Pharmacological Toxicological Effects 51 Dermatological Effects

Clinical evidence of nutritional supplementation with OEP to correct dermal conditions is mixed. One theory for the mixed results is that in some persons, once sensitized, immunological factors may override what help OEP can offer. Very high doses of OEP or linoleic acid, or modest doses of y-linolenic acid, with corresponding correction of plasma EFA levels, produce some clinical improvement (8).

A defect in the capability of the enzyme 8-6-desaturase to convert linoleic acid to y-linolenic acid is known to occur in patients with atopic dermatitis (9). Patients with atopic eczema have a dietary deficiency in metabolites of linoleic: y-linolenic acid, dihomo-y-linolenic acid, arachi-donic acid, adrenic acid, and docosapentaenoic acid caused by a reduced rate of activity in the 8-6-desturase enzyme (8). Galli et al. compared blood samples from babies born to parents who suffered from atopic eczema. Results showed that dihomo-y-linolenic acid and arachidonic acid were consistently and significantly lower in children who later had atopic eczema (10).

Some studies have shown that OEP administration can improve the percentage of body surface involvement, itch, dryness, scaling, and inflammation associated with atopic eczema. A meta-analysis (11) of nine controlled trials involving OEP in the treatment of atopic eczema showed a highly significant improvement in the symptom of itch over placebo (p < 0.0001). In 1993, Berth-Jones et al. conducted a randomized, double-blind, parallel-group-designed study to investigate whether supplementation with OEP alone or a combination of OEP and fish oil helped with clinical symptoms of atopic dermatitis. A total of 133 patients (adults and children were evenly distributed) with chronic hand dermatitis enrolled and were randomized to receive either Epogam® (per 500 mg capsule of OEP [321 mg linoleic acid and 40 mg y-linolenic acid]), Efamol Marine (per 430 mg capsule of OEP/fish oil [17 mg eicosapentaenoic acid and 11 mg docosahexaenoic acid]), or placebo (paraffin/olive oil). No improvement with OEP was found (12).

In 1996, Whitaker et al. conducted a clinical trial to test if OEP supplementation affected the changes in lamellar bodies and lipid layers of the stratum corneum in patients with chronic (longer than 12 months) hand dermatitis. This parallel, double-blind, placebo-controlled trial had 39 patients with chronic hand dermatitis or eczema and 10 age- and sex-matched healthy controls for statistical comparison. Treatment lasted for 16 weeks, with the active group taking OEP (twelve 500-mg Epogam capsules daily for a total dose of 600 mg y-linolenic acid) and the placebo group taking placebo (twelve 500-mg sunflower capsules daily), after which there was an 8-week washout period. Although the Epogam group improved in the clinical impressions of dermatitis, there was no statistical difference between groups and no structural change in skin specimens was seen (13).

5.2. Anti-Inflammatory Effects

Increased concentrations of eicosanoids (leukotriene B4, prostaglandin E2 [PGE2] and thromboxane A2) have been reported to exist in the colon mucosa and rectal areas of patients with ulcerative colitis (14). In 1993, a randomized, placebo-controlled study was conducted by Greenfield et al. examining the effect of OEP and fish oil supplementation on cell membranes and symptom control in 43 patients diagnosed with stable ulcerative colitis. Treatment with OEP increased red-cell membrane concentrations of dihomo-y-linolenic acid by 40% at 6 months (p < 0.05), and compared to MaxEPA® and placebo, OEP significantly improved stool consistency at 6 months, with this difference being maintained 3 months after OEP treatment was discontinued (p < 0.05). There was no difference in stool frequency, rectal bleeding, relapse rates, sigmoidoscopic findings between the three groups. OEP appeared to be of minimum benefit over placebo and fish oils (14).

5.3. Autoimmune

In a randomized, double-blind, placebo-controlled, three-arm, parallel study that used OEP treatment, 49 adult participants with a diagnosis of rheumatoid arthritis that required nonsteroidal anti-inflammatory medication (NSAID) but not second-line therapy were included. Treatment groups consisted of the control group (liquid paraffin placebo), OEP group (OEP daily dose containing 540 mg y-linolenic acid), and OEP/fish oil group (dose not recorded). At 12 months, both active treatment groups reported significant subjective improvement compared to the placebo group and had significantly reduced their NSAID use. However, at 15 months, both treatment groups had relapsed. There was no evidence that OEP or OEP with fish oil had modified the disease process in any way. The reviewers stated that insufficient data was given by the study (15,16).

Researchers conducted a 6-month, double-blind, placebo-controlled study involving 40 patients (male and female) with rheumatoid arthritis and upper gastrointestinal lesions caused by NSAIDs (17). For 6 months, 19 patients (17 females and 2 males) received 6 g of OEP daily (total daily dose of y-linolenic acid 540 mg) and 21 patients (15 females and 6 males) received 6 g of olive oil daily. The results of this study found that there was a significant reduction in morning stiffness after 3 months. No patient was able to stop NSAID medication after completing OEP treatment and only 23 percent of patients could reduce their dose. These results were similar to that of the placebo (olive oil) group. Jantti et al. examined the effect of OEP on clinical symptoms and plasma prostaglandin levels of patients with rheumatoid arthritis. Study results showed that plasma concentrations of PGE2 decreased and thromboxane B2 increased in both groups in addition to no clinical benefits reported (18). Other experimental studies have also concluded that oral OEP has no general therapeutic effect in patients with rheumatoid arthritis.

Manthorpe et al. examined the effect of OEP supplementation on lacrimal gland function in patients with primary Sjogren's syndrome using a doubleblind, crossover design. The active treatment group received the following twice daily: Efamol (1500 mg [9% y-linolenic acid, 73% as-linoleic acid]), Efavit® (375 mg vitamin C, 75 mg pyridoxine, 75 mg niacin, 15 mg zinc sulfate), and vitamin E (40.8 IU). The control group received the same num ber of placebo capsules and directions. Study results were mixed, with benefit seen in the lacrimal film function (Schirmer's I-test, p < 0.03) and nonsignificant findings for the remaining outcome measures. Because of the vitamins given with the OEP, it is difficult to say whether the OEP was of any benefit (19). In a randomized, placebo-controlled trial by Theander et al., 90 patients diagnosed with primary Sjogren's syndrome (with or without signs of autoimmunity) were given either OEP or corn oil (placebo) for 6 months and their symptom levels recorded. Patients were evaluated at baseline, 3, and 6 months. No significant improvements were found for any of the outcomes with OEP supplementation (20).

Increased levels of arachidonic acid and 4-series leukotriene have been reported in the skin plaques of patients with psoriasis (21). OEP is rich in three fatty acids (eicosapentaenoic, y-linolenic, and docosahexaenoic acid), and eicosapentaenoic acid may help improve psoriasis by inhibiting the formation of 4-series leukotrienes by forming the 5-series leukotrienes, which are considered biologically less active than the 4-series.

In a double-blind, placebo-controlled trial by Veale et al., the effect of OEP supplementation on the improvement of psoriatic arthritis was examined in 38 patients with chronic stable plaque psoriasis and inflammatory arthritis. Results reported no changes in outcome measurements except a decrease in leukotriene B4 production during the active phase in the Efamol Marine group compared to baseline (p < 0.03) and a rebounding increase in thromboxane B2 during the group's placebo phase run-out phase. The authors suggest that the dose used in this study was sufficient to show some competition with arachidonic acid in its metabolic pathways but not high enough to show improvement in clinical outcomes (21).

5.4. Neurological System Effects

In diabetes, the 8-6-desaturation of linoleic acid into y-linolenic acid is impaired. With evidence that a high intake of linoleic acid may have some benefit in cardiovascular problems in diabetics, there are hypotheses that supplementation with products high in y-linolenic acid might benefit diabetic neuropathy. The 1993 study by the Gamma-Linolenic Acid Multicenter Trial Group specifically investigated the effects of OEP (12 capsules daily of a product identical to Epogam, 480 mg total daily dose of y-linolenic acid) on the clinical outcomes of 111 patients with mild diabetic neuropathy over 1 year using a randomized, double-blind, placebo-controlled, parallel design. Participants were evaluated at baseline, 3, 6, and 12 months. Compared to placebo, OEP supplementation improved 8 out of 10 neurophysi-

ological measures and 5 out of 6 neurological assessments (p < 0.05). The authors noted that the changes seen were of a magnitude that was clinically meaningful and consistent among the clinical, thermal, and neurophysical assessments (22). Using a double-blind, placebo-controlled study design, Jamal and Carmichael investigated the effect of 6-month OEP supplementation in clinical improvement in 22 patients with either type I or II diabetes mellitus with distal diabetic polyneuropathy. OEP (a total daily dose of 4 g containing 360 mg y-linolenic acid) was given to 12 patients, and placebo was given to 10. Compared with the placebo group, the OEP group showed statistically significant improvement (p < 0.05) in neuropathy symptom scores, median nerve motor conduction velocity/compound muscle action/potential amplitude, peroneal nerve motor conduction velocity/compound muscle action/ potential amplitude, median sensory nerve action potential amplitude, ankle heat threshold, and cold threshold (23).

Two major controlled trials have examined supplementation of OEP and its effect on attention-deficit/hyperactivity disorder (ADHD) with mixed results. In a double-blind, placebo-controlled, crossover study, Aman et al. examined the effect of OEP supplementation on ADHD in 31 children with ADHD (4 girls, 27 boys). A total of 26 children (mean age of 9 years [age range not reported]) fulfilled the following inclusion criteria: 90th percentile or greater scores on both the Attention Problem subscale III of the Revised Behavior Problem Checklist and the Inattention subscale II of the Teacher Questionnaire (24,25). Each child received either OEP supplementation (6 Efamol capsules daily containing a total daily content of 2.16 g linoleic acid and 270 mg y-linolenic acid) or placebo (500 mg liquid paraffin) for 4 weeks each, then switched to the other treatment with a 1-week washout period between crossovers. When the experiment-wise probability level was set at 0.05, the authors concluded that OEP supplementation showed no effect in hyperactive children (26). In the second trial, Arnold et al. compared rf-amphet-amine to OEP treatments using a double-blind, placebo-controlled, crossover treatment of 18 boys suffering from ADHD. Outcomes were parent and teacher ratings using standardized hyperactivity scales at screening, baseline, and every 2 weeks during the 3-month study period. Parent ratings showed no effect regarding OEP treatment. Teachers' ratings showed a trend of OEP effect between placebo and rf-amphetamine with the only statistically significance (p < 0.05) demonstrated on the Conners Hyperactivity Factor (27).

Only one double-blind, crossover study has been conducted to examine the effect of OEP supplementation in 13 patients (8 men, 5 women) diagnosed with schizophrenia. Active treatment (4 g OEP, 40 mg vitamin E, 1000

mg vitamin C, 200 mg vitamin B6, 300 mg vitamin B3, and 40 mg zinc sulfate) lasted 4 months, with a 2-month washout period before crossing over to placebo treatment (content not described) for 4 months. Nonsignificant results were obtained when comparing mean scores during the active and placebo treatment periods (28).

5.5. Endocrine System Effects

Because levels of y-linolenic acid are lower in women with PMS compared to non-PMS women (29), it is thought that a defect in converting linoleic acid to y-linolenic acid may contribute to the sensitivity to normal changes in prolactin that happen during the menstrual cycle (6). Unfortunately, most studies of OEP in treatment of PMS have been open-label, nonplacebo-controlled studies. Only two small studies are considered well-designed and are summarized below. Khoo et al. examined the effect of OEP on PMS symptoms of 38 women, aged 20 to 40 years, using a randomized, double-blind, placebo-controlled, crossover study design. Treatment duration for the first phase lasted 3 cycles, after which women crossed over into the other group for the next 3 months. Active treatment was OEP supplementation (8 Efamol Vita-Glow® capsules daily, each capsule containing 72% linoleic acid, 9% y-linolenic acid, and 12% oleic acid). Content of placebo capsule was not stated. Results reported showed that over 6 months, there were no significant differences in the symptom scoring between the active and placebo groups. The authors determined that the slight improvements noted by women with moderate PMS were caused by a placebo effect (30). Collins et al. conducted a 10-month randomized, double-blind crossover trial to determine the effect of OEP supplementation in 27 women diagnosed with PMS using Diagnostic Manual of Mental Disorders, 3rd Edition, Revised criteria. All women were given placebo in the first month, which was considered the baseline month. All women with PMS received placebo in the second cycle to reduce placebo effects. For the OEP phase, total daily dose was 12 Efamol capsules (each capsule contained 4.32 g linoleic acid, 540 mg y-linolenic acid). For the placebo phase, the same number of capsules was given and contained paraffin. After starting the treatment in the third cycle, women in one group crossed over to the other group in the seventh cycle. Of the 68 women who participated, 38 completed the study. Analyses of all outcome measures showed that OEP did not improve PMS symptoms or their cyclic nature. All women had improvements in their PMS symptoms over time. The study investigators stated that this result came from a placebo or study participation effect (31).

Chenoy et al. conducted a randomized, double-blind, placebo-controlled study of 56 women that examined the effects of OEP on menopausal flushing (hot flashes). Inclusion criteria were that women had (1) suffered hot flashes at least 3 times a day, and (2) had increased follicle-stimulating hormone and luteinizing hormone levels and/or amenorrhea for at least 6 months. Baseline levels were taken for 1 month when no treatment was given. At the beginning of the second month, 6 months of treatment began with the OEP group taking 4 g of OEP daily (4 capsules twice a day, each capsule containing 500 mg of OEP with 10 mg of vitamin E) and the control group taking the same regimen of placebo capsules. Women recorded the number and severity of flushing and sweating episodes in daily diaries. Assessments were conducted at baseline, 1, 4, and 7 months. Of the 35 women who finished the study, improvements between control cycle and last treatment cycle were statistically significant for the placebo group but not for the OEP group, showing that OEP offered no benefit over placebo in treating menopausal flushing (32).

Although there has been no direct evidence, hormone imbalances (e.g., progesterone deficiency in the luteal phase, high estrogen levels or increased sensitivity to estrogen, higher-than-normal basal prolactin levels) have been associated with mastalgia (33,34). It is suggested that women with breast pain have low levels of y-linolenic acid, possibly caused by the competition from high levels of saturated fatty acids that make the woman less able to convert linoleic acid to y-linolenic acid. Another proposed mechanism suggests that OEP may help reduce pain through decreased peripheral prolactin via 1-series pros-taglandins that is made from an OEP constituent, dihomo-y-linolenic acid (34).

OEP was found to have a favorable response in 45% of patients treated at the Cardiff Mastalgia Clinic for cyclical mastalgia (33). In this study, results from clinical trials (ranging in design from randomized and placebo-controlled to open-label) of drug treatment for mastalgia were grouped and descriptively analyzed. Four drugs were compared: bromocriptine, danazole, OEP, and progestins (dydrogesterone and norethisterone). Typical doses and durations were different for each drug. The usual dose of OEP used was six capsules daily for 3 to 6 months; milligram, product name, or percent of fatty acids was not disclosed. Study results report that of the 291 women who received medications, 45% of those with cyclical mastalgia reported good responses using OEP compared to 70% using danazol. Women with noncyclical mastalgia had less impressive good responses from all the drugs (31% danazol vs 27% OEP). No statistical analyses were performed to control for study biases, so study results are suspect (33). In a later study by Wetzig, 170 women with severe mastalgia who were treated at a single clinic were followed for 3 years, with assessments performed on their responses to various medications. Sequence of drugs given depended on previous responses: vitamin B6 (50-100 mg twice daily), OEP (1 g two to three times daily), danazol (100 mg twice daily tapering to 100 mg daily when pain was controlled). In some cases, progesterone, tamoxifen, or NSAIDs were also prescribed. Results regarding the effect of OEP supplementation on mastalgia were similar to placebo (35). A more recent study by Blommers et al. examined the effect of OEP and fish oil supplementation on severe mastalgia using a randomized, double-blind, controlled design. A total of 120 women were randomly placed into four groups. Group 1 took fish oil and one control oil, group 2 took OEP and a control oil, group 3 took fish oil and OEP, and group 4 took two control oils. Duration of therapy was 6 months. Results showed that neither OEP or fish oil were better than placebo in decreasing the number of days with pain (36).

Prostaglandins may be an important factor in the cervical ripening process of labor (37). Topical or oral OEP is promoted as an agent to speed cervical ripening (38). For this particular condition, continuing OEP use is typically reevaluated after 1 week. If no cervical change is noted, the woman may choose to continue for another week or change to another ripening agent (39). A 1999 retrospective cohort study investigated the effect of oral OEP on pregnancy length, duration of labor, incidence of postdates induction, incidence of prolonged rupture of membranes, occurrence of abnormal labor patterns, and cesarean delivery in low-risk nulliparous women. The sample (54 subjects receiving OEP and 54 random controls) was drawn from records of all nulliparous women registered for care at one birth center in the northeastern region of the United States from 1991 to 1998. Results of this study showed that there were no apparent benefits from taking oral OEP with regards to reducing the incidence of adverse labor outcomes or decreasing the overall length of labor. In fact, the study reported a trend of increased incidence of birthing problems such as prolonged rupture of membranes and the need for oxytocin augmentation or vacuum extraction (37).

5.6. Cardiovascular System Effects

Low levels of linoleic acid and dihomo-y-linolenic acid may predispose coronary heart disease (6,40). For this benefit, linoleic acid needs to be converted by the enzyme 8-6-desaturase to other highly unsaturated, long-change fatty acids, such as y-linolenic acid. OEP contains both linoleic and y-lino-lenic acid, and OEP has been reported to reduce elevated serum cholesterol levels, with y-linolenic acid having a more dramatic effect of the two (6).

In 1986, Boberg et al. examined the effects of n-3 and n-6 long-chain polyunsaturated fatty acid supplementation on serum lipoproteins and platelet function in 28 adults with high triglyceride levels. Using a placebo-controlled, double-blind, crossover design, 14 adults were randomized to either Efamol supplement group (total daily dose of 4 g had a content of 2.88 g of linoleic acid and 0.36 g of y-linolenic acid) or the placebo group for 8 weeks, then switched to the other group for another 8 weeks. Another 14 adults were randomized to either MaxEPA supplement group (total daily dose of 10 g had a content of 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid) or the placebo group for 8 weeks, with the same group switching noted previously. Results showed that although OEP supplementation increased y-lino-lenic and dihomogammalinolenic acid content in plasma triglycerides and cholesterol esters, compared to placebo, no statistically significant changes were demonstrated in serum lipoprotein lipids or apolipoproteins, triglyceride levels, platelet aggregation, or plasma P-thromboglobulin levels (41). In a randomized, placebo-controlled study of healthy men aged 35 to 54 years who had low levels of dihomo-y-linolenic acid, the effect of OEP on the fatty acid composition of their adipose tissue and serum lipids was investigated. A total of 35 subjects were enrolled in the study and randomized into four groups. Group 1 (n = 9) received 10 mL OEP daily, Group 2 (n = 8) received 20 mL OEP daily, Group 3 (n = 9) received 30 mL OEP daily, and Group 4 (n = 9) received 20 mL of safflower oil daily for 4 months. Results showed that whereas 20 mL daily OEP supplementation increased adipose dihomo-y-linolenic acid levels (p < 0.01), no effects were seen on serum cholesterol, low-density lipoprotein (LDL) cholesterol, or high-density lipoprotein (HDL) cholesterol. OEP was deemed to be an ineffective cholesterol-lowering agent (40).

In a randomized, blinded, crossover study, 12 males with hyperlipidemia took 3 g of OEP daily (containing linoleic acid 2200 mg and y-linolenic acid 240 mg). After a receiving a placebo for 4 weeks, participants were randomly divided into the treatment or placebo group. For 4 months, the treatment group received OEP (total daily dose of 3 g containing 2.2 g linoleic acid and 240 mg y-linolenic acid) and placebo group received liquid paraffin. After 4 months, each group received 4 weeks of placebo (washout period) then crossed over to the alternate group for 4 more months of supplementation. Comparing blood samples taken at placebo phase and after 4 months of OEP use, serum triglyceride levels, serum cholesterol, and LDL cholesterol had decreased 48, 32, and 49%, respectively, and HDL cholesterol had increased by 22% (p < 0.01). Adenosine diphosphate- and adrenaline-induced platelet aggregation were reduced 50 and 60%, respectively, after 2 and 4 months of OEP use (p-values not reported), and platelet production of thromboxane B2 went from 26 ± 1.8

to 11.8 ± 3.8 ng/mL plasma (p < 0.001) after OEP use. Compared with placebo, after 3 or 4 months of OEP use, bleeding time increased 40% (from 6.8 ± 0.3 minutes to 12.0 ± 0.8 percent [p < 0.001]) (42).

Using a randomized, placebo-controlled design, Leng et al. examined the effect of y-linolenic acid on cholesterol and lipoprotein levels in patients with lower limb atherosclerosis. A total of 120 adults with stable intermittent claudication (ankle brachial pressure index of < 0.9 in at least one limb) were given either active treatment or placebo for 2 years. Active treatment was three capsules twice daily of polyunsaturated fatty acid (one capsule contained 280 mg y-linolenic acid and 45 mg eicosapentaenoic acid) or the same doses of placebo capsules (one capsule contained 500 mg sunflower oil) for 2 years. Of the 120 participants, 39 (65%) taking active treatment and 36 (60%) taking placebo completed the trial. Lipid concentrations and walking distance were not different between groups. However, hematocrit was higher (p < 0.01) and systolic blood pressure lower (p < 0.05) in the y-linolenic acid groups (43).

Dietary supplementation with OEP, which contains the fatty acid pros-taglandin precursors linoleic and y-linolenic acid, may enhance the synthesis of prostaglandins, which might help lower vascular sensitivity to increased levels of angiotensin II in pregnancy (44). To examine the effect that OEP supplementation has in hypertension during pregnancy, randomized, placebo-controlled studies have investigated its use in women diagnosed with preec-lampsia. Unfortunately, OEP did not lower blood pressure in women suffering from hypertension in pregnancy (44,45).

5.7. Cytotoxic Effects

Mansel et al. conducted a randomized, double-blind, placebo-controlled clinical trial in 200 women with proven recurrent breast cysts that could be aspirated and were determined to be noncancerous by mammography and biopsy. For 1 year, one group took six Efamol capsules per day (total daily OEP dose of 3 g containing 9% y-linolenic acid) and the other group took placebo. After 1 year, only 15 women had dropped out of the study (eight from the placebo group, seven from the OEP group). The overall cyst recurrence rate was 44% (46% for the placebo group, and 43% for the OEP group) and statistically nonsignificant. Cyst fluid electrolyte ratio was unremarkable. Fatty acid analysis results were not stated (46).

5.8. Miscellaneous

Chronic fatigue syndrome (CFS) is a condition in which the etiology is unclear. The illness is characterized by persistent and relapsing fatigue, and other varying symptoms throughout the body. In 2000, a critique of the litera-

ture on all randomized, controlled trials (RCTs) regarding treatment for CFS reported mixed results for OEP therapy (47). The reviewers reported two RCTs comparing OEP with placebo in patients with either a diagnosis of postviral fatigue syndrome or CFS.

In the first double-blind, randomized, placebo-controlled study, Behan et al. examined the physical and psychological effects of high doses of OEP/ fish oil supplementation on 63 adults (27 men, 36 women) with postviral fatigue syndrome. Participants were randomly assigned to placebo group (liquid paraffin containing a total daily dose of 400 mg linoleic acid and 80 IU of vitamin E) or treatment group (total daily OEP/fish oil preparation [Efamol Marine] containing 288 mg y-linolenic acid, 136 mg eicosapentaenoic acid, 88 mg docosahexaenoic acid, 2.04 g linoleic acid, and 80 IU of vitamin E) for 3 months and were evaluated at baseline, 1, and 3 months. At 3 months, 85% of the OEP group showed improvement compared to 17% of the placebo group (scale of better, worse, unchanged; p < 0.0001). The EFA levels were abnormal at the baseline and were corrected in the OEP group by study end (p < 0.05) (48). The second study was a double-blind, placebo-controlled, randomized design in which Warren et al. looked at the effect of 3 months of OEP supplementation on physical and psychological outcome measures of 50 patients (21 men, 29 women) who were diagnosed with CFS using the Oxford Criteria. Patients were randomized into the placebo group (sunflower oil) or treatment group (eight Efamol Marine 500 mg daily, which contained, in the OEP and fish oil components, a total daily dose of 288 mg y-linolenic acid, 136 mg eicosapentanoic acid, 88 mg of docosahexanoic acid, and 2.04 g of linoleic acid) or placebo group (sunflower oil). At the end of the 3 months, seven participants from the treatment group and five from the placebo group had quit the study because of lack of clinical response. Results showed that although both physical and psychological symptoms improved with time, the differences before and after treatment between groups were not statistically significant (49).

Khan et al. examined the effects of n-3 and n-6 fatty acid supplements (two of which contained OEP) on the microvascular blood flow and endothelial function in 173 healthy men and women aged 40 to 65 years in an 8-month, double-blind, randomized, placebo-controlled study. For the single OEP supplementation, the group received a total daily OEP of 5 g (which contained 400 mg/day of y-linolenic acid). For the tuna oil/OEP supplementation, the group received a total daily tuna oil of 5 g (which contained 6% of eicosapentaenoic acid and 27% of docosahexaenoic acid per day) and OEP of 5 g. Results showed that there although there were significant improvements in the tuna oil supplementation group, there were no significant changes in any of the outcome measures with either single OEP or tuna oil/OEP supplementation group (50).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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