The neuropsychiatric effects of vitamin C deficiency: a systematic review.

BACKGROUND: Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency. METHODS: Relevant studies were identified via systematic literature review. RESULTS: Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified. CONCLUSIONS: Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence.

Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.

Dietary Vitamin C Deficiency Is Associated With Health-Related Quality of Life and Cardiac Event-free Survival in Adults With Heart Failure.

BACKGROUND: Vitamin C deficiency is prevalent in adults with heart failure (HF). Little is known about the relationship of dietary vitamin C deficiency with health outcomes in adults with HF. OBJECTIVE: The study's aim was to determine the relationships of vitamin C deficiency measured at baseline with health-related quality of life (HRQOL) and cardiac event-free survival in patients with HF measured 1 year later. METHOD: A total of 251 patients with HF completed a 4-day food diary. Dietary vitamin C deficiency was defined as daily intake less than the estimated average requirement from the Institute of Medicine of 75 mg/d for men and 60 mg/d for women. Health-related quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire at 12 months. Patients were followed for a median of 1 year to determine time to the first event of cardiac-related hospitalization or death. Data were analyzed by hierarchical linear and Cox proportional hazards regressions. RESULTS: One hundred patients (40%) had vitamin C deficiency. Dietary vitamin C deficiency was associated with poorer HRQOL at 12 months (ß = 0.16, P = .02) after controlling for demographic and clinical variables. During the follow-up period, 59 patients (24%) had cardiac events. In Cox regression, vitamin C deficiency predicted shorter cardiac event-free survival after adjusting for the same covariates (hazards ratio, 1.95; 95% confidence interval, 1.08-3.51). CONCLUSION: Vitamin C deficiency was associated with poorer HRQOL and shorter cardiac event-free survival in patients with HF. The findings suggest that encouraging patients with HF to consume a diet rich in fruits/vegetables to prevent vitamin C deficiency may lead to better health outcomes.

Lessons in early identification and treatment from a case of disabling vitamin C deficiency in a child with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder is a heterogenous neurodevelopmental condition accompanied by a variety of associated features. Case reports suggest one such associated feature, food selectivity, increases risk for nutritional deficiencies; however, little attention has been given to prevent and treat nutritional deficiencies in youth with autism spectrum disorder. METHOD: Single case report. RESULTS: This single case report presents a child with autism spectrum disorder and food selectivity difficulties that resulted in severe vitamin C deficiency. Although eventually corrected, the nutritional deficiency was debilitating, required invasive interventions, and resulted in significant social/emotional and economic costs. CONCLUSIONS: We review the course of treatment and highlight strategies to prevent and more effectively treat nutritional deficiencies in youth with autism spectrum disorder.

Severe vitamin C deficiency in a child newly diagnosed with T-cell ALL due to nutrient gap.

A 10-year-old boy developed a perifollicular rash during interim maintenance of T-Cell acute lymphoblastic leukaemia. Differential diagnoses included drug reaction and inflammatory process. Before diagnosis, the patient had a limited diet--low in vegetables and fruits--due to selective eating, with later anorexia and taste aversions due to chemotherapy treatment. Despite nutritional counselling and starting a multivitamin, the patient incurred severe weight loss (18.5% of his usual body weight). Serum levels of ascorbic acid were non-detectable, at <5 µmol/L, indicative of vitamin C deficiency. The patient began vitamin C supplementation containing 125 mg ascorbic acid three times a day for 7 days, then 125 mg once daily for 3 months to normalise serum vitamin C. After ascorbic acid treatment was completed, the patient started a complete multivitamin and made efforts to eat fruits and vegetables rich in vitamin C. His serum ascorbic acid concentrations normalised to 52 µmol/L 3 months after receiving supplementation.

Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aß1-42 and a higher Aß1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-ß plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice.

Vitamin C is a powerful antioxidant and its levels are decreased in Alzheimer's patients. Even sub-clinical vitamin C deficiency could impact disease development. To investigate this principle we crossed APP/PSEN1 transgenic mice with Gulo knockout mice unable to synthesize their own vitamin C. Experimental mice were maintained from 6 weeks of age on standard (0.33 g/L) or reduced (0.099 g/L) levels of vitamin C and then assessed for changes in behavior and neuropathology. APP/PSEN1 mice showed impaired spatial learning in the Barnes maze and water maze that was not further impacted by vitamin C level. However, long-term decreased vitamin C levels led to hyperactivity in transgenic mice, with altered locomotor habituation and increased omission errors in the Barnes maze. Decreased vitamin C also led to increased oxidative stress. Transgenic mice were more susceptible to the activity-enhancing effects of scopolamine and low vitamin C attenuated these effects in both genotypes. These data indicate an interaction between the cholinergic system and vitamin C that could be important given the cholinergic degeneration associated with Alzheimer's disease.

Cognitive effects of nutritional deficiency.

Deficiencies of various nutrients, primarily vitamins, impair cognition. The link is strongest for vitamin B12, thiamine, and niacin. Yet even for these, the role of mild "subclinical" or multiple deficiencies in the genesis of mental dysfunction is unclear. Most information in this field is based on animal studies often poorly applicable to the human condition or on clinical pathology complicated by advanced age, alcoholism, and intercurrent disease. There is a need for well controlled, double-blind, prospective trials to elucidate the cognitive effects of malnutrition.