While the skeletal effects of nutrient deficiency are well-known, it’s important to consider how deficiency impacts the endocrine system
By Ricardo Correa, MD, EdD, FACP, FACE
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Traditionally, research on vitamin D and calcium in elderly populations has focused primarily on skeletal health. But with the discovery of vitamin D receptors in the nervous, cardiovascular and endocrine systems, the role of vitamin D and its impact on these systems has become an important area of research, especially as the aging population is expected to continue expanding. A significant percentage of older adults suffer from vitamin D deficiency — a National Health and Nutrition Examination survey reported more than 40% of the adult participants (≥ 20 years) were vitamin D deficient.1 An even higher prevalence of vitamin D deficiency exists among people of advanced age and institutionalized people. Because of the prevalence of vitamin D deficiency and its associated impact, it is important to understand how to recognize and treat the condition.
After the body absorbs vitamin D from either dietary ingestion or UV exposure to the skin, it circulates first to the liver where it undergoes hydroxylation by vitamin D 25-hydroxylase (25-OHase) to 25 hydroxyvitamin D [25(OH)D3]. From there, [25(OH)D3] circulates to the kidneys and undergoes a second hydroxylation by 25-hydroxyvitamin D-1-α-hydroxylase (1-OHase) to 1,25-dihydroxyvitamin D [1,25(OH)2D]. This is the biologically active form of vitamin D (calcitriol). As the level of [1,25(OH)2D] increases, the body’s vitamin D nuclear reactors (VDR) are stimulated and activate gene transcription. When [1,25(OH)2D] interacts with these VDR sites across several organs of the body, it leads to several biological actions, including calcium regulation in the bones and insulin sensitivity and secretion in the pancreas. When vitamin D levels are low, the body cannot sufficiently absorb calcium, which can lead to a multitude of health problems.
Vitamin D deficiency is one of the causes of secondary hyperparathyroidism as a response to negative calcium balance. When the body is deficient in these two nutrients, the parathyroid glands compensate by producing too much parathyroid hormone (PTH), which can in turn lead to osteoporosis as well as muscle weakness. Secondary hyperparathyroidism is also common in patients over 75 years. The pathogenesis is multifactorial (decreased skin production of vitamin D from lower sunlight exposure, decreased intestinal absorption and decreased synthesis), and it can lead to osteomalacia.
Elderly patients are at a higher risk for vitamin D deficiency due to several risk factors. These include diminished diet, certain medications, reduced sunlight exposure, thinning skin thickness, impaired intestinal absorption and impaired hydroxylation in the liver and kidneys. To reduce vitamin D and calcium deficiency, the Endocrine Society and the Institute of Medicine released recommended daily allowances (RDA) for both, as well as maximum daily consumption amounts that should not be exceeded for safety.
For patients between 1-70 years, the RDA for vitamin D is 600 IU/d, and 800 IU/d for patients 71 years and older. For patients 51-70+ years, the maximum daily value for vitamin D is 4,000 IU/d. For male patients between 51-70 years, the RDA for calcium is 1,000 mg/d, and for female patients between 51-70 years and all patients over 71, the RDA for calcium is 1,200 mg/d. The maximum daily value of calcium for all patients between 51-70+ years is 2,000 mg/d.2 However, these recommendations may depend on medications the patient is taking or if they are obese. While vitamin D toxicity is rare, high levels of vitamin D for extensive periods of time are associated with cardiovascular and kidney damage. Patients treated with high doses of vitamin D supplements should have their lab values monitored closely.
Evaluation of serum 25(OH)D and bone mineral density are the primary evaluations of vitamin D deficiency. When patients are diagnosed as vitamin D deficient, the first-line therapy is often oral vitamin D3 and calcium. Vitamin D3 has demonstrated long-term benefits by normalizing the 25(OH)D and PTH concentration, and it has shown benefits in regard to the final treatment goals of intestinal absorption of calcium, which can lead to fewer bone fractures and falls. Calcium carbonate is the preferred calcium supplement due to its better absorption with meals. However, it can be poorly absorbed if there is hypo or achlorhydria or in patients taking proton pump inhibitors (PPIs) or H2 blockers. In these cases, calcium citrate is the preferred option. In certain situations (liver failure, patients treated with glucocorticoids and cases of intestinal malabsorption after bariatric derivative surgery), calcidiol is the preferred treatment for vitamin D deficiency. In situations of chronic renal failure, calcitriol is most useful, but its administration should be monitored closely due to an increased risk of stimulating calcifications, particularly in the kidney, muscle and basal ganglia.3
The Endocrine Society notes that an estimated 33% of adults aged 65 and older have diabetes.4 While findings are inconsistent, accumulating evidence suggests that disruption in vitamin D regulation may contribute to the development of Type 2 diabetes.5 Vitamin D supplementation could help treat patients with deficiency while also providing preventive benefits for reducing the condition in a population where one in three patients are affected. However, results from larger studies are still needed to better understand the relationship between low levels of vitamin D and diabetes before supplementation can be recommended as an effective preventive therapy for diabetes. In the meantime, the benefits from vitamin D and calcium supplementation are extensive and reducing the frequency of deficiency in the geriatric population remains an important goal for endocrinologists.
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