Vitamin D: Requirements for Optimal HealthWilliam B. Grant, Ph.D.

Sunlight, Nutrition, and Health Research Center (SUNARC)

Presented to:

Smart Life Forum, Palo Alto, CA

October 21, 2004

Outline

• Historical science perspective

• Diseases and conditions affected by vitamin D

• Sources of vitamin D

• How much we need in our blood

• Concerns regarding ultraviolet radiation

• Sources of additional information

Historical Perspective

• Our ancestors spent a considerable amount of time in the sun

• They developed skin pigmentation appropriate for the UV conditions in early fall: pale enough for vitamin D production, yet dark enough to reduce the risk of DNA damage and destruction of folate

• Our relationship with the sun changed with increased urbanization and migration

Production of Vitamin D from Ultraviolet-B (UVB) Radiation

• UVB radiation (290-315 nm) converts 7-dehydrocholesterol into pre-vitamin D

• Previtamin D3 undergoes a thermal isomerization that results in the formation of vitamin D3 (25 hydroxyvitamin D (25(OH)D))

• This is converted to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the liver and kidney

Diseases and Conditions that Vitamin D Helps Prevent

• Rickets and other bone diseases

• Internal cancers

• Multiple sclerosis

• Other diseases – given later

Rickets

• Rickets was the first disease associated with lack of sunlight in urban settings in the 19th century

• Associated with vitamin D deficiency in the 1920s

• Cod liver oil given to supply vitamin D

• Breast fed African-American babies in NC are still getting rickets

Bone Diseases

• Vitamin D plays a key role in calcium absorption and metabolism

• Low values of serum 25(OH)D increase parathyroid hormone (PTH).

• PTH pulls calcium from bones to maintain proper calcium levels in blood

• Thus, vitamin D is essential for proper bone development and continued strength

Internal Cancers

• Vitamin D was first suggested as a cancer risk reduction factor by Cedric and Frank Garland in 1980.

• They noted that the latitudinal increased in colon cancer mortality rates in the U.S. was inversely correlated with annual sunshine doses, and suggested that vitamin D was the active agent

• The importance of calcium was realized later

Internal Cancers - 2

• Over the next decade, they noted similar patterns for breast, ovarian, and others did for prostate cancer

• However, the mechanisms were unknown until the late 1990s and early 2000s

• In addition, many associate solar UV radiation with skin cancer and melanoma

Cancer – Mechanisms of Vitamin D

• Increases cell differentiation• Suppresses growth stimulatory signals

and amplifies growth inhibitory signals, leading to induction of cell death

• Reduces angiogenesis around tumors• Reduces metastasis• Suppresses genes responsible for

enhancing cellular proliferation• Modulates immune responsiveness

Cancer – Geographic Variations of Mortality Rates in the U.S.

• When I saw the maps in the Atlas of Cancer Mortality in the U.S., 1950-94, I first tried to explain the factor of two between the northeast (high) and the southwest (low) based on dietary factors

• However, this would entail the northern European diet in the northeast and the southeast Asian diet in the southwest

Solar Ultraviolet B Radiation

• Working for NASA and studying ozone, I was aware of the UV measurements made using the Total Ozone Mapping Spectrometer operated by the NASA Goddard Spaceflight Center

• The UVB for July is very asymmetric due to high surface elevation in the west and the prevailing westerlies that push up the tropopause as they cross the Rockies

DNA-weighted UVB

Colon cancer – white females

Seasonal Variation of Vitamin D and Cancer Risk

• The July UVB doses provide the strongest (inverse) correlation with cancer mortality rates in general

• I attribute this to the effect of a large dose of an anti-cancer agent having an impact sometime during the 15-20 year period of development of cancer

• For prostate cancer, both low and high serum 25(OH)D levels are risk factors

Additional Risk Factors

• My first paper, published in Cancer in 2002, was not fully accepted since I had not considered other risk factors.

• To remedy the situation, I added the following factors: alcohol consumption, Hispanic heritage, population changes, living in poverty, smoking effects, and urban/rural residence

Breast Cancer Morality Rates vs. Regression Based on UVB, Urban/Rural Residence,Alcohol, and Poverty, With and Without Urban Residence

Regression Rate (deaths/100,000/year)

14 16 18 20 22 24 26 28 30 32

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UVB Associated with Reduced Risk for 18 Types of Cancer

• Aerodigestive tract – colon, esophagus, larynx, rectum, stomach

• Breast• Reproductive organs – ovary, prostate,

testes, uterus, vulva• Other organs – bladder, gallbladder,

kidney, lungs, pancreas• Blood – Hodgkin’s lymphoma, non-

Hodgkin’s lymphoma

Urban/Rural Residence and UVB

• Seven types of cancer (breast, colon, etc.) were inversely correlated to both solar UVB radiation and rural residence.

• Urban residence was not independently associated with cancers related to smoking.

• Thus, urban residence reduces UVB dose

Cancer – Results for Other Risk Factors

• Lung cancer (cigarette smoking) was associated with 12 cancers

• Hispanic heritage was associated (risk) with 5 cancers (genetics and diet)

• Alcohol consumption was associated with 7 cancers

• These results agree very well with the literature, thus strengthening the UVB/ vitamin D findings

Multiple Sclerosis

• How many in the audience know someone who has multiple sclerosis (MS)?

• How many have heard that vitamin D very likely reduces both the risk of and symptoms of MS?

Multiple Sclerosis, UVB, Vitamin D

• Strong latitudinal gradients are found in Australia, Europe south of 60o N, and the U.S.

• Childhood UV exposure, especially in winter, reduces the risk of MS in Tasmania

• Those in the U.K. with skin cancer were found to have half the rate of multiple sclerosis (MS) of the rest of the population

Multiple Sclerosis Prevalence for U.S. WWII, KC Veterans at Time of Entery into the Armed Forces vs. Latitude

Latitude (degrees N)

25 30 35 40 45 50

MS

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Multiple Sclerosis, Vitamin D - 2

• U.S. nurses taking the most vitamin D had a relative risk of MS of 0.66 vs. least vitamin D

• Fish consumption also reduces the risk of MS. Fish is a good source of vitamin D.

Multiple Sclerosis - 3

• These findings seem related to solar UVB doses and vitamin D in winter, likely to immune system strengthening at a time when infectious disease rates are highest

• 1,25(OH)(2)D(3) inhibits production of IL-12, a cytokine involved in the development of Th1 cells and in the pathogenesis of Th1-mediated autoimmune diseases

• However, it should be noted that this is a scientific conclusion, not yet adopted by the medical community

Multiple Sclerosis: Prevention by Vitamin D

• I estimate that 40-70% of MS in the U.S. could have been prevented through adequate vitamin D, especially in winter

• This is the season when infectious diseases are most common; MS appears to be caused by infectious disease

• Circulating vitamin D levels are lowest in winter

Multiple Sclerosis Treatment

• Annual variation in MS lesions (high in winter) tied to solar cycle in Germany, Canada, San Diego

• Those who have MS can benefit from vitamin D, from supplements or natural or artificial UVB radiation

• Ashton Embry, Ph.D. in Canada is raising funds for clinical studies in treatment

Other Diseases that UVB/Vitamin D Helps Prevent

• Muscle pain, weakness• Progression of rheumatoid and osteo-arthritis• Type 1 diabetes mellitus in infancy• Type 2 diabetes mellitus• Body, brain disorders during fetal development• Irritable bowel syndrome, Crohn’s disease• High blood pressure, heart disease• Tuberculosis

Secret to summer loving: Vitamin D

• THE reason why many couples seem to conceive while they are on holiday may have been explained by scientists: sunlight might be good for a man’s sperm.

• New research has indicated that vitamin D — which is produced by the human body when exposed to the sun — is critical to the production of sperm, and that a lack of the nutrient may be linked to male infertility.

• The findings, from a team at the Dartmouth-Hitchcock Medical Centre in Lebanon, New Hampshire, suggest that boosting vitamin D production, either by increasing exposure to sunlight or by taking dietary supplements, might improve fertility among men.

Sources of Vitamin D

• Solar UVB radiation is the most important source for most people on Earth

• Dietary sources provide some vitamin D, especially fish in Scandinavia and Japan

• Fortified food provides some vitamin D

• Supplements can provide vitamin D

• UV lamps that mimic the solar UVR reaching the Earth’s surface are also good

Annual Variation of Serum 25(OH)D

• In temperate and polar regions, serum 25(OH)D levels are highest near the end of summer and lowest in late winter or early spring

• It is impossible to make vitamin D in sunlight in Boston for the 4 or 5 darkest months of the year

• 25(OH)D is stored in fatty tissues and stays in the body for weeks or months

Levels of Serum 25(OH)D

• Deficiency is <10 ng/ml (25 nmol/L)

• Insufficiency is between 10 and 30 ng/ml (25-75 nmol/L)

• Below 40 nmol/L, circulating 1,25(OH)D levels fall

• For bone health and other conditions, optimal is up to 90 nmol/L; 100 nmol/L for those over the age of 70 years

Vitamin D conversion to 25(OH)D

• One mcg (40 I.U.) per day of Vitamin D(3) on a routine basis increases circulating 25(OH)D by 1-4 nmol/L (0.4-1.6 ng/mL)

• Thus, 25 mcg (1000 I.U.)/day corresponds to 25-100 nmol/L 25(OH)D

• This varies by individual – One can make too much 25(OH)D using both

supplements and UVB exposure– Others have poor absorption/conversion rates

How Much Vitamin D is Required?

• Present-day guidelines call for 400 I.U./day for young and middle-aged persons, 600 I.U. for those around 50-70 years of age, and 800 I.U. for those over the age of 70 years

• These guidelines were developed a number of years ago and are based on developing and maintaining strong bones

New Guidelines?

• However, with the realization that vitamin D plays important roles in reducing the risk of many soft-tissue diseases, and that the guidelines do not provide for high enough levels for these diseases, the recommended amounts will likely be revised upward

Testing Serum 25(OH)D

• The only way to accurately determine one’s UVB dose and vitamin D intake requirements is through serum 25(OH)D testing

• This can be done through LabOne (1-800-646-7788), with blood drawn locally

• One should obtain a LabOne card

Who Should be Tested

• Doctors should request serum 25(OH)D tests for any patients who have diseases for which vitamin D is thought to reduce the risk, progression, or symptoms, or who live largely indoors

• I would be interested in working with MDs to interpret the findings as well as see whether scientific papers could be developed

Who Should be Tested – 2

• Anyone wanting to take 1000 I.U./day should also have serum 25(OH)D levels tested

• The dangers of high serum 25(OH)D include:– Reduced bone mineral density– Apparent increased risk of prostate cancer,

possibly due to harmful derivatives of 25(OH)D

How Much Solar UVB Exposure?

• Michael Holick, MD, PhD, Boston University, author of The UV Advantage, now estimates that one needs to expose 25% of the body to midday solar radiation, 2-3 times a week, during summer, to produce the amount of vitamin D considered optimal

• This is for light-skinned individuals; darker skinned ones need more exposure

Vitamin D from Solar Radiation

• However, since cancer mortality rates vary by about a factor of 2 from the southwest to the northeast, I think that the time in the sun for vitamin D production varies by location

• I plan to develop vitamin D production maps for the U.S.

What About Skin Cancer?

• The risk factors for skin cancer include skin type, number of moles, number of painful sunburns in youth, diet (high-fat, low-vegetable), smoking, alcohol consumption, and lifetime dose of ultraviolet radiation

• Beta carotene and vitamin C and other antioxidants (internal or external) reduce the risk of sunburn and skin cancer

And Melanoma?

• Melanoma risk is also related to a number of factors including sunburning, diet, smoking, number of moles, use of sunscreen, etc.

• Interestingly, melanoma rates increase with latitude for those living in their ancestral homelands– This is likely due to skin pigmentation– It could also be related to dietary factors

Melanoma and Skin Cancer Risks vs. Other Cancers

• My estimate of premature cancer deaths from 18 types of cancer for the period 1970-94 is 21,000 males and 25,000 females per year.

• During this period, 5000 died annually from melanoma and 1900 from NMSC

• The ratio is 6.6 from other cancer to 1 from melanoma and NMSC

Why Has Vitamin D Been Underappreciated?

• No one profits from selling natural solar UVB

• Only the indoor tanning folks profit from selling artificial solar ultraviolet radiation

• Vitamin D as a supplement is cheap

• Fear of sunburns, wrinkles, skin cancer, and melanoma

• Slow research on health benefits

Summary and Conclusion

• Vitamin D is essential for optimal health

• Solar UVB is the primary source of vitamin D for most people on Earth

• Optimal serum 25(OH)D levels are >40 nmol/L up to 90 nmol/L

• In the absence of solar UVB, supplements, food sources, and UVB lamps such as in tanning salons can supply vitamin D

For Further Information

• www.sunarc.org

• (hosted by Aegis Corp., Florida; Robert Wagner, Tony Cowdrey)

• wgrant@sunarc.org

Proposed Policy Statement on Vitamin D and Ultraviolet Radiation• Recognize that relatively high levels of

vitamin D are required for optimal health

• Recognize that solar ultraviolet radiation is the primary source of vitamin D for most people on Earth

• Recognize that dietary sources of vitamin D are generally inadequate unless one consumes large amounts of fatty seafood

Policy Statement - 2

• Thus, solar UVB radiation exposure should be encouraged with these considerations:– Develop a tan gradually during the sunny

season– Do not sun bathe to the point of reddening– Try to obtain UVB radiation near midday daily

(the ratio of UVB to UVA is highest then, and exposure time is minimized)

Policy Statement - 3

• Solar UVB radiation exposure, continued– If planning a trip to a sunny vacation spot,

consider indoor tanning for preparation– If one has skin that does not tan easily,

perhaps freckled, be very careful in the sun– If one has skin that is dark for the latitude, one

should spend more time in the sun or take vitamin D supplements

– Do not tan excessively

Policy Statement - 4

• In winter, non-solar sources of vitamin D should be used:– Vitamin D supplements– Fish or vitamin D fortified food– UV lamps that mimic the UV spectrum

reaching the Earth’s surface (3-5% UVB (290-315 nm), the rest UVA (315-400 nm))

Policy Statement - 5

• If using vitamin D supplements at or above 1000 I.U./day, it is recommended that serum 25(OH)D levels be measured

• This can be done through LabOne (1-800-646-7788), with blood drawn locally

• The adverse effects of too much vitamin D include hypercalcaemia (more calcium in blood and less calcium in bones) and increased risk of prostate cancer

Policy Statement - 6

• Additional research on the roles of vitamin D in maintaining optimal health and the population impact should be encouraged

• Doctors should consider requesting serum 25(OH)D tests for patients who:– Have diseases for which vitamin D helps– Are advanced in age – Live or work largely indoors– Have dark skin pigmentation