On 2015 Jan 27, William Grant commented:

The paper on hypovitaminosis D by Daniel Podd [1] is useful in drawing attention to the problem but has a number of factual errors. This comment suggests a number of corrections.

Ref. 1 states that vitamins D2 and D3 have equivalent biological activity. Vitamin D researchers disagree on this point [2]. A recent meta-analysis of vitamin D trials found that supplementation with vitamin D3 lowered mortality rate significantly by 10% while supplementation with vitamin D2 increased mortality rate by a non-significant 3 to 15% [3].

Regarding lower vitamin D levels for those who are obese, another suggestion is that volumetric dilution rather than fat sequestration that explains the findings [4]. However, both may be important.

Regarding cancer, the findings for vitamin D levels and breast cancer are very similar to those for colorectal cancer [5]. The problem in determining this has been that prospective observational studies with longer than three-years follow up have not found a significant inverse correlation between vitamin D levels and breast cancer incidence rates [6]. The reason is that breast cancer develops very rapidly, which is why mammography is recommended annually. Case-control studies consistently find strong inverse correlations between vitamin D levels and breast cancer incidence rates [6]. The evidence that solar UVB and vitamin D reduce the risk of cancer incidence and mortality rates for many types of cancer is strong based on geographical ecological studies and laboratory investigations of the mechanisms [7]. Vitamin D plus calcium supplementation has also been found to reduce risk of breast cancer [8].

Regarding vitamin D production from solar UVB: it is very difficult to impossible to make vitamin D in winter for about six months in locations pole ward of about 40 degrees [9]. When the solar elevation angle is below 45 degrees, it is difficult to make vitamin D since most of the UVB is scattered out [9]. Thus, time of day and season are very important considerations regarding vitamin D production. Also important is skin pigmentation. Black Americans have vitamin D levels about 40% lower than white Americans [10].

Regarding calcium supplementation, 1.5 to 2.0 g/d is too high. There is increased risk of cardiovascular disease with higher calcium intake [11]. A recent meta-analysis found that dietary calcium intake of 800 to 1000 mg/d was associated with the lowest risk of cardiovascular disease, with intakes above 1200 mg/d associated with significantly increased risk [12].

Regarding the best time to take vitamin D, it is with the largest meal of the day [13]. That way vitamin D stays in the intestines longer.

Regarding frequency of dosing, daily may be optimal. A meta-analysis found "Supplementation of intermittent, high dose vitamin D may not be effective in preventing overall mortality, fractures, or falls among older adults." [14]. By intermittent, they meant once or once a month. Others have shown good results for weekly dosing. Daily dosing is similar to being in the sun daily, which is the physiological way to produce vitamin D.

While there is mounting evidence that vitamin D has important health benefits [15], there is also mounting evidence that some of the benefits attributed to vitamin D may, in fact, be due to other effects of solar UVB exposure. Non-vitamin D effects of UV exposure have been found for multiple sclerosis [16, 17], hypertension/cardiovascular disease [18] and intestinal cancer [19]. Thus, midday sun exposure may be a better option for increasing vitamin D levels when possible.

An additional critique of Ref. 1 can be found at http://vitamindwiki.com/tiki-index.php?page_id=6196

References 1. Podd D. Hypovitaminosis D: A common deficiency with pervasive consequences. JAAPA. 2015;28(2):20-26. 2. Heaney RP, Recker RR, Grote J, et al. Vitamin D3 is more potent than vitamin D2 in humans. J Clin Endocrinol Metab. 2011;96(3):E447-52. 3. Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903. 4. Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring). 2012;20(7):1444-8. 5. Grant WB. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B, 2010;101(2):130–6. 6. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines. Dermatoendocrinol. 2011;3(3):199-204. 7. Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrients. 2013;5(10):3993-4023. 8. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011;94(4):1144-9. 9. Engelsen O. The relationship between ultraviolet radiation exposure and vitamin D status. Nutrients. 2010;2(5):482-95. 10. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009;169(6):626-32. 11. Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf. 2013;4(5):199-210. 12. Wang X, Chen H, Ouyang Y, et al. Dietary calcium intake and mortality risk from cardiovascular disease and all causes: a meta-analysis of prospective cohort studies. BMC Med. 2014;12:158 13. Mulligan GB, Licata A. Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25-hydroxyvitamin D. J Bone Miner Res. 2010;25(4):928-30. 14. Zheng YT, Cui QQ, Hong YM, Yao WG. A meta-analysis of high dose, intermittent vitamin D supplementation among older adults. PLoS One. 2015;10(1):e0115850. 15. Pludowski P, Holick MF, Pilz S, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality- a review of recent evidence. Autoimmun Rev. 2013;12(10):976-89. 16. Knippenberg S, Damoiseaux J, Bol Y, et al. Higher levels of reported sun exposure, and not vitamin D status, are associated with less depressive symptoms and fatigue in multiple sclerosis. Acta Neurol Scand. 2014;129(2):123-31. 17. Wang Y, Marling SJ, Beaver EF, et al UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis. Arch Biochem Biophys. 2014;567C:75-82. 18. Liu D, Fernandez BO, Hamilton A, Lang NN, et al. UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. J Invest Dermatol. 2014;134(7):1839-46. 19. Rebel H, der Spek CD, Salvatori D, et al. UV exposure inhibits intestinal tumour growth and progression to malignancy in intestine-specific Apc mutant mice kept on low vitamin D diet. Int J Cancer. 2015;136(2):271-7.

Disclosure I receive funding from Bio Tech Pharmacal (Fayetteville, AR), MediSun Technology (Highland Park, IL), and the Vitamin D Council (San Luis Obispo, CA).

On 2015 Jan 27, William Grant commented:

The paper on hypovitaminosis D by Daniel Podd [1] is useful in drawing attention to the problem but has a number of factual errors. This comment suggests a number of corrections.

Ref. 1 states that vitamins D2 and D3 have equivalent biological activity. Vitamin D researchers disagree on this point [2]. A recent meta-analysis of vitamin D trials found that supplementation with vitamin D3 lowered mortality rate significantly by 10% while supplementation with vitamin D2 increased mortality rate by a non-significant 3 to 15% [3].

Regarding lower vitamin D levels for those who are obese, another suggestion is that volumetric dilution rather than fat sequestration that explains the findings [4]. However, both may be important.

Regarding cancer, the findings for vitamin D levels and breast cancer are very similar to those for colorectal cancer [5]. The problem in determining this has been that prospective observational studies with longer than three-years follow up have not found a significant inverse correlation between vitamin D levels and breast cancer incidence rates [6]. The reason is that breast cancer develops very rapidly, which is why mammography is recommended annually. Case-control studies consistently find strong inverse correlations between vitamin D levels and breast cancer incidence rates [6]. The evidence that solar UVB and vitamin D reduce the risk of cancer incidence and mortality rates for many types of cancer is strong based on geographical ecological studies and laboratory investigations of the mechanisms [7]. Vitamin D plus calcium supplementation has also been found to reduce risk of breast cancer [8].

Regarding vitamin D production from solar UVB: it is very difficult to impossible to make vitamin D in winter for about six months in locations pole ward of about 40 degrees [9]. When the solar elevation angle is below 45 degrees, it is difficult to make vitamin D since most of the UVB is scattered out [9]. Thus, time of day and season are very important considerations regarding vitamin D production. Also important is skin pigmentation. Black Americans have vitamin D levels about 40% lower than white Americans [10].

Regarding calcium supplementation, 1.5 to 2.0 g/d is too high. There is increased risk of cardiovascular disease with higher calcium intake [11]. A recent meta-analysis found that dietary calcium intake of 800 to 1000 mg/d was associated with the lowest risk of cardiovascular disease, with intakes above 1200 mg/d associated with significantly increased risk [12].

Regarding the best time to take vitamin D, it is with the largest meal of the day [13]. That way vitamin D stays in the intestines longer.

Regarding frequency of dosing, daily may be optimal. A meta-analysis found "Supplementation of intermittent, high dose vitamin D may not be effective in preventing overall mortality, fractures, or falls among older adults." [14]. By intermittent, they meant once or once a month. Others have shown good results for weekly dosing. Daily dosing is similar to being in the sun daily, which is the physiological way to produce vitamin D.

While there is mounting evidence that vitamin D has important health benefits [15], there is also mounting evidence that some of the benefits attributed to vitamin D may, in fact, be due to other effects of solar UVB exposure. Non-vitamin D effects of UV exposure have been found for multiple sclerosis [16, 17], hypertension/cardiovascular disease [18] and intestinal cancer [19]. Thus, midday sun exposure may be a better option for increasing vitamin D levels when possible.

An additional critique of Ref. 1 can be found at http://vitamindwiki.com/tiki-index.php?page_id=6196

References 1. Podd D. Hypovitaminosis D: A common deficiency with pervasive consequences. JAAPA. 2015;28(2):20-26. 2. Heaney RP, Recker RR, Grote J, et al. Vitamin D3 is more potent than vitamin D2 in humans. J Clin Endocrinol Metab. 2011;96(3):E447-52. 3. Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903. 4. Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring). 2012;20(7):1444-8. 5. Grant WB. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B, 2010;101(2):130–6. 6. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines. Dermatoendocrinol. 2011;3(3):199-204. 7. Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrients. 2013;5(10):3993-4023. 8. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011;94(4):1144-9. 9. Engelsen O. The relationship between ultraviolet radiation exposure and vitamin D status. Nutrients. 2010;2(5):482-95. 10. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009;169(6):626-32. 11. Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf. 2013;4(5):199-210. 12. Wang X, Chen H, Ouyang Y, et al. Dietary calcium intake and mortality risk from cardiovascular disease and all causes: a meta-analysis of prospective cohort studies. BMC Med. 2014;12:158 13. Mulligan GB, Licata A. Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25-hydroxyvitamin D. J Bone Miner Res. 2010;25(4):928-30. 14. Zheng YT, Cui QQ, Hong YM, Yao WG. A meta-analysis of high dose, intermittent vitamin D supplementation among older adults. PLoS One. 2015;10(1):e0115850. 15. Pludowski P, Holick MF, Pilz S, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality- a review of recent evidence. Autoimmun Rev. 2013;12(10):976-89. 16. Knippenberg S, Damoiseaux J, Bol Y, et al. Higher levels of reported sun exposure, and not vitamin D status, are associated with less depressive symptoms and fatigue in multiple sclerosis. Acta Neurol Scand. 2014;129(2):123-31. 17. Wang Y, Marling SJ, Beaver EF, et al UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis. Arch Biochem Biophys. 2014;567C:75-82. 18. Liu D, Fernandez BO, Hamilton A, Lang NN, et al. UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. J Invest Dermatol. 2014;134(7):1839-46. 19. Rebel H, der Spek CD, Salvatori D, et al. UV exposure inhibits intestinal tumour growth and progression to malignancy in intestine-specific Apc mutant mice kept on low vitamin D diet. Int J Cancer. 2015;136(2):271-7.

Disclosure I receive funding from Bio Tech Pharmacal (Fayetteville, AR), MediSun Technology (Highland Park, IL), and the Vitamin D Council (San Luis Obispo, CA).