Borage Oil 1,000 mg [Discontinued] by Vitamer Laboratories

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 EFFECTIVE

• Coronary heart disease (CHD). Supporting, but not conclusive, evidence suggests that consuming fats and oils rich in oleic acid might reduce the risk of CHD (26466,95745,98563,101821). However, the relationship between blood levels of oleic acid and risk of CHD or CVD is unclear (101832,101834,101838). In 2018, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that replacing dietary fats and oils higher in saturated fat with oils containing at least 70% oleic acid may reduce the risk of CHD. To achieve this benefit, high-oleic acid containing oils should not increase total daily energy intake. The suggested daily dietary intake is about 20 grams (1.5 tablespoons) of high oleic acid oils in place of other fats and oils. These oils include olive oil, high-oleic acid sunflower oil, and high-oleic acid canola oil (98563). A meta-analysis of clinical studies shows that replacing 7.5% of energy from partially hydrogenated vegetable oils with high oleic acid sunflower oil can reduce coronary heart disease risk by about 9% to 19%. Furthermore, analysis of results from observational studies found that replacing partially hydrogenated oil with high oleic acid sunflower oil is associated with a 16% to 35% reduction in the risk of coronary heart disease events (95745). Clinical research in patients with cardiovascular disease (CVD) risk shows that taking high-oleic acid canola oil 60 grams per 3000 kcal of energy daily as part of a fixed composition diet for 4-6 weeks reduces the Framingham 10-year coronary heart disease risk scores by 6.8% compared to baseline (26466,101821). However, taking the high-oleic acid canola oil is no more effective than regular canola oil, which contains approximately 62% oleic acid (26466,101821). The relationship between blood levels of oleic acid and risk of CHD or CVD is unclear. While some population research has found that having the highest blood levels of oleic acid is associated with an increased risk of CVD when compared to having the lowest blood levels of oleic acid, other research suggests an inverse association or no association at all (101832,101834,101838). One study has found that having the highest blood levels of oleic acid is associated with a 1.4- to 2-fold increased risk of heart failure, other cardiovascular events, and all-cause mortality (101832). In contrast, another found that the highest blood levels of oleic acid is associated with a 73% reduced risk of having a stroke (101838). A third study found no association at all between plasma levels of oleic acid and risk of heart failure (101834). The clinical significance of these findings is unclear, and results should not necessarily be extrapolated to dietary oleic acid (101832). While plasma oleic acid levels seem to be a weak indirect marker of moderate to high olive oil use, it is also a weak marker of intake of butter and avian fats (101838). Furthermore, there is no clear evidence that plasma levels of oleic acid directly correlate with dietary oleic acid, especially where dietary oleic acid intake is relatively low (101832). As a non-essential fatty acid, oleic acid is endogenously synthesized in the liver from saturated fats (101832,101834,101838).
• Hypercholesterolemia. Evidence from small studies shows that consuming oils rich in oleic acid as part of the diet in place of other dietary fats may improve cholesterol levels (21698,26466,67569,101821). Preliminary clinical research in patients with hypercholesterolemia shows that consuming oleic acid as part of a high oleic sunflower oil- or high oleic canola oil-rich diet for 3-4 weeks decreases total and low-density lipoprotein (LDL) cholesterol levels by a moderate amount when compared with diets rich in palm oil, medium-chain triglycerides, or a blend of fats found in a regular Western diet (21698,67569). Other clinical research in patients with at least one cardiovascular risk factor shows that consuming oleic acid as part of high oleic acid canola oil for up to 4 weeks reduces total cholesterol by up to 9.4% and LDL cholesterol by up to 12.5% compared to baseline or a diet higher in saturated fats. However, taking the high oleic acid canola oil is no more effective than regular canola oil, also a source of oleic acid (26466,101821).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bladder cancer. Population research has found that the highest blood levels of oleic acid are associated with a 46% decreased risk of having bladder cancer when compared to the lowest blood levels (101844). However, plasma oleic acid levels are only a weak indirect marker of dietary intake of oleic acid. As a non-essential fatty acid, oleic acid is endogenously synthesized in the liver from saturated fats (101832,101834,101838). The effect of oleic acid supplementation on bladder cancer risk is unknown.
• Breast cancer. Population research has found no association between dietary fatty acid intake, including oleic acid, and the risk of breast cancer (96528). The effect of oleic acid supplementation on breast cancer risk is unknown.
• Depression. An observational study in perimenopausal patients aged 42-52 years has found that increasing dietary intake of oleic acid is associated with an increase in depression symptom scores. The odds ratio for depressive symptoms was approximately 2-fold higher for the highest quartile of oleic acid intake when compared with the lowest quartile (108924).
• Diabetes. A small clinical trial in patients with type 2 diabetes shows that taking oleic acid as part of a low-fat diet containing 15% monounsaturated fatty acids for 3 weeks does not alter levels of total or low-density lipoprotein (LDL) cholesterol or the change in LDL oxidation when compared with taking linoleic acid as part of a low-fat diet containing 15% polyunsaturated fatty acids (101847).
• Diarrhea. Preliminary clinical research in patients with chronic diarrhea shows that taking oleic acid 1.6 or 3.2 mL before a meal reduces bowel movements over the next 24 hours by approximately 22% compared with taking no oleic acid. Intestinal transit time was also increased by 28 and 54 minutes, respectively (101848). Since the specific cause of chronic diarrhea differed among the patients included in this study, it is unclear if oleic acid is beneficial for most or only certain forms of chronic diarrhea.
• Hypertension. Preliminary clinical research in patients with central obesity and at least one other cardiovascular disease risk factor shows that taking oleic acid as high oleic acid canola oil for 4 weeks does not reduce systolic or diastolic blood pressure compared to baseline (26466).
• Obesity. Preliminary clinical research in patients with central obesity shows that taking oleic acid as high oleic acid canola oil for 4 weeks reduces abdominal fat mass by approximately 0.1 kg compared to baseline (98564). Other preliminary clinical research in patients with central adiposity and at least one other risk factor of cardiovascular disease shows that taking high oleic acid canola oil for 6 weeks reduces total and low-density lipoprotein (LDL) cholesterol by 3.4% and 5.6%, respectively, compared with a control oil lower in monounsaturated fats and higher in saturated fats (101821). However, in these studies, taking the high oleic acid canola oil is no more effective than regular canola oil, also a source of oleic acid (98564,101821). Any effect of oleic acid itself is unclear.
• Pancreatic cancer. The association between dietary oleic acid and pancreatic cancer risk is unclear. Most population research shows no association between dietary oleic acid and pancreatic cancer risk. However, one large population study has found that the highest intake of oleic acid, at least 23.7 grams daily, is associated with a 71% decreased risk of pancreatic cancer when compared with the lowest intake. The benefit is only observed in overweight or obese individuals. (101833). The effect of oleic acid supplementation on pancreatic cancer risk is unknown.
• Short bowel syndrome. A small preliminary clinical trial in patients with surgical short bowel syndrome of at least 2 years shows that taking oleic acid 3.2 mL in 50 mL of a beverage daily for 3 months does not reduce intestinal transit time or diarrhea, or improve body weight, when compared with placebo. In addition, energy absorption was reduced by 14% (101843).
• Stroke. Population research has found that highest blood levels of oleic acid are associated with a 73% reduced risk of stroke when compared with lowest blood levels of oleic acid (101838). However, plasma oleic acid levels are only a weak indirect marker of dietary oleic acid. As a non-essential fatty acid, oleic acid is endogenously synthesized in the liver from saturated fats (101832,101834,101838). The effect of oleic acid supplementation on stroke risk is unknown.
• Ulcerative colitis. Although some contradictory evidence exists, a large population study has found that, after adjusting for dietary intake of omega-3 fatty acids, highest dietary intake of oleic acid is associated with a 97% reduced odds of developing ulcerative colitis when compared with the lowest intake (101846). The effect of oleic acid supplementation on ulcerative colitis risk is unknown.

(Read more about OLEIC ACID)

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 food amounts. Edible oils containing high amounts of oleic acid are commonly used in foods (26466,90681,94452,101821,101824,101828,101830,101838). There is insufficient reliable information available about the safety of oleic acid when used as medicine.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts greater than those commonly found in foods.

(Read more about OLEIC ACID)

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).

(Read more about BORAGE)

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).

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

(Read more about OLEIC ACID)

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).

(Read more about BORAGE)

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).

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

General ...Orally, oleic acid generally well tolerated when used as part of oils and fats in the diet (26466,90681,94452,101821,101824,101828,101830,101838). Temporary burning in the mouth or throat has occurred in some patients (101848).

Gastrointestinal ...Orally, oleic acid has caused temporary burning in the mouth or throat in some patients in one clinical study (101848).

(Read more about OLEIC ACID)