Efficacy of Flaxseed Oil in Treating Mild to Moderate Psoriasis Vulgaris Compared with Topical Betamethasone: A Randomized, Double-Blind, Clinical Trial

Abstract

Background:

Psoriasis vulgaris poses health challenges to humans. Despite notable progress in the understanding of disease pathogenesis and the availability of various treatment options, a definitive cure remains elusive. Given the various side effects and high treatment costs, many patients seek natural remedies. This study aimed to assess the effectiveness of novel topical flaxseed oil in individuals with mild to moderate plaque psoriasis.

Materials and Methods:

The outcomes of topical flaxseed oil were compared with those of betamethasone ointment in a two-arm parallel, randomized, controlled clinical trial involving 60 patients. The participants applied the medication as a thin layer to the skin lesions, massaging it twice a day for 4 weeks. Before and after the intervention, they were assessed using two standard questionnaires: the Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index.

Results:

Statistical analysis showed that, after 4 weeks, flaxseed oil significantly decreased the PASI score (2.43 ± 1.83 vs. 5.85 ± 5.08, P: 0.001) and enhanced the quality of life of patients (3.47 ± 3.16 vs. 8.48 ± 5.53, P = 0.001) in comparison to betamethasone ointment. Notably, no side effects were observed in the flaxseed oil group.

Conclusion:

The outcomes suggest that topical flaxseed oil can be an effective complementary therapy for psoriasis vulgaris.

INTRODUCTION

Psoriasis is a common, distressing, chronic, and inflammatory skin disease, with a prevalence rate ranging from 0.5% to 11.4% in adults worldwide and an equal sex distribution.[1,2] The incidence of new cases varies from place to place, and the majority of cases occur in individuals with a family background. Disease dispersion is also variable; nonetheless, it seems that the further away from the equator, the higher the incidence rate.[3]

Chronic-relapsing plaque psoriasis is the most common subtype of the disease, manifesting as thick, red plaques with overlying coarse scales. However, other parts of the body, such as joints and nails, can be affected.[4,5] Although the disease is not life-threatening, it has a significant impact on the quality of life and psychosocial burden.[6] Dysregulation of immune cell function and disturbance of keratinocyte proliferation and differentiation in skin layers are responsible for plaque development.[5,7]

Despite the absence of an absolute cure for psoriasis, depending on the severity of the disease, several topical and systemic therapies are used to treat the skin manifestations of the disease.[5,8] Emollients, corticosteroids, vitamin D analogs, topical retinoids, calcineurin inhibitors, and tar are the most frequently used topical anti-psoriasis drugs.[7] Moderate-to-severe psoriasis requires phototherapy or systemic therapies, such as immunomodulatory medications and biologics, with long-term adverse effects.[6]

Unfortunately, most of these medications can cause complications and side effects, such as cutaneous atrophy, telangiectasia, photosensitivity, increased risk of opportunistic infections, and a variety of cancers.[7] Therefore, it is necessary to develop less complicated treatments with higher efficacies. In recent years, despite the variety of conventional treatment options, there has been an increasing trend in the use of complementary and alternative medicines in patients with psoriasis.[7,9]

Persian medicine (PM), from a holistic perspective, is an ancient traditional system of medicine with a history that dates back thousands of years.[6,10] PM scholars have described a skin disease called “Ghooba” with dry and crusty plaques closely compatible with psoriasis.[4,5] They recommended topical herbal and natural remedies such as flaxseed (Linum usitatissimum L.) oil for the management of such skin conditions.[11,12]

Flaxseeds are rich in natural antioxidants such as phenolics, flavonoids, omega-3 fatty acids, proteins, carbohydrates, vitamins, minerals, and lignans. Flaxseed oil exhibits anti-inflammatory and anti-proliferative properties.[13,14] Consequently, a randomized controlled clinical trial was designed to assess the efficacy of topical flaxseed oil in psoriatic plaques.

MATERIALS AND METHODS

Study design

The study was a 4-week, two-arm, parallel, randomized controlled clinical trial. Patient recruitment took place in the dermatology clinics of Rasool Akram Hospital, affiliated with Iran University of Medical Sciences, from April 2020 to March 2021.

Ethical issues

This clinical trial complied with the principles of the Declaration of Helsinki. After obtaining permission from the ethics committee of the Iran University of Medical Sciences (Code: IR.IUMS.REC.1398.466), the study protocol was registered in the Iranian Registry of Clinical Trials (identifier: IRCT20191211045692N1), and subsequent patient recruitment commenced. All procedures were free of charge for the patients, who retained the right to withdraw from the study at any point. Written consent was obtained from all eligible patients before entry into the trial.

Drug preparation

Standard flaxseed oil prepared with the cold press method was purchased from Noshad Co. (Tehran, Iran). It obtained a license from the Iranian Food and Drug Organization (FDO) with registration code “104/7533/1335328.” In the next step, flaxseed oil was mixed with beeswax (90:10) to achieve a similar texture, color, and scent to betamethasone ointment. Topical betamethasone 0.1% ointment was purchased from Aburaihan Pharmaceutical Co. (Tehran, Iran).

Inclusion and exclusion criteria

Patients were enrolled in the study according to the eligibility criteria recorded in Table 1.

Table 1.

Inclusion and exclusion criteria

Inclusion criteria		Exclusion criteria
1. Age between 18 and 60 years 2. Mild to moderate plaque psoriasis confirmed by a dermatologist (PASI score <30) 3. Less than <10% of body surface area involvement 4. Willingness to participate in the study		1. Pregnancy or lactation 2. Treatment with topical treatment within the previous 2 weeks 3. Systemic treatment or phototherapy 4 months before the study. 4. Use of medications affecting psoriasis, such as beta-blockers, lithium, antimalarial, systemic corticosteroids, calcium channel blockers, interleukin, and psoralen. 5. Dermal infection or malignancy in the treatment region 6. Uncontrolled underlying diseases such as metabolic, kidney, and allergic diseases 7. Failure to continue treatment

Randomization and blinding

Eligible patients were randomly assigned to the intervention or control group at a 1:1 ratio using a randomized list adopted from Microsoft Excel. Physicians, outcome assessors, statisticians, and patients were blinded to the allocation and type of medications. To improve the blinding of participants, the color, appearance, consistency, weight, and packaging of the two ointments were similar.

Sample size

Based on previous studies and the following formula, the sample size was estimated at 30 individuals in each group, considering a significance level of 5%, a power of 80%, and a probable 10% loss to follow-up.

Statistical analysis

SPSS 24 software was used for data analysis. Data were analyzed using the Chi-square test and one-way analysis of covariance (ANCOVA). P values < 0.05 were considered significant.

Intervention

At the beginning of the study, all eligible participants completed the informed consent form. For 4 weeks, they received flaxseed oil or betamethasone twice daily. They were instructed to apply and massage the medication onto the affected area until fully absorbed.

Outcome assessment

For all patients, the Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were assessed at week 4 and compared to the baseline. The PASI is a tool used by dermatologists to measure the severity (induration, scaling, and erythema) and extent of psoriasis. The score ranges from 0 to 72, and the disease is considered to have the highest severity at a score of 72.[15,16]

The quality of life of participants was evaluated using a validated Persian version of the DLQI questionnaire.[17] The total score on the questionnaire ranged from 0 to 30. Higher scores indicate that skin problems have a greater impact on patients’ quality of life.[18] Furthermore, patients were asked to report any side effects throughout the study.

RESULTS

Out of the 95 individuals meeting the eligibility criteria, 60 (34 women and 26 men) met the inclusion criteria and were enrolled in this study. Thirty patients completed the treatment course in each group. The flow of participants throughout the study is presented in a consort diagram [Figure 1].

Figure 1.

Consort diagram of the study

Baseline characteristics

Before the interventions, the two groups were similar in age and gender. 56% of participants were female. The average age of the patients was 34.8 ± 13.3 years (range, 18–60 years). As shown in Table 2, the mean baseline PASI scores in the betamethasone and flaxseed oil groups were 6.840 and 5.260, respectively. There was no significant difference in the PASI scores between the two groups (P > 0.05).

Table 2.

Baseline PASI score in study groups

		Group		Mean		Std. deviation
PASI baseline score		Betamethasone (n=30)		6.840		5.1793
		Flaxseed oil (n=30)		5.260		4.0793
P*		0.194

PASI=The Psoriasis Area Severity Index. *Tested by Chi-square

Pairwise comparison (Baseline and fourth week)

Flaxseed oil group:

The head erythema score 4 weeks after the intervention decreased significantly compared to the baseline (1.27 ± 1.34 to 0.63 ± 0.76, P = 0.001). This significant decreasing trend was also observed in induration (1.10 ± 1.16 to 0.57 ± 0.63, P = 0.001), scaling (1.57 ± 1.68 to 0.70 ± 0.84, P = 0.001), as well as the head area score (0.90 ± 1.30 to 0.63 ± 0.76, P = 0.04). The decrease of erythema, induration, and scaling scores in the arms, trunk, and legs was also significant. However, the change in the areas’ score in the mentioned body sections was not statistically significant. More details are shown in Table 3.

Table 3.

Pairwise comparison of psoriasis severity indices in flaxseed oil and betamethasone groups

		Item		Baseline score Mean±SD		Fourth-week score Mean±SD		P*
Flaxseed oil
Head		Erythema		1.27±1.34		0.63±0.76		0.001
		Induration		1.10±1.16		0.57±0.63		0.001
		Scaling		1.57±1.68		0.70±0.84		0.001
		Areas		0.90±1.30		0.63±0.76		0.04
Arms		Erythema		2.03±1.50		1.10±0.92		0.001
		Induration		1.73±1.28		0.90±0.71		0.001
		Scaling		1.93±1.44		0.93±0.78		0.001
		Areas		0.80±0.61		0.73±0.52		0.16
Trunk		Erythema		1.43±1.70		0.87±1.07		0.001
		Induration		1.17±1.37		0.63±0.81		0.001
		Scaling		1.30±1.53		0.57±0.73		0.001
		Areas		0.57±0.68		0.53±0.63		0.32
Legs		Erythema		1.20±1.61		0.73±1.08		0.001
		Induration		1.00±1.39		0.47±0.68		0.001
		Scaling		1.03±1.40		0.40±0.62		0.001
		Areas		0.53±0.73		0.50±0.68		0.32
Betamethasone
Head		Erythema		2.10±1.42		1.67±1.35		0.001
		Induration		1.97±1.40		1.63±1.22		0.001
		Scaling		2.10±1.37		1.43±1.14		0.001
		Areas		0.90±0.61		0.90±0.61		–
Arms		Erythema		2.07±1.44		1.60±1.22		0.001
		Induration		1.90±1.42		1.63±1.30		0.002
		Scaling		1.73±1.36		1.30±1.18		0.001
		Areas		0.86±0.57		0.86±0.57		–
Trunk		Erythema		2.14±1.56		1.75±1.35		0.001
		Induration		1.93±1.51		1.66±1.29		0.009
		Scaling		1.83±1.49		1.50±1.22		0.03
		Areas		0.80±0.61		0.80±0.61		–
Legs		Erythema		1.87±1.50		1.57±1.22		0.02
		Induration		2.00±1.49		1.62±1.35		0.005
		Scaling		1.86±1.46		1.45±1.21		0.001
		Areas		0.86±0.58		0.86±0.58		–

*Tested by Chi-square

In comparing the changes of overall and combined indices of severity of psoriasis, by the end of 4 weeks, the mean of the PASI, DLQI, scaling, erythema, and induration scores declined significantly in this group. The PASI score decreased from 5.26 ± 4.08 to 2.43 ± 1.83 with P = 0.001. Regarding the DLQI score, the score decreased from 8.00 ± 6.35 to 3.47 ± 3.16 (P = 0.001). The changes in overall scaling, erythema, and induration are shown in Table 4.

Table 4.

Pairwise comparison of psoriasis overall and combined indices of severity of psoriasis in flaxseed oil and betamethasone groups

		Item n2		Baseline Mean±SD		Fourth-week Mean±SD		P*
Flaxseed oil		Erythema		5.93±3.13		3.33±2.19		0.001
		Induration		5.00±3.07		2.57±1.65		0.001
		Scaling		5.83±3.13		2.60±1.81		0.001
		PASI		5.26±4.08		2.43±1.83		0.001
		DLQI		8.00±6.35		3.47±3.16		0.001
Betamethasone		Erythema		8.43±4.45		6.75±4.06		0.001
		Induration		7.64±4.60		6.43±4.16		0.001
		Scaling		7.41±4.30		5.59±3.66		0.001
		PASI		7.35±6.21		5.85±5.08		0.001
		DLQI		10.07±6.50		8.48±5.53		0.003

PASI=The Psoriasis Area Severity Index, DLQI=Dermatology Life Quality Index. *Tested by Chi-square

Betamethasone group:

The erythema score on the head 4 weeks after the intervention significantly decreased compared to the baseline (2.10 ± 1.42 to 1.67 ± 1.35, P = 0.001). A notable decreasing trend was also observed in induration (1.97 ± 1.40 to 1.63 ± 1.22, P = 0.001) and scaling (2.10 ± 1.37 to 1.43 ± 1.14, P = 0.001). However, the area score remained unchanged. Significant reductions in erythema, induration, and scaling scores were observed in the arms, trunk, and legs. Nonetheless, the area scores in these regions showed no change. Additional details are provided in Table 3.

In this group, the PASI and DLQI scores decreased from 9 to 4 and 9 to 3, respectively, after 4 weeks, and these changes were statistically significant (P < 0.05). More details about the other indices are shown in Table 4.

Comparison of two groups in the fourth week

In comparing psoriasis severity indices between two groups after 4 weeks, adjusted for baseline values using ANCOVA, the mean ± standard deviation of the PASI score in the betamethasone group was significantly higher than in the flaxseed oil group (5.85 ± 5.08 vs. 2.43 ± 1.83, P = 0.001). The DLQI score in the betamethasone and flaxseed oil groups was 8.48 ± 5.53 and 3.47 ± 3.16, respectively (P = 0.001). Also, the erythema, induration, and scaling scores in the betamethasone group were significantly higher than those in the flaxseed oil group [Table 5].

Table 5.

Comparing score of scaling, induration, erythema, and PSI in the fourth week in flaxseed oil and betamethasone group

Item		Mean±SD		P †		F		Partial Eta squared
Erythema
Flaxseed oil 1		3.33±2.19		0.001		14.19		0.21
Betamethasone		6.75±4.06
Induration
Flaxseed oil 1		2.57±1.65		0.001		34.06		0.39
Betamethasone		6.43±4.16
Scaling
Flaxseed oil 1		2.60±1.81		0.001		20.57		0.27
Betamethasone		5.59±3.66
PASI
Flaxseed oil 1		2.43±1.83		0.001		23.91		0.30
Betamethasone		5.85±5.08
DLQI
Flaxseed oil 1		3.47±3.16		0.001		38.04		0.41
Betamethasone		8.48±5.53

PASI=The Psoriasis Area Severity Index, DLQI=Dermatology Life Quality Index. ^†Tested by ANCOVA

During the intervention, a participant in the betamethasone group reported itching, while no side effects or allergies were observed in the flaxseed group.

DISCUSSION

This study aimed to evaluate the effects of flaxseed oil on psoriatic plaques. The patients were assigned to 30-member groups and treated with betamethasone or flaxseed oil. PASI score and DLQI questionnaires were used to assess each patient. Statistical analysis revealed that after 4 weeks, flaxseed oil, compared to betamethasone, significantly reduced the PASI score and improved the quality of life (P = 0.001).

Psoriasis is a common disorder involving inflammation and immune responses and is characterized by increased levels of inflammatory mediators and epidermal hyperplasia in skin lesions. The pathogenesis involves the production of pro-inflammatory cytokines, such as interleukins (ILs) and tumor necrosis factor-alpha (TNF-α), leading to the activation of keratinocyte proliferation and T-cell involvement.[6,19]

Flaxseed, recognized as a superfood, has numerous bioactive components such as high levels of omega-3 fatty acids, lignans, and dietary fiber, and offers many health-promoting effects.[14,20] The unique chemical composition of flaxseed oil contributes to its potential advantages, including its anti-inflammatory, antioxidant, anti-microbial, anti-cancer, anti-ulcer, anti-osteoporotic, metabolic, cardioprotective, and neuroprotective effects.[21]

Flaxseed oil has also been found to have potential benefits for enhancing skin health. The presence of α-linolenic acid (ALA, an omega-3 polyunsaturated fatty acid), oleic acid (an omega-9 monounsaturated fatty acid), linoleic acid (LA, an omega-6 fatty acid), and B vitamins in flaxseed can help alleviate skin flakiness and dryness. Moreover, ALA helps to strengthen the skin barrier and retain moisture, leading to improved skin hydration and elasticity.[14,22,23]

Recent research has indicated a link between skin barrier disruption and psoriasis. Any problem with the outermost layer, the stratum corneum (SC) barrier, can trigger the overgrowth of skin cells and the release of cytokines. The SC, composed of corneocytes within a lipid matrix, relies on crucial lipids to maintain barrier function. LA, the predominant fatty acid in the SC, is the main component of ceramides, highlighting its vital role in maintaining skin barrier integrity.[7,24,25]

In 2016, Yang et al.[26] studied the impact of fermented flaxseed oil (FFSO) on NC/Nga mice with atopic dermatitis (AD)-like skin lesions, closely resembling psoriasis symptoms such as epithelial damage, redness, swelling, and pruritus. The findings showed that FFSO could alleviate the symptoms of AD by restoring the protective function of the skin barrier and suppressing inflammation.

Furthermore, flaxseed oil is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and has anti-inflammatory activity. In an in vivo study on mice with psoriasis-like inflammation, the nanoemulsion gel containing flaxseed oil demonstrated significantly higher anti-psoriatic activity than a marketed ointment.[27]

Following the data provided, flaxseed oil can alleviate the symptoms of skin inflammation and improve various dry skin conditions, including psoriasis, AD, and acne.[14,22,23,26,27,28] In addition to anti-inflammatory compounds, flaxseed is rich in antioxidants, particularly lignans, which can reduce the presence of free radicals. Consequently, the antioxidant properties of flaxseed oil can protect the skin from oxidative stress and damage by free radicals.[28,29]

Recently, in a randomized clinical trial involving 112 patients with a total burn surface area of 20%–50%, the wound healing properties of topical flaxseed oil and olive oil were evaluated over 3 weeks.

The study revealed that the combination of flaxseed oil and olive oil (OF) effectively decreased inflammation, reduced the levels of cytokines (TNF-α and IL-6) in the skin, and improved wound healing in the participants.[30] These findings support our study’s conclusions on the significant impact of flaxseed oil on the skin repair process after various skin problems associated with inflammation, such as burns and psoriasis.

In a 2018 study of 37 patients with psoriasis plaque, the efficacy and safety of chamomile pumpkin oleogel (ChP) were examined. The study reported a significant improvement in the Psoriasis Area and Severity Index (PASI) score (P = 0.019), attributed to the anti-inflammatory and antioxidant properties of the herbal ingredients. Chamomile, comparable to flaxseed, inhibits the production of inflammatory mediators, such as IL-6 and TNF-α. Additionally, pumpkin seed oil, which is rich in linoleic acid (LA), is necessary for skin integrity.[7]

Another study evaluated the effectiveness of a cream containing frankincense oil, pumpkin oil, and licorice aqueous extract in 108 patients with plaque psoriasis. Compared to the vehicle group, the Boswellia-based cream group showed a significant reduction in the mean PASI score from baseline to week 2 and from week 2 to week 4 (both P < 0.001). Following 2 weeks of therapy, there was a decrease in the DLQI in both groups, but the intervention group showed a greater decrease in comparison to the control group (P = 0.004).[6]

This evidence suggests that flaxseed oil can be as effective as several herbal formulations and may outperform them in some instances. Also, it can help reduce the PASI and improve the quality of life. Therefore, flaxseed oil may be a good choice for patients with psoriasis.

This randomized study presents several strengths, such as using a topical treatment that is safe, affordable, and easy to access compared to standard therapies for psoriasis. However, it had several limitations. The absence of post-intervention follow-up prevented assessment of long-term efficacy. The study sample was limited to individuals with mild to moderate psoriasis, which reduced generalizability. Financial limitations precluded biochemical assessments, and the active components of the flaxseed oil, such as α-linolenic and LAs, were not measured. Additionally, the small sample size limits statistical power, and larger studies are recommended.

CONCLUSION

This study is the first to evaluate the efficacy of topical flaxseed oil in treating psoriasis vulgaris. These findings indicate that flaxseed oil could be a safe and effective option for the amelioration of psoriasis vulgaris. This product is an herbal source of unsaturated fatty acid molecules, and its therapeutic response could be ascribed to these ingredients. Further research is needed to fully understand the specific benefits and mechanisms of flaxseed oil on skin health.

Authors’ contributions

Farshad Mohammadian Rasanan: Concepts, Literature search, Design, Clinical studies, Data acquisition, Manuscript preparation.

Ali Ghobadi: Concepts, Design, Formulation, and Production of the drug, Manuscript editing, and Review.

Hoorieh Mohammadi Kenari: Concepts, Design, Data acquisition, Manuscript editing, and Review.

Mohammadreza Ghassemi: Concepts, Design, Manuscript editing, and Review.

Maryam Taghavi Shrazi: Concepts, Data acquisition, Manuscript preparation, Editing, and Review.

Roshanak Ghods: Manuscript preparation and Editing.

Ethics approval and consent to participate

This clinical trial adhered to the Declaration of Helsinki. After obtaining ethics committee approval from the Iran University of Medical Sciences (Code: IR.IUMS.REC.1398.466), the study protocol was registered in the Iranian Registry of Clinical Trials (identifier: IRCT20191211045692N1), and patient recruitment began. All procedures were provided at no cost, and participants could withdraw at any time. Written consent was obtained from all eligible patients before they entered into the trial.

Consent for publication

All authors have consented to the publication of the manuscripts.

Availability of data and materials

The identified datasets analyzed during this study are available from the corresponding author upon reasonable request.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.