Does Vitamin D Raise or Lower SHBG?
Vitamin D supplementation raises SHBG levels in adults, particularly in women, though the clinical significance of this increase remains modest and the effect may vary by baseline vitamin D status and sex.
The Direct Evidence on Vitamin D and SHBG
The relationship between vitamin D and SHBG appears to be positive but modest:
In eumenorrheic women, higher vitamin D levels are associated with higher SHBG concentrations (4% increase in SHBG per 10 ng/mL increase in vitamin D), which translates to lower free androgen index and reduced bioavailability of androgens 1.
A 2019 meta-analysis of randomized controlled trials in men found no significant effect of vitamin D supplementation on SHBG levels (mean difference 1.56,95% CI: -0.85 to 3.97, p = 0.204), suggesting the effect is either absent or too small to detect in male populations 2.
In a 2024 randomized trial of 307 infertile men, vitamin D supplementation (300,000 IU bolus followed by 1400 IU daily for 150 days) showed no significant changes in SHBG between treatment and placebo groups 3.
The Mechanistic Explanation
The biological rationale for vitamin D affecting SHBG involves its steroid hormone properties:
Vitamin D functions as a steroid hormone with cross-talk capabilities with other steroid and nuclear hormone receptors, potentially affecting their actions and the production of hormone-binding proteins 4.
SHBG synthesis is stimulated by estrogens, and vitamin D has effects similar to estrogen through cross-talk with steroid receptors, which may explain why the effect is more pronounced in women than men 4.
In chronic liver disease, SHBG levels are often elevated, and clinicians must use the ratio of total testosterone/SHBG (free testosterone index) for accurate gonadal assessment, with a ratio <0.3 indicating hypogonadism 5, 4.
Clinical Context: When This Matters
The vitamin D-SHBG relationship has practical implications in specific populations:
In men and postmenopausal women, the combined presence of low vitamin D AND low SHBG is associated with much higher odds of moderate-severe NAFLD (men: OR 6.57; women: OR 8.16), suggesting these markers interact in metabolic disease 6.
In older men, the combination of vitamin D deficiency with low bioavailable estradiol and/or high SHBG is associated with lower bone mineral density, higher hip bone loss, and 1.6-fold increased fracture risk compared to men with normal levels of both 7.
Important Caveats
The effect size is small and may not be clinically meaningful in most patients, as the meta-analysis confidence intervals crossed zero and individual studies showed inconsistent results 2.
Sex differences are important: the positive association between vitamin D and SHBG appears more consistent in women than men, possibly due to differences in estrogen-mediated SHBG regulation 1.
Baseline vitamin D status matters: effects may be more pronounced in those with vitamin D insufficiency (<50 nmol/L or <20 ng/mL), though even in this subgroup, SHBG changes were not the primary finding 3.
When assessing gonadal status in patients receiving high-dose vitamin D supplementation (>4,000 IU daily), be aware that SHBG levels may be elevated, potentially affecting interpretation of total testosterone measurements 4.