ArticlePDF AvailableLiterature Review

Abstract and Figures

Osteoporosis affects women twice as often as men. Additionally, it is estimated that 0.3 million and 1.7 million people have hip fractures in the USA and Europe, respectively. Having a proper peak bone mass and keeping it as long as possible is especially important for osteoporosis prevention. One of the most important calcium sources is milk and dairy products. Breast milk is the best infant food, but milk should not be avoided later in life to prevent losing bone mass. On the other hand, more and more people limit their milk consumption and consume other dairy or non-dairy products. For example, they are usually replaced with plant beverages, which should be consumed carefully in several age groups. Additionally, an important element of milk and dairy products, as well as plant beverages, are probiotics and prebiotics, which may modulate bone turnover. Dietary recommendations focused on milk, and dairy products are an important element for the prevention of osteoporosis.
Content may be subject to copyright.
nutrients
Review
Milk and Dairy Products: Good or Bad for Human Bone?
Practical Dietary Recommendations for the Prevention and
Management of Osteoporosis
Alicja Ewa Ratajczak * , Agnieszka Zawada , Anna Maria Rychter , Agnieszka Dobrowolska and
Iwona Krela-Ka´zmierczak *


Citation: Ratajczak, A.E.; Zawada,
A.; Rychter, A.M.; Dobrowolska, A.;
Krela-Ka´zmierczak, I. Milk and Dairy
Products: Good or Bad for Human
Bone? Practical Dietary
Recommendations for the Prevention
and Management of Osteoporosis.
Nutrients 2021,13, 1329. https://
doi.org/10.3390/nu13041329
Academic Editor: Dennis Savaiano
Received: 17 March 2021
Accepted: 15 April 2021
Published: 17 April 2021
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affil-
iations.
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences,
61-701 Poznan, Poland; aga.zawada@gmail.com (A.Z.); a.m.rychter@gmail.com (A.M.R.);
agdob@ump.edu.pl (A.D.)
*Correspondence: alicjaewaratajczak@gmail.com (A.E.R.); krela@op.pl (I.K.-K.); Tel.: +48-667-385-996 (A.E.R.);
+48-8691-343 (I.K.-K.); Fax: +48-8691-686 (A.E.R.)
Abstract:
Osteoporosis affects women twice as often as men. Additionally, it is estimated that
0.3 million and 1.7 million people have hip fractures in the USA and Europe, respectively. Having a
proper peak bone mass and keeping it as long as possible is especially important for osteoporosis
prevention. One of the most important calcium sources is milk and dairy products. Breast milk is the
best infant food, but milk should not be avoided later in life to prevent losing bone mass. On the other
hand, more and more people limit their milk consumption and consume other dairy or non-dairy
products. For example, they are usually replaced with plant beverages, which should be consumed
carefully in several age groups. Additionally, an important element of milk and dairy products, as
well as plant beverages, are probiotics and prebiotics, which may modulate bone turnover. Dietary
recommendations focused on milk, and dairy products are an important element for the prevention
of osteoporosis.
Keywords:
cow’s milk; plant milk; osteoporosis; bone mineral density; lactose intolerance; cow’s
milk allergy; nutrition; osteoporosis; bone health
1. Introduction
Osteoporosis is a skeletal disorder with decreased bone mineral density (BMD) and
bone strength, leading to increased risk of fractures. Osteoporosis may be divided into
primary and secondary (70% and 30% of all cases, respectively). Secondary osteoporosis
can be caused by several diseases, e.g., inflammatory bowel diseases, celiac disease, or
endocrinology disorders [
1
]. Risk factors of osteoporosis are, among others, malabsorption,
cigarette smoking, stress, air pollution, older age, low physical activity, and co-occurring
diseases (Figure 1) [
2
,
3
]. Osteoporosis affects women twice as often as men. Additionally,
it is estimated that 0.3 million and 1.7 million people have hip fractures in the USA and
Europe, respectively [
4
]. Having a proper peak bone mass and maintaining it as long as
possible is especially important for osteoporosis prevention.
It is vital to note that 1/3 adult people achieve their total bone mass between 2 and 4
Tanner stages, and 95% of peak bone mass is reached before the age of 16. For this reason,
puberty is a key time for bone mass formation [
5
,
6
]. Data about the age of peak bone mass
are inconsistent, and it is suggested that a peak bone mass is reached at around 18 years of
age for women and 20 years of age for men [
7
]. However, other authors suggest peak bone
mass is reached between 20 and 30 years of age [8].
Additionally, peak bone mass is influenced by genetic and environmental factors,
including diet [
9
]. Therefore, proper intake of minerals and vitamins, especially vitamin
D and calcium, is essential, especially in a period of rapid growth, such as childhood
Nutrients 2021,13, 1329. https://doi.org/10.3390/nu13041329 https://www.mdpi.com/journal/nutrients
Nutrients 2021,13, 1329 2 of 15
and adolescence. The next stage is bone remodeling, which leads to total rebuilding of
the skeleton—once every ten years with no change in bone net weight. Proper intake of
calcium and vitamin D helps maintain peak bone mass. The next stage is bone resorption,
associated with higher activity of osteoclasts than osteoblasts, which results in a decreased
bone mass and increased risk of fracture [5].
It is vital to notice that low vitamin D concentration causes hyperparathyroidism and
decreases intestinal absorption of calcium, leading to bone resorption [
10
,
11
]. Vitamin D
deficiency is associated with osteoporosis [
12
]. Moreover, women with fractures presented
higher prevalence of vitamin D deficiency [13].
Nutrients 2021, 13, x FOR PEER REVIEW 2 of 16
Figure 1. Risk factors of osteoporosis.
Additionally, peak bone mass is influenced by genetic and environmental factors,
including diet [9]. Therefore, proper intake of minerals and vitamins, especially vitamin
D and calcium, is essential, especially in a period of rapid growth, such as childhood and
adolescence. The next stage is bone remodeling, which leads to total rebuilding of the
skeleton—once every ten years with no change in bone net weight. Proper intake of cal-
cium and vitamin D helps maintain peak bone mass. The next stage is bone resorption,
associated with higher activity of osteoclasts than osteoblasts, which results in a decreased
bone mass and increased risk of fracture [5].
It is vital to notice that low vitamin D concentration causes hyperparathyroidism and
decreases intestinal absorption of calcium, leading to bone resorption [10,11]. Vitamin D
deficiency is associated with osteoporosis [12]. Moreover, women with fractures pre-
sented higher prevalence of vitamin D deficiency [13].
An important element of osteoporosis prevention is physical activity [14]. Physical
activity increases BMD [15]. Additionally, regular exercise increases muscle strength, de-
creasing risk of fall and fracture [16].
Tables 1 and 2 show calcium content in selected products and the Recommended
Daily Intake of calcium for various age groups.
Table 1. Calcium content in selected products [17].
Products. Portion Calcium Content (mg)
Whole milk 200 mL 236
Semi-skimmed milk 200 mL 240
Skimmed milk 200 mL 244
Sheep milk 200 mL 380
Soy dring (non-enriched) 200 mL 26
Soy drink (calcium-enriched) 200 mL 240
Rice drink 200 mL 22
Almond milk 200 mL 90
Flavoured yoghurt 150 g 197
Natural yoghurt 150 g 207
Hard cheese (e.g., Parmesan, Cheddar) 30 g 240
Fresh cheese (e.g., Ricotta, cottage cheese) 200 138
Mozzarella 60 242
Table 2. Recommended Daily Intake of calcium for various age groups [18].
Age RDI (mg)
Figure 1. Risk factors of osteoporosis.
An important element of osteoporosis prevention is physical activity [
14
]. Physical
activity increases BMD [
15
]. Additionally, regular exercise increases muscle strength,
decreasing risk of fall and fracture [16].
Tables 1and 2show calcium content in selected products and the Recommended Daily
Intake of calcium for various age groups.
Table 1. Calcium content in selected products [17].
Products. Portion Calcium Content (mg)
Whole milk 200 mL 236
Semi-skimmed milk 200 mL 240
Skimmed milk 200 mL 244
Sheep milk 200 mL 380
Soy dring (non-enriched) 200 mL 26
Soy drink (calcium-enriched) 200 mL 240
Rice drink 200 mL 22
Almond milk 200 mL 90
Flavoured yoghurt 150 g 197
Natural yoghurt 150 g 207
Hard cheese (e.g., Parmesan, Cheddar) 30 g 240
Fresh cheese (e.g., Ricotta, cottage cheese)
200 138
Mozzarella 60 242
Nutrients 2021,13, 1329 3 of 15
Table 2. Recommended Daily Intake of calcium for various age groups [18].
Age RDI (mg)
0–6 months 200
7–12 months 260
1–3 years 700
4–8 years 1000
9–13 years 1300
14–18 years 1300
19–50 years 1000
51–70 years
Women 1200
Men 1000
71 years and older 1200
Pregnant and breastfeeding
Teenagers 1300
Adults 1000
RDI-Recommended Daily Intake.
2. Milk and BMD
2.1. Breast Milk
Compounds of breast milk may come from three sources: the diet of the mother,
stocks storage by mother, and lactocytes [
19
]. The amount of produced milk was negatively
correlated with maternal age and weight gained during pregnancy, but these factors did not
affect the content of fat in milk. Diet also did not influence the amount and compounds of
milk, especially the content of protein, fat, carbohydrates, iron, and calcium. Additionally,
fat-soluble vitamins content depended on a mother’s diet to a smaller extent and water-
soluble vitamins to a significant one [20,21].
Lactose is the main carbohydrate of human milk. It is made up of glucose and
especially important galactose, which supports the development of the central nervous
system. Additionally, breast milk contains oligosaccharides (about 15–23 g/L in colostrum
and 1–10 g/L in mature milk) [22].
Supplementation of protein in the mother’s diet did not affect milk composition [
23
].
The main proteins in breast milk are casein, whey protein and mucin; however, protein
content decreases with the child’s age [22].
Fats—mostly triacylglycerols (98%)—are a source of about 44% of total breast milk
energy. Additionally, breast milk contains more than 200 various fatty acids (FA). The breast
milk of European women contains 35–40% of saturated FA, 45–50% mono-unsaturated FA
and 15% poly-unsaturated FA [
22
]. Moreover, the amount of long-chain FA and free FA
is greater in human milk than cow’s milk [
21
]. Fat in human milk is absorbed at around
92%. It is vital to notice that the amount of cholesterol was lower in breast milk than in
cow’s or sheep milk [24]. The composition of FA is dependent on the mother’s diet. Patin
et al. have shown that, after consumption of 100g of fish (sardines) three times a week by
breastfeeding women, the amount of omega-3 FA in breast milk was raised [25].
The optimum calcium:phosphorus (Ca:P) ratio is between 1:1 and 1:2 [
26
]. Further-
more, the Ca:P ratio is better in breast milk than cow’s milk (1.4–1.7:1 and 1.24:1, respec-
tively) [
27
]. Additionally, the Ca:P ratio in cow’s milk is dependent on fat content and is
higher in whole milk than skimmed [28].
Breast milk is also a source of immune factors, including Il2 (Interleukin 2), Il4, Il10, IgA
(immunoglobulin A) total IgG, or macrophages. There were no significant differences in the
amount of immune factors in breast milk from women after exposure to stress. However,
two weeks after the stressful situation, the level of cortisol in milk was significantly higher.
Moreover, breast milk also contains growth hormones [19,29].
Nutrients 2021,13, 1329 4 of 15
2.2. Lactation and BMD
Breastfeeding may affect the BMD of both mother and child. Children who were
initially (first six months of life) breastfed and later fed milk formula (up to 2 years old)
had higher BMD than children only breastfed or only fed with milk formula (for the first
two years of life) [
30
]. According to Blanco et al., exclusive breastfeeding for the first six
months of life was associated with higher BMD in adolescents, when compared with mixed
feeding [
31
]. Additionally, 6-year-old children who were breastfed presented higher BMD
than children who were never breastfed. Among breastfed children, the group that was
exclusively breastfed for minimum the first four months presented lower BMD and higher
bone area (BA) than children who were not breastfed for the first four months [32].
On the other hand, among mothers, a breastfeeding period was negatively correlated
with BMD of the lumbar spine. Additionally, the frequency of osteoporosis was higher
among women who were breastfeeding for a minimum of 37 months than women who were
breastfeeding for a shorter period. However, the age of the mother and number of deliveries
did not correlate with BMD [
33
]. According to Tsvetov et al., a negative correlation between
the number of deliveries and BMD was reported [
34
]. Moreover, breastfeeding for more
than 18 months increased vertebral fracture risk more than twice in postmenopausal
women [
35
]. In turn, Cooke-Hubley et al. reported that parity and lactation are not
associated with higher risk of decreased BMD, clinical fragility or radiographic vertebral
fractures over 10 years [
36
]. It is vital to notice that absorption of calcium during pregnancy
increases, but this does not occur during lactation, and calcium is resorbed from the
mother’s bones [37].
2.3. Cow’s Milk and Dairy Products and BMD
Milk and dairy products contain protein, minerals and vitamins (Figure 2), which
may be beneficial for bone health [
38
]. Cultured dairy products (e.g., yoghurt and kefir)
are formed by adding starter cultures, which convert the lactose in milk to lactic acid. For
this reason, fermented dairy products may also contain bacteria, which are beneficial for
human health [39].
Nutrients 2021, 13, x FOR PEER REVIEW 5 of 16
impact of dairy products on BMD may depend on serum vitamin D levels. Intake of dairy
products, fluid dairy and milk was associated with higher BMD of the femoral neck and
lumbar spine among subjects with normal 25(OH)D concentration but not in a group with
vitamin D deficiency [48]. Among 70-year-old women and men, total dairy product intake
was positively associated with trabecular and cortical cross-sectional areas in the tibia and
the areal bone mineral density of the radius [49].
On the other hand, as Michaëlsson et al. have reported, dairy product intake was
linked with higher mortality in women and men and a higher risk of fracture among
women in Sweden [50]. However, it should be mentioned that in Sweden, milk was forti-
fied with vitamin A in the years 1987–1990 and 1997, which may influence the abovemen-
tioned results [51]. About 60% of dietary calcium should come from dairy products. Meet-
ing dairy calcium requirements correlated positively with children’s BMD [52]. Meta-
analysis has not shown a clear association between the group with an enormous amount
of milk intake and risk of osteoporotic fracture and hip fracture. Additionally, results were
heterogeneous and did not allow for clear conclusions [53].
Figure 2. The effect of cow’s milk on bone.
2.4. Plant Milk (Plant Beverages) and BMD
In the last years, the market availability of plant products, substitutes for cow’s milk,
has increased. These products are made from, among others, soybeans, rice, oats, al-
monds, coconut and are called plant milk or plant beverages. The most similar protein
content to cow’s milk occurs in soya beverages. In turn, the content of protein in rice, oats
and almond milk is very low. Plant beverages contain a lower amount of saturated fatty
acids and do not contain cholesterol. However, producers frequently add fat and sugar to
these products, which may increase the risk of metabolic disorders. Moreover, plant bev-
erages contain a lower amount of iodine, potassium, phosphorus and selenium compared
with semi-skimmed milk [41].
Data about the differences between the absorption of calcium from dairy and soy
products are unclear [54,55]. It is vital to note that the Ca:P ratio in unfortified soya milk
is lower than in cow’s milk (2:1 and 1.3:1, respectively). However, calcium fortification
changes this ratio for the better (1.8:1) [56]. Nevertheless, calcium and vitamin D fortifica-
tion of plant beverages is not obligatory in every country [57].
Soy products contain isoflavones, which show an affinity with the estrogen receptor
and protects from loss of bone mass. 18-months of intake of cow’s milk fortified with cal-
cium by postmenopausal women increased the BMD of the femoral neck significantly.
Figure 2. The effect of cow’s milk on bone.
Studies have confirmed that dairy product consumption is essential for human health,
especially in the pediatric group. Bone mineral content (BMC) was lower by about 5.6% in
women aged 20–49 years who had consumed less than one portion of milk weekly during
childhood, when compared with women who had consumed more than one portion. Addi-
tionally, low milk consumption during adolescence was associated with a 3% reduction
in the BMD and BMC of the hip in adulthood. Among women over 50 years old, there
Nutrients 2021,13, 1329 5 of 15
was a non-linear association between milk consumption in childhood and adolescence and
BMD and BMC of the hip. Moreover, low milk intake in childhood was linked with two
times higher fracture risk [
40
]. For this reason, osteoporosis is called pediatric disease with
geriatric consequences [
41
]. It is vital to note that children who had avoided milk and had
not eaten food fortified with calcium reported fracture before puberty more frequently than
children who had consumed cow’s milk [
42
]. Adults’ height correlated positively with the
amount of milk consumed between the ages of 5–12 and 13–17 [
43
]. Higher consumption
of dairy products was associated with higher total BMD among 6-year-old girls and boys.
Additionally, positive association occurred between total BMD and intake of a minimum
one portion of dairy products daily [
44
]. Sioen et al. have reported that consumption of
dairy products by children (6–12 years old) positively affected total BMC and areal bone
mineral density (aBMD) after adjusting for confounding factors [
45
]. Among young people
(18–30 years old), total BMD was lower among people with lower dairy product consump-
tion than subjects with proper intake. There was no significant difference in lumbar spine
BMD among groups. It is vital to note that lower intake of dairy products was associated
with higher BMI (Body Mass Index) and adipose tissue percentage [
46
]. On the other hand,
as van Dongen et al. have shown, higher intake of milk, milk + yoghurt, and milk + yogurt
+ cheese was associated with higher trabecular and integral vBMD and VCS among men
but not women [
47
]. Additionally, the positive impact of dairy products on BMD may
depend on serum vitamin D levels. Intake of dairy products, fluid dairy and milk was
associated with higher BMD of the femoral neck and lumbar spine among subjects with
normal 25(OH)D concentration but not in a group with vitamin D deficiency [
48
]. Among
70-year-old women and men, total dairy product intake was positively associated with
trabecular and cortical cross-sectional areas in the tibia and the areal bone mineral density
of the radius [49].
On the other hand, as Michaëlsson et al. have reported, dairy product intake was
linked with higher mortality in women and men and a higher risk of fracture among women
in Sweden [
50
]. However, it should be mentioned that in Sweden, milk was fortified with
vitamin A in the years 1987–1990 and 1997, which may influence the abovementioned
results [
51
]. About 60% of dietary calcium should come from dairy products. Meeting dairy
calcium requirements correlated positively with children’s BMD [
52
]. Meta-analysis has
not shown a clear association between the group with an enormous amount of milk intake
and risk of osteoporotic fracture and hip fracture. Additionally, results were heterogeneous
and did not allow for clear conclusions [53].
2.4. Plant Milk (Plant Beverages) and BMD
In the last years, the market availability of plant products, substitutes for cow’s milk,
has increased. These products are made from, among others, soybeans, rice, oats, almonds,
coconut and are called plant milk or plant beverages. The most similar protein content
to cow’s milk occurs in soya beverages. In turn, the content of protein in rice, oats and
almond milk is very low. Plant beverages contain a lower amount of saturated fatty acids
and do not contain cholesterol. However, producers frequently add fat and sugar to these
products, which may increase the risk of metabolic disorders. Moreover, plant beverages
contain a lower amount of iodine, potassium, phosphorus and selenium compared with
semi-skimmed milk [41].
Data about the differences between the absorption of calcium from dairy and soy prod-
ucts are unclear [
54
,
55
]. It is vital to note that the Ca:P ratio in unfortified soya milk is lower
than in cow’s milk (2:1 and 1.3:1, respectively). However, calcium fortification changes this
ratio for the better (1.8:1) [
56
]. Nevertheless, calcium and vitamin D fortification of plant
beverages is not obligatory in every country [57].
Soy products contain isoflavones, which show an affinity with the estrogen receptor
and protects from loss of bone mass. 18-months of intake of cow’s milk fortified with
calcium by postmenopausal women increased the BMD of the femoral neck significantly.
However, consumption of soy-fortified milk decreased (not significantly) femoral neck
Nutrients 2021,13, 1329 6 of 15
BMD [
58
]. Additionally, intake of cow’s milk with soy isoflavones led to an increase
in the level of 25OHD and a decrease in the concentration of bone turnover markers
(osteoprotegerin and tartrate-resistant acid phosphatase) [
59
]. As Lydeking-Olsen et al.
have reported among women divided into four groups—consuming soy products, treated
with transdermal progesterone (TDP), combined group (consuming soy products and
treated with TDP) and control group—BMD and BMC decreased significantly in combined
and control groups. BMD and BMC increased in the soy group only, but differences were
not significant [
60
]. An animal study has shown that isoflavones inhibited bone loss in
mature female rats with a decreased level of estradiol [61].
An
in vitro
study has shown that germinated soy germ extracts increased expression
of osteocalcin and alkaline phosphatase [62].
Among individuals who weekly drink 1.3 cups of soy milk fortified with calcium,
decreased low T-score risk was decreased by 57% when compared with individuals who
did not drink soy milk, even if they consumed dairy products [
63
]. Children are the group
who are particularly vulnerable to nutrients deficiencies. Children that consumed plant
beverages presented lower serum concentration of vitamin D than children who drank
cow’s milk [57].
Cow’s milk is often replaced with plant milk by vegans. According to Ambroszkiewicz
et al., people on a vegan diet consume an insufficient amount of calcium and vitamin D,
which may lead to osteoporosis [64].
Consumption of unfortified beverages instead of breast milk, cow’s or modified milk
may be especially harmful to children in the first year of life because it could lead to the
development of rickets, failure in thrive, kwashiorkor, anaemia, metabolic alkalosis, scurvy
and hyperoxaluria [65].
Tables 3and 4present the content of nutrients in dairy products and various milks.
Table 3. Content of nutrients in 100 g of human, cow and plant milk.
Human [66] Cow’s [67] Plant [68]
Fat (g) 3.8 3.7–3.9 0.66–49.2
Proteins (g) 1.0 3.2–3.5 0.59–19.00
Casein (g) 0.3 2.8 0
Carbohydrates (g) 7.0 7.0 27.3–50.0
Lactose (g) 7.0 0.9–4.9 0
Calcium (mg) 34 118 4.0–180.0
Phosphorus (mg) 15 89.6 49.0–1000.0
Sodium (mg) 15 44.5 2.2–140.01
Potassium (mg) 58 150 65.00–2000.0
Table 4. Content of macronutrients, calcium, phosphorus and vitamin D in milk and dairy products [69].
Protein (g) Fat (g) Carbohydrates (g) Calcium (mg) Phosphorus (mg) Ca:P Ratio Wit.D (µg)
Milk, 3.5% fat 3.3 3.5 4.8 118 85 1.38 0.03
Milk, 2% fat 3.4 2.0 4.9 120 86 1.40 0.02
Cream, 18% 2.5 18.0 3.6 99 71 1.39 0.14
Natural yoghurt, 2% 4.3 2.0 6.2 170 122 1.39 0.03
Berries yoghurt 3.7 1.5 8.8 134 96 1.40 0.02
Cheddar cheese 27.1 31.7 0.1 703 487 1.44 0.26
Cottage cheese 12.3 4.3 3.3 80 140 0.57 0.09
3. Intolerance and Allergy
3.1. Lactose Intolerance
Lactose may be absorbed after decomposing into glucose and galactose by lactase,
which is produced in the small intestine. Lactase deficiency—called lactose intolerance
(LI)—may cause cramps in the abdomen and pain, diarrhea, and bloating. LI can lead to
lower consumption of dairy products [
70
,
71
]. LI is genetically conditioned and associated
with single polymorphism nucleotide of the MCM6 gene in 13910CC and 22018GG [
72
].
Nutrients 2021,13, 1329 7 of 15
Lactose intolerance is different in various countries and affects about 99% of China’s
population, 20% of people in the USA, and below 10% of Scandinavia and Netherland
inhabitants [73].
Milk and dairy products are the main sources of calcium in many regions around the
world. It is vital to note that lactose stimulates calcium absorption in children but not in
adults [
5
]. LI is probably not a direct factor of osteoporosis development; nevertheless,
decreased consumption of dairy products due to lactase deficiency and not replacing them
with other calcium-rich products may cause decreased BMD.
Among Turkish emigrants in Germany, many presented LI, but it did not affect calcium
intake, bone turnover markers or BMD [
74
]. Meta-analysis has shown that there were no
significant differences between subjects with and without lactose LI. The BMD of the total
hip was higher among people with lactose tolerance when compared with subjects with
LI [
73
]. BMD was higher among lactose-tolerant subjects with genotype LCT-13910 TT and
LCT-13910 CT than lactose-intolerant people with genotype LCT-13910 CC but differences
were not significant [
75
]. For osteoporosis prevention, patients with LI should consume
fermented dairy products, lactose-free milk and non-dairy products that are a good source
of calcium [72].
3.2. Cow’s Milk Allergy
Cow’s milk allergy is a disorder that occurs less frequently than lactose intolerance
and is associated with total elimination of milk and dairy products [
76
]. Patients with
IgE-mediated cow’s milk allergy consumed a significantly lower amount of calcium than a
control group. Additionally, IgE-mediated cow’s milk allergy increased risk of lower BMD
and osteoporosis [
77
]. Children with cow’s milk allergy had lower BMD in the lumbar spine
and femoral neck and consumed less calcium when compared with children without the
allergy. The concentration of vitamin D was not different between groups [
78
]. Therefore,
cow’s milk allergy may be associated with development of rickets, and supplementation
with calcium and vitamin D may be necessary [79].
4. Milk and Dairy Products and Gut Microbiota-Modulation of BMD
Gut microbiota—through the production of biologically active compounds, such as
short-chain fatty acids, indole derivatives, polyamines and secondary bile acids—affects
not only intestinal cells but also extra-intestinal cells and modulates the immune response.
Immune cells correlate with bone cells. Therefore, gut microbiota may affect bone turnover
and BMD.
Breast milk is the primary source of nutrition from birth and an important factor for
modulating gut microbiota and the further skeletal system. Human milk oligosaccharides
(HMU), including galactooligosaccharides (GOS), are important for proper gut microbiota
colonization. Bifidobacterium ferments GOS and produces short-chain fatty acids [
23
,
80
].
Bifidobacterium contains lacto-N-biosidase, which facilitates absorption of GOS [
81
]. Ac-
cording to Matsuki et al., an increase in the number of Bifidobacterium increased the amount
of HMO in faces. HMO presented a probiotic effect through selective stimulation of Bifi-
dobacterium [
82
]. The study has shown that the amount of Roseburia, Bifidobacterium and
Lactobacillus correlated positively with BMD and T-score.
Additionally, BMD increased proportionally with an increase in the number of Bifi-
dobacterium [
83
]. Breast milk contains many factors that modulate the immune systems
of infants. There are immunoglobin (IgA, IgG), lysozyme, lactoferrin, and cytokines reg-
ulating immunity (TGF
β
-Transforming growth factor beta and IL-10), which cause a
selection of bacteria colonizing the gastrointestinal tract. IL-10 and TGF-
β
from breast milk
increase immune system toleration for intestine bacteria and promote Il-10 production
in infants [
84
,
85
]. Additionally, the number of Bifidobacterium infantis correlates with the
amount of produced IgA and has an anti-inflammatory effect [
86
]. Breast milk is not sterile
and contains about 600 various bacteria spices and cells of bacteria—mainly Lactobacillus,
Weisella, Streptococcus, Lactococcus, Leuconostoc and Enterococcus, as well as some spices of
Nutrients 2021,13, 1329 8 of 15
Bifidobacterium [
87
,
88
]. It is vital to note that infant formula has a different effect on gut
microbiota composition when compared with breast milk. As Brink et al. have reported,
in the first years of life, the number of Bifidobacterium among infants fed soy formula was
2.6–5 times lower than in breastfed infants [89].
Animal milk contains exosomes, which affect bone formation. Among mice with
glucocorticosteroid-induced osteoporosis, administration of exosomes improved BMD
when compared with a placebo group (without exosomes administration). Additionally,
the amount of Lactobacillus decreased in osteoporosis but increased after the use of ex-
osomes. It appears that exosomes isolated from bovine colostrum may be a potential
element of the prevention of osteoporosis through modification of gut microbiota and bone
remodeling [90].
Fermented dairy products containing probiotic strain may also affect bone metabolism.
The randomized study has shown that Lactobacillus reuteri decreased bone loss in Swedish
women aged 75–80 years with low BMD [
91
]. Additionally, symbiotics containing Lac-
tobacillus,Bifidobacterium and FOS (which are components of dairy products) decreased
bone turnover among postmenopausal women in Iran [
92
]. Moreover, Lactobacillus reuteri
increased serum level of 25OHD among healthy subjects, which affects calcium absorption
and may influence on the rising activity of liver 25-hydroxylase [
93
]. It is vital to notice that
consumption of fermented dairy products had a positive effect on bone health indepen-
dently of total energy, calcium, or protein intakes. This effect was not observed among milk
and cheese consumers [
94
]. Potentially, the probiotics included in these products influence
the bone and should be used in patients with lactose intolerance.
Mice fed fermented peptides from kefir had lower trabecular separation and higher
BMD among ovariectomy mice. Additionally, animal bone had higher mechanical strength
and fracture toughness. Additionally, differentiation of gut microbiota was higher in a
group with kefir supplementation than placebo [95].
Probiotic oligosaccharides occur in breast and plant milk [
96
]. Oligofructose in oat
milk has strong prebiotic properties. Consumption of these beverages increases short-chain
fatty acid production (butyrate, acetate, propionate), decreases the moderate pH of the
colon, increases the faecal mass, and reduces the amount of nitrogen end products and
faecal enzymes, which improves immune system function and increases bone mass [
97
,
98
].
FOS and GOS increase the percentage of Bifidobacterium, which inhibits osteoporosis devel-
opment [
99
,
100
]. Additionally, bacterial fermentation maintains osmotic water retention
in the intestine and increases area absorption [
101
], affecting calcium and phosphorus
absorption. Moreover, there is promotion of calcium-binding protein expression and degra-
dation of molecule-binding minerals (among other oxalates, phytic acid). Among healthy
postmenopausal women, fermented milk increased the availability of serum isoflavones,
which decrease the risk of bone mass loss [102].
Gut microbiota affects bone metabolism through intestinal serotonin (5HT) production.
Duodenal enterochromaffin cells are modulated by gut microbiota and are responsible
for the synthesis of 5HT. Additionally, short-chain fatty acids increase the production of
5HT [
103
]. 5HT decreases osteoblasts proliferation through activation of 5-HT1B receptors
in preosteoblasts [
104
]. Regulation of 5HT by gut microbiota may a therapeutic strategy
for improving bone health.
Probiotic bacteria may affect bone metabolism. An animal study showed pasteurized
Akkermansia muciniphila increased parathyroid hormone concentration and the expres-
sion of calcium transporters in the kidney [
105
]. On the other hand, supplementation of
probiotics containing 7 bacteria spices decreased the parathyroid hormone in osteopenic
patients [
92
]. Additionally, Lactocaseibacillus supplementation decreased high-sensitivity
C-reactive protein [106].
Table 5shows a composition of microorganisms in the selected products.
Nutrients 2021,13, 1329 9 of 15
Table 5. Composition of microorganisms in the selected products.
Milk Bacteria Strain References
Breast milk
Lactocaseibacillus casei
Limosilactobacillus fermentum
Lactobacillus gasseri
Lactobacillus gastricus
Lactiplantibacillus plantarum
Lactobacillus reuteri
Limosilactobacillus rhamnosus
Ligilactobacillus salivarius
Lactobacillus vaginalis
Bifidobacterium breve
Bifidobacterium longum
Streptococcus mitis
Streptococcus salivarius
Streptococcus parasanguinis
Enterococcus faecalis
Enterococcus gallinarum
Staphylococcus epidermidis
Staphylococcus lugdunensis
Staphylococcus aureus
Staphylococcus haemolyticus
Staphylococcus pasteuri
Veillonella atypical
Lactococcus
Weissella
Serratia
Pseudomonas
Veillonella
Leptotrichia
Prevotella
[88,107,108]
Cow’s milk
Lactococcus lactis,
Streptococcus salivarius ssp.
thermophilus,
Lactobacillus acidophilus,
Lacticaseibacillus casei
Limosilactobacillus fermentum.
[109]
Goast milk
Lactococcus lactis,
Lacticaseibacillus paracasei,
Pediococcus pentosaceus,
Leuconostoc mesenteroides,
Streptococcus salivarius subsp.
Thermophilus
Enterococcus faecium
[110]
Soy milk-added probiotics
Lactococcus acidophilus
Lactococcus acidophilus
Lactococcus casei
Bifidobacterium longum
[111,112]
Oats milk-added probiotics Lactococcus plantarum 1010 [113]
Kefir (from cow’s milk)
Acetobacter orientalis
Lactococcus lactis
Lactobacillus gallinarum
Kazachstania unispora
Galactomyces candidum
Geotrichum bryndzae
Saccharomyces cerevisiae
Pichia kudriavzevii
[114]
Kefir (from soy milk)
Lactococcus lactis
Kazachstania unispora
Saccharomyces cerevisiae
Lactobacillus nagelii
Lactiplantibacillus plantarum
[114]
5. Summary—Recommendation for Milk and Dairy Products in the Prevention and
Treatment of Osteoporosis
Intake of milk and dairy products is beneficial for every age group but especially for
children and adolescents, when the development of bone mass is dynamic. Milk and dairy
products are sources of not only high bioavailability calcium but also of vitamin D and
Nutrients 2021,13, 1329 10 of 15
proteins. Patients with a lactose intolerance or cow’s milk allergy should avoid or limit
milk and dairy product consumption.
Breast milk is an optimal food for infants [
96
]. Children should be exclusively breastfed
for the first six months of their life [20].
Human milk is also preferred food for children with a cow’s milk allergy [115].
Breastfeeding should be recommended for one-year-old children and higher as an
element of the diet, if desired by the mother and child [
116
]. However, it should be
reminded that long breastfeeding may affect the BMD of a mother negatively.
Consumption of infant formula between 7 and 12 months of life results in a Ca:P ratio
equal to 1.49:1, which complies with recommendations (1:1–1:2) [26].
Homogenized, pasteurized milk (3.25% fat) may be introduced between 9 and 12
months of life. After 9–12 months, sheep’s milk fortified with vitamin D may be introduced
as an alternative to cow’s milk [117].
One-year-old children should consume 500 mL (two cups) of milk daily [117].
Skimmed milk (1–2% of fat) may be introduced after the second year of life [
117
].
According to the World Health Organization, semi-skimmed milk may be introduced after
12 months of life. Skimmed milk is not recommended for children aged less than 12 months
because it does not contain essential fatty acids, fat-soluble vitamins, and high potential
renal solute load in relation to energy [28].
Plant milk (soy, rice, almond and others) should not be introduced as an alternative to
cow’s milk for children under two years of age [117].
Young child formulae are not necessary for children aged 1–3 years, but their imple-
mentation is one of the strategies used in order to increase intake of vitamin D, iron and
omega-3 fatty acids, which are present in smaller quantities in cow’s milk [116].
Dairy products are a good source of calcium and other nutrients with high bioavailabil-
ity. Three portions of dairy products may cover the daily need for calcium [
51
]. According
to the recommendation for the population of America, adults should consume three cup-
equivalents of fat-free or low-fat (1%) dairy (including milk, yoghurt, cheese or fortified
soy beverages) per day [118].
The elderly should not avoid milk and dairy products, because they are a source of
high-availability protein, vitamin D, calcium, and phosphorus, which are important for
preventing disorders occurring in the elderly, e.g., osteoporosis [
119
]. It is vital to note that
lactose intolerance is often common among older people, and for this group of patients,
fermented dairy products (kefir, yoghurt) and lactose-free milk is the best choice.
It is vital to note that cow’s milk and plant beverages are various products, and plant
milk cannot be considered as a fully valuable alternative to cow’s milk [41].
According to The National Osteoporosis Foundation, data about the impact of dairy
products on bone are moderate [8].
Beneficial modification of gut microbiota due to the consumption of dairy products
may increase calcium absorption and the production of short-chain fatty acids and sero-
tonin, which affect bone metabolism directly.
Author Contributions:
Conceptualization, I.K.-K.; writing—original draft preparation, A.E.R. and
A.Z.; writing—review and editing—A.E.R., A.Z., A.M.R., A.D. and I.K.-K.; visualization—A.M.R.;
supervision—I.K.-K.; project administration—A.D. and I.K.-K.; funding acquisition—A.D. All authors
have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments: Figures were created with Biorender.com (accessed on 16 March 2021).
Conflicts of Interest: The authors declare no conflict of interest.
Nutrients 2021,13, 1329 11 of 15
References
1.
Janiszewska, M.; Kulik, T.; Dziedzic, M.; ˙
Zołnierczuk-Kieliszek, D.; Bara´nska, A. Osteoporosis as a Social Problem- Pathogenesis,
Symptoms and Risk Factors of Postmenopausal Osteoporosis. Probl. Hig. Epidemiol. 2015,96, 106–114.
2.
Pouresmaeili, F.; Kamalidehghan, B.; Kamarehei, M.; Goh, Y.M. A Comprehensive Overview on Osteoporosis and Its Risk Factors.
Ther. Clin. Risk Manag. 2018,14, 2029–2049. [CrossRef]
3.
Ratajczak, A.E.; Rychter, A.M.; Zawada, A.; Dobrowolska, A.; Krela-Ka´zmierczak, I. Nutrients in the Prevention of Osteoporosis
in Patients with Inflammatory Bowel Diseases. Nutrients 2020,12, 1702. [CrossRef]
4. Rosen, C.J. The Epidemiology and Pathogenesis of Osteoporosis; MDText.com, Inc.: South Dartmouth, MA, USA, 2020.
5.
Hodges, J.K.; Cao, S.; Cladis, D.P.; Weaver, C.M. Lactose Intolerance and Bone Health: The Challenge of Ensuring Adequate
Calcium Intake. Nutrients 2019,11, 718. [CrossRef]
6.
Gordon, C.M.; Zemel, B.S.; Wren, T.A.L.; Leonard, M.B.; Bachrach, L.K.; Rauch, F.; Gilsanz, V.; Rosen, C.J.; Winer, K.K. The
Determinants of Peak Bone Mass. J. Pediatrics 2017,180, 261–269. [CrossRef]
7.
Osteoporosis: Peak Bone Mass in Women|NIH Osteoporosis and Related Bone Diseases National Resource Center. Available
online: https://www.bones.nih.gov/health-info/bone/osteoporosis/bone-mass (accessed on 19 December 2020).
8.
Weaver, C.M.; Gordon, C.M.; Janz, K.F.; Kalkwarf, H.J.; Lappe, J.M.; Lewis, R.; O’Karma, M.; Wallace, T.C.; Zemel, B.S. The
National Osteoporosis Foundation’s Position Statement on Peak Bone Mass Development and Lifestyle Factors: A Systematic
Review and Implementation Recommendations. Osteoporos. Int. 2016,27, 1281–1386. [CrossRef] [PubMed]
9.
McGuigan, F.E.A.; Murray, L.; Gallagher, A.; Davey-Smith, G.; Neville, C.E.; Van’t Hof, R.; Boreham, C.; Ralston, S.H. Genetic and
Environmental Determinants of Peak Bone Mass in Young Men and Women. J. Bone Miner. Res. 2002,17, 1273–1279. [CrossRef]
10.
Muscogiuri, G.; Barrea, L.; Altieri, B.; Di Somma, C.; Bhattoa, H.P.; Laudisio, D.; Duval, G.T.; Pugliese, G.; Annweiler, C.; Orio, F.;
et al. Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk. Curr. Vasc. Pharmacol.
2019,17, 610–617. [CrossRef] [PubMed]
11. Fischer, V.; Haffner-Luntzer, M.; Amling, M.; Ignatius, A. Calcium and Vitamin D in Bone Fracture Healing and Post-Traumatic
Bone Turnover. Eur. Cell Mater. 2018,35, 365–385. [CrossRef] [PubMed]
12.
Dadra, A.; Aggarwal, S.; Kumar, P.; Kumar, V.; Dibar, D.P.; Bhadada, S.K. High Prevalence of Vitamin D Deficiency and
Osteoporosis in Patients with Fragility Fractures of Hip: A Pilot Study. J. Clin. Orthop. Trauma 2019,10, 1097–1100. [CrossRef]
13.
Lee, J.S.; Kim, J.W. Prevalence of Vitamin D Deficiency in Postmenopausal High- and Low-Energy Fracture Patient. Arch.
Osteoporos. 2018,13, 109. [CrossRef] [PubMed]
14.
Warburton, D.E.R.; Nicol, C.W.; Bredin, S.S.D. Health Benefits of Physical Activity: The Evidence. CMAJ
2006
,174, 801–809.
[CrossRef] [PubMed]
15.
Maggio, A.B.R.; Rizzoli, R.R.; Marchand, L.M.; Ferrari, S.; Beghetti, M.; Farpour-Lambert, N.J. Physical Activity Increases Bone
Mineral Density in Children with Type 1 Diabetes. Med. Sci. Sports Exerc. 2012,44, 1206–1211. [CrossRef] [PubMed]
16.
Chan, D.-C.; Chang, C.-B.; Han, D.-S.; Hong, C.-H.; Hwang, J.-S.; Tsai, K.-S.; Yang, R.-S. Effects of Exercise Improves Muscle
Strength and Fat Mass in Patients with High Fracture Risk: A Randomized Control Trial. J. Formos. Med. Assoc.
2018
,117, 572–582.
[CrossRef]
17.
Calcium Content of Common Foods | International Osteoporosis Foundation. Available online: https://www.osteoporosis.
foundation/patients/prevention/calcium-content-of-common-foods (accessed on 14 December 2020).
18.
Office of Dietary Supplements-Calcium. Available online: https://ods.od.nih.gov/factsheets/Calcium-Consumer/ (accessed on
8 December 2020).
19.
Ballard, O.; Morrow, A.L. Human Milk Composition: Nutrients and Bioactive Factors. Pediatr. Clin. North. Am.
2013
,60, 49–74.
[CrossRef]
20.
Hytten, F.E. Clinical and Chemical Studies in Human Lactation. VIII. Relationship of the Age, Physique, and Nutritional Status of
the Mother to the Yield and Composition of Her Milk. Br. Med. J. 1954,2, 844–845. [CrossRef]
21. Thomson, A.M.; Black, A.E. Nutritional Aspects of Human Lactation. Bull. World Health Organ. 1975,52, 163–177.
22. Mosca, F.; Giannì, M.L. Human Milk: Composition and Health Benefits. Pediatr. Med. Chir. 2017,39, 155. [CrossRef]
23. Gopalan, C. Effect of Nutrition on Pregnancy and Lactation. Bull. World Health Organ. 1962,26, 203–211.
24.
Pietrzak-Fie´cko, R.; Kamelska-Sadowska, A.M. The Comparison of Nutritional Value of Human Milk with Other Mammals’ Milk.
Nutrients 2020,12, 1404. [CrossRef] [PubMed]
25.
Patin, R.V.; Vítolo, M.R.; Valverde, M.A.; Carvalho, P.O.; Pastore, G.M.; Lopez, F.A. The Influence of Sardine Consumption on the
Omega-3 Fatty Acid Content of Mature Human Milk. J. Pediatr. 2006,82, 63–69. [CrossRef]
26.
Loughrill, E.; Wray, D.; Christides, T.; Zand, N. Calcium to Phosphorus Ratio, Essential Elements and Vitamin D Content of Infant
Foods in the UK: Possible Implications for Bone Health. Matern. Child. Nutr. 2017,13, e12368. [CrossRef]
27.
Mahdi, A.A.; Brown, R.B.; Razzaque, M.S. Osteoporosis in Populations with High Calcium Intake: Does Phosphate Toxicity
Explain the Paradox? Ind. J. Clin. Biochem. 2015,30, 365–367. [CrossRef]
28.
Burgess, K. Milk and Dairy Products in Human Nutrition; Muehlhoff, E., Bennett, A., McMahon, D., Eds.; Food and Agriculture
Organisation of the United Nations (FAO): Rome, Italy, 2013; ISBN 978-92-5-107864-8. [CrossRef]
29.
Aparicio, M.; Browne, P.D.; Hechler, C.; Beijers, R.; Rodríguez, J.M.; de Weerth, C.; Fernández, L. Human Milk Cortisol and
Immune Factors over the First Three Postnatal Months: Relations to Maternal Psychosocial Distress. PLoS ONE
2020
,15, e0233554.
[CrossRef] [PubMed]
Nutrients 2021,13, 1329 12 of 15
30.
Al-Agha, A.E.; Kabli, Y.O.; AlBeiruty, M.G.; Milyani, A.A. Determinants of Bone Mineral Density through Quantitative Ultrasound
Screening of Healthy Children Visiting Ambulatory Paediatric Clinics. Saudi Med. J. 2019,40, 560–567. [CrossRef] [PubMed]
31. Blanco, E.; Burrows, R.; Reyes, M.; Lozoff, B.; Gahagan, S.; Albala, C. Breastfeeding as the Sole Source of Milk for 6 Months and
Adolescent Bone Mineral Density. Osteoporos. Int. 2017,28, 2823–2830. [CrossRef] [PubMed]
32.
van den Hooven, E.H.; Gharsalli, M.; Heppe, D.H.M.; Raat, H.; Hofman, A.; Franco, O.H.; Rivadeneira, F.; Jaddoe, V.W.V.
Associations of Breast-Feeding Patterns and Introduction of Solid Foods with Childhood Bone Mass: The Generation R Study. Br.
J. Nutr. 2016,115, 1024–1032. [CrossRef]
33.
Hwang, I.R.; Choi, Y.K.; Lee, W.K.; Kim, J.G.; Lee, I.K.; Kim, S.W.; Park, K.G. Association between Prolonged Breastfeeding and
Bone Mineral Density and Osteoporosis in Postmenopausal Women: KNHANES 2010–2011. Osteoporos. Int.
2016
,27, 257–265.
[CrossRef]
34.
Tsvetov, G.; Levy, S.; Benbassat, C.; Shraga-Slutzky, I.; Hirsch, D. Influence of Number of Deliveries and Total Breast-Feeding
Time on Bone Mineral Density in Premenopausal and Young Postmenopausal Women. Maturitas 2014,77, 249–254. [CrossRef]
35.
Bolzetta, F.; Veronese, N.; De Rui, M.; Berton, L.; Carraro, S.; Pizzato, S.; Girotti, G.; De Ronch, I.; Manzato, E.; Coin, A.; et al.
Duration of Breastfeeding as a Risk Factor for Vertebral Fractures. Bone 2014,68, 41–45. [CrossRef]
36.
Cooke-Hubley, S.; Gao, Z.; Mugford, G.; Kaiser, S.M.; Goltzman, D.; Leslie, W.D.; Davison, K.S.; Brown, J.P.; Probyn, L.; Lentle, B.;
et al. Parity and Lactation Are Not Associated with Incident Fragility Fractures or Radiographic Vertebral Fractures over 16 Years
of Follow-up: Canadian Multicentre Osteoporosis Study (CaMos). Arch. Osteoporos. 2019,14, 49. [CrossRef]
37.
Kovacs, C.S. Calcium and Phosphate Metabolism and Related Disorders during Pregnancy and Lactation. In Endotext; Feingold,
K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dungan, K., Grossman, A., Hershman, J.M., Hofland, J., Kaltsas, G.,
et al., Eds.; MDText.com, Inc.: South Dartmouth, MA, USA, 2000.
38.
Tunick, M.H.; Van Hekken, D.L. Dairy Products and Health: Recent Insights. J. Agric. Food Chem.
2015
,63, 9381–9388. [CrossRef]
39.
Aryana, K.J.; Olson, D.W. A 100-Year Review: Yogurt and Other Cultured Dairy Products. J. Dairy Sci.
2017
,100, 9987–10013.
[CrossRef]
40.
Kalkwarf, H.J.; Khoury, J.C.; Lanphear, B.P. Milk Intake during Childhood and Adolescence, Adult Bone Density, and Osteoporotic
Fractures in US Women. Am. J. Clin. Nutr. 2003,77, 257–265. [CrossRef]
41.
Thorning, T.K.; Raben, A.; Tholstrup, T.; Soedamah-Muthu, S.S.; Givens, I.; Astrup, A. Milk and Dairy Products: Good or Bad for
Human Health? An Assessment of the Totality of Scientific Evidence. Food Nutr. Res. 2016,60, 32527. [CrossRef]
42.
Goulding, A.; Rockell, J.E.P.; Black, R.E.; Grant, A.M.; Jones, I.E.; Williams, S.M. Children Who Avoid Drinking Cow’s Milk Are at
Increased Risk for Prepubertal Bone Fractures. J. Am. Diet. Assoc. 2004,104, 250–253. [CrossRef]
43.
Wiley, A.S. Does Milk Make Children Grow? Relationships between Milk Consumption and Height in NHANES 1999–2002. Am.
J. Hum. Biol. 2005,17, 425–441. [CrossRef] [PubMed]
44.
Bielemann, R.M.; dos S Vaz, J.; Domingues, M.R.; Matijasevich, A.; Santos, I.S.; Ekelund, U.; Horta, B.L. Are Consumption of
Dairy Products and Physical Activity Independently Related to Bone Mineral Density of 6-Year-Old Children? Longitudinal and
Cross-Sectional Analyses in a Birth Cohort from Brazil. Public Health Nutr. 2018,21, 2654–2664. [CrossRef]
45.
Sioen, I.; Michels, N.; Polfliet, C.; De Smet, S.; D’Haese, S.; Roggen, I.; Deschepper, J.; Goemaere, S.; Valtueña, J.; De Henauw,
S. The Influence of Dairy Consumption, Sedentary Behaviour and Physical Activity on Bone Mass in Flemish Children: A
Cross-Sectional Study. BMC Public Health 2015,15, 717. [CrossRef] [PubMed]
46.
Torres-Costoso, A.; López-Muñoz, P.; Ferri-Morales, A.; Bravo-Morales, E.; Martínez-Vizcaíno, V.; Garrido-Miguel, M. Body Mass
Index, Lean Mass, and Body Fat Percentage as Mediators of the Relationship between Milk Consumption and Bone Health in
Young Adults. Nutrients 2019,11, 2500. [CrossRef] [PubMed]
47.
van Dongen, L.H.; Kiel, D.P.; Soedamah-Muthu, S.S.; Bouxsein, M.L.; Hannan, M.T.; Sahni, S. Higher Dairy Food Intake Is
Associated With Higher Spine Quantitative Computed Tomography (QCT) Bone Measures in the Framingham Study for Men
But Not Women. J. Bone Miner. Res. 2018,33, 1283–1290. [CrossRef]
48.
Mangano, K.M.; Noel, S.E.; Sahni, S.; Tucker, K.L. Higher Dairy Intakes Are Associated with Higher Bone Mineral Density among
Adults with Sufficient Vitamin D Status: Results from the Boston Puerto Rican Osteoporosis Study. J. Nutr.
2019
,149, 139–148.
[CrossRef]
49.
Hallkvist, O.M.; Johansson, J.; Nordström, A.; Nordström, P.; Hult, A. Dairy Product Intake and Bone Properties in 70-Year-Old
Men and Women. Arch. Osteoporos. 2018,13, 9. [CrossRef]
50.
Michaëlsson, K.; Wolk, A.; Langenskiöld, S.; Basu, S.; Warensjö Lemming, E.; Melhus, H.; Byberg, L. Milk Intake and Risk of
Mortality and Fractures in Women and Men: Cohort Studies. BMJ 2014,349, g6015. [CrossRef] [PubMed]
51.
Rozenberg, S.; Body, J.-J.; Bruyère, O.; Bergmann, P.; Brandi, M.L.; Cooper, C.; Devogelaer, J.-P.; Gielen, E.; Goemaere, S.; Kaufman,
J.-M.; et al. Effects of Dairy Products Consumption on Health: Benefits and Beliefs—Commentary from the Belgian Bone Club
and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases. Calcif.
Tissue Int. 2016,98, 1–17. [CrossRef]
52.
Infante, D.; Tormo, R. Risk of Inadequate Bone Mineralization in Diseases Involving Long-Term Suppression of Dairy Products. J.
Pediatric Gastroenterol. Nutr. 2000,30, 310–313. [CrossRef] [PubMed]
53.
Matía-Martín, P.; Torrego-Ellacuría, M.; Larrad-Sainz, A.; Fernández-Pérez, C.; Cuesta-Triana, F.; Rubio-Herrera, M.Á. Effects of
Milk and Dairy Products on the Prevention of Osteoporosis and Osteoporotic Fractures in Europeans and Non-Hispanic Whites
from North America: A Systematic Review and Updated Meta-Analysis. Adv. Nutr. 2019,10, S120–S143. [CrossRef]
Nutrients 2021,13, 1329 13 of 15
54.
Tang, A.L.; Walker, K.Z.; Wilcox, G.; Strauss, B.J.; Ashton, J.F.; Stojanovska, L. Calcium Absorption in Australian Osteopenic
Post-Menopausal Women: An Acute Comparative Study of Fortified Soymilk to Cows’ Milk. Asia Pac. J. Clin. Nutr.
2010
,19,
243–249. [PubMed]
55.
Heaney, R.P.; Dowell, M.S.; Rafferty, K.; Bierman, J. Bioavailability of the Calcium in Fortified Soy Imitation Milk, with Some
Observations on Method. Am. J. Clin. Nutr. 2000,71, 1166–1169. [CrossRef]
56.
Geiker, N.R.W.; Mølgaard, C.; Iuliano, S.; Rizzoli, R.; Manios, Y.; van Loon, L.J.C.; Lecerf, J.-M.; Moschonis, G.; Reginster, J.-Y.;
Givens, I.; et al. Impact of Whole Dairy Matrix on Musculoskeletal Health and Aging–Current Knowledge and Research Gaps.
Osteoporos. Int. 2020,31, 601–615. [CrossRef]
57.
Lee, G.J.; Birken, C.S.; Parkin, P.C.; Lebovic, G.; Chen, Y.; L’Abbé, M.R.; Maguire, J.L. TARGet Kids! Collaboration Consumption of
Non-Cow’s Milk Beverages and Serum Vitamin D Levels in Early Childhood. CMAJ
2014
,186, 1287–1293. [CrossRef] [PubMed]
58.
Gui, J.-C.; Braši´c, J.R.; Liu, X.-D.; Gong, G.-Y.; Zhang, G.-M.; Liu, C.-J.; Gao, G.-Q. Bone Mineral Density in Postmenopausal
Chinese Women Treated with Calcium Fortification in Soymilk and Cow’s Milk. Osteoporos. Int.
2012
,23, 1563–1570. [CrossRef]
59.
García-Martín, A.; Quesada Charneco, M.; Alvárez Guisado, A.; Jiménez Moleón, J.J.; FonolláJoya, J.; Muñoz-Torres, M. Effect of
milk product with soy isoflavones on quality of life and bone metabolism in postmenopausal Spanish women: Randomized trial.
Med. Clin. 2012,138, 47–51. [CrossRef] [PubMed]
60.
Lydeking-Olsen, E.; Beck-Jensen, J.-E.; Setchell, K.D.R.; Holm-Jensen, T. Soymilk or Progesterone for Prevention of Bone Loss—A
2 Year Randomized, Placebo-Controlled Trial. Eur. J. Nutr. 2004,43, 246–257. [CrossRef]
61.
Yanaka, K.; Higuchi, M.; Ishimi, Y. Anti-Osteoporotic Effect of Soy Isoflavones Intake on Low Bone Mineral Density Caused by
Voluntary Exercise and Food Restriction in Mature Female Rats. J. Nutr. Sci. Vitam. 2019,65, 335–342. [CrossRef] [PubMed]
62.
Choi, C.-W.; Choi, S.-W.; Kim, H.-J.; Lee, K.-S.; Kim, S.-H.; Kim, S.-L.; Do, S.H.; Seo, W.-D. Germinated Soy Germ with Increased
Soyasaponin Ab Improves BMP-2-Induced Bone Formation and Protects against in Vivo Bone Loss in Osteoporosis. Sci. Rep.
2018,8, 12970. [CrossRef]
63.
Matthews, V.L.; Knutsen, S.F.; Beeson, W.L.; Fraser, G.E. Soy Milk and Dairy Consumption Are Independently Associated with
Ultrasound Attenuation of the Heel Bone among Postmenopausal Women: The Adventist Health Study-2 (AHS-2). Nutr. Res.
2011,31, 766–775. [CrossRef] [PubMed]
64.
Ambroszkiewicz, J.; Klemarczyk, W.; Gajewska, J.; Chełchowska, M.; Franek, E.; Laskowska-Klita, T. The Influence of Vegan Diet
on Bone Mineral Density and Biochemical Bone Turnover Markers. Pediatr. Endocrinol. Diabetes Metab. 2010,16, 201–204.
65.
Vitoria, I. The Nutritional Limitations of Plant-Based Beverages in Infancy and Childhood. Nutr. Hosp.
2017
,34, 1205–1214.
[CrossRef]
66. Kowalska, D.; Gruczy´nska, E.; Bry´s, J. Mother ’s Milk—First Food in Human Life. Probl. Hig. Epidemiol. 2015,96, 387–398.
67.
Guetouache, M.; Guessas, B.; Medjekal, S. Composition and Nutritional Value of Raw Milk. Issues Biol. Sci. Pharm. Res.
2014
,2,
115–122.
68.
Paul, A.A.; Kumar, S.; Kumar, V.; Sharma, R. Milk Analog: Plant Based Alternatives to Conventional Milk, Production, Potential
and Health Concerns. Crit. Rev. Food Sci. Nutr. 2020,60, 3005–3023. [CrossRef] [PubMed]
69.
Kunachowicz, H.; Przygoda, B.; Nadolna, I.; Iwanow, K. Tabele Skł ˛adu I Warto´sci Od˙
zywczej ˙
Zywno´sci, 2nd ed.; PZWL Wydawnictwo
Lekarskie: Warszawa, Poland, 2017.
70. Heaney, R.P. Dairy Intake, Dietary Adequacy, and Lactose Intolerance12. Adv. Nutr. 2013,4, 151–156. [CrossRef]
71.
Keith, J.N.; Nicholls, J.; Reed, A.; Kafer, K.; Miller, G.D. The Prevalence of Self-Reported Lactose Intolerance and the Consumption
of Dairy Foods among African American Adults Are Less than Expected. J. Natl. Med. Assoc. 2011,103, 36–45. [CrossRef]
72.
Ratajczak, A.E.; Rychter, A.M.; Zawada, A.; Dobrowolska, A.; Krela-Ka´zmierczak, I. Lactose Intolerance in Patients with
Inflammatory Bowel Diseases and Dietary Management in Prevention of Osteoporosis. Nutrition
2020
,82, 111043. [CrossRef]
[PubMed]
73.
Treister-Goltzman, Y.; Friger, M.; Peleg, R. Does Primary Lactase Deficiency Reduce Bone Mineral Density in Postmenopausal
Women? A Systematic Review and Meta-Analysis. Osteoporos. Int. 2018,29, 2399–2407. [CrossRef]
74.
Klemm, P.; Dischereit, G.; Lange, U. Adult Lactose Intolerance, Calcium Intake, Bone Metabolism and Bone Density in German-
Turkish Immigrants. J. Bone Miner. Metab. 2019,38, 378–384. [CrossRef]
75.
Mnich, B.; Spinek, A.E.; Chyle´nski, M.; Sommerfeld, A.; Dabert, M.; Juras, A.; Szostek, K. Analysis of LCT-13910 Genotypes and
Bone Mineral Density in Ancient Skeletal Materials. PLoS ONE 2018,13, e0194966. [CrossRef] [PubMed]
76.
Domínguez-García, V.; Flores-Merino, M.V.; Morales-Romero, J.; Bedolla-Pulido, A.; Mariscal-Castro, J.; Bedolla-Barajas, M.
Allergy to cow’s milk protein, or lactose intolerance: A cross-sectional study in university students. Rev. Alerg. Mex.
2019
,66,
394–402. [CrossRef]
77.
Nachshon, L.; Goldberg, M.R.; Schwartz, N.; Sinai, T.; Amitzur-Levy, R.; Elizur, A.; Eisenberg, E.; Katz, Y. Decreased Bone Mineral
Density in Young Adult IgE-Mediated Cow’s Milk-Allergic Patients. J. Allergy Clin. Immunol.
2014
,134, 1108–1113.e3. [CrossRef]
78.
Mailhot, G.; Perrone, V.; Alos, N.; Dubois, J.; Delvin, E.; Paradis, L.; Des Roches, A. Cow’s Milk Allergy and Bone Mineral Density
in Prepubertal Children. Pediatrics 2016,137, e20151742. [CrossRef]
79.
Yu, J.W.; Pekeles, G.; Legault, L.; McCusker, C.T. Milk Allergy and Vitamin D Deficiency Rickets: A Common Disorder Associated
with an Uncommon Disease. Ann. Allergy Asthma Immunol. 2006,96, 615–619. [CrossRef]
80.
Marcobal, A.; Barboza, M.; Froehlich, J.W.; Block, D.E.; German, J.B.; Lebrilla, C.B.; Mills, D.A. Consumption of Human Milk
Oligosaccharides by Gut-Related Microbes. J. Agric. Food Chem. 2010,58, 5334–5340. [CrossRef]
Nutrients 2021,13, 1329 14 of 15
81.
Sakurama, H.; Kiyohara, M.; Wada, J.; Honda, Y.; Yamaguchi, M.; Fukiya, S.; Yokota, A.; Ashida, H.; Kumagai, H.; Kitaoka,
M.; et al. Lacto- N-Biosidase Encoded by a Novel Gene of Bifidobacterium Longum Subspecies Longum Shows Unique Substrate
Specificity and Requires a Designated Chaperone for Its Active Expression. J. Biol. Chem.
2013
,288, 25194–25206. [CrossRef]
[PubMed]
82.
Matsuki, T.; Yahagi, K.; Mori, H.; Matsumoto, H.; Hara, T.; Tajima, S.; Ogawa, E.; Kodama, H.; Yamamoto, K.; Yamada, T.; et al.
A Key Genetic Factor for Fucosyllactose Utilization Affects Infant Gut Microbiota Development. Nat. Commun.
2016
,7, 11939.
[CrossRef]
83.
Li, C.; Huang, Q.; Yang, R.; Dai, Y.; Zeng, Y.; Tao, L.; Li, X.; Zeng, J.; Wang, Q. Gut Microbiota Composition and Bone Mineral
Loss—Epidemiologic Evidence from Individuals in Wuhan, China. Osteoporos. Int. 2019,30, 1003–1013. [CrossRef] [PubMed]
84.
Levast, B.; Li, Z.; Madrenas, J. The Role of IL-10 in Microbiome-Associated Immune Modulation and Disease Tolerance. Cytokine
2015,75, 291–301. [CrossRef] [PubMed]
85.
Brandtzaeg, P. Mucosal Immunity: Integration between Mother and the Breast-Fed Infant. Vaccine
2003
,21, 3382–3388. [CrossRef]
86.
Chichlowski, M.; De Lartigue, G.; German, J.B.; Raybould, H.E.; Mills, D.A. Bifidobacteria Isolated From Infants and Cultured on
Human Milk Oligosaccharides Affect Intestinal Epithelial Function. J. Pediatric Gastroenterol. Nutr.
2012
,55, 321–327. [CrossRef]
87.
Jeurink, P.V.; van Bergenhenegouwen, J.; Jiménez, E.; Knippels, L.M.J.; Fernández, L.; Garssen, J.; Knol, J.; Rodríguez, J.M.; Martín,
R. Human Milk: A Source of More Life than We Imagine. Benef. Microbes 2013,4, 17–30. [CrossRef]
88.
Jost, T.; Lacroix, C.; Braegger, C.; Chassard, C. Assessment of Bacterial Diversity in Breast Milk Using Culture-Dependent and
Culture-Independent Approaches. Br. J. Nutr. 2013,110, 1253–1262. [CrossRef]
89.
Brink, L.R.; Mercer, K.E.; Piccolo, B.D.; Chintapalli, S.V.; Elolimy, A.; Bowlin, A.K.; Matazel, K.S.; Pack, L.; Adams, S.H.; Shankar,
K.; et al. Neonatal Diet Alters Fecal Microbiota and Metabolome Profiles at Different Ages in Infants Fed Breast Milk or Formula.
Am. J. Clin. Nutr. 2020,111, 1190–1202. [CrossRef]
90.
Yun, B.; Maburutse, B.E.; Kang, M.; Park, M.R.; Park, D.J.; Kim, Y.; Oh, S. Short Communication: Dietary Bovine Milk–Derived
Exosomes Improve Bone Health in an Osteoporosis-Induced Mouse Model. J. Dairy Sci. 2020,103, 7752–7760. [CrossRef]
91.
Nilsson, A.G.; Sundh, D.; Bäckhed, F.; Lorentzon, M. Lactobacillus Reuteri Reduces Bone Loss in Older Women with Low Bone
Mineral Density: A Randomized, Placebo-Controlled, Double-Blind, Clinical Trial. J. Intern. Med.
2018
,284, 307–317. [CrossRef]
[PubMed]
92.
Jafarnejad, S.; Djafarian, K.; Fazeli, M.R.; Yekaninejad, M.S.; Rostamian, A.; Keshavarz, S.A. Effects of a Multispecies Probiotic
Supplement on Bone Health in Osteopenic Postmenopausal Women: A Randomized, Double-Blind, Controlled Trial. Null
2017
,
36, 497–506. [CrossRef] [PubMed]
93.
Jones, M.L.; Martoni, C.J.; Prakash, S. Oral Supplementation With Probiotic L. Reuteri NCIMB 30242 Increases Mean Circulating
25-Hydroxyvitamin D: A Post Hoc Analysis of a Randomized Controlled Trial. J. Clin. Endocrinol. Metab.
2013
,98, 2944–2951.
[CrossRef] [PubMed]
94.
Biver, E.; Durosier-Izart, C.; Merminod, F.; Chevalley, T.; van Rietbergen, B.; Ferrari, S.L.; Rizzoli, R. Fermented Dairy Products
Consumption Is Associated with Attenuated Cortical Bone Loss Independently of Total Calcium, Protein, and Energy Intakes in
Healthy Postmenopausal Women. Osteoporos. Int. 2018,29, 1771–1782. [CrossRef]
95.
Tu, M.-Y.; Han, K.-Y.; Chang, G.R.-L.; Lai, G.-D.; Chang, K.-Y.; Chen, C.-F.; Lai, J.-C.; Lai, C.-Y.; Chen, H.-L.; Chen, C.-M. Kefir
Peptides Prevent Estrogen Deficiency-Induced Bone Loss and Modulate the Structure of the Gut Microbiota in Ovariectomized
Mice. Nutrients 2020,12, 3432. [CrossRef]
96. Whisner, C.M.; Castillo, L.F. Prebiotics, Bone and Mineral Metabolism. Calcif. Tissue Int. 2018,102, 443–479. [CrossRef]
97.
Markowiak, P.; ´
Sli ˙
zewska, K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients
2017
,9, 1021. [CrossRef]
98. Lee, Y.K.; Salminen, S. (Eds.) Handbook of Probiotics and Prebiotics; Wiley: Hoboken, NJ, USA, 2008; ISBN 978-0-470-13544-0.
99.
Bornet, F.R.J.; Brouns, F.; Tashiro, Y.; Duvillier, V. Nutritional Aspects of Short-Chain Fructooligosaccharides: Natural Occurrence,
Chemistry, Physiology and Health Implications. Dig. Liver Dis. 2002,34, S111–S120. [CrossRef]
100.
Vulevic, J.; Juric, A.; Walton, G.E.; Claus, S.P.; Tzortzis, G.; Toward, R.E.; Gibson, G.R. Influence of Galacto-Oligosaccharide
Mixture (B-GOS) on Gut Microbiota, Immune Parameters and Metabonomics in Elderly Persons. Br. J. Nutr.
2015
,114, 586–595.
[CrossRef]
101.
Scholz-Ahrens, K.E.; Ade, P.; Marten, B.; Weber, P.; Timm, W.; A
ς
il, Y.; Glüer, C.-C.; Schrezenmeir, J. Prebiotics, Probiotics, and
Synbiotics Affect Mineral Absorption, Bone Mineral Content, and Bone Structure. J. Nutr.
2007
,137, 838S–846S. [CrossRef]
[PubMed]
102.
Timan, P.; Rojanasthien, N.; Manorot, M.; Sangdee, C.; Teekachunhatean, S. Effect of Synbiotic Fermented Milk on Oral
Bioavailability of Isoflavones in Postmenopausal Women. Null 2014,65, 761–767. [CrossRef] [PubMed]
103.
Yano, J.M.; Yu, K.; Donaldson, G.P.; Shastri, G.G.; Ann, P.; Ma, L.; Nagler, C.R.; Ismagilov, R.F.; Mazmanian, S.K.; Hsiao, E.Y.
Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell 2015,161, 264–276. [CrossRef]
104.
Kode, A.; Mosialou, I.; Silva, B.C.; Rached, M.-T.; Zhou, B.; Wang, J.; Townes, T.M.; Hen, R.; DePinho, R.A.; Guo, X.E.; et al.
FOXO1 Orchestrates the Bone-Suppressing Function of Gut-Derived Serotonin. J. Clin. Investig.
2012
,122, 3490–3503. [CrossRef]
105.
Lawenius, L.; Scheffler, J.M.; Gustafsson, K.L.; Henning, P.; Nilsson, K.H.; Colldén, H.; Islander, U.; Plovier, H.; Cani, P.D.; de
Vos, W.M.; et al. Pasteurized Akkermansia Muciniphila Protects from Fat Mass Gain but Not from Bone Loss. Am. J. Physiol.
Endocrinol. Metab. 2020,318, E480–E491. [CrossRef] [PubMed]
Nutrients 2021,13, 1329 15 of 15
106.
Lei, M.; Guo, C.; Wang, D.; Zhang, C.; Hua, L. The Effect of Probiotic Lactobacillus Casei Shirota on Knee Osteoarthritis: A
Randomised Double-Blind, Placebo-Controlled Clinical Trial. Benef. Microbes 2017,8, 697–703. [CrossRef] [PubMed]
107.
Soto, A.; Martín, V.; Jiménez, E.; Mader, I.; Rodríguez, J.M.; Fernández, L. Lactobacilli and Bifidobacteria in Human Breast Milk:
Influence of Antibiotherapy and Other Host and Clinical Factors. J. Pediatr. Gastroenterol. Nutr. 2014,59, 78–88. [CrossRef]
108.
Cabrera-Rubio, R.; Collado, M.C.; Laitinen, K.; Salminen, S.; Isolauri, E.; Mira, A. The Human Milk Microbiome Changes over
Lactation and Is Shaped by Maternal Weight and Mode of Delivery. Am. J. Clin. Nutr. 2012,96, 544–551. [CrossRef] [PubMed]
109. Igras, S. Characteristics of milk of various animal and human species. J. NutriLife 2012,5.
110.
Pisano, M.B.; Deplano, M.; Fadda, M.E.; Cosentino, S. Microbiota of Sardinian Goat’s Milk and Preliminary Characterization of
Prevalent LAB Species for Starter or Adjunct Cultures Development. BioMed Res. Int.
2019
,2019, e6131404. [CrossRef] [PubMed]
111.
Yeo, S.-K.; Liong, M.-T. Angiotensin I-Converting Enzyme Inhibitory Activity and Bioconversion of Isoflavones by Probiotics in
Soymilk Supplemented with Prebiotics. Null 2010,61, 161–181. [CrossRef] [PubMed]
112.
Zieli´nska, D. Selecting Suitable Bacterial Strains of Lactobacillus and Identifying Soya Drink Fermentation Conditions. ˙
Zywno´c.
Nauka. Technologia. Jako´c 2005,2, 189–297.
113.
Gupta, S.; Cox, S.; Abu-Ghannam, N. Process Optimization for the Development of a Functional Beverage Based on Lactic Acid
Fermentation of Oats. Biochem. Eng. J. 2010,52, 199–204. [CrossRef]
114.
Gamba, R.R.; Yamamoto, S.; Abdel-Hamid, M.; Sasaki, T.; Michihata, T.; Koyanagi, T.; Enomoto, T. Chemical, Microbiological,
and Functional Characterization of Kefir Produced from Cow’s Milk and Soy Milk. Int. J. Microbiol.
2020
,2020, 1–11. [CrossRef]
115.
Vandenplas, Y.; Brueton, M.; Dupont, C.; Hill, D.; Isolauri, E.; Koletzko, S.; Oranje, A.P.; Staiano, A. Guidelines for the Diagnosis
and Management of Cow’s Milk Protein Allergy in Infants. Arch. Dis. Child. 2007,92, 902–908. [CrossRef]
116.
Hojsak, I.; Bronsky, J.; Campoy, C.; Domellöf, M.; Embleton, N.; Fidler Mis, N.; Hulst, J.; Indrio, F.; Lapillonne, A.; Mølgaard, C.;
et al. Young Child Formula: A Position Paper by the ESPGHAN Committee on Nutrition. J. Pediatric Gastroenterol. Nutr.
2018
,66,
177–185. [CrossRef]
117.
Services, A.H. Healthy Infants and Young Children. Available online: https://www.albertahealthservices.ca/info/Page8567.aspx
(accessed on 15 December 2020).
118.
2015–2020 Dietary Guidelines|Health.Gov. Available online: https://health.gov/our-work/food- nutrition/2015-2020-dietary-
guidelines/guidelines/#subnav-3 (accessed on 14 December 2020).
119.
Marangoni, F.; Pellegrino, L.; Verduci, E.; Ghiselli, A.; Bernabei, R.; Calvani, R.; Cetin, I.; Giampietro, M.; Perticone, F.; Piretta, L.;
et al. Cow’s Milk Consumption and Health: A Health Professional’s Guide. J. Am. Coll. Nutr. 2019,38, 197–208. [CrossRef]
... The Mediterranean diet pyramid suggests the daily consumption of moderate amounts of dairy products, principally yoghurt and cheese [5], while dietary recommendations for dairy products throughout the world are 2-3 servings daily [6,7]. Bacillus bulgaricus (now L. bulgaricus), lactic acid bacteria that is still used in yoghurt cultures today, was discovered by Stamen Grigorov, a Bulgarian medical student, in 1905. ...
Article
Full-text available
Probiotic fermented milks and yoghurts are acidified and fermented by viable bacteria, usually L. bulgaricus and S. thermophilus, resulting in a thicker product with a longer shelf life. They are a nutrition-dense food, providing a good source of calcium, phosphorus, potassium, vitamin A, vitamin B2, and vitamin B12. Additionally, they deliver high biological value proteins and essential fatty acids. There is accumulating evidence suggesting that yoghurt and fermented milk consumption is related to a number of health advantages, including the prevention of osteoporosis, diabetes, and cardiovascular diseases, as well as the promotion of gut health and immune system modulation. This review aims at presenting and critically reviewing the beneficial effects from the consumption of probiotic fermented milks in human health, whilst revealing potential applications in the food industry.
... It is widely agreed upon that food supplementation or the use of drug supplements is necessary to improve calcium and vitamin D levels and then prevent the development of osteoporosis (79,80). It is widely established that the progress of bone loss may be significantly delayed by focusing on a diet of milk and dairy products, leading to a healthy lifestyle, and taking appropriate calcium and vitamin supplements (81,82). ...
Article
Full-text available
Osteoporosis is a systemic metabolic disease, mainly characterized by reduced bone mineral density and destruction of bone tissue microstructure. However, the molecular mechanisms of osteoporosis need further investigation and exploration. Increasing studies have reported that circular RNAs (circRNAs), a novel type of RNA molecule, play crucial roles in various physiological and pathological processes and bone-related diseases. Based on an in-depth understanding of their roles in bone development, we summarized the multiple regulatory roles and underlying mechanisms of circRNA–miRNA–mRNA networks in the treatment of osteoporosis, associated with bone marrow mesenchymal stem cells (BMSCs), osteoblasts, and osteoclasts. Deeper insights into the vital roles of circRNA–miRNA–mRNA networks can provide new directions and insights for developing novel diagnostic biomarkers and therapeutic targets in the treatment of osteoporosis.
... Moreover lower consumption of milk in childhood was associated with two times higher fracture risk. Due to this reason, osteoporosis is known as pediatric disease with geriatric consequences (Ratajczak et al. 2021). ...
Chapter
Full-text available
Abstract Milk is the foodstuff that contains nearly all different substances essential for human nutrition. Milk and milk products health benefits are known to humanity and many biological active compounds also exist in milk. In mammalian species it is not only the primary source of nutrition for newborn, but also an excellent source of nutrition for all age groups, which required great amount of nutrition in all over the world. Milk and milk products nutrient-dense foods they provide energy and high biological value protein and all essential minerals such as calcium, magnesium, potassium, zinc, and phosphorus in easily absorbed form. Scientific evidence suggests that milk has therapeutic importance in different diseases such as hypertension, diabetes, hyperlipidemia, heart diseases, overweight, and liver disease, wound healing, lactose intolerance, diarrhea, autism, osteoporosis and cancer etc.
... Moreover lower consumption of milk in childhood was associated with two times higher fracture risk. Due to this reason, osteoporosis is known as pediatric disease with geriatric consequences (Ratajczak et al. 2021). ...
Chapter
Full-text available
Abstract Milk is the foodstuff that contains nearly all different substances essential for human nutrition. Milk and milk products health benefits are known to humanity and many biological active compounds also exist in milk. In mammalian species it is not only the primary source of nutrition for newborn, but also an excellent source of nutrition for all age groups, which required great amount of nutrition in all over the world. Milk and milk products nutrient-dense foods they provide energy and high biological value protein and all essential minerals such as calcium, magnesium, potassium, zinc, and phosphorus in easily absorbed form. Scientific evidence suggests that milk has therapeutic importance in different diseases such as hypertension, diabetes, hyperlipidemia, heart diseases, overweight, and liver disease, wound healing, lactose intolerance, diarrhea, autism, osteoporosis and cancer etc.
Article
Polychlorinated dibenzo‐p‐dioxins and dibenzofurans (PCDD/Fs) are a group of persistent organic pollutants with well‐known toxic effects and potential carcinogenicity. Human exposure to PCDD/Fs is mainly through food, including dairy products. The scientific information on the concentrations of PCDD/Fs in milk and dairy products is here reviewed. It also includes the intake of PCDD/Fs through the consumption of these products. PCDD/Fs concentrations in milk and dairy products are currently decreasing. A similar trend is also noted for their contributions to the total dietary intake of PCDD/Fs. No significant health risks due to exposure to PCDD/Fs through the consumption of dairy products are expected. Environmental dioxins and furans reach the food chain including milk.
Article
Lactase persistence is an autosomal dominant trait characterized by sustained expression of lactase gene throughout adulthood. This trait is mostly prevalent in populations with pastoral or agro-pastoral ancestry and allows lactase persistent individuals to benefit from milk nutrients. Several genetic variants have been identified to be responsible for lactase persistence in different populations and other genetic variants associated with lactase persistence are expected to be found. In this study, we aimed to investigate the lactase persistence phenotype and genotype in two isolated populations, the Iranian Mazani-Shahmirzadi and Afghan Hazaras living in Iran. For this purpose, we genotyped five single nucleotide polymorphisms −13.907C/G, −13.910C/T, −13.913T/C, −13.915T/G and −22.018A/G in 45 Mazanis from Shahmirzad and 50 Hazaras living in the suburb of Tehran. We also investigated lactase persistence by inquiring about digestive symptoms and measuring blood glucose levels after 50g lactose consumption. Our results show that 24.2% of Mazani-Shahmirzadis and 14% of Hazaras are lactase persistent based on blood glucose levels. Genotype investigation shows that only two SNPs, 13.910 C/T and 22.018 A/G display variation in the studied populations. The −13.910*T allele has a frequency of 7.7% in Mazani-Shahmirzadis and 12.7% in Hazaras. The frequency of −22.018*A was 16.6% in Mazani-Shahmirzadis and 17% in Hazaras. Importantly, we found a new genetic variant at −13.913 single nucleotide polymorphism which has not been previously reported. Given that the −13.913 single nucleotide polymorphism is within the enhancer Oct-1 binding site, the presence of this variant could affect lactase gene expression in adults. Further studies are required to elucidate the impact of this variant on LCT gene enhancer function.
Article
Milk and dairy products are important sources of proteins, fats and vitamins. Although Brazil is the fourth largest milk producer in the world, mastitis, metritis, enteritis and respiratory diseases are still important in this industry. A number of antibiotics are employed for treatment and prophylaxis for these diseases, including cephalosporins, lincosamides, aminoglycosides, penicillins, tetracyclines and macrolides. Vaccination offers an important opportunity to reduce the demand for antibiotics. In this review, we present insights into milk production, antibiotic use in the Brazilian dairy industry, the consequences of these activities and perspectives for the control and surveillance of antibiotic resistance. Brazil has an important role in dairy production worldwide, and antibiotics are widely used to control dairy cattle diseases. Improper use of antibiotics can lead to residues in milk and dairy products, as well as antimicrobial resistance in dairy microbiota, relevant hazards for Public Health. Thus, this review presents insights into the antibiotics use in Brazilian dairy cattle, including benefits, consequences and alternatives.
Article
Few studies have characterized bone mineral density (BMD) among health young African women. In our study of 496 Ugandan women age ≤25 years, we found that women had healthy BMD that were lower on average than the standard reference ranges. Reference ranges available for BMD measurements need greater precision. Purpose: Data describing bone mineral density (BMD), nutrient intake, and body composition among healthy, young women in sub-Saharan Africa are limited. Using baseline data from a cohort of young, healthy Ugandan women, we summarize bone health and associated risk factors for reduced bone mass. Methods: Using baseline data from Ugandan women ages 16-25 years who enrolled in an ongoing cohort study of bone health with concurrent use of injectable contraception and oral HIV pre-exposure prophylaxis, we describe the distribution of BMD, nutrient intake, physical activity, and body composition. The association of low BMD (1 or more standard deviations below the age, sex, and race-matched reference range from the USA) and calcium intake, vitamin D intake, physical activity, and body composition was estimated using multivariable logistic regression. Results: In 496 healthy, Ugandan women with median age of 20 years (interquartile range [IQR] 19-21) and median fat:lean mass ratio of 0.55 (IQR 0.46-0.64), median lumbar spine and total hip BMD was 0.9g/cm2 (IQR 0.9-1.0) each. For lumbar spine, Z-score distributions were lower overall than the reference population and 9.3% and 36.3% of women had Z-score >2 and >1 standard deviations below the reference range, respectively. For total hip, Z-scores were similar to the reference population and 1.0% and 12.3% of women had Z-score >2 and >1 standard deviations below the reference range, respectively. In the week prior to enrollment, 41.1% of women consumed >7 servings of calcium, 56.5% had >7 servings of vitamin D, and 98.6% reported ≥2.5 h of physical activity. Having greater body fat was associated with greater frequency of low lumbar spine BMD (p<0.01 for fat:lean mass ratio, total body fat percentage, waist circumference, and BMI). Conclusion: Young Ugandan women exhibited healthy levels of BMD that were lower than the reference range population.
Article
Zusammenfassung Auf fleischfreie Kost und Nahrungsmittel ohne tierische Produkte wird von einer wachsenden Zahl von Bürgern und Bürgerinnen zurückgegriffen. Damit einher gehen Veränderungen des Eiweiß- und Knochenstoffwechsels bei Betroffenen. Aufgrund der vielfältigen Kostformen und häufig auch des veränderten Lebensstils sind Aussagen zu Risiken die Knochen betreffend problematisch. Oft werden den fleischfreien Nahrungsmitteln bestimmte Nährstoffe und Mineralien zugesetzt. Eine antioxidative Wirkung der vegetarischen Kost ist für den Stoffwechsel wahrscheinlich und günstig. Studien zu Frakturen zeigen zumindest in einer großen Studie eine erhöhte Zahl von Brüchen bei veganer Ernährung. Risiken entstehen durch ein geringeres Gewicht und eine verminderte Kalzium- und Eiweißaufnahme. Menschen, die sich vegan ernähren, werden Krafttraining sowie Eiweiß- und Kalzium-Supplementierung empfohlen. Eine abschließende Bewertung dieser Kost- und Lebensformen im Hinblick auf das Risiko, eine Osteoporose zu entwickeln, ist derzeit problematisch und sollte mit Zurückhaltung getroffen werden.
Article
Probiotic dairy products satisfy people's pursuit of health, and are widely favored because of their easy absorption, high nutritional value, and various health benefits. However, its effectiveness and safety are still controversial. This proposal aims to analyze the effect of probiotics on the quality characteristics of dairy products, clarify a series of physiological functions of probiotic dairy products and critically evaluate the effectiveness and safety of probiotic dairy products. Also, dairy products containing inactivated microorganisms were compared with probiotic products. The addition of probiotics enables dairy products to obtain unique quality characteristics, and probiotic dairy products have better health-promoting effects. This review will promote the further development of probiotic dairy products, provide directions for the research and development of probiotic-related products, and help guide the general public to choose and purchase probiotic fermentation products.
Article
Full-text available
Osteoporosis is a major skeletal disease associated with estrogen deficiency in postmenopausal women. Kefir-fermented peptides (KPs) are bioactive peptides with health-promoting benefits that are produced from the degradation of dairy milk proteins by the probiotic microflora in kefir grains. This study aimed to evaluate the effects of KPs on osteoporosis prevention and the modulation of the composition of the gut microbiota in ovariectomized (OVX) mice. OVX mice receiving an 8-week oral gavage of 100 mg of KPs and 100 mg of KPs + 10 mg Ca exhibited lower trabecular separation (Tb. Sp), and higher bone mineral density (BMD), trabecular number (Tb. N) and bone volume (BV/TV), than OVX groups receiving Ca alone and untreated mice, and these effects were also reflected in bones with better mechanical properties of strength and fracture toughness. The gut microbiota of the cecal contents was examined by 16S rDNA amplicon sequencing. α-Diversity analysis indicated that the gut microbiota of OVX mice was enriched more than that of sham mice, but the diversity was not changed significantly. Treatment with KPs caused increased microbiota richness and diversity in OVX mice compared with those in sham mice. The microbiota composition changed markedly in OVX mice compared with that in sham mice. Following the oral administration of KPs for 8 weeks, the abundances of Alloprevotella, Anaerostipes, Parasutterella, Romboutsia, Ruminococcus_1 and Streptococcus genera were restored to levels close to those in the sham group. However, the correlation of these bacterial populations with bone metabolism needs further investigation. Taken together, KPs prevent menopausal osteoporosis and mildly modulate the structure of the gut microbiota in OVX mice.
Article
Full-text available
The chronic character of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, results in various complications. One of them is osteoporosis, manifested by low bone mineral density, which leads to an increased risk of fractures. The aetiology of low bone mineral density is multifactorial and includes both diet and nutritional status. Calcium and vitamin D are the most often discussed nutrients with regard to bone mineral density. Moreover, vitamins A, K, C, B12; folic acid; calcium; phosphorus; magnesium; sodium; zinc; copper; and selenium are also involved in the formation of bone mass. Patients suffering from inflammatory bowel diseases frequently consume inadequate amounts of the aforementioned minerals and vitamins or their absorption is disturbed, resulting innutritional deficiency and an increased risk of osteoporosis. Thus, nutritional guidelines for inflammatory bowel disease patients should comprise information concerning the prevention of osteoporosis.
Article
Full-text available
Background Many biologically active factors are present in human milk including proteins, lipids, immune factors, and hormones. The milk composition varies over time and shows large inter-individual variability. This study examined variations of human milk immune factors and cortisol concentrations in the first three months post-partum, and their potential associations with maternal psychosocial distress. Methods Seventy-seven healthy mothers with full term pregnancies were enrolled, of which 51 mothers collected morning milk samples at 2, 6 and 12 weeks post-delivery. Maternal psychosocial distress was assessed at 6 weeks post-delivery using questionnaires for stress, anxiety, and depressive symptoms. Immune factors were determined using multiplex immunoassays and included innate immunity factors (IL1β, IL6, IL12, IFNγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors (IL5, IL7, GCSF, GMCSF, TGFβ2) and immunoglobulins (IgA, total IgG, IgM). Cortisol was quantified using liquid chromatography-tandem mass spectrometry. A linear mixed effects model was fit to test whether stress, anxiety, and depressive symptoms individually predicted human milk cortisol concentrations after accounting for covariates. Repeated measurement analyses were used to compare women with high (n = 13) versus low psychosocial distress (n = 13) for immune factors and cortisol concentrations. Results Virtually all immune factors and cortisol, with the exception of the granulocyte-macrophage colony-stimulating factor (GMCSF), were detected in the human milk samples. The concentrations of the immune factors decreased during the first 3 months, while cortisol concentrations increased over time. No correlation was observed between any of the immune factors and cortisol. No consistent relationship between postnatal psychosocial distress and concentrations of immune factors was found, whereas higher psychosocial distress was predictive of higher cortisol concentrations in human milk. Conclusion In the current study we found no evidence for an association between natural variations in maternal distress and immune factor concentrations in milk. It is uncertain if this lack of association would also be observed in studies with larger populations, with less uniform demographic characteristics, or with women with higher (clinical) levels of anxiety, stress and/or depressive symptoms. In contrast, maternal psychosocial distress was positively related to higher milk cortisol concentrations at week 2 post-delivery. Further investigation on maternal psychosocial distress in relation to human milk composition is warranted.
Article
Full-text available
1) Background: The variation in the concentration of different components found in milk depends on mammalian species, genetic, physiological, nutritional factors, and environmental conditions. Here, we analyse, for the first time, the content of different components (cholesterol concentration and fatty acids composition as well as the overall fat and mineral content determined using the same analytical methods) in milk of different mammal species. (2) Methods: The samples (n = 52) of human, cow, sheep, goat and mare milk were analyzed in triplicate for: cholesterol concentration, fatty acids profile and fat and mineral content (calcium, magnesium, sodium, potassium, iron, zinc). (3) Results: The highest fat content was reported in sheep milk (7.10 ± 3.21 g/dL). The highest cholesterol concentration was observed in bovine (20.58 ± 4.21 mg/dL) and sheep milk (17.07 ± 1.18 mg/dL). The saturated fatty acids were the lowest in human milk (46.60 ± 7.88% of total fatty acids). Goat milk had the highest zinc (0.69 ± 0.17 mg/dL), magnesium (17.30 ± 2.70 mg/dL) and potassium (183.60 ± 17.20 mg/dL) content. Sheep milk had the highest sodium (52.10 ± 3.20 mg/dL) and calcium (181.70 ± 17.20 mg/dL) concentration values. (4) Conclusions: The differences in nutritional value of milk could be perceived as a milk profile marker, helping to choose the best food for human nutrition.
Article
Full-text available
Kefir is a functional beverage that contains lactic and acetic acid bacteria (LAB, AAB) and yeasts. This work’s aim was to study the chemical, microbial, and functional characteristics of kefir produced from cow’s milk and soy milk. After fermentation, free amino acids were 20.92 mg 100 mL−1 and 36.20 mg 100 mL−1 for cow’s milk and soy milk kefir, respectively. Glutamic acid was majority in both, suggesting that microbial proteolysis leads to an increase in free amino acids including glutamic acid. 108–109 CFU mL−1 LAB, 106–107 CFU mL−1 AAB, and 106–107 CFU mL−1 yeasts were counted in cow’s milk kefir, whereas soy milk kefir contained greatly lower yeasts and AAB. Lactococcus lactis, Kazachstania unispora, and Saccharomyces cerevisiae were isolated as major microorganisms in both kefirs. Acetobacter orientalis only existed in cow’s milk kefir. Cow’s milk and soy milk showed ACE inhibitory activity, which significantly increased after fermentation. Both kefirs also exhibited antioxidant activity and bactericidal activity against Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus.
Article
Full-text available
Background Neonatal diet has a large influence on child health and might modulate changes in fecal microbiota and metabolites. Objectives The aim is to investigate fecal microbiota and metabolites at different ages in infants who were breastfed (BF), received dairy-based milk formula (MF), or received soy-based formula (SF). Methods Fecal samples were collected at 3 (n = 16, 12, and 14, respectively), 6 (n = 20, 19, and 15, respectively), 9 (n = 12, 11, and 12, respectively), and 12 mo (n = 14, 14, and 15, respectively) for BF, MF, and SF infants. Infants that breastfed until 9 mo and switched to formula were considered as no longer breastfeeding at 12 mo. Microbiota data were obtained using 16S ribosomal RNA sequencing. Untargeted metabolomics was conducted using a Q-Exactive Hybrid Quadrupole-Orbitrap mass spectrometer. The data were analyzed using R (version 3.6.0) within the RStudio (version 1.1.463) platform. Results At 3, 6, and 9 mo of age BF infants had the lowest α-diversity, SF infants had the highest diversity, and MF was intermediate. Bifidobacterium was 2.6- to 5-fold lower in SF relative to BF infants through 1 y of life. An unidentified genus from Ruminococcaceae higher in the SF (2%) than in the MF (0.4%) and BF (0.08%) infants at 3 mo of age was observed. In BF infants higher levels of butyric acid, d-sphingosine, kynurenic acid, indole-3-lactic acid, indole-3-acetic acid, and betaine were observed than in MF and SF infants. At 3 mo Ruminococcaceae was positively correlated to azelaic, gentisic, isocitric, sebacic, and syringic acids. At 6 mo Oscillospira was negatively correlated with 3-hydroxybutyric-acid, hydroxy-hydrocinnamic acid, and betaine whereas Bifidobacterium was negatively associated with 5-hydroxytryptamine. At 12 mo of age, Lachnospiraceae was negatively associated with hydroxyphenyllactic acid. Conclusions Infant diet has a large impact on the fecal microbiome and metabolome in the first year of life.
Article
Full-text available
Background: Factors like ethnic origin and geographical area affect the frequency of cow’s milk protein allergy (CMPA) and lactose intolerance (LI). Epidemiological information about the non-pediatric population is still missing. Objective: To determine the prevalence of CMPA and LI in university students. Methods: A cross-sectional study of 1200 students of 18 to 25-year-old. A structured questionnaire was applied in order to identify the clinical manifestations triggered by the intake of cow’s milk (CM), and these were categorized as linked to CMPA or linked to LI. Results: Thirty students met the criteria for CMPA (prevalence of 2.5 %; CI 95 % = 1.7-3.6 %) and 128 for LI (prevalence of 10.7 %, CI 95 % = : 9.0 % - 12.5 %). The frequency of personal history of food allergy and dust mite allergy was higher in students with CMPA than in students with LI. Oral pruritus, skin and respiratory discomforts were predominant in CMPA. Abdominal cramps and flatulence were predominant in LI. Conclusions: IL is more frequent than CMPA; which frequency was one in every 10 students; and the frequency of CMPA was one in 400.
Article
Lactose intolerance affects 33-75% of the world population and may be associated with various genetic factors. Lactose in the diet can be found in milk and dairy products which simultaneously constitute the primary sources of calcium. Gut microbiota also influences lactose tolerance. Patients with lactose intolerance often resign from milk and dairy products, which may lead to calcium and vitamin deficiency and osteoporosis. Insufficient production of lactase also occurs in patients suffering from diseases of the gastrointestinal tract, such as inflammatory bowel diseases. Moreover, Crohn's disease and ulcerative colitis are a risk factors for osteoporosis, and the intake of the proper amount of calcium is an essential element in preventing the decrease of bone mineral density. Diet may prevent the development of osteoporosis, thus, educating patients regarding proper diet should constitute a part in the treatment and prevention process. Patients should consume low-lactose, or lactose-free milk and bacterially fermented dairy products. Additionally, plant milk supplemented by calcium and vitamin D, mineral water with calcium, and certain vegetables may also be good sources of calcium.
Article
Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase–stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications.
Article
Probiotic bacteria can protect from ovariectomy (ovx)-induced bone loss in mice. Akkermansia muciniphila is considered to have probiotic potential due to its beneficial effect on obesity and insulin resistance. The purpose of the present study was to determine if treatment with pasteurized Akkermansia muciniphila (p Akk) could prevent ovx-induced bone loss. Mice were treated with vehicle or p Akk for 4 weeks, starting 3 days before ovx or sham surgery. Treatment with p Akk reduced fat mass accumulation confirming earlier findings. However, treatment with p Akk decreased trabecular and cortical bone mass in femur and vertebra of gonadal intact mice and did not protect from ovx-induced bone loss. Treatment with p Akk increased serum parathyroid hormone (PTH) levels and increased expression of calcium transporter Trpv5 in kidney suggesting increased reabsorption of calcium in the kidneys. Serum amyloid A 3 (SAA3) can suppress bone formation and mediate the effects of PTH on bone resorption and bone loss in mice and treatment with p Akk increased serum levels of SAA3 and gene expression of Saa3 in colon. Moreover, regulatory T cells can be protective of bone and p Akk treated mice had decreased number of regulatory T cells in mesenteric lymph nodes and bone marrow. In conclusion, treatment with p Akk protected from ovx-induced fat mass gain but not from bone loss and reduced bone mass in gonadal intact mice. Our findings with p Akk differ from some probiotics that have been shown to protect bone mass, demonstrating that not all prebiotic and probiotic factors have the same effect on bone.