The Ultimate Guide to: VITAMIN D

What You Need to Know

Vitamin D is commonly labeled a vitamin, but biologically it functions as a hormone. Vitamin D receptors are present in nearly every tissue, including the thyroid, immune cells, brain, muscle, and reproductive organs (1). Despite its importance, vitamin D deficiency and insufficiency are widespread, even among individuals whose laboratory values fall within the standard “normal” range.

Why Vitamin D Matters

Vitamin D plays a central role in multiple physiologic systems:

• Bone and Musculoskeletal Health: Improves intestinal calcium absorption and supports bone mineralization (2)

• Immune Regulation: Modulates innate and adaptive immunity and reduces inflammatory cytokines (3)

• Hormonal Health: Influences thyroid signaling, testosterone production, estrogen balance, and insulin sensitivity (4)

• Autoimmune and Inflammatory Conditions: Low vitamin D levels are associated with increased autoimmune disease activity (5)

Symptoms of suboptimal vitamin D can include fatigue, muscle aches, low mood, frequent infections, and impaired metabolic or hormonal function—even before disease is diagnosed.

How We Obtain Vitamin D (and Why It’s Usually Not Enough)

Sun Exposure

Vitamin D is synthesized in the skin via UVB radiation. However, production is reduced by:

• Indoor lifestyles

• Sunscreen use

• Latitude and season

• Skin pigmentation

• Aging (6)

Dietary Sources

Natural food sources are limited:

• Fatty fish (salmon, sardines)

• Egg yolks

• UV-exposed mushrooms

Even with optimal dietary intake, diet alone is insufficient to maintain adequate or optimal vitamin D levels (7).

Why Multivitamins Are Not Enough

Many patients assume a multivitamin provides sufficient vitamin D and K—but this is rarely the case.

• Most multivitamins contain only 400–800 IU of vitamin D3, which is inadequate to correct deficiency or optimize levels (8)

• Most contain no vitamin K2, or only vitamin K1

• When K2 is included, doses are typically far below the clinically relevant 90–200 mcg of MK-7

Bottom line: Multivitamins are not designed to optimize vitamin D or calcium metabolism.

Understanding Lab Reference Ranges vs. Functional Optimal Levels

Conventional Lab Ranges

Most laboratories define:

• Deficiency: <20 ng/mL

• Insufficiency: 20–30 ng/mL

• “Normal”: ≥30 ng/mL (9)

These cutoffs were established to prevent bone disease, not to optimize immune, inflammatory, or hormonal health.

Functional and Therapeutic Ranges

Clinical data suggest benefits at higher serum concentrations:

25-Hydroxyvitamin D	Interpretation
30–40 ng/mL	Minimal sufficiency
40–60 ng/mL	Good
60–80 ng/mL	Optimal for many
80–100 ng/mL	Therapeutic range for select patients
>150 ng/mL	Toxicity risk

Patients with autoimmune disease, chronic inflammation, thyroid disorders, or poor response to hormone therapy often remain symptomatic at 30–50 ng/mL and may improve only at higher levels (80–100 ng/mL) (10).

When appropriately monitored, these levels have been shown to be safe and non-toxic (11).

Vitamin D3 Supplementation: Dosing and Safety

Vitamin D3 (cholecalciferol) is the preferred form because it is more effective than D2 at raising and maintaining serum levels (12).

• RDA: 600–800 IU/day

• Endocrine Society upper intake level: 10,000 IU/day (13)

In clinical practice:

• 2,000–5,000 IU/day is often needed for maintenance

• 5,000–10,000 IU/day or higher may be used therapeutically under medical supervision

High-Dose Safety

Studies demonstrate:

• 50,000 IU daily without hypercalcemia or renal toxicity (11)

• 50,000–100,000 IU weekly for up to one year with normal calcium and kidney function (14)

Vitamin D toxicity is rare and typically occurs only when serum levels exceed 150–200 ng/mL, usually in the setting of prolonged excessive dosing or underlying disease (15).

Why Vitamin K2 (MK-7) Is Essential

Vitamin D increases calcium absorption. Vitamin K2—especially MK-7—directs calcium into bones and teeth and away from arteries by activating osteocalcin and matrix Gla protein (16).

Recommended dose:

• 90–200 mcg MK-7 daily, particularly when using moderate to high doses of vitamin D

  
  

Key Cofactors That Improve Vitamin D Effectiveness

• Magnesium: Required for vitamin D activation and receptor signaling; deficiency may blunt response (17)

• Zinc: Supports immune and hormone receptor function

• Dietary Fat: Vitamin D is fat-soluble and absorbs best when taken with a fatty meal (18)

  
  

-FAQ-

Vitamin D & Hormone Therapy: Frequently Asked Questions

Is vitamin D important for both women and men?

Yes. Vitamin D is essential for men and women regardless of hormone therapy status. It supports immune, bone, metabolic, and hormonal health (1).

Is vitamin D more important if I’m on HRT or TRT?

Yes. Vitamin D supports hormone receptor sensitivity, bone density, and cardiovascular health. Suboptimal vitamin D may reduce the effectiveness of hormone therapy (4,10).

Can low vitamin D make hormone therapy less effective?

Yes. Adequate hormone levels do not guarantee adequate cellular response if vitamin D is insufficient.

Do men on TRT need vitamin D?

Yes. Vitamin D supports androgen receptor signaling, bone density, muscle function, and immune health (4).

Do women on estrogen therapy need vitamin D?

Yes. Estrogen protects bone only when vitamin D and calcium metabolism are adequate (2).

Is vitamin D supplementation safe?

When appropriately dosed and monitored, vitamin D supplementation is very safe. Toxicity is rare and related to calcium imbalance, not routine supplementation (11,15).

Clinical Takeaway

Vitamin D optimization is not one-size-fits-all. Standard lab ranges do not always reflect what is optimal for an individual’s immune, hormonal, or inflammatory health. Rather than relying on a one-size-fits-all target, proper testing and clinical evaluation are necessary. At Vantage Health Clinic, we measure and interpret vitamin D levels as part of a personalized care approach to determine what is appropriate for each patient.

References

1. Christakos, Sylvia, et al. “Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.” Physiological Reviews, vol. 96, no. 1, Jan. 2016, pp. 365–408.

2. Holick, Michael F. “Vitamin D Deficiency.” New England Journal of Medicine, vol. 357, no. 3, July 2007, pp. 266–281.

3. Aranow, Cynthia. “Vitamin D and the Immune System.” Journal of Investigative Medicine, vol. 59, no. 6, Aug. 2011, pp. 881–886.

4. Pilz, Stefan, et al. “Role of Vitamin D in the Endocrine System.” Nature Reviews Endocrinology, vol. 14, no. 12, Dec. 2018, pp. 679–691.

5. Murdaca, Giuseppe, et al. “Vitamin D and Autoimmune Diseases.” Autoimmunity Reviews, vol. 18, no. 5, May 2019.

6. Holick, Michael F. “Sunlight and Vitamin D for Bone Health.” American Journal of Clinical Nutrition, vol. 80, no. 6, Dec. 2004.

7. Heaney, Robert P. “Vitamin D—Baseline Status and Effective Dose.” New England Journal of Medicine, vol. 367, no. 1, July 2012.

8. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press, 2011.

9. Holick, Michael F., et al. “Evaluation, Treatment, and Prevention of Vitamin D Deficiency.” Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 7, July 2011.

10. Vieth, Reinhold. “Vitamin D Toxicity, Policy, and Science.” Journal of Bone and Mineral Research, vol. 22, no. S2, Dec. 2007.

11. McCullough, Paul J., et al. “Daily Oral Dosing of Vitamin D3 Using 5,000–50,000 IU.” Journal of Steroid Biochemistry and Molecular Biology, vol. 189, Apr. 2019.

12. Tripkovic, Laura, et al. “Comparison of Vitamin D2 and D3 Supplementation.” American Journal of Clinical Nutrition, vol. 95, no. 6, June 2012.

13. Endocrine Society. Clinical Practice Guideline on Vitamin D Deficiency. 2011.

14. Glueck, Charles J., et al. “Safety of 50,000–100,000 IU Vitamin D3 Weekly.” North American Journal of Medical Sciences, vol. 8, no. 4, Apr. 2016.

15. Taylor, Paul N., et al. “Vitamin D Toxicity.” BMJ, 2018.

16. Schurgers, Leon J., et al. “Vitamin K–Dependent Proteins and Vascular Health.” Thrombosis and Haemostasis, vol. 100, no. 4, Oct. 2008.

17. Uwitonze, Alice M., and Razzaque, Mohammed S. “Role of Magnesium in Vitamin D Activation.” Journal of the American Osteopathic Association, vol. 118, no. 3, Mar. 2018.

18. Mulligan, Gerald B., and Licata, Angelo. “Taking Vitamin D with the Largest Meal Improves Absorption.” Journal of Clinical Endocrinology & Metabolism, vol. 95, no. 12, Dec. 2010.

    
    

MEDICAL DISCLAIMER

This content is for educational purposes only and does not constitute medical advice. Please consult your healthcare provider for personalized medical guidance.