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231
Psoriasis and diet
1 Direttore del “Centro di
Invecchiamento Cellulare”, IDI
(IRCCS), Roma
2 Direttore di “Immunologia”, IDI
(IRCCS), Roma
3 Scottish Agricultural College,
Edinburgh
Indirizzo per la corrispondenza:
Dr. Siro Passi
C/o IDI Farmaceutici
Via dei Castelli Romani, 83/85
00040 Pomezia (Roma)
MONOGRAFIA
PASSI S.1,DEPITÀ O.2,
COCCHI M.3
PROGRESS IN NUTRITION
VOL.6,N.4, 231-247, 2004
TITOLO
Psoriasi e dieta
KEY WORDS
Genetic predisposition, triggering
factors, diet, psychological stress
PAROLE CHIAVE
Predisposizione genetica, fattori
scatenanti, dieta, stress psicologico
Summary
Psoriasis is a complex, recurrent, inflammatory disease of unknown causa-
tion, involving immune attacks in skin with chronic inflammation and
exuberant overgrowth of the outer layers of the skin. There are at least two
features that are thought to play some role: genetic predisposition and
psoriasis triggers. The incidence of psoriasis in Europe and USA ranges
between 1.5-2.5% and 0.7-2.0% respectively. The disease is rare in Blacks,
Indians and Yellow race, whereas in Eskimos it is not found at all. When
one parent or both parents have psoriasis, about 8% and 41% respectively
of offspring develop psoriasis. In these cases, the onset of psoriasis requires
the action of so called provocative factors, triggering the hereditary ele-
ments. These factors (streptococcal infections, drug use, alcohol, smoking,
skin traumas (Koebner), psychological stress, climate,metabolic problems,
hormones, oxidative stress, imbalanced diet etcetera) are significantly in-
volved also in the more or less frequent relapses of psoriasis. Infact, indi-
pendently of the type of psoriasis (vulgaris, guttate,plaque, pustular, inver-
se,erythrodermic, arthritis,...), no pharmacological therapy (keratolytics,
lubricants, coal-tar,ichtamol, topical corticosteroids, narrow band UV
treatment, topical vitamin D3 derivatives, PUVA, systemic cyclosporine,
systemic metotrexate, systemic retinoids, hydroxyurea, fumaric acid esters,
capsaicin, alefacept....) assures patients of a lasting recovery. In particular
diet and psychological stress are two important triggering factors. There
have been numerous dietary approaches for psoriasis dating back many
years, despite no consistent linkage with psoriasis have yet been found.
Simplistic models of dietary effects in psoriasis invariably fall short of vali-
dation. However there are certain important guidelines one should follow.
In particular a psoriatic patient should follow a well balanced low caloric
mediterranean like diet, containing: fresh fruit and vegetables rich in an-
tioxidants, folate, zinc, fiber, selenium, n-3 PUFA, monounsaturated fatty
acids, ....., and avoid or reduce red meats, eggs, dairy products, alcohol,
spice and condiments, gluten, sugars, n-6 PUFA, saturated fatty acids, ......
In our opinion an effective and rational treatment of psoriasis, indipen-
dently of the type, ought to provide for an holistic approach, which asso-
ciates conventional pharmacological therapies with an appropriate diet
and psychological stress reduction.
232
VOLUME 6
Riassunto
La psoriasi è una malattia complessa, ricorrente, ad eziologia ignota, carat-
terizzata da reazioni immunologiche sulla cute, da infiammazione cronica e
da una crescita esuberante degli strati più esterni della pelle. Ci sono alme-
no due aspetti che giocano un ruolo imporatnet nella malattia: predisposi-
zione genetica e fattori predisponenti. L’incidenza della psoriasi in Europa
e negli Stati Uniti varia rispettivamente dall’1.5 al 2.5% e dallo 0.7 al 2.0%.
Essa è rara nelle razze negra, indiana e gialla, mentre non si rinviene affat-
to tra gli eschimesi della Groenlandia. Se un genitore o ambo i genitori
hanno psoriasis, è molto probabile che rispettivamente circa l’8% ed il 41%
della figliolanza la sviluppino. In questi casi, la comparsa della psoriasi ri-
chiede l’intervento di fattori scatenanti, che innescano gli elementi eredita-
ri. Gli stessi fattori (infezioni da streptococco, uso di farmaci, alcol, fumo
traumi di varia natura sulla cute (Koebner), stress psicologico, clima, pro-
blemi metabolici, ormoni, stress ossidativo, dieta non idonea,ecc.) sono co-
involti significativamente anche nelle ricadute più o meno frequenti della
malattia. Infatti, indipendemente dal tipo di psoriasi (vulgaris, guttata, a
placca, pustulare, inversa, eritrodermica, artritica, ecc.) nessuna terapia far-
macologia sia topica (cheratolitici, lubrificanti, coal-tar,ictamolo, cortico-
steroidi topici, derivati della vit D3, capsaicina…) che sistemica (ciclospo-
rina, metotrexate, retinoidi, idrossiurea, esteri dell’acido fumarico, l’alefa-
cept...) oltre alle ben note PUVA e UV a banda stretta, assicura ai pazienti
la guarigione duratura.. In particolare dieta e stress psicologico rappresen-
tano due importanti fattori scatenanti. Ci sono stati e ci sono diversi ap-
procci dietetici per la psoriasi, ma nessuno di essi si è dimostrato convin-
centemente valido. Ci sono comunque alcuni importanti orientamenti, che
meritano di essere evidenziati. In particolare un paziente psoriasisco do-
vrebbe seguire una dieta ben bilanciata e a basso indice calorico tipo dieta
mediterranea a base di: frutta fresca e vegetali ricchi in antiossidanti, fola-
to, zinco, fibre, selenio, n-3 PUFA, acidi grassi monoinsaturi ….., ed evita-
re o ridurre carni rosse, uova, prodotti caseari, alcol, spezie e condimenti
eccessivi, glutine, zuccheri, n-6 PUFA, acidi grassi saturi...... Secondo la
nostra opinione un trattamento efficace e razionale per la psoriasi dovrebbe
prevedere un approccio di tipo olistico, in grado cioè di associare le terapie
farmacologiche convenzionali specifiche per il tipo di malattia, con una
dieta idonea e con la riduzione dello stress psicologico.
Introduction
Historically nutrition has been ne-
glected in medical education, and
dietary fads have been regarded by
physicians with skepticism.
In an attempt to ward off diseases,
including cancer, hearth disease,
and the manifestations of aging,
the public and scientists around the
wordl have begun to question the
efficacy and safety of dietary mani-
pulations, specifically nutrition, vi-
tamins, and healthy foods. The role
of diet in disease prevention and
treatment has become the basis of
lay press releases, cover stories in
magazines, newpapers, and new re-
search.
For what concerns the skin, mo-
dern nutritional science is develo-
ping new insights into the relation
between food intake and health,
and effects of food ingredients may
prove to be biologically relevant for
optimal skin condition. Skin condi-
tion and functioning are affected by
environmental factors, such as UV
irradiation, reactive oxygen and ni-
trogen species and other radicals
(ROS, RNS, R•), toxic and allergic
compounds, and mechanical chan-
ges, and by endogenous factors,
such as genetic predisposition, im-
mune and hormone status, and
stress. As a consequence, the skin
may undergo alterations leading to
photo-aging, inflammation, immu-
ne dysfunction, imbalanced epider-
mal homeostasis, or other skin dis-
orders. Diet is an exogenous factor
but, following its absorption and
metabolism, it can be considered as
an endogenous factor.
Although the literature does sup-
port the idea that diet can have si-
gnificant positive effects on psoria-
tic symptoms, the evidence is com-
plex and open to various interpreta-
tions.
Psoriasis is a complex, recurrent, in-
flammatory disease of unknown
causation, involving immune attacks
in skin (autoimmune disease*) with
chronic inflammation and exuberant
overgrowth of the outer layers of the
epidermis (1, 2). This is constantly
manufactoring new cells and shed-
ding off old ones. In healthy human
skin, the process takes about 28
days, whereas in psoriatic skin it
speeds up to 4-5 days. Instead of
shedding inconspicuously, the outer
cells form scales, which remain hea-
ped up on the skin. Psoriasis is cha-
racterized by the infiltration of T
cells and macrophages into the der-
mis. It has been hypothesized that
psoriatic lesions erupt when an epi-
dermal influx of antigen presenting
cells and helper T lymphocytes
overrides the normal epidermal sup-
pressor mechanism (3).
There are several different mor-
phological types of psoriasis (vulga-
ris, guttate, plaque, pustular, inver-
se, erythrodermic, arthitis,...), for a
close examination of which it is
suggested to refer to dermatological
books.
Except for psychological stigma of
an unsightly skin disease, general
health is unaffected by psoriasis
unless arthritis, bowel diseases, in-
tractable exfoliative or severe wide-
spread pustulation develop. In any
case, psoriasis can cause as much
disability as other major diseases,
and its impact on life quality can be
dramatical (4-6).
There are at least two features that
are thought to play some role: ge-
netic predisposition and psoriasis
triggers. The incidence of psoriasis
in Europe and USA ranges bet-
ween 1.5-2.5% and 0.7-2.0% re-
spectively. The disease is rare in
Blacks, Indians and Yellow race,
whereas in Eskimos it is not found
at all. When one parent or both pa-
rents have psoriasis, about 8% and
41% respectively of offspring deve-
lop psoriasis. In these cases, the on-
set of psoriasis requires the action
of so called provocative factors,
triggering the hereditary elements.
Candidate genes for involvement in
psoriasis have been identified by
various approaches, which indicate
a higher than expected frequency of
certain white cell antigens (class 1
human leukocyte antigens or
HLAs) on cells of people with pso-
PROGRESS IN NUTRITION 4/2004
233
* It should be important to remind that au-
toimmune diseases are caused by over stimu-
laation of the body’s own immune defences,
in which the immune cells attack healthy
cells. In psoriasis, immune system T cells be-
come activated and stay turned on causing
the skin to constantly regenerate itself.
riasis and their close relatives. The
gene(s) may be on the chromosome
that hold genes for HLA, a com-
plex having a critical role in the im-
mune system. Infact it is involved
in the timing, onset and severity of
many diseases, in which immune
system dysfunction or immune
system-environmental inter-rela-
tionships are suspected (7, 8).
What triggers psoriasis?
•Streptococcal infection. This in-
fection is a common cause of sore
throats and tonsillitis, particularly
in children and young adults. It
can trigger guttate psoriasis.
• Drug use. Some drugs may wor-
sen pre-existing psoriasis (li-
thium, which is commonly used
in the treatment of maniac de-
pression), β-blocking agents, cal-
cium antagonists, some FANS,
steroids taken orally, indometha-
cin, antimalarials (quinacrine,
chloroquine, and hydroxychloro-
quine), etcetera (9, 10).
• Alcohol. In tests, alcohol con-
sumption in people who develo-
ped psoriasis was twice that of
control group without the disease
(11-13).
• Smoking. Smoking more than 15
cigarettes a day was found to be
linked with the development of
pustular psoriatic lesions (13).
•Koebner phenomenon. Skin
trauma including physical, che-
mical, electrical, surgical, infecti-
ve, and inflammatory insults, may
result in psoriasis outbreaks 5 or
6 weeks later at the site of the in-
jury.
• Sunburn. Sunlight can generally
improve psoriasis, but in approxi-
mately 5-10% patients it can be a
trigger factor. Sunburn may also
cause psoriasis to flare up.
• Psychological factors (14, 15).
Stress reduction, including
hypnosis, suggestion, restful va-
cation mainly on a sunny beach,
has been shown to accelerate
healing of psoriatic plaques, fur-
ther supporting the role of stress
in the disorder.
•Climate. Cold, dry winter wea-
ther tends to trigger a flare-up of
psoriatic symtoms. In contrast,
sunlight and humid, sunny clima-
tes are, as a rule,helpful. In this
connection dead sea bathings ha-
ve been successful particularly in
mild cases. Due to high salt con-
tent, they may improve some ca-
ses of psoriasis, mainly if bathing
is followed by sunbathes However
hot, humid environments may
make severe cases of psoriasis
worse.
• Metabolic problems and hormo-
nes. There are many factors asso-
ciated with psoriasis, such as me-
tabolic problems (faulty utiliza-
tion of fat by the liver), colon pro-
blems, low tyroid function.In the
last case, prolactin (anterior lobe
of pituitary) increases, giving rise
to increased cell division. Sunlight
is known to decrease prolactin ge-
neration, whereas darkness and
stress can increase its formation.
And this may explain the skin im-
provement of psoriasis patients
during the summer months. A
further involvement of hormones
can occur during pregnacy, when
the psoriatic lesions can disap-
pear, only to reappear after child-
birth.
•Oxidative stress*. According to
Rocha-Pereira et al. (16) psoriasis
is associated with oxidative stress,
abnormal plasma lipid metabo-
lism, and with high frequency of
cardiovascular events. Infact it was
observed a rise in lipoperoxidation
products, a reduction of the levels
of vitamins A and E and in total
antioxidant activity. Changes in
lipid profile concerned a rise in
CH, TG, LDL, VLDL, apolipro-
tein B, lipoprotein A, and a re-
duction of HDL. The worsening
of psoriasis was associated with an
enhancement of oxidative stress
and of the lipid risk changes. Ser-
win et al. (17) demonstrated that
the selenium nutritional status
seems to be insufficient, especially
234
VOLUME 6
*Any imbalance between prooxidant and an-
tioxidant forces, in which the former ones pre-
vail, may be broadly defined as oxidative
stress, of which PUFA oxidation is the most
intensively studied aspect. The higher the
number of double bonds in a PUFA, the more
susceptible to peroxidation it becomes, frag-
menting to a plethora of more or less reactive
byproducts (18).
in females with psoriasis of no
longer than 10 months’ duration
and in males with long-lasting
psoriasis. In these males the pla-
sma and erythrocyte glutathione
peroxidase activity, a marker of
oxidative stress, was inversely cor-
related to the severity of the dis-
ease. Selenium dietary intake co-
uld be one of the contributing
factor in the pathogenesis and co-
urse of psoriasis.
• Imbalanced diet (see below).
•........
Therapies (19-22)
It is worthy mentioning that, inde-
pendently of the type of psoriasis,
no pharmacological therapy assures
patients of a lasting recovery. Ta-
king into accout that the etiology
of psoriasis involves varied both
specific and non specific factors,
the common more or less effective
treatments are:
• Lubricants, such hydrogenated
vegetable oils or white petrola-
tum.
• Keratolytics, such as salicylic acid
(1-4%) or resorcin (1-2%).
• Anthralin (dithranol) (normally
0,1-1%). It inhibits cellular respi-
ration by inactivation of mito-
chondria. The “short contact the-
rapy “ lies in applying topically
dithranol, at increasing concen-
trations from 1 to 4% for a short
time (from 10 to 60 min), and
then removing it. Following topi-
cal application, its primary side
effects are staining and irritation
of the uninvolved skin, so that
monitoring of irritation and care-
ful progression of the treatment
are necessary.
• Coal-tar (2-5%). It is manufactu-
red as a byproduct of the proces-
sing of coke and gas from bitu-
minous coal and is extremely
complex in composition. Little is
known about its mode of action,
which can be related to antimito-
tic effects. Coal tar alone is active
as is UV-B alone.The Goecke-
man method is based on the
combination between coal-tar
and exposure to UV-B radiations.
It seems to sensitize the skin to
UV-A, but not to UV-B,and the
phototoxicity is of photodynamic
type. Controindication of coal-
tar therapy (folliculitis is the pri-
mary side effect): infants and
young children, anogenital areas
and axillary folds, erythodermic
or generalized pustular psoriasis,
pre-existing folliculitis, severe ac-
ne, sensitivity to tar and its deri-
vatives. It has been shown to be a
carcinogen in animal experi-
ments. Today is also used ichtha-
mol, obtained by sulfation and
ammoniation of a distillate from
bitominous schists.
•Topical corticosteroids. Cortico-
steroids, keratolytics, anthralin
and crude coal tar are normally
incorporated in lubricants. They
are generally applied twice daily
after bathing, while the skin is
still damp. Corticosteroids are
most effective when used under
occlusion, and their potency
should be selected according to
the extent of the involvement. As
lesions improved, the corticoste-
roid should be applied less fre-
quently or at lower potency to
minimize local atrophy, striae
formation, or teleangiectases. Po-
tent fluorinated topical cortico-
steroids applied to large areas of
the body, in particular under oc-
clusion, may cause systemic ef-
fects and exacerbate psoriasis, as
with systemic corticosteroids.
• Narrow band treatment (UV-B,
311-312 nm). This range has pro-
ved to be the most beneficial
component of natural sunlight for
psoriasis and is also promising in
the treatment of vitiligo. Compa-
red with broadband UV-B it dis-
plays the following features: 1)
higher efficacy (exposure times
are shorter but of higher inten-
sity); 2) the course of treatment is
shorter; 3) it is more likely to
clear the psoriasis; 4) it produces
longer periods of remission before
psoriasis reappears; 5) it can indu-
ce more epidermal damage and
therefore must be used with care-
ful individualization of dosage.
• Topical vitamin D3 derivatives.
Calcipotriol and tacalcitol are
synthetic 1,25-dihydroxyvitamin
D3 analogues, that have been
PROGRESS IN NUTRITION 4/2004
235
found to reduce skin lesions either
by preventing the excessive kerati-
nocyte proliferation in the affec-
ted skin of psoriatic people or by
stimulating their differentiation.
In addition they displays anti-in-
flammatory and immunomodula-
ting activities, and are about 200-
times less potent than 1,25 dihy-
droxyvitamin D3 in causing
hypercalcemia and hypercalciuria.
Calcipotriol is normally applied
twice daily to the lesions, while
tacalcitol once daily. The main si-
de effect is cutaneous irritation,
and so such drugs are inadeguate
for the tretment of face and folds.
•PUVA (psoralen-ultraviolet A).
This therapy is used for extensive
psoriasis. Methoxalen, (8-me-
thoxypsoralen -8-MOP-) a
synthetic psoralen or 5-me-
thoxypsoralen (5-MOP), are gi-
ven orally (0.6 and 1.2 mg/kg) 2-
3 hours before exposure of skin
to long-wave UV or UV-A (320
to 400 nm). Serious burns can
occur if the levels of psoralen and
UV-A are excessive. Repeated
treatments may increase the inci-
dence of UV-A induced skin
cancer or aging, and induce ga-
stric intolerance and hepatotoxi-
city.
• The immunosoppressive drug
cyclosporine has been used in se-
vere and recalcitrant cases. It must
be considered it can induce se-
rious systemic side effects, in par-
ticular hypertension and renal
dysfunction. It has been shown
that cyclosporine inhibits antigen
presentation by Langerhans’ cells
and degranulation of mast cells
that contribute to the pathogene-
sis of psoriasis. It should be consi-
dered that even something as
simple as drinking too much gra-
pe fruit juice when taking cyclo-
sporine can elevate the blood le-
vels of cyclosporine which can re-
sult hypertension and kidney toxi-
city. Grape fuit and grape fruit
juice block the CYP3A enzymatic
system (microsomal enzymes) and
increase cyclosporine blood con-
centration. In contrast drugs that
induce CYP3A activity, such as
rifampicin, phenobarbital, pheny-
toin, octreotide etc., are able to
increase cyclosporine metabolism
and decrease blood levels.
• Metotrexate,is an analog of folic
acid that competively inhibits
dihydrofolate reductase. It is the
most effective treatment in severe
psoriatic arthritis or widespread
erythrodermic or pustular psoria-
sis, unresponsible to topical
agents or PUVA. Metotrexate is
administered by oral or intramu-
scolar routes at the dose of 10-30
mg a week. Patients who take this
cytostatic drug must be carefully
monitored to prevent liver dama-
ge.
•The retinoids (vitamin A derivati-
ves) etretinate, acitretin ( the ma-
jor metabolite of etretinate) and
isotretinoin orally given may be
useful for severe and recalcitrant
cases, including pustular, erythro-
dermic and hyperkeratotic palmo-
plantar psoriasis. These drugs are
potent teratogens and may cause
major human fetal abnormalities.
Toxicity can resemble hypervita-
minosis A; common side effects
include dry skin and mucous
membranes, xerophthalmia, and
hair thinning. In addition, exces-
sive intake of fish oil, containing
high amounts of vitamin A pal-
mitate, with the above mentioned
retinoids could increase their liver
toxicity.
Tarazotene is the first topical reti-
noid indicated for the treatment
of psoriasis, which can be used as
monotherapy or in combination
with other medications. In as
much as this topical drug is mem-
ber of retinoid family, it is terato-
gen and may cause effects of bur-
ning, itching, and skin irritation
in some patients.
• Hydroxyurea. Hydroxyurea is an
antiblastic, mutagenic and terato-
genic drug that acts by inhibiting
DNA synthesis.The main side ef-
fects are myelopathy, liver toxicity,
anorexia, and nausea. In any case,
compared with methotrexate, it
has less side effects.
• Fumaric acid esters (mono ethyl
fumarate and di ethyl fumarate).
It has been shown that fumaric
acid esters are effective against
symptoms of psoriasis in some in-
dividuals affected with this disea-
236
VOLUME 6
se. They are administered orally at
increasing doses: from 30-100 mg
daily to 700-1200 mg daily. Since
the esters can cause significant si-
de effects, it should be necessary
the supervision of a medical doc-
tor familiar with their use.
• Capsaicin. Capsaicin (Capsicum
frutescens) under the form of an
ointment can stop production of
the chemicals that cause the skin
to become inflamed and hats the
runaway production of new skin
cells. It shoud be used under a
doctor’s supervision in order to
prevent burns and skin damages.
• Alefacept. In 2003 the FDA ap-
proved this drug,that is able to
suppress the immune system to
slow down the production of skin
cells, for the treatment of psoria-
sis. Alefacept is administered as
an injection once per week. It may
increase the risk of malignancy or
infection, may cause allergy or in-
flammation or swelling of the
throat or tongue.
• .......................
In the 70-80% cases the therapy is
essentially topical, due to the light
or moderate degree of psoriasis. In
the remaining 20-30% cases syste-
mic or systemic plus topical treat-
ments are required (19-22). Thera-
peutical combination without ex-
cessive toxicity risks are: topical
corticosteroids + topical vit D3
analogues; topical corticosteroids +
topical retinoids; topical corticoste-
roids + dithranol; phototherapy +
acitretin; photherapy + topical
drugs; cyclosporin + topical drugs,
acitretin + topical drugs, metotre-
xate + topical drugs. Conversely, re-
tinoids + cyclosporine can produce
hepatotoxicity; the same occurs
with metotrexate + acitretin, while
cyclosporine + phototherapy can
induce cutaneous carcinogenesis.
How important is diet in psoriasis?
A - Food deprivation and poor diet
A cure for all psoriatic patients
simply does not exist. Even if most
cases can be well controlled, the
dramatic problem of psoriasis con-
sists in more or less frequent relap-
ses. Any treatment ought to first
address the imbalance that has af-
fected the immune system before
lasting benefits can occur. This ap-
plies using either recognized medi-
cal therapies or any of the so called
“miracle treatments” and “magic
potions”. Sherlock Holmes said: if
all the common explanations fail to
solve a problem, than the answer
must be an uncommon one. The
uncommon answer might be the
triggering factors and, in particular,
the diet.
There have been numerous dietary
approaches for psoriasis dating
back many years, despite no consi-
stent linkage with psoriasis have yet
been found. Simplistic models of
dietary effects in psoriasis inva-
riably fall short of validation. Ho-
wever there are certain important
guidelines one should follow.For
example, an increased frequency of
obesity in psoriasis is a well known
fact. Schamberg (23) reported re-
markable treatment efficacy using a
low-protein diet containing about
30 gm of protein in patients hospi-
talized for three to four weeks. Ler-
ner and Lerner (24) found a 69-
year-old man whose psoriasis im-
proved on a low-protein diet and
exacerbated on a high-protein steak
diet. Roe (25) reported good results
with a low-taurine diet in psoriasis,
that means a low protein diet, since
the principal source of taurine is
animal protein. It is worthy remin-
ding that low protein diets have
been shown to be therapeutical in
other types of autoimmune disea-
ses. Food deprivation has been as-
sociated with improvement in pso-
riatic symptoms. Simons (26) re-
ported that 8 of 13 Dutch prisoners
with psoriasis improved in Japanese
concentration camps in Java in
World War II, while on a near star-
vation diet. Some observers feel
that psoriasis is exacerbated with
weight gain (27, 28). Spiera and
Lefkovits (29) found dramatic im-
provement in four psoriatic patients
who were placed on a diet believed
to be low in tryptophan.
Also Rucevic et al. (30) emphasized
the therapeutical role of low energy
diet in the treatment of non pustu-
lar psoriasis.
PROGRESS IN NUTRITION 4/2004
237
Pagano (31) reportes significant
improvement of psoriasis in pa-
tients using a restrictive diet and
dietary supplementation with her-
bal teas (most ofter yellow saffron
and slippery elm) and olive oil. Yel-
low saffron (Carthamus tinctorius)
has beer shown to possess anti-in-
flammatory (32) and immunosup-
pressive properties (33). Slippery
elm (Ulmus fulva) is an herb used
traditionally for digestive difficul-
ties, stomach and intestinal ulcers,
and colitis. Slippery elm is a de-
mulcent, high in mucilage, noted
for its ability to soothe or protect
irritated mucous membranes (34-
35). In good agreement with the
findings of Kavli et al. (8), Naldi et
al. (36) reported that psoriasis ap-
peared to be correlated positively
associated with body mass index
(BMI) (body weight (kg)/squared
value of height in metres) and was
inversely related to the consump-
tion of carrots, tomatoes, and fresh
fruit, and to the index of β-carote-
ne intake. BMI correlates fairly
well with the degree of adiposity,
and available evidences suggest that
both genetic and environmental
factors may contribute. Socioeco-
nomic status, alcohol consumption,
stressfull life events etc. are inde-
pendently associated with BMI. In
addition it may be influenced by
the composition of the diet and is,
for instance, correlated with meat
intake and inversely associated with
a vegetarian diet.
Carrots, tomatoes and fresh fruit
are importany sources of antioxi-
dants (β-carotene, lycopene, vit. C,
vit. A etc.), that are important de-
terminants of immunocompetence.
Early and active psoriatic lesions
are characterized by the intraepi-
dermal penetration of polymorpho-
nuclear leukocytes, and it is well
known that during the process of
their activation ROS RNS and R•
(*) play a central role.
Although some physicians feed
that psoriasis diminishes during
periods of food deprivation or poor
nutrition, there is no consensus on
this point. Zackheim and Farber
(37) failed to see significant impro-
vement in 13 psoriatic patients who
were hospitalized for periods of 4
to 17 weeks. Kwitten and Kantor
(38) reported on a 37-year-old man
whose psoriasis failed to improve
on a starvation diet, in which the
estimated protein consumption was
4.7 gm per day.
An example of impaired nutrition
come from the study of Michaels-
son et al. (39), who showed that
16% of psoriatic patients had IgA
and/or IgG antibodies to gliadin
(AGA). Therefore they evaluated
the effect of a gluten-free diet
(GFD) administered for 3 months
to 33 AGA-positive and 6 AGA-
negative patients. Gluten is usually
found in wheat, oats, rye etcetera.
Thirthy of the 33 AGA-positive
patients improved significantly fol-
lowing GFD, and the AGA values
were lower in 82% of those who
improved. When the ordinary diet
was resumed, the psoriasis deterio-
rated in 18 of the 30 patients who
had improved previously. The
AGA-negative patients were not
affected at all by the GFD.
B - n-3 polyunsaturated fatty acids
(n-3 PUFA)
The involvement of dietary fatty
acids upon the immune system was
suggested by the observations that
linoleic and arachidonic acids are
able to inhibit mitogen-stimulated
238
VOLUME 6
*A well-established conseguence of aerobic
metabolism is the generation of deleterious
reactive oxygen and nitrogen species (ROS,
RNS), and other radicals (R•), which are
able to damaging, in a way characteristic of
of the oxidizing species, biomolecules such as
DNA, lipids, proteins, and carbohydrate, and
are involved in a number of normal and pa-
thological processes such as aging, carcinoge-
nesis, lipoperoxidation, atherogenesis, in-
flammation, antimicrobial defence, etc. It
must be remembered infact that almost any
form of tissue damage is accompanied by in-
creased free radical activity.
During the course of evolution several antio-
xidant molecules, occurring at different loca-
tions within the cell, have developed to pro-
tect living systems against ROS, RNS and
R•,and to prevent uncontrolled oxidative
processes.
Until recently, it was thought that each an-
tioxidant played its role in isolation from
others. Conversely interactions among antio-
xidants occur in the test tube,and nutritional
interaction studies support this idea for the
whole organism. Thus a picture is emerging
of a complex interplay among the defence
systems, with the various antioxidant cycles
acting to prevent cell damage and diseases.
proliferation of periferal blood
lymphocytes in vitro and that sub-
cutaneous injection of these fatty
acids prolongs the survival of skin
allografts in mice (40, 41).
Linoleic (LA, C18:n-6) and α-li-
nolenic acids (LLA, C18:3 n-3) are
required for the synthesis of longer
chained polyunsaturated fatty acids
(PUFA) such as arachidonic (AA,
C20:4 n-6), eicosapentaenoic
(EPA, C20:5 n-3) and docosahe-
xaenoic (DHA, C22:6 n-3) acids.
Since as they cannot be synthesized
de novothey are referred to as es-
sential fatty acids (EFA). PUFA
have been shown to partake in nu-
merous cellular functions affecting
fluidity and enzyme activities of
membranes, synthesis of eicosa-
noids and modulation of cytokine
biology, which are known to exert a
wide range of biological actions.
According to Grimble & Tappie
(42), n-6 PUFA enhance IL-1 pro-
duction and tissue responsiveness
to cytokines; n-3 PUFA have the
opposite effects; monoene FA de-
crease tissue responsiveness to
cytokines; total UFA intake enhan-
ces IL-6 generation.
A number of studies showed that
feeding rats, mice, rabbits, or chi-
chens diets rich in fish oils results
in suppressed ex vivo lymphocyte
proliferation (43-47), interleukin-2
(IL-2) production (48), natural kil-
ler (NK) cell activity (49, 50), cito-
kine (IL-1, IL-6, TNFα −tumor
necrosis factor α−) production by
inflammatory macrophages (51,
52), and macrophage-mediated
cytotoxicity (52, 53).
Relatively low levels of n-3 PUFA
are required to induce some of the-
se suppressive effects; studies with
single PUFA show that both die-
tary C20:5 n-3 and C22:6 n-3 in-
hibit lymphocyte proliferation, but
only the former the NK cell activity
(48, 54).
Rats or guinea pigs given large
amounts of fish oil either intrave-
nously or by diet show significantly
enhanced survival following the ad-
ministration of a high dose of bac-
terial endotoxin (55, 56) and the
reduction of anorexia which ac-
companies administration of IL-1
or TNF-α(57, 58).
Fish oil feeding also ameliorates
the symtoms of lupus prone mice
(an autoimmune disease), so in-
creasing the lifespan of such ani-
mals (59). These changes are asso-
ciated with the abolition of proin-
flammatory cytokines production
and the induction of antinflamma-
tory cytokines and antioxidant
enzymes (60).
N-3 PUFA from fish are more sup-
pressive than linseed oil containing
high percentages of C18:3 n-3. Jef-
fery et al. (61) showed that the sup-
pressive effect of α-linolenic acid
depended on both the concentra-
tion of the acid and the total PUFA
content of the diet. Also in healthy
human volunteers supplementation
of the diet with fish oil (1.2-1.4
g/d) results in decreased lymphocy-
te proliferation (62, 63), monocyte
and neutrophil chemotaxis (64, 65),
and reduced production of IL-1,
IL-2, IL-6 and TNF-α(62, 63). In
addition, it protects against the da-
maging effects of inflammatory
challenge, which are mediated by
the overproduction of pro-inflam-
matory cytokines such as TNF, IL-
1 and IL-6.
α-linolenic acid suppresses human
IL-1 and TNF production at a do-
se of 15 g/d (66). It has been repor-
ted that an important mechanisms
by which n-3 PUFA influence im-
mune cell function involves the
modulation of the amount and
types of eicosanoid synthetized.
Under normal conditions most ei-
cosanoids derive from arachidonic
acid. When high levels of n-3 PU-
FA are consumed in the diet, less
arachidonic acid derived eicosa-
noids are produced. Eicosanoids
generated from C20:5 and C20:6
n-3 are usually less biologically po-
tent than those formed from C20:4
n-6 (Fig. 1). Thus a n-3 PUFA-in-
duced change in the amount and
type of different eicosanoids produ-
ced will have a significant influence
on the functioning of immune and
inflammatory cells and might par-
tially account for the antinflamma-
tory and immunomodulatory ac-
tion of fish oils.
It has been suggested that n-3 PU-
FA might elicit some of their ef-
fects also by eicosanoid indepen-
PROGRESS IN NUTRITION 4/2004
239
dent mechanisms, including actions
upon intracellular signalling path-
way, regulation of transcription fac-
tor activity, and altered antioxidant
status (67, 68).
An immunomodulatory effect of n-
3 PUFA comes from epidemiologi-
cal studies on Greenland Eskimos,
who consume large quantities of
marine mammals and fish oils and
have a very low incidence of in-
flammatory and autoimmune dis-
orders (69). In addition, fish oil
supplementation has some benefi-
cial effects in diseases other than
psoriasis, such as rheumatoid arth-
ritis, lupus, inflammatory bowel
disease, and risk of sudden death.
Eskimos as compared with Danes,
are not affected with psoriasis and
this, according to Kromann and
Greene (69) is due to the fact that
Eskimos have a high intake of very
long chain n-3 PUFA (especially
C20:5 n-3 and C22-6 n-3), mainly
found in seal and fish oil, whereas
Danes have a high intake of n-6
fatty acids (mainly linoleic acid)
obtained from vegetable and ani-
mal fat. Both n-3 and n-6 PUFA
are essential, and one cannot be
converted to the other. Dietary
C18:2 n-6 is converted to arachi-
donic acid (C20:4 n-6), which is
metabolized through the lipoxyge-
nase and cycloxygenase pathways to
potent inflammatory derivatives of
the 2 series (Fig. 1). The levels of
some of these byproducts are mar-
kedly increased in psoriatic plaques
(Fig.2), and they may be involved
in the pathogenesis of psoriasis
through their chemotactic and pro-
liferative effect in human skin. In
psoriatic plaques the content of
C20:4 n-6 is about 25-fold higher
than in uninvolved skin, in which it
is in turn 35% higher than in non
psoriatic skin (70, 71). This means
that a very high phospholipase A2
activity, stimulated by physical in-
jury, histamine, bradykinin, ROS,
RNS, R•, etcetera, occurs in psoria-
tic skin, mainly in psoriatic plaques.
(Phospholipase A2 can be inhibi-
ted by corticosteroids via lipomo-
dulin or macrocortin, and in some
tissues also by cAMP).
When dietary n-3 PUFA are con-
sumed, they are incorporated into
cell membranes and compete with
n-6 PUFA as substrate for cycloxy-
240
VOLUME 6
Figura 1 - Possible regulatory mechanism of prostaglandins and leukotrienes
deriving from n-6 and n-3 PUFA
genase and lipoxygenase. Eicosa-
noids from n-3 PUFA are generally
less potent than metabolites from
n-6 series, and inflammatory reac-
tion can result therefore smaller.
The large increase in arachidonic
acid in involved psoriatic skin, led
to 8100% increase in the level of
12-HETE (12-hydroxy tetraenoic
acid) generated by 12-lipoxygenase,
to 500% increase in LTB4 produ-
ced by 5-lipoxygenase, but only to
40-80% in the concentration of
PGs of the 2 series formed by
cyclo-oxygenase (PGE2,+ 40%,
PGF2a,+ 80%) (Fig. 2) (70, 71).
This shunting of C20:4 n-6 meta-
bolites from the cylo-oxygenase to
the lipoxygenase pathway may be
due to the presence of cycloxygena-
se inhibitors (lysolecitins?) in active
psoriatic lesions (72). The 4-series
leukotrienes are potent proinflam-
matory metabolites and may be, in
part, responsible for the vascular
changes, erythema, edema, neutro-
phil chemotaxis, cell proliferation
characteristic of psoriasis. Arachi-
donic acid and 12-HETE can both
stimulate guanylate cyclase activity
and inhibith adenylate cyclase acti-
vity, that are changes associated
with epidermal proliferation (73).
Clinical evidences support the im-
portance of C20:4 n-6 metabolites
in the psoriasis pathology. Gluco-
corticosteroids may produce some
of their antipsoriatic effects by pro-
moting the formation of a cell sur-
face protein called macrocortin that
is able to inhibith the phospholipa-
se A2 activity (74-79). In contrast,
non steroidal antinflammatory
drugs (NSAID), such as topical in-
domethacin or systemin phenylbu-
tazone, which are potent cycloxyge-
nase inhibitors and are capable of
shunting arachidonic acid metabo-
lism farther down the lipoxygenase
pathway, exacerbate psoriasis (74,
75). Benoxaprofen (inhibitor of 5-
lipoxygenase activity), antralin (in-
hibitor of 5-HETE production),
and a number of bland emollients
and vehicle components which are
able to reduce C20:4 n-6 metabo-
lism on the skin improve psoriasis
(76-79).
The findings of Kromann and
Greene, combined with evidence
PROGRESS IN NUTRITION 4/2004
241
Figura 2 - The relative shunting of C20:4 n-6 from cyclo-oxygenase to li-
poxygenase metabolites in psoriasis results in inflammation, erythema, ede-
ma, neutrophil chemotaxis, and cell proliferation
for epidermally derived eicosanoids
in the pathogenesis of psoriasis, led
Ziboh et al. (80) to investigate the
effect of fish oil dietary supplemen-
tation on psoriatic symptoms. After
8 wk of supplementation, most of
the patients showed a mild-to-mo-
derate improvement in their le-
sions, which corresponded to hi-
gher EPA and DHA levels in the
epidermal, serum, and neutrophil
lipids. No alterations in arachidonic
acid in the epidermal lipids was
evident. It was suggested that, par-
ticulary in neutrophils, a possible
increase in the ratio of leukotriene
B5 (LTB5), derived from EPA, to
LTB4, derived from arachidonic acd,
was responsible for the reduction in
inflammation.
The beneficial effects of fish oil
were confirmed by Maurice et al
(81). In their study,10 patients
with severe chronic psoriasis recei-
ved 12 g EPA/d for 6 wk. A reduc-
tion in erythema and scaling was
observed in 8 of 10 patients after
treatment. Mean plasma and plate-
let ratios of EPA to arachidonic
acid increased in subjects who re-
sponded to treatment. In addition,
a marked suppression in LTB4pro-
duction by polymorphonuclear leu-
kocytes in vitro was shown, but
only a modest improvement in cli-
nical condition was seen. This im-
plied the involvement of other me-
diators in the inflammatory process
in psoriasis.
In a follow-up study of 27 psoriasis
patients treated with 1.8 g EPA/d
for 8 wk, there was no improve-
ment in their clinical condition re-
lative to the placebo group (82).
Nevertheless, in the treated group,
n-3 fatty acids in serum phospholi-
pids increased and n-6 fatty acids
decreased, whereas no changes in
phospholipid fatty acids were de-
tected in the placebo group. The
authors concluded that the dura-
tion of treatment was possibly too
short or the dose too low to detect
any beneficial effect.
Bittiner et al. (83) administered
daily a similar dose of fish-oil ex-
tract (containing 1.8 g EPA) to 28
psoriasis patients for a longer time,
12 wk. At 8 and 12 weeks itching
and erythema decreased signifi-
cantly in the fish-oil group,whe-
reas there was no significant chan-
ge in the placebo group.The au-
thors suggested that an increase in
the dietary intake of fish oil and a
reduction in the intake of food rich
in arachidonic acid would be a use-
ful treatment to counteract the ex-
cessive inflammation in psoriasis.
Supplementation of the diet of 80
patients with chronic psorasis with
1122mg EPA ethyl ester/d and 756
mg DHA ethyl ester/d resulted in
an improvement in the overall skin
condition and in individual disease
indexes (pruritus, scaling, indura-
tion, and erythema) after 4 and 8
weeks (84). Serum triacylglycerol
concentrations decreased from ba-
seline, but unfortunately no data on
fatty acid composition were presen-
ted. It was suggested that the bene-
ficial effects of polyunsaturated
ethyl ester lipids from sea fish may
have been mediated either by the
formation of biologically less active
leukotrienes and prostaglandins ra-
ther than those derived from ara-
chidonic acid or by slowing down
the inflammatory pathways by ac-
ting as a less favorable substrate for
cyclooxygenase and lipoxygenase.
Søyland et al. (85) treated 124 pso-
riasis patients with either 6 g ethyl
ester of very-very-long-chain n-3
fatty acids (51% EPA and 32%
DHA as ethyl ester) or 6 g corn oil
(26% oleic acid and 56% linoleic
acid) for 4 months. In the fish oil
group,scaling decreased and less
cellular infiltration was seen. In the
corn oil group,scaling and redness
decreased and desquamation im-
proved. Nevertheless, the clinical
condition of the patients treated
with fish oil did not improve more
than in the corn oil group. In the
fish-oil group, the radio of n-3 to
n-6 fatty acids increased in serum
phospholipids, as did the ratio of
EPA to arachidonic acid. In the
corn oil group, only DHA concen-
trations increased and, remarkably,
the increase in n-3 fatty acids cor-
responded to clinical improvement
in this group only. The authors
suggested that the inhibition of
proliferation of T cells by arachido-
nic acid in corn oil and n-3 PUFA
in fish oil may explain the compa-
242
VOLUME 6
rable clinical results in the 2
groups.
In any case, taking into account fi-
gure 1, it must be considered that:
1)- Greenland Eskimos have not
psoriasis or other autoimmune dis-
eases because, according to Kro-
mann & Greene (69), consume
mainly large amounts of marine
fish anf fish oils from infancy. The-
refore it is likely that their PUFA
in epidermal phospholipids are es-
sentially of n-3 type. 2)- We have
found that the levels of C20:4 n-6,
C20:5 n-3 and C22:6 n-3 in epi-
dermal phospholipids of healthy
humans are respectively about 10%,
0,1%, and 1,5%*. This means that
in order to reach higher amounts of
n-3 PUFA in epidermal phospholi-
pids, whose eicosanoids should be
able to counteract efficaciously
C20:4 n-6 derived-eicosanoids, it
should be necessary both to admi-
nister large quantities of fish or fish
oils and to reduce n-6 PUFA con-
taining foods for long periods (>4-
5 months). And this type of thera-
peutical approach is normally ne-
glected in psoriasis.
Possible side effects of fish oils:
belching, flatulence, nausea, diar-
rhea, and blothing may occur as a
result of either poor quality in the
fish supplements or reduced bile
acid production or other intestinal
problems. High doses may cause
internal bleeding and impair the
formation of blood colts: this pro-
blem must be underlined in case of
surgery.
Recently it has been suggested by
Namazi (86) that maize, the staple
diet in most part of Africa may ac-
count for the reduced incidence of
psoriasis in Africans. Maize con-
tains high levels of linoleic acid
(C18: n-6) and low amounts of
other PUFA and riboflavin. Lino-
leic acid is the precursor of PG E2,
that according to the author is able
to suppress cellular immunity, re-
sulting in decreased expression of
psoriasis. This paper is at odds with
the effects of n-3 PUFA, that have
been underlined by a large number
of authors. Probably psoriasis in
uncommon in Africans because of
their low caloric diet, in addition to
genetic factors.
What a psoriatic patient should eat
and why:
• Low caloric diet. A well balanced
diet is desirable. Proper nutrition
may diminish the severity of the
disease, may help to build stress
resistance, increase physical en-
durance, increase the resistance
to the disease, and promote in-
creased emotional stability.
•Fresh fruits and vegetables. Bur-
dock, milk thistle, yellow dock,
mountain grape, sarsaparilla, red
clover, Goa powder, aloe vera,
masterwort, etc. have been taken
into consideration. Anecdotally
reports of improvement have
been reported and this could be
due to vitamin C, vitamin E, ca-
rotenoids and other antioxidants
present in these foods, which im-
prove the strength of the immune
system. Also psoralen containing
foods, such as celery, carrots, figs,
fennel, and parsnip, taken prior
to sun exposure, are indicated.
Infact they may make skin more
sensitive to the positive effects of
UV-A.
• Folate. Some studies have sugge-
sted that folate may be deficient
in some people with psoriasis.
Food sources of folic acid are:
asparagus, beets, broccoli, Brussels
sprouts, spinach, avocados, soy-
beans, chick-peas, beans, cabbage,
savoy, turkey, peas, oranges, lentils
etc.
• n-3 PUFA and flax seed oil. Fish
oils and flax seed oils are impor-
tant sources of n-3 PUFA.
• (Zn). Skin contains one fifth of
total body’s zinc supply. The US
RDA for zinc is 15 mg a day, even
if researches have shown that sup-
plements of this metal are safe up
to about 500 mg a daily. A dose of
50-100 mg a day can be maintai-
ned for as long as desidered (87).
The amino acid chelate form of
zinc is better tolerate and better
PROGRESS IN NUTRITION 4/2004
243
* In plasma, tissue, and epidermal phospholi-
pids the percentages of C22:6 n-3 are largely
higher than those of its precursor C20:5 n-3.
However the eicosanoids from both these n-3
PUFA display very similar behaviour
absorbed than Zn sulfate or other
inorganic form of Zn. It is part, in
addition to copper, of SOD,
which is a very powerful free radi-
cal scavenger. Refined foods, i.e,
white flour, maintain only traces
of Zn and other minerals. Zn
sources such as shellfish and who-
legrain foods, also provide copper.
Zn is very important for immune
response, and its loss is common
in psoriasis. It has been shown
that rats and mice that are defi-
cient in Zn develop keratogenesis,
a skin condition similar to human
psoriasis.
• Fiber. Fibers are essential in main-
taining a healthy colon. In addition
they help to bind bowel toxins and
eliminate them in the feces. Solu-
ble fibres, such as psyllium, pectin,
and guar gum, are especially useful
in binding toxins),
• Selenium. Selenium is a compo-
nent of glutathione peroxidase
(GPx), an enzyme found in mito-
chondria and cytosol of animal
tissues, which helps to reduce
hydrogen peroxide to water, using
reduced glutathione as substrate.
In vivo GPx acts on a range of
peroxides in addition to hydrogen
peroxide, including cumene
hydroperoxide, several steroid
hydroperoxides, thymine hydro-
peroxide, linoleic acid hydropero-
xide, and numerous other peroxi-
des. Brasil nuts are a rich source
of selenium.
•....................
Foods to avoid or reduce:
• Red meats, eggs, and dairy pro-
ducts. They contain precursors of
arachidonic acid and can irritate
the intestinal tract and perpetuate
the psoriasis outbreaks,
• alcohol,
• spice and condiments,
• gluten,
• sugars,
• n-6 PUFA,
• .............
Conclusions
The etiology of psoriasis involves
varied both specific and non specific
factors, including genetic ones. In-
dipendently of the type of psoriasis
no therapy assures patients of a la-
sting recovery. Even if most cases
can be well controlled, the real, dra-
matic problem of psoriasis consists
in more or less frequent relapses,
mainly due to triggering factors. In
our opinion an effective and ratio-
nal treatment ought to provide for a
holistic approach, which associates
conventional pharmacological the-
rapies with an appropriate mediter-
ranean like diet and stress reduction
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