Sunlight, Nutrition and Health Research Center (SUNARC)

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Ultraviolet Radiation
Vitamin D recommendations
Vitamin D requirements during pregnancy and lactation
Why is the public misinformed about UV and vitamin D?

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Position of health organizations and agencies in Australia, Canada, New Zealand, the United Kingdom, and the United States, and the World Health Organization, on UV radiation and vitamin D

wbgrant@infionline.net

William B. Grant, Ph.D.
wbgrant@infionline.net

Bibliography

Position Papers

 
AUTISM
 
 

An overview of vitamin D and autism (Word Document)

 
       
 

What is the role of vitamin D in autism?

Cannell JJ1, Grant WB2.

   
       
 

Abstract

A growing body of literature suggests that higher serum 25-hydroxyvitamin D [25(OH)D] concentrations, either in utero or in early life, may reduce the risk of autism. For example, an ecological study in the companion paper inversely correlated solar UV-B doses in the United States with prevalence of autism among those aged 6-17 y. That study proposed that vitamin D deficiency during pregnancy could account for this finding, although the findings are also consistent with childhood vitamin D deficiency contributing to the condition. Also, in a recent study, children with autism had lower serum 25(OH)D concentrations than did control subjects (19 vs. 33 ng/ml), despite parents of each group reporting the same amount of sun exposure. The same study found highly significant inverse correlations between 25(OH)D and autism rating scales and between 25(OH)D and levels of an antineuronal antibody. This finding indicates that higher serum 25(OH)D concentrations may reduce the symptoms of established autism. Because activated vitamin D, a secosteroid, upregulates DNA-repair genes, vitamin D deficiency during development may inhibit the repair of de novo DNA mutations in fetuses and infants and thus contribute to risk of autism. Vitamin D might also reduce the risk or severity of autism through its anti-inflammatory actions, antiautoimmune effects, increasing seizure threshold, increasing T-regulatory cells, protecting the mitochondria, and upregulating glutathione, which scavenges oxidative by-products and chelates (captures and excretes) heavy metals. Vitamin D deficiency during pregnancy and childhood is a widespread and growing epidemic.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897590/

Dermatoendocrinol 2013 Jan 1;5(1):199-204. doi: 10.4161/derm.24356.

   
       
 

Autism prevalence in the United States with respect to solar UV-B doses: An ecological study.

Grant WB1, Cannell JJ2.

   
 

Abstract

Evidence is mounting that vitamin D deficiency is intimately involved in autism. We report on autism prevalence by US state for those aged 6-17 y in 2010 with respect to indices of solar UV-B (UVB) doses. We calculated autism prevalence rates for white, black and Asian Americans by using total prevalence and relative populations of minors for each ethnic group by state. Analyses omit AK and HI (considered extreme cases), WY (no data), along with AZ and ND for black Americans (low numbers) and DC, ME, MT, ND and SD for Asian Americans (low numbers). For white Americans, the regression coefficient for solar UVB doses and autism prevalence ranged from -0.52 in January to -0.57 in October. For black Americans, the regression coefficient for latitude was 0.61, whereas those for solar UVB ranged from -0.55 to -0.61. For Asian Americans, the values for solar UVB ranged from -0.28 to -0.38. The inverse correlation between solar UVB and autism prevalence is similar to that for many types of cancer in the US. The journal literature indicates that adverse effects on fetal brain development during pregnancy due to vitamin D deficiency can explain these findings. However, we cannot rule out a role of vitamin D deficiency in early life. These results add to the evidence that vitamin D deficiency may be an important risk factor for autism and suggest that pregnant women and autistic individuals raise their serum 25-hydroxyvitamin D concentrations above 30 ng/ml.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897584/

Dermatoendocrinol. 2013 Jan 1;5(1):159-64. doi: 10.4161/derm.22942.

   
       
 
ALZHEIMER'S DISEASE
   
 

Observational and Ecological Studies of Dietary Advanced Glycation End Products in National Diets and Alzheimer's Disease Incidence and Prevalence.

Perrone L1, Grant WB2.

   
 

Abstract

BACKGROUND:

Considerable evidence indicates that diet is an important risk-modifying factor for Alzheimer's disease (AD). Evidence is also mounting that dietary advanced glycation end products (AGEs) are important risk factors for AD. Objective: This study strives to determine whether estimated dietary AGEs estimated from national diets and epidemiological studies are associated with increased AD incidence. Methods: We estimated values of dietary AGEs using values in a published paper. We estimated intake of dietary AGEs from the Washington Heights-Inwood Community Aging Project (WHICAP) 1992 and 1999 cohort studies, which investigated how the Mediterranean diet (MeDi) affected AD incidence. Further, AD prevalence data came from three ecological studies and included data from 11 countries for 1977-1993, seven developing countries for 1995-2005, and Japan for 1985-2008. The analysis used dietary AGE values from 20 years before the AD prevalence data. Results: Meat was always the food with the largest amount of AGEs. Other foods with significant AGEs included fish, cheese, vegetables, and vegetable oil. High MeDi adherence results in lower meat and dairy intake, which possess high AGE content. By using two different models to extrapolate dietary AGE intake in the WHICAP 1992 and 1999 cohort studies, we showed that reduced dietary AGE significantly correlates with reduced AD incidence. For the ecological studies, estimates of dietary AGEs in the national diets corresponded well with AD prevalence data even though the cooking methods were not well known. Conclusion: Dietary AGEs appear to be important risk factors for AD.


J Alzheimers Dis. 2015 Jan 29. [Epub ahead of print]

   
       
 

Nutrition and the prevalence of dementia in mainland China, Hong Kong, and Taiwan: an ecological study.

Wu YT1, Grant WB2, Prina AM3, Lee HY4, Brayne C1.

   
 

Abstract

BACKGROUND:

Western diets are associated with obesity, vascular diseases, and metabolic syndrome and might increase dementia risk in later life. If these associations are causal, those low- and middle-income countries experiencing major changes in diet might also see an increasing prevalence of dementia.

OBJECTIVE:

To investigate the relationship of dietary supply and the prevalence of dementia in mainland China, Hong Kong, and Taiwan over time using existing data and taking diagnostic criteria into account.

METHODS:

Estimated total energy supply and animal fat from the United Nations was linked to the 70 prevalence studies in mainland China, Hong Kong, and Taiwan from 1980 to 2012 according to the current, 10 years, and 20 years before starting year of investigation. Studies using newer and older diagnostic criteria were separated into two groups. Spearman's rank correlation was calculated to investigate whether trends in total energy, animal fat supply, and prevalence of dementia were monotonically related.

RESULTS:

The supply of total energy and animal fat per capita per day in China increased considerably over the last 50 years. The original positive relationship of dietary supply and dementia prevalence disappeared after stratifying by newer and older diagnostic criteria and there was no clear time lag effect.

CONCLUSION:

Taking diagnostic criteria into account, there is no cross-sectional or time lag relationship between the dietary trends and changes in dementia prevalence. It may be too early to detect any such changes because current cohorts of older people did not experience these dietary changes in their early to mid-life.

J Alzheimers Dis. 2015 Jan 1;44(4):1099-106. doi: 10.3233/JAD-141926.

   
       
 

Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries.

Grant WB1.

   
 

Abstract

BACKGROUND:

Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD.

OBJECTIVE:

This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible.

METHODS:

This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data.

RESULTS:

For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan.

CONCLUSION:

Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.

J Alzheimers Dis. 2014;38(3):611-20. doi: 10.3233/JAD-130719.

   
       
 
CANCER
   
 

25-Hydroxyvitamin D and Breast Cancer, Colorectal Cancer, and Colorectal Adenomas: Case-Control versus Nested Case-Control Studies.

Grant WB1.

   
 

Abstract

Background: Existing literature includes concerns regarding reliability of case-control studies of breast cancer incidence with respect to 25-hydroxyvitamin D (25(OH)D) concentrations. For breast cancer, only case-control studies consistently find inverse correlations between 25(OH)D and breast cancer. However, for colorectal cancer, nested case-control studies find significant inverse correlations with respect to 25(OH)D concentrations at baseline for mean follow-up times of 7 years. Materials and Methods: This is a review of results currently existing in literature. Results: I provide evidence that 25(OH)D concentration values are only useful for short follow-up times for breast cancer since it develops rapidly. To support the robust nature of breast cancer case-control studies, I show that results from 11 studies from seven countries align in a robust power-law fit to the odds ratio versus mean 25(OH)D concentrations. Conclusion: Case-control studies of breast cancer incidence rates provide reliable results.

   
       
 

Molecular link between vitamin D and cancer prevention.

Moukayed M1, Grant WB.

   
 

Abstract

The metabolite of vitamin D, 1α,25-dihydroxyvitamin D₃ (also known as calcitriol), is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D₃ signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol) in modulating cellular growth and development. Vitamin D (calcitriol) acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise--yet where sunlight and, hence, vitamin D may be easily acquired--adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence.


http://www.mdpi.com/2072-6643/5/10/3993  

Nutrients. 2013 Sep 30;5(10):3993-4021. doi: 10.3390/nu5103993.

   
       
 

A multicountry ecological study of cancer incidence rates in 2008 with respect to various risk-modifying factors.

Grant WB1.

   
 

Serum 25-hydroxyvitamin D (25(OH)D) levels have been found to be inversely associated with both prevalent and incident cardiovascular disease (CVD) risk factors; dyslipidemia, hypertension and diabetes mellitus. This review looks for evidence of a causal association between low 25(OH)D levels and increased CVD risk. We evaluated journal articles in light of Hill's criteria for causality in a biological system. The results of our assessment are as follows. Strength of association: many randomized controlled trials (RCTs), prospective and cross-sectional studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Consistency of observed association: most studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors in various populations, locations and circumstances. Temporality of association: many RCTs and prospective studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Biological gradient (dose-response curve): most studies assessing 25(OH)D levels and CVD risk found an inverse association exhibiting a linear biological gradient. Plausibility of biology: several plausible cellular-level causative mechanisms and biological pathways may lead from a low 25(OH)D level to increased risk for CVD with mediators, such as dyslipidemia, hypertension and diabetes mellitus. Experimental evidence: some well-designed RCTs found increased CVD risk factors with decreasing 25(OH)D levels. Analogy: the association between serum 25(OH)D levels and CVD risk is analogous to that between 25(OH)D levels and the risk of overall cancer, periodontal disease, multiple sclerosis and breast cancer.

CONCLUSION:

All relevant Hill criteria for a causal association in a biological system are satisfied to indicate a low 25(OH)D level as a CVD risk factor.

http://www.mdpi.com/2072-6643/6/9/3403

Nutrients. 2014 Sep 2;6(9):3403-30. doi: 10.3390/nu6093403.

   
       
 

A multicountry ecological study of cancer incidence rates in 2008 with respect to various risk-modifying factors.

Grant WB1.

   
 

Abstract

Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15-25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.

http://www.mdpi.com/2072-6643/6/1/163

Nutrients. 2013 Dec 27;6(1):163-89. doi: 10.3390/nu6010163.

   
       
 
CARDIOVASCULAR DISEASE
   
 

Review

Emphasizing the Health Benefits of Vitamin D for Those with Neurodevelopmental Disorders and Intellectual Disabilities

   
 

Abstract

People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies. - See more at:

http://www.mdpi.com/2072-6643/7/3/1538

Nutrients 2015, 7(3), 1538-1564; doi:10.3390/nu7031538

   
       
 

Does sufficient evidence exist to support a causal association between vitamin D status and cardiovascular disease risk? An assessment using Hill's criteria for causality.

Weyland PG1, Grant WB2, Howie-Esquivel J3.

   
 

Abstract

Serum 25-hydroxyvitamin D (25(OH)D) levels have been found to be inversely associated with both prevalent and incident cardiovascular disease (CVD) risk factors; dyslipidemia, hypertension and diabetes mellitus. This review looks for evidence of a causal association between low 25(OH)D levels and increased CVD risk. We evaluated journal articles in light of Hill's criteria for causality in a biological system. The results of our assessment are as follows. Strength of association: many randomized controlled trials (RCTs), prospective and cross-sectional studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Consistency of observed association: most studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors in various populations, locations and circumstances. Temporality of association: many RCTs and prospective studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Biological gradient (dose-response curve): most studies assessing 25(OH)D levels and CVD risk found an inverse association exhibiting a linear biological gradient. Plausibility of biology: several plausible cellular-level causative mechanisms and biological pathways may lead from a low 25(OH)D level to increased risk for CVD with mediators, such as dyslipidemia, hypertension and diabetes mellitus. Experimental evidence: some well-designed RCTs found increased CVD risk factors with decreasing 25(OH)D levels. Analogy: the association between serum 25(OH)D levels and CVD risk is analogous to that between 25(OH)D levels and the risk of overall cancer, periodontal disease, multiple sclerosis and breast cancer.

CONCLUSION:

All relevant Hill criteria for a causal association in a biological system are satisfied to indicate a low 25(OH)D level as a CVD risk factor.

http://www.mdpi.com/2072-6643/6/9/3403

Nutrients. 2014 Sep 2;6(9):3403-30. doi: 10.3390/nu6093403.

   
       
 
GENERAL/OTHER VITAMIN D INFORMATION
   
 

Vitamin D status in Central Europe.

Pludowski P1, Grant WB2, Bhattoa HP3, Bayer M4, Povoroznyuk V5, Rudenka E6, Ramanau H7, Varbiro S8, Rudenka A9, Karczmarewicz E1, Lorenc R1, Czech-Kowalska J10, Konstantynowicz J11.

   
 

Abstract

Little published information is available regarding epidemiological data on vitamin D status in the large geographical region of Central Europe (CE). We searched the journal literature with regard to 25(OH)D concentrations among community-dwelling or healthy people living in CE. 25(OH)D concentrations varied by age, season, study sample size, and methodological approach [i.e., 25(OH)D assay used]. Concentrations of 25(OH)D in CE appeared lower than 30 ng/mL, and the magnitude of hypovitaminosis D was similar to that reported in Western Europe. While most of the studies reviewed were cross-sectional studies, a longitudinal study was also included to obtain information on seasonal variability. The longitudinal study reported wintertime 25(OH)D values close to 21-23 ng/mL for all studied age groups, with a significant increase of 25(OH)D in August reaching 42 ng/mL for those aged 0-9 years, but only 21 ng/mL for the elderly aged 80-89 years. The decrease in 25(OH)D with respect to age was attributed to decreased time spent in the sun and decreased vitamin D production efficiency. Based on the literature review on vitamin D status in the CE populations, it can be concluded that 25(OH)vitamin D levels are on average below the 30 ng/mL level.

http://www.hindawi.com/journals/ije/2014/589587/

Int J Endocrinol. 2014;2014:589587. doi: 10.1155/2014/589587. Epub 2014 Mar 26.

   
       
 

Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency.

Płudowski P1, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sokół D, Czech-Kowalska J, Dębski R, Decsi T, Dobrzańska A, Franek E, Głuszko P, Grant WB, Holick MF, Yankovskaya L, Konstantynowicz J, Książyk JB, Księżopolska-Orłowska K, Lewiński A, Litwin M, Lohner S, Lorenc RS, Lukaszkiewicz J, Marcinowska-Suchowierska E, Milewicz A, Misiorowski W, Nowicki M, Povoroznyuk V, Rozentryt P, Rudenka E, Shoenfeld Y, Socha P, Solnica B, Szalecki M, Tałałaj M, Varbiro S, Żmijewski MA.

   
 

Abstract

INTRODUCTION:

Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolism as well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activity appear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest that Vitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conference focused on overcoming Vitamin D deficiency.

METHODS:

After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses on recommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to Scientific Committee members of the 'Vitamin D - minimum, maximum, optimum' conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting 'Vitamin D - minimum, maximum, optimum' was held on October 19-20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists' voting were reviewed and discussed during eight plenary sessions and two workshops.

RESULTS:

Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges of serum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20-30 ng/mL(50-75 nmol/L)], and target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]. General practical guidelines regarding supplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, children and adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed.

CONCLUSIONS:

Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementation guidance and population strategies for Vitamin D in Central Europe.

http://czasopisma.viamedica.pl/ep/article/view/35659

Endokrynol Pol. 2013;64(4):319-27.

   
       
 

Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence.

Pludowski P1, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, Shoenfeld Y, Lerchbaum E, Llewellyn DJ, Kienreich K, Soni M.

   
 

Abstract

BACKGROUND:

Optimal vitamin D intake and its status are important not only for bone and calcium-phosphate metabolism, but also for overall health and well-being. Vitamin D deficiency and insufficiency as a global health problem are likely to be a risk for wide spectrum of acute and chronic illnesses.

METHODS:

A review of randomized controlled trials, meta-analyses, and other evidence of vitamin D action on various health outcomes.

RESULTS:

Adequate vitamin D status seems to be protective against musculoskeletal disorders (muscle weakness, falls, fractures), infectious diseases, autoimmune diseases, cardiovascular disease, type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive dysfunction and mental illness, and other diseases, as well as infertility and adverse pregnancy and birth outcomes. Vitamin D deficiency/insufficiency is associated with all-cause mortality.

CONCLUSIONS:

Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for the spectrum of disorders. Supplementation guidance and population strategies for the eradication of vitamin D deficiency must be included in the priorities of physicians, medical professionals and healthcare policy-makers.

Autoimmun Rev. 2013 Aug;12(10):976-89. doi: 10.1016/j.autrev.2013.02.004. Epub 2013 Mar 28.