Each
day, Apollo’s fiery chariot makes its way across the sky, bringing
life-giving light to the planet. For the ancient Greeks and Romans,
Apollo was the god of medicine and healing as well as of sun and
light—but Apollo could bring sickness as well as cure. Today’s
scientists have come to a similarly dichotomous recognition that
exposure to the ultraviolet radiation (UVR) in sunlight has both
beneficial and deleterious effects on human health.
Most
public health messages of the past century have focused on the hazards
of too much sun exposure. UVA radiation (95–97% of the UVR that reaches
Earth’s surface) penetrates deeply into the skin, where it can
contribute to skin cancer indirectly via generation of DNA-damaging
molecules such as hydroxyl and oxygen radicals. Sunburn is caused by too
much UVB radiation; this form also leads to direct DNA damage and
promotes various skin cancers. Both forms can damage collagen fibers,
destroy vitamin A in skin, accelerate aging of the skin, and increase
the risk of skin cancers. Excessive sun exposure can also cause
cataracts and diseases aggravated by UVR-induced immunosuppression such
as reactivation of some latent viruses.
However,
excessive UVR exposure accounts for only 0.1% of the total global burden
of disease in disability-adjusted life years (DALYs), according to the
2006 World Health Organization (WHO) report The Global Burden of Disease Due to Ultraviolet Radiation.
DALYs measure how much a person’s expectancy of healthy life is reduced
by premature death or disability caused by disease. Coauthor Robyn
Lucas, an epidemiologist at the National Centre for Epidemiology and
Population Health in Canberra, Australia, explains that many diseases
linked to excessive UVR exposure tend to be relatively benign—apart from
malignant melanoma—and occur in older age groups, due mainly to the
long lag between exposure and manifestation, the requirement of
cumulative exposures, or both. Therefore, when measuring by DALYs, these
diseases incur a relatively low disease burden despite their high
prevalence.
In contrast, the same WHO report noted that a
markedly larger annual disease burden of 3.3 billion DALYs worldwide
might result from very low levels of UVR exposure. This burden subsumes
major disorders of the musculoskeletal system and possibly an increased
risk of various autoimmune diseases and life-threatening cancers.
The
best-known benefit of sunlight is its ability to boost the body’s
vitamin D supply; most cases of vitamin D deficiency are due to lack of
outdoor sun exposure. At least 1,000 different genes governing virtually
every tissue in the body are now thought to be regulated by
1,25-dihydroxyvitamin D3 (1,25[OH]D), the active form of the
vitamin, including several involved in calcium metabolism and
neuromuscular and immune system functioning.
Although
most of the health-promoting benefits of sun exposure are thought to
occur through vitamin D photosynthesis, there may be other health
benefits that have gone largely overlooked in the debate over how much
sun is needed for good health [see “Other Sun-Dependent Pathways,” p.
A165]. As for what constitutes “excessive” UVR exposure, there is no
one-size-fits-all answer, says Lucas: “‘Excessive’ really means
inappropriately high for your skin type under a particular level of
ambient UVR.”
Vitamin D Production
Unlike
other essential vitamins, which must be obtained from food, vitamin D
can be synthesized in the skin through a photosynthetic reaction
triggered by exposure to UVB radiation. The efficiency of production
depends on the number of UVB photons that penetrate the skin, a process
that can be curtailed by clothing, excess body fat, sunscreen, and the
skin pigment melanin. For most white people, a half-hour in the summer
sun in a bathing suit can initiate the release of 50,000 IU (1.25 mg)
vitamin D into the circulation within 24 hours of exposure; this same
amount of exposure yields 20,000–30,000 IU in tanned individuals and
8,000–10,000 IU in dark-skinned people.
The initial photosynthesis produces vitamin D3,
most of which undergoes additional transformations, starting with the
production of 25-hydroxyvitamin D (25[OH]D), the major form of vitamin D
circulating in the bloodstream and the form that is routinely measured
to determine a person’s vitamin D status. Although various cell types
within the skin can carry out this transformation locally, the
conversion takes place primarily in the liver. Another set of
transformations occurs in the kidney and other tissues, forming
1,25(OH)D. This form of the vitamin is actually a hormone, chemically
akin to the steroid hormones.
1,25(OH)D accumulates in
cell nuclei of the intestine, where it enhances calcium and phosphorus
absorption, controlling the flow of calcium into and out of bones to
regulate bone-calcium metabolism. Michael Holick, a medical professor
and director of the Bone Health Care Clinic at Boston University Medical
Center, says, “The primary physiologic function of vitamin D is to
maintain serum calcium and phosphorous levels within the normal
physiologic range to support most metabolic functions, neuromuscular
transmission, and bone mineralization.”
Without
sufficient vitamin D, bones will not form properly. In children, this
causes rickets, a disease characterized by growth retardation and
various skeletal deformities, including the hallmark bowed legs. More
recently, there has been a growing appreciation for vitamin D’s impact
on bone health in adults. In August 2007, the Agency for Health Care
Policy and Research published Effectiveness and Safety of Vitamin D in Relation to Bone Health,
a systematic review of 167 studies that found “fair evidence” of an
association between circulating 25(OH)D concentrations and either
increased bone-mineral density or reduced falls in older people (a
result of strengthened muscles as well as strengthened bones). “Low
vitamin D levels will precipitate and exacerbate osteoporosis in both
men and women and cause the painful bone disease osteomalacia,” says
Holick.
Evolution of the Great Solar Debate
In the 2002 book Bone Loss and Osteoporosis in Past Populations: An Anthropological Perspective,
Reinhold Vieth, a nutrition professor at the University of Toronto,
writes that early primates probably acquired their relatively high
vitamin D requirements from frequent grooming and ingestion of oils rich
in vitamin D precursors that were secreted by their skin onto their
fur. The first humans evolved in equatorial Africa, where the direct
angle of sunlight delivers very strong UVR most of the year. The gradual
loss of protective fur may have created evolutionary pressure to
develop deeply pigmented skin to avoid photodegradation of
micronutrients and protect sweat glands from UVR-induced injury.
In the July 2000 issue of the Journal of Human Evolution,
California Academy of Sciences anthropologists Nina Jablonski and
George Chaplin wrote that because dark skin requires about five to six
times more solar exposure than pale skin for equivalent vitamin D
photosynthesis, and because the intensity of UVB radiation declines with
increasing latitude, one could surmise that skin lightening was an
evolutionary adaptation that allowed for optimal survival in low-UVR
climes, assuming a traditional diet and outdoor lifestyle. Cooler
temperatures in these higher latitudes resulted in the need for more
clothing and shelter, further reducing UVR exposure. With shorter winter
days and insufficient solar radiation in the UVB wavelengths needed to
stimulate vitamin D synthesis, dietary sources such as fatty fish became
increasingly important.
Over time, clothing became the
norm in higher latitudes and then eventually a social attribute in many
societies. By the 1600s, peoples in these regions covered their whole
body, even in summertime. Many children who lived in the crowded and
polluted industrialized cities of northern Europe developed rickets. By
the late 1800s, approximately 90% of all children living in
industrialized Europe and North America had some manifestations of the
disease, according to estimates based on autopsy studies of the day
cited by Holick in the August 2006 Journal of Clinical Investigation and the October 2007 American Journal of Public Health.
Doctors
throughout Europe and North America began promoting whole-body
sun-bathing to help prevent rickets. It was also recognized that
wintertime sunlight in the temperate zone was too feeble to prevent
rickets. For this reason, many children were exposed to UVR from a
mercury or carbon arc lamp for one hour three times a week, which proved
to be an effective preventive measure and treatment.
Around
the time the solar solution to rickets gained widespread traction in
medical circles, another historic scourge, tuberculosis (TB), was also
found to respond to solar intervention. TB patients of all ages were
sent to rest in sunny locales and generally returned in good health.
Dermatology professor Barbara A. Gilchrest of Boston University School
of Medicine says that, whereas sun exposure was shown to improve
cutaneous TB, sanatorium patients with pulmonary TB likely responded as
much or more to rest and good nutrition than to UVR. Nevertheless, a
meta-analysis published in the February 2008 International Journal of Epidemiology found that high vitamin D levels reduce the risk of active TB (i.e., TB showing clinical symptoms) by 32%.
Almost
overnight, as awareness of the sun’s power against rickets and TB
spread, attitudes toward sun exposure underwent a radical shift. The
suntan became valued in the Western world as a new status symbol that
signified both health and wealth, as only the affluent could afford to
vacation by the sea and play outdoor sports. Phototherapy quickly
emerged as a popular medical treatment not only for TB, but also for
rheumatic disorders, diabetes, gout, chronic ulcers, and wounds. The
“healthy tan” was in, and “sickly-looking” pale skin was out.
Cancer: Cause, Protection, or Both?
The
first reports of an association between sun exposure and skin cancer
began to surface in dermatology publications in the late nineteenth
century. Nevertheless, it was not until the 1930s that the U.S. Public
Health Service began issuing warnings about sun-related health risks.
People were cautioned to avoid the midday summer sun, cover their heads
in direct sunlight, and gradually increase the time of sun exposure from
an initial 5–10 minutes per day to minimize the risk of sunburn.
In
the decades that followed, the skin cancer hazards of excessive sun
exposure would be extensively studied and mapped. Today, the three main
forms of skin cancer—melanoma, basal cell carcinoma, and squamous cell
carcinoma—are largely attributed to excessive UVR exposure. Skin cancers
became the most common form of cancer worldwide, especially among
groups such as white residents of Australia and New Zealand.
When
atmospheric scientists first called attention to possible chemical
destruction of the stratospheric ozone layer in the early 1970s, one
predicted consequence of the increased UVB radiation was a rise in skin
cancer rates, especially in Australia, New Zealand, South Africa, and
Latin America. To counter this threat, the WHO, the United Nations
Environment Programme, the World Meteorological Organization, the
International Agency for Research on Cancer, and the International
Commission on Non-Ionizing Radiation Protection established INTERSUN,
the Global UV Project, with the express goal of reducing the burden of
UVR-related disease. INTERSUN activities have included the development
of an internationally recognized UV Index to help frame sun protection
messages related to the daily intensity of UVR. [For more information on
these activities, see “WHO Ultraviolet Radiation Website,” p. A157 this
issue.]
Australia was among the first countries to
spearhead large-scale sun protection programs, with the Slip-Slop-Slap
initiative (short for “slip on a shirt, slop on some sun-screen, and
slap on a hat”) introduced in the early 1980s. “This program and the
subsequent SunSmart campaign have been highly effective in informing
Australians of the risks and providing clear, practical instructions as
to how to avoid excessive UVR exposure,” says Lucas. As a result of
increased use of hats, sunscreen, and shade, the incidence of malignant
melanoma has begun to plateau in Australia, New Zealand, Canada, and
Northern Europe among some age groups. However, because other
UVR-induced skin cancers typically take longer than melanoma to develop,
their incidence rates continue to rise in most developed countries.
Lucas says a gradual improvement in these rates is to be expected as
well.
Whereas skin cancer is associated with too much
UVR exposure, other cancers could result from too little. Living at
higher latitudes increases the risk of dying from Hodgkin lymphoma, as
well as breast, ovarian, colon, pancreatic, prostate, and other cancers,
as compared with living at lower latitudes. A randomized clinical trial
by Joan Lappe, a medical professor at Creighton University, and
colleagues, published in the June 2007 issue of the American Journal of Clinical Nutrition, confirmed that taking 2–4 times the daily dietary reference intake of 200–600 IU vitamin D3
and calcium resulted in a 50–77% reduction in expected incidence rates
of all cancers combined over a four-year period in post-menopausal women
living in Nebraska.
Moreover, although excessive sun
exposure is an established risk factor for cutaneous malignant melanoma,
continued high sun exposure was linked with increased survival rates in
patients with early-stage melanoma in a study reported by Marianne
Berwick, an epidemiology professor at the University of New Mexico, in
the February 2005 Journal of the National Cancer Institute.
Holick also points out that most melanomas occur on the least
sun-exposed areas of the body, and occupational exposure to sunlight
actually reduced melanoma risk in a study reported in the June 2003 Journal of Investigative Dermatology.
Other Health Links
Various
studies have linked low 25(OH)D levels to diseases other than cancer,
raising the possibility that vitamin D insufficiency is contributing to
many major illnesses. For example, there is substantial though not
definitive evidence that high levels of vitamin D either from diet or
from UVR exposure may decrease the risk of developing multiple sclerosis
(MS). Populations at higher latitudes have a higher incidence and
prevalence of MS; a review in the December 2002 issue of Toxicology
by epidemiology professor Anne-Louise Ponsonby and colleagues from The
Australian National University revealed that living at a latitude above
37° increased the risk of developing MS throughout life by greater than
100%.
Still to be resolved, however, is the question of
what levels of vitamin D are optimal for preventing the disease—and
whether the statistical associations reflect different gene pools rather
than different levels of 25(OH)D. (Interestingly, Holick reported in
the August 1988 issue of The Journal of Clinical Endocrinology & Metabolism that no previtamin D3
formed when human skin was exposed to sunlight on cloudless days in
Boston, at 42.2°N, from November through February or in Edmonton, at
52°N, from October through March.)
“Scientific evidence
on specific effects of vitamin D in preventing MS or slowing its
progression is not sufficient,” says Alberto Ascherio, a nutritional
epidemiologist at the Harvard School of Public Health. “Nevertheless,
considering the safety of vitamin D even in high doses, there is no
clear contraindication, and because vitamin D deficiency is very
prevalent, especially among MS patients, taking vitamin D supplements
and getting moderate sun exposure is more likely to be beneficial than
not.”
As with MS, there appears to be a latitudinal
gradient for type 1 diabetes, with a higher incidence at higher
latitudes. A Swedish epidemiologic study published in the December 2006
issue of Diabetologia found that sufficient vitamin D status in
early life was associated with a lower risk of developing type 1
diabetes. Nonobese mice of a strain predisposed to develop type 1
diabetes showed an 80% reduced risk of developing the disease when they
received a daily dietary dose of 1,25(OH)D, according to research
published in the June 1994 issue of the same journal. And a Finnish
study published 3 November 2001 in The Lancet showed that
children who received 2,000 IU vitamin D per day from 1 year of age on
had an 80% decreased risk of developing type 1 diabetes later in life,
whereas children who were vitamin D deficient had a fourfold increased
risk. Researchers are now seeking to understand how much UVR/vitamin D
is needed to lower the risk of diabetes and whether this is a factor
only in high-risk groups.
There is also a connection
with metabolic syndrome, a cluster of conditions that increases one’s
risk for type 2 diabetes and cardiovascular disease. A study in the
September 2006 issue of Progress in Biophysics and Molecular Biology
demonstrated that in young and elderly adults, serum 25(OH)D was
inversely correlated with blood glucose concentrations and insulin
resistance. Some studies have demonstrated high prevalence of low
vitamin D levels in people with type 2 diabetes, although it is not
clear whether this is a cause of the disease or an effect of another
causative factor—for example, lower levels of physical activity (in this
case, outdoor activity in particular).
People living
at higher latitudes throughout the world are at higher risk of
hypertension, and patients with cardiovascular disease are often found
to be deficient in vitamin D, according to research by Harvard Medical
School professor Thomas J. Wang and colleagues in the 29 January 2008
issue of Circulation. “Although the exact mechanisms are poorly
understood, it is known that 1,25(OH)D is among the most potent
hormones for down-regulating the blood pressure hormone renin in the
kidneys,” says Holick. “Moreover, there is an inflammatory component to
atherosclerosis, and vascular smooth muscle cells have a vitamin D
receptor and relax in the presence of 1,25(OH)D, suggesting a multitude
of mechanisms by which vitamin D may be cardioprotective.”
To
determine the potential link betwen sun exposure and the protective
effect in preventing hypertension, Rolfdieter Krause of the Free
University of Berlin Department of Natural Medicine and colleagues
exposed a group of hypertensive adults to a tanning bed that emitted
full-spectrum UVR similar to summer sunlight. Another group of
hypertensive adults was exposed to a tanning bed that emitted UVA-only
radiation similar to winter sunlight. After three months, those who used
the full-spectrum tanning bed had an average 180% increase in their
25(OH)D levels and an average 6 mm Hg decrease in their systolic and
diastolic blood pressures, bringing them into the normal range. In
constrast, the group that used the UVA-only tanning bed showed no change
in either 25(OH)D or blood pressure. These results were published in
the 29 August 1998 issue of The Lancet. According to Krause,
who currently heads the Heliotherapy Research Group at the Medical
University of Berlin, a serum 25(OH)D level of at least 40 ng/mL should
be adequate to protect against hypertension and other forms of
cardiovascular disease (as well as cancers of the prostate and colon).
William
Grant, who directs the Sunlight, Nutrition, and Health Research Center,
a research and education organization based in San Francisco, suspects
that sun exposure and higher 25(OH)D levels may confer protection
against other illnesses such as rheumatoid arthritis (RA), asthma, and
infectious diseases. “Vitamin D induces cathelicidin, a polypeptide that
effectively combats both bacterial and viral infections,” Grant says.
“This mechanism explains much of the seasonality of such viral
infections as influenza, bronchitis, and gastroenteritis, and bacterial
infections such as tuberculosis and septicemia.” For example, RA is more
severe in winter, when 25(OH)D levels tend to be lower, and is also
more prevalent in the higher latitudes. In addition, 25(OH)D levels are
inversely associated with the clinical status of RA patients, and
greater intake of vitamin D has been linked with lower RA risk, as
reported in January 2004 in Arthritis & Rheumatism.
Some reports, including an article in the October–December 2007 issue of Acta Medica Indonesiana,
indicate that sufficient 1,25(OH)D inhibits induction of disease in RA,
collagen-induced arthritis, Lyme arthritis, autoimmune
encephalomyelitis, thyroiditis, inflammatory bowel disease, and systemic
lupus erythematosus. Nonetheless, interventional data are lacking for
most autoimmune disorders and infectious diseases, with the exception of
TB.
How Much Is Enough?
Gilchrest
points out a problem with the literature: “Everyone recommends
something different, depending on the studies with which they are most
aligned. One study reports an increased risk of prostate cancer for men
with 25(OH)D levels above 90 ng/mL, for example.” In the June 2007 Lappe
article, she notes, subjects in the control “high-risk” unsupplemented
group had 25(OH)D levels of 71 nmol/L and the supplemented group had
levels of 96 nmol/L.
Nevertheless, given the
epidemiologic backdrop described above, there are now calls to rethink
sun exposure policy or to promote vitamin D supplementation in
higher-risk populations. Such groups include pregnant or breastfeeding
women (these states draw upon a mother’s own reserves of vitamin D), the
elderly, and those who must avoid the sun. Additionally, solely
breastfed infants whose mothers were vitamin D deficient during
pregnancy have smaller reserves of the nutrient and are at greater risk
of developing rickets. Even in the sun-rich environment of the Middle
East, insufficient vitamin D is a severe problem among breast-fed
infants of women who wear a burqa (a traditional garment that covers the body from head to foot), as reported in the February 2003 Journal of Pediatrics.
Several
recent reports indicate an increase in rickets particularly among
breastfed black infants, though white babies also are increasingly at
risk. A study in the February 2007 Journal of Nutrition
concluded that black and white pregnant women and neonates in the
northern United States are at high risk of vitamin D insufficiency, even
when mothers take prenatal vitamins (which typically provide 100–400 IU
vitamin D3). Studies by Bruce Hollis, director of pediatric
nutritional sciences at the Medical University of South Carolina, and
colleagues suggest that a maternal vitamin D3 intake of 4,000 IU per day is safe and sufficient to ensure adequate vitamin D status for both mother and nursing infant.
These
days, most experts define vitamin D deficiency as a serum 25(OH)D level
of less than 20 ng/mL. Holick and others assert that levels of 29 ng/mL
or lower can be considered to indicate a relative insufficiency of
vitamin D. Using this scale and considering various epidemiologic
studies, an estimated 1 billion people worldwide have vitamin D
deficiency or insufficiency, says Holick, who adds, “According to
several studies, some forty to one hundred percent of the U.S. and
European elderly men and women still living in the community [that is,
not in nursing homes] are vitamin D deficient.” Holick asserts that a
large number of infants, children, adolescents, and postmenopausal women
also are vitamin D insufficient. “These individuals have no apparent
skeletal or calcium metabolism abnormalities but may be at much higher
risk of developing various diseases,” Holick says.
In
the context of inadequate sunlight or vitamin D insufficiency, some
scientists worry that the emphasis on preventing skin cancers tends to
obscure the much larger mortality burden posed by more life-threatening
cancers such as lung, colon, and breast cancers. Many studies have shown
that cancer-related death rates decline as one moves toward the lower
latitudes (between 37°N and 37°S), and that the levels of ambient UVR in
different municipalities correlate inversely with cancer death rates
there. “As you head from north to south, you may find perhaps two or
three extra deaths [per hundred thousand people] from skin cancer,” says
Vieth. “At the same time, though, you’ll find thirty or forty fewer
deaths for the other major cancers. So when you estimate the number of
deaths likely to be attributable to UV light or vitamin D, it does is
not appear to be the best policy to advise people to simply keep out of
the sun just to prevent skin cancer.”
To maximize
protection against cancer, Grant recommends raising 25(OH)D levels to
between 40 and 60 ng/mL. Research such as that described in Holick’s
August 2006 Journal of Clinical Investigation article indicates that simply keeping the serum level above 20 ng/mL could reduce the risk of cancer by as much as 30–50%.
Cedric
F. Garland, a medical professor at the University of California, San
Diego, says that maintaining a serum level of 55–60 ng/mL may reduce the
breast cancer rate in temperate regions by half, and that incidence of
many other cancers would be similarly reduced as well. He calls this
“the single most important action that could be taken by society to
reduce the incidence of cancer in North America and Europe, beyond not
smoking.” Moreover, these levels could be readily achieved by consuming
no more than 2,000 IU/day of vitamin D3 at a cost of less
than $20 per year and, unless there are contraindications to sunlight
exposure, spending a few minutes outdoors (3–15 minutes for whites and
15–30 minutes for blacks) when the sun is highest in the sky, with 40%
of the skin area exposed.
Holick, Vieth, and many other experts now make a similar daily recommendation: 4,000 IU vitamin D3
without sun exposure or 2,000 IU plus 12–15 minutes of midday sun. They
say this level is quite safe except for sun-sensitive individuals or
those taking medications that increase photosensitivity.
Gilchrest
says some sunlight enters the skin even through a high-SPF sunscreen,
so people can maximize their dermal vitamin D production by spending
additional time outdoors while wearing protection. “Without the
sunscreen, this same individual would be incurring substantially more
damage to her skin but not further increasing her vitamin D level,” she
says.
Creating a Balanced Message
A
growing number of scientists are concerned that efforts to protect the
public from excessive UVR exposure may be eclipsing recent research
demonstrating the diverse health-promoting benefits of UVR exposure.
Some argue that the health benefits of UVB radiation seem to outweigh
the adverse effects, and that the risks can be minimized by carefully
managing UVR exposure (e.g., by avoiding sunburn), as well as by
increasing one’s intake of dietary antioxidants and limiting dietary fat
and caloric intake. Antioxidants including polyphenols, apigenin,
curcumin, proanthocyanidins, resveratrol, and silymarin have shown
promise in laboratory studies in protecting against UVR-induced skin
cancer, perhaps through antimutagenic or immune-modulating mechanisms.
Central
to the emerging debate is the issue of how to best construct public
health messages that highlight the pros and cons of sun exposure in a
balanced way. Such messages must necessarily take into account
variations in skin pigmentation between groups and these groups’
differing susceptibilities to the dangers and benefits of sun exposure.
Moreover, says Patricia Alpert, a nursing professor at the University of
Las Vegas, age matters. “The elderly [have a] declining capacity to
make vitamin D,” she says. “Many elderly, especially those living in
nursing homes, are vitamin D deficient, [even] those living in areas
considered to have adequate sunshine.”
Many experts are
now recommending a middle-ground approach that focuses on modest sun
exposures. Gilchrest says the American Academy of Dermatology and most
dermatologists currently suggest sun protection in combination with
vitamin D supplementation as a means of minimizing the risk of both skin
cancer and internal cancers. Furthermore, brief, repeated exposures are
more efficient at producing vitamin D. “Longer sun exposures cause
further sun damage to skin and increase the risk of photo-aging and skin
cancer, but do not increase vitamin D production,” she explains.
Lucas
adds that people should use sun protection when the UV Index is more
than 3. As part of Australia’s SunSmart program, “UV Alerts” are
announced in newspapers throughout the country whenever the index is
forecast to be 3 or higher. “Perhaps,” she says, “this practice should
be extended to other nations as well.” U.S. residents can obtain UV
Index forecasts through the EPA’s SunWise website (
http://epa.gov/sunwise/uvindex.html).
In
the near future, vitamin D and health guidelines regarding sun exposure
may need to be revised. But many factors not directly linked to sun
protection will also need to be taken into account. “Current
observations of widespread vitamin D insufficiency should not be
attributed only to sun protection strategies,” says Lucas. “Over the
same period there is a trend to an increasingly indoor lifestyle,
associated with technological advances such as television, computers,
and video games.” She says sun-safe messages remain important—possibly
more so than ever before—to protect against the potentially risky
high-dose intermittent sun exposure that people who stay indoors may be
most likely to incur.
Serotonin, Melatonin, and Daylight
As
diurnal creatures, we humans are programmed to be outdoors while the
sun is shining and home in bed at night. This is why melatonin is
produced during the dark hours and stops upon optic exposure to
daylight. This pineal hormone is a key pacesetter for many of the body’s
circadian rhythms. It also plays an important role in countering
infection, inflammation, cancer, and auto-immunity, according to a
review in the May 2006 issue of Current Opinion in Investigational Drugs. Finally, melatonin suppresses UVR-induced skin damage, according to research in the July 2005 issue of Endocrine.
When
people are exposed to sunlight or very bright artificial light in the
morning, their nocturnal melatonin production occurs sooner, and they
enter into sleep more easily at night. Melatonin production also shows a
seasonal variation relative to the availability of light, with the
hormone produced for a longer period in the winter than in the summer.
The melatonin rhythm phase advancement caused by exposure to bright
morning light has been effective against insomnia, premenstrual
syndrome, and seasonal affective disorder (SAD).
The
melatonin precursor, serotonin, is also affected by exposure to
daylight. Normally produced during the day, serotonin is only converted
to melatonin in darkness. Whereas high melatonin levels correspond to
long nights and short days, high serotonin levels in the presence of
melatonin reflect short nights and long days (i.e., longer UVR
exposure). Moderately high serotonin levels result in more positive
moods and a calm yet focused mental outlook. Indeed, SAD has been linked
with low serotonin levels during the day as well as with a phase delay
in nighttime melatonin production. It was recently found that mammalian
skin can produce serotonin and transform it into melatonin, and that
many types of skin cells express receptors for both serotonin and
melatonin.
With our modern-day penchant for indoor
activity and staying up well past dusk, nocturnal melatonin production
is typically far from robust. “The light we get from being outside on a
summer day can be a thousand times brighter than we’re ever likely to
experience indoors,” says melatonin researcher Russel J. Reiter of the
University of Texas Health Science Center. “For this reason, it’s
important that people who work indoors get outside periodically, and
moreover that we all try to sleep in total darkness. This can have a
major impact on melatonin rhythms and can result in improvements in
mood, energy, and sleep quality.”
For people in jobs in
which sunlight exposure is limited, full-spectrum lighting may be
helpful. Sunglasses may further limit the eyes’ access to full sunlight,
thereby altering melatonin rhythms. Going shades-free in the daylight,
even for just 10–15 minutes, could confer significant health benefits.
Other Sun-Dependent Pathways
The
sun may be best known for boosting production of vitamin D, but there
are many other UVR-mediated effects independent of this pathway.
Direct immune suppression.
Exposure to both UVA and UVB radiation can have direct
immunosuppressive effects through upregulation of cytokines (TNF-α and
IL-10) and increased activity of T regulatory cells that remove
self-reactive T cells. These mechanisms may help prevent autoimmune
diseases.
Alpha melanocyte-stimulating hormone (α-MSH).
Upon exposure to sunshine, melanocytes and keratinocytes in the skin
release α-MSH, which has been implicated in immunologic tolerance and
suppression of contact hypersensitivity. α-MSH also helps limit
oxidative DNA damage resulting from UVR and increases gene repair, thus
reducing melanoma risk, as reported 15 May 2005 in Cancer Research.
Calcitonin gene-related peptide (CGRP).
Released in response to both UVA and UVB exposure, this potent
neuropeptide modulates a number of cytokines and is linked with impaired
induction of immunity and the development of immunologic tolerance.
According to a report in the September 2007 issue of Photochemistry and Photobiology,
mast cells (which mediate hypersensitivity reactions) play a critical
role in CGRP-mediated immune suppression. This could help explain
sunlight’s efficacy in treating skin disorders such as psoriasis.
Neuropeptide substance P.
Along with CGRP, this neuropeptide is released from sensory nerve
fibers in the skin following UVR exposure. This results in increased
lymphocyte proliferation and chemotaxis (chemically mediated movement)
but may also produce local immune suppression.
Endorphins.
UVR increases blood levels of natural opiates called endorphins.
Melanocytes in human skin express a fully functioning endorphin receptor
system, according to the June 2003 Journal of Investigative Dermatology, and a study published 24 November 2005 in Molecular and Cellular Endocrinology suggests that the cutaneous pigmentary system is an important stress-response element of the skin.
Research Challenges
Growing
evidence of the beneficial effects of UVR exposure has challenged the
sun-protection paradigm that has prevailed for decades. Before a
sun-exposure policy change occurs, however, we need to know if there is
enough evidence to infer a protective effect of sun exposure against
various diseases.
Only through well-designed randomized
clinical trials can cause-and-effect relationships be established.
However, most sunlight-related epidemiologic research to date has relied
on observational data that are subject to considerable bias and
confounding. Findings from observational studies are far less rigorous
and reliable than those of interventional studies. But interventional
studies would need to be very large and carried out over several decades
(since most UVR-mediated diseases occur later in life). Moreover, it is
not at all clear when, over a lifetime, sun exposure/vitamin D is most
important. So for now scientists must rely on the results of
well-conducted observational analytic studies.
In
sunlight-related research, there are two main exposures of interest:
vitamin D status, which is measured by the serum 25(OH)D level; and
personal UVR dose, which involves three fundamental factors: ambient UVR
(a function of latitude, altitude, atmospheric ozone levels, pollution,
and time of year), amount of skin exposed (a function of behavioral,
cultural, and clothing practices), and skin pigmentation (with dark skin
receiving a smaller effective dose to underlying structures than light
skin).
When measuring sun exposure at the individual
level, many scientists have relied on latitude or ambient UVR of
residence. But these measures are fraught with uncertainties. “While
ambient UVR varies, . . . so too do a variety of other possible
etiological factors, including diet, exposure to infectious agents,
temperature, and possibly even physical activity levels,” says Robyn
Lucas, an epidemiologist at Australia’s National Centre for Epidemiology
and Population Health. “Additionally, under any level of ambient UVR,
the personal UV dose may vary greatly. In short, there is no real
specificity for ambient UVR.”
Researchers also assess
history of time in the sun at various ages, history of sunburns, dietary
and supplemental vitamin D intake, and other proxy measures.
Nonetheless, says Lucas, “there are drawbacks to inferring that a
relationship with any proxy for the exposure of interest is a
relationship with personal UV dose or vitamin D status.” On the bright
side, she adds, our ability to accurately gauge an individual’s UV dose
history has been enhanced with the use of silicone rubber casts of the
back of subjects’ hands. The fine lines recorded by the cast provide an
objective measure of cumulative sun damage.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2290997/
Don't they look similar? What Do you guys think? Heo Gyungyoung is a famous Korean scammer who claims He can do everything like God, so I think He could be the this man. I thought this man could be a Southern European because he looks like one but now I think He could be Heo Gyungyoung!
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Latinus = Latin (the Roman form of the Greek Lateinos) Lateo "to lie
hid" or the hidden one)==> Romulos = Founder of the Roman Empire
==> Me an E-V13
나로호 교신 성공 후에도 엘클라시코가 네이버 검색어 1위임, 나로호가 2위