Borage Oil by Herbal Select

POSSIBLY INEFFECTIVE

• Atopic dermatitis (eczema). Oral borage seed oil does not seem to improve symptoms of atopic dermatitis. Details: Taking borage seed oil orally 500-4000 mg daily for up to 24 weeks does not seem to improve symptoms of atopic dermatitis in adults or children (7632,7633,11341,36805,36824). Meta-analyses of clinical trials also indicate that borage oil and gamma-linolenic acid from borage and other sources do not significantly affect atopic dermatitis (13758,88185).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral borage seed oil is beneficial for acne. Details: In patients with mild to moderate acne, preliminary clinical research shows that taking borage oil 2 grams providing gamma-linolenic acid levels of 400 mg daily for 10 weeks improves inflammatory and non-inflammatory acne lesion counts by 33% and 16%, respectively, when compared with baseline. Acne severity was also improved. These changes were significant when compared with a group receiving no treatment and were equivalent to patients taking 1000 mg each of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (105842).
• Acute respiratory distress syndrome (ARDS). Enteral borage seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Borage seed oil, providing gamma-linolenic acid (GLA), has been investigated in combination with fish oil and antioxidants for improving outcomes in patients with ARDS. A meta-analysis of randomized controlled trials evaluating these ingredients, provided as a specific enteral formula (Oxepa, Abbott Nutrition) or a combination supplement given as a bolus, shows that there is no effect on overall all-cause mortality or ventilator- or ICU-free days when compared with generally isonitrogenous and isocaloric control formulas. A sub-group analysis of lower quality research shows that there may be a modest benefit for patients with a higher risk of mortality (105250). Two more recent meta-analyses have yielded similar results (105248,105249). Most studies included in these analyses investigated the use of Oxepa and found there was no effect on mortality when compared with control enteral formulas. However, studies investigating other sources of enteral or intravenous fish oil were also included in these analyses (105248,105249). In one of these analyses, some low- to very low-quality evidence suggests that use of Oxepa modestly reduces mortality at 28 days, as well as ICU length of stay and duration of mechanical ventilation (105248). However, these benefits were not found in the second meta-analysis (105249). Although most studies investigated the use of an enteral formula containing borage seed oil, fish oil was used alone or in combination in all included studies. Any benefit of borage seed oil alone is unclear from these meta-analyses.
• Alcoholism. Although there is interest in using oral borage seed oil for alcoholism, there is insufficient reliable information about the clinical effects of borage seed oil for this condition.
• Asthma. It is unclear if oral borage seed oil is beneficial for asthma. Details: Preliminary clinical research shows that taking borage seed oil containing gamma-linolenic acid levels of approximately 2 grams daily for 12 months does not improve asthma symptoms in patients with mild to moderate asthma when compared with placebo (36812).
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral borage seed oil for ADHD, there is insufficient reliable information about the clinical effects of borage seed oil for this condition.
• Cardiovascular disease (CVD). Although there is interest in using oral borage seed oil for CVD prevention, there is insufficient reliable information about the clinical effects of borage seed oil for this purpose.
• Coronavirus disease 2019 (COVID-19). Oral borage seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small open label trial of patients in the intensive care unit (ICU) with severe COVID-19 infection shows that taking 5 mL of a syrup containing borage oil, providing gamma-linolenic acid 100 mg, plus extracts of lemongrass, yarrow, chamomile, and chicory daily for 5 days in combination with standard care reduces the length of ICU stay by around 1 day but does not improve mortality rates when compared with standard care alone (112147). The validity of these findings is limited by a lack of placebo control. Further, it is unclear if these findings are due to borage, other ingredients, or the combination.
• Diabetes. Although there is interest in using oral borage seed oil for diabetes, there is insufficient reliable information about the clinical effects of borage seed oil for this condition.
• Hangover. Although there is interest in using oral borage seed oil for symptoms of hangover, there is insufficient reliable information about the clinical effects of borage seed oil for this purpose.
• Neurodermatitis. Although there is interest in using oral borage seed oil for neurodermatitis, there is insufficient reliable information about the clinical effects of borage seed oil for this condition.
• Obesity. It is unclear if oral borage seed oil is beneficial in patients with obesity. Details: A very small clinical trial in adults aged 30-46 years with obesity shows that taking 4 capsules of a specific borage seed oil (Barlean's Naturals), providing gamma-linolenic acid 880 mg total, daily for 6 weeks does not improve resting metabolic rate or body mass index when compared with placebo. Improvements in triglyceride and high-density lipoprotein cholesterol levels were observed when compared with baseline; however, patients had normal lipid profiles at baseline (108755). Due to its very small size, this study may have been inadequately powered to detect a difference between groups.
• Periodontitis. It is unclear if oral borage seed oil is beneficial for periodontitis. Details: Preliminary clinical research shows that taking borage seed oil 3 grams daily for 12 weeks improves gingival inflammation but does not reduce plaque in patients with periodontitis when compared with placebo (36804).
• Premenstrual syndrome (PMS). Although there is interest in using oral borage seed oil for PMS symptoms, there is insufficient reliable information about the clinical effects of borage seed oil for this purpose.
• Prematurity. It is unclear if formula containing borage seed oil is beneficial for neurodevelopment in premature infants. Details: Clinical research shows that giving infant formula supplemented with long-chain polyunsaturated fatty acids from borage oil and fish oil does not improve overall neurodevelopment at 9 or 18 months after term when compared with a control infant formula. However, in males, some but not all measures of neurodevelopment were modestly improved at 18 months. Additionally, length, but not weight, was improved in males, with no growth improvements in females. The infant formula in this study was supplemented with borage oil and fish oils to provide gamma-linolenic acid (GLA) 0.9 grams per 100 grams fat, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) 0.1 and 0.5 grams per 100 grams fat, respectively (13745).
• Pressure ulcers. Enteral borage seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with acute lung injury, preliminary clinical research shows that giving a specific enteral emulsion (Oxepa, Ross Laboratories) providing borage oil, fish oil, and vitamins A, C and E for 7 days does not improve the healing of existing pressure ulcers when compared with a control enteral formula. Although the number of pressure ulcers in the group given the borage oil-containing formula was lower when compared with the control formula, these patients also seemed to have fewer pressure ulcers at baseline and no statistical comparison was conducted. The clinical significance of this finding is unclear (105252).
• Rheumatoid arthritis (RA). Small clinical studies suggest that borage seed oil may be beneficial for reducing symptoms of RA. Details: Some small clinical studies show that taking borage seed oil in combination with conventional analgesics or anti-inflammatory agents might help decrease symptoms of RA after 6 weeks of treatment, with improvements sustained for up to 24 weeks. In these studies, borage seed oil decreased the number of tender joints by 36%, the tender joint score by 45%, the number of swollen joints by 28%, and the swollen joint score by 41% when compared to baseline. Borage seed oil 4.5-7.2 grams daily for up to 24 weeks was used in these studies (1985,8458).
• Seborrheic dermatitis. Preliminary research suggests that topical borage seed oil is beneficial for infantile seborrheic dermatitis. Details: Small clinical studies suggest that topical application of borage seed oil 0.5 mL twice daily can lead to resolution of symptoms within 10-12 days. After discontinuation of topical borage seed oil application, symptoms recurred within 1 week (7630,13305). After lesion resolution, borage seed oil has been applied 2-3 times each week until 6-7 months of age without lesion recurrence (7630). The validity of these findings is limited by the small study sizes and lack of comparator groups.
• Stress. Although there is interest in using oral borage seed oil for stress, there is insufficient reliable information about the clinical effects of borage seed oil for this purpose. More evidence is needed to rate borage for these uses.

(Read more about BORAGE)

POSSIBLY EFFECTIVE

• Diabetic neuropathy. Clinical research suggests that oral GLA may improve nerve function and symptoms of diabetic neuropathy in patients with type 1 and type 2 diabetes. Details: Two clinical trials in patients with type 1 or type 2 diabetes and diabetic neuropathy show that taking GLA 360-480 mg daily for 6-12 months improves measures of nerve function and symptoms of neuropathy, including muscle weakness, impaired tendon reflexes, and impaired sensation, when compared with placebo (1984,8926). GLA seems to be more effective in patients with better glucose control when compared with patients with poor glucose control (8926).

POSSIBLY INEFFECTIVE

• Atopic dermatitis (eczema). Most research suggests that oral GLA does not improve the symptoms or severity of atopic dermatitis in children and adults. Details: A meta-analysis of 11 small clinical studies in children and adults with atopic dermatitis shows that taking GLA from borage oil or evening primrose oil does not improve the severity of atopic dermatitis when compared with placebo oils. Adult doses in these studies ranged from 132-720 mg daily for 3-24 weeks. Child doses ranged from 90-480 mg daily for 3-16 weeks (13758). Also, a more recent clinical study in adults with mild-to-moderate atopic dermatitis shows that taking a food product containing GLA 200 mg daily for 12 weeks does not improve skin hydration, itching, or redness when compared with a control (92868). Conversely, one small open-label clinical trial in infants with atopic dermatitis shows that taking GLA 3 grams daily for 4 weeks might reduce redness, itching, and use of antihistamines when compared to baseline (51042). The validity of these findings is limited by a lack of placebo control.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute respiratory distress syndrome (ARDS). Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of randomized controlled trials evaluating GLA, fish oil, and antioxidants, provided as a specific enteral formula (Oxepa, Abbott Nutrition) or a combination supplement given as a bolus, shows that there is no effect on overall all-cause mortality or ventilator- or ICU-free days when compared with generally isonitrogenous and isocaloric control formulas. A subgroup analysis of lower quality research shows that there may be a modest benefit for patients with a higher risk of mortality (105250). Two more recent meta-analyses have yielded similar results. Although most of the studies included in these meta-analyses investigated the use of Oxepa, some studies investigating other sources of enteral or intravenous fish oil were also included (105248,105249). In one of these analyses, some low- to very low-quality evidence suggests that use of Oxepa modestly reduces mortality at 28 days, as well as ICU length of stay and duration of mechanical ventilation (105248). However, these benefits were not found in the second meta-analysis (105249). It is unclear if GLA, when used alone, is beneficial in patients with ARDS.
• Asthma. Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with asthma shows that taking 10 grams of a medical food emulsion providing GLA 0.75 grams with eicosapentaenoic acid (EPA) 0.5 grams, or 15 grams of a medical food emulsion providing GLA 1.13 grams with EPA 0.75 grams, daily for 4 weeks does not improve self-reported overall symptoms of asthma and bronchodilator use at 2 or 4 weeks when compared with placebo. Another small clinical study shows that taking medical food EFF1009, providing GLA 0.75 grams and EPA 0.5 grams, daily for 4 weeks modestly reduces bronchodilator use and improves quality of life and symptoms such as wheezing when compared to baseline (105251). The validity of this finding is limited by the lack of a comparator group and a high dropout rate.
• Attention deficit-hyperactivity disorder (ADHD). Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in drug-naïve children ages 6 to 12 years with mild to moderate ADHD shows that taking GLA 60 mg in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily for 12 months results in some small beneficial effects on inattentive symptoms when compared with placebo. However, these changes are unlikely to be clinically useful. Also, there was no change in blood levels of fatty acids (111058). The effect of GLA itself is unclear from this study.
• Autism spectrum disorder. Although there has been interest in using oral GLA for autism spectrum disorder, there is insufficient reliable information about the clinical effects of GLA for this purpose.
• Back pain. Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical trial in patients with back pain due to compressive radiculopathy syndrome shows that taking GLA 360 mg and alpha-lipoic acid 600 mg daily for 6 weeks while undergoing rehabilitation therapy reduces pain intensity and improves disability status when compared with rehabilitation therapy alone (20489). It is unclear if these findings are due to GLA, alpha-lipoic acid, or the combination.
• Breast cancer. It is unclear if oral GLA is beneficial in patients with breast cancer. Details: A small clinical study in patients with various stages of endocrine-sensitive breast cancer shows that taking GLA 2.8 grams daily along with tamoxifen for 6 weeks seems to improve the response to tamoxifen when compared with tamoxifen alone (5902).
• Hyperlipidemia. Although there has been interest in using oral GLA for hyperlipidemia, there is insufficient reliable information about the clinical effects of GLA for this purpose.
• Hypertension. Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with modestly elevated diastolic blood pressure (DBP) shows that taking a combination of GLA 0.12 grams plus eicosapentaenoic acid (EPA) 0.48 grams does not reduce DBP when compared with olive oil (13771). However, another small clinical study in patients with hypertension shows that taking 4 grams of an oil preparation rich in GLA, EPA, and docosahexaenoic acid (DHA) daily for 6 weeks reduces DBP when compared with sunflower seed oil (51022). It is unclear if these findings are due to GLA, other ingredients, or the combination.
• Mastalgia. Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial in patients with mastalgia shows that taking GLA 100 mg daily in combination with vitamin C and vitamin B12 as methylcobalamin for 12 weeks does not improve the proportion of patients with minimal or no pain when compared with taking placebo (111059).
• Menopausal symptoms. Although there has been interest in using oral GLA for menopausal symptoms, there is insufficient reliable information about the clinical effects of GLA for this purpose.
• Pressure ulcers. Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with acute lung injury shows that taking a specific enteral emulsion (Oxepa, Ross Laboratories) providing GLA from borage oil along with fish oil and vitamins A, C and E for 7 days does not improve the healing of existing pressure ulcers when compared with a control enteral formula. Although the number of pressure ulcers in the group given the GLA-containing formula was lower when compared with the control formula, these patients also had fewer pressure ulcers at baseline and no statistical comparison was conducted. The clinical significance of this finding is unclear (105252).
• Psoriasis. Although there has been interest in using oral GLA for psoriasis, there is insufficient reliable information about the clinical effects of GLA for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral GLA for RA, there is insufficient reliable information about the clinical effects of GLA for this purpose.
• Rosacea. It is unclear if oral GLA is beneficial in patients with rosacea. Details: A small clinical study in adults with rosacea shows that taking GLA (Evoprim) 320 mg daily along with minocycline 50 mg twice daily for 8 weeks improves patient satisfaction and measures of skin hydration and increases the rate of treatment success, defined as an investigator global assessment score of 1 or lower, indicating clear or minimal symptoms, by 2-fold when compared with placebo plus minocycline (107927).
• Scleroderma. It is unclear if oral GLA is beneficial in patients with scleroderma. Details: A small clinical study in patients with scleroderma shows that taking GLA (dose unknown) for 6 months does not reduce symptoms of scleroderma when compared with placebo (1977).
• Ulcerative colitis. Oral GLA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with ulcerative colitis shows that taking a combination of GLA 1.6 grams, eicosapentaenoic acid (EPA) 270 mg, and docosahexaenoic acid (DHA) 45 mg daily for 12 months does not reduce symptoms when compared with placebo (51013). More evidence is needed to rate GLA for these uses.

(Read more about GAMMA-LINOLENIC ACID (GLA))

POSSIBLY INEFFECTIVE

• Cardiovascular disease (CVD). Most research suggests that increasing dietary intake of omega-6 fatty acids does not reduce the risk of CVD. Details: A meta-analysis including 19 low-quality randomized controlled trials that followed patients for 1-8 years shows that higher intake of omega-6 fatty acids for at least 12 months does not reduce the risk of primary or secondary CVD events, coronary heart disease (CHD) events, stroke, or all-cause or CVD mortality when compared with a lower intake. The intake of omega-6 fatty acids ranged from 0.8% to 20.6% of energy (99973). Population research conducted over about 7.3 years has also found that baseline red blood cell omega-6 fatty acid levels are not associated with CVD events, CHD events, ischemic strokes, CVD deaths, or all-cause mortality (99974), and red blood cell omega-6 fatty acid levels do not differ between people with or without coronary artery disease in patients hospitalized for coronary angiography (96918). However, some research suggests that individual omega-6 fatty acids may have differing effects in the body. One population study has found that increased levels of shorter chain omega-6 fatty acids in red blood cells, including linoleic acid, gamma linolenic acid, and dihomo-gamma linolenic acid, are associated with a reduced risk of CVD mortality. Higher levels of the longer chain omega-6 fatty acids adrenic acid and docosapentaenoic acid are associated with a moderately increased risk of overall mortality in these patients (96918). Higher quality studies are needed to confirm these findings.
• Child development. Most research suggests that supplementing infant formula with arachidonic acid, an omega-6 fatty acid, and docosahexaenoic acid (DHA), an omega-3 fatty acid, does not improve infant or child development. Details: Meta-analyses of clinical research show that inclusion of arachidonic acid in infant formula at levels of up to 0.84% of fatty acids, in addition to DHA, for 2-12 months does not improve visual or neurodevelopmental outcomes in preterm or full-term infants up to 18 months of age (96919,96920). Also, giving infants DHA- and arachidonic acid-supplemented formula during infancy does not appear to improve neurodevelopment by the age of 6 years (92503).
• Hyperlipidemia. Increasing dietary intake of omega-6 fatty acids does not seem to lower plasma cholesterol or triglyceride levels. Details: A meta-analysis of clinical research shows that increasing intake of omega-6 fatty acids, specifically linoleic acid or gamma-linolenic acid, by replacing dietary saturated or monounsaturated fatty acids modestly reduces levels of total cholesterol. However, the clinical significance is unclear. Also, increasing intake of omega-6 fatty acids does not seem to affect levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides (99973).
• Multiple sclerosis (MS). Most research suggests that taking omega-6 fatty acids is not beneficial for MS. Details: A meta-analysis of the available literature shows that taking omega-6 fatty acids, mainly as linoleic acid, does not seem to prevent disease progression in relapsing-remitting MS patients or chronic progressive MS patients at 24 months (107318).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if increased dietary omega-6 fatty acid intake is beneficial for preventing age-related cognitive decline. Details: Population research has found that the highest blood levels of omega-6 fatty acids during middle age are associated with the best overall cognitive functioning 13 years later when compared with lower intakes (99979). In addition, the highest tertile of omega-6 fatty acid intake in older adults, at least 8.8 mg per kcal daily, is inversely associated with having low cognitive performance. However, the same pattern was observed for the highest tertile of omega-3 fatty acids, and the omega-6 to omega-3 fatty acid ratio in the diet had no overall association with cognitive performance (103308).
• Attention deficit-hyperactivity disorder (ADHD). Oral omega-6 fatty acids have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of omega-3 and omega-6 fatty acids twice daily for 3-6 months does not improve symptoms of ADHD in most children when compared with placebo, although it may improve ADHD symptoms in a subgroup of children with ADHD inattentive subtype plus comorbid neurodevelopmental disorders (65864).
• Blepharitis. It is unclear if oral omega-6 fatty acids are beneficial for blepharitis. Details: One preliminary clinical study in patients with Meibomian gland dysfunction shows that taking a specific product (Medilar, Fidia Oftal Bausch & Lomb Pharmaceuticals), which contains the omega-6 fatty acids linoleic acid 28.5 mg and gamma-linolenic acid 15 mg, once daily for 180 days in combination with eyelid hygiene can improve cloudiness from eye secretions and gland obstruction when compared with baseline (66665). However, the lack of a control group limits the validity of these results. Population research involving postmenopausal adults has also found that moderate dietary intake of omega-6 fatty acids is associated with a reduced risk of developing Meibomian gland dysfunction. However, high intake was not associated with a reduced risk in these patients, and the protective effect of omega-6 fatty acids, if any, in the general population is unclear (99978). Higher quality research is needed to confirm these results.
• Cancer. It is unclear if increased dietary intake of omega-6 fatty acids is beneficial for cancer prevention. Details: In a meta-analysis of clinical research, increasing intake of dietary omega-6 fatty acids does not seem to reduce cancer risk or mortality. However, the included research is of low quality (107005). Also, a meta-analysis of population research has found that dietary intake of omega-6 fatty acids is not associated with cancer risk. However, high blood levels of omega-6 fatty acids were associated with an 8% reduced risk of cancer when compared to low blood levels, with breast cancer carrying the strongest association. Each 5% increase in blood levels of omega-6 fatty acids was associated with a 2% decreased cancer risk (107006). These results should be interpreted with caution, since factors other than omega-6 fatty acid intake, such as alcohol intake or overall diet, may affect blood levels of omega-6 fatty acids (100516).
• Developmental coordination disorder (DCD). Oral omega-6 fatty acids have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of omega-6 and omega-3 fatty acids for 3 months can improve reading, spelling, and behavior, but not motor skills, when compared with placebo in children with DCD (13748).
• Diabetes. It is unclear if higher dietary or supplemental intake of omega-6 fatty acids is associated with a reduced risk of diabetes. Details: Population research has found that the highest blood levels of the omega-6 fatty acid linoleic acid are associated with a 43% reduced risk of developing diabetes over a period of 5-42 years when compared with the lowest blood levels. Blood levels of another omega-6 fatty acid, arachidonic acid, do not seem to be linked to diabetes risk (96914). These results should be interpreted with caution, since factors other than omega-6 fatty acid intake, such as alcohol intake or overall diet, may affect blood levels of omega-6 fatty acids (100516). In addition, a meta-analysis of low-quality clinical research does not support any benefit of omega-6 fatty acids in the prevention or treatment of type 2 diabetes (101504).
• Diarrhea. It is unclear if formula supplemented with arachidonic acid is beneficial for diarrhea prevention in infancy. Details: Preliminary clinical research shows that infant formula supplemented with arachidonic acid 34 mg/100 kcal and docosahexaenoic (DHA) acid, an omega-3 fatty acid, 17 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) can reduce the incidence of diarrhea in the first year of life when compared with non-supplemented infant formula (92505).
• Dry eye. It is unclear if dietary intake of omega-6 fatty acids is beneficial for dry eye prevention. Details: Population research has found that higher intake of dietary omega-6 fatty acids is not associated with a reduced risk of dry eye after menopause (99978).
• Hypertension. It is unclear if dietary intake of omega-6 fatty acids is beneficial for blood pressure reduction. Details: Population research has found that higher dietary intake of omega-6 fatty acids, especially linoleic acid, is inversely associated with the odds of hypertension in non-diabetic individuals. However, in patients with diabetes, higher intake of omega-6 fatty acids is associated with an increased odds of hypertension (99975).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if dietary intake of omega-6 fatty acids is beneficial for NAFLD prevention. Details: Cross-sectional population research is mixed with respect to dietary intake of omega-6 fatty acids in patients with NAFLD when compared with healthy controls. One large cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) between 2007-2014 has found that consuming omega-6 fatty acids at a dose of at least 250 mg/kg daily is associated with an 82% reduced risk of having NAFLD when compared with consuming less than 121.3 mg/kg daily (107002).
• Obesity. It is unclear if oral omega-6 fatty acids are beneficial for reducing cholesterol or triglyceride levels in adults with obesity. Details: In individuals with abdominal obesity, a small clinical trial shows that taking linoleic acid 15 grams (females) or 20 grams (males) (Pharmatech AS) daily for 7 weeks from safflower oil has modest beneficial effects on levels of low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-, and total cholesterol when compared with baseline or taking fish oil. However, there was no effect on triglyceride levels (107003).
• Photoreactive keratectomy. Oral omega-6 fatty acids have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in patients who have undergone photoreactive keratectomy shows that taking a tablet containing the omega-6 fatty acids linoleic acid and gamma-linolenic acid, as well as beta-carotene, B vitamins, and trace minerals, daily for 30 days can improve tear production and eye healing when compared with a control group (66679).
• Respiratory tract infections. It is unclear if supplementing infant formula with arachidonic acid is beneficial for preventing respiratory tract infections. Details: Preliminary clinical research shows that infant formula supplemented with arachidonic acid 34 mg/100 kcal and docosahexaenoic acid (an omega-3 fatty acid) 17 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) can reduce the incidence of respiratory illness in the first year of life when compared with non-supplemented infant formula (92505). More evidence is needed to rate omega-6 fatty acids for these uses.

(Read more about OMEGA-6 FATTY ACIDS)

POSSIBLY SAFE ...when borage seed oil is used orally or topically and appropriately. Borage seed oil has been used with apparent safety in clinical trials at a dose of up to 4 grams daily for up to 12 weeks (7632,8458,11341,13305,36804,88185,5244).

LIKELY UNSAFE ...when products containing hepatotoxic pyrrolizidine alkaloids (PA) are used orally. Borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Repeated exposure to low concentrations of hepatotoxic PAs can cause severe veno-occlusive disease. Hepatotoxic PAs might also be carcinogenic and mutagenic (12841,12842). Tell patients not to use borage preparations that are not certified and labeled as hepatotoxic PA-free.

CHILDREN: POSSIBLY SAFE
when borage seed oil is used orally and appropriately. Borage seed oil has been used with apparent safety at a dose of 2 grams daily for 12 weeks (11341).

CHILDREN: LIKELY UNSAFE
when products containing hepatotoxic PAs are used orally. Borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Repeated exposure to low concentrations of hepatotoxic PAs can cause severe veno-occlusive disease. Hepatotoxic PAs might also be carcinogenic and mutagenic (12841,12842). Tell patients to avoid borage preparations that are not certified and labeled as hepatotoxic PA-free.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when products containing hepatotoxic pyrrolizidine alkaloids (PA) are used orally. Borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Repeated exposure to low concentrations of hepatotoxic PAs can cause severe veno-occlusive disease. Hepatotoxic PAs might also be carcinogenic, mutagenic, and teratogenic. These constituents are also excreted in breast milk (12841,12842). Tell patients to avoid borage preparations that are not certified and labeled as hepatotoxic PA-free. There is insufficient reliable information available about the safety of borage seed oil when used orally or topically during pregnancy or lactation.

(Read more about BORAGE)

POSSIBLY SAFE ...when used orally and appropriately. GLA appears to be safe when taken in oral doses of up to 2.8 grams daily for up to a year (1983,7701,7702,8926,107927).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about GAMMA-LINOLENIC ACID (GLA))

LIKELY SAFE ...when used orally in amounts found in foods. Dietary intake in amounts of 5% to 10% of daily calories are appropriate according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723). There is insufficient reliable information available about the safety of omega-6 fatty acids when used orally in medicinal amounts.

CHILDREN: LIKELY SAFE
when consumed by children over the age of 12 months as part of the diet in amounts between 5% to 10% of daily calories according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723).

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed as part of the diet in amounts between 5% and 10% of daily calories according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when high amounts of omega-6 fatty acids are consumed in the diet. Population research suggests that the highest maternal intakes of omega-6 fatty acids (15.2-47.6 grams or 137-428 kcal daily) during pregnancy is associated with a 2.4-times greater odds of giving birth to an infant below the 10th percentile for birth weight when compared with the lowest maternal intakes (0.4-5.7 grams daily) (96913). In addition, population research in women with a history of atopy suggests that the highest blood levels of omega-6 fatty acids during the second trimester is associated with an increased odds of having a child develop atopic dermatitis by age 4-6 years when compared with the lowest intakes (103309). There is insufficient reliable information available about supplemental omega-6 fatty acids; avoid using.

(Read more about OMEGA-6 FATTY ACIDS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, borage seed oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In healthy individuals, borage seed oil supplementation does not seem to affect platelet aggregation (36823). However, gamma-linolenic acid, a constituent of borage seed oil, seems to decrease platelet aggregation by 45% and increase the risk of bleeding by 40% in animal and clinical research (1979).

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking borage with drugs that induce CYP3A4 might increase levels of pyrrolizidine alkaloid (PA) toxic metabolites.  Details Although borage seed oil contains little to no PAs, some borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Hepatotoxic PAs are substrates of CYP3A4, which converts these chemicals into toxic metabolites (12841,12860). Tell patients to avoid borage preparations that are not certified and labeled as hepatotoxic PA-free.

PHENOTHIAZINES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking borage sed oil with phenothiazines might increase the risk of seizures.  Details Borage seed oil contains gamma-linolenic acid (GLA). There is concern that taking supplements containing GLA might cause seizures, or lower the seizure threshold, when taken with phenothiazines. This is based on limited data from two reports published in the 1980s. In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with evening primrose, another source of GLA. However, none experienced an actual seizure (21013). In the other report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose 4 grams daily was added. One of these patients had a prior history of seizures (21010). It is unclear whether evening primrose had any additive epileptogenic effects with the phenothiazines, but there is no evidence that taking GLA-containing supplements alone can cause seizures (88187).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, GLA might increase the risk of bleeding when taken with anticoagulant or antiplatelet rugs.  Details Animal and human research suggests that GLA reduces platelet aggregation (1979).

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General ...Orally, borage seed oil seems to be well tolerated. However, borage plant parts, such as the leaf, flower, and seed, that contain hepatotoxic pyrrolizidine alkaloid (PA) constituents should be avoided.
Most Common Adverse Effects:
Orally: Belching, bloating, diarrhea, and soft stools.
Serious Adverse Effects (Rare):
Orally: Borage plant parts that contain PA constituents can be hepatotoxic.

Gastrointestinal ...Orally, borage seed oil can cause soft stools, diarrhea, belching, and bloating (8013,11341).

Hepatic ...The pyrrolizidine alkaloid (PA) constituents of borage can cause significant hepatotoxicity (12841,12842). PAs can occur in borage leaf, flower, and seed; borage seed oil contains little to no PAs. Chronic exposure to other plants containing hepatotoxic PA constituents has been associated with veno-occlusive disease (VOD). Subacute VOD causes vague symptoms with persistent liver enlargement (4021). Symptoms of acute VOD include colicky pains in epigastrium, vomiting and diarrhea, and ascites within several days. Enlargement and induration of the liver occurs within a few weeks (12842).

Oncologic ...The pyrrolizidine alkaloid (PA) constituents of borage are potentially carcinogenic and mutagenic (12841,12842).

Pulmonary/Respiratory ...The pyrrolizidine alkaloid (PA) constituents of borage are potentially pneumotoxic (12841,12842).

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General ...Orally, GLA seems to be well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal adverse effects, including belching, bloating, diarrhea, dyspepsia, flatulence, nausea, and vomiting.

Gastrointestinal ...Orally, GLA may cause mild gastrointestinal effects such as dyspepsia, nausea, bloating, vomiting, soft stools, diarrhea, flatulence, and belching (7701,7702,8926,107927).

Hematologic ...Orally, GLA might prolong bleeding time (1979).

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General ...Orally, consuming omega-6 fatty acids in amounts found in foods is well tolerated.

Cardiovascular ...Dietary intake of the omega-6 fatty acid linoleic acid in amounts of 5% to 10% of daily calories is appropriate according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723). However, higher intake levels, especially when compared with omega-3 fatty acid intake, might be detrimental. For example, a higher ratio of dietary omega-6 to omega-3 fatty acids is thought to increase the risk of cardiovascular disease compared to a lower ratio (66678). However, the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism, the Council on Cardiovascular Nursing, and the Council on Epidemiology and Prevention, suggest that reduction of omega-6 fatty acids in the diet is unlikely to be beneficial for the cardiovascular system if replaced with saturated or trans-fatty acids (66692). Population research has found that higher intake of omega-6 fatty acids might be associated with hypertension and increased levels of plasma homocysteine, a risk factor for cardiovascular disease and atherosclerosis (65498,66640,66642).

Musculoskeletal ...In epidemiological research, increased intake of omega-6 fatty acids was associated with elevated risk of fracture in the elderly (66662).

Neurologic/CNS ...In epidemiological research, an increased dietary ratio of omega-6 fatty acids to omega-3 fatty acids has been associated with an elevated risk of having a sleep disorder (107001).

Oncologic ...Some population research has found that high omega-6 fatty acid intake or blood levels are associated with an increased risk for cancer, including breast cancer and prostate cancer (3508,7824,66660,66664,66729).

Psychiatric ...In epidemiological research, adolescents with attention-deficit hyperactivity disorder (ADHD) had higher levels of omega-6 and lower levels of omega-3 fatty acids in red blood cells (48200). The role of omega-6 fatty acids in ADHD is unclear; it is possible that the low levels of omega-3 fatty acids and essential fatty acids in general may be playing a role. Also, higher levels of some omega-6 fatty acids in the body are associated with greater depressive symptomology and neuroticism (65815,66659). Higher concentrations of some omega-6 fatty acids in red blood cells of patients with schizophrenia are correlated with positive schizotypal trait measures in healthy adults (66635). This may be related to increased intake of omega-6 fatty acids in the diet of patients with schizophrenia (96916).

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