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Low-Histamine Diets: Is the Exclusion of Foods Justified by Their Histamine Content?

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A low-histamine diet is currently the most advised strategy to prevent the symptomatology of histamine intolerance. Conceptually, these diets should be founded on the exclusion of histamine-containing foods, although a certain disparity is found within the list of excluded foods in accordance with the different low-histamine diets available in the literature. This study aimed to critically review low-histamine diets reported in the scientific literature, according to the histamine and other biogenic amine contents of the excluded foods. A total of ten scientific studies that provided specific recommendations on the foods that must be avoided within the framework of a low-histamine diet were found. Overall, the comparative review brought out the great heterogenicity in the type of foods that are advised against for histamine intolerant individuals. Excluded foods were, in most cases, different depending on the considered diet. Only fermented foods were unanimously excluded. The exclusion of 32% of foods could be explained by the occurrence of high contents of histamine. The presence of putrescine, which may interfere with histamine degradation by the DAO enzyme at the intestinal level, could partly explain the reason why certain foods (i.e., citrus fruits and bananas) were also frequently reported in low-histamine diets. Finally, there was a range of excluded foods with an absence or very low levels of biogenic amines. In this case, certain foods have been tagged as histamine-liberators, although the mechanism responsible has not yet been elucidated.
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nutrients
Article
Low-Histamine Diets: Is the Exclusion of Foods Justified by
Their Histamine Content?
Sònia Sánchez-Pérez 1,2,3, Oriol Comas-Basté1,2,3 , M. Teresa Veciana-Nogués1,2,3,
M. Luz Latorre-Moratalla 1,2,3 and M. Carmen Vidal-Carou 1,2,3,*


Citation: Sánchez-Pérez, S.;
Comas-Basté, O.; Veciana-Nogués,
M.T.; Latorre-Moratalla, M.L.;
Vidal-Carou, M.C. Low-Histamine
Diets: Is the Exclusion of Foods
Justified by Their Histamine Content?.
Nutrients 2021,13, 1395.
https://doi.org/10.3390/
nu13051395
Academic Editor: Bahram
H. Arjmandi
Received: 26 March 2021
Accepted: 19 April 2021
Published: 21 April 2021
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Attribution (CC BY) license (https://
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4.0/).
1Departament de Nutrició, Ciències de l’Alimentaciói Gastronomia, Facultat de Farmàcia i Ciències de
l’Alimentació, Campus de l’Alimentacióde Torribera, Universitat de Barcelona (UB), Av. Prat de la Riba 171,
8921 Santa Coloma de Gramenet, Spain; soniasanchezperez@ub.edu (S.S.-P.); oriolcomas@ub.edu (O.C.-B.);
veciana@ub.edu (M.T.V.-N.); mariluzlatorre@ub.edu (M.L.L.-M.)
2Institut de Recerca en Nutriciói Seguretat Alimentària (INSA·UB), Universitat de Barcelona (UB),
Av. Prat de la Riba 171, 8921 Santa Coloma de Gramenet, Spain
3Xarxa d’InnovacióAlimentària (XIA), C/Baldiri Reixac 4, 8028 Barcelona, Spain
*Correspondence: mcvidal@ub.edu; Tel.: +34-934-031-984
Abstract:
A low-histamine diet is currently the most advised strategy to prevent the symptomatology
of histamine intolerance. Conceptually, these diets should be founded on the exclusion of histamine-
containing foods, although a certain disparity is found within the list of excluded foods in accordance
with the different low-histamine diets available in the literature. This study aimed to critically
review low-histamine diets reported in the scientific literature, according to the histamine and other
biogenic amine contents of the excluded foods. A total of ten scientific studies that provided specific
recommendations on the foods that must be avoided within the framework of a low-histamine diet
were found. Overall, the comparative review brought out the great heterogenicity in the type of foods
that are advised against for histamine intolerant individuals. Excluded foods were, in most cases,
different depending on the considered diet. Only fermented foods were unanimously excluded. The
exclusion of 32% of foods could be explained by the occurrence of high contents of histamine. The
presence of putrescine, which may interfere with histamine degradation by the DAO enzyme at the
intestinal level, could partly explain the reason why certain foods (i.e., citrus fruits and bananas)
were also frequently reported in low-histamine diets. Finally, there was a range of excluded foods
with an absence or very low levels of biogenic amines. In this case, certain foods have been tagged as
histamine-liberators, although the mechanism responsible has not yet been elucidated.
Keywords:
histamine; low-histamine diet; histamine-free diet; histamine intolerance; biogenic
amines; histamine-releasing foods
1. Introduction
In recent years, a significant increase in the frequency of food intolerances (i.e., non-
toxic and non-immune mediated reactions to food) has been detected in most developed
societies. Food intolerances are disabling disorders that provoke an important decrease in
the quality of life of this population [
1
,
2
]. Among them, histamine intolerance, also referred
to as food histaminosis or hypersensitivity to food histamine, arises from the failure of the
diamine oxidase (DAO) enzyme to degrade dietary histamine at the intestinal level. DAO
deficit results in an increase in systemic histamine concentrations and the subsequent onset
of symptoms [
3
5
]. This enzyme deficiency may have a genetic or pathological etiology
(i.e., secondary to certain inflammatory bowel diseases) [
6
,
7
]. Moreover, some widely used
pharmacologic drugs have also been described as potential DAO inhibitors, although in a
punctual and reversible manner [
8
,
9
]. More recently, a potential etiological relationship has
been suggested between a dysbiosis in the intestinal microbiota and histamine intolerance,
although this hypothesis still needs to be further studied [10].
Nutrients 2021,13, 1395. https://doi.org/10.3390/nu13051395 https://www.mdpi.com/journal/nutrients
Nutrients 2021,13, 1395 2 of 10
Plasma histamine accumulation can provoke a wide number of nonspecific gastroin-
testinal and extraintestinal clinical manifestations (i.e., dermatological, respiratory, neu-
rological and hemodynamic complaints) [
3
5
]. The most frequent and severe symptoms,
according to a recent comprehensive study, were abdominal distension, diarrhea, post-
prandial fullness, abdominal pain and constipation, followed by headaches, dizziness, and
palpitations [
2
]. Moreover, in 97% of cases the onset of three or more symptoms concerning
different organs were reported, thus, underlining the complexity of the clinical picture of
histamine intolerance [2].
Currently, the most advised strategies to prevent the onset of symptoms are the follow-
up of a low-histamine diet and the supplementation with exogenous DAO enzyme to
enhance the intestinal histamine degradation [
11
13
]. As regards low-histamine diets,
several clinical studies are continuously gathering increasing evidence on their efficacy on
the improvement or remissions of symptoms [5,1423]. The vast majority of these studies
report efficacy rates higher than 70%, although some of them face certain limitations in
terms of the number of patients and/or in the duration of the dietary intervention [3].
Conceptually, low-histamine diets should be based on the exclusion of histamine-
containing foods. Histamine in foods is mainly formed by the bacterial decarboxylation
of its precursor amino acid, histidine [
24
]. Therefore, foods susceptible to accumulating
high contents of this amine are those that are microbiologically altered by spoilage bacteria;
fermented products, due to the histaminogenic capacity of fermentative bacteria [25].
The design of a low-histamine diet is challenging due to different handicaps. One
of these is the lack of consensus on the histamine level below which a food is said to be
considered low in histamine. Thus, variable histamine levels in food ranging between
5–50 mg/kg have been pointed out as potential thresholds, while other authors are much
more demanding and consider foods with low histamine concentrations to be those that
contain amounts below 1 mg/kg [
12
,
26
28
]. Moreover, there is no specific regulation for
the food industry to declare the occurrence or absence of histamine in food labelling, which
could help histamine intolerant individuals to make suitable and informed choices.
Overall, providing dietary recommendations and guidelines in the frame of a low-
histamine diet is difficult for healthcare professionals. In fact, disparity is found in the list of
excluded foods reported by the different available low-histamine diets. Therefore, the aim
of this work was to critically review the low-histamine diets from the literature, according
to the contents of histamine and other biogenic amines found in the excluded foods.
2. Materials and Methods
2.1. Identification of Low-Histamine Diets
A selective search of scientific articles concerning low-histamine diets was performed
through the PubMed and Web of Science bibliographic databases using the following
keywords: “low-histamine diet”, “histamine-free diet”, ”histamine elimination diet”, “his-
tamine restricted diet”, “histamine intolerance treatment” and “dietary management of
histamine intolerance”. Only studies that clearly specified the foods allowed and/or
excluded within a low-histamine diet were considered for further assessment.
2.2. Content of Histamine and Other Biogenic Amines in Foods and Beverages Excluded from
Low-Histamine Diets
Data on histamine and other biogenic amines (i.e., putrescine, cadaverine, tyramine,
spermidine and spermine) content in foods and beverages from the Spanish market were
obtained from the self-produced and updated database [11,29].
3. Results
The selective search performed in this study resulted in a total of ten scientific publications,
which provided specific recommendations about the range of foods that may be consumed
or must be avoided within the framework of a low-histamine diet [
14
,
16
,
17
,
20
,
23
,
26
,
30
33
].
Overall, most of these studies based their recommendations on previous studies (mainly
Nutrients 2021,13, 1395 3 of 10
dealing with histamine contents in foods) or on those foods that patients associated with the
onset of symptoms. Figure 1graphically summarizes the extensive list of the avoided foods
according to the literature review and the count of low-histamine diets that exclude each
foodstuff. This comparative review showed great heterogenicity in the foods that should be
excluded by histamine intolerant people. Firstly, all low-histamine diets unanimously advised
the elimination of many fermented foods and beverages (i.e., dry-fermented sausages, cured
cheese, wine and beer). On the other hand, it is worth highlighting that the majority of foods
were only excluded by 50% or less of the revised diets. These results confirm the lack of
consensus that currently exists in this type of diet.
Nutrients 2021, 13, x FOR PEER REVIEW 3 of 10
3. Results
The selective search performed in this study resulted in a total of ten scientific publi-
cations, which provided specific recommendations about the range of foods that may be
consumed or must be avoided within the framework of a low-histamine diet
[14,16,17,20,23,26,30–33]. Overall, most of these studies based their recommendations on
previous studies (mainly dealing with histamine contents in foods) or on those foods that
patients associated with the onset of symptoms. Figure 1 graphically summarizes the ex-
tensive list of the avoided foods according to the literature review and the count of low-
histamine diets that exclude each foodstuff. This comparative review showed great het-
erogenicity in the foods that should be excluded by histamine intolerant people. Firstly,
all low-histamine diets unanimously advised the elimination of many fermented foods
and beverages (i.e., dry-fermented sausages, cured cheese, wine and beer). On the other
hand, it is worth highlighting that the majority of foods were only excluded by 50% or less
of the revised diets. These results confirm the lack of consensus that currently exists in
this type of diet.
Figure 1. List of the avoided foods according to the literature review on low-histamine diets and
count of references that exclude each foodstuff [14,16,17,20,23,26,30–33].
The distribution of histamine levels in all excluded foods is shown in Figure 2. The
exclusion of all foods listed above could not be explained by the occurrence of histamine.
In fact, most of the foodstuffs retailed in Spain showed histamine levels below 1 mg/kg,
considered by some authors as the threshold to define a food low in histamine. Contrarily,
fermented foods had a large variability, even within samples of the same production batch
Figure 1.
List of the avoided foods according to the literature review on low-histamine diets and count of references that
exclude each foodstuff [14,16,17,20,23,26,3033].
The distribution of histamine levels in all excluded foods is shown in Figure 2. The
exclusion of all foods listed above could not be explained by the occurrence of histamine.
In fact, most of the foodstuffs retailed in Spain showed histamine levels below 1 mg/kg,
considered by some authors as the threshold to define a food low in histamine. Contrarily,
fermented foods had a large variability, even within samples of the same production batch
due to the essentially microbial origin of histamine. Moreover, the nature of the food, the
Nutrients 2021,13, 1395 4 of 10
bacterial strain and many other factors that influence the growth and metabolic activity
of the bacteria can also have an impact on the accumulation of this compound. This
variability is precisely one of the causes of the complexity of issuing recommendations and,
consequently, as a precautionary measure all the foods, that a priori may contain histamine,
are eliminated.
Nutrients 2021, 13, x FOR PEER REVIEW 4 of 10
due to the essentially microbial origin of histamine. Moreover, the nature of the food, the
bacterial strain and many other factors that influence the growth and metabolic activity of
the bacteria can also have an impact on the accumulation of this compound. This variabil-
ity is precisely one of the causes of the complexity of issuing recommendations and, con-
sequently, as a precautionary measure all the foods, that a priori may contain histamine,
are eliminated.
Figure 2. Histamine distribution (mg/kg or L) in foods marketed in Spain excluded from low-histamine diets [11,29].
Fermented foods (i.e., dry-fermented sausages, cured-cheese, sauerkraut and soy-fer-
mented derivatives) are products that can potentially accumulate high histamine contents
(Figure 2). In fermented foods, the presence of histamine depends on both the hygienic
quality of the raw materials and/or manufacturing processes, and the histaminogenic ca-
pacity of technological bacteria [34,35]. As can be seen in Table 1, histamine levels in fer-
mented foods marketed in Spain were relatively low (with mean values ranging between
22 and 74 mg/kg), but in certain cases these types of foods reached high histamine levels,
with 5% of samples measuring above 203 mg/kg in cheese, 130 mg/kg in dry-fermented
sausages and 486 mg/kg in soy-fermented products. Apart from histamine, in this food
category, other biogenic amines could be frequently found, mainly tyramine. The pres-
ence of tyramine is strongly associated with the enzymatic activity of many fermentative
lactic acid bacteria species. Maximum tyramine levels of 750 mg/kg in dry-fermented
products, 1500 mg/kg in cheese and 1700 mg/kg in fermented vegetables were found. The
occurrence of putrescine and cadaverine was also frequent, though at lower and more
variable levels than tyramine (Table 1).
Table 1. Biogenic amines occurrence (mg/kg or L) found in different food and beverages from the
Spanish market. Data are presented as average (standard deviation), P95 and minimum–maxi-
mum. [11,29].
Foods n Occurrence of Biogenic Amines (mg/kg or L)
Histamine Putrescine Cadaverine Tyramine Spermidine Spermine
Dry-fermented 424 21.57 (52.10) 68.23 (101.40) 32.45 (72.96) 140.9 (119.59) 5.39 (5.94) 25.12 (23.85)
sausages 129.95 280.3 172.10 378.51 18.80 59.94
ND-474.82 ND-537.05 ND-658.05 ND-742.60 3.04–32.65 0.34–224.15
Figure 2. Histamine distribution (mg/kg or L) in foods marketed in Spain excluded from low-histamine diets [11,29].
Fermented foods (i.e., dry-fermented sausages, cured-cheese, sauerkraut and soy-
fermented derivatives) are products that can potentially accumulate high histamine con-
tents (Figure 2). In fermented foods, the presence of histamine depends on both the
hygienic quality of the raw materials and/or manufacturing processes, and the histamino-
genic capacity of technological bacteria [
34
,
35
]. As can be seen in Table 1, histamine levels in
fermented foods marketed in Spain were relatively low (with mean values ranging between
22 and 74 mg/kg), but in certain cases these types of foods reached high histamine levels,
with 5% of samples measuring above 203 mg/kg in cheese, 130 mg/kg in dry-fermented
sausages and 486 mg/kg in soy-fermented products. Apart from histamine, in this food
category, other biogenic amines could be frequently found, mainly tyramine. The presence
of tyramine is strongly associated with the enzymatic activity of many fermentative lactic
acid bacteria species. Maximum tyramine levels of 750 mg/kg in dry-fermented products,
1500 mg/kg in cheese and 1700 mg/kg in fermented vegetables were found. The occur-
rence of putrescine and cadaverine was also frequent, though at lower and more variable
levels than tyramine (Table 1).
Nutrients 2021,13, 1395 5 of 10
Table 1.
Biogenic amines occurrence (mg/kg or L) found in different food and beverages from the Spanish market. Data are
presented as average (standard deviation), P95 and minimum–maximum [11,29].
Foods n
Occurrence of Biogenic Amines (mg/kg or L)
Histamine Putrescine Cadaverine Tyramine Spermidine Spermine
Dry-fermented 424 21.57 (52.10)
68.23 (101.40)
32.45 (72.96)
140.9 (119.59)
5.39 (5.94) 25.12 (23.85)
sausages 129.95 280.3 172.10 378.51 18.80 59.94
ND-474.82 ND-537.05 ND-658.05 ND-742.60 3.04–32.65 0.34–224.15
Cured, semi-cured 80 33.10 (77.10)
68.90 (141.30) 87.25 (283.55)
128 (264.41) 8.49 (12.40) 1.84 (4.46)
and 203.30 423.00 356.52 613.46 36.38 12.58
grated cheese ND-389.86 ND-666.92 ND-2036.90 ND-1567.50 ND-68.92 ND-21.03
Soy-fermented 21
73.95 (184.51)
13.48 (6.71) 6.88 (11.97) 187.24
(446.59) 34.84 (38.23) 4.81 (5.24)
products 486.31 22.2 35.08 930 105.47 11.15
ND-730.06 2.73–31.06 ND-36.95 ND-1730.17 ND-124.03 ND-21.89
Sauerkraut 5 43.74 (51.45) 232.66
(148.53) 76.49 (73.85) 43.47 (28.05) 5.29 (3.86) 0.85 (0.40)
76.48 327.18 123.49 61.32 7.75 1.10
7.36–80.12 127.63–
337.68 24.27–128.71 23.63–63.3 2.56–8.02 0.56–1.13
Beer 176 1.23 (2.47) 3.16 (2.89) 1.28 (3.94) 6.31 (8.04) 0.48 (0.81) 0.19 (0.61)
3.28 7.61 4.66 25.44 1.7 1.14
ND-21.60 ND-14.50 ND-31.40 0.55–46.80 ND-6.30 ND-3.90
Wine 299 3.63 (5.86) ND ND 2.42 (2.47) ND ND
12.3 7.5
0.09–34.25 ND-15.85
Fresh white fish 31 1.14 (6.46) 1.33 (2.67) 1.61 (6.01) 1.03 (3.39) 2.25 (1.91) 6.78 (2.65)
ND 7.43 4.8 6.51 5.32 11.27
ND-36.55 ND-10.50 ND-33.65 ND-17.10 ND-7.85 2.05–13.50
Fresh oily fish 49 3.27 (15.71) 2.37 (6.71) 13.22 (67.40) 1.18 (5.43) 6.69 (3.09) 14.47 (9.75)
6.66 5.02 10.45 2.19 11.39 31.67
ND-111.26 ND-39.89 ND-400.23 ND-37.20 1.20–11.90 1.05 -37.03
Preserved and 151 10.03 (53.32) 2.79 (3.81) 7.41 (10.79) 8.23 (14.87) 3.61 (2.78) 7.48 (6.05)
semi-preserved 20.39 9.02 29.23 40.6 7.94 17.05
fish ND-657.05 ND-21.15 ND-55.80 ND-88.50 0.37–11.80 ND-35.20
Seafood 7 ND 3.02 (3.01) ND 0.15 (0.27) 4.03 (3.23) 10.63 (6.92)
7.62 0.58 7.94 19.21
1.44–9.79 ND-0.65 0.82–8.37 4.93–19.73
Fresh meat 199 ND 1.35 (2.66) 5.02 (14.55) 4.32 (8.62) 1.16 (4.59) 17.08 (4.59)
3.04 28.71 35.89 3.4 29.55
ND-9.68 ND-51.16 ND-38.77 ND-13.96 9.70–25.69
Cured meat 23 4.89 (22.70) 4.65 (5.18) 38.03 (92.82) 3.43 (10.56) 6.05 (0.92) 37.82 (10.46)
3.54 9.24 49.64 42.58 6.88 42.58
ND-150 ND-17.40 ND-305 ND-46.50 4.5–7.30 24.9–62.10
Milk 5 ND ND ND ND ND ND
Yogurt 5 ND 2.04 (2.01) ND ND 1.07 (0.75) 0.28 (0.39)
2.23 0.69 0.3
ND-4.05 0.50–1.75 ND-0.50
Eggs 14 ND ND ND ND 3.61 (1.54) 4.48 (1.72)
4.43 5.27
ND-4.47 0.32–5.31
Soybeans 5 ND 19.07 (4.39) 9.04 (1.09) ND 99.55 (3.52) 25.92 (7.34)
21.86 9.74 101.79 30.58
15.96–22.17 8.27–9.81 97.06–102.04 20.73–31.10
Eggplant 23 39.42 (30.66) 34.30 (6.98) ND 0.60 (0.90) 5.06 (1.93) 0.47 (0.48)
98.84 46.29 2.24 7.7 1.29
4.17–100.64 24.10–48.63 ND-2.27 2.54–7.97 ND-1.38
Spinach 18 31.77 (17.02) 4.48 (2.46) ND (0.02) 2.05 (0.83) 28.22 (9.72) 3.33 (1.89)
63.37 7.70 0.01 3.10 44.53 6.13
9.46–69.72 0.14–9.20 ND-0.08 0.79–4.28 15.63–52.98 ND-8.85
Nutrients 2021,13, 1395 6 of 10
Table 1. Cont.
Foods n
Occurrence of Biogenic Amines (mg/kg or L)
Histamine Putrescine Cadaverine Tyramine Spermidine Spermine
Tomato 53 2.51 (4.08) 16.48 (6.93) 0.50 (0.48) 0.49 (0.92) 3.04 (1.41) 0.08 (0.16)
13.83 30.16 1.42 1.21 5.69 0.36
ND-17.07 6.29–35.55 ND-2.33 ND-6.38 2.91–7.90 ND-0.73
Pumpkin 13 ND 9.87 (6.19) 0.58 (0.78) ND 10.32 (2.83) 1.77 (1.99)
19.17 1.82 13.88 5.21
2.95–24.23 ND-2.15 6.19–14.98 0.5–6.88
Apricot 4 ND ND ND ND 5.86 (1.59) ND
6.50
4.16–7.68
Avocado 5 ND ND ND 1.81 (2.06) 3.15 (3.27) 4.50 (2.52)
4.65 6.69 7.61
0.58–5.44 0.18–6.72 2.02–7.92
Banana 8 ND 37.94 (8.32) ND 0.53 (0.79) 11.91 (2.90) 1.33 (0.97)
47.37 ND 15.10 2.67
25.50–49.49 ND-1.85 7.62–15.79 ND- 2.75
Citrus fruits 38 ND 79.75 (44.36) ND ND 2.57 (1.28) 0.12 (0.36)
146.16 4.86 1.02
1.21–173.81 0.18–6.24 ND-1.14
Cherry 5 ND 3.42 (0.06) ND ND 2.37 (0.16) ND
3.46 2.47
3.42–3.46 2.26–2.47
Grapes 10 ND 2.69 (0.34) ND ND 5.25 (2.61) 2.59 (0.11)
4.05 8.6 2.56
1–4.30 ND-9.70 2.35–2.68
Kiwi 13 ND 1.47 (0.47) ND ND 5.35 (1.06) 0.73 (0.56)
2.07 6.39 1.41
0.48–2.17 2.72–6.39 ND-1.50
Papaya 6 ND 7.25 (5.80) ND ND 14.35 (4.32) 1.16 (1.59)
11.86 15.45 2.06
ND-12.48 10.32–19.07 ND-2.99
Pineapple 5 ND 2.69 (1.42) ND ND 1.92 (1.26) 0.48 (0.21)
3.89 3.15 0.75
0.56–3.97 0.27–3.18 0.32–0.77
Plum 6 ND ND ND 4.02 (4.32) 2.68 (0.30) 1.74 (2.47)
6.76 2.87 3.31
0.96–7.07 2.47–2.89 ND- 3.48
Red fruits 7 ND ND ND 7.37 (1.03) 5.58 (1.16) 1.97 (1.61)
9.36 2.54 1.65
3.34–11.52 0.78–3.98 ND–3.73
Strawberries 9 ND 3.77 (1.52) ND ND 6.00 (1.56) 0.46 (0.69)
6.09 8.52 1.5
2.04–6.41 4.62–9.86 ND-1.62
Olives 5 ND 2.64 (1.58) ND 1.95 (1.85) ND ND
4.2 3.7
1.54–4.45 0.28–3.94
Nuts 47 ND 4.40 (7.11) 0.25 (1.69) 0.11 (0.41) 28.64 (24) 11.14 (8.91)
12.58 ND 0.66 55.23 23.73
ND-39.51 ND-11.58 ND-2.63 6.21–140.55 ND-50.81
Chocolate 15 ND 0.41 (0.65) 0.42 (0.96) 3.70 (1.24) 3.11 (0.70) 2.00 (0.90)
1.89 ND 5.69 4.23 2.65
ND- 1.98 ND-2.78 2.27–5.81 2.17–4.65 ND-2.72
Tea 9 ND 2.61 (0.49) ND 5.07 (3.80) 5.86 (1.18) 18.32 (5.31)
3.12 8.34 6.59 22.84
2.66–3.37 ND-10.08 3.66–7.64 8.23–23.94
In fermented beverages (e.g., wine and beer) histamine and other biogenic amine
contents were much lower than those reported for other fermented foods. However, it must
Nutrients 2021,13, 1395 7 of 10
be noted that the presence of alcohol will enhance the toxic effect of histamine [
11
,
36
,
37
].
In fact, alcohol and its metabolite, acetaldehyde, compete with histamine for the enzyme
responsible for their metabolization (aldehyde dehydrogenase), thus, resulting in the
accumulation of this amine in the organism [35,38].
Fish and fish derivatives are also usually excluded in low-histamine diets. As shown
in Table 1, in most of the fresh fish and derivatives retailed in Spain (i.e., semi-preserved
and preserved) no histamines or only in low amounts were detected (P95 below 20 mg/kg).
The low occurrence of histamine was also reported by EFSA for this same food category.
In fact, only 27% of a total of 6329 European fishery products showed histamine, and
generally at low levels [
38
]. Nevertheless, high histamine concentrations could be achieved
in the case of inadequate freshness of raw fish and/or hygienic deficiencies during the
manufacturing of fish derivatives. An example is the 111 mg/kg found in fresh salmon
and the 657 mg/kg of histamine determined in canned sardines (Table 1). For this reason,
low histamine diets usually advise the against the consumption of fish, specifically certain
scombroid species (e.g., mackerel, tuna, sardines and anchovy), which are susceptible
to histamine accumulation due to their high free histidine contents [
25
]. Moreover, the
action of some of spoilage bacteria derived from the lack of freshness could also entail the
formation of other amines, especially putrescine and cadaverine (Table 1). The thermostable
nature of biogenic amines implies that thermal treatments applied for the obtention of
preserved canned fish do not help diminish their occurrence [5].
As regards fresh, cooked and cured meat, as in fish, the absence of histamine or other
biogenic amines is expected, so long as freshness and correct hygienic conditions of the
products or manufacturing processes are guaranteed (Table 1). In fact, as can be seen in
Figure 1, fresh and cured meat were only excluded by three and two low-histamine diets,
respectively. However, the presence of these foods in most low-histamine diets could entail
a risk for histamine intolerant individuals if freshness is not guaranteed.
Histamine was also found in some plant-origin products, such as tomato, eggplant and
spinach (Figure 2). The origin of low histamine levels in these foods may be physiological,
but a high accumulation of this amine has been related to bacterial decarboxylase activity
which occurs during storage [
11
,
39
]. The study performed by Lavizzari et al., showed a
significant increase in histamine concentrations in spinach samples during 15 days of re-
frigerated storage [
39
]. The relatively high pH of spinach would allow for the implantation
and growth of some Gram-negative bacteria (Enterobacteriaceae and Pseudomonadaceae
groups), which would ultimately be responsible of histamine formation [39].
On the other hand, 68% of the not-allowed foods in low-histamine diets did not
show significant histamine levels in any of the analyzed samples (Figure 2). Among
them, citrus fruits, bananas, soybeans, pumpkins and nuts showed relevant amounts of
putrescine (Table 1). In the case of citrus fruits, outstanding levels of putrescine are very
often found, with mean levels of 79 mg/kg and maximum levels up to 173 mg/kg in the
case of mandarines. In fact, despite the absence of histamine in citrus fruits, 60% of the
revised low-histamine diets advised for their exclusion (Figure 1). Paradoxically, there are
also certain foods with relevant amounts of putrescine, the exclusion of which is not listed
in low-histamine diets [
11
,
36
,
37
]. This is the case for zucchini, peas, green peppers and
sweet corn, among others, which could achieve maximum levels of putrescine ranging
25–150 mg/kg, depending on the product.
It has been reported that certain biogenic amines, mainly putrescine and cadaverine,
could interfere with histamine degradation by the DAO enzyme at the intestinal level,
being responsible for the major absorption and subsequent toxic potential enhancement of
histamine. However, there is still scarce experimental evidence supporting this working
hypothesis. The studies carried out years ago by Arunlakshana et al. (1954), Mongar (1957)
and Hui and Taylor (1985) pointed out this potentially inhibitory effect of other biogenic
amines on histamine metabolism both through
in vitro
assays and in animal models [
40
42
].
Concretely, Mongar (1957) observed that different aliphatic diamines, such as putrescine
Nutrients 2021,13, 1395 8 of 10
and cadaverine, could potentiate histamine-induced contractions of guinea pig ileum due
to the fact that they could competitively inhibit the DAO enzyme [41].
Apart from the foods containing histamine or significant levels of putrescine, there
was a wide range (53%) of excluded foods without histamine and with no detected or a
low/very low occurrence of putrescine, cadaverine, tyramine, spermidine and/or spermine.
Thus far, the available evidence does not help to explain to what extent the presence of
low levels of these amines (alone or combined) may interfere with histamine degradation
by the DAO enzyme and be responsible for the triggering of the symptoms of histamine
intolerance. According to our knowledge, there is only one study on this topic, which was
performed back in 1985 by Hui and Taylor, demonstrating the inhibitory effect of putrescine
and cadaverine on histamine degradation in rats when these amines were present at levels
four to five-fold higher [
42
]. Curiously, as may be seen in Figure 1, the vast majority of
these foods are only excluded in one to three of the low-histamine diets, with the exception
of chocolate, strawberry, eggs, pineapple and yogurt.
Moreover, certain foods have been tagged as histamine-liberators, as they could trigger
the release of endogenous histamine. The list of foods with suggested histamine-releasing
capacity, that may be found in various scientific articles, includes citrus fruits, seafood,
papaya, tomato, nuts, pineapple, spinach, chocolate and strawberries, among others [
4
,
5
,
43
].
However, the mechanism responsible for this potential effect has not yet been elucidated.
In fact, the only available extensive review as regards the putative histamine-releasing
capacity of certain foods performed by Vlieg-Boerstra et al. (2005), clearly stated that there
is a lack of evidence supporting this mechanism. There are no clinical studies in humans
supporting the widely held belief that foods could have the ability to release histamine and
this hypothesis is only based on few and no conclusive in vitro or animal studies [43].
In summary, while the evidence supporting the clinical efficacy of low-histamine
diets is progressively growing, there is still a lack of consensus on the foods that must be
avoided in the dietary management of histamine intolerance. The critical review performed
herein demonstrates that the exclusion of only 32% of foods could be justified by their
histamine content. The presence of other biogenic amines could partly help to explain
the relationship that some patients have established between the consumption of certain
histamine-free foods and the onset of symptoms. However, low-histamine diets continue
to require the attention of researchers, both to clarify the specific interaction of other
amines in histamine metabolism and to elucidate the potential mechanisms of the so-called
histamine-releasing foods.
Author Contributions:
Conceptualization, M.T.V.-N., M.L.L.-M., M.C.V.-C.; investigation, S.S.-P.,
O.C.-B., M.L.L.-M.; writing—original draft preparation, S.S.-P., O.C.-B., M.L.L.-M.; writing—review
and editing, S.S.-P., O.C.-B., M.T.V.-N., M.L.L.-M., M.C.V.-C.; supervision, M.C.V.-C. All authors have
read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Acknowledgments:
Sònia Sánchez-Pérez is a recipient of a doctoral fellowship from the University
of Barcelona (APIF2018).
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Tuck, C.J.; Biesiekierski, J.R.; Schmid-Grendelmeier, P.; Pohl, D. Food Intolerances. Nutrients 2019,11, 1684. [CrossRef]
2.
Schnedl, W.J.; Lackner, S.; Enko, D.; Schenk, M.; Holasek, S.J.; Mangge, H. Evaluation of Symptoms and Symptom Combinations
in Histamine Intolerance. Intest. Res. 2019,17, 427–433. [CrossRef]
3.
Comas-Basté, O.; Sánchez-Pérez, S.; Veciana-Nogués, M.T.; Latorre-Moratalla, M.; Vidal-Carou, M.C. Histamine Intolerance: The
Current State of the Art. Biomolecules 2020,10, 1181. [CrossRef]
4.
Kovacova-Hanuskova, E.; Buday, T.; Gavliakova, S.; Plevkova, J. Histamine, Histamine Intoxication and Intolerance. Allergol.
Imunopathol. 2015,43, 498–506. [CrossRef]
5. Maintz, L.; Novak, N. Histamine and Histamine Intolerance. Am. J. Clin. Nutr. 2007,85, 1185–1196. [CrossRef]
Nutrients 2021,13, 1395 9 of 10
6.
García-Martín, E.; García-Menaya, J.; Sánchez, B.; Martínez, C.; Rosendo, R.; Agúndez, J.A.G. Polymorphisms of Histamine-
Metabolizing Enzymes and Clinical Manifestations of Asthma and Allergic Rhinitis. Clin. Exp. Allergy
2007
,37, 1175–1182.
[CrossRef] [PubMed]
7.
Enko, D.; Meinitzer, A.; Mangge, H.; Kriegshaüser, G.; Halwachs-Baumann, G.; Reininghaus, E.Z.; Bengesser, S.A.; Schnedl, W.J.
Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption. Can. J. Gastroenterol. Hepatol.
2016,2016, 1–4. [CrossRef] [PubMed]
8.
Sattler, J.; Häfner, D.; Klotter, H.-J.; Lorenz, W.; Wagner, P.K. Food-Induced Histaminosis as an Epidemiological Problem: Plasma
Histamine Elevation and Haemodynamic Alterations after Oral Histamine Administration and Blockade of Diamine Oxidase
(DAO). Agents Actions 1988,23, 361–365. [CrossRef] [PubMed]
9.
Leitner, R.; Zoernpfenning, E.; Missbichler, A. Evaluation of the Inhibitory Effect of Various Drugs / Active Ingredients on the
Activity of Human Diamine Oxidase in Vitro. Clin. Transl. Allergy 2014,4, 23. [CrossRef]
10.
Schink, M.; Konturek, P.C.; Tietz, E.; Dieterich, W.; Pinzer, T.C.; Wirtz, S.; Neurath, M.F.; Zopf, Y. Microbial Patterns in Patients
with Histamine Intolerance. J. Physiol. Pharmaco. 2018,69, 579–593. [CrossRef]
11.
Sánchez-Pérez, S.; Comas-Basté, O.; Rabell-González, J.; Veciana-Nogués, M.T.; Latorre-Moratalla, M.L.; Vidal-Carou, M.C.
Biogenic Amines in Plant-Origin Foods: Are They Frequently Underestimated in Low-Histamine Diets? Foods
2018
,7, 205.
[CrossRef]
12.
San Mauro Martin, I.; Brachero, S.; Garicano Vilar, E. Histamine Intolerance and Dietary Management: A Complete Review.
Allergol. Immunopathol. 2016,44, 475–483. [CrossRef]
13.
Comas-Basté, O.; Latorre-Moratalla, M.L.; Rabell-González, J.; Veciana-Nogués, M.T.; Vidal-Carou, M.C. Lyophilised Legume
Sprouts as a Functional Ingredient for Diamine Oxidase Enzyme Supplementation in Histamine Intolerance. LWT Food Sci.
Technol. 2020,125, 109–201. [CrossRef]
14.
Wagner, N.; Dirk, D.; Peveling-Oberhag, A.; Reese, I.; Rady-Pizarro, U.; Mitzel, H.; Staubach, P. A Popular Myth–Low-Histamine
Diet Improves Chronic Spontaneous Urticari–Fact or Fiction? J. Eur. Acad. Dermatol. Venereol. 2017,31, 650–655. [CrossRef]
15.
Worm, M.; Fiedler, E.M.; Dölle, S.; Schink, T.; Hemmer, W.; Jarisch, R.; Zuberbier, T. Exogenous Histamine Aggravates Eczema in
a Subgroup of Patients with Atopic Dermatitis. Acta Derm. Venereol. 2009,89, 52–56. [CrossRef]
16.
Rosell-Camps, A.; Zibetti, S.; Pérez-Esteban, G.; Vila-Vidal, M.; Ferrés-Ramis, L.; García-Teresa-García, E. Histamine Intolerance
as a Cause of Chronic Digestive complaints in Pediatric Patients. Rev. Esp. Enferm. Dig.
2013
,105, 201–207. [CrossRef] [PubMed]
17.
Mušiˇc, E.; Korošec, P.; Šilar, M.; Adamiˇc, K.; Košnik, M.; Rijavec, M. Serum Diamine Oxidase Activity as a Diagnostic Test for
Histamine Intolerance. Wien. Klin. Wochenschr. 2013,125, 239–243. [CrossRef] [PubMed]
18. Steinbrecher, I.; Jarisch, R. Histamin Und Kopfschmerz. Allergologie 2005,28, 85–91. [CrossRef]
19.
Siebenhaar, F.; Melde, A.; Magerl, M.; Zuberbier, T.; Church, M.K.; Maurer, M. Histamine Intolerance in Patients with Chronic
Spontaneous Urticaria. J. Eur. Acad. Dermatol. Venereol. 2016,30, 1774–1777. [CrossRef]
20.
Wantke, F.; Gotz, M.; Jarisch, R. Histamine-Free Diet: Treatment of Choice for Histamine-Induced Food Intolerance and Supporting
Treatment for Chronical Headaches. Clin. Exp. Allergy 1993,23, 982–985. [CrossRef] [PubMed]
21.
Lackner, S.; Malcher, V.; Enko, D.; Mangge, H.; Holasek, S.J.; Schnedl, W.J. Histamine-Reduced Diet and Increase of Serum
Diamine Oxidase Correlating to Diet Compliance in Histamine Intolerance. Eur. J. Clin. Nutr. 2019,73, 102–104. [CrossRef]
22.
Guida, B.; de Martino, C.; de Martino, S.; Tritto, G.; Patella, V.; Trio, R.; D’agostino, C.; Pecoraro, P.; Agostino, L.D. Histamine
Plasma Levels and Elimination Diet in Chronic Idiopathic Urticaria. Eur. J. Clin. Nutr. 2000,54, 155–158. [CrossRef] [PubMed]
23.
Son, J.H.; Chung, B.Y.; Kim, H.O.; Park, C.W. A Histamine-Free Diet Is Helpful for Treatment of Adult Patients with Chronic
Spontaneous Urticaria. Ann. Dermatol. 2018,30, 164–172. [CrossRef] [PubMed]
24.
Latorre-Moratalla, M.L.; Comas-Basté, O.; Bover-Cid, S.; Vidal-Carou, M.C. Tyramine and Histamine Risk Assessment Related to
Consumption of Dry Fermented Sausages by the Spanish Population. Food Chem. Toxicol. 2017,99, 78–85. [CrossRef] [PubMed]
25.
Comas-Basté, O.; Latorre-Moratalla, M.L.; Sánchez-Pérez, S.; Veciana-Nogués, M.T.; Vidal-Carou, M.C. Histamine and Other
Biogenic Amines in Food. From Scombroid Poisoning to Histamine Intolerance. In Biogenic Amines; Proestos, C., Ed.; IntechOpen:
London, UK, 2019.
26.
Joneja, J.M.; Carmona-Silva, C. Outcome of a Histamine-Restricted Diet Based on Chart Audit. J. Nutr. Environ. Med.
2001
,
11, 249–262. [CrossRef]
27. Lehane, L.; Olley, J. Histamine Fish Poisoning Revisited. Int. J. Food Microbiol. 2000,58, 1–37. [CrossRef]
28.
Veciana-Nogués, M.T.; Vidal-Carou, M.C. Dieta baja en histamina. In Dieta y Nutrición Clínica; Salas-Salvadó, J., Bonada Sanjaume,
A., Trallero Casaña, R., Trallero Casaña, R., Burgos Peláez, R., Eds.; Elsevier: Barcelona, Spain, 2008; pp. 443–448.
29.
Bover-Cid, S.; Latorre-Moratalla, M.L.; Veciana-Nogués, M.T.; Vidal-Carou, M.C. Processing Contaminants: Biogenic Amines.
In Encyclopedia of Food Safety; Motarjemi, Y., Moy, G.G., Todd, E.C.D., Eds.; Elsevier Inc.: Waltham, MA, USA, 2014; Volume 2,
pp. 381–391. [CrossRef]
30.
King, W.; McCargar, L.; Joneja, J.M.; Barr, S.I. Benefits of a Histamine-Reducing Diet for Some Patients with Chronic Urticaria and
Angioedema. Can. J. Diet. Pract. Res. 2000,61, 24–26. [PubMed]
31.
Maintz, L.; Benfadal, S.; Allam, J.P.; Hagemann, T.; Fimmers, R.; Novak, N. Evidence for a Reduced Histamine Degradation
Capacity in a Subgroup of Patients with Atopic Eczema. J. Allergy Clin. Immunol. 2006,117, 1106–1112. [CrossRef]
Nutrients 2021,13, 1395 10 of 10
32.
Böhn, L.; Störsrud, S.; Törnblom, H.; Bengtsson, U.; Simrén, M. Self-Reported Food-Related Gastrointestinal Symptoms in IBS
Are Common and Associated with More Severe Symptoms and Reduced Quality of Life. Am. J. Gastroenterol.
2013
,108, 634–641.
[CrossRef] [PubMed]
33.
Lefèvre, S.; Astier, C.; Kanny, G. Intolérance àl’histamine Ou Fausses Allergies Alimentaires de Mécanisme Histaminique. Rev.
Fr. Allergol. 2017,57, 24–34. [CrossRef]
34.
Naila, A.; Flint, S.; Fletcher, G.; Bremer, P.; Meerdink, G. Control of Biogenic Amines in Food–Existing and Emerging Approaches.
J. Food Sci. 2010,75, 139–150. [CrossRef]
35.
Vidal-Carou, M.C.; Veciana-Nogués, M.T.; Latorre-Moratalla, M.L.; Bover-Cid, S. Biogenic amines: Risks and control. In HandBook
of Fermented Meat and Poultry; Toldrá, F., Hui, Y., Astiasarán, I., Sebranek, J., Talon, R., Eds.; John Wiley & Sons, Ltd.: Oxford, UK,
2015; pp. 413–428.
36.
Kalaˇc, P.; Švecová, S.; Pelikánová, T. Levels of Biogenic Amines in Typical Vegetable Products. Food Chem.
2002
,77, 349–351.
[CrossRef]
37.
Moret, S.; Smela, D.; Populin, T.; Conte, L.S. A Survey on Free Biogenic Amine Content of Fresh and Preserved Vegetables. Food
Chem. 2005,89, 355–361. [CrossRef]
38.
EFSA Panel on Biological Hazards (BIOHAZ). Scientific Opinion on Risk Based Control of Biogenic Amine Formation in
Fermented Foods. EFSA J. 2011,9, 1–93. [CrossRef]
39.
Lavizzari, T.; Veciana-Nogués, M.T.; Weingart, O.; Bover-Cid, S.; Mariné-Font, A.; Vidal-Carou, M.C. Occurrence of Biogenic
Amines and Polyamines in Spinach and Changes during Storage under Refrigeration. J. Agric. Food Chem.
2007
,55, 9514–9519.
[CrossRef]
40.
Arunlakshana, O.; Mongar, J.L.; Schild, H.O. Potentiation of Pharmacological Effects of Histamine by Histaminase Inhibitors.
J. Physiol. 1954,123, 32–54. [CrossRef] [PubMed]
41.
Mongar, J.L. Effect of Chain Length of Aliphatic Amines on Histamine Potentiation and Release. Br. J. Pharmacol.
1957
,12, 140–148.
[CrossRef]
42.
Hui, J.Y.; Taylor, S.L. Inhibition of in Vivo Histamine Metabolism in Rats by Foodborne and Pharmacologic Inhibitors of Diamine
Oxidase, Histamine N-Methyltransferase, and Monoamine Oxidase. Toxicol. Appl. Pharmacol. 1985,81, 241–249. [CrossRef]
43.
Vlieg-Boerstra, B.J.; van der Heide, S.; Oude Elberink, J.N.G.; Kluin-Nelemans, J.C.; Dubois, A.E.J. Mastocytosis and Adverse
Reactions to Biogenic Amines and Histamine-Releasing Foods: What Is the Evidence? Neth. J. Med. 2005,63, 244–249.
... The MPED categories were created by the United States Department of Agriculture and assess the intake of food groups such as fruit, vegetables, whole grains, seafood, proteins, and fish. The following MPED food categories, which have high histamine content based on chemical analysis (Sánchez-Pérez et al., 2021), were used: (1) frankfurters, sausage, luncheon meats (in ounces); (2) cheese (in cups); and (3) soy products (in ounces). ...
... We did not find an association between intake of highhistamine food groups and urinary histamine levels. The categories of high-histamine foods were chosen based on biochemical analysis of foods for their histamine content (Sánchez-Pérez et al., 2021). In that analysis, cured meats had 21.6 mg/kg of histamine; cheese had 33.1 mg/kg; and soy fermented products had 74.0 mg/kg. ...
... In that analysis, cured meats had 21.6 mg/kg of histamine; cheese had 33.1 mg/kg; and soy fermented products had 74.0 mg/kg. The lack of association with urinary histamine levels may be due to several factors: histamine levels in food can vary based on storage condition and storage time (Sánchez-Pérez et al., 2021), and the food categories used in the Vioscreen™ did not differentiate between aged versus young cheeses or cured versus fermented meats, factors which could significantly affect the foods' histamine levels. The histamine in foods may be detoxified by the liver, or homeostatic mechanisms may reduce the amount produced endogenously when more is ingested. ...
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... This paper investigates the presence of eight BAs in white brined cheeses sourced from various supermarket chains in the Czech Republic, specifically focusing on histamine, tyramine, tryptamine, putrescine, cadaverine, spermine, spermidine, and phenylethylamine. The selection of these BAs is based on their relevance to food safety and quality, as they are commonly associated with adverse health effects [37,38]. Histamine and tyramine are well-documented for their potential to cause toxic reactions in sensitive individuals, making their presence in cheese a significant concern [2,38]. ...
... The selection of these BAs is based on their relevance to food safety and quality, as they are commonly associated with adverse health effects [37,38]. Histamine and tyramine are well-documented for their potential to cause toxic reactions in sensitive individuals, making their presence in cheese a significant concern [2,38]. In addition to monitoring BA, fundamental microbiological analyses are conducted, including the isolation and identification of microorganisms present in the cheeses. ...
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... This metabolite has been detected, but not quantified in vegetables and fruit such as green beans, cauliflower and citrus [38], but is found in highest concentrations in beer [62] which is more likely to explain the negative relationship identified than fruit and vegetables in the current study. Both histamine and its precursor histidine have been associated with fruit and vegetable intakes [38,63,64]. They have been reported in specific vegetables including broccoli and tomato [63,64] which were provided as part of the intervention and therefore may explain why these metabolites were higher post intervention. ...
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Background/Objectives: Histamine intolerance is primarily caused by a deficiency in the diamine oxidase (DAO) enzyme at the intestinal level. The reduced histamine degradation in the gut leads to its accumulation in plasma, thereby causing multiple clinical manifestations, such as urticaria, diarrhea, headache, dyspnea, or tachycardia, among others. The dietary management of this food intolerance consists of the follow-up of a low-histamine diet, often combined with DAO supplementation. To date, around twenty studies have investigated the effectiveness of these dietary strategies in reducing the frequency and/or intensity of symptoms, with promising results. However, the limitations of these studies (small patient cohort, lack of control group, and short dietary intervention periods) highlight the need for more ambitiously designed research. Therefore, the main objective of this prospective, unicentric, double-blind, randomized, and placebo-controlled trial is to evaluate the efficacy of a low-histamine diet and/or DAO supplementation over a three-month period in improving symptoms of histamine intolerance. Additionally, the impacts of these dietary strategies on the intestinal microbiota composition, urinary profile of histamine metabolites, serum DAO activity, and plasma histamine levels will be assessed throughout the intervention. Methods: The trial will enroll 400 patients who will be randomly assigned to one of two groups: the intervention group, which will follow a low-histamine diet, or the control group, which will maintain their habitual dietary habits. Within each of these groups, participants will be further divided into four subgroups to receive either exogenous DAO enzyme supplementation (from porcine or plant sources, with the latter administered at two different dosages) or a placebo. Therefore, a total of eight distinct intervention groups will be considered. The comparison of these groups will allow the evaluation of the individual effects of the low-histamine diet or DAO enzyme supplementation, as well as their possible synergistic effect. Results: The results of this study should help to improve dietary recommendations for histamine-intolerant patients and ultimately enhance their quality of life.
... A low-histamine diet, direct DAO supplementation and H1R antihistamines may be useful in controlling symptoms, as may the administration of DAO cofactors (ascorbic acid, copper, vitamin B6) [42,43]. Also, in this case, a GFD can dangerously favor histamine-rich or histamine-releasing foods, causing worsening of symptoms in predisposed subjects; this happens, for example, in cases of high consumption of legumes, dried fruit, nuts, mushrooms and some types of fruit and vegetables (e.g., aubergine, spinach, tomato, avocado, bananas, strawberries) [44]. ...
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... However, as histamine and other biogenic amines are widely distributed in different food categories with highly variable concentrations (Gardini et al., 2016;Sánchez-Pérez et al., 2018), such diets are extremely restrictive and complex, and adherence is difficult (Cucca et al., 2022;Kovacova-Hanuskova et al., 2015;Schnedl et al., 2019). Moreover, the current food-related regulations do not consider the declaration of the absence or specific content of histamine in food labelling, which could help histamine intolerant individuals to make safer and informed choices (Sánchez-Pérez et al., 2021). ...
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