ArticlePDF AvailableLiterature Review

Abstract

Vitamin A is the generic term for a variety of fat-soluble substances including retinol, retinyl palmitate and the provitamin A carotenoids such as all-trans-beta-carotene. Vitamin A is commonly known as the anti-infective vitamin and has an essential role in vision and cellular differentiation, the latter providing a unique core mechanism helping to explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial lining of vital organs occur early in deficiency, suggesting a potentially important role for the barrier function. Vitamin A deficiency (VAD) is most commonly recognized in the eye. The conjunctival-impression cytology test detects the presence of larger irregular keratinized cells and the absence of mucous-secreting goblet cells, indicative of VAD. The method is simple, quick and sensitive in populations where VAD is present. In the respiratory tract, observational studies all show an association with VAD, although vitamin A supplementation studies appear to have little effect on respiratory disease. Organ-specific targeting may improve success rates. The dual-sugar intestinal-permeability test allows the effect of vitamin A supplementation to be monitored on the gastrointestinal tract. Two vitamin A supplementation studies were carried out recently in Orissa State, India. Healthy infants of weaning age were administered orally eight weekly doses of 5.0 mg retinol equivalents and hospitalized infants received one large oral dose 60 mg retinol equivalents in the form of retinyl palmitate. Improvements in gut integrity and haematological status were observed in both studies. In summary, the response of the eye to vitamin A supplementation is well established; the present review highlights some of the more recent observations examining the effects of vitamin A.
Proceedings of the Nutrition Society (1999), 58, 289–293 289
Abbreviations:
CIC, conjunctival-impression cytology; L, lactulose; M, mannitol; VAD, vitamin A deficiency.
*Corresponding author:
Fiona McCullough, fax +44 (0)1265 324965, email f.mccullough@ulst.ac.uk
CAB International
The effect of vitamin A on epithelial integrity
F. S. W. McCullough*, C. A. Northrop-Clewes and D. I. Thurnham
Fiona M cCullough,
Northern Ireland Centre for Diet and Health (NICHE), University of Ulster, Coleraine BT52 1SA, UK
fax +44 ( 0)1265 324965, email f.mccu llough@ulst.ac .uk
Vitamin A is the generic term for a variety of fat-soluble substances including retinol,
retinyl palmitate and the provitamin A carotenoids such as all-
trans
-
β
-carotene. Vitamin
A is commonly known as the anti-infective vitamin and has an essential role in vision
and cellular differentiation, the latter providing a unique core mechanism helping to
explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial
lining of vital organs occur early in deficiency, suggesting a potentially important role
for the barrier function. Vitamin A deficiency (VAD) is most commonly recognized in
the eye. The conjunctival-impression cytology test detects the presence of larger
irregular keratinized cells and the absence of mucous-secreting goblet cells, indicative
of VAD. The method is simple, quick and sensitive in populations where VAD is
present. In the respiratory tract, observational studies all show an association with VAD,
although vitamin A supplementation studies appear to have little effect on respiratory
disease. Organ-specific targeting may improve success rates. The dual-sugar intestinal-
permeability test allows the effect of vitamin A supplementation to be monitored on the
gastrointestinal tract. Two vitamin A supplementation studies were carried out recently
in Orissa State, India. Healthy infants of weaning age were administered orally eight
weekly doses of 5·0mg retinol equivalents and hospitalized infants received one large
oral dose 60 mg retinol equivalents in the form of retinyl palmitate. Improvements in gut
integrity and haematological status were observed in both studies. In summary, the
response of the eye to vitamin A supplementation is well established; the present review
highlights some of the more recent observations examining the effects of vitamin A.
Vitamin A: Conjunctival-impression cytology test: Dual-sugar intestinal-permeability test
Vitamin A builds fences that keep germs out.’ E.V.
McCollum 1935
‘Vitamin A’ is a generic term for a variety of related
compounds, including retinol, retinyl palmitate, retinoic
acid and the pro-vitamin A carotenoids. The fat-soluble
substance is usually found in animal and dairy products as
the ester, retinyl palmitate. The alcohol retinol is formed
during hydrolysis in the small intestine where it is taken
up actively by the enterocytes. The most active provitamin
A carotenoid is all-
trans
-
β
-carotene, which is present in
yellow–orange fruits and dark-green leafy vegetables.
Intestinal cells convert provitamin A carotenoids to retinal-
dehyde, the majority of which is reduced to retinol.
Bioavailability of provitamin A carotenes varies widely,
depending on how the food is prepared and consumed.
Vitamin A is commonly known as the anti-infective
vitamin. At the beginning of the twentieth century, animals
fed on ‘pure’ diets containing only lard and carbohydrates
with no vitamins ceased to grow, lost weight and became
susceptible to infections. Administration of ‘accessory
factors’ found in dairy products and cod-liver oil reversed
the process. McCollum (McCollum & Davis, 1915) termed
the critical factor ‘Fat-soluble A’. By 1920 the clinical
manifestation of vitamin A deficiency (VAD), and its cause
and cure were well established.
Vitamin A has an essential role in vision and cellular
differentiation, the latter being particularly important in
growth, reproduction and immune response, and in main-
taining epithelial integrity. The critical function vitamin A
plays in regulating cellular differentiation provides a unique
‘core’ mechanism that would at least partly explain its influ-
ence on epithelial barriers, immune competence, healing,
resistance and recovery (Ross, 1992). No nutritional
deficiency is more synergistic with infection than vitamin A.
The two main mechanisms involved in the prevention of
disease are the effect of vitamin A on the immune system
AMA PNS0071.fm Page 289 Thursday, June 24, 1999 3:13 PM
290 F. S. W. McCullough et al.
and the effect on epithelial integrity, the subject of
the present review. All epithelial surfaces, including the
eye, skin, trachea, salivary gland, vaginal epithelium
and gastrointestinal tract, are involved. Alterations in the
epithelial lining of vital organs occur early in VAD, suggest-
ing a potentially important role for the ‘barrier function’.
Tissue integrity is vitally important for protection against
environmental pathogenic organisms.
Epithelial tissues
Eye
VAD is most commonly recognized in the eye. Night-
blindness and its successful treatment with animal liver was
known to the ancient Egyptians at least 3500 years
ago (Wolf, 1978), and was mentioned by Hippocrates.
Xerophthalmia (from the Greek: xero, dry; ophthalmia,
inflamed eye) is a constellation of ocular manifestations
long associated with VAD, representing the ‘classical’
presentation of this particular form of malnutrition.
Deficiency symptoms are progressive from night-blindness,
conjunctival xerosis, Bitot’s spots and corneal xerosis
to corneal ulceration (keratomalacia), corneal scar and
xerophthalmia fundus (World Health Organization, 1995).
Vitamin A status can be assessed by functional tests that
measure epithelial integrity. Keratinizing metaplasia is a
potentially practical index, and as early as 1925 the scrap-
ings of cornea, nose, mouth and vagina were recommended
as a diagnostic tool of VAD (Wolbach & Howe, 1925). The
early studies were neither qualitative nor validated against
any other index of vitamin A status. More detailed know-
ledge about the normal and deficient nature of conjunctival
epithelium, particularly the geographic distribution of goblet
cells (Kessing, 1968) and their response to vitamin A defi-
ciency (Sommer
etal
. 1982), created renewed interest in
the approach. The system of ‘simple conjunctival biopsy’
was described by Egbert
etal
. (1971), and Nelson
etal
.
(1988). Cellulose acetate filter paper was briefly applied
to the conjunctival surface to remove the superficial
layers of the conjunctival epithelium. The biopsy technique,
renamed conjunctival-impression cytology (CIC) provides
evidence of keratinizing metaplasia. Vitamin A-
unresponsive and -responsive Bitot’s spots have an identical
biological appearance; however, the CIC test detects the
absence of mucous-secreting goblet cells and the presence
of larger irregular keratinized cells. Initial trials demon-
strated markedly abnormal CIC from children with mild
xerophthalmia when compared with normal children or
following vitamin A treatment (Wittpenn
etal
. 1986). There
was a close correlation between the prevalence of abnormal
CIC and the severity of deficiency suggested by three other
indicators of vitamin A status (serum retinol, relative dose
response and modified relative dose response). Of the chil-
dren with clinically-responsive xerophthalmia and low
vitamin A levels 93% had abnormal cytology, and 6% of
children with normal eyes and serum retinol levels between
0·09 and 0·10
µ
mol/l (250–290
µ
g/l) had abnormal CIC
(Natadiastra
etal
. 1988). The validity of CIC has been
further confirmed by the following: comparison of liver
retinol concentrations and relative dose response in French
children with normal eyes but with hepatic disease
(Amedee-Manesme
etal
. 1988); comparisons of abnormal
CIC rates in xerophthalmic and non-xerophthalmic children
in India (Reddy
etal
. 1989); correlation of CIC with serum
and breast-milk retinol in Indonesian women (Miller
etal
.
1993) and by correlations of CIC with other indices of
vitamin A status (Tanumihardjo & Olsen, 1991).
CIC is of particular advantage under field conditions as it
does not require sophisticated laboratory analysis, storage or
transport. However, there are problems of compliance with
small children, who can be frightened of the paper being
set on their eye. CIC is not without its limitations and
several reports (for example, see Gadomski
etal
. 1989) have
questioned its validity and/or interpretation. In theory,
although not always in practice, and ideal marker would
detect subclinical deficiency, when stores are below ‘safe’
levels. By definition, a functional abnormality is evidence
that physiologically-significant deficiency already exists.
Hence, the CIC marker has been more successfully used
in epidemiological studies than as a diagnostic tool for
individuals, especially in areas of marginal deficiency
(Natadiastra
etal
. 1988). When using CIC Coutsoudis &
Way (1996) noted that allergic conjunctivitis could be
mistaken for VAD in South African children.
Respiratory tract
Observational studies (see Vijayaraghavan
etal
. 1990)
all show an association between VAD and respiratory
infection. However, a meta-analysis (Bates, 1995) showed a
lack of impact of vitamin A supplementation, although there
were some indications of reduced severity and possibly
reduced duration of respiratory symptoms. Interestingly,
some researchers suggest that increased cough following
supplementation may indicate greater mucus production
and removal of infective material (Herrera
etal
. 1996). A
promising method of treating respiratory infections using
organ-specific targeting was suggested by Biesalski (1996).
In rats direct inhalation of 0·9mg retinol equivalents as
retinyl esters, produced an increase in plasma retinyl ester
from 0·16
µ
mol/l (45
µ
g/l) to 0·66
µ
mol/l (190
µ
g/l) with no
side-effects.
It was suggested by Shenai
etal
. (1987) that vitamin A
supplementation in preterm infants was of benefit in
bronchopulmonary dysplasia. It was reported by Coutsoudis
etal
. (1993) that initial VAD in preterm infants does
not predispose them to respiratory distress syndrome or
pneumonia, but by 3 months post-partum vitamin A status
was adequate and similar to that of full-term infants.
Gastrointestinal tract
Until recently, mucosal damage could only be assessed by
endoscopy and/or biopsy of the small intestine. Using such
techniques a number of studies have shown a substantial
reduction in the number of goblet cells per duodenal villus
when compared with control and pair-fed mice (Ahmed
etal
. 1990), a reduction in luminal mucus (Meneghetti
etal
.
1989), and decreased cellular division preceding histo-
logical abnormalities in mildly-VAD animals (Zile
etal
.
1981).
AMA PNS0071.fm Page 290 Thursday, June 24, 1999 3:13 PM
Postgraduate symposium 291
Non-invasive techniques (Lunn
etal
. 1989; Northrop
etal
. 1990) have been introduced which estimate specific
aspects of mucosal function and integrity and allow repeated
measurements to be carried out, even under field conditions.
Absorption across healthy intestinal mucosa is highly selec-
tive. ‘Inert molecules’ pass across the absorptive surfaces
at rates determined by concentration gradient, surface area
and time, as well as the permeability of the intestinal
mucosa. The mucosa demonstrates marked discrimination
with respect to the molecular dimension and solubility of
inert molecules, this discrimination becoming impaired
with mucosal damage (Menzies
etal
. 1983). The xylose-
absorption test has been used as a preliminary screening
procedure for gastrointestinal integrity (Hubble &
Littlejohn, 1963), but has limitations. Gastric emptying,
intestinal transit, blood flow and renal function variables
reduce the correlation between xylose absorption or
excretion and the degree of mucosal damage (Lamabadu-
suriya
etal
. 1975). Dual-sugar absorption tests are not
affected to the same extent by such limitations. A variety
of markers have been utilized to indicate gastrointestinal
integrity, e.g. ingestion of lactulose and rhamnose showed
that during kwashiorkor, abnormal intestinal permeability
correlated with disease severity and improved only slowly
with nutritional rehabilitation (Brewster
etal
. 1997). Elia
etal
. (1987) investigated the factors affecting the intestinal
uptake and urinary excretion of mannitol (M), lactulose (L)
and Cr-EDTA in normal subjects and three patients
with ileostomy. They suggested that the uptake of L is
slower than that of M, and Cr-EDTA is readily absorbed
in the colon. L and M are two non-metabolizable sugars
that cross the mucosa paracellularly and transcellularly
respectively. The ratio L:M in blood is an indicator of
mucosal damage, L:M greater than 0·02 being considered
abnormal. L:M values discriminated well between subjects
with normal biopsy and those with villous atrophy. Fleming
etal
. (1996) successfully measured L and M by HPLC in
serum 90 min after intake, while other workers have used
automated enzymic assays (Lunn
etal
. 1989; Northrop
etal
.
1990). The HPLC results agree well with L:M values
determined enzymically following a 5h urine collection
(
r
0·88,
P
=0·05), hence the two methods can be used inter-
changeably.
Northrop-Clewes
etal
. (1997) investigated the role of
vitamin A on epithelial integrity using the L:M dual-sugar
intestinal-permeability test. This test uses a weight-
dependent dose of the two sugars (L and M) which are given
to the infant dissolved in water. A urine bag is used to
collect the urine produced during the following 5h. The
sugars are measured enzymically and the L : M value is an
indicator of epithelial integrity. A healthy mucosal surface
has villi which are long finger-like projections allowing
maximal absorption of M, while L, the larger molecule,
can only pass between the cells. Absorption of L is therefore
minimal, resulting in a low L:M value. Damage to villi
could include either a reduced surface area, e.g. by a flatten-
ing of the surface area, and/or damage caused by parasitic
infestation (e.g. hookworms) causing leakiness of the
gastrointestinal tract. In both situations the absorption of L
increases relative to that of M, resulting in an elevated L:M
value.
Faltering growth, infections, diarrhoea and anaemia
remain major problems in the developing world. Retinol and
Fe are transported in the bloodstream by negatively-charged
acute-phase proteins which decrease during infection, hence
retinol and Fe are ‘trapped’ in the liver and spleen during
disease. Foods are frequently contaminated with pathogens,
thus exposure to infections is increased in developing
countries, and the risk of infection may be exacerbated by
poor gastrointestinal integrity. Impaired gastrointestinal
integrity may facilitate the translocation of bacteria across
the mucosa. Studies carried out in rural Gambian infants
showed evidence of impaired intestinal integrity and
elevated acute-phase response, which accounted for up to
50% of the growth faltering noted during the first 2 years
of life (Northrop-Clewes
etal
. 1997). Seasonal data from
the same Gambian infants suggested that during the
mango (
Mangifera indica
) season there were improvements
in gastrointestinal integrity and growth, and the acute-phase
reponse normalized for a period of approximately 3 months
(Northrop-Clewes
etal
. 1997). Mangoes are a rich source of
β
-carotene and the main supply of vitamin A for the year in
this community. During infection, an acute-phase reaction is
initiated which results in reduced levels of plasma retinol.
Thus, increasing the availability of vitamin A throughout the
year may help infants to restore gastrointestinal integrity,
fight off infection and reduce the problem of faltering
growth. It is hypothesized that vitamin A acts by restoring
the physical and biochemical integrity of epithelial surfaces,
particularly the gastrointestinal tract, so that the risk of
infection and trauma will be reduced.
Effect of vitamin A supplementation on gastrointestinal
integrity.
Two vitamin A supplementation studies were
carried out in Rourkela, Orissa State, India. Low serum
retinol levels and growth faltering had previously been
reported in this region (Das etal. 1996). The first study was
carried out in four rural villages, where eighty infants
aged 4–18 months were recruited (Northrop-Clewes etal.
1997). The infants were randomly allocated to receive
either 5·0mg retinol equivalents as retinyl palmitate and
40mg
α
-tocopherol in 4ml groundnut oil weekly for
8 weeks or 40mg
α
-tocopherol in 4ml groundnut oil as
placebo. Baseline L:M values were 0·74 and 0·64 for the
treatment and placebo group respectively. L:M values were
reduced after 4 and 8 weeks in both groups, but only the
change in the treatment group was significant (P<0·05).
Mean haemoglobin concentration also showed slight but
non-significant improvement. However, the placebo group
displayed a significant (
P
<0·05) decrease in haemoglobin
from 91·95 to 88·33g/l after 8 weeks.
The second study investigated the effect of vitamin A
supplementation on hospitalized infants with diarrhoea and
respiratory infections (FSW McCullough, CA Northrop-
Clewes, BD Das and DI Thurnham, unpublished results).
Infants of weaning age (4–18 months;
n
100) admitted with
diarrhoeal disease or respiratory infection were randomly
assigned to one of three treatment groups as follows: treat-
ment 1, 60mg retinol equivalents as retinyl palmitate (30mg
retinol equivalents for infants under 12 months) and
40mg
α
-tocopherol on the day following admission;
treatment 2, 60mg retinol equivalents as retinyl palmitate
and 40mg
α
-tocopherol 5d post-admission; treatment 3,
AMA PNS0071.fm Page 291 Thursday, June 24, 1999 3:13 PM
292 F. S. W. McCullough et al.
placebo (no vitamin A, only 40mg
α
-tocopherol 5d post-
admission). Gastrointestinal integrity and haemoglobin
measurements were carried out at baseline, and 5, 10
and 30d post-admission. Gastrointestinal integrity was
measured using the dual-sugar intestinal-permeability test.
Haemoglobin was measured using the Hemocue device
(Hemocue, Angelholm, Sweden). Differences in L:M
and haemoglobin between baseline and day 5 were not
significant for any treatment. By day 10, however, both
L:M values and haemoglobin levels were significantly
(
P
<0·05) improved in the groups receiving the vitamin A,
whereas there was no improvement in the placebo group. By
day 30, the responses in the groups receiving vitamin A
were still better than those of the placebo group, although
not as significant (
P
>0·05).
Traditionally, micronutrient supplementation is pre-
scribed on admission of patients to Ispat General Hospital
(Rourkela City, Orissa State, India). The hospital policy
should be re-examined and more vitamin A supplied, since
the results of these studies suggest that gastrointestinal
integrity is severely impaired during illness, but responsive
to the additional vitamin A. Gastrointestinal integrity and
haemoglobin were significantly (
P
<0·05) more rapidly
improved in the vitamin A-treated groups than in the
placebo group. However, there were no statistical differ-
ences between the two vitamin A groups, therefore there
was no apparent advantage in giving vitamin A on admis-
sion. In addition, the majority of the children were
discharged within 5d.
In conclusion, marginal vitamin A status clearly impairs
the integrity of epithelial tissues. These effects are more
clearly seen in the eye as a result of the availability of the
CIC test. Use of the dual-sugar intestinal-permeability test
now opens up the possibility of examining more closely the
influence of vitamin A on the gastrointestinal tract.
Acknowledgements
The authors are grateful to Hoffmann-la-Roche Inc., Basel,
Switzerland who supplied the vitamin A and assisted
with fieldwork costs in India and Dr B. Dash, Director of
Health for permission to base the study at Ispat General
Hospital.
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... Given that diets rich in carotenoids are likely to support a healthy gut microbiome [18] and the multiple beneficial effects of vitamin A on immune function and gut barrier integrity [18,19], we hypothesised a positive relationship between alpha diversity and vitamin A. ...
Article
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Background Vitamin A is essential for physiological processes like vision and immunity. Vitamin A’s effect on gut microbiome composition, which affects absorption and metabolism of other vitamins, is still unknown. Here we examined the relationship between gut metagenome composition and six vitamin A-related metabolites (two retinoid: -retinol, 4 oxoretinoic acid (oxoRA) and four carotenoid metabolites, including beta-cryptoxanthin and three carotene diols). Methods We included 1053 individuals from the TwinsUK cohort with vitamin A-related metabolites measured in serum and faeces, diet history, and gut microbiome composition assessed by shotgun metagenome sequencing. Results were replicated in 327 women from the ZOE PREDICT-1 study. Results Five vitamin A-related serum metabolites were positively correlated with microbiome alpha diversity (r = 0.15 to r = 0.20, p < 4 × 10⁻⁶). Carotenoid compounds were positively correlated with the short-chain fatty-acid-producing bacteria Faecalibacterium prausnitzii and Coprococcus eutactus. Retinol was not associated with any microbial species. We found that gut microbiome composition could predict circulating levels of carotenoids and oxoretinoic acid with AUCs ranging from 0.66 to 0.74 using random forest models, but not retinol (AUC = 0.52). The healthy eating index (HEI) was strongly associated with gut microbiome diversity and with all carotenoid compounds, but not retinoids. We investigated the mediating role of carotenoid compounds on the effect of a healthy diet (HEI) on gut microbiome diversity, finding that carotenoids significantly mediated between 18 and 25% of the effect of HEI on gut microbiome alpha diversity. Conclusions Our results show strong links between circulating carotene compounds and gut microbiome composition and potential links to a healthy diet pattern.
... In pig nutrition, synthetic retinyl acetate supplementation is essential to fulfil the dietary requirements of vitamin A, as plant-based feedstuffs are deficient in vitamin A [48]. Vitamin A plays a crucial role in maintaining the functionality of the epithelium of the gastrointestinal tract and has also been shown to promote mucin secretion [49]. Furthermore, it is of great importance for the maturation of the immune system. ...
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... In our search for potential therapeutic for tracheal stenosis, retinoic acid emerged as the top candidate given its ability to regulate several of the most highly dysregulated genes. Retinoic acid is well-known for its role in maintaining epithelial integrity and promoting mucosal immunity [23]. Topical retinoic acid can improve the regeneration of a mucociliary respiratory epithelium after iatrogenic mucosal injury [24]. ...
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Introduction: While most patients with iatrogenic tracheal stenosis (ITS) respond to endoscopic ablative procedures, approximately 15% experience a recalcitrant, recurring disease course that is resistant to conventional management. We aimed to explore genetic profiles of patients with recalcitrant ITS to understand underlying pathophysiology and identify novel therapeutic options. Methods: We collected 11 samples of granulation tissue from patients with ITS and performed RNA sequencing. We identified the top 10 most highly up- and down-regulated genes and cellular processes that these genes corresponded to. For the most highly dysregulated genes, we identified potential therapeutic options that favorably regulate their expression. Results: The dysregulations in gene expression corresponded to hyperkeratinization (upregulation of genes involved in keratin production and keratinocyte differentiation) and cellular proliferation (downregulation of cell cycle regulating and pro-apoptotic genes). Genes involved in retinoic acid (RA) metabolism and signaling were dysregulated in a pattern suggesting local cellular RA deficiency. Consequently, RA also emerged as the most promising potential therapeutic option for ITS, as it favorably regulated seven of the ten most highly dysregulated genes. Conclusion: This is the first study to characterize the role of hyperkeratinization and dysregulations in RA metabolism and signaling in the disease pathophysiology. Given the ability of RA to favorably regulate key genes involved in ITS, future studies must explore its efficacy as a potential therapeutic option for patients with recalcitrant ITS.
... Conversely, milk and dairy products included in the human diet represent a relevant source of the lipophilic vitamin A and of several of the hydrophilic B-complex vitamins [131]. Vitamin A is involved in visual function, sustains fetal development and embryonic growth [132], and promotes cellular differentiation in epithelial cells and bone tissue [133]. It also keeps the immune system active, strengthens its humoral and cellular components [134], and improves protein synthesis, metabolism, and cell proliferation, acting as an effective age delayer [135]. ...
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Milk has become a staple food product globally. Traditionally, milk quality assessment has been primarily focused on hygiene and composition to ensure its safety for consumption and processing. However, in recent years, the concept of milk quality has expanded to encompass a broader range of factors. Consumers now also consider animal welfare, environmental impact, and the presence of additional beneficial components in milk when assessing its quality. This shifting consumer demand has led to increased attention on the overall production and sourcing practices of milk. Reflecting on this trend, this review critically explores such novel quality parameters, offering insights into how such practices meet the modern consumer’s holistic expectations. The multifaceted aspects of milk quality are examined, revealing the intertwined relationship between milk safety, compositional integrity, and the additional health benefits provided by milk’s bioactive properties. By embracing sustainable farming practices, dairy farmers and processors are encouraged not only to fulfill but to anticipate consumer standards for premium milk quality. This comprehensive approach to milk quality underscores the necessity of adapting dairy production to address the evolving nutritional landscape and consumption patterns.
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Whether the fat-soluble vitamins A, D, E, and K are associated with development of graft-versus-host disease (GvHD) after allogeneic stem cell transplantation, is unclear. We assessed if the levels of these vitamins were associated with development of GvHD during the first year after transplantation using data from a two-armed randomized nutritional intervention trial. Changes in plasma levels during 1-year follow-up were analyzed using a linear mixed model for repeated measurements. Vitamin A, D, E, and K levels changed significantly the first year in both study arms (p < 0.001). Higher levels of vitamin E over time were associated with less acute GvHD grades 3–4 (OR = 0.997, 95% CI: (0.994, 0.999), p = 0.017). No associations were found with vitamin A, D, E and K levels and chronic GvHD. Multivariable analysis adjusted for treatment group, age, pre-transplant vitamin level and risk factors for GvHD did not change the results. Six weeks post-transplantation, higher levels of vitamin E were associated with less acute GvHD grades 3–4, (p = 0.012). In conclusion, we found an association between higher levels of vitamin E over time and less severe acute GvHD. Whether this reflects a causal relationship warrants further study. ClinicalTrials.gov (NCT01181076). Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-84805-2.
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In this review, we will highlight infants' immune responses to food, emphasizing the unique aspects of early‐life immunity and the critical role of breast milk as a food dedicated to infants. Infants are susceptible to inflammatory responses rather than immune tolerance at the mucosal and skin barriers, necessitating strategies to promote oral tolerance that consider this susceptibility. Breast milk provides nutrients for growth and cell metabolism, including immune cells. The content of breast milk, influenced by maternal genetics and environmental exposures, prepares the infant's immune system for the outside world, including solid foods. To do this, breast milk promotes immune system development through antigen‐specific and non‐antigen‐specific immune education by exposing the newborn to food and respiratory allergens and acting on three key targets for food allergy prevention: the gut microbiota, epithelial cells, and immune cells. Building knowledge of how the maternal exposome and human milk composition influence offspring's healthy immune development will lead to recommendations that meet the specific needs of the developing immune system and increase the chances of promoting an appropriate immune response to food in the long term.
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Background Vitamin A deficiency (VAD) is a common micronutrient deficiency that imposes a substantial burden worldwide. This study examined the burden of VAD from 1990 to 2019 in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI). Methods The data were obtained from the Global Burden of Disease (GBD) 2019 database. We reported the prevalence, incidence, and years lived with disability (YLDs) that were attributable to VAD for the MENA region, along with its constituent countries. Results In 2019, the MENA region had 30.6 million prevalent cases of VAD, with an age-standardized prevalence rate of 5249.9 per 100,000 population. In addition, VAD was responsible for 62.2 thousand YLDs, with an age-standardized YLD rate of 10.2 per 100,000. The age-standardized prevalence [50.3% (−55.9 to −44.7)] and YLD [−49.3% (−55.3 to −43.1)] rates of VAD have significantly decreased since 1990. In 2019, the MENA region’s VAD-attributable YLD rate was below the global average for males and females across all age groups. Additionally, SDI was negatively associated the age-standardized YLD rate of VAD. Conclusion This study underscores the necessity of frequently updating health data and developing guidelines and regulations to prevent, detect early, and effectively treat VAD in the MENA countries.
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Background The association between vitamin A and single cardiometabolic diseases has been extensively studied, but the relationship between dietary vitamin A intake and the risk of cardiometabolic multimorbidity (CMM) has not been studied. Therefore, the present study was conducted to explore the association with CMM risk by analyzing different sources of vitamin A. Methods This study utilized 13,603 subjects aged ≥ 18 years from 1997–2015 from the China Health and Nutrition Survey (CHNS). Dietary intake was calculated from 3 consecutive 24-h dietary recalls combined with a house hold food inventory. CMM is defined as the development of at least two cardiometabolic diseases. Results After a median follow-up of 9.1 years, there were 1050 new cases of CMM. The risk of CMM was significantly lower in those with higher vitamin A intake (Q1 vs Q5 HR 0.66, 95% CI 0.54–0.81). β-carotene (Q1 vs Q5 HR 0.82, 95% CI 0.66–1.02) and retinol (Q1 vs Q5 HR 0.59, 95%CI 0.48–0.73) intake had a similarly negative correlation. Using restricted cubic spline found an L-shaped relationship between retinol intake and CMM (p non-linear < 0.001). In subgroup analyses, protective effects were stronger for participants aged ≥ 44 years (HR 0.72, 95%CI 0.57–0.92) and for the female group (HR 0.62, 95%CI 0.45–0.84). Conclusion Dietary vitamin A was a protective factor for CMM, and this effect was stronger in age ≥ 44 years and in the female group. There was a ceiling effect on the protective effect of retinol intake on the risk of CMM.
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The specific tissue changes which follow the deprivation of fat-soluble vitamin A in albino white rats and in the human concerns epithelial tissues. This effect is the substitution of stratified keratinizing epithelium for normal epithelium in various parts of the respiratory tract, alimentary tract, eyes, and paraocular glands and the genitourinary tract. We have described the morphological sequences which clearly show that the replacement of epithelium arises from focal proliferation of cells arising from the original epithelium and not by differentiation or change of preexisting cells. Young rats respond to the deficiency more promptly than adults. Growth activity of epithelium is not diminished. On the contrary, there is convincing evidence that it is greatly augmented. In a few of our animals the behavior of the replacing epithelium in respect to numbers of mitotic figures and response on the part of connective tissue and blood vessels suggests the acquisition of neoplastic properties. While the epitheliums which are the seats of these changes are largely of covering types, glandular epithelium is involved, specifically in the paraocular glands and salivary glands. It is highly probable also that the epithelium of gland ducts, respiratory mucosa, and genitourinary tract have secretory functions so that we conclude that the deficiency results in loss of specific (chemical) functions of the epitheliums concerned, while the power of growth becomes augmented. Explanation for the substitution of a chemically inactive (nonsecretory) epithelium, common in type for all locations, remains a matter of speculation. We can only speculate also in regard to the absence of change in the epithelium of such organ as the liver, parenchyma of the kidney, stomach, and intestines. The significance of the order or sequence in which different organs exhibit this change has not been determined. In general the respiratory mucosa in nares, trachea, and bronchi respond first, then the salivary glands, eye, genitourinary tract, then paraocular glands and pancreas, although as has been noted there are exceptions to this order. Our studies show that the mitochondrial apparatus is not primarily affected. Study of individual cells indicates that the first morphological evidence of avitaminosis will be found in the nucleus. We have not devoted sufficient study to be certain, but an increase of chromatin and in some instances in size of nucleoli are early morphological manifestations. Other important effects of fat-soluble A deficiency are atrophy of glandular organs, emaciation, localized edema of testes, submaxillary gland, and connective tissue structures of the lungs and focal myocardial lesions. From our own limited experience with rats fed on a water-soluble B deficient diet and from work by Cramer, Drew, and Mottram, the loss of fat in water-soluble B deficiency is as great, if not greater than in vitamin A deuciency, so that tor tne present we assume that this is not a specific manifestation of any one avitaminosis. The same applies to glandular atrophy. Both of these effects probably concern the nutrition as a whole and may be ascribed to inanition. The occurrence of transient edema in testes and salivary gland coinciding with a period of maximum atrophic change, suggests the hypothesis that this edema is the result of failure of epithelium to utilize transported material, which leads further to the hypothesis that the capillaries of these organs are differentiated in regard to permeability to the respective materials utilized by the cells. It would seem that in the case of the testis we have a unique instance of complete atrophy producible at will without impairment of circulation and supporting tissues. This phenomenon may possibly be followed with advantage in the study of the mechanism of edema. Vascularization of the cornea, as we have shown it to be independent of infection, must be a physiological response to the increased demands of the rapidly growing epithelium which has replaced the corneal epithelium. We have assumed throughout this work that the diet on which we kept our animals was deficient in respect to a single substance or group of substances having similar physiological properties, designated by the term fat-soluble vitamin A. Whether or not more than one so called vitamin or accessory substance was missing in the diet we employed does not affect the theoretical importance of the morphological results. Work by Evans and Bishop would indicate that other factors affecting fertility in addition to the so called antixerophthalmic or vitamin A factor may have been missing. Our own experience leads us to believe the specific effects we have described upon epithelial tissues were in all probability due to withdrawal of a single factor. We have shown how these effects, that is the replacement of uterine epithelium by keratinizing epithelium can account for sterility in the female. Whether or not the atrophy of the testis is due to the same factor remains to be proved, but presumptive evidence is strong that this is the case. The study of the reverse changes that follow in the rapid amelioration when the rats are restored to an adequate diet has been begun and will be reported later. We have shown that the substitution of keratinizing epithelium in all locations is not secondary to infections, and presumably is a primary effect of the withdrawal of factors essential for the chemical activities or maintenance of differentiation of the epitheliums concerned. It is, of course, possible that the phenomenon is produced in a roundabout way in that it may be secondary to the effects of the avitaminosis upon the metabolism of tissue-sustaining substances. This possibility is supported by the cessation of growth of the skeleton and teeth, although we know that other avitaminoses produce retardation of growth.
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Vitamin A (retinol and its derivatives) is essential for a variety of biologic processes, many of which are related to growth, cellular differentiation, and cell-cell or cell-substrate interactions. Within the last 5 years, there has been a renaissance of interest in vitamin A and immunity that is based largely on three important advances. First, a number of controlled, field-based or hospital-based, studies have demonstrated that vitamin A supplementation can decrease mortality in preschool children in populations at high risk for vitamin A deficiency. Although a mechanistic link between child survival and improved immunity has yet to be established, it seems quite probable that at least some of the benefit of vitamin A is due to restoration of epithelial barriers and improved resistance to respiratory and gastrointestinal infections. Second, vitamin A, either in the form of retinol or its metabolite, retinoic acid, has been shown to stimulate the rejection of certain immunogenic tumors; this effect may ...
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