PATHCHAT Edition No. 44
June 2017
Please contact your local Ampath pathologist for more information.
Author: Dr. Marita du Plessis
Vitamin D: Revised Cut-Offs for Adequacy
✅ New Ampath Cut-Offs for Vitamin D Status (Based on Institute of Medicine & NOFSA Guidelines):
- Deficient: <12 ng/mL
- Insufficient: 12–19 ng/mL
- Sufficient: ≥20 ng/mL
📌 These new cut-offs align with recommendations from the National Osteoporosis Foundation of South Africa (NOFSA) and the Institute of Medicine (IOM).
Prevalence of Vitamin D Deficiency
🔹 Global Data:
- 41.6% of US adults (aged 20+) have vitamin D levels below 20 ng/mL (NHANES 2005–2006).
🔹 South African Data:
- 41% of tested samples at Tygerberg Hospital had vitamin D levels below 15 ng/mL.
- NHLS study in Johannesburg:
- 28.6% of Indian patients had levels below 12 ng/mL.
- Only ~5% of Black African patients had levels below 12 ng/mL.
📌 Ethnic, seasonal, and gender differences influence vitamin D levels in South Africa.
Vitamin D & Health
✅ Primary Function of Vitamin D:
- Maintains calcium and phosphate homeostasis.
- Essential for bone mineralization and skeletal health.
✅ Potential Extraskeletal Benefits (Not Yet Conclusively Proven):
- Immune system regulation.
- Cardiovascular health.
- Reduced risk of cancers, diabetes, and autoimmune diseases.
📌 Vitamin D's strongest proven role remains in bone health, reducing fracture risk and osteoporosis progression.
Sources of Vitamin D
✅ 1. Sunlight (Main Source)
- UVB exposure converts 7-dehydrocholesterol to vitamin D3 (cholecalciferol).
- Factors influencing synthesis:
- Season & latitude.
- Skin pigmentation.
- Indoor lifestyles.
- Sunscreen & clothing habits.
✅ 2. Dietary Sources (Limited Contribution)
- Fatty fish (salmon, sardines, tuna).
- Fortified dairy products, cereals, and infant formula.
📌 Sun exposure remains the dominant source of vitamin D, especially in regions with limited dietary fortification.
Vitamin D Metabolism & Regulation
✅ 1. Skin Synthesis:
- UVB exposure converts 7-dehydrocholesterol to previtamin D3.
- Heat-dependent isomerization forms vitamin D3 (cholecalciferol).
✅ 2. Liver Conversion:
- Vitamin D3 is hydroxylated to 25-hydroxyvitamin D [25(OH)D] (calcifediol), the primary circulating form.
✅ 3. Kidney Activation:
- 1α-hydroxylase enzyme converts 25(OH)D to 1,25-dihydroxyvitamin D (calcitriol), the biologically active form.
✅ 4. Regulation by Hormones & Feedback Mechanisms:
- Parathyroid hormone (PTH) stimulates renal 1α-hydroxylase, increasing calcitriol levels.
- Fibroblast growth factor 23 (FGF23) inhibits calcitriol synthesis.
- Calcitriol negatively regulates PTH and FGF23 production.
📌 Dysregulated vitamin D metabolism contributes to conditions like hypercalcaemia in granulomatous diseases and lymphoma.
Recommended Vitamin D Levels & Guidelines
✅ Vitamin D Adequacy (Ampath’s New Guidelines, 2017):
- Deficient: <12 ng/mL (30 nmol/L)
- Insufficient: 12–19 ng/mL (30–49 nmol/L)
- Sufficient: ≥20 ng/mL (50 nmol/L)
🔹 International Guidelines:
- National Osteoporosis Foundation (NOF) & American Geriatric Society (AGS):
- Target 30–50 ng/mL in older adults.
- Endocrine Society (2011):
- Deficiency: <20 ng/mL; Insufficiency: 20–29 ng/mL.
📌 Ampath now follows the IOM and NOFSA 2017 guidelines, which define sufficiency at 20 ng/mL or above.
Vitamin D Deficiency: Causes & Risk Factors
✅ 1. Inadequate Sun Exposure:
- Limited outdoor activity.
- Use of sunscreen & protective clothing.
- High skin melanin content (darker skin tones).
✅ 2. Poor Dietary Intake or Absorption Issues:
- Fat malabsorption syndromes (e.g., celiac disease, Crohn’s disease).
- Chronic liver or kidney disease.
- Exclusive breastfeeding without supplementation.
✅ 3. Increased Catabolism or Resistance:
- Drugs that induce P450 enzymes (e.g., phenytoin, rifampicin, carbamazepine).
- Nephrotic syndrome (urinary loss of vitamin D-binding protein).
- Hereditary vitamin D resistance syndromes.
📌 High-risk groups include the elderly, pregnant women, obese individuals, and those with chronic diseases affecting vitamin D metabolism.
Vitamin D Deficiency: Diagnosis & Testing
✅ 1. Serum 25(OH)D Measurement (Gold Standard)
- Reflects dietary & sun-derived vitamin D status.
- NOT affected by PTH or acute calcium changes.
✅ 2. Additional Laboratory Tests (When Indicated):
- Serum calcium, phosphate, alkaline phosphatase (ALP).
- Parathyroid hormone (PTH) for secondary hyperparathyroidism.
- Renal function tests (urea, creatinine) in chronic kidney disease.
📌 1,25-dihydroxyvitamin D (calcitriol) testing is reserved for specific disorders (e.g., granulomatous diseases, inherited rickets).
Vitamin D Supplementation & Treatment
✅ Recommended Daily Allowances (RDA):
- Adults (19–70 years): 600 IU/day.
- Elderly (>70 years): 800 IU/day.
- Pregnancy & lactation: 600 IU/day.
- Obese patients, those with malabsorption, or on enzyme-inducing drugs: 2–3× standard dose.
✅ Deficiency Treatment Guidelines:
- Severe Deficiency (<10 ng/mL):
- 50,000 IU Vitamin D2/D3 weekly for 6–8 weeks, then maintenance of 800 IU daily.
- Moderate Deficiency (10–20 ng/mL):
- 800–1,000 IU daily, re-test in 3 months.
📌 High-dose intermittent bolus therapy (>50,000 IU) increases fall risk in elderly and is not recommended.
Key Takeaways for Clinicians
✅ Vitamin D sufficiency is now defined as ≥20 ng/mL, per IOM and NOFSA guidelines.
✅ Sunlight exposure remains the primary vitamin D source.
✅ High-risk groups (elderly, pregnant women, those with malabsorption) require screening.
✅ Oral vitamin D supplementation is preferred over high-dose intermittent therapy.
✅ Excessive vitamin D (>60 ng/mL) is associated with hypercalcaemia and increased mortality risk.