what do i need to absorb vitamin d

• Journal List
• J Nutrient Sci Technol
• v.54(12); 2017 Nov
• PMC5643801

J Nutrient Sci Technol. 2017 Nov; 54(12): 3753–3765.

Factors influencing the absorption of vitamin D in GIT: an overview

Vaibhav Kumar Maurya

Department of Basic and Engineering science, National Plant of Food Engineering science, Entrepreneurship and Management, Kundli, Sonepat, Haryana 131028 India

Manjeet Aggarwal

Section of Basic and Applied Science, National Institute of Nutrient Technology, Entrepreneurship and Management, Kundli, Sonepat, Haryana 131028 India

Revised 2017 Aug 22; Accepted 2017 Aug 28.

Abstruse

Vitamin D refers to a grouping of secosteroid compounds and recognized every bit the antirachitic vitamin, as information technology counters rickets, mineral desorption from fully-grown bones (Osteodistrophy), bone, joint disorders, and fragility of bones. On one hand, there is scarcity of vitamin D rich food while on other mitt a number of factors negotiate its assimilation efficiency in man gastrointestinal tract (GIT). These factors include variations in the physiochemical state of the vitamin D (molecular forms, potency and their physiological linkages), the complexity of food matrix (the amount and type of fatty acids, dietary fibers and presence/absence of vitamin D enhancer and inhibitor), and its interaction of other fat soluble compounds with vitamin D as well equally the host-associated factors (age, affliction, surgery, obesity, genetic variation etc.). Information technology is hypothesized that the bioavailability of vitamin D in GIT is compromised if in that location changes within these factors. Present commodity is intended to review the contribution of these factors anticipated to be influencing vitamin D absorption in GIT.

Keywords: Vitamin D, Ergocalciferol, Cholecalciferol, Vitamin D_ii, Vitamin D₃, Bioavailability, GIT

Introduction

Vitamin D is the generic name for a group of compounds imparting antirachitic functions. Although vitamin D₃ (cholecalciferol) and vitamin D_ii (ergocalciferol) are the two major physiological forms of vitamin D but vitamin D₃ is considered as major dietary source for vitamin D. A significant portion of vitamin D (estimated around fourscore% but varies with lord's day exposure) is synthesized endogenously in the pare from seven-dehydrocholecalciferol as the function of UV low-cal. While 25-hydroxy cholecalciferol and 1, 25-dihydroxycholecalciferol are source of vitamin D from diet. The liver oil and flesh of fatty fish are the best known source of vitamin D. Information technology can also exist obtained from beef liver, dairy product, egg yolk in small quantity. The few sources of plant origin are as well reported such as mushrooms and it is present in form of vitamin D₂ (ergocalciferol).

Particular population subsets such as neonates, elderly person (not adequately exposed lord's day radiations), patient (affected by fatty metabolism and genetic variations in protein associated to vitamin D uptake in intestine) obligated to go vitamin D from supplements and fortified food in guild to run into the recommended daily allowance (RDA) and to retain plasma 25(OH)D level above 30 ng/ml (Wimalawansa 2012). Mechanism of vitamin D absorption and the factors suspected to influence the assimilation procedure have been reviewed by the time. Vitamin D seems to follow league of lipid metabolism in homo GIT thus information technology is assumed that fat does influence the fate of vitamin D. Moreover, vitamin D is diffused in chylomicron which does facilitate its transportation to liver. Information technology seems that the bioavailability of vitamin D is a function of various factors such equally absorption, transportation and metabolism.

Bioavailability

It is defined as the proportion of ingested amount (total vitamin in nutrient) which ultimately ends up in the systemic circulation. It is significant to illustrate the major factors limiting the bioavailability of lipophilic bioactive compounds since this data may help in the designing the efficacious excipient foods (Fig.1).

Chemical structures of naturally occuring dietary forms of vitamin D (I) Cholecalciferol, (II) 25(OH) cholecalciferol, and (3) ergocalciferol

Bioavailability of lipophilic agents

The cognition about how vitamin D released from food matrix and absorbed in GIT (Fig.4), can assist in designing the efficient delivery organisation. For any lipophilic agent incorporated in food, the bioavailability (F) could be defined equally

where F_B: Bioavailability coefficient/proportion of the lipophilic agents which released from food matrix into the gastric juice in GIT, F_T: Transport coefficient/ratio of the release lipophilic agent which is transported through the intestinal epithelium, F_Thousand: The proportion of the lipophilic agent that reaches the blood circulation without being metabolized, The F_Grand depends on the route taken by lipophilic amanuensis to reach the claret apportionment. Earlier reaching the systemic circulation these lipophilic vitamins transported through the portal vein system and metabolized in liver (Drevon 1991).

The bioavailability of lipophilic agent. Where, F _B : bioavailability coefficient/proportion of the lipophilic agents which released from food matrix into the gastric juice in GIT, F _T : Transport coefficient/ratio of the release lipophilic amanuensis which is transported through the intestinal epithelium, F _M : The proportion of the lipophilic agent that reaches the blood circulation without existence metabolized

Vitamin D condition in GIT

The fate of the vitamin D in GIT is monitored past those factors which have been intimately involved with major lipid (phospholipid and triglycerides) (Tso and Fujimoto 1991). These involve emulsification, dissolution in micelles, diffusion through the stagnant water layer and penetration across enterocytes membranes. The future of vitamin D in GIT seems to be a multistep process including physiochemical as well every bit enzymatic involvement (Fig.2). The acidic pH of gastric juice may affect the bioavailability of vitamin D. It is apparent that no data bachelor on the susceptibility of major dietary forms of vitamin D to GIT pH weather. Further, a hypothesis can be fabricated that protein digestive enzymes (pepsin and trypsin) are also intimately involved in vitamin D absorption as they cleave vitamin D binding proteins present in nutrient and thus facilitate its release. Further, in duodenum digestive enzyme (amylases, lipase and protease) continues the release of vitamin D from nutrient matrix.

Schematic diagram of the man digestive organization and the various physiochemical and physiological processes involved in digestion and absorption of vitamin D

Mechanism of vitamin D absorption

The machinery of assimilation of nonhydroxylated species of vitamin D (i.e. vitamin D_ii and vitamin D₃) are suspected to be medicated by an unsaturable passive diffusion process. Furthermore, contempo studies on human being abdominal cell line CaCO_ii (Caucasian colon adenocarcinoma) and HEK (Human embryonic kidney) transfected cells clearly demonstrated the intimacy of intestinal cell membrane protein in the absorption of these nonhydroxylated forms at the border side of the enterocytes. Absorption of cholesterol and other lipophilic compounds (tocopherol, carotenoids) is as well facilitated by these proteins which are SR-BI (scavenge receptor class B type 1), CD 36 (cluster Determinant 36) and NPC1L1 (Neimann-Option C1-Like 1).

The observations made from these proteins postulate that in that location is a fashion shift in absorption of vitamin D from protein mediated transport to passive diffusion, depending on the concentration of vitamin D: protein mediated ship at low concentration (dietary concentration of vitamin D) and passive diffusion at high concentration (pharmacological concentration) (Reboul et al. 2011). Farther, the difference in vitamin D uptake between jejunum and duodenum clearly indicates the presence of another transporter particularly expressed in the jejunum (Goncalves et al. 2015). Conversely absorption efficiency of hydroxylated forms of vitamin D is significantly higher than that of the nonhydroxylated forms just at that place is non a single report dealing with uptake mechanism of hydroxylated species of vitamin D. A Effigythree is depicted to summarize the bachelor literature on vitamin D bioavailability.

Summary of important information and lack of data on vitamin D status in GIT

Possible variables influencing assimilation of vitamin D

Vitamin D needs to be released from nutrient matrix, in which information technology is physically or chemically jump, in order to get accessed to enterocytes and get absorbed in human GIT. It is hypothesized that assimilation efficiency of vitamin D is controlled by a syndicate of factors.

Status of vitamin D in food

It is believed that the vitamin D, synthesized in skin, solitary suffice to meet the daily vitamin D requirement but there are profound show that sun exposure does not fulfil RDA of vitamin D which could be due to variation in sun exposure depending on atmospheric components, article of clothing, pare pigmentation, age, obesity, latitude, season and time of solar day. This obligates patient to get vitamin D via dietary sources to meet the RDA. The major dietary vitamin D comprised of vitamin D_ii and vitamin D_iii that could exist derived from pharmaceutical supplements, fortified foods or foods from plant or animal origin. Diet and cutaneous in vivo synthesis are being 2 lateral routes for vitamin D needs to be highly regulated past each in lodge to avert the overriding of vitamin D in body. To avoid the overdosing, the 1997 RDA standing commission of the Usa Department of Agriculture, therefore, accept recommended diverse vitamin D dose depending upon the age i.e. 200 International Unit of measurement/day (IU/day) for children, 400 IU/day for adults and 600–800 IU/day for elders (70 years). Further, Food and Nutrition Board declared 2000 IU/twenty-four hours as the upper limit to be prophylactic to swallow. Due to lack of representative survey data, it is hard to estimate vitamin D daily intake accurately as the food consumption pattern varies with social economic condition. A study carried out to speculate the daily intake of vitamin D via nutrient alone and combining supplements and foods. The daily intake of vitamin D was plant to be 153–213.vi IU (African American), 174–278 IU (White American), 158–251.6 IU (Mexican) via food alone while 209.6–330 IU (African American), 258.8–383.2 IU (white American) and 227.six–320.four IU (Mexican via combining supplements and foods (Calvo et al. 2004). In improver to this, several excellent studies clearly suggest that the daily vitamin D intake via food alone and combining food and supplements, differs with target population and the food consumption pattern (Calvo et al. 2005; Moore et al. 2005).

Molecular forms of vitamin D: vitamin D_two, vitamin D_iii and 25(OH)D

Vitamin D_2, vitamin D₃ and hydroxylated vitamin D (25(OH) D₃) contribute significantly in dietary vitamin D and in combination referred as full dietary vitamin D. Molecular structure is recalled in Fig.1. The assimilation of vitamin D is facilitated past protein mediated send depending upon its concentration and the affinity of these transporters which may vary depending upon the molecular forms of vitamin D (Fig.4).

Bioavailability and potency of various forms of vitamin D

The offset report comparison bioavailability of vitamin D₂ and vitamin D_iii was produced by injecting a high dose of 5000 IU in male subjects and it was observed that they follow same pattern in elevating the serum 25(OH)D level. From this study it tin be hypothesized that there is no intestinal discrepancy betwixt absorption efficiency of these two forms of vitamin D. The data produced by farther studies followed like pattern in elevating serum vitamin D level when vitamin D_ii and vitamin D₃ were administrated through vitamin D fortified orangish juice or through vitamin D supplement.

The variation in authority of vitamin D_ii and vitamin D₃ to enhance the serum vitamin D level could exist due to high metabolism and clearance of vitamin D₂ than that of vitamin D_three in liver and kidney respectively. In order to avoid the influence of these organs (kidney and liver) intestinal prison cell line CaCO₂ cell were used and similar assimilation efficiency was documented for both vitamin D₂ and vitamin D_three in these cells.

Hydroxylated versus non hydroxylated vitamin D: Bioavailability and say-so

Apart from vitamin D_ii and vitamin D_three, hydroxylated vitamin D (25(OH) D_three) also contributes significantly in dietary vitamin D if food derived from animal origin. Further, the literature reports nearly the college bioavailability of vitamin D if it is administrated in hydroxylated form (25(OH)D_iii) than that of the non hydroxylated forms (vitamin D₂ and vitamin D₃). However, the relative bioavailability of nonhydroxylated (vitamin D₂ and vitamin D₃) and hydroxylated (25(OH)D₃) forms of vitamin D is well documented. Several reports suggest that the college bioavailability of hydorxylated vitamin D (25(OH)D_three) could be due to greater retention than that of not nonhydroxylated vitamin D (vitamin D₂ and vitamin D_three).

The difference in their polarity (polar-hydroxylated form and nonpolar-nonhydroxylated form) may contribute to their biological equivalence inconsistency. From these results an assumption tin can be fabricated that the machinery absorption and storage for nonhydroxylated and hydroxylated vitamin D significantly varies. The hypothesis was tested on the patient suffering from lipid metabolism by administrating hydroxylated and nonhydroxylated vitamin D and it was establish that bioavailability of hydroxylated form (25(OH)D₃) is 10 times greater than that of the non hydroxylated forms (vitamin D₂ and vitamin D_three) vitamin D.

Physiochemical linkage of vitamin D

The patients suffering from vitamin D deficiency are bound to eat vitamin D via pharmaceutical supplements and fortified food. Calcitriol (25-hydroxyvitamin D), calcidiol (1,25- dihydroxyvitamin D), cholecalciferol (previtamin D₃), ergocalciferol (previtamin D₂) and vii-dehydrocholecalciferol (provitamin D) are the major pharmaceutical supplements bachelor in market place with various make names. Calcitriol (25-hydroxyvitamin D) is considered as most active class while calcidiol (1,25- dihydroxyvitamin D) is an inactive grade of vitamin D which helps in storage of vitamin D in tissue. Further, vitamin D₂ and vitamin D₃ are precursor of the active vitamin D. These diverse form of vitamin D supplements are supposed to follow the same route in GIT every bit they share same physiochemical beliefs. Nevertheless, there is scarcity of information addressing the relative absorption of these supplements in GIT. These supplements are designed to showroom high bioavailability of vitamin D. The bioavailability of vitamin D in oil vehicles is greater than that of pulverization-based vehicles such as starch and cellulose. In contrast to this the bioavailability of vitamin D in lactose capsule is college than that of oily drop formulation. These supplements are made by changing physical properties (encapsulation of vitamin D) as well as chemic alteration of vitamin (vitamin D ester and table salt).

The effect of physical modification such emulsification, encapsulation and nanoparticle of vitamin D is well documented and it was plant that these concrete modifications make vitamin D more than accessible to enterocyte and helpful to penetrate the lipid bilayer thus enhancing the absorption efficiency. But very scant data is available addressing the chemic modification (ester and salt of vitamin D).

Though the absorption of vitamin D is facilitated past protein mediated/passive diffusion transport depending upon the concentration of vitamin D, therefore the variation in these protein transporters and vitamin D receptors may change their structure thus their affinity to vitamin D. Just in that location is no data present addressing this outcome. The difference in affinity of VDR Vitamin D Receptor (VDR) betwixt vitamin D_ii and vitamin D₃ suggests the involvement of some other mechanism of transport which yet to be discovered. Furthermore, in that location is not a single data produced how concentration of vitamin D₃ tin can affect the affinity of these poly peptide transporters to vitamin D₂ and vice versa.

Nutrient matrix and its complexity

Since nutrient is multitude of nutrients and their supportive matrix in which these nutrients are embedded. Earlier absorption vitamin D demand to be released from its matrix and go accessible to enterocytes. An assumption can be fabricated that the bioavailability of vitamin D is affected past amount of ingested nutrient and its complexity.

Amount of ingested food in meal

This factor has non been discussed much in present literature. Recently i written report reported the improvement of vitamin D (vitamin D₂ and vitamin D₃) absorption with the largest meal of day and in consequences about a 50% ascent of serum level of 25(OH)D. The data obtained from this study could be effect of either high secretion of digestive enzymes (afterward heavy meal) or some specific food components (Mulligan and Licata 2010). These results were non reproduced when subjects were served vitamin D with and without food (Wagner et al. 2008). More supplementary studies are required to understand the event of food amount on bioavailability of vitamin D.

Food matrix

Vitamin D needs to be extracted from the food matrix in which it is embedded in guild to get bioavailable to enterocytes i.e. need to solubilize in micelles and accessible for absorption. It is essential to determine the bioavailability of nutrient in which vitamin D is delivered. Though several foods (fortified such as bread, milk, meat, orange juice, vegetable oil, other dairy products and naturally rich in vitamin D i.e. meat, fish oil, mushroom etc.) have been used as potential candidate for vitamin D vehicle. But information technology is remarkable that the bioavailability of these foods is not well reported.

When vitamin D was supplied through meat, its bioavailability was estimated to be 60% every bit compared to vitamin D supplement. The vitamin D₂ from UV radiated mushroom was too tested. The reports on two mushrooms (Lentinula edoes and Agaricus biosporus) propose the high bioavailability of its vitamin D (Jasinghe et al. 2005; Koyyalamudi et al. 2009) but their bioavailability were not compared with any other food matrix. Furthermore, the 25(OH)D serum level was higher in group 1 and grouping 2 when 27 subjects, randomized in 3 groups each having nine persons, were assigned to receive no supplementation (grouping 3), 14 μg vitamin D₂/solar day (group two) through pharmaceutical conception and mushroom containing xiv μg vitamin D_two/day (group i) in tiffin for iii weeks, excluding Saturdays and Sundays (Outila et al. 1999). These results were farther supported past a five week unmarried blinded, randomized, placebo controlled report in 26 healthy Caucasian adults with 25(OH)D serum level below 20 ng/ml (Urbain et al. 2011). Farther the trials, conducted by serving capsules containing 2000 IU vitamin D₂, 2000 IU vitamin D_iii or 2000 IU mushroom vitamin D₂ (dried white excerpt of button mushroom or Monterey mushrooms), demonstrate that the mushrooms containing vitamin D₂ take similar biological equivalence as supplemental vitamin D₂ and vitamin D_three (Keegan et al. 2013).

Results of clinical study demonstrate no significant difference in rise of full 25(OH)D serum levels in good for you subjects who were served orangish juice (fortified with grand IU of vitamin D_two or g IU of vitamin D_iii) as compared to ingesting a supplement containing either grand IU of vitamin D₂ or 1000 IUs of vitamin D₃ (Biancuzzo et al. 2010). The high bioavailability of vitamin D in mushroom was confirmed by several studies (Calvo et al. 2013; Ko et al. 2008). It is remarkable that the difference in food matrix does non impose whatsoever variation of bioavailability of vitamin D and information technology was found as effective every bit vitamin D₃ supplements in increasing the 25(OH)D serum level (Natri et al. 2006). These results were supported past another study when vitamin D_two rich yeast were baked in bread (Hohman et al. 2011).

Dietary lipids

In general lipids are nigh widely used vitamin D delivery medium and considered crucial for fat soluble micronutrients. It facilitates the absorption lipophilic components of food through a multisequence process. Start lipids mediate diffusion of these fat soluble nutrient components from food matrix every bit it behaves as hydrophobic phase within which fat soluble nutrients get solubilized. Then these lipids stimulate the secretion of bile juice resulting into micelle germination. In adjacent pace the digestive enzymes catalyze the lipids and release fat acid, monoglycerides and phospholipid which again generate more micelles available for lipophilic nutrients to solubilize (Hofmann 1963). At last these lipids mediate lipophilic nutrients out the enterocyte avoiding the accumulation of vitamin D in enterocytes thus increasing the vitamin D assimilation in GIT. These steps depend on the amount of fat (triglycerides), type of triglycerides, amount of phospholipids, types of phospholipids etc.

Amount of lipids (triglycerides)

This factor is believed to be important because it is hypothesized that vitamin D absorption is facilitated by lipid. Several studies are conducted to verify this hypothesis (Johnson et al. 2005; Weber 1980). In dissimilarity, the absorption charge per unit of vitamin D was found to be decreasing when rats were served with 2.5 mM fatty acid differing in concatenation length and degree of saturation (Hollander et al. 1978). When the bioavailability of vitamin D was evaluated in 2 beverages (orange and milk), information technology was noticed that the lipid content of milk does non significantly affect the bioavailability of vitamin D (Tangpricha et al. 2003). Similar results were obtained in the case of ii vitamin D fortified foods (cheddar cheese with 33% fat and low fat cheese vii%) (Wagner et al. 2008). These results were reproduced by two multivitamin supplements (one supplement with vitamin D in tablet and other vitamin D in fish oil) (Holvik et al. 2007). Recently a team of researchers has also disbanded this hypothesis when they observed, the consumption of vitamin D with 2 g fish oil per week did non increase vitamin D absorption (Korkor and Bretzmann 2009). Thus reports bachelor till date conspicuously fail the hypothesis that loftier corporeality of fat in repast improves the vitamin D bioavailability.

Type of fatty acids

The get-go report on this factor came from Hollander'due south study when the decrease in vitamin D uptake was registered by add-on of fatty acids of different chain length and caste of saturation i.e. butyric acid, octanoic acrid, oleic acid and linoleic acids (Hollander et al. 1978). In this report the oleic and linoleic acids exhibited greater inhibition of vitamin D absorption every bit compared to octanoic acid. Authors propose that unlike medium chain fatty acids (practice not integrated in micelles), long chain fatty acids impair the vitamin D absorption by increasing the micellar size hence decelerating their diffusion towards the enterocytes. Nevertheless this result was not reproduced at pharmacological dose of vitamin D when information technology was ingested with either long concatenation triacylglycerols (peanut oil) or medium chain triacylglycerol. In contrast to this, the comeback in the serum level of vitamin D₃ was registered when it was served in peanut oil (long chain triglycerides) than when information technology was served in medium chain triglycerides (Holmberg et al. 1990). More clear observations were made in experimental trials conducted to evaluate the bioavailability of vitamin D in monounsaturated and polyunsaturated fatty acids. It was found that monosaturated fatty acid rich diet may increase the efficacy of vitamin D supplements than that of polyunsaturated fat acids (Niramitmahapanya et al. 2011).

In summary, literature suggests that the species of fatty acids can affect the bioavailability of vitamin D. Nevertheless more than inquiry is needed to draw firm conclusion on bioavailability of vitamin D.

Dietary fibers

Dietary fibers have been assumed a key player in deciding the fate of vitamin D in GIT. It affects the bioavailability of vitamin D in following ways:

• Impairs the micelle formation

• Affects triacylglycerol lipolysis and emulsification of fatty soluble food component

• Affects the release of lipophilic food nutrient from fat droplet (oil phase)

• Increases the viscosity of chyme hence confines the diffusion of lipophilic food nutrients containing micelles to enterocytes

High fiber intake was suspected the reason for the reduced bioavailability of vitamin D for higher prevalence of rickets and osteomalacia in Asian immigrant's population (Compston et al. 1981). This assumption was supported by a written report on relative disappearance of radiolabelled 25(OH)D₃ in good for you volunteers served with either higher fiber nutrition (20 g/twenty-four hours) or normal nutrition. Result reveals that the mean serum half-life of 3H-25(OH)D_iii in the normal diet group was longer (27.5 ± 2.ane day) than that of loftier cobweb diet group (19.2 ± 1.7 day). High clearance of 3H-25(OH)D_iii in loftier fiber diet group could be due to interference of the fiber metabolite in enterohepatic circulation i.e. binding of 3H-25(OH)D₃ to dietary fibers.

In contrast, the serum levels of 25(OH)D in two groups (consuming vitamin D fortified depression fiber wheat bread (iii m/100 g) and high fiber rye staff of life (12 g/100 g)) were not significantly dissimilar from each other. Conversely, these results could exist refuted as volunteers in these groups were immune to consume other breads. Due to very scant data available on uptake of vitamin D in presence of fibers, it could be too early to conclude the role of fibers. Besides more than dedicated studies are required to understand the consequence of fibers on vitamin D bioavailability.

Nutrient status in the host

Information technology can be hypothesized that absorption of vitamin D in GIT is also controlled by nutrient status of host.

Condition of vitamin D in the host

The complete vitamin D status of host is comprised of both food derived as well every bit cutaneous synthesized vitamin D. However, information technology is very difficult to establish the correlation between the contribution of orally ingested and cutaneous synthesized vitamin D. Due to lipophilic nature vitamin D stored in adipose tissue and release at its demand. High intake equally well as high de novo synthesis of vitamin D could be toxic, therefore, it can be hypothesized that loftier intake of oral vitamin D and excessive radiation with UV may cause hypervitaminosis D then there will be feedback inhibition between absorption of orally ingested vitamin D and cutaneous synthesis. Nevertheless, there is not a single study performed to investigate of touch on of absorption of vitamin D on cutaneous synthesized vitamin D. The master problem in establishing correlation between dietary and cutaneous synthesized vitamin D is the variation in the surface surface area of pare exposed and in the frequency and elapsing of UV exposure.

Interaction with micronutrients

Vitamin East and Thou follow common pathway used in vitamin D uptake then they may impose competitions for vitamin D absorption in intestine. This assumption was verified by a written report on CaCO₂ cell line which confirms the role of vitamin East in impairing the vitamin D absorption (reduced 15% at medium concentration of vitamin E and 17% at high concentration of vitamin E) absorption in intestine (Goncalves et al. 2015). Phytosterols, plant sterols traditionally, are applied as functional ingredients to reduce cholesterol absorption in GIT. Every bit vitamin D possesses a steroid structure and parades mutual absorption pathways as cholesterol, we hypothesized that phytosterols could likewise hamper vitamin D₃ uptake. This supposition was confirmed by an in vitro study on CaCO_two intestinal cell where phytosterol was found to exist potential candidate to impair the vitamin D₃ absorption by xvi–36% (depending on micellar limerick) in these prison cell line (Goncalves et al. 2011).

Concentration of vitamin A was likewise found to be antagonist to vitamin D absorption (Aburto and Britton 1998). In addition, vitamin A also discriminates dietary D₃ (coming from food) and endogenous D₃ (synthesized in pare by action of sunlight) in their utilization i.e. negatively affect the utilization of dietary vitamin D_iii, but not the endogenous vitamin D₃ (Johansson and Melhus 2001). Recently a research demonstrated that high concentration of vitamin A reduce bioavailability of vitamin D by 30%. However the mechanisms, how vitamin A hampers the vitamin D absorption, does remain unknown and requires further investigation.

Enhancers and inhibitors for vitamin D assimilation

Literature reports about diverse agents which can stimulate or impair the vitamin D absorption in GIT. These agents could exist present in food naturally or could be added to meliorate absorption efficiency of vitamin D. Information from available literature is presented hither.

Inhibitors of fat absorption

Person suffering from obesity consumes several antiobesity drugs and fat substitutes to reduce the fat quantity. These drugs and fatty substitutes reduce the absorption of triglycerides. Since vitamin D follows the similar league of triglyceride in GIT lumen it tin exist assumed that these antiobesity drugs could impede vitamin D bioavailability leading to reduction in absorption. The absorption of vitamin D was found to exist impaired when vitamin D was served with a fat substitute (olestra: sucrose polyester) was ingested in 102 good for you males and females (James et al. 1997; Schlagheck et al. 1997). The serum level of vitamin D in African-American and Caucasian adolescents was significantly reduced after 1 month supplementation of 400 IU vitamin D with orlistat (Tetrahydrolipstatin: inhibitors of gastric and pancreatic lipases) 120 mg iii times/day (McDuffie et al. 2002). Furthermore, the cholesterol derivatives from found origin, used equally reduce the cholesterol assimilation, may bear upon the bioavailability of vitamin D. This assumption was confirmed by various studies. The decrease in vitamin D level both in serum as well as in liver was registered in rats when they assigned stanol ester for 13 weeks (Turnbull et al. 1999). Even these results were reproduced for diverse phytosterols in mice and in vitro and institute that phytocholesterols do hinder the micelles formation and its diffusion in enterocytes thus reducing the bioavailability. Though some recent findings of clinical trials have disowned this hypothesis by negating the result of phytosterol on bioavailability of vitamin D (Gylling et al. 2010; Gylling and Miettinen 1999; Gylling et al. 1999; Hendriks et al. 2003; Korpela et al. 2006; Nguyen et al. 1999). But these conclusions could be refuted as the evaluation was made on the basis of the serum level of 25(OH)D which could be altered past endogenous vitamin D synthesis depending on the several factors i.e. lord's day exposure and season. Furthermore this hypothesis was again supported by results of 2 clinical trials in which the serum level of 25(OH)D was observed significantly different in subjects, who assigned plant sterol ester enriched spread. Although these fat reducing agents limit the fat absorption hence hamper the absorption of vitamin D (James et al. 1997; McDuffie et al. 2002) only the verbal corporeality of lipid needed for maximal absorption of vitamin D has not been optimized.

Enhancers of vitamin D

It is thought that the vitamin D delivery in specialized formulation (encapsulated in micro/nano particles, micellar/liposomal grade, embedded in β-cyclodextrin and some proteins β-lactoglobulin) may enhance the bioavailability of vitamin D in GIT. Their ability to improve the uptake of vitamin D was tested in various studies. Higher absorption charge per unit of vitamin D in children affected with severe chronic cholestasis was registered when information technology was administered with tocopherol succinate polyethylene glycol 1000 (TPGS) (Argao et al. 1992). Similar observation was fabricated when vitamin D was served with β-cyclodextrin in rat (Szejtli et al. 1983). It is hypothesized that encapsulated vitamin D remain embedded inside non digested nano/microparticles, rather being released. These micro/nanoparticles may transport paracelluarly to the blood portal through tight junction, thus bypassing the liver. This may result in the greater bioavailability for micro/nano encapsulated vitamin D than that of its fortified food and supplement. Limited literature is available on this factor thus it will too early to conclude about the outcome of these formulations on the bioavailability of vitamin D and this assumption should be varied by extensive clinical trials.

Physiochemical interaction with GIT secretions

It is assumed that the absorption of vitamin D in GIT remains maximal inside a range of table salt ionic strength and pH beyond which the vitamin D uptake could exist affected. This assumption was addressed in various studies. It was observed that the uptake of vitamin D₃ is affected with variation of salt concentration within physiological concentration. For example the progressive reduction in vitamin D₃ assimilation was noticed every bit the sodium taurocholate salt concentration was increased to a higher place the v mM (10 or 15 mM) n (Hollander et al. 1978).

High concentration may facilitate the conversion of monomeric vitamin D into its micellar form thus enhances the solubility of vitamin D₃. Since lipophilic compounds such as vitamin D₃ have greater penetration power in enterocyte's membrane in monomer form than that of micellar particles (Simmonds 1974), The high salt concentration may cause the decrease the vitamin D assimilation (Simmonds 1974)

The variation in the hydrogen ion concentrations (pH 5.3–8.three) in the perfusate decreases the negative charge of both the micelle and the luminal cell membrane, therefore, reduces the repulsion between the micelles and the cell membrane thus increasing the absorption of vitamin D (Hollander et al. 1978).

Host associated factors

Literature clearly suggests the interest of diverse host associated factors which could be suspected players in deciding the bioavailability of vitamin D. Thus several studies have been conducted to optimize recommended dietary allowance (RDA) every bit the functions of these factors (historic period and disease obesity).

Age of host

Physiological changes in torso role have been witnessed with aging. It is causeless that the historic period stimulated physiological (age associated GIT functions) changes may straight or indirectly influence vitamin D bioavailability. Crumbling associated variations in lipoprotein metabolism was suspected for reduction of assimilation and postprandial transport of vitamin E (Borel et al. 1997). Several studies have conducted to find out the reason for low vitamin D condition in elderly people than that of young adults (Clemens et al. 1986; Ikuma et al. 1996; Russell 1992; Vellas et al. 1991). The first report on this gene was made in twenty elderly women, who had low serum [3H]cholecalciferol than that of younger females. This was explained that GIT of elderly women was less efficient as compared to younger ones (Barragry et al. 1978). Nevertheless, this effect was not reproduced in mice written report (Hollander and Tarnawski 1984). Conclusive statements regarding changes in serum 25OHD levels in elderly than in young adults could be due to low endogenous vitamin D synthesis in skin, lower sunlight exposure and low dietary intake.

Obesity

Obesity is generally negatively correlated to vitamin D deficiency. This was supported by Liel et al. (1988) work in which they observed improved absorption and college clearance of vitamin D by obese subjects than that of normal weights. Conversely vitamin D is deposited in adipose tissue and does not released when required (Wortsman et al. 2000) resulting into high supplementation of vitamin D. This was confirmed by a study on elderly subjects served with 700 IU of vitamin D per day for every addition 15 kg of weight above normal subjects (Blum et al. 2008). The low serum level in obese subjects could be due to dilution of vitamin D (ingested or cutaneous vitamin D) in their big fat mass (Drincic et al. 2012). The inference of these findings is that vitamin D stored in fat tissue is not easily available, and obese individuals may oblige larger dose of vitamin D to meet a serum 25OHD level equivalent to that of their normal weight counterparts (Wortsman et al. 2000). The ascension in serum 25(OH)D level during weight loss in obese individual verifies this hypothesis (Riedt et al. 2005; Zittermann et al. 2009)

Digestive tube surgery/diseases

Several clinical and experimental animal studies confirmed that vitamin D is most efficiently absorbed when consumed with foods containing fat (Johnson et al. 2005; Weber 1980). Early studies suggested that subjects suffering from impaired GIT i.e. obstructive jaundice (depression bile juice release) or pancreatic insufficiency, cystic fibrosis or adult coelic disease and gastric surgery could demonstrate significantly reduced absorption of vitamin D. Reduction of serum level vitamin D₃ by 30% was registered in case of Roux-en-Y gastric bypass surgery than before (Aarts et al. 2011). Despite of high dose of vitamin D supplementation (2500–5000 IU/day) vitamin D₂ and D_iii were non detected in infants and children suffering from extrahepatic biliary atresia (whose portoenterostomy failed to produce bile menstruum) (Heubi et al. 1990). Similarly in children with cholestasis serum vitamin D₂ level remained undetectable instead of high dose of vitamin D supplementations (2500–5000 IU/day) (Heubi et al. 1989). Furthermore, the patients afflicted with cystic fibrosis were plant to be less efficient in vitamin D absorption than that of their normal counterparts (Farraye et al. 2011; Distraction et al. 2001). Likewise it is also hypothesized that the vitamin D positively alter the gut microbiota and CD8⁺ cells which may lead to retain the integrity of the GIT mucosal barrier by controlling the intercellular junctions thus decision-making mucosal permeability and increasing the CD8⁺ cell (Bashir et al. 2016; Kanhere et al. 2016). Additionally some clinical studies also demonstrated the function of vitamin D in inhibiting the various cancers including GIT cancer past modulating cancer stem cell markers and VDR polymorphism and other VDR regulation (Lappe et al. 2017; Li et al. 2017; P Peppelenbosch et al. 2017). Though these studies practice verify the interest of vitamin D in different illness prevention only at that place is scarcity of data how vitamin D absorption in GIT is influenced under these diseases (Messa et al. 2017; Scragg et al. 2017; Yao et al. 2017). Still, the deleterious effect of diseases was partially rectified by sunlight exposure or by applying 25(OH)D which does not depend on the fat assimilation in GIT and take portal vein.

Genetic variations

The absorption of vitamin D is monitored past diverse factors such equally vitamin D protein transporter, nuclear vitamin D binding poly peptide, enzyme involved in fat digestion, bile secretion, liver enzyme catalyzing vitamin D. Literature has described the key role of genetic variations in modulating serum level 25(OH)D (Fu et al. 2009). It is articulate at present that vitamin D is absorbed in enterocyte through protein mediated transport. The expression and action of these proteins can be modulated past altering the genetic code which may result into consummate or partial loss of its activity. Furthermore, variation in genetic code of nearby gene may besides interrupt bounden of transcription factor leading into absence of these poly peptide transporters. Till date literature lacks data addressing this cistron (Hernández-Romano et al. 2009). Similarly any genetic variation in fatty digestive enzyme and vitamin D binding poly peptide may also affect the vitamin D absorption.

Enquiry gaps and time to come prospects

Later on thorough review of literature the gaps in present literature were identified and these research gaps could be addressed past time to come defended studies. The future enquiry prospects identified from present literature are as follows:

1. The acidic pH of gastric juice may bear upon the bioavailability of vitamin D. It is apparent that no information available on the susceptibility of major dietary forms of vitamin D with respect to pH variation in GIT.

2. It have been observed that various digestive enzymes facilitate the release of vitamin D from food matrix just the part of these enzyme is not fully recognized with respect to bioavailability of vitamin D. The evaluation of effect of enzymes individually or in syndicate and their concentration on vitamin D bioavailability will help in amend agreement their impact on vitamin D uptake.

3. It has been assumed that vitamin esters are at least partially cleaved past gastric lipase, simply this problem in not addressed in nowadays literature. Thus further studies needed to evaluate the effect of gastric lipase on vitamin D ester hydrolysis.

4. In duodenum digestive enzyme (amylases, lipase and protease) continues the release of vitamin D from food matrix. Vitamin D released from food matrix during digestion need to transfer from oil (naturally retained in dietary lipid) to the fat phase of meal (micelles). Only kinetics of vitamin D transfer from nutrient matrix into micelles is not completely understood. More dedicated research is needed to get better understanding near the touch of vitamin D transfer from nutrient oil phase to micelle on the bioavailability of vitamin D.

5. Since these micelles comprise lipophilic nutrients in their phospholipid bilayer only in that location is express reports on these nutrients (other lipophilic vitamins, phytosterol etc.) addressing how they touch the transfer of vitamin D in micelle. More than focused studies, discussing the affect of concentrations of these lipophilic nutrients on vitamin D uptake in GIT, will aid better understanding on bioavailability of vitamin D.

6. Though inside physiological concentration, vitamin D is absorbed in enterocyte via poly peptide mediated transport but in that location is shift in send mode from protein medicated to passive diffusion at pharmacological concentration (high dose of vitamin D). The optimal concentration of vitamin D at which this way shift in vitamin D transport occurs is still unknown.

7. Difference in vitamin D uptake efficiency in jejunum of rat than that of it ileum clearly suspects near the presence of another transporter especially expressed in the jejunum (Goncalves et al. 2015). More research on these transporters is required to understand complete mechanism of vitamin D uptake in intestine.

8. Hydroxylated vitamin D forms practice take unlike path for their absorption past enterocytes but the machinery of hydroxylated species of vitamin D absorption is withal remains unaddressed.

9. Vitamin D remains embedded in lipid stage of food as well as leap with specific proteins. The diverse food items differ in their complexity to retain vitamin D. At that place is express documents bachelor dealing with consequence of food matrix complexity on bioavailability of vitamin D. Conversely more studies comparing bioavailability of vitamin D are required in club to know the effect of complexity of nutrient matrix on vitamin D bioavailability.

10. Non hydroxylated vitamin D forms are absorbed through poly peptide mediated transporters just their affinity may vary with variation in molecular forms (vitamin D₂ or vitamin D₃). Effect of concentration of vitamin D₂ on the assimilation of vitamin D₃ and vice versa is still not much discussed.

11. The mechanism how the esters of vitamin D does effect the assimilation of vitamin D is still remained unaddressed

12. Though vitamin East impairs the vitamin D absorption (reduced xv% at medium concentration of vitamin Eastward and 17% at loftier concentration of vitamin E) in intestine but the concentration at which vitamin E completely end the vitamin D absorption is not optimized.

13. Compressive review of relative bioavailability of vitamin D in unlike food matrix is essential to evaluate the bioavailability of vitamin D in different food.

14. Effect of special vitamin D formulations (encapsulated vitamin D in micro/nanoparticle) on bioavailability of vitamin D is not addressed in present literature.

Decision

Broad range of food products are bachelor in unlike parts of the world; each nutrient product displays variations in their matrix due to difference vitamin content, fat content, dietary fibers etc. All these factors contribute difficulty in determining the bioavailability of vitamin D in particular food. The present literature lacks complete knowledge about the mechanism of vitamin D absorption. Although some factors governing fate of vitamin D in GIT is well documented simply several factors i.e. genetic variation, dietary fiber, host vitamin D status, result of nano/microparticle of vitamin D which may influence the bioavailability of vitamin D, are either not addressed or have very little information to conclude. For better understanding near bioavailability of vitamin D more dedicated studies with labeled vitamin D are required addressing the hereafter research prospects mentioned above.

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