Very interesting thread, although too much technical reading for me
I avoid the sun like the plauge since being diagnosed with basal cell carcenoma and my brother with malignant melanoma. I wear long sleeve shirts and pants and hats and use sunscreen when ever outside, I also limit my time outside to mornings and only for a few hours at most.

So, will vit D, magnesium, and calcium supplements alone help or will I have to expose myself to the sun more? Also, does time of day in the sun make a diff?

Hi, ...kate

At this time of year, in Utah, you can forget getting enough sun to stimulate Vit D production.

Yes, the supplements you are speaking of will help, but you will probably need additional Vit D, unless you are sticking with the bare minimum, which these days is controversial anyway, but ranges from 800-1200.

Even if the sun won't stimulate Vit D, you can be out in it and let it stimulate the pineal gland.

A lot of people (as in tanned people) get the Vit D during the summer and it is stored for the winter. People who have fair skin and avoid the sun will most likely not get enough and not store enough.

My daughter is a prime example of how good it can be...she spent the summer past at the beach and got really tan and stayed outside every day and she had the best winter ever last winter. this year, she's right back to being very SAD indeed.

There is another side of the sunlight and skin cancer argument:

http://www.healthresearchforum.org....ightrobbery.pdf
page 23-26
Oliver Gillie Sunlight robbery ■
Part 3: Risks and benefits of sunlight
Melanoma
Melanoma is the most serious form of skin cancer. There are some 7,000 cases a year in the UK and about
1750 deaths. Other types of skin cancer cause only a few hundred deaths annually, making altogether around
2,000 deaths annually from skin cancer in the UK. Melanoma is some six times more common in northern tropical
parts of Australia than in the colder southern parts [183]. These and similar observations have given rise to the
widely held belief that melanoma is caused by sunlight.
However, there are real doubts about the way in which sun exposure causes melanoma [17]. Adults who
work outdoors and children who play outdoors are regularly exposed to the sun and are less likely to develop
melanoma than those who work or play more indoors [184, 185]. While people who have irregular exposure to the
sun and those who recall being sunburnt have a higher risk of melanoma, especially if they have a fair skin type [186].
Occasional exposure of skin to sunlight appears to carry the greatest risk of melanoma, while regular exposure of
skin to sunlight appears to protect against melanoma, probably because it provides higher levels of vitamin D which
are protective against cancer in general.
Furthermore, melanomas occur most commonly on the backs of men and the upper legs of women, areas
which do not get so much exposure to the sun as face or hands [187]. In people under 50 melanoma is most
frequent on sites which are exposed irregularly to the sun [188]. In black people melanomas occur predominantly
on the lower legs and commonly on the sole of the foot, an area which gets virtually no sun at all [189].
This evidence shows that the relationship between melanoma and sunlight is not simple.
It is widely accepted that as many as two-thirds of melanomas are caused by excessive exposure to the
sun [190]. However, other methods of analysis challenge this figure. A person who has had melanoma may
develop a second primary melanoma which occurs completely independently of the first tumour. Analysis of data
on second primary melanomas has enabled the importance of risk factors such as sun exposure, skin and eye colour,
and skin type to be calculated. Using this method it has been found that these known risk factors account for only
about 23% of variation of melanoma risk [191]. Since skin type is a very important variable it leaves sun
exposure accounting for perhaps 10-15% of the overall risk of melanoma according to this method.
Other risk factors that increase the risk of melanoma include increased body weight (obesity), lack of
exercise [192], and diet [193]. Indeed the steady increase in incidence of melanoma over the last 10 to 20 years
(24% increase in the last five years) parallels the increase in other cancers such as breast, colorectal, prostate,
testis, leukaemia and lymphoma [194].
The increase in obesity and decrease in regular exercise in the UK over this period may account for the increase
in melanoma [195, 196]. Much of this epidemic of obesity appears to be the result of increased consumption of
fast foods and snacks with a high energy density [197] and these should be identified as a likely cause of
melanoma.
These considerations are enough to explain why the SunSmart programme has not been successful in
reducing deaths from melanoma in the UK where the average intensity of sunlight is much less than in Australia.
Indeed it is possible that reduction of exposure to the sun in the UK actually increases the incidence of melanoma
rather than decreases it, and that regular careful exposure of skin to the sun in the UK would actually reduce the
incidence of melanoma. The evidence certainly does not provide adequate support for a policy favouring
reduction of sun exposure.
The risk of a person suffering from melanoma is about 10 in 100,000 which is described as ‘very low’ in
Professor Sir Kenneth Calman’s ‘language of risk’ [17]. Only part of this very low risk, perhaps 10-15%,
may be attributable to sunlight. So the risk of contracting melanoma as a result of exposure to sunlight could be
as low as one in a 100,000. So even the most forceful campaign advocating sun avoidance could be expected to
prevent only a few hundred deaths [198].
For practical purposes the risk of death from any kind of skin cancer caused by exposure to sunlight is negligible
when compared with the high risk of other diseases of many different types which are caused, at least in part,
by D deficiency.
Health Research Forum Occasional Reports: No 1 24
Oliver Gillie ■ Sunlight robbery
Non-melanoma skin cancer
More than 60,000 cases of non-melanoma skin cancer occur every year in the UK. In the vast majority of cases the
lesions are removed without problems as a simple out-patient procedure.
But problems associated with these cancers should not be underestimated. These cancers cause a few hundred
deaths each year in the UK. In a relatively small proportion of people the lesions are in an awkward position that
requires delicate surgery or the lesion may be extensive and require a more difficult procedure. Some of these
cancers require surgery which leaves a disfiguring scar or causes disfiguring removal of tissue.
Basal cell carcinoma, which generally grows quite slowly, is the most common type of non-melanoma skin
cancer. Squamous cell carcinoma which can spread to other parts of the body if untreated is the second commonest
type. Both types occur most commonly in old people. Regular exposure to sunlight during work outdoors is a risk
factor for squamous cell carcinoma but probably not for basal cell carcinoma. While squamous cell carcinoma is
clearly caused by sun exposure the relationship between basal cell carcinoma and sunlight, like that of melanoma,
is more complicated.
Basal cell carcinoma had an incidence of 114 per 100,000 population in South Wales in 1998 compared with 726
per 100,000 in Australia, suggesting an association with sunlight. In the United States it has recently increased in
incidence at a rate of 10% a year. Exposure to sunlight is widely accepted to be a cause of basal cell carcinoma but
it does not explain why particular people get these tumours and others do not, or the fact that these tumours
often occur on the body in clusters, and are found mainly on the trunk rather than on areas such as the head that
are exposed for longer periods [199].
Diet appears to have an important effect on susceptibility to skin cancer and actinic keratosis, a form of skin
aging [200, 201] that may lead on to squamous cell carcinoma. A trial at Baylor College of Medicine in Houston, Texas,
has shown that a low fat diet can reduce recurrence of skin cancer and actinic keratosis over a period of two years.
Patients who had suffered skin cancer (basal cell or squamous cell carcinoma) were randomised to one of two groups
at the beginning of the study. One group continued with their normal diet which contained 36% fat. The second group
were given dietary advice and reduced fat to under 21%, while also losing 2-4kgs of body weight. The number of skin
cancers in the diet group declined from eight to one over 16 months of the study compared with a steady six in the
first eight months and six in the second eight months for the control group. The reduced risk of skin cancer (both
basal cell and squamous cell) in the diet group may be the result of loss of body weight or the change to a low fat
diet.
Other types of study have produced equivocal results. The view that excess energy consumption is a cause of
basal cell carcinoma is supported by a cohort study of 73,366 women in the Nurses’ Health Study [202]. But the Health
Professionals Follow-up Study of some 43,000 men has failed to confirm a link between basal cell cancer and fat
consumption [203].
Nevertheless the randomised studies suggest that there is an effect of diet on recurrence of skin cancer, and that
much more is involved in the initiation of these cancers than simply exposure to the sun. It may be that
only certain people who have a relatively rich diet, those who are relatively overweight, or, have a high calorie
consumption compared with energy output, are at high risk of developing these skin cancers. More research is
needed in this area but it is a mistake to assume that sunlight is necessarily the most important risk factor for these
two cancers.
Risks to children and young people
Current skin cancer prevention programmes warn of a special risk to children and young people from
exposure to the sun. Official literature asserts that exposure to the sun in childhood may disproportionately increase
the risk of skin cancer many years later [204, 205]. In fact this idea is controversial and has been challenged by
several authors.
Whiteman et al [206] undertook a systematic review of the literature and found that the way in which sun
exposure was measured made a striking difference to the association between melanoma and age at which
exposure occurred. Case/control studies produced no consistent associations between melanoma
and childhood sun exposure. On the other hand ecological studies (which measure sunlight exposure of geographical
areas rather than of individuals) did show a relationship between early exposure and melanoma risk. However it is
unwise to come to firm conclusions when these two types of study produce widely differing results.
A recent study of 603 melanoma cases and 627 controls in seven European countries concludes
that there is no evidence for a critical period of high susceptibility in childhood when solar radiation is more
likely to induce melanoma [207]. The study concluded that more than five different sunburns doubled the risk of
Health Research Forum Occasional Reports: No 1 25
Oliver Gillie Sunlight robbery ■
melanoma regardless of their timing in life. Another study has found that outdoor activities in childhood are associated
with a lower risk of melanoma [185].
Basal cell carcinoma has also been reported to be more common after sunburn in childhood [208, 209] but the
research findings are not clear. One study found that living in a region of high solar radiation in childhood does not
increase risk of basal cell carcinoma whereas living in such a region as an adult does increase the risk [210].
This study found that risk of basal cell carcinoma was proportional to lifetime accumulation of blistering sunburns
[210]. Other studies have found no clear link between sunburn in adulthood and basal cell carcinoma [209].
On the other hand an Italian study found that an average summer holiday exposure of eight weeks per year
throughout childhood increased the risk of basal cell carcinoma almost fivefold [208]. The research results are
conflicting and so it is by no means certain that childhood and adolescence are critical periods for this cancer.
A skin cancer policy for children and young people
Summarising the scientific evidence reviewed above: sunburn or sunlight exposure in childhood may
possibly increase the risk of basal cell carcinoma, the commonest form of skin cancer, but this is not firmly
established. On the other hand sunburn/sunlight exposure in childhood does not seem to increase the risk of the
most serious form of skin cancer, melanoma. Relevant evidence appears to be lacking for the third type of skin
cancer, squamous cell carcinoma.
Children should obviously be protected against sunburn but they also need exposure to the sun so that they can
synthesise vitamin D. This may mean accepting an uncertain risk of causing basal cell carcinoma in later life.
The vast majority of basal cell carcinomas are readily treated and so the risk of serious consequences is small. This
small, and possibly non-existent, risk may be further reduced by avoiding sunburn.
In conclusion, children can safely be allowed to run about in strong sun wearing brief clothing without suncreams
for limited periods of time, so long as care is taken to avoid burning. This will enable children to benefit from
vitamin D production in the skin. Suncreams cannot be relied upon to prevent cancer (see discussion in Part 4,
section 8), so burning is best avoided by encouraging children to seek the shade after a suitable time in the sun.
Time that may safely be spent in the sun depends upon skin type, previous exposure to the sun, time of day,
season (early, middle or late summer), latitude, and whether or not the sky is at all overcast. Suncreams can be used
when extended exposure cannot easily be avoided e.g. when playing sports.
Skin wrinkling and aging
Warnings that exposure to the sun may cause wrinkling and aging of skin are frequently made at the same
time as warnings about skin cancer. Although sunlight can cause wrinkling this does not seem to be common in
the UK.
Studies in Japan have found that the average 40-year-old woman from Kagoshima (32ºN) in the south of the
country has facial wrinkling equivalent to that of a 48-year-old woman living further north in Akita (40ºN) [211],
suggesting that sunlight induces wrinkles. However, a study of 792 people over 60 in South Glamorgan, UK, found
no association between sun exposure and wrinkling of skin on the face, neck or back of the hand [212]. This is
probably because the average person in Glamorgan gets relatively little intense exposure to the sun compared with
people in Japan. Glamorgan is located at latitude 51ºN, a great deal further north than either of the Japanese
locations.
On the other hand, daily cigarette smoking has been found to be closely associated with the development of
wrinkles in people in Glamorgan, as in other parts of the world. Smoking 20 cigarettes a day in Glamorgan increased
wrinkles sufficient to give a person the appearance of someone 10 years older. Strangely, people with wrinkles have
been found to be less likely to develop basal cell carcinoma, one of the common types of skin cancer, showing that
other factors, and not just sunlight, must be involved in these skin changes [213]. Another study has found that a diet
with a high intake of vegetables, legumes (beans and peas), olive oil, apples, prunes or tea is associated with fewer
wrinkles [214].
In summary, sun exposure is only one factor influencing wrinkling of skin and not necessarily the most
important one. In the UK sunlight does not seem to be a significant cause of wrinkling for most people. Nevertheless
regular sunbathing in the UK could cause wrinkling. A healthy ‘five a day’ fruit and vegetable diet
recommended for prevention of cancer and heart disease may reduce or prevent wrinkling.
While wrinkling is obviously undesirable it seems a small, perhaps even insignificant risk to take, in return for the
benefits of increased vitamin D levels that follow from sunbathing. Anyone choosing to avoid sun exposure for fear
of wrinkling should take a vitamin D supplement all year round.
Health Research Forum Occasional Reports: No 1 26
Oliver Gillie ■ Sunlight robbery
Cost of disease caused by vitamin D deficiency
The large number of chronic diseases caused at least in part by vitamin D deficiency make a formal estimate of the
total cost very difficult to make. Nevertheless the cost of vitamin D deficiency diseases in the UK or USA has been
put at billions of pounds or dollars per year [215].
There is no doubt that the cost of disease caused by D deficiency is much greater than the cost of disease caused
by excessive exposure to sunlight. This is clear from the fact that the 2,000 deaths per year from skin cancer in the
UK are a tenth of the deaths from other types of cancer that are attributable to D-deficiency [139, 216]. Sunlight is
our primary source of vitamin D. So it must be concluded that any public health policy regarding sunlight should
favour exposure to sunlight rather than avoidance of it. This conclusion is reinforced when it is considered that a
substantial proportion of skin cancer deaths are not caused by sunlight and that many other chronic diseases apart
from cancer are caused at least in part by D deficiency.

http://vvv.com/healthnews/dsunscre.html
Sunscreens and Cancer

by Hans R. Larsen, MSc ChE

In 1991 Professor Johan Moan of the Norwegian Cancer Institute made an astounding discovery. He found that the yearly incidence of melanoma in Norway had increased by 350% for men and by 440% for women during the period 1957 to 1984. He also determined that there had been no change in the ozone layer over this period of time. He concludes his report in the British Journal of Cancer by stating "Ozone depletion is not the cause of the increase in skin cancers"(1).

SKIN CANCER
There are three major forms of skin cancer.

BASAL CELL CARCINOMA is the most common form of skin cancer. It occurs most frequently in men who spend a great deal of time outdoors and primarily produces lesions on the head and neck(2). Basal cell carcinoma rarely spreads throughout the body but can invade neighbouring bone and nerves(3).

SQUAMOUS CELL CARCINOMA is the second most common skin cancer. It primarily affects people who sunburn easily, tan poorly, and have blue eyes and red or blonde hair. Squamous cell carcinoma most commonly develops from actinic keratoses and can metastasize if left untreated. Squamous cell carcinoma of the lip is 12 times more common among men than among women(4).

MALIGNANT MELANOMA is the rarest form of skin cancer but is the most deadly. It affects the cells which produce melanin and seems to be more prevalent among city-dwellers than among people who work out-of-doors. It does not necessarily occur on sun-exposed areas of the body and is thought to be linked to brief, intense periods of sun exposure and a history of severe sunburn in childhood or adolescence. Malignant melanoma metastasizes easily and is often fatal if not caught in time(2,5).

The skin cancer epidemic is a worldwide phenomenon. In 1978 there were approximately 480,000 cases of non-melanoma skin cancer in the United States alone. This is expected to rise to over one million in 1994(6). Malignant melanoma is growing at a rate of 7% per year in the United States. In 1991 cancer experts estimated that there would be about 32,000 cases during the year of which 6,500 would be fatal(7). In Canada melanoma incidence rose by 6% per year for men and by 4.6% per year for women during the period 1970-1986(8). Australia has the highest melanoma rate in the world. For men the rate doubled between 1980 and 1987 and for women it increased by more than 50%(9). It is now estimated that by age 75 two out of three Australians will have been treated for some form of skin cancer(10).
If the ozone layer has not yet changed significantly except at the poles, then what is causing the enormous increase in skin cancer?

The sunscreen connection
The Australian experience provides the first clue. The rise in melanoma has been exceptionally high in Queensland where the medical establishment has long and vigorously promoted the use of sunscreens. Queensland now has more incidences of melanoma per capita than any other place. Worldwide, the greatest rise in melanoma has been experienced in countries where chemical sunscreens have been heavily promoted(11).

Drs. Cedric and Frank Garland of the University of California are the foremost opponents of the use of chemical sunscreens. They point out that, although sunscreens do protect against sunburn, there is no scientific proof that they protect against melanoma or basal cell carcinoma in humans(11). There is, however, some evidence that regular use of sunscreens helps prevent the formation of actinic keratoses, the precursors of squamous cell carcinoma(12).

The Garland brothers strongly believe that the increased use of chemical sunscreens is the primary cause of the skin cancer epidemic. They emphasize that people using sunscreen tend to stay longer in the sun because they do not get a sunburn - they develop a false sense of security(7). Chemical sunscreens are formulated to absorb UVB radiation, they let most of the UVA rays through(7). UVA rays penetrate deeper into the skin and are strongly absorbed by the melanocytes which are involved both in melanin production (sun tanning) and in melanoma formation(11). UVA rays also have a depressing effect on the immune system(13).

ULTRAVIOLET RADIATION
UVA rays constitute 90-95% of the ultraviolet light reaching the earth. They have a relatively long wavelength (320-400 nm) and are not absorbed by the ozone layer. UVA light penetrates the furthest into the skin and is involved in the initial stages of suntanning. UVA tends to suppress the immune function and is implicated in premature aging of the skin(2,13,14).

UVB rays are partially absorbed by the ozone layer and have a medium wavelength (290-320 nm). They do not penetrate the skin as far as the UVA rays do and are the primary cause of sunburn. They are also responsible for most of the tissue damage which results in wrinkles and aging of the skin and are implicated in cataract formation(2).

UVC rays have the shortest wavelength (below 290 nm) and are almost totally absorbed by the ozone layer. As the ozone layer thins UVC rays may begin to contribute to sunburning and premature aging of the skin(2).

All forms of ultraviolet radiation are believed to contribute to the development of skin cancer(2).

Most chemical sunscreens contain from 2 to 5% of benzophenone or its derivatives (oxybenzone, benzophenone-3) as their active ingredient. Benzophenone is one of the most powerful free radical generators known to man. It is used in industrial processes to initiate chemical reactions and promote cross-linking(15). Benzophenone is activated by ultraviolet light. The absorbed energy breaks benzophenone's double bond to produce two free radical sites. The free radicals desperately look for a hydrogen atom to make them "feel whole again"(15). They may find this hydrogen atom among the other ingredients of the sunscreen, but it is conceivable that they could also find it on the surface of the skin and thereby initiate a chain reaction which could ultimately lead to melanoma and other skin cancers. Researchers at the Harvard Medical School have recently discovered that psoralen, another ultraviolet light-activated free radical generator, is an extremely efficient carcinogen. They found that the rate of squamous cell carcinoma among patients with psoriasis, who had been repeatedly treated with UVA light after a topical application of psoralen, was 83 times higher than among the general population(16).

The benefits of sunlight
Some scientists believe that UV light causes skin cancer through the combined effect of suppression of the immune system and damage to DNA(10,17). Exposure to UV light is, however, not all bad. Most of the body's vitamin D supply, about 75% of it, is generated by the skin's exposure to UVB rays(18). Using a sunscreen drastically lowers the cutaneous production of vitamin D3(19). A low blood level of vitamin D is known to increase the risk for the development of breast and colon cancer and may also accelerate the growth of melanoma(18,19,20).

Dr. Gordon Ainsleigh in California believes that the use of sunscreens causes more cancer deaths than it prevents. He estimates that the 17% increase in breast cancer observed between 1991 and 1992 may be the result of the pervasive use of sunscreens over the past decade(20). Recent studies have also shown a higher rate of melanoma among men who regularly use sunscreens and a higher rate of basal cell carcinoma among women using sunscreens(11,21).

Dr. Ainsleigh estimates that 30,000 cancer deaths in the United States alone could be prevented each year if people would adopt a regimen of regular, moderate sun exposure(20).

Although the medical establishment still strongly supports the use of sunscreens there is a growing consensus among progressive researchers that the use of sunscreens does not prevent skin cancer and, as a matter of fact, may promote skin cancers as well as colon and breast cancer.

The bottom line
So what should you do to protect yourself as much as possible against these cancers? Summarizing current research the following recommendations appear reasonable:

DO NOT rely on the use of sunscreens to protect you against skin cancer.
DO NOT try to get a tan by visiting a tanning studio. The rays from their UV lamps are extremely harmful and the tan produced does not have the protective effect of a sunlight-induced tan(2,7).
DO try to develop a moderate natural suntan unless you have extremely sensitive skin and burn easily. Regular and moderate unprotected sun exposure in the early morning or late afternoon will help maintain a protective tan and keep your vitamin D stores at an optimum level(20).
DO wear protective clothing and a wide-brimmed hat when you are outside. Avoid sun exposure between 10 AM and 3 PM if at all possible. Remember that UV rays, particularly UVA, are present even on cloudy days(7).
DO wear sunglasses that filter out 100% of the ultraviolet light to protect yourself against the development of cataracts(7).
DO remember that sunlight is strongly reflected from sand, snow, ice, and concrete and can increase your direct sunlight exposure by 10 to 50%(2).
DO make sure you get enough vitamin D3 and beta-carotene, if necessary through supplementation. Recent research has shown that taking 30 mg of beta-carotene a day protects against the suppression of the immune system by UVA rays(13).
DO make sure to supplement your diet with antioxidants. Dr. Abram Hoffer in Victoria, Canada recommends that vitamin C, vitamin E, and selenium be used as a protection against the damages of excessive ultraviolet radiation. He suggests daily dosages of 3 grams or more of vitamin C, 800 IU of vitamin E, and 200 micrograms of selenium (l-selenomethionine)(22). Vitamins C and E also protect against cataract formation(23,24).
DO cut down on the fat in your diet. Recent research has shown that patients with non- melanoma skin cancers can reduce their risk of developing additional actinic keratoses (precursors to skin cancer) by switching to a low fat diet(25).

SUNSCREENS
Sunscreens are designed to protect against sunburn (UVB rays) and generally provide little protection against UVA rays. They come in two forms:

CHEMICAL SUNSCREENS contain chemicals such as benzophenone or oxybenzone (benzophenone-3) as the active ingredient. They prevent sunburn by absorbing the ultraviolet (UVB) rays(2).

PHYSICAL SUNSCREENS contain inert minerals such as titanium dioxide, zinc oxide, or talc and work by reflecting the ultraviolet (UVA and UVB) rays away from the skin(2).

A sunscreen with a SPF of 15 filters out approximately 94% of the UVB rays. One with a SPF of 30 filters out 97%. The SPF applies for UVB rays only. The protection provided against UVA rays in chemical sunscreens is about 10% of the UVB rating(26).

DO wear a physical sunscreen with a SPF of 15 if you absolutely must be out in the sun for extended periods of time(22). Physical sunscreens containing titanium dioxide, zinc oxide, or talc work by reflecting the UV radiation rather than by absorbing it. Sunscreens are tested by using artificial UV light and a screen with a SPF of 30 is not twice as effective as one with a factor of 15(17). Also, reapplying sunscreen during the day does not extend the period of protection. Even "broad-spectrum" sunscreens are not very good in filtering out UVA rays(26). A natural suntan is probably more effective.

DO see your healthcare provider if you spot any unusual moles or growth on your skin - particularly if they are irregular in shape, bleed, itch, or appear to be changing. Most skin cancers can be cured if caught in time(27).
The saga of sunscreens and skin cancer is far from over. Research is continuing and new findings are being published at an accelerated pace. But until we know the whole story, it would seem prudent to take precautions based on what we do know.

REFERENCES

Moan, J. & Dahlback, A. The relationship between skin cancers, solar radiation and ozone depletion. British Journal of Cancer, Vol. 65, No. 6, June 1992, pp. 916-21
Harmful effects of ultraviolet radiation. Journal of the American Medical Association, Vol. 262, No. 3, July 21, 1989, pp. 380-84
Haynes, Harley A. Primary cancer of the skin. Harrison's Principles of Internal Medicine, McGraw- Hill, 7th ed., 1974, pp. 2024-25
Hacker, Steven M. & Flowers, Franklin P. Squamous cell carcinoma of the skin. Postgraduate Medicine, Vol. 93, No. 8, June 1993, pp. 115-26
Lee, John A.H. The relationship between malignant melanoma of skin and exposure to sunlight. Photochemistry and Photobiology, Vol. 50, No. 4, 1989, pp. 493-96
Miller, Dena L. & Weinstock, Martin A. Nonmelanoma skin cancer in the United States: incidence. Journal of the American Academy of Dermatology, Vol. 30, No. 5, Pt. 1, May 1994, pp. 774-78
Skolnick, Andrew A. Revised regulations for sunscreen labelling expected soon from FDA. Journal of the American Medical Assocation, Vol. 265, No. 24, June 26, 1991, pp. 3217-20
Statistics Canada, Canadian Cancer Statistics 1991.
Reynolds, Tom. Sun plays havoc with light skin down under. Journal of the National Cancer Institute, Vol. 84, No. 18, September 16, 1992, pp. 1392-94
Ozone depletion and health. The Lancet, December 10, 1988, p. 1377
Garland, Cedric F., et al. Could sunscreens increase melanoma risk? American Journal of Public Health, Vol. 82, No. 4, April 1992, pp. 614-15
Dover, Jeffrey S. & Arndt, Kenneth A. Dermatology. Journal of the American Medical Association, Vol. 271, No. 21, June 1, 1994, pp. 1662-63
Fuller, Cindy J., et al. Effect of beta-carotene supplementation on photosuppression of delayed-type hypersensitivity in normal young men. American Journal of Clinical Nutrition, Vol. 56, 1992, pp. 684-90
Fitzpatrick, T.B. & Haynes, H.A. Photosensitivity and other reactions to light. Harrison's Principles of Internal Medicine, McGraw-Hill, 7th ed., 1974, pp. 281-84
Kirk-Othmer Encyclopedia of Chemical Technology, Vol. 13, 3rd ed., 1981, pp. 367-68
Stern, Robert S. and Laid, Nan. The carcinogenic risk of treatments for severe psoriasis. Cancer, Vol. 73, No. 11, June 1, 1994, pp. 2759-64
Wright, Brett. Sunscreens and the protection racket. New Scientist, January 22, 1994, pp. 21-2
Garland, Frank C., et al. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Preventive Medicine, Vol. 19, 1990, pp. 614-22
Koh, Howard K. & Lew, Robert A. Sunscreens and melanoma: implications for prevention. Journal of the National Cancer Institute, Vol. 86, No. 2, January 19, 1994, pp. 78-9
Ainsleigh, H. Gordon. Beneficial effects of sun exposure on cancer mortality. Preventive Medicine, Vol. 22, February 1993, pp. 132-40
Garland, Cedric F. et al. Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. Journal of the National Cancer Institute, Vol. 86, No. 10, May 18, 1994, pp. 798-801
Goodall, John & Hoffer, Abram. Protection against ultraviolet radiation. Canadian Medical Association Journal, Vol. 147, No. 6, September 15, 1992, pp. 839-40
Robertson, J.M., et al. Vitamin E intake and risk of cataracts in humans, Annals of the New York Academy of Science, Vol. 570, 1989, pp. 372-82
Knekt, Paul, et al. Serum antioxidant vitamins and risk of cataracts. British Medical Journal, Vol. 305, December 5, 1992, pp. 1392-94
Black, Homer S., et al. Effect of a low-fat diet on the incidence of actinic keratosis. The New England Journal of Medicine, Vol. 330, No. 18, May 5, 1994, pp. 1272-75
Kaidbey, Kays & Gange, R. William. Comparison of methods of assessing photoprotection against ultraviolet A in vivo. Journal of the American Academy of Dermatology, Vol. 16, No. 2, Pt. 1, February 1987, pp. 346-53
McDonald, Charles J. Status of screening for skin cancer. Cancer (supplement), Vol. 72, No. 3, August 1, 1993, pp. 1066-70

This article was first published in the International Journal of Alternative & Complementary Medicine,
Vol 12, No 12, December 1994, pp.17-19

Wow, it seems we are damnd if we do damnd if we don't.
My family has a very very high risk of cancer:
Mom died from breast cancer at 62
Dad survivor of prostate cancer
brother died from malignant melanoma at 42
Niece survivor of non-hodkins lymphoma
me basel cell carcenoma, blond and blue eyed, sunburnd severely too many times and spent a lot of time in the garden as a kid. Always "layed" out to get a tan and "fake baked" as a teen. 32 when diagnosed with basel cell skin cancer with severe skin damage and age spots on face and hands. Lesian was on the ridge of my nose, my brothers was on his back. This experiece was not an insignificant one like the article hinted. The dr took 6 layers of skin off with mohs surgery to remove all of the cancer and cut down to the bone. 6 months of skin regrowth and still had to have a skin graph from inside my left ear to replace the skin on my nose, and dermasanding to sand away the ridge scare around the graph and it still looks bad. The skin color is blotchy and red and the pgraph is sunken in.
So, I'll avoid the sun when I can and start taking a vit d supplement.

Good idea on the spplements. I'm not fearful of the sun, I just know there isn't enough this time of year.

I've also had basel cell carcinomas and the doctor said that the longer you wait the more skin has to go. If you get it taken care of right away, there is much less of a scar. And my mom had melanoma, which we all saw immediately and sent her to the doctor and it was removed easily and she needed no chemo or anything else and has been free of it since (so far). She's a red head.

I've had three now, all on my left leg, which hardly ever sees the sun. So I know for a fact the sun is not the only factor. If I'd had them on my arms or face or neck then yes, I would have believed that. But two were on the back of my left leg and the third on the front of the same leg (the doctor also said if you get more than one, it's usually in the same place). And at the time of the discovery of the first, I wore long pants every day of my life. I didn't even own a pair of shorts because my legs are so white. I believe that it also has something to do with the skin in the area. My legs are extreemly dry and have very little natural oil in them, so I think that has something to do with it.

I'm guessing...I might not be accurate...that your family has a Northern European heritage. Northern Europeans, especially from Sweden, Norway, and Greenland have a hereditarily impaired ability to produce adequate vitamin D levels from the sun. Thus your family's cancer history is based on this. JMO.

I suggest you get your vitamin D tested. Or you and your family can take megadoses of vitamin D. Especially have your Dad take a lot of vitamin D. There are a lot of articles posted on the vitamin D and prostate cancer connection on a previous page of this thread.

Acadkate - I'm sorry for your loses - my heart goes out to you. We have cancer in my family too - like you my Mom and Brother.

I get a lot of sun in the summer here since I swim most days - but I barely ever burn cause I'm in the water before ten - still I worry.
LizzyLC

Hi Everyone,
I am from Trinidad and of mixed parents, so my skin tone is very light brown. In Trinidad it's sunny 99% of the time, I now live in Canada and find the winters very difficult, not because of the cold, I can dress to suit, but the grey days (like today) without sunshine, gets me very down. I don't feel to do anything with my day. I work from home and live out in the country. So most days there is not a need to leave the house, in the summer when it is warm I am very active and outside every day. I must need Vit. D3 I am guessing. I take aM.Vit. which has a low dose of Vit. D. now I need to know how much I need to get me through this Winter. Also there is a type of light that one can purchase to help with this. I need to buy one but I do not know where to find same and the correct name.
Any information is greatly appreciated.
Thanking you in advance.
Warmest Regards,
Joy.

I have a light box. You can do a google for "Seasonal Affective Disorder"and "light" and sellers will come up. However, with enough vitamin D in my system I no longer need my light. I would start with 4,000 IU vitamin D and keep increasing it on a weekly bases until you feel more alert and like your normal self. Don't be afraid to take it up to 7,000-10,000 IU if necessary. Vitamin D is not toxic at anywhere near those levels. I suggest you get the dry form of vitamin D3 as some people react to the soy oil that's in the vitamin D gels. I buy the dry vitamin D in the 1,000 IU dose per capsule.

When you take vitamin D be sure that you take at least 1200 mg of calcium and 600-800 mg magnesium with it as they work together. If your body does not have enough calcium to work with the D, the D will pull it out of your bones.

[QUOTE=Zuleikaa]I'm guessing...I might not be accurate...that your family has a Northern European heritage. Northern Europeans, especially from Sweden, Norway, and Greenland have a hereditarily impaired ability to produce adequate vitamin D levels from the sun. Thus your family's cancer history is based on this. JMO.QUOTE]

Zule you hit it right on the head, I'm of Swedish and English heritage. I'm very fair and blue/green eyes and blond hair, although my hair has darkened since having kids. My brother turned grey while still in high school and my Dad has white hair.

My brother did have surgery but the Dr. apperently didn't get all of the cancer before it spread. We went down to Vegas to see him his last Easter just a few weeks before he died. 2 of his wishes came true for him, a bunch of corvette owners had a parade thru his neighborhood and he got to drive one of the stingrays, that was truly awesome. The other was that he died at home with his mind clear and aware.

I, on the other hand didn't know what was on my nose. I had this flat pearly bump for years. Then one day it started bleeding. I thought no big deal, I get blemishes all the time, it'll go away in a day or two. But it never did, it got worse. I finally got some time off and had it examined, to my horror it was cancer. DB had already died, I spiraled into depression compounded by loseing my job and insurance. It took 3 months to get in to see the dermatologist, and a year and a half later I was finally finished and on the mend. Thankfully, it was only basal cell.

Lizzy, thanks for the sentiments. Even though it has been several years the pain of losing a loved one never completely fades away. I'm so sorry to hear of your family cancer struggle too. Somewhere I heard that everyone has had or knows someone who has had cancer of some sort or another. It's pretty scary when you know so many tho.

My career keeps me inside most of the time, so even if I didn't have the cancer I'd still be as white as a ghost. It's good to learn of the vit D benifits. Next time I'm at Vitaminworld I'll pick some up.

Try to get the dry form of 1000 IUs.

Something I've noticed the past few days and was wondering if anyone else has done this... When I take D in equal doses, I start getting frequent headaches that just won't quit... I cut down to taking a dose in the am and one in the pm, but then I started adding in more at night before going to bed. Before I had to stay between 1200 IU and 1600 IU, but the past few days I've been taking about 800 IU in the morning and a total of between 1200 and 1600 IU at night! No headaches when I wake during the night and no headaches in the morning or during the day.

I'm not sure why it's like that, but I figure as long as I can take it like that and don't have problems, I'll continue like that.

I'm taking my D in three now. One dose immediately upon arising...well after a bathroom visit, lol!!...one at breakfast and one at lunch. I'm now taking 8,000--10,000 IU/day but most of it is upon arising and at breakfast 4 and 2-4 and 2 at lunch. I always make sure to get the 4 upon arising.

I haven't noticed any downside. And I'm sleeping a lot better since I upped the dose. I found that obese store D in fat and can't access all of it and so can require up to twice as much D as a normal person.

I really feel a difference when I don't get the last 2-4. Now I might just divide it into two doses.

I'm running out of ideas on D connection postings. Anyone have any connections to illnesses they'd like me to research?

http://www.ajcn.org/cgi/content/full/79/5/717
Assessment of dietary vitamin D requirements during pregnancy and lactation1,2
Bruce W Hollis and Carol L Wagner
1 From the Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston.

2 Address reprint requests to BW Hollis, Medical University of South Carolina, 114 Doughty Street, PO Box 250770, Charleston, SC 29403. E-mail: hollisb~musc.edu.

Concerns about vitamin D have resurfaced in medical and scientific literature because the prevalence of vitamin D deficiency in the United States, particularly among darkly pigmented persons, has increased. The primary goals of this review were to discuss past and current literature and to reassess the dietary reference intake for vitamin D in adults, with particular focus on women during pregnancy and lactation. The appropriate dose of vitamin D during pregnancy and lactation is unknown, although it appears to be greater than the current dietary reference intake of 200–400 IU/d (5–10 µg/d). Doses of 10 000 IU vitamin D/d (250 µg/d) for up to 5 mo do not elevate circulating 25-hydroxyvitamin D to concentrations > 90 ng/mL, whereas doses < 1000 IU/d appear, in many cases, to be inadequate for maintaining normal circulating 25-hydroxyvitamin D concentrations of between 15 and 80 ng/mL. Vitamin D plays no etiologic role in cardiac valvular disease, such as that observed in Williams syndrome, and, as such, animal models involving vitamin D intoxication that show an effect on cardiac disease are flawed and offer no insight into normal human physiology. Higher doses of vitamin D are necessary for a large segment of Americans to achieve concentrations equivalent to those in persons who live and work in sun-rich environments. Further studies are necessary to determine optimal vitamin D intakes for pregnant and lactating women as a function of latitude and race.

The primary goal of this review was to discuss and begin to reassess the dietary reference intake (DRI) for vitamin D during pregnancy and lactation in women. This reassessment is critical because the current recommendations result in a high degree of vitamin D deficiency, especially in the African American population (1). This avenue of research already has begun in the healthy adult population (2, 3) and serves as a model for vitamin D supplementation during pregnancy and lactation. The history of dietary vitamin D requirements and recommendations, issues of toxicity and hypervitaminosis D, and the specific issues that pertain to pregnancy and lactation are highlighted in this review.

The first issue addressed is the definition of vitamin D. When we refer to vitamin D, we are speaking of the parent compound cholecalciferol—the form found in vitamin supplements and fortified dairy products and not the hormonal form of vitamin D, namely 1,25-dihydroxycholecalciferol. Thus, we do not discuss studies in which the focus is on the hormonal form of the vitamin, because these studies are pharmacologic in nature and have no bearing on normal physiology. Rather, we focus on physiologically based studies that reevaluated the actual nutritional requirement for vitamin D during human pregnancy and lactation and that accounted for racial factors.

DIETARY REFERENCE INTAKE FOR VITAMIN D: WHAT IS THE EVIDENCE?

An excellent review by Vieth (4) addresses how arbitrary the determination of the vitamin D requirements in the general adult population was. In the next 3 paragraphs, we paraphrase from this review (4). Before 1997, the DRI for vitamin D in infants and children was 10 µg (400 IU) (5). In essence, the scientific basis for this dose was that it approximated what was in a teaspoon (5 mL) of cod-liver oil and had long been considered safe and effective in preventing rickets (6). The basis for adult vitamin D recommendations is even less well defined. Forty years ago, an expert committee on vitamin D provided only anecdotal support for what it referred to as " the hypothesis of a small requirement" for vitamin D in adults, and it recommended one-half the infant dose to ensure that adults obtain some from the diet (7). In England, an adult requirement of only 2.5 µg/d (100 IU/d) was substantiated on the basis of findings in 7 adult women with severe nutritional osteomalacia whose bones showed a response when given this amount (8). The adult DRI of 5 µg/d (200 IU/d) was described as a "generous allowance" in the 1989 version of American recommended dietary allowances (RDA; 5). What is truly remarkable is that the basis for these recommendations was made before it was possible to measure the circulating concentration of 25-hydroxyvitamin D [25(OH)D], the indicator of nutritional vitamin D status (9, 10).


LOWEST OBSERVED ADVERSE EFFECT LEVEL

Equally important with respect to daily vitamin D intakes is the lowest observed adverse effect level (LOAEL). Again, there is a lack of evidence to support statements about the toxicity of moderate doses of vitamin D. For instance, in the 1989 US RDA it is stated that 5 times the DRI for vitamin D may be harmful (5). This recommendation relates back to a 1963 expert committee report (6), which then refers back to the primary reference, a 1938 report in which linear bone growth was suppressed in infants given 45–158 µg (1800–6300 IU) vitamin D/d (11). The study was not conducted in adults and, thus, does not form a scientific basis for a safe upper limit in adults. The same applies to a statement in the 1987 council report from the American Medical Association: "dosages of 10 000 IU/d for several months have resulted in marked disturbances in calcium metabolism, and, in some cases—death." Two references were cited to substantiate this claim. One reference was to a review article about vitamins in general, which gave no evidence for and cited no other reference for its claim of toxicity at vitamin D doses as low as 250 µg/d (10 000 IU/d) (12). The other reference dealt with 10 patients with vitamin D toxicity reported in 1948, for whom the vitamin D dose was actually 3750–15 000 µg/d (150 000–600 000 IU/d) (13); of note, all of the patients recovered. These same points were rehashed in the 1990 Institute of Medicine Publication, Nutrition During Pregnancy (14). The issue of poorly substantiated claims of toxicity extends even to the most recent revision for vitamin D intakes published by the National Academy of Sciences (15).

The only study cited to address the question of critical endpoint doses for vitamin D (potential adverse effect level) was one by Narang et al (16). The current no observed adverse effect level (NOAEL) of 50 µg/d (2000 IU/d) is based on the finding of Narang et al of a mean serum calcium concentration > 11 mg/dL in the 6 "normal" subjects given 95 µg (3800 IU) vitamin D/d; this intake became the LOAEL. The next lowest test dose used by Narang et al, 60 µg/d (2400 IU/d), with 20% less as the safety margin, became the NOAEL. Narang et al reported only serum electrolyte changes; the doses of vitamin D were not verified, and circulating 25(OH)D concentrations were not reported. It is unfortunate that the National Academy of Sciences based any recommendation on such a limited study. Recent reports by Vieth et al (2) and Heaney et al (3) have proven the above claims to be incorrect. As originally stated by Vieth (4), we have yet to find published evidence of toxicity in adults from an intake of 250 µg/d (10 000 IU/d) that is verified by the circulating 25(OH)D concentration. The DRI, LOAEL, and NOAEL for vitamin D in adult humans have been established with insufficient scientific evidence and thus require correction through sound scientific studies.

The question that has intrigued our group for years is the following: How is it possible that the DRI for vitamin D is the same for a 1-kg premature human infant, a 3.5-kg term infant, and a 90-kg adult? The recommendation for all of three of these groups is 400 IU/d (10 µg/d)! To answer this question, it is necessary to ascertain the effect of a daily intake of 400 IU vitamin D/d on circulating 25(OH)D concentrations in infants and adults. We published the results of a study in infants more than a decade ago (17). In that study, term (weight: 3.4 ± 0.4 kg; ± SD) and preterm (1.3 ± 0.2 kg) infants were supplemented with 400 IU (10 µg) vitamin D/d for 4 mo. The circulating 25(OH)D concentration (in ng/mL), the nutritional indicator of vitamin D status, increased during this period in the term (from 11 ± 9 to 26 ± 12 ng/mL; ± SD) and preterm (from 11 ± 5 to 51 ± 19 ng/mL) infants. These are healthy increases; thus, a daily dose of 400 IU (10 µg) vitamin D appears to be effective in raising the vitamin D concentration to the accepted normal range for infants (15–80 ng/mL).

What effect does a daily dose of 400 IU vitamin D for an extended time (months) have in adults? The answer is little or nothing. At this dose (10 µg/d) in an adult, circulating 25(OH)D concentrations usually remain unchanged or decline. This was first shown in both adolescent girls and young women (18, 19). So the question is, what vitamin D intake is required to maintain or preferably improve the nutritional vitamin D status in adults in general and in pregnant or lactating adults specifically? This is a complex scientific question, yet recent well-controlled studies have provided some provisional answers (2, 3). First, what is the "normal" circulating concentration of 25(OH)D in the adult population? Data taken from the Mayo Medical Laboratories in Rochester, MN, list the normal range to be 15–80 ng/mL (20). This range is in accordance with what we have found in our laboratory; however, the circulating 25(OH)D concentration is dependent on season and latitude, as evidenced by the reference ranges (21). In sun-rich environments, circulating 25(OH)D ranges from 54 to 90 ng/mL (22-24).


NORMATIVE ADULT DATA IN A SUN-RICH ENVIRONMENT

Humans have evolved at exposures of > 20 000 IU (500 µg) vitamin D/d from the sun. In fact, a 0.5-h exposure to the summer sun between 1000 and 1400 in a bathing suit (3 times the minimal erythemal dose) will initiate the release of 50 000 IU (1.25 mg) vitamin D into the circulation within 24 h of exposure in white persons (25). African Americans require up to 5 times this solar exposure to achieve the same response (26, 27). In whites who have a deep tan because of melanin deposition in the skin, the response is 50% of that stated above, ie, only 20 000–30 000 IU (500–750 µg) vitamin D will be liberated (28). Finally, if wearing clothing or total body sunscreen, the cutaneous release of vitamin D is completely blunted (24, 29-31). So, in light of the above facts, a DRI of 400 IU/d (10 µg/d) in adults seems woefully inadequate to maintain normal circulating concentrations of vitamin D in adults with minimal solar exposure.


VITAMIN D INTAKES REQUIRED TO SUSTAIN AN ADEQUATE NUTRITIONAL STATUS OF VITAMIN D


On the basis of 25(OH)D concentrations in sun-replete adults, what vitamin D intake is required to sustain an adequate nutritional status of vitamin D? In whites who experience significant solar exposure to the body routinely, this is not an important question. As a population, however, our unprotected exposure to the sun is declining rapidly because if the fear of skin cancer and premature aging resulting from public education campaigns. For persons with darker pigmentation, the answer is more complicated. The darker pigmentation of the African American population is a powerful natural sunscreen, which adversely affects cutaneous vitamin D synthesis.

The first study to address this topic was published by Vieth et al in 2001 (2). In this study, the investigators supplemented healthy adults daily with either 25 µg (1000 IU) or 100 µg (4000 IU) vitamin D for 5 mo. Circulating 25(OH)D concentrations increased from 16.3 ± 6.2 to 27.5 ± 6.8 ng/mL and from 18.7 ± 6.0 to 38.6 ± 5.8 ng/mL in the 1000- and 4000-IU groups, respectively. Not a single adverse event or episode of hypercalciuria was observed in the 60 subjects enrolled in the study. In an even more detailed report, Heaney et al (3) studied 67 men divided into 4 groups that received 200 IU (5 µg), 1000 IU (25 µg), 5000 IU (125 µg), or 10 000 IU (250 µg) vitamin D/d for 5 mo. The 200-IU/d group failed to maintain circulating 25(OH)D concentrations during the study period. The remaining 3 groups responded in a dose-response fashion with respect to elevations in circulating 25(OH)D concentrations. From these data, with the use of regression analysis, it has become possible to calculate a response of circulating 25(OH)D from a given oral intake of vitamin D. The data show that for every 1 µg (40 IU) of vitamin D intake, circulating 25(OH)D increases by 0.28 ng/mL over 5 mo on a given supplemental regimen. Note that a steady state appears to be achieved after 90 d of each dose tested (2, 3). Thus, doses of 400 IU (10 µg), 1000 IU (25 µg), 4000 IU (100 µg), and 10 000 IU (250 µg) vitamin D/d for 5 mo will result in theoretical increases in circulating concentrations of 2.8, 7.0, 28, and 70 ng 25(OH)D/mL, respectively, all of which values are in the normal range of circulating concentrations according to reference data (20). In the study by Heaney et al (3), not one case of hypercalcemia or hypercalciuria was observed. The data from the studies of Vieth et al (2) and Heaney et al (3) are summarized in Table 1.

We are conducting an ongoing study that involves the supplementation of lactating mothers with 2000 IU (50 µg; n = 9) or 4000 IU (100 µg; n = 9) vitamin D/d for 3 mo. Our preliminary data show increased mean (± SD) circulating 25(OH)D concentrations in the 2000-IU/d group (from 27.6 ± 9.8 to 36.1 ± 7.0 ng/mL) and in the 4000-IU/d group (from 32.6 ± 6.9 to 44.5 ± 11.4 ng/mL), all of which are within the normal reference range (38). We note that the breastfeeding infants of these mothers have a substantially improved nutritional vitamin D status because of the transfer of vitamin D into the mother’s milk. Circulating 25(OH)D concentrations in the infants of mothers receiving the 4000-IU/d dose increased into the normal range after only 3 mo of breastfeeding (38).
Given the results of more recent scientific studies that evaluated high-dose vitamin D supplementation, it appears that the current RDA, DRI, LOAEL, and NOAEL for adults were based on limited scientific methods and small sample sizes and, therefore, are misleading and potentially harmful. New scientific evidence, including a study by the Centers for Disease Control and Prevention (1), suggests that the DRI for vitamin D should be much higher to achieve adequate nutritional vitamin D status, especially in the African American population because of their darker pigmentation. Further studies are necessary to determine the optimal therapeutic doses of vitamin D during pregnancy and lactation. Given the scientific data that are accumulating about the need for a higher DRI for vitamin D, how does one reconcile past concerns about vitamin D toxicity and hypervitaminosis D? The first step is to define hypervitaminosis D and to examine the medical literature describing these medical conditions.

HYPERVITAMINOSIS D

Nutritional hypervitaminosis results when pharmacologic doses of vitamin D are consumed for a prolonged period of time and is defined by a large increase in circulating 25(OH)D concentrations (4). The exact amount of vitamin D required to induce toxicity, ie, the amount ingested over a given period of time, is unknown in humans. However, Vieth (4) suggests that this amount is 20 000 IU/d (500 µg/d). In our experience, the amount of circulating 25(OH)D that induces toxicity would have to exceed 100 ng/mL. Eventually, as circulating 25(OH)D increases to toxic concentrations, the classic situation of hypercalciuria, hypercalcemia, and, finally, extraskeletal calcification becomes evident. Hypercalciuria due to excessive vitamin D intakes is always accompanied by circulating 25(OH)D concentrations > 100 ng/mL (39-41). To attain circulating 25(OH)D concentrations that exceed 100 ng/mL, a daily vitamin D intake well in excess of 10 000 IU/d (250 µg/d) for several months would be required (3). Vieth (4) estimates that the physiologic limit for daily vitamin D intake is 250–500 µg (10 000–20 000 IU/d). This amount also makes sense from a physiologic standpoint because this daily vitamin D load (10 000–20 000 IU) would be easily achieved from ultraviolet (UV) light–induced cutaneous synthesis in subjects of all races who work outside in sun-rich environments (22-25). Hypervitaminosis D is a serious, albeit very rare, condition. However, hypervitaminosis D has never occurred when physiologic amounts of vitamin D are ingested. In addition, no case of hypervitaminosis D from sun exposure has ever been reported.


HIGH-DOSE VITAMIN D SUPPLEMENTATION IN INFANTS

The concern regarding excessive vitamin D supplementation during infancy came to the forefront in post-World War II Britain. During that time, it was the practice to supplement each quart (0.95 L) of milk with 1000 IU (25 µg) vitamin D and to fortify many foodstuffs, such as cereals, bread, and flour, with vitamin D (42). It was calculated that most of the infants in Great Britain at that time received between 2000 and 3000 IU (50–75 µg) vitamin D/d (42). In many cases, it could have been much higher because of indiscriminate vitamin D supplementation. Thus, the highest doses that some infants received during this period will never be known because blood concentrations of vitamin D could not be assessed at that time. The indiscriminate use of vitamin D during this time was blamed for a dramatic increase in infantile idiopathic hypercalcemia (43); undoubtedly, uncontrolled vitamin D intakes from a variety of sources contributed to this outbreak. However, 2 important issues remain. First, the actual amount of vitamin D ingested by these infants who were afflicted with idiopathic hypercalcemia will never be known. Second, the contribution of other unknown underlying diseases, such as Williams syndrome, to the idiopathic hypercalcemia will remain unknown.

There is a model of "controlled" high-dose vitamin D supplementation (ie, a supplement given from a single source) during infancy that did not show the problems encountered in Britain. In Finland, from the mid-1950s until 1964, the recommended intake of vitamin D for infants was 4000–5000 IU/d (100–125 µg/d) (44). In 1964 it was reduced to 2000 IU/d (50 µg/d), and in 1975 it was further reduced to 1000 IU/d (25 µg/d) (44). In 1992, on the basis of the US RDA (5), the dose was reduced again to 400 IU/d (10 µg/d). Under this controlled supplementation regimen, even at the highest intakes, neither idiopathic infantile hypercalcemia nor any other health problem was ever described. However, what was described in a retrospective study was a dramatic decrease in type 1 diabetes later in life in infants who received high-dose daily vitamin D supplementation (44).


HYPERVITAMINOSIS D AS A CAUSE OF SUPRAVALVULAR AORTIC STENOSIS SYNDROME: AN ERRONEOUS ASSOCIATION

Because of the British experience with idiopathic infantile hypercalcemia attributed to hypervitaminosis D, a terribly inaccurate association occurred that had a profound effect on the potential of vitamin D supplementation, not only during infancy but also during pregnancy. In 1963, Black and Bonham-Carter (45) recognized that elfin facies observed in patients with severe idiopathic infantile hypercalcemia resembled the peculiar facies observed in patients with supravalvular aortic stenosis (SAS) syndrome. Shortly thereafter, Garcia et al (46) documented the occurrence of idiopathic hypercalcemia in an infant with SAS who also had peripheral pulmonary stenosis, mental retardation, elfin facies, and an elevated blood concentration of vitamin D. This is an interesting observation because, in 1964, when the article was published, there were no quantitative means of assessing circulating concentrations of vitamin D. In fact, at that time, it was not even proven that vitamin D was further metabolized within the body. By 1966 vitamin D was viewed by the medical community as the cause of SAS syndrome (42, 47). As a result of the theory that maternal vitamin D supplementation during pregnancy caused SAS syndrome (48, 49), animal models were developed to show that toxic excesses of vitamin D during pregnancy would result in SAS (reviewed in the next section) (50-62). In these earlier cases (42, 45-49), vitamin D had nothing to do with the etiology of SAS. What was described as vitamin D–induced SAS syndrome is now known as Williams syndrome (63). Unfortunately, a low vitamin D intake during pregnancy is still associated with SAS.

Williams syndrome is a severe genetic affliction related to elastin gene disruption (64) that is caused by deletion of elastin and contiguous genes on chromosome 7g11.23. This syndrome is characterized by multiorganic involvement (including SAS), dysmorphic facial features, and a distinctive cognitive profile (64). Such patients often exhibit abnormal vitamin D metabolism, which makes them susceptible to bouts of idiopathic hypercalcemia (65-70). This relation was suspected as early as 1976 (71). Subsequently, it was shown that children with Williams syndrome exhibit an exaggerated response of circulating 25(OH)D to orally administered vitamin D (65). Thus, the fear of vitamin D–induced SAS is based on studies that are no longer valid yet continue to be cited.


ANIMAL MODELS OF VITAMIN D TOXICITY DURING PREGNANCY

As mentioned previously, animal models of vitamin D toxicity during pregnancy developed in the 1960s and 1970s were used to study vitamin D–induced SAS syndrome in humans (50-62). These animal models, almost without exception, focused on feeding or injecting rodents, rabbits, or pigs with toxic concentrations of vitamin D or on administering the active form of vitamin D (1,25-dihydroxyvitamin D) and assessing the biological consequences. The results arising from vitamin D–induced hypercalcemia were devastating: extraskeletal calcifications of the aorta (a defect not observed in Williams syndrome) and other tissues that were usually followed by death. In most of these studies, the animals received 200 000–300 000 IU (5000–7500 µg) vitamin D/kg body wt to elicit these horrendous effects. An equivalent dose to a 60-kg human would be 15 000 000 IU/d (375 000 µg/d). In fact, toxic amounts of vitamin D have been used as a rodenticide, as an alternative to warfarin. However, to achieve the same results in humans, millions of units of vitamin D would have to be ingested.

Two relatively recent publications dealing with vitamin D supplementation during pregnancy and fetal cardiac abnormalities that used animal models need to be addressed. The first of these articles was published in 1985 in a Japanese science journal (59). These investigators fed 2 pregnant pigs different doses of vitamin D. One pig was fed a nearly vitamin D–deficient diet, and the other pig was fed a diet with a relatively normal vitamin D content. The piglets from the mother fed the nearly vitamin D–deficient diet exhibited borderline hypovitaminosis D [15 ng/mL circulating 25(OH)D], whereas piglets from the other sow had normal circulating concentrations of 25(OH)D. The authors attempted to relate normal circulating 25(OH)D concentrations in the piglets to coronary arterial lesions and made the inference that this could be the reason why Americans have a high rate of coronary disease. This study lacked the power to detect any statistically significant differences.

Only one other study has been reported that attempts to repeat the results of the porcine study with the use of a rat model (62). In this study, investigators fed pregnant rats the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], directly. The intake of 1,25(OH)2D3 by these pregnant rats was shown to influence aortic structure, function, and elastin content. These investigators collected blood using EDTA, a calcium-chelating agent, as an anticoagulant; as a consequence, circulating calcium could not even be measured! Thus, clinically significant hypervitaminosis D was not evident on the basis of its primary effect—hypercalcemia, which invalidated the study. In addition, because the authors used the hormonal form of vitamin D [1,25(OH)2D3], the study was considered to be pharmacologic and, thus, did not represent or recapitulate normal physiology in humans, ie, the hormonal form bypassed the body’s normal regulation of the conversion of 25(OH)D to 1,25-dihydroxyvitamin D. Thus, these animal studies have no bearing on normal human nutrition.


ANIMAL MODELS OF VITAMIN D DEFICIENCY DURING PREGNANCY

Conversely, other studies have shown just how important adequate nutritional intakes of vitamin D are to skeletal, cardiovascular, and neurologic development in experimental animals (72-76). Weishaar and Simpson (72) showed that lengthy periods of vitamin D deficiency in rats are associated with profound changes in cardiovascular function, including increases in cardiac and vascular muscle contractile function. These investigators later showed by histologic examination that ventricular muscles from vitamin D–deficient rats showed a significant increase in extracellular space (73). Morris et al (74) reported that low maternal consumption of vitamin D retarded metabolic and contractile development in the neonatal rat heart. The authors concluded that low maternal vitamin D intakes result in a general, but significant, slowing of neonatal cardiac development.

It has been suggested that vitamin D could be involved in brain function and neurodevelopment (77, 78). A recent study provides startling evidence with respect to the consequences of vitamin D deficiency on the neurodevelopment of the fetus during pregnancy in a rat model (75). Pups born to vitamin D–deficient mothers had cortex abnormalities, enlarged lateral ventricles, and more cell proliferation throughout the brain. Furthermore, the rats showed a reduction in the brain content of nerve growth factor and glial cell line–derived neurotrophic factor and a reduction in the expression of p75NTR, the low-affinity neurotrophin receptor. These findings suggest that low maternal vitamin D has important ramifications for the developing brain.

It has been known for decades that adequate vitamin D is required for normal skeletal development. The importance of vitamin D to skeletal integrity has been shown in a study involving rodents (76). This study showed that hypovitaminosis D during pregnancy impaired endosteal bone formation, which resulted in trabecular bone loss, and concluded that vitamin D is indispensable for normal bone mineralization during the reproductive period in rats.


HUMAN STUDIES INVOLVING PHARMACOLOGIC DOSES OF VITAMIN D DURING PREGNANCY

A study in human subjects involved the administration of 100 000 IU vitamin D/d (2.5 mg/d) throughout pregnancy to hypoparathyroid women to maintain serum calcium (79, 80). The infants from the larger of the 2 studies (79; n = 15) underwent an examination of facial structure, a palpation of pulses, and an auscultation for significant murmurs or bruits over the entire chest, back, abdomen, and peripheral vessels. Furthermore, the children were examined at ages ranging from 6 wk to 16 y. Many of the children were examined several times over a 4-y period. None of the children had any of the craniofacial stigmata associated with infantile hypercalcemia. Specifically, none had micrognathia or evidence of SAS, pulmonary stenosis, or other detectable cardiovascular anomalies. Greer et al (80) showed that an infant delivered from a hypoparathyroid mother who had received 100 000 IU (2.5 mg) vitamin D/d had circulating 25(OH)D concentrations of 250 ng/mL at birth; yet, this infant was perfectly normal and healthy. This woman again became pregnant and subsequently delivered another healthy term infant. Thus, there is no evidence in humans that even a 100 000 IU/d dose of vitamin D for extended periods during pregnancy results in any harmful effects. Pharmacologic doses of 1,25(OH)2D3 given to a woman to treat hypocalcemic rickets during her pregnancy produced no ill effects on the developing fetus; these infants were specifically evaluated for elfin facies and SAS (81).

VITAMIN D SUPPLEMENTATION DURING HUMAN PREGNANCY
The Cochrane Library recently issued a review of vitamin D supplementation during pregnancy (82) and identified 7 studies on the topic in question (32-34, 36, 83-85); however, only 4 reported clinical outcomes (32, 33, 83, 84). The Cochrane review concluded that there is not enough evidence to evaluate the requirements and effects of vitamin D supplementation during pregnancy. Presented below are the clinically relevant studies offered by the Cochrane review plus 3 additional studies identified by our group.

Initial vitamin D supplementation studies during pregnancy were carried out in the early 1980s. Brooke et al (32), who studied British mothers of Asian descent, found a greater incidence of small-for-gestational-age infants born to mothers who received placebo than in mothers who received 1000 IU (25 µg) vitamin D2/d during the final trimester of pregnancy. Neonates in the placebo group also had a greater fontanelle area than did the supplemented group. It must be noted that the placebo group in this study showed profound hypovitaminosis D. Follow-up studies by Brooke et al (83) were conducted in Asian mothers who again were provided with either placebo or 1000 IU vitamin D2/d during the last trimester of pregnancy. The follow-up data provided evidence that, during the first year of life, the infants of the maternal placebo group gained less weight and had a lower rate of linear growth than did the infants of the maternal supplemented group.

Cockburn et al (33) undertook a large vitamin D supplementation study of > 1000 pregnant subjects in the United Kingdom who were supplemented with 400 IU (10 µg) vitamin D2/d or received a placebo from week 12 of gestation onward. At this level of supplementation, serum concentrations of 25(OH)D in the supplemented group were only slightly higher than those in the placebo group. A defect in dental enamel formation was observed in a higher proportion of the children at 3 y of age in the maternal placebo group. Maxwell et al (84) conducted a double-blind trial of vitamin D (1000 IU/d) during the last trimester of pregnancy in Asian women living in London. They found that the supplemented mothers had greater weight gains and, at term, had significantly higher plasma concentrations of retinol-binding protein and thyroid-binding prealbumin, which indicated better protein-calorie nutrition. Almost twice as many infants of the unsupplemented group weighed < 2500 g at birth and had significantly lower retinol-binding protein concentrations than did infants of the supplemented mothers. Brunvard et al (86) followed 30 pregnant Pakistani women who were free of chronic diseases and had uncomplicated pregnancies. Nearly all of the women had low (< 15 ng/mL) circulating 25(OH)D concentrations, and nearly 50% exhibited secondary hyperparathyroidism. The maternal circulating parathyroid hormone concentration was inversely related to the neonatal crown-heel length. These authors concluded that maternal vitamin D deficiency affected fetal growth through an effect on maternal calcium homeostasis.

HOW DOES VITAMIN D SUPPLEMENTATION DURING PREGNANCY AFFECT THE NUTRITIONAL VITAMIN D STATUS IN BOTH MOTHER AND FETUS?

This is an important question that remains to be addressed. In the United States, the current DRI for vitamin D during pregnancy is 200–400 IU/d (5–10 µg/d). However, supplementation of mothers, by Cockburn et al (33), with 400 IU vitamin D/d during the last trimester of pregnancy did not significantly increase circulating 25(OH)D concentrations in the mothers or their infants at term. This finding agrees with current data in healthy men published by Heaney et al (3). Supplementation with 1000 IU (25 µg) vitamin D/d during the last trimester of pregnancy has produced mixed results. The initial study by Brooke et al (32) described a dramatic increase, 50–60 ng/mL, in circulating 25(OH)D in both mothers and neonates at term (Table 1). However, these results are highly suspect in light of later and current work (2, 3, 35, 37, 38) and are consistent with a dose response obtained after consumption of 10 000 IU (250 µg) vitamin D/d for 3 mo. There also is a possibility that the 25(OH)D assay method used in this study was flawed, as was common during this early period of investigation.

Mallet et al (35) reported that vitamin D supplementation (1000 IU/d, or 25 µg/d) during the last trimester of pregnancy resulted in an increase in circulating 25(OH)D concentrations of only a 5–6 ng/mL in maternal and cord serum. In the most recent study, by Datta et al (37), 160 pregnant minority women in the United Kingdom were provided with 800–1600 IU (20–40 µg) vitamin D/d for the duration of their pregnancy. Using modern assay technology for the measurement of circulating 25(OH)D concentrations (21), these investigators found a mean (± SD) increase in circulating 25(OH)D concentrations (ng/mL) of from 5.8 ± 0.9 at the beginning of pregnancy to 11.2 ± 6.3 at term after vitamin D supplementation. A normal serum circulating 25(OH)D concentration in the United States is considered to be > 15 ng/mL (20). However, a circulating concentration of 15 ng 25(OH)D/mL is marginal for nutritional vitamin D status (10). In other words, mothers who were vitamin D deficient at the beginning of their pregnancy were still deficient at the end of their pregnancy after being supplemented with 800–1600 IU vitamin D/d throughout their pregnancy. In other words, mothers who were vitamin D deficient at the beginning of their pregnancy were still deficient at the end of their pregnancy after being supplemented with 800–1600 IU vitamin D/d throughout their pregnancy. This result is precisely what the regression analysis from Heaney et al (3) predicted would happen at this vitamin D intake, and this is a problem (Table 1). The results of this study again point out that the DRI for vitamin D during pregnancy is grossly inadequate, especially in ethnic minorities. The data of Vieth et al (2) and Heaney et al (3) and our own data in lactating women (38) suggest that doses exceeding 1000 IU vitamin D/d (2000–10 000 IU/d) are required to achieve a robust normal concentration of circulating 25(OH)D. This should be the goal of future research in this area.


MATERNAL AND CORRESPONDING FETAL VITAMIN D CONCENTRATIONS
Many studies in human subjects have shown a strong relation between maternal and fetal (cord blood) circulating 25(OH)D concentrations (87-90). Our group showed that vitamin D status at birth is closely related to that of the mother and is greatly influenced by race (90). The data showed that the fetus at birth (cord blood) will contain 50–60% of the maternal circulating concentrations of 25(OH)D. This relation appears to be linear, even at pharmacologic intakes of vitamin D (80). With respect to the more polar metabolites of vitamin D, a similar (but lesser) relation is observed between mother and fetus (90). Interestingly, there appears to be little, if any, relation with respect to the parent vitamin, vitamin D (90). This lack of placental transfer of parent vitamin D from mother to fetus was also observed in a porcine experimental animal model (91). Thus, in the human fetus, vitamin D metabolism in all likelihood begins with 25(OH)D. As a result, the nutritional vitamin D status of the human fetus and neonate is totally dependent on the vitamin D stores of the mother (90); thus, if the mother has hypovitaminosis D, her fetus will experience depleted vitamin D exposure throughout the developmental period.

Finally, let us discuss a scenario that occurs thousands of times daily in the United States. A pregnant woman visits her obstetrician, who prescribes prenatal vitamins containing 400 IU (10 µg) vitamin D. The patient and physician both assume that this supplement will fulfill all the nutritional requirements for the duration of the pregnancy. However, in the case of vitamin D, it will not even come close unless the pregnant woman has adequate sun exposure. The woman, especially if African American, and her developing fetus are at high risk of remaining vitamin D deficient during the entire pregnancy (1). Even if the physician were to prescribe a vitamin D supplement of 1000 IU/d (25 µg/d), the mother would likely remain vitamin D deficient (35, 37). As scientists and health care providers, we simply cannot accept this any longer. The true requirement for vitamin D during pregnancy must be determined scientifically.

Scientific data pertaining to vitamin D supplementation during lactation in the humans is even scarcer than data on vitamin D supplementation during pregnancy. As during pregnancy, an arbitrary DRI has been set at 400 IU/d (10 µg/d). For the reasons stated in the previous sections, we consider a 400-IU/d vitamin D supplement to lactating mothers to be inadequate. This level of supplementation will do nothing to increase or even sustain the nutritional vitamin D status of mothers or their breastfeeding infants. We believe that vitamin D supplementation of lactating mothers has a dual purpose: 1) to increase the nutritional vitamin D status of the mother and 2) to improve the vitamin D nutriture of the breastfeeding infant. A maternal intake of 400 IU vitamin D/d will accomplish neither of these goals. To our knowledge, not a single prospective study has been performed to evaluate the effects of supplementing lactating mothers with 400 IU vitamin D/d. In other words, we have no idea what effect this dose would have on the nutritional vitamin D status of the mother or her infant. However, on the basis of the regression model of Heaney et al (3), supplementation of pregnant women with 400 IU vitamin D/d would only increase circulating 25(OH)D concentrations by 2.8 ng/mL after 5 mo.

We found only a single study that prospectively examined vitamin D supplementation during lactation (92). In this study, lactating mothers were supplemented with either 1000 IU (25 µg) or 2000 IU (50 µg) vitamin D/d for 15 wk. Increases in circulating 25(OH)D concentrations during this period of supplementation were 16 and 23 ng/mL in the 1000- and 2000-IU groups, respectively. We conducted preliminary studies in which lactating mothers were supplemented with 2000 and 4000 IU vitamin D/d for 3 mo (38). Our data also showed an increase in circulating maternal 25(OH)D concentrations, although not as pronounced as those observed by Ala-Houhala et al (92). It is clear that larger, more detailed studies are required to determine the vitamin D requirements of lactating mothers.

In the past, human milk was thought to be an adequate source of antirachitic activity for neonates and growing infants. Even before the discovery of vitamin D, McCollum et al (93) and Park (94) stated that rickets was due to the deprivation of sunlight and dietary factor X. They observed that factor X was found in "good breast milk" and cod liver oil and that, although rickets did develop in breastfed children, it was rarely as severe as in artificially fed infants. These investigators did not know that the source of vitamin D in the mother’s milk was the mother’s exposure to the sun, which cutaneously generated large amounts of vitamin D. Ultimately, this solar-derived vitamin D ended up in the mother’s milk for the infant. Early attempts to quantify the antirachitic potential of human milk were crude and yielded little information (95-97). For a time, it was believed that vitamin D sulfate was responsible for the antirachitic activity in human milk (98, 99); however, this was later shown not to be the case (100).

In the 1980s, the antirachitic activity of human milk was defined with sensitive assay technology to be 20–70 IU/L (101-103). Furthermore, almost all of the activity was attributable to vitamin D and 25(OH)D. These studies also showed that dietary maternal vitamin D supplementation and ultraviolet (UV) light exposure increase the vitamin D content of human milk (102, 104, 105). Specker et al (106) determined that the antirachitic activity of human milk was lower in African American than in white mothers. This difference was attributed to variations in the dietary intake of vitamin D and exposure to UV light. As presented earlier, the woman with hypoparathyroidism treated with 100 000 IU (2.5 mg) vitamin D/d for the maintenance of her plasma calcium concentration throughout pregnancy delivered a healthy child at term and then breastfed her infant (80). Analysis of breast milk from this mother showed it to contain 7000 IU/L of antirachitic activity. From our current studies involving lactating mothers receiving up to 4000 IU (100 µg) vitamin D/d, we showed elevations in the antirachitic activity of some of the mothers’ milk to > 400 IU/L (38). Thus, it is clear that the vitamin D content of human milk can be influenced by maternal diet, UV light exposure, or both. If a lactating mother has a limited exposure to UV light, a limited vitamin D intake [such as occurs at the current DRI of 400 IU/d (10 µg/d)], or both, the vitamin D content of her milk will be low, especially if she has darker skin pigmentation.

Thirty-five years ago the incidence of nutritional rickets was thought to be disappearing (107). Many reports since then, however, indicate that this is not the case (108-112). Most of the cases of rickets reported in the last few years have been in darkly pigmented infants who had been breastfed exclusively. Hypovitaminosis D in breastfed infants is also a severe problem in sun-rich environments, such as the Middle East (113). This hypovitaminosis D results because sun exposure to both mothers and infants is extremely limited. Furthermore, dietary supplementation in this population is not a common practice.

From the prior discussion in this report, it is clear that the antirachitic activity of human milk is variable and is affected by season, maternal vitamin D intake, and race. How then is the nutritional vitamin D status of neonates and infants affected if they are exclusively breastfed? Cancela et al (114) reported that circulating 25(OH)D concentrations in breastfed infants are directly related to the vitamin D content of the mothers’ milk. Available evidence indicates that if the vitamin D status of the lactating mother is adequate, her breastfeeding infant will maintain a "minimally normal" nutritional vitamin D status. The best example of this was presented by Greer and Marshall (115). These investigators found that white infants who were exclusively breastfed during the winter in a northern climate maintained a "minimally normal" vitamin D status for 6 mo. Note, however, that the circulating 25(OH)D concentrations in the breastfeeding infants from this study actually decreased as the study progressed. This decrease occurred despite a maternal vitamin D intake of 700 IU/d (17.5 µg/d) (115). In contrast, a Finnish study showed that maternal supplementation with 1000 IU (25 µg) vitamin D/d resulted in a minimal increase in circulating 25(OH)D concentrations in breastfeeding infants (36). These same investigators repeated a similar study with 2000 IU (50 µg) vitamin D/d and found that the vitamin D status of the breastfeeding infants improved significantly (92). Our group recently performed similar studies, supplementing lactating women with 2000 or 4000 IU vitamin D/d for 3 mo (38). We found that high-dose maternal vitamin D supplementation not only improves the nutritional vitamin D status of breastfeeding infants but also elevates the maternal concentrations into the mid-normal range. Thus, a dual benefit is achieved from high-dose maternal supplementation. It is noteworthy that in the Finnish study, the authors added a disclaimer, "A sufficient supply of vitamin D to the breastfed infant is achieved only by increasing the maternal supplementation up to 2000 IU/d. Such a dose is far higher than the RDA [DRI] for lactating mothers [and therefore] its safety over prolonged periods is not known and should be examined by further study." This point of concern was valid when this study was conducted in 1986 (92); however, on the basis of the current findings of Vieth et al (2) and of Heaney et al (3)—which showed that vitamin D intakes 10 000 IU/d (250 µg) are safe for prolonged periods (up to 5 mo)—we believe that it is time to reexamine the understated DRI of vitamin D for lactating mothers. This work is now being conducted in our clinics and laboratory.

ACKNOWLEDGMENTS

We thank Sebastiano Gattoni-Celli and L Lyndon Key for their thoughtful review and editorial assistance with this manuscript.

REFERENCES