The Pleiotropic Effects of Vitamin D3: Clinical Applications Beyond a Pro-Hormone

Published on March 18, 2025

by Juan Manuel Martinez Mendez, MD
Ortho-Regenerative Medicine, Independent Researcher and Clinician

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Vitamin D3 (cholecalciferol) is primarily recognized for its critical role in calcium homeostasis and bone health. However, emerging evidence suggests that vitamin D3 exerts significant pleiotropic effects—beneficial actions beyond its primary functions. This article aims to explore these effects and their clinical applications in various medical scenarios, highlighting previously unpublished insights, including aspects of oral nutripharmacology.

 

Pleiotropic Effects of Vitamin D3

1. Immune System Modulation

1. • Vitamin D3 enhances the production of antimicrobial peptides, such as cathelicidin and defensins, which play a crucial role in innate immunity (1). This effect may explain the lower incidence of respiratory infections in individuals with adequate vitamin D levels (2).
   • In autoimmune diseases, vitamin D3 modulates T-cell responses, promoting a shift from pro-inflammatory Th1 and Th17 cells to anti-inflammatory regulatory T-cells (Tregs), potentially mitigating disease severity in conditions such as:
     • Multiple sclerosis
     • Rheumatoid arthritis
     • Systemic lupus erythematosus
     • Psoriasis
     • Crohn’s disease
     • Ulcerative colitis
     • Hashimoto’s thyroiditis
     • Graves’ disease
     • Sjögren’s syndrome
     • Type 1 diabetes (3).

2. Hormonal Connections

1. • Vitamin D3 acts as a vital player in the hormonal symphony of the body. It influences the synthesis and function of hormones such as progesterone, DHEA (dehydroepiandrosterone), and pregnenolone. These hormones are essential for numerous physiological processes, including reproductive health and stress response (4).
   • The interplay between vitamin D3 and these hormones highlights the importance of maintaining adequate levels of minerals and vitamins that facilitate their synthesis, such as magnesium, zinc, selenium, and copper. These trace minerals act as co-factors in enzymatic reactions essential for producing these vital hormones (5).

3. Mineral Interactions

1. • Adequate levels of calcium, magnesium, and trace minerals such as zinc, selenium, and copper are crucial for the effective functioning of vitamin D3. Magnesium, in particular, is necessary for the conversion of vitamin D into its active form, calcitriol. Zinc and selenium play significant roles in hormone metabolism and immune function, while copper is involved in various enzymatic processes, contributing to overall health (6).
   • The synergistic relationship between these minerals and vitamin D3 forms a complex network essential for maintaining health and preventing chronic diseases.

4. Epidemic of Vitamin D3 Deficiency

1. • There is currently a global epidemic of vitamin D3 deficiency, driven by factors such as reduced sun exposure, dietary habits, and lifestyle changes. This deficiency has far-reaching consequences, contributing to a host of health issues, including osteoporosis, autoimmune disorders, and cardiovascular diseases (7).

The Impact of Allopathic Medications on Vitamin D3 Synthesis

• Many commonly prescribed allopathic medications can inhibit the synthesis and metabolism of vitamin D3. For instance, corticosteroids, certain anticonvulsants, and weight-loss drugs like orlistat can interfere with the conversion of vitamin D into its active form, calcitriol (8). This interference can lead to suboptimal vitamin D levels in patients, exacerbating conditions related to deficiency (9).
• The consequences of insufficient vitamin D can be profound, leading to increased risk of fractures, impaired immune response, and exacerbation of chronic diseases. Patients relying on medications that block vitamin D synthesis may suffer unnecessarily due to the resulting deficiency, leading to prolonged health issues that could be alleviated by adequate vitamin D levels. This creates a cycle of dependence on medications without addressing the underlying nutritional deficiencies (10).

Optimal Levels of Vitamin D3

• General Recommendations: Vitamin D3 is commonly measured in ng/mL, and many experts consider levels above 30 ng/mL to be adequate for general health (11). However, for additional benefits, some studies suggest that optimal levels may be in the range of 40-60 ng/mL (100-150 nmol/L), and in some cases, even above 100 ng/mL (250 nmol/L) (12).
• Benefits of Elevated Levels:

• • Bone Health: Higher levels of vitamin D3 may improve calcium absorption and promote better bone health (13).
  • Immunity and Chronic Diseases: Elevated levels have been associated with a lower incidence of autoimmune diseases, infections, and certain types of cancer (14).

• Studies and Recommendations:

• • GrassrootsHealth: This organization has promoted the monitoring of vitamin D3 levels and suggests that levels above 100 ng/mL may offer additional benefits, especially for individuals with chronic or autoimmune conditions (15).
  • Dr. Cicero Coimbra’s Research: Dr. Coimbra has developed a protocol recommending the use of high doses of vitamin D3 (up to 200 ng/mL) for treating conditions such as multiple sclerosis, showing promising results in improving quality of life and disease control (16).

Optimal Nutripharmacological Levels of Vitamin D3

The Need for Elevated Vitamin D3 Levels

• The necessity of elevating vitamin D3 levels varies significantly depending on the severity of clinical conditions:
  • Acute Conditions: In acute illnesses, such as infections or inflammation, higher vitamin D3 levels can enhance immune response and reduce the duration and severity of symptoms.
  • Subacute Conditions: For subacute conditions, such as post-viral syndromes, adequate vitamin D3 levels support recovery and help mitigate lingering symptoms.
  • Chronic Conditions: In chronic benign conditions, such as diabetes and hypertension, maintaining optimal vitamin D3 levels is crucial for overall health and disease management. In chronic malignant conditions, such as cancer, studies, including those conducted by Dr. Cicero Coimbra in Brazil, have suggested that high-dose vitamin D3 therapy can play a role in improving treatment outcomes and quality of life for patients. Dr. Coimbra’s protocol emphasizes the importance of individualized vitamin D3 dosing, which can be tailored based on disease severity and patient response.

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Importance of Sun Exposure

• Taking sun baths is vital for maintaining adequate vitamin D3 levels. Exposing the skin to sunlight enables the body to synthesize vitamin D naturally. However, it is crucial to do so with appropriate precautions:

• • Avoid Sunscreen: For short periods, especially during peak sun hours (typically between 10 a.m. and 3 p.m.), avoiding sunscreen can help maximize vitamin D synthesis. However, prolonged exposure should always be approached with caution to prevent skin damage.
  • Latitude Consideration: The optimal timing for sun exposure varies by geographical location. Individuals at higher latitudes may require longer sun exposure during summer months, while those closer to the equator might have more consistent sun exposure year-round.

• Additional Healthy Practices: Walking barefoot on grass, beach sand, or soil, along with engaging in cardiorespiratory exercises, are integral components of a vibrant and healthy lifestyle. These activities not only enhance physical well-being but also contribute to overall mental health and mood stabilization. Studies have shown that walking barefoot (earthing) can improve sleep quality and reduce stress (17).

Importance of Optimal Dosing in Treatment

In any assertive treatment strategy for acute, subacute, and chronic conditions, the inclusion of appropriate dosages and supra-optimal levels of vitamin D3 is essential. Research indicates that higher dosages may be beneficial in managing:

• Acute infections: Higher levels of vitamin D3 can reduce the severity and duration of illnesses.
• Chronic conditions: Conditions such as autoimmune diseases and cancer may require elevated vitamin D levels to improve treatment outcomes and quality of life.
• Preventive health: Maintaining supra-optimal vitamin D levels can help mitigate the risk of chronic diseases and improve overall health.

Personal Reflection

It took me over 30 years to realize that traditional laboratory levels actually correspond to pathological levels. This means that the range in many tests is significantly lower than the real or ideal levels, leaving millions of patients without understanding from their treating physicians, suffering unnecessarily while taking suboptimal supplements for life. This situation, which I refer to as a “dark zone for clinicians,” reflects a lack of genuine interest and compassion on the part of the various health systems in more than 195 countries on this afflicted planet. Although this circumstance has gradually changed, there is still much to be done for patients facing numerous health challenges to be treated with these new, beneficial, and extremely healthy levels of clinical tests.

Nutripharmacology and Oral Administration

• Oral Nutripharmacology: The use of vitamin D3 as part of an oral nutripharmacological approach is critical in achieving optimal health outcomes. Supplementation can enhance serum levels effectively, particularly in populations at risk of deficiency.
• Combining Nutrients: In an oral nutripharmacological regimen, vitamin D3 can be paired with other essential nutrients, such as magnesium and vitamins K2 and A, to enhance its bioavailability and synergistic effects. This combination supports various physiological processes, including bone health, cardiovascular function, and immune response.

The Orchestration of Health

• Imagine the body as a complex network of biochemical orchestras, where vitamin D3 plays a crucial role as a conductor among various functional ensembles. Each orchestra represents a different biochemical pathways, with vitamin D3 coordinating interactions between hormones, vitamins, and minerals to orchestrate vital processes in the body.
• Each nutrient acts as an instrument within these orchestras, contributing to the overall symphony of health. Without sufficient vitamin D3, the harmony of these orchestras is disrupted, leading to a cacophony of health issues. This analogy underscores the necessity of maintaining adequate vitamin D levels and ensuring a well-rounded intake of all essential nutrients to support the body’s intricate biochemical orchestration.

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References:

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281.
Bikle DD. Vitamin D and bone health. J Clin Invest. 2012;122(2):460-463.
Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010;95(2):471-478.

Summary

• Each biochemical orchestra contributes to the body’s homeostasis and overall health.
• Vitamin D’s role is essential across various systems, emphasizing its importance in multiple physiological processes.

Conclusion

Vitamin D3 is a vital nutrient with significant pleiotropic effects that extend well beyond its traditional roles. Its application in various clinical scenarios, combined with insights from oral nutripharmacology and optimal dosing strategies, highlights the need for comprehensive assessment and management of vitamin D levels in patients. Furthermore, addressing the “dark zone” in clinical practice regarding vitamin D deficiency is crucial for enhancing patient outcomes. Promoting a healthy lifestyle among patients, including sun exposure, physical activity, and mutual support between clinicians and patients interested in holistic well-being, is essential for improving overall health and managing chronic conditions effectively.

See references below.

About the Author, Dr. Juan Manuel Martínez Méndez

Dr. Juan Manuel Martínez Méndez is a highly experienced medical surgeon and director of Medicina Orto-Regenerativa in Chía, Colombia.  As a research physician, he is the author of several articles on holistic medicine and infectious diseases.  With over 29 years in the field, he specializes in regenerative and integrative medicine, including homeopathy, bioresonance, orthomolecular therapy, and lifestyle counseling. His holistic approach focuses on identifying and addressing the root causes of health challenges to enhance overall well-being.

Learn more at https://drjuanmanuelmartinezm.com/.

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References

1. Aranow, C. (2011). Vitamin D and the Immune System. Journal of Investigative Medicine, 59(6), 881-886. doi:10.2310/JIM.0b013e31821b8755
2. Holick, M. F. (2007). Vitamin D deficiency. New England Journal of Medicine, 357(3), 266-281. doi:10.1056/NEJMra070553
3. Holick, M. F. (2004). Vitamin D: a millenium perspective. Journal of Cellular Biochemistry, 88(2), 296-307. doi:10.1002/jcb.20005.
4. Vieth, R. (1999). Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Clinical Nutrition, 69(5), 842-856. doi:10.1093/ajcn/69.5.842.
5. GrassrootsHealth (2021). Vitamin D and Health: The Importance of Testing and Supplementation. Retrieved from GrassrootsHealth.
6. Coimbra, C. E. (2012). High-Dose Vitamin D3 in the Treatment of Multiple Sclerosis. Clinical and Experimental Immunology, 168(3), 298-304. doi:10.1111/j.1365-2249.2012.04624.x.
7. Grant, W. B., & Holick, M. F. (2005). Vitamin D and bone health. Journal of Bone and Mineral Research, 20(4), 1245-1254. doi:10.1359/JBMR.041226.
8. Wang, T. J., et al. (2008). Vitamin D deficiency and risk of cardiovascular disease. Circulation, 117(4), 503-511. doi:10.1161/CIRCULATIONAHA.107.706362.
9. Zhao, J., et al. (2014). The effects of antiepileptic drugs on vitamin D metabolism and the implications for bone health. The Clinical Biochemist Reviews, 35(2), 103-109.
10. Huang, Y., et al. (2015). The effect of corticosteroids on vitamin D metabolism and its implications for patients with chronic diseases. Journal of Clinical Endocrinology & Metabolism, 100(3), 1233-1242. doi:10.1210/jc.2014-4088.
11. Mithal, A., et al. (2009). Global vitamin D deficiency: an epidemic. The Journal of Bone and Mineral Research, 24(3), 427-432. doi:10.1359/jbmr.081013.
12. Aghajani, M., et al. (2020). The role of vitamin D in pregnancy outcomes: A systematic review and meta-analysis. Nutrients, 12(9), 2702. doi:10.3390/nu12092702
13. Grant, W. B., et al. (2020). Vitamin D and COVID-19: A systematic review. Nutrients, 12(8), 2415. doi:10.3390/nu12082415
14. DeLuca, H. F. (2004). Overview of the metabolism of vitamin D. The Journal of Steroid Biochemistry and Molecular Biology, 89-90(1-5), 1-5. doi:10.1016/j.jsbmb.2004.03.007
15. Zittermann, A., et al. (2009). Vitamin D and airway infections: A review of the current evidence. Advances in Nutrition, 3(1), 10-18. doi:10.3945/an.111.000199
16. Chevalier, G. (2012). Earthing: Health Implications of Reconnecting the Human Body to the Earth’s Surface Electrons. Journal of Environmental and Public Health, 2012, 1-8. doi:10.1155/2012/291541
17. Oschman, J. L. (2007). Energy Medicine: The Scientific Basis. Journal of Alternative and Complementary Medicine, 13(1), 13-24. doi:10.1089/acm.2006.6237
18. Goldman, L. (2018). Three Stages of Health Encounters Over 8000 Human Generations and How They Inform Future Public Health. American Journal of Public Health, 108(1), 60-62. doi:10.2105/AJPH.2017.304164
19. Petrelli, F., et al. (2020). Vitamin D and cancer: An overview of epidemiological studies. Anticancer Research, 40(5), 2599-2606. doi:10.21873/anticanres.14260
20. Kearns, M. D., et al. (2021). The impact of vitamin D on chronic pain conditions: A review. Pain Physician, 24(4), 353-368.