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Food Science & Technology
Lactose is the principal sugar of mammal milk, with a few exceptions (e.g., sea lions and walruses), and is the source of nourishment for newborns. As a sugar, it has a major role as a source of energy, providing 4 kcal/g, and also having a low glycemic index.
- lactose
- chemical properties
- food application
- excipient
- legislation
- lactose intolerance
- lactose-free
1. Introduction
Lactose is the principal sugar of mammal milk, with a few exceptions (e.g., sea lions and walruses), and is the source of nourishment for newborns [1]. After weaning, mammals are not capable of digesting milk, and humans are the only species that continue to consume and digest milk daily, thanks to a phenomenon of gene–culture coevolution [2].
The main food products in which lactose can be found are dairy products, milk being their raw material, or recipes in which these products are used. Lactose can also be extracted from milk and employed as an ingredient or additive in a large variety of products. In this case, lactose is found in goods which are not directly linked to milk and for this reason it is called “hidden lactose” [3]. Regardless of its origin, lactose intake can have positive or negative effects in the human body, depending on the persistence or not of lactase-phlorizin hydrolase (LPH). This enzyme is usually located in the small intestine brush border epithelial cells and is responsible for cleaving lactose into its constituents, glucose and galactose, that can be rapidly absorbed into the bloodstream [4].
As a sugar, it has a major role as a source of energy, providing 4 kcal/g, and also having a low glycemic index [5]. It is also considered relevant in bone health due to its role in calcium absorption [6,7]. On the other hand, lactose can also induce adverse reactions. Indeed, as reported by Storhaug et al. in 2017, it is estimated that 70% of the world population suffer from lactose malabsorption. This condition makes people incapable of digesting lactose due to the non-persistence of LPH, possibly leading to the symptomatic condition of lactose intolerance (LI) [8]. Recently, an increasing number of people have become aware of this condition, resulting in a growing demand for lactose-free (LF) products suitable for their diet [9].
Unfortunately, LF product labelling is not often clear because, to date, a univocal and shared regulation in the EU about the definition and claims of LF products is lacking. Well-identified LF products suitable for the diet of people with LI are required to meet the needs of these patients. In this regard, the apposition of a recognizable mark, such as the Lfree® international certification trademark, could assist consumers with LI to make a safe and immediate choice [10].
2. Physical and Chemical Characteristics of Lactose
The only natural source of lactose is mammal milk, representing its main carbohydrate, but lactose can also be extracted from it and used in various food and drug preparations as an ingredient or additive. Regarding its natural origin, lactose is synthesized in the epithelial secretory cells of the mammary gland exclusively throughout lactation. More specifically, glucose, absorbed from the bloodstream, enters the cells and is converted into uridine diphosphate-galactose (UDP-D-galactose) before being transported into the Golgi apparatus where D-glucose is located. Lactose-synthase, namely α-lactalbumin-galactosyltransferase, synthesizes lactose, joining UDP-D-galactose and D-glucose through the loss of UDP and the formation of a β-(1–4) glycosidic bond. Once lactose is produced, it is excreted with milk [11]. The lactose content in milk is inversely proportional to protein and fat, and varies according to the mammal species [3,12,13].
Moreover, lactose can be artificially isolated and purified for industrial uses from milk whey, which is usually a by-product in dairy industries. Before use, whey undergoes ultrafiltration in order to remove its proteins and obtain a permeate [14]. A concentration of the lactose solution is obtained by evaporation or, sometimes, by reverse osmosis. Successively, crystallization can occur by cooling down the supersaturated solution. The outcome products are recovered by decantation or centrifugation and dried in flash or fluidized beds [14,15].
Lactose is a disaccharide composed of two monosaccharides: D-glucose and D-galactose molecules joined in a β-1,4-glycosidic linkage [4]. Lactose can be found in two isomeric forms: α-lactose and β-lactose, according to the steric configuration of the C1 substituent group (OH and H), belonging to the glucose moiety; the two anomeric forms can be distinguished by means of their specific rotation [15].
α-lactose and β-lactose also differ in their chemical and physical characteristics, such as solubility, temperature, pH, and crystallization, leading to different features when employed as ingredients in food and drug preparations.
Solubility is an important factor concerning dissolved lactose because of its mutarotation properties. The two anomeric forms of lactose coexist in aqueous solution and are convertible between them through the open chain form of the glucose moiety of lactose, a property called mutarotation [16]. At the equilibrium, the α-lactose form represents 37% of the dissolved solute while β-lactose represents 63% [17,18].
When α-lactose is added to water at 20 °C it dissolves until saturation. The adding of more α-lactose to the solution makes mutarotation occur, so that the α-form starts converting into β-lactose. This phenomenon happens until an equilibrium is established between the two isomers [17,18].
Temperature has a direct influence on the amount of lactose dissolved in the solution, reaching 100 g of lactose in 100 g of water at 80 °C. The solubility of the two lactose isomers, and thus their amounts at the equilibrium, is also strongly temperature-dependent. When increasing the temperature, the α-form raises its solubility, shifting the equilibrium towards the β-form. Indeed, at 93.5 °C, the latter is the prevalent anomer in the solution [17,19,20]. However, in water, lactose does not dissolve easily compared to other simple sugars, while in liquids containing protein and fat (i.e., dairy liquids), its dissolution is slowed down due to the scarcity of available water, bound by those molecules [16].
pH does not affect the proportion of the lactose anomers at equilibrium, while it influences the rate at which mutarotation happens. At pH 5, mutarotation rate is at its minimum, but it increases at higher or lower pH values [17].
Another important aspect concerning lactose is its crystallization, which can occur when water is removed from a lactose-supersaturated solution or when temperature is reduced. Many different crystalline forms can originate from lactose, depending on the condition of the process. The main ones are the α-lactose monohydrate and β-anhydrous forms, from α-lactose and β-lactose, respectively. In particular, when the crystallization conditions are met, α-lactose originates its monohydrate form at temperatures below 93.5 °C. As the process continues, the equilibrium in the solution shifts from the β-lactose to the α-form, originating more and more α-lactose monohydrate [16], which are harder and more stable than the β-anhydrous form, also being less hygroscopic. Nevertheless, depending on the processing temperature, the α-lactose monohydrate stability can be modified, affecting its hygroscopicity. The β-anhydrous crystals, produced slowly at temperatures over 93.5 °C, have greater hygroscopicity and a much higher solubility compared to the α-lactose monohydrate crystals. These characteristics lead β-lactose to achieve a sweetness which is around 1.05–1.22 times higher compared to the other anomer. α-lactose monohydrate has the most stable crystalline form, while β-anhydrous crystals, in high moisture conditions, can rapidly turn into the α-lactose monohydrate form because of their instability. The same happens with amorphous lactose or lactose glass, originating from the rapid drying of lactose and containing both α- and β-lactose anomers. Being unstable and highly hygroscopic, it can be easily converted into α-lactose monohydrate by the addition of water [14,15,16,17].
3. Lactose in Food and Drug Industries
3.1. Lactose Uses in Food Industries
Lactose can have many applications in the food industries, being exploited for the realization of different kinds of food. It is important to mention that lactose can be employed as part of an ingredient (e.g., milk, butter, yoghurt) or as an ingredient itself (e.g., cured meat, confectioneries, spray-dried preparations). The most relevant roles of lactose in food industries are summarized below, also considering the negative impact it may have [3].
3.1.1. Sweetener
Sugar sweetness is measured in relation to sucrose, which is the reference sugar. Thus, a solution of 30 g/L of sucrose at 20 °C has a sweetening power of 1. Compared to sucrose, lactose sweetness ranges from 0.2 to 0.4, being one of the least sweet sugars among the main sweeteners in commerce (Table 3) [42].
Table 3. Main sugars and their sweetening power compared to sucrose, modified from [42].
| SUGAR | SWEETENING POWER Compared to Sucrose (=1) |
|---|---|
| Advantame | 37,000 |
| Neohesperidin | 1500–2000 |
| Aspartame | 200 |
| Fructose | 1.1–1.15 |
| Sucrose | 1 |
| Glucose | 0.75 |
| Mannitol | 0.6 |
| Sorbitol | 0.6 |
| Isomaltose | 0.55 |
| Maltose | 0.4 |
| Lactose | 0.2–0.4 |
| Lactitol | 0.35 |
| Galactose | 0.3 |
| Raffinose | 0.2 |
Lactose plays a major role as a sweetener in confectionery, sweets, and baked goods. In confectionery, lactose is used for enhancing flavor, texture, color and stability. Its employment ranges from being an ingredient for the coating of candies, caramels, and fudges to its use in icing, avoiding cracking and chipping. Depending on the amount of lactose employed, the texture of the product can also be changed: this is noticeable in the preparation of condensed milk, where high amounts of lactose result in a grainy feel while lower amounts cause a slimy texture [14]. Because lactose sweetness is one-sixth of that of sucrose, considerable amounts can be added to food preparations, increasing the product weight without affecting sweetness as other common sugars do. Lactose can also be used to replace sucrose: the replacement of 15–20% of sucrose with lactose, in most systems, does not alter the food acceptability and makes the product more palatable, also increasing its mouthfeel and viscosity. Lactose is also used in the beer industry, especially in the production of porters and stouts. This is due to the ability of lactose in the sweetening of beer and improving mouthfeel, because brewer’s yeasts do not ferment this sugar [23].
3.1.2. Browning Agent
The Maillard reaction is characterized by the reaction between amino acids and reducing sugars originating various intermediates by means of different pathways. These compounds are responsible for flavors or colors that are desirable in many food products, such as coffee or bread. The occurrence of a Maillard Reaction during storage instead is often undesirable and leads to a reduction in quality [28]. Lactose, as a reducing sugar, is involved in the Maillard reaction and, thanks to the reducing activity of its glucose moiety, the browning characteristics as well as flavor and odor in baked goods are enhanced. For this reason, lactose is used in sweet or savory bakery goods to obtain a golden crust and suitable toasting quality [21,29]. During the leavening of the dough, sugars are usually fermented by microorganisms, but some of them do not use lactose as a source of energy, so that it remains in the final mass. This not only leads to the enhancement of the browning of the loaf during its baking, but also that of its slices when toasted [23]. Nevertheless, lactose vulnerability to browning can also result in an excessive and undesired color-change in dried milk and dried whey powder during storage.
Furthermore, lactose is involved in baking as it increases the volume of loaves and biscuits. Moreover, thanks to lactose hygroscopicity, the tenderness of baked products is improved, resulting in a better mouthfeel and texture of the baked goods, prolonging their shelf-life [14].
3.2. Lactose Uses in Pharmaceutical Formulations
Drugs are composed of active pharmaceutical ingredients (APIs), commonly considered the most important substances in the formulation because of their pharmaceutical action, and excipients, usually critical for drug bioavailability. Lactose is one of the most commonly used excipients in the pharmaceutical industry, owing to its physical and chemical properties such as chemical inertia, stability, and non-toxicity, besides being moderately priced [25,26,27].
Considering the organoleptic characteristics of lactose powder, i.e., it being white and odorless and having a sweet taste, its acceptance as a component in pharmaceutical formulations is notable. There are many ways to use lactose as an excipient and different pharmaceutical forms contain it; indeed it is found in about 20% of prescription medicines and in 6% of over-the-counter medicines. For instance, lactose can be used as a diluent in tablets, lozenges, capsules, and powder for intravenous injections [35]. Tablets are the most common pharmaceutical form on the market containing lactose. In order to ensure adequate product processability throughout manufacturing, a precise volume of powder is needed to create tablets. Therefore, when the quantity of API is low, diluents, such as lactose, are necessary to adjust the mass of the solid dose. Sometimes diluents, also referred to as fillers, may constitute up to 90% of the total dosage weight. Lactose can act as a soluble diluent in formulations due to its excellent flowability and compressibility as well as its rheological properties [25,35]. In tablets, lactose powder can be used in different sizes of granulation and crystal forms in order to modulate its properties in the formulation. Moreover, lactose particles of the same size-range produce granules of higher porosity, which will improve the drug’s dissolution after being compressed. In this context, β-lactose crystals provide better compressibility properties and superior tensile strength values in comparison to α-lactose [27,43,44].
In Dry Powder Inhaler (DPI) formulations, lactose is often used as a carrier. The API used in DPIs should be aerodynamic and smaller than 5 µm, as well as having rheological properties such as flowability, stability, and uniformity. α-lactose monohydrate has all of these performing characteristics along with a well-established safety profile and compatibility with most available low-molecular-weight APIs [45,46]. Unfortunately, lactose carrier particles are too large to penetrate into the deep parts of the respiratory system, so that most of the lactose deposits in the oropharynx. In this case, if the molecule is swallowed, lactose can reach the gastrointestinal tract, giving rise to intolerance effects in case of LI [47]. Furthermore, lactose can work as a cryo/lipoprotective excipient during the freeze-drying process thanks to its adsorption properties, which can protect drugs against moisture [32]. Lactose is also used as a cross-linker in hydrogel of gelatin, obtaining a rigid layer able to provide mechanical strength and protection to the dressing [40].
In conclusion, the lactose content in drugs ranges from 100 to 200 mg, usually not exceeding 400 mg per tablet or capsule; however, this amount can have undesirable effects in patients who suffer from LI. However, it is very difficult to predict how the amount of the lactose intake changes depending on API doses or on the digestive process, due to different rates of gastric emptying, pH, and intestinal motility [25].
3.3. Undesirable Properties of Lactose
Lactose utilization can also result in undesirable effects during the preparation of food or in the final product [21].
3.3.1. Solubility
One of the undesirable properties of lactose utilization is its low solubility, which can result in crystallization, giving a gritty and sandy mouthfeel in the final product. Usually, in supersaturated solution, sugars tend to crystallize, also forming big agglomerates, depending on the process condition [23]. The tendency of sucrose and lactose to form big crystals can be influenced by the relative concentration of other sugars in the solution. In particular, to avoid the sandy mouthfeel caused by their crystallization, lactose is usually added to the formulation, delaying the process [21]. In this context, in confectionery, the adding of lactose to a sucrose solution progressively induces the formation of smaller crystals, leading to a smoother crystalline mass [22]. In condensed milk, the typical graininess caused by lactose crystallization is avoided by a rapid cooling of the solution and by seeding with powdered α-lactose monohydrate. The seeding technique ensures that lactose crystals are 10 μm or less [24].
3.3.2. Stickiness and Caking
Caking can be defined as a phenomenon in which a low-moisture, free-flowing powder is transformed into lumps and then into an agglomerated solid, losing its quality and function. Among the substances studied, amorphous lactose and dairy milk powder can be found [33,34]. In particular, low-molecular-weight sugars are known to cause caking during storage [48]. Lactose powders can undergo chemical changes due to humidity and/or exposure to high temperature. Under these conditions, amorphous or crystalline lactose absorbs water, becoming progressively stickier and resulting in its plasticization [27,43]. The glass transition temperature of anhydrous amorphous lactose has been indicated as 101 °C or 115 °C, whereas that of skim milk solids has been reported as 92 °C [16]. When lactose is used as a coat for powdered substances, when water is absorbed, its plasticization can therefore result in a lactose glass transition, creating viscosity problems and stickiness [31].
This entry is adapted from the peer-reviewed paper 10.3390/foods11101486
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