Charles Darwin

"The love for all living creatures is the most noble attribute of man." Charles Darwin

Wednesday, June 24, 2015

Vitamin D: The Sunshine Vitamin






I remember there was this one time, during a dinner at my in-law's home, many years ago, when I stood listening as my father-in-law said: “If science could cure one thing, rickets should be the first.”  

A stark, confused silence filled the room as everyone within hearing range attempted to gauge whether or not he was being serious (he is a rather serious kind of man). 

Though in our blink of confusion, not one amongst us was willing to give voice to the words we were all thinking (or more precisely, the tone in which they were being thought), although they must have read plainly on our expressions in variations of: ‘Uh, they have already, Phil, it’s called fortified milk.’

Still, one must be respectful, yes? After all, it isn't always what people say so much as what motivated them to say it. Maybe rickets was a serious problem for lads growing up in post-war Guildford; and maybe he was left scarred by some childhood memory; or maybe, in his profound insight, he had glimpsed the forthcoming (now present) age of dietary intolerance and SPF 15. It wouldn’t surprise me, he is a rather insightful kind of man.



Without ever giving much thought as to why, I have always taken cod liver oil pills. My mom told me they were good for me and I believed her. 

Mind you, she also enjoyed puncturing open the capsules in her mouth and savoring the yummy cod liver oil flavor, which should have made me a little suspicious of her sound judgement.

What I have since learned (since, as in this past week) is that when it comes to vitamin D (or any vitamin for that matter) it is important to remember that it is intended to act as a dietary supplement; as in, only take as required, and preferably with your physician’s prior knowledge.

And to never blindly accept translucent amber pills from someone who actually enjoys the taste of cod liver oil, even if she is your mom. 



Vitamin D3
VITAMIN D is the name given to a group of fat-soluble prohormones. [63][11]

The most important compounds in this group are vitamin D3 and vitamin D2. [12]

Both of which are converted to 25-hydroxyvitamin D (calcidiol) in the liver, and then further modified in the kidneys to 1,25-dihydroxyvitamin D (calcitriol).

Calcitriol, the biologically active form of vitamin D [13] circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth of bone. Calcitriol also affects neuromuscular and immune function. [14]



Vitamin D production is greatest in two innermost strata of the 

epidermis, the stratum basale and the stratum spinosum.
Vitamin D3 is produced photochemically within our skin when exposed to sunlight (specifically UVB radiation). [2][58][63][11]

    Adequate amounts of vitamin D can be produced with moderate sun exposure to the face, arms and legs, averaging 5–30 minutes twice per week without sunscreen. [59][60][31]










    Sunscreen with an SPF of 15 based on the UVB spectrum has been reported to decrease vitamin D synthetic capacity by 98%. [62] (SVP do NOT take this to mean you should stop wearing sunscreen in general!)



    DIETARY SOURCES OF VITAMIN D INCLUDE:
    • Fortified foodstuffs, such as: dairy, juices and cereals;
    • Shiitake Mushrooms, Portobello Mushrooms, and alfalfa shoot;  [3,4]
    • Cod liver oil, oily fish (eg: salmon, mackerel, tuna, sardines, trout) eggs, and beef liver. [3]
    • In terms of cooking, vitamin D is not entirely heat stable. [6]

    Source: webmd.com




    The Institute of Medicine (IOM) has developed the following recommended daily allowances (RDA) of vitamin D, assuming minimal sun exposure: [63, 75-76]





    VITAMIN D DEFICIENCY


    • A normal level is 20-50 ng/mL, deficiency is considered anything less than 20 ng/mL, and a vitamin D level greater than 50 ng/mL is considered high.


    • Getting tested for vitamin D deficiency makes sense if you have osteoporosis, or a disorder such as kidney disease that affects your ability to make the active form of vitamin D, or intestinal malabsorption caused by medications or conditions such as celiac disease. [79] (This is not a comprehensive list, but you get the idea.)

    • A diet deficient in vitamin D in conjunction is known to cause rickets in children and osteomalacia in adults. [21][22]


    • Rickets can be caused by calcium or phosphorus deficiency, as well as (though not solely due to) a lack of vitamin D. [24][25]  
    • It is characterized by bowing of the legs due to softening of the bones. [23]
    • Today, it is largely found in developing countries, [26] in children with genetic disorders such as pseudo-vitamin D deficiency rickets, [27] as well as within some Aboriginal populations.
    • Hedy Fry, a physician and the former head of the British Columbia Medical Association, points to an increase in the cases of rickets among Aboriginal children, with a rate four to five times higher than the national average, and says the dietary shift away from cold-water fish—which is rich in vitamin D—to a more typical Western diet is the cause. [5]


    • Osteomalacia is a disease which reduces calcium absorption and increases calcium loss from bone in adults. 
    • It is characterized by softening of the bones, leading to bending of the spine, bowing of the legs, proximal muscle weakness, bone fragility, and increased risk for fractures. [28]
    • Osteomalacia is usually present when 25-hydroxyvitamin D levels are less than about 10 ng/mL. [12] 

    The role of vitamin D in Ca2+ regulation is shown in orange.




    VITAMIN D TOXICITY

    • Hypervitaminosis D, (vitamin D toxicity) is rare. [31][40-42]
    • In healthy adults, sustained intake of more than 1250 μg/day (50,000 IU) can produce overt toxicity after several months and can increase serum 25-hydroxyvitamin D levels to 150 ng/ml and greater. [31][32]
    • Those with certain medical conditions, such as primary hyperparathyroidism, [33] (overactivity of the parathyroid glands which control the bodies' Ca2+ levels [29]) are far more sensitive to vitamin D and develop hypercalcemia (elevated Ca2+ level in the blood [30]) in response to any increase in vitamin D nutrition.
    • If hypercalcemia is not treated, it results in excess deposits of calcium in soft tissues and organs such as the kidneys, liver, and heart, resulting in pain and organ damage. [31][34][35]

    •  In this randomized, placebo controlled trial,163 women (aged 57 to 90) took calcium citrate tablets to meet their recommended intake of 1,200 mg/day. They also took various doses of vitamin D, ranging from 400 to 4,800 IU/day.
    • About 9% of participants developed hypercalcemia, and 31% developed excess levels of calcium in their urine (hypercalciuria). [57][58]

    • Maternal hypercalcemia during pregnancy may increase fetal sensitivity to effects of vitamin D and lead to a syndrome of mental retardation and facial deformities. [36][37]

    • Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity. The concentrations of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D produced is degraded. [33]



    THE RESEARCH


    Dietary Fat Increases Vitamin D-3 Absorption

    Dawson-Hughes et al (2014) found that, 
    "The presence of fat in a meal with which a vitamin D-3 supplement is taken significantly enhances absorption of the supplement." [9][10]


    Vitamin D and childhood obesity

    • In this 2010 study, researchers tracked the vitamin D levels, BMI, waist circumference and subscapular-to-triceps skin fold ratio in school children, aged 5-12 over a period of 2.5 years and found low levels of vitamin D to be a likely risk factor in childhood obesity. [8]



    Cardiovascular Disease

    • According to the findings of this meta-analysis of existing randomized controlled trials, the taking of vitamin D supplements with or without calcium may reduce the risk of stroke, cerebrovascular disease, cardial infarction, or ischaemic heart disease by no more than 15%. [43] 
    • Supplementation has no effect on blood pressure. [44] 



    Cognition and Dementia [45][46]

    • In this 2014 study, researchers found that participants who were severely vitamin D deficient were more than twice as likely to develop dementia and Alzheimer's disease.

    • The study looked at 1,658 adults aged 65 and over, who were able to walk unaided and were free from dementia, cardiovascular disease and stroke at the start of the study. The participants were then followed for six years to investigate who went on to develop Alzheimer's disease and other forms of dementia.
    "Clinical trials are now needed to establish whether eating foods such as oily fish or taking vitamin D supplements can delay or even prevent the onset of Alzheimer's disease and dementia. We need to be cautious at this early stage and our latest results do not demonstrate that low vitamin D levels cause dementia.”

    • The study also found evidence to confirm that vitamin D levels above 50 nmol/L are most strongly associated with good brain health.



    Infectious Disease

    • Low levels of Vitamin D have been associated with an increased risk of both viral (HIV and Influenza) and bacterial infections (TB). This is believed to be because of the role vitaminD3 plays in autophagy. [47-50][79]



    Pregnancy

    • Low levels of vitamin D in pregnancy are associated with gestational diabetes, pre-eclampsia, and "small for gestational age infants." [51] 



    Cancer
    "Early epidemiologic research showed that incidence and death rates for certain cancers were lower among individuals living in southern latitudes, where levels of sunlight exposure are relatively high, than among those living at northern latitudes. 
    Because exposure to ultraviolet light from sunlight leads to the production of vitamin D, researchers hypothesized that variation in vitamin D levels might account for this association." [63]

    • In studies of cancer cells and of tumors in mice, vitamin D has been found to have several activities that might slow or prevent the development of cancer, including promoting cellular differentiation, decreasing cancer cell growth, stimulating cell death (apoptosis), and reducing tumor blood vessel formation (angiogenesis) [63-67]


    "Certain cancers and immune dysfunctions are strongly associated with vitamin D deficiency." [5]


    • In this 2010 study, researchers found that patients with insufficient vitamin D levels at the time of being diagnosed with chronic lymphocytic leukemia were 66% more likely to suffer worsening condition and require chemotherapy when re-assessed for the study 3 three years later. [7]

    • Numerous epidemiologic studies have shown that higher intake or blood levels of vitamin D are associated with a reduced risk of colorectal cancer. [63] [68-71]

    But not all ...


    • In this 2013 systematic review[39] researchers found that intervention studies did not show an effect of vitamin D supplementation on colorectal cancer occurrence. 
    • To explain the consistent association of low vitamin D status with disease states, the authors suggest that inflammatory processes and clinical treatments may be responsible for the reduced 25-hydroxyvitamin D levels.

    • Taken all together, the data currently available are not comprehensive enough to establish whether taking vitamin D supplements have a preventive effect on the development of cancer. [63][73] 

    Cancer Studies Currently Underway
    "The VitaminD/Calcium Polyp Prevention Study is testing whether vitamin D supplements, given alone or with calcium, can prevent the development of colorectal  adenomas  (precancerous growths) in patients who previously had an adenoma removed. The study’s estimated completion date is December 2017." [63][78]

    "The Vitamin D and Omega-3 Trial  (VITAL) is an ongoing research study in 25,875 men and women across the U.S. investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk for developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses." [63][74][77]


    Autoimmune Diseases [54]

    • Deficiencies of vitamin D interfere with D-cell (dendrites) function and contribute to autoimmunity.
    • That said, vitamin D deficiency in patients with autoimmune disease may be a result rather than a cause of disease. 


    Multiple Sclerosis

    • "Multiple sclerosis (MS) is thought to arise due to an interplay of genetic and environmental risk factors." [53]
    • Low vitamin D has been shown to be one such environmental risk factor. [52][53]
    • Research suggests that a connection between vitamin D and MS could be tied to the positive effects vitamin D has on the immune system. [53]
    • The link between vitamin D and MS is strengthened by the association between sunlight and the risk of MS. The farther away from the equator a person lives, the higher the risk of MS. [52]
    • As well, populations with a high oral intake of vitamin D have a decreased risk of MS. [53]


    Cholesterol in Post-menopausal Women [55][56]


    • This 2014 study found that supplemental intake of both calcium and vitamin D in post-menopausal women significantly increased 25-hydroxyvitamin D concentrations.
    • And that this led to more favorable lipid profiles, including increased HDL cholesterol (good cholesterol), lower LDL cholesterol (bad cholesterol), and lower triglycerides.




    Vitamin D and its Beneficial Effects on Various Disease States

    • Beyond its benefit for bone health and the prevention of rickets, the evidence for other health benefits in the general population is inconsistent. [15-17][38]




    • A University of Edinburgh 2014 review of vitamin D and its effects on 137 health outcomes, including: skeletal, malignant, cardiovascular, autoimmune, infectious and metabolic diseases, found the only effect of statistical significance was maternal vitamin D status and birth weight:
     "On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. 
    In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people.” [57]









    • Land vertebrates have been making their own vitamin D for more than 350 million years. [1]
    • In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the feathers or fur and is obtained orally during grooming. [61]






    ***
    FIN

















    REFERENCES

    [1] Holick MF (2011). The Vitamin D Solution: A 3-Step Strategy to Cure Our Most Common Health Problems. New York: Plume. p. 27. ISBN 0-452-29688-9.
    [2] Crissey SD, Ange KD, Jacobsen KL, Slifka KA, Bowen PE, Stacewicz-Sapuntzakis M, Langman CB, Sadler W, Kahn S, Ward A; Ange; Jacobsen; Slifka; Bowen; Stacewicz-Sapuntzakis; Langman; Sadler; Kahn; Ward (2003). "Serum concentrations of lipids, vitamin D metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos". The Journal of nutrition 133 (1): 160–6.PMID 12514284.
    [3] "Search, National Nutrient Database for Standard Reference Release 27". US Department of Agriculture, Agricultural Research Service. 2014. 
    [4] Duke J. "Dr. Duke's Phytochemical and Ethnobotanical Databases". U.S. Agricultural Research Service.
    [6] Jakobsen, Jette; Knuthsen, Pia. "Stability of vitamin D in foodstuffs during cooking".Food Chemistry 148: 170–175. doi:10.1016/j.foodchem.2013.10.043. Retrieved 30 April2015.
    Blood First Edition Paper, prepublished online November 3, 2010; DOI 10.1182/blood-2010-07-295683
    [10] Source: Dawson-Hughes B, Harris SS, Lichtenstein AH, Dolnikowski G, Palermo NJ, and Rasmussen H. Dietary Fat Increases Vitamin D-3 Absorption. Journal of the Academy of Nutrition and Dietetics. 2014.
    Journal of the American Academy of Nutrition and Dietetics (Impact Factor: 2.44). 11/2014; 115(2). DOI: 10.1016/j.jand.2014.09.014
    Source: PubMed
    Dietary Fat Increases Vitamin D-3 Absorption - ResearchGate. Available from: http://www.researchgate.net/publication/270653238_Dietary_Fat_Increases_Vitamin_D-3_Absorption
    [11] https://en.wikipedia.org/?title=Vitamin_D
    [12] Holick MF (March 2006). "High prevalence of vitamin D inadequacy and implications for health". Mayo Clin. Proc. 81 (3): 353–73. doi:10.4065/81.3.353.PMID 16529140.
    [13] Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ (1971). "Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine".Biochemistry 10 (14): 2799–804. doi:10.1021/bi00790a023PMID 4326883.
    [14] "Dietary Supplement Fact Sheet: Vitamin D". Office of Dietary Supplements (ODS).National Institutes of Health (NIH).
    [15] Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, Lichtenstein AH, Lau J, Balk EM; Chung; Trikalinos; Mitri; Brendel; Patel; Lichtenstein; Lau; Balk (Mar 2010)."Vitamin D and Cardiometabolic Outcomes: A Systematic Review". Annals of internal medicine 152 (5): 307–14. doi:10.7326/0003-4819-152-5-201003020-00009.PMC 3211092PMID 20194237.
    [16] Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, Lichtenstein A, Patel K, Raman G, Tatsioni A, Terasawa T, Trikalinos TA; Balk; Brendel; Ip; Lau; Lee; Lichtenstein; Patel; Raman; Tatsioni; Terasawa; Trikalinos (August 2009). "Vitamin D and calcium: a systematic review of health outcomes". Evidence report/technology assessment (183): 1–420. PMID 20629479.
    [17] Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (January 2011). "The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know". J. Clin. Endocrinol. Metab. 96 (1): 53–8. doi:10.1210/jc.2010-2704PMC 3046611.PMID 21118827.
    [18] Holick, MF; Deluca, HF; Avioli, LV (1972). "Isolation and identification of 25-hydroxycholecalciferol from human plasma". Archives of Internal Medicine 129 (1): 56–61.doi:10.1001/archinte.1972.00320010060005PMID 4332591.
    [19] Bender, David A.; Mayes, Peter A (2006). "Micronutrients: Vitamins & Minerals". In Victor W. Rodwell; Murray, Robert F.; Harper, Harold W.; Granner, Darryl K.; Mayes, Peter A. Harper's Illustrated Biochemistry. New York: Lange/McGraw-Hill. pp. 492–3. ISBN 0-07-146197-3
    [21] "Rickets"National Health Service. March 8, 2012.
    [23]  Brown JE (2008). Nutrition through the life cycle. Belmont, CA: Thomson/Wadsworth. ISBN 0-495-11637-8.
    [24] Oramasionwu GE, Thacher TD, Pam SD, Pettifor JM, Abrams SA (2008). "Adaptation of calcium absorption during treatment of nutritional rickets in Nigerian children". The British journal of nutrition 100 (2): 387–92. doi:10.1017/S0007114507901233.PMID 18197991.
    [25] Fischer PR, Rahman A, Cimma JP, Kyaw-Myint TO, Kabir AR, Talukder K, Hassan N, Manaster BJ, Staab DB, Duxbury JM, Welch RM, Meisner CA, Haque S, Combs GF (1999). "Nutritional rickets without vitamin D deficiency in Bangladesh". Journal of tropical pediatrics 45 (5): 291–3. doi:10.1093/tropej/45.5.291PMID 10584471.
    [26] Lerch C, Meissner T (2007). Lerch, Christian, ed. "Interventions for the prevention of nutritional rickets in term born children". Cochrane database of systematic reviews (Online)(4): CD006164. doi:10.1002/14651858.CD006164.pub2PMID 17943890.
    [27] Zargar AH, Mithal A, Wani AI, Laway BA, Masoodi SR, Bashir MI, Ganie MA (June 2000). "Pseudovitamin D deficiency rickets—a report from the Indian subcontinent".Postgraduate Medical Journal 76 (896): 369–72. doi:10.1136/pmj.76.896.369.PMC 1741602PMID 10824056.
    [28]  Insel PM, Turner ER, Ross D (2006). Discovering nutrition (2nd ed.). Boston: Jones and Bartlett Publishers. ISBN 0-7637-3555-8.
    [29] https://en.wikipedia.org/wiki/Hyperparathyroidism
    [31] Holick MF (July 2007). "Vitamin D deficiency". N. Engl. J. Med. 357 (3): 266–81. doi:10.1056/NEJMra070553PMID 17634462.
    [32] Vitamin D at Merck Manual of Diagnosis and Therapy Professional Edition
    [33] Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, Li P, Davidson KW (2014). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety" (PDF). The American Journal of Clinical Nutrition 76 (3): 190–6.doi:10.1097/psy.0000000000000044PMID 24632894.
    [34] Brown JE (2008). Nutrition through the life cycle. Belmont, CA: Thomson/Wadsworth. ISBN 0-495-11637-8.
    [35] Insel PM, Turner ER, Ross D (2006). Discovering nutrition (2nd ed.). Boston: Jones and Bartlett Publishers. ISBN 0-7637-3555-8.
    [36] Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, Li P, Davidson KW (2014). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety" (PDF). The American Journal of Clinical Nutrition 76 (3): 190–6.doi:10.1097/psy.0000000000000044PMID 24632894.
    [38] Tseng L, Brehm, JM, Alcorn, JF, Holguín, F, Aujla, SJ, Celedón, JC (2003)."Controversies in Vitamin D Supplementation". Nutrition Bytes 9 (1).
    [39] Autier P, Boniol M, Pizot C, Mullie P; Boniol; Pizot; Mullie (December 2013). "Vitamin D status and ill health: a systematic review". The Lancet Diabetes & Endocrinology 2: 76. doi:10.1016/S2213-8587(13)70165-7.
    [40] Dudenkov, Daniel V. et al. Changing Incidence of Serum 25-Hydroxyvitamin D Values Above 50 ng/mL: A 10-Year Population-Based Study Mayo Clinic Proceedings. Volume 90, Issue 5 , 577 – 586.
    [41]  Holick, Michael F. (May 2015) Vitamin D Is Not as Toxic as Was Once Thought: AHistorical and an Up-to-Date Perspective. Mayo Clinic Proceedings, Volume 90 , Issue 5 , 561 – 564.
    [43] Bolland MJ, Grey A, Gamble GD, Reid IR (January 2014). "The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis" Lancet Diabetes Endocrinol (Meta-analysis). doi:10.1016/S2213-8587(13)70212-2.
    [44] Beveridge, Louise A.; Struthers, Allan D.; Khan, Faisel; Jorde, Rolf; Scragg, Robert; Macdonald, Helen M.; Alvarez, Jessica A.; Boxer, Rebecca S.; Dalbeni, Andrea; Gepner, Adam D.; Isbel, Nicole M.; Larsen, Thomas; Nagpal, Jitender; Petchey, William G.; Stricker, Hans; Strobel, Franziska; Tangpricha, Vin; Toxqui, Laura; Vaquero, M. Pilar; Wamberg, Louise; Zittermann, Armin; Witham, Miles D. (16 March 2015). "Effect of Vitamin D Supplementation on Blood Pressure". JAMA Internal Medicine.doi:10.1001/jamainternmed.2015.0237.
    [45] Thomas J. Littlejohns, William E. Henley, Iain A. Lang, Cedric Annweiler, Olivier Beauchet, Paulo H.m. Chaves, Linda Fried, Bryan R. Kestenbaum, Lewis H. Kuller, Kenneth M. Langa, Oscar L. Lopez, Katarina Kos, Maya Soni, and David J. Llewellyn. Vitamin D and the risk of dementia and Alzheimer disease. Neurology, August 2014 DOI:10.1212/WNL.0000000000000755
    [46] University of Exeter. "Link between vitamin D, dementia risk confirmed." ScienceDaily. ScienceDaily, 6 August 2014. <www.sciencedaily.com/releases/2014/08/140806161659.htm>.
    [47] Beard JA, Bearden A, Striker R (Mar 2011). "Vitamin D and the anti-viral state". Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology50 (3): 194–200. doi:10.1016/j.jcv.2010.12.006PMC 3308600PMID 21242105.
    [48] Spector SA (Feb 2011). "Vitamin D and HIV: letting the sun shine in". Topics in antiviral medicine 19 (1): 6–10. PMID 21852710.
    [49] Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E (2006). "Epidemic influenza and vitamin D". Epidemiology and Infection134 (6): 1129–40. doi:10.1017/S0950268806007175PMC 2870528.PMID 16959053.
    [50] Nnoaham KE, Clarke A (Feb 2008). "Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis". International Journal of Epidemiology 37 (1): 113–9.doi:10.1093/ije/dym247PMID 18245055.
    [51]  Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O'Beirne M, Rabi DM (2013). "Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies". BMJ346: f1169. doi:10.1136/bmj.f1169PMID 23533188.
    Int J Appl Basic Med Res. 2011 Jul-Dec; 1(2): 71–74.doi:  10.4103/2229-516X.91146 PMCID: PMC3657971
    [54] [52] Dr. Manole Cojocaru et al. ASSOCIATION BETWEEN VITAMIN D DEFICIENCY AND AUTOIMMUNE DISEASES REVISTA MEDICALÅ ROMÂNÅ – VOLUMUL LXI, NR. 1, An 2014.
    [56] The North American Menopause Society (NAMS). "Calcium, vitamin D improve cholesterol in postmenopausal women." ScienceDaily. ScienceDaily, 5 March 2014. <www.sciencedaily.com/releases/2014/03/140305125307.htm>.
    [57] John Christopher Gallagher, Lynette M. Smith, Vinod Yalamanchili. Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women. Menopause, 2014; 1 DOI: 10.1097/GME.0000000000000270
    [58] The North American Menopause Society (NAMS). "Supplements of calcium, vitamin D may have too much for some older women." ScienceDaily. ScienceDaily, 18 June 2014. <www.sciencedaily.com/releases/2014/06/140618072045.htm>.
    [59] Theodoratou Evropi, Tzoulaki Ioanna, Zgaga Lina,Ioannidis John P A. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials 2014; 348 :g2035
    [60] Crissey SD, Ange KD, Jacobsen KL, Slifka KA, Bowen PE, Stacewicz-Sapuntzakis M, Langman CB, Sadler W, Kahn S, Ward A; Ange; Jacobsen; Slifka; Bowen; Stacewicz-Sapuntzakis; Langman; Sadler; Kahn; Ward (2003). "Serum concentrations of lipids, vitamin D metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos". The Journal of nutrition 133 (1): 160–6.PMID 12514284.
    [61] Holick MF (February 2002). "Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health". Current Opinion in Endocrinology, Diabetes and Obesity 9 (1): 87–98. doi:10.1097/00060793-200202000-00011.
    [62] Holick MF (September 2002). "Sunlight and Vitamin D". Journal of General Internal Medicine 17 (9): 733–735. doi:10.1046/j.1525-1497.2002.20731.xPMC 1495109.
    [63] Stout SD, Agarwal SC (2003). Bone loss and osteoporosis: an anthropological perspective. New York: Kluwer Academic/Plenum Publishers. ISBN 0-306-47767-X.
    [64] Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium (2011). "8, Implications and Special Concerns". In Ross AC, Taylor CL, Yaktine AL, Del Valle HB. Dietary Reference Intakes for Calcium and Vitamin D. Washington DC: National Academies Press. ISBN 0-309-16394-3PMID 21796828.
    [65] http://www.cancer.gov/about-cancer/causes-prevention/risk/diet/vitamin-d-fact-sheet
    [64] Thorne J, Campbell MJ. The vitamin D receptor in cancer. Proceedings of the Nutrition Society. 2008;67(2):115-127. [PubMed Abstract]
    [65] Moreno J, Krishnan AV, Feldman D. Molecular mechanisms mediating the antiproliferative effects of vitamin D in prostate cancer. Journal of Steroid Biochemistry and Molecular Biology 2005; 97(1–2):31–36. [PubMed Abstract]
    [66] Holt PR, Arber N, Halmos B, et al. Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. Cancer Epidemiology, Biomarkers, and Prevention 2002; 11(1):113–119. [PubMed Abstract]
    [67] Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Reviews Cancer. 2007;7(9):684-700 [PubMed Abstract]
    [68] Ma Y, Zhang P, Wang F, et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. Journal of Clinical Oncology.2011;29(28):3775-3782. [PubMed Abstract]
    [69] Gandini S, Boniol M, Haukka J, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. International Journal of Cancer. 2011;128(6):1414-1424 [PubMed Abstract]
    [70] Woolcott CG, Wilkens LR, Nomura AM, et al. Plasma 25-hydroxyvitamin D levels and the risk of colorectal cancer: the multiethnic cohort study. Cancer Epidemiology, Biomarkers & Prevention. 2010;19(1):130-134. [PubMed Abstract]
    [71] Jenab M, Bueno-de-Mesquita HB, Ferrari P, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study. BMJ. 2010;340:b5500. [PubMed Abstract]
    [72] Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. New England Journal of Medicine2006; 354(7):684–696. [PubMed Abstract]
    [73] Chung M, Lee J, Terasawa T, et al. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2011;155(12):827-838. [PubMed Abstract]
    [74] Manson JE, Bassuk SS, Lee IM, et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemporary Clinical Trials. 2012;33(1):159-171. [PubMed Abstract]
    [75] Otten JJ, Hellwig JP, Meyers LD. Vitamin D. In: Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: National Academies Press, 2006.
    [76] Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011.
    [78] https://clinicaltrials.gov/ct2/show/NCT00153816
    [79] Wu S, Sun J. Vitamin D, Vitamin D Receptor, and Macroautophagy in Inflammation and Infection. Discovery Medicine. 2011;11(59):325-335. 
    [79] "Why and How Much Vitamin D do we Need?" by Consumer Reports via the Washington Post. (May 11, 2015)




    ADDITIONAL REFERENCES





    IMAGE CREDITS

    "The Sower" by Vincent van Gogh - 1. vggallery.com2. The Bridgeman Art Library, Object 593575. Licensed under Public Domain via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:The_Sower.jpg#/media/File:The_Sower.jpg

    "Cod Liver Oil Capsules" by Orange-kun - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Cod_Liver_Oil_Capsules.jpg#/media/File:Cod_Liver_Oil_Capsules.jpg

    "Cholecalciferol-3d" by Sbrools - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Cholecalciferol-3d.png#/media/File:Cholecalciferol-3d.png

    "SPF15SunBlock" by Simon Speed - Own work. Licensed under Public Domain via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:SPF15SunBlock.JPG#/media/File:SPF15SunBlock.JPG

    "Skinlayers" by Modified from the original Grey's diagram here: http://en.wikipedia.org/wiki/Image:Gray941.png. Licensed under Public Domain via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Skinlayers.png#/media/File:Skinlayers.png

    "Calcium regulation" by Mikael Häggström - All used images are in public domain.. Licensed under Public Domain via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Calcium_regulation.png#/media/File:Calcium_regulation.png

    "The More You Know Logo 2013" by Source (WP:NFCC#4). Licensed under Fair use via Wikipedia - https://en.wikipedia.org/wiki/File:The_More_You_Know_Logo_2013.jpg#/media/File:The_More_You_Know_Logo_2013.jpg







    1 comment:

    1. Thank you for this article. My worst life experience was when I took care of my grandmother faced with Alzheimer's disease. This was emotionally draining because I wished I could take her pains away. I watched my grandmother gradually lose to Alzheimer's disease. When she stepped out for exercise, she couldn't find her way back home. On several occasions, neighbors helped return her home and some days; we had to call 911 for a search mission. We couldn’t find help and we lost her. It still breaks my heart to think of all the pains she went through and all battles with her OTC medications which couldn’t slow down her memory loss progression or cure the disease, but had terrible side effects on her health. Losing my grandmother to Alzheimer's disease wasn’t a pleasant experience. When my Uncle had the same fate, I sought an alternative from OTC medications. In search of natural medicine that could help him, I read blogs and followed comments which mentioned Dr. Fredrick treatment through Ganzino-Sana herbal medicine. I did not hesitate to make the choice, because I knew what my grandmother went through with Alzheimer's disease. He began the treatment without delay and, in 2 months of use; the result was excellent memory recovery! Here is the blog I found help www.ganzinosanaherbalmedicine.blogspot.com

      ReplyDelete