Vitamin D: Optimal Levels and How to Get There

Evolving recommendations for vitamin D illustrate the need to assess serum biomarkers from an optimal perspective. Evaluation of both optimal vitamin D levels and intake have been gaining attention.

Traditionally, serum 25-hydroxyvitamin D (25(OH)D) levels above 20 ng/mL (50 nmol/L) were accepted as “normal.” Insufficiency was defined as 12-20 ng/mL (30-50 nmol/L), and deficiency was defined as a value lower than 12 ng/mL (30 nmol/L).[i]

However, over time, research revealed that minimum sufficiency wasn’t achieved until levels reached above 30 ng/mL (75 nmol/L),[ii] [iii] while levels of 40 ng/mL (100 nmol/L) or greater were associated with a reduction in all-cause mortality.[iv]

Corroborating these findings, research during the COVID-19 pandemic revealed that a 25(OH)D level of 30 ng/mL (75 nmol/L) or greater was associated with reduced disease severity and mortality.[v] Researchers recommend maintaining a serum 25(OH)D level of 55 ng/mL (137 nmol/L) or greater to reduce cancer risk.[viii] 

How much is too much? Serum 25(OH)D does not reflect tissue stores and toxicity is a potential concern, though at what level it may occur is debated. Pharmacokinetics research suggests that while levels of 25(OH)D must “rise above 300 ng/mL (750 nmol/L) to produce vitamin D toxicity, the more prudent upper limit of 100 ng/mL (250 nmol/L) might be retained to ensure a wide safety margin.”[vi] Serum calcium levels should also be assessed as 25(OH)D levels rise.

Currently, conventional lab normal range is 30−100 ng/mL (75-250 nmol/L),[vii] with an optimal goal of 50-90 ng/mL (125-225 nmol/L).[viii]

Vitamin D Intake and Supplementation

The recommended intake of vitamin D has been a subject of debate as well.

The US recommended dietary allowance (RDA) for vitamin D remains fairly low at 600-800 IU/day (15-20 ug) with a tolerable upper intake of 4000 IU (100 ug) per day.[ix] However, researchers indicate that due to statistical error, the estimated RDA for vitamin D was set too low and will not promote serum vitamin D levels consistent with optimal health. Research and reanalysis of the data suggests:[x]

• 8895 IU/day (222 ug) was needed for 97.5% of individuals to achieve 20 ng/mL (50 nmol/L) or greater
• 6201 IU/day (155 ug) was needed to achieve 30 ng/mL (75 nmol/L)
• 9122 IU/day (228 ug) was needed to reach 40 ng/mL (100 nmol/L)
• 8000 IU/day (200 ug) is general recommendation for adults
• In general, each 1000 IU (25 ug) dose of vitamin D3 should increase blood levels by 10 ng/mL (25 nmol/L).[xi]

Vitamin D status should be evaluated as part of a general health checkup considering its wide range of effects and functions including musculoskeletal health, immune regulation, skin health, cardiovascular integrity, apoptosis, and cell proliferation and differentiation.[xii]

Vitamin D also plays an important role in homocysteine metabolism as it activates the cystathionine synthase gene which facilitates one of the biochemical pathways for processing Hcy. Supplementation with vitamin D, 50,000 IU/week for two months, significantly decreased Hcy, CRP, AST, and ALT in vitamin D deficient women. Results also indicated an increase in urea to 12 mg/dL (4.3 mmol/L) and creatinine to 0.65 mg/dL (57.5 umol/L), and a decrease in eGFR to 167.6 mls/min though values remained within optimal range.[xiii]

According to the Endocrine Society, vitamin D deficient adults should be treated with 50,000 IU (1250 ug) of vitamin D weekly [equal to 7143 IU (179 ug) daily] for eight weeks to achieve a blood level greater than 30 ng/mL (75 nmol/L). Maintenance therapy thereafter should be at least 1500-2000 IU (38-50 ug) per day.

In obesity, malabsorption syndromes, or medication-induced depletions, higher doses of 6000-10000 IU (150-250 ug) per day may be needed to reach 30 ng/mL (75 nmol/L), with maintenance therapy of 3000-6000 IU (75-150 ug) per day.[xiv]

Classification of Serum 25(OH)D Levels:[xv]

*some sources found that 150 ng/ml was not harmful.

Source: Benskin, Linda L. “A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency.” Frontiers in public health vol. 8 513. 10 Sep. 2020, doi:10.3389/fpubh.2020.00513 This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).  

Endogenous production of vitamin D is stimulated when a cholesterol compound in the skin is exposed to UVB light, with subsequent hydroxylation and activation at the liver and kidney level. From 10000 to 25000 IU of vitamin D can be produced endogenously when exposed to one erythemal dose of UV radiation (leaves a slight pinkness in the skin 24 hours following exposure). Endogenous vitamin D remains in the blood longer than ingested vitamin D.[xvi]

Keep in mind that a wide range of variables can influence serum 25(OH)D including age, gender, body weight, obesity, genetic factors, skin pigmentation, sun exposure, sunblock, season, geographic location/latitude, physical activity, diet, and lifestyle factors.[xvii] [xviii] [xix] [xx] Vitamin D deficiency is more likely in those with fair to poor health status, diabetes, obesity, no college education, smokers, and individuals with dark skin.[xxi]

A literature review of randomized trials, systematic reviews, meta-analyses, and international consensus conferences were conducted and published in March 2021. Researchers conclude that optimal serum 25(OH)D levels be maintained above 50 ng/mL (125 nmol/L).[xxii]

References

[i] NIH Office of Dietary Supplements Vitamin D Fact Sheet for Professionals.

[ii] Holick, Michael F et al. “Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.” The Journal of clinical endocrinology and metabolism vol. 96,7 (2011): 1911-30. doi:10.1210/jc.2011-0385

[iii] Papadimitriou, Dimitrios T. “The Big Vitamin D Mistake.” Journal of preventive medicine and public health = Yebang Uihakhoe chi vol. 50,4 (2017): 278-281. doi:10.3961/jpmph.16.111 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ()

[iv] Papadimitriou, Dimitrios T. “The Big Vitamin D Mistake.” Journal of preventive medicine and public health = Yebang Uihakhoe chi vol. 50,4 (2017): 278-281. doi:10.3961/jpmph.16.111

[v] Maghbooli, Zhila et al. “Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection.” PloS one vol. 15,9 e0239799. 25 Sep. 2020, doi:10.1371/journal.pone.0239799

[vi] Jones, Glenville. “Pharmacokinetics of vitamin D toxicity.” The American journal of clinical nutrition vol. 88,2 (2008): 582S-586S. doi:10.1093/ajcn/88.2.582S

[vii] Labcorp. 25-hydroxyvitamin D. Quest 25-hydroxy Vitamin D.

[viii] Garland, Cedric F et al. “What is the dose-response relationship between vitamin D and cancer risk?.” Nutrition reviews vol. 65,8 Pt 2 (2007): S91-5. doi:10.1111/j.1753-4887.2007.tb00349.x

[ix] US DRIs RDAs.

[x] Papadimitriou, Dimitrios T. “The Big Vitamin D Mistake.” Journal of preventive medicine and public health = Yebang Uihakhoe chi vol. 50,4 (2017): 278-281. doi:10.3961/jpmph.16.111 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ().

[xi] Moyad, Mark A. “Vitamin D: a rapid review.” Dermatology nursing vol. 21,1 (2009): 25-30, 55.

[xii] Umar, Meenakshi et al. “Role of Vitamin D Beyond the Skeletal Function: A Review of the Molecular and Clinical Studies.” International journal of molecular sciences vol. 19,6 1618. 30 May. 2018, doi:10.3390/ijms19061618

[xiii] Al-Bayyari, N et al. “Vitamin D3 reduces risk of cardiovascular and liver diseases by lowering homocysteine levels: double-blinded, randomised, placebo-controlled trial.” The British journal of nutrition vol. 125,2 (2021): 139-146. doi:10.1017/S0007114520001890

[xiv] Holick, Michael F et al. “Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.” The Journal of clinical endocrinology and metabolism vol. 96,7 (2011): 1911-30. doi:10.1210/jc.2011-0385

[xv] Benskin, Linda L. “A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency.” Frontiers in public health vol. 8 513. 10 Sep. 2020, doi:10.3389/fpubh.2020.00513 

[xvi] Nair, Rathish, and Arun Maseeh. “Vitamin D: The "sunshine" vitamin.” Journal of pharmacology & pharmacotherapeutics vol. 3,2 (2012): 118-26. doi:10.4103/0976-500X.95506

[xvii] Altowijri, Albaraa et al. “Impact of Nutritional and Environmental Factors on Vitamin D Deficiency.” Asian Pacific journal of cancer prevention : APJCP vol. 19,9 2569-2574. 26 Sep. 2018, doi:10.22034/APJCP.2018.19.9.2569

[xviii] Barrea, Luigi et al. “Low serum vitamin D-status, air pollution and obesity: A dangerous liaison.” Reviews in endocrine & metabolic disorders vol. 18,2 (2017): 207-214. doi:10.1007/s11154-016-9388-6

[xix] Linus Pauling Institute Micronutrient Center OSU. Vitamin D.

[xx] Richardson, David P, and Julie A Lovegrove. “Nutritional status of micronutrients as a possible and modifiable risk factor for COVID-19: a UK perspective.” The British journal of nutrition, 1-7. 20 Aug. 2020, doi:10.1017/S000711452000330X

[xxi] Parva, Naveen R et al. “Prevalence of Vitamin D Deficiency and Associated Risk Factors in the US Population (2011-2012).” Cureus vol. 10,6 e2741. 5 Jun. 2018, doi:10.7759/cureus.2741

[xxii] Zotarelli Filho, Idiberto José, et al. “Major Meta-Analysis, Randomized Clinical Studies, and International Consensus on Serum Levels and Importance of Supplementing Vitamin D:State of the Art.” MedNEXT Journal of Medical and Health Sciences, 2021, pp. 54–66., doi:10.34256/mdnt2129.