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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.

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. 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. Mean blood pressure was significantly reduced by 5.0±2.1 mmHg (P=0.016) systolic, and in responders by 11.5±1.9 mmHg systolic and 6.3±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 TNFα, 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. 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.

Background COVID-19 is a global pandemic. Treatment with hydroxychloroquine (HCQ), zinc, and azithromycin (AZM), also known as the Zelenko protocol, and treatment with intravenous (IV) vitamin C (IVC) have shown encouraging results in a large number of trials worldwide. In addition, vitamin D levels are an important indicator of the severity of symptoms in patients with COVID-19. Objectives Our multicenter, randomized, open-label study aimed to assess the effectiveness of HCQ, AZM, and zinc with or without IVC in hospitalized patients with COVID-19 in reducing symptom severity and duration and preventing death. Methods Hospitalized patients with COVID-19 in seven participating hospitals in Turkey were screened for eligibility and randomly allocated to receive either HCQ, AZM, and zinc (group 1) or HCQ, AZM, zinc plus IV vitamin C treatment (group 2) for 14 days. The patients also received nontherapeutic levels of vitamin D3. The trial is registered on the Australian and New Zealand Clinical Trial Registry ACTRN12620000557932 and has been approved by the Australian Therapeutic Goods Administration (TGA). Results A total of 237 hospitalized patients with COVID-19 aged 22-99 years (mean: 63.3 ± 15.7 years) were enrolled in the study. Almost all patients were vitamin D deficient (97%), 55% were severely vitamin D deficient (<25 nmol/L) and 42% were vitamin D deficient (<50 nmol/L); 3% had insufficient vitamin D levels (<75 nmol/L), and none had optimal vitamin D levels. Of the patients, 73% had comorbidities, including diabetes (35%), heart disease (36%), and lung disease (34%). All but one patient (99.6%; n = 236/237) treated with HCQ, AZM, and zinc with or without high-dose IV vitamin C (IVC) fully recovered. Additional IVC therapy contributed significantly to a quicker recovery (15 days versus 45 days until discharge; p = 0.0069). Side effects such as diarrhea, nausea, and vomiting, reported by 15%-27% of the patients, were mild to moderate and transient. No cardiac side effects were observed. Low vitamin D levels were significantly correlated with a higher probability of admission to the intensive care unit (ICU) and longer hospital stay. Sadly, one 70-year-old female patient with heart and lung disease died after 17 days in ICU and 22 days in the hospital. Her vitamin D level was 6 nmol/L on admission (i.e., severely deficient). Conclusions Our study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery. Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study's patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels. Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C.

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 ( = 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 ( = 188 ± 4 vs. 167 ± 9, = 0.039), immediate recognition memory ( = 81 ± 3 vs. 68 ± 6, = 0.03), congruent Stroop ( = 134 ± 3 vs. 116 ± 7, = 0.024), and delayed recognition tasks ( = 72 ± 2 vs. 62 ± 4, = 0.049), after adjusting for age ( < 0.05). Significantly higher scores in immediate recall on the HVLT-R ( = 10.64 ± 0.16 vs. 9.17 ± 0.37, = 0.001), delayed recall ( = 9.74 ± 0.22 vs. 7.64 ± 0.51, < 0.001), total recall ( = 27.93 ± 0.48 vs. 24.19 ± 1.11, = 0.003) were shown in participants with adequate plasma Vitamin-C concentrations, after adjusting for vitamin-C supplementation dose ( < 0.05). Similarly, higher SDMT scores were observed in participants with adequate plasma Vitamin-C concentrations ( = 49.73 ± 10.34 vs. 41.38 ± 5.06, = 0.039), after adjusting for age ( < 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. ACTRN 12615001140549, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440.

There is increasing evidence that sex differences in the brain may contribute to gender-related behavioral differences, including cognitive function. Literature has revealed gender dimorphisms in cognitive function between males and females. Additionally, several risk factors associated with cognitive decline depend on chronological age. It is well recognized that the process of aging is associated with a decline in cognitive ability and brain function. Various explanations may account for these gender-related cognitive differences and age-associated cognitive changes. Recent investigations have highlighted the importance of vitamin C in maintaining brain health and its association with cognitive function in both cognitively intact and impaired cohorts. The present review explores previous literature that has evaluated differences in plasma/brain vitamin C between genders and during aging. It then assesses whether these age and gender-related differences may affect the relationship between plasma/brain vitamin C and cognition. The purpose of this review was to examine the evidence for a link between plasma/brain vitamin C and cognition and the impact of gender and age on this relationship. Epidemiological studies have frequently shown higher vitamin C plasma concentrations in women. Similarly, aging has been systematically associated with reductions in plasma vitamin C levels. A range of animal studies has demonstrated potential gender and age-related differences in vitamin C brain distribution and utilization. The reviewed literature suggests that gender differences in plasma and brain vitamin C may potentially contribute to differences in gender-associated cognitive ability, particularly while females are pre-menopausal. Additionally, we can propose that age-associated differences in plasma and brain vitamin C may be potentially linked to age-associated cognitive differences, with older cohorts appearing more vulnerable to experience declines in plasma vitamin C concentrations alongside compromised vitamin C brain regulation. This review encourages future investigations to take into account both gender and age when assessing the link between plasma vitamin C concentrations and cognitive function. Further large scale investigations are required to assess whether differences in cognitive function between genders and age groups may be causally attributed to plasma vitamin C status and brain distribution and utilization.

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered.

Abstract Background Vitamin C (ascorbic acid) is a micronutrient imperative for many bodily functions, with research revealing its functional support of leukocytes. The purpose of this meta-analysis was to determine the effects of surgery on leukocyte vitamin C concentrations by assessing the amount and longevity of post-operative leukocyte vitamin C change. Data Sources We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases for relevant research papers. Studies were included until January 2022, with no time limits. Studies that reported means and standard deviations of leukocyte/buffer layer vitamin C concentrations before and after surgery were included into the meta-analysis. The meta-analysis comprised of eight studies. Results Seven studies (which included 8 individual studies) were included into our meta-analysis. Combined data from the meta-analysis displayed a significant depletion in mean leukocyte vitamin C concentrations during the first 24 hours following the surgery by a mean of 5.37 µg/108 (32.3%) (CI = -6.35, -4.40) (n = 6, p < 0.001) and during the first post-operative week by 4.43 µg/108 (23%) (-7.27, -1.58) (n = 7, p < 0.001). However, this depletion was followed by an uprise in mean ascorbic acid leukocyte concentrations of 0.93 µg/108 (4.8%) (-0.79, 2.66) (n = 6, p = 0.29) at 7 days (or beyond) post-operatively. Conclusion Significant post-operative leukocyte vitamin C depletions were particularly observed during the first post-operative week. Further research is required to validate the observed results and to determine whether the observed depletions may be linked to compromised immunological function and pathophysiologies that arise during the post-operative period.

Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels ( p =.022) and enhanced mood ( p =.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints. Conclusion This represents the first documented qualitative investigation of participants’ experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being. Trial registration Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au ) ACTRN12611000092998

Surgical procedures for the symptomatic removal of the gallbladder and the vermiform appendix have been posited to adversely shift the assemblage of the intestinal microbiome increasing the risk of disease. The associated mechanisms have been linked with dysbiosis of the gut microbiota. Cholecystectomy causes changes of bile acid compositions and bile secretion patterns as bile acids interact with the intestinal microbiota in a bidirectional capacity. An appendectomy precludes the further recolonization of the proximal colon with a commensal biofilm that could maintain a stable intestinal microbiome. Epidemiological studies indicate that there is an increased risk of disease rather than causality following a cholecystectomy and appendectomy. This narrative review summarizes studies that report on the role that bile salts and the appendix, contribute to the assemblage of the intestinal microbiome in health and disease.

Arterial stiffness is a cardiovascular risk factor that increases with age. Kyolic aged garlic extract has been shown to reduce arterial stiffness, while normalizing blood pressure, cholesterol and blood thickness. The present study hypothesized that increased flexibility of arteries could lead to slower blood flow and increased oxygen uptake and overall aerobic fitness. The present 12 week trial aimed to assess the effect of Kyolic aged garlic extract (AGE) on arterial stiffness, aerobic fitness, lactate threshold, recovery from muscle soreness and cardiovascular proteomic biomarkers in middle-aged (40-65 years) endurance athletes with elevated arterial stiffness. A total of 75 middle-aged recreational endurance athletes completed the trial, after being randomly allocated for 12 weeks to either the placebo or Kyolic aged garlic extract groups: low-dose cohort 1 (n=37), 2 capsules/day containing 1.2 g AGE powder and 1.2 mg S-allylcysteine (SAC); and the high-dose cohort 2 (n=38), 4 capsules/day of 2.4 g AGE powder and 2.4 mg SAC. Arterial stiffness was assessed through pulse wave velocity measurements and aerobic fitness was measured by volume-maximal-oxygen-consumption (VO2max) and lactate thresholds during high-intensity exercise using a cycle-ergometer-test-station, as well as measuring the levels of muscle fatigue and recovery time at 12 weeks compared with the baseline results. Urinary proteomic analysis was performed in a subgroup of participants and measured the levels of certain relevant proteins used as biomarkers for risk of cardiovascular events, at 12 weeks compared with baseline results. The Kyolic aged garlic extract group significantly improved their aerobic fitness, as was evidenced by increased VO2max, increased aerobic power, higher lactate threshold-to-oxygen uptake, higher lactate threshold-to-power output and quicker recovery times compared with the placebo group. Pulse wave velocity, a measure for arterial flexibility, was improved in the Kyolic aged garlic extract group compared with the placebo. The proteomics analysis demonstrated that a subset of polypeptides associated with cardiovascular risk, such as heart attacks and stroke, decreased in the Kyolic aged garlic extract group at 12 weeks compared with the baseline, which was contrary to the effects observed in the placebo group. Therefore, the results of the present study suggested that Kyolic aged garlic extract significantly improved aerobic fitness, lactate threshold, recovery and cardiovascular proteomic biomarkers in middle-aged endurance athletes within 12 weeks. The present clinical trial was registered on 11/03/2020 at the Australian New Zealand Clinical Trial Registry (trial registration no. ACTRN12620000340932).