Vitamin D, Oxidative Stress, and Aging
Sunil Wimalawansa
This article is associated with the MDPI-Biology special Journal article,
“Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging.”
 Download the FULL version PDF from VitaminDWiki
Which includes the following graphic
Sunil J. Wimalawansa, MD, PhD, MBA, FRCP, FACP, FACE, FRCPath, DSc
Professor of Medicine, Endocrinology & Nutrition; Cardiometabolic & Endocrine Institute, North Brunswick, NJ, USA; suniljw at hotmail.com
Drugs
- Drugs which create deficiencies in Vitamin D, Vitamin K, Magnesium, Zinc, Iron, etc. – Sept 2017
- Child Asthma increased 2.1 X by antibiotics, Child milk allergy increased 4.4 X by PPI – April 2018
- Drugs that may harm bone (vitamin D needed) -April 2016
- More vitamin D needed if person is taking Glucocorticoids – June 2015
- Some anticonvulsant drugs significantly reduce vitamin D levels – many studies
- Hormonal contraceptives associated with higher vitamin D levels - 2013, 2018
- Review of vitamin D interaction with drugs – Jan 2014
- Acid Reflux drugs decrease Vitamin D and Magnesium – Jan 2013
- Proton pump inhibitors decrease Vitamin D and Magnesium – Dec 2018
- Drugs Deplete Magnesium
- Drug–Vitamin D Interactions, A Systematic Review – Jan 2013
Plastics and Chemicals
- Endocrine Disrupting Chemicals - book April 2019
- Household chemicals found to be the source of half of urban pollution (and thus decreased urban vitamin D) – Feb 2018
- Increase of plastic compounds (phthalates) in urine during pregnancy associated with decreased Vitamin D – Aug 2017
- Plastics, BPA, PCB and Vitamin D deficiency
- PCBs increased the chance of being Vitamin D deficient by 3 percent – May 2013
- Autism risks include chemicals, deficiency of vitamin D, Omega-3 – mini-review April 2016
- Investigation on Roundup - glyphosate at VitaminDWiki
Heavy Metals
- Cadmium liver problem 5 X less likely when vitamin D is greater than 40 ng – April 2018
- Lead in breastmilk reduced vitamin D levels in blood by a third (in rats) – Feb 2018
- A good Vitamin D Receptor (or perhaps more vitamin D) protects against lead during pregnancy
Pesticides
- Pesticides increase risk of Cancers, Alz, ALS, Asthma, ADHD, etc. (all related to low vitamin D) – Oct 2016
- DDT 3.8 X more prevalent with Alzheimer disease (no mention that DDT decreases vitamin D) – Jan 2014
- DDT and other pesticides decrease vitamin D
- Pesticides increase risk of Cancers, Alz, ALS, Asthma, ADHD, etc. (all related to low vitamin D) – Oct 2016
Toxins
- Investigation on Roundup - glyphosate at VitaminDWiki
- The Greatest Public Health Mistake of the 20th Century (sunscreen block Vitamin D) - 2017
- Air pollution, toxins, heavy metals and smoking each result in lower Vitamin D levels – Nov 2018 Which contains the following
EDC = Endocrine-disrupting chemicals
Smoking
Air Pollution
- Air Pollution reduces Vitamin D VitaminDWiki overview
- Air pollution, toxins, heavy metals and smoking each result in lower Vitamin D levels – Nov 2018
- Traffic pollution increases asthma unless supplement with Vitamin D (mice) June 2018
- Vitamin D level: 27 ng if low pollution, 12 ng if high pollution (Delhi children) – June 2018
- Air Pollution 2000-2012 nice interactive maps
Fertility
- Male fertility 4 X higher if high Vitamin D – Nov 2015
- Infertility rate is 2X higher for blacks than whites (no mention of vitamin D, nor the man) – April 2014
- Association between vitamin D and sperm parameters: Clinical evidence – Dec 2016
- Vitamin D and Human Reproduction – 51 page chapter – April 2017
- Global sperm count dropped by 59 percent in 40 years – meta-analysis Aug 2017
 Download the SHORT version PDF from VitaminDWiki
Vitamin D affects all systems in the body. Both 25 dihydroxy vitamin D [25(OH)2D] and its active hormonal form, 1,25-dihydroxyvitamin D [1,25(OH)2D; calcitriol] are essential for human physiological functions, including damping down inflammation [1] and the excessive intracellular oxidative stresses [2-4]. Vitamin D is a potent anti-oxidant that improves mitochondrial activity, preventing oxidative stress-related protein oxidation, lipid peroxidation, and DNA damage [5]. Recent data support less known, key functions of vitamin D on non-musculoskeletal functions, particularly on mitochondrial respiratory functions/energy generation, oxidative stress, and the aging process [6, 7].
Role of calcitriol on inflammation and oxidative stress:
Calcitriol dampen inflammation, oxidative stress, cell/tissue damage, and thereby, the aging process. Hypovitaminosis D, on the other hand, accelerates these processes. Consequently, vitamin D deficiency increases the incidence and/or severity of many age-related metabolic disorders that are linked to oxidative stress and accelerates the aging process [8]. Diseases that get worsen by vitamin D inadequacy include, insulin resistance, type 2 diabetes, obesity, hypertension, memory disorders, osteoporosis, certain cancers, and systemic inflammatory diseases, and pregnancy-associated complications [9].
In addition to hypovitaminosis D, toxins, metabolic abnormalities, and the aging process itself causes mitochondrial dysfunction [10-14]. Abnormal mitochondria produce suboptimal amounts of ATP while generating excess ROS; a double whammy, creating a vicious cycle of enhancing the effects from excessive oxidative stress [13-15]. Moreover, in the presence of vitamin D deficiency, DNA damage, impair DNA repair systems, premature cell death, and accelerated aging get accelerated [12, 16]. Vitamin D deficiency causes mitochondrial dysfunction that is synergized by intracellular inflammation [17-20].
Adequately powered, properly designed randomized controlled clinical studies in subjects with vitamin D deficiency (i.e., serum 25(OH)D concentrations less than 20 ng/mL) using the nutrient vitamin D as the key intervention and predefined hard endpoints/primary outcomes are still lacking [21]. Protective effects of vitamin D improves mitochondrial and endocrine functions, reducing the risks of autoimmunity, infections, metabolic derangements, and impairment of DNA repair. Whereas, deficiency worsen these and aids the aging process [22-24]. To generate adequate vitamin D in situ, one needs to have a healthy balance of sun exposure in favor of benefits while avoiding potential harmful effects [25-27].
Role of calcitriol on aging process:
Advancing age promotes cellular accumulation of toxic products, particularly those related to oxidative stress such as methylation of DNA. In conjunction with mitochondrial dysfunction and reduced viability of cells, lead to premature cell deaths [28]. It also reduces the immune functions, immune-senescence, together with inflammation, as demonstrable with increased circulating pro-inflammatory cytokines [29, 30]. Combination of these contribute to many age-related disorders, such as Alzheimer’s disease, cardiovascular and pulmonary diseases, and increased susceptibility to autoimmunity and infections [29, 30].
Preventative effects of vitamin D on inflammation and oxidative stress:
Vitamin D works in conjunction with micronutrients, vitamins and antioxidants. In the presence of physiological serum 25(OH)D concentration of between 30 and 60 ng/mL (75 and 150 nmol/L), metabolomics, transcriptomics, epigenetics effects of vitamin D [31] and suppression of oxidative stress and systemic inflammation, lead to improved clinical outcomes.
The benefits derived from savings and reducing the risks of common diseases by increasing the population serum 25(OH)D concentrations beyond 30 ng/mL, are orders of magnitude higher that the vitamin D deficiency associated investigations and treatment costs. Thus, a country-wide replacement of vitamin D is a highly cost-effective public health approach that would lead to tangible positive impact on people and the economy.
Figure 1. Environmental, microbial, biological and chemical interactions that modify DNA and mitochondrial functions and epigenetics, which modifies the aging process. Vitamin D deficiency is one of many factors that enhances this oxidative-stress cycle, accelerating premature cell death [abbreviations used: DNA = deoxyribonucleic acid; iNOS = inducible nitric oxide enzyme].
Multiple factros that are associated with the aging process. Normal serum concentrations of both 25(OH)D and 1,25(OH)2D are essential for optimal cellular function and protect from the excessive oxidative stress-related DNA damage.
Conclusion: However, increased risk for illnesses and reduced longevity can occur despite the presence of physiologic concentrations of calcitriol because this is not the only mechanism protecting cells from oxidative stress. For reductions in the incidence of diseases, longer-term maintenance of a steady state of the serum 25(OH)D concentration is necessary [32]. The minimal level is considered to be 30 ng/mL (50 nmol/L), while the optimal range is between 30 and 60 ng/mL [33].
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