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Vitamin D supplements and reasonable solar

UVB should be recommended to prevent
escalating incidence of chronic diseases




Michael F Holick Sunil J Wimalawansa

Boston University Cardio Metabolic Institute


Available from: Sunil J Wimalawansa

Retrieved on: 30 November 2015
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h321 (Published 29 January 2015)
Cite this as: BMJ 2015;350:h321

Vitamin D supplements and reasonable solar UVB should

be recommended to prevent escalating incidence of
chronic diseases
William B. Grant, Michael F. Holick, and Sunil J. Wimalawansa

There is strong evidence from observational studies that 25-hydroxyvitamin D [25(OH)D]

concentrations above 75 nmol/L (30 ng/mL) are associated with better outcomes for chronic
diseases [1-3]. In addition, for African-Americans, there is evidence that the poor survival
rates after diagnosis of cancer in this community is linked to lower 25(OH)D concentrations
independent of socioeconomic status, stage at diagnosis and treatment [4].

Unfortunately, most vitamin D randomized controlled trials (RCTs) conducted to date, as

well as the major ones currently underway that are listed in Meyer et al [5], have not been
designed to answer the question of the relationship of serum 25(OH)D to intended health
outcomes. Therefore, if studies are not conducted in vitamin D deficient or insufficient
populations, one would not expect a positive outcome [6].

In fact, most published vitamin D RCTs were based on the guidelines for pharmaceutical
agents, assuming that the trial agent is the only source of intervention and there is a linear
dose-response relation; however, this is not the case. Neither assumption is satisfied for
vitamin D. Heaney recently outline guidelines that are applicable for RCTs designed to assess
the impact of nutrient supplementation [6]. The main steps for conducting vitamin D RCTs
should include, (A) start with an understanding of the 25(OH)D concentration-health
outcome relation; (B) measure 25(OH)D concentrations prior to the clinical study in all
prospective participants and only include those with concentrations below the optimal
threshold; (C) supplement with adequate vitamin D 3 to raise (and titrate) serum 25(OH)D
concentrations to near the upper end of the expected relation; (D) measure 25(OH)D
concentrations following enrolment to the trial to assure the right serum concentrations have
been achieved; and (E) optimize co-nutrients in all participants.

In this regard, we refer to the recent paper by Meyer and colleagues who concluded that
vitamin D supplementation for preventing chronic diseases is not recommended due to lack
of supporting evidence [5]. However, their paper overlooked a large body of evidence that
supports higher 25(OH)D concentrations in reducing risk of chronic diseases [7, 8]. There are
only three ways that 25(OH)D concentrations can be raised: by UVB exposure, diet, and
supplements. This commentary intended to presents some of that missing and important
evidence that supports why supplementing with vitamin D is imperative in reducing the
escalating incidence of chronic disease, worldwide.

First, inflammation is a risk factor for many types of chronic disease [9] and adequate levels
of vitamin D have the potential to reduce inflammation [10]. A meta-analysis of vitamin D
RCTs found that those studies using vitamin D3 in subjects with mean baseline 25(OH)D
concentrations below 48 nmol/L had a 49% chance of finding reduced biomarkers of
inflammation but only 27% of those with higher 25(OH)D concentrations did [11]. Raising
25(OH)D concentrations to the range 35-82 nmol/L resulted in 55% beneficial reduction in
inflammation. This study and many other studies, support a value of 75 nmol/L as more
protective against chronic disease than 50 nmol/L.

Another approach is to use sensible and adequate exposure to solar UVB radiation to improve
the humans well-being. There are many new findings in the recent literature supporting
exposure to solar UVB radiation B reducing risk for many chronic diseases including
multiple sclerosis, type 1 diabetes and many types of cancer [12]. Moreover, solar UVB,
UVA and visible light exposure has beneficial effects independent of vitamin D production

A mouse model of UVB exposure found that UVB exposure raising 25(OH)D concentrations
the same amount as oral vitamin D intake decreased the progression of intestinal tumours
more than oral vitamin D [16]. This finding could further explain why geographical and
ecological studies reporting strong evidence of inverse correlation of solar UVB doses with
the incidence and mortality rates of many types of cancers [17]. In addition, outdoor
occupation has been shown to inversely correlate with incidence rates of many types of
cancer in Nordic countries [18].

There are many other benefits of appropriate exposure to solar and artificial UVB and UVA,
including lowering blood pressure, increasing beta endorphin concentrations, improving
wound healing and many other benefits [19]. However, incidental short exposures are
inadequate to generate appreciable amounts of vitamin D in the skin, especially during non-
summer months. A study found an increased risk of MS for young people who spent less time
in the sun in summer in Norway and during the wintertime in Italy [15]. Another study in
Sweden found that those who avoided sun exposure had significantly higher all-cause
mortality rates [19].

It should be noted that the understanding of the mechanisms whereby solar UVB exposure
reduces risk of chronic diseases independent of vitamin D production is limited at present
[13]. In addition, some people are concerned about the risk of skin cancer and melanoma
from UV exposure, but data suggest that sun-exposure is only applicable and specific to
squamous cell carcinoma of the skin [20]. In fact most melanomas occur on the least sun
exposed areas, and occupational sun exposure in fact, reduces risk for this deadly skin cancer

It is well documented not only in the United States but worldwide that it is not possible to
obtain even the minimum 600 IUs daily of vitamin D that is recommended by the Institute of
Medicine for most children and adults from dietary sources.

Thus, without adequate sun exposure most of the world population is vitamin D deficient.
The only way to guarantee sufficiency is to recommend a three-part strategy to improve
everyones vitamin D status. This includes (A): Encouraging consuming more foods that
naturally contain vitamin D including oily fish such as salmon and foods fortified with
vitamin D. There needs to be an evaluation by health regulatory agencies for regulations to
promote vitamin D fortification of local foods. (B): The World Health Organization and local
health regulatory agencies should provide guidelines for sensible sun exposure which would
improve the worlds vitamin D status while minimizing risk for skin cancer. And (C):
Because vitamin D deficiency is pandemic all children and adults who were unable to obtain
adequate vitamin D from dietary, food fortification, and solar sources should be encouraged
to take a vitamin D supplement to satisfy their vitamin D requirement.

Based on the evidence to date from ecological and observational studies and RCTs, serum
25(OH)D concentrations should be above 75 nmol/L (30 ng/mL) for optimal health through a
combination of UVB exposure, diet, and supplements. Available results to date support that
this would cost-effectively decrease the escalating incidences of chronic non-communicable
disease worldwide.

Disclosure and conflicts of interests: WBG receives funding from Bio-Tech Pharmacal
(Fayetteville, AR), MediSun Technology (Highland Park, IL), and the Vitamin D Council
(San Luis Obispo, CA). MFH and SJW have no conflicts of interests.

1. Wang L, Song Y, Manson JE, Pilz S, Mrz W, Michalsson K, et al. Circulating 25-
hydroxy-vitamin D and risk of cardiovascular disease: A meta-analysis of prospective
studies. Circ Cardiovasc Qual Outcomes. 2012;5(6):819-29.
2. Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, et al. Vitamin D
effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease,
cancer, fertility, pregnancy, dementia and mortality- a review of recent evidence.
Autoimmun Rev. 2013;12(10):976-89.
3. Garland CF, Kim JJ, Mohr SB, Gorham ED, Grant WB, Giovannucci EL, et al. Meta-
analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Pub
Health. 2014;104(8):e43-50.
4. Grant WB, Peiris AN. Differences in vitamin D status may account for unexplained
disparities in cancer survival rates between African and White Americans.
Dermatoendocrinol. 2012;4(2):85-94.
5. Meyer HE, Holvik K, Lips P. Should vitamin D supplements be recommended toprevent
chronic diseases? BMJ. BMJ 2015;350:h321doi: 10.1136/bmj.h321
6. Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient
effects. Nutr Rev. 2014;72(1):48-54.
7. Grber U, Spitz J, Reichrath J, Kisters K, Holick MF. Vitamin D: Update 2013: From
rickets prophylaxis to general preventive healthcare. Dermatoendocrinol. 2013;5(3):331-
8. Hossein-Nezhad A, Holick MF. Vitamin D for health: A global perspective. Mayo Clin
Proc. 2013;88(7):720-55.
9. Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation
and cancer.Curr Pharm Des. 2012;18(26):3831-52.
10. Yin K, Agrawal DK. Vitamin D and inflammatory diseases.J Inflamm Res. 2014;7:69-87.
11. Cannell JJ, Grant WB, Holick MF. Vitamin D and inflammation. Dermatoendocrinol.
2014;6(1): e983401-1-10.
12. Wacker M, Holick MF. Sunlight and vitamin D: A global perspective for health.
Dermatoendocrinol. 2013;5(1) :51-108.
13. Juzeniene A, Moan J. Beneficial effects of UV radiation other than via vitamin D
production. Dermatoendocrinol. 2012;4(2):109-17.

14. Liu D, Fernandez BO, Hamilton A, Lang NN, Gallagher JM, Newby DE, et al. UVA
irradiation of human skin vasodilates arterial vasculature and lowers blood pressure
independently of nitric oxidesynthase. J Invest Dermatol. 2014;134(7):1839-46.
15. Bjrnevik K, Riise T, Casetta I, Drulovic J, Granieri E, Holmy T, et al. Sun exposure
and multiple sclerosis risk in Norway and Italy: The EnvIMSstudy. MultScler.
16. Rebel H, der Spek CD, Salvatori D, van Leeuwen JP, Robanus-Maandag EC, de Gruijl
FR.UV exposure inhibits intestinal tumour growth and progression to malignancy in
intestine-specific Apc mutant mice kept on low vitamin D diet.Int J Cancer.
17. Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention.
Nutrients. 2013;5(10):3993-4023.
18. Grant WB. Role of solar UV irradiance and smoking in cancer as inferred from cancer
incidence rates by occupation in Nordic countries. Dermatoendocrinol. 2012;4(2):203-11.
19. Lindqvist PG, Epstein E, Landin-Olsson M, Ingvar C, Nielsen K, Stenbeck M, et al.
Avoidance of sun exposure is a risk factor for all-cause mortality: results from the MISS
cohort. J Intern Med. 2014;276(1):77-86.
20. English DR, Armstrong BK, Kricker A, Fleming C. Sunlight and cancer.Cancer Causes
Control. 1997;8(3):271-83.
21. Chang YM, Barrett JH, Bishop DT, Armstrong BK, Bataille V, Bergman W, et al. Sun
exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and
7216 controls. Int J Epidemiol. 2009;38(3):814-30.
Competing interests:
WBG receives funding from Bio-Tech Pharmacal (Fayetteville, AR),MediSun Technology
(Highland Park, IL), and the Vitamin D Council (San Luis Obispo, CA). MFH and SJW have
no conflicts of interests.