Part 34: The Importance of Maintaining Longer-term, Stable 25(OH)D Blood Levels

Recent data from epidemiological, cross-sectional, and longitudinal studies support the need for maintaining physiological serum concentrations of 25(OH)D (i.e., ≥ 30 ng/mL) over a long period (10, 11). The data indicate that to achieve such benefits, serum 25(OH)D concentrations of more than 30 ng/mL (75 nmol/L) need to be maintained throughout the life. 

It is important to note that most adults need a maintenance dose of between 1,000 and 2,000 IU/day. However, people who are at risk and vulnerable to the development of hypovitaminosis D or have comorbidities, and pregnant women, may need between 4,000 and 6,000 IU/day to have optimal physiological effects. Whereas, dosages as great as 10,000 IU/day have been reported to be safe. Various safe regimes and replenishment modes of vitamin D are presented in a tabulated format in the following book [“Vitamin D: Everything you need to know:” https://www.amazon.com/gp/product/9559098942].

Effective ways of replenishing vitamin D: 

Vitamin D facilitates dietary calcium and phosphorus absorption from the intestines. Being a fat-soluble vitamin, its intestinal absorption of vitamin D depends on availability of dietary fat. Adequate exposure to sunlight, food fortification with vitamin D, especially in dairy products have reduced the incidence of vitamin D deficiency. However, incidence has reemerged, especially in infants, children, elderly, and in certain ethnic groups, worldwide.

Vitamin D suppresses the release of parathyroid hormone (the release of which is dependent on magnesium sufficiency), a hormone that causes bone resorption. Having normal serum 25(OH)D concentration keeps the parathyroid hormone under control, and thus, prevents excessive bone resorption and future fractures.   

In the absence of such conditions, those with hypovitaminosis D will benefit from a loading dose (calculations based on the deficit and body weight). This will allow rapid achievement of adequate serum 25(OH)D concentration and replenishment of body stores, in persons with vitamin D deficiency. Thus, upfront oral loading dose (much cost-effective) should be administered in all persons with vitamin D deficiency. This can be easily accomplished by the administration of 50,000 IU (i.e., one gel capsule), once or twice a week for several weeks, depending on the baseline serum 25(OH)D concentration (12-14). 

In the absence of giving a loading dose to a person with vitamin D deficiency, he or she is going to take several years to fill-up their body storage. This inappropriate (and unethical) delay can make patients unnecessarily vulnerable to diseases. For example, those who are having very low serum 25(OH)D concentrations need between 600,000 IU and a million IU of vitamin D to refill their tissue storage. The next section provides few examples.

Examples of loading-doses of vitamin D and maintenance doses:

The goal of the loading dose regimens is to rapidly correct the deficiency status and replenish the body storage tissues with vitamin D. However, after a loading dose is administered, such individuals are going to need a daily maintenance dose of vitamin D to prevent serum 25(OH)D levels reverting to deficiency conditions. This will assure longer term benefits from the intervention. For example, a person of 70 kg body weight with a serum 25(OH)D concentration of 18 to 24 ng/mL can be treated with either 5,000 IU/day for 2 months (or 50,000 IU once a week for 6 weeks), followed by a maintenance dosage of 2,000 IU/day. 

A person with a vitamin D level of 8 to 12 ng/mL needs a total loading dose of more than 600,000 IU to replenish body stores and restore blood levels. Those with levels of less than 7 ng/mL, might require approximately, 1 million IU to replenish the body vitamin D stores. Such can be provided with a capsule of 50,000 IU twice a week for 6 weeks (or once capsule a week for 12 weeks, but some may need repeat of the course), followed by a maintenance dose of 2,000 IU/day.

Those who are severely deficient, with serum 25(OH)D concentrations of less than 10 ng/mL (concomitantly having osteomalacia and proximal myopathy), are likely to have a deficit of between 800,000 and 1.2 million IU. To replenish their body stores, they are likely to need a 50,000 IU capsule twice a week for 8 to 12 weeks, followed by a maintenance dosage of 2,000 and 5,000 IU/day.

In such patients, it is a mistake for a healthcare provider to advise a patient to take over the counter, vitamin D preparations of 400, 1,000 or even 2,000 IU/day, because it would take more than 2 to 3 years to obtain the needed dose, not even counting the patient’s needs during that period. Such deficits must be provided within weeks, not in years. 

Cautious approaches needed in certain populations:

Vitamin D supplementation is contraindicated (or its administration requires great caution) for anyone who had or has the potential to experience hypercalciuria (i.e., excess calcium in urine) or hypercalcemia (i.e., increased calcium in blood). The latter group includes but is not limited to persons with granulomatous diseases (e.g., tuberculosis, leprosy and  sarcoidosis), Williams syndrome, hyperparathyroidism, and so forth. Next article will describe these in detail.

Basic principles of vitamin D supplementation:

The best route and form of vitamin D is oral administered D3; preferably administered as a daily maintenance dose. Doses administered too infrequent (e.g., less than once a month) and extremely high doses (e.g., upwards of 300,000 IU, given intermittently) are ineffective and may cause adverse effects. Moreover, vitamin D should never be administered as an intramuscular injection (because it is painful and should be administered orally), although such preparations are not available in United States but are available in some other countries. However, the contents of such vials can be effectively administered orally as part of an up-front loading strategy.  

Activated vitamin D has no place in vitamin D supplementation:

Except in those with liver or kidney failures, there is no scientific reason to prescribe any form of activated vitamin D. Activated forms of vitamins D, such as derivatives of one-alpha or 25-hydroxylase activated forms, are expensive and can have major adverse effects; thus, they should never be prescribe as vitamin D supplementation. 

Taking cod liver oil (and some fish oils) is not a good option for vitamin D supplementation because these oils contain too much vitamin A; excessive vitamin A that can cause liver damage and skeletal fractures. Individuals with some conditions, especially diseases affecting the intestinal tract, such as celiac disease, Crohn's disease, and ulcerative colitis, and gastric bypass surgery or cystic fibrosis, have significant problems with intestinal absorption of vitamin D and thus are unable to maintain serum 25(OH)D levels. Such patients require much higher doses of daily, oral vitamin D supplementation.  

The need for sustained levels of serum 25(OH)D levels:

Severe and prolonged vitamin D deficiency causes rickets in children and osteomalacia in adults. In addition, vitamin D insufficiency and milder deficiencies increase the risks for many diseases, including osteoporosis, falls and fractures. Serum 25(OH)D levels below 20 ng/mL (<50 nmol/L) further increase risks for chronic conditions including such as diabetes mellitus, autoimmune diseases, cardiovascular disease, hypertension, inflammatory disorders and certain cancers. 

Many clinical studies have reported the value of longer-term maintenance of 25(OH)D levels in the sufficient range. In addition, one recent study reported that vitamin D supplementation in obese patients with type 2 diabetes improved their blood sugar control (15). More information is available at: https://www.vitamindcouncil.org/vitamin-d-pharmacology/#.Xatr025Fxpw

The  consequences of vitamin D deficiency include impaired immunity, increased autoimmunity, myopathy, metabolic disorders (e.g., obesity, metabolic syndrome, diabetes mellitus), and an increased risk of colon, breast, and prostate cancers (16). In addition, hypovitaminosis D increases the risks and the severity of higher blood pressure, and serum 25(OH)D has a positive association with increased longevity (17) and reduced all-cause mortality (17). 

The need for country-specific vitamin D guidelines:

The United States (north America) or European guidelines are designed and validated only for those populations. Thus, other countries should not depend on these guidelines. Instead, other countries and regions (e.g., the Gulf region, Asian countries, etc.) should develop their own ethnic-specific, culturally acceptable, practical vitamin D-related clinical practice guidelines and recommendations for supplementation, together with safe-sun exposure guidance, based on the needs of the population. 

However, progress in this matter has been somewhat hampered by the confusion caused by a few recently published, extensive, large clinical trials related to vitamin D; these trials contained multiple study design flaws.

For the benefit of their populations, it is prudent for individual countries, or at least countries within geographic regions, to generate their own vitamin D guidelines. This could be facilitated by adopting the best practices from the published data and guidelines, considering pertinent ethnic, cultural, and dietary habits, as well as geographic locations with restricted UVB availability. Recommendations also should be given that reflect the increased need of vitamin D during the winter months, when UVB availability is minimal or absent.

Summary:

With increasing longevity of humans and the need to maintain optimal health, it is important to have physiological intakes of micronutrient including antioxidants, preferably coming from the diet, to achieve physiological concentrations in the body. These includes, vitamins and antioxidants, and essential fatty acids, ideally should coming from natural food sources (but these sources do not need to be organic). These nutrients are important for eliminating invading pathogens and preventing autoimmunity and certain cancers.

Despite ethnic variations, the optimal range of serum 25(OH)D concentration for human does not vary from country to country. Considering ethnic, cultural, dietetic, social, and geographic differences, each country (or regions) should generate its own population-based guidelines for dietary and supplementation of vitamin D, calcium, and other essential micronutrients, with the goal of reducing healthcare costs and preventing acute and chronic diseases.  

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Professor Sunil J. Wimalawansa, MD, PhD, MBA, DSc, is a physician-scientist, educator, social entrepreneur, and process consultant. He is a philanthropist with experience in long-term strategic planning, and cost-effective investment and interventions globally for preventing non-communicable diseases [recent charitable work]. The author has no conflicts of interest and received no funding for this work.