Addressing Vitamin D in Disease

Vitamin D, for most, is associated with calcium absorption and bone health. Osteoporosis, osteomalacia, muscle weakness and increased risk of falls are conditions associated with chronic vitamin D deficiency in adults.
However, vitamin D also plays an important role in immunity and homeostasis of multiple organs. Deficiency then may result in illness beyond bone health. Poor intake of vitamin D and low levels of vitamin D metabolites have been associated with such autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA) , type 1 diabetes mellitus, systemic lupus erythematosus (SLE) and psoriasis (Ps). Lower levels of vitamin D, adjusted to body mass index, have also been associated with increased risk of hypertension, myocardial infarction and cardiovascular disease. On the other hand, higher levels of vitamin D have been seen in observational studies to be associated with reduced recurrence and mortality from breast, colon and ovarian cancers.

While there is a lot of direct evidence linking vitamin D supplementation to improvements in muscle strength, reduced incidence of falls and fractures from osteoporosis, there has been poor data that such intervention impacts on cancer incidence or recurrence and other disease associations.
SOURCES AND SUPPLEMENTATION. Vitamin D sufficiency is defined by measuring serum levels of the prohormone 25 (OH) vitamin D. Maintenance of bone health requires levels of 30-32ng/ml which can be obtained from 2200-3000 IU/day of vitamin D from all sources (sun exposure, diet and supplements). Based on international recommendations, oral vitamin D supplementation should be 200IU/day from birth to age 50, 400IU/day from age 51 to 70, and 600IU/day from age 71 and beyond. These values presume some amount of sun exposure and vitamin D intake from food.
Optimal levels are achieved when 25 (OH) Vitamin D is between 30-60ng/ml. Levels between 20-30ng/ml are seen in insufficiency, 10-20ng/ml are seen in deficiency while those <10ng/ml are seen in severe deficiency. Higher levels up to 100ng/ml have been seen in individuals with outdoor occupations receiving intense sun exposure without ill effects. However, levels of 150ng/ml or more are seen in vitamin D intoxication resulting in renal stones and hypercalcemia.
Traditionally, much of the vitamin D is obtained from UV light-induced manufacture of cholecalciferol (vitamin D3). However, contrary to popular belief, only 15-20 minutes of sun exposure WITHOUT sunscreen BETWEEN 10AM and 3PM is usually sufficient to ensure adequate vitamin D synthesis. The rationale here is that UV-B which is relevant to vitamin D synthesis is mostly dispersed in the atmosphere before 10AM and after 3PM. Thus, minimal amounts reach the earth’s surface. On the other hand, we need not worry about being over-exposed to the sun as large excesses of vitamin D metabolites can be destroyed in the skin making vitamin D toxicity improbable.
Food is a poor source of vitamin D, with the exception of cold-water ocean fish. Three ounces of herring (which people infrequently consume) already provides 1300IU but 3.5 ounces of salmon (which is more often ingested) only gives 350IU. One cup of fortified milk or orange juice provides 100IU while 1 cup of cereals provides only 50-100IU.
With today’s lifestyle of spending much time indoors and with the more prevalent use of sunscreens, supplements are fast becoming a more important source of vitamin D. Thus reading the labels of vitamin D supplements is a must in considering what meds to give. Higher levels of basal vitamin intake (1000-2000IU/day) from supplements are recommended to avoid vitamin D deficiency. And not all vitamin D supplements are the same! At similar doses, vitamin D3 (cholecalciferol) is more potent than vitamin D2 (ergocalciferol, obtained mostly from plants) in raising 25 (OH) vitamin D.
THE POPULATION AT RISK. The following are more likely to suffer vitamin D deficiency:
  • Those not taking supplements
  • The elderly
  • Those who are darkly pigmented
  • Obese individuals
  • Those with osteoporosis or osteopenia
  • Those who avoid sun exposure without sunscreen
  • Those living in highly polluted environments
  • Those with Crohn’s disease and other reasons for fat malabsorption
Likewise, individuals who are about to start treatment that could impact bone mineralization should have baseline 25 (OH) vitamin D levels measured. This include premenopausal women who are about to undergo chemotherapy, medical or surgical ovarian ablation and postmenopausal women in whom aromatase-inhibitors are to be given. Estrogen upregulates the enzyme converting 25 (OH) vitamin D to 1, 25 (OH) vitamin D and increases levels of vitamin D receptor proteins. Estrogen depleting therapies then may lead to vitamin D deficiency.
SYMPTOMS OF VITAMIN D DEFICIENCY. Osteoporosis and osteomalacia result from chronic deficiency of vitamin D. However, other symptoms attributable to vitamin D deficiency tend to be non-specific and include fatigue, altered mood and depression, insomnia, non-radicular back pain (non-specific back pain), arthralgias (involving the wrists, ankles, shoulders and shin), proximal muscle weakness (osteomalacic myopathy), headaches and hair loss. Symptoms are uncommon at levels >20ng/ml.
CORRECTING VITAMIN D DEFICIENCY. The first step is actually to obtain baseline 25 (OH) vitamin D levels and then to determine the target replacement. A commonly used guide is that 100IU Vitamin D3 increased 25 (OH) vitamin D by 1 ng/ml after a few weeks (usually after 6-12 weeks). The replacement therapy to be given then should be added to the baseline ingested amount/ recommended daily dose of vitamin D. It is important also to remember that obese individuals may need higher doses of vitamin D supplements as the vitamin tends to be sequestered in adipose tissue. Repeat determinations of 25 (OH) vitamin D depends on the “urgency” of achieving targets which is mostly based on the presence of symptoms.
The following table shows the recommended treatment based on baseline serum 25 (OH) vitamin D levels
The following examples show how we treat vitamin D deficiency.
SCENARIO 1: A 55 year old female is referred following work-up for osteoporosis detected on bone densitometry. The patient has no other co-morbid conditions and on review of symptoms is asymptomatic. Baseline 25 (OH) vitamin D level was 15ng/ml.
RESPONSE: Since the goal would be to achieve optimal levels for bone health, our target would be 30ng/ml. This means the patient needs an additional 1500IU/day (Remember? 100IU to increase by 1ng/ml). Since the patient is 55 years old, the recommended daily dose in health is 400 IU/day. Thus, we would start supplementing this patient with 1900IU Vit D/day (150000IU to correct the deficit + 400IU recommended daily dose) and repeat measurements of 25 (OH) vitamin D levels after 3 months.
SCENARIO 2: A 60 year old breast CA patient is referred to the clinic for complaints of fatigue, muscle weakness and diffuse arthralgias. The referring oncologist also informs you that they are preparing the patient for anti-hormonal treatment. Being the astute clinician, you recognize the symptoms as possibly due to vitamin D deficiency. And true enough, baseline 25 (OH) Vit D levels were 9ng/ml.
RESPONSE: Since the goal for this patient is to resolve symptoms of vitamin D deficiency and cover for possible losses to be incurred during anti-hormonal treatment, a target of 40 ng/ml of 25 (OH) vitamin D may be needed. So to increase the prohormone levels from 9 to 40, we would be needing 3100IU of vitamin D. And since the patient is only 45 years old, the 3100IU is to be added to the 400IU recommended daily dose (total amount to be given per 3500IU).
We could then proceed to supplement this patient with 3000-4000IU/day or 35,000IU once weekly then repeat prohormone levels after 6 weeks. Once the target is achieved and the patient starts anti-hormonal therapy, we may opt to continue supplementing this patient with 2000IU/day of vitamin D to maintain levels at 40ng/ml. It would then be best to discuss serial monitoring of vitamin D levels every 3-4 months while the patient is on anti-hormonal cancer therapy.
Reference: Khan QJ, Fabian CJ. How I treat vitamin D deficiency. J Oncol Prac 2010; 6 (2): 97-101.

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