Effects of androstenedione-herbal supplementation on serum sex hormone concentrations in 30- to 59-year-old men.

The effectiveness of a nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogens from the ingested androgens was investigated in healthy 30- to 59-year old men. Subjects were randomly assigned to consume DION (300 mg androstenedione, 150 mg dehydroepiandrosterone, 540 mg saw palmetto, 300 mg indole-3-carbinol, 625 mg chrysin, and 750 mg Tribulus terrestris per day; n = 28) or placebo (n = 27) for 28 days. Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured before and throughout the 4-week supplementation period. Serum concentrations of total testosterone and PSA were unchanged by supplementation. DION increased (p < 0.05) serum androstenedione (342%), free testosterone (38%), dihydrotestosterone (71%), and estradiol (103%) concentrations. Serum HDL-C concentrations were reduced by 5.0 mg/dL in DION (p < 0.05). Increases in serum free testosterone (r2 = 0.01), androstenedione (r2 = 0.01), dihydrotestosterone (r2 = 0.03), or estradiol (r2 = 0.07) concentrations in DION were not related to age. While the ingestion of androstenedione combined with herbal products increased serum free testosterone concentrations in older men, these herbal products did not prevent the conversion of ingested androstenedione to estradiol and dihydrotestosterone.

Endocrine and lipid responses to chronic androstenediol-herbal supplementation in 30 to 58 year old men.

OBJECTIVE: The effectiveness of an androgenic nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogen was investigated in healthy 3 to 58 year old men. DESIGN: Subjects were randomly assigned to consume a nutritional supplement (AND-HB) containing 300-mg androstenediol, 480-mg saw palmetto, 450-mg indole-3-carbinol, 300-mg chrysin, 1,500 mg gamma-linolenic acid and 1.350-mg Tribulus terrestris per day (n = 28), or placebo (n = 27) for 28 days. Subjects were stratified into age groups to represent the fourth (30 year olds, n = 20), fifth (40 year olds, n = 20) and sixth (50 year olds, n = 16) decades of life. MEASUREMENTS: Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate specific antigen and lipid concentrations were measured before supplementation and weekly for four weeks. RESULTS: Basal serum total testosterone, estradiol, and prostate specific antigen (PSA) concentrations were not different between age groups. Basal serum free testosterone concentrations were higher (p < 0.05) in the 30- (70.5 +/- 3.6 pmol/L) than in the 50 year olds (50.8 +/- 4.5 pmol/L). Basal serum androstenedione and dihydrotestosterone (DHT) concentrations were significantly higher in the 30- (for androstenedione and DHT, respectively, 10.4 +/- 0.6 nmol/L and 2198.2 +/- 166.5 pmol/L) than in the 40- (6.8 +/- 0.5 nmol/L and 1736.8 +/- 152.0 pmol/L) or 50 year olds (6.0 +/- 0.7 nmol/L and 1983.7 +/- 147.8 pmol/L). Basal serum hormone concentrations did not differ between the treatment groups. Serum concentrations of total testosterone and PSA were unchanged by supplementation. Ingestion of AND-HB resulted in increased (p < 0.05) serum androstenedione (174%), free testosterone (37%), DHT (57%) and estradiol (86%) throughout the four weeks. There was no relationship between the increases in serum free testosterone, androstenedione, DHT, or estradiol and age (r2 = 0.08, 0.03, 0.05 and 0.02, respectively). Serum HDL-C concentrations were reduced (p < 0.05) by 0.14 mmol/L in AND-HB. CONCLUSIONS: These data indicate that ingestion of androstenediol combined with herbal products does not prevent the formation of estradiol and dihydrotestosterone.

Engineering the prion protein using chemical synthesis.

In recent years, the technology of solid-phase peptide synthesis (SPPS) has improved to the extent that chemical synthesis of small proteins may be a viable complementary strategy to recombinant expression. We have prepared several modified and wild-type prion protein (PrP) polypeptides, of up to 112 residues, that demonstrate the flexibility of a chemical approach to protein synthesis. The principal event in prion disease is the conformational change of the normal, alpha-helical cellular protein (PrPc) into a beta-sheet-rich pathogenic isoform (PrP(Sc)). The ability to form PrP(Sc) in transgenic mice is retained by a 106 residue 'mini-prion' (PrP106), with the deletions 23-88 and 141-176. Synthetic PrP106 (sPrP106) and a His-tagged analog (sPrP106HT) have been prepared successfully using a highly optimized Fmoc chemical methodology involving DCC/HOBt activation and an efficient capping procedure with N-(2-chlorobenzyloxycarbonyloxy) succinimide. A single reversed-phase purification step gave homogeneous protein, in excellent yield. With respect to its conformational and aggregational properties and its response to proteinase digestion, sPrP106 was indistinguishable from its recombinant analog (rPrP106). Certain sequences that proved to be more difficult to synthesize using the Fmoc approach, such as bovine (Bo) PrP(90-200), were successfully prepared using a combination of the highly activated coupling reagent HATU and t-Boc chemistry. To mimic the glycosylphosphatidyl inositol (GPI) anchor and target sPrP to cholesterol-rich domains on the cell surface, where the conversion of PrPc is believed to occur, a lipophilic group or biotin, was added to an orthogonally side-chain-protected Lys residue at the C-terminus of sPrP sequences. These groups enabled sPrP to be immobilized on either the cell surface or a streptavidin-coated ELISA plate, respectively, in an orientation analogous to that of membrane-bound, GPI-anchored PrPc. The chemical manipulation of such biologically relevant forms of PrP by the introduction of point mutations or groups that mimic post-translational modifications should enhance our understanding of the processes that cause prion diseases and may lead to the chemical synthesis of an infectious agent.

Endocrine responses to chronic androstenedione intake in 30- to 56-year-old men.

In young men, chronic ingestion of 100 mg androstenedione (ASD), three times per day, does not increase serum total testosterone but does increase serum estrogen and ASD concentrations. We investigated the effects of ASD ingestion in healthy 30- to 56-yr-old men. In a double-blind, randomly assigned manner, subjects consumed 100 mg ASD three times daily (n = 28), or placebo (n = 27) for 28 days. Serum ASD, dihydrotestosterone (DHT), free and total testosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured at week 0 and each week throughout the supplementation period. Serum total testosterone and PSA concentrations did not change with supplementation. Elevated serum concentrations of ASD (300%), free testosterone (45%), DHT (83%), and estradiol (68%) were observed during weeks 1-4 in ASD (P < 0.05). There was no relationship between age and changes in serum ASD (r2 = 0.024), free testosterone (r2 = 0.00), or estradiol (r2 = 0.029) concentrations with ASD, whereas the serum DHT response to ASD ingestion was related to age (r2 = 0.244; P < 0.05). Serum concentrations of high-density lipoprotein cholesterol were decreased by 10% during the supplementation period (P < 0.05). These results suggest that the ingestion of 100 mg ASD, three times per day, does not increase serum total testosterone or PSA concentrations but does elicit increases in ASD, free testosterone, estradiol, and DHT and decreases serum high-density lipoprotein cholesterol concentrations.

Effects of anabolic precursors on serum testosterone concentrations and adaptations to resistance training in young men.

The effects of androgen precursors, combined with herbal extracts designed to enhance testosterone formation and reduce conversion of androgens to estrogens was studied in young men. Subjects performed 3 days of resistance training per week for 8 weeks. Each day during Weeks 1, 2, 4, 5, 7, and 8, subjects consumed either placebo (PL; n = 10) or a supplement (ANDRO-6; n = 10), which contained daily doses of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto. Serum androstenedione concentrations were higher in ANDRO-6 after 2, 5, and 8 weeks (p <.05), while serum concentrations of free and total testosterone were unchanged in both groups. Serum estradiol was elevated at Weeks 2, 5, and 8 in ANDRO-6 (p <.05), and serum estrone was elevated at Weeks 5 and 8 (p <.05). Muscle strength increased (p <.05) similarly from Weeks 0 to 4, and again from Weeks 4 to 8 in both treatment groups. The acute effect of one third of the daily dose of ANDRO-6 and PL was studied in 10 men (23 +/- 4 years). Serum androstenedione concentrations were elevated (p <.05) in ANDRO-6 from 150 to 360 min after ingestion, while serum free or total testosterone concentrations were unchanged. These data provide evidence that the addition of these herbal extracts to androstenedione does not result in increased serum testosterone concentrations, reduce the estrogenic effect of androstenedione, and does not augment the adaptations to resistance training.

Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men.

This study examined the effects of acute dehydroepiandrosterone (DHEA) ingestion on serum steroid hormones and the effect of chronic DHEA intake on the adaptations to resistance training. In 10 young men (23 +/- 4 yr old), ingestion of 50 mg of DHEA increased serum androstenedione concentrations 150% within 60 min (P < 0.05) but did not affect serum testosterone and estrogen concentrations. An additional 19 men (23 +/- 1 yr old) participated in an 8-wk whole body resistance-training program and ingested DHEA (150 mg/day, n = 9) or placebo (n = 10) during weeks 1, 2, 4, 5, 7, and 8. Serum androstenedione concentrations were significantly (P < 0.05) increased in the DHEA-treated group after 2 and 5 wk. Serum concentrations of free and total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases were unaffected by supplementation and training, while strength and lean body mass increased significantly and similarly (P < 0.05) in the men treated with placebo and DHEA. These results suggest that DHEA ingestion does not enhance serum testosterone concentrations or adaptations associated with resistance training in young men.

Central nervous system infections. Basic concepts.

Central nervous system infections have the potential to be very dangerous and life-threatening. Advances in the understanding and care of patients experiencing these infections have aided in their detection and treatment. Caring for these patients requires a thorough knowledge of the diseases as well as a holistic approach which encompasses the patient and family.

Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial.

CONTEXT: Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known. OBJECTIVES: To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function. DESIGN AND SETTING: Eight-week randomized controlled trial conducted between February and June 1998. PARTICIPANTS: Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training. INTERVENTIONS: Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n = 10), or placebo (n = 10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men. MAIN OUTCOME MEASURES: Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration. RESULTS: Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation. CONCLUSIONS: Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.

Effects of a low-dose amino acid supplement on adaptations to cycling training in untrained individuals.

The purpose of this study was to determine if amino acid supplementation influences blood and muscle lactate response to exercise and the time course of the metabolic adaptations to training. Two groups of untrained males (n = 7 each) were given (double-blind) a daily supplement (2.9 g.day-1) containing a mixture of leucine, isoleucine, valine, glutamine, and carnitine (EXP) or 3 g.day-1 of lactose (CON). Following 7 days of supplementation there was no significant change in VO2peak, time to exhaustion (TTX) at 120% VO2peak, or muscle and blood lactate in either EXP or CON. Subjects then initiated 6 weeks of combined aerobic and anaerobic training on a Monark cycle ergometer. It was found that amino acid supplementation had no effect on either blood or muscle lactate accumulation during exercise, while supplementation resulted in a faster adaptation in buffer capacity. Performance during intense exercise was not improved with amino acid supplementation.

Type II fiber activation with electrical stimulation: a preliminary report.

Electrical stimulation to augment or maintain muscle performance has been well documented. The purpose of this preliminary report is to present the results of a single-case study conducted to determine the order of activation of skeletal muscle fibers as a result of electrical stimulation. The subject's quadriceps femoris muscles were electrically stimulated at 80% of maximal isometric torque. Pre-stimulation and immediate post-stimulation muscle biopsy samples were obtained, and a modification of the glucogen-depletion method was used to determine activation of muscle fibers. The pre-stimulation muscle biopsy sample demonstrated uniform periodic acid-Schiff (PAS)-positive staining in all fiber types, whereas the post-stimulation muscle biopsy sample showed glycogen depletion of type II muscle fibers. The most PAS-negative muscle fibers were type IIa skeletal muscle fibers. The results of this single-case study provide evidence that electrical stimulation, as described, selectively activates type II skeletal muscle fibers. The implication of this finding is that, in many chronic diseases, type II fibers are selectively and preferentially affected. Electrical stimulation may be a clinically viable technique to use in patients with type II fiber involvement.