Zhiren Lu

Vitamin D and Skin Physiology: A D-Lightful Story

Throughout evolution, exposure to sunlight and the photosynthesis of vitamin D3 in the skin has been critically important for the evolution of land vertebrates. During exposure to sunlight, the solar UVB photons with energies 290–315 nm are absorbed by 7‐dehydrocholesterol in the skin and converted to previtamin D3. Previtamin D3 undergoes a rapid transformation within the plasma membrane to vitamin D3. Excessive exposure to sunlight will not result in vitamin D intoxication because both previtamin D3 and vitamin D3 are photolyzed to several noncalcemic photoproducts. During the winter at latitudes above ∼35°, there is minimal, if any, previtamin D3 production in the skin. Altitude also has a significant effect on vitamin D3 production. At 27° N in November, very little (∼0.5%) previtamin D3 synthesis was detected in Agra (169 m) and Katmandu (1400 m). There was an ∼2‐ and 4‐fold increase in previtamin D3 production at ∼3400 m and at Everest base camp (5300 m), respectively. Increased skin pigmentation, application of a sunscreen, aging, and clothing have a dramatic effect on previtamin D3 production in the skin. It is estimated that exposure in a bathing suit to 1 minimal erythemal dose (MED) is equivalent to ingesting between 10,000 and 25,000 IU of vitamin D2. The importance of sunlight for providing most humans with their vitamin D requirement is well documented by the seasonal variation in circulating levels of 25‐hydroxyvitamin D [25(OH)D]. Vitamin D deficiency [i.e., 25(OH)D < 20 ng/ml] is common in both children and adults worldwide. Exposure to lamps that produce UVB radiation is an excellent source for producing vitamin D3 in the skin and is especially efficacious in patients with fat malabsorption syndromes. The major cause of vitamin D deficiency globally is an underappreciation of sunlights role in providing humans with their vitamin D3 requirement. Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D3 compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being.

Photobiology of Vitamin D

The major function of vitamin D (either vitamin D2 or D3) is to maintain healthy bone. Most humans obtain their vitamin D requirement through casual exposure of the skin to solar ultraviolet B and from dietary intake. The cutaneous synthesis of vitamin D is a function of 7-dehydrocholesterol concentration in epidermis, melanin pigmentation, and the solar zenith angle which depends on latitude, season, and time of day. Our recent study also indicates that altitude may influence the production of previtamin D3. One area which has shown more progress during the past decade is the use of simulated sunlamp to improve vitamin D production in patients with intestinal malabsorption and elderly who were infirmed or living in northern latitude. Vitamin D deficiency is common in infants, children, and adults worldwide. The major cause of vitamin D deficiency globally is an underappreciation of the crucial role of sunlight in providing humans with their vitamin D requirement. The association between vitamin D deficiency and the increased risk of cancers, autoimmune diseases, infectious diseases, and cardiovascular disease indicates the importance of sunlight, vitamin D, and overall health and well-being of the general population.

An Evaluation of the Vitamin D3 Content in Fish: Is the Vitamin D Content Adequate to Satisfy the Dietary Requirement for Vitamin D?

It has been suggested that the major source of vitamin D should come from dietary sources and not sun exposure. However, the major fortified dietary source of vitamin D is milk which often does not contain at least 80% of what is stated on the label. Fish has been touted as an excellent source of vitamin D especially oily fish including salmon and mackerel. Little is known about the effect of various cooking conditions on the vitamin D content in fish. We initiated a study and evaluated the vitamin D content in several species of fish and also evaluated the effect of baking and frying on the vitamin D content. Surprisingly, farmed salmon had approximately 25% of the vitamin D content as wild salmon had. The vitamin D content in fish varied widely even within species. These data suggest that the tables that list the vitamin D content are out-of-date and need to be re-evaluated.

Indoor husbandry of the panther chameleon Chamaeleo [Furcifer] pardalis: Effects of dietary vitamins A and D and ultraviolet irradiation on pathology and life-history traits

To assess the importance of diet and light for indoor maintenance, hatchling panther chameleons were reared for 1 year on crickets fed diets that differed in vitamin concentrations and in different light environments. Dietary transfer of vitamins from the cricket diet to the lizards via the crickets was quantified, as was UV irradiance. There was a statistically significant dietary enhancement of growth by both vitamins on males. UV-A irradiation significantly suppressed growth of females. Low vitamin A shortened life span and resulted in a number of gross and histological pathologies. Hepatocellular lipidosis, indicating a possible toxicosis, occurred with all diets and light treatments. Higher vitamin A resulted in mild soft-tissue mineralization, and high vitamin D shortened the life span of females. Low vitamin A drastically reduced reproduction in both sexes. The intermediate levels of dietary vitamins resulted in the best production of viable eggs by females. However, without high UV-B irradiation, all viable eggs died at term and contained different vitamin levels than hatching eggs from wild-caught females. Baseline levels of egg calcium are given for hatching eggs from wild-caught females. Modifications in current husbandry procedures are recommended.

Vitamin D in adipose tissue and serum 25-hydroxyvitamin D after roux-en-Y gastric bypass.

Vitamin D is stored in body fat. The purpose of this study was to determine vitamin D concentration in abdominal fat of obese patients who underwent roux‐en‐Y gastric bypass (RYGB), and to describe changes in serum 25‐hydroxyvitamin D (25(OH)D) levels in relation to loss of body fat. Subjects from a single clinic who were scheduled for RYGB were invited into the study. Abdominal subcutaneous, omental, and mesenteric fat were obtained at time of surgery. Adipose vitamin D2 and vitamin D3 concentrations were measured by high‐performance liquid chromatography (HPLC). Weight and serum 25(OH)D were assessed at baseline and every 3 months up to 1 year. Seventeen subjects were included, and fat samples were available from eleven. Total vitamin D content in subcutaneous abdominal fat was 297.2 ± 727.7 ng/g tissue, and a wide range was observed (4–2,470 ng/g). Both vitamin D2 and vitamin D3 were detected in some of the fat samples. At baseline, 25(OH)D was 23.1 ± 12.6 ng/ml. Average weight loss was 54.8 kg at 12 months, of which ∼40 kg was fat mass. Despite daily vitamin D intake of ≥2,500 IU throughout the study, no significant increase in serum 25(OH)D was observed, with mean serum concentration of 25(OH)D at 1 year of 26.2 ± 5.36 ng/ml (P = 0.58). We conclude that vitamin D in adipose tissue does not significantly contribute to serum 25(OH)D despite dramatic loss of fat mass after RYGB.

Photobiology of vitamin D in mushrooms and its bioavailability in humans.

Mushrooms exposed to sunlight or UV radiation are an excellent source of dietary vitamin D2 because they contain high concentrations of the vitamin D precursor, provitamin D2. When mushrooms are exposed to UV radiation, provitamin D2 is converted to previtamin D2. Once formed, previtamin D2 rapidly isomerizes to vitamin D2 in a similar manner that previtamin D3 isomerizes to vitamin D3 in human skin. Continued exposure of mushrooms to UV radiation results in the production of lumisterol2 and tachysterol2. It was observed that the concentration of lumisterol2 remained constant in white button mushrooms for up to 24 h after being produced. However, in the same mushroom tachysterol2 concentrations rapidly declined and were undetectable after 24 h. Shiitake mushrooms not only produce vitamin D2 but also produce vitamin D3 and vitamin D4. A study of the bioavailability of vitamin D2 in mushrooms compared with the bioavailability of vitamin D2 or vitamin D3 in a supplement revealed that ingestion of 2000 IUs of vitamin D2 in mushrooms is as effective as ingesting 2000 IUs of vitamin D2 or vitamin D3 in a supplement in raising and maintaining blood levels of 25-hydroxyvitamin D which is a marker for a persons vitamin D status. Therefore, mushrooms are a rich source of vitamin D2 that when consumed can increase and maintain blood levels of 25-hydroxyvitamin D in a healthy range. Ingestion of mushrooms may also provide the consumer with a source of vitamin D3 and vitamin D4.

An evaluation of the biologic activity and vitamin D receptor binding affinity of the photoisomers of vitamin D3 and previtamin D3.

Skin is in the site of previtamin D3 and vitamin D3 synthesis and their isomerization in response to ultraviolet irradiation. At present, little is known about the function of the photoisomers of previtamin D3 and the vitamin D3 in skin cells. In this study we investigated the antiproliferative activity of the major photoisomers and their metabolites in the cultured human keratinocytes by determining their influence on 3H-thymidine incorporation into DNA. Our results demonstrated at both 10(-8) and 10(-6) M in a dose-dependent manner. Lumisterol, tachysterol3, 5,6-trans-vitamin D3, and 25-hydroxy-5,6-trans-vitamin D3 only induced significant inhibition at 10(-6) M. 25-Hydroxytachysterol3 was approximately 10- to 100-fold more active than tachysterol3. 7-Dehydrocholesterol was not active even at 10(-6) M. The dissociation constants of vitamin D receptor (VDR) for 25-hydroxytachysterol3, 25-hydroxy-5,6-trans-vitamin D3, and 5,6-trans-vitamin D3 were 22, 58, and 560 nM, respectively. The dissociation constants for 7-dehydrocholesterol, tachysterol, and lumisterol were greater than 20 microM. In conclusion, vitamin D3, its photoisomers and the photoisomers of previtamin D3 have antiproliferative activity in cultured human keratinocytes. However, the antiproliferative activity did not correlate with their binding affinity for VDR. The results suggest that some of the photoproducts may be metabolized to their 25-hydroxylated and 1 alpha,25-dihydroxylated counterparts before acting on VDR. Alternatively, a different receptor may recognize these photoproducts or another mechanism may be involved in modulating the antiproliferative activity of the photoisomers examined.

Determination of vitamins D, A, and E in sera and vitamin D in milk from captive and free‐ranging polar bears (Ursus maritimus), and 7‐dehydrocholesterol levels in skin from captive polar bears

The difference between serum levels from 36 captive and 56 free-ranging polar bears (Ursus maritimus) for 25-hydroxyvitamin D (25-OH-D) was found not to be significant (mean ± SD = 348 ± 215 nmol/L [captive], 360 ± 135 nmol/L [free-ranging], t = 0.30, df = 52.8, P = 0.76), whereas the difference for retinol and α-tocopherol was significant (retinol, 1.37 ± 0.67 μmol/L [captive] 1.89 ± 0.63 μmol/L [free-ranging], t = 3.88, df = 72.4, P <0.001, α-tocopherol, 18.56 ± 18.56 μmol/L [captive], 48.76 ± 13.92 μmol/L [free-ranging], t = 7.85, df = 61.9, P < 0.001). Due to the high fat content in the polar bear diet, seal blubber may be the source of these fat-soluble vitamins. Six skin biopsies were analyzed from captive polar bears at the Denver Zoological Gardens for 7-dehydrocholesterol levels and found to contain 0.11 ± 0.03 nmol/cm2. This finding also helps to support the contention that the source of vitamin D for polar bears may be ingestion and not cutaneous production. Vitamin D content in the milk from one captive sow in the den (0.14 nmol/g) and 10 free-ranging sows with cubs of the year out on the ice pack (0.0042 ± 0.0073 nmol/g) were also evaluated. It would be helpful to evaluate additional milk samples from denning and non-denning sows with cubs to see whether vitamin D content varies according to the stage of lactation. Zoo Biol 17:285–293, 1998.

Production of Previtamin D3 by a Mercury Arc Lamp and a Hybrid Incandescent/Mercury Arc Lamp

Most vertebrates including reptiles and amphibians need a source of ultraviolet B radiation in order to promote an adequate production of vitamin D to satisfy their body’s requirement (1). Reptiles routinely sun themselves, not only to warm their bodies, but also to produce vitamin D3 in their skin. Amphibians exposed to sunlight also have the ability to produce vitamin D3 in their skin (1). It is estimated that there are over ten million households in the United States that have a reptile or amphibian as a pet. Often these animals are housed in a glass enclosure, and are exposed to incandescent lighting. Since incandescent lighting does not emit any ultraviolet B radiation, these animals depend solely on their diet for their vitamin D requirement. Frequently, diets including vegetable matter or live or dead animals do not contain an adequate amount of vitamin D to satisfy their requirements resulting in these animals developing severe vitamin D deficiency. Vitamin D deficiency causes rickets and osteomalacia that can lead to fractures, muscle weakness and ultimately, death. Many zoos also house reptiles and amphibians indoors, in glass enclosures and often experience vitamin D deficiency in these prized animals. The appreciation that these animals require a source of ultraviolet B radiation has prompted the lamp manufactures and distributors to produce florescent lamps that emit ultraviolet B radiation that is similar to lamps used in tanning salons.

Vitamin D intakes by cotton‐top tamarins (Saguinus oedipus) and associated serum 25‐hydroxyvitamin D concentrations

Rickets and osteomalacia have been reported frequently in captive callitrichids. Some have assumed that these conditions are a consequence of unmet, unusually high requirements for vitamin D and that these high requirements are characteristic of all New World primates. As a consequence, certain commercial diets formulated for New World primates contain such high concentrations of vitamin D that their consumption by other species has resulted in signs of vitamin D toxicity. This study was conducted to assess the vitamin D status of captive cotton-top tamarins consuming diets providing either 2,500 or 26,000 IU of vitamin D3/kg dry matter. These diets had been consumed for at least 2 years before the study, with the lower vitamin D intakes by six tamarins (0.5 to 9 years old) in a zoo colony and the higher vitamin D intakes by 24 tamarins (2 to 12 years old) in a pharmaceutical research laboratory. Although not measured in this study, none of the dietary ingredients has been shown to contain vitamin D2. Serum 25-hydroxyvitamin D (25(OH)D) concentrations in the captive tamarins were compared with serum 25(OH)D concentrations (range, 25.5–120 ng/mL; 64–300 nmol/L) reported by others in healthy wild tamarins in Colombia, South America. Concentrations of 25(OH)D in serum from zoo tamarins consuming 2,500 IU vitamin D3/kg dietary dry matter ranged from 48 to 236 ng/mL (120–590 nmol/L), whereas those in serum from laboratory tamarins fed 26,000 IU vitamin D3/kg dietary dry matter ranged from 11 to 560 ng/mL (28–1,400 nmol/L), with no significant (P > 0.05) association between serum 25(OH)D concentration and sex or age. However, in the laboratory tamarins, serum 25(OH)D concentrations ranged from 46 to 60 ng/mL (115–150 nmol/L) in one 8-year-old male and four 12-year-old females that had four to nine pregnancies each. Younger females (2–5 years old) that had zero or one pregnancy and the other males (3–12 years old) generally had serum 25(OH)D concentrations above 126 ng/mL (315 nmol/L). None of the individuals in the zoo colony showed signs of colitis. Of the two tamarins in the laboratory group with 25(OH)D levels below 50 ng/mL (125 nmol/L), one was a 4-year-old male with anorexia and cachexia associated with severe colitis. The second was a 7-year-old clinically normal, multiparous (five) female with normal hematology and clinical chemistry but histologic evidence of severe colitis. Because all other individuals in this group had histologic evidence of moderate to severe colitis but were normal in other respects, an unequivocal association between low serum 25(OH)D concentrations and colitis was not apparent. A dietary vitamin D3 concentration of 2,500 IU/kg dry matter was more than sufficient to support serum 25(OH)D concentrations equivalent to those found in the wild and, although the number of observations was small, supported apparently normal growth and adult weights, reproduction through five parities, and general health in a zoo colony showing no evidence of colitis. Zoo Biol 18:473–480, 1999.