Livestock Industry Overview

Dairy Products and Health: Recent Insights Michael H. Tunick* and Diane L. Van Hekken

Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, 600 East Mermaid Lane, Wyndmoor, Pennsylvania 19038, United States

ABSTRACT: Milk, cheese, yogurt, and other dairy products have long been known to provide good nutrition. Major healthful contributors to the diets of many people include the protein, minerals, vitamins, and fatty acids present in milk. Recent studies have shown that consumption of dairy products appears to be beneficial in muscle building, lowering blood pressure and low- density lipoprotein cholesterol, and preventing tooth decay, diabetes, cancer, and obesity. Additional benefits might be provided by organic milk and by probiotic microorganisms using milk products as a vehicle. New research on dairy products and nutrition will improve our understanding of the connections between these products, the bioactive compounds in them, and their effects on the human body.

KEYWORDS: dairy, health, nutrition

■ INTRODUCTION Dairy products have long been advertised as being excellent sources of nutrition, and a large segment of the U.S. population consumes them as a part of a well-balanced diet. Recent investigations have suggested benefits from dairy products beyond the classic “building strong bones”. Some components in milk and milk products play roles that were not imagined just one or two generations ago, such as benefits to gastrointestinal health and the immune system.1 These advantageous effects arise from the proteins, minerals, vitamins, lipids, and carbohydrates in dairy products, the amounts of which have been tabulated by the USDA2 and are compared in Table 1. Earlier perceptions of dairy products being harmful to health

are no longer supported by the evidence. The most-cited general review in the past 10 years that highlighted the advantages conveyed by dairy products was by Huth et al.3 The review was written in 2005, and much has been accomplished since then. This paper will cover more recent findings concerning the contributions to human health of the components in milk and products derived from milk. Using milk to deliver bioactive compounds will also be discussed, as will differences between organic milk and milk from herds under conventional management.

■ PROTEIN About 80% of the protein in milk consists of αs1-, αs2-, β-, and κ- caseins, and about 20% is classified as whey protein, which is mostly α-lactalbumin, β-lactoglobulin, and serum albumin. Milk fat globule membrane (MFGM) protein represents a small percentage and is described under Lipids below. The Food and Agriculture Organization of the United Nations has recom- mended a new assessment method that ranks proteins based on the bioavailability of their amino acids, and milk protein scores high on their list.4 The Digestible Indispensable Amino Acid Score reveals that the true digestibility values of milk protein (95%) and of casein alone (94.1%) are higher than those of soy, pea, wheat, lupin, and rapeseed proteins (84−91.5%).4 A number of milk-derived peptides have been found to be bioactive and have been added to commercial products such as

Special Issue: 1st ACS-AGFD and ACS-Thailand Chapter Joint Symposium

Received: September 3, 2014 Revised: November 5, 2014 Accepted: November 13, 2014 Published: November 13, 2014

Table 1. Constituents of Milk, Cheddar Cheese, and Yogurt2

milk, 3.25% fat, vitamin D added

Cheddar cheese

yogurt, plain low-fat

proximates (g/100 g) protein 3.15 24.90 5.25 lipid 3.25 33.14 1.55 carbohydrate 4.80 1.28 7.04

minerals (mg/100 g) calcium 113 721 183 copper 0.025 0.031 0.013 iron 0.03 0.68 0.08 magnesium 10 28 17 manganese 0.004 0.010 0.004 phosphorus 84 512 144 potassium 132 98 234 selenium 0.0037 0.0014 0.0031 sodium 43 621 70 zinc 0.37 3.11 1.51

vitamins (μg/100 g) A 46 265 14 B1 (thiamin) 46 27 44 B2 (riboflavin) 169 375 214 B3 (niacin) 89 80 114 B6 (pyridoxine) 36 74 49 B9 (folate) 5 18 11 B12 (cobalamin) 0.45 0.83 0.56 C 0 0 0.8 D 1.3 0.6 0 E 70 290 30 K1 0.3 2.8 0.2

Review

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This article not subject to U.S. Copyright. Published 2014 by the American Chemical Society

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soft drinks.5 Most of these products are not available in the United States. The benefits of dairy proteins are described below. Building and Maintaining Muscle Mass. Over one-third

of those who exercise say they seek out products that contain protein to help build and maintain strong, healthy muscles.6 Of the amino acids in whey protein, 26% are of the branched-chain variety (notably leucine), which have been identified in building muscle mass.6 The amino acid composition of whey proteins is quite similar to that of skeletal muscle, making whey an effective anabolic supplement.6 People who are interested in physical fitness often supplement their diet with whey protein concentrate (containing <90% protein) or isolate (at least 90% protein). Whey protein powders are obtained from cheesemaking,

which generates on average 10 kg of liquid whey for every kilogram of cheese produced. Most cheeses, including the Cheddar in Table 1, contain little whey. A meta-analysis of 14 studies and over 600 participants supported a modest favorable effect of whey protein on body composition, with significant decreases in body weight and body fat when whey protein was provided as a dietary replacement and resistance exercise was performed.7

Older people often eat less than half of the recommended daily intake of protein, which may lead to sarcopenia, a loss of muscle mass. People are strongly motivated to keep their health and independence as they age, and they feel that maintaining strong bones and muscles will help them accomplish this.1

Ingestion of whey protein by 15 subjects aged 60−85 years has been found to improve accrual of skeletal muscle, and this increase of muscle mass was greater than that obtained by ingesting a mixture of the amino acids found in whey.8 This finding may have practical implications for the formulation of nutritional supplements. Casein may also promote muscle building. A study of 56

novice weightlifters who exercised 1 h/day and 5 days/week for 12 weeks showed that consuming skim milk following their workouts resulted in greater development of lean muscle mass than consumption of soy or carbohydrate drinks.9

Blood Pressure. The caseins facilitate absorption of Ca and phosphate in the small intestine and are the main substrates for production of bioactive peptides.10 These small dairy peptides are the product of either fermentation of milk by lactobacilli or by digestion of milk protein in the small intestine, with the peptides absorbed intact. Some of these bioactive molecules are lactotripeptides, including Ile-Pro-Pro and Val-Pro-Pro, which have been the subject of much research.10 Ile-Pro-Pro and Val- Pro-Pro are present in Swiss-type cheeses at concentrations ranging from 19 to 182 mg/kg.11 These lactotripeptides inhibit

angiotensin-converting enzyme (ACE) in vitro. ACE converts angiotensin I to angiotensin II, a hormone that restricts blood vessels and leads to hypertension, and ACE from milk products have been shown to have a positive association with lower blood pressure.12 A study of over 2500 Welsh men over a 22.8 year period revealed that high milk intake (>586 mL/day) was associated with lower systolic blood pressure (by 10.4 mmHg) and less arterial stiffness. Apart from butter, which had some negative effects, dairy products were found be cardioprotec- tive.13 A study of over 2200 residents of a Rotterdam suburb who were at least 55 years old showed that consumption of low-fat dairy products was associated with a 20% reduction in the incidence of hypertension.14 A review of other recent work concluded that the preponderance of evidence indicates a strong likelihood that eating dairy products helps to lower blood pressure.15

Dental Caries. Cheese has been tied to protection against dental caries, or tooth decay, through a series of mechanisms that are partially understood and involve more than the presence of Ca. It appears that casein-derived bioactive peptides inhibit bacteria, engage in competitive exclusion of enamel binding sites, improve buffering capacity in the pellicle surrounding teeth, reduce enamel demineralization, and improve enamel remineralization.16 Even when casein, lactose, and fat were removed as factors in one study, milk was found to largely prevent demineralization of teeth, apparently due to proteose-peptone, which is derived from β-casein and is a minor component of whey proteins.17

Learning and Memory. A peptide from β-casein, β- casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), is a μ-opioid receptor agonist (other such agonists, such as morphine, are analgesics) and may assist in learning and memory. Administration of a low dose of β-casomorphin-5 has been shown to alleviate impairment of learning and memory in tests on mice.18 β- Casomorphins are important for the psychomotor development of infants, with breast milk having more of an effect than bovine milk.19

Cancer. Studies have shown that the minor milk protein lactoferrin has anticancer properties. In research on mice containing a human gene that induces lung tumors, lactoferrin significantly decreased the proliferation of cancer cells and lung cell inflammation.20 Lactoferrin decreased the viability of breast cancer cell lines,21 and a lactoferrin peptide was shown to reduce DNA damage from colon cancer cells.22 Our laboratory has succeeded in cloning peptides from lactoferrin and αs1- casein into Streptococcus thermophilus, a common starter culture for cheese and yogurt, which would optimize the activity of these peptides.23 A significant antiproliferative effect on CaCo2 cancer cells was demonstrated by peptides isolated from the

Table 2. Dietary Elements Required by Humans and Commonly Found in Dairy Products26

function Ca Mg P K Na Mn Cu Zn Se Fe

muscular activity, neural transmission, vascular constriction and dilation; maintaining normal acid−base balance, osmotic pressure, and water balance

+ + + + +

forming and maintaining bones + + + + blood clotting + energy metabolism + + + component of cell membranes, nucleic acids, and nucleotides + components of enzyme systems or cofactors in enzymatic reactions + + + + defense against oxidative damage + + + structural role in some proteins + oxygen and electron transport +

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waste whey from the manufacture of water buffalo mozzarella; β-casomorphin-5 and -7 have been identified in this material.24

■ MINERALS More correctly referred to as dietary elements, Ca, Cu, Fe, K, Mg, Mn, Na, P, Se, and Zn are found in dairy products and are responsible for a number of essential processes in the body.25,26

A summary is shown in Table 2. An adequate Ca intake increases bone mineral density during

skeletal growth and prevents bone loss and osteoporotic fractures in the elderly.27 Clinical trials have shown that intake of dairy Ca is 50−100% more effective than supplemental Ca.5 Ca and other minerals in dairy products, whether full or reduced fat, decrease accumulation of body fat and accelerate loss of weight and fat during dieting.28 In a short-term human and animal study using a high-fat diet containing a milk mineral concentrate, the dietary elements significantly attenuated the increase in total and LDL cholesterol concentrations; HDL did not decrease.29 Ca reduces absorption of fat in the intestine through formation of soaps and also decreases serum cholesterol levels through binding of calcium phosphate with bile acids, which have to be regenerated in the liver from LDL and total cholesterol.30 Dairy products, which supply at least 70% of the Ca in the diet,3 have been cited as the best sources of Ca due to their high content of this mineral, high absorptive rate, and relatively low cost.31

Obesity, glucose intolerance, hypertension, and dyslipidemia (elevated blood lipids) are components of metabolic syndrome, which increases the risk for type 2 diabetes mellitus (T2DM) and heart disease. Components of insulin resistance syndrome and T2DM appear to decrease as dairy food consumption increases, a result that was associated with intake of dairy foods, Ca, and vitamin D.32 In a French study of 288 men aged 28−60 years, a higher intake of dairy products was associated with improvement in the metabolic profile in a 5 year period, and a higher Ca intake was associated with a lower 5 years increase of the BMI and waist circumference.33 No significant difference was observed in the 300 women in the study, however, which the authors suggest may have been due to sex-related behaviors and attitudes toward diet and lifestyle.

■ VITAMINS Milk is a source of all vitamins except vitamin C, which is broken down by pasteurization. Vitamin A (retinol) is critical for vision and is involved in immune function, reproduction, and cellular communication, differentiation, and growth.34

Vitamin B1 (thiamin) helps with metabolism of branched- chain amino acids, carbohydrates, and fatty acids.26 Vitamin B2 (riboflavin) is involved in the metabolism of carbohydrates, fats, and proteins.26 Vitamin B3 (niacin) is the precursor for coenzymes NAD and NADP, which are responsible for the catabolism of alcohol, carbohydrates, fats, and protein and the synthesis of macromolecules.26 Vitamin B6 (pyridoxine) has a role in more than 100 enzyme reactions, mostly concerned with protein metabolism, and is involved in cognitive development and immune function.34 Vitamin B9 (folate) is used to make DNA, RNA, and amino acids.34 Vitamin B12 (cobalamin) helps to create DNA and hemoglobin and to maintain nerve cells.34

Vitamin D (calciferol) levels are fortified in milk to help with calcium and phosphate absorption, which promotes bone growth.34 Vitamin E (tocopherol) is an antioxidant that helps prevent cell injury.34 Vitamin K1 (phylloquinone) and vitamin

K2 (the menaquinones), produced by bacteria in fermented dairy products, are necessary for blood clotting.26

A meta-analysis of 16 studies showed that consumption of 200 g of dairy products per day resulted in a 6% reduction of risk of T2DM, with a significant association between reduction of incidence of T2DM and intake of cheese, yogurt, and low-fat dairy products.35 The authors attributed the cheese and yogurt correlation with the presence of vitamins D and K2, which have recently been linked to a reduced risk of T2DM.36 Another study used daily food diaries instead of retrospective data (which involves a recall period ranging up to a year) and also found a reduced risk of T2DM.37 This relationship was observed only in fermented dairy food (cheese and yogurt), and the result was also attributed to vitamin K2 generated by bacterial fermentation. A meta-analysis of over 26000 cases of colorectal cancer showed that higher consumption of dairy products reduced the risk of colon cancer, with Ca and vitamin D being associated with a reduction of risk of cancer.38 A study of over 800 Japanese subjects also showed a decreased risk of colorectal cancer with increased consumption of calcium and vitamin D.39

■ LIPIDS The lipids in milk are in the form of droplets, consisting mostly of triacylglycerols, surrounded by a MFGM containing 60% protein and 40% lipids, including polar lipids (phospholipids and sphingolipids), cholesterol, and some minor components.40

The polar lipids amount to <40 mg/100 g milk, but contribute biological activity such as inhibition of colon cancer and intestinal pathogens.40 Phosphatidylserine seems to be related to cognitive function.41 The MFGM proteins are mostly glycoproteins such as butyrophilin, which may suppress multiple sclerosis, and BRCA1 and BRCA2, which appear to inhibit breast cancer.42

Milk fat, which is approximately 72% saturated, 25% monounsaturated, and 3% polyunsaturated (w/w), carries flavor compounds as well as fat-soluble vitamins A, D, E, and K.43 Lipids, although essential for humans, have historically been thought to elevate blood cholesterol and therefore been considered as dangerous to health. This attitude has been changing in recent years. A meta-analysis of 76 studies concluded that guidelines encouraging high consumption of polyunsaturated fatty acids and low consumption of total saturated fats is not clearly supported by the evidence.44

Moreover, dairy products and other foods high in saturated fat contain an array of saturated and unsaturated fatty acids, each of which affects metabolism of lipoproteins in various ways. These foods also contribute significant amounts of other nutrients, which may be beneficial. Areas in which milk lipids may be healthful are as follows.

Cardiovascular Disease. Observational studies and meta- analyses have shown no connection between the intake of milk fat and the risk of cardiovascular disease, coronary heart disease, or stroke. In fact, most clinical studies have shown that consumption of full-fat natural cheese significantly lowers low- density lipoproteins (LDL or “bad cholesterol”) compared with consumption of butter containing the same total fat and saturated fat content.45 These results may be due to the high level of Ca in cheese as well as the presence of fermentation products from the bacteria. Higher consumption of cheese in a study of 1750 Iranian adults was associated with higher high- density lipoprotein (HDL or “good cholesterol) and lower LDL, cholesterol, and triglycerides.46 The authors theorized

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that their results could be due to consumption of Ca and fermenting bacteria. Some studies have shown that yogurt products have beneficial effects on plasma lipids and lipoproteins, although these advantages appear to be specific to the strain of bacteria used to ferment the product.45

Anticarcinogenesis. In 1996, the National Academy of Sciences stated that conjugated linoleic acid (CLA) is the only fatty acid that definitely inhibits carcinogenesis in experimental animals.47 Many studies using in vivo and in vitro models have shown that relatively low dietary levels of CLA inhibit multistage carcinogenesis at different sites.48 Research has also indicated that CLA influences weight control, possibly by exerting an effect on hypothalamic appetite regulation.49 CLA is a mixture of isomers of linoleic acid (18:2), with the predominant isomer, rumenic acid (cis-9,trans-11 18:2), being the biologically active form.50 Dairy products are the major sources of CLA in the human diet, and its concentration in these products is not affected by heat processing.51

Trans fatty acids have been implicated in increases in LDL and decreases in HDL in humans. These effects have been tied to the trans fatty acids in hydrogenated fats, predominately elaidic acid (trans-9 18:1). Elaidic acid is present in only trace amounts in bovine milk. One-fourth of the trans fatty acids in milk fat is rumenic acid, and most of the rest is vaccenic acid (trans-11 18:1).52 Rumenic acid may be associated with anticarcinogenic properties in humans,53 and vaccenic acid may decrease tumor growth and the risk of coronary heart disease.54 On average, humans convert about a fifth of dietary vaccenic acid into rumenic acid.55

Obesity. Many people believe that increasing their intake of dairy fat will result in an increase in weight. However, the opposite appears to be the case. A 12 year study of over 1500 rural Swedish men revealed that a high intake of dairy fat was associated with a lower risk of developing central obesity (ratio of waist and hip measurements >1) and a low dairy fat intake was associated with a higher risk of central obesity.56 Moreover, a 9 year study of over 19000 Swedish women aged 40−55 years showed that at least one serving per day of whole milk and sour milk and of cheese was inversely associated with weight gain.57

The mechanisms for this effect may involve elevated Ca levels resulting in more fecal fat excretion,58 oxidation of fat by Ca,59

or satiety effects. A study of 70 overweight and obese individuals whose diet

was supplemented with whey protein experienced significant decreases in blood triglycerides, total cholesterol, LDL, and insulin levels over 12 weeks.60 The results may have been due to effects of whey protein on cholesterol biogenesis, adsorption, or excretion. Another 12 week study of 108 overweight and obese men and women on a calorie-restricted diet showed that high dairy consumption significantly increased fat loss.61 The authors attributed the effectiveness of the dairy foods to suppression of 1,25-dihydroxyvitamin D, which has been implicated in the retention of fat. Inflammation. A study of sheep’s milk cheese rich in CLA

showed a significant reduction in inflammatory parameters such as interleukin.62 Phospholipids have been identified as having anti-inflammatory properties and may also protect against liver damage.63

■ CARBOHYDRATES AND OLIGOSACCHARIDES Lactose comprises >99% of the carbohydrates in milk, with citrate accounting for 0.2%. Some dairy flavors arise from citrate breakdown, but no health effects have been reported. Lactose

stimulates intestinal absorption of Ca64 and can be enzymati- cally hydrolyzed in the gut to form galacto-oligosaccharides, which are readily utilized by bifidobacteria and contribute to improved digestive function.1 The majority of the world population is lactose intolerant and cannot digest this carbohydrate, but lactose-reduced milk, developed in our laboratory in the 1970s, allows consumers to drink milk without suffering digestive issues.65 In cheese, yogurt, and other fermented dairy products, lactic acid bacteria break down the lactose into digestible glucose and galactose. Bovine milk contains about 1 g oligosaccharides/L, whereas

the concentration in human milk is estimated at 7−12 g/L.5 Oligosaccharides in milk pass through the upper gastro- intestinal tract and are bioavailable to beneficial bacteria in the colon, stimulating their growth. These probiotics are credited with inhibiting the binding of pathogens and toxins by competing with the host’s binding sites.66 Glycoproteins have oligosaccharide chains attached and are also protective against microbes, toxins, and viruses in newborns.67

■ HEALTH ASPECTS OF MILK COMPONENTS IN COMBINATION

The various components of dairy products confer health benefits when in combination, and the substitution of milk products with other foods adversely affects the balance of nutrients consumed. Replacing dairy products with foods containing equivalent amounts of Ca has been shown to alter the overall nutritional profile of the diet, affecting intake of protein, magnesium, phosphorus, potassium, and vitamins A, B2, B12, and D.

68 The investigators concluded that eating nondairy Ca replacement foods (such as bony fish, Ca-set tofu, leafy greens, or fortified soy drink, rice drink, or orange juice) is not realistic because these foods are rarely consumed in the amounts needed to replace milk products.68 Some studies have demonstrated advantages of milk products arising from interactions among the components, as outlined below.

Cognitive Function. In a study of nearly 1000 people, participants who ate dairy products at least once per day scored significantly higher in several tests of cognitive function compared with those who rarely or never consumed dairy food.69 The reason is not yet known but is likely due to a synergistic effect among several milk components. A review of the methodology of eight studies about dementia pointed out that no research has been conducted on dairy intake and cognitive function across all ages, but that a beneficial effect is probably present.70

Satiety. Three fourths of shoppers in a survey said they are interested in satiety, the feeling of being full after eating.6 The dairy industry has conducted research revealing that dairy products are viewed by consumers as reasonably satiating; they are not as filling as fruit, meat, nuts, or pasta, but they are on a par with oatmeal and soup, and are considered more filling than snacks such as cookies and potato chips.6 A diet rich in Ca and dairy food did not result in weight loss in a study of 49 people, but did increase blood levels of a particular peptide that was associated with greater satiety and reduced fat intake.71

Consumption of milk products may therefore have an indirect role in improving health by enhancing satiety, thus aiding loss of fat and body weight.72

Mortality. A meta-analysis of over 62000 study participants showed no connection between consumption of milk and all- cause mortality and a modest inverse correlation with cardiovascular disease.73 All-cause mortality showed a reduction

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associated with dairy food intake in a meta-analysis of five studies in England and Wales covering 509,000 deaths in 2008.74 The same laboratory found that the risk of stroke also appears to decrease with increasing dairy intake, although further research in this area is needed. The cause of this effect may be inhibition of platelet aggregation.75 The authors concluded that there was a large discrepancy between evidence from long-term studies and perceptions of harm from dairy foods.

■ DELIVERY OF BIOACTIVES Dairy products are the primary vehicles for probiotic bacteria, which commonly include species of lactobacilli, lactococci, and bifidobacteria. Probiotics are live strains that confer benefits by improving the balance of microorganisms in the intestine by enhancing the population of beneficial bacteria and suppressing pathogens.76 A study of 571 Finnish children aged 1−6 showed that milk fortified with Lactobacillus rhamnosus GG stimulated immune response and reduced respiratory infections and days of absence from school.77

Casein films exhibit high tensile strength, making them good tablet coatings, and drug−milk preparations seem to confer higher bioavailability than drugs alone.78 Casein micelles act as a natural delivery system, which should lead to their use as nanocarriers.78 They bind ions and small molecules, form complexes with other macromolecules, possess good gelation, self-assembly, and surface properties, and exhibit pH-responsive gel swelling behavior that helps with programmable release.79

Epigallocatechin gallate (EGCG), the major extractable polyphenol found in green tea and the most bioactive one, has been shown to prevent proliferation of colon cancer cells. When EGCG was nanoencapsulated in casein micelles of skim milk, the proliferation of HT-29 cancer cells in vitro was decreased.80 Encapsulation did not decrease the bioavailability of EGCG, which may lead to the development of other delivery systems using casein. Curcumin, which may have anti- inflammatory, antimutagenic, and anticancer properties, and thymol, an antimicrobial, can be encapsulated in sodium caseinate, improving solubility and presumably bioavailabil- ity.81,82

■ ORGANIC VERSUS CONVENTIONAL MILK In the United States, the “organic” regulations for foods were established by the U.S. Department of Agriculture under the National Organic Program in 2000.83 The most important rules for dairy farms are as follows. Animals must be fed and managed according to approved organic practices for a full year before the milk that is produced can be certified and sold as organic. The animals must be given feed that is 100% organic and must obtain a minimum average of 30% of their dry matter intake from pasture during a minimum 120 day grazing season. Sick animals must be treated, and if the medicine is not on the approved-for-organic list, the animal is no longer considered organic and must be removed from the herd. All feed and medicine given to the organic animals must be documented. Growth hormones, antibiotics, genetic engineering, and cloning cannot be used in organic systems. The farming system must adhere to all regulations, whether they raise animals or grow feed for them.83

The compositions of organic and conventional milk are similar except for some of the fatty acids.84 The key question is whether the fatty acid profile of milk obtained from organic

dairies is more healthful than the milk fat from conventional (not certified as organic) dairies. CLA and ω-3 fatty acids (α- linolenic, eicosapentaenoic, and docosapentaenoic) are im- portant for cell membrane function, and many studies have shown the beneficial effects of ω-3 fatty acids in cancer prevention, cardiovascular disease, and infant development.85

ω-3 fatty acids also have positive roles in some mental conditions, including attention deficit hyperactivity disorder, dementia, and depression.85 ω-6 fatty acids (linoleic, 8,11,14- eicosatrienoic, and arachidonic) are also necessary for health maintenance; the optimum ratio of ω-6 to ω-3 is thought to be about 2.3, but Americans are consuming these fatty acids at a ratio around 10.86 A 2013 analysis of milk from 14 commercial processors from seven regions throughout the United States showed that, averaged over a year, organic milk contained 25% fewer ω-6 fatty acids and 62% more ω-3 fatty acids than conventional milk, leading to a favorable ratio of the two (Table 3).86 Organic dairy farmers can elevate the levels of CLA in

milk and the cheese manufactured from it by supplemeting the diet of their cows, for example, with sunflower oil.87

Homogenization and pasteurization have little effect on CLA concentration.5

Our laboratory has completed a 3 year study of milk from two adjacent farms; one was conventional and the other transitioned to organic during the first year (Tunick et al., unpublished results). The fatty acid analyses focused on CLA and the most predominant ω-6 and ω-3 fatty acids, linoleic acid and α-linolenic acid, respectively. In the final year of the study, the organic milk contained 26% fewer ω-6 fatty acids and 41% more ω-3 fatty acids than conventional milk (Table 4). As in

Table 3. Concentrations of Selected Fatty Acids in Organic and Conventional Milk from a National Study86

fatty acid, abbreviation organic milk

(mg/100 g milk) conventional milk (mg/100 g milk)

conjugated linoleic acid, CLA 22.7 19.2 ω-3 fatty acids

α-linolenic, 18:3 25.5 15.9 eicosapentaenoic, 20:5 3.3 2.5 docosapentaenoic, 22:5 4.4 3.7

ω-6 fatty acids linoleic, 18:2 (nonconjugated)

63.9 85.6

8,11,14-eicosatrienoic, 20:3 3.2 4.3 arachidonic, 20:4 4.8 5.8

all fatty acids 3108 3098 ω-6/ω-3 ratio 2.28 5.77

Table 4. Concentrations of Selected Fatty Acids in Organic and Conventional Milk in a Study by Our Laboratory (Tunick et al., Unpublished Results)

fatty acid, abbreviation organic milk

(mg/100 g milk) conventional milk (mg/100 g milk)

conjugated linoleic acid, CLA 32.8 27.7 ω-3 fatty acid

α-linolenic, 18:3 29.7 21.1 ω-6 fatty acid

linoleic, 18:2 (nonconjugated)

101 137

all fatty acids 3622 356 ω-6/ω-3 ratio 3.40 6.49

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the national study,86 the CLA content of the organic milk was 18% higher than that of the conventional milk. The ω-6 to ω-3 ratio was also more desirable in the organic milk.

■ FUTURE EFFORTS Despite advertising and educational efforts, many consumers are still not fully aware that dairy foods and dairy ingredients are a good source of high-quality proteins.6 The public should also be taught about the benefits of milk fat and milk in general. These efforts will have to be supported by further research on the mechanisms whereby milk components benefit humans. As scientists continue to investigate food as it relates to health, people will realize the importance of dairy products in the diet.

■ AUTHOR INFORMATION Corresponding Author *(M.H.T.) Phone: (215) 233-6454. E-mail: michael.tunick@ ars.usda.gov.

Notes Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorse- ment by the U.S. Department of Agriculture. The authors declare no competing financial interest.

■ REFERENCES (1) Ha, E.; Zemel, M. B. Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review). J. Nutr. Biochem. 2003, 14, 251− 258. (2) USDA National Nutrient Database for Standard Reference, release 26; http://www.ars.usda.gov/ba/bhnrc/ndl (accessed July 14, 2014). (3) Huth, P. J.; DiRienzo, D. B.; Miller, G. D. Major scientific advances with dairy foods in nutrition and health. J. Dairy Sci. 2006, 89, 1207−1221. (4) Moughan, P. J.; Gilani, S.; Rutherfurd, S. M.; Tome,́ D. True ileal amino acid digestibility coefficients for application in the calculation of Digestible Indispensable Amino Acid Score (DIAAS) in human nutrition. Report of a Sub-Committee of the 2011 FAO Consultation on Protein Quality Evaluation in Human Nutrition; http://www.fao. org/ag/humannutrition/36216-04a2f02ec02eafd4f457dd2c9851b4c45. pdf (accessed July 14, 2014). (5) Mills, S.; Ross, R. P.; Hill, C.; Fitzgerald, G. F.; Stanton, C. Milk intelligence: mining milk for bioactive substances associated with human health. Int. Dairy J. 2011, 21, 377−401. (6) Ward, L. Increasing awareness of the health benefits of dairy products. Food Manuf. 2013, 26 (9), 38. (7) Miller, P. E.; Alexander, D. D.; Perez, V. Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials. J. Am. Coll. Nutr. 2014, 33, 163−175. (8) Katsanos, C. S.; Chinkes, D. L.; Paddon-Jones, D.; Zhang, X.-J.; Aarsland, A.; Wolfe, R. R. Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content. Nutr. Res. (N.Y.) 2008, 28, 651−658. (9) Hartman, J. W.; Tang, J. E.; Wilkinson, S. B.; Tarnopolsky, M. A.; Lawrence, R. L.; Fullerton, A. V.; Phillips, S. M. Consumption of fat- free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. Am. J. Clin. Nutr. 2007, 86, 373−381. (10) McGrane, M. M.; Essery, E.; Obbagy, J.; Lyon, J.; MacNeil, P.; Spahn, J.; Van Horn, L. Dairy consumption, blood pressure, and risk of hypertension: an evidence-based review of recent literature. Curr. Cardiovasc. Risk Rep. 2011, 5, 287−298.

(11) Bütikofer, U.; Meyer, J.; Sieber, R.; Walther, B.; Wechsler, D. Occurrence of the angiotensin-converting enzyme-inhibiting tripep- tides Val-Pro-Pro and Ile-Pro-Pro in different cheese varieties of Swiss origin. J. Dairy Sci. 2008, 91, 29−38. (12) Ricci, I.; Artacho, R.; Olalla, M. Milk protein peptides with angiotensin I-converting enzyme inhibitory (ACEI) activity. Crit. Rev. Food Sci. Nutr. 2010, 50, 390−402. (13) Livingstone, K. M.; Lovegrove, J. A.; Cockcroft, J. R.; Elwood, P. C.; Pickering, J. E.; Givens, D. I. Does dairy food intake predict arterial stiffness and blood pressure in men? Evidence from the Caerphilly Prospective Study. Hypertension 2013, 61, 42−47. (14) Engberink, M. F.; Hendriksen, M. A.; Schouten, E. G.; van Rooij, F. J.; Hofman, A.; Witteman, J. C.; Geleijnse, J. M. Inverse association between dairy intake and hypertension: the Rotterdam Study. Am. J. Clin. Nutr. 2009, 89, 1877−1883. (15) Park, K. M.; Cifelli, C. J. Dairy and blood pressure: a fresh look at the evidence. Nutr. Rev. 2013, 71, 149−157. (16) Llena, C.; Forner, L.; Baca, P. Anticariogenicity of casein phosphopeptide-amorphous calcium phosphate: a review of the literature. J. Contemp. Dent. Pract. 2009, 10, 1−9. (17) Merritt, J.; Qi, F.; Shi, W. Milk helps build strong teeth and promotes oral health. J. Calif. Dental. Assoc. 2006, 34, 361−366. (18) Sakaguchi, M.; Koseki, M.; Wakamatsu, M.; Matsumura, E. Effects of systemic administration of β-casomorphin-5 on learning and memory in mice. Eur. J. Pharmacol. 2006, 530, 81−87. (19) Kost, N. V.; Sokolov, O. Y.; Kurasova, O. B.; Dmitriev, A. D.; Tarakanova, J. N.; Gabaeva, M. V.; Zolotarev, Yu. A.; Dadayan, A. K.; Grachev, S. A.; Korneeva, E. V.; Mikheeva, I. G.; Zozulya, A. A. β- Casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Peptides 2009, 30, 1854−1860. (20) Tung, Y.-T.; Chen, H.-L.; Yen, C.-C.; Lee, P.-Y.; Tsai, H.-C.; Lin, M.-F.; Chen, C.-M. Bovine lactoferrin inhibits lung cancer growth through suppression of both inflammation and expression of vascular endothelial growth factor. J. Dairy Sci. 2013, 96, 2095−2106. (21) Duarte, D. C.; Nicolau, A.; Teixeira, J. A.; Rodrigues, L. R. The effect of bovine milk lactoferrin on human breast cancer cell lines. J. Dairy Sci. 2011, 94, 66−76. (22) Freiburghaus, C.; Lindmark-Man̊sson, H.; Paulsson, M.; Oredsson, S. Reduction of ultraviolet light-induced DNA damage in human colon cancer cells treated with a lactoferrin-derived peptide. J. Dairy Sci. 2012, 95, 5552−5560. (23) Renye, J. A., Jr.; Somkuti, G. A. Cloning of milk-derived bioactive peptides in Streptococcus thermophilus. Biotechnol. Lett. 2008, 30, 723−730. (24) De Simone, C.; Picariello, G.; Mamone, G.; Stiuso, P.; Dicitore, A.; Vanacore, D.; Chianese, L.; Addeo, F.; Ferranti, P. Characterisation and cytomodulatory properties of peptides from Mozzarella di Bufala Campana cheese whey. J. Pept. Sci. 2009, 15, 251−258. (25) Ervin, R. B.; Wang, C. Y.; Wright, J. D.; Kennedy-Stephenson, J. Dietary Intake of Selected Minerals for the United States Population: 1999−2000. Advance Data from Vital and Health Statistics; National Center for Health Statistics: Hyattsville, MD, USA, 2004. (26) Higdon, J. Micronutrient information center; http://lpi. oregonstate.edu/infocenter (accessed Aug 1, 2014). (27) Caroli, A.; Poli, A.; Ricotta, D.; Banfi, G.; Cocchi, D. Invited review: Dairy intake and bone health: a viewpoint from the state of the art. J. Dairy Sci. 2011, 94, 5249−5262. (28) Soares, M. J.; Murhadi, L. L.; Kurpad, A. V.; Chan She Ping- Delfos, W. L.; Piers, L. S. Mechanistic roles for calcium and vitamin D in the regulation of body weight. Obes. Rev. 2012, 13, 592−605. (29) Lorenzon, J. K.; Jensen, S. K.; Astrup, A. Milk minerals modify the effect of fat intake on serum lipid profile: results from an animal and a human short-term study. Br. J. Nutr. 2014, 111, 1412−1420. (30) Ditscheid, B.; Keller, S.; Jahreis, G. Cholesterol metabolism is affected by calcium phosphate supplementation in humans. J. Nutr. 2005, 135, 1678−1682. (31) Sunyecz, J. A. The use of calcium and vitamin D in the management of osteoporosis. Ther. Clin. Risk Manag. 2008, 4, 827− 836.

Journal of Agricultural and Food Chemistry Review

dx.doi.org/10.1021/jf5042454 | J. Agric. Food Chem. 2015, 63, 9381−93889386

(32) Tremblay, A.; Gilbert, J. A. Milk products, insulin resistance syndrome and type 2 diabetes. J. Am. Coll. Nutr. 2009, 28 (Suppl. 1), 91S−102S. (33) Samara, A.; Herbeth, B.; Ndiaye, N. C.; Fumeron, F.; Billod, S.; Siest, G.; Visvikis-Siest, S. Dairy product consumption, calcium intakes, and metabolic syndrome-related factors over 5 years in the STANISLAS study. Nutrition 2013, 29, 519−524. (34) National Institutes of Health. Fact sheets for health professionals; http://ods.od.nih.gov/factsheets (accessed Aug 1, 2014). (35) Gao, D.; Ning, N.; Wang, C.; Wang, Y.; Li, Q.; Meng, Z.; Liu, Y.; Li, Q. Dairy products consumption and risk of type 2 diabetes: systematic review and dose-response meta-analysis. PLoS One 2013, 8 (9), No. e73965. (36) Beulens, J. W. J.; van der A, D. L.; Grobbee, D. E.; Sluijs, I.; Spijkerman, A. M. W.; van der Schouw, Y. T. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care 2010, 33, 1699−1705. (37) O’Connor, L. M.; Lentjes, M. A. H.; Luben, R. N.; Khaw, K.-T.; Wareham, N. J.; Forouhi, N. G. Dietary dairy product intake and incident type 2 diabetes: a prospective study using dietary data from a 7-day food diary. Diabetologia 2014, 57, 909−917. (38) Huncharek, M.; Muscat, J.; Kupelnick, B. Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta- analysis of 26,335 cases from 60 observational studies. Nutr. Cancer 2008, 61, 47−69. (39) Mizoue, T.; Kimura, Y.; Toyomura, K.; Nagano, J.; Kono, S.; Mibu, R.; Tanaka, M.; Kakeji, Y.; Maehara, Y.; Okamura, T.; Ikejiri, K.; Futami, K.; Yasunami, Y.; Maekawa, T.; Takenaka, K.; Ichimiya, H.; Imaizumi, N. Calcium, dairy foods, vitamin D, and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. Cancer Epidemiol. Biomarkers Prev. 2008, 17, 2800−2807. (40) Rombaut, R.; Dewettinck, K. Properties, analysis and purification of milk polar lipids. Int. Dairy J. 2006, 16, 1362−1373. (41) Liu, S. H.; Chang, C. D.; Chen, P. H.; Su, J. R.; Chen, C. C.; Chaung, H. C. Docosahexaenoic acid and phosphatidylserine supplementations improve antioxidant activities and cognitive functions of the developing brain on pentylenetetrazol-induced seizure model. Brain Res. 2012, 1451, 19−26. (42) Spitsberg, V. L. Invited review: Bovine milk fat globule membrane as a potential nutraceutical. J. Dairy Sci. 2005, 88, 2289− 2294. (43) MacGibbon, A. K. H.; Taylor, M. W. Composition and structure of bovine milk lipids. In Advanced Dairy Chemistry, 3rd ed.; Fox, P. F., McSweeney, P. L. H., Eds.; Springer: New York, 2006; Vol. 2, pp 1− 42. (44) Chowdhury, R.; Warnakula, S.; Kunutsor, S.; Crowe, F.; Ward, H. A.; Johnson, L.; Franco, O. H.; Butterworth, A. S.; Forouhi, N. G.; Thompson, S. G.; Khaw, K.-T.; Mozaffarian, D.; Danesh, J.; Di Angelantonio, E. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann. Int. Med. 2014, 160, 398−406. (45) Huth, P. J.; Park, K. M. Influence of dairy product and milk fat consumption on cardiovascular disease risk: a review of the evidence. Adv. Nutr. 2012, 3, 266−285. (46) Sadeghi, M.; Khosravi-Boroujeni, H.; Sarrafzadegan, N.; Asgary, S.; Roohafza, H.; Gharipour, M.; Sajjadi, F.; Khalesi, S.; Rafieian- Kopaei, M. Cheese consumption in relation to cardiovascular risk factors among Iranian adults- IHHP study. Nutr. Res. Prac. 2014, 8, 336−341. (47) National Academy of Sciences. Carcinogens and Anticarcinogens in the Human Diet: A Comparison of Naturally Occurring and Synthetic Substances; National Academy Press: Washington, DC, USA, 1996; p 85. (48) Lee, K. W.; Lee, H. J.; Cho, H. Y.; Kim, Y. J. Role of the conjugated linoleic acid in the prevention of cancer. Crit. Rev. Food Sci. Nutr. 2005, 45, 135−144.

(49) Kennedy, A.; Martinez, K.; Schmidt, S.; Mandrup, S.; LaPointa, K.; McIntosh, M. Antiobesity mechanisms of action of conjugated linoleic acid. J. Nutr. Biochem. 2010, 21, 171−179. (50) Ip, C.; Scimeca, J. A.; Thompson, H. J. Conjugated linoleic acid: a powerful anticarcinogen from animal fat sources. Cancer 1994, 74, 1050−1054. (51) Lin, H.; Boylston, T. D.; Chang, M. J.; Luedecke, O.; Shultz, T. D. Survey of the conjugated linoleic acid contents of dairy products. J. Dairy Sci. 1995, 78, 2358−2365. (52) Parodi, P. W. Nutritional significance of milk lipids. In Advanced Dairy Chemistry, 3rd ed.; Fox, P. F., McSweeney, P. L. H., Eds.; Springer: New York, 2006; Vol. 2, pp 601−639. (53) Elgersma, A.; Tamminga, S.; Ellen, G. Modifying milk composition through forage. Anim. Feed Sci. Technol. 2006, 131, 207−225. (54) Field, C. J.; Blewett, H. H.; Proctor, S.; Vine, D. Human health benefits of vaccenic acid. Appl. Physiol. Nutr. Metab. 2009, 34, 979− 991. (55) Turpeinen, A. M.; Mutanen, M.; Aro, A.; Salminen, I.; Basu, S.; Palmquist, D. L.; Griinari, J. M. Bioconversion of vaccenic acid to conjugated linoleic acid in humans. Am. J. Clin. Nutr. 2002, 76, 504− 510. (56) Holmberg, S.; Thelin, A. High dairy fat intake related to less central obesity: a male cohort study with 12 years’ follow-up. Scand. J. Prim. Health 2013, 31, 89−94. (57) Rosell, M.; Hakansson, N. N.; Wolk, A. Association between dairy food consumption and weight change over 9 y in 19352 perimenopausal women. Am. J. Clin. Nutr. 2006, 84, 1481−1488. (58) Christensen, R.; Lorenzen, J. K.; Svith, C. R.; Bartels, E. M.; Melanson, E. L.; Saris, W. H.; Tremblay, A.; Astrup, A. Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials. Obes. Rev. 2009, 10, 475−486. (59) Gonzalez, J. T.; Rumbold, P. L. S.; Stevenson, E. J. Effect of calcium intake on fat oxidation in adults: a meta-analysis of randomized, controlled trials. Obes. Rev. 2012, 13, 848−857. (60) Pal, S.; Ellis, V.; Dhaliwal, S. Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals. Br. J. Nutr. 2010, 104, 716−723. (61) Zemel, M. B.; Teegarden, D.; Van Loan, M.; Schoeller, D. A.; Matkovic, V.; Lyle, R. M.; Craig, B. A. Dairy-rich diets augment fat loss on an energy-restricted diet: a multicenter trial. Nutrients 2009, 1, 83− 100. (62) Sofi, F.; Buccioni, A.; Cesari, F.; Gori, A. M.; Minieri, S.; Mannini, L.; Casini, A.; Gensini, G. F.; Abbate, R.; Antongiovanni, M. Effects of a dairy product (pecorino cheese) naturally rich in cis-9, trans-11 conjugated linoleic acid on lipid, inflammatory and haemorheological variables: a dietary intervention study. Nutr. Metab. Cardiovasc. Dis. 2010, 20, 117−124. (63) Küllenberg, D.; Taylor, L. A.; Schneider, M.; Massing, U. Health effects of dietary phospholipids. Lipids Health Dis. 2012, 11, 1−16. (64) Kwak, H. S.; Lee, W. J.; Lee, M. R. Revisiting lactose as an enhancer of calcium absorption. Int. Dairy J. 2012, 22, 147−151. (65) Somkuti, G. A.; Holsinger, V. H. Microbial technologies in the production of low-lactose dairy foods. Food Sci. Technol. Int. 1997, 3, 163−169. (66) Casado, B.; Affolter, M.; Kussmann, M. OMICS-rooted studies of milk proteins, oligosaccharides and lipids. J. Proteomics 2009, 73, 196−208. (67) Newburg, D. S. Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans. J. Anim. Sci. 2009, 87, 26−34. (68) Fulgoni, V. L., III; Keast, D. R.; Auestad, N.; Quann, E. E. Nutrients from dairy foods are difficult to replace in diets of Americans: food pattern modeling and an analyses of the National Health and Nutrition Examination Survey 2003−2006. Nutr. Res. (N.Y.) 2011, 31, 759−765.

Journal of Agricultural and Food Chemistry Review

dx.doi.org/10.1021/jf5042454 | J. Agric. Food Chem. 2015, 63, 9381−93889387

(69) Crichton, G. E.; Elias, M. F.; Dore, G. A.; Robbins, M. A. Relation between dairy food intake and cognitive function: the Maine- Syracuse Longitudinal Study. Int. Dairy J. 2012, 22, 15−23. (70) Crichton, G. E.; Bryan, J.; Murphy, K. J.; Buckley, J. Review of dairy consumption and cognitive performance in adults: findings and methodological issues. Dement. Geriatr. Cogn. Disord. 2010, 30, 352− 361. (71) Jones, K. W.; Eller, L. K.; Parnell, J. A.; Doyle-Baker, P. K.; Edwards, A. L.; Reimer, R. A. Effect of a dairy- and calcium-rich diet on weight loss and appetite during energy restriction in overweight and obese adults: a randomized trial. Eur. J. Clin. Nutr. 2013, 67, 371− 376. (72) McGregor, R. A.; Poppitt, S. D. Milk protein for improved metabolic health: a review of the evidence. Nutr. Metab. 2013, 10, 46. (73) Soedamah-Muthu, S. S.; Ding, E. L.; Al-Delaimy, W. K.; Hu, F. B.; Engberink, M. F.; Willett, W. C.; Geleijnse, J. M. Milk and dairy consumption and incidence of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies. Am. J. Clin. Nutr. 2011, 93, 158−171. (74) Elwood, P. C.; Givens, D. I.; Beswick, A. D.; Fehily, A. M.; Pickering, J. E.; Gallacher, J. The survival advantage of milk and dairy consumption: an overview of evidence from cohort studies of vascular diseases, diabetes and cancer. J. Am. Coll. Nutr. 2008, 27, 723S−734S. (75) Elwood, P. C.; Pickering, J. E.; Givens, D. I.; Gallacher, J. E. The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence. Lipids 2010, 45, 925−939. (76) Nagpal, R.; Behare, P. V.; Kumar, M.; Mohania, D.; Yadav, M.; Jain, S.; Menon, S.; Parkash, O.; Marotta, F.; Minelli, E.; Henry, C. J. K.; Yadav, H. Milk, milk products, and disease free health: an updated overview. Crit. Rev. Food Sci. Nutr. 2012, 52, 321−333. (77) Hatakka, K.; Savilahti, E.; Pönka,̈ A.; Meurman, J. H.; Poussa, T.; Nas̈e, L.; Saxelin, M.; Korpela, R. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. Br. Med. J. 2001, 322, 1327−1331. (78) Elzoghby, A. O.; Abo El-Fotoh, W. S.; Elgindy, N. A. Casein- based formulations as promising controlled release drug delivery systems. J. Controlled Release 2011, 153, 206−216. (79) Livney, Y. D. Milk proteins as vehicles for bioactives. Curr. Opin. Colloid Interface Sci. 2010, 15, 73−83. (80) Haratifar, S.; Meckling, K. A.; Corredig, M. Antiproliferative activity of tea catechins associated with casein micelles, using HT29 colon cancer cells. J. Dairy Sci. 2014, 97, 672−678. (81) Pan, K.; Luo, Y.; Gan, Y.; Baek, S. J.; Zhong, Q. pH-driven encapsulation of curcumin in self-assembled casein nanoparticles for enhanced dispersibility and bioactivity. Soft Matter 2014, 10, 6820− 6830. (82) Pan, K.; Chen, H.; Davidson, P. M.; Zhong, Q. Thymol nanoencapsulated by sodium caseinate: physical and antilisterial properties. J. Agric. Food Chem. 2014, 62, 1649−1657. (83) Code of Federal Regulations. Title 7, Part 205. National Organic Program; http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&tpl=/ ecfrbrowse/Title07/7cfr205_main_02.tpl (accessed July 14, 2014). (84) Smith-Spangler, C.; Brandeau, M. L.; Hunter, G. E.; Bavinger, J. C.; Pearson, M.; Eschbach, P. J.; Sundaram, V.; Liu, H.; Schirmer, P.; Stave, C.; Olkin, I.; Bravata, D. M. Are organic foods safer or healthier than conventional alternatives? A systematic review. Ann. Int. Med. 2012, 157, 348−366. (85) Riediger, N. D.; Othman, R. A.; Suh, M.; Moghadasian, M. H. A systemic review of the roles of n-3 fatty acids in health and disease. J. Am. Diet. Assoc. 2009, 109, 668−679. (86) Benbrook, C. M.; Butler, G.; Latif, M. A.; Leifert, C.; Davis, D. R. Organic production enhances milk nutritional quality by shifting fatty acid composition: a United States-wide, 18-month study. PLoS One 2013, 8 (12), No. e82429. (87) Coakley, M.; Barrett, E.; Murphy, J. J.; Ross, R. P.; Devery, R.; Stanton, C. Cheese manufacture with milk with elevated conjugated linoleic acid levels caused by dietary manipulation. J. Dairy Sci. 2007, 90, 2919−2927.

Journal of Agricultural and Food Chemistry Review

dx.doi.org/10.1021/jf5042454 | J. Agric. Food Chem. 2015, 63, 9381−93889388