Plasma Vitamin C Concentrations and Cognitive Function: A Cross-Sectional Study

Vitamin-C is a water soluble molecule that humans have lost the ability to produce. Vitamin-C plays a role in CNS functions such as neuronal differentiation, maturation, myelin formation and modulation of the catecholaminergic systems. A recent systematic review by our team indicated the need for further research into the relationship between plasma vitamin C and cognition in cognitively intact participants using plasma vitamin C concentrations instead of estimates derived from food-frequency-questionnaires (FFQ), and more sensitive cognitive assessments suitable for cognitive abilities vulnerable to aging. It was hypothesized that higher plasma vitamin C concentrations would be linked with higher cognitive performance. This cross-sectional trial was conducted on healthy adults (n = 80, Female = 52, Male = 28, 24–96 years) with a range of plasma Vitamin C concentrations. Cognitive assessments included The Swinburne-University-Computerized-Cognitive-Assessment-Battery (SUCCAB) and two pen and paper tests, the Symbol-Digits-Modalities-Test (SDMT) and Hopkins-Verbal-Learning-Test-Revised (HVLT-R). The pen and paper assessments were conducted to establish whether their scores would correlate with the computerized tasks. Plasma-Vitamin C concentrations were measured using two biochemical analyses. Participants were grouped into those with plasma vitamin-C concentrations of adequate level (≥28 μmol/L) and deficient level (<28 μmol/L). The SUCCAB identified a significantly higher performance ratio (accuracy/reaction-time) in the group with adequate vitamin-C levels vs. deficient vitamin-C on the choice reaction time (M = 188 ± 4 vs. 167 ± 9, p = 0.039), immediate recognition memory (M = 81 ± 3 vs. 68 ± 6, p = 0.03), congruent Stroop (M = 134 ± 3 vs. 116 ± 7, p = 0.024), and delayed recognition tasks (M = 72 ± 2 vs. 62 ± 4, p = 0.049), after adjusting for age (p < 0.05). Significantly higher scores in immediate recall on the HVLT-R (M = 10.64 ± 0.16 vs. 9.17 ± 0.37, p = 0.001), delayed recall (M = 9.74 ± 0.22 vs. 7.64 ± 0.51, p < 0.001), total recall (M = 27.93 ± 0.48 vs. 24.19 ± 1.11, p = 0.003) were shown in participants with adequate plasma Vitamin-C concentrations, after adjusting for vitamin-C supplementation dose (p < 0.05). Similarly, higher SDMT scores were observed in participants with adequate plasma Vitamin-C concentrations (M = 49.73 ± 10.34 vs. 41.38 ± 5.06, p = 0.039), after adjusting for age (p < 0.05). In conclusion there was a significant association between vitamin-C plasma concentrations and performance on tasks involving attention, focus, working memory, decision speed, delayed and total recall, and recognition. Plasma vitamin C concentrations obtained through vitamin C supplementation did not affect cognitive performance differently to adequate concentrations obtained through dietary intake.Clinicaltrials.gov Unique Identifier: ACTRN 12615001140549, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440

The Effect of Kyolic Aged Garlic Extract on Gut Microbiota, Inflammation, and Cardiovascular Markers in Hypertensives: The GarGIC Trial

Background: Previous research suggests Kyolic-aged-garlic-extract to be effective in reducing blood pressure in a large proportion of hypertensive patients similar to first-line standard antihypertensive medication. High blood pressure has been linked to gut dysbiosis, with a significant decrease in microbial richness and diversity in hypertensives compared to normotensives. Furthermore, gut dysbiosis has been associated with increased inflammatory status and risk of cardiovascular events.Objective: To assess the effect of Kyolic aged GARlic extract on Gut microbiota, Inflammation, and Cardiovascular markers, including blood pressure, pulse wave velocity and arterial stiffness.Methods: A total of 49 participants with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12-weeks, investigating the effect of daily intake of aged-garlic-extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, pulse wave velocity and arterial stiffness, inflammatory markers, and gut microbiota.Results: Mean blood pressure was significantly reduced by 10 ± 3.6 mmHg systolic and 5.4 ± 2.3 mmHg diastolic compared to placebo. Vitamin B12 status played a role in responsiveness to garlic on blood pressure in 17% of patients. Garlic significantly lowered central blood pressure, pulse pressure and arterial stiffness (p < 0.05). Trends observed in inflammatory markers TNF-α and IL-6 need to be confirmed in larger trials. Furthermore, aged-garlic-extract improved gut microbiota, evident by higher microbial richness and diversity with a marked increase in Lactobacillus and Clostridia species after 3 months of supplementation.Conclusions: Kyolic-aged-garlic-extract is effective in reducing blood pressure in patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and gut microbial profile. Aged-garlic-extract is highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment, with multiple benefits for cardiovascular health.Trial Registration: Australian New Zealand Clinical Trial Registry ACTRN12616000185460 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370096

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders

Glucosinolates from cruciferous vegetables and their potential role in chronic disease: Investigating the preclinical and clinical evidence

An increasing body of evidence highlights the strong potential for a diet rich in fruit and vegetables to delay, and often prevent, the onset of chronic diseases, including cardiometabolic, neurological, and musculoskeletal conditions, and certain cancers. A possible protective component, glucosinolates, which are phytochemicals found almost exclusively in cruciferous vegetables, have been identified from preclinical and clinical studies. Current research suggests that glucosinolates (and isothiocyanates) act via several mechanisms, ultimately exhibiting anti-inflammatory, antioxidant, and chemo-protective effects. This review summarizes the current knowledge surrounding cruciferous vegetables and their glucosinolates in relation to the specified health conditions. Although there is evidence that consumption of a high glucosinolate diet is linked with reduced incidence of chronic diseases, future large-scale placebo-controlled human trials including standardized glucosinolate supplements are needed

Glucosinolates from cruciferous vegetables and their potential role in chronic disease: Investigating the preclinical and clinical evidence

An increasing body of evidence highlights the strong potential for a diet rich in fruit and vegetables to delay, and often prevent, the onset of chronic diseases, including cardiometabolic, neurological, and musculoskeletal conditions, and certain cancers. A possible protective component, glucosinolates, which are phytochemicals found almost exclusively in cruciferous vegetables, have been identified from preclinical and clinical studies. Current research suggests that glucosinolates (and isothiocyanates) act via several mechanisms, ultimately exhibiting anti-inflammatory, antioxidant, and chemo-protective effects. This review summarizes the current knowledge surrounding cruciferous vegetables and their glucosinolates in relation to the specified health conditions. Although there is evidence that consumption of a high glucosinolate diet is linked with reduced incidence of chronic diseases, future large-scale placebo-controlled human trials including standardized glucosinolate supplements are needed

High ultra-processed food consumption is associated with elevated psychological distress as an indicator of depression in adults from the Melbourne Collaborative Cohort Study

Background: Few studies have tested longitudinal associations between ultra-processed food consumption and depressive outcomes. As such, further investigation and replication are necessary. The aim of this study is to examine associations of ultra-processed food intake with elevated psychological distress as an indicator of depression after 15 years. Method: Data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 23,299). We applied the NOVA food classification system to a food frequency questionnaire (FFQ) to determine ultra-processed food intake at baseline. We categorised energy-adjusted ultra-processed food consumption into quartiles by using the distribution of the dataset. Psychological distress was measured by the ten-item Kessler Psychological Distress Scale (K10). We fitted unadjusted and adjusted logistic regression models to assess the association of ultra-processed food consumption (exposure) with elevated psychological distress (outcome and defined as K10 ≥ 20). We fitted additional logistic regression models to determine whether these associations were modified by sex, age and body mass index. Results: After adjusting for sociodemographic characteristics and lifestyle and health-related behaviours, participants with the highest relative intake of ultra-processed food were at increased odds of elevated psychological distress compared to participants with the lowest intake (aOR: 1.23; 95%CI: 1.10, 1.38, p for trend = 0.001). We found no evidence for an interaction of sex, age and body mass index with ultra-processed food intake. Conclusion: Higher ultra-processed food intake at baseline was associated with subsequent elevated psychological distress as an indicator of depression at follow-up. Further prospective and intervention studies are necessary to identify possible underlying pathways, specify the precise attributes of ultra-processed food that confer harm, and optimise nutrition-related and public health strategies for common mental disorders

Vitamin C Status and Cognitive Function: A Systematic Review

Vitamin C plays a role in neuronal differentiation, maturation, myelin formation and modulation of the cholinergic, catecholinergic, and glutaminergic systems. This review evaluates the link between vitamin C status and cognitive performance, in both cognitively intact and impaired individuals. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library from 1980 to January 2017, finding 50 studies, with randomised controlled trials (RCTs, n = 5), prospective (n = 24), cross-sectional (n = 17) and case-control (n = 4) studies. Of these, 36 studies were conducted in healthy participants and 14 on cognitively impaired individuals (including Alzheimer’s and dementia). Vitamin C status was measured using food frequency questionnaires or plasma vitamin C. Cognition was assessed using a variety of tests, mostly the Mini-Mental-State-Examination (MMSE). In summary, studies demonstrated higher mean vitamin C concentrations in the cognitively intact groups of participants compared to cognitively impaired groups. No correlation between vitamin C concentrations and MMSE cognitive function was apparent in the cognitively impaired individuals. The MMSE was not suitable to detect a variance in cognition in the healthy group. Analysis of the studies that used a variety of cognitive assessments in the cognitively intact was beyond the scope of this review; however, qualitative assessment revealed a potential association between plasma vitamin C concentrations and cognition. Due to a number of limitations in these studies, further research is needed, utilizing plasma vitamin C concentrations and sensitive cognitive assessments that are suitable for cognitively intact adults

Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended

The acute effect of high-dose intravenous Vitamin C and other nutrients on blood pressure: A cohort study

BACKGROUND: Regular intake of vitamin C/ascorbate reduces blood pressure (BP) in hypertensives. High-dose intravenous vitamin C (IVC) achieves higher plasma levels; however, there is a paucity of research on acute BP effects. Our study is the first to investigate the effect of high-dose IVC, with or without concomitant i.v. nutrients, on BP during i.v. treatment. METHODS: A cohort of adult patients scheduled to receive IVC treatment for infection, cancer or fatigue, as prescribed by their treating doctor, participated at a Melbourne clinic, Australia. Ambulatory BP was assessed every 10 min over 90 min during i.v. treatment. Patients received 15–100 g of IVC alone or in addition to i.v. vitamin B, glutathione, magnesium or zinc. BP change over time adjusted for baseline BP, IVC dosage, i.v. treatment and BMI was analysed. RESULTS: A total of 77 mostly normotensive patients participated, with a third receiving IVC alone (42±20 g), and two-thirds also received other i.v. nutrients. IVC alone (>30 g) reduced the mean BP up to 8–9 mmHg in prehypertensive patients. In contrast, concomitant intravenous vitamin B12 (IVB12) significantly increased the mean BP by 11–13 mmHg. Comparison of BP change during IVC versus IVC+IVB12 indicated a highly significant difference [systolic blood pressure: mean difference (SD)=16.6 (17.8) mmHg, P<0.001; diastolic blood pressure: mean difference (SD)=12.5 (16.7) mmHg, P=0.003]. CONCLUSION: Our study suggests an acute BP-reducing effect of high-dose IVC, particularly with dosages above 30 g, and in patients with prehypertension and normal BMI. Furthermore, our study indicated a marked and clinically relevant hypertensive effect of IVB12, suggesting routine BP monitoring during i.v. therapy in clinical practice

The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: The AGE at Heart trial

Background: Hypertension affects 30% of adults worldwide. Garlic supplements have shown promise in the treatment of uncontrolled hypertension, and the mechanism of action is biologically plausible. Our trial is the first to assess the effect of aged garlic extract on central blood pressure and arterial stiffness, regarded as important risk factors for cardiovascular morbidity. Subjects and methods: A total of 88 general practice patients and community members with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12 weeks investigating the effect of daily intake of aged garlic extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, and secondary outcome measures of central-hemodynamics and other cardiovascular markers, including cholesterol, homocysteine, platelet function, and inflammatory markers. Results: Mean blood pressure was significantly reduced by 5.0&plusmn;2.1 mmHg (P=0.016) systolic, and in responders by 11.5&plusmn;1.9 mmHg systolic and 6.3&plusmn;1.1 mmHg diastolic compared to placebo (P,0.001). Central hemodynamic-measures tended to improve in the garlic group more than in the placebo group, including central blood pressure, central pulse pressure, mean arterial pressure, augmentation pressure, pulse-wave velocity, and arterial stiffness. While changes in other cardiovascular markers did not reach significance due to small numbers in subgroups with elevated levels, trends in beneficial effects of garlic on the inflammatory markers TNF&alpha;, total cholesterol, low-density lipid cholesterol, and apolipoproteins were observed. Aged garlic extract was highly tolerable and acceptable, and did not increase the risk of bleeding in patients on blood-thinning medication. Conclusion: Our trial suggests that aged garlic extract is effective in reducing peripheral and central blood pressure in a large proportion of patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and other cardiovascular markers in patients with elevated levels. Aged garlic extract was highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment