Calcium (Ca) is the main mineral found in milk, divided into the soluble and micellar phases. In the watery phase, Ca is present in its free form combined with citrate, inorganic phosphate and whey proteins. Two thirds of Ca is bound to casein in the micellar phase, related to organic phosphate (phosphoseryl residues of casein molecules) [26]. Partitioning of this mineral between these phases is complex, highly dynamic and influenced by different factors, such as temperature, ionic strength and pH. The Ca is thermodynamically equilibrated between the water and micellar phase, in relation to the chemical condition. Biological acidification processes such as lactose fermentation, during processing of dairy products, are primarily responsible for moving Ca into the water phase [38]. Ca bioavailability in milk is high [39] and certain milk components, e.g., lactose and phosphopeptide may improve the uptake of this mineral [40]. Ca milk content is lower in human and donkey milk compared to cow’s milk, while in sheep’s and goat’s milk is present a higher concentration (Table 3, Ref. [7, 36, 41, 42, 43, 44]). Milk represents an important source of Ca to the human diet.

Phosphorus (P), an important component of milk and dairy products, is present in different forms of organic and inorganic phosphates and in various localizations. The organic form of P binds various molecules, mainly to casein molecules, in the micellar phase. The inorganic form of P is divided between the water and micellar phase. This mineral is transferred into the water phase mainly during acidification processes. P is mostly abundant in goat’s and sheep’s milk (Table 3) and is present in various animal foods [45]. Therefore, there is no shortage of this mineral for humans.

In contrast to Ca and P, magnesium (Mg) is not a very abundant component in milk and milk products. The effects of Mg on physiochemical stability of whey protein are similar to those for Ca. It is present in the micellar phase bound to casein proteins, while in the water phase is associated with citrate and P. Two thirds of Mg is present in the soluble part of milk [46]. This distribution, as well as Ca and P, depends on the physiochemical condition. Mg is found in higher concentrations in sheep’s and goat’s milk (Table 3). Milk and dairy products are good contributors of dietary Mg.

Sodium (Na) and potassium (K) are present mainly as free ions in the water phase of milk and milk products and their concentrations are increased by salting [47]. These minerals contribute to the cheese’s physical-chemical properties [48], to the micro-organism’s selection and to enzymatic activities throughout maturation processes. Na is a mineral quite present in milk and found in different concentration in animal species. Indeed, it is in twice the concentration in goat’s, sheep’s and cow’s milk than in human and donkey milk, as reported in Table 3. Similarly, K, the most abundant mineral in milk, is present especially in ruminant milk, while its concentration is lower in human and donkey milk (Table 3). Iron is deficient in milk; indeed, is present in low concentration and associated with casein and whey proteins [49, 50]. Selenium (Se) is a mineral found particularly in milk and dairy products [51], and mainly present bound to casein molecules and whey proteins [52]. Se can be found in two distinct forms: inorganic and organic. Inorganic forms include selenate (Na${}_2$SeO${}_4$) and selenite (Na${}_2$SeO${}_3$), whereas the organic form includes selenomethionine (SeMet) and selenocysteine (SeCys). The organic forms of selenium are better absorbed by animals and humans [53]. Studies demonstrated that its content in milk depends largely on selenium supply in feed ration for cows [54]. Animal products, such as milk, are considered the basic source of this micronutrient in the diet of human, representing a good source of Se for human needs [27]. Milk and milk products are the main sources of iodine (I) for human in a large number of countries [55, 56]. The concentration of this micronutrient in milk is affected by different factors, such as: iodine content of the animal’ diet, sanitation practices used for teat dipping, season, farming system and dietary supplement [57]. I compounds are soluble in water, and it is likely that milk I increases in partially skim milk. Recent evidence showed that this micronutrient might be partially associated with casein micelles [36]. Furthermore, the analysis of the I content in different milk showed that goat milk and donkey milk provided a greatest and a lowest iodine content, respectively [36] (Table 3).

In milk from different animal species, the minerals are distributed differently in soluble and non-soluble fractions (mainly casein micelles). K and Na are present in the water phase, while P, Ca, Mg, Se and I are partly linked to casein micelles. Mineral composition in milk is regarded as relatively constant, but the mineral content can vary mainly according to the lactation stage, the nutritional and health status of the animals [58]. In summary, milk is a food rich in precious minerals with mineral composition varying according to the animal species. Comparing the different animal species considered, it appears that sheep’s and goat’s milk are the richest in minerals compared to other types of milk, as reported in Table 3.

Vitamins play an important role in intermediate metabolism as co-factors in many enzymatic reactions or in non-enzymatic physiologic functions, and do not function as structural components within the cell. The vitamin content in milk varies considerably among mammals and is closely related to the type of feeding given to the animals. In particular, increased vitamin E and carotenoids have been observed in milk and dairy products obtained from pasture-fed cows compared with those obtained from milk of cows on corn silage feeds [59]. Milk and milk products contain both water-soluble vitamins (vitamins B-complex and vitamin C), and liposoluble vitamins (A, D, E and K) [60]. The water-soluble vitamins are situated in the watery phase of milk and therefore present in skim milk; while the liposoluble vitamins found in the lipidic phase, as in whole milk, cream and cheese. B complex vitamins perform numerous and important cellular functions, being implicated as cofactors in anabolic and catabolic reactions. Thiamine or vitamin B${}_1$ and riboflavin or vitamin B${}_2$, are produced from plants and micro-organisms [61]. In particular, riboflavin is produced especially from bacteria present in the rumen and is thus very present in the milk of ruminants. In general, both vitamin B${}_1$ and vitamin B${}_2$ are present in higher levels in ruminant animals compared with non-ruminant species. However, both these vitamins have also been found in abundant quantities in donkey’s milk (Table 4, Ref. [7, 29, 41]) and are relatively stable to heat treatment and acid condition. Niacin or vitamin B${}_3$ is primarily produced by microbial organisms of the rumen [61] and found in high concentrations, especially in sheep’s milk. Recent investigations have also found a good concentration of vitamin B${}_3$ in donkey milk [28]. Pyridoxine or vitamin B${}_6$, synthesized from plants and micro-organisms, is involved in several biochemical pathways, such as in the metabolism of amino acids, lipids and glucogenesis [62]. The concentration of this vitamin is higher in sheep’s and cow’s milk than in milk of other animal species reported in Table 4. Folic acid or vitamin B${}_9$ is a micronutrient involved in nucleic acids synthesis, is very sensitive to different physicochemical conditions [63] and is found in a higher content in cow’s milk and human milk, compared to other species (Table 4). Milk provides a significant source of folic acid to humans [29]. Cobalamin or vitamin B${}_{12}$ originates from microorganisms in the digestive tract, through microbial synthesis in the rumen [64, 65]. It is involved in various important functions of the organism and in milk is mainly bound to proteins. Vitamin B${}_{12}$ is mostly present in ruminant milk, which contributes largely to human intake. In particular, the vitamin is found in higher concentration in cow’s and sheep’s milk. Ascorbic acid or vitamin C has been known as an antioxidant molecule [66], found in milk but not in milk derivatives, as a result of its degradation during their processing. Vitamin C has a high sensitivity to light and heat treatments and milk cannot be considered an interesting source.

The fat-soluble vitamin content of milk is related to the overall fat content of milk. Vitamin A is found in various forms: retinol, retinal and retinoic acid and is highly sensitive to oxidation, light or different oxidant factors [67]. The concentration in milk declines after heat-treating and acidification processes [68]. The content of vitamin A is higher in breast and sheep’s milk compared to other animal species listed in Table 4. In western countries, there is no lack of vitamin A, and milk may be regarded as a good source of the vitamin. Vitamin D is a group of components, the most important are ergocalciferol (vitamin D${}_2$) and cholecalciferol (vitamin D${}_3$), synthesized by plants and in the animals’ skin under the effect of the sun, respectively. This vitamin exerts many important physiologic functions for human health, is unstable to light, oxidation factors, heat and acidic conditions [30]. As illustrated in Table 4, milk contains a very low amount of vitamin D, and the lowest level is found in breast milk. Therefore, milk should not be regarded as a major source of this vitamin. The term vitamin E refers to a group of eight molecular forms with antioxidant activity, produced by plants and divided into 2 groups: tocopherol and tocotrienol. The main vitamin E in milk is alpha tocopherol, is found in higher concentration in breast milk, representing a good source compared to other animal species (Table 4). Phylloquinone or vitamin K${}_1$ and menaquinone or vitamin K${}_2$ are vitamins produced by plants and by micro-organisms present in the rumen, and its content is higher in cow’s milk [69] as reported in Table 4. Vitamin K content is low in milk, but in fermented products is present in significant quantities. Nevertheless, both milk and milk derivatives are not considered to be an important source of the vitamin. As reported in Table 4, ruminant milk is a good source of B-complex vitamins, while human milk is distinguished by its vitamin A and vitamin E content.

Ca is the major mineral in the human body and plays different structural and functional roles. Indeed, it is important to proper skeletal development [70] and many cellular metabolic processes, such as nerve and muscular cells and for normal blood pressure maintainance [71]. This ion helps to form and maintain the excitability of tissues and conduction of nerve tissue stimuli [72]. Ca plays an important role in the blood coagulation processes. Maintenance of a constant concentration is therefore of vital importance. Vitamin D, lactates and citrates support its absorption in the digestive tract. Dietary Ca derives from milk and milk products, primarily from cheese. Therefore, the main sources of this mineral are skim milk, yogurt and semi-skim cheese, since the lactose they contain promotes its absorption.

Despite milk and dairy products being sources of calcium, the bioavailability of this mineral is influenced by several factors, such as the physiological intestinal barrier, the ratio of calcium to phosphorus, the presence of lactose, vitamin D, oxalates, phytates or some fiber components [73]. In particular, plant foods contain considerable anti-nutritional factors, such as oxalates and phytates. These bind to calcium and form insoluble salt complexes, resulting in lower absorption [74].

As well as for other micronutrients, in some conditions such as aging and during pregnancy, the need Ca intake increases and it is quite difficult to meet recommended Ca levels, leading to the necessary use of Ca-fortified dairy-based products. In fact, the lack of calcium mainly has repercussions on bone health at all ages, since it causes rickets in infants, delays the acquisition of proper bone mass at the time of skeletal development in adolescents and is responsible for accelerated bone loss in adulthood in both women and men, leading to the development of osteoporosis [75].

Selenium (Se) is an essential trace element for humans and animals. Most of the Se in milk is protein bound [76]. Indeed, this mineral is often found in the form of selenoprotein and is involved in various physiological functions, such as the enhancement of immunity and oxidation resistance [77]. Se is important as enzymatic cofactor in various biological systems and plays an important role in antioxidant enzyme processes [78]. The absorption of Se is mainly through the diet and the dietary levels of antioxidant agents, such as vitamins C and E, methionine and total protein can increase the bioavailability of Se. Milk and its products contribute over 4% of the total dietary Se consumed by humans [79]. In milk, about 60–80% of Se is bound to caseins. Se content of forages/feeds generally depends on the season and agro-ecological conditions, which can subsequently affect its milk content. Studies have been conducted in different places around the world in order to document the Se content in milk from dairy cows, evidencing a considerable variability, depending mainly on the amount of this element in the soil. The selenium content in cow’s milk from European countries is in a wide range: in Greece, 110 $\mu$g/L; in Hugary, 41–90 $\mu$g/L; in England, 12–43 $\mu$g/L and in Scotland, 30–60 $\mu$g/L [54, 80, 81]. Therefore, the levels of Se within human tissue depends on dietary intake, which is related to Se availability in the soil and its geographical distribution [82]. Findings obtained in Finland showed that Se content of milk was doubled, increasing its content in the mineral fertilizers [83]. Se is a common ingredient in food supplements, allowing for adequate dietary intake. Both excessive Se intake and Se deficiency can have adverse effects on human health. Indeed, the excessive consumption can also lead to gastrointestinal disturbances, skin lesions, liver cirrhosis and pulmonary edema [53]. The deficiency for this element in the body may contribute to some issues related to cancer, cardiovascular disease, and nervous system alterations [84].

Iodine (I) is an important element in human health, as it is key component of thyroid hormone [85]. Thyroid hormones are essential for the cellular metabolism and the proper fetal development [86]. In addition to being a structural and functional component of thyroid hormones, it also plays a significant role as a bactericidal because of its oxidative properties [87]. The amount of I in natural foods is highly variable and mainly depends on the soil where plants and animals grow [88]. Milk and milk products can have a significant I concentration and therefore considered among the most common dietary sources of this mineral [89]. Several studies showed that a low I intake results in poor development of neurological and physical functions in children [90]. Furthermore, in adults mild-to-moderate I deficiency increases the incidence of hyperthyroidism due to toxic goiter [91]. On the other hand, the excess I intake has been associated with the development of autoimmune thyroiditis and hypothyroidism [92].

Vitamin A represents a group of organic compounds represented by two principal forms in foods: retinol, found in animal-sourced foods; and provitamin A, known as beta-carotene, present in animal and vegetable foods [93]. Vitamin A is an important nutrient required throughout life, which generally functions as a mediator in various metabolic and physiological processes within the body. Vitamin A is one of the key components involved with visual function, but also in development and cellular differentiation, primary epithelial cells and bone tissue [94]. It also sustains fetal development and embryonic growth [95]. Furthermore, it keeps the immune system active and strengthens its humoral and cellular components [96]. Vitamin A represents one of the most efficient substances in delaying aging, as is involved in maintenance, regulation, and repair of adult tissues [97]. It accelerates skin regeneration by influencing protein synthesis, metabolism and cell proliferation. Lack of vitamin A leads to night blindness, xerophthalmia (progressive blindness due to drying of the cornea of the eye), keratinization (accumulated keratin in the digestive, respiratory and urinary-genital tract tissues) and at last exhaustion and death [98]. A good source of vitamin A is represented from milk and milk products, and the fat content of milk facilitates the dissolving and absorption of vitamin A. Vitamin A is stored in the body and, therefore, deficiency disease is difficult. Nevertheless, the lack of vitamin A is a serious public health problem in many low- and middle-income countries. This primarily concerns young children, women of reproductive age and pregnant women [31]. Especially in this context the intake of milk and milk products fortified with vitamin A can have a positive impact on the functioning of the immune system [99].

The term vitamin D refers to a group of fat-soluble secosteroids: the two main forms are vitamin D${}_3$ (cholecalciferol) of animal origin and vitamin D${}_2$ (ergocalciferol) present in fungi and certain plants [100, 101]. Vitamin D${}_3$ is synthesized by sunlight into the skin of humans and animals. These two forms of vitamin share essentially the same metabolism. Vitamin D actives several molecular pathways and mediates a multitude of functions. The classic role of vitamin D is the regulation Ca and P homeostasis and bone metabolism, regulating the mineralization and remodeling during growth [102]. Indeed, it increases the uptake of Ca and phosphate in the gastro-intestinal tract, promoting bone mineralization processes [102]. Also, vitamin D plays an important role in the innate and the adaptive immune system [103, 104]. In addition, it plays an important potential protective effect against cancer development and progression [105]. Vitamin D overdoses occur less frequently than deficiencies. In adults, a lack of vitamin D causes disorders of bone structure, such as osteomalacia a disease characterized by the incomplete mineralization of osteoid, whereas in children, it is responsible for rickets. Rickets is a disease characterized by a decrease in the mineralization of bone tissue and growth plates, resulting in weak bones in infants and children [34]. Chronic lack of vitamin D dietary intake is the cause of secondary hyperparathyroidism, which is a cause for increased bone turnover, with consequent progressive bone loss and finally an increased risk of bones fracture [106]. Several studies showed that vitamin D deficiency is evident in a large part of the population, a concern prevalence rate, requiring public health intervention [107] and in certain countries (e.g., United States, Canada, Finland, Poland), some vitamin D-enriched foods are used to compensate for shortages. Vitamin D content in milk is low, and various foods on the national market are already improved by manufacturers with the vitamin, such as milk and milk beverages, yogurt [108].

Vitamin E (primary its isoform a-tocopherol) is an essential antioxidant, which protects cell and sub-cell membranes against attacks of endogenous and exogenous free radicals [109]. The main role of vitamin E is the protection of lipids against oxidative damage. It has been demonstrated that vitamin E acts not only as an antioxidant but also, as a modulator of signal transduction and a regulator of genetic expression. Indeed, some isoforms regulate gene expression in different tissues and cell types [110, 111] and are essential in preventing cardiovascular diseases, especially in coronary artery disease and atherosclerosis. The non-antioxidizing functions of vitamin E can involve several cell- signaling pathways which cause inhibition of the proliferation of smooth muscle cells, platelet adhesion, and aggregation of adhesion molecules. Signs of vitamin E deficiency include ataxia, retinopathy, peripheral neuropathy, musculoskeletal myopathy, and immune response disorders [112]. Vitamin E content in animal foods is generally low, but such products can provide important sources of the vitamin for humans due to their high intake. While the vitamin E content of milk is low, fortification of milk with this vitamin may have an important impact on public health.

Vitamin B is a complex of a broad array of compounds which are essential for maintaining good health and well-being [113]. Vitamin B${}_1$ or thiamine is regarded as one of the least stable vitamins [114]. It is a cofactor of several critical enzymes, linked to the metabolism of carbohydrates and branched-chain amino acids [115]. Indeed, vitamin B${}_1$ is a coenzyme implied in transketolation reactions of the pentose-phosphate pathway, and pyruvate dehydrogenase catalyzed oxidative decarboxylation. In addition, thiamine is important for many other cellular processes, such as nucleic acid precursor synthesis, myelin, and neurotransmitters [116]. Thiamine deficiency can affect the cardiovascular, nervous, and immune systems, both severely and chronically as beriberi or Wernicke-Korsakoff syndrome [117]. Vitamin B${}_2$ or riboflavin is the precursor of flavin mononucleotide and flavin adenine dinucleotide. The flavoprotein coenzymes are implicated in oxidation-reduction reactions which enter into numerous metabolic pathways, affecting cell respiration in fats, protein, and carbohydrate metabolism [118]. In addition to increasing energy, riboflavin acts as an antioxidant for a healthy immune system. Its deficiency may be linked to numerous developmental abnormalities, growth delay, cardiac disease and anemia [119]. The term niacin is frequently used to refer to a group of related chemicals, mainly nicotinamide (pyridine-3-carboxamide) and its derivatives. Vitamin B${}_3$ has a broad spectrum of functions, as cofactor of many oxidoreductase enzymes involved in glycolysis, lipid metabolism, protein metabolism and detoxifying processes. Vitamin B${}_3$ deficiency causes a condition called pellagra, which is characterized by photosensitive dermatitis, diarrhea, dementia and death [120]. Vitamin B${}_6$ consists of a variety of compounds, implicated as coenzyme in different biochemical reactions. It is a coenzyme of many reactions linked to protein metabolism, in particular involving decarboxylation and transamination reactions. Vitamin B${}_6$ is also involved in metabolizing carbohydrates, lipids, amino acids, and nucleic acids, and contributes to cell signaling. Several of the B${}_6$ vitamers have been reported to have potent antioxidant activity [121]. Vitamin B${}_9$ or folic acid naturally exists in multiple forms and plays a role as cofactors in essential biochemical reactions critical for cell division [122]. It is critical for the synthesis, replication, and repair of nucleotides for DNA and RNA and is therefore necessary for cellular proliferation and survival [123]. Also, this vitamin has a protective effect against neural tube defects, ischemic events and cancer [124]. Vitamin B${}_9$ deficiency also decrease lymphocyte proliferative response and natural killer cell activity [123]. Among B vitamins, vitamin B${}_{12}$ occupies a very special niche. It is a molecule containing ion cobalt and involved in multiple metabolic reactions. This vitamin is only produced if the cobalt supply is adequate [125]. Vitamin B${}_{12}$ functions primarily as a coenzyme in the intermediate metabolism, in particular in transmethylate reactions. It is essential to the health of nerve tissue, the functioning of the brain and the production of red blood cells [126]. Higher levels of vitamin B${}_{12}$ are found in ruminants, indeed, is biosynthesized by rumen microorganisms and related to the cow’s cobalt consumption [127]. Major effects of vitamin B${}_{12}$ deficiency in humans include pernicious anemia and neuropathy, due to its important function on cell division [128]. Among the B vitamins, milk is a particularly rich source of riboflavin or vitamin B${}_2$ and vitamin B${}_{12}$.

Vitamin C or ascorbic acid exhibits many biological functions, such as antioxidant, collagen, and neurotransmitter synthesis [129]. Vitamin C is important to maintain the integrity of the intracellular matrix and to improve the immune system [130]. Vitamin C deficiency manifests symptomatically with irritability and anorexia, poor wound healing, gingival swelling with loss of teeth, mucocutaneous petechiae, bruising, and hyperkeratosis [131]. Milk is not usually considered an important source of vitamin C, mainly because concentrations are significantly reduced during handling and storage.