The efficacy of vitamin E in preventing arthrofibrosis after joint replacement.

BACKGROUND: Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues. Vitamin E is an antioxidant with potential anti-fibroblastic effect. The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis. METHODS: We simulated knee replacement in 16 male Sprague-Dawley rats. We immobilized the surgical leg with a suture in full flexion. The control groups were killed at 2 and 12 weeks (n = 5 per group), and the test group was supplemented daily with vitamin E (0.2 mg/mL) in their drinking water for 12 weeks (n = 6). We performed histological staining to investigate the presence and severity of arthrofibrosis. Immunofluorescent staining and α2-macroglobulin (α2M) enzyme-linked immunosorbent assay (ELISA) were used to assess local and systemic inflammation. Static weight bearing (total internal reflection) and range of motion (ROM) were collected for functional assessment. RESULTS: The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups. Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue. Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels. The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group. CONCLUSIONS: This model is viable for simulating arthrofibrosis after joint replacement. Vitamin E may benefit postsurgical arthrofibrosis, and further studies are needed for dosing requirements.

Evaluation of therapeutic use of a combination of pentoxifylline and vitamin E in radiation-induced renal fibrosis.

Radiation-induced renal fibrosis (RIRF) is a progressive, irreversible condition causing chronic kidney disease. Pentoxifylline (PTX) and vitamin E may mitigate radiation-induced damage and fibrosis. This study assesses their effectiveness. We used four groups, each with six rats: radiation therapy alone (RT-only), radiation therapy plus drug treatment (RT + drug), drug treatment alone (drug-only), and a control group. Rats were monitored for three months, with weight measurements every four weeks. Afterward, rats were analyzed biochemically and histologically, with blood and tissue samples taken for statistical comparison. No significant differences in serum creatinine levels and body weight were observed. RT-only group had more severe kidney tubule effects. Histomorphological, immunohistochemical, and TUNEL analyses showed significant RIRF mitigation in the RT + drug group. Our study highlighted molecular pathways (SMAD, TGF-beta, VEGF) and histological markers (collagens, a-SMA, fibronectin, metalloproteinases) associated with RIRF. PTX and vitamin E reduced ionizing radiation's impact on renal cells and mitigated radiation-induced kidney fibrosis. Further human studies are needed to confirm these findings.

Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction.

Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, reperfusion after an ischemic insult and sudden oxygen exposure lead to the exacerbated synthesis of additional reactive oxidative species and the persistence of increased oxidation levels. Attempts based on antioxidant treatment have failed to achieve an effective therapy for cardiovascular disease patients. The controversial use of vitamin C as an antioxidant in clinical practice is comprehensively systematized and discussed in this review. The dose-dependent adsorption and release kinetics mechanism of vitamin C is complex; however, this review may provide a holistic perspective on its potential as a preventive supplement and/or for combined precise and targeted therapeutics in cardiovascular management therapy.

Intermittent Fasting and Vitamin E Supplementation Attenuates Hypothyroidism-Associated Ophthalmopathy.

Visualization is a complex-integrated procedure of the eyes and brain that allows to see this colorful world. Hypothyroidism-associated ophthalmopathy (HAO), often known as dry eyes, swelling around the eyes, blurred vision, glaucoma, and cataracts, are some eye-related issues caused by hypothyroidism. Yet there is no permanent cure for hypothyroidism; taking medicine throughout life is the only solution to keep its harmful effects under control. This study used intermittent fasting (IF) and vitamin E (Vit.E) supplementation to prevent hypothyroidism-associated ophthalmopathy. This study hypothesized that intermittent fasting-like diet regimens and vitamin supplementation should reduce the propagation of HAO by its antioxidant potential. In the present study, experimental animals are divided into five groups: normal, hypothyroidism control, dual, Vit. E, and IF. Hypothyroidism is generated in the experimental groups by taking propylthiouracil (PTU) for 24 days while also taking IF and Vit. E supplements. The hypothyroid-induced experimental animals demonstrated an increase in IOP and lipid peroxidation while thyroid hormone levels depicted a massive decline which is a clear denotation of the effects of the thyroid on eyes and lifestyle. Ancient Ayurveda inspires these proposed therapies and has successfully reduced all the damage to the thyroid gland and the eye.

Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production.

To date only four recombinant growth factors, including Filgrastim (rhG-CSF), have been approved by FDA as radiomitigators to ameliorate hematopoietic acute radiation syndrome (H-ARS). These approved agents are not stable under room-temperature, needing to be stored at 2-8 °C, and would not be feasible in a mass casualty scenario where rapid and cost-effective intervention is crucial. Delta-tocotrienol (δ-T3H), the most potent G-CSF-inducing agent among vitamin E isoforms, exhibited efficiency and selectivity on G-CSF production in comparison with TLR and STING agonists in mice. Five-dose δ-T3H was utilized as the optimal therapeutic regimen due to long-term G-CSF production and the best peripheral blood (PB) recovery of irradiated mice. Comparable with rhG-CSF, sequential administration of δ-T3H post-irradiation improved hematologic recovery and accelerated the regeneration of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the bone marrow (BM) and spleen of 6.5Gy irradiated mice; and consistently enhanced repopulation of BM-HSCs. In 4.0Gy irradiated nonhuman primates, δ-T3H exhibited comparable efficacy as rhG-CSF to promote PB recovery and colony-formation of BM-HPCs. Altogether, we demonstrated that sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production, indicated δ-T3H as a promising radiomitigator for the management of H-ARS, particularly in a mass casualty scenario.

Tocotrienol isoforms: The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials.

Tocotrienols are found in a variety of natural sources, like rice bran, annatto seeds and palm oil, and have been shown to have several health-promoting properties, particularly against chronic diseases such as cancer. The incidence of cancer is rapidly increasing around the world, not only a result of continued aging and population growth, but also due to the adoption of aspects of the Western lifestyle, such as high-fat diets and low-physical activity. The literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers, including breast, lung, ovarian, prostate, liver, brain, colon, myeloma and pancreatic cancers. These findings, along with the reported safety profile of tocotrienols in healthy human volunteers, encourage further research into these compounds' potential use in cancer prevention and treatment. The current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks, such as cellular proliferation, apoptosis, angiogenesis and metastasis. MEDLINE/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive benefits. Following an overview of pre-clinical studies, we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.

Effect of vitamin E with and without saffron on the sexual function in women of reproductive age with sexual dysfunction: a randomized controlled trial.

BACKGROUND: Sexual satisfaction is a crucial part of a fulfilled life, and the ability to have satisfying sexual function is crucial to one's sexual health. This study investigated the effect of the combined administration of saffron and vitamin E and vitamin E alone on the sexual function of women in their reproductive years. METHODS: A triple-blind randomized controlled trial was conducted with 50 participants experiencing sexual dysfunction without comorbid sleep disorders or severe depression. They were allocated into two groups using a block randomization method (stratified based on the severity of moderate or mild/normal depression). During the 8-week intervention period, participants in the experimental group were administered a 15 mg saffron capsule (safrotin) in the morning and a combination capsule containing 15 mg saffron and 50 mg vitamin E (safradide) in the evening. During the same period, the control group consumed one saffron placebo capsule in the morning and one capsule containing 50 mg of vitamin E and saffron placebo in the evening (in identical appearance to safradide). The Female Sexual Function Index was used to assess sexual function, and the Depression, Anxiety, and Stress Scale-21 (DASS-21) was used to measure levels of depression, anxiety, and stress. These measures were administered at baseline as well as four and eight weeks post-intervention, with an additional measurement taken four weeks after the intervention ceased. The repeated measures ANOVA, ANCOVA, and Mann-Whitney U tests were used to compare the groups. RESULTS: Following the intervention, the experimental group (saffron and vitamin E) demonstrated a statistically significant increase in the overall mean score of sexual function compared to the control group (placebo of saffron and vitamin E) (adjusted mean difference (AMD): 4.6; 95%CI: 3.1 to 6.1; p < 0.001). The mean scores for sexual function dimensions, namely libido, arousal, orgasm, and satisfaction, except for pain, were consistently higher than those of the control group across all time points (p < 0.001). Additionally, the mean score for lubrication was significantly higher only at the eighth-week measurement (p = 0.004). The mean depression score in the experimental group was significantly lower than in the control group at all-time points, i.e., four (p = 0.011) and eight weeks after the intervention (p = 0.005), and four weeks after the end of the intervention (p = 0.007). The experimental group exhibited a statistically significant decrease in mean anxiety score compared to the control group at four weeks into the intervention (p = 0.016) and four weeks following the end of the intervention (p = 0.002). At eight weeks post-intervention, however, there was no significant difference between the groups (p = 0.177). Additionally, the experimental group exhibited a significant reduction in the overall mean stress score compared to the control group after the intervention (AMD: -2.3; 95%CI: -3.1 to -1.5; p < 0.001). CONCLUSION: Using the combination of saffron and vitamin E is more effective in improving sexual function and its domains compared to vitamin E alone in women of reproductive age with sexual dysfunction without severe depression. Also, it diminishes the degree of depression, anxiety, and stress more compared to vitamin E alone. However, further research is required to arrive at a more definitive conclusion. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20100414003706N36. Date of registration: 17/05/2020; URL: https://en.irct.ir/trial/45992 ; Date of first registration: 21/05/2020.

Effects of postoperative antioxidants on the salivary glands in patients with thyroid cancer undergoing radioactive iodine-131 treatment.

OBJECTIVE: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.

Protective effects of vitamin E against acrylamide-induced hepatotoxicity and nephrotoxicity from fetal development to adulthood: Insights into Akt/NF-κB and Bcl-xL/Bax signaling pathways.

Acrylamide (ACR), a toxin present in fried and baked carbohydrate-rich foods, is known to cause liver and kidney damage. This study aimed to investigate the mechanisms of oxidative stress, inflammation, and apoptosis that contribute to liver and kidney damage induced by chronic administration of ACR. Additionally, the effectiveness of vitamin E in mitigating these toxic effects was examined. The study initially involved dividing 40 pregnant rats into four groups. After lactation, the research continued with male offspring rats from each group. The offspring rats were divided into Control, Vitamin E, ACR, and ACR + Vitamin E groups. Following ACR administration, liver and kidney function tests were performed on serum samples. Biochemical analyses, evaluation of inflammation markers, histopathological examination, and assessment of protein levels of Akt/IκBα/NF-κB, Bax, Bcl-xL, and Caspase-9 were conducted on liver and kidney tissues. The analysis demonstrated that ACR adversely affected liver and kidney function, resulting in oxidative stress, increased inflammation, and elevated apoptotic markers. Conversely, administration of vitamin E positively impacted these parameters, restoring them to control levels. Based on the results, the mechanism of ACR's action on oxidative stress and inflammation-induced liver and kidney damage may be associated with the activation of apoptotic markers such as Bax and Caspase-9, as well as the Akt/IκBα/NF-κB signaling pathway. Consequently, the protective properties of vitamin E establish it as an essential vitamin for the prevention or mitigation of various ACR-induced damages.

From A to E: Uniting vitamins against stroke risk-A systematic review and network meta-analysis.

BACKGROUND AND AIM: Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. METHODS: A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. RESULTS: A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR: .85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). CONCLUSION: Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

Effect of vitamin B2, vitamin C, vitamin D, vitamin E and folic acid in adults with essential hypertension: a systematic review and network meta-analysis.

OBJECTIVES: The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched from their inception to 25 September 2023. OUTCOMES: The primary outcomes were the difference between the intervention group and the control group in changes in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) from baseline. The secondary outcomes were the difference between the intervention group and the control group in changes in 24-hour mean ambulatory systolic blood pressure (24 hours SBP), 24-hour mean ambulatory diastolic blood pressure (24 hours DBP) and heart rate (HR) from baseline. RESULTS: A total of 23 studies comparing five vitamins (vitamin B2, vitamin C, vitamin D, vitamin E, folic acid) and involving 2218 participants were included. The included trials were all vitamin versus placebo, so the network was star-shaped. Among the five vitamins, only vitamin E was significantly more effective at reducing SBP (mean difference: -14.14 mm Hg, 95% credible intervals: -27.62 to -0.88) than placebo. In addition, no evidence was found that any of the five vitamins influenced DBP, 24 hours SBP, 24 hours DBP, or HR. The dose of vitamins, geographical region and percentage of males (only SBP) might be sources of heterogeneity. Sensitivity and subgroup analysis revealed that the effect of vitamin intervention on blood pressure varies according to different doses of vitamins. CONCLUSIONS: According to the results, vitamin E might be an effective measure to reduce SBP, but more research is needed to validate this finding. PROSPERO REGISTRATION NUMBER: CRD42022352332.

A prospective study to evaluate the efficacy and safety of vitamin E and levocarnitine prophylaxis against doxorubicin-induced cardiotoxicity in adult breast cancer patients.

BACKGROUND: Doxorubicin induces acute and chronic cardiotoxicity. This study is aimed to evaluate the efficacy and safety of vitamin E and levocarnitine (EL) as cardioprotective agents against acute doxorubicin cardiotoxicity in female adult breast cancer patients. METHODS: A prospective, randomized controlled study was conducted in patients treated with doxorubicin and cyclophosphamide (AC). Patients were randomly assigned to EL plus AC or AC alone for the duration of 4 cycles. Cardiac enzymes (B-type natriuretic peptide, creatine kinase, troponin I (Trop)) and cardiac events were monitored during treatment to evaluate the cardioprotective efficacy of EL. RESULTS: Seventy-four patients were recruited and received four cycles of chemotherapy. The intervention group (n = 35) showed a significant reduction in both the B-type natriuretic peptide and creatine kinase cardiac enzymes compared to the control group (n = 39). The median (IQR) change for BNP was 0.80 (0.00-4.00) for IG versus 1.80 (0.40-3.60) for CG groups (p < 0.001); creatine kinase was -0.08 (-0.25-0.05) for IG versus 0.20 (0.05-0.50) for CG (p < 0.001). The addition of EL decreased the cardiac events by 24.2% (p = 0.02). All adverse events were tolerable and manageable. CONCLUSION: This study supports the addition of EL as prophylaxis against acute doxorubicin cardiotoxicity and it was also very well tolerated by a majority of the patients. The co-administration of EL at higher doxorubicin (240 mg/m2) dose should be further investigated.

Effects of emulsified and non-emulsified palm tocotrienol on bone and joint health in ovariectomised rats with monosodium iodoacetate-induced osteoarthritis.

Postmenopausal women are susceptible to osteoporosis and osteoarthritis. Tocotrienol, a bone-protective nutraceutical, is reported to prevent osteoarthritis in male rats. However, its efficacy on joint health in oestrogen deficiency has not been validated. Besides, data on the use of emulsification systems in enhancing bioavailability and protective effects of tocotrienol are limited. Ovariectomised adult female Sprague-Dawley rats (3 months old) were treated with refined olive oil, emulsified (EPT, 100 mg/kg/day with 25% vitamin E content), non-emulsified palm tocotrienol (NEPT, 100 mg/kg/day with 50% vitamin E content) and calcium carbonate (1% w/v in drinking water) plus glucosamine sulphate (250 mg/kg/day) for 10 weeks. Osteoarthritis was induced with monosodium iodoacetate four weeks after ovariectomy. Baseline control was sacrificed upon receipt, while the sham group was not ovariectomised and treated with refined olive oil. EPT and NEPT prevented femoral metaphyseal and subchondral bone volume decline caused by ovariectomy. EPT decreased subchondral trabecular separation compared to the negative control. EPT preserved stiffness and Young's Modulus at the femoral mid-shaft of the rats. Circulating RANKL was reduced post-treatment in the EPT group. Joint width was reduced in all the treatment groups vs the negative control. The EPT group's grip strength was significantly improved over the negative control and NEPT group. EPT also preserved cartilage histology based on several Mankin's subscores. EPT performed as effectively as NEPT in preventing osteoporosis and osteoarthritis in ovariectomised rats despite containing less vitamin E content. This study justifies clinical trials for the use of EPT in postmenopausal women with both conditions.

Yellow Nail Syndrome: Analysis of 23 Consecutive Patients and Effect of Combined Fluconazole-Vitamin-E Treatment.

INTRODUCTION: Yellow nail syndrome (YNS), a very rare disorder of unknown etiology, is characterized by a triad associating yellow nails, respiratory manifestations, and lymphedema. YNS treatment remains non-codified. METHOD: This retrospective study was conducted from January 2008 to December 2022 in a single tertiary department exclusively dedicated to lymphatic diseases. All consecutive patients with YNS were included. RESULTS: Thirteen men and 10 women were included. Three patients had yellow nails at birth or during childhood. For the other 20 patients, median (Q1-Q3) age at first sign was 50.8 (43-61) years, with first-YNS-sign-to-diagnosis interval of 17 (10-56) months. For 4 patients, YNS was associated with primary intestinal lymphangiectasia. The first YNS sign was chronic cough (45.5%), followed by yellow nails (27.3%), chronic sinusitis (18.2%), and lymphedema (9.1%). At first consultation for all patients, 69.6% had the complete triad, all had yellow nails and cough, 82.6% had chronic sinusitis, and 69.6% had lymphedema. Twelve patients' lymphedema involved only the lower limb(s), 2 the lower and upper limbs, and 2 the lower and upper limbs and face. Nineteen (82.6%) patients were prescribed fluconazole (100 mg/day [n = 8] or 300 mg/week [n = 11]) combined with vitamin E (1,000 mg/day) for a median of 13 months. Responses were complete for 4 (21.1%) patients, partial for 8 (42.1%), and therapeutic failures for 7 (36.8%). CONCLUSIONS: YNS is a rare disease that almost always starts with a chronic cough. Despite inconstant efficacy, fluconazole-vitamin E in combination can be prescribed to treat yellow nails.

Effect of antioxidants on semen parameters in men with oligo-astheno-teratozoospermia: a network meta-analysis.

BACKGROUND: Although antioxidants are largely used in subfertile men with oligo-astheno-teratozoospermia (OAT), the choice among different molecules is challenged by the lack of comparative head-to-head studies. The network meta-analysis (NMA) can overcome limitations of pairwise meta-analyses, since it incorporates direct and indirect evidence into a single model generating an effectiveness hierarchy. OBJECTIVE: To assess with a NMA the effects of antioxidants in improving seminal parameters in idiopathic OAT. MATERIALS AND METHODS: PubMed, Scopus, Cinahl, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing any antioxidant treatment to each other or placebo in men with at least one idiopathic seminal abnormality. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). RESULTS: 29 RCTs provided information on 2045 men (mean age: 33.5 years) with idiopathic OAT and 19 antioxidant preparations. Compared to placebo, l-carnitine, especially in combination with l-acetyl-carnitine (LAC), had the highest SUCRA for sperm concentration, progressive motility, and morphology. Folate was the only other compound effective on sperm concentration. Vitamin E+selenium or zinc had the highest SUCRA for total motility. A contribution on progressive motility was revealed for pentoxifylline and vitamin E+CoQ10.

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.

BACKGROUND/IMPORTANCE: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases. OBJECTIVE: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults. EVIDENCE REVIEW: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence. FINDINGS: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies. CONCLUSIONS: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.

Effects of perioperative vitamin E and zinc co-supplementation on systemic inflammation and length of stay following coronary artery bypass graft surgery: a randomized controlled trial.

OBJECTIVES: Coronary artery bypass graft (CABG) surgery has been reported to be associated with lower postoperative plasma antioxidant and zinc levels. We hypothesized that perioperative supplementation of vitamin E and zinc might improve short-term postoperative outcomes. METHODS: In this placebo-controlled double-blind, randomized study, patients undergoing CABG performed with cardiopulmonary bypass were recruited. The intervention group received zinc and vitamin E supplementation (1200 IU vitamin E and 120 mg elemental zinc) the day before surgery, followed by postoperative daily supplementation of 30 mg zinc and 200 IU vitamin E from the 2nd day after surgery to 3 weeks. The control group received placebos. Length of stay (LOS) in the intensive care unit and hospital, sequential organ failure assessment score on 3rd day after surgery, and plasma inflammatory markers on days 3 and 21 post-surgery were evaluated. RESULTS: Seventy-eight patients completed the study (40 in the intervention group and 38 in the placebo group). The hospital LOS was significantly shorter (p < 0.05) in the intervention group. Postoperative changes in plasma albumin levels were not different between the two groups. The plasma zinc level was higher (p < 0.0001), but plasma C-reactive protein (p = 0.01), pentraxin 3 (p < 0.0001), interferon γ (p < 0.05), malondialdehyde (p < 0.05), and aspartate aminotransferase (p < 0.01) were lower in the intervention group compared to the placebo group. CONCLUSIONS: Perioperative vitamin E and zinc supplementation significantly reduced hospital LOS and the inflammatory response in CABG surgery patients. In these patients, the optimal combination and dose of micronutrients need further study but could include zinc and vitamin E. CLINICAL TRIAL REGISTRY: This trial was registered at ClinicalTrials.gov website (NCT05402826).

Effect of vitamin E on doxorubicin and paclitaxel-induced memory impairments in male rats.

PURPOSE: In addition to peripheral neuronal dysfunction, conventional chemotherapy can be associated with other neurological treatment-limiting adverse effects, including cognitive dysfunction, memory impairment, and anxiety, which are referred to as "chemobrain". This study aimed to investigate the effects of doxorubicin (DOX) and paclitaxel (PAC) on learning and memory in rats using radial arm water maze (RAWM) and investigated a potential beneficial effect of vitamin E (Vit. E). METHODS: Adult male rats were injected with four doses of 2 mg/kg/week DOX, or 2 mg/kg PAC every other day intraperitoneally. Vit. E was co-administered with these drugs in other groups to study its antioxidative effects. Using the RAWM, each rat was assessed for learning and memory performance through two sets of six trials separated by a 5-min rest period evaluating both short- and long-term effects on memory. RESULTS: There was no deficit in learning or long-term memory in both drug groups compared to control. However, rats in both drug groups made significantly more errors in all short-term memory trials. This effect was mitigated when Vit. E was co-administered with either drug. Moreover, PAC (but not DOX) induced hippocampal lipid peroxidation by increasing the levels of standard biomarker thiobarbituric acid reactive substances (TBARS). Interestingly, Vit. E prevented PAC-induced hippocampal oxidative stress. Furthermore, both DOX and PAC were correlated with reduction in Brain-Derived Neurotrophic Factor (BDNF) expression levels in the hippocampus, which was overcome by the co-administration of Vit. E. CONCLUSION: There is a potential role of Vit. E in alleviating short-term memory impairment in rats exposed to chemotherapy, possibly by reducing hippocampal oxidative stress and neurodegeneration.

Effect of Medicago sativa seed powder (Plus vitamin E vs. vitamin E alone) on semen analysis in men with idiopathic infertility: A double blind randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of the alfalfa plant (Medicago sativa L.), especially its seeds, have been introduced as a semen quality enhancer in the folk medicine of different regions of Iran as well as in the traditional Persian medicine (PM) books. The seeds of this plant are also used in many combined medicines to treat male infertility in PM. AIM OF THE STUDY: This study was designed to investigate the effect of M. sativa seed powder plus vitamin E vs. vitamin E alone on semen analysis of men with idiopathic infertility. MATERIALS AND METHODS: In this randomized clinical trial, 60 participants were randomly divided into two groups and then received M. sativa seed powder (6 g daily) or placebo for three months, as add-on to vitamin E (100 U). Results of semen analysis (sperm total count, motility, and morphology as well as semen volume) of these two groups and their changes were compared before and after treatment as the primary outcome. The number of pregnancies after one month and probable side effects were also assessed. RESULTS: After 12 weeks, sperm total count changed from 36.2 ± 21.8 × 106/ml to 48.5 ± 19.1 × 106/ml in M. sativa and from 39.5 ± 23.5 × 106/ml to 41.2 ± 20.9 × 106/ml in placebo, percentage of normal morphology changed from 1.8 ± 0.8% to 2.6 ± 1.2 % in M. sativa and from 2.0 ± 0.9% to 2.6 ± 1.2% in placebo and percentage of motile sperm changed from 36.5 ± 11.8 % to 39.7 ± 12.0% in M. sativa and from 39.3 ± 10.1 % to 38.1 ± 12.1% in placebo. The improvements in M. sativa group are significantly better than placebo group (P = 0.00, 0.01 and 0.04, respectively). However, semen volume decreased in both groups, but its changes were not significant. The number of pregnancies was four in the intervention and zero in placebo group. One case with abdominal bloating and one with respiratory allergy withdrew from the intervention group. No other adverse effect was reported. CONCLUSIONS: In this study, significant improvement was detected in sperm parameters (except semen volume) of men with idiopathic infertility in M. sativa plus vitamin E group in compare to vitamin E alone after 12 weeks. These findings suggest that the M. sativa, as a complementary therapy, may have a beneficial effect on semen quality. More clinical trials with larger sample size are needed.

Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects.

Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1ß, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFß), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.