Endothelium (lining of blood vessels, heart) and Vitamin D - several studies

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Vitamin D and Endothelial Function - Jan 2020

Nutrients 2020, 12(2), 575; https://doi.org/10.3390/nu12020575
Do-Houn Kim 1,2ORCID,Cesar A. Meza 1ORCID,Holly Clarke 1,Jeong-Su Kim 1,2,3 andRobert C. Hickner 1,3,4,*

• 1 Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA
• 2 Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL 32306, USA
• 3 Institute of Sports Sciences and Medicine, College of Human Sciences, Florida State University, Tallahassee, FL 32306, USA
• 4 Department of Biokinetics, Exercise and Leisure Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville 4041, South Africa

Vitamin D is known to elicit a vasoprotective effect, while vitamin D deficiency is a risk factor for endothelial dysfunction (ED). ED is characterized by reduced bioavailability of a potent endothelium-dependent vasodilator, nitric oxide (NO), and is an early event in the development of atherosclerosis. In endothelial cells, vitamin D regulates NO synthesis by mediating the activity of the endothelial NO synthase (eNOS). Under pathogenic conditions, the oxidative stress caused by excessive production of reactive oxygen species (ROS) facilitates NO degradation and suppresses NO synthesis, consequently reducing NO bioavailability. Vitamin D, however, counteracts the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which produces ROS, and improves antioxidant capacity by enhancing the activity of antioxidative enzymes such as superoxide dismutase. In addition to ROS, proinflammatory mediators such as TNF-α and IL-6 are risk factors for ED, restraining NO and eNOS bioactivity and upregulating the expression of various atherosclerotic factors through the NF-κB pathway. These proinflammatory activities are inhibited by vitamin D by suppressing NF-κB signaling and production of proinflammatory cytokines. In this review, we discuss the diverse activities of vitamin D in regulating NO bioavailability and endothelial function.
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Beneficial Role of Vitamin D on Endothelial Progenitor Cells (EPCs) in Cardiovascular Diseases - April 2022

J Lipid Atheroscler v.11(3); 2022 Sep PMC9515729 doi: 10.12997/jla.2022.11.3.229
Atanu Sen,1 Vinnyfred Vincent,2 Himani Thakkar,2 Ransi Abraham,1 and Lakshmy Ramakrishnan corresponding author1

Cardiovascular diseases (CVDs) are the leading cause of death in the world. Endothelial progenitor cells (EPCs) are currently being explored in the context of CVD risk. EPCs are bone marrow derived progenitor cells involved in postnatal endothelial repair and neovascularization. A large body of evidence from clinical, animal, and in vitro studies have shown that EPC numbers in circulation and their functionality reflect endogenous vascular regenerative capacity. Traditionally vitamin D is known to be beneficial for bone health and calcium metabolism and in the last two decades, its role in influencing CVD and cancer risk has generated significant interest. Observational studies have shown that low vitamin D levels are associated with an adverse cardiovascular risk profile. Still, Mendelian randomization studies and randomized control trials (RCTs) have not shown significant effects of vitamin D on cardiovascular events. The criticism regarding the RCTs on vitamin D and CVD is that they were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals. Overall, the association between vitamin D and CVD remains inconclusive. Recent clinical and experimental studies have demonstrated the beneficial role of vitamin D in increasing the circulatory level of EPC as well as their functionality. In this review we present evidence supporting the beneficial role of vitamin D in CVD through its modulation of EPC homeostasis.
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Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases - Jan 2023

Nutrients Volume 15 Issue 2 10.3390/nu15020334
Éva Pál 1,2,*ORCID,Zoltán Ungvári 3,4,5,6,Zoltán Benyó 1,2,†ORCID andSzabolcs Várbíró 7,8,†ORCID
1

Deficiency in vitamin D (VitD), a lipid-soluble vitamin and steroid hormone, affects approximately 24% to 40% of the population of the Western world. In addition to its well-documented effects on the musculoskeletal system, VitD also contributes importantly to the promotion and preservation of cardiovascular health via modulating the immune and inflammatory functions and regulating cell proliferation and migration, endothelial function, renin expression, and extracellular matrix homeostasis. This brief overview focuses on the cardiovascular and cerebrovascular effects of VitD and the cellular, molecular, and functional changes that occur in the circulatory system in VitD deficiency (VDD). It explores the links among VDD and adverse vascular remodeling, endothelial dysfunction, vascular inflammation, and increased risk for cardiovascular and cerebrovascular diseases. Improved understanding of the complex role of VDD in the pathogenesis of atherosclerotic cardiovascular diseases, stroke, and vascular cognitive impairment is crucial for all cardiologists, dietitians, and geriatricians, as VDD presents an easy target for intervention.
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Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives March 2022

Critical Reviews in Food Science and Nutrition Vol 63, 2023 - Issue 25 https://doi.org/10.1080/10408398.2022.2050349 PDF behind $53 paywall
Vivek Rihal, Heena Khan, Amarjot Kaur &Thakur Gurjeet Singh ORCID

Vitamin D deficiency has been linked to several major chronic diseases, such as cardiovascular and neurodegenerative diseases, diabetes, and cancer, linked to oxidative stress, inflammation, and aging. Vitamin D deficiency appears to be particularly harmful to the cardiovascular system, as it can cause endothelial dysfunctioning and vascular abnormalities through the modulation of various downstream mechanisms. As a result, new research indicates that therapeutic approaches targeting vitamin D inadequacies or its significant downstream effects, such as impaired autophagy, abnormal pro-inflammatory and pro-oxidant reactions, may delay the onset and severity of major cerebrovascular disorders such as stroke and neurologic malformations.
Vitamin D modulates the various molecular pathways, i.e.,

• Nitric Oxide,
• PI3K-Akt Pathway,
• cAMP pathway,
• NF-kB Pathway,
• Sirtuin 1,
• Nrf2,
• FOXO, in cerebrovascular disorder.

The current review shows evidence for vitamin D’s mitigating or slowing the progression of these cerebrovascular disorders, which are significant causes of disability and death worldwide.

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Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19 - Sept 2020

Rev. Cardiovasc. Med. 2020, 21(3), 339–344; https://doi.org/10.31083/j.rcm.2020.03.131
Jun Zhang1,[email protected] , Peter A. McCullough1,2,3, Kristen M. Tecson1
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1 Baylor Heart and Vascular Institute, Dallas, TX 75226, USA
2 Baylor University Medical Center, Dallas, TX 75226, USA
3 Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX 75226, USA

There is emerging evidence to suggest that vitamin D deficiency is associated with adverse outcomes in COVID-19 patients. Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse. The mechanisms by which vitamin D deficiency exacerbates COVID-19 pneumonia remain poorly understood. In this review we describe the rationale of the putative role of endothelial dysfunction in this event. Herein, we will briefly review

• (1) anti-inflammatory and anti-thrombotic effects of vitamin D,
• (2) vitamin D receptor and vitamin D receptor ligand,
• (3) protective role of vitamin D against endothelial dysfunction,
• (4) risk of vitamin D deficiency,
• (5) vitamin D deficiency in association with endothelial dysfunction,
• (6) the characteristics of vitamin D relevant to COVID-19,
• (7) the role of vitamin D on innate and adaptive response,
• (8) biomarkers of endothelial cell activation contributing to cytokine storm, and
• (9) the bidirectional relationship between inflammation and homeostasis.

Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α . A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.
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Note: COVID protects itself by de-activation of the Vitamin D Receptor 33+ studies

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Vitamin D Life – Cardiovascular category:

507 items In Cardiovascular category

Cardiovascular category is associated with other categories: Diabetes 31, Omega-3 31 , Vitamin K 25 , Intervention 22 . Mortality 20 , Skin - Dark 18 , Magnesium 17 , Calcium 14 , Hypertension 14 , Trauma and surgery 13 , Stroke 13 , Kidney 12 , Metabolic Syndrome 11 , Seniors 10 , Pregnancy 8 as of Aug 2022

• Overview Cardiovascular and vitamin D
• Cardiovascular Disease is treated by Vitamin D - many studies 39+ meta-analyses
• Coronary Artery Disease and Vitamin D - many studies 18+
• Cardiovascular problems reduced by Omega-3 - many studies 34+
• Arteries and Atherosclerosis and Vitamin D - many studies 71+
• Atrial Fibrillation decreased by Vitamin D or Magnesium - many studies 26+
• Statins and Vitamin D - many studies 25+
• Arterial Stiffness and Vitamins – only Vitamin D was found to help – meta-analysis Feb 2022
• Those raising Vitamin D above 30 ng were 1.4 X less likely to die of Heart Attack (VA 19 years) – Oct 2021
• Giving free vitamin D to every Iranian would pay for itself by just reducing CVD – Oct 2021
• Sudden Cardiac Arrest – 2.8 X higher risk if low vitamin D – 2019
• Peripheral arterial disease risk is 1.5X higher if low vitamin D – meta-analysis March 2018
• Heart attack ICU costs cut in half by Vitamin D – Oct 2018
• Cardiovascular disease 2.3 X more-likely if poor Vitamin D Receptor – Aug 2022

Cholesterol, Statins

• Cholesterol is needed to produce both Vitamin D and Cortisol
• Overview Cholesterol and vitamin D
• Statins and Vitamin D - many studies statins often reduce levels of vitamin D
• Statin side-effects are reduced by Vitamin D – US patent Application – April 2019

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Vitamin D Life – Stroke category contains

122 items in stroke category - see also Overview Stroke and vitamin D,
Overview Hypertension and Vitamin D  Overview Cardiovascular and vitamin D

Stroke more likely if low Vitamin D

• Stroke 74% less likely if high vitamin D (7,295 women 20-50 years old) – July 2017
• Stroke is 13.5 X more likely if low vitamin D and high blood pressure – March 2015
• Ischemic stroke 17 X more likely if low vitamin D – April 2017
• Stroke is strongly associated with Calcification of cerebral arteries (perhaps low Vitamin D, Vitamin K, Mg…) – March 2018
• Ischemic Stroke 3X more likely if Vitamin D Receptor gene change (Fok 1) – Jan 2014

Post-Stroke worse if low Vitamin D

• Poor Acute Ischemic Stroke 4X more likely if low Vitamin D - Nov 2023
• Stroke risks increased if low Vitamin D: Death 3.6 X, recurrence 5.5 X – Meta-analysis Nov 2019
• Stroke outcome at 3 months was 3X worse if bad stroke and low vitamin D – Jan 2020
• Death after Ischemic Stroke 2.5 X more likely if less than 10 ng of Vitamin D – May 2019
• Vascular dementia (after strokes) 32X more likely in Hypertensives with low vitamin D – Oct 2015
• Depression following a stroke is 2.7 X more likely if low vitamin D – Sept 2018
• Stroke incidence not associated with low Vitamin D (but stroke outcome is) – Aug 2019

Post-Stroke better if add Vitamin D

• Post-stroke Vitamin D supplementation helped in 11 ways – May 2023
• Improved recovery from ischemic stroke with Vitamin D (300,000 IU injection) – RCT June 2018
• Better outcome following Ischemic stroke if injected with 600,000 IU of vitamin D – RCT Feb 2017
• Ischaemic stroke – Vitamin D doubled survival (Injection followed by monthly 60,000 IU) – RCT Aug 2016
• Stroke patients need more than 2,000 IU of vitamin D (found this time in Japan) – RCT June 2019

Post-Stroke better if Vitamin D actually gets to cells

• Resveratrol fights Parkinson, Alzheimers, Diabetes, Cardiovascular, ALS, Stroke, etc.– Nov 2018
• Stroke rehabilitation (and prevention) requires Vitamin D actually getting to cells – March 2020

9 studies in both categories Depression and Stroke

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See also: Nitric oxide (from sun, Mg, Vit D, etc) reduces some health problems - many studies.