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| Photo by Brooke Cagle on Unsplash |
* Anorexia nervosa was a fad in the 1960s and 1970s in California. Hippies were often thin and wore Bohemian-styled clothes. They probably suffered from severe acidosis and osteomalacia and vitamin D deficiency.
* In many poor communities, children do not receive adequate nutritious food. Often, young children had big heads and tummies and bowed legs. Children developed rickets due to malnutrition.
* In the modern world where mothers work, babies and toddlers are left at nurseries. Nurseries can leave the children in walkers for long periods. This adds burden to tiny legs, which will eventually bow as the bones are still soft to bear the body's weight.
* Cancer has become quite common today worldwide. Apart from the effects of the atomic bombing of Hiroshima and Nagasaki, and the Bopal carbide disaster, there is breast cancer, colon cancer, bone cancer, brain tumour, pancreatic cancer, prostate cancer and many other cancers which have afflicted many people, young and old.
* Researchers have tried creating vitamin D analogues for use in alternative cancer therapy. However, lack of evidence-based medicine has plagued its acceptance and adoption for widespread use for otherwise prospective cancer sufferers.
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Precursors of vitamin D
- cholesterol
- 7-dehydrocholesterol (7-DHC)
- pre-D3
Forms of vitamin D
- Vitamin D3 (cholecalciferol, made by skin via UV light) ... found in fish
- Vitamin D2 (ergocalciferol, derived from plant sterol ergosterol) ... used for food fortification ... a vitamin D analogue
- 25-hydroxyvitamin D (25OHD)
- 1,25-dihydroxyvitamin D (1,25(OH)2D) ... active form, a hormone
Enzymes in vitamin D metabolism
- CYP2R1 (25-hydroxylase)
- CYP27B1 (1-hydroxylase)
- CYP24A1 (catabolism)
- 3-epimerase
- CYP11A1
CYP2R1 is the most important 25-hydroxylase.
CYP27B1 is the key 1-hydroxylase.
Both 25OHD and 1,25(OH)2D are catabolised by CYP24A1.
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Sources of vitamin D
- Vitamin D3 is made in the skin from 7-dehydrocholesterol with exposure to UV light
- Vitamin D2 (ergocalciferol) is derived from ergosterol, a plant sterol
Production of vitamin D
The production of vitamin D3 (D3) in the skin is not an enzymatic process but requires UV light from sunshine. Both UVB intensity and skin pigmentation level contribute to the rate of D3 formation.
* Exposure of the skin to sunshine in the morning for 15 minutes daily is sufficient for vitamin D production. Babies can also be exposed to the soft sun-rays in the morning for this purpose.
D3 (cholecalciferol) is produced from 7-dehydrocholesterol (7-DHC) through a two-step process in which the B ring is broken by UV light (spectrum 280–320 UVB) radiation from sunshine, forming pre-D3 that isomerizes to D3 in a heat-sensitive but non enzymatic (non catalysed) process.
* Melanin in the skin blocks UVB from reaching 7-DHC, thus limiting D3 production. However, Blacks have large amount of melanin in their skin and yet have good strong bones. Kareem Abdul-Jabbar is a tall, dark and handsome successful famous professional basketball player who played for the National Basketball Association (NBA), USA.
* Sun-screens are worn for sun bathing or when spending time outdoors as they block sunshine and prevent sunburn, which is painful. Even with sun-screen, basking is limited as sun bathing gives headaches and migraine from excessive UV irradiation.
* Clothing also blocks sunshine from reaching the skin, but not completely. Women who wear thick clothing as a jacket, such as the abaya or jubah, are thought to lack vitamin D or suffer from vitamin D deficiency. This is untrue. These women only wear such long protective jacket when they go out in public, ie for a short time only. They do not wear such clothing at home. This misconception should be corrected among Western researchers and professors.
The intensity of UVB from sunlight varies according to season and latitude. The further one lives from the equator, the less time of the year one can rely on solar exposure to produce D3.
* The Incas of Bolivia live in the highlands of the Andes where the air is thin. They rely on chewed coca leaves or coca drink before climbing to such heights and avoiding dizziness and vomiting. They are exposed to strong levels of UV radiation. La Paz is heavily polluted with brown industrial smog as a result of thinning of the ozone layer and high ozone chemical activity.
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| Inca women in Copacabana, Lake Titicaca shore, Bolivia 30 Sept 2018. Courtesy of Noraini Ismail and her travel buddies. Copacabana is on the shore of Lake Titicaca at 3,841 m (12,602 ft) above sea-level. |
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| Highest navigable lake with surface elevation of 3,812 m (12,507 ft) above sea-level. Reed boats of the Incas at Lake Titicaca, Bolivia 30 Sept 2018. Courtesy of Noraini Ismail. |
***
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| Highest capital city at 3,640 m (11,942 ft) above sea-level. Entering La Paz by coach, Bolivia 30 Sept 2018. Courtesy of Noraini Ismail. |
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| Highest capital city, La Paz skyline, Bolivia 30 Sept 2018. Courtesy of Noraini Ismail. |
* People who live in the equator have full exposure to sunshine for at least eight hours a day. They have good dentition, dark skin and strong bones. The sea Bajau of Semporna, Sabah (in Borneo) spend a lot of time at sea. They are a great example of sufficient vitamin D intake and exposure to sunshine.
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| Bajau boy, Semporna, Sabah. Photo by Logan Lambert on Unsplash |
* Apart from the skin, vitamin D can also be obtained from the diet such as milk, liver and eggs.
* Most natural and processed foods, with the exception of freshwater fatty fish (eg ikan patin), contain little vitamin D unless fortified. The Incas consume freshwater trout from Lake Titicaca as a source of EFAs and vitamin D. They have thus good strong bodies.
* The vitamin D in fish is D3, whereas that used for fortification of processed ingredients (eg milled white all-purpose flour) and foodstuff (eg milk, bread, cornflakes, biscuits) is often D2 (ergocalciferol). Many native communities consume fish as a protein and vitamin D source. Fast food outlets offer fish fillet.
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| Amazon 14 Sept 2018 |
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| Brazil 14 Sept 2018 |
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| Rio de Janeiro, Brazil 17 Sept 2018 |
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| Trout at Copacabana from Lake Titicaca, Bolivia 30 Sept 2018 All photos of fish above are courtesy of Noraini Ismail. |
* Phytosterols compete with cholesterol for absorption in the small intestines. When we eat vegetables, phytosterols are preferentially absorbed, and less cholesterol is absorbed. It is therefore advisable to eat vegetables when eating steak and meat dishes.
D2 is produced by UVB irradiation of the ergosterol in plants and fungi (e.g., mushrooms).
* Algae grow to confluence in freshwater. They are a good source of essential fatty acids (EFAs). Seaweeds grow in seawater and are used for making jellies, which can withstand hot temperatures of the equatorial countries.
* Mushrooms, papaya, mangoes and beansprouts are good for encouraging fertility in otherwise barren women.
* Structure-wise, vitamin D resembles cholesterol but with many hydroxyl groups. D2 differs from D3 in having a double bond (C=C) between C22 and C23 and a methyl group (CH3) at C24 in the side chain.
* Since D2 is structurally and chemically different from the active form of vitamin D, D2 can be considered a natural analogue of bioactive vitamin D.
These differences from D3 in the side chain lower its affinity for vitamin D binding protein (DBP), resulting in faster clearance from the circulation, and limit its conversion to 25-hydroxyvitamin D (25OHD) by at least some of the 25-hydroxylases, and alter its catabolism by the 24-hydroxylase (CYP24A1).
Unless given daily, D2 supplementation does not result in as high a blood level of 25OHD as comparable amounts of D3.
On the other hand, 1,25(OH)2D2 and 1,25(OH)2D3 have comparable affinities for the vitamin D receptor (VDR).
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Metabolism of vitamin D
Once it is made under the skin, vitamin D is metabolised first to 25-hydroxyvitamin D (25OHD) in the liver, then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D) in the kidneys.
Vitamin D is transported in blood by a vitamin D binding protein (DBP).
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Vitamin D receptor
The vitamin D receptor (VDR) is found in nearly every tissue except in rbcs (anucleated)
VDR is located in the nucleus and is found in almost all nucleated cells.
1,25(OH)2D is the ligand for the vitamin D receptor (VDR).
1,25(OH)2D is a transcription factor. It binds to sites in the DNA called vitamin D response elements (VDREs).
There are thousands of VDR binding sites throughout the genome, and they regulate hundreds of genes in a cell-specific fashion.
VDR-regulated transcription is dependent on co-modulators, the profile of which is also cell specific.
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External links
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968073/
https://www.ncbi.nlm.nih.gov/pubmed/21197695
https://www.nature.com/articles/s12276-018-0038-9.pdf
https://medschool.ucr.edu/faculty_research/faculty_profiles/norman_anthony
https://www.researchgate.net/figure/Vitamin-D-synthesis
https://www.nature.com/articles/nrc2196/figures/1
https://www.nature.com/articles/srep37593/figures/1
https://www.semanticscholar.org/paper/Vitamin-D
https://www.researchgate.net/figure/Vitamin-D-metabolism_fig1
http://www.biochemj.org/content/441/1/61.figures-only
https://www.researchgate.net/figure/Overlay-of-the-systemic-phosphate-homeostasis-with-the-major-players-in-the-phosphate_fig2
https://www.pinterest.com/pin/565905509402816520/?lp=true
https://www.researchgate.net/figure/Photochemical-synthesis-of-vitamin-D-and-main-target-tissues-Classical-pathway-of_fig2
https://www.semanticscholar.org/paper/Vitamin-D Metabolism-Molecular-Mechanism
https://www.researchgate.net/figure/Direct-and-indirect-effects-of-vitamin-D-on-muscle-Data-on-direct-effects-come_fig4
https://www.mdpi.com/1422-0067/18/10/2184
http://acuarios-self-help-health-wellness.blogspot.com/2012/11/vitamin-d.html
http://www.revistanefrologia.com/en-publicacion-nefrologia-articulo-vitamin-d-vitamin-d-receptor-importance-its-activation-in-patients
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