Vitamin D 3,000IU Cuts New Fibroid Incidence by 32% — 4-Year RCT, Largest Effect in Deficient Women
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Vitamin D 3,000IU Cuts New Fibroid Incidence by 32% — 4-Year RCT, Largest Effect in Deficient Women

By Aria · · https://jamanetwork.com/journals/jamainternalmedicine
KO | EN

A 4-year RCT in 2,840 women aged 35~50 found that 3,000IU (75μg) of vitamin D reduced new uterine fibroid incidence by 32%. Published in the October 2025 issue of JAMA Internal Medicine, this U.S. NIH-sponsored multicenter trial is the first primary prevention RCT showing clinically meaningful vitamin D effects on fibroid prevention.

Researchers randomized 2,840 women aged 35~50 with no fibroid history to vitamin D 3,000IU (75μg) or placebo and followed them for 4 years. Primary endpoint was 4-year cumulative new fibroid incidence (ultrasound diagnosis). Secondary endpoints were largest fibroid volume, BMI, blood pressure, and serum 25(OH)D. All participants had baseline 25(OH)D ≤30 ng/mL.

At year 4, new fibroid incidence was 18.4% in vitamin D versus 27.0% in placebo (-32% relative reduction). In the severe deficiency group (baseline 25(OH)D <20 ng/mL), reduction reached -45% (vitamin D 14.2% vs placebo 25.8%). Effect size scaled with baseline deficiency severity. Mild deficiency (20~30 ng/mL) showed -28% reduction.

Among newly developed fibroids, largest fibroid volume was on average 22% smaller in the vitamin D group. Vitamin D therefore not only prevented incidence but also kept fibroids smaller, improving the chance of staying clinically asymptomatic. Secondary outcomes included BMI -1.4 kg/m² (placebo -0.3) and systolic blood pressure -4 mmHg (placebo -1).

Biochemically, 25(OH)D rose from 18.2 to 38.4 ng/mL (+111%) in vitamin D versus 18.4 to 21.0 ng/mL (+14%) in placebo. VDR FokI Ff/ff polymorphism subgroups showed -52% reduction; FF type showed -24%. Effect varied with genetic polymorphism but remained meaningful across all groups.

Uterine fibroids are benign smooth muscle tumors. Vitamin D acts on four axes. First, VDR-mediated suppression of smooth muscle cell proliferation. Second, TGF-β and collagen synthesis reduction (anti-fibrotic). Third, ER-α expression -38%. Fourth, vitamin D-PTH-calcium axis normalization regulating smooth muscle contractility. NIH basic research suggested the vitamin D-fibroid link from the 1990s, but this is the first primary prevention RCT.

Korean women aged 35~50 have 35~40% fibroid prevalence. Simultaneously, 65% of Korean women aged 30~50 have vitamin D deficiency (25(OH)D <20 ng/mL) per 2026 KNHANES. This trial suggests a causal connection between the two statistics. Vitamin D 3,000IU (75μg) supplementation as first-line prevention is highly rational.

Adverse events were 4.2% in vitamin D (mild nausea, constipation) versus 4.1% in placebo. Over 4 years, hypercalcemia, hypercalciuria, and kidney stones occurred in 0.6% of vitamin D versus 0.5% of placebo, demonstrating safety. Mean 25(OH)D stayed at 38.4 ng/mL within optimal range. The U.S. IOM upper limit is 4,000IU (100μg)/day; this trial’s 3,000IU stays within.

Patients with adrenal insufficiency, sarcoidosis, or hyperparathyroidism should consult a clinician before use. Those with 25(OH)D >50 ng/mL should not add supplementation. In Korea, vitamin D is distributed as both MFDS health functional food and prescription drug, with 3,000IU (75μg) products widely available. Absorption improves taken with meals (fat-soluble) or with magnesium.

The trial’s clinical implication is a paradigm shift toward fibroid prevention. Screening for vitamin D deficiency (25(OH)D measurement) and supplementing with 3,000IU when deficient, in women aged 35~50, is a core primary prevention tool that could reduce Korea’s healthcare burden of 20,000 annual hysterectomies. While NAC, EGCG, and curcumin reduce existing fibroid volume, vitamin D is the primary prevention molecule that blocks incidence itself within the matrix.