Over the past 50years, our understanding of the role of trace elements in animals and humans has significantly expanded. Some elements have been recognized as essential for vital body functions. Since the 1950s, with advances in histochemical and spectrometric methods, the distribution of trace elements in different structures of the brain has been studied. Scientific knowledge about the effects of trace elements on brain function has accumulated tremendously as well.

Riboflavin (also named vitamin B2) is a water-soluble vitamin mainly used as a substrate for the synthesis of its two derived co-factors, FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide), that act as essential cofactors for numerous and various enzymes, named flavoenzymes, involved in several metabolic pathways. Among several genetic diseases involving the riboflavin metabolism or flavoenzymes, riboflavin transporter deficiency (RTD), caused by SLC52A2 and SLC52A3 genes mutations, has a quite singular clinical presentation, characterized by generalized weakness due to a lower motor neuron (LMN) degeneration, potentially leading to death by respiratory compromise. RTD may mimic other LMN disorders including the far more common amyotrophic lateral sclerosis (ALS). Pathophysiology of RTD is not understood, and future research aiming at improving this knowledge could also give broader insights on the LMN biology and its susceptibility to degeneration.

Copper (Cu) is an essential trace metal, and either a Cu deficiency or excess is life-threatening. Recent studies have indicated that an imbalance of Cu levels and a high burden of oxidative stress are contributors of Alzheimer's disease (AD), the main cause of dementia in the elderly. AD Cu imbalance can be described as a reduction of functional Cu bound to proteins and a shift of the metal to the non-ceruloplasmin (non-Cp) Cu pool, prone to oxidative stress. The shift/displacement of the metal from bound to labile toxic Cu in the brain can explain mitochondrial deficits, energy depletion, protein misfolding of amyloid beta, and other proteins associated to dementia. We suggest a diet-gene interplay at the basis of the “CuAD,” a subset of AD patients typified by higher-than-normal non-Cp Cu. A description of the Cu-regulating pathways and suggestions for a low-copper diet to improve preventive strategies are reported herein.

B vitamins play an important role in the functioning of both the central and peripheral nervous systems. Some of its mechanisms of action include serving as a cofactor in neuronal metabolic processes, myelin generation, and neurotransmitter synthesis, as well as through antioxidative mechanisms. Its deficiency may be associated with multiple well-known neurological syndromes such as Wernicke-Korsakov encephalopathy, subacute degeneration of the spinal cord, and beriberi, among others. However, for several years, the role of B-vitamin deficiency in the development of different types of peripheral neuropathies (including their association with alcoholic and diabetic neuropathy) has been recognized. In this chapter, we will review the main physiological role of B vitamins in the nervous system, focusing on the so-called neurotropic B vitamins thiamine, pyridoxine, and cyanocobalamin, in the pathophysiology of peripheral neuropathy and their therapeutic potential, and even in neuropathies of different etiology without a demonstrated nutritional deficiency. We will also review the safety profile of the administration of B vitamins in the management of these pathologies.

In this chapter, we will cover some of the main metabolic characteristics of copper and the impact of its effects on the nervous system. Copper is an essential micronutrient, obtained from the diet and water intake, which plays a fundamental role in the metabolic balance of several systems, ranging from the production of ATP in the mitochondrial electron transport chain to the activation of the immune system and even the control of synaptic stabilization in the nervous system, exerted by APP and prion proteins. Therefore, it is important to note that copper deficiency is just as harmful as its excess, and the imbalance in the rates of metal excretion and absorption tends to induce oxidative stress and tissue inflammation. These elements being at the center of some of the main disorders of the nervous system, such as Wilson's disease, Menkes’ disease, Alzheimer's disease, hypotonia, epilepsy, some of which will be discussed here. It is worth noting that studies already stressed to the introduction of dietary supplementation, potentially capable of returning the balance to copper homeostasis, with the consequence, the prevention or even remission of some pathologies like Alzheimer's and dementias.

Calcium nutritional status is substandard in many nations around the globe, when examined classically through dietary intake and osteoporosis. The multifaceted role of calcium extends to neurological illnesses such as Parkinson's disease (PD), and the wealth of factors influencing calcium levels make it difficult to determine an optimal dietary intake for calcium in the aging population. Calcium can be found in foods, supplements, and herbs. Also, source of calcium (e.g., plant and animal) may be a factor in its linkage to PD. Dairy intake and calcium concentrations have been recently introduced as a potential risk factor for PD. However, discrepancies exist among the literature. The present chapter rapidly reviews the possible role of calcium in PD and nutritional neuroscience underlying this link.

The water-soluble vitamin thiamine or vitamin B1 has historically been associated with beriberi and Wernicke-Korsakoff syndrome in a deficiency state, largely due to malnutrition. Thiamine is back into focus owing to the modernization of dietary practices with abundance of processed foods, reducing the nutritional quality of food and leading to thiamine deficiency even in the apparently “well-nourished” population. Thiamine is involved in over 20 biochemical reactions in the body, mainly involving the energy metabolism in brain, heart, and muscle. Though required in very small quantities, it is rapidly excreted from the body owing to its water-soluble nature and hence needs to be replenished on a daily basis. In this chapter, we aim to describe thiamine absorption and transportation and its crucial role in metabolic pathways leading to energy production, with special focus on neurological functions and related disorders. Early recognition of thiamine deficiency is paramount as supplementation of thiamine can be life-saving, reverting symptoms as early as in hours, even in the severely affected individuals.

Parkinson's disease is a common, long-term, age-related neurodegenerative disease with no known cure. Vitamin D hypovitaminosis has emerged as a common medical condition in people with Parkinson's disease; nevertheless, whether it is a factor implicated in the cause or consequences of disease still remains to be elucidated. A number of biological processes associated with Parkinson's disease are regulated by vitamin D and its metabolites. This chapter has focused on the links between vitamin D and Parkinson's disease. Vitamin D metabolism and Parkinson's disease are concisely summarized. Relevant research findings about the impact of vitamin D on Parkinson's disease are briefly given, and gut dysfunction in the disease is addressed in a separate topic.

Paucity of vitamin D significantly affects the consequences of a brain injury. Deficiency of vitamin D along with traumatic brain injury (TBI) elevates the risk of severity of the injury. This possibly affects the therapeutic regimen prescribed for TBI which may have a negative effect on its outcome. Pre-clinical trials suggested that the levels of vitamin D influence the recovery and outcome after a TBI. Vitamin D deficiency has been found to cause more deterioration in patients with severe TBI than in the ones with mild TBI. This clearly validates the necessity of screening the levels of vitamin D in neural deficit in order to reduce the risk of morbidity, neurocognitive disorders, osteomalacia, and cardiovascular disease. This review focuses on the incidence of vitamin D deficiency in TBI and how it affects the recovery and subsequent quality of life of the patient.

Neuroinflammation comprises an orchestrated cascade of cellular and molecular processes triggered in response to insults and aiming at protecting the central nervous system. The main agent of this response is the microglia, but astrocytes, neurons, oligodendrocytes, vascular pericytes, and infiltrated peripheral immune cells are also involved. Paradoxically, imbalanced and uncontrolled neuroinflammation is recognized as a major feature of neuropsychiatric disorders. B12 (cobalamin) vitamers, besides being key players in the energy metabolism and the sulfur amino acids pathway, also attenuate neuroinflammation by acting in various underlying and interconnected processes such as scavenging reactive species, maintaining adequate levels of H2S, preventing some harmful effects of excess homocysteine, and decreasing NMDA receptor-mediated excitotoxicity in central nervous system cells. B12 also modulates different chromatin remodeling mechanisms that can downregulate some pivotal genes in neuroinflammation. This pleiotropic mode of action in the control of various components of neuroinflammation makes B12 one of the most promising nutrients for neuroprotection in many neuropsychiatric disorders.