You are on page 1of 10

Blackwell Publishing LtdOxford, UKOBRobesity reviews1467-7881© 2006 The Authors; Journal compilation © 2006 The International Association for

the Study of Obesity200682109118


Review ArticleMilk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir

obesity reviews doi: 10.1111/j.1467-789X.2006.00265.x

Diagnostic in Obesity Comorbidities

Milk and the metabolic syndrome

M. Pfeuffer and J. Schrezenmeir

Institute for Physiology and Biochemistry of Summary


Nutrition, Federal Research Centre for Nutrition The metabolic syndrome is a cluster of metabolic disorders, namely dyslipidaemia,
and Food, Kiel, Germany hypertension, obesity and glucose intolerance. Insulin resistance is the core phe-
nomenon. Co-occurrence is associated with increased cardiovascular disease
Received 8 December 2005; revised 7 March (CVD) risk. Observational studies found no increased CVD risk with increasing
2006; accepted 10 March 2006 consumption of milk and other dairy products. In several studies dairy consump-
tion was inversely associated with the occurrence of one or several facets of the
Address for correspondence: M Pfeuffer, metabolic syndrome. Many dairy components may contribute to the beneficial
Institute for Physiology and Biochemistry of effects. Milk and particularly whey appeared insulinotropic when given in a single
Nutrition, Federal Research Centre for Nutrition meal, but not in longer-term intervention. Medium chain fatty acids improve
and Food, Location Kiel, Hermann-Weigmann- insulin sensitivity. Whey proteins, amino acids, medium chain fatty acids and in
Str. 1, 24103 Kiel, Germany. E-mail: particular calcium and other minerals may contribute to the beneficial effect of
maria.pfeuffer@bfel.de dairy products on body weight and body fat. Peptides, calcium and other minerals
reduce blood pressure. Fermented products and probiotic bacteria decrease
absorption of cholesterol, sphingomyelin of cholesterol and fat, calcium of cho-
lesterol, bile acids and fat. Proteins, peptides and bacteria may also reduce plasma
cholesterol. Lactose, citrate, proteins and peptides improve weight control, blood
pressure and plasma lipids indirectly, by improving calcium bioavailability. Fur-
thermore, dairy consumption improves the bioavailability of folate and other
secondary plant components.

Keywords: Dairy, metabolic syndrome, milk.

obesity reviews (2006) 8, 109–118

The perspective has broadened further. Interest is now


Introduction
focused on a cluster of metabolic disorders, termed the
The longest-known predictive factor for enhanced cardio- metabolic syndrome, insulin resistance syndrome or syn-
vascular disease (CVD) risk is a high cholesterol level, drome X. The disorders belonging to the syndrome are
particularly low-density lipoprotein (LDL) cholesterol dyslipidaemia (as judged by high fasting triglyceride and
level, while high high-density lipoprotein (HDL) choles- low HDL cholesterol levels), glucose intolerance (type 2
terol levels are associated with a decreased risk. Thus, milk diabetes, impaired glucose tolerance or impaired fasting
fat soon became a suspect, as milk fat is rich in saturated glycaemia), hypertension and (central) obesity. Depending
fatty acids and high intakes of saturated fatty acids increase on the definition vascular changes evidenced by microalbu-
cholesterol levels. Yet fatty acids are also precursors of minuria are included. Hyperinsulinaemia or insulin resis-
eicosanoids, affecting inflammatory and thrombogenic pro- tance is the core phenomenon of the metabolic syndrome.
cesses, blood pressure regulation, and thus vascular func- The facets are interlinked and the co-occurrence is associ-
tion (1,2). It needs to be examined how dairy fatty acids ated with increased CVD risk (3,4). Insulin resistance is
affect these mechanisms. also associated with an increased proinflammatory and

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118 109
110 Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir obesity reviews

prothrombotic state (5). According to the definition of the


Does dairy consumption promote individual
World Health Organization (WHO), a person afflicted with
disorders of the metabolic syndrome? Insulin
three out of the above-mentioned disorders is considered
resistance, diabetes or several disorders of the
to suffer from the metabolic syndrome (6). As it has been
metabolic syndrome combined
recognized as a worldwide increasing condition with seri-
ous implications for human health (3,4), there is growing Milk intake led to a significantly lower glycaemic response
interest in a possible link between dairy food consumption compared with mixed meals (15) or lactose-equivalent
and symptoms of the metabolic syndrome. meals of white wheat bread as reference (16,17). In diabetic
subjects a lower glycaemic response to whey was not seen
after the breakfast test meal, but lateron after lunch (18).
Does milk or dairy consumption affect the risk
The insulin response to milk was not different from that of
of cardiovascular disease?
the reference meals (16,17) and the insulin response to
There is no evidence from epidemiological data that milk whey was even higher (16). This indicates that milk and
and dairy consumption is linked with increasing risk of particularly whey appear insulinotropic, as judged from the
CVD. Elwood et al. (7) reviewed the available evidence up severalfold higher insulinaemic indexes than expected from
to 2001, identifying in total 10 prospective and two case– the corresponding glycaemic indexes. Addition of fer-
control studies. Their analysis showed a high degree of mented milk (yogurt) and pickled cucumber to a reference
consistency in the reported risk for heart disease and breakfast meal significantly lowered both postprandial gly-
stroke, all but one study suggesting a relative risk of less caemia and insulinaemia compared with the reference meal
than one in subjects with the highest intake of milk com- alone (17). This suggests that fermentation or the resulting
pared with subjects with the lowest intake. A pooled esti- organic acids may counteract the insulinotropic effect of
mate of relative odds in these subjects, relative to the risk milk. A delayed gastrointestinal passage may explain the
in subjects with the lowest consumption, was 0.87 (95% attenuated glucose response. Release of glucose-dependent
confidence interval [CI] 0.74–1.03) for ischaemic heart dis- insulinotropic polypeptide and glucagon-like peptide 1
ease and 0.83 (0.77–0.90) for ischaemic stroke. In a case– (16,18), may be responsible for the enhanced insulin secre-
control study (8) there was a significant inverse association tion. A role of bioactive peptides or branched-chain amino
with yogurt consumption. Correction for energy intake did acids is also discussed (16).
not change the outcome. These results relate to the con- But an insulinotropic effect is not necessarily observed in
sumption of mainly full-fat milk, as at the time when these longer-term intervention studies. When insulin-resistant
studies were carried out more full-fat than low-fat milk was rats were fed a high-protein diet for 6 weeks, either whey
on the market (7). Anyhow, no matter whether full- or low- or meat protein, the whey protein concentrate reduced
fat, questions on milk intake are only a rough estimate of plasma insulin by 40% and increased insulin sensitivity
the whole dairy food intake. Reports from the Caerphilly (19). An ancillary study of the PREMIER Collaborative
cohort indicated a trend towards a decreased risk for stroke Research Group found that including the Dietary
(9) or ischaemic heart disease (10) with increasing milk Approaches to Stop Hypertension (DASH) dietary pattern
intake. A Swedish case–control study (11) found a signifi- as part of a comprehensive 6-month intervention for blood
cant inverse association between milk intake and the risk pressure control improved insulin sensitivity beyond the
of a first myocardial infarction, a Norwegian case–control effects of a comprehensive intervention that did not include
study observed a non-significant trend (12). In both studies DASH in humans (20). The DASH dietary pattern is high
milk intake estimate was based on biomarkers. The find- in fruits, vegetables plus low-fat dairy products, while
ings from prospective studies are in contrast to those from being lower in total fat, saturated fat and cholesterol. Par-
several ecological studies. When the intake of various foods ticipants of this study were on average 52 years of age,
was plotted country-by-country against coronary heart dis- 69% female, 67% non-Hispanic white, obese (body mass
ease death rates (13), milk consumption showed a positive index [BMI] 33 kg m−2), and with an above-optimal blood
correlation, but cheese consumption was negatively corre- pressure (20). The beneficial effect of the DASH dietary
lated. Based on data from 40 countries a positive correla- regimen was confirmed in another study from Iran (21).
tion between coronary heart disease mortality and milk and Only a recent study in 24 boys aged 8 years found
butterfat intake was observed in another ecological study, increased fasting insulin levels and insulin resistance with
but Finland and France provided important paradoxes to milk as compared with meat intake (22). During this 7-d
the lipid hypothesis (14). Indeed, the discrepancy of low intervention, milk (around 2 L d−1) or meat provided an
CVD risk despite a diet high in saturated fatty acids and additional 53-g protein per day. This resulted in an exces-
cholesterol, in large part of dairy origin, has become widely sive supply of total protein for this age. Furthermore, the
known as the ‘French paradox’. However, ecological stud- diets were not well balanced. The milk group had a higher
ies provide generally the weakest evidence. carbohydrate and total energy intake and gained weight

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
obesity reviews Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir 111

during the intervention. It may be asked what the outcome prises 3157 adults aged 18–30 years, 45% black and 55%
of a more balanced intervention would have been. white, 71% with a BMI < 25 kg m−2, who were followed
A diet high in saturated fat is linked to the pathogenesis up for 10 years. Among the overweight subjects, dairy con-
of insulin resistance (23,24). There seems to be a modifying sumption was inversely associated with the incidence of all
role of gender and age. No association was seen for men components of the metabolic syndrome. This association
as compared with women, and not in older as compared was similar for blacks and whites and for men and women.
with younger subjects (25). Dairy fat is considered a satu- Interestingly, there was no association for persons with a
rated fat, but it contains also a large amount of oleic acid, BMI < 25 kg m−2 at baseline. Dairy consumption was also
as well as short-chain and medium-chain fatty acids, on inversely associated with the risk of the metabolic syn-
average 26.5%, 3.6% and 9.7% by weight. Medium-chain drome in a cross-sectional study from Iran (38). In a study
fatty acids (6:0–12:0) can improve insulin sensitivity. Dif- from France, bread and dairy intake were both inversely
ferent from long-chain fatty acids their transport across related to the frequency of the metabolic syndrome in men,
membranes and within cells does not require binding to but not in women, while there was no association between
fatty acid-binding proteins (26). This affects a number of the intake of meat or fish and the metabolic syndrome (39).
regulatory pathways. A high-fat diet decreased insulin- A Swedish case–control study (11) estimated milk-fat
stimulated glucose oxidation (27), but medium-chain fatty intake from the proportion of pentadecanoic and heptade-
acids reduced glucose oxidation less than long-chain fatty canoic acid in serum phospholipids. The proportion of
acids in man (28). The other way round, the oxidation of these biomarkers was significantly and negatively corre-
fatty acids is usually depressed when the diet is simulta- lated to serum concentrations of plasminogen activator
neously high in carbohydrates. But glucose infusion inhibitor-1, tissue-type plasminogen activator, triglyceride,
decreased only long-chain, but not medium-chain fatty acid insulin, specific insulin, pro-insulin and leptin, suggesting
oxidation in muscle cells (29). Most human intervention an inverse relationship to the insulin resistance syndrome
studies found no clear-cut effect of medium-chain fatty and the risk of CVD. The validity of the biomarkers was
acids on fasting or postprandial glucose and insulin levels ascertained in a prior study by relating them with dairy
(30). In a small study in five overweight diabetics, 15 mL intake from 7-d dietary protocols (40). In this study, intake
d−1 of medium-chain triglycerides administered over 4 of milk fat and cream was significantly inversely associated
weeks attenuated the postprandial glucose response (31). with fasting glucose levels and an oral glucose tolerance
Enhanced insulin sensitivity following consumption of test (40). Only the British Women’s Heart and Health
medium-chain triglycerides was demonstrated in clamping Study, comprising 4024 women aged 60–79 years, came to
experiments (32,33). In obese subjects on a very-low-calo- a different conclusion. Women who never drank milk had
rie diet, 9.9 g d−1 of medium-chain triglycerides decreased lower insulin resistance [homeostasis model assessment
fasting glucose and particularly insulin levels more than the (HOMA)] scores, triglyceride levels and BMI, higher HDL
control diet (34). The insulin resistance syndrome disturbs cholesterol, and suffered less frequently from diabetes than
metabolism of muscle, liver and adipose tissue. That those who drank milk. Fat content in milk played no role,
medium-chain fatty acids affect adipocyte metabolism ben- and there was no correlation with cheese consumption
eficially will be outlined in the chapter on obesity. (41). Non-drinkers were, however, a very small group of
Observational studies give little indication that milk con- 111 persons, and the authors themselves did not exclude
sumption would increase risk of diabetes or insulin resis- that genetic factors associated with lactose intolerance may
tance. When a cohort of 27 529 California Seventh-day be involved, as may indeed be the case (42).
Adventist adults were followed for mortality because of all
causes combined, coronary heart disease, stroke, diabetes
Obesity
and cancer between 1960 and 1980, there was no relation-
ship of milk or cheese consumption with any cause of death The current epidemics of diabetes and obesity seem to be
(35). The 41 254 male participants in the Health Profes- related (43). As several epidemiological and cross-sectional
sionals Follow-up Study with no history of diabetes, CVD, studies identified calcium intake as a dietary constituent
and cancer at baseline were followed for 12 years. It turned that was inversely related to body weight and body fat, a
out that each serving-per-day increase in total dairy intake number of reviews addressed this topic (44–47). Several
was associated with a 9% lower risk for type 2 diabetes observational studies detected inverse associations between
(multivariate relative risk 0.91). The corresponding relative dairy intake and body weight, both in children (48,49) and
risk was 0.88 for low-fat dairy intake (36). adults (40). Similar findings came from the CARDIA study,
A few observational studies have examined the whole in that high dairy intake protects from weight gain (37). A
array of the metabolic syndrome. Hallmark findings came high whey protein diet attenuated weight gain more than
from the Coronary Artery Risk Development in Young a meat diet in rats (19). In a recent 12-week randomized,
Adults (CARDIA) study (37). The study population com- placebo-controlled trial isocaloric substitution of yogurt

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
112 Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir obesity reviews

for other foods accelerated weight loss in obese subjects. (30). In clinical trials, humans fed diets containing medium-
Not only was weight loss augmented, there was also a chain fatty acids lost more body fat than those on a control
favourable shift towards more fat loss from the abdominal oil diet (57–59). Beta-oxidation of long-chain but not
region (50). In a 6-month intervention study dairy products medium-chain fatty acids was impaired in obese subjects
exerted a substantially greater effect on both fat loss and (60). Resting glucose and lipid oxidation and postprandial
fat distribution relative to supplemental calcium (51). lipid oxidation was higher in butter-fed as compared with
However, another 1-year intervention study found no sig- soybean oil-fed obese rats, and the butter diet seemed to
nificantly different weight loss between the high-dairy and prevent fat accumulation in the long term. But there was
low-dairy group (52). The authors speculated that differ- no clear beneficial effect of butter in lean animals (61).
ences in baseline calcium intake and degree of adiposity at These findings add to the idea that medium-chain fatty
onset may affect the response to dietary regimens (52). acids may especially assist in the dietary management of
There is no unequivocal consensus in the effect of dairy on existing obesity. Outcome of recent trials suggest that a
body weight, neither from controlled trials nor observa- moderate supply may be more beneficial than an ample
tional studies. As Huang & McCrory (2005) point out, amount (30).
part of the discrepant findings may be due to the uncer-
tainty over whether the effect of dairy is independent of
Hypertension
energy intake or other eating variables (44). There may be
other yet unknown mechanisms, or there may be an addi- High blood pressure is defined as a systolic blood pressure
tive effect of multiple factors. Dairy intake may be associ- above 140 mg Hg and/or a diastolic blood pressure above
ated with other healthy dietary habits or lifestyles that 90 mg Hg. Individuals with high blood pressure are three
promote weight control. to four times more likely to develop coronary heart disease.
Concerning the possible mechanisms, one hypothesis Strokes account for 17% of CVD in the United States and
postulates that dietary calcium plays a critical role in the hypertension is the strongest risk factor for stroke (62).
regulation of energy metabolism. Studied in cell culture and Results from the Framingham study show that even per-
in animal models like the agouti mouse demonstrated a key sons with high-normal blood pressure have a significantly
role for intracellular Ca2+ in the regulation of adipocyte increased risk of CVD as compared with persons with ideal
metabolism. Increased dietary calcium reduces 1,25- levels (63). Weight loss, sodium reduction, increased phys-
dihydroxyvitamin D activity and intracellular Ca2+ influx, ical activity and limited alcohol intake are established rec-
decreasing fatty acid synthesis and increasing lipolysis, ommendations that reduce blood pressure. In the CARDIA
leading to decreased triglyceride stores. Furthermore, study population the risk for 10-year cumulative incidence
decreased 1,25-dihydroxyvitamin D activity may up-regu- of hypertension was less than 50% from the lowest cate-
late the expression of uncoupling protein 2 (UCP2) and this gory of dairy intake (<10 times per week) to the highest
may contribute to the increased thermogenesis observed category (≥35 times per week) (37). A DASH intervention
with high-calcium diets (45). Calcium increases also faecal trial showed that a diet rich in fruits, vegetables and low-
fat excretion, presumably by formation of insoluble cal- fat dairy foods reduces blood pressure significantly more
cium-fatty acid soaps or by binding of bile acids that impair than a fruits and vegetables diet alone, in individuals with
the formation of micelles (53). In addition to dietary cal- both optimal and elevated blood pressure (64). Inclusion
cium other dairy-derived bioactive compounds may con- of dairy products nearly doubled the effect. Participants of
tribute to the augmented effect of whole dairy food intake this study were on average 44 years of age, 49% female,
vs. calcium supplementation alone. Preliminary data sug- 60% African-American, overweight (BMI 28 kg m−2), and
gest that this additional activity lies in the whey fraction had above-optimal blood pressure. In a further study of the
(54). The whey fraction contains angiotensin-converting DASH Collaborative Research Group the benefit of follow-
enzyme (ACE) inhibitor activity. As angiotensin II regulates ing the DASH dietary pattern was shown to apply through-
in part adipocyte lipogenesis, this may be a way for whey out the range of sodium intakes (65). In another study a
proteins to control this process. A role of branched-chain supplement of skim milk decreased blood pressure in sub-
amino acids is also discussed (46). Furthermore, dairy fatty jects with both optimal and elevated blood pressure (66).
acids may help to keep weight down. Octanoic acid sup- The blood pressure-reducing effect of milk is in part due
pressed de novo lipogenesis and triglyceride synthesis in to calcium. Numerous animal and human epidemiologic
mouse pre-adipocytes and human adipocytes (55). Dietary and intervention studies have demonstrated an inverse rela-
medium-chain fatty acids reduced fat mass in rodents, tionship between dietary calcium and blood pressure
through down-regulation of adipogenic genes (56). (62,67). Besides calcium, intake of magnesium and potas-
Medium-chain fatty acids are preferentially oxidized rather sium is inversely correlated with blood pressure, the appro-
than deposited in adipose tissue triglycerides. They increase priate metabolic balance of all three being important (62).
resting metabolic rate and postprandial energy expenditure That blood pressure is beneficially influenced by the

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
obesity reviews Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir 113

increasing provision of calcium, magnesium and potas- apolipoprotein B levels in adolescents (78). Increased milk
sium, was confirmed in the Vanguard intervention study consumption, assessed by biomarker fatty acids and 7-d
(68). It was assumed that the action might be by virtue of dietary records, was associated with a more favourable
their suppressive effects on circulating vasoactive calcium- LDL particle size, i.e. less small dense LDL, as well as with
regulating hormones. Milk contains 1200 mg calcium L−1, lower plasma triglyceride and fasting insulin levels, and
and dairy foods are also a good source of potassium. Lac- higher HDL cholesterol (79). Small dense LDL is associated
tose, citrate, proteins and peptides may improve bioavail- with increased risk for CVD.
ability of calcium from milk. Dairy proteins and peptides Early intervention studies showed that skim milk or
also improve the bioavailability of other minerals and trace yogurt consumption might decrease plasma cholesterol lev-
elements like magnesium, manganese, zinc, selenium and els, while whole milk had neither a hypo- nor hypercholes-
iron (69). terolaemic effect (80). The DASH dietary regimen, relative
Peptides containing up to 10 amino acids may be to the control diet, decreased total, LDL and HDL choles-
released from milk proteins through the proteolytic activity terol, but had no effect on triglyceride levels. The effects
of lactic acid bacteria, are thus found in fermented dairy were more pronounced in men than in women, but did not
products, or may be released during the digestive process. differ significantly by race or baseline lipid levels, except
Many of these peptides have ACE-inhibitory (70) and for HDL (81). It is not clear yet what component(s) play
endothelin release-inhibitory activity (71). ACE is a key the part of a hypocholesterolaemic ‘milk factor’. Calcium
enzyme in the regulation of peripheral blood pressure. The and magnesium from dairy products can affect lipid levels
antihypertensive potential of the peptides requires that they and CVD risk beneficially. The possible hypolipidaemic
reach target sites without being degraded and thus inacti- mechanism of calcium includes decreased intestinal absorp-
vated by intestinal or plasma peptidases. Milk fermented tion of cholesterol, of bile acids, and of fat (53). For mag-
with Lactobacillus (L.) helveticus CP 790 (72), sour milk nesium there is no obvious mechanism (82). Milk proteins
fermented with L. helveticus and Saccharomyces cerevisiae, (83) or peptides (84) may also play a role. At equal fat
as well as the two ACE-inhibitory tripeptides, Val-Pro-Pro content, cheese consumption decreased total and LDL cho-
and Ile-Pro-Pro, isolated from the latter sour milk (73), all lesterol as compared with butter (85). When 52 hypercho-
showed blood pressure-reducing effect in spontaneous lesterolaemic men and women received 5 g d−1 of a serum
hypertensive rats. Not surprising then, that small amounts bovine immunoglobulin for 6 weeks, total and LDL cho-
of fermented dairy products were sufficient to reduce blood lesterol was progressively and significantly decreased by up
pressure in humans. Supply of just 95 mL of sour milk to 5.7% and 6.8% (86).
instead of control milk for 8 weeks did so in elderly hyper- That fairly small amounts of fermented milk products
tensive patients. Blood pressure remained low for another may decrease cholesterol levels more than non-fermented
4 weeks after end of the intervention, a phenomenon also products was corroborated in animal (80) as well as in
observed with other antihypertensive treatments (74). The human studies (87,88). Certain strains of (probiotic) bac-
beneficial effect on blood pressure was confirmed in hyper- teria seem to be more efficient than others. In a series of
tensive subjects consuming 150 mL d−1 of either L. helveti- six double-blind studies in normo- or hypercholestero-
cus LBK-16H fermented milk or a control product for laemic subjects (87), a probiotic yogurt as compared with
21 weeks (75). In another placebo-controlled double-blind a chemically fermented product decreased total cholesterol
34-week study (76), a daily dose of skim milk powder in normo- and slightly hypercholesterolaemic subjects on
equivalent to 1 L of milk from immunized cows lowered average by 4% and LDL cholesterol by 5%. Yogurt pre-
blood pressure along with plasma cholesterol, both in nor- pared with additional Bifidum longum strain BL1
motensive and hypertensive hypercholesterolaemic sub- decreased cholesterol levels as compared with yogurt con-
jects. Therefore, consumption of adequate amounts of taining only Streptococcus thermophilus and L. delbrueckii
dairy products may decrease the risk of hypertensive heart ssp. Bulgaricus, and this effect was more pronounced
disease (77). among moderately hypercholesterolaemic subjects (88).
One explanatory model is that some bacteria strains are
relatively resistant towards bile and show in vitro a potency
Lipid metabolism
to assimilate cholesterol, which would decrease cholesterol
Recent observational studies confirm that the consumption absorption (89). Sphingomyelin is a potentially hypocho-
of milk products can actually lower cholesterol levels. In lesterolaemic compound of the lipid fraction. Sphingomy-
obese subjects in the CARDIA study (37) there was a trend elin is an inhibitor of pancreatic lipase-colipase and may
towards less dyslipidaemia with more frequent consump- also decrease micellar solubilization and thus absorption
tion of dairy products (P = 0.07). There was an inverse efficiency. Milk is a rich source of sphingomyelin, and
association between milk-specific fatty acids in serum cho- because of its high degree of saturation and long-chain fatty
lesterol esters and serum cholesterol levels and with serum acyl groups, milk sphingomyelin seems to be more effective

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
114 Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir obesity reviews

than egg sphingomyelin (90). As sphingomyelin is a com-


Other effects of dairy products with relevance
ponent of the milk fat globule membrane, it stays largely
for the metabolic syndrome
with the buttermilk or whey fraction during processing
rather than with the butter fraction (91). Hyperhomocyst(e)inaemia is one of the established inde-
Dairy fat can be enriched with mono- and polyunsatu- pendent risk factors for CVD. Elevated total homocysteine
rated at the expense of saturated fatty acids by modified levels (tHcy) are associated with increased risk of coro-
feeding regimens. Consumption of a modified as compared nary heart disease (myocardial infarction), stroke, periph-
with a regular milk fat reduced total and LDL cholesterol eral vascular disease, and thrombosis. The correlation is
by 7.9% and 9.5% respectively, in healthy, normocholes- graded and continuous (109,110). Moderate hyperho-
terolaemic and normal-weight men (92). The effect was mocyst(e)inaemia, generally defined as plasma tHcy con-
more pronounced than would be predicted from the change centrations above 15–16 µmol L−1, occurs in 20–40% of
in the fatty acid pattern (93). Consumption of at least 250- patients with such vascular diseases (109). Dietary intake
g milk and 150-g yogurt per day, modified as compared or plasma levels of folate are inversely related to plasma
with regular products, decreased LDL and increased HDL tHcy levels. Folates are found in a wide variety of foods,
cholesterol in another not strictly controlled intervention especially liver, leafy vegetables, fruit, pulses and yeast.
study (94). As little as 300 mg d−1 of eicosapentaenoic and Milk and milk products do not rank very high as a source,
docosahexaenoic acid, given together with semi-skimmed but they contribute their share, particularly in countries
milk for 6 weeks, decreased plasma triglyceride levels by with high-milk intake. In a cross-sectional study of Nor-
19% and increased HDL cholesterol by 19% as compared wegian workers those with the highest intake of bread,
with milk without these supplements (95). Plasma levels of vegetables and skim milk had the lowest tHcy levels (111).
the ω3-fatty acids were increased by 44% and 31% An inverse association between milk or yogurt intake and
respectively. The authors’ reasoning for this pronounced tHcy levels was also found in a US population (112). Vice
effect is that the small fat globule size and thus large surface versa, there was an positive association between milk
of milk fat improved availability and absorption efficiency intake and folate levels in the Hordaland Homocysteine
of the supplement. A similar intervention strategy signifi- Study (113). When participants of a DASH intervention
cantly decreased triglyceride, total and LDL cholesterol trial consumed a control diet, a diet rich in fruits and
levels in a larger cohort, by 24%, 9% and 13% respectively vegetables or such a diet with additional low-fat dairy
(96). However, these studies (95,96) were not strictly con- products for 8 weeks, tHcy levels were progressively
trolled, and more well-designed studies are needed to decreased. The DASH regimen as compared with the con-
examine this effect. trol diet increased also plasma folate levels by 29% (114).
Plasma triglyceride levels increase after a fat meal and In another study the inclusion of milk in the diet enhanced
return to baseline 6–12 h later. The degree of this post- the bioavailability of food folate as assessed by the
prandial response is positively correlated with CVD risk changes in erythrocyte folate and plasma tHcy concentra-
(97). It is higher in obese and insulin-resistant than in tions (115). The whey protein fraction of milk contains a
lean and non-insulin-resistant subjects, because of an high-affinity folate-binding protein that protects folates
accumulation of triglyceride-rich remnant lipoproteins from degradation and may improve their bioavailability
(98,99). This postprandial triglyceride response, expressed (116). It is a compelling speculation that milk, even the
as area under the postprandial curve (AUC), is usually low-fat version, improves bioavailability of several benefi-
more pronounced with saturated rather than polyunsatu- cial ingredients from fruits and vegetables, whatever the
rated fatty acids. But several times the response to milk mechanism. This may mean that the success story of low-
fat in a mixed meal was comparable to that of an oil rich fat dairy products in the DASH dietary regimen is not so
in polyunsaturated fatty acids (100–102) or was even less much or at least not solely due to the action of dairy foods
(103). Different dairy products differed in their effect themselves, but by uniquely enhancing the availability of
with respect to degree (104) or kinetics (105) of the plant compounds. That a very moderate supplement of
response. This attenuated response is most probably due around 300 mg ω3-fatty acids given together with milk
to short-chain and medium-chain fatty acids in dairy fat had a pronounced effect on serum levels of eicosapen-
(30). In numerous studies it was lower with intake of taenoic and docosahexaenoic acid (95,96), adds to this
medium-chain rather than mono- or polyunsaturated interpretation. Low-fat milk or low-fat yogurt enriched
long-chain fatty acids (106,107). Not surprising, obese with plant sterols or stanols inhibited cholesterol absorp-
subjects profited more from this attenuating effect than tion (117) and reduced LDL cholesterol by 14–16%
lean subjects (108). Postprandial cholesterol response was (118,119), i.e. to the same extent as oil-based products
also reduced. The difference was mainly in what the (118) and almost three times more efficient than in bread
authors called LDL, but what might be an (atherogenic) or cereals (119). Thus low-fat dairy products may be a
remnant fraction (108). particularly suited matrix for functional foods.

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
obesity reviews Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir 115

2. Jagla A, Schrezenmeir J. Postprandial triglycerides and endot-


Conclusions helial function. Exp Clin Endocrinol Diabetes 2001; 109: S533–
S547.
Until not so long ago, nutrition research focused on single-
3. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity
nutrient interventions. Recognizing that nutrients are not and mortality associated with the metabolic syndrome. Diabetes
consumed individually but as combined constituents of a Care 2001; 24: 683–689.
varied diet, efforts in this area have shifted to the role of 4. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic
the overall diet, or dietary patterns. That eating habits play syndrome and total and cardiovascular disease mortality in mid-
dle-aged men. JAMA 2002; 288: 2709–2719.
a role in the development of the metabolic syndrome has
5. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome.
also been concluded from the CARDIA study (120). Fast- Lancet 2005; 365: 1415–1428.
food frequency was directly associated with changes in 6. Alberti KG, Zimmet PC. Definition, diagnosis and classification
body weight and insulin resistance in both black and white of diabetes mellitus and its complications. Part 1. diagnosis and
people. New food-based dietary recommendations by the classification of diabetes mellitus provisional report of a WHO
consultation. Diabet Med 1998; 15: 539–553.
American Heart Association, with the objective of reducing
7. Elwood PC, Pickering JE, Hughes J, et al. Milk drinking,
risk for CVD, promote an inclusionary approach. Obvi- ischaemic heart disease and ischaemic stroke II. Evidence from
ously several risk factors for CVD can be reduced with diets cohort studies. Eur J Clin Nutr 2004; 58: 718–724.
that meet the current recommended dietary guidelines. The 8. Tavani A, Gallus S, Negri E, La Vecchia C. Milk, dairy prod-
DASH dietary pattern, which is rich in fruits, vegetables ucts, and coronary heart disease. J Epidemiol Community Health
2002; 56: 471–472.
and low-fat dairy products, has become famous as a suc-
9. Elwood PC, Strain JJ, Robson PJ, et al. Milk consumption,
cessful approach to tackle several disorders of the meta- stroke, and heart attack risk: evidence from the Caerphilly cohort
bolic syndrome. of older men. J Epidemiol Community Health 2005; 59: 502–505.
Observational studies found no increased CVD risk with 10. Elwood PC, Pickering JE, Fehily AM, et al. Milk drinking,
increasing consumption of milk and other dairy products. ischaemic heart disease and ischaemic stroke I. Evidence from the
Caerphilly cohort. Eur J Clin Nutr 2004; 58: 711–717.
In several studies dairy consumption was inversely associ-
11. Warensjo E, Jansson JH, Berglund L, et al. Estimated intake
ated with the occurrence of one or several facets of the of milk fat is negatively associated with cardiovascular risk factors
metabolic syndrome. Several dairy ingredients may contrib- and does not increase the risk of a first acute myocardial infarction.
ute to the beneficial effects, by affecting insulin sensitivity, A prospective case-control study. Br J Nutr 2004; 91: 635–642.
weight, blood pressure and lipid levels, and possibly others. 12. Biong AS, Veierod MB, Ringstad J, et al. Intake of milk fat,
reflected in adipose tissue fatty acids and risk of myocardial inf-
The extent of the benefits is not clear yet. But even small
arction: a case-control study. Eur J Clin Nutr 2006; 60: 236–244.
effects are relevant if additive and if exerted during a life- 13. Moss M, Freed D. The cow and the coronary: epidemiology,
time. The fact that dairy consumption may improve the biochemistry and immunology. Int J Cardiol 2003; 87: 203–216.
bioavailability of folate and other secondary plant compo- 14. Artaud-Wild SM, Connor SL, Sexton G, Connor WE. Differ-
nents makes it plausible that the DASH dietary pattern is ences in coronary mortality can be explained by differences in
cholesterol and saturated fat intakes in 40 countries but not in
more effective than the same diet without low-fat dairy
France and Finland. Circulation 1993; 88: 2771–2779.
products. Dairy intake may be associated with other pru- 15. Schrezenmeir J, Tato F, Tato S, et al. Comparison of glycemic
dent eating habits or healthy lifestyles. Medium-chain fatty response and insulin requirements after mixed meals of equal
acids may play a role, as they affect spontaneous behaviour carbohydrate content in healthy, type I- and type II-diabetic men.
such that food and thus energy intake is reduced (30). It Klin Wochenschr 1989; 67: 985–994.
16. Nilsson M, Stenberg M, Frid AH, et al. Glycemia and
may be that a great deal of the benefit of dairy consumption
insulinemia in healthy subjects after lactose-equivalent meals of
observed in epidemiological studies derives from the fact milk and other food proteins: the role of plasma amino acids and
that dairy consumption, especially liquid dairy food, may incretins. Am J Clin Nutr 2004; 80: 1246–1253.
displace sweetened soda drinks. This may be an explana- 17. Ostman EM, Liljeberg Elmstahl HG, Bjorck IM. Inconsis-
tion for the negative association between frequency of milk tency between glycemic and insulinemic responses to regular and
fermented milk products. Am J Clin Nutr 2001; 74: 96–100.
consumption and body mass in children (49).
18. Frid AH, Nilsson M, Holst JJ, Bjorck IM. Effect of whey on
blood glucose and insulin responses to composite breakfast and
Conflict of interest statement lunch meals in type 2 diabetic subjects. Am J Clin Nutr 2005; 82:
69–75.
The authors declare that they have no conflict of interest. 19. Belobrajdic DP, McIntosh GH, Owens JA. A high-whey-
protein diet reduces body weight gain and alters insulin sensitivity
Acknowledgement relative to red meat in Wistar rats. J Nutr 2004; 134: 1454–1458.
20. Ard JD, Grambow SC, Liu D, et al. The effect of the PRE-
Not applicable. MIER interventions on insulin sensitivity. Diabetes Care 2004; 27:
340–347.
References 21. Azadbakht L, Mirmiran P, Esmaillzadeh A, et al. Beneficial
effects of a Dietary Approaches to Stop Hypertension eating plan
1. Vessby B. Dietary fat, fatty acid composition in plasma and the on features of the metabolic syndrome. Diabetes Care 2005; 28:
metabolic syndrome. Curr Opin Lipidol 2003; 14: 15–19. 2823–2831.

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
116 Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir obesity reviews

22. Hoppe C, Molgaard C, Vaag A, et al. High intakes of milk, 42. Meloni GF, Colombo C, La Vecchia C, et al. High preva-
but not meat, increase s-insulin and insulin resistance in 8-year- lence of lactose absorbers in Northern Sardinian patients with
old boys. Eur J Clin Nutr 2005; 59: 393–398. type 1 and type 2 diabetes mellitus. Am J Clin Nutr 2001; 73:
23. Purnell JQ, Brunzell JD. The central role of dietary fat, not 582–585.
carbohydrate, in the insulin resistance syndrome. Curr Opin Lip- 43. Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of
idol 1997; 8: 17–22. obesity, diabetes, and obesity-related health risk factors. JAMA
24. Riccardi G, Giacco R, Rivellese AA. Dietary fat, insulin sen- 2003; 289: 76–79.
sitivity and the metabolic syndrome. Clin Nutr 2004; 23: 447– 44. Huang TTK, McCrory MA. Dairy intake, obesity, and meta-
456. bolic health in children and adolescents: knowledge and gaps.
25. Jakobsen MU, Overvad K, Dyerberg J, et al. Dietary fat and Nutr Rev 2005; 63: 71–80.
risk of coronary heart disease: possible effect modification by 45. Zemel MB. Role of calcium and dairy products in energy
gender and age. Am J Epidemiol 2004; 160: 141–149. partitioning and weight management. Am J Clin Nutr 2004; 79:
26. Meunier-Durmort C, Poirier H, Niot I, et al. Up-regulation 907S–912S.
of the expression of the gene for liver fatty acid-binding protein 46. Zemel MB, Miller SL. Dietary calcium and dairy modulation
by long-chain fatty acids. Biochem J 1996; 319: 483–487. of adiposity and obesity risk. Nutr Rev 2004; 62: 125–131.
27. Bisschop PH, de Metz J, Ackermans MT, et al. Dietary fat 47. Barr SI. Increased dairy product or calcium intake: is body
content alters insulin-mediated glucose metabolism in healthy weight or composition affected in humans? J Nutr 2003; 133:
men. Am J Clin Nutr 2001; 73: 554–559. 245S–248S.
28. Stouthard JM, Endert E, Romijn JA, Sauerwein HP. Infusion 48. Novotny R, Daida YG, Acharya S, et al. Dairy intake is
of long-chain or medium-chain triglycerides inhibits peripheral associate with lower body fat and soda intake and with greater
glucose metabolism in men. J Parenter Enteral Nutr 1994; 18: weight in adolescent girls. J Nutr 2004; 134: 1905–1909.
436–441. 49. Barba G, Troiano E, Russo P, et al. Inverse association
29. Sidossis LS, Stuart CA, Shulman GI, et al. Glucose plus insulin between body mass and frequency of milk consumption in chil-
regulate fat oxidation by controlling the rate of fatty acid entry dren. Br J Nutr 2005; 93: 15–19.
into the mitochondria. J Clin Invest 1996; 98: 2244–2250. 50. Zemel MB, Richards J, Mathis S, et al. Dairy augmentation
30. Marten B, Pfeuffer M, Schrezenmeir J. Medium chain triglyc- of total and central fat loss in obese subjects. Int J Obes 2005; 29:
erides. Int Dairy J 2006 (in press). 391–397.
31. Yost TJ, Erskine JM, Gregg TS, et al. Dietary substitution of 51. Zemel MB, Thompson W, Milstead A, et al. Calcium and
medium chain triglycerides in subjects with non-insulin-dependent dairy acceleration of weight and fat loss during energy restriction
diabetes mellitus in an ambulatory setting: impact on glycemic in obese adults. Obes Res 2004; 12: 582–590.
control and insulin-mediated glucose metabolism. J Am Coll Nutr 52. Harvey-Berino J, Gold BC, Lauber R, Starinski A. The impact
1994; 13: 615–622. of calcium and dairy product consumption on weight loss. Obes
32. Eckel RH, Hanson AS, Chen AY, et al. Dietary substitution Res 2005; 13: 1720–1726.
of medium-chain triglycerides improves insulin-mediated glucose 53. Shahkhalili Y, Murset C, Meirim I, et al. Calcium supplemen-
metabolism in NIDDM subjects. Diabetes 1992; 41: 641–647. tation of chocolate: effect on cocoa butter digestibility and blood
33. Yost TJ, Eckel RH. Hypocaloric feeding in obese women: lipids in humans. Am J Clin Nutr 2001; 73: 246–252.
metabolic effects of medium-chain triglyceride substitution. Am J 54. Ha E, Zemel MB. Functional properties of whey, whey com-
Clin Nutr 1989; 49: 326–330. ponents, and essential amino acids: mechanisms underlying health
34. Krotkiewski M. Value of VLCD supplementation with benefits for active people (review). J Nutr Biochem 2003; 14: 251–
medium chain triglycerides. Int J Obes 2001; 25: 1393–1400. 258.
35. Snowdon DA. Animal product consumption and mortality 55. Guo W, Lei T, Wang T, Corkey BE, Han J. Octanoate inhibits
because of all causes combined, coronary heart disease, stroke, triglyceride synthesis in 3T3-L1 and human adipocytes. J Nutr
diabetes, and cancer in Seventh-day Adventists. Am J Clin Nutr 2003; 133: 2512–2518.
1988; 48: 739–748. 56. Han J, Hamilton JA, Kirkland JL, et al. Medium-chain oil
36. Choi HK, Willett WC, Stampfer MJ, et al. Dairy consumption reduces fat mass and down-regulates expression of adipogenic
and risk of type 2 diabetes mellitus in men: a prospective study. genes in rats. Obes Res 2003; 11: 734–744.
Arch Intern Med 2005; 165: 997–1003. 57. St-Onge MP, Ross R, Parsons WD, Jones PJH. Medium-chain
37. Pereira MA, Jacobs DR Jr, Van Horn L, et al. Dairy consump- triglycerides increase energy expenditure and decrease adiposity in
tion, obesity, and the insulin resistance syndrome in young adults: overweight men. Obes Res 2003; 11: 395–402.
the CARDIA Study. JAMA 2002; 287: 2081–2089. 58. Tsuji H, Kasai M, Takeuchi H, et al. Dietary medium-chain
38. Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi F. Dairy triacylglycerols suppress accumulation of body fat in a double-
consumption is inversely associated with the prevalence of the blind controlled trial in healthy men and women. J Nutr 2001;
metabolic syndrome in Tehranian adults. Am J Clin Nutr 2005; 131: 2853–2859.
82: 523–530. 59. Nosaka N, Maki H, Suzuki Y, et al. Effects of margarine
39. Mennen LI, Lafay L, Feskens EJM, et al. Possible protective containing medium-chain triacylglycerols on body fat reduction in
effect of bread and dairy products on the risk of the metabolic humans. J Atheroscler Thromb 2003; 10: 290–298.
syndrome. Nutr Res 2000; 20: 335–347. 60. Binnert C, Pachiaudi C, Beylot M, et al. Influence of human
40. Smedman AEM, Gustafsson IB, Vessby BOH. Pentadecanoic obesity on the metabolic fate of dietary long- and medium-chain
acid in serum as a marker for intake of milk fat: relations between triacylglycerols. Am J Clin Nutr 1998; 67: 595–601.
intake of milk fat and metabolic risk factors. Am J Clin Nutr 1999; 61. Rolland V, Roseau S, Fromentin G, et al. Body weight,
69: 22–29. body composition, and energy metabolism in lean and obese
41. Lawlor DA, Ebrahim S, Timpson N, Davey Smith G. Avoiding Zucker rats fed soybean oil and butter. Am J Clin Nutr 2002;
milk is associated with a reduced risk of insulin resistance and the 75: 21–30.
metabolic syndrome: findings from the British Women’s Heart and 62. Massey L. Dairy food consumption, blood pressure and
Health Study. Diabet Med 2005; 22: 808–811. stroke. J Nutr 2001; 131: 1875–1878.

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
obesity reviews Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir 117

63. Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal to Stop Hypertension (DASH) Trial. Am J Clin Nutr 2001; 74:
blood pressure on the risk of cardiovascular disease. N Engl J Med 80–89.
2001; 245: 1291–1297. 82. Vaskonen T. Dietary minerals and modification of cardiovas-
64. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of cular risk factors. J Nutr Biochem 2003; 14: 492–506.
the effects of dietary patterns on blood pressure. DASH 83. Takeuchi T, Shimizu H, Ando K, Harada E. Bovine lactoferrin
collaborative Research Group. N Engl J Med 1997; 336: 1117– reduces plasma triacylglycerol and NEFA accompanied by
1124. decreased hepatic cholesterol and triacylglycerol contents in
65. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, et al. Effects rodents. Br J Nutr 2004; 91: 533–538.
on blood pressure of reduced dietary sodium and the Dietary 84. Nagaoka S, Futamura Y, Miwa K, et al. Identification of novel
Approaches to Stop Hypertension (DASH) diet. DASH-Sodium hypocholesterolemic peptides derived from bovine milk beta-lac-
Collaborative Research Group. N Engl J Med 2001; 344: 3–10. toglobulin. Biochem Biophys Res Commun 2001; 281: 11–17.
66. Buonopane GJ, Kilara A, Smith JS, McCarthy RD. Effect of 85. Biong AS, Muller H, Seljeflot I, et al. A comparison of the
skim milk supplementation on blood cholesterol concentration, effects of cheese and butter on serum lipids, haemostatic variables
blood pressure and triglycerides in a free-living human population. and homocysteine. Br J Nutr 2004; 92: 791–797.
J Am Coll Nutr 1992; 11: 56–67. 86. Earnest CP, Jordan AN, Safir M, et al. Cholesterol-lowering
67. McCarron DA, Reusser ME. Hypertensive cardiovascular dis- effects of bovine serum immunoglobulin in participants with mild
ease: risk reduction by dietary calcium and dairy foods. Sci Des hypercholesterolemia. Am J Clin Nutr 2005; 81: 792–798.
Aliments 2002; 22: 415–421. 87. Agerhol-Larsen L, Bell ML, Grunwald GK, Astrup A. The
68. Resnick LM, Oparil S, Chait A, et al. Factors affecting blood effect of a probiotic milk product on plasma cholesterol: a meta-
pressure responses to diet: the Vanguard study. Am J Hypertens analysis of short-term intervention studies. Eur J Clin Nutr 2000;
2000; 13: 956–965. 54: 856–860.
69. Vegarud GE, Langsrud T, Svenning C. Mineral-binding milk 88. Xiao JZ, Kondo S, Takahashi N, et al. Effects of milk prod-
proteins and peptides; occurrence, biochemical and technological ucts fermented by Bifidobacterium longum on blood lipids in rats
characteristics. Br J Nutr 2000; 84: S91–S98. and healthy adult male volunteers. J Dairy Sci 2003; 86: 2452–
70. FitzGerald RJ, Meisel H. Milk protein-derived peptide inhib- 2461.
itors of angiotensin-I-converting enzyme. Br J Nutr 2000; 84: S33– 89. St-Onge MP, Farnworth ER, Jones PJ. Consumption of fer-
S37. mented and nonfermented dairy products: effects on cholesterol
71. Maes W, Van Camp J, Vermeirssen V, et al. Influence of the concentrations and metabolism. Am J Clin Nutr 2000; 71: 674–
lactokinin Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR) on the 681. Review.
release of endothelin-1 by endothelial cells. Regulatory Peptides 90. Noh SK, Koo SI. Milk sphingomyelin is more effective than
2004; 118: 105–109. egg sphingomyelin in inhibiting intestinal absorption of cholesterol
72. Yamamoto N, Akino A, Takano T. Antihypertensive effect of and fat in rats. J Nutr 2004; 134: 2611–2616.
the peptides derived from casein by an extracellular proteinase 91. Rombaut R, Camp JV, Dewettinck K. Analysis of phospho-
from lactobacillus helveticus CP790. J Dairy Sci 1994; 77: 917– and sphingolipids in dairy products by a new HPLC method. J
922. Dairy Sci 2005; 88: 482–488.
73. Nakamura Y, Yamomoto N, Sakai K, Takano T. Antihyper- 92. Poppitt SD, Keogh GF, Mulvey TB, et al. Lipid-lowering
tensive effect of sour milk and peptides isolated from it that are effects of a modified butter-fat: a controlled intervention trial in
inhibitors to angiotensin I-converting enzyme. J Dairy Sci 1995; healthy men. Eur J Clin Nutr 2002; 56: 64–71.
78: 1253–1257. 93. Mensink RP, Zock PL, Kester ADM, Katan MB. Effects of
74. Hata Y, Yamomoto M, Ohni M, et al. A placebo-controlled dietary fatty acids and carbohydrates on the ratio of serum total
study of the effect of sour milk on blood pressure in hypertensive to HDL cholesterol and on serum lipids and apolipoproteins: a
subjects. Am J Clin Nutr 1996; 64: 767–771. meta-analysis of 60 controlled trials. Am J Clin Nutr 2003; 77:
75. Seppo L, Jauhiainen T, Poussa T, Korpela R. A fermented 1146–1155.
milk high in bioactive peptides has a blood pressure-lowering 94. Seidel C, Deufel T, Jahreis G. Effects of fat-modified dairy
effect in hypertensive subjects. Am J Clin Nutr 2003; 77: 326–330. products on blood lipids in humans in comparison with other fats.
76. Sharpe SJ, Gamble GD, Sharpe DN. Cholesterol-lowering and Ann Nutr Metab 2005; 49: 42–48.
blood pressure effects of immune milk. Am J Clin Nutr 1994; 59: 95. Visioli F, Risè P, Plasmati E, et al. Very low intakes of n-3
929–934. fatty acids incorporated into bovine milk reduce plasma triacylg-
77. Miller GD, DiRienzo DD, Reusser ME. McCarron DA. Ben- lycerol and increase HDL-cholesterol concentrations in healthy
efits of dairy product consumption on blood pressure in humans: subjects. Pharmacol Res 2000; 41: 571–576.
a summary of the biomedical literature. J Am Coll Nutr 2000; 19: 96. Carrero JJ, Baro L, Fonolla J, et al. Cardiovascular effects of
147S–164S. milk enriched with omega-3 polyunsaturated fatty acids, oleic
78. Samuelson G, Bratteby LE, Mohsen R, Vessby B. Dietary acid, folic acid, and vitamins E and B6 in volunteers with mild
intake in healthy adolescents: inverse relationship between the hyperlipidemia. Nutrition 2004; 20: 521–527.
estimated intake of saturated fatty acids and serum cholesterol. Br 97. Cohn JS. Postprandial lipemia: emerging evidence for athero-
J Nutr 2001; 85: 333–341. genicity of remnant lipoproteins. Can J Cardiol 1998; 14: 18B–27B.
79. Sjogren P, Rosell M, Skoglund-Andersson C, et al. Milk- 98. Martins IJ, Redgrave TG. Obesity and post-prandial lipid
derived fatty acids are associated with a more favorable LDL metabolism. Feast or famine? J Nutr Biochem 2004; 15: 130–141.
particle size distribution in healthy men. J Nutr 2004; 134: 1729– 99. Schrezenmeir J, Fenselau S, Keppler I, et al. Postprandial
1735. triglyceride high response and the metabolic syndrome. Ann NY
80. Pfeuffer M, Schrezenmeir J. Bioactive substances in milk with Acad Sci 1997; 827: 353–386.
properties decreasing risk of cardiovascular diseases. Br J Nutr 100. Dworatzek PDN, Hegele RA, Wolever TMS. Postprandial
2000; 84: S155–S159. lipemia in subjects with the threonine 54 variant of the fatty acid-
81. Obarzanek E, Sacks FM, Vollmer WM, et al. Effects on blood binding protein 2 gene is dependent on the type of fat ingested.
lipids of a blood pressure-lowering diet: the Dietary Approaches Am J Clin Nutr 2004; 79: 1110–1117.

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118
118 Milk and the metabolic syndrome M. Pfeuffer and J. Schrezenmeir obesity reviews

101. Mero N, Syvanne M, Rosseneu M, et al. Comparison of 111. Oshaug A, Bugge KH, Refsum H. Diet, an independent
three fatty meals in healthy normolipidaemic men: high post- determinant for plasma total homocysteine. A cross sectional
prandial retinyl ester response to soybean oil. Eur J Clin Invest study of Norwegian workers on platforms in the North Sea. Eur
1998; 28: 407–415. J Clin Nutr 1998; 52: 7–11.
102. Salomaa V, Rasi V, Pekkanen J, et al. The effects of saturated 112. Ganji V, Kafai MR. Frequent consumption of milk, yogurt,
fat and n-6 polyunsaturated fat on postprandial lipemia and hemo- cold breakfast cereals, peppers, and cruciferous vegetables and
static activity. Atherosclerosis 1993; 103: 1–11. intakes of dietary folate and riboflavin but not vitamins B-12 and
103. Mekki N, Charbonnier M, Borel P, et al. Butter differs from B-6 are inversely associated with serum total homocysteine con-
olive oil and sunflower oil in its effects on postprandial lipemia centrations in the US population. Am J Clin Nutr 2004; 80: 1500–
and triacylglycerol-rich lipoproteins after single mixed meals in 1507.
healthy young men. J Nutr 2002; 132: 3642–3649. 113. Brevik A, Vollset SE, Tell GS, et al. Plasma concentration of
104. Sanggaard KM, Holst JJ, Rehfeld JF, et al. Different folate as a biomarker for the intake of fruit and vegetables: the
effects of whole milk and a fermented milk with the same fat Hordaland Homocysteine Study. Am J Clin Nutr 2005; 81: 434–
and lactose content on gastric emptying and postprandial 439.
lipaemia, but not on glycaemic response and appetite. Br J Nutr 114. Appel LJ, Miller ER 3rd, Jee SH, et al. Effect of dietary
2004; 92: 447–459. patterns on serum homocysteine: results of a randomized, con-
105. Clemente G, Mancini M, Nazzaro F, et al. Effects of differ- trolled feeding study. Circulation 2000; 102: 852–857.
ent dairy products on postprandial lipemia. Nutr Metab Cardio- 115. Picciano MF, West SG, Ruch AL, et al. Effect of cow milk
vasc Dis 2003; 13: 377–383. on food folate bioavailability in young women. Am J Clin Nutr
106. Asakura L, Lottenberg AMP, Neves MQTS, et al. Dietary 2004; 80: 1565–1569.
medium-chain triacylglycerol prevents the postprandial rise of 116. Parodi PW. Cow’s milk folate binding protein: its role in
plasma triacylglycerols but induces hypercholesterolemia in pri- folate nutrition. Aust J Dairy Technol 1997; 52: 109–118.
mary hypertriglyceridemic subjects. Am J Clin Nutr 2000; 71: 117. Pouteau EB, Monnard IE, Piguet-Welsch C, et al. Non-
701–705. esterified plant sterols solubilized in low fat milks inhibit choles-
107. Borel P, Tyssandier V, Mekki N, Grolier P, et al. Chylomi- terol absorption – a stable isotope double-blind crossover study.
cron β-carotene and retinyl palmitate responses are dramatically Eur J Nutr 2003; 42: 154–164.
diminished when men digest β-carotene with medium-chain rather 118. Mensink RP, Ebbing S, Lindhout M, et al. Effects of plant
than long-chain triglycerides. J Nutr 1998; 128: 1361–1367. stanol esters supplied in low-fat yoghurt on serum lipids and
108. Kasai M, Maki H, Nosaka N, et al. Effect of medium-chain lipoproteins, non-cholesterol sterols and fat soluble antioxidant
triglycerides on the postprandial triglyceride concentration in concentrations. Atherosclerosis 2002; 160: 205–213.
healthy men. Biosci Biotechnol Biochem 2003; 67: 46–53. 119. Clifton PM, Noakes M, Sullivan D, et al. Cholesterol-low-
109. Duell PB, Malinow MR. Homocyst(e)ine: an important risk ering effects of plant sterol esters differ in milk, yoghurt, bread
factor for atherosclerotic vascular disease. Curr Opin Lipidol and cereal. Eur J Clin Nutr 2004; 58: 503–509.
1997; 8: 28–34. 120. Pereira MA, Kartashov AI, Ebbeling C, et al. Fast-food
110. Verhoef P, Stampfer MJ, Rimm EB. Folate and coronary habits, weight gain, and insulin resistance (the CARDIA study):
heart disease. Curr Opin Lipidol 1998; 9: 17–22. 15-year prospective analysis. Lancet 2005; 365: 36–42.

© 2006 The Authors


Journal compilation © 2006 The International Association for the Study of Obesity. obesity reviews 8, 109–118

You might also like