Considering bioavailability of injectable vitamin products in cattle and swine

Getty ImagesWhen veterinarians administer injectable vitamin products in food animals such as cattle and swine, they can't simply assume these supplements are absorbed and used by the body as promised. In fact, there are dramatic differences in bioavailability among the private-labeled products on the market.

In addition to reputable injectables, lesser-value vitamin-based products exist that provide little or no bioavailability. And several injectable fat-soluble vitamin products with labels identical to the pioneer product are being marketed with no bioavailability data. Without this data from the manufacturer or supplier to ensure product effectiveness, efforts to enhance vitamin status in food animals may be a futile endeavor.

Determining bioavailability

Biopotency is defined as the “capacity of a chemical substance to function in a biological system.”1 Vitamin E biopotency, for example, is determined by clinical endpoints, as classically defined by the gestation-resorption assay in vitamin-E-depleted rats.2 The ability of different forms of vitamin E to prevent the resorption (death) of implanted rat embryos represents the biopotency of those vitamin E formulations.1

Livestock, on the other hand, lack these sensitive clinical endpoints, or biomarkers, so bioavailability studies are used to determine the utilization of different vitamin E sources. Bioavailability is defined as “the plasma concentration of a water-soluble substance after oral dosage compared with plasma concentration of the same substance after intravenous injection.”3 Because fat-soluble substances are injected either intramuscularly or subcutaneously, not intravenously, the term “relative bioavailability” is used.3

From a nutritional aspect, bioavailability may be defined as the proportion of vitamin E ingested that undergoes intestinal absorption and utilization in the body. For fat-soluble vitamin E, injected intramuscular bioavailability is noted in the enhanced plasma or serum concentration post-injection.

As stated by Li and Peisker, the definition of bioavailability “encompasses the process of vitamin E absorption, transport, distribution to the tissues and metabolism.”1 Bramley and co-authors define bioavailability as “the proportion of vitamin E that is absorbed from the gut and made potentially available to the body.”4

Misleading results

Using a product with little bioavailability presents two distinct problems: the animal receives little to no benefit from supplementation and, more disconcerting, the veterinarian may come to an improper conclusion about an injection's usefulness and efficacy. When a veterinarian administers a vitamin that produces no change or improvement, he or she may assume the change in vitamin status was not useful, when in fact the product was simply not absorbed and used by the body in the first place.

This will be apparent if the veterinarian makes the effort to measure post-injection plasma concentrations. It is not that the vitamins are of no value, but that the specific product is of no value because it lacks bioavailability.

The problem with knockoffs

During the mid-1990s, several companies manufactured private-labeled products containing vitamins A, D and E. They were essentially knockoffs of the original pioneer product but didn't offer adequate bioavailability. Although labeled by various companies, all of the knockoffs contained the same non-bioavailable formulation. Typically, generic products offer the same potency as the pioneer product, but that was not the case with this group of supplements. Studies conducted at universities and private research facilities have all shown the lack of bioavailability of the knockoff products for enhancing vitamin E and A status of cattle compared with the pioneer product.

Consider this example: In a study measuring the effects of injecting vitamin A and D on infectious bovine keratoconjunctivitis (IBK) in calves, researchers administered two doses of 1 ml injectable vitamin A and vitamin D3. Each milliliter contained 500,000 IU of vitamin A propionate and 75,000 IU of vitamin D3. Doses were given 30 days apart. Control animals received similar amounts of saline. Calves were observed for IBK incidence after the second injection. The injectable vitamin supplement did not provide any positive outcome to IBK. In the end, the study provided little evidence to support the use of vitamin A supplementation to reduce the incidence of IBK.5

But as it turns out, the particular vitamin A injectable researchers used in that study did not produce the desired outcome because it was not bioavailable. This is a classic example of the importance of bioavailability. Had the investigators determined post-injection vitamin A levels, they would have recognized that the product used was of no value to their research and, perhaps, there would have been different findings.

This is often the case. Researchers who administer an injectable fat-soluble vitamin product intramuscularly must measure a product's efficacy based on its bioavailability.

Product testing

Veterinarians should similarly evaluate products they inject regularly to determine bioavailability. For example, there are injectable products that contain vitamins A, D and E that can be administered intramuscularly or subcutaneously. If the veterinarian measures plasma concentration post-injection, the bioavailable product will show adequate improvements in post-injection plasma concentrations. The product that is not bioavailable will show no positive plasma response. There should always be a dose response when a vitamin is injected.

Recent results presented at a recent meeting of the American Dairy Science Association, American Society of Animal Science and Canadian Society of Animal Science clearly showed dramatic differences in bioavailability of injectable vitamin E and A products. Vitamin E and vitamin A bioavailability were determined for two different products in two different groups of calves.6 In both experiments, the pioneer injectable fat-soluble vitamins had dramatically superior serum vitamin E and vitamin A status compared with the knockoff. In one experiment, calves were bled initially then 24, 48 and 72 hours post-injection. In the second experiment, calves were bled initially then four, eight, 12 and 24 hours post-injection. In both of the experiments, the pioneer injectable fat-soluble product showed superior bioavailability over the knock-off product.

These data demonstrate that before veterinarians use injectable fat-soluble vitamins or any other injectable nutritional supplement, they should be confident that the product has proven bioavailability.

Just because a generic product is cheaper than the pioneer product does not mean that it is more economical or equal in bioavailability, even though the labels may look identical.

Summary thoughts

> There are dramatic differences in bioavailability among injectable vitamin products, even when labels report similar vitamin potencies.

> Before using injectable fat-soluble vitamins, be sure the manufacturer can provide bioavailability data.

> Some products are excellent sources of supplemental fat-soluble vitamins, i.e., vitamins E, A, D, while others are not bioavailable, offering no nutrient value.

References

1. Dersjant-Li Y, Peisker M. A critical review of methodologies used in determination of relative bio-availability ratio of RRR-α-tocopheryl acetate and all-rac-α-tocopheryl acetate. J Food Sci Agr 2010;90:1571.

2. Harris PL, Ludwig MI. Relative vitamin E potency of natural and synthetic alpha-tocopherol. J Biol Chem 1949;179:1111.

3. Traber MG. The bioavailability bugaboo. Am J Clin Nutr 2000;71:1029.

4. Bramley PM, Elmadfa I, Kafatos A. Vitamin E. J Sci Food Agr 2000;80:913.

5. Gould SA, O'Connor AM. Injectable vitamin A effects on infectious bovine keraconjunctivitis in beef calves. Iowa State University Research Farm Progress Reports 2012:15-16.

6. Snider DB, Zinn RA, Stuart RL. Differences in formulation and bioavailability of commercial injectable fat-soluble vitamin products. J Anim Sci 2014;92, E-Suppl 2:919.