ARTICLE
Auteur(s) : Jean-Marc Maurette
53 rue Auguste Buisson 92250 La Garenne-Colombes France
The fatty acids of the omega-6/omega-3 families
Fatty acids (FA), in general, are long chain molecules. If they
have more than a single bound they are called polyunsaturated fatty
acids (PUFAs).
Roughly, PUFAs from the omega-6 series is starting with the
linoleic acid (LA) (C18:2 n-6), an essential FA coming from the
diet, metabolized through desaturation and elongations by other
PUFAs, such as C18:3 n-6: γ-linolenic acid (GLA) and C20:4 n-6,
arachidonic acid (AA).
In the normal diet the long chain PUFAs, such as AA are supplied
by animal foods (meat, eggs, breast milk…). Omega-6 are also widely
present in vegetal oils (borage, evening primrose, black current,
sunflower…).
In parallel to the omega-6 family, the omega-3 one is
represented by a large population, starting from the α-Linolenic
acid (ALA), C18:3 n-3, down to the docosahexaenoic acid (DHA) C22:6
n-3, via various processes of elongation and desaturation. Figure 1 shows the
simplified steps in the metabolism pattern of both series.
Omega-3 and physiology
It’s of common knowledge to point out the combined role of omega-6
and omega-3 in human physiology, for example in the homeostasis of
the inflammatory status of the body.
Omega-3 have numerous known impacts in human health conditions,
in various fields, such as:
- – diabetes and obesity [1-3];
- – cardiovascular diseases [4-6];
- – inflammation [7-10];
- – vision [11].
Among this wide range of activities, omega-3 has a great impact
on skin physiology. Basic skin functions such as the barrier
function, temperature regulation, photo protection, water
homeostasis are impacted by supplementary or dietary intervention
[12, 13]. The modulation of these functions is generally coupled
with changes in skin structure which produce some changes in skin
appearance.
Linoleic acid (AA), γ-linolenic acid (GLA) or α-linolenic acid
(ALA) play a role in cellular signaling interfering with
eicosanoids pathways or influencing the regulation of gene
expression [13, 14].
Further, epidermal lipids are known to play a crucial role in
the mediation of desquamation and the deficiency of essential fatty
acids seems to be involved in cutaneous scaling disorders (xerosis,
psoriasis, atopic dermatitis) [15].
Two recent orientation studies were performed in dermatology,
focusing on skin hydration and skin sensitivity. They were
successively designed and performed in order to verify under real
conditions of use whether or not the oral administration of ALA
(through flaxseed oil, 55% ALA) have any influence on these skin
conditions.
In other words, among the general properties of PUFAs, is it
possible to determine some concrete facts showing the interest of
consuming reasonable amounts of omega-3 and to see an improvement
of skin health conditions. This is the aim of the two study
performed which conditions and results will be described in this
paper [16, 17].
Physiological activity of flaxseed oil: two clinical trials in
dermatology.
Skin sensitivity I
Study design
This first study was carried out as a monocentric, double-blind,
randomized and placebo controlled application test on 26 healthy
volunteers with dry (Corneometer value < 40 au1 [18]) and sensitive skin. Subjects were
divided into two subgroups of 13 (1 verum – 1 reference group).
Verum was composed of 555.32 mg of flaxseed oil (i.e. ≥
289 mg ALA/capsule) associated with stabilizing antioxidants
(D-α-tocopherol and Rosemary extract). The daily dose of ALA was of
at least 1,155 mg. Reference was composed of 560 mg safflower
oil, with a minimum LA content of 70% (i.e. ≥
392 mg/capsule).
The study lasted for 12 weeks, dosage regimen being 4
capsules/day (2 at breakfast; 2 at diner).
Parameters of the study were measured before supplementation and
at weeks 6 and 12 (end point).
Methods
Skin parameters were evaluated by measurement of skin hydration
(Corneometer CM825® – Courage & Khazaka),
transepidermal water loss (TEWL, barrier function of the skin)
(Tewameter TM 300® – Courage & Khazaka) [18, 19] and
skin surface structure (SELS, Visioscan® – Courage &
Khazaka) for the evaluation of the following items : roughness,
scaling, smoothness and wrinkles [20].
The sensitivity of the skin was assessed by the Nicotinate
irritation test according to Primavera & Berardesca [21].
Measurements were performed on the inner forearm of the volunteers.
After application of nicotinate (0.25%, 5 μL/cm2),
inducing a local inflammation, reddening of the skin was measured
by chromametry as “a” value (Minolta CR 300®).
Additionally, capillary surface blood flow was measured by
Laser-Doppler-Flowmetry (O2C-System, Lea Instruments, Giessen,
Germany).
Statistics
For all parameters and all time points (week 0, week 6, week 12)
descriptive statistics (mean, standard deviation, minimum, lower
quartile, median, upper quartile and maximum) were calculated. For
all parameters pre-post differences were calculated and analyzed
descriptively.
For the pre-post differences the two treatment groups were
compared using the Wilcoxon rank-sum test
Within the two treatment groups each combination of two time
points was compared using the Wilcoxon signed-rank test.
Results
In summary this orientation study clearly demonstrates the effect
of the supplementation by ALA (1.15 g/day on the average) on
skin parameters and inflammation induced by the nicotinate test as
shown in table 1.
The following results were observed.
Treatment A: Flaxseed oil
After 6 weeks of treatment:
- – For treatment A, statistically significant changes (p
< 0.05) for the parameters “Blood Flow” (decrease) and “SELS:
roughness” (increase) were observed, compared to baseline.
- – For treatment B a statistically significant increase
(p < 0.05) for the parameter “SELS: roughness” was observed
compared to week 0.
After 12 weeks of treatment:
- – For treatment A a statistically significant increase
(p < 0.05) for the parameters skin hydration and smoothness was
observed after twelve weeks compared to week 0.
A statistically significant decrease (p < 0.05) for the
parameters TEWL, roughness, scaling, redness a-value and blood
flow, was observed after twelve weeks compared to week 0.
Table 1 Percentual changes vs T0 after 6 and 12
weeks.
|
Flaxseed oil (Omega-3) – A
|
Safflower oil (Omega-6) – B
|
|
Week 6
|
Week 12
|
Week 6
|
Week 12
|
|
ARRAY(0x2433a0)
|
|
Hydration
|
+7% (ns)
|
+39%a,b
|
–2% (ns)
|
+13%a
|
|
TEWL
|
–21%a
|
–31%a
|
–6% (ns)
|
–12% (ns)
|
|
SELS
|
|
|
|
|
|
Roughness
|
–22%a
|
–30%a,b
|
–10%a
|
–10%a
|
|
Scaling
|
–15% (ns)
|
–31%a
|
–6% (ns)
|
–14% (ns)
|
|
Smoothness
|
+3% (ns)
|
+7%a
|
–1% (ns)
|
+2% (ns)
|
|
Wrinkles
|
–0.4% (ns)
|
+2% (ns)
|
+2% (ns)
|
+4% (ns)
|
|
Nicotinate test
|
|
|
|
|
|
Redness (a-values)
|
–22% (ns)
|
–48%a,b
|
–0.2% (ns)
|
–7% (ns)
|
|
Blood flow
|
–34%a,b
|
–66%a,b
|
+11% (ns)
|
+7% (ns)
|
aSignificant (p < 0.05, Wilcoxon Rank sum Test).
bA significantly different from B (p < 0.05,
Wilcoxon signed rank test).
Treatment B: Safflower oil
After 6 weeks of treatment:
- – Treatment B showed a statistically significant increase
(p < 0.05) for the parameter “skin hydration” (+13%) compared to
week 0.
After 12 weeks of treatment:
- – A statistically significant decrease (p < 0.05) for
the parameter roughness was observed after twelve weeks compared to
week 0.
Comparison within groups (A vs B)
For the pre-post differences “week 0 – week 6” the comparison of
the two treatment groups showed statistically significant
differences (p < 0.05) in favor of treatment A for the parameter
blood flow.
For the pre-post differences “week 0 – week 12” the comparison
of the two treatment groups showed statistically significant
differences (p < 0.05) in favor of treatment A for the
parameters skin hydration, roughness, redness a-value, blood
flow.
For all the other parameters, on the pre-post differences, no
statistically significant differences can be shown.
Skin sensitivity II
In the second study the effects of flaxseed oil were compared with
the one of a reference product, the borage oil, known to have
hydrating properties on the skin [22].
It seemed interesting to have an idea of the performances of
both oils on the previously studied parameters as described in the
Sensitive Skin I study.
Study design
The study was carried out as a monocentric, randomized,
double-blind, placebo-controlled application test in three parallel
groups of fifteen subjects each (45 healthy non-smoking women,
between 18 and 65 years) with dry (Corneometer value < 40 au
[18] and sensitive skin.
Exclusion criteria were: pregnancy and breast-feeding, history
of fat malabsorption, liver diseases, and diseases regarding lipid
metabolism or any photosensitizing disorder. BMI of the
participants were between 18 to 25 kg/m2. They did
not take lipid or vitamin supplements or any other medication.
Daily doses amounted to 2.22 g flaxseed (1,100 mg ALA
C18:3n-3) or borage oil (480 mg GLA C18:3 n-6); in both groups,
intake of D-α-tocopherol was 10 mg/d.
Placebo was made of 565 mg medium chain triglycerides (caprilic
and capric acid). Daily intake of the placebo was of 2.26 g.
The study lasted for 12 weeks, dosage regimen being
4 capsules/day: 2 at breakfast; 2 at diner.
Methods
Parameters of the study were measured before supplementation and at
weeks 6 and 12 (end point): Skin hydration in arbitrary units
(Corneometer C285®), TEWL in g/h per m2
(TEWA-Meter TM 300 – Courage & Khazaka Electronics [18, 19],
SELS (Visioscan – Courage & Khazaka) [20] for the evaluation of
the following items: roughness, scaling, smoothness and wrinkles.
Nicotinate irritation was used to test the sensitivity of the
skin according to Primavera et al. [21]. Measurements were
performed on the inner forearm of the volunteers. No treatment with
any ointment on the tested areas was allowed during the whole
study. Nicotinate (0.25%; 5 μL/cm2) was applied
inducing an inflammation of the skin; reddening was measured by
chromametry (Minolta CR 300, Ahrensburg, Germany) as “a-value”
before and after treatment. Erythema intensity is given as
Δa-value; a-value after treatment minus a-value before treatment.
Additionally, capillary blood flow was determined by
Laser-Doppler-Flowmetry (O2C-System, Lea Instruments, Giessen,
Germany) in the irritated area.
Statistics
For all parameters and all time points (week 0, week 6, week 12)
descriptive statistics (mean, standard deviation, minimum, lower
quartile, median, upper quartile and maximum) were calculated. For
all parameters pre-post differences were calculated and analyzed
descriptively.
For the pre-post differences the two treatment groups were
compared using the Wilcoxon rank-sum test. Within the two treatment
groups each combination of two time points was compared using the
Wilcoxon signed-rank test. In addition, the two pre-post
differences Week 6/Week 0 and Week 12/Week 0 were compared by an
ANOVA with parameter treatment as the independent variable. The
least square means for the pre-post differences and the respective
95% confidence intervals were calculated. These confidence
intervals were used to assess whether the pre-post difference was
significantly different from [17].
Results
The effects of the supplementation by ALA or GLA on skin parameters
and inflammation induced by the nicotinate test are shown in table 2.
One can see that the results of this second study are consistent
with the ones of the Skin Sensitivity I study despite the limited
number of healthy volunteers in each study. The data are of the
same order of magnitude for the parameters TEWL, SELS, redness and
blood flow for both flaxseed oil groups. The results on hydration
were in both cases significantly different from time 0 inside of
each group. However, in this second study, hydration was not
significantly different from the corresponding placebo group after
12 weeks of treatment (+19% vs. +9%).
It is also interesting to note that significant effects are seen
already at week 6 (hydration, TEWL, roughness, scaling, redness and
blood flow) which was less clear for study I were significant
differences from time 0 at 6 weeks were reached for TEWL, roughness
and blood flow only.
Table 2 Percentual changes vs T0 after 6 and 12
weeks.
|
Flaxseed oil (Omega-3) – A
|
Borage oil (Omega-6) – B
|
Placebo - C
|
|
Week 6
|
Week 12
|
Week 6
|
Week 12
|
Week 6
|
Week 12
|
|
ARRAY(0x2694f8)
|
|
Hydration
|
+12%a
|
+19%a
|
+7.9% (ns)
|
+16.6%a
|
+3% (ns)
|
+9%a
|
|
TEWL
|
–8%a
|
–26%a
|
–9%a,d
|
–11.2%a,d
|
–0.6% (ns)
|
–1.2% (ns)
|
|
SELS
|
|
|
|
|
|
|
|
Roughness
|
–15%a
|
–34%a,b,c
|
–7.6% (ns)
|
–14.7%a
|
–0.61% (ns)
|
+1% (ns)
|
|
Scaling
|
–29%a,b
|
–35%a,b
|
–25.1% (ns)
|
–26.5%a
|
–4.3% (ns)
|
–12.6% (ns)
|
|
Smoothness
|
+5% (ns)
|
+4%a
|
–0.2% (ns)
|
+2.6% (ns)
|
–4.3%a
|
–2.3% (ns)
|
|
Wrinkles
|
–1% (ns)
|
0% (ns)
|
+0.8% (ns)
|
+1.1% (ns)
|
+1.5% (ns)
|
+1.7% (ns)
|
|
Nicotinate test
|
|
|
|
|
|
|
|
Redness (a-values)
|
–32%a
|
–45%a
|
–29.9%a
|
–35.1%a,d
|
0% (ns)
|
–2% (ns)
|
|
Blood flow
|
–34%a
|
–81%a,b,c
|
–28%a
|
–33.8%a
|
–10% (ns)
|
–8.5% (ns)
|
aSignificant (p < 0.05, Wilcoxon Rank sum Test).
bA significantly different from C (p < 0.05,
Wilcoxon signed rank test).
cA significantly different from B (p < 0.05,
Wilcoxon signed rank test).
dB significantly different from C (p < 0.05,
Wilcoxon signed rank test).
Discussion
Flaxseed oil, cold pressed from the seeds of the flax plant (Linum
usitatissimum), is one of richest sources of n-3 fatty acids (FA)
in the vegetal world. With more than 50% of total FA, ALA is
predominant in the oil which also contains the n-6 Linoleic acid
(16%) and the monounsaturated oleic acid (20%) as major
constituents (table 3). The flaxseed oil
supplement used in the present study is typical with respect to its
composition of fatty acids [23]. Borage oil is pressed from the
seeds of the borage plant (Borago officinalis) and rich in the n-6
fatty acids GLA (22%) and LA (39%); oleic acid (15%) is also
present in quite high amounts (table 3).
Its composition is also typical regarding its FA pattern [23].
Facing the lack of omega-3 consumption in the modern diet as
shown by N. Combe et al (2001) [24], it was interesting to see if
oils of vegetable origin may have a significant impact on human
health with a special focus to skin physiology, via ALA
supplementation.
Fish oils were traditionally used as the “ideal” tool to restore
omega-6/omega-3 ratio and contribute to body homeostasis. However
fish oils, in the current “modern life” are not anymore really used
either crude or through fatty fishes diets, despite their great
interested in health benefits.
Due to the lack of omega-3 in the western food, to find another
way to consume Omega 3 from natural origin may have sense,
nutrition wise.
As shown by A. Morise et al. [25], absorption and storage of ALA
is very efficient in the hamster. It powerfully increased EPA.
However dietary ALA failed to increase DHA, but decreased AA. The
authors concluded that dietary supply of ALA was a very efficient
means of improving the balance omega-6/omega-3 (AA/EPA) in Red
Blood Cells and cardiomyocytes.
It has also been shown (unpublished data) a significant
bioconversion of ALA into EPA in Sensitive Skin I for the flaxseed
oil group at week 12, compared to the reference group (safflower
oil).
The two studies presented in this article confirm this concept
in showing interesting results in the field of skin hydration,
inflammation and skin surface structure with acceptable doses of
flaxseed oil compatible with the recommended daily allowances
published by the French Food Safety Agency (AFSSA [26]) amounting
at 1.6 g/day for non pregnant adult females.
Furthermore, the consumption of flaxseed oil has been recognized
as an acceptable dietary practice by AFSSA in 2006 as far as
flaxseed oil is consumed exclusively cold and with less than 1% of
all trans fatty acids [27].
The use of flaxseed oil may also contribute to restore a better
ratio Omega 3/Omega 6 and further studies would be necessary with
greater populations and on a longer period to appreciate the full
benefits suggested in these two orientation studies.
However, it should be pointed out that flaxseed oil, despite its
interest as shown in this paper, cannot be a substitute to a
healthy and equilibrated diet.
Table 3 Fatty acid composition (% of total fatty acids)
(From De Spirt et al. 2008 [17]).
|
Fatty acid
|
Flaxseed oil
|
Borage oil
|
Placebo
|
|
8:0
|
0.00
|
0.00
|
36.9
|
|
10:0
|
0.00
|
0.00
|
21.8
|
|
14:0
|
4.73
|
1.87
|
0.24
|
|
18:0
|
4.12
|
2.82
|
0.00
|
|
18:1n-9
|
19.6
|
15.0
|
0.60
|
|
18:2n-6
|
16.0
|
38.7
|
0.00
|
|
18:3n-6
|
0.00
|
21.6
|
0.18
|
|
18:3n-3
|
52.8
|
0.38
|
0.00
|
|
20:0
|
0.16
|
0.21
|
0.00
|
|
20:1
|
0.20
|
3.95
|
0.00
|
|
20:2
|
0.00
|
0.23
|
0.00
|
|
22:1
|
0.00
|
2.23
|
0.00
|
|
24:0
|
0.00
|
0.00
|
0.00
|
|
24:1
|
0.00
|
1.30
|
0.00
|
|
Non-identified fatty acids
|
2.39
|
11.7
|
38.3
|
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1 Arbitrary units.
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