In this second half of our coverage of complementary and alternative psoriasis treatments, we examine the use of oral supplements for psoriasis.
I will never forget a patient I saw in our psoriasis clinic about a year ago. He was a concert pianist whose psoriasis was so bad on his palms that he couldn’t play the piano on more days than not. He was a long-term patient and had been on everything from narrow-band UVB treatments to methotrexate to various biologics. When I saw him, he had been on an injectable biologic for the past several months and had seen minimal improvement in his skin disease but vast improvement in his joint pains. He told me that his palms cleared dramatically within a month of starting daily fish oil capsules (prescribed by his primary physician to help improve his lipid panel). It’s hard to ignore that kind of a success story. Although many people have substantial relief and therapeutic success with conventional psoriasis treatments, there are patients out there who are frustrated because they have not responded to conventional treatments or they have experienced negative side effects from the treatments. Or maybe these patients just want to add something extra to their current plan. Your patients may ask you about other options, especially since some of the systemic therapies offered traditionally can have powerful side effects and can be potentially toxic. OMEGA-3 FATTY ACIDS What are they? Omega-3 fatty acids are in the category of “essential fatty acids” (EFAs), along with omega-6 fatty acids. EFAs are termed as such because they cannot be synthesized by the human body and thus must be derived from exogenous sources, namely, food. The nomenclature refers to the location of the double bond within the carbon backbone of the molecule. They are also characterized as polyunsaturated fatty acids (PUFA), which refers to the presence of two or more double bonds in their molecular structure.1 Linoleic acid (LA) and a-linolenic acid (ALA) are essential PUFA of the omega-6 and omega-3 families, respectively. LA must first be converted to gamma-linolenic acid (GLA) and then to arachidonic acid (AA), the biologically active compound. The downstream products of ALA are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two long-chain omega-3 PUFAs.2 Where are they found? Omega-3 fatty acids are composed of EPA and DHA. Because humans cannot make these, we must get them from our food. Omega-3 fatty acids can be found in cold-water oily fish, such as salmon, black cod, herring, mackerel, tuna and halibut, other marine life such as algae and krill, certain plants (purslane), and nuts/seeds (walnuts, pumpkin seeds, chia seeds, hemp seeds, flaxseeds).2,3,4 What do they do? Omega-3 fatty acids play a crucial role in brain function as well as normal brain growth and development in utero and in childhood. In addition to this well-known role, there are numerous conditions that benefit from omega-3 fatty acid supplementation. It is clearly established that omega-3 fatty acid supplementation prevents heart disease, coronary artery restenosis after angioplasty, and in particular, sudden cardiac death. Omega-3 fatty acids also lower triglyceride levels, increase HDL (“good”) cholesterol, and decrease vascular inflammation and blood clotting.5 Rheumatoid arthritis is another condition that benefits from supplementation, with improvement in symptoms and diminished use of nonsteroidal anti-inflammatory drugs (NSAIDs). Psychiatric disorders, particularly schizophrenia, major depressive disorder, and attention deficit-hyperactivity disorder have shown positive results when supplementation has been used as an adjunct to standard pharmacotherapy. What is the mechanism and theory? The medical literature involving omega-3s in general is voluminous and includes a multitude of randomized controlled trials, meta-analyses, population studies and case reports. Although most of the available literature involves the cardiovascular and neurological systems, there are several investigations of the use of omega-3s in the field of dermatology, particularly in psoriasis and atopic dermatitis. The rationale of using omega-3s is supported by findings suggesting that they have strong anti-inflammatory properties. This is based on the fact that EFAs play an important role in cell membrane composition (phospholipid structure) which, in turn, influences fluidity and cell surface biochemical signaling, and may serve as natural ligands for certain nuclear receptors that affect gene expression.1,2 Additionally, disordered AA metabolism is found in psoriasis, characterized by significantly increased levels of AA and leukotriene B4 (LTB4) in psoriatic plaques.6,7,8 The observation that Eskimos have a lower incidence of psoriasis as compared with the Danes9 led to speculation that dietary supplementation with fish oil, rich in EPA, may induce clinical improvement in skin symptoms and several studies have confirmed this suspicion.10,11 Interestingly, Eskimos living a traditional lifestyle also have a lower incidence of RA and, in a similar way to psoriasis, dietary supplementation with fish oil and essential fatty acids has been shown to improve symptoms and some clinical parameters in RA.12,13 Psoriasis is a dermatologic disease processes that is mediated by an overly robust immune system resulting in keratinocyte hyperproliferation and leukocyte infiltration, both postulated to result from an overabundance of AA metabolites in the epidermis. The therapeutic theory is that omega-3 fatty acid supplementation will decrease the omega-6 to omega-3 ratio, thereby diminishing the substrate availability of “pro-inflammatory” omega-6s (AA) and increasing the amount of “anti-inflammatory” omega-3s (DHA and EPA).14,15 Some studies say omega-3s do not help. The earliest studies done with omega-3 supplementation showed some degree of improvement in psoriatic lesions, but these studies were not controlled. Four of these uncontrolled studies with EPA/DHA or fish oil supplementation with daily dosages between 2 g and 12 g of omega-3 fatty acids reported beneficial effects of the intervention on psoriasis severity.3,8,16,17,18 Another study, also uncontrolled, showed a positive effect of a combination of omega-6 and omega-3 fatty acids in 17 patients with psoriasis after 4 months.19 Another uncontrolled trial had patients with psoriasis eating 170 g of non-oily white fish daily for 4 weeks before being randomized either to continue with the white fish diet or to replace it with 170 g of oily fish (mackerel, sardine, salmon, pilchard, kipper or herring) daily for 6 weeks in a crossover design. Modest significant clinical improvement was observed after the oily fish diet only, whereas the white fish diet had no effect.20 Another uncontrolled study tested the effects of fish oil supplementation in 26 patients with plaque-type and pustular psoriasis. This study showed marked improvement in one patient with pustular psoriasis but no clinically significant improvement in plaque-type psoriasis.21 Results from randomized controlled trials are less positive and conflicting. Among four studies, improvement in psoriatic lesions with omega-3 supplementation was reported in just one study,11 whereas no beneficial effects compared with placebo were observed in the other three studies.22,23,24 The study that showed improvement (Bittiner et al) was a randomized placebo-controlled trial involving patients with psoriasis receiving 3 g of oral omega-3 fatty acid (predominantly EPA) from fish oil daily. Within this treatment group, a significant lessening of itching, erythema and scaling was observed after 8 weeks, with a trend toward an overall decrease in affected body surface area, whereas no change occurred in the olive oil (placebo) group.11 Conversely, two randomized double-blind controlled studies, both using fish oil supplementation of either 1.8 g EPA for 8 weeks22 or 10 capsules of fish oil three times a day for 3 weeks,21 showed no benefit compared with olive oil supplementation. No benefit of fish oil supplementation compared with corn oil (which contains mostly omega-6s), was seen in a 4-month, double-blind, randomized multi-center trial.24 In this study, 145 patients with moderate-to-severe psoriasis received either 5 g of EPA/DHA or an isoenergetic amount of corn oil in their diet. Although the ratio of AA and EPA in serum phospholipids decreased significantly in the fish oil group, the Psoriasis Area and Severity Index (PASI) score did not change significantly in either group. Scaling was reduced compared to baseline in both groups, but only a selected area of skin in the corn oil group showed a significant reduction in clinical signs. There was no significant difference in clinical manifestations between the groups. Clinical improvement was not correlated with an increase of n-3 fatty acid concentration in serum phospholipids among the patients in the fish oil group, whereas there was a significant correlation between clinical improvement and an increase in EPA and total n-3 fatty acids in the corn oil group.24 The positive effect of corn oil rich in linoleic acid may be because LTB4 production is suppressed at high intakes of linoleic acid.25 And in another double-blind trial, no effect on chronic stable plaque psoriasis was observed after supplementation with a combination of an omega-3 fatty acid-rich marine oil with omega-6 fatty acid-rich evening primrose oil in 37 patients with psoriasis.26 And some studies say they do help. In contrast to the mostly negative results from oral supplementation studies with omega-3 fatty acids, promising results have been seen with parenteral (intravenous) administration of omega-3s.27 In a 10-day trial, 20 patients hospitalized for acute guttate psoriasis with a minimum of 10% of body surface area involvement were randomly assigned to receive daily infusions with an omega-3 fatty acid-based lipid emulsion (2.1 g EPA and 21 g DHA daily) or a conventional omega-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml daily). The severity of disease, which was evaluated by daily scoring of erythema, infiltration, desquamation and by a subjective scoring of clinical manifestations, decreased markedly in all patients of the omega-3 group, with significant improvements in all score systems ranging between 45% and 76% within 10 days. Only moderate improvement was observed in the omega-6 group (16% to 25% score changes from baseline).28 The benefit of infusions with omega-3 fatty acids (4.2 g of both EPA and DHA) has been confirmed in a double-blind, randomized, multicenter study with 83 patients hospitalized for chronic plaque-type psoriasis. After 14 days of intervention, the total PASI score decreased significantly in both groups, the omega-3 group and the omega-6 fatty acid control group, by 42% and 31%, respectively. A decrease in total PASI of at least 50% between the admission and the last value was stated in 37% of the patients receiving the omega-3 emulsion and in 23% of those receiving omega-6 fatty acid-based conventional emulsion.29 The rapid effect of omega-3 fatty acid supplementation in these studies indicates that intravenous supplementation may be more beneficial for inflammatory skin lesions than oral supplementation. On the other hand, a Cochrane review of acute guttate psoriasis, concluded that there is currently no firm evidence for intravenous n-3 fatty acids as a base treatment for acute guttate psoriasis.30 More recently, Mayser et al looked at parenteral administration of an omega-3 fatty acid lipid emulsion.31 This same group had previously used dietary supplementation. They performed several trials (presented in one article), two of which were randomized, controlled designs that showed as high as 76% responders in the omega-3 cohort compared to 25% in the omega-6 group within 10 days to 14 days. The measured clinical parameters were erythema, lymphocyte infiltration, desquamation and subjective scores. In addition, they showed that parenteral administration of omega-3 fatty acids resulted in a rapid increase of EPA metabolites within just 3 days. What to tell your patients: The evidence so far suggests omega-3s do indeed have a potential role in the treatment of psoriasis, in particular for parenteral treatments, either as an active anti-inflammatory agent by itself, or as an adjunct with conventional psoriasis treatments. Although the results of oral fish oil supplementation are inconsistent, omega-3s have such well-established multi-system benefits that I think all patients should be on them daily (or get from their diet if possible). And if your patient with psoriasis happens to experience an improvement in his or her psoriasis, wonderful! A remarkable aspect of omega-3s is that there have been virtually no deleterious side effects reported. However, patients with bleeding disorders and/or on blood thinners should use caution and work with their primary doctors if they want to take these. Patients may complain of unpleasant side effects such as diarrhea, flatulence and “fishy burps,” but these are certainly not critical. I tell my patients to put the capsules in the freezer as this seems to eliminate any fishy taste or fishy burps later on. From a cost-benefit perspective, oral preparations of omega-3 are widely available without a prescription and at reasonable prices. Just make sure to tell your patients to buy preparations that are derived from molecularly distilled fish oil that is independently tested to be guaranteed free of heavy metals (mercury and lead) and other contaminants including polychlorinated biphenyls (PCBs). Your vegan patients can get algae-derived supplements. GAMMA-LINOLENIC ACID What is it? 32 Gamma-linolenic acid (GLA) is an essential fatty acid (EFA) in the omega-6 family that is found primarily in plant-based oils. Where is it found?32 GLA is found primarily in evening primrose oil, borage seed oil or black currant seed oil. Evening primrose is a plant native to North America, but it grows in Europe and parts of the Southern Hemisphere as well. The plant is so named because of its yellow flowers that bloom in the evening. Evening primrose oil is extracted from the seeds of the evening primrose. The oil is usually put into capsules for use. Evening primrose oil is the most researched source of GLA. Does it help with psoriasis? There is not much to speak of in the literature involving psoriasis and GLA. Interest in treating patients with psoriasis with GLA-rich supplementation developed following studies where this skin condition was found to benefit from treatment with fish oils.10,11 A double-blind, placebo-controlled study of 38 patients,33 showed no obvious benefit of GLA supplementation in psoriasis patients. More convincing evidence exists in support of EFA use in rheumatoid arthritis; the study by Zurier et al34 in which a high dose of GLA was evaluated is particularly interesting. What to tell your patients: There is not enough evidence to support the use of GLA supplements (in the forms of evening primrose or borage oils) for psoriasis. Safety has not been confirmed in pregnancy, so advise against use in your female patients who are pregnant. Most people tolerate both oils well with the most common side effects being gastrointestinal upset and headache,32 so if your patients want to try it, there is likely no harm (but no established benefit). EXTRACT of MILK THISTLE What is it?35 Extract of milk thistle (Silybum marianum) is an herb whose active agent is silymarin, a flavonoid isolated from the seeds of the herb. Where is it found?35 Milk thistle is a flowering herb that is native to the Mediterranean region. Silymarin (extracted from the seeds) is used to prepare capsules, extracts and infusions (strong teas). Does it help with psoriasis? No. While there are numerous studies and reviews available regarding milk thistle and various hepatic ailments such as Hepatitis B and C, there are no reports of any sort regarding psoriasis. It has however, been minimally studied as a possible preventive agent in non-melanoma skin cancer.36-38 What to tell your patients: Despite what your patients may be reading on the Internet, you can tell them that there is absolutely no evidence for this supplement in improving their psoriasis. If your patients want to try it, it appears to be safe and non-toxic.35,39 Caution patients, though, that if they take high doses (>1500 mg per day), they may experience an unpleasant laxative effect and bloating. 35,39 Recommendations Of the supplements reviewed, only omega-3 had substantial evidence to support its use in psoriasis.The holistic approach recognizes that a chronic disease such as psoriasis is multifactorial, involving a confluence of genetic, environmental, social, psychological and physical events. Because of this, if your patient wants to give one of these options a try, advise them to take an omega-3 supplement because of its numerous health benefits and possible benefit for psoriasis. Dr. Taylor, a Fellow in the Department of Dermatology at Wake Forest University Baptist Medical Center in Winston-Salem, NC, is board-certified in Family Medicine, which she practices in Winston-Salem, NC.
In this second half of our coverage of complementary and alternative psoriasis treatments, we examine the use of oral supplements for psoriasis.
I will never forget a patient I saw in our psoriasis clinic about a year ago. He was a concert pianist whose psoriasis was so bad on his palms that he couldn’t play the piano on more days than not. He was a long-term patient and had been on everything from narrow-band UVB treatments to methotrexate to various biologics. When I saw him, he had been on an injectable biologic for the past several months and had seen minimal improvement in his skin disease but vast improvement in his joint pains. He told me that his palms cleared dramatically within a month of starting daily fish oil capsules (prescribed by his primary physician to help improve his lipid panel). It’s hard to ignore that kind of a success story. Although many people have substantial relief and therapeutic success with conventional psoriasis treatments, there are patients out there who are frustrated because they have not responded to conventional treatments or they have experienced negative side effects from the treatments. Or maybe these patients just want to add something extra to their current plan. Your patients may ask you about other options, especially since some of the systemic therapies offered traditionally can have powerful side effects and can be potentially toxic. OMEGA-3 FATTY ACIDS What are they? Omega-3 fatty acids are in the category of “essential fatty acids” (EFAs), along with omega-6 fatty acids. EFAs are termed as such because they cannot be synthesized by the human body and thus must be derived from exogenous sources, namely, food. The nomenclature refers to the location of the double bond within the carbon backbone of the molecule. They are also characterized as polyunsaturated fatty acids (PUFA), which refers to the presence of two or more double bonds in their molecular structure.1 Linoleic acid (LA) and a-linolenic acid (ALA) are essential PUFA of the omega-6 and omega-3 families, respectively. LA must first be converted to gamma-linolenic acid (GLA) and then to arachidonic acid (AA), the biologically active compound. The downstream products of ALA are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two long-chain omega-3 PUFAs.2 Where are they found? Omega-3 fatty acids are composed of EPA and DHA. Because humans cannot make these, we must get them from our food. Omega-3 fatty acids can be found in cold-water oily fish, such as salmon, black cod, herring, mackerel, tuna and halibut, other marine life such as algae and krill, certain plants (purslane), and nuts/seeds (walnuts, pumpkin seeds, chia seeds, hemp seeds, flaxseeds).2,3,4 What do they do? Omega-3 fatty acids play a crucial role in brain function as well as normal brain growth and development in utero and in childhood. In addition to this well-known role, there are numerous conditions that benefit from omega-3 fatty acid supplementation. It is clearly established that omega-3 fatty acid supplementation prevents heart disease, coronary artery restenosis after angioplasty, and in particular, sudden cardiac death. Omega-3 fatty acids also lower triglyceride levels, increase HDL (“good”) cholesterol, and decrease vascular inflammation and blood clotting.5 Rheumatoid arthritis is another condition that benefits from supplementation, with improvement in symptoms and diminished use of nonsteroidal anti-inflammatory drugs (NSAIDs). Psychiatric disorders, particularly schizophrenia, major depressive disorder, and attention deficit-hyperactivity disorder have shown positive results when supplementation has been used as an adjunct to standard pharmacotherapy. What is the mechanism and theory? The medical literature involving omega-3s in general is voluminous and includes a multitude of randomized controlled trials, meta-analyses, population studies and case reports. Although most of the available literature involves the cardiovascular and neurological systems, there are several investigations of the use of omega-3s in the field of dermatology, particularly in psoriasis and atopic dermatitis. The rationale of using omega-3s is supported by findings suggesting that they have strong anti-inflammatory properties. This is based on the fact that EFAs play an important role in cell membrane composition (phospholipid structure) which, in turn, influences fluidity and cell surface biochemical signaling, and may serve as natural ligands for certain nuclear receptors that affect gene expression.1,2 Additionally, disordered AA metabolism is found in psoriasis, characterized by significantly increased levels of AA and leukotriene B4 (LTB4) in psoriatic plaques.6,7,8 The observation that Eskimos have a lower incidence of psoriasis as compared with the Danes9 led to speculation that dietary supplementation with fish oil, rich in EPA, may induce clinical improvement in skin symptoms and several studies have confirmed this suspicion.10,11 Interestingly, Eskimos living a traditional lifestyle also have a lower incidence of RA and, in a similar way to psoriasis, dietary supplementation with fish oil and essential fatty acids has been shown to improve symptoms and some clinical parameters in RA.12,13 Psoriasis is a dermatologic disease processes that is mediated by an overly robust immune system resulting in keratinocyte hyperproliferation and leukocyte infiltration, both postulated to result from an overabundance of AA metabolites in the epidermis. The therapeutic theory is that omega-3 fatty acid supplementation will decrease the omega-6 to omega-3 ratio, thereby diminishing the substrate availability of “pro-inflammatory” omega-6s (AA) and increasing the amount of “anti-inflammatory” omega-3s (DHA and EPA).14,15 Some studies say omega-3s do not help. The earliest studies done with omega-3 supplementation showed some degree of improvement in psoriatic lesions, but these studies were not controlled. Four of these uncontrolled studies with EPA/DHA or fish oil supplementation with daily dosages between 2 g and 12 g of omega-3 fatty acids reported beneficial effects of the intervention on psoriasis severity.3,8,16,17,18 Another study, also uncontrolled, showed a positive effect of a combination of omega-6 and omega-3 fatty acids in 17 patients with psoriasis after 4 months.19 Another uncontrolled trial had patients with psoriasis eating 170 g of non-oily white fish daily for 4 weeks before being randomized either to continue with the white fish diet or to replace it with 170 g of oily fish (mackerel, sardine, salmon, pilchard, kipper or herring) daily for 6 weeks in a crossover design. Modest significant clinical improvement was observed after the oily fish diet only, whereas the white fish diet had no effect.20 Another uncontrolled study tested the effects of fish oil supplementation in 26 patients with plaque-type and pustular psoriasis. This study showed marked improvement in one patient with pustular psoriasis but no clinically significant improvement in plaque-type psoriasis.21 Results from randomized controlled trials are less positive and conflicting. Among four studies, improvement in psoriatic lesions with omega-3 supplementation was reported in just one study,11 whereas no beneficial effects compared with placebo were observed in the other three studies.22,23,24 The study that showed improvement (Bittiner et al) was a randomized placebo-controlled trial involving patients with psoriasis receiving 3 g of oral omega-3 fatty acid (predominantly EPA) from fish oil daily. Within this treatment group, a significant lessening of itching, erythema and scaling was observed after 8 weeks, with a trend toward an overall decrease in affected body surface area, whereas no change occurred in the olive oil (placebo) group.11 Conversely, two randomized double-blind controlled studies, both using fish oil supplementation of either 1.8 g EPA for 8 weeks22 or 10 capsules of fish oil three times a day for 3 weeks,21 showed no benefit compared with olive oil supplementation. No benefit of fish oil supplementation compared with corn oil (which contains mostly omega-6s), was seen in a 4-month, double-blind, randomized multi-center trial.24 In this study, 145 patients with moderate-to-severe psoriasis received either 5 g of EPA/DHA or an isoenergetic amount of corn oil in their diet. Although the ratio of AA and EPA in serum phospholipids decreased significantly in the fish oil group, the Psoriasis Area and Severity Index (PASI) score did not change significantly in either group. Scaling was reduced compared to baseline in both groups, but only a selected area of skin in the corn oil group showed a significant reduction in clinical signs. There was no significant difference in clinical manifestations between the groups. Clinical improvement was not correlated with an increase of n-3 fatty acid concentration in serum phospholipids among the patients in the fish oil group, whereas there was a significant correlation between clinical improvement and an increase in EPA and total n-3 fatty acids in the corn oil group.24 The positive effect of corn oil rich in linoleic acid may be because LTB4 production is suppressed at high intakes of linoleic acid.25 And in another double-blind trial, no effect on chronic stable plaque psoriasis was observed after supplementation with a combination of an omega-3 fatty acid-rich marine oil with omega-6 fatty acid-rich evening primrose oil in 37 patients with psoriasis.26 And some studies say they do help. In contrast to the mostly negative results from oral supplementation studies with omega-3 fatty acids, promising results have been seen with parenteral (intravenous) administration of omega-3s.27 In a 10-day trial, 20 patients hospitalized for acute guttate psoriasis with a minimum of 10% of body surface area involvement were randomly assigned to receive daily infusions with an omega-3 fatty acid-based lipid emulsion (2.1 g EPA and 21 g DHA daily) or a conventional omega-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml daily). The severity of disease, which was evaluated by daily scoring of erythema, infiltration, desquamation and by a subjective scoring of clinical manifestations, decreased markedly in all patients of the omega-3 group, with significant improvements in all score systems ranging between 45% and 76% within 10 days. Only moderate improvement was observed in the omega-6 group (16% to 25% score changes from baseline).28 The benefit of infusions with omega-3 fatty acids (4.2 g of both EPA and DHA) has been confirmed in a double-blind, randomized, multicenter study with 83 patients hospitalized for chronic plaque-type psoriasis. After 14 days of intervention, the total PASI score decreased significantly in both groups, the omega-3 group and the omega-6 fatty acid control group, by 42% and 31%, respectively. A decrease in total PASI of at least 50% between the admission and the last value was stated in 37% of the patients receiving the omega-3 emulsion and in 23% of those receiving omega-6 fatty acid-based conventional emulsion.29 The rapid effect of omega-3 fatty acid supplementation in these studies indicates that intravenous supplementation may be more beneficial for inflammatory skin lesions than oral supplementation. On the other hand, a Cochrane review of acute guttate psoriasis, concluded that there is currently no firm evidence for intravenous n-3 fatty acids as a base treatment for acute guttate psoriasis.30 More recently, Mayser et al looked at parenteral administration of an omega-3 fatty acid lipid emulsion.31 This same group had previously used dietary supplementation. They performed several trials (presented in one article), two of which were randomized, controlled designs that showed as high as 76% responders in the omega-3 cohort compared to 25% in the omega-6 group within 10 days to 14 days. The measured clinical parameters were erythema, lymphocyte infiltration, desquamation and subjective scores. In addition, they showed that parenteral administration of omega-3 fatty acids resulted in a rapid increase of EPA metabolites within just 3 days. What to tell your patients: The evidence so far suggests omega-3s do indeed have a potential role in the treatment of psoriasis, in particular for parenteral treatments, either as an active anti-inflammatory agent by itself, or as an adjunct with conventional psoriasis treatments. Although the results of oral fish oil supplementation are inconsistent, omega-3s have such well-established multi-system benefits that I think all patients should be on them daily (or get from their diet if possible). And if your patient with psoriasis happens to experience an improvement in his or her psoriasis, wonderful! A remarkable aspect of omega-3s is that there have been virtually no deleterious side effects reported. However, patients with bleeding disorders and/or on blood thinners should use caution and work with their primary doctors if they want to take these. Patients may complain of unpleasant side effects such as diarrhea, flatulence and “fishy burps,” but these are certainly not critical. I tell my patients to put the capsules in the freezer as this seems to eliminate any fishy taste or fishy burps later on. From a cost-benefit perspective, oral preparations of omega-3 are widely available without a prescription and at reasonable prices. Just make sure to tell your patients to buy preparations that are derived from molecularly distilled fish oil that is independently tested to be guaranteed free of heavy metals (mercury and lead) and other contaminants including polychlorinated biphenyls (PCBs). Your vegan patients can get algae-derived supplements. GAMMA-LINOLENIC ACID What is it? 32 Gamma-linolenic acid (GLA) is an essential fatty acid (EFA) in the omega-6 family that is found primarily in plant-based oils. Where is it found?32 GLA is found primarily in evening primrose oil, borage seed oil or black currant seed oil. Evening primrose is a plant native to North America, but it grows in Europe and parts of the Southern Hemisphere as well. The plant is so named because of its yellow flowers that bloom in the evening. Evening primrose oil is extracted from the seeds of the evening primrose. The oil is usually put into capsules for use. Evening primrose oil is the most researched source of GLA. Does it help with psoriasis? There is not much to speak of in the literature involving psoriasis and GLA. Interest in treating patients with psoriasis with GLA-rich supplementation developed following studies where this skin condition was found to benefit from treatment with fish oils.10,11 A double-blind, placebo-controlled study of 38 patients,33 showed no obvious benefit of GLA supplementation in psoriasis patients. More convincing evidence exists in support of EFA use in rheumatoid arthritis; the study by Zurier et al34 in which a high dose of GLA was evaluated is particularly interesting. What to tell your patients: There is not enough evidence to support the use of GLA supplements (in the forms of evening primrose or borage oils) for psoriasis. Safety has not been confirmed in pregnancy, so advise against use in your female patients who are pregnant. Most people tolerate both oils well with the most common side effects being gastrointestinal upset and headache,32 so if your patients want to try it, there is likely no harm (but no established benefit). EXTRACT of MILK THISTLE What is it?35 Extract of milk thistle (Silybum marianum) is an herb whose active agent is silymarin, a flavonoid isolated from the seeds of the herb. Where is it found?35 Milk thistle is a flowering herb that is native to the Mediterranean region. Silymarin (extracted from the seeds) is used to prepare capsules, extracts and infusions (strong teas). Does it help with psoriasis? No. While there are numerous studies and reviews available regarding milk thistle and various hepatic ailments such as Hepatitis B and C, there are no reports of any sort regarding psoriasis. It has however, been minimally studied as a possible preventive agent in non-melanoma skin cancer.36-38 What to tell your patients: Despite what your patients may be reading on the Internet, you can tell them that there is absolutely no evidence for this supplement in improving their psoriasis. If your patients want to try it, it appears to be safe and non-toxic.35,39 Caution patients, though, that if they take high doses (>1500 mg per day), they may experience an unpleasant laxative effect and bloating. 35,39 Recommendations Of the supplements reviewed, only omega-3 had substantial evidence to support its use in psoriasis.The holistic approach recognizes that a chronic disease such as psoriasis is multifactorial, involving a confluence of genetic, environmental, social, psychological and physical events. Because of this, if your patient wants to give one of these options a try, advise them to take an omega-3 supplement because of its numerous health benefits and possible benefit for psoriasis. Dr. Taylor, a Fellow in the Department of Dermatology at Wake Forest University Baptist Medical Center in Winston-Salem, NC, is board-certified in Family Medicine, which she practices in Winston-Salem, NC.
In this second half of our coverage of complementary and alternative psoriasis treatments, we examine the use of oral supplements for psoriasis.
I will never forget a patient I saw in our psoriasis clinic about a year ago. He was a concert pianist whose psoriasis was so bad on his palms that he couldn’t play the piano on more days than not. He was a long-term patient and had been on everything from narrow-band UVB treatments to methotrexate to various biologics. When I saw him, he had been on an injectable biologic for the past several months and had seen minimal improvement in his skin disease but vast improvement in his joint pains. He told me that his palms cleared dramatically within a month of starting daily fish oil capsules (prescribed by his primary physician to help improve his lipid panel). It’s hard to ignore that kind of a success story. Although many people have substantial relief and therapeutic success with conventional psoriasis treatments, there are patients out there who are frustrated because they have not responded to conventional treatments or they have experienced negative side effects from the treatments. Or maybe these patients just want to add something extra to their current plan. Your patients may ask you about other options, especially since some of the systemic therapies offered traditionally can have powerful side effects and can be potentially toxic. OMEGA-3 FATTY ACIDS What are they? Omega-3 fatty acids are in the category of “essential fatty acids” (EFAs), along with omega-6 fatty acids. EFAs are termed as such because they cannot be synthesized by the human body and thus must be derived from exogenous sources, namely, food. The nomenclature refers to the location of the double bond within the carbon backbone of the molecule. They are also characterized as polyunsaturated fatty acids (PUFA), which refers to the presence of two or more double bonds in their molecular structure.1 Linoleic acid (LA) and a-linolenic acid (ALA) are essential PUFA of the omega-6 and omega-3 families, respectively. LA must first be converted to gamma-linolenic acid (GLA) and then to arachidonic acid (AA), the biologically active compound. The downstream products of ALA are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two long-chain omega-3 PUFAs.2 Where are they found? Omega-3 fatty acids are composed of EPA and DHA. Because humans cannot make these, we must get them from our food. Omega-3 fatty acids can be found in cold-water oily fish, such as salmon, black cod, herring, mackerel, tuna and halibut, other marine life such as algae and krill, certain plants (purslane), and nuts/seeds (walnuts, pumpkin seeds, chia seeds, hemp seeds, flaxseeds).2,3,4 What do they do? Omega-3 fatty acids play a crucial role in brain function as well as normal brain growth and development in utero and in childhood. In addition to this well-known role, there are numerous conditions that benefit from omega-3 fatty acid supplementation. It is clearly established that omega-3 fatty acid supplementation prevents heart disease, coronary artery restenosis after angioplasty, and in particular, sudden cardiac death. Omega-3 fatty acids also lower triglyceride levels, increase HDL (“good”) cholesterol, and decrease vascular inflammation and blood clotting.5 Rheumatoid arthritis is another condition that benefits from supplementation, with improvement in symptoms and diminished use of nonsteroidal anti-inflammatory drugs (NSAIDs). Psychiatric disorders, particularly schizophrenia, major depressive disorder, and attention deficit-hyperactivity disorder have shown positive results when supplementation has been used as an adjunct to standard pharmacotherapy. What is the mechanism and theory? The medical literature involving omega-3s in general is voluminous and includes a multitude of randomized controlled trials, meta-analyses, population studies and case reports. Although most of the available literature involves the cardiovascular and neurological systems, there are several investigations of the use of omega-3s in the field of dermatology, particularly in psoriasis and atopic dermatitis. The rationale of using omega-3s is supported by findings suggesting that they have strong anti-inflammatory properties. This is based on the fact that EFAs play an important role in cell membrane composition (phospholipid structure) which, in turn, influences fluidity and cell surface biochemical signaling, and may serve as natural ligands for certain nuclear receptors that affect gene expression.1,2 Additionally, disordered AA metabolism is found in psoriasis, characterized by significantly increased levels of AA and leukotriene B4 (LTB4) in psoriatic plaques.6,7,8 The observation that Eskimos have a lower incidence of psoriasis as compared with the Danes9 led to speculation that dietary supplementation with fish oil, rich in EPA, may induce clinical improvement in skin symptoms and several studies have confirmed this suspicion.10,11 Interestingly, Eskimos living a traditional lifestyle also have a lower incidence of RA and, in a similar way to psoriasis, dietary supplementation with fish oil and essential fatty acids has been shown to improve symptoms and some clinical parameters in RA.12,13 Psoriasis is a dermatologic disease processes that is mediated by an overly robust immune system resulting in keratinocyte hyperproliferation and leukocyte infiltration, both postulated to result from an overabundance of AA metabolites in the epidermis. The therapeutic theory is that omega-3 fatty acid supplementation will decrease the omega-6 to omega-3 ratio, thereby diminishing the substrate availability of “pro-inflammatory” omega-6s (AA) and increasing the amount of “anti-inflammatory” omega-3s (DHA and EPA).14,15 Some studies say omega-3s do not help. The earliest studies done with omega-3 supplementation showed some degree of improvement in psoriatic lesions, but these studies were not controlled. Four of these uncontrolled studies with EPA/DHA or fish oil supplementation with daily dosages between 2 g and 12 g of omega-3 fatty acids reported beneficial effects of the intervention on psoriasis severity.3,8,16,17,18 Another study, also uncontrolled, showed a positive effect of a combination of omega-6 and omega-3 fatty acids in 17 patients with psoriasis after 4 months.19 Another uncontrolled trial had patients with psoriasis eating 170 g of non-oily white fish daily for 4 weeks before being randomized either to continue with the white fish diet or to replace it with 170 g of oily fish (mackerel, sardine, salmon, pilchard, kipper or herring) daily for 6 weeks in a crossover design. Modest significant clinical improvement was observed after the oily fish diet only, whereas the white fish diet had no effect.20 Another uncontrolled study tested the effects of fish oil supplementation in 26 patients with plaque-type and pustular psoriasis. This study showed marked improvement in one patient with pustular psoriasis but no clinically significant improvement in plaque-type psoriasis.21 Results from randomized controlled trials are less positive and conflicting. Among four studies, improvement in psoriatic lesions with omega-3 supplementation was reported in just one study,11 whereas no beneficial effects compared with placebo were observed in the other three studies.22,23,24 The study that showed improvement (Bittiner et al) was a randomized placebo-controlled trial involving patients with psoriasis receiving 3 g of oral omega-3 fatty acid (predominantly EPA) from fish oil daily. Within this treatment group, a significant lessening of itching, erythema and scaling was observed after 8 weeks, with a trend toward an overall decrease in affected body surface area, whereas no change occurred in the olive oil (placebo) group.11 Conversely, two randomized double-blind controlled studies, both using fish oil supplementation of either 1.8 g EPA for 8 weeks22 or 10 capsules of fish oil three times a day for 3 weeks,21 showed no benefit compared with olive oil supplementation. No benefit of fish oil supplementation compared with corn oil (which contains mostly omega-6s), was seen in a 4-month, double-blind, randomized multi-center trial.24 In this study, 145 patients with moderate-to-severe psoriasis received either 5 g of EPA/DHA or an isoenergetic amount of corn oil in their diet. Although the ratio of AA and EPA in serum phospholipids decreased significantly in the fish oil group, the Psoriasis Area and Severity Index (PASI) score did not change significantly in either group. Scaling was reduced compared to baseline in both groups, but only a selected area of skin in the corn oil group showed a significant reduction in clinical signs. There was no significant difference in clinical manifestations between the groups. Clinical improvement was not correlated with an increase of n-3 fatty acid concentration in serum phospholipids among the patients in the fish oil group, whereas there was a significant correlation between clinical improvement and an increase in EPA and total n-3 fatty acids in the corn oil group.24 The positive effect of corn oil rich in linoleic acid may be because LTB4 production is suppressed at high intakes of linoleic acid.25 And in another double-blind trial, no effect on chronic stable plaque psoriasis was observed after supplementation with a combination of an omega-3 fatty acid-rich marine oil with omega-6 fatty acid-rich evening primrose oil in 37 patients with psoriasis.26 And some studies say they do help. In contrast to the mostly negative results from oral supplementation studies with omega-3 fatty acids, promising results have been seen with parenteral (intravenous) administration of omega-3s.27 In a 10-day trial, 20 patients hospitalized for acute guttate psoriasis with a minimum of 10% of body surface area involvement were randomly assigned to receive daily infusions with an omega-3 fatty acid-based lipid emulsion (2.1 g EPA and 21 g DHA daily) or a conventional omega-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml daily). The severity of disease, which was evaluated by daily scoring of erythema, infiltration, desquamation and by a subjective scoring of clinical manifestations, decreased markedly in all patients of the omega-3 group, with significant improvements in all score systems ranging between 45% and 76% within 10 days. Only moderate improvement was observed in the omega-6 group (16% to 25% score changes from baseline).28 The benefit of infusions with omega-3 fatty acids (4.2 g of both EPA and DHA) has been confirmed in a double-blind, randomized, multicenter study with 83 patients hospitalized for chronic plaque-type psoriasis. After 14 days of intervention, the total PASI score decreased significantly in both groups, the omega-3 group and the omega-6 fatty acid control group, by 42% and 31%, respectively. A decrease in total PASI of at least 50% between the admission and the last value was stated in 37% of the patients receiving the omega-3 emulsion and in 23% of those receiving omega-6 fatty acid-based conventional emulsion.29 The rapid effect of omega-3 fatty acid supplementation in these studies indicates that intravenous supplementation may be more beneficial for inflammatory skin lesions than oral supplementation. On the other hand, a Cochrane review of acute guttate psoriasis, concluded that there is currently no firm evidence for intravenous n-3 fatty acids as a base treatment for acute guttate psoriasis.30 More recently, Mayser et al looked at parenteral administration of an omega-3 fatty acid lipid emulsion.31 This same group had previously used dietary supplementation. They performed several trials (presented in one article), two of which were randomized, controlled designs that showed as high as 76% responders in the omega-3 cohort compared to 25% in the omega-6 group within 10 days to 14 days. The measured clinical parameters were erythema, lymphocyte infiltration, desquamation and subjective scores. In addition, they showed that parenteral administration of omega-3 fatty acids resulted in a rapid increase of EPA metabolites within just 3 days. What to tell your patients: The evidence so far suggests omega-3s do indeed have a potential role in the treatment of psoriasis, in particular for parenteral treatments, either as an active anti-inflammatory agent by itself, or as an adjunct with conventional psoriasis treatments. Although the results of oral fish oil supplementation are inconsistent, omega-3s have such well-established multi-system benefits that I think all patients should be on them daily (or get from their diet if possible). And if your patient with psoriasis happens to experience an improvement in his or her psoriasis, wonderful! A remarkable aspect of omega-3s is that there have been virtually no deleterious side effects reported. However, patients with bleeding disorders and/or on blood thinners should use caution and work with their primary doctors if they want to take these. Patients may complain of unpleasant side effects such as diarrhea, flatulence and “fishy burps,” but these are certainly not critical. I tell my patients to put the capsules in the freezer as this seems to eliminate any fishy taste or fishy burps later on. From a cost-benefit perspective, oral preparations of omega-3 are widely available without a prescription and at reasonable prices. Just make sure to tell your patients to buy preparations that are derived from molecularly distilled fish oil that is independently tested to be guaranteed free of heavy metals (mercury and lead) and other contaminants including polychlorinated biphenyls (PCBs). Your vegan patients can get algae-derived supplements. GAMMA-LINOLENIC ACID What is it? 32 Gamma-linolenic acid (GLA) is an essential fatty acid (EFA) in the omega-6 family that is found primarily in plant-based oils. Where is it found?32 GLA is found primarily in evening primrose oil, borage seed oil or black currant seed oil. Evening primrose is a plant native to North America, but it grows in Europe and parts of the Southern Hemisphere as well. The plant is so named because of its yellow flowers that bloom in the evening. Evening primrose oil is extracted from the seeds of the evening primrose. The oil is usually put into capsules for use. Evening primrose oil is the most researched source of GLA. Does it help with psoriasis? There is not much to speak of in the literature involving psoriasis and GLA. Interest in treating patients with psoriasis with GLA-rich supplementation developed following studies where this skin condition was found to benefit from treatment with fish oils.10,11 A double-blind, placebo-controlled study of 38 patients,33 showed no obvious benefit of GLA supplementation in psoriasis patients. More convincing evidence exists in support of EFA use in rheumatoid arthritis; the study by Zurier et al34 in which a high dose of GLA was evaluated is particularly interesting. What to tell your patients: There is not enough evidence to support the use of GLA supplements (in the forms of evening primrose or borage oils) for psoriasis. Safety has not been confirmed in pregnancy, so advise against use in your female patients who are pregnant. Most people tolerate both oils well with the most common side effects being gastrointestinal upset and headache,32 so if your patients want to try it, there is likely no harm (but no established benefit). EXTRACT of MILK THISTLE What is it?35 Extract of milk thistle (Silybum marianum) is an herb whose active agent is silymarin, a flavonoid isolated from the seeds of the herb. Where is it found?35 Milk thistle is a flowering herb that is native to the Mediterranean region. Silymarin (extracted from the seeds) is used to prepare capsules, extracts and infusions (strong teas). Does it help with psoriasis? No. While there are numerous studies and reviews available regarding milk thistle and various hepatic ailments such as Hepatitis B and C, there are no reports of any sort regarding psoriasis. It has however, been minimally studied as a possible preventive agent in non-melanoma skin cancer.36-38 What to tell your patients: Despite what your patients may be reading on the Internet, you can tell them that there is absolutely no evidence for this supplement in improving their psoriasis. If your patients want to try it, it appears to be safe and non-toxic.35,39 Caution patients, though, that if they take high doses (>1500 mg per day), they may experience an unpleasant laxative effect and bloating. 35,39 Recommendations Of the supplements reviewed, only omega-3 had substantial evidence to support its use in psoriasis.The holistic approach recognizes that a chronic disease such as psoriasis is multifactorial, involving a confluence of genetic, environmental, social, psychological and physical events. Because of this, if your patient wants to give one of these options a try, advise them to take an omega-3 supplement because of its numerous health benefits and possible benefit for psoriasis. Dr. Taylor, a Fellow in the Department of Dermatology at Wake Forest University Baptist Medical Center in Winston-Salem, NC, is board-certified in Family Medicine, which she practices in Winston-Salem, NC.
