|Year : 2018 | Volume
| Issue : 3 | Page : 101-105
The global D-Lemma: The vitamin D deficiency pandemic even in sun-drenched countries
Michael F Holick
Department of Medicine; Department of Physiology and Biophysics, Boston University Medical Center, Boston, MA, USA
|Date of Web Publication||8-Apr-2019|
Michael F Holick
Department of Medicine, Boston University Medical Center, Boston, MA; Department of Physiology and Biophysics, Boston University Medical Center, Boston, MA
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Holick MF. The global D-Lemma: The vitamin D deficiency pandemic even in sun-drenched countries. J Clin Sci Res 2018;7:101-5
(See the review article by Harinarayan, on page 131-40, doi: 10.4103/JCSR.JCSR_1_19)
It has been assumed, especially in areas of the world where sunlight is plentiful year-round that children and adults would be obtaining their requirements of the sunshine Vitamin D. However, as documented by Harinarayan in one of the most sun-drenched countries of the world, India, Vitamin D deficiency is an epidemic similar to what has been observed in countries in the Middle East and South America., This deficiency has enormous negative health consequences for children and adults. He has provided a comprehensive review on the physiology, biochemistry, nutrition, guidelines and health consequences of vitamin D deficiency, and therefore, I will focus on a few aspects regarding vitamin D's actions and recommendations on how to prevent one of the world's most common medical conditions, vitamin D deficiency.
The production of the sunshine vitamin D has been occurring in various life forms for at least 500 million years. Phytoplankton that has existed in the oceans unchanged for >500 million years was shown to produce vitamin D2 when exposed to solar ultraviolet radiation. As vertebrates evolved in the oceans and ventured onto land they required an adequate source of calcium for their mineralized skeletons. Calcium was easily accessible in their ocean environment but was scarce on terra firma. To overcome this potentially evolution halting problem, an intimate relationship developed between environmental sunlight and skeletal health. Vertebrates exposed to sunlight produced vitamin D in their skin which, in turn, entered the circulation and became activated to 1,25-dihydroxyvitamin D [1,25(OH)2D]. This hormone travelled to the small intestine and unlocked genetic information that resulted in the efficient absorption of calcium from the diet, thereby permitting the evolution of vertebrates to develop into creatures of the enormous size during the Jurassic period. An asteroid essentially extinguished the dinosaur's evolutionary path which, in turn, favoured the rise of nocturnal mammalian vertebrates which had evolved a separate non-sunlight/vitamin D mechanism for maintaining their calcium and bone metabolism. The return of sunlight and the absence of large predators gave rise to the mammalian evolutionary tree, including humans that have dominated the planet.
There are a variety of observations that provide insight for how much vitamin D humans require for maximum health. Maasai herders and the Hadzeba tribe, who are a good representation of our hunter-gatherer forefathers, are exposed to sunlight at 2°–4° south of the equator in Tanzania on a daily basis. They have evolved to have deeply pigmented skin so that they can be exposed to equatorial sunlight throughout their life without risk for skin cancer. However, as effective as their natural dark melanin sunscreen pigment was for protecting their skin from the damaging effects of the sun; their skin tone was designed to permit enough solar ultraviolet B (UVB) to enter the epidermis to produce vitamin D3 for their skeletal health and overall well-being. Maasai and Hadzeba tribes with hunter-gatherer-like lifestyles were found to have a healthy vitamin D status with a mean blood levels of 25-hydroxyvitamin D [25(OH)D] of 48 ng/mL (46 ± 10 ng/mL) and 44 ng/mL (42 ± 12 ng/mL). To achieve these levels would require an adult to ingest between 3000 and 5000 IU of vitamin D daily., How do we know that this is the likely human requirement for vitamin D rather than the approximately 5–10 fold less, i.e. 600 IU daily requirement that has been suggested by the Institute of Medicine and other organizations for most children and adults?,, One of the most compelling observations is the fact that human's breast milk contains on an average 25 IUs/L of vitamin D which is inadequate for an infant's health and well-being., It makes little sense that this source of infant nutrition would not contain an adequate amount of vitamin D. Hollis et al. reported that when lactating women received 6000 IU vitamin D3 daily they put enough vitamin D in their milk to satisfy their infant's requirement. Pregnant women who achieved blood levels of 25(OH)D in the range of 40 ng/mL have demonstrated marked reductions in developing preeclampsia, having premature births and requiring a caesarean section.,,, To achieve these levels, pregnant women needed to ingest 4000 IUs Vitamin D3 daily throughout their pregnancy. There was no evidence of toxicity when pregnant women ingested 4000 IU of vitamin D daily throughout their pregnancy. There were no significant changes in either their serum calcium levels or in the most sensitive indicator for potential toxicity in their 24-h urinary calcium excretion.
In the 1940s, it was determined that the minimum vitamin D requirement to prevent overt rickets, i.e., skeletal deformities were 100 IU of vitamin D. Based on this observation, it was recommended that children required 200 IUs vitamin D daily for the bone health. However, vitamin D deficiency has subtle effects on the skeleton that are not visibly obvious, i.e., bowed legs, short stature, rachitic rosary, etc. Vitamin D deficiency results in an increase in parathyroid hormone (PTH) which has two consequences on the skeleton. The first is that PTH increases the production of new osteoclasts which remove matrix and mineral from the skeleton causing osteopenia and osteoporosis. The second is an indirect effect caused by the phosphaturic action of PTH. This results in a lower blood phosphorus level, and therefore, there is an inadequate calcium-phosphorus product. Any newly laid down jello-like collagen matrix cannot be mineralized. This results in rickets in children and osteomalacia in adults., Therefore, the presence of osteomalacia and increased blood levels of PTH are good surrogates for vitamin D deficiency and insufficiency. There are numerous studies reporting that to have the PTH levels plateau, blood levels of 25(OH)D need to be in the range of 30–40 ng/mL., Priemel et al. reported that healthy adult men and women ages 20–90 years who had blood levels of 25(OH)D of at least 30 ng/mL had no evidence of vitamin D deficiency osteomalacia. They also found 24% of their adults who had 25(OH)D levels of between 21 and 29 ng/mL had histologic evidence of osteomalacia. Therefore, it is reasonable to assume based on this evidence for maximum bone health children and adults should maintain a blood level of 25(OH)D of at least 30 ng/mL.
There is a robust literature that supports the important role of adequate sun exposure and vitamin D status for reducing a wide variety of chronic and acute illnesses and conditions. These include reduced risk for autoimmune diseases, including multiple sclerosis, Type 1 diabetes and rheumatoid arthritis, cardiovascular disease, Type 2 diabetes, neurocognitive dysfunction, including depression and Alzheimer's disease, infectious diseases, deadly cancers and wheezing disorders.,, However with little forethought and for >50 years, many medical and dermatology societies as well as national and international organizations have recommended avoidance of all direct sun exposure because of concern for skin cancer. Some societies promote sun avoidance for religious and social reasons., They did not take into account that human skin pigment evolved and devolved for permitting an adequate amount of vitamin D to be produced without causing risk for skin cancer. A good example is the Neanderthals who developed a mutation of their melanin receptor resulting in them having a fair celtic skin tone. This gene mutation permitted them to produce an adequate amount of vitamin D at northern latitudes in Europe that had markedly reduced solar UVB radiation for producing vitamin D.,, This adaptation was critically important for their survival. Female infants born of mothers with very dark skin tone would have been vitamin D deficient and had infantile rickets. Vitamin D deficiency not only causes growth retardation and long bone deformities but it also has an effect on the pelvis causing it to be flattened with a small pelvic outlet. Therefore, during their childbearing years, these females would have had difficulty in passing their infant through their birth canal leading to increased risk for both maternal and infant morbidity and mortality.
To support the concept for hypopigmented skin evolving for ensuring an adequate amount of sunlight-induced vitamin D synthesis in a European environment Felton et al. conducted a study in fair-skinned adults (skin type II) and Indians (skin type IV). These group of adults were exposed to simulated UK summer sunlight three times a week for 6 weeks. They demonstrated after the 1st week of exposure there was UVB-induced DNA damage in the fair-skinned participants and very little in the dark-skinned participants. After 6 weeks, there was little additional accumulation of DNA damage, and there was a significant increase in their blood level of 25(OH)D. Those participants with dark skin had little accumulating DNA damage in their epidermis and had no significant increase in their blood levels of 25(OH)D.
How important is it to maintain a healthy blood level of 25(OH)D as well as a healthy blood level of vitamin D3 as our ancestors did when they were being exposed to sunlight on almost a daily basis? One insight for how maintaining a blood level of vitamin D3 may have its own health benefit was the observation that vitamin D3 was 10 and 1000 times more effective than 1,25(OH)2D3 and 25(OH)D3, respectively in stabilising endothelial membranes which is associated with reduced risk for vascular leaking and inflammation. Endothelial membrane destabilization has been associated with a wide variety of chronic illnesses, including autoimmune diseases and cardiovascular disease.
There are several studies that have reported that Vitamin D deficiency is associated with increased risk for mortality mainly due to increased risk for cardiovascular disease. Another benefit of Vitamin D is on the ageing process. Leucocyte telomere length shortening is associated with ageing and is a hallmark of genomic instability and carcinogenesis. An analysis of data from the US National Health and Nutrition Examination Survey (NHANES) 2001–2002 study revealed that middle-aged participants (40–59 years) who had a blood level of 25(OH)D >20 ng/mL had longer leucocyte telomere lengths. Ageing is also associated with protein cross-linking. A study in roundworms found that feeding them vitamin D significantly prolonged their life by inducing genes responsible for preventing cross-linking of proteins which is a key factor in the ageing process.
Harinarayan recommends that there should be global recommendations for sensible sun exposure along with adequate vitamin D intake from supplements and fortified foods. The World Health Organization, British Association of Dermatologist and the Cancer Council, Australia are all recognising that some sun exposure is important for satisfying children and adults vitamin D requirement [Table 1]. However, it is not realistic in the 21st century to expect children and adults to expose enough of their skin surface between the hours of 10 a.m. and 3 p.m. to produce an adequate amount of vitamin D3 to satisfy their requirement. It is also unrealistic due to cost, availability and compliance to expect all children and adults to take a daily vitamin D supplement. Food fortification should be a major focus of government health agencies to combat the global vitamin D deficiency pandemic. Before the 1950s, milk, beer, custard, soap and even hot dogs were fortified with vitamin D because of its perceived health benefits. However, in the early 1950s, a few isolated reports of children in England presenting with hypercalcaemia, altered faces and mild mental retardation that the experts concluded was due to vitamin D intoxication because of over fortification of milk with vitamin D resulted in laws forbidding the fortification of any food or product used by humans with vitamin D. This concept quickly spread throughout Europe and most of the world and remains a major impediment for food fortification programs with vitamin D or even the availability of a vitamin D supplement without obtaining a doctor's prescription. Even though the more likely explanation to explain the cause for the hypercalcaemia, mild mental retardation and altered faces was due to the rare genetic disorder Williams syndrome, that is also associated with a hypersensitivity to vitamin D causing hypercalcaemia, only a few countries besides the United States and Canada that include Finland, Sweden and now India permit and encourage some foods, including dairy products such as milk to be fortified with vitamin D. In India, cooking oil is now also fortified with Vitamin D. Since vitamin D is very heat stable up to about 200°C, this is a reasonable strategy to improve the Vitamin D status of both children and adults in India. What is needed, however, as recommended by Harinarayan, is that additional foods commonly consumed, including flour, rice, juice products and other foods specifically related to societal requirements should be fortified with Vitamin D. There is little concern about ingesting a variety of foods fortified with vitamin D along with sun exposure as causing vitamin D intoxication. Vitamin D intoxication usually only occurs when extremely high amounts of vitamin D are ingested for a significant period.
|Table 1: Comments by the World Health Organisation and Professional Societies and Uniform Resource Locators|
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An effective strategy to treat vitamin D deficiency and prevent recurrence as outlined in the Endocrine Society's Practice Guidelines is to give adults 50,000 IU (in India 60,000 IUs is available) of vitamin D2 or Vitamin D3 once a week for 8–12 weeks to fill the empty vitamin D tank., To prevent recurrence, a useful strategy is to give 50,000 IU (or 60,000 IUs) of vitamin D once every 2 weeks forever. For children, 50,000 IUs (or 60,000 IUs) of vitamin D once a week for 6 weeks was effective in treating vitamin D deficiency. I recommend for my patients that infants and children take 1000 IU daily, teenagers and adults 2000 IU daily to maintain a 25(OH)D >30 ng/mL. For those who are obese require 2–3 times more vitamin D to both treat and prevent recurrence of vitamin D deficiency.,
Another major deficiency that can impact on bone health is calcium deficiency. This is more common in some African countries, India, Bangladesh and some Asian countries Severe calcium deficiency leads to secondary hyperparathyroidism and causes the same consequences as vitamin D deficiency on the skeleton, i.e. bone loss as well as rickets in children and osteomalacia in adults.
Therefore, to control the global vitamin D pandemic there is a need for simple, inexpensive and effective strategies to improve the vitamin D status of children and adults world wide.
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