Review of Liquid Vitamin A and E Formulations in Veterinary and Livestock Production: Applications and Perspectives
Abstract
:Simple Summary
Abstract
1. Introduction
2. Roles and Nutritional Needs across Animal Species
2.1. Vitamin A
- 1 IU of vitamin A is equivalent to
- ○
- 0.3 μg of retinol (vitamin A alcohol);
- ○
- 0.344 μg of retinyl acetate (vitamin A acetate);
- ○
- 0.359 μg of retinyl propionate (vitamin A propionate);
- ○
- 0.55 μg of retinyl palmitate (vitamin A palmitate).
2.2. Vitamin E
- 1 mg of DL-alpha-tocopheryl acetate is equivalent to 1.0 IU of vitamin E;
- 1 mg of D-alpha-tocopheryl acetate is equivalent to 1.36 IU of vitamin E.
2.3. Interplay between Vitamins A and E
2.4. Nutritional Requirements in Different Animal Species
3. Consequences of Deficiencies in Vitamins A and E
4. Liquid Vitamin A and E Supplements
4.1. Stability and Formulation Strategies
4.2. Liquid Formulations of Vitamins A and E
- Oil-based solutions: Oil-based formulations often use vegetable oils, such as sunflower oil, as carriers for vitamins [111,112]. These formulations may also incorporate hydrophobic solvents like short-chain saturated triglycerides, ethyl stearate, or liquid paraffin [11]. A high-quality oil, especially one rich in α-tocopherol, can enhance the stability of vitamin A by protecting it from oxidation and improving its absorption in the gastrointestinal tract [113]. To further stabilize these formulations, compounds like BHT are frequently added, particularly in products containing retinyl propionate or retinyl palmitate [114]. It is important to note that vitamin A tends to be more stable in oily solutions compared to aqueous ones [11]. In these oil-based products, vitamin E acetate can be included either in its undiluted form or mixed with oils.
- Emulsions: Emulsions are a versatile and widely used drug formulation designed to enhance the solubility and bioavailability of vitamins, particularly for lipophilic vitamins such as A and E. These formulations are especially beneficial in aqueous environments where solubility can be challenging. The effectiveness of emulsions is often due to the creation of transparent microemulsions, which significantly improve the solubility and stability of these vitamins [110,115].These emulsions are particularly advantageous for species with less efficient fat digestion or in scenarios where rapid vitamin absorption is required. For instance, a standard emulsion product may contain 50,000 IU/mL of vitamin A, emulsified with lecithin and polysorbate 80 [11]. This combination creates a stable and homogeneous mixture, which ensures effective delivery and absorption of the vitamin. Polysorbate 80, a non-ionic solubilizer commonly used in both oral and topical pharmaceuticals, has hydrophobic and hydrophilic components. The primary hydrophobic part in polysorbate 80 is polyethylene glycol-20 sorbitan oleate, which plays a crucial role in the solubilization process [116].Another example of an emulsion is a vitamin A/D/E preparation for injection, which includes 23.0 g of retinyl propionate, 0.2 g of cholecalciferol, 5.5 g of DL-α-tocopheryl acetate, 15.0 g of PEG-15 hydroxystearate (as a solubilizer), 0.5 g of butylated hydroxytoluene, 1.0 g of benzyl alcohol, and water to make up 100 mL [11].A specialized type of emulsion is the microemulsion, where retinyl esters, for example, are emulsified in an aqueous solution containing substances such as gelatin and sugar [104]. Microemulsions consist of droplets of the oily phase, approximately 1 μm in diameter, and remain stable within a temperature range of 50–60 °C [115]. Additionally, various types of fat-soluble vitamin emulsions can be formulated, including oil-in-water, water-in-oil, and oil-in-water-in-oil emulsions, offering a range of options depending on the desired application [117].
- Aqueous Solutions: To effectively produce aqueous solutions of lipophilic vitamins such as A, D, E, and K, the use of solubilizers is essential. Key solubilizers include Polysorbate 80, PEG glyceryl trihydroxystearate, PEG glyceryl triricinoleate, and PEG hydroxystearate, all of which are known to form micelles that encapsulate these lipophilic vitamins, thereby facilitating their dissolution in water [11]. The quantity of solubilizer required can vary considerably depending on the specific vitamin. For instance, the solubilizer needed for vitamin E acetate differs from that required for vitamin A.Specific formulations can be used to prepare clear aqueous solutions, as detailed by Buehler [11]. For example, to produce unstabilized vitamin A drops (50,000 IU/mL), the formulation may include 3.0 g of retinyl palmitate, 10.0 g of PEG 40 glyceryl trihydroxystearate, 5.0 g of polyethylene glycol 400, and 100 mL of water. A vitamin E acetate solution (20 mg/mL) might consist of 2.0 g of DL-α-tocopheryl acetate, 8.0 g of polysorbate 80, and 100 mL of water. Additionally, a formulation for combined vitamin A and E drops (825,000 IU + 50 mg per ml, respectively) could use 1.50 g of retinyl palmitate, 5.0 g of DL-α-tocopheryl acetate, and 20.0 g of PEG 40 glyceryl trihydroxystearate, along with an appropriate amount of antioxidant, preservative, and flavoring, all dissolved in 100 mL of water. It is important to note that when using solubilizers, the effectiveness of preservatives must be carefully evaluated, as solubilizers can potentially diminish their efficacy.
5. Comparative Bioavailability
6. Applications in Veterinary Medicine and Livestock Production
6.1. Use of Injectable Forms for Enhancing Reproductive Performance
6.2. Use of Injectable Forms in Enhancing Animal Growth and Performance
6.3. Incorporating Liquid Vitamin A and E into Veterinary Practices via Water Administration
6.4. Usage of Liquid Vitamin A and E Drops in Veterinary Practice
6.5. Regulatory Guidance
7. Challenges in Applying Liquid Formulations across Animal Species
7.1. Cattle
7.2. Swine
7.3. Poultry
7.4. Pets
8. Perspectives and Future Directions
9. Conclusions and Recommendations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AKT | Serine-threonine kinase B |
ATRA | All-trans-retinoic acid |
BHA | Butylhydroxyanisole |
BHT | Butylhydroxytoluene |
BW | Body weight |
DM | Dry matter |
EFSA | European Food Safety Authority |
EMA | European Medicines Agency |
FEEDAP | The Panel on Additives and Products or Substances used in Animal Feed |
FRAP | Ferric Reducing Ability of Plasma |
i.m. | Intramuscular |
IBV | Infectious bronchitis virus |
ID3 | DNA-binding inhibitor 3 |
IgG | Immunoglobulin G |
IU | International Unit |
KEAP1 | Kelch-like ECH-associated protein 1 |
mTOR | Mammalian Target for Rapamycin |
MYF5 | Myogenic Factor 5 (a protein coding gene) |
MYOD | Myoblast Determination Protein |
MYOG | Myogenin |
NASEM | The National Academies of Sciences, Engineering, and Medicine |
NFκB | Nuclear Factor kappa-light-chain-enhancer of activated B cells |
NRF2 | Nuclear Factor Erythroid 2–related factor 2 |
PAX7 | Paired Box 7 (a protein-coding gene) |
PEG | Polyethylene glycol |
RFM | Retained fetal membranes |
s.c. | Subcutaneous |
UV | Ultraviolet |
40BHLHE40 | Class E basic helix-loop-helix protein |
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Committee | Adequate Intake of Vitamin A, IU/kg BW | |||
---|---|---|---|---|
Growing Heifers | Dry Cows | Lactating Cows, (<35 kg milk/d) | Lactating Cows, (>35 kg milk/d) | |
NASEM [58] | 110 | 110 | 110 | n/a |
NASEM [17] | 110 | 110 | 110 | 110 + (1000 × (milk-35)) |
Adequate Intake of Vitamin E, IU/kg BW | ||||
NASEM [58] | 0.8 | 1.6 | 0.8 | n/a |
NASEM [17] | 0.8 | 1.6 | 0.8 (3) * | 0.8 (3) * |
Committee | Adequate Intake of Vitamin A, IU/kg DM Intake | ||
---|---|---|---|
Growing and Finishing | Gestating Cows | Lactating Cows | |
NASEM [57] | 2200 | 2800 | 3900 |
NASEM [59] | 2200 | 2800 | 3900 |
Adequate Intake of Vitamin E, IU/kg DM Intake | |||
NASEM [57] | 15–60 | - | - |
NASEM [59] | 15–60 | 15–20 | 40–60 |
Animal Species | Vitamin A Recommendation, IU/kg Feed | Vitamin E Recommendation, IU/kg Feed | Source |
---|---|---|---|
Broilers | 10,000–13,000 | 55–80 | [71,72] |
Laying hens | 8000–13,000 | 20–30 | [73,74] |
Turkeys | 5000–12,500 | 20–100 | [75,76] |
Broiler breeders | 10,000–13,000 | 100 | [77,78] |
Piglets | 8000–16,000 | 84–150 | [79,80,81,82] |
Finishing gilts and barrows | 4000–10,000 | 33–80 | [79,80,81,82] |
Lactating gilts and sows | 9920–14,000 | 60–100 | [79,80,81,82] |
Dogs | 8000–12,000 | 80–120 | [83] |
Cats | 15,000–25,000 | 100–150 | [83] |
Disorder | Animal Model | Compromised Organ/Tissue |
---|---|---|
Immune deficiency | Chick, pig | Mononuclear phagocyte system |
Myopathic disorders | Rabbit, duck, lamb, calf, turkey, chicken | Heart, skeletal muscles, gizzard |
Reproductive dysfunction | ||
embryonic apoptosis | Hen, turkey, cow | Embryonic circulatory system |
infertility (male) | Rooster, rabbit | Testes |
Kidney, pancreas, liver, brain, blood | ||
necrobiosis | Pig | Liver |
erythrocyte hemolysis | Chick, calf | Red blood cells |
hypoproteinemia | Chick, turkey | Ricin |
cerebral softening | Chick, duckling | Encephalon |
hemorrhagic diathesis | Chick, turkey | Vascular system |
nephrosis | Mink, rat | Renal tubular |
yellow fat disease | Pig | Adipose tissue |
Parameter | 0 IU (n = 9) | 150,000 IU (n = 7) | 300,000 IU (n = 9) | SE |
---|---|---|---|---|
Birth to weaning | ||||
Birth weight, kg | 35.1 | 35.6 | 35.6 | 0.58 |
Average daily gain, kg/d | 0.88 b | 0.98 a | 1.00 a | 0.02 |
Backgrounding | ||||
Weaning weight at d 210, kg | 219.2 | 248.7 | 246.0 | 5.98 |
Gain/feed ratio, kg | 0.149 | 0.153 | 0.156 | 0.031 |
Finishing | ||||
Weight at 308 d, kg | 312.1 b | 333.0 ab | 339.7 a | 8.65 |
Feed/gain ratio, kg | 4.35 | 4.76 | 4.79 | 0.13 |
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Shastak, Y.; Pelletier, W. Review of Liquid Vitamin A and E Formulations in Veterinary and Livestock Production: Applications and Perspectives. Vet. Sci. 2024, 11, 421. https://doi.org/10.3390/vetsci11090421
Shastak Y, Pelletier W. Review of Liquid Vitamin A and E Formulations in Veterinary and Livestock Production: Applications and Perspectives. Veterinary Sciences. 2024; 11(9):421. https://doi.org/10.3390/vetsci11090421
Chicago/Turabian StyleShastak, Yauheni, and Wolf Pelletier. 2024. "Review of Liquid Vitamin A and E Formulations in Veterinary and Livestock Production: Applications and Perspectives" Veterinary Sciences 11, no. 9: 421. https://doi.org/10.3390/vetsci11090421