Evening primrose

Evening primrose oil/Drug Interactions:

  • AlcoholAlcohol: Individuals administered EPO showed increased 5-HT platelet aggregation after one week of treatment compared to the effects after alcohol alone. Furthermore, participants administered alcohol and EPO showed significantly increased platelet aggregation compared to participants administered alcohol without EPO treatment and compared to participants who lacked alcohol and EPO treatment (129).
  • Aldose reductase inhibitorsAldose reductase inhibitors: In animal research, nerve conduction velocity and blood flow responses increased 10-fold following EPO and aldose reductase inhibitor combination (202).
  • AnestheticsAnesthetics: According to case reports of seizures (103; 104), it has been hypothesized that evening primrose oil (EPO) may increase risk of seizure when used concomitantly with general anesthetics.
  • AntiarthriticsAntiarthritics: In individuals with rheumatoid arthritis, evening primrose oil increased pro-inflammatory precursor arachidonic acid (AA) and decreased eicosapentaenoic acid (EPA) (203). In addition, in RA individuals, EPO reduced NSAID intake compared to placebo (204).
  • AntibioticsAntibiotics: In vitro, Oenothera biennis extract lacked, or had weak, antimicrobial activity against Neisseria gonorrhoeae (205).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human and animal research, platelet aggregation was decreased following consumption of EPO (112), although effects on platelet function were lacking in other human research (206; 207; 208). In vitro, dihomo-GLA inhibited platelet aggregation (112). In vitro and in vivo animal research also resulted in inhibited platelet aggregation secondary to EPO (112). In human research, platelet adhesiveness was reported (114). In vivo, dietary intake of the polyunsaturated omega-6 essential fatty acids (EFAs), linolenic, and gamma-linolenic acids (GLA) increased bleeding time in humans and rats (111). In animal research, EPO decreased collagen-induced thrombocytopenia and platelet aggregation following celecoxib administration (113). According to reviews, anticoagulants may interact with EPO (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14). Healthy, non-pregnant females receiving a combination of low dose aspirin and EPO had a non-significant decrease in platelet angiotensin II binding following one month of treatment, while those receiving EPO alone lacked an effect (209). EPO has also been used in pregnant females with a high risk of toxemia to assess the effects on platelet functions (199).
  • AnticonvulsantsAnticonvulsants: In several reported cases, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): According to secondary sources, evening primrose may interact with antidepressants.
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): According to secondary sources, evening primrose may interact with antidepressants.
  • AntidiabeticsAntidiabetics: Animal studies (211; 212; 213) and controlled human trials (214; 128; 215; 24) have demonstrated beneficial effects of evening primrose oil (EPO) (29) on serum markers in diabetes mellitus, including prostaglandin levels and serum fatty acids. Changes in hemoglobin A1C were lacking. In animal research, nerve conduction velocity and blood flow responses increased 10-fold following EPO and aldose reductase inhibitor combination (202). In animal research, an increase in diabetes-induced type I nitric oxide synthase activity was completely avoided in the ileum in streptozotocin-diabetic rats receiving GLA dietary supplements (216).
  • AntihypertensivesAntihypertensives: In animal research, gamma-linolenic acid decreased central venous blood pressure in both normotensive and hypertensive animals (106; 107; 108; 109; 110). In animal research, EPO decreased blood pressure elevated following celecoxib administration (113). Preliminary human evidence is equivocal, with some data suggesting a blood pressure-lowering effect in humans (184), and other data showing a lack of an effect on blood pressure (185). According to reviews, EPO may interact with beta-blockers (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14).
  • Anti-inflammatory agentsAnti-inflammatory agents: EPO has been reported to have anti-inflammatory effects (217; 218; 19; 35; 12). According to a review, anti-inflammatory drugs may interact with EPO (189). In vitro, GLA decreased interleukin-1beta (IL-1beta) release in human cells and decreased joint inflammation in individuals with rheumatoid arthritis (219). In human research, EPO decreased oleic acid, eicosapentaenoic acid, and apolipoprotein B levels and increased linoleic acid, GLA, DGLA, and arachidonic acid levels (203).
  • Antilipemic agentsAntilipemic agents: In human research, EPO affected serum lipids levels in patients with rheumatoid arthritis (203). In human research, EPO decreased plasma cholesterol, LDL, LDL-triglycerides, LDL-phospholipids, and apolipoprotein B levels and increased HDL levels (151; 133).
  • Antineoplastic agentsAntineoplastic agents: Evening primrose oil was taken with tamoxifen in humans with evidence of benefit (220), and EPO exhibited evidence of benefit in animals in the development of mammary tumorogenesis (221); however, the potential anti-cancer effects of primrose oil are unclear. According to a review, EPO may be an empiric agent used for individuals with chemotherapy-induced neuropathy (27). In laboratory research, the combination of Oenothera paradoxa Hudziok defatted seeds extract, containing pentagalloylglucose and procyanidins, with vincristine increased cancer cell death more than vincristine alone (by greater than 4 vs. 1.5 times, respectively) (222). In human research, EPO combined with vitamin C decreased tumor size in individuals with liver cancer and in one individual decreased serum alkaline phosphatase and gamma-glutamyl transaminase (223). In laboratory research, efficacy increased and estrogen receptor expression was limited following the combination of GLA/tamoxifen and GLA/Falsodex? in human breast cancer cells (224).
  • Antiobesity agentsAntiobesity agents: According to secondary sources, primrose oil may have additive effects when taken with antiobesity agents; however, evidence is lacking (225; 184). In human research, EPO increased weight (135; 123; 116; 143).
  • AntipsychoticsAntipsychotics: According to a review, antipsychotics may interact with EPO (189). According to case reports, seizures have been reported following the combination of EPO and phenothiazine neuroleptics (103; 104).
  • Antiviral agentsAntiviral agents: According to a review, primrose may have additive effects when taken concomitantly with antivirals (226).
  • Beta-blockersBeta-blockers: According to reviews, beta-blockers may interact with EPO (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14).
  • CelecoxibCelecoxib: In animal research, EPO decreased blood pressure that was elevated following celecoxib administration and decreased collagen-induced thrombocytopenia and platelet aggregation (113).
  • CNS depressantsCNS depressants: In human research, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189). According to case reports of seizures (103; 104), it has been hypothesized that EPO may lower seizure threshold.
  • CNS stimulantsCNS stimulants: In human research, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189). According to case reports of seizures (103; 104), it has been hypothesized that EPO may lower seizure threshold.
  • CorticosteroidsCorticosteroids: According to a review, corticosteroids may interact with EPO (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14).
  • COX-2 inhibitorsCOX-2 inhibitors: In animal research, EPO decreased collagen-induced thrombocytopenia and platelet aggregation following celecoxib administration (113).
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: In vitro, cis-linoleic acid, a constituent of EPO, inhibited cDNA human P450 isoforms (227). According to secondary sources, EPO may interact with cytochrome P450 2D6 inhibitors.
  • Dermatologic agentsDermatologic agents: In human research, dermatologic complaints, such as cellulitis, itchy, and fatty skin (123), acne (123; 158), skin rash (158; 29), and skin reactions (138) were reported following EPO supplementation. Conversely, EPO has been used orally and topically to treat atopic dermatitis (155; 228; 229).
  • Faslodex?Faslodex?: In laboratory research, efficacy increased and estrogen receptor expression was limited following the combination of GLA and Falsodex? in human breast cancer cells (224).
  • Gastrointestinal agentsGastrointestinal agents: According to experts, EPO may induce nausea and stool softening; however, it is unclear whether these effects were observed in clinical or animal studies (14). Gastrointestinal complaints, including abdominal pain, nausea, belching, vomiting, diarrhea, acidity, bloating, gas, dyspepsia, pain, fullness, and loose stools have been reported in clinical studies and reviews (29; 178; 123; 187; 158; 110; 188; 189; 190; 126; 191; 154; 164; 115; 14; 172; 130; 11; 16; 146; 166).
  • Neurologic agentsNeurologic agents: In human research, EPO may interact with neurologic agents, including anticonvulsants (103; 104), antidepressants, phenothiazine neuroleptics, and CNS stimulants. Cases of dizziness (158) and headache have been reported in reviews and clinical trials (29; 188; 189; 115; 110; 11; 16; 14; 24; 191; 187; 166; 162).
  • NSAIDsNSAIDs: According to reviews, EPO may interact with non-steroidal anti-inflammatory drugs (NSAIDs) (69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14).
  • PhenothiazinesPhenothiazines: According to reviews, EPO may interact with phenothiazines (69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14).
  • Seizure threshold-lowering agentsSeizure threshold-lowering agents: In several reported cases, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189). According to case reports of seizures (103; 104), it has been hypothesized that EPO may lower seizure threshold.
  • TamoxifenTamoxifen: Evening primrose oil was taken with tamoxifen in humans with evidence of benefit (220), and EPO exhibited evidence of benefit in animals in the development of mammary tumorogenesis (221); however, the potential anti-cancer effects of primrose oil are unclear. In laboratory research, efficacy increased and estrogen receptor expression was limited following the combination of GLA and tamoxifen in human breast cancer cells (224).
  • VincristineVincristine: The combination of Oenothera paradoxa Hudziok defatted seeds extract, containing pentagalloylglucose and procyanidins, with vincristine increased cancer cell death more than vincristine alone (by greater than 4 vs. 1.5 times, respectively) (222).

    • Evening primrose oil/Herb/Supplement Interactions:

  • AnestheticsAnesthetics: According to case reports of seizures (103; 104), it has been hypothesized that evening primrose oil (EPO) may increase risk of seizure when used concomitantly with general anesthetics.
  • Antiarthritic herbs and supplementsAntiarthritic herbs and supplements: In individuals with rheumatoid arthritis (RA), evening primrose oil increased pro-inflammatory precursor arachidonic acid (AA) and decreased eicosapentaenoic acid (EPA) (203). In addition, in RA individuals EPO also reduced NSAID intake compared to placebo (204).
  • AntibacterialsAntibacterials: In vitro, Oenothera biennis extract lacked, or had weak, antimicrobial activity against Neisseria gonorrhoeae (205).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human and animal research, platelet aggregation was decreased following consumption of EPO (112), although effects on platelet function were lacking in other human research (206; 207; 208). In vitro, dihomo-GLA inhibited platelet aggregation (112). In vitro and in vivo animal research also resulted in inhibited platelet aggregation secondary to EPO (112). In human research, platelet adhesiveness was reported (114). In vivo, dietary intake of the polyunsaturated omega-6 essential fatty acids (EFAs), linolenic, and gamma-linolenic acids (GLA) increased bleeding time in humans and rats (111). In animal research, EPO decreased collagen-induced thrombocytopenia and platelet aggregation following celecoxib administration (113). According to reviews, anticoagulants may interact with EPO (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14). Healthy, non-pregnant females receiving a combination of low dose aspirin and EPO had a non-significant decrease in platelet angiotensin II binding following one month of treatment, while those receiving EPO alone lacked an effect (209). EPO has also been used in pregnant females with a high risk of toxemia to assess the effects on platelet functions (199).
  • AnticonvulsantsAnticonvulsants: In several reported cases, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs) : According to secondary sources, evening primrose may interact with antidepressants.
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs) : According to secondary sources, evening primrose may interact with antidepressants.
  • Anti-inflammatory agentsAnti-inflammatory agents: EPO has been reported to have anti-inflammatory effects (217; 218; 19; 35; 12). According to a review, anti-inflammatory drugs may interact with EPO (189). In vitro, GLA decreased interleukin-1beta (IL-1beta) release in human cells and decreased joint inflammation in individuals with rheumatoid arthritis (219). In human research, EPO decreased oleic acid, eicosapentaenoic acid, and apolipoprotein B levels and increased linoleic acid, GLA, DGLA, and arachidonic acid levels (203).
  • Antilipemic agentsAntilipemic agents: In human research, EPO affected serum lipids levels in patients with rheumatoid arthritis (203). In human research, EPO decreased, plasma cholesterol, LDL, LDL-triglycerides, LDL-phospholipids , and apolipoprotein B levels and increased HDL levels (151; 133).
  • AntineoplasticsAntineoplastics: Evening primrose oil was taken with tamoxifen in humans with evidence of benefit (220) and EPO exhibited evidence of benefit in animals in the development of mammary tumorogenesis (221); however, the potential anti-cancer effects of primrose oil are unclear. According to a review, EPO may be an empiric agent used for individuals with chemotherapy-induced neuropathy (27). In laboratory research, the combination of Oenothera paradoxa Hudziok defatted seeds extract, containing pentagalloylglucose and procyanidins, with vincristine increased cancer cell death more than vincristine alone (by greater than 4 vs. 1.5 times, respectively) (222). In human research, EPO combined with vitamin C decreased tumor size in individuals with liver cancer and in one individual decreased serum alkaline phosphatase and gamma-glutamyl transaminase (223). In laboratory research, efficacy increased and estrogen receptor expression was limited following the combination of GLA/tamoxifen and GLA/Falsodex? in human breast cancer cells (224).
  • Antiobesity herbs and supplementsAntiobesity herbs and supplements: According to secondary sources, primrose oil may have additive effects when taken with antiobesity agents; however, evidence is lacking (225; 184). In human research, EPO increased weight (135; 123; 116; 143).
  • AntioxidantsAntioxidants: According to a review, EPO seeds contain antioxidative properties (230). In human research, Cholactiv?, a botanical combination product, decreased C-reactive protein, malondialdehyde, and superoxide dismutase levels (231).
  • Antipsychotic agentsAntipsychotic agents: According to a review, antipsychotics may interact with EPO (189). According to case reports, seizures have been reported following the combination of EPO and phenothiazine neuroleptics (103; 104).
  • AntiviralsAntivirals: According to a review, primrose may have additive effects when taken concomitantly with antivirals (226).
  • CNS depressantsCNS depressants: In several reported cases, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189). According to case reports of seizures (103; 104), it has been hypothesized that EPO may lower seizure threshold.
  • CNS stimulantsCNS stimulants: In several reported cases, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189). According to case reports of seizures (103; 104), it has been hypothesized that EPO may lower seizure threshold.
  • COX inhibitorsCOX inhibitors: In animal research, EPO decreased collagen-induced thrombocytopenia and platelet aggregation following celecoxib administration (113).
  • Cytochrome P450 metabolized herbs and supplementsCytochrome P450 metabolized herbs and supplements: In vitro, cis-linoleic acid, a constituent of EPO, inhibited cDNA human P450 isoforms (227). According to secondary sources, EPO may interact with cytochrome P450 2D6 inhibitors.
  • Dermatologic agentsDermatologic agents: In human research, dermatologic complaints, such as cellulitis, itchy and fatty skin (123), acne (123; 158), skin rash (158; 29), and skin reactions (138) were reported following EPO supplementation. Conversely, EPO has been used orally and topically to treat atopic dermatitis (155; 228; 229).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: According to experts, EPO may induce nausea and stool softening; however, it is unclear whether these effects were observed in clinical or animal studies (14). Gastrointestinal complaints, including abdominal pain, nausea, belching, vomiting, diarrhea, acidity, bloating, gas, dyspepsia, pain, fullness, and loose stools have been reported in clinical studies and reviews (29; 178; 123; 187; 158; 110; 188; 189; 190; 126; 191; 154; 164; 115; 14; 172; 130; 11; 16; 146; 166).
  • Hyperglycemics and hypoglycemicsHyperglycemics and hypoglycemics: Animal studies (211; 212; 213) and controlled human trials (214; 128; 215; 24) have demonstrated beneficial effects of evening primrose oil (EPO) (29) on serum markers in diabetes mellitus, including prostaglandin levels and serum fatty acids. Changes in hemoglobin A1C were lacking. In animal research, nerve conduction velocity and blood flow responses increased 10-fold following EPO and aldose reductase inhibitor combination (202). In animal research, an increase in diabetes-induced type I nitric oxide synthase activity was completely avoided in the ileum in streptozotocin-diabetic rats receiving GLA dietary supplements (216).
  • Hypertensives and hypotensivesHypertensives and hypotensives: In animal research, gamma-linolenic acid decreased central venous blood pressure in both normotensive and hypertensive animals (106; 107; 108; 109; 110). In animal research, EPO decreased blood pressure elevated following celecoxib administration (113). Preliminary human evidence is equivocal, with some data suggesting a blood pressure-lowering effect in humans (184), and other data suggesting the lack of an effect on blood pressure (185). According to reviews, EPO may interact with beta-blockers (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: In human research, EPO may interact with neurologic agents, including anticonvulsants (103; 104), antidepressants, phenothiazine neuroleptics, and CNS stimulants. Cases of dizziness (158) and headache have been reported in reviews and clinical trials (29; 188; 189; 115; 110; 11; 16; 14; 24; 191; 187; 166; 162).
  • Seizure threshold-lowering agentsSeizure threshold-lowering agents: In several reported cases, EPO caused seizures (110) and altered seizure threshold in humans (191; 188; 210); however, there is mixed evidence of EPO lowering the seizure threshold (192) and the association of EPO with seizures (105). According to a review, epileptogenic agents are possible theoretical interactions with EPO (189). According to case reports of seizures (103; 104), it has been hypothesized that EPO may lower seizure threshold.
  • ThymeThyme: EPO has been used concomitantly with thyme in a fixed combination of thyme fluid extract and primrose root tincture (Bronchicum? Tropfen) and thyme-primrose nonalcoholic extract (Bronchicum? Elixir S) have been used in trials with evidence of benefit (1; 2). Headache was reported in one clinical trial using a combination product of thyme-primrose (N=1 of 189) (1).
  • Vitamin CVitamin C: In animal research, GLA combined with ascorbate increased GLA effects (202). In human research, EPO combined with vitamin C decreased tumor size in individuals with liver cancer and in one individual decreased serum alkaline phosphatase and gamma-glutamyl transaminase (223).
  • ZincZinc: Individuals receiving Efamol? displayed benefit in response to zinc with borderline zinc patients vs. those that were zinc-adequate and zinc-deficient (232). In animal research, zinc-adequate and zinc-deficient pregnant rats received EPO subcutaneously for the duration of the gestation and three days post-partum. Three day-old nursing pups received zinc-65 intragastrically, and the amount of total zinc four hours after injection, post-sacrifice, was significantly higher in nursed pups of zinc-adequate and zinc-deficient mothers who received EPO (233).

    • Evening primrose oil/Food Interactions:

  • Vitamin C containing foodsVitamin C containing foods: In animal research, GLA combined with ascorbate increased GLA effects (202). In human research, EPO combined with vitamin C decreased tumor size in individuals with liver cancer and in one individual decreased serum alkaline phosphatase and gamma-glutamyl transaminase (223).

    • Evening primrose oil/Lab Interactions:

  • Alkaline phosphataseAlkaline phosphatase: In human research, EPO combined with vitamin C decreased serum alkaline phosphatase (223).
  • Alpha-adrenic acidAlpha-adrenic acid: In human research, EPO increased the percentage of alpha-adrenic acid (22:4; n-6) in the corpuscular phase after 60 days of treatment (168).
  • Alpha-linolenic acidAlpha-linolenic acid: In human research, EPO decreased the percentage of alpha-linolenic acid (18:3; n-3) in the follicular phase after 30 days of treatment (168).
  • Alpha-tocopherolAlpha-tocopherol: In human research, EPO increased alpha-tocopherol plasma concentration (234).
  • Apolipoprotein BApolipoprotein B: In human research, EPO decreased apolipoprotein B levels (203).
  • Arachidonic acidArachidonic acid: In human research, EPO increased DGLA levels (235; 203), although lacked an effect on arachidonic acid (235). In other human research, EPO increased arachidonic acid (236; 203).
  • Blood pressureBlood pressure: In animal research, gamma-linolenic acid decreased central venous blood pressure in both normotensive and hypertensive animals (106; 107; 108; 109; 110). In animal research, EPO decreased blood pressure elevated following celecoxib administration (113). Preliminary human evidence is equivocal, with some data suggesting a blood pressure-lowering effect in humans (184), and other data suggesting a lack of effect on blood pressure (185). According to reviews, EPO may interact with beta-blockers (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14).
  • Bone markersBone markers: In human research, EPO plus fish oil increased levels of osteocalcin and procollagen (237).
  • ChlorideChloride: In human research, EPO lacked an effect on chloride mean intake, urinary excretion, fecal excretion, and balances (238) and in individuals with cystic fibrosis lacked an effect on sweat chloride concentrations (239).
  • Coagulation panelCoagulation panel: In human and animal research, platelet aggregation was decreased following consumption of EPO (112), although effects on platelet function were lacking in other human research (206; 207; 208). In vitro, dihomo-GLA inhibited platelet aggregation (112). In vitro and in vivo animal research also resulted in inhibited platelet aggregation secondary to EPO (112). In human research, platelet adhesiveness was reported (114). In vivo, dietary intake of the polyunsaturated omega-6 essential fatty acids (EFAs), linolenic, and gamma-linolenic acids (GLA) increased bleeding time in humans and rats (111). In animal research, EPO decreased collagen-induced thrombocytopenia and platelet aggregation following celecoxib administration (113). According to reviews, anticoagulants may interact with EPO (189; 69); however, it is unclear if these interactions were observed in clinical trials or animal studies (14). Healthy, non-pregnant females receiving a combination of low dose aspirin and EPO had a non-significant decrease in platelet angiotensin II binding following one month of treatment, while those receiving EPO alone lacked an effect (209). EPO has also been used in pregnant females with a high risk of toxemia to assess the effects on platelet functions (199).
  • Dihomo-gamma-linolenic acid (DGLA)Dihomo-gamma-linolenic acid (DGLA): In human research, EPO increased DGLA proportion in plasma phospholipids (234), and DGLA levels elevated in plasma lipid esters and platelet phospholipids (206). In human research, EPO increased DGLA levels (240; 235; 203; 141; 144). In human research, DGLA concentration decreased and arachidonic acid increased following EPO administration (236).
  • Eicosapentaenoic acidEicosapentaenoic acid: In human research, EPO decreased eicosapentaenoic acid (203).
  • Gamma-glutamyl transaminaseGamma-glutamyl transaminase: In human research, EPO (145) and EPO combined with vitamin C (223) decreased gamma-glutamyl transaminase (GGT).
  • Gamma-interferonGamma-interferon: In human research, EPO increased serum gamma-interferon levels (154).
  • Gamma-linolenic acid (GLA)Gamma-linolenic acid (GLA): In human research, EPO increased GLA levels (203).
  • Immunoglobulin E (IgE)Immunoglobulin E (IgE): In human research, EPO decreased IgE levels (154).
  • Interleukin-1betaInterleukin-1beta: In vitro, GLA decreased interleukin-1beta (IL-1beta) release in human cells and decreased joint inflammation in individuals with rheumatoid arthritis (219).
  • Linoleic acidLinoleic acid: In human research, EPO increased linoleic acid levels (203).
  • Lipid panelLipid panel: In human research, EPO reduced levels of plasma cholesterol, TC, TG, LDL-triglycerides, LDL-phospholipids, beta-lipoprotein, and apolipoprotein B, and increased levels of HDL (133; 114; 166; 241; 242).
  • Oleic acidOleic acid: In human research, EPO decreased the percentage of oleic acid (18:1) in the follicular phase after 60 days of treatment (168). In human research, EPO decreased oleic acid levels (203).
  • Palmitic acidPalmitic acid: In human research, EPO increased the percentage of palmitic acid (16:0) in the plasma after 30 days of treatment (168).
  • PotassiumPotassium: In human research, EPO lacked an effect on potassium mean intake, urinary excretion, fecal excretion, and balances (238).
  • ProstaglandinsProstaglandins: In human research, EPO decreased PGE2 and increased concentration of 6-keto-prostaglandin F1 alpha and thomboxane B2; however, effects also were also demonstrated in the control group and significant between-group differences were lacking (173).
  • SodiumSodium: In human research, EPO lacked an effect on sodium mean intake, urinary excretion, fecal excretion, and balances (238), and individuals with cystic fibrosis had decreased sweat sodium concentrations (239).
  • Urine calciumUrine calcium: In human research, EPO decreased urine calcium levels and Tiselius risk index in healthy male individuals (43).
  • Urine citrateUrine citrate: In human research, EPO increased urine citrate levels in healthy male individuals (43).
  • Urine oxylateUrine oxylate: In human research, EPO decreased urine oxalate levels in healthy black individuals (43).
  • ZincZinc: Individuals receiving Efamol? displayed benefit in response to zinc with borderline zinc patients vs. those that were zinc-adequate and zinc-deficient (232). In animal research, zinc-adequate and zinc-deficient pregnant rats received EPO subcutaneously for the duration of the gestation and three days post-partum. Three day-old nursing pups received zinc-65 intragastrically, and the amount of total zinc four hours after injection, post-sacrifice, was significantly higher in nursed pups of zinc-adequate and zinc-deficient mothers who received EPO (233).