Oenothera biennis is the plant commonly referred to as evening primrose, tree primrose, and sun drop. It is a member of the Onagraceae, or willow, family.  Botanically, evening primrose is a biennial plant; Characterized by an erect, rough branching stem growing 2 to 5 feet in height.  The leaves are ovate-lanceolate. The large flowers are numerous and appear in a pale-yellow in color. They are considered nocturnal plants, blooming only once and lasting for only one day. The leaves and oil of evening primrose are the parts of the plant used medicinally. However, most preparations only consist of the oil and are referred to as EPO (evening primrose oil).
In understanding how evening primrose oil works, one must first comprehend the metabolism of essential fatty acids. Essential fatty acids are termed as such because they cannot be synthesized, or are not naturally occuring, within the body and therefore must be provided for in the diet. The metabolic pathways of essential fatty acids fall into two categories, based on their chemical structures: omega-3 fatty acids and omega-6 fatty acids. Omega-3 fatty acids are commonly found in cold water fish, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
Evening primrose oil contains a fatty acid that is categorized in the omega-6 fatty acid pathway; beginning with linoleic acid. Linoleic acid is found in plants and cannot be made in the body. It is converted to gamma-linolenic acid (GLA) by the enzyme, delta-6 desaturase, which removes two hydrogen molecules effectively adding another double bond (these essential fatty acids are all polyunsaturated meaning they have more than one double bond). GLA is the fatty acid found in evening primrose oil.
Although GLA can be made in the body, in some individuals the conversion is problematic due to polymorphisms in the enzyme. Persons may also by lacking in enzyme cofactors like vitamin B6, magnesium, and zinc. Furthermore, the delta-6 desaturase enzyme can be inhibited by other compounds, such as trans fatty acids, alcohol, and saturated fats.  Therefore, it can be quite important to have a preformed source of GLA as is found in evening primrose oil.
Following either conversion or consumption of GLA, it is then metabolized to dihomo-GLA (D-GLA) by an elongase enzyme which adds two carbon units to the chain. This is an important point in the omega-6 pathway because it is then shuttled into one of two pathways:
- Prostaglandin 1 series - the most favorable. Aids GLAs conversion to arachadonic acid; which is further metabolized via the,
- Prostaglandin 2 series - or inflammatory leukotriene pathway (associated with inflammation and are unfavorable).
Interestingly, and fortunately, the enzyme that converts D-GLA to arachidonic acid is also used in the omega-3 series pathway. When there are more of these favorable omega-3 fatty and omega-6 fatty acids, like GLA in evening primrose oil, the enzyme prefers to act on the omega-3 series, which often results in D-GLA being converted to the prostaglandin 1 series (the series not associated with inflammation). The balance of dietary essential fatty acids in the body is vital to proper functioning. Imbalances can lead to a variety of disorders linked mainly to inflammation, platelet aggregation, and smooth muscle spasm. These problems can be addressed through diet and supplementation with certain omega-3 and omega-6 fatty acids, like evening primrose oil.
Constituents in evening primrose include; fixed oil (15 - 20%), 65% essential fatty acids (i.e. linoleic acid), gamma-linolenic acid (8 - 10%), and triacylglycerols (trilinolein and dilinoleoyl-mono-gamma-linolenin).[4 -6] GLA is also found in borage oil, blackcurrant oil, and even certain fungal lipids. However, most of the evidence on the medicinal uses of GLA is derived from studies using evening primrose oil.
Medicinal actions ascribed to the evening primrose oil include:
- inhibitor of platelet aggregation
- assisting in the correction of omega-6 essential fatty acid deficiency states
The leaves also possess digestive restorative and anti-inflammatory properties. [1, 2]
A clinical trial of patients with atopic dermatitis (or eczema) presenting with itchy dry scaly skin examined EPO’s effect. The results showed that supplementation with EPO reduced the extent of the skin lesions and pruritis (itching) in all patients studied. Serum interferon (IFN)-gamma levels were increased after the treatment to those of the normal control group, while serum IgE levels showed a significant decrease. The authors concluded that EPO could be a highly effective treatment for ‘grossly,’ non-inflammatory type atopic dermatitis. The effect of EPO may be through the modulation of the immunological mechanism involving IFN-gamma. 
Another double-blind, placebo-controlled clinical trial in children with atopic dermatitis supports the use of EPO. A significant improvement in the overall severity of the clinical condition, independent of whether the children had manifestations of IgE-mediated allergy was recorded. The content percentage of omega-6 fatty acids in the erythrocyte cell membrane increased, especially in the children treated with high doses of EPO. In this high dose group, dihomo-gamma-linolenic acid (D-GLA) also increased. 
It appears that EPO may also be equally beneficial for treating patients with diabetic neuropathy. In one double-blind, placebo-controlled study, 111 people with mild diabetic neuropathy received either 480 milligrams (mg) of GLA or placebo daily. After a year, the group taking GLA improved significantly in 13 of the 16 parameters measured.  Smaller study, and comparative animal research, has also found that evening primrose oil can protect nerves from diabetes-induced injury. [10-12]
Evening primrose oil has been recommended to women for treatment of symptoms associated with premenstrual syndrome. Evidence supporting this use has been conflicting, however a number of negative studies were so small that the effectiveness of EOP was difficult to rule out. A positive study demonstrated that EPO was better than placebo for treating depression and other PMS symptoms.  It appears that EPO most effectively addresses mastalgia (breast pain) associated with the menstrual cycle. In fact, in a large study of women with this symptom, EPO demonstrated an equal level of effectiveness as bromocriptine (a pharmaceutical commonly prescribed for cyclical mastalgia).  Most importantly, EPO has a very low incidence of adverse effects, unlike its prescription drug counterparts.
Additionally, EPO may be beneficial for the treatment of obesity, Raynaud’s phenomenon, schizophrenia, withdrawal from alcohol, rheumatoid arthritis, chronic fatigue syndrome, systemic lupus erythematosus, hepatic carcinoma, preeclampsia, endometriosis, and ulcerative colitis. [15-20]
Dosages are dependent on the type of preparation and the intended condition to be treated. If using the oil, a range of 250 - 500 mg of GLA (or 2.6 - 5.2 grams of EPO) daily can be an effective dose for conditions like atopic dermatitis and mastalgia. For many of the other conditions listed above (i.e. diabetic neuropathy and inflammatory diseases) a higher range of 500 - 600 mg GLA would be necessary. 
Caution must be taken in patients with a history of epilepsy. One case report described seizures in a patient using evening primrose oil capsules along with Cimicifuga racemosa and Vitex-agnus castus for four months. Evening primrose oils may also have the potential to instigate undiagnosed temporal lobe epilepsy. [21, 22]
Based on this information and the potentiation of phenothiazines, EPO should be avoided in patients with seizure disorders. There is also speculation that EPO will adversely affect those with mania, as it will increase PGE1, which is already in excess in this condition.
Evening primrose may interact with a number of prescription medications.  It may potentiate the epileptogenic potential of phenothiazines. There is also speculation that anticoagulants may be potentiated due to decreases in plasma heparin-neutralizing activity and platelet aggregation inhibition associated with PGE-1, formed from metabolism of DGLA. On the other hand, EPO may favorably affect other medications, such as administration of GLA with tamoxifen. Study has shown a faster clinical response to tamoxifen in 38 patients with estrogen-dependent breast cancer. Also, kidney damage induced by cyclosporine was reduced by the co-administration of 10 mg/kd of EPO in rats.
Adverse effects of EPO can include headache and mild nausea.  No overdose symptoms have been reported with the use of EPO. 
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