Fat-soluble vitamins: precious allies of the immune system and beyond

The aim of clinical nutrition is to improve animal health and reducing the use of antibiotics to the bare minimum. If the immune system of dairy cows is efficient, there is a reduction in pathologies prevalence and they have a better recovery, especially for metritis and mastitis, without the use of a large amount of antibiotics. Nutrition and clinical nutrition are very different from each other. Nutrition studies nutritional requirements and how to fulfill them with the diet during the animal’s whole life. Clinical and functional nutrition, studies the effect of specific nutrients on metabolic pathologies, reproduction, and immune system, administering these molecules in different dosages and chemical forms, to understand the dose-response effect and to improve their bioavailability for the animal.

Animal nutritional requirements were defined between the late 1800s and the early 1900s, as well as nutritional recommendations to meet these requirements with the diet. These guidelines were defined taking into account nutrient bioavailability after ingestion, the variability of nutrients in different feeds, and their degradation during technological processing before diet administration to the animals.

Fat-soluble vitamins are studied by both basal and clinical nutrition. This article will focus on vitamin A, D, and E in dairy cow and ruminants nutrition. These animals have the rumen and its microflora, that use and degrade vitamins normally contained in the feed as well as the ones artificially added to the diet. This degradation is variable according to the vitamin, to its rumen transit time, and to rumen microflora composition.

Each feed ingredient contains different fat-soluble vitamin concentrations on the basis of the feed type (fat content), its storage conditions (fresh, dry, ensiled), and its technological modification before the inclusion in the feed (grinding, flaking, extrusion, etc.). Moreover, fat-soluble vitamins titration is an expensive analysis that cannot be done routinely: it is difficult for nutritionists to correctly balance the diet by adding these molecules in a rational way.

Vitamin A

The term “vitamin A” includes retinol and its analogs, the retinoids. This fat-soluble vitamin is mostly contained in animal origin feeds. Among vegetables, there are carotenoids (particularly β-carotene) that give the characteristic yellow-orange color to the feed. This pro-vitamin concentration in feed is generally low: i.e. 5-100 mg/kg in the hay, 1.6 mg/kg in the corn silage. The rumen normally degrades the vast majority of the ingested β-carotene: only 23% reaches the intestine and is absorbed by the enterocytes as retinol or retinoids. In the bloodstream, both retinol and carotenoids form esters with palmitate, stearate, and oleate, which are transported in the liver by the chylomicrons. Even retinol is degraded by rumen microflora. Standard diets for dairy ruminants contain forages/concentrates ratio from 50%:50% to 30%:70%: in these conditions, 62-72% of the dietary retinol is degraded in the rumen. If the ratio increase to 75%:25%, the degraded retinol decrease to 16-20%.

Vitamin A plasma concentration is regulated to maintain physiological homeostasis and is important for mucosal integrity, immune system, fertility, and tissue keratinization.

Vitamin D

Vitamin D (both D2, ergocalciferol, and D3, cholecalciferol) has a pivotal role in dairy cows and ruminants for calcium and phosphorus homeostasis and the innate immune system. Vitamin D3 is only in animal tissue because it is synthesized from cholesterol, while vitamin D2 comes from vegetables. Ergocalciferol is synthesized from ergosterol (vegetable origin) after UV rays exposure, while cholecalciferol comes from irradiated 7-di-hydro-cholesterol. Vitamin D is absorbed like the other fat-soluble vitamins: after intestinal absorption reaches tissue through the lymphatic system. Tissue vitamin D3 is hydroxylated becoming 25- hydroxycholecalciferol (also called 25(OH)D); this molecule passes into the bloodstream and links a specific protein named DBP. This conjugated molecule reaches the kidney and is hydroxylated in both an inactive and an active form (calcitriol, also called 1,25-dihydroxycholecalciferol or 1,25(OH)2D3). Calcitriol stimulates kidney calcium reabsorption, intestinal absorption of phosphorus and calcium, and bone mineralization, and has an activity similar to the steroid hormones because it stimulates protein production (especially calcium carrier) in the tissue cells. Calcium and phosphorus concentrations in the organism are mainly regulated by two important hormones: calcitonin and parathyroid hormone (PTH). Calcitonin reduces serum calcium stimulating the urinary elimination and bone deposition of the element. PTH increases kidney calcium retention, stimulates the renal synthesis of 1,25(OH)D, and the bone release of calcium. The result is the serum calcium increase. Hypocalcemia stimulates PTH and 1,25(OH)D synthesis, while hypercalcemia stimulates calcitonin. Moreover, it seems that vitamin D promotes epidermis keratinocytes and bone osteoclasts differentiation.

Vitamin E

Vitamin E (tocopherol) is a well-known antioxidant molecule that protects the organism against lipid peroxidation. The term “vitamin E” includes different forms of tocotrienol and tocopherols, among which the α-tocopherol is the most active and effective. The concentration of this vitamin in feed is highly variable because a large amount is lost during storage, feed processing, and digestion (strong rumen degradation). The intestinal bioavailability of vitamin E is low, frequently less than 30% of the ingested. Passing from the fresh (60-100 UI/kg) to the dry hay or the silage (20-80 UI/kg) causes up to 80% of the α-tocopherol loss. Diets for the dairy cows during the dry period may contain 1800 UI/day of vitamin E if it is based on fresh hay, while 200 UI/day with dry hay. During lactation, the hay intake is reduced by 50% with a vitamin E intake of about 400 UI/day (1500 UI/day if part of the diet is from graze, or 2500 UI/day if the animals only graze). Concentrates contain lower α-tocopherol dosages than the hay. If there is a high incidence of mastitis, their chronicization, and placenta retention, there may be a vitamin E deficiency. A correct plasma concentration of α-tocopherol improves the kill-ability of macrophages and neutrophils against phagocytized pathogens. Moreover, vitamin E improves chemotaxis, the migration of neutrophils to infection.

Requirements, recommendations, and deficiencies

Fat-soluble vitamins and in particular vitamin A, D3 and E are extremely important for dairy cows and for all ruminants. They are commonly added to the diet (rumen-protected forms give better results because of the bypass of rumen degradation), but it is always hard to detect some deficiency. Some metabolic pathologies (placenta retention, hypocalcemic syndrome, metritis, or mastitis) can be used as biomarkers if their incidence is particularly high. An objective way to diagnose a fat-soluble vitamin deficiency is to measure the plasma concentrations of these molecules (Table 1).

Table 1: Blood fat-soluble vitamins in dairy cows (NRC, 2001)
Vitamin A


β-carotene Vitamin D Vitamin E


> 80 μg/dL > 300 μg/dL 20–50 ng/mL 3–3.5 μg/mL


Currently, the dietary integrations of vitamin A, D3, and E for dairy cows are based on the Nutrient Requirements of Dairy Cattle (NRC, 2001) and on the published papers, even if the NRC is not very updated and the research results are often conflicting. Dietary inclusions have frequently doubled (or more) compared to the NRC indications. Vitamins A, D, and E are extremely important but also extremely variable in feed ingredients and requirements are not well defined: it is suggested to randomly analyze their plasma concentration in some animals per herd. The useful dietary concentrations in dairy cows seem to be 100.000–150.000 UI/day for vitamin A, 25.000-30.000 UI/day for vitamin D3, and 1.000 UI/day for vitamin E. The integration with 4.000 UI/day of vitamin E and 4 mg/day of organic selenium gave interesting results during the dry period (Table 2 reports detailed requirements).

The most effective form of vitamin integration for ruminants is the rumen-protected one with high bioavailability at the intestinal level: they guarantee the concentration absorbed by the animal with no interferences by rumen degradation. Rumen microflora uses the fat-soluble vitamins contained in the feed ingredients, taking advantage of these sources instead of using those added artificially.

Table 2: Fat-soluble vitamins requirements in dairy cows (NRC, 2001).
Growing heifers
BCS: 3.00
Age at calving:
24 months
Dry cows
Weight: 680 kg
BCS: 3.30 Calf
Weight: 45 kg
0.67 kg/day
Lactating cows
Holstein cows
Weight: 680 kg
BCS: 3.30
Age: 58 months
Milk fat: 3.50%
Milk protein: 3.00 %
Lactose: 4.80%
6 months 12 months 18 months 240 days 270 days 279 days 11 days in the middle of lactation
Production: 35 kg
90 days in the middle of lactation
Production: 45 kg
Vitamin A
(UI/kg DM.)
3076 3380 3185 5576 6030 8244 4795 2780
Vitamin D
(UI/kg DM)
1154 1268 1195 1520 1645 2249 1308 1758
Vitamin E
(UI/kg DM)
31 34 32 81 88 120 35 20

For more information: marketing@vetagro.comOriginal article here: part #1 and #2.