THE SUNLIGHT, VITAMIN D AND HUMAN LONGEVITY

Introduction

The living things have been existed on this earth for 3.8 billion years, 700 million years after the earth was formed. The sun however was formed some 7 to 8 billion years ago or about 7 billion years after the universe was created (14 billion years ago). As far as the Homo sapiens specie (modern man) is concern, we have existed on this earth for only 250,000 years or just a nick of life time on earth. We have been evolved from ape like primate to become human (hominid species) around 7 million years ago. The reason we evolved to be modern human are due to the influence of environment most likely are foods such as meat (protein) and fat especially omega 3 fatty acid, the sun and vitamin D which is produced by our skin from cholesterol (7-dehydrocholesterol) which requires the ultraviolet B from the sun to synthesize (please see human origin on this website). In order to understand the relationships between human longevity and the sunlight and vitamin D, we need to learn more about the sun, the sunlight and the vitamin D in detail.

Vitamin D has been known to control the bone, calcium and phosphorus homeostasis. However during the last 30 years the research related to vitamin D metabolism has been exploded. Now we have realized that almost all the cells of our bodies contend receptors for vitamin D (VDRs) which regulate the cellular functions. Today vitamin D deficiency has been known to relate to many kind of diseases what I called the diseases of civilization.

THE SUN and THE SOLAR ULTRAVIOLET B IRRADIATION

“WITHOUT THE SUN THERE WOULDN’T BE LIFE ON EARTH”

Outline for discussion

1. Introduction

2. Why you need sunlight?

3. The benefits of optimal sun exposure

4. Why sunlight is so important to your health?

5. How much and how much sunlight exposure we need for optimal health?

6. How to get exposure to the sun to get optimal UVB:

7.  Basic knowledge

8. Conclusion

1. Introduction: The sunlight is essential for life. However over exposure to the sun can create many medical problems such as heat stroke, heat exhaustion, sun burn,  many types of skin cancer, skin damage ; actinic keratosis, senile keratosis , skin wrinkle and even death. For these reasons medical authorities especially the

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Dermatologists recommend to avoid the sun exposure and using the sun screen to

protect the skin. So the people try to avoid the sunlight. The results of lacking of

adequate sun exposure is not known until the last 30 years even we knew that the sunlight  can cure rickets over 200 years before. Around mid 1920s vitamin D was discovered and later on also proved that vitamin D produced in the skin after exposure to the sun. But the most important finding is; beside the vitamin D is essential for bone and calcium metabolism, the active form of vitamin D is produced in every cell in our body. Since we are able to measure vitamin D blood level (Calcidiol or 25 hydroxy vitamin D) in 1985 we also discovered that at least 70% of the people world wide low in vitamin D level. Low vitamin D less than optimal level at 50 ng/ml or 125 nmol/L is associated with almost all medical problems we have today.
2. Why you need sunlight?
             Beside the light and heat we want from the sun, we need to expose to the sunlight long enough in order to produce vitamin D naturally from our skin. The people who live in the temperate zones, the skin unable to produce enough vitamin D due to low in  UVB from the sunlight during winter time and need vitamin D supplement orally. The government recommends the vitamin D supplements from 200 to 600 units daily. These dose of vitamin D supplement simply is not enough for optimal health but for only prevention of rickets in children and osteomalacia in adult. Sooner you will find out that exposure to the sunlight is the best method to obtain vitamin D without the side effect from it.

3. Here are the benefits of optimal sun exposure:

1. Prevent rickets, osteomalacia, osteoporosis
2. Prevent cancers, including skin cancer
3. May cure Psoriasis, eczema (atomic dermatitis)
4. May reduce blood pressure
5. May prevent osteoarthritis and rheumatoid arthritis
6. May prevent diabetes both types as well as syndrome X and obesity
7. May improve fatigue, depression and seasonal Affective disorder
8. May prevent infertility and Premenstrual syndrome
9. May prevent multiple sclerosis
10. and other benefits…

Every body needs sunlight and vitamin D. Deficiency or insufficiency has been associated with:
· Adrenal insufficiency
· Alzheimer's
· Allergy
· fatigue
· Decreased sex drive
· Insomnia

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· Weakened immune system (autoimmune disorders)

· SAD (seasonal affective disorder)
· Depression, suicide
· PMS (post menopausal syndrome)
· Alcoholism infertility
· Obesity
· Decreased ability to pay attention or concentrate or learning disorder
· Increased cravings for carbohydrates, sugar, and caffeine
· Weakened, fragile bones (osteomalacia, osteoporosis)
· Rickets
· Cancers of the colon, breast, skin and prostate
· Diabetes, Type 1 and 2 and Syndrome X
· Gluten intolerance
· Heart disease, hypertension, heart failure
· Heavy metal toxicity
· Lecithin intolerance
· Misaligned teeth and cavities
· Myopia
· Parkinson's
· Multiple sclerosis
· Psoriasis
· Use of corticosteroids and more...

4. Let me explain to you why sunlight is so important to your health.

             Sunlight is the main(90 to 95 percent) and the best source of the vitamin D production that we need every day. 70 percent of Americans deficient in vitamin D most likely lack enough exposure to sunlight. Low in Vitamin D will cause the above-mentioned medical problems.
            As you know, our ancestors originated from Africa (which is very close to the earth’s equator. 7 million years ago, we moved from the forest to savannahs. Our ancestors were then optimally exposed to the sun and we became stronger and taller (progressively increasing in height from less than 4 feet to over 6 feet). We have been naked for at least a million years.
           Most importantly, it is very difficult to get adequate UVB sunlight. Most people who live above 30 degree latitude will not get enough UVB to produce enough vitamin D during the winter time. Glass windows or doors block almost all UVB, but don’t block harmful UVA (please click on ultraviolet below for more detail). Sunscreen will block UVB completely, but not block UVA (up to 50 percent only).

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5. How much and how sunlight exposure we need for optimal health?

How can we get enough vitamin D without the side effects?
The best way is by maximum sun exposure where there is no chance to get Vitamin D toxicity. According to recent research if we maximally expose to the sun we will obtain vitamin D3 equivalent to 20,000 IU a day. Any more exposure to the sun longer, vitamin D3 will be destroyed by ultraviolet rays. So the chance of vitamin D toxicity is unlikely. The people who woke out door in the sun all day and wear working suite naturally will get approximately 5000 IU of vitamin D3 daily.

According to the expert, exposure the face, arms and legs (50 percent body surface area) to the sunlight during the summer time between 10 a.m. to 3 p.m. about 5-30 minutes twice a week is often adequate

6. How to get exposure to the sun to get optimal UVB:
1. Check the UV INDEX for your location (http://www.epa.gov/sunwise/uvindex.html )
2. Expose your body to the sun gradually in order to increase your melanin pigment (which is your natural sunscreen that prevents UVA skin damage) depending on your skin color. Generally, the darker the skin the longer you can be exposed.
3. Expose the skin (the whole body is the best) to the sun until it turns somewhat red (MED or minimal erythemal dose). You have to do some experimenting to find out how long it will take. Try not to get yourself burnt (which is an indicator of skin damage that may cause cancer).
4. If you have to stay in the sun longer than necessary, you must protect your skin with a hat that covers your face, long pants and long sleeve shirt.
5. Use sunscreen as a last resort (remember it protect you from 50 percent at best, even though you use the highest SPF).
6. Expose yourself to the sun as stated above, at least 3 times per week.

7. Basic knowledge

The sun: the self –luminous, gaseous sphere about which the earth and other planets revolve and which furnishes light, heat, and energy for the solar system, and has been active for 4.6 billion years.
Size: 864,400 miles in diameter
Distance from the earth: 93 million miles
The time it takes light from the sun to reach the earth: 8 minutes
Composition: Same chemical elements as the earth - about 92.1 % hydrogen, 7.8 % helium.
Surface temperature - 11,000 degree F (6000 degree C)
How the sun creates energy: The sun is a star - a furnace in which hydrogen nuclei undergo fusion to produce helium (and much rarer and heavier elements), and during which, about 0.3% of their mass is converted to energy

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Sunlight: total spectrum of electromagnetic radiation given off by the sun with yellow light and heat

Solar radiation: is radiant energy emitted by the sun, particularly electromagnetic energy. About half of the radiation is in the visible short-wave part of the electromagnetic spectrum. The other half is mostly in the near-infrared part, with some in the ultraviolet part of the spectrum.

To learn more try the following links:

The Solar System
Solar views
The Sun
The Earth
Sunlight (electromagnetic spectrum):
Nasa

How to locate your hometown latitude and longitude:

http://itouchmap.com/latlong.html 
Electromagnetic Spectrum

Ultraviolet light:
UV – A (NUV= near ultraviolet)) (315-400 nm) 90 to 95 percent of UV light. The longest-wavelength range, UV - A is connected to the development of skin cancer).

UV – B (FUV= far ultraviolet) (280-315 nm) UVB rays are responsible for tanning and it also helps convert cholesterol (7dehydrocholesterol) to vitamin D.

UV - C (EUV=extreme ultraviolet) ((100 to 280nm) (UV UVC is entirely absorbed by the ozone layer in the atmosphere and does not reach the earth’s surface.

Ultraviolet
UV Minerals

Ultraviolet light (from artificial lamps):
Nagonline.net and/or Light Therapy

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ULTRAVIOLET INDEX (UVINDEX)

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Human body surface area (skin) for adult:

-20 square feet or 18,600 square centimeters divides into 6 portions (rule of nine) as follow
-Head & Neck 10 %
-Each upper extremity (arm, forearm & hand) 9 %
-Body 36 %
-Each lower extremity (Thigh, lower leg & foot) 18 %

-Face and hands (typically for business man suite and veiled women in certain countries): 5% sun exposure

-Face, neck and upper arms (typically for casual dressing):25-30 % sun exposure

-Face, neck, upper and lower extremities (typical summer walking suite with short pant): 50-60% sun exposure

-Total body (swimming suite with bra and underwear):  sun exposure 90 %

How much vitamin D does the skin (epidermis) make after exposure to Ultraviolet B?
According to research study, reveal that for the light-skinned person; vitamin D production is 163 IU per square centimeter per day and 69 IU per square centimeter per day for the dark-skinned person. Or about approximately 2 million IU per day depend on the skin type. Or if the head and neck (10% of total skin surface area) expose to the sun (summer) only for 12 hours the vitamin D production will be 200,000 IU or 278 IU per minute or 16667 IU per hour. (Normally after skin production over 20,000 IU the vitamin D will degraded by ultraviolet ray and never become toxic)

Here are the estimations for the maximum vitamin D production:

-The person in the bathing suit expose to the sun at noon time to a minimal erythemal dose (MED) in June or July at 42 N latitude (Boston) about 15-20 minutes will make vitamin D equivalent to taking 20,000 vitamin D3 orally.

-Full- body exposure to sunlight will get vitamin D equivalent to an oral intake of 10,000 IU (250 microgram) per day

-The people who woke out door in the sun all day and wear working suite naturally will get approximately 5000 IU of vitamin D3 daily.

-The farmer in Puerto Rico obtained vitamin D from the sunshine had serum 25(OH) D level up to 90 ng/ml (225nmol/L). Total- body sun exposure easily provides the equivalent of 250 microgram (10000 IU) vitamin D/d.

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Ozone (O3): is a substance consisting of three oxygen atoms per molecule. At standard temperature and pressure, this is a blue gas. Ozone forms a dark blue liquid below -112 degrees C, and a dark blue solid below -193 degrees C. Ozone is notable for its ability to absorb UV-B radiation. Ozone is created naturally within the ozone layer. Ozone is "depleted" by chlorofluorocarbons and other upper atmospheric contaminants.
Ozone

Africa
Chad (Where our ancestors came from)
The United States

Are you exposed to enough sun at your home location? http://www.bcca.org/misc/qiblih/latlong_us.html
What is the Ultraviolet index (UV index)? : http://www.epa.gov/sunwise/uvwhat.html
What is UV index in your hometown today? EPA Index Map
and/or EPA UV Index

Sunscreen: Almost always blocks UVB. Sunscreen with a sun protection factor of 8 will reduce your body’s ability to make vitamin D by about 95%. Sunscreen of SPF 8 will not reduce your chances of developing skin cancer (due to UVA rays).

7. Conclusion:

The sunlight is essential for life. As far as we know, life only exists on earth. We are not just need the sunlight for heat and light. Now we know that the majority of vitamin D that body obtain is produced by 7-dehydro cholesterol in the epidermis layer of the skin expose to the ultraviolet B. Vitamin D and it metabolites is very important hormone and performs as endocrine and autocrine functions that not just essential for calcium, phosphorus and bone metabolism but also essential for optimal cellular functions. Therefore exposure to the sunlight less than normal will get less vitamin D production. Hypovitaminosis D now has been known to related to the many diseases so called the diseases of civilization. So it is very important to expose to the sun optimally. Exposure to the sun is free and the best way to obtain vitamin D. The government and medical authority should educate the public, patients to expose to the sunlight properly and optimally, definitely we will live longer.

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VITAMIN D

Outline for discussion

1.      Introduction

2.      History of Vitamin D

3.      Pharmacology of vitamin D production

4.      Vitamin D in Health and Disease

5. The exact action and mechanism of Vitamin D and it Receptor at the cellular level

6. How much vitamin D we need and how can we obtain vitamin D optimally?

a.      from the solar ultraviolet irradiation

b.      from food and oral supplements

7. The sources of Vitamin D

8.  Vitamin D toxicity

9.  What is the best method to check the vitamin D level?

10. Vitamin D and human longevity

11. Conclusion

1. Introduction:

Rickets has been recognized as medical entity since the mid 1600s, however the cause and the cure of rickets, is not known until about 200 years later. The sun bath and cod liver oil were found to cure the rickets, Around mid 1920s Vitamin D was discovered and proved to be the vitamin that cure rickets. During the past 40 years the research related to vitamin D has been exploded. Now vitamin D deficiency has been related to all kind of illnesses and diseases so called diseases of civilization including osteoporosis, cardiovascular disease, hypertension, diabetes mellitus, many kind of cancers, autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis. Because vitamin D deficiency is very common worldwide regardless to race, ethnicity, sex and countries and temperature climates. It is worthwhile to review the subjects related to vitamin D and its mechanism.

2. History of vitamin D

Rickets, medical entity recognized since the 17th century by both Dr. Daniel Whisler (1645) and Professor Francis Glisson (1650). However, the causative factors of rickets were unknown until the years 1919/20 when Sir Edward Mellanby and Huldschinsky showed that adding Cod liver oil to the diet or exposure to sunlight cured the disease. In 1923 Goldblatt and Soames identified that when a precursor of vitamin D in the skin (7-dehydrocholesterol) was irradiated with sunlight or

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ultraviolet light, a fat-soluble substance or vitamin was produced. In 1930 the chemical structures of the vitamin D2 were identified by Professor A. Windaus at the University of Göttingen in Germany. Vitamin D2, which could be produced by

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ultraviolet irradiation of ergo sterol, was chemically characterized in 1932. In 1936,

vitamin D3, was identified by ultraviolet irradiation of 7-dehydrocholesterol. The discovery of metabolic functions of vitamin D was studied by DeLuca in United States and Kodicek in England 1974-1976.

To learn more please click below
http://vitamind.ucr.edu/history.html

3. Basic chemistry and physiology of vitamin D

Vitamin D(calciferol) is a general name to represent a group fat soluble prohormones and hormone in the broken-open steroid group(secosteroids) including ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), calcidiol 25-hydroxycholecalciferol (25(OH)D₃ ) and calcitriol (1- alpha dihydroxy vitamin D3), the active form. Naturally it manufactures from cholesterol; 7-dehydrocholesterol  in animal skin (stratum basale and stratum spinosum) when it reacts to ultraviolet light at wavelengths between 290–315 nm, with peak synthesis occurring between 295-297 nm (UVB). to form cholescalciferol (Vitamin D3)  then transported to the liver(hepatocytes) by vitamin D binding protein(DBP) and hydroxylate  by the enzyme 25 hydroxylase to be 25 hydroxy vitamin D3{25(OH)D3] or CALCIDIOL( This serum level of 25-hydroxycholecalciferol (25(OH) D3 that we measure in the lab for vitamin D status {half-life 2-3 weeks}).  25-hydroxycholecalciferol (25(OH) D3   is a storage form which will store in the liver and release when needed. It is also store in the fatty tissue. Once -hydroxy Cholecalciferol (25(OH) D3 release to blood stream it will transport to the cells all over body. The first pathway is go to the kidneys , 25-hydroxycholecalciferol (25(OH)D₃  then convert by kidney cells by the enzyme 1alpha- hydroxylase (1-alphaOHase or CYP27B1) to form the active forms of vitamin D called CALCITRIOL  or 1,25-dihydroxycholecalciferol (1,25(OH)2D₃) and 24R,25(OH)2D₃. Calcitriol (half- life less than 4 hours) acts as endocrine and autocrine and paracrine functions. The second pathway of calcidiol is transported practically to all other cells including cancer cells and converted by cellular1-alphaOHase to be CALCITRIOL which will mediates its biological effects by binding to the vitamin D receptor (VDR) on the nuclei that be able to turn genes on and off and influent the function of individual cells to produce certain proteins that the body need.

Calcitriol is an active form of vitamin D and act as a hormone, the most potent hormone in our body. This hormone is controlled by Hormone parathyroid hormone(PTH), as well as by it own action by stimulate another catabolic enzyme 25 hydroxy vitamin D- 24 hydroxylase(24-Ohase) or CYP24 which will breakdown calcitriol  and calcidiol into biologically inactive water soluble form called CALCITROIC ACID then excrete into the bile.

During the past 10 years the researchers have gained abundance of knowledge related to the actions of active form of vitamin D (CALCITRIOL) to our

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body and its many roles to our health. The exact mechanism of action had not been delineated completely. Here is the summary of the action of CALCITRIOL.

It has been well known that the main action of CALCITRIOL is controlling the calcium and phosphorus homeostasis along with PARATHYROID HORMONE and CALCITONIN by increasing absorption of calcium and phosphorus by the gut and reabsorption of calcium by the kidneys. Without CALCITRIOL calcium will be able to absorb by only 15 % and phosphorus by 60% with CALCITRIOL calcium will be absorbed up to 30-40% and phosphorus by 80%. CALCITRIOL also involve in bone ossification formation.

Another general function of Calcitriol and VDR is on celling proliferation, differentiation, affects the immune system. VDR are expressed in several white blood cells including monocytes and activated T and B cells.^[cell differentiation and cell apoptosis.

To learn more click

http://vitamind.ucr.edu/biochem.html
 Oregon State Infocenter

Cholecalciferol-council

http://vitamind.ucr.edu/about.html

Sunlight and Vitamin D

4. Vitamin D in Health and Disease

Today vitamin D (Cholecalciferol orD3 and Ergocalciferol orD2) and its metabolites have been found to have very important effects to our well-being. The deficiency of Vitamin D can cause varieties of medical problems including:

Adrenal insufficiency
Alzheimer's
Allergy
Fatigue
Decreased sex drive
Insomnia
Weakened immune system (autoimmune disorders)
SAD (seasonal affective disorder)
Depression, suicide
PMS (post menopausal syndrome)
Alcoholism
Infertility
Obesity
Decreased ability to pay attention or concentrate or learning disorder
Increased cravings for carbohydrates, sugar, and caffeine
Weakened, fragile bones (osteomalacia, osteoporosis)
Rickets
Cancers of the colon, breast, skin and prostate
Diabetes, Type 1 and 2 and Syndrome X
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Gluten intolerance

Heart disease, hypertension, heart failure
Heavy metal toxicity
Lecithin intolerance
Misaligned teeth and cavities
Myopia
Parkinson's
Multiple sclerosis
Psoriasis
Use of corticosteroids and more...


5.The exact action and mechanism of Vitamin D and it Receptor at the cellular level

As mentioned earlier once CALCIDIOL enter the cells of the kidneys and parathyroid hormone gland and the bone for controlling calcium, phosphorus and bone homeostasis and other cells to regulate normal function of the cells. Once enter the cells, it will be converted to be CALCITRIOL by the cellular enzyme 1-alpha OHase. The active form of vitamin D or calcitriol act as the ligand which binds to

1.VDR at the cell membrane(VDRmem) or  caveolaeVDR which perform the rapid action functions.

2. Nuclear vitamin D receptors (VDRnuc) which function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor (VDR) has hormone-binding and 6 DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor (RXR), and that heterodimer is what binds to DNA on the genes that have a vitamin D response element (VDRE) in their promoter region. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Researchers estimate that the VDR polymorphisms can regulate the expression of as many as 500 of the20488 genes in human genomes.

The extra renal CALCITRIOL is not controlled by Parathyroid hormone. The enzyme 25 hydroxy vitamin D3-24-hydroxylase (CYP24) is responsible for catabolizes cellular CALCITRIOL. This enzyme (CYP24) might be controlled by genistein from soy and by other chemicals such as folic acid.

The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1, 25-dihydroxycholecalciferol is roughly 1000 times that for 25-hydroxycholecalciferol, which explains their relative biological potencies

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Vitamin D (CALCITRIOL) and HYPERTENSION

In case of Hypertension as we know RAS (rennin- angiotensin system) control hypertension, this protein production that activated by calcitriol suppresses the rennin gene expression in the kidneys. When the rennin is low the blood pressure will return to

normal.

Vitamin D and ATHEROSCLEROSIS:

Low vitamin D increases the PTH level and bone reabsorption and cause osteomalacia in adult. The studies also showed that high PTH also increases the calcium in the artery wall and arterial cell wall proliferation as well as cardiomyocyte hypertrophy and interstitial fibrosis. Two reasons to explain these are one, the calcium is unable to deposit in the bone, secondly, low vitamin D increase inflammatory process in the arterial wall by a few processes; first vitamin D inhibits T lymphocyte to produce pro-inflammatory cytokines such as IL-6 and secondly stimulate Th2 lymphocytes that lead to a reduction of matrix metalloproteinase (MMP2, 9) and leading to reducing plaque production, thirdly vitamin D stimulate the production of anti-inflammatory cytokine IL-10. Adequate vitamin D also prevents thrombosis in mice.

Vitamin D and DIBETES MELLITUS type one and type two

In type I DM, low in vitamin D:

Type 1 DM is an autoimmune disease same as multiple sclerosis, rheumatoid arthritis, SLE, inflammatory bowel disease  and other kinds of autoimmune diseases. The mechanism is due to the over active of T cell-mediated immunity. Calcitriol stimulates transforming growth factor TGFbeta-1 and interleukin 4 (IL-4) productions which in turn may suppress inflammatory T cell activity. Calcitriol also stimulate T cells that produce anti-inflammatory interleukin-10(IL-10). The researcher found that Calcitriol along with high calcium suppress and control autoimmune diseases as well as acting as selective immunosuppressant

In type 2 DM calcitriol directly control and stimulate insulin secretion from beta cells of the pancreas

Vitamin D (calcitriol) and Cancer risk. Low vitamin D increases the risk of many kinds of cancer. The explain for this is vitamin D promote cell differentiation and cell apoptosis by a down-regulated of Bcl-2 and Bcl-X(L) proteins which protect cells from undergoing apoptosis. Vitamin D also reduces inflammation which cause cell damage and lead to cancer.

Also vitamin D can protect the cells from oxidative stress. In normal metabolism in cells generates reactive oxygen species (ROS), molecules of peroxide. High level of ROS can damage DNA and lead to cancer. Vitamin D links with gene known as G6PD (glucose-6-phosphate dehydrogenase) and increase the production of enzyme G6PD activity which will neutralize ROS. Vitamin D also prevent cancer cell to spread by reducing the activity of protease enzymes matrix metalloproteinase’s (MMP) and cathepsin

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Prostaglandins are known stimulators prostate cell growth. Calcitriol

significantly repressed the mRNA and protein expression of prostaglandin

endoperoxide synthase/cyclooxygenase-2 (COX-2), the key PG synthesis enzyme. Calcitriol also up-regulated the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme initiating PG catabolism. This dual action was associated with decreased prostaglandin E₂ secretion into the conditioned media of prostate cancer cells exposed to calcitriol. Calcitriol also repressed the mRNA expression of the PG receptors EP2 and FP, providing a potential additional mechanism of suppression of the biological activity of PGs.

Bile acid called lithocholic cid (LCA) in excess (due to eating too much fatty food which will require more bile acid to digest) claim to cause colon cancer. LCA found to activate vitamin D receptor (VDR) in cells. LCA naturally is detoxified by enzyme CYP3A. VDR also act as a sensor for high levels of LCA. When vitamin D or LCA bind to VDR will trigger the increase in expression of the gene for CYP3A. Low vitamin D level, less CYP3A enzyme produced and therefore more LCA in the colon that cause cancer.

Vitamin D and muscular system: Low vitamin D increase incident of fall due to muscular weakness the reason for this is low vitamin D reduce calcium in actin and myosin muscle cells and unable to perform it function normally.

Vitamin D and myocardial infarction: Low level of serum 25(OH)D(CALCIDIOL) are associated with higher risk of myocardial  infarction(15). As mentioned above CALCITRIOL involve and control pathogenesis of diabetes, hypertension and atherosclerosis, inflammation; the risk factors for myocardial infarction.

Vitamin D and multiple sclerosis and other autoimmune diseases: The incidence of MS is higher in the temperate zone. The reason for this is low vitamin D due to low in UVB. Low Vitamin D increases the production of chemical that causes inflammation in the brain cells related to vitamin D modulate both innate immune systems by increasing antimicrobial protein that will kill organisms that enter the cells. Also initiate the adaptive immune system either suppress pro-inflammatory T cells and stimulate anti-inflammatory T cells to produce the good cytokines as described earlier.

Vitamin D and infection: when monocytes or macrophages exposed to microbial agents such as tuberculosis. The lipopolysaccharide part of the organism will interact with the toll-like receptor that will activate the enzyme 1 alpha-hydroxylase to produce 1alpha 25 (D3)2(calcitriol) leading to induction of antimicrobial protein(microbicidal) called CATHELICIDIN and killing of intracellular organisms including influenza viruses. Also calcitriol activates T lymphocytes to produce or regulate cytokine synthesis and activate B lymphocytes to produce immunoglobulin.

Vitamin D and adipogenesis and obesity:

Vitamin D may control fat cell growth. VDR presents in adipocyte cell and play a significant role in biology ad functions; unliganded VDR is necessary for lipid accumulation and calcitriol-liganded VDR blocks adipogenesis by down- regulating both C/EBPbeta mRNA expression and C/EBPbeta nuclear protein level at the critical stage of differentiation.

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6.Vitamin D requirement

Due to many factors related to vitamin D uptake either by oral intake and vitamin D production in the skin. The blood Calcidiol level is varied greatly here is the guideline

Health Implications of Various Levels of Serum 25(OH) D

Vitamin D Deficiency <20 ng/ml or <50 nmol/L

Vitamin D Insufficiency   20-32 ng/ml or 50-80 nmol/L

Vitamin D Sufficiency   32-100 ng/ml or 80-250 nmol/L

Normal in sunny countries 54-90 ng/ml or 135-225 nmol/L

Vitamin D Excess > 100 ng/ml or >250 nmol/L

Vitamin D Intoxication > 150 ng/ml or 325 nmol/L

In 1998 the Food and nutrition board (FNB) established an AI for vitamin D that represents a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people.

Adequate Intakes (AIs) for Vitamin D

In October08 the American Academy of Pediatrics has doubled the recommended daily vitamin D intake from 200 IU to 400 IU for infants, children, and adolescents.

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Tolerable Upper Intake Levels (ULs) for Vitamin D

However during the past 10 years the researchers found out that the doses requirement of vitamin D for optimal health are higher than FNB recommended. For example

The vitamin D3 dosages for anyone should be at least 1000 IU per day.

The ideal doses of vitamin D for optimal health

Due to following factors the requirement is varied from one person to another depend on food intake and amount of sun exposure

-Age

-Sex

-Culture, habits

-Race, ethnicity

-Food

-The skin color

-Body weight

-Weather, seasons

-Geographic regions, location, latitude

The best way to find out is by measuring 25 HYDROXY VITAMIN D (CALCIDIOL). The ideal blood level at least 32ng/ml or 80 nmol/L. The optimal level is 50-70 ng/ml.

Here is the rule of thumbs for supplement depends on the baseline blood level result. Vitamin D3 (cholecalciferol) 100 IU(2.5 mcg) will increase vitamin D level 1 ng/ml,  for example if your blood level is 20 ng/ml  and you need to increase to 50 ng/ml  then you need to take vitamin D3 3000 IU/d. Based on data from the Centers of Disease Control and Prevention(CDC)  vitamin D level in the US population average level  are 15 to 35 ng/ml. The average American will need Vitamin D 20 to25 IU per pound (40 to 60 IU per kilogram).

7. The sources of Vitamin D

A. The best source is from solar ultraviolet irradiation naturally we obtain from this source 90 to 95 percent at the time

B. From food and food supplements

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-Cod Liver Oil, 1 tablespoon= 1360 IU of vitamin D

-Salmon, 3 ounces =425 IU of vitamin D

-Herring, 3 ounces =765 IU of vitamin D

-Sardine, Canned, 3 ounces =255 IU of vitamin D

-A glass of milk (fortified) 8 ounces = 100 IU of vitamin D

-A glass of juice (fortified), 6 ounces =100 IU of vitamin D

-One a day multivitamin: contain 400-1000 IU of vitamin D

-Calcium with vitamin D normally contend 200 IU per tablet

8.Vitamin D toxicity:

Symptoms related to vitamin D toxicity is related to hypercalcemia and hyperphosphatemia .These symptoms include nausea, vomiting, lost of appetite, weight lost even death. However so far there is no case report in medical literatures related to vitamin D over dose. The farmer in Puerto Rico obtained vitamin D from the sunshine had serum 25 (OH) D levels up to 90 ng/ml (225nmol/L). Total- body sun exposure easily provides the equivalent of 250 microgram (10000 IU) vitamin D/d. Doses of 10.000 IU of vitamin D3 per days for up to 5 months do not cause toxicity.

Serum 25-Hydroxyvitamin D [25(OH) D] Concentrations consistently >200 ng/ml or >500 nmol/L Considered potentially toxic, although human data are limited. In an animal model, concentrations ≤400 ng/ml (≤1,000 nmol/L) demonstrated no toxicity.

(Serum concentrations of 25(OH) D are reported in both monograms per milliliter (ng/ml) and nanomoles per liter (nmol/L).
** 1 ng/ml = 2.5 nmol/L. or 1 nmol/L= O.4 ng/ml)

So the safe upper intake level for the vitamin D3 is 10,000 IU/d

9. What is the best method to check vitamin D is 25 hydroxy vitamin D or 25(OH) D or calcidiol?

There are two vitamin D tests -- 1, 25(OH) D, and 25(OH) D.

25(OH) D is the better marker of overall D status. It is this marker that is most strongly associated with overall health.

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The normal level report by reference labs is 25-Hydroxyvitamin D Values
32-100 ng/ml or
80-250 nmol/L

The optimal level
25-Hydroxyvitamin D Values
45-50 ng/ml or
115-128 nmol/L

If you have the above test performed, please recognize that many commercial labs are using the older, dated reference ranges. The above values are the most recent ones based on large-scale clinical research findings.

There are a number of different companies that have FDA approval to perform vitamin D testing, but the gold standard is DiaSorin. Their radioimmunoassay (RIA) method for measuring total vitamin D levels has become the gold standard, not because it’s more accurate than the others, but because it’s the one used in almost every major vitamin D study, on which the recommended blood levels for clinical efficacy are based.

Therefore, in order for any other testing method to offer clinically relevant results, the test values must agree with DiaSorin RIA results, since those were used to establish the recommended levels.

Vitamin D status is measured by looking at blood levels of 25-hydroxyvitamin D3. There are three common methods used for measuring vitamin D3:

1. LC-MS/MS -- This test measures 25-hydroxyvitamin D2 and D3 separately
2. RIA (DiaSorin) -- Developed in 1985, it accurately measures total 25-hydroxyvitamin D (It does not separate D2 and D3)
3. Liaison (DiaSorin) -- a more recently developed automated immunoassay by DiaSorin that has largely replaced the RIA

The LC-MS/MS (liquid chromotatography-mass spectrometry) or HPLC(high-performance liquid chromatography) method is the preferred method for many labs, including the Mayo Clinic, Quest Labs, Esoterix, ZRT, and others, while Liaison is favored by other testing labs like LabCorp.

Since the DiaSorin assay (RIA) was used in the major clinical studies that led to the recommended vitamin D levels, any lab using the LC-MS/MS method needs to make sure their test correlates with the RIA test values in order to accurately determine your vitamin D status.

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Liaison, which is a more recently developed DiaSorin test that renders clinically accurate results, is also a much more accurate testing method for high volume throughput of tests, and does not depend as much on lab technician’s expertise.

Therefore DiaSorin test method is preferable with accurate results at reasonable cost

To learn more please log on Dr. Mercola website below

http://articles.mercola.com/sites/articles/archive/2008/09/20/warning-are-your-vitamin-d-test-results-valid.aspx?source=nl

10. Vitamin D and human longevity

Many epidemiological studies showed that increase vitamin D intake either by increase exposure to solar ultraviolet B irradiation and or increasing intake vitamin D orally in the form of   CHOLECALCIFEROL (vitamin D3) or ERGOCALCIFEROL (vitamin D2) and keep blood level of 25 HYDROXY VITAMIN D (CALCIDIOL) at least 32 ng/ml (80nmol/L) ideally close to 50 ng/ml (125nmol/L) year round will reduce all causes of mortality in general population.

Recent study on the human leukocyte telomere length (LTL) which conversely associated with chronic inflammation. They found that the people who had higher blood Calcidiol level had low C-reactive protein and longer LTL. And among the highest and the lowest Calcidiol level the length of telomere was equivalent to 5 years of aging difference.

11. Conclusion

Since the time when we moved out from the forest to the savannah in Africa over 7 million years ago, we have become stronger, taller, and smarter. People who still live in Africa have darker skin because melanin skin pigment is the best natural protection from ultraviolet radiation. The skin of people who moved away from the equator became lighter with good reason. Their skin became lighter to absorb more ultraviolet rays that the body needed (same as the plants need the sunlight for photosynthesis to survive). Almost all of our cell types have Vitamin D receptors for reasons not well understood yet.

Taking adequate amount of vitamin D is not just good for the bone health alone but also proved to keep anyone from dying prematurely from common causes such as cancers, cardiovascular diseases, diabetes mellitus type I and type II, autoimmune diseases, infection and so on. The cost of vitamin D is very reasonable.

Our government and healthcare professionals should educate the patients related to the benefit of this vitamin. I believe human longevity will be prolonged perhaps for another five years.

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VITAMIN D REFERENCES

1.      Vitamin D and Health in the 21st Century: an Update

Summary of roundtable discussion on vitamin D research needs^{1, 2, 3}

Patsy M Brannon, Elizabeth A Yetley, Regan L Bailey and Mary Frances Picciano

American Journal of Clinical Nutrition, Vol. 88, No. 2, 587S-592S, August 2008

http://www.ajcn.org/cgi/content/abstract/88/2/587S

2.      Dietary Supplement Fact Sheet: Vitamin D

Office of Dietary Supplements • National Institutes of Health

http://ods.od.nih.gov/factsheets/vitamind.asp

3.      Vitamin D Deficiency

Michael F. Holick, M.D., Ph.D.

N Engl J Med 2007; 357:1980-1982, Nov 8, 2007

http://content.nejm.org/cgi/content/full/357/19/1980

4.      Vitamin D in Health and Disease

Robert P. Heaney

Clin J Am Soc Nephrol 3: 1535-1541, 2008

http://cjasn.asnjournals.org/cgi/content/abstract/3/5/1535

5.      Benefits and Requirements of Vitamin D

For Optimal Health: A Review

William B. Grant, PhD, and Michael F. Holick, PhD, MD.

Altern Med Rev. 2005 Jun; 10(2):94-111

http://www.thorne.com/media/vitamin_d10-2.pdf

6.      25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men

A Prospective Study

Edward Giovannucci, MD, ScD; Yan Liu, MS; Bruce W. Hollis, MD, PhD; Eric B. Rimm, ScD

Arch Intern Med. 2008; 168(11):1174-1180.

http://archinte.ama-assn.org/cgi/content/short/168/11/1174

7.      Vitamin D Deficiency and Risk of Cardiovascular Disease

Thomas J. Wang MD^*, Michael J. Pencina PhD, Sarah L. Booth PhD, Paul F. Jacques DSc, Erik Ingelsson MD, PhD, Katherine Lanier BS, Emelia J. Benjamin MD, MSc, Ralph B. D’Agostino PhD, Myles Wolf MD, MMSc, and Ramachandran S. Vasan MD

January 7, 2008, doi: 10.1161/CIRCULATIONAHA.107.706127

http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.706127v1

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8.      Vitamin D Supplementation and Cardiovascular Disease Risk

Erin D. Michos, MD; Roger S. Blumenthal, MD

Circulation. 2007; 115:827-828.

http://circ.ahajournals.org/cgi/content/full/115/7/827

9.      Vitamin D: its role and uses in immunology

Deluca HF, Cantorna MT.

FASEB J. 2001 Dec;15(14):2579-85

10.  Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety^1,2

American Journal of Clinical Nutrition, Vol. 69, No. 5, 842-856, May 1999

Reinhold Vieth

http://www.ajcn.org/cgi/content/full/69/5/842

11.  Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.

Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R.

Am J Clin Nutr. 2006 Apr; 83(4):754-9.

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&uid=16600924&cmd=showdetailview&indexed=google

12.  Vitamin D in congestive heart failure^1,2

Reinhold Vieth and Samantha Kimball

American Journal of Clinical Nutrition, Vol. 83, No. 4, 731-732, April 2006

http://www.ajcn.org/cgi/content/full/83/4/731

13.  25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men

A Prospective Study

Edward Giovannucci, MD, ScD; Yan Liu, MS; Bruce W. Hollis, MD, PhD; Eric B. Rimm, ScD

Arch Intern Med. 2008; 168(11):1174-1180.

http://archinte.ama-assn.org/cgi/content/short/168/11/1174

14.  Vitamin D: A negative endocrine regulator of the rennin-angiotensin system and blood pressure. J. Steroid Biochem. Mol. Biol., 89-90:387-392

Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. (2004).

http://www.uninet.edu/cin2003/conf/cyan/cyan.html

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15.  Active Serum Vitamin D Levels Are Inversely Correlated With Coronary Calcification

Karol E. Watson, MD; Marla L. Abrolat, MD; Lonzetta L. Malone, BS; Jeffrey M. Hoeg, MD; Terry Doherty, BA; Robert Detrano, MD, PhD; ; Linda L. Demer, MD, PhD

Circulation. 1997; 96:1755-1760

http://www.circ.ahajournals.org/cgi/content/full/96/6/1755

16.  Regulation of lymphokine production and human T lymphocyte activation by 1, 25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA.

W F Rigby, S Denome, and M W Fanger

J Clin Invest. 1987 June; 79(6): 1659–1664.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=424495

17.  Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women

J Brent Richards, Ana M Valdes, Jeffrey P Gardner, Dimitri Paximadas, Masayuki Kimura, Ayrun Nessa, Xiaobin Lu, Gabriela L Surdulescu, Rami Swaminathan, Tim D Spector and Abraham Aviv

American Journal of Clinical Nutrition, Vol. 86, No. 5, 1420-1425, November 2007

http://www.ajcn.org/cgi/content/abstract/86/5/1420

18.  Vitamin D Supplementation and Total Mortality

A Meta-analysis of Randomized Controlled Trials

Philippe Autier, MD; Sara Gandini, PhD

Arch Intern Med. 2007; 167(16):1730-1737.

http://archinte.ama-assn.org/cgi/content/abstract/167/16/1730

19.  Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP.

Am J Clin Nutr. 2007 Jun; 85(6):1586-91.

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20.  An International Comparison of Vitamin D Metabolite Measurements

Mat J. M. Jongen,1Floris C. Van Ginkel,Wim J. F. van der Vijgh,2Symen Kulper,J. Coen Netelenbos,and Paul Lips

CLIN. CHEM. 30/3, 399-403 (1984)

CLINICAL CHEMISTRY, Vol. 30, No. 3, 1984 399

http://www.clinchem.org/cgi/reprint/30/3/399?ijkey=6e7a769192ad7d6d2975cd58e38bdb62697dc49e

21.  Vitamin D and bone health in the elderly

A Michael Paı/utt,’ MB, BChir, JC Gallagher, 2 MD, Robert P Heaney, 3 MD,

CC Johnston, MD, Robert Neer, 5 MD, and G Donald Whedon, 6 MD

American Journal of Clinical Nutrition, Vol 36, 1014-1031

http://www.ajcn.org/cgi/reprint/36/5/1014?ijkey=6eb1f4d54dbfaec01a75c67c3a6c31ade0ef3ff1

22.  Regulation of Prostaglandin Metabolism by Calcitriol Attenuates Growth Stimulation in Prostate Cancer Cells

Jacqueline Moreno¹, Aruna V. Krishnan¹, Srilatha Swami¹, Larisa Nonn², Donna M. Peehl² and David Feldman¹

Cancer Research 65, 7917-7925, September 1, 2005

http://cancerres.aacrjournals.org/cgi/content/abstract/65/17/7917

23.  Lithocholic acid can carry out in vivo functions of vitamin D

Jamie A. Nehring*, Claudia Zierold^†, and Hector F. DeLuca*,^‡

PNAS June 12, 2007 vol. 104 no. 24 10006-10009

http://www.pnas.org/content/104/24/10006.full

24.  Prevention of Rickets and Vitamin D

Deficiency in Infants, Children, and Adolescents

Carol L. Wagner, MD, Frank R. Greer, MD, and the Section on Breastfeeding and Committee on Nutrition

http://www.aap.org/new/VitaminDreport.pdf

25.  Vitamin D Protects Cells from Stress That Can Lead to Cancer

http://www.urmc.rochester.edu/pr/news/story.cfm?id=1985

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26.  1 ,25-dihydroxyvitamin D₃ inhibits prostate cancer cell invasion via modulation of selective proteases

Carcinogenesis 2006 27(1):32-42; doi:10.1093/carcin/bgi170

Bo-Ying Bao ^1, 2,  , Shauh-Der Yeh ^3,  and Yi-Fen Lee ^1, *

http://carcin.oxfordjournals.org/cgi/content/abstract/27/1/32

27.  Complex Role of the Vitamin D Receptor and Its Ligand in Adipogenesis in 3T3-L1 Cells^*

J. Biol. Chem., Vol. 281, Issue 16, 11205-11213, April 21, 2006

Jeffrey M. Blumberg, Iphigenia Tzameli, Inna Astapova, Francis S.                                          Lam, Jeffrey S. Flier, and Anthony N. Hollenberg¹

http://www.jbc.org/cgi/content/abstract/281/16/11205

28.  Warning: Are Your Vitamin D Test Results Valid?

http://articles.mercola.com/sites/articles/archive/2008/09/20/warning-    are-your-vitamin-d-test-results-valid.aspx?source=nl

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Revised 11/07/08