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Efficacy of dietary hempseed oil in patients with atopic dermatitis

Authors:

Abstract

Hempseed oil is a rich and balanced source of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). Anecdotal evidence indicated that dietary hempseed oil might be useful in treating symptoms of atopic dermatitis. Dietary hempseed oil and olive oil were compared in a 20-week randomized, single-blind crossover study with atopic patients. Fatty acid profiles were measured in plasma triglyceride, cholesteryl and phospholipid fractions. A patient questionnaire provided additional information on skin dryness, itchiness and usage of dermal medications. Skin transepidermal water loss (TEWL) was also measured. Levels of both essential fatty acids (EFAs), linoleic acid (18:2n6) and alpha-linolenic acid (18:3n3), and gamma-linolenic acid (GLA; 18:3n6) increased in all lipid fractions after hempseed oil, with no significant increases of arachidonic acid (20:4n6) in any lipid fractions after either oil. Intra-group TEWL values decreased (p=0.074), qualities of both skin dryness and itchiness improved (p=0.027) and dermal medication usage decreased (p=0.024) after hempseed oil intervention. Dietary hempseed oil caused significant changes in plasma fatty acid profiles and improved clinical symptoms of atopic dermatitis. It is suggested that these improvements resulted from the balanced and abundant supply of PUFAs in this hempseed oil.
ORIGINAL ARTICLE
Efficacy of dietary hempseed oil in patients with atopic dermatitis
JAMES CALLAWAY
1
, URSULA SCHWAB
2
, ILKKA HARVIMA
3
, PIRJO HALONEN
4
,
OTTO MYKKA
¨NEN
2
, PEKKA HYVO
¨NEN
5
& TOMI JA
¨RVINEN
1
Departments of
1
Pharmaceutical Chemistry,
2
Clinical Nutrition,
5
Clinical Research Centre and,
4
Computing Center,
University of Kuopio and
3
Department of Dermatology, Kuopio University Hospital, Finland
Abstract
Background: Hempseed oil is a rich and balanced source of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs).
Anecdotal evidence indicated that dietary hempseed oil might be useful in treating symptoms of atopic dermatitis. Patients
and methods: Dietary hempseed oil and olive oil were compared in a 20-week randomized, single-blind crossover study with
atopic patients. Fatty acid profiles were measured in plasma triglyceride, cholesteryl and phospholipid fractions. A patient
questionnaire provided additional information on skin dryness, itchiness and usage of dermal medications. Skin
transepidermal water loss (TEWL) was also measured. Results: Levels of both essential fatty acids (EFAs), linoleic acid
(18:2n6) and alpha-linolenic acid (18:3n3), and gamma-linolenic acid (GLA; 18:3n6) increased in all lipid fractions after
hempseed oil, with no significant increases of arachidonic acid (20:4n6) in any lipid fractions after either oil. Intra-group
TEWL values decreased (p50.074), qualities of both skin dryness and itchiness improved (p50.027) and dermal
medication usage decreased (p50.024) after hempseed oil intervention. Conclusions: Dietary hempseed oil caused significant
changes in plasma fatty acid profiles and improved clinical symptoms of atopic dermatitis. It is suggested that these
improvements resulted from the balanced and abundant supply of PUFAs in this hempseed oil.
Key words: Cannabis, hemp, SDA, stearidonic acid, desaturase, eczema
Introduction
Dietary fatty acids can influence symptoms of atopic
dermatitis (1,2) and other aspects of health (3). Seed
oils that are rich in both essential fatty acids (EFAs),
i.e. linoleic acid (18:2n6) and alpha-linolenic acid
(18:3n3), and particularly seed oils that contain
gamma-linolenic acid (GLA, 18:3n6), have been
studied in patients with atopic dermatitis (4–9), with
varying degrees of success, and more recently in
regard to immune response (10).
The seed oil from some varieties of Cannabis sativa
L. can have over 80% polyunsaturated fatty acids
(PUFAs). Hempseed oil, pressed from non-drug
varieties of the Cannabis seed, is an especially rich
source of both EFAs (Table I), in addition to their
immediate biologic metabolites, GLA and steari-
donic acid (SDA; 18:4n3) (11). Moreover, these
PUFAs are present in hempseed oil at a metaboli-
cally favourable omega-6 to omega-3 ratio (n-6/n-3),
in addition to tocopherols (12,13).
The EFAs were already recognized as being
essential to human health by the 1930s (14,15). In
human metabolism, both EFAs must compete for
access to the same rate-limiting enzyme, delta-6
desaturase; a metabolic point at which the transfor-
mation of omega-6 and omega–3 fatty acids bifur-
cate into a cascade of bioactive metabolites (16).
Moreover, delta-6-desaturase has a higher affinity
for alpha-linolenic acid than linoleic acid (17). Thus,
metabolic competition between the EFAs for access
to delta-6 desaturase suggests some optimal balance
between dietary omega-6 to omega-3 fatty acids (16–
19). Recent research indicates this optimal n-6/n-3
dietary ratio to be somewhere between 2:1 and 3:1
(20). By contrast, evening primrose and borage oils
are totally lacking in omega-3 PUFAs, i.e. alpha-
linolenic acid and SDA, which may account for their
poor or inconclusive performance in some clinical
studies with these seed oils (6–9,21–23). This idea is
supported by effective increases in immunologic
vigour from blackcurrant seed oil (10), which has an
Correspondence: James Callaway, Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. Tel: +358 17
163601. Fax: +358 17 162456. E-mail: callaway@uku.fi
(Received 3 March 2004; accepted 9 March 2005)
Journal of Dermatological Treatment. 2005; 16: 87–94
ISSN 0954-6634 print/ISSN 1471-1753 online #2005 Taylor & Francis Group Ltd
DOI: 10.1080/09546630510035832
excellent n-6/n-3 balance and PUFA profile that is
remarkably similar to hempseed oil (11–13,22).
Hempseed oil has been used as a food and
medicine for at least 3000 years in China (24), and
has recently become available in specialty food shops
throughout Europe and North America (25). The
recent availability of hempseed oil in Western
cultures has led to anecdotal reports of improved
health after its oral administration (e.g.26,27). In
most cases, noticeable healing of chronic skin
problems begins within 2 weeks after initiating
regular use of hempseed oil. Thicker, and thus
stronger, hair and nails have also been observed
after longer periods of regular use (unpublished
observations).
Atopic dermatitis, more commonly known as
eczema, is a chronic skin condition that can result
from various allergenic challenges, but its precise
aetiology remains unknown. Several likely factors
have been investigated, such as diet (3,19,28),
decreased delta-6-desaturase activity (21,29,30),
decreased ceramide function (31,32,33), problems
in sphingomyelin metabolism (34), bacterial skin
flora (35), skin lipid profiles (2), use of alcohol (36)
and environmental influences; such as sodium lauryl
sulfate (SLS, a detergent found in many body care
products) and light (37), in addition to age, season,
temperature and humidity (38–40). None of these
factors are mutually exclusive, and it seems that
dietary fatty acids play some fundamental role in the
manifestation of this complex metabolic system,
which is more or less dysfunctional in patients
who develop symptoms of atopic dermatitis (41).
Considering the fatty acid profile of hempseed oil
(Table I) with the frequency of subjective reports
that claim improvement in skin conditions, its
seemed worthwhile to investigate the possibility
that hempseed oil might have functional benefits
that could also be measured objectively in a clinical
trial.
The aim of the present study was to compare the
effects of dietary hempseed oil and olive oil on
plasma lipid profiles, transepidermal water loss
(TEWL), skin quality and dermal medication usage
in patients with atopic dermatitis in a randomized
crossover design.
Patients and methods
Study design
This was a controlled, randomized single-blind
crossover study. The two intervention periods were
8 weeks in duration, with a 4-week washout period
in between (Figure 1). A group of 20 patients with
atopic dermatitis were included, divided into two
groups by electronically generated random digits and
instructed to orally consume 30 ml (2 tbsp) of the
assigned study oil during each day of the interven-
tion period. Only one member for the study team
(US) was privy to patient and sample identity, and
this information was not available during the study
period or data analysis.
The study was conducted at latitude 63˚N,
beginning in early January and ending in late May.
The patients visited the research unit at the
beginning of each intervention period, after 4 weeks
and at the end of each intervention period, for a total
of six visits. Body weight was measured using
the same calibrated electronic scale throughout the
study. Patients also met with a nutritionist at the
beginning of each study period to receive their
intervention oil and detailed information for incor-
porating the oils into their daily diet. The same
Table I. Fatty acid profiles of the hempseed oil and olive oil used in this study.
Fatty acid (code) Hempseed oil Olive oil Class
Palmitic acid (16:0) 6% 15% Saturated
Stearic acid (18:0) 2 0 Saturated
Oleic acid (18:1n9) 9 75 MUFA, omega-9
Linoleic acid (18:2n6) 54 7 PUFA, omega-6
alpha-Linolenic acid (18:3n3) 22 v1 PUFA, omega-3
*GLA (18:3n6) 4 0 PUFA, omega-6
*SDA (18:4n3) 2 0 PUFA, omega-3
% PUFA 82% 7% omega-6 +omega-3
n6/n3 ratio 2.2:1 w7:1 omega-6/omega-3
*GLA and SDA are abbreviations for gamma-linolenic acid and stearidonic acid, which are the biological metabolites of linoleic acid and
alpha-linolenic acid, respectively. MUFA5monounsaturated and PUFA5polyunsaturated fatty acids.
Figure 1. The crossover study design for comparing the study oils
in atopic patients, who visited the clinic at 4-week intervals for a
total of six visits.
88 J. Callaway et al.
dermatologist (IH) examined and cared for all
patients throughout the study. All participants gave
their prior written informed consent, and the study
protocol was approved by the Ethics Committee of
Kuopio University Hospital.
To monitor the diet, all patients kept a 7-day food
record (consecutive days) during the third week of
each intervention period, and a 4-day food record
(consecutive days; 3 weekdays plus one weekend
day) during the third week of the washout period.
Data from the food records were compiled using the
Micro-NutricaHdietary analysis software version 2.5
(42).
Patients
Inclusion criteria were a body mass index (BMI)
v30 kg/m
2
, age between 25 and 60 years and a
diagnosis of atopic dermatitis, as previously
described (43). Patients who were concurrently
taking lipid-lowering medications were excluded
from the study, and none of the patients were taking
antihypertensive medications. The patients were
instructed to continue any other medication as
needed, such as common skin creams or the
occasional use of anti-inflammatory agents, and to
maintain their normal level of physical activity
during the study period. Patients were also
instructed to avoid nutrient supplements, steroids
(e.g. in skin creams), oral cyclosporine, asthma
medications or solariums during the study or 1
month prior.
Intervention oils
Hempseed oil for this study was cold-pressed from
hempseed that was cultivated in Finland during
2001. Olive oil was cold-pressed extra virgin, and
obtained from a commercial source in Southern
Europe. Both oils were bottled without any addi-
tives, in unlabelled 200-ml brown glass and stored at
+5˚C until use. The peroxide value was below
5 mmeqv/L and the level of free fatty acids was
below 1% for both oils at the time of use. Fatty acid
profiles and other important properties are presented
in Table I for each of the intervention oils.
Patient questionnaire and measurements of
transepidermal water loss (TEWL)
All patients responded to a simple questionnaire to
determine their perception of changes in skin
dryness and itchiness throughout the study period,
using a rating scale from 0 (no dryness or itching) to
5 (severe dryness or itching, sleep disturbance). Use
of any dermal medication was also rated on a similar
scale: 0 (no medication) and 5 (regular usage). The
permeability barrier function of skin was determined
by measuring transepidermal water loss (TEWL)
with a VapoMeter SWL-3 (Delfin Technologies Ltd,
Kuopio, Finland), as previously described (44).
Plasma fatty acid analyses
All blood samples were drawn after an overnight fast
(12 h). Plasma lipid fractions were isolated and their
fatty acid methyl esters (FAMEs) were analysed by
capillary gas chromatography (Hewlett-Packard
5890 series II, Hewlett-Packard Company,
Waldbronn, Germany) using an FFAP-column
(length 25 m, inner diameter 0.2 mm and film
thickness 0.33 mm, Hewlett-Packard), with flame
ionization detection with helium as the carrier gas, as
previously described (45). Heptanoic acid (17:0)
was used as an internal standard and individual fatty
acid concentrations were calculated as molar per-
centages of the FAME profile by an eight-point
external calibration curve for each FAME, using a 37
component FAME standard (Supelco). Verification
of each FAME signal was made by gas chromato-
graphy with mass spectrometric detection (Agilent
Technologies 6890N Network GC System +5973
Network Mass Selective Detector).
Statistical analyses
Data were analysed by the SPSS software package
for Windows, Release 10.0 (Chicago, IL, USA).
Before further analyses, the normal distribution of
variables was checked by the Shapiro-Wilk’s test.
Variables with non-symmetrical distributions were
log-transformed and these values were used in
further analyses. Repeated measures analysis of
variance (ANOVA) was used to test changes within
time and possible interactions between time and the
intervention period. In cases where the result of an
analysis was significant, a paired t-test was used for
two-tailed comparisons to identify significant inter-
actions between time and intervention period.
Bonferroni corrections were made for all plasma
fatty acid results. Wilcoxon matched pairs signed
ranks tests were used to analyse patients’ reported
usage of dermal medication and their perceptions of
both skin dryness and itchiness. All data are
expressed as the mean¡standard deviation (SD).
Apvalue v0.05 was considered to be statistically
significant.
Results
A total of 20 patients were recruited for this study,
but only 16 (1 male, 15 females) completed the
entire course. Three patients dropped out within the
first week for personal reasons, and another dropped
out during week 13, due to the taste of the hempseed
oil. No patients experienced any negative side effects
or adverse reactions to either oil during the course of
this study. Baseline characteristics (mean¡SD)
Efficacy of dietary hempseed oil in atopic dermatitis 89
included age, 38.1¡8.5 years; weight, 67.7¡
13.2 kg; and BMI, 24.9¡4.5 kg/m
2
.
There were no significant differences in body
weight during this study (data not shown), and
relatively less ‘fat’ and energy were ingested during
the washout, compared with the intervention periods
(Table II). Otherwise, no other remarkable changes
were seen in estimated intake of energy, carbo-
hydrates, protein, fibre or cholesterol for either oil.
Consumption of oleic acid (as MUFA in Table II)
during olive oil intervention was nearly equivalent to
the levels of PUFAs (i.e. the two EFAs plus GLA
and SDA) ingested during the hempseed oil inter-
vention (Table II).
Statistically significant modifications in plasma
fatty acid profiles were observed in all lipid fractions
after hempseed oil intervention (Tables III–V). In
particular, levels of GLA increased after hempseed
oil intervention (pv0.05, inter-group comparisons),
Table II. Average dietary intake throughout the study (mean¡
standard deviation, n516).
Hempseed oil Olive oil Wash out
Energy (MJ) 7.8¡1.4 7.7¡1.5 6.9¡1.4
Fat (E%) 37.4¡7.1 36.3¡3.5 30.5¡5.3
Saturated 9.6¡2.1 10.2¡2.1 10.2¡2.5
MUFA 9.7¡3.8 17.1¡1.6 10.5¡3.3
PUFAs 15.1¡3.2 6.4¡2.3 6.1¡2.3
18:2n6 10.7¡2.6 5.0¡1.8 4.7¡2.2
18:3n3 3.3¡0.6 1.0¡0.5 0.9¡0.2
Carbohydrates (E%) 45.1¡7.5 46.6¡4.6 50.8¡6.7
Protein (E%) 15.6¡3.2 15.6¡3.0 17.6¡3.6
Alcohol (E%) 2.0¡3.5 1.4¡2.3 1.1¡1.9
Fibre (grams) 21.0¡6.2 21.6¡5.4 23.5¡8.7
(g/MJ) 2.7¡0.7 2.9¡0.9 3.4¡1.3
Cholesterol (mg) 178¡67 163¡43 162.0¡50
(mg/MJ) 22¡8 22.0¡8 24.4¡10
*E%5percent of energy; MUFA5monounsaturated fatty acids;
PUFAs5polyunsaturated fatty acids; 18:2n65linoleic acid;
18:3n35alpha-linolenic acid.
Table IV. Fatty acid profiles of plasma 1-cholesteryl esters at the beginning (0 wk) and end (8 wk) of the oil intervention periods, expressed
as mole per cent (n516, mean¡standard deviation); paired t-test, ns5non-significant (pw0.05).
Fatty acid
Hempseed oil Olive oil
p
a
0wk 8wk 0wk 8wk
Myristic (14:0) 1.31¡0.58 1.42¡1.14 1.17¡0.30 1.11¡0.36 ns
Palmitic (16:0) 12.15¡0.23 13.61¡6.42 11.60¡1.48 10.90¡1.78 ns
Palmitoleic (16:1n-7) 3.27¡1.60 2.34¡0.89
b
3.21¡1.40 2.90¡1.35 0.041
Stearic (18:0) 1.57¡0.57 2.05¡1.95 1.60¡0.57 1.43¡0.60 ns
Oleic (18:1n9) 17.05¡2.34 13.66¡2.33
f,g
17.16¡1.92 18.75¡2.60
b
0.000
Linoleic (18:2n6) 54.90¡7.21 56.48¡11.89 54.30¡6.16 55.08¡6.69 ns
GLA (18:3n6) 0.67¡0.26 0.94¡0.32
c
0.58¡0.26 0.61¡0.19 0.041
alpha-Linolenic (18:3n3) 0.87¡0.16 1.47¡1.05 0.85¡0.18 0.88¡0.16 0.060
Dihomo-GLA (20:3n6) 3.44¡5.13 3.19¡4.21 3.95¡4.32 3.27¡5.29 ns
Arachidonic (20:4n6) 4.41¡1.20 4.46¡1.39 5.18¡2.74 4.23¡1.24 ns
Docosahexaenoic (22:6n3) 0.35¡0.34 0.39¡0.47 0.38¡0.38 0.41¡0.37 ns
a
ANOVA probability of interaction between time and intervention period,
b
within a period (intra-group comparison) pv0.05,
c
between
period ends (inter-group comparison) pv0.05,
f
within a period (intra-group comparison) pv0.001,
g
between period ends (intra-group
comparison) pv0.001.
Table III. Fatty acid profiles of plasma triglyceride esters at the beginning (0 wk) and end (8 wk) of the oil intervention periods, expressed
as mole per cent (n516, mean¡standard deviation); paired t-test, ns5non-significant (pw0.05).
Fatty acid
Hempseed oil Olive oil
p
a
0wk 8wk 0wk 8wk
Myristic (14:0) 2.71¡0.99 2.14¡0.66 2.72¡1.22 3.06¡1.27 0.052
Palmitic (16:0) 24.40¡4.72 20.46¡3.94
f,c
25.19¡7.79 25.63¡6.04 0.037
Palmitoleic (16:1n-7) 4.26¡1.53 3.20¡0.97
b
4.33¡1.33 3.71¡1.12 ns
Stearic (18:0) 3.16¡0.43 2.94¡0.47 3.26¡0.88 3.40¡0.58 ns
Oleic (18:1n9) 33.75¡3.02 29.84¡4.76
b
35.12¡3.87 35.56¡9.53 ns
Linoleic (18:2n6) 23.69¡7.48 31.24¡7.43
f,g
22.11¡7.46 21.19¡5.78 0.000
GLA (18:3n6) 0.43¡0.26 0.93¡0.46
d,g
0.40¡0.27 0.46¡0.25 0.000
alpha-Linolenic (18:3n3) 1.87¡0.54 3.95¡1.16
f,g
1.96¡0.84 1.84¡0.48 0.000
Dihomo-GLA (20:3n6) 1.76¡2.96 1.47¡2.18 1.18¡1.31 1.82¡2.53 ns
Arachidonic (20:4n6) 2.38¡0.95 2.63¡1.10 2.35¡0.85 2.14¡0.85 ns
Docosahexaenoic
(22:6n3)
1.60¡1.18 1.20¡0.69 1.39¡0.69 1.19¡0.77 ns
a
ANOVA probability of interaction between time and intervention period,
b
within a period (intra-group comparison) pv0.05,
c
between
period ends (inter-group comparison) pv0.05,
d
within a period (intra-group comparison) pv0.01,
f
within a period (intra-group
comparison) pv0.001,
g
between period ends (inter-group comparison) p(0.001.
90 J. Callaway et al.
while plasma levels of arachidonic acid (20:4n6) did
not change significantly after either oil.
Results from the patient questionnaire are pre-
sented in Table VI, and values of TEWL are
presented in Table VII. Subjective decreases in both
skin dryness and itchiness (Table VI) were statisti-
cally significant after hempseed oil intervention
(p50.027 and 0.023, respectively, as intra-group
comparisons), which were reflected as a trend
towards decreased TEWL values (p50.074, intra-
group comparison) after hempseed oil intervention
(Table VII), while no such improvements were
observed after olive oil intervention. A decrease in
the usage of dermal medication was also observed
after hempseed oil intervention (p50.024, intra-
group comparison), with no such improvement after
olive oil intervention (Table VI). An inter-group
comparison of the TEWL values in Table VII,
comparing the end values for both oils, was not
statistically significant (p50.274).
Discussion
The two intervention oils differed significantly in
their respective fatty acid profiles (Table I). While
hempseed oil is over 80% PUFAs, and includes both
GLA and SDA, olive oil is a fairly poor source of
PUFAs and is totally lacking in either GLA or SDA.
The intervention oils also differed in both appear-
ance and taste; the hempseed oil was dark green and
nutty in flavour while the olive oil was light green
and tasted of olives. The difference in colour was
due to more or less chlorophyll, respectively. Other
natural components, such as tocopherols, also
vary in high quality, cold-pressed oils. Not only do
Table V. Fatty acid profiles of plasma phospholipid esters at the beginning (0 wk) and end (8 wk) of the oil intervention periods, expressed
as mole per cent (n516, mean¡standard deviation); paired t-test, ns5non-significant (pw0.05).
Hempseed oil Olive oil
p
a
0wk 8wk 0wk 8wk
Myristic (14:0) 1.34¡0.37 1.26¡0.22 1.33¡0.28 1.38¡0.40 ns
Palmitic (16:0) 31.48¡4.53 28.92¡1.90 31.10¡3.23 32.67¡8.99 ns
Palmitoleic (16:1n-7) 0.86¡0.40 0.64¡0.20 0.86¡0.33 0.73¡0.33 ns
Stearic (18:0) 13.96¡5.97 14.56¡5.41 13.46¡3.33 13.24¡3.45 ns
Oleic (18:1n9) 9.92¡1.48 8.32¡1.40
f,c
10.21¡1.07 11.15¡1.71 0.000
Linoleic (18:2n6) 24.32¡5.53 27.12¡4.17 24.57¡4.29 23.59¡6.49 0.055
GLA (18:3n6) 0.04¡0.06 0.15¡0.10
f,e
0.06¡0.09 0.06¡0.08 0.000
alpha-Linolenic (18:3n3) 0.43¡0.09 0.61¡0.13
f,c
0.43¡0.09 0.42¡0.12 0.003
Arachidic (20:0) 0.45¡0.20 0.51¡0.07 0.49¡0.11 0.43¡0.13 ns
Eicosenoic (20:1n9) 0.42¡0.12 0.28¡0.09 0.29¡0.11 0.27¡0.14 ns
Dihomo-GLA (20:3n6) 2.69¡1.29 3.80¡1.58 3.08¡1.51 3.29¡1.42 ns
Arachidonic (20:4n6) 6.55¡1.51 6.77¡1.78 6.77¡1.37 6.08¡2.10 ns
Eicosapentaenoic (20:5n3) 1.17¡0.78 0.99¡0.41 1.12¡0.82 1.13¡0.68 ns
Docosahexaenoic (22:6n3) 4.50¡1.27 3.93¡0.80 4.49¡1.18 4.02¡1.50 ns
Behemic (22:0) 0.87¡0.17 0.96¡0.20 0.92¡0.16 0.81¡0.28 0.039
Lignoceric (24:0) 1.18¡1.43 1.16¡1.18 0.83¡0.13 0.72¡0.24 ns
a
ANOVA probability of interaction between time and intervention period,
c
between period ends (inter-group comparison) pv0.05,
e
between period ends (inter-group comparison) pv0.01,
f
within a period (intra-group comparison) pv0.001.
Table VI. Patient ratings (n516, mean¡standard deviation) of atopic symptoms (05no dryness or itching, 55severe dryness itching, sleep
disturbance) and use of dermal medication (05none, 55regular usage); Wilcoxon non-parametric t-test.
Hempseed oil Olive oil
Week 0 Week 8 p*Week 0 Week 8 p*p**
Skin dryness 3.19¡1.17 2.25¡1.18 0.027 3.44¡0.81 3.06¡1.29 0.380 0.064
Skin itchiness 2.56¡1.50 1.56¡1.21 0.023 2.44¡1.26 2.38¡1.59 0.995 0.087
Use of medication 2.69¡1.14 1.69¡1.08 0.024 2.75¡1.00 2.56¡1.31 0.734 0.118
Within period changes (p*) are intra-group comparisons of the beginning (week 0) and end (week 8) values for each intervention period.
Between period changes (p**) are inter-group comparisons of the end values for each intervention period.
Table VII. Transepidermal water loss (TEWL) values (g/m
2
h;
mean¡standard deviation, n516) for each intervention period;
Wilcoxon non-parametric t-test.
Intervention oil Week 0 Week 8 p*
Hempseed oil 12.2¡5.3 9.6¡3.7 0.074
Olive oil 12.8¡6.3 11.8¡7.5 0.813
*Within period changes are intra-group, comparing the beginning
and end values of each intervention period. The inter-group
comparison at week 8 was not statistically significant (p50.274).
Efficacy of dietary hempseed oil in atopic dermatitis 91
antioxidants protect dietary oils from oxidation in situ
but also lipid peroxidation in vivo (46,47).
The food oil peroxide value is another important
parameter that is typically overlooked, or simply
assumed to be low, in studies of unsaturated dietary
oils. PUFAs, in particular, will oxidize over time to
eventually form varnish. As these peroxides are not
known to have any therapeutic value, it is important
to demonstrate that intervention oils have low
peroxide values, as in the present study (v5 mmeqv/L).
Light can also affect symptoms of atopic derma-
titis (37). In the present study, patients avoided the
use of solariums throughout the study period, which
ran from early January until the end of May. In
Finland, ambient outdoor temperatures are too low
during this period of time for significant amounts of
solar exposure to affected atopic areas of the body.
Moreover, the rigorous crossover design employed
in this study was intended to compensate for any
such changes over time.
Changes in plasma fatty acid profiles were
especially significant after hempseed oil in all lipid
fractions, particularly for linoleic acid, alpha-
linolenic acid and GLA (Tables III–V). Variability
in plasma fatty acid values was due to individual
heterogeneity in the sample sets, and not the
quantitative method. Thus, it is possible that more
than one type of atopic patient was included in the
present study (48). Dietary GLA (0.48–1.5 g/day)
from both borage seed oil and blackcurrant seed oil
has been shown to significantly increase levels of
its immediate biological metabolite, dihomo-
gamma-linolenic acid (DGLA) in healthy humans
(49), as measured in polymorphonuclear neutrophils
(PMN), where a corresponding decrease in pro-
inflammatory leukotriene B4 (LTB
4
) was also noted.
It has been suggested that dietary GLA is rapidly
metabolized in skin to DGLA, which suppresses the
ability of PMNs to produce LTB
4
(50). The daily
amount of GLA in hempseed oil was about 1.2 g/day
in the present study, but a slight increase of DGLA
in plasma phospholipids (Table V) did not reach
statistical significance after hempseed oil interven-
tion. If eicosanoids are involved in atopic dermatitis,
perhaps through the production of pro-inflammatory
prostaglandins (4,50), then a dietary increase in
GLA would provide the requisite substrate in the
production of DGLA.
SDA was detected in all plasma samples, but it
was below the limit of quantitation and its signal did
not always exhibit baseline resolution in all samples.
This rare, omega-3 fatty acid is certainly better than
alpha-linolenic acid for the in vivo production of
eicosapentaenoic acid (EPA). A recent study found
that 0.75–1.50 g of dietary SDA increased levels of
EPA in both erythrocytes and plasma phospholipids
(51), but a significant increase in phospholipids for
EPA was not seen in the present study, where the
daily amount of SDA was about 0.60 g/day.
Unfortunately, the present study did not examine
fatty acid profiles in erythrocyte membranes.
Decreased levels of ceramides in the stratum
corneum may be another important aetiological
factor in atopic dermatitis (32). Ceramides may
have an important role in skin barrier function, and
linoleic acid is metabolically esterified to ceramide 1,
while oleic acid is not. Such a metabolite could
function as a molecular rivet in the stabilization of
lipid lamellar sheets, thus reducing the loss of
moisture through skin (31), especially in the elderly
(39).
Despite the high levels of oleic acid in olive oil, it is
surprising to see how little impact the consumption
of this oil actually had on plasma lipid profiles of this
fatty acid (Tables III–V). Oleic acid is not essential
for health and is clearly not taken up as aggressively
into plasma lipids as PUFAs. Overall changes in
fatty cholesteryl esters were less robust than those
for triglycerides or phospholipids for both oils
(Table IV, in relation to Tables III and V, respec-
tively). However, if symptoms of atopic dermatitis
were more closely related to membrane function,
rather than eicosanoid production, then such a
significant increase of PUFAs in phospholipid
bilayers (Table V) could effectively increase mem-
brane fluidity and function (3,52).
Patients in the present study reported statistically
significant decreases in skin dryness, itchiness and
use of dermal medication after hempseed oil inter-
vention (Table VI). A functional skin barrier is
essential to maintain skin moisture (53,54).
Decreased TEWL values (Table VII) are a good
indication that less water was being lost through the
skin after hempseed oil, which supports the sub-
jective results from the patient questionnaire in
Table VI. Although this trend (p50.074, intra-
group comparison) was not statistically significant,
it is worth noting in light of the subjective evaluation
from the patients, especially in regard to skin
dryness. This is important because skin dryness
and subsequent itchiness often lead to the use of
medication in atopic patients, especially during the
dry winter conditions in Finland, where ambient
indoor humidity can be v30% moisture for months
on end.
It was mentioned in the Introduction that indivi-
duals who have used hempseed oil for longer periods
of time report increased strength in finger nails
(months) and thicker hair (years), in addition to the
improvements in skin conditions within weeks. The
times required for these varied effects roughly
correspond to the amounts of time required for the
newly formed cells of each tissue to become
physically apparent. These three cell lines are
constructed by dermal stem cells from fatty acids
that are available in the diet at the time of their
formation. Here is yet another interesting facet to
consider in the complexity of tissue formation, which
92 J. Callaway et al.
is dependent on dietary fatty acids; i.e. optimal
construction of skin, hair and nails at the dermal
stem cell level.
The apparent efficacy of dietary hempseed oil in
this study could be due to the exceptionally high
level of PUFAs in this oil (w80%), which had a
metabolically favourable n-6/n-3 ratio of approxi-
mately 2:1. These fatty acids are already known to
play vital roles in immune response (55). The fatty
acid profile of this hempseed oil is remarkably
similar to that of blackcurrant seed oil, which has
been reported to have a beneficial impact on
immunologic vigour (10,22). The presence of both
GLA and SDA in hempseed oil (the metabolic
products of EFAs linoleic acid and alpha-linolenic
acid, respectively) allows the rate-limiting enzymatic
step with delta-6-desaturase to be bypassed [e.g. 16],
which could be the biochemical mechanism that was
responsible for the improvement of atopic symptoms
observed in the present study after hempseed oil.
Skin dryness and itchiness, in particular, are very
serious problems in atopic dermatitis, which often
lead to additional complications, such as opportu-
nistic infections. In any event, it seems that the
reduction of atopic symptomology observed in this
study is a direct result of ingested hempseed oil.
These preliminary results confirm anecdotal obser-
vations of improved skin quality after ingesting
modest amounts of hempseed oil on a daily basis
over a relatively short period of time. From these
observations, further study is warranted to deter-
mine the value of regular use of dietary hempseed in
the treatment of atopic dermatitis.
Acknowledgements
The authors wish to thank Mrs Kaija Kettunen and
Riitta Kivela¨ for excellent technical assistance.
Support for this study was provided by TEKES,
the National Technology Agency of Finland. Full
disclosure: J.C. Callaway, PhD, has a financial
interest in the production and sales of hempseed oil.
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The first indication that dietary fat may be essential for healthy growing animals was presented in 1918 by Aron, who proposed that butter has a nutrient value that cannot be provided by other dietary components (1). This report suggested that there was a special nutritive value inherent in fat apart from its caloric contribution and that this possibly was related to the presence of certain lipids. In 1929, Burr and Burr (2) presented the first in a series of articles outlining a “new deficiency disease produced by the rigid exclusion of fat from the diet.” In the series of conclusions put forth, they developed the hypothesis that warm-blooded animals, in general, cannot synthesize appreciable quantities of certain fatty acids. In 1930, both investigators significantly added to their earlier work by presenting evidence that the dietary inclusion of linoleic acid alone could reverse all deficiency symptoms resulting from a fat-free diet and thus linoleic acid (LA or 18:2n-6)’ was heralded as an essential fatty acid (EFA) (3). The recognition that some unsaturated fatty acids could not be synthesized from endogenous precursors by mammals and were essential dietary elements led to the designation of essential and nonessential fatty acids. It was originally thought that there are only two essential fatty acids, linoleic acid (9,12-octadecadienoic acid, LA, 18:2n-6) and α-linolenic acid (9,12,15-octadecatrienoic acid [ALA], 18:3n-3), but continued nutritional studies revealed positive essential growth responses not only for linoleic acid and a-linolenic acid, but also for arachidonic acid as well as the long-chain highly unsaturated fatty acids in fish oil (eicosapentaenoic acid, 20:5n-3) and docosahexaenoic acid, 22:n-3) (4–6). More recent reports on the biological significance of the longer-chain n-3 PUFAs do qualify these long-chain fatty acids as essential PUFAs.
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The recently reported cases of skin lesions discussed here were produced under conditions which indicate a lack of some growth factor. In no case were conditions such that uncomplicated fat-deficiency could result. It would be impossible, therefore, for these rats to respond to small doses of unsaturated fats. An adequate supply of all water soluble growth factors must be fed if the typical fat deficiency results are to be obtained. Growth should approximate that given by the daily consumption of 0.65 gm. or more of high grade dried yeast.
Article
The seed of Cannabis sativa L. has been an important source of nutrition for thousands of years in Old World cultures. Non-drug varieties of Cannabis, commonly referred to as hemp, have not been studied extensively for their nutritional potential in recent years, nor has hempseed been utilized to any great extent by the industrial processes and food markets that have developed during the 20th century. Technically a nut, hempseed typically contains over 30% oil and about 25% protein, with considerable amounts of dietary fiber, vitamins and minerals. Hempseed oil is over 80% in polyunsaturated fatty acids (PUFAs), and is an exceptionally rich source of the two essential fatty acids (EFAs) linoleic acid (18:2 omega-6) and alpha-linolenic acid (18:3 omega-3). The omega-6 to omega-3 ratio (n6/n3) in hempseed oil is normally between 2:1 and 3:1, which is considered to be optimal for human health. In addition, the biological metabolites of the two EFAs, gamma-linolenic acid (18:3 omega-6; GLA) and stearidonic acid (18:4 omega-3; SDA), are also present in hempseed oil. The two main proteins in hempseed are edestin and albumin. Both of these high-quality storage proteins are easily digested and contain nutritionally significant amounts of all essential amino acids. In addition, hempseed has exceptionally high levels of the amino acid arginine. Hempseed has been used to treat various disorders for thousands of years in traditional oriental medicine. Recent clinical trials have identified hempseed oil as a functional food, and animal feeding studies demonstrate the long-standing utility of hempseed as an important food resource.
Article
The oil content, the tocopherol composition, the plastochromanol-8 (P-8) content and the fatty acid composition (19 fatty acids) of the seed of 51 hemp (Cannabis sativa L.) genotypes were studied in the 2000 and 2001 seasons. The oil content of the hemp seed ranged from 26.25% (w/w) to 37.50%. Analysis of variance revealed significant effects of genotype, year and of the interaction (genotype year) on the oil content. The oil contents of the 51 genotypes in 2000 and 2001 were correlated (r = 0.37**) and averaged 33.19 1.45% in 2000 and 31.21 0.96% in 2001. The -tocopherol, -tocopherol, -tocopherol, P-8- and -tocopherol contents of the 51 genotypes averaged 21.68 3.19, 1.82 0.49, 1.20 0.40, 0.18 0.07 and 0.16 0.04 mg 100g–1 of seeds, respectively (2000 and 2001 data pooled). Hierarchical clustering of the fatty acid data did not group the hemp genotypes according to their geographic origin. The -linolenic acid yield of hemp (3–30 kg ha–1) was similar to the -linolenic acid yield of plant species that are currently used as sources of -linolenic acid (borage (19–30 kg ha–1), evening primrose (7–30 kg ha–1)). The linoleic acid yield of hemp (129–326 kg ha–1) was similar to flax (102–250 kg ha–1), but less than in sunflower (868–1320 kg ha–1). Significant positive correlations were detected between some fatty acids and some tocopherols. Even though the average content of P-8 in hemp seeds was only 1/120th of the average -tocopherol content, P-8 content was more closely correlated with the unsaturated fatty acid content than -tocopherol or any other tocopherol fraction. The average broad-sense heritabilities of the oil content, the antioxidants (tocopherols and P-8) and the fatty acids were 0.53, 0.14 and 0.23, respectively. The genotypes Fibrimon 56, P57, Juso 31, GB29, Beniko, P60, FxT, Flina 34, Ramo and GB18 were capable of producing the largest amounts of high quality hemp oil.
Article
Research from the 1930s to the 1950s established that a deficit of n-6 essential fatty acids (EFAs) leads to an inflammatory skin condition in both animals and humans. In a common inherited skin condition, atopic dermatitis (eczema), there was evidence of low blood EFA concentrations and of a therapeutic response to exceptionally high doses of linoleic acid. More recently, it has been established that there is no deficit of linoleic acid in atopic eczema. Concentrations of linoleic acid instead tend to be elevated in blood, milk, and adipose tissue of patients with atopic eczema, whereas concentrations of linoleic acid metabolites are substantially reduced. This suggests reduced conversion of linoleic acid to gamma-linolenic acid (GLA). In most but not all studies, administration of GLA has been found to improve the clinically assessed skin condition, the objectively assessed skin roughness, and the elevated blood catecholamine concentrations of patients with atopic eczema. Atopic eczema may be a minor inherited abnormality of EFA metabolism.