Significance: Excess oxidative stress and neuroinflammation are risk factors in the onset and progression of Alzheimer's disease (AD) and its association with amyloid-β plaque accumulation. Oxidative stress impairs acetylcholine (ACH) and N -methyl- d -aspartate receptor signaling in brain areas that function in memory and learning. Glutathione (GSH) antioxidant depletion positively correlates with the cognitive decline in AD subjects. Treatments that upregulate GSH and ACH levels, which simultaneously decrease oxidative stress and inflammation, may be beneficial for AD. Recent Advances: Some clinical trials have shown a benefit of monotherapy with vitamin D (VD), whose deficiency is linked to AD or with l -cysteine (LC), a precursor of GSH biosynthesis, in reducing mild cognitive impairment. Animal studies have shown a simultaneous decrease in ACH esterase (AChE) and increase in GSH; combined supplementation with VD and LC results in a greater decrease in oxidative stress and inflammation, and increase in GSH levels compared with monotherapy with VD or LC. Therefore, cosupplementation with VD and LC has the potential of increasing GSH, downregulation of oxidative stress, and decreased inflammation and AChE levels. Future Directions: Clinical trials are needed to determine whether safe low-cost dietary supplements, using combined VD+LC, have the potential to alleviate elevated AChE, oxidative stress, and inflammation levels, thereby halting the onset of AD. Goal of Review: The goal of this review is to highlight the pathological hallmarks and current Food and Drug Administration-approved treatments for AD, and discuss the potential therapeutic effect that cosupplementation with VD+LC could manifest by increasing GSH levels in patients. Antioxid. Redox Signal. 40, 663–678.

Vitamin D is known to have a positive effect on bone health. Despite the greater frequency of vitamin D deficiency in African Americans (AA), they have a higher bone mineral density (BMD) compared to whites, demonstrating a disconnect between BMD and vitamin D levels in AA. Another intriguing relationship seen in AA is the triglyceride (TG) paradox, an unusual phenomenon in which a normal TG status is observed even when patients house conditions known to be characterized by high TG levels, such as Type II diabetes. To the best of our knowledge, no study has examined whether these two paradoxical relationships exist simultaneously in AA subjects with Type II diabetes. In this study, we compared levels of blood markers, including HbA1c, TG, and vitamin D, measured as serum 25-hydroxyvitamin D [25(OH)VD] µM/mL, [25(OH)VD]/TG, calcium, and BMD in AA (n = 56) and white (n = 26) subjects with Type II diabetes to see whether these relationships exist concurrently. We found that AA subjects had significantly lower TG and [25(OH)VD] levels and a significantly higher BMD status compared to white subjects, even when the ages, BMI, duration of diabetes, HbA1c, and calcium levels were similar between the two groups. This demonstrates that these two paradoxical relationships exist simultaneously in Type II diabetic AA subjects. In addition to these findings, we discuss the current hypotheses in the literature that attempt to explain why these two intriguing relationships exist. This review also discusses four novel hypotheses, such as altered circulating levels and the potential role of estrogen and hydrogen sulfide on BMD and HMG-CoA reductase as a possible contributor to the TG paradox in AA subjects. This manuscript demonstrates that there are still many unanswered questions regarding these two paradoxical relationships and further research is needed to determine why they exist and how they can be implemented to improve healthcare.

Context. Population studies have shown a trend in decreasing vitamin C status and increasing prevalence of osteoporosis in patients with diabetes and non-diabetic people. Dietary vitamin C consumption is linked to improvement in bone mineral density (BMD) in epidemiological studies. VCAM-1 and adiponectin are known to activate osteoclasts, which increase bone loss. Aim: This study examined whether there is any association between the circulating level of vitamin C and BMD and whether the beneficial effect of vitamin C on BMD was linked to a simultaneous decrease in circulating levels of adiponectin and VCAM-1 in subjects with diabetes. Methods: Patients with diabetes (T2D, n = 74) and age-matched non-diabetic controls (n = 26) were enrolled in this study. Fasting blood levels of glycemia, adiponectin, VCAM-1, inflammation biomarkers, and vitamin C were determined in both groups. The BMD of the lumbar spine (L1–L4), left femur, and right femur was determined using a DXA scan in subjects with diabetes. Results: Patients with diabetes had lower levels of vitamin C and higher levels of VCAM-1 and inflammatory cytokines. There was a significant positive association between vitamin C blood levels and lumbar spine BMD as well as a significant negative association between total adiponectin and VCAM-1 levels with that of vitamin C and lumbar BMD in patients with diabetes. Total adiponectin and VCAM-1 also showed a negative association with BMD of both the right and left femurs. The inter-relationship among the circulating levels of vitamin C and VCAM-1 and BMD was strong and is a novel finding. Conclusions: This study reports a positive association of circulating vitamin C levels and the BMD and that the beneficial effects of vitamin C on BMD could be linked to a simultaneous lowering in circulating VCAM-1 and total adiponectin levels. Thus, dietary vitamin C consumption has potential to lower inflammation and the risk of osteoporosis in subjects with diabetes.

Hepatic encephalopathy (HE) is a neuropsychiatric condition frequently associated with cirrhosis and portosystemic shunting (PSS). It imposes a significant clinical and economic burden, with increasing attention toward identifying modifiable factors that could improve outcomes. Emerging evidence suggests that vitamin D deficiency (VDD), prevalent in patients with cirrhosis, may contribute to the development and severity of HE. This review explores the association between VDD and HE by analyzing the underlying pathophysiology, including oxidative stress, ammonia accumulation, and impaired hepatic function. Additionally, we summarize recent studies highlighting the correlation between low serum 25-hydroxy vitamin D (25-OHD) levels and worsening grades of HE. Despite strong observational data, interventional studies on vitamin D (VD) supplementation for HE remains limited. Current evidence suggests that VD’s antioxidant properties may alleviate oxidative stress in HE, with potential benefits in mitigating disease severity. Future research should focus on longitudinal studies and randomized controlled trials to evaluate the clinical impact of VD supplementation on HE outcomes and explore VD’s role in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedures. Understanding the therapeutic potential of VD could lead to improved management strategies for HE and cirrhotic patients at large.

Herein, we report the case of a 20-year-old Caucasian male with a previous psychiatric history of schizophreniform, autism, unspecified intellectual disorder, and past medical history of hypertension, who presented after a suicidal attempt. One month prior to admission for the suicidal attempt, the patient had mutism. While admitted, the patient showed signs of mutism, posturing, negativism, and waxy flexibility. Treatment with both aripiprazole and lorazepam was effective and reversed the patient’s catatonia after low-dose titration. This case highlights the importance of reviewing patient history and presenting symptoms in the management of catatonia. Additionally, this case provides an opportunity to review the diagnostic approach and treatment type used for patients presenting with catatonia.