Preventive and therapeutic potential of ascorbic acid in neurodegenerative diseases

Abstract

In this review, we summarize the involvement of ascorbic acid in neurodegenerative diseases by presenting available evidence on the behavioral and biochemical effects of this compound in animal models of neurodegeneration as well as the use of ascorbic acid as a therapeutic approach to alleviate neurodegenerative progression in clinical studies. Ascorbate, a reduced form of vitamin C, has gained interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. In the brain, ascorbate exerts neuromodulatory functions and scavenges reactive oxygen species generated during synaptic activity and neuronal metabolism. These are important properties as redox imbalance and abnormal protein aggregation constitute central mechanisms implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Indeed, several studies have indicated an association between low serum ascorbate concentrations and neurodegeneration. Moreover, ascorbic acid is a suitable candidate for supplying either antioxidant defense or modulation of neuronal and astrocytic metabolism under neurodegenerative conditions. Ascorbic acid acts mainly by decreasing oxidative stress and reducing the formation of protein aggregates, which may contribute to the reduction of cognitive and/or motor impairments observed in neurodegenerative processes. Although several studies support a possible role of ascorbic acid administration against neurodegeneration, more researches are essential to substantiate the existing results and accelerate the knowledge in this field.

Neuroprotective Effect of Antioxidants in the Brain

“…Ascorbate can easily enter the brain through the glucose transporter (GLUT1) when a considerable amount of DHA is present in the blood. Ascorbate or DHA in the cerebrospinal fluid enters the neuron via sodium-dependent transporter-2 (SVCT-2) or GLUT1 transporters [ 130 , 131 ]. Once they enter the neuron, DHA can be reduced to ascorbate or released by GLUT1.…”

Corticostriatal network dysfunction in Huntington's disease: Deficits in neural processing, glutamate transport, and ascorbate release

“…88 It is interesting, however, that the huntingtin gene plays a role in the translocation of the ascorbate transporter to the plasma membrane, leaving open the possibility of a disruption in cellular storage of ascorbate. 89 Although a 3-day injection regimen of sodium ascorbate (300 mg/kg/d) in R6/2 mice restored striatal extracellular ascorbate to WT levels and improved striatal function, 40 such a high dose is unlikely to be an effective long-term treatment solution, especially in light of stringent control of ascorbate entry into brain tissue from blood. 31 At this point, the bulk of the evidence indicates that the ascorbate problem in HD is one of release, which links it directly to down-regulation of GLT-1.…”

Nutritional composition of fad diets published on websites and blogs

“…This result differs from that reported by Floriano et al [5] who found that 5 of the 20 diets analyzed had lower values of vitamin A than the recommended level. Excess vitamin C, as found in the intermittent fasting and gluten-free diets, causes diarrhea, urinary oxalate excretion and formation of renal calculus [24], whereas its deficiency, as found in the low-carb diet, is associated with neurodegenerative diseases including Alzheimer's, Parkinson's and Huntington's diseases, multiple sclerosis and amyotrophic lateral sclerosis [25]. In the studies of Floriano et al [5] and Abreu et al [12], 80% and 82% of the analyzed diets, respectively, had adequate levels of vitamin C. Similarly, Marangoni & Maniglia [22] found adequate vitamin C levels in their study, as recommended by the DRI.…”