Colorectal Cancer Protective Effects and the Dietary Micronutrients Folate, Methionine, Vitamins B6, B12, C, E, Selenium, and Lycopene

 Mainly for me to keep track of this information, One friend has stage 2 colon cancer and another has stage 4.

Colorectal Cancer Protective Effects and the Dietary Micronutrients Folate, Methionine, Vitamins B6, B12, C, E, Selenium, and Lycopene

Gabriel Kune

&

Lyndsey Watson

Pages 11-21 | Published online: 18 Nov 2009

• Cite this article
• https://doi.org/10.1207/s15327914nc5601_3

Abstract

Abstract: The data reported here were obtained from the case-control arm of a large, comprehensive, population-based investigation of colorectal cancer incidence, etiology, and survival, the Melbourne Colorectal Cancer Study, conducted in Melbourne, Australia. This part of the case-control study was designed to identify dietary factors associated with colorectal cancer risk in 715 incident cases compared with 727 age/sex frequency-matched randomly chosen community controls, in which a quantitative assessment of all foods eaten was made. New data are presented on the potential of two groups of micronutrients as protective agents, namely, those involved in DNA methylation, synthesis, and repair (folate, methionine, and vitamins B6 and B12) and those with antioxidant properties (selenium, vitamins E and C, and lycopene). The adjusted odds ratios showed that for folate there was significant protection for rectal cancer in second and third quintiles of consumption but not for colon cancer, and this was similar for methionine consumption. Vitamin B6 consumption was significantly protective for both colon and rectal cancer at the higher quintiles, and this was similar for vitamin B12. Dietary selenium was significantly protective at middle quintiles of consumption at both cancer sites. Dietary vitamins E and C were statistically significantly protective for both colon and rectal cancer at all levels of consumption, and for both vitamins there was a dose-response effect of increasing protection, particularly so for colon cancer. Lycopene was not associated with colorectal cancer risk. A combined model included vitamins E, C, and B12 and selenium as micronutrients protective for colorectal cancer and folate, which, however, showed an increased risk at the highest level of consumption. These data support the proposition that a diet containing the dietary micronutrients involved in DNA methylation (folate, methionine, and vitamins B6 and B12) and some of those with antioxidant properties (selenium and vitamins E and C) may have a role to play in lowering colorectal cancer risk and also that such protection can be achieved by dietary means alone.

Associations between essential trace elements and Alzheimer's disease and related dementias

 Ask your doctors about the benefits of selenium and iron as described in the following posts. Then get AN EXACT PROTOCOL from them on all trace minerals.

• selenium (15 posts to May 2015)
• iron (13 posts to December 2012)

Associations between essential trace elements and Alzheimer's disease and related dementias

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

Xin Wang,Roger L. Albin,Bruno Giordani,Bhramar Mukherjee,Henry L. Paulson,Kelly M. Bakulski

First published: 26 August 2026

https://doi.org/10.1002/dad2.70467Digital Object Identifier (DOI)

 

Abstract

INTRODUCTION

 Dysregulation of essential trace elements has been implicated in Alzheimer's disease (AD) pathogenesis, yet comprehensive epidemiologic evidence remains limited. We investigated associations of seven plasma essential trace elements, including manganese, iron, cobalt, copper, zinc, selenium, and molybdenum, with AD and all-cause dementia risk.

METHODS

We analyzed 1,737 participants from the National Alzheimer's Coordinating Center. Cross-sectional analyses assessed prevalent disease; longitudinal analyses evaluated incident cases among 1,101 initially dementia-free participants (median follow-up: 2.05 years). Multivariable logistic regression, Cox proportional hazards models, and quantile-based g-computation evaluated individual and mixture effects.

RESULTS

A simultaneous one-quartile increase in the seven-element mixture was associated with lower prevalent AD (odds ratio [OR] = 0.69; 95% confidence interval [CI]: 0.52–0.91). Longitudinally, higher plasma iron was associated with lower incident AD (hazard ratio [HR] = 0.41; 95% CI: 0.19–0.92, Q4 vs. Q1), while selenium predicted higher incident AD risk (HR = 2.42; 95% CI: 1.11–5.27, Q4 vs. Q1).

DISCUSSION

Lower plasma iron and higher plasma selenium were each associated with greater dementia risk, identifying iron and selenium as potentially modifiable factors for dementia prevention, especially in selenium-replete populations.

Highlights

• Higher plasma iron consistently associated with lower dementia risk.

• Plasma selenium paradoxically linked to higher incident Alzheimer's disease (AD) risk.

• Seven-element mixture associated with 30% lower odds of prevalent AD.(Your competent? doctor needs to create AN EXAXT PROTOCOL for these! Can't do that? PURE INCOMPETENCE!)

Safety and efficacy of selenium in improving the outcomes of stroke patients: a systematic review and meta-analysis with GRADE system

 Let's see how much earlier research there is on selenium and the incompetence of your doctor in not doing something with it!

Here is how long your doctor has been incompetent! Call the president and ask for competent stroke medical 'professionals' to be hired.  You really should expect your 'professionals' to know more that stroke-addled me!

selenium (15 posts to May 2015)

Safety and efficacy of selenium in improving the outcomes of stroke patients: a systematic review and meta-analysis with GRADE system

• Esraa Y. Salama, 
• Mariam A. Shaltout, 
• Rahma Abdelaziz Ismail, 
• Eslam Afifi, 
• Rana Abdelnasser A. Azab, 
• Abdelrahman Abdelshafi & 
• Rahma Sameh Shaheen 

Abstract

Background

Stroke represents the second most common cause of death worldwide and a significant cause of long-term morbidity. Although the brain is incapable of regeneration, the element selenium (Se) has been found to have a role in regenerating the antioxidant systems and improving cell proliferation and viability. So, we conduct this systematic review and meta-analysis to assess its effectiveness in enhancing cell proliferation and viability.

Aims

Our study aims to determine the efficacy and safety of selenium in alleviating the impact of brain injury and promoting recovery in patients with stroke.

Summary of review

We finally included five randomized clinical trials. Our meta-analysis showed a statistically significant difference between selenium and placebo in the outcomes of interest: Glasgow Outcome Scale after 1 month (OR: 1.54, 95% CI [1.10, 2.15], P = 0.01) and respiratory infection (OR: 0.55, 95% CI [0.34, 0.88], P = 0.01). There is no statistically significant difference in Glasgow Outcome Scale after 3 months (OR: 1.36, 95% CI [0.97, 1.91], P = 0.07), mortality (OR: 0.76, 95% CI [0.45, 1.30], P = 0.31).

Conclusion

Selenium showed a promising contribution to minimizing the damage caused by brain injuries. Further studies, including randomized-controlled trials, must be conducted on the efficacy of selenium and its association with better neurological outcomes.(What about the ones I refer to above? Or don't you know about them?)

Selenium and brain aging: A comprehensive review with a focus on hippocampal neurogenesis

 

Do you really think your competent? doctor will instruct the dietician to create diet protocols on this in the hospital and for home use? I really doubt you have a functioning stroke doctor as proven by doing nothing with this! I'm doing supplements, don't know if food intake is better and how to get it. I don't have time to wait for that research which will never occur.

Here is how long your doctor has been incompetent! Call the president and ask for competent stroke medical 'professionals' to be hired.  You really should expect your 'professionals' to know more that stroke-addled me!

selenium (15 posts to May 2015)

Selenium and brain aging: A comprehensive review with a focus on hippocampal neurogenesis

Author links open overlay panel, , , , , , , , 

https://doi.org/10.1016/j.arr.2025.102898Get rights and content

Highlights

• •
  Selenium regulates oxidative stress, neuroinflammation, and synaptic plasticity to modulate brain aging via selenoproteins.
• •
  Selenium influences key molecular pathways (PI3K/Akt/Wnt and BDNF/TrkB) to enhance neural progenitor cell proliferation.
• •
  The SEPP1-LRP8 axis delivers selenium to the hippocampus, and exercise enhances this system to promote neurogenesis.
• •
  Selenium prevents ferroptosis and reduces microglial activation, promoting a healthy neurogenic environment.
• •
  Large clinical trials and longitudinal multi-omics research are needed to confirm selenium’s role in healthy brain aging.

Abstract

Brain aging is accompanied by progressive cognitive decline and increased risk of neurodegenerative diseases, with adult hippocampal neurogenesis (AHN) playing a pivotal role in maintaining cognitive resilience. Selenium, an essential trace element, exerts significant neuroprotective and neurogenic effects predominantly through its incorporation into selenoproteins, which regulate oxidative stress, neuroinflammation, and synaptic plasticity. This review synthesizes recent advances delineating selenium’s metabolism, bioavailability, and its multifaceted roles in brain development, function, and aging, emphasizing mechanisms underpinning hippocampal neurogenesis. Key molecular pathways influenced by selenium include phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Wingless/Integrated (Wnt) and brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathways that promote neural progenitor cell proliferation and differentiation. Selenium transport via selenoprotein P and its receptor low-density lipoprotein receptor-related protein 8 (LRP8) is critical for adequate selenium delivery to the hippocampus to support neurogenesis, with exercise demonstrated to potentiate this axis. Selenium also mitigates ferroptosis, preserves mitochondrial integrity, and modulates neuroimmune interactions by attenuating microglial activation and inflammasome signaling, fostering a neurogenic environment. Emerging evidence highlights selenium’s regulatory effects on RNA expression, including microRNAs modifications, further influencing neuronal health. Despite promising preclinical and observational data, clinical translation remains limited by heterogeneous and short-term studies. Future research priorities include multi-omics investigations, longitudinal cohorts, and addressing global selenium intake disparities through policy initiatives and precision nutrition. By consolidating mechanistic insights with clinical perspectives, this review underscores selenium’s potential as a modifiable factor to enhance AHN and cognitive health, advocating for integrated translational strategies to combat brain aging and neurodegeneration.

Graphical Abstract

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Higher Dietary Selenium Intake Linked to Reduced Cardiovascular Disease Risk: Study

 Do you really think your competent? doctor will instruct the dietician to create diet protocols on this in the hospital and for home use? I really doubt you have a functioning stroke doctor as proven by doing nothing with this! This talks about food intake, but I'm doing supplements, I don't have time to wait for that research which will never occur.

Here is how long your doctor has been incompetent! Call the president and ask for competent stroke medical 'professionals' to be hired.  You really should expect your 'professionals' to know more that stroke-addled me!

selenium (13 posts to May 2015)

Higher Dietary Selenium Intake Linked to Reduced Cardiovascular Disease Risk: Study

Exploring the Neuroprotective Role of Selenium: Implications and Perspectives for Central Nervous System Disorders

Didn't your competent? doctor prepare protocols on selenium based on these two recent research articles? NO? So you DON'T have a functioning stroke doctor?

Selenium-containing compounds: a new hope for innovative treatments in Alzheimer’s disease and Parkinson’s disease June 2024 

The Role of Gut Microbiota in the Neuroprotective Effects of Selenium in Alzheimer’s Disease July 2024  

And even earlier ones, so you can see how fucking long your stroke doctor and hospital have been incompetent!

selenium (12 posts to May 2015)

Don't do this without a doctor's prescription.

Taken at normal doses, selenium does not usually have side effects. An overdose of selenium may cause bad breath, fever, and nausea, as well as liver, kidney and heart problems and other symptoms. At high enough levels, selenium could cause death.

Exploring the Neuroprotective Role of Selenium: Implications and Perspectives for Central Nervous System Disorders

Exploration
REVIEW
Exploring the Neuroprotective Role of Selenium:
Implications and Perspectives for Central Nervous System
Disorders
Guanning Huang Ying Liu Xiadong Zhu Lizhen He Tianfeng Chen
Department of Neurology and Stroke Center of The First Affiliated Hospital, College of Chemistry and Materials Science, Key Laboratory for Regenerative
Medicine of Ministry of Education, Jinan University, Guangzhou, China
Correspondence: Lizhen He (hlz6371@jnu.edu.cn) Tianfeng Chen (tchentf@jnu.edu.cn) Received: 13 November 2024 8 January 2025 Accepted: 10 March 2025 Funding: This work was supported by National Key R&D Program of China (Grant ID: 2023YFC3402800), National Science Fund for Distinguished Young Scholars (Grant ID: 82225025), National Natural Science Foundation of China (Grant IDs: 32171296, 32271351, and 32471435), Guangdong Basic and Applied Basic Research Foundation for Distinguished Young Scholars (Grant ID: 2024B1515020057), and China Postdoctoral Science Foundation (Grant IDs: 2023TQ0134, 

Selenium (Se) is a crucial element in selenoproteins, key biomolecules for physiological function in vivo. As a selenium-rich organ, the central nervous system can express all 25 kinds of selenoproteins, which protect neurons by reducing oxidative stress and inflammatory response. However, decreased Se levels are prevalent in a variety of neurological disorders, which is not conducive tothe treatment and prognosis of patients. Thus, the biological study of Se has emerged as a focal point in investigating the pivotal role of trace elements in neuroprotection. This paper presents a comprehensive review of the pathogenic mechanism of neurologicaldiseases, the protective mechanism of Se, and the neurological protective function of selenoproteins. Additionally, the application of Se as a neuroprotective agent in neurological disorder therapy, including ischemic stroke, Alzheimer’s, Parkinson’s, and other neurological diseases, is summarized. The present review aims to offer novel insights and methodologies for the prevention and treatment of neurological disorders with trace Se, providing a scientific basis for the development of innovative Se-basedneuroprotectants to promote their clinical application against neurological diseases.Selenium (Se) is an essential trace element found in the human through the 21 necessary amino acid, selenocysteine (Sec) [1]. In the synthesis of selenoproteins, Sec is encoded by the codon UGA, which is transferred to the synthetic selenoprotein polypeptide chain by selenocysteine transporter RNA (tRNA) under specific translation conditions [2–4]. In 1957, Schwarz et al. found that a lack of Se in food could cause liver necrosis in rats, first revealing the protective effects of Se on the liver and its role in animal nutrition. Keshan disease, found in northeast China, is a myocardial disease caused by patients susceptible to the Coxsackie virus due to reduce glutathione peroxidase1 expression induced by dietary Se deficiency [5]. The World Health Organization confirmed Se as an essential trace element for humans recommending a daily intake of 40 μg to effectively prevent the incidence of a variety of diseases [6]. Subsequent studies have confirmed the importance of selenoproteins in maintaining oxidation/reduction balance, promoting neuronal development, and regulating immune function and other physiological processes[7–11]. Brain is the nervous system’s central organ and is highly riched with Se. The dietary deficiency of Se can lead to reduced Se content and lower expression levels of selenoproteins in many organs, but the brain tissue can still maintain high Se content and a stable level of selenoproteins [12]. Moreover, the Se content in the brain is the first to return to normal levels after Se supplementation. This reveals that the brain initiatively maintains Se content for special regulatory mechanisms. Due to their high oxygen consumption, easy oxidation of polyunsaturated fatty acids, and relative lack of antioxidant enzymes, cerebral nerve cells in the brain are susceptible to the oxidative damage of reactive oxygen species (ROS) [13]. More than half of selenoproteins in the body have an antioxidant function and redox regulation ability, with their reduction of causing neuronal damage, cognitive impairment, depression, and anxiety [14, 15]. Based on the strong correlation between the occurrence of nervous system diseases

and the expression of selenoproteins, this review summarizes

the role of Se and provides a new direction for the study of neuroprotection (Figure 1). 2 Biological Functions of Selenium in Neurological Disease It is estimated that 25 selenoproteins are present in the human body at present, including glutathione peroxidase1 (GPX1), glutathione peroxidase2 (GPX2), glutathione peroxidase3 (GPX3), glutathione peroxidase4 (GPX4), glutathione peroxidase6 (GPX6), thioredoxin reductase1 (TrxR1), thioredoxin reductase2 (TrxR2), thioredoxin reductase3 (TrxR3), iodothyronine deiodinases1 (DIO1), iodothyronine deiodinases2 (DIO2), iodothyronine deiodinases3 (DIO3), methionine-Rsulfoxide reductase B1 (SelR), selenophosphate synthetase 2 (SPS2), selenoproteins F (SelF), selenoproteins H (SelH), selenoproteins I (SelI), selenoproteins K (SelK), selenoproteins N (SelN), selenoproteins M (SelM), selenoproteins O (SelO), selenoprotein P (SelP), selenoproteins V (SelV), selenoproteins S (SelS), selenoproteins T (SelT), and selenoproteins W (SelW) [16, 17]. Different selenoproteins types have different biological functions (Table 1). For example, GPXs such as glutathione peroxidase 4 (GPX4) can remove toxic metabolites such as hydrogen peroxide, lipid peroxides, and organic peroxides from the human cell membrane and cytoplasm, demonstrating the potential antioxidant function of Se [18–20]. TrxR reduces thioredoxin >(Trx) via nicotinamide adenine dinucleotide phosphate to initiate oxidation/reduction reactions [21]. In addition, SelT has a similar enzymatic mechanism to TrxR [22]. SelP-enriched plasma is not only responsible for the storage and transport of Se in vivo but also functions as an antioxidant role in protecting vascular endothelial cells [23]. Furthermore, SelS localized in the endoplasmic reticulum (ER) not only reduces ER stress but also relieves inflammation [24]. Previous studies have confirmed the importance of these antioxidant selenoproteins in protecting neurons and astrocytes from oxidative damage [25–28]. Neurological diseases, including strokes, Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), have been correlated with increased oxidative stress [29, 30]. Hence, selenoproteins deficiency or decreased selenoprotein activity are both closely linked to the biological function of Se in neurological diseases [31, 32]. Herein, the relationship between Se and the occurrence and development of nervous system diseases is summarized, providing a reference for the development of new strategies to utilize the biological activities of Se to treat neurological diseases. 2.1 Application of Selenium in Ischemic Stroke Patients experiencing stroke can only benefit from thrombolysis and vascular recirculation within 4.5 h of onset [54, 55]. In an emergency, prompt hospital admission for conventional intravenous thrombolysis is essential to recovery [54, 56]. Ischemic stroke is a common type of stroke that has become the second most lethal globally [57, 58]. According to the characteristics of stroke pathogenesis, the clinical treatment of ischemic stroke primarily focuses on the use of thrombolytic medicines to increase blood flow and neuroprotective therapy [59–61]. For example, Edaravone is a small molecule antioxidative drug used to repair brain oxidative injury, but its short half-life and low bioavailability greatly limit its efficacy and clinical application [62–66]. Following blood flow obstruction in the stroke-affected cerebral area, the oxygen and glucose requirements are not satisfied in vivo[58]. This causes a complex chain of cellular events, including oxidative stress, neuroinflammation, neuroexcitatory toxicity, and apoptosis, leading to neuronal injury and death [67]. For example, N-methyl-d-aspartate receptor (NMDAR)-mediated calcium influx has been shown to activate nitric oxide (NO) synthase [68]. In addition to elevated NO levels, a stroke can generate toxic chemicals, such as ROS, by stimulating xanthine oxidase and altering the electron transport chain in the mitochondria [69, 70]. Selenoproteins and other Se compounds have been considered in the treatment of ischemia/reperfusion injury owing to the antioxidant activity of Se [71]. Sodium selenite inhibits the reversal of mitochondrial membrane potential and ROS generation, notably reducing glutamate toxicity and hypoxia-induced cell death in mouse hippocampus cells (HT22 cell line). According to Peroal et al., the risks of ischemic stroke were increased by mutations of the SelS gene, which upregulated the expression of inflammatory markers [72]. This was determined by examining changes in the expression level of SelS after cerebral ischemia reperfusion. Additionally, Joseph Loscalzo et al. reported that the deletion of GPX1 increased the amount of neuronal injury in MCAO mice models, which was represented by an increase in the number of TdT-mediated dUTP nick end labeling positive cells in the brain, the size of the cerebral infarction, and the level of lipid hydrogen peroxide [73]. Ebselen is an organic Se molecule drug with GPX enzyme-like activity that has shown excellent potential in clinical trials for the treatment of multiple systemic diseases [74–76]. Huang et al. observed that GPX1−/− MCAO mice treated with ebselen showed distinct recovery in cerebral blood flow, blood–brain barrier permeability, and the area of cerebral infarction [77]. Previous studies have shown that ferroptosis is the secondary cause of cell death in neurons after stroke and is characterized by the excessive accumulation of lipid peroxides and ROS [80]. Interestingly, Xiao et al. demonstrated that BSA-stabilized Se nanoparticles (BSA-SeNPs) can inhibit secondary brain damage caused by ferroptosis after hemorrhagic stroke by activating the Nrf2/GPX4 pathway [81]. Se can protect particular neurons depressing induced by ferroptosis through adding selenocysteine during the translation of the selenoprotein, GPX4 (Figure 2)[78]. This adaptive response is regulated by factors, for exam-ple, cellular tumor antigen p53 and nuclear factor erythroid2-related factor 2, and is critical in preventing ferroptosis to promote cell survival [82–84]. However, Se deficiency enhances this response, requiring additional Se to enhance selenoprotein transcriptional regulation. Recently, Alim et al. demonstrated that ferroptosis stimulation can cause the nervous system to produce selenoproteins (including GPX4) during transcription in vitro and in vivo (Figure 3A) [85]. In addition, sodium selenite supplementation can inhibit ferroptosis and non-ferroptosis-dependent cell death by coordinating the activation of transcription factors such as transcription factor family activator protein 2 and specific protein 1 (Sp1) to up-regulate the transcriptional expression of selenoproteins. Polypeptides containing selenocysteine can improve brain function recovery by delivering Se to the ventricles after stroke to improve, the adaptive transcriptional response linked to ferroptosis. Particularly, in a hemorrhagic stroke model, the intraperitoneal injection of a single dose of Se upregulated the expression of Sp1 and GPX4, promoting the recovery of neurological function and reducing the size of cerebral infarction (Figure 3B). Furthermore, weighted correlation network analysis revealed an up-regulation in the expression of genes linked to resistance to endoplasmic reticulum stress and neuroexcitatory toxicity after Se supplementation. Notably, selenoproteins can shield neurons against excitatory neurotoxicity, ER stress, and ferroptosis. Overall, this study highlights the potential of Se supplements as a neuroprotective agent for stroke treatment, with important guiding implications in nutritional care and the subsequent treatment of cerebral hemorrhage. Histone deacetylases (HDACs) can regulate transcription processes by catalyzing the removal of acetyl groups from the lysine residues of histone and non-histone proteins [86]. HDAC9 is overexpressed in neurons during stroke and exerts neurotoxic effects by inhibiting autophagy, activating inhibitor kappa B alpha/nuclear factor kappa-B (IκBα/NF-ĸb) and mitogen-activated protein kinases (MAPKs) signaling pathways, and reducing the expression of miR-20a, upregulating its target gene Neurod1 [87–89]. According to Sanguigno et al., HDAC9 interacts with hypoxia-inducing factor 1 (HIF-1) and Sp1, transcriptional activators of the GPX4 and transferrin receptor 1 (TfR1) genes, respectively, in nerve cells exposed to oxygen-glucose deprivation/reperfusion(Figure 3C) [90]. This binding results in elevated levels of HIF-1, which promote the transcription of the ferrophilic TfR1 gene and decreased levels of the Sp1 protein. The reduced Sp1 levels also lead to the downregulation of the iron-resistant GPX4 gene. Oppositely, neuronal death induced by ferroptosis stimulation was reduced by silencing HDAC9, HIF-1, TfR1, Sp1, and GPX4. Overall, stroke-induced neuronal ferroptosis was suppressed by inhibiting the downregulation of GPX4. Researchers further investigated the function of GPX in protecting neurons following stroke. Hoehn et al. investigated the protective effects of gene therapy, namely the overexpression of the GPX in stroke induction, which effectively decreased the release of the proapoptotic protein cytochrome C and increased the neuronal survival ratio (Figure 3D) [91]. Even after transfection following ischemia, GPX could prevent stroke with a 9–11 h therapeutic window. GPX overexpression dramatically decreased the cytoplasmic translocation of cytochrome C and raised the percentage of B-cell lymphoma-2 positive cells compared to the control vector-transfected cells. Furthermore, GPX overexpression inhibited processes associated with apoptosis by downregulating Bcl2-Associated X and triggering caspase-3. In summary, this study revealed that the overexpression of GPX can be utilized in neuroprotection to reverse ischemia injury in stroke patients.