Lack of effects of beta-carotene on lipids and sex steroid hormones in hyperlipidemics.

Beta-carotene in doses of up to 300 mg daily raises high-density lipoprotein cholesterol levels within 2 to 4 weeks in healthy subjects. The authors, in this study, investigate the short-term effects of high-dose beta-carotene upon serum lipids, lipoproteins, and selected sex steroid hormones in 59 adult patients with Type IIa or IIb hyperlipidemia and 36 healthy subjects. Volunteers took beta-carotene (300 mg) or wheat germ oil capsules daily for 30 days. Lipids were measured on days 1, 14, 21, and 30. Beta-carotene, retinol, free and total testosterone, and estradiol levels were measured on days 1 and 30. Total high-density lipoprotein cholesterol levels increased 10% (p < 0.01) over baseline in all groups by day 14 but returned to baseline by day 30. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels transiently increased between days 14 and 21 by up to 9%, 8%, and 20%, respectively, only in the patients with hyperlipidemia treated with beta-carotene, but returned to baseline on day 30. Apolipoproteins A and B were unchanged. Despite 20-fold increases of plasma beta-carotene levels there, were no reports of carotenodermia and no alteration in sex steroid hormones, retinol levels, hepatic transaminases, or persistent changes in serum lipids that were attributable to beta-carotene.

Phlebotomy of 500 or 750 milliliters of whole blood followed by isovolemic hemodilution or autologous transfusion yields similar hemodynamic, hematologic, and biochemical effects.

The purpose of this study was to evaluate the effects of phlebotomy of 500 or 750 ml of whole blood followed by isovolemic hemodilution or autologous transfusion on hemodynamic, hematologic, and biochemical parameters in healthy subjects. Four groups of normovolemic male subjects (n = 6 or 7 per group), aged 18 to 41 years, participated in this 10-day study at Upjohn Research Clinics, Kalamazoo, Mich. On day 1 two groups had phlebotomy of 500 ml; of these, one group underwent immediate postphlebotomy autologous transfusion (group 1) and the other underwent immediate postphlebotomy isovolemic hemodilution and then autologous transfusion on day 3 (group 2). Two other groups had 750 ml phlebotomy, also on day 1; of these, one group underwent immediate postphlebotomy autologous transfusion (group 3) and one underwent immediate postphlebotomy isovolemic hemodilution followed by autologous transfusion on day 3 (group 4). Noninvasive measurement of vital signs, blood pressure, and cardiac function; oximetry; and select hematologic and biochemical parameters were made. On day 1 in groups 2 and 4 transient reductions in hematocrit, hemoglobin, red blood cell count, fibrinogen, and albumin were seen concurrent with prolongation of coagulation studies. Erythropoietin was increased severalfold on day 3 (groups 2 and 4, p < 0.001). The physiologic response to phlebotomy of 500 or 750 ml was similar and was well tolerated in normal subjects.

Effects of fish oil and endorphins on the cold pressor test in hypertension.

The effects of fish oil and naloxone on blood pressure, catecholamines, and endorphins during the cold pressor test were evaluated in a randomized, double-blind, placebo-controlled, two-way crossover trial of normotensive and medication-free hypertensive men (n = 13 each). Subjects were given 5 gm omega-3 fatty acids per day or placebo for 30 days with a 1-month washout between interventions. The cold pressor test (hand in ice water for 5 minutes) was done at the end of the treatment periods. Intravenous naloxone (10 mg) or placebo was given before the cold pressor test. Fish oil-treated, normotensive, or hypertensive groups had similar changes in blood pressure, plasma catecholamine levels, and beta-endorphins during the cold pressor test, but naloxone treatment was associated with fivefold and tenfold increases in plasma epinephrine and cortisol levels, respectively. Naloxone may modulate sympathomedullary discharge through blockade of endorphin activity. It is unlikely that endorphins are involved in the blood pressure increase during the cold pressor test or that fish oil alters this response.

Fish oil produces an atherogenic lipid profile in hypertensive men.

The effects of fish oil supplements on plasma and platelet membrane lipids, lipoproteins, sex steroid hormones, glucose, insulin, platelet aggregation, and blood pressure in normal subjects (n = 13) and patients with essential hypertension (n = 13) were studied in this randomized, double-blind, placebo-controlled, two-way crossover study. Treatments consisted of 30 days of 5 g of n-3 fatty acids (ten 1-g capsules of fish oil daily) or placebo capsules (ten wheat germ oil capsules daily) with a one-month washout in between each crossover. Serum lipids and lipoproteins were measured before dosing and every two weeks during the study. Sex steroid hormones, glucose, insulin, and fatty acid composition in platelet membrane phospholipids were measured before dosing and at the end of each crossover. During treatment with fish oil, only the hypertensive had increases in total cholesterol (8%, p less than 0.026), LDL cholesterol (19%, p less than 0.006) and apolipoprotein B (18%, p less than 0.026). Serum androgens (total and free testosterone) were 30% lower in hypertensives than normotensives before any dosing, but were unchanged with placebo or fish oil capsules in either group. Plasma glucose, insulin, platelet aggregation, and the incorporation of n-3 fatty acids into platelet membrane phospholipid subfractions were similar in both normotensive and hypertensive men. Blood pressure was not affected by fish oil treatment in either group of men. These results provide evidence that fish oil may adversely affect serum lipids to yield an atherogenic lipid profile in hypertensive men.

Normal vitamin D and mineral metabolism in essential hypertension.

The effects of dietary sodium upon serum and urinary calcium and selected vitamin D metabolites were studied in two groups (n = 10 each) of age and gender matched, white normotensive subjects and patients with normal-renin hypertension. Isocaloric diets were consumed on a metabolic ward with sequential daily sodium intake of 109 meq for 5 days and 9 meq and 259 meq for 6 days each. Values for serum and urinary calcium, phosphorus, magnesium and electrolytes, creatinine clearance, plasma immunoreactive parathyroid hormone, and serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were similar in both study groups on each diet. Measurements of plasma renin activity and serum aldosterone levels were higher in the hypertensive than in the normotensive group on each diet (p less than .05-.01). Serum 1,25-dihydroxyvitamin D and urinary calcium increased on the high sodium diet in the normotensive (p less than .05) and the hypertensive groups (p less than .01). When the data for normotensive subjects and hypertensive patients were pooled by gender, males had a 1 1/2 to 3 times the urinary calcium excretion than females, regardless of diet. The present study indicates that there are no differences in the selected components of calcium and vitamin D metabolism in response to sodium intake in patients with essential hypertension and normal plasma renin activity as compared to normal controls.

Response of plasma beta-endorphins to transcutaneous electrical nerve stimulation in healthy subjects.

A study of 31 healthy volunteers was done to test the hypothesis that analgesia produced by low frequency/high intensity (LoF/Hil) transcutaneous electrical nerve stimulation (TENS) is mediated by release of beta-endorphin (beta-E). After randomization, Group 1 (n = 10) received no stimulation (placebo); Group 2 (n = 9) received 30 minutes of high frequency/low intensity (HiF/Lol) TENS; and Group 3 (n = 12) received 30 minutes of low frequency/high density (LoF/Hil) TENS. Blood pressure, pulse, plasma beta-E levels, and evoked potential response were measured before and after treatment. Mean plasma beta-E increased with treatment in Groups 2 and 3 and fell in Group 1, but the difference between the groups was not statistically significant. Sixty-seven percent of Groups 2 and 3 showed an increase in plasma beta-E levels compared with 30 percent in Group 1 (two-sample test of proportions, p less than .05). Evoked potential response, a measure of pain threshold, varied directly with plasma beta-E level independent of the type of treatment applied. This study did not demonstrate a difference between the effects of HiF/Lol versus Lof/Hil TENS on plasma beta-E in healthy subjects.