Supplementation with antioxidants and phenolic compounds in ruminant feeding and its effect on dairy products: a systematic review

Abstract

Milk and dairy products have great importance in human nutrition related to the presence of different nutrients, including protein, fatty acid profile and bioactive compounds. Dietary supplementation with foods containing these types of compounds may influence the chemical composition of milk and dairy products and hence, potentially, the consumer. Our objective was to summarize the evidence of the effect of supplementation with antioxidants and phenolic compounds in the diets of dairy animals and their effects on milk and dairy products. We conducted a systematic search in the MEDLINE/PubMed database for studies published up until July 2022 that reported on supplementation with antioxidants and phenolic compounds in diets that included plants, herbs, seeds, grains and isolated bioactive compounds of dairy animals such as cows, sheep and goats and their effects on milk and dairy products. Of the 94 studies identified in the search, only 15 met the inclusion criteria and were analyzed. The review revealed that supplementation with false flax cake, sweet grass, Acacia farnesiana, mushroom myceliated grains and sweet grass promoted an effect on the milk lipid profile, whereas supplementation with dried grape pomace and tannin extract promoted an effect on the milk and cheese lipid profiles. In six studies, the addition of Acacia farnesiana, hesperidin or naringin, durum wheat bran, mushroom myceliated grains, dried grape pomace and olive leaves increased the antioxidant activity of milk. In conclusion, supplementation with bioactive compounds had a positive impact which ranged from an increase in antioxidant capacity to a decrease in oxidative biomarkers such as malondialdehyde.

Full text

Journal of Dairy Research
cambridge.org/dar
Invited Review
*Both authors contributed equally.
Cite this article: Avila-Nava A, Medina-Vera I,
Toledo-Alvarado H, Corona L and Márquez-
Mota CC. Supplementation with antioxidants
and phenolic compounds in ruminant feeding
and its effect on dairy products: a systematic
review. Journal of Dairy Research https://
doi.org/10.1017/S0022029923000511
Received: 9 November 2022
Revised: 6 July 2023
Accepted: 10 July 2023
Keywords:
Bioactive compounds; dairy products; diet;
milk; supplementation
Corresponding author:
Claudia C. Márquez-Mota;
Email: c.marquez@unam.mx
© The Author(s), 2023. Published by
Cambridge University Press on behalf of
Hannah Dairy Research Foundation. This is an
Open Access article, distributed under the
terms of the Creative Commons Attribution
licence (http://creativecommons.org/licenses/
by/4.0/), which permits unrestricted re-use,
distribution and reproduction, provided the
original article is properly cited.
Supplementation with antioxidants and
phenolic compounds in ruminant feeding and
its effect on dairy products: a systematic review
Azalia Avila-Nava1,*, Isabel Medina-Vera2,*, Hugo Toledo-Alvarado3, Luis Corona4
and Claudia C. Márquez-Mota4
1
Hospital Regional de Alta Especialidad de la Península de Yucatán (HRAEPY), Mérida, México;
2
Departamento de
Metodología de la Investigación, Instituto Nacional de Pediatría (INP), Ciudad de México, México;
3
Departamento
de Genética y Bioestadística, Facultad de Medicina Veterinaria y Zootecnia (FMVZ), Universidad Nacional
Autónoma de México, Ciudad de México, México and
4
Departamento de Nutrición Animal y Bioquímica, Facultad
de Medicina Veterinaria y Zootecnia (FMVZ), Universidad Nacional Autónoma de México, Ciudad de México, México
Abstract
Milk and dairy products have great importance in human nutrition related to the presence of
different nutrients, including protein, fatty acid profile and bioactive compounds. Dietary sup-
plementation with foods containing these types of compounds may influence the chemical
composition of milk and dairy products and hence, potentially, the consumer. Our objective
was to summarize the evidence of the effect of supplementation with antioxidants and phen-
olic compounds in the diets of dairy animals and their effects on milk and dairy products. We
conducted a systematic search in the MEDLINE/PubMed database for studies published up
until July 2022 that reported on supplementation with antioxidants and phenolic compounds
in diets that included plants, herbs, seeds, grains and isolated bioactive compounds of dairy
animals such as cows, sheep and goats and their effects on milk and dairy products. Of the
94 studies identified in the search, only 15 met the inclusion criteria and were analyzed.
The review revealed that supplementation with false flax cake, sweet grass, Acacia farnesiana,
mushroom myceliated grains and sweet grass promoted an effect on the milk lipid profile,
whereas supplementation with dried grape pomace and tannin extract promoted an effect
on the milk and cheese lipid profiles. In six studies, the addition of Acacia farnesiana, hesper-
idin or naringin, durum wheat bran, mushroom myceliated grains, dried grape pomace and
olive leaves increased the antioxidant activity of milk. In conclusion, supplementation with
bioactive compounds had a positive impact which ranged from an increase in antioxidant cap-
acity to a decrease in oxidative biomarkers such as malondialdehyde.
Milk is the sole and primary source of nutrition for newborns, and it has been demonstrated to
be important for children’s growth and adult health (Zhang et al., 2021). The beneficial effects
are related to the presence of different nutrients, including protein, fat, lactose, essential miner-
als including calcium and magnesium, fat-soluble vitamins (A, D, E, and K) and bioactive
compounds (Gil and Ortega, 2019; Scholz-Ahrens et al., 2020). Among these bioactive com-
pounds are polyphenols, peptides and polyunsaturated fatty acids (PUFA), which are related to
improved health. For children and adults, the main sources of milk and dairy products are
dairy cattle, buffaloes, goats and sheep (Ferro et al., 2017). However, the chemical composition
and presence of different bioactive compounds in the milk of these species can fluctuate due to
several factors, such as animal breed, stage of lactation, season, management and nutrition.
Many strategies have been implemented to enhance dairy ruminant product quality, one of
which is to focus on the influence of dietary supplementation.
The enrichment of ruminant diets with agro-industrial by-products ( for example, citrus
pulp, grape pomace and pulp, molasses and olive leaves) that are rich in bioactive compounds
such as polyphenols has been demonstrated to improve the nutritional and chemical compos-
ition of milk and dairy products (Křížová et al., 2021). Dietary supplementation has an
important role regarding the presence of antioxidants in milk and dairy products. For example,
supplementation with citrus pulp (9–18%) increased the polyphenol and flavonoid concentra-
tions in Holstein milk (Santos et al., 2014). The identification of these types of compounds is
important because they are thought to have health benefits, such as lowering blood pressure,
stopping Gram-negative pathogens like Escherichia coli and Salmonella typhi (Murakami et al.,
2004) and having anti-inflammatory and antioxidant effects (Marcone et al., 2017).
Fatty acids also play a significant role in the nutritional value of ruminant products and can
be influenced by the enrichment of ruminant diets. The type and quantity of fatty acids in milk
are influenced by the animal’s breed, lactation stage, husbandry and diet (Tzamaloukas et al.,
2021). Ianni et al., 2019 found that adding grape pomace to the diet of Friesian cows increased
https://doi.org/10.1017/S0022029923000511 Published online by Cambridge University Press

the concentration of polyphenols and linoleic (C18:3n-3), vacce-
nic (C18:1 trans 11) and rumenic (C18:2 cis 9, trans 11) acids
in the cheese. It is known that polyunsaturated fatty acid
(PUFA) content in milk plays an important role in consumer
health (Chilliard and Ferlay, 2004). Thus, this review aimed to
summarize evidence of the effects of dietary supplementation
with antioxidants and phenolic compounds on the milk and
dairy products of the main dairy animals.
Materials and methods
The present study was performed following the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis (PRISMA) guide-
lines (Page et al., 2021). The study design required neither
Institutional Review Board approval nor patient informed consent.
Search strategy
Two authors (AAN and IMV) performed the search strategy inde-
pendently. The studies were identified through the online source
MEDLINE/PubMed. The search was conducted for articles pub-
lished until July 2022. We applied the description of the popula-
tion, intervention, control and outcomes (PICO) strategy as
described by Methley et al.(2014), where the population was
dairy ruminants, the interventions were bioactive compounds
and antioxidants in diets, a standard ruminant diet was the con-
trol and the outcomes were the fatty acid profile, bioactive com-
pounds and antioxidant levels in the milk and dairy products of
the population (online Supplementary Table S1).
Potential articles were searched using keywords by construct-
ing blocks of descriptors in English. The Boolean operators
AND (to add at least one word from each group) and OR (to
list at least one word from each block), parentheses (to combine
search terms by outcome categories) and quotation marks (to
search for exact terms or expressions) were used. The groups of
descriptors for the search strategy related to the outcome in
dairy products were Ruminants AND bioactive compound
AND dairy products NOT a review, Ruminants AND bioactive
compound supplementation AND dairy product.
Selection of studies
After removing duplicates, the same authors (AAN and IMV)
independently screened the titles and abstracts for eligibility
evaluation based on the inclusion criteria. The title and abstract
candidates to enter the review were evaluated in accordance
with their eligibility criteria by all authors. Finally, data extraction
of the full texts was carried out. Original studies were included if
they met the following criteria:
(1) performed on ruminants ( for this review, the search only
focused on dairy goats, cows and sheep)
(2) reporting dietary interventions that included bioactive com-
pounds and antioxidants in the diet of ruminants
(3) a design with a standard diet as a comparator
(4) reporting change or concentration of the fatty acid profile,
bioactive compounds and antioxidants in milk and dairy pro-
ducts of the ruminants.
Exclusion criteria were:
(1) in vitro studies
(2) characterization of antioxidant concentrations in milk and
dairy products without intervention studies
(3) studies where the intervention was focused on comparing
feeding by different types of grazing and did not supplement.
Data extraction
Data extraction for all selected articles was performed in-
dependently by all authors. This information included the
ruminant species, the bioactive compound(s), the description of
the intervention, the comparator, the follow-up time, the type of
product studied, the main findings about dairy products and finally
the first author’s name and year of publication. The process of iden-
tification and extraction is given at online Supplementary Fig. S1
and the complete list of references is at online Supplementary
Table S2.
Results
According to the search, 94 articles were identified, and when
duplicates were excluded 81 records were evaluated with title
and abstract. In accordance with the eligibility criteria 66 articles
were excluded (online Supplementary Table S2). The principal
reasons to exclude articles by title and abstract were:
no-intervention (n= 17), no-intervention in ruminants (n= 14),
food characterization study (n= 12), in vitro study (n= 8), inter-
vention different from the stated objective (n= 6), study of sup-
plementation food or food creation (n= 5), review study (n=2)
and interventions that did not involve bioactive compounds (n
= 2). Finally, 15 articles were included in the review (online
Supplementary Fig. S1).
Animal models, study designs and dairy products
The studies included in the analysis showed a range of publica-
tions from 2014 to 2022 (Table 1). Animal models included
were sheep (2 papers), cows (9 papers) and goats (4 papers).
Some studies also reported the progeny of the animals such as
primiparous (Safari et al., 2018;Liet al., 2021) and multiparous
(Hausmann et al., 2018; Safari et al., 2018;Liet al., 2021; Wang
et al., 2021) and included the period of lactation (Ianni et al.,
2019,2021; Bonanno et al., 2019b; Mapato et al., 2021; Menci
et al., 2021) or specified mid-lactation (Scuderi et al., 2019;
Simitzis et al., 2019). Design of the studies included randomized
(Cais-Sokolińska et al., 2015; Hausmann et al., 2018; Safari et al.,
2018; Ianni et al., 2019; Bonanno et al., 2019a; Walkenhorst et al.,
2020;Liet al., 2021; Wang et al., 2021), stratified (Scuderi et al.,
2019; Walkenhorst et al., 2020), allocated (Delgadillo-Puga et al.,
2019; Simitzis et al., 2019) and 4 × 4 Latin square design with a
2 × 2 factorial arrangement (Mapato et al., 2021). Dairy products
evaluated in different studies included kefir (Cais-Sokolińska
et al., 2015), milk (all other papers) and, additionally, cheese
(Ianni et al., 2019; Bonanno et al., 2019a,2019b; Menci et al.,
2021).
Types of supplementation
Interventions with plants, herbs, seeds, grains and isolated bio-
active compounds were used in the studies. Among the plants
included in the interventions were Acacia farnesiana
(Delgadillo-Puga et al., 2019), bamboo grass (Mapato et al.,
2021), olive leaves (Ianni et al., 2021), herbal feed additives
2 Azalia Avila‐Nava et al.
https://doi.org/10.1017/S0022029923000511 Published online by Cambridge University Press

Table 1. Bioactive compounds and nutritional interventions used in dairy cattle and its effect on milk and dairy products
Ruminant
specie (P) Bioactive compounds Intervention (I) Comparator (C)
Follow-up
time
Type of
product
studied Main findings (O) Article
Holstein
dairy cows
(n= 36)
Pomegranate seeds (PS)
Total phenolic compounds (1.61
g/kg) and Total tannins (1.31 g/
kg)
Pomegranate seed pulp and peels
(PSP)
Total phenolic compounds (25.5
g/kg) and Total tannins (21.9 g/
kg)
Diet supplemented
with PS (400 g/cow/d)
Diet supplemented
with PSP (400 gof
seeds/cow per day +
1200 gof peels/
cow/d)
Control diet no
pomegranate
by-products (CON)
From 25 d
before the
expected
calving date
to 25 d
postpartum
Milk In PS and PSP
Yield (kg/d):
↑3.5% FCM
↑ECM
↑Fat
There were no changes in milk
composition.
↓lipid oxidation
↓peroxidation
Safari et al.
(2018)
Holstein
dairy cows
(n= 140)
Plant bioactive lipid compounds
+ biotin (PBLC + B)
Timol, eugenol, limonene and
vainilln
Diet supplemented
with PBLC + B (2 g/d
and 40 mg/d)
Diet supplemented
with monensin.
(MON)
Non-supplemented
control diet (CON)
Phase1: d-21
to d-1
prepartum
Phase 2: d1-37
d postpartum
Phase 3: d38
to d58
postpartum
Milk There was not difference in milk
yield in PBLC and MON in d 21
and 37 after calving.
On d 21
there was no difference in fat in
PBLC and MON
↑(trend) on milk protein in PBLC
vs. MON
On d 37
↑fat in PBLC + B vs. MON
↑(trend) in ECM in PBLC vs. MON
Phase 2
↑ECM in PLBLC + B vs. MON and
CON
Phase 3
↑ECM in PLBLC + B and MON vs.
CON
Hausmann et al.
(2018)
Holstein
dairy cows
(n= 14)
Perilla frutescens leaf (PFL)
Clareolide (13.1%), betaine
(8.26%), sucrose (7.48%),
scutellarin (6.15%) and apigenin
(5.24%)
Total mixed ration
diet with dietary PFL
at 300 g/d per cow
Total mixed ration diet
(CON)
1-week
adaptation
and 8-week
sampling
period
Milk PFL vs. CON
↑oleanolic acid, DG (18:0/20:4
(5Z,8Z,11Z,14Z)/0:0), PE-NMe(18:1
(9Z)/18:1(9Z)), thymidine,
thymine, 6-phospho-D-gluconate,
2-ketobutyric acid,
2-phenylacetamide,
1-phenylethylamine,
N-acetyl-D-Glucosamine
6-Phosphate, 3- methyluridine,
azelaic acid, deoxythymidine 5′
-phosphate, D-ribulose
1,5-bisphosphate, stearic acid,
and palmitic acid
↓LysoPC (18:1(9Z)), ononin,
glyceric acid, acetylcholine,
D-glucono-1,5-lactone, ribitol,
2-hydroxycaprylic acid, Leu-Ala,
daidzin, and 3-methylhistidine
Wang et al.
(2021)
(Continued)
Journal of Dairy Research 3
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Table 1. (Continued.)
Ruminant
specie (P)
Bioactive compounds Intervention (I) Comparator (C) Follow-up
time
Type of
product
studied
Main findings (O) Article
Dairy sheep,
Chio breed
(n= 36)
Hesperidin
Naringin
α-tocopheryl acetate
H: Alfalfa hay and
concentrate
supplemented with
Hesperidin (6000 mg/
kg)
Alfalfa hay and
concentrate
supplemented with
Naringin (N) (6000
mg/kg)
Alfalfa hay and
concentrate
supplemented with
α-tocopheryl acetate
(VE) (200 mg/kg)
Alfalfa hay and
concentrate (CON)
1-week
adaptation
4-week
treatment
Milk H, N and VE vs. C
There was not difference in milk
yield (mL)
There was not difference in milk
fat (%)
There was not difference in milk
protein (%)
↓MDA
↑Oxidative stability after 14d with
H and N vs. VE and C
Simitzis et al.
(2019)
Dairy goats,
Polish
White
Improved
(n= 66)
Camelina sativa cake
Tocopherols (CS) (700 mg/kg)
Concentrate
supplemented with
CS (120 g/d)
Concentrate without
supplementation
(CON)
During
lactation
Kefir CS vs. CON
↑proportion of PUFA in CS ↑CLA
↑n-3 fatty acids
Cais-Sokolińska
et al.(2015)
Italian Red
Pied dairy
cows
(n= 36)
Durum wheat bran at 0% (DWB0),
10%(DWB10) and 20% (DWB20)
Ferulic acid
Total mixed ratio
supplemented with
DWB10 (1.5 kg/d per
cow)
Total mixed ratio
supplemented with
DWB20 (3 kg/d per
cow)
Total mixed ratio
without DWB0
100 d of
lactation
Milk and
cheese
DWB10 and DWB20 did not
modify milk yield.
DWB20 vs. DWB10 and DWB0
↑casein and curd firmness
↑polyphenol content in chesses
↑antioxidant capacity in cheeses
↓peroxidation in cheeses
Bonanno et al.
(2019a)
Dairy sheep,
Valle del
Belice
(n= 21)
Mushroom myceliated grains at
different percentages 0% (MMG0),
10% (MMG10) and 20% (MMG20)
Total phenolic compounds (0.84 g
GAE/kg DM)
Sulla hay and
concentrate
supplemented with
MMG10
Sulla hay and
concentrate
supplemented with
MMG20
Sulla hay and
concentrate with
MMG0
8 weeks Milk and
cheese
MMG20 vs. MMG10 and MMG0
↑milk casein content
↑Trolox equivalent antioxidant
capacity in cheese
Bonanno et al.
(2019b)
Dairy goats,
French
Alpine
(n= 50)
Acacia farnesiana (AF)
Quercetin, gallic acid, catechin
and epicatechin
Conventional diet +
10% of AF pods
(AF10)
Conventional diet +
20% AF (AF20)
Conventional diet +
30% AF (AF30)
Grazing (G) without
supplementation
Conventional diet
without AF (CD)
Lactation
period of 150
d
Milk AF20 and AF30 vs. AF10 and C
↑antioxidant activity
↑Polyphenols
↓cholesterol content
Delgadillo-Puga
et al.(2019)
Dairy goats
(n= 24)
Fumaric acid (FUM)
N-[2-(nitrooxy)
ethyl]-3-pyridinecarboxamide
(NPD)
Basal diet
supplemented with
FUM (34 g/d)
Basal diet
Basal diet without any
additives (CON)
12 weeks Milk NPD
↑Daily milk production
↑(trend) fat corrected milk
↑T-AOC ↑SOD
Li et al.(2021)
4 Azalia Avila‐Nava et al.
https://doi.org/10.1017/S0022029923000511 Published online by Cambridge University Press

supplemented with
NDP (0.5 g/d)
Basal diet
supplemented with
both FUM (34 g/d)
and NPD (0.5 g/d)
FUM
↓Milk fat content
↓(trend) daily far yield
↓MDA ↑T-AOC
Dairy cows
(n= 14)
Tannins (TAN) Diet supplemented
with TAN (150 g/
head/d)
Diet without TAN
supplementation
(CON)
23 d Milk and
cheese
TAN vs. CON
There was no difference in milk
yield, milk fat.
or milk protein (g/kg)
There was no difference in cheese
yield (g /100 g)
Menci et al.
(2021)
Dairy cows
(n=4)
Bamboo grass (BP)
Condensed Tannins (3.2 g/ 100 g
MS)
Rice straw (RS) and
concentrate
supplemented with
BP (150 g/d)
Sweet straw and
concentrate
supplemented with
BP (150 g/d)
(SG-150BP)
and concentrate
supplemented without
BP (RS-0BP)
Sweet straw and
concentrate
supplemented without
BP (SG-0BP)
14 d
adaptation
and 7 d
sampling
period
Milk SG-150BP and SG-0BP vs.
RS-150BP and RS-0BP
↑Milk yield (kg/day)
↑3.5% FCM (kg/ day)
↑UFA, MUFA and PUFA (g/100 g
FA)
SG-150BP vs. SG-0BP, RS-150BP
and RS-0BP
↑Fat (%)
↑Protein (%)
RS-150BP and RS-0BP vs.
SG-150BP and SG-0BP
↑MCFA ( g/100 gFA)
Mapato et al.
(2021)
Dairy goats,
Saanen (n=
30)
Olive leaves (OL)
Oleuropeosides, flavones, caffeic
acid, tyrosol, and hydroxytyrosol
Polyphite hay and
concentrate
supplemented with
10% OL (EG)
Polyphite hay and
concentrate without
OL (CG)
30 d Milk EG vs. CG
↑Total phenolic compounds
↑Antioxidant activity
↑Apigenin
↑Kaempferol
↑Luteolin
↑Rutin
Ianni et al.(2021)
Friesian
dairy cows
(n= 18)
Grape pomace (GP)
Phenolic acids, flavonoids,
tannins and proanthocyanidins
Maize silage, alfalfa
hay and concentrate
supplemented with
5.1% of grape
pomace.
(GP + )
Maize silage, alfalfa
hay and concentrate
supplemented without
grape pomace.
(GP-)
60 d Milk,
cheese
GP + vs GP-
↑linoleic, vaccenic, and rumenic
acids in milk and cheese
↑Antioxidant activity
↑Total phenolic compounds
Ianni et al.(2019)
Dairy cows
(n= 10)
Grape marc (GPM)
Condensed tannins
Grass silage, corn
silage and
concentrate
supplemented with
GPM (1.5 kg dry
matter/cow/d)
Grass silage, corn
silage and concentrate
supplemented
without) (CON)
14 d
adaptation
and 7 d
sampling
period
Milk GPM vs. CON
There was no difference in milk
yield or milk composition.
Scuderi et al.
(2019)
Dairy cows
(n= 81)
Multicomponent herbal feed
additive (HFA)
Phenolic acids and tannins
Diet supplemented
with two
multicomponent HFA
(50 g/d) (HFA-50)
Diet supplemented
with two
multicomponent HFA
(100 g/d) (HFA-100)
Placebo (PL) 21 December
2012 to 22
July 2013
Milk HFA-50 and HFA-100 vs. PL
There was no difference in milk
yield or major components.
HFA-100
↓Milk Urea,
↓Milk acetone
Walkenhorst
et al.(2020)
Abbreviations: d, days; FCM, Fat-corrected milk; ECM, Energy-corrected milk; PUFA, polyunsaturated fatty acids; CLA, conjugated linoleic acid; CON, Control.
Journal of Dairy Research 5
https://doi.org/10.1017/S0022029923000511 Published online by Cambridge University Press

(Walkenhorst et al., 2020) and Perilla frutescens leaf (Wang et al.,
2021). Other studies included seeds such as false flax cake
(Cais-Sokolińska et al., 2015) and pomegranate seeds (Safari
et al., 2018). There were studies whose interventions were based
on food components like durum wheat bran (Bonanno et al.,
2019b), grape pomace or marc (Ianni et al., 2019; Scuderi et al.,
2019) and mushroom myceliated grains (Bonanno et al.,
2019a). Intervention with isolated bioactive compounds included
plant bioactive lipid compounds plus biotin and monensin
(Hausmann et al., 2018), hesperidin or naringin or
α-tocopheryl acetate (Simitzis et al., 2019), tannin extract
(Menci et al., 2021), and finally N-[2-(nitrooxy) ethyl]-3-
pyridinecarboxamide combined with fumaric acid (Li et al.,
2021). The main beneficial effects of the dairy interventions are
summarized in Table 1.
Effects of supplementation on fatty acids profile of dairy
products
Six studies investigated the impact of dietary intervention on the
fat content of milk. Supplementation with plant bioactive lipid
compounds and biotin (PBLC + B: Hausmann et al.,2018),
fumaric acid (FUM: Li et al.,2021), rice straw and sweet grass
(Mapato et al., 2021) all promoted an increase in milk fat concen-
tration. It has been reported that cattle diets have an important
role in properties such as milk fat composition (Chen et al.,
2017), particularly grass feeding and grazing, which promote
higher levels of PUFA in comparison with concentrate (Mohan
et al., 2021).
Due to its high phytochemical content, pomegranate has been
widely studied for its health properties, and several products
aimed at human health have been developed, causing an increase
in agro-industrial residues (Varma et al., 2018). Pomegranate peel
extract and pomegranate pulp improve in vitro dry matter digest-
ibility and volatile fatty acid production (Jami et al., 2012; Shaani
et al., 2016). Thus, the use of pomegranate residues in ruminant
feed might have an important role in milk production. However,
interventions with pomegranate seeds or pomegranate seed pulp
did not show differences in milk fat (Safari et al., 2018).
There were seven instances of lipid profile being altered by
supplementation. False flax cake increased the content of PUFA
(by 1.5 times) and n-3 fatty acid levels (by 1.7 times) compared
to the control group (Cais-Sokolińska et al., 2015). Intervention
with sweet grass increased the concentration of monounsaturated
fatty acids (MUFA) and PUFA by modest but significant amounts
compared with rice straw (Mapato et al., 2021). It is important to
increase the content of PUFA in dairy products because it has
been established that PUFA, among other health benefits, regu-
lates the inflammatory response (Bentsen, 2017). During this pro-
cess, immune cells produce inflammatory mediators such as
tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-12,
interferon gamma, and IL-8. These mediators activate
pro-inflammatory signaling cascades, including the nuclear
factor-kB (NF-kB) signaling pathway, the Janus kinase/signal
transducer and activator of transcription signaling pathway and
the mitogen-activated protein kinase signaling pathway
(Kahkhaie et al., 2019). It has been demonstrated that PUFA, spe-
cifically n-3 PUFA, inhibits the synthesis of IL-1, IL-2, and IL-6
and the NF-kB signaling pathway (Oppedisano et al., 2020).
Thus, the increase in PUFA concentration observed in the evalu-
ated supplementations indicates that it is possible to enhance the
nutritional value of milk and, therefore, might improve the
consumer health. It must be cautioned that there is no direct evi-
dence for this, nevertheless, it is an exciting prospect.
Among the PUFA compounds that showed the most change
through interventions were linolenic acid, linoleic acid, eicosa-
pentaenoic acid (EPA), and docosahexaenoic acid (DHA).
Intervention with Acacia farnesiana at 30% significantly
increased the concentration in milk of linoleic acid and DHA
compared with control (Delgadillo-Puga et al., 2019).
Similarly, dietary supplementation with dried grape pomace
promoted an increase in the percentage of linoleic acid and
linolenic acid (Ianni et al., 2019). One of these studies showed
that EPA was only detected in the milk of groups fed mushroom
myceliated grains (MMG), but this intervention did not show an
effect on other PUFA such as linoleic (C18:2 n-6), rumenic
(CLA, C18:2 c9 t11), α-linolenic (C18:3 n-3) and arachidonic
(C20:4 n-6) acids (Bonanno et al., 2019b). Also, sweet grass
increased the proportion of C18:1 cis-9, C18:2, C18:2 cis-9,
trans-11andC18:3(Mapatoet al., 2021). PUFA have an
important role as active dietary compounds, particularly CLA
has shown different beneficial effects, such as antihypertensive
and anti-carcinogenic activities (Koba and Yanagita, 2014). In
this aspect, when compared to women who consumed 1 serv-
ing/d, those who consumed >4 servings of high-fat dairy
foods and CLA per day (including whole milk, full-fat cultured
milk, cheese, cream, sour cream and butter) had a tendency to
decrease the incidence of colorectal cancer (rate ratio = 0.59
[95% CI: 0.44, 0.79; Pfor trend = 0.002]), and the increment
of 2 servings of high-fat dairy foods/d decreased by 13% risk
of colorectal cancer (multivariate rate ratio: 0.87, 95% CI:
0.78, 0.96). Thus, consuming high-fat dairy products rich in
CLA may lower the risk of developing colorectal cancer
(Larsson et al., 2005). Once again, a caveat is needed since
these effects are small and have not been confirmed in bigger
studies.
A further note of caution is needed. Supplementation not only
showed an effect on these potentially beneficial fatty acids but also
promoted an effect on saturated fatty acids. Supplementation with
MMG increased the amounts of saturated fatty acids (80.3 vs.
77.94g/100 gof fatty acid, P< 0.01: Bonanno et al., 2019a). For
several years, the consumption of saturated fatty acids was asso-
ciated with the prevalence of cardiovascular disease (Siri-Tarino
et al., 2010) and metabolic diseases such as metabolic syndrome
and type 2 diabetes (Warensjö et al., 2005), however, recent evi-
dence indicates that there is a clear difference between dietary
and circulating saturated fatty acids, and multiple studies indicate
that there is no association between the consumption of saturated
fatty acids and the risk of chronic disease (Astrup et al., 2020). It
is important to note that milk and dairy products are food matrix
foods rich in saturated fatty acids and beneficial compounds such
as PUFA, and their consumption should not be associated with an
increase in cardiovascular and metabolic risk.
Four studies showed the effect of the intervention on the fat
composition of cheese. Supplementation with grape pomace
resulted in a significant increase in the concentration of oleic
acid, linoleic acid and rumenic acid (all P< 0.01) compared
with the control group (Ianni et al., 2019) and intervention
with tannin extract during the dry season increased the concen-
tration of conjugated linoleic acid (Menci et al., 2021).
However, durum wheat bran and MGG supplementation did
not modify the chemical composition of the cheeses (Bonanno
et al., 2019a,2019b) despite the latter’s effect on milk
composition.
6 Azalia Avila‐Nava et al.
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Identification of bioactive compounds in dairy products altered
by supplementation
One of the most important aspects of interventions with bioactive
compounds in the feeding of dairy animals is that these com-
pounds need to be bioavailable in the products obtained.
Among the studies included, five reported the presence of bio-
active compounds in milk (Delgadillo-Puga et al., 2019; Ianni
et al., 2019,2021; Bonanno et al., 2019a,2019b) and three in
the composition of cheese (Ianni et al., 2019; Bonanno et al.,
2019a,2019b). The inclusion of Acacia farnesiana at 20 and
30% in the diet of goats significantly increased the total phenolic
content in the milk and bioactive compounds such as gallic,
chlorogenic, ferulic acids and catechin were only detected in
milk from supplemented goats (Delgadillo-Puga et al., 2019).
The same group tested the impact of consuming goat milk supple-
mented with 30% Acacia farnesiana in conjunction with a high-
fat diet to assess metabolic alterations in a mouse model, and
decreased body weight and body fat mass, improved glucose tol-
erance, and prevention of hypertrophy of adipose tissue and hep-
atic steatosis. The effect of supplementation on body weight and
body fat mass could be explained because a higher energy expend-
iture was documented, evidenced by a higher oxygen consump-
tion in indirect calorimetry. Additionally, it has been
documented that a lower amount of lipids in brown adipose tissue
is related to an increased abundance of uncoupling protein 1. The
effects demonstrated in this study might indicate that the con-
sumption of goat’s milk supplemented with Acacia farnesiana
would be a dietary strategy to improve the metabolic alterations
induced by the high-fat diet. However, human studies are
required before any definitive conclusions can be drawn.
According to the body surface area normalization method
(FDA, 2005), the mouse dosage would equate to an equivalent
daily human intake of 1.4–2.8 cups (250 ml per cup/d) of fresh
goat’s milk for a 60 kg adult, so this dose could be the reference
to show its effectiveness in clinical studies.
Supplementation with grape pomace caused an increase in
the total phenolic compounds in milk in comparison with the
non-supplemented group (Ianni et al., 2019). Grape pomace is
a product with prebiotic activity because it contains up to
75% dietary fiber (Yu and Ahmedna, 2013), however, the pre-
biotic effect in addition to the fiber could be given by the phen-
olic compounds, as they also have a significant effect on
the composition and activity of the intestinal microbiota by
stimulating or inhibiting specific bacterial groups (Seo et al.,
2017). Phenolic compounds are poorly absorbed in the small
intestine and do, therefore, reach the colon, where they are
metabolized by the resident microbiota into biologically active
metabolites (Ozdal et al., 2016). This results in the appearance
of a wide range of phenolic metabolites (phenylacetic acids,
phenylpropionic acids, valeric acids, cinnamic acids, benzoic
acids, and phenols, among others: Mena et al., 2019). Grape
derivatives, such as phenolic compounds, can promote the
growth of probiotic bacteria, including Bifidobacterium teen-
ageris,Bifidobacterium bifidum,Lactobacillus acidophilus,and
Lactobacillus rhamnosus (Parkar et al., 2008; Gwiazdowska
et al., 2015). This modulation in the intestinal microbiota
has a positive effect on the health of the host because experi-
mental studies have shown effects in decreasing weight, waist
circumference and fat mass and also in decreasing insulin re-
sistance after probiotic treatments, mainly Lactobacillus and
Bifidobacterium (Ejtahed et al., 2019).
Unfortunately, phenolic compounds are not particularly stable
in refrigerated milk. Dairy products that were enriched with poly-
phenolic compounds showed a decrease in the phenolic content
after 28 d of refrigerated storage, which was attributed to their oxi-
dation (Deolindo et al., 2019). One option to prevent oxidation
would be the encapsulation of polyphenols, since encapsulation
can protect the bioactive compounds from oxidation. However,
encapsulation is more favorable for the enrichment of the dairy
product than for the interventions to the diets of the ruminants.
Olive leaf supplementation is another intervention that signifi-
cantly increases the concentration of phenolic compounds in
milk. The main compounds detected in this milk were cinnamic
acid, chlorogenic acid and tyrosol (Ianni et al., 2021). An interest-
ing finding in the profile of bioactive compounds in milk was the
content of chlorogenic acids (CGAs), since these are among the
most common bioactive compounds in plant foods such as coffee,
apples, tea and berries, as well as in beverages such as wine
(Zanotti et al., 2015). These compounds are esters that are
made when quinic acid and trans-cinnamic acids join together.
They are usually partially absorbed in the small intestine and par-
tially absorbed in the large intestine after being broken down by
bacteria (Olthof et al., 2001,2003). The concentration of CGAs
in milk is relevant because, according to the literature, their con-
sumption could have an important impact on the improvement of
glucose and lipid metabolism. Various mechanisms have been
proposed, including that they are involved in the inhibition of
α-amylase, an enzyme responsible for the decomposition of starch
present in saliva that inhibits the absorption of sugar from diet
(Narita and Inouye, 2009). In addition, they could modulate
gastrointestinal peptides such as gastric inhibitory polypeptide
and glucagon-like peptide 1 (Johnston et al., 2003) as well as
stimulating glucose transporter 4, thereby increasing glucose
uptake by peripheral tissues (Song et al., 2014). All these mechan-
isms result in a significant reduction in blood glucose levels (Van
Dam, 2006). On the other hand, for lipid metabolism it has been
shown that CGAs could down-regulate sterol regulatory element-
binding protein 1C (Murase et al., 2011) which is the main gen-
etic switch that controls lipogenesis. Both CGA and caffeic acid
stimulate the peroxisome expression of nuclear transcription
receptor proliferator-activated receptor alpha in obese mice
induced by a high-fat diet. This receptor, when activated, acts
as a sensor of lipids, and regulates lipid metabolism. The liver is
its main target tissue, and its key genes are enzymes involved in
the β-oxidation of fatty acids (Cho et al., 2010). Although highly
speculative, all of this together may result in improvements in
lipid metabolism. However, not all supplementations have posi-
tive effects. Intervention with durum wheat bran (20%) only
showed a tendency in phenolic compounds in milk with respect
to the control group (Bonanno et al., 2019b), and none of the
cheese studies yielded positive changes on total phenolic
compounds.
Antioxidant compounds in dairy products affected by
supplementation
An outcome of interest from supplementation is the antioxidant
effect generated by dairy products. Of the fifteen selected studies,
six of these reported an antioxidant effect in milk after the inter-
vention of Acacia farnesiana (Delgadillo-Puga et al., 2019),
hesperidin or naringin (Simitzis et al., 2019), durum wheat bran
(Bonanno et al., 2019b), MMG (Bonanno et al., 2019a), grape
pomace (Ianni et al., 2019), and olive leaves (Ianni et al., 2021).
Journal of Dairy Research 7
https://doi.org/10.1017/S0022029923000511 Published online by Cambridge University Press

Intervention with Acacia farnesiana at different concentrations
significantly increased antioxidant activity determined both by
oxygen radical absorbance capacity assay and ferric reducing anti-
oxidant power assay compared with conventional diet
(Delgadillo-Puga et al., 2019). Similarly, supplementation with
MMG at 20% showed a significant increase in total equivalent
antioxidant capacity with respect to the control without interven-
tions (Bonanno et al., 2019a), antioxidant activity in milk from
animals that were fed grape pomace (Ianni et al., 2019) or olive
leaf (Ianni et al., 2021) increased significantly compared with
the control groups and 14 d of hesperidin, naringin or
α-tocopheryl acetate dietary supplementation achieved the same
effect (Simitzis et al., 2019).
The role of antioxidants is relevant because they can contrib-
ute to the reduction of reactive oxygen species (ROS). Where
there is an abundance of ROS and a deficiency of antioxidants,
oxidative stress is generated, which in turn causes oxidative dam-
age to biomolecules such as DNA, proteins and lipids
(Aranda-Rivera et al., 2022). Since lipid oxidation, also known
as lipid peroxidation, produces oxidative biomarkers such as mal-
ondialdehyde (MDA) and oxidized LDL (ox-LDL), an increase in
these biomarkers has been associated with metabolic alterations
and cardiovascular complications (Lee et al., 2012).
Scientific evidence to support the use of antioxidants from
food, such as dairy products, as a strategy to prevent pathologies
and/or complications related to oxidative stress would be of con-
siderable value, but simply showing their presence in the raw
product is only a part of the solution. There are only a few studies
that demonstrate the antioxidant effect of dairy products. One of
these studies in a healthy population showed that after 21 d of
consumption of goats’milk there was a small but significant
increase in the percentage of total antioxidant activity and a
decrease in the relationship of levels of the endogenous antioxi-
dant glutathione (oxidized glutathione:reduced glutathione:
Kullisaar et al.,2003). A second asked participants to consume,
for 4 weeks, an experimental cheese that was made from the
milk of cows fed a diet containing 5% linseed oil. In this case,
serum ox-LDL decreased significantly (Intorre et al., 2011).
It is not only important to consider that antioxidant activity
increases, but also that it is able to decrease levels of ROS.
Excessive ROS oxidizes cell components, which produce altera-
tions in their structure, causing interruption of signaling pathways
or even generating dysfunction of metabolic pathways. Thus, the
importance of antioxidants showing this effect on health is to pro-
mote benefits in populations with pathologies associated with oxi-
dative stress such as obesity, type 2 diabetes, dyslipidemia and
cardiovascular disease (Forrester et al., 2018). A study that
included patients with a diagnosis of metabolic syndrome and a
12-week intervention with several serves of dairy per day
(adequate dairy) or less than one (low dairy) showed that
adequate dairy consumption significantly decreased levels of
MDA and ox-LDL (Stancliffe et al., 2011). The decrease in
these markers is potentially of great importance, however, it is
an isolated example and more evidence about the consumption
of dairy products in different types of populations is needed to
demonstrate the antioxidant effect it may generate.
Discussion
In recent years, bioactive compounds and agro-industrial residues
have been used as feed for dairy animals because they may have
positive effects on animal production, such as regulating ruminal
fermentation, stopping methane production and protein break-
down, boosting the immune response, and increasing antioxidant
activities in animal tissues (Niderkorn and Jayanegara, 2021).
There are a great variety of bioactive compounds that can be
used in the nutrition of dairy animals. In this review, 19 different
types of supplements were used. Only one of them, biotin, is an
approved additive according to the EU Register on Nutrition
Health Claims; pomegranate seed, alfalfa hay, hesperidin, narin-
gin, mushroom myceliated grains, and tannins are not approved.
Meanwhile, the remaining interventions do not appear on any list
as authorized or non-authorized. To ensure food safety and ani-
mal welfare, it is essential to regulate the feeding of dairy animals
with bioactive substances and agro-industrial residues.
Milk and milk products are important foods for human nutri-
tion, constituting 25–30% of the diet. Their nutritional value is, in
part, associated with the lipid content due to the inclusion of fatty
acids, vitamins and minerals (Visioli and Strata, 2014).
Epidemiological data have shown associations between health
effects and dairy product intake (Givens, 2020). On the other
hand, many other studies have linked the consumption of dairy
products with the risk of developing pathologies, mainly because
of their lipid content (Fontecha and Juárez, 2017). Thus, health
policies have suggested the consumption of fat-free milk and
milk-derived products to prevent the risk of cardiometabolic
pathologies (You, 2015). More recent analysis employing system-
atic review has shown inconclusive or contradictory results about
the health effects of dairy product consumption (Nieman et al.,
2021). Epidemiological studies have shown an inverse association
between the intake of dairy products and hypertension, stroke,
and colorectal cancer, but there is no evidence of an association
between the consumption of dairy products and breast cancer.
There is some weak evidence of the protective capacity of dairy
products for bone health (Alvarez-León et al., 2006). A
meta-analysis showed that milk and total dairy products, but
not cheese or other dairy products, are associated with a reduction
in colorectal cancer risk. Inverse associations were observed in
both men and women but were restricted to colon cancer,
where there was evidence of a significant nonlinear association
between milk and total dairy products and colorectal cancer
risk, and the inverse associations appeared to be the strongest at
the higher range of intake (Aune et al., 2012). The nutritional
benefits of milk and dairy products are undeniable, but the intri-
cacies of specific health or disease consequences are very difficult
to establish.
Dairy products may contain antioxidants such as vitamins A
and E, which may provide health benefits due to their ability to
reduce oxidative stress and inflammation, but note the term
‘may’. Depending on factors such as animal diet, breed and pro-
duction methods, the antioxidant content of dairy products can
vary. Some studies indicate that feeding dairy animal diets rich
in antioxidants, such as those containing high levels of vitamin
E or plant-based compounds, can increase the antioxidant con-
tent of their milk (Delgadillo-Puga et al., 2019,2020), which is
encouraging but we are far from understanding whether such
increases actually achieve health benefits. Nevertheless, we can
say that improving the diet of dairy animals could potentially
increase the nutritional value of the milk they produce.
Efforts have been made to maximize the potential health ben-
efits of dairy products and increase their clinical relevance. Studies
have demonstrated that improved chemical composition or
enrichment with bioactive compounds such as PUFA, peptides
and antioxidants can contribute to the enhancement of the
8 Azalia Avila‐Nava et al.
https://doi.org/10.1017/S0022029923000511 Published online by Cambridge University Press

quality of these products by promoting positive effects. Recent
evidence suggests that benefits from dairy products on health
include regulation of carbohydrate and lipid metabolism through
effects on abundance and composition of gut microbiota, cardio-
vascular diseases, type 2 diabetes, modulation of the immune
response and decreased risk of different types of cancer (Tong
et al., 2011; Sharafedtinov et al., 2013; Nilsen et al., 2015;
Brassard et al., 2017; Santurino et al., 2020).
Changes in these types of products brought about by the pres-
ence of bioactive compounds can also have positive outcomes for
the production animal. For example, the increase in milk fat con-
centration due to plant bioactive lipid compounds and biotin can
be explained by the prevention of postpartum weight loss and an
increase in back fat thickness (Hausmann et al., 2018). Fumaric
acid had a negative impact on total fat content. The authors the-
orized that this was due to the decreased proportion of precursors
for the de novo synthesis of milk fatty acids, such as butyrate and
the acetate-to-propionate ratio (Li et al., 2021). The higher pro-
duction of fat in milk when sweet grass was supplemented was
accompanied by an increase in digestibility and feed intake,
thereby increasing the nutrients available for the rumen microbes
and enhancing rumen fermentation, total milk production and
milk composition (Mapato et al., 2021). Also, sweet grass
increases the concentration of MUFA in milk because fresh
grass increases milk fatty acids that are ruminal biohydrogenation
intermediates (C18:1, C18:2, C18:3). It has been demonstrated
that MUFA can improve glycemic control and prevent the devel-
opment of metabolic syndrome and its complications (Sheashea
et al., 2021). Similar results are shown in the intervention with
Acacia farmesiana, dried grape pomace, and MMG that increased
the long-chain fatty acids, like linoleic and alpha-linolenic acids.
This effect can probably be related to ruminal kinetic modifica-
tions due to the rich bioactive compounds found in supplements
(Delgadillo-Puga et al., 2019). Enrichment in the content of
PUFA in this study has an important role in consumer health
because PUFA are associated with preservation of insulin sensitiv-
ity, regulation of blood pressure, adequate coagulation and
enhanced endothelial function (Julibert et al., 2019).
The use of tannin extract in the diet, by contrast, had a nega-
tive effect on C18:1 trans-10, which may affect the pathway of
microbial conversion of C18:3 cis-9, cis-12, and cis-15 to C18:1
trans-10 in the rumen. However, these effects were not reflected
on cheese-making parameters (Menci et al., 2021). Mapato
et al.(2021) found that adding bamboo grass with bioactive com-
pounds like condensed tannins improved the rumen microbiome,
which had a positive effect on total volatile fatty acids and propio-
nic acid. The increment of saturated fatty acids due to the inclu-
sion of MMG in the diet was explained by an increment in
palmitic acid (C16:0) (Bonanno et al., 2019a).
Variation in milk composition may also be accompanied
by the presence of bioactive compounds such as phenols and feru-
lic acid in milk, with a subsequent presence in processed products.
A positive effect on oxidative damage was observed in cheese,
which was less prone to proteolysis during ripening without any
changes in sensory characteristics (Ianni et al., 2019). Another
example of the antioxidant capacity was also described in cheeses
induced by MMG in the diet due to the presence of phenolic
acids, flavonoids, polysaccharides, carotenoids, ascorbic-acids,
and tocopherols.
In conclusion, consumption of products with antioxidants and
an adequate lipid profile can be considered a strategy to prevent
the damage caused by oxidative stress (Rani et al., 2016).
This systematic review compiles scientific studies about sup-
plementation with bioactive compounds to improve the nutrition
profile and composition of milk and dairy products. It was
observed that supplementation with bioactive compounds in the
diet of dairy animals had a positive impact on dairy products,
which ranged from an increase in antioxidant capacity to a
decrease in metabolites such as malondialdehyde. Future studies
should focus on exploring the impact of consuming these pro-
ducts on human health.
Supplementary material. The supplementary material for this article can
be found at https://doi.org/10.1017/S0022029923000511
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