Is sunlight good for our heart?
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ABSTRACT: Previous research has suggested that vitamin D and sunlight are related to cardiovascular outcomes, but associations between sunlight and risk factors have not been investigated. We examined whether increased sunlight exposure was related to improved cardiovascular risk factor status.BMC Neurology 06/2014; 14(1):133. · 2.49 Impact Factor
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ABSTRACT: The incidence of hypertension and cardiovascular disease correlates with latitude and rises in winter. The molecular basis for this remains obscure. As nitric oxide (NO) metabolites are abundant in human skin we hypothesised that exposure to UVA may mobilise NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers irradiation of the skin with 2 Standard Erythemal Doses of UVA lowered BP, with concomitant decreases in circulating nitrate and rises in nitrite concentrations. Unexpectedly, acute dietary intervention aimed at modulating systemic nitrate availability had no effect on UV-induced hemodynamic changes, indicating that cardiovascular effects were not mediated via direct utilization of circulating nitrate. UVA irradiation of the forearm caused increased blood flow independently of NO-synthase activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labelled with the NO-imaging probe DAF2-DA revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent fashion, with the majority of the light-sensitive NO pool in the upper epidermis. Collectively, our data provide mechanistic insights into an important function of the skin in modulating systemic NO bioavailability which may account for the latitudinal and seasonal variations of BP and cardiovascular disease.Journal of Investigative Dermatology accepted article preview online, 20 January 2014. doi:10.1038/jid.2014.27.Journal of Investigative Dermatology 01/2014; · 6.19 Impact Factor
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ABSTRACT: Time and environmental physical activity are involved in timing of many medical events. In a recent study published by the National Acad-emy of Science, USA it was shown that month of birth is related to longevity. The aim of this study was to check the month of birth distribu-tion in a great group of AMI patients of both gender, one of the great killers in the developed countries, to check the mentioned paradigm of month of birth and longevity. Methods & Pa-tients: Patients admitted to Cardiology Depart-ments of a tertiary University Hospital in Kaunas, Lithuania with AMI at years 1990-2010 (n-22047) were studied. Month of birth of these patients, total and both gender were checked. Monthly, quarterly and trimester comparison were done. Statistical differences established using t-Stu-dent test and distribution by percents of the yearly months of birth. Results: It was a sig-nificant difference in the month of birth of the studied AMI population. January and first quar-ter and trimester born patients were more often in the studied AMI patients group. The higher morbidity by Cardiovascular diseases can be a significant ingredient in the structure of popula-tion longevity. Possible mechanisms explaining our findings are discussed. Conclusion: In the AMI population people born in January, first quarter or trimester of the year are dominating in both gender groups. The results of this study can be an additional confirmation of the para-digm about links between month of birth and longevity.
Is sunlight good for our heart?
Martin Feelisch1*, Victoria Kolb-Bachofen2, Donald Liu3, Jon O Lundberg4,
Lucia P. Revelo5, Christoph V. Suschek6, and Richard B. Weller3*
1Clinical Sciences Research Institute, University of Warwick Medical School, Coventry CV4 7AL, UK;2Medizinische Einrichtungen, Immunobiologie, Heinrich-Heine-Universitat,
Dusseldorf D-40001, Germany;3Department of Dermatology, University of Edinburgh, Edinburgh EH3 9HA, UK;4Department of Physiology and Pharmacology, Karolinska
Institutet, SE-171 77 Stockholm, Sweden;5The Mayfair Medical Center, London W1K 5LS, UK; and6Department of Plastic and Reconstructive Surgery, Hand Surgery, and
Burn Center, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
Received 3 November 2009; revised 14 January 2010; accepted 2 February 2010
Humans evolved being exposed for about half of the day to the
light of the sun. Nowadays, exposure to sunlight is actively discour-
aged for fear of skin cancer, and contemporary lifestyles are associ-
ated with long hours spent under artificial light indoors. Besides an
life-style-related behavioural changes on our chronobiology, the
balance between the beneficial and harmful effects of sunlight on
human health is the subject of considerable debate, in both the
scientific and popular press, and the latter is of major public
health significance. While there is incontrovertible evidence that
ultraviolet radiation (UVR) in the form of sunlight is a significant
predisposing factor for non-melanoma and melanoma skin
cancers in pale skinned people,1a growing body of data suggest
general health benefits brought about by sunlight.2These are
believed to be mediated either by melatonin or vitamin
D. Melatonin is produced from serotonin by the pineal gland
located in the centre of the brain during periods of darkness,
and its release is suppressed as a function of the visible light inten-
sity sensed through ocular photoreceptors. Vitamin D is formed by
ultraviolet B (UVB)-mediated photolysis of 7-dehydrocholesterol
in the skin. Both melatonin and vitamin D are pleiotropic hor-
mones that exert a multitude of cellular effects by interacting
with membrane and nuclear receptors, and receptor-independent
actions. People with more heavily pigmented skin require higher
doses of UVB to produce adequate amounts of vitamin D, and
this may have been an evolutionary driver to the variation of
human skin colour with latitude and intensity of solar irradiation.
Our degree of exposure to sunlight is easily modified by behav-
ioural factors such as the use of clothing, sunglasses, and
sun-blocking creams, and time spent outdoors. Balancing the car-
cinogenic risks with the requirement for vitamin D has led to
advice on moderating sun exposure, while supplementing food
with vitamin D. Guidance on such behaviour is part of the public
health campaigns in most countries with Caucasian populations.
Following these suggestions, we may, however, be missing out
on other health benefits provided by natural sunlight that are
less obvious and unrelated to the above classical mediators.
We propose here that many of the beneficial effects of sunlight,
particularly those related to cardiovascular health, are mediated
by mechanisms that are independent of melatonin, vitamin D,
and exposure to UVB alone. Specifically, we suggest that the skin
is a significant store of nitric oxide (NO)-related species that can
be mobilized by sunlight and delivered to the systemic circulation
to exert coronary vasodilator and cardioprotective as well as anti-
hypertensive effects (Figure 1). We further hypothesize that this
dermal NO reservoir is a product of local production and
dietary supply with nitrate-rich foods.
Sunlight and cardiovascular
The roots of photomedicine are ancient, dating back to the begin-
nings of civilization when heliotherapy was found to improve
certain disease states. Sunlight was observed to have cardiovascu-
lar effects during the MRC hypertension trials of the 1970s with
blood pressure being consistently lower in summer than winter.3
The prevalence of hypertension and mean population diastolic
and systolic blood pressures correlate directly with latitude,
being higher in populations living further from the equator.4This
may be due to a number of racial and environmental factors
other than sunlight. Yet, within the UK, all-cause mortality (of
which the major cause is ischaemic heart disease) correlates line-
arly with latitude (relative risk 1.0 at 508N, 1.46+.03 at 558N),
even after accounting for all known risk factors and possible pro-
tective variables such as fruit and vegetable consumption.5More-
over, following migration, the mortality risk changes to that of
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
*Corresponding author. Email: email@example.com or firstname.lastname@example.org
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2010. For permissions please email: email@example.com.
European Heart Journal
European Heart Journal Advance Access published March 9, 2010
the new place of residence.6Seasonal variations in light intensity,
caused by the inclination of the Earth’s rotary axis (contrary to
common belief, the intensity of solar radiation is not governed
by the distance between Earth and sun; paradoxically, our planet
is closest to the sun in winter, not summer), are accompanied
by seasonal variations in incidence and mortality of cardiovascular
disease (CVD). Similar to stroke, rates of acute coronary syn-
dromes (including unstable angina, acute myocardial infarction,
atrial fibrillation, and sudden cardiac death) are highest in the
winter months with shorter hours of daylight.7Temperature
stress and sympathetic activation have been suggested as a cause
for this, but the same effect is seen in countries such as Kuwait,
where temperatures in winter are most comfortable and impose
least physiological stress.8Sunlight exposure in temperate climates
is markedly reduced in winter not only because of the reduction in
daylight hours, but also because of increased light-impenetrable
Recent findings and possible
impact on cardiovascular disease
Recently, Suschek and co-authors9demonstrated that irradiation
of healthy individuals with biologically relevant doses of UVA
leads to a sustained reduction in blood pressure. This is an impor-
tant finding as small changes in population blood pressure can
produce significant reductions in deaths from cerebral and coron-
ary vascular disease. The fall in mortality due to stroke, ischaemic
heart disease, and other vascular diseases is directly and linearly
proportional to the degree of reduction in blood pressure, and a
20 mmHg lower systolic blood pressure leads to a two-fold
reduction in overall mortality in both men and women aged 40–
69 years.10These dramatic effects on major causes of morbidity
and mortality highlight the benefits expected from even small
UV-mediated reductions in blood pressure. Besides their positive
impact on the burden of disease from a human, family, and societal
perspective, moderate exposure to sunlight may also reduce the
economic burden of CVD. The latter has been estimated to
amount to E169 billion annually for the European Union11and
$519 billion for hypertension, heart disease, and stroke in the
USA12(combined impact of healthcare costs and lost economic
output in 2003). Thus, even minor reductions in blood pressure
due to enhanced exposure to sunlight could translate into
hundred thousands of person-years of life and billions of dollars
and Euros saved every year.
What mechanisms may be
involved and what other effects
can be expected from moderate
exposure to sunlight?
Nitric oxide, produced from L-arginine by nitric oxide synthase
(NOS) in the endothelium, has been recognized as a key vasodila-
tor in the vascular system since the identification of EDRF as NO,13
and systemic inhibition of NO formation is accompanied by an
immediate rise in blood pressure. In vivo, NO is rapidly inactivated
by reaction with oxygenated haemoglobin and reactive oxygen
species, giving rise to the formation of nitrate (NO3
life of NO should prevent it from having major actions at a distance
from its site of production, although conversion to longer-lived
species with vasodilator properties is known to occur in the circu-
lation.14Nitrite, for long considered biologically inert at low con-
centrations, is now known not only to dilate blood vessels in its
own right but to also protect organs against ischaemia/reperfusion
(I/R) damage (reviewed in ref.15,16). Haemoglobin, myoglobin,
xanthine oxidoreductase, cytochrome P-450, and mitochondrial
enzymes can all generate NO from nitrite, in particular under
hypoxic conditions. Apart from continuous enzymatic NO pro-
duction, blood vessels ‘photorelax’ on direct irradiation with
UVA, and this effect is potentiated in the presence of sodium
nitrite.17Endogenous nitrite and S-nitrosothiols (RSNOs) in the
vasculature have been shown to account for this phenomenon,
and both compounds have absorption peaks within the UVA wave-
length range.18Similarly, UVA irradiation of skin in vitro leads to
photodecomposition of ‘NO stores’ and release of NO.19By
weight, the skin is one of the largest organs in the body, with a
surface area of around 2 m2in the average adult. All three NOS
isoforms are expressed in the dermis and epidermis,20and in
addition to this, nitrite and NO are generated on the skin
surface by reduction of sweat nitrate21and possibly by the oxi-
dation of ammonia22(Figure 2). The epidermis is particularly rich
in cysteine-containing proteins and their sulfhydryl groups are
readily nitrosated to form RSNOs. Nitrite, nitrate, and RSNOs
are found in the dermis and epidermis at concentrations one or
two orders of magnitude higher than those in plasma.19,23In
adults, skin and blood are of comparable weight and volume, and
nitrite in the epidermis alone amounts to ?135 mmoles, while
total nitrite in blood rarely exceeds 13–15 mmoles.23Thus, mobil-
ization of only a fraction of the relatively large epidermal pool of
e.g. nitrite by sunlight is likely sufficient to transiently increase
2), and several reactive nitrogen oxide species. The short half-
Figure 1 Sunlight-induced export of nitric oxide bioactivity
from storage forms in the skin.
M. Feelisch et al.
Page 2 of 5
plasma nitrite concentrations. The exact mechanism of release and
nature of the dermal ‘NO stores’ is unknown (in addition to the
species discussed above it may include metal nitrosyls such as dini-
trosyl iron complexes and NO-haem species), but increases in sys-
temic nitrite availability would rapidly translate into higher
concentrations of nitroso products in blood and tissues,24and
this is likely to contribute to cytoprotection and vasodilatation.
A recent human study has demonstrated that UVA irradiation
can increase plasma nitrite levels by 40%.9This is intriguing consid-
ering that in animal models, a similar increase in nitrite is associated
with cardioprotection following I/R injury.25Dietary nitrate intake
(predominantly from green leafy vegetables) may provide an
alternative source of nitrite. An entero-salivary circulation of
nitrate ensures that part of this dietary nitrate is reduced to
nitrite by facultative anaerobic bacteria in the mouth. Thus, a
high nitrate meal leads to a sustained increase in circulating
nitrite,26and this nitrite increase is paralleled by reduction in sys-
temic blood pressure suggesting further reduction to NO.27,28In
addition to the commensal bacterial flora, mammalian tissues are
endowed with the capacity of sequential nitrate ? nitrite ?
NO reduction.29Skin bound NO stores are in equilibrium with cir-
culating nitrite in unirradiated individuals,23and dietary-derived
nitrite may therefore ‘top up’ the skin reservoir. In addition, circu-
lating nitrate may be photolysed by UVA reaching the superficial
dermal vasculature and give rise to the formation of NO, nitrite,
and nitroso species.30Thus, multiple processes in the skin and in
the circulation may contribute to light-induced blood pressure
reduction and cardioprotection, with changes in nitrite and
nitroso species concentrations playing key roles (Figure 3). Lower
levels of sunlight reaching the skin during the winter season may
translate into lower nitrite and nitroso species concentrations in
the skin and circulation, and this may contribute to seasonal vari-
ations in CVD. Unfortunately, little is known about seasonal differ-
ences in NO-related species concentrations; no data are available
on nitroso species variations and information about circulating
nitrite/nitrate levels is conflicting,31,32possibly due to confounding
Even small bursts in systemic nitrite levels can have profound
effects on cardiac redox status and trigger long-lasting changes
in abundance and post-translational modification (including oxi-
dation, nitrosation, nitrosylation, nitration, and phosphorylation)
of a large number of proteins.33The magnitude and breadth of
nitrite-induced changes to the cytosolic and mitochondrial
cardiac proteome is rather surprising and includes enzymes
involved in metabolism, energy production, redox regulation,
contractile function, and serine/threonine kinase signaling33as
well as effects on complex I of the respiratory chain.34Some
alterations are reminiscent of ischaemic preconditioning and con-
sistent with a cardioprotective phenotype, although the overall
complexity of changes observed suggest involvement of additional
mechanisms. To this end, nitrite has recently been shown to
affect T- cell function and cytokine release,35raising the possi-
bility that it may also affect inflammatory processes. Effects of
nitrite and nitroso products on inflammation and immune cell
function would be of obvious significance for CVD, and a sys-
temic increase in circulating nitrite following whole body
exposure to UVR may account for the well-known effects of sun-
light on the immune system. The situation is likely to be even
more complex as both, melatonin and vitamin D, are known to
affect the formation and availability of NO at multiple levels, pro-
viding ample opportunity for cross-talk between these pathways.
Although nitrite would seem to be a likely source and nitroso
species possible mediators of the effects of sunlight on blood
pressure, the processes conferring cardioprotection may well
involve additional metabolic pathways and signalling processes.
Which NO metabolite ultimately accounts for what biological
effect is currently unclear and elucidation of the pathways
involved in local and systemic responses to sunlight will require
further investigation. Nevertheless, it would appear that enhan-
cing the availability of NO-related metabolites by sunlight has
the potential to confer cardiovascular protective effects not
afforded by other mediators typically associated with exposure
to sunlight. Some of the effects described here may not be
limited to the heart but provide benefit for other organ
systems as well (Figure 3).
Figure 2 Enzymatic and non-enzymatic sources and location of
major nitric oxide-related biomolecules in the skin.
Figure 3 Possible molecular mechanisms involved in mediating
the beneficial cardiovascular effects of sunlight.
Is sunlight good for our heart?
Page 3 of 5
Hypothesis testing and outlook
Hypertension and ischaemic heart disease are major causes of mor-
bidity and mortality, particularly in northern Europe, but excessive
sun exposure carries significant risks. It appears challenging to
appropriately measure and quantify sunlight exposure, evaluate its
weighted relevance compared with overt traditional risk factors,
and establish its actual relationship with vascular function and endo-
major implications for public health advice. If true, we would expect
to find an inverse correlation between markers of sun exposure,
such as actinic keratoses and skin cancers and prevalence of hyper-
tension, ischaemic heart disease, and stroke. Such relationships can
be investigated by interrogation of population diagnostic databases.
Differentiating the effects of sunlight on cardiovascular and hyper-
tensive mortality will requirecarefulstratification for expected con-
founding variables associated with differing sun exposure patterns,
and data on these factors (e.g. smoking history, diet, and social
class) will need to be available. At the experimental level, we need
a better understanding of precisely how different wavelengths of
the electromagnetic solar radiation interact with NO-related
species and what the subsequent fate of the reaction products is.
Of note, also near-infrared and infrared light, which penetrate skin
to reach much deeper tissue layers compared with UV, can
release NO from nitrosyl-haem species.36Thus, light of various
wavelengths—perhaps even visible light—may affect NO status,
provided overall photic energy levels are sufficient for the mobiliz-
ation of dermal NO stores. We also need to measure the
dose-response relationship of sunlight’s effects on blood pressure
and other cardiovascular parameters such as coronary and systemic
vascular distensibility and total peripheral resistance. This and other
information will be crucial to identify how much of an NO-related
cardiovascular effects, and whether this pool is skin-bound, or
present in the superficial dermal vasculature. The stage of life at
which UV exposure occurs may be significant. Episodic sunburn in
childhood is a particular risk factor for malignant melanoma, the
most serious of the UV-related skin cancers. The most marked
effect of seasonal variation in blood pressure is seen in older age
cohorts.3Cardiovascular mortality of individuals who moved
relates to the geographical destination, not the childhood origin of
the migrant subjects.6The adult cardiovascular system may thus
be more susceptible to the beneficial effects of sunlight-related
sition to an ageing world population with enhanced CVD risk, this
differentiation may be significant. If confirmed, it will enable public
hood, with increased exposure later in life, to limit the carcinogenic
effects of sunlight on the skin early on, while allowing full benefit to
be obtained from its cardiovascular effects later. In conclusion, har-
nessing the powerof the sun forourhealth may not stop atthe pro-
duction of melatonin and vitamin D, but include pathways under
control of NO and nitrite/nitrate. Irrespective of the precise mech-
anism(s) of action, a modulation (e.g. by dietary measures) of the
NO-related store in the skin and cautious bodily exposure to sun-
light would seem to provide cardiovascular benefits. The future is
bright—let a little sunshine into your heart.
The authors acknowledge support from the UK Medical Research
Council (Strategic Appointment Scheme, to MF), the EU 7th Frame-
work Program (Flaviola, to JOL), Vinnova (CIDaT, to JOL), and
Chest, Heart & Stroke Scotland (to RW).
Conflict of interest: none declared.
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