Bovine milk contains about 32 g protein/l 9 (Table 1). The milk protein has a high biological value, and milk is therefore a good source for essential amino acids. In addition, milk contains a wide array of proteins with biological activities ranging from antimicrobial ones to those facilitating absorption of nutrients, as well as acting as growth factors, hormones, enzymes, antibodies and immune stimulants 9596. The nitrogen in milk is distributed among caseins, whey proteins and non-protein nitrogen. The casein content of milk represents about 80% of milk proteins. Caseins biological function is to carry calcium and phosphate and to form a clot in the stomach for efficient digestion. The milk whey proteins are globular proteins that are more water soluble than caseins, and the principle fractions are beta-lactoglobin, alpha-lactalbumin, bovine serum albumin and immunoglobulins. Whey is the liquid remaining after milk has been curdled to produce cheese, and it is used in many products for human consumption, such as ricotta and brown cheese, and concentrated whey is an additive to several products e.g. bread, crackers, pastry and animal feed. The rate at which the amino acids are released during digestion and absorbed into the circulation may differ among the milk proteins, and whey proteins are considered as rapid digested protein that gives high concentrations of amino acids in postprandial plasma 97. The benefit of drinking whey has been known for centuries, and two ancient proverbs from the Italian city of Florence say, "If you want to live a healthy and active life, drink whey" and, "If everyone was raised on whey, doctors would be bankrupt" 98.

Some of the milk proteins (e.g. secretory immunoglobulin A, lactoferrin, 1-antitrypsin, β-casein and lactalbumin) may be relatively resistant to digestive enzymes, and the whole protein or peptides derived from it, may exert their function in the small intestine before being fully digested 99.

As several bioactive proteins and peptides derived from milk proteins are potential modulators of various regulatory processes in the body, some of these are produced on an industrial scale, and are considered for application as ingredients in both 'functional foods' and pharmaceutical preparations. Although the physiological significance of several of these substances is not yet fully understood, both the mineral binding and cytomodulatory peptides derived from bovine milk proteins are now claimed to be health enhancing components that can be used to reduce the risk of disease or to enhance a certain physiological function 100. Milk protein composition may differ among breeds 101. For example the concentration of beta-casein A1 is low in milk from cows in Iceland and in New Zealand. It has been speculated that this proteins may have a role in the development of diabetes and cardiac disease 102. However, later it was concluded in a review article that there is no convincing evidence that the A1 beta-casein of cow milk has any adverse effect in humans 103.

The calcium concentration in bovine milk is about 1 g/l (Table 1). Dairy products provide more than half of the calcium in the typical American diet 4, and daily intake of milk and milk products thus has a central role in securing calcium intake. In human nutrition adequate calcium intake is essential. Getting enough calcium in the diet gives healthy bones and teeth, and it may also help prevent hypertension, decrease the odds of getting colon or breast cancer, improve weight control and reduce the risk of developing kidney stones 4.

The selenium concentration in body fluids and tissues are directly related to selenium intake. The selenium concentration in Scandinavian food is low, and the concentration in Norwegian bovine milk is about 11 ug/l (own results, 2006), and 37 ug/l in the US 9. For plant products the situation is even worse; the selenium concentration in wheat flour (whole grain) is less than 20 ug/kg in Norwegian wheat (own results), compared to 707 ug/kg in the US 9.

Selenium is important in human health; it has a role in the immune- and antioxidant system and in DNA synthesis and DNA repair 120. Selenoprotein P is an antioxidative defence enzyme having similar function as the selenoenzyme phospholipid hydro peroxide glutathione peroxidase (Gpx-4) inside the cells and it also protects LDL towards peroxidation 121122. A strong negative correlation between the concentration of selenium and the concentration of plasma lipid peroxidation products has been reported in a Canadian study 123. These observation are in line with epidemiological observations from USA, where a strong negative correlation between mortality of ischemic cardiac disease and hypertension among men and women in the age group 55–64 years comparing states with different selenium intake 124125.

Selenium protects against many (but not all) types of cancer 4. There are indications that selenium may protect against asthma, and that low selenium intake may worsen the asthma symptoms 126. Selenium deficiency has even been linked to adverse mood states 127. Selenium is also a component of enzymes involved in metabolism of thyroid hormone.

As selenium is of fundamental importance to human health, the low selenium availability in Scandinavian soil is of concern. Different strategies can be used to increase human selenium intake, and addition of selenium-rich yeast to the feed of domestic animals is one option. Recommended daily intake of selenium is 55 ug 4, and the optimal selenium concentration in bovine milk may be discussed. If milk contains about 50–100 ug selenium/l, it would be a good selenium source.

Iodine is an essential component of the thyroid hormones. These hormones control the regulation of body metabolic rate, temperature regulation, reproduction and growth.

The recommended iodine intake is 150 ug/d for adults 4. Accordingly, a daily intake of 0.5 litres milk with an average content of 160 ug iodine/l meets about 50% of the requirement (Table 1). However, it is important to underline the great seasonal variation in iodine content of milk (see later).

Magnesium is ubiquitous in foods, and milk is a good source, containing about 100 mg/l milk 9. Recommended intake is 400 mg/day for men and 310 mg/day for women 4. Magnesium has many functions in the body, participating in more than 300 reactions. Magnesium deficiency has been linked to atherosclerosis, as studies have shown that deficiency may give oxidative stress 128. Magnesium may also have a role in reducing asthma, and experimental studies of persons with asthma suggest that magnesium infusion may have a place in the acute treatment of asthma 129. A possible mechanism may be that magnesium together with taurine dampens the signaling effects of a too high calcium release inside the cells 111130. Magnesium deficiency may occur following kidney disease and after use of some diuretic drugs. Magnesium deficiency in elderly is observed, and may be a result of poor appetite or unbalanced diet.

Zinc is an essential part of several enzymes and metalloproteins. Zinc has several functions in the body, in DNA repair, cell growth and replication, gene expression, protein and lipid metabolism, immune function, hormone activity, etc 4. Milk is a good zinc source; containing about 4 mg/l 9. Recommended intake is 8 and 11 mg/day for adult female and male 4. The bioavailability of zinc is better from milk than from vegetable food 4, and inclusion of milk in the diet may improve total bioavailability of zinc 131.

Vitamin E concentration in milk is about 0,6 mg/l 9 (Table 1), but may increase 3–4 folds by proper feeding regimes (see later). Recommended intake is 15 mg/day 4. Vitamin E is not a single compound; it includes tocoferols and tocotrienols. In whole milk, alpha-tocopherol is the major form of vitamin E (>85%); gamma-tocopherol and alpha-tocotrienol are present to a lesser extent, about 4 % each of the sum of tocoferols and tocotrienols 132. Observational studies indicate that high dietary intake of vitamin E are associated with decreased risk for cancer and coronary heart disease, and that vitamin E can stimulate T-cells and increase the immune defence system. Milk seems to be a food item favouring absorption and transportation of vitamin E from ingested food into the chylomicrons 133.

Milk is a good source of retinoids, containing 280 ug/l 9 (Table 1). Recommended daily intake is 700–900 ug/day 4. Vitamin A has a role in vision, proper growth, reproduction, and immunity, cell differentiation, in maintaining healthy bones as well as skin and mucosal membranes 4.

Bovine milk contains 50 ug folate/l 9. Studies indicate that 5-methyl-tetrahydrofolate is the major folate form in milk 134. Recommended intake of folate is 400 ug/day for adults 4. Many scientists believe that folate deficiency is the most prevalent of all vitamin deficiencies 4. It is generally accepted that folate supplementation (400 ug/day) before conception and during the first weeks of pregnancy reduces the risk of neural tube defects. A recent study has shown that higher total folate intake was associated with a decreased risk of incident hypertension, particularly in younger women 135. In addition, folates may have a protective role to play against coronary heart disease and certain forms of cancer, but sufficient evidence is not yet available 136. The complexity of the folate metabolism suggest that different metabolites of folate are involved in different reactions, and that dihydrofolate and 5-methyl-tetrahydrofolate are the active compounds in growth-inhibition in colon cancer cells 137.

The bioavailability of folate varies 138. Folate-binding proteins occur in unprocessed milk, pasteurised milk, spray-dried skim milk powder and whey 134. Animal and human studies have suggested that these components enhance food folate bioavailability, and it is shown that inclusion of cow milk in the diet enhanced the bioavailability of food folate 139. In a population-based study, the consumption of milk and yogurt were inversely associated with serum total homocysteine concentrations, and the authors explained this association by intakes of folate and riboflavin 140.

Milk is a good source of riboflavin, 1.83 mg riboflavin/l milk (Table 1). Daily recommended intake is 1.1 and 1.3 mg for women and men, respectively 4. Riboflavin is part of two important coenzymes participating in a numerous metabolic pathways in the cell. It has a role in the antioxidant performance of glutathione peroxidase and DNA repair via the ribonucleotid reductase pathway.

Milk is also a good source of vitamin B₁₂, being 4.4 ug/l 9. The daily recommendation is 2.4 μg 4. Vitamin B₁₂ is found only in animal foods, and plays a central role in folate and homocysteine metabolism, by transferring methyl groups. Vitamin B₁₂ deficiency may cause megaloblastic anaemia and breakdown of the myelin sheath.

Most milk proteins, even proteins present at low concentrations, are potential allergens. A person may be allergic to casein or whey proteins or to both. Milk allergy may arise in small children (0–3 years) and it is estimated that 2–5% of the children has milk allergy 155. After the age of three years it is no longer a problem for most children.

Milk allergy reactions may either be of the type 'rapid onset' or the 'slower-onset' type. The rapid type comes suddenly with symptoms of e.g. wheezing, vomiting, anaphylaxis. The slower-onset reactions are more common and symptoms develop over a period of hours or days after ingesting milk, and may include loose stool, vomiting, fussiness, reduced weight gain etc. As these symptoms are more general, this type is difficult to diagnose.

Cow's milk allergy may be treated by completely avoiding milk proteins. Epitopes on milk proteins have been shown to be both conformational and linear epitopes, widely spread throughout the protein molecules. Due to the great variability and heterogeneity of the human IgE response, no single allergen or particular structure has been found to be a major part of milk allergenicity 156.

An interesting study from Germany showed that the children of farmers had less allergy, in spite of the fact that these children were drinking more whole- milk than other children not living on farms157.

There has been speculation if milk proteins may have a role in Attention Deficit Hyperactivity Disorder (ADHD), autism, depressions and schizophrenia in some cases. There are major supports to the hypothesis that ADHD may be linked to increased levels of neuroactive peptides and increased urinary peptide levels 158159. A diet free of milk, milk products and gluten may in many cases give reduced ADHD symptoms 158. Further, opioid peptides derived from food proteins (exorphins) have been found in urine of autistic patients 160. This area of investigation is important and large scale, good quality randomised controlled trials are needed.

The lactose concentration in bovine milk is about 53 g/l 9. People often confuse a milk allergy with lactose intolerance, but they are not the same thing. Lactose intolerance is common in many adults throughout the world, and is caused by deficiency of intestinal lactase (hypolactasia). Lactose maldigestion occurs in about 75 % of the worldwide population and about 25 % of the US population 4. In Scandinavian counties it varies between 2% and 18% 4. Avoiding all lactose is seldom necessary, and persons with hypolactasia can usually ingest limited amounts of milk without having annoying symptoms. Individual differences in gut micro flora may be one reason for large variations in amounts of milk that is tolerated. To ingest milk with a meal may also improve tolerance. Instead of drinking regular milk, fermented milk may be an option, because fermented milk contains less lactose than fresh milk, and that it also may contain bacterial lactase that may be activated when the fermented milk reaches the gut 161.

Digestion of lactose in the intestine, and fermentation of milk gives increased concentrations of galactose. Galactose is catabolized by the Leloir pathway by phosphorylation at position 1, and then converted to UDP-galactose and glucose-1-phosphate 162. Defects in enzymes in this pathway may result in galactosemia in humans, and early onset cataract. In young women ovarian failure at a very early age has been observed following galactose accumulation. Cramer et al. 163 studied the relation between age-specific fertility rates, the prevalence of adult hypolactasia and per capita milk consumption. They found that fertility at high ages is lower with high per capita consumption of milk and greater ability to digest its lactose component. These demographic data thus add to existing evidence that dietary galactose may deleteriously affect ovarian function.

The level of galactose in fermented milk products depends on growth conditions of the different organisms and fermentation time, and for example after 24 h fermentation, the concentration of galactose has been reported to about 20 g/litre 164. A study in rats showed that administration of galactose in the form of lactose seemed to be less toxic than when galactose was fed 165. High levels of galactose as well as glucose may cause glycation of proteins, form advanced glycation end products, and the activation of polyol metabolism. This may accelerate generation of reactive oxygen species (ROS) and increases in oxidative chemical modification of lipids, DNA, and proteins in various tissues.

The fatty acids of bovine milk are derived from two sources. The first source is fatty acids supplied to the udder by the blood, composed of fatty acids absorbed from the intestine and mobilized from the adipose fat tissue, mainly palmitic acid (16:0), stearic acid (18:0) and longer chained fatty acids. The second source is derived from circulating blood acetate and butyrate produced during fermentation in the rumen (de novo synthesis), and fatty acids up till 14 carbon atoms are synthesised in the udder. Palmitic acid in milk originates from both de novo synthesis and from circulating blood. Due to the extensively biohydrogenation of dietary unsaturated fatty acids in the rumen, the supply of these fatty acids to the udder is low. However, in the udder desaturation of fatty acids like 12:0, 14:0, 16:0 and 18:0 take place, and the products being 12:1, 14:1, 16:1 and 18:1, respectively. The preferred substrate for the desaturating enzyme; delta-9-desaturase, is stearic acid. Therefore is bovine milk a relatively good source of oleic acid (18:1, cis 9). The udder enzymes can not make double bonds in omega-3 and omega-6 positions. Consequently, milk content of linoleic acid and alpha-linolenic acid depends on the supply of these to the udder.

Conjugated linoleic acid (9c,11t-CLA) in milk originates from two sources. A small part originates from incomplete biohydrogenation of linoleic acid in the rumen which are absorbed from the small intestine transported to the udder and included in the fat synthesis. Most of the 9c,11t-CLA originates, however, from vaccenic acid which is an intermediate from biohydrogenation of unsaturated fatty acids in the rumen. After absorption and transportation by the blood to the udder, a portion of the vaccenic acid is desaturated by delta-9-desaturase to CLA. There is a close positive correlation between milk content of vaccenic acid and 9c,11t-CLA 86169.

The effect of feed on milk fat content and fatty acid composition is comprehensively discussed 68170171172. There are large variations in fat synthesis in the udder, and the fat content and fatty acid composition are the most modifiable of the main components in milk. Some feeding strategies to obtain milk with altered fatty acid composition are summarized in Table 2. There are seasonal variations for the major fatty acids 6782. Milk from grazing dairy cows contain significantly higher proportion of oleic acid than milk produced on traditional indoor feeding composed of concentrates and conserved roughages 67. Typically, CLA content in milk produced on pasture is at least twice of that obtained by indoor feeding 6782. Moreover, the proportion of alpha-linolenic acid increases more than linoleic acid, resulting in a lower ratio between omega-6 and omega-3 fatty acids. Milk fat from cows fed an in-door diet consisting of conserved grass and concentrate have a ratio between omega-6 and omega-3 fatty acids of about 4:1 6782, but in summer when the cows are out on pasture and have a high intake of grass the ratio may be reduced to about 2:1 86782172. These positive effects of pasture on the fatty acid composition of milk are mainly attributed to the high content of polyunsaturated fatty acids, especially alpha-linolenic acid, in grasses at early stage of maturity 173.

In general, milk protein content is relatively unresponsive to feeding factors. However, under most conditions, energy-, but also protein supply, is feed related factors with most pronounced effect on milk protein content (Table 2). Milk protein content may be negatively influenced by high intake of dietary fat by the lactating cow 168. Thus, there may be a conflict between milk fatty acid composition and protein content. The feeding regime has only small impact on the proportion of the different types of milk proteins and consequently the amino acid composition 101, and will therefore not be further discussed in this review. However, heat treatment of dairy products leads to structural changes of proteins and main whey proteins are modified to lactulosyl residues 174.

Bovine milk contain a vide range of minerals 4. Milk concentrations of some minerals that are of special importance in human nutrition are given in Table 2. The calcium concentration in milk is relatively constant, with some variations throughout lactation. Most of the calcium is in the aqueous compartment and it is primarly (65%) associated with casein 175. The calcium concentration in milk is relatively constant because milk content of casein is unresponsive to feeding factors. Milk content of magnesium and zinc also show only small variations.

The concentration of selenium in bovine milk is related to selenium concentration in the feed, and there are great variations worldwide. In South Dakota the selenium concentration in milk is reported to be between 160 and 1300 ug/l, whereas the concentrations in milk from low-selenium regions may be from 5 to 30 ug/l 176, as in Scandinavia and northern Europe. A Swedish study showed that the average selenium concentration in milk was 14 ug/l and the concentration was more than doubled after supplementation with 3 mg selenium daily from selenium-enriched yeast 177.

As much as about 25 percent of the iodine intake may be excreted in milk 178. Therefore, milk content of iodine also varies depending on the iodine content and availability in the feeds used. A study on milk and milk products in Norway 179, showed that milk from the summer season had significantly lower iodine concentration (88 ug/l) compared with milk from the winter season (232 ug/l). This is explained by the use of more supplementary feeds enriched with iodine during the winter season. Dairy products supply much of the dietary intake of iodine; in Norway the most 179, and in US the second most 4 of the iodine intake.

Vitamins are not synthesized in the udder. Milk content of the fat-soluble vitamins A and E reflects their content in the feed (Table 2). In general, the content of these vitamins in feed plants decrease with maturity and are higher in fresh than conserved material. There are therefore regional and seasonal variations in these vitamins due to feeding regimes 180, with the highest concentrations in fresh grasses at early stage of maturity. For example a study in Finland shows that the concentration of vitamin E in milk is 3–4 times higher during summer than in winter 181. Enriching the supplementary feeds with proper sources of these vitamins may increase the milk content during the winter season.

All vitamins of the B-complex (riboflavin and vitamin B₁₂, in Table 2) are synthesized by the rumen microbes, normally in sufficient amounts to cover the animal's needs. Milk content of B-vitamins are, however, relatively unrelated to their intake because the amount synthesized by the rumen microbes are unregulated according to the amount ingested 182.