Activated vitamin D: Connecting parents and offspring

Vitamin D, often referred to as the "sunshine vitamin," is a unique nutrient that can be synthesized in the skin of animals when exposed to sunlight. However, for sows in confinement systems or areas with limited sunlight, ensuring adequate Vitamin D intake becomes a critical factor for their overall health and reproductive success.

Our expert guest for today's interview is Katia Pedrosa, our Technical Manager with the years long experience in animal nutrition. Together with Katia we will shed light on importance of Vitamin D in sow nutrition, its functions within the sow's body, the current recommendations for Vitamin D levels in sow diets for optimal health in intensive pork production, the potential consequences of deficiencies, and strategies to optimize Vitamin D levels in sow diets.

Results from different surveys concluded that concentration of 25(OH)D in numerous serum samples analyzed were lower than the reference values in all age categories as reported in literature. It is therefore easy to say that the vitamin D levels in feed are too low. This might be supported considering that serum samples from outdoor herds exposed to sunlight had significantly higher 25(OH)D concentrations than samples from indoor pigs. In one of the surveys, two-thirds of the animals showed lower vitamin D contents, when the measured 25(OH)D levels were compared to the human thresholds. These low levels were detected in all age categories, meaning young animals, subadults and adults. But does such a comparison between man and swine make sense?

Overall, feed producers in the EU may use a maximum of 2000 IU of vitamin D /kg of feed in pig nutrition. This value has not changed since 1970. However, feed conversion and growth of finishers has increased considerably since then and sows produce more piglets with the genetic improvement.

Although surveys base their conclusions on vitamin D status on serum 25(OH)D as the circulating metabolite, it does not give any indication on the efficiency of its activation into 1,25 in the kidneys. This means that if 25(OH)D is indeed too low for the current genetics and production levels, it does not tell if it is also true for 1,25, the only metabolically active form.

During the past Covid times, the role of vitamin D metabolites on resilience and vaccination response in humans was stressed many times, indicating that vitamin D not only affects calcium metabolism, but also has some ‘non-classical’ effects. In fact, vitamin D receptors are present in almost all tissues in the body.

Even if vitamin D levels are sufficient to support high productive animals it does not tell if they are also for these “non-classical” functions such as immunity, and reproductive performance. We have shown that when adding a plant-based source of 1,25 to sows fed diets with the double level of vitamin D than EU maxima, several vitamin D based response parameters are improved. This indicates that highly productive sows indeed might have issues with vitamin D levels in feed or with limited efficiency of activation in the kidneys.

It is well-known that serum 25(OH)D can be increased by sunlight or by higher intake of vitamin D or 25(OH)D in the diet. However, an increased 25(OH)D concentration does not automatically lead to an increased 1,25 concentration in the blood. This is due to the tight regulation of this vitamin D metabolite. Too high levels of vitamin D in the diet for example results in an increase of the plasma concentrations of 25(OH)D and its degradation product 24,25(OH)2D, but it rarely raises plasma 1,25. The latter is dependent on the level of calcium in the blood.

A direct proportional relationship between 24,25(OH)2D and 25(OH)D concentrations has been shown, indicating that excess 25(OH)D will be excreted as 24,25(OH)2D3 before being available for activation in the kidney. A correlation in serum concentrations of 25(OH)D and the metabolically active metabolite 1,25 could not be shown.

As said, 1,25(OH)2D is tightly regulated. It can directly inhibit the expression of 1α-hydroxylase, to reduce the activation of 25(OH)D and indirectly inhibit it by suppressing PTH and stimulating FGF23 production (responsible for P excretion). This negative feedback system provides an essential safeguard mechanism against hypercalcaemia. It can also be that 1α-hydroxylase in older multiparous sows is lacking, meaning that older sows are not able to efficiently activate 25(OH)D anymore, like it is known from laying hens in the second half of their production period.

Therefore, increasing dietary levels of vitamin D or 25(OH)D have no direct impact in blood content of 1,25(OH)2D. This is the reason why 25(OH)D as the storage and transport form of vitamin D in the body is used as a blood marker for vitamin D status and not 1,25(OH)2D. Moreover, the serum concentration of the latter is a factor 1000 less than 25(OH).

Vitamin D is activated in two steps, first step is done in the liver into 25(OH)D and the second step in the kidney into the bio-active form. Adequate liver and kidney metabolism is therefore essential for an adequate vitamin D metabolism. Feedstuffs contaminated with molds or mycotoxins decrease the production of 25(OH)D in liver and increase degradation of 1,25 in the kidneys as trials at INRAE in France showed. Stress and metabolic disorders can limit the activation of endogenous enzymes in liver and kidney. In addition, the age of the animal significantly limits the activation of vitamin D. For instance, in rodents, humans and birds it has been proven that ageing individuals have a higher reduction of the activity of 1α-hydroxylase in the kidney that converts 25(OH)D to 1,25 than the enzyme in the liver responsible to convert vitamin D into 25(OH)D. Possibly also the weight of the sow has an impact. Overweight sows may have limitations in activating vitamin D to 25(OH)D as it is reported in overweight humans.

It is important to understand the differences between the different molecules and their biopotency. Vitamin D is generally known as ‘parent form’, 25(OH)D or calcidiol as the circulating or storage form and is used to assess the vitamin D status of men and animals and at last 1,25or calcitriol is the bio-active form of vitamin D which is tightly regulated.

As said 1,25 is the bio-active form. Its biological activity varies according to the parameter measured. The dietary requirement of vitamin D is defined in international units (IU). IU of vitamin D are defined based on its biological effects to prevent rickets in birds. Up to date no scientifically approved conversion factors exists for other vitamin D metabolites, neither in humans nor in animals.

The relative activity of the molecules has been studied in chicken assays, where vitamin D needs two activation steps, and 25(OH) one activation step. 1,25 is immediately active. A single dose of the tested vitamin D metabolites was given for 3 weeks, and the response was measured at a time known to give the maximum effect. In each instance the response obtained with vitamin D was set equal to 1.0 and the responses obtained from an equal molar quantity of the other vitamin D metabolites calculated accordingly. Results of the parameters measured (intestinal Ca transport, bone Ca mobilization, bone ash, body weight) indicated a ratio of approx. 1:2 for vitamin D and the metabolite 25(OH)D, and a ratio of 1:3-13 for vitamin D and 1,25, meaning a much higher biological activity of 1,25 when compared to 25(OH)D, but the equivalence was highly variable depending on the parameter measured.

Yes, correct. In the last decade, sow mortality (natural death and/or culled/replacement) increased significantly (more than 60% from 2012 to 2021). This is indeed a concern and affects animal welfare. The main reasons for such high mortality is still primarily unknown, meaning sudden deaths without obvious cause. On second and third places are death/cullings because of feet, leg and general bone and reproductive problems of the sows. Issues related to prolapses, troubles during farrowing and lame sows that did not breed back are the major causes.

Knowing the importance and functions of vitamin D on bone mineralization and integrity, support in different reproductive phases such as farrowing by stimulating muscle contractions to expulse piglets and placenta (helping sows to recover faster); at the start of lactation by stimulating lactogenesis, we have shown that the supplementation of plant-based 1,25 can help reducing locomotion and reproductive problems as well as stimulate milk production after farrowing.

I just want to list a few points:

It is common to correlate vitamin D with serum 25(OH)D concentration. Indeed, supplementing 25(OH)D in the diet increases serum 25(OH)D faster and higher than vitamin D alone. However, the efficiency of the conversion into the bio-active metabolite 1,25 can be limited based on liver and kidney health or age. Such effects are generally underestimated.