Vitamin D Deficiency

A Clinical and Genetic Overview for Patients and Practitioners
by Dr. Elizaveta Kutis, MD

Overview

Vitamin D deficiency is one of the most overlooked causes of fatigue, mood instability, muscle weakness, metabolic slowdown, and accelerated aging. Even in regions with year-round sunlight—like Miami—deficiency remains common due to genetics, liver activation issues, hormonal imbalances, poor absorption, and modern indoor lifestyle patterns.

Vitamin D functions more like a hormone than a vitamin. It influences more than 3,000 genes, regulates immune and endocrine systems, stabilizes mood, protects bone density, and plays a key role in metabolic health.

Symptoms of Vitamin D Deficiency

Patients may experience:
Low energy or fatigue despite adequate sleep
Depressive mood, irritability, or emotional instability
Brain fog and difficulty concentrating
Frequent illnesses or slow recovery
Muscle weakness or body aches
Weight gain and increased carb cravings
Low libido and hormonal imbalance
Poor stress tolerance
Hair thinning or skin dryness
These symptoms often remain unexplained until a blood test reveals low Vitamin D levels.

Causes of Vitamin D Deficiency

1. Limited Sun Activation

Even daily sun exposure may not be enough due to:
sunscreen use, indoor lifestyle, air pollution, aging (skin converts less Vitamin D), darker skin tone (more melanin = less Vitamin D synthesis)

2. Liver Activation Problems

Vitamin D requires activation in the liver (25-hydroxylation) and kidneys.
If liver activation is slowed, deficiency persists even with supplements.

3. Genetic Variants (Key Factor)

Some patients cannot activate Vitamin D effectively due to SNPs such as:
CYP2R1 rs10741657 — reduces liver conversion of Vitamin D into its usable form
GC (Vitamin D Binding Protein) — affects transport
VDR variants — affect receptor responsiveness
In these individuals, oral Vitamin D often does not work. For patients with CYP2R1 variants or poor response to supplements, the most effective option is an intramuscular Vitamin D injection. 

4. Malabsorption

Common in patients with: gut dysbiosis, low stomach acid, celiac tendencies, inflammatory bowel disease, bariatric surgery history

5. Hormonal Imbalances

Low Vitamin D is associated with: low estrogen, low testosterone, adrenal stress, impaired thyroid conversion

Complications of Untreated Deficiency

Vitamin D deficiency accelerates several aging pathways:

Bone & Musculoskeletal System

Early bone loss, osteopenia / osteoporosis, weak muscles and poor balance, increased fracture risk
DEXA scans often reveal early structural changes years before symptoms appear.

Hormonal Disruption

Low Vitamin D affects: thyroid receptors, ovarian and testicular hormone production, adrenal cortisol regulation

Metabolic Effects

Increased visceral fat, insulin resistance, chronic inflammation (“silent aging”)

Neurological & Emotional Effects

Seasonal mood changes, low serotonin and dopamine tone, poor sleep quality

Genetics and Vitamin D (CYP2R1 Focus)

The CYP2R1 gene controls the liver enzyme responsible for converting Vitamin D into 25-OH Vitamin D, the form measured in blood. Patients with the rs10741657 variant (especially homozygous) typically experience: chronically low Vitamin D, minimal improvement from oral supplements, poor response to sprays, capsules, even high doses, significant mood and energy improvements once Vitamin D bypasses the liver. This subtype of deficiency requires injectable Vitamin D for effective correction.

Diagnosis

1. Blood Test

The primary marker is 25-hydroxyvitamin D (25-OH-D).
Optimal range for longevity: 50–90 ng/mL.

2. Genetic Testing

Testing for CYP2R1, GC, and VDR variants helps explain why supplements fail.

3. DEXA Scan

Evaluates: early bone loss, bone quality, muscle mass, visceral fat, metabolic aging markers. Patients with negative changes often benefit from aggressive Vitamin D correction.

Treatment Options

1. Oral Vitamin D (not effective for everyone)

Best for patients without genetic variants and with good gut function.

2. Liquid or Spray Vitamin D

Absorbs faster, but still requires liver activation.

3. Injectable Vitamin D (Most Effective)

For patients with:
CYP2R1 variants
low response to supplements
early bone loss
chronic fatigue
depression or mood instability
visceral fat increase
hormonal imbalance

Intramuscular Vitamin D bypasses liver conversion and delivers the active form directly into circulation.
Most patients feel improvements in 1–3 weeks.

Prevention & Maintenance

Regular bloodwork (every 3–6 months)
15–20 minutes of safe sun exposure
Magnesium, zinc, and boron to support Vitamin D activation
Healthy gut function (probiotics, digestive support)
Strength training to stimulate bone density

When to See a Doctor

Seek evaluation if you experience:
-persistent fatigue
-low mood
-chronic stress intolerance
-muscle pain or weakness
-weight gain without cause
-low libido
-sleep issues
-difficulty recovering from exercise

Or if your Vitamin D remains low despite supplementation.

FAQ

Why don’t supplements work for some people?
Because of genetic variants such as CYP2R1, which slow liver activation.

How fast do injections work?
Most patients notice improvements within 1–3 weeks.

Is it safe?
Yes, when monitored with periodic bloodwork.

How often do I need it?
Weekly or monthly, depending on deficiency and genetics.