Effect of vitamin E on severity and duration of cyclic mastalgia: A systematic review and meta-analysis

Hajizadeh K, Alizadeh Charandabi SM, Hasanzade R, Mirghafourvand M

Complement Ther Med. 2019 Jun;44:1-8. doi: 10.1016/j.ctim.2019.03.014. Epub 2019 Mar 22.

Abstract

OBJECTIVES:

A systematic review was conducted to assess the effect of vitamin E on the severity and duration of Cyclic Mastalgia compared to vitamin B6, fish oil, herbal medicines and placebo.

DESIGN:

A systematic review and meta-analysis of clinical trials.

METHODS:

A search was carried out in PubMed, Cochrane Library, Embase, Scopus and Google Scholar and Persian databases for articles published from 1980 to 2018. The data obtained were analyzed in RevMan and reported in forest plots. The Odds Ratio (OR) was used to find the effect for the dichotomous data and the Standardized Mean Difference (SMD) for the continuous data. The heterogeneity of the studies was assessed using I² and the Random Effects Model was used instead of the Fixed Effects Model if I²>25%.

RESULTS:

A total of 1051 titles and abstracts were extracted. Fourteen articles ultimately remained, and 11 of them were entered into the meta-analysis. The meta-analysis showed significant differences between vitamin E and placebo in the severity (SMD=-0.51; 95% CI=-0.21 to -0.82) and duration (MD=-1.47; 95% CI=-0.91 to -2.57) of cyclic mastalgia, although herbal medicines had a greater effect on the severity of mastalgia than vitamin E (SMD = 0.51, 95% CI = 0.06 to 0.96).

CONCLUSION:

Although herbal medicines are more effective than vitamin E, vitamin E reduces both the severity and duration of the disorder compared to placebos, which only reduce its severity, and can therefore be considered a treatment with minimum side-effects. Due to the high heterogeneity of the studies, the researchers recommend further research on the subject using a standard tool based on the CONSORT statement.

Ramdas P, Radhakrishnan AK, Abdu Sani AA, Abdul-Rahman PS

Nutr Cancer. 2019 May 14:1-9. doi: 10.1080/01635581.2019.1607407. [Epub ahead of print]

Abstract

Tocotrienols (T3), a family of vitamin E, are reported to possess potent anti-cancer effects but the molecular mechanisms behind these effects still remain unclear. The aim of this study was to investigate how T3 exert anti-cancer effects on MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were chosen for this study as they are triple-negative and highly metastatic cells, which form aggressive tumors in experimental models. The MDA-MB-231 cells were treated with varying concentrations (0-20 µg mL^-1) of gamma (γ) or delta (δ) T3 and the secretome profiles of these cells treated with half maximal inhibitory concentration (IC₅₀) of γT3 (5.8 µg mL^-1) or δT3 (4.0 µg mL^-1) were determined using label-free quantitative proteomic strategy. A total of 103, 174 and 141 proteins were identified with ProteinLynx Global Server (PLGS) score of more than 200 and above 25% sequence coverage in the untreated control and T3-treated cell culture supernatant respectively. A total of 18 proteins were dysregulated between untreated control and T3 (δT3 or γT3) treated conditions. The results showed that T3 treatment downregulated the exogenous Cathepsin D and Serpine1 proteins but upregulated Profilin-1 protein, which play a key role in breast cancer in the MDA-MB-231 cells. These findings strongly suggest that T3 may induce differential expression of secreted proteins involved in the cytoskeletal regulation of RHO GTPase signaling pathway.

Mehrabi S, Nasirinezhad F, Barati M, Abutaleb N, Barati S, Dereshky BT, Amini N, Milan PB, Jahanmahin A, Sarveazad A, Samadikuchaksaraei A, Mozafari M

Recent Pat Biotechnol. 2019;13(2):137-148. doi: 10.2174/1872208312666181120105333.

Abstract

BACKGROUND:

The increase of oxidant compounds is the most well-known reasons for the tolerance to the analgesic properties of Morphine. Additionally, the production of proxy-nitrite impairs receptors, proteins and enzymes involved in the signaling pathways of analgesia, apoptosis and necrosis. Also, we revised all patents relating to opioid tolerance control methods.

OBJECTIVE:

The aim of this study was to assess the effects of Alpha-tocopherol as an anti-oxidant agent to reduce Morphine tolerance.

METHOD:

Forty male rats randomly divided into four groups. 10 mg/kg of morphine was injected subcutaneously to create the desired level of tolerance. After modeling, 70 mg/kg Alpha- Tocopherol was injected intraperitoneal. Also, the hot plate recorded pain threshold alterations was used to evaluate the behavioral test. All tissue samples were extracted from the spinal cord, thalamus and frontal cortex for molecular and gene expression evaluations. Also, the effect of Alpha- Tocopherol on the apoptosis and necrosis parameters was analyzed using nissl staining and tunel test.

RESULTS:

The time latency results showed that there were no significant differences in the different days in groups treated with Morphine plus Alpha-Tocopherol. However, our data highlighted that the pain threshold and their time latency in respond to it had substantially increased in comparison with the control group. Furthermore, we found that the Alpha-Tocopherol obviously decreased c-fos gene expression, especially in the spinal cord.

CONCLUSION:

Thus, co-administration of Alpha-Tocopherol with Morphine can decrease the adverse effects of nitrite proxy, which is released due to repeated injections of Morphine.

Yumusak N, Sadic M, Akbulut A, Aydinbelge FN, Koca G, Korkmaz M

Bratisl Lek Listy. 2019;120(4):263-269. doi: 10.4149/BLL_2019_048.

Abstract

OBJECTIVES:

The aim of the present study was to investigate the radioprotective effect of vitamin E in the prevention of radioiodine (RAI) induced gastrointestinal damage.

METHOD:

Twenty-four rats were randomly divided into three groups as follows: Group-1 was untreated control group, Group-2 was orally administered single dose of 111 MBq RAI, and Group-3 was orally administered 111 MBq RAI and 1 mL of oral vitamin E. Vitamin E was started two days before RAI administration and was continued for five days once daily after RAI. Pathomorphological parameters of gastrointestinal tissues (stomach, small intestines and bowels) were measured using Hematoxylin-Eosin and Masson’s trichrome staining.

RESULTS:

Varying degrees of inflammation, edema, ulcer, mucosal degeneration, necrosis and fibrosis were seen in the stomach, small intestine and bowel tissues of the rats in both study groups and not in the control group. The differences were statistically significant between these groups for all parameters (p < 0.05). The histopathological damage in the vitamin E treated group was significantly less than the damage in the RAI only group (p < 0.05 for all pathomorphological parameters).

CONCLUSION:

The results of this study showed that vitamin E has a radioprotective property with antiinflammatory and antifibrotic effects protecting against gastrointestinal damage caused by radioiodine.

Iqbal S, Hameed U, Hasan B, Zia-Ul-Islam, Ahmed M, Brohi AH

Int J Health Sci (Qassim). 2019 May-Jun;13(3):19-23.

Abstract

OBJECTIVE:

Attention deficit hyperactivity disorder ranks among the top neuropsychiatric disorder of childhood and adolescents. Methylphenidate (MPH) is the most frequently used pharmacologic agent to treat this condition. Its long-term use has been associated with many unwanted and adverse effects on many organs including male gonads, but so far no study has been done to find out a protective agent. This study investigated the protective potential of Vitamin E (Vit E) against the microscopic and morphometric alterations in male gonads induced by MPH, using albino rats.

METHODS:

Adult male albino rats were assigned into three equal groups including one control and two experimental groups. Experimental groups administered with MPH (10 mg/kg) and MPH (10 mg/kg) + Vit E orally (50 mg/kg), daily for 40 days. Testes of the sacrificed animals were removed, processed, and stained with hematoxylin and eosin for examining the microscopic and morphometric alterations and protective potential of Vit E. Data were analyzed using ANOVA.

RESULTS:

Experimental animals treated with MPH showed a significant decrease in the diameter of seminiferous tubules (296.86 ± 14.70 µm) and height of germinal epithelium (51.73 ± 3.15 µm) with a corresponding gain in the thickness of the interstitium (47.05 ± 4.94 µm). Animals treated with MPH + Vit E did not reveal any significant testicular microscopic changes and seminiferous tubular alterations induced by MPH.

CONCLUSION:

Vit E demonstrated a protective potential against the adverse changes induced by MPH in the male gonads in albino rats.

Malik A, Eggersdorfer M, Trilok-Kumar G

Int J Vitam Nutr Res. 2019 May 24:1-14. doi: 10.1024/0300-9831/a000590. [Epub ahead of print]

Abstract

Vitamin E is a lipid soluble antioxidant which mainly circulates as α-tocopherol in the human plasma. Its deficiency is associated with ataxia, neuropathy, anaemia and several other health conditions. Although substantial data on vitamin E status has been published worldwide, there is paucity of data on the extent of deficiency from most Asian countries, including India. Part of the problem is lack of validated biomarkers for vitamin E and no consensus on cut offs for defining deficiency and sufficiency. Thus, interpretation of the data on the vitamin E status is difficult. Limited available data from 31 studies on vitamin E status in healthy people from Asia, the most populated continent, has been collated for the purpose of this review. Broadly, the results suggest inadequate vitamin E status in most age groups, with the prevalence of deficiency reaching 67%, 80%, 56% and 72% in infants, children and adolescents, adults, elderly and pregnant women, respectively, based on varying cut offs. The findings are not surprising as both, vitamin E intakes and its status have not received too much attention in the past. Lack of conclusive data accentuates the need for more research on the vitamin E status across all age groups and to define age, gender and physiological state specific cut offs for vitamin E levels.

Hakiminia B, Goudarzi A, Moghaddas A

J Biochem Mol Toxicol. 2019 May 21:e22349. doi: 10.1002/jbt.22349. [Epub ahead of print]

Abstract

Cisplatin is one of the highly consumed and effective antitumor agents whose clinical application is accompanied by nephrotoxicity adverse reaction. Also, other complications such as ototoxicity and hepatotoxicity are a matter of concern. Today, it is suggested that cisplatin-associated toxicities are mainly induced by free radicals production, which will result in oxidative organ injury. The evidence is growing over the protective effects of antioxidants on cisplatin-induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin-induced nephrotoxicity and ototoxicity are reviewed here at the light of pertinent results from basic and clinical research. Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decreasing the level of malondialdehyde, reducing serum urea and creatinine, and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione-S-transferase, and superoxide dismutase. Although the data from most of the studies are in favors of protective effects of vitamin E against cisplatin-induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.

Huang J, Weinstein SJ, Yu K, Männistö S, Albanes D

J Natl Cancer Inst. 2019 May 11. pii: djz077. doi: 10.1093/jnci/djz077. [Epub ahead of print]

Abstract

BACKGROUND:

Epidemiologic data are inconsistent regarding the vitamin E-lung cancer association, and no study has examined serologic changes in vitamin E status in relation to subsequent risk.

METHODS:

In a cohort of 22,781 male smokers in the ATBC Study, we ascertained 3,184 lung cancer cases during up to 28 years of observation. Cox proportional hazards models examined whether higher serum alpha-tocopherol concentrations at baseline, 3 years, or the interval change were associated with lower lung cancer risk. All statistical tests were two-sided.

RESULTS:

After adjustment for age, body mass index, smoking intensity and duration, serum total cholesterol, and trial intervention group, we found lower lung cancer risk in men with high baseline alpha-tocopherol (5th quintile (Q5) vs Q1, hazard ratio (HR)=0.76, 95%CI =0.66 to 0.87; Ptrend<0.001). A similar reduction in risk was seen for serum alpha-tocopherol at 3 years (Q5 vs Q1, HR = 0.78, 95%CI =0.67 to 0.91; Ptrend=0.004). The inverse risk association appeared stronger for younger men and those having smoked fewer years, but was similar across trial intervention groups. We also found reduced risk among un-supplemented men with a lower serum alpha-tocopherol at baseline who had greater increases in concentrations at 3 years (3rd tertile vs 1st tertile of serum alpha-tocopherol change, HR = 0.74, 95% CI = 0.59 to 0.91, P=0.005).

CONCLUSION:

Higher vitamin E status, as measured by serum alpha-tocopherol concentration, as well as repletion of a low vitamin E state, was related to decreased lung cancer risk during a 28-year period. Our findings provide evidence supporting the importance of adequate physiological vitamin E status for lung cancer risk reduction.

Ranard KM, Kuchan MJ, Erdman JW Jr

Lipids. 2019 May;54(5):289-299. doi: 10.1002/lipd.12149. Epub 2019 Apr 16.

Abstract

Of the antioxidant vitamin E isoforms, α-tocopherol (αT) and γ-tocopherol (γT) are the most abundant in the human diet, and αT is consumed from both natural and synthetic sources. αT and γT may differentially impact inflammation and influence cardiovascular outcomes, in part by modulating gene expression. The goal of this study was to compare the effects of natural αT, synthetic αT, and γT on gene expression in two human cell lines. Human aortic smooth muscle cells (HASMC) and endothelial cells (HAEC) were either: (1) treated with 25 μM tocopherolsalone, or (2) pretreated with tocopherols prior to a pro-inflammatory cytokine (tumor necrosis factor-alpha, TNF-α) stimulation. The expression of atherosclerosis-related genes was measured using RT² Profiler PCR arrays. Tocopherol treatments alone did not significantly modulate the expression of genes in unstimulated HASMC or HAEC. TNF-α stimulation significantly upregulated genes involved with apoptosis and stress response in both cell lines. Pretreating cells with tocopherols did not normalize the gene expression changes induced by TNF-α. However, αT pretreatments, but not γT pretreatments, attenuated TNF expression in both HASMC and HAEC. These findings suggest that under stimulated conditions, αT modestly modulates the expression of selective genes and that αT may be more anti-inflammatory than γT.

Li D, Tang H, Wei P, Zheng J, Daniel CR, Hassan MM

J Nutr. 2019 May 17. pii: nxz081. doi: 10.1093/jn/nxz081. [Epub ahead of print]

Abstract

BACKGROUND:

Previous studies have found that meat-derived mutagens increase, and vitamin C or E decrease, the risk of pancreatic cancer.

OBJECTIVE:

The aim of this study was to determine whether intake of vitamin C or E modulates the association between meat-derived mutagen exposure and risk of pancreatic cancer.

DESIGN:

We conducted a case-control study in 1321 patients with pathologically confirmed pancreatic ductal adenocarcinoma (PDAC) and 1061 healthy controls (aged 28-88 y). Cases and controls were frequency-matched by age, sex, and race/ethnicity. Mutagen intake was assessed using a meat preparation questionnaire. Intakes of vitamin C, E, and other dietary components were assessed via a food-frequency questionnaire in a subset of 811 cases and 818 controls. ORs and 95% CIs were estimated in multivariable-adjusted logistic regression models.

RESULTS:

The risk of PDAC was not associated with meat intake but was associated with consumption of well-done grilled or barbecued chicken (OR: 1.57; 95% CI: 1.18, 2.09; P = 0.001). Intake of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was associated with increased PDAC risk (Ptrend = 0.047). Participants in the highest, as compared with the lowest, quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (PhIP) intake experienced a 38% increased risk of PDAC (95% CI: 1.00, 1.90; P = 0.048). Intakes of total vitamin C or E from food and supplements or from supplements alone were each inversely associated with PDAC risk. Stratified analyses showed differential associations for PhIP intake and PDAC risk, such that risk increased among individuals with lower intake of vitamin C or E and decreased among those with higher vitamin intake. Significant interactions of dietary vitamin C, dietary vitamin E, and total vitamin E with PhIP intake were detected (Pinteraction = 0.023, <0.001, and 0.013, respectively).

CONCLUSIONS:

Consistent with experimental evidence, this study of 811 cases and 818 controls has shown that high intake of dietary vitamin C or E mitigates the risk of PhIP-related PDAC.