 3 Different glycerophosphates as % dry weight from human (all male Caucasian, n=1 in each age group) gray matter, white matter and myelin (data taken from O’Brien et al. [117]). CGP = choline glycerophosphates; EGP = ethanolamine glycerophosphates; SGP = serine glycerophosphates. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Fig. 4 Proportion of fatty acids in CGP (A; choline glycerophosphates), EGP (B; ethanolamine glycerophosphates) and SGP (C; serine glycerophosphates). 22:6n-3 = DHA; 22:5n-3 = docosapentaenoic acid (n-3); 22:5n-6 = docosapentaenoic acid (n-6); 20:4n-6 = arachidonic acid; 18:1n-9 = oleic acid; 18:00 = stearic acid; 16:00 = palmitic acid. All male Caucasian, n=1 in each age group (data taken from O’Brien et al. [127]). Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Fig. 5 Levels of the different phospholipid classes (PC, PS, PE, PI) in the whole brain (gray and white matter) for the first 40 years of life (data taken from Rouser et al. [183]; extrapolated from 13 healthy male whole brains aged 6 months to 98 years). Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Fig. 6 B vitamins and homocysteine metabolism. B6 = vitamin B6; B12 = vitamin B12; HCY = homocysteine; MTHF = 5-methlytetrahydrofolate; SAH = S-adenosylhomocysteine; SAM = S-adenosyl methionine; THF = tetrahydrofolate. Adapted from Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Letters 2006;580:2994-3005. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Fig. 7 Roles of B vitamins and homocysteine in one-carbon metabolism, transsulfuration pathway and brain function. Homocysteine can be transported into neurons via a specific membrane transporter. Remethylation of homocysteine to methionine occurs in the presence of folate and B12. Methionine is an important source of methyl groups in the brain. Homocysteine can also be converted to cysteine (a precursor of glutathione) in the presence of B6. Homocysteine can cause DNA damage directly or through reduction in DNA methylation, leading to synaptic dysfunction and apoptosis. Homocysteine can lead to excitotoxicity through direct actions on glutamate receptors. Although the pathway for remethylation of homocysteine via BHMT does not occur in the brain, it may still influence brain function through actions on systemic homocysteine levels. Adapted from Mattson and Shea [237]. B2 = Vitamin B2 (riboflavin); BHMT = betaine-homocysteine methyltransferase; MS = methionine synthase; MTHFR = 5, 10-methylenetetrahydrofolate reductase; SAH = S-adenosylhomocysteine; SAM = S-adenosylmethionine. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Diagram 1 Neuron associated glial cells. d.2 - see Diagram 2; d.3 - see Diagram 3; d.4 - see Diagram 4; d.5 - see Diagram 5; d.6 - see Diagram 6; d.7 - Diagram 7. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Diagram 2 The effect of DHA on neurite growth. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Diagram 3 Phospholipid bilayer DHA. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Diagram 4 DHA and neurotransmitters. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Diagram 5 Eicosanoids and blood-brain barrier. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Diagram 6 Neural survival (PS-DHA). Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions

Diagram 7 Preventing cognitive decline and neurodegeneration. Journal of Nutritional Biochemistry 2013 24, 725-743DOI: (10.1016/j.jnutbio.2013.01.002) Copyright © 2013 Elsevier Inc. Terms and Conditions