A growing body of evidence has strongly demonstrated the involvement of Vitamin D (VitD) in several physiological and pathological processes (Heaney Citation2008). Adequate levels of VitD are essential for human health as it is involved in the regulation of several cellular functions. Of note, VitD is a fat-soluble vitamin that can be obtained from foods like fatty fish (such as salmon, tuna or trout) or at a lower concentration from beef, eggs and cheese in the form of vitamin D3 (cholecalciferol) and mushrooms in the form of vitamin D2 (ergocalciferol). However, the major amount of VitD is endogenously produced in the lower layers of the epidermis of the skin after ultraviolet (UV) rays exposure (Dominguez et al. Citation2021).
The activation of VitD consists of two consecutive hydroxylation reactions: the first one takes place in the liver to form 25-hydroxyvitamin D or 25(OH)D and the second one occurs in the kidneys to form the physiologically active 1-25-dihydroxy vitamin D or 1,25(OH)2D (Saponaro et al. Citation2020). This latter active metabolite is able to enter the cells and binds the vitamin D receptor (VDR), also called calcitriol receptor. Finally, the calcitriol-VDR complex is able to bind specific genomic regions called Vitamin D response elements (VDREs) inducing the expression or silencing of specific gene products involved in the regulation of different cellular and molecular pathways. As a consequence of this intricated molecular cascade driven by VitD, the imbalance of this vitamin may have detrimental effects on key biological functions thus predisposing to the development of diseases or worsening the clinical conditions of patients affected by different pathologies (Amrein et al. Citation2020).
Among its physiological roles, VitD promotes the absorption of calcium in the gut favouring its deposition in bones to maintain a correct mineralisation. In addition, VitD has important functions in extra-skeletal tissues including pancreas, skin, brain and muscle cells where VitD is involved in the regulation of cell growth, cell proliferation and homeostasis (Umar et al. Citation2018).
Optimal blood levels of VitD range from 30 to 60 ng/ml, however, a significant fraction of individuals have insufficient (20–29 ng/ml) or deficient levels (<20 ng/ml) of VitD with consequent pathophysiological manifestations (Kennel et al. Citation2010).
The first indicator of VitD deficiency is represented by the reduction of the absorption of calcium and phosphorus which can be detected by measuring the blood levels of ionised calcium. Such reduction in calcium absorption increases the circulating levels of parathyroid hormone (PTH) whose function is to maintain adequate levels of blood calcium (Dominguez et al. Citation2021). VitD deficiency is also associated with fatigue, bone pain, muscle weakness, muscle aches or muscle cramps, mood changes and immune system depression (Umar et al. Citation2018). On the contrary, VitD hypervitaminosis (>100 ng/ml) may induce toxic manifestations including weakness, anorexia, bone pains, kidney stones, confusion, nausea, etc. (Marcinowska-Suchowierska et al. Citation2018). At present, many epidemiological studies are concordant in observing insufficient VitD levels in the general population also in individuals living in countries with sufficient sun exposure or in subjects with good patterns of sun exposure. In addition, VitD deficiency is observed in both healthy individuals and patients affected by chronic degenerative diseases (Pereira-Santos et al. Citation2019; Amrein et al. Citation2020). These data suggest that sun exposure alone is not sufficient to induce the production of normal levels of VitD. Moreover, insufficient levels of VitD observed also in healthy individuals may predispose the development of different diseases due to the suppression of the immune system or through other mechanisms not well characterised yet.
All these observations have prompted researchers, nutritionists and experts in this field to propose dietary strategies aimed at increasing the absorption of VitD as well as the circulating levels of its active form 1,25(OH)2D. Therefore, functional foods and other biofortified foods have been developed and proposed to reduce the incidence of VitD deficiency.
In this context, the studies of Neill HR et al. and Karras SN et al. represent two examples of strategies that could be implemented to improve VitD absorption.
Specifically, in their work Neill and collaborators described a food-based strategy that could improve the 1,25(OH)2D blood concentration thanks to the consumption of biofortified pork meat compared to circulating levels obtained through the consumption of normal meat. For this purpose, the authors exposed pigs to daily UVB (biofortified pork) or non-UVB (control group) light for nine weeks and then they evaluated the vitamin D3:25(OH)D3 ratio for UVB-irradiated and control pork samples revealing a 2-fold increment VitD (6.45 vs 3.48, respectively). Through further investigations, they also evaluated the serum levels of 25(OH)D3 at different time points after the consumption of UVB pork meat, control pork meat or VitD supplement. Such investigations revealed a significant effect of time (p < 0.01) and a significant treatment time interaction (p < 0.05) where the consumption of UVB pork and supplement significantly increased the 25(OH)D3 serum concentrations over time- points (p < 0.05). Although significant data were obtained, only slight increments of VitD were observed (1.5 nmol/L (3.5%) for supplement, 0.9 nmol/L (2.2%) for UVB pork meat and 0.7 nmol/L (1.9%) for control pork meat). Although interesting, the data obtained raise several technical and ethical issues. First of all, pig farms should be equipped with UVB lamps for the irradiation of pigs to obtain only a slight increase in the levels of vitamin D in the meat. More important, no studies on the effects of UVB irradiation on pig health have been done and are strongly recommended due to the potential direct and indirect DNA damages associated with UVB exposure. Finally, as stated by the authors, biofortification protocols should be further optimised and standardised to obtain optimal increment of VitD and studies on a more representative number of pork and subjects should be performed (Neill et al. Citation2023).
To increase the serum concentration of 25(OH)D, Karras SN and colleagues proposed a different strategy based on the consumption of different diets and intermittent fasting. More in detail, the authors evaluated changes in 25(OH)D and vitamin D binding protein (VDBP) serum levels in individuals treated with pescatarian Orthodox (OF) intermittent fasting diet a 12:12 low-fat diet. Dietary, hematological and anthropometric data were collected at baseline, at the end of the treatment (after 7 weeks) and at the follow-up (after 12 weeks from the recruitment) revealing an increase in amino acid intake that was positively correlated with the increment of 25(OH)D serum levels. The authors observed a reduction of BMI in both groups, a 2-fold increment of free 25(OH)D concentrations and an increment of VDBP at the end of the study and during the follow-up in subjects treated OF diet. Consequently, they also observed a reduction in PTH levels in OF group and an increase in the intake of specific amino acids between baseline and follow-up visits which correlated with higher 25(OH)D concentrations. Therefore, these results suggest that different diets can have different effects on 25(OH)D concentrations and that VitD absorption may strongly depend on the intake of other nutrients, including amino acids (Karras et al. Citation2023).
Overall, these two studies suggest how dietary interventions and biotechnologies could improve the absorption of VitD with consequent beneficial effects on human health in line with other studies on this topic (Vivarelli et al. Citation2019; Montagnese et al. Citation2020; Porciello et al. Citation2020).
In addition, the studies from Neill and Karras represent potential examples of strategies that could be implemented to reduce the incidence of VitD deficiency. However, further efforts are needed to clearly establish the best strategy to improve VitD intake and bioavailability.
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References
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