Phosphatidyl-Serine Complex [Discontinued] by OL Olympian Labs Incorporated

POSSIBLY INEFFECTIVE

• Hyperlipidemia. Clinical research suggests that alpha-linolenic acid does not lower lipid levels in adults with hyperlipidemia. Details: A meta-analysis of 20 small clinical trials in patients with hyperlipidemia shows that taking foods or supplements containing alpha-linolenic acid does not reduce lipid levels when compared with control (104256). The findings from this analysis are limited by the heterogeneity of the alpha-linolenic acid supplementation regimens and patient populations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. Some research suggests that increasing dietary alpha-linolenic acid intake may decrease atherosclerosis. Details: Epidemiological research in White adults has found that high dietary intake of linolenic acid is associated with reduced calcified atherosclerotic plaques in the coronary arteries. Most dietary linolenic acid is alpha-linolenic acid (only a small fraction is gamma-linolenic acid). For every gram of linolenic acid consumed, risk of coronary artery calcification appears to decrease by 62% (12990). The effects of linolenic acid intake in other populations are unclear.
• Atopic dermatitis (eczema). Although there is interest in using oral alpha-linolenic acid (ALA) for atopic dermatitis, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if alpha-linolenic acid is beneficial in patients with ADHD. Details: Small clinical trials show that taking alpha-linolenic acid does not improve symptoms of previously untreated ADHD in children aged 6-16 years. Taking alpha-linolenic acid 1 gram daily for 8 weeks, or taking a combination of alpha-linolenic acid 60 mg, linoleic acid 240 mg, mineral oil 95 mg, and alpha-tocopherol 5 mg twice daily for 7 weeks does not affect ADHD symptom scores when compared with placebo (100660,100661). However, these studies might have been inadequately powered to detect a difference between groups.
• Cancer. It is unclear if increased dietary intake of alpha-linolenic acid affects mortality in patients with cancer. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with a 6% increased risk of mortality from cancer when compared with low dietary intake of alpha-linolenic acid (106661).
• Cardiovascular disease (CVD). Population research has found that increased dietary intake of alpha-linolenic acid may have some benefit for CVD, but results from clinical research are generally less positive. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with an 8% or 11% reduced risk of mortality from CVD or coronary heart disease (CHD), respectively, when compared with low dietary intake of alpha-linolenic acid. A dose-response analysis and meta-analysis show that a 1-gram increase in daily dietary intake is associated with a 5% reduction in CVD mortality (106661,107741). Other population research has found that consumption of 1-2 grams of dietary alpha-linolenic acid daily is associated with a reduced risk of a first myocardial infarction (MI) by as much as 59% in both males and females (7152,7156). The risk of fatal ischemic heart disease is reduced by 65% in females (7153). In patients who have had a previous MI, following a Mediterranean diet rich in alpha-linolenic acid (1.2-1.6 grams daily) and low in saturated fat and cholesterol for 27 months appears to reduce the risk for a second MI by 73% and the risk for death from any cause by 70% when compared to the standard postinfarction diet (7150). Overall, increasing dietary intake of alpha-linolenic acid by 1-1.2 grams daily appears to reduce the risk of fatal coronary heart disease by 20% in people with no history of heart disease and by 20% or more in people with existing heart disease (12978,91403). However, clinical research has not supported these findings. A meta-analysis of a small number of low to moderate quality clinical studies shows that higher intake of alpha-linolenic acid has little to no benefit for primary prevention of CVD, and does not reduce all-cause mortality, CVD mortality, or CHD events. Any reductions in CVD mortality, arrhythmias, or CHD events in individual trials are very small (103955). This may be due in part to the difficulty in separating the effects of alpha-linolenic acid from those of other dietary, lifestyle, or drug interventions (12917). Some research suggests alpha-linolenic acid has a greater effect on coronary heart disease when intake of fish oils is low (12989).
• Chronic obstructive pulmonary disease (COPD). Although there is interest in using oral alpha-linolenic acid (ALA) for COPD, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Cognitive function. It is unclear if oral alpha-linolenic acid improves cognitive function in healthy adults.
• Crohn disease. Although there is interest in using oral alpha-linolenic acid (ALA) for Crohn disease, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Crohn disease. Although there is interest in using oral alpha-linolenic acid (ALA) for Crohn disease, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Depression. It is unclear if oral alpha-linolenic acid is beneficial in patients with depression. Details: Clinical research in patients aged 60-80 years who have had a myocardial infarction shows that consuming margarine containing alpha-linolenic acid 2 grams daily for 40 months does not reduce symptoms of depression when compared with placebo margarine (104978).
• Diabetes. It is unclear if oral alpha-linolenic acid is beneficial in patients with diabetes. Details: Epidemiological research involving overweight and obese individuals has found that eating at least 1.69 grams alpha-linolenic acid daily is associated with a 45% to 47% reduced risk of developing type 2 diabetes when compared with eating only 0.73 grams daily. However, higher intake of alpha-linolenic acid does not appear to be associated with a reduced risk of diabetes in people who are not overweight (101025). In patients with diabetes, epidemiological research shows that lower intake of alpha-linolenic acid is associated with an increased risk of diabetic nephropathy (101024). However, a meta-analysis of clinical research in adults with diabetes who are stable on oral antidiabetic medications shows that adding alpha-linolenic acid 1.5-7.4 grams daily, in the form of flaxseed oil, walnuts, or chia seeds, to a regular diet for 2-12 months does not improve glycemic control when compared with placebo (98002).
• Influenza. Although there is interest in using oral alpha-linolenic acid (ALA) for influenza, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Hypertension. Some research suggests that increasing dietary alpha-linolenic acid may decrease the risk of hypertension. Details: Epidemiological research has found that high dietary intake of linolenic acid is associated with a reduced risk of hypertension in White adults. Most dietary linolenic acid is alpha-linolenic acid (only a small fraction is gamma-linolenic acid). Eating a diet high in linolenic acid seems to reduce the risk of hypertension by about 33% (12991). The effects of linolenic acid intake in other populations are unclear.
• Kidney transplant. Observational research suggests that alpha-linolenic acid is not beneficial after a kidney transplant, and may actually increase the risk of mortality. Details: Epidemiological research has found that dietary intake of alpha-linolenic acid is not associated with improved graft function in kidney transplant. However, kidney transplant recipients in the highest tertile of alpha-linolenic acid intake appear to have a 2.2-fold increased risk of death from any cause when compared with those in the lowest tertile of dietary intake (98003). It is not clear whether this difference is specifically due to alpha-linolenic acid intake or to total fat intake.
• Migraine headache. Although there is interest in using oral alpha-linolenic acid (ALA) for migraine headache, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Multiple sclerosis. Although there is interest in using oral alpha-linolenic acid (ALA) for MS, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Overall mortality. It is unclear if increased dietary intake of alpha-linolenic acid affects all-cause mortality. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with a 10% reduced risk of all-cause mortality when compared with low dietary intake of alpha-linolenic acid. A dose-response analysis shows that a 1-gram increase in daily dietary intake is associated with a 5% reduction in overall mortality (106661). However, a meta-analysis of 250,000 individuals did not find an association between dietary alpha-linolenic acid intake and all-cause mortality (107741). The validity of this finding is limited by the use of dietary surveys to assess intake and the heterogeneity of the included studies.
• Prostate cancer. There is contradictory evidence about the role of alpha-linolenic acid in prostate cancer. Details: Some epidemiologic research suggests that high dietary intake of alpha-linolenic acid is associated with an increased risk for prostate cancer (1337,2558,7823,7147,12978). Other research suggests high intake or serum levels of alpha-linolenic acid is not associated with increased levels of prostate specific antigen (PSA) or the overall risk of prostate cancer (12961,15736,91402). However, it might increase the risk of advanced prostate cancer (12961). The best evidence to date, which comes from a meta-analysis of five prospective population studies, suggests that increasing intake of alpha-linolenic acid by 0.5 grams daily is associated with a modest 1% reduction in the risk of prostate cancer. However, this analysis is dominated by a single study. A meta-analysis of results from nine prospective population studies suggests that a 0.1% increase in blood levels of alpha-linolenic acid is not associated with prostate cancer risk (90677). Reasons for the discrepancies are not entirely clear, but the source of alpha-linolenic acid appears to be important. Alpha-linolenic acid from dairy and meat sources has been positively associated with prostate cancer. Alpha-linolenic acid from plant sources, such as flaxseed, may not affect prostate cancer risk (12909).
• Pneumonia. It is unclear if dietary alpha-linolenic acid reduces the risk for pneumonia. Details: Epidemiological research has found that increasing dietary alpha-linolenic acid consumption is associated with a reduced risk of community-acquired pneumonia (13760).
• Psoriasis. Although there is interest in using oral alpha-linolenic acid (ALA) for psoriasis, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Respiratory tract infections. It is unclear if oral alpha-linolenic acid is beneficial for reducing the incidence of respiratory tract infections in children. Details: Preliminary clinical research in children aged 3-4 years shows that taking alpha-linolenic acid 855 mg, in combination with linoleic acid 596 mg daily from November through February in 2 consecutive years, might reduce the number of recurrent respiratory infections when compared with placebo (10785).
• Rheumatoid arthritis (RA). It is unclear if oral alpha-linolenic acid is beneficial in patients with RA. Details: Preliminary clinical research shows that taking an alpha-linolenic acid-rich oil (flaxseed oil) for 3 months does not improve symptoms or laboratory parameters of RA when compared with baseline or with a linoleic acid-rich oil (safflower oil) (5898).
• Systemic lupus erythematosus (SLE). Although there is interest in using oral alpha-linolenic acid (ALA) for SLE, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Ulcerative colitis. Although there is interest in using oral alpha-linolenic acid (ALA) for ulcerative colitis, there is insufficient reliable information about the clinical effects of ALA for this condition. More evidence is needed to rate alpha-linolenic acid for these uses.

(Read more about ALPHA-LINOLENIC ACID (ALA))

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.

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POSSIBLY EFFECTIVE

• Age-related cognitive decline. Oral bovine cortex-derived phosphatidylserine seems to improve attention and memory in patients with age-related cognitive decline. It is unclear if plant-derived phosphatidylserine is beneficial or whether phosphatidylserine is beneficial for preventing cognitive decline. Details: Clinical studies in people with age-related cognitive decline show that phosphatidylserine improves attention, arousal, verbal fluency, and memory (2440,2441,7119,7120,15539). Bovine- and plant-sourced phosphatidylserine 100 mg three times daily for up to 6 months has been used in these studies (2440,2441,15539). Most clinical studies have used phosphatidylserine derived from bovine cortex. However, most supplements now use soy- or cabbage-derived phosphatidylserine. There is some preliminary evidence that plant-derived phosphatidylserine also improves memory in people with age-associated memory impairment (15539). Also, clinical research in elderly females with complaints of memory loss shows that taking 1-3 capsules of a specific product (Vayacog, Enzymotec Ltd.) containing soybean-derived phosphatidylserine 100 mg/capsule, enriched with docosahexaenoic acid (DHA) 19.5 mg/capsule and eicosapentaenoic acid (EPA) 6.5 mg/capsule, daily for 15 weeks modestly improves immediate memory and sustained attention when compared with placebo (66055,90711). A post-hoc analysis of the results from this study suggests that cognitive improvements are greatest in patients with relatively good cognitive performance at baseline (66055). There is also interest in using phosphatidylserine to prevent age-related cognitive decline. In 2003, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming phosphatidylserine may reduce the risk of developing age-related cognitive decline. However, the FDA has determined that there is very little scientific evidence supporting this claim (102363).
• Alzheimer disease. Oral bovine cortex-derived phosphatidylserine seems to improve cognitive function and behavior in patients with Alzheimer disease when used for up to 12 weeks, although benefits may disappear after 16 weeks. It is unclear if plant-derived phosphatidylserine is beneficial. Details: Taking phosphatidylserine orally can improve cognitive function and global improvement rating scales and improve behavioral rating scales over 6-12 weeks of treatment (2255,2437,2438,2439,7114,7118). Bovine-sourced phosphatidylserine 300-400 mg in divided doses daily for up to 16 weeks has been used (2255,2437,2438,2439). Phosphatidylserine seems to be most effective in patients with less severe symptoms (2437,2439). Phosphatidylserine might lose its effectiveness with extended use. After 16 weeks of treatment, progression of Alzheimer disease seems to overcome any benefit of phosphatidylserine (2255). Most clinical studies have used phosphatidylserine derived from bovine cortex. However, most supplements now use soy- or cabbage-derived phosphatidylserine. Clinical studies have not yet evaluated phosphatidylserine from soy or other sources. It is not known if phosphatidylserine from these sources is as effective as bovine-derived products.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral phosphatidylserine is beneficial for athletic performance. Details: One small clinical trial in golfers shows that taking nutritional bars containing phosphatidylserine 200 mg daily for 6 weeks improves the number of good ball flights, which may improve golf score; however, perceived stress levels and heart rate are not significantly affected (68855). A clinical study in recreationally active adults shows that taking phosphatidylserine 400 mg and caffeine 100 mg daily, along with niacin 28 mg, vitamin C 60 mg, vitamin B1 1.5 mg, vitamin B5 10 mg, vitamin B6 2 mg, vitamin E 12 IU, calcium 100 mg, magnesium 40 mg, and carbohydrates in the form of evaporated cane juice, brown rice syrup, and rice syrup solids 16 grams (Nutravail Technologies) for 14 days modestly reduces post-exercise mood disturbances and perception of fatigue when compared with vitamins and minerals alone. The combination does not appear to improve cognitive function or reaction time (91463). It is not clear if the effect of the combination supplement is due to phosphatidylserine, caffeine, or the combination.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral phosphatidylserine is beneficial for ADHD. Details: A meta-analysis of three generally low-quality randomized clinical trials shows that taking phosphatidylserine 200-300 mg daily for 8-15 weeks modestly improves symptoms of inattention in children with ADHD when compared with placebo. However, there were no significant effects on hyperactivity-impulsivity or on overall ADHD symptoms. Also, two of the three clinical trials included in the analysis investigated the effects of phosphatidylserine in combination with the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (105247). One preliminary clinical trial included in the analysis shows that taking soy-derived phosphatidylserine 200 mg daily for 2 months improves ADHD symptoms, including inattention, hyperactivity-impulsivity, and short-term memory, when compared to baseline in treatment-naïve children with ADHD aged 4-14 years. However, results from this study are limited due to a lack of statistical comparison to the placebo group (89498).
• Cognitive function. Although there is interest in using oral phosphatidylserine for improving cognitive function in healthy adults, there is insufficient reliable information about the clinical effects of phosphatidylserine for this purpose.
• Dementia. It is unclear if oral phosphatidylserine is beneficial for dementia prevention or treatment. Details: In 2003, the FDA determined that it would allow a qualified health claim stating that consuming phosphatidylserine may reduce the risk of dementia in the elderly. However, the FDA has determined that there is very little scientific evidence supporting this claim (102363).
• Depression. It is unclear if oral phosphatidylserine is beneficial for depression. Details: One very small clinical study in elderly adults with depression shows that taking phosphatidylserine 300 mg daily for 30 days modestly improves depression scores when compared to baseline (7113).
• Exercise-induced muscle soreness. It is unclear if oral phosphatidylserine is beneficial for exercise-induced muscle soreness. Details: One small clinical study in athletes shows that taking soybean-derived phosphatidylserine 800 mg daily for 2 weeks during periods of over-training reduces muscle soreness post-exercise when compared with those not taking phosphatidylserine (2264). More evidence is needed to rate phosphatidylserine for these uses.

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LIKELY SAFE ...when used orally in amounts typically found in foods (7141,7142,7144). There is insufficient reliable information available about the safety of alpha-linolenic acid when used in larger, medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts typically found in foods (7141,7142,7145). There is insufficient reliable information available about the safety of alpha-linolenic acid during pregnancy and lactation when used in larger, medicinal amounts; avoid using.

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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.

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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.

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POSSIBLY SAFE ...when used orally and appropriately. Phosphatidylserine has been used with apparent safety at dose of up to 300 mg daily for up to 6 months (2255,2437,2438,2439,2440,2441,7118,15539,68855).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term (7117). Phosphatidylserine has been used with apparent safety in clinical research in doses of 200-300 mg daily for up to 4 months in children aged 4-18 years (7117,89498).

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

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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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ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.  Details Phosphatidylserine is thought to increase acetylcholine levels (2437,8857,8858), which could theoretically interfere with the activity of anticholinergic agents.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, phosphatidylserine might have additive effects with cholinergic drugs.  Details Phosphatidylserine is thought to increase acetylcholine levels (2437,8857,8858), which could theoretically lead to additive cholinergic effects when used with cholinergic drugs.

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General ...Orally, alpha-linolenic acid from dietary sources is well tolerated when used in the diet as a replacement for other sources of fat, such as saturated fats.
Serious Adverse Effects (Rare):
Orally: There is some concern that high dietary intake of alpha-linolenic acid might increase the risk for prostate cancer, although research is conflicting.

Oncologic ...Epidemiologic research suggests that high dietary intake of alpha-linolenic acid might increase risk for prostate cancer (1337,2558,7823,7147,12978). Other research suggests high intake or serum levels of alpha-linolenic acid does not increase the overall risk of prostate cancer (12961,15736); however, it might increase the risk of advanced prostate cancer (12961). Association with prostate cancer appears to depend on the sources of alpha-linolenic acid. Dairy and meat sources has been positively associated with prostate cancer, whereas plant sources, such as flaxseed, don't seem to affect prostate cancer risk (12909). According to a clinical trial, intake of alpha-linolenic acid does not appear to increase levels of prostate specific antigen (PSA) (91402). Also, longer-chain omega-3 fatty acids in fish oils are associated with a decreased risk of total and advanced prostate cancer (12961).

Other ...Alpha-linolenic acid is a type of fat, containing 9 kilocalories/gram, and may result in weight gain if consumed in excess. Patients should be advised that it's best to substitute alpha-linolenic acid in the diet for other sources of fat, such as saturated fats.

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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, 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).

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General ...Orally, phosphatidylserine is generally well tolerated.
Most Common Adverse Effects:
Orally: Flatulence, gastrointestinal upset, headache, insomnia, and nausea.

Gastrointestinal ...Orally, phosphatidylserine can cause gastrointestinal upset such as flatulence or nausea. Gastrointestinal upset can occur at doses of 200-300 mg/day (7116,7121,15539,68862,90711).

Neurologic/CNS ...Orally, phosphatidylserine can cause insomnia. Insomnia is more likely to occur with a higher dose of 600 mg (7121,68844). Headache has also been reported (90711).

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