Dose-dependent response of serum lutein and macular pigment optical density to supplementation with lutein esters

We conducted a study to determine the effect of different doses of a lutein supplement on serum lutein concentration and macular pigment optical density (MPOD). Lutein is one of the major components of human macular pigment. Eighty-seven subjects received daily doses of 5, 10, or 20 mg of lutein, or a placebo, over a 140 day period. Serum lutein concentration was determined by HPLC and MPOD by heterochromatic flicker photometry (HFP). Serum lutein responded positively, except in the placebo group, reaching a plateau that, averaged for each dosage group, was linearly dependent on dose. Likewise MPOD, on average, increased at a rate that varied linearly with dose. For subjects deemed more proficient at HFP, approximately 29% of the variability in MPOD response could be attributed to a linear dependence on the fractional change in serum lutein concentration. We did not detect any significant influence of age on serum lutein uptake or MPOD response.     

Supplementation with lutein or lutein plus green tea extracts does not change oxidative stress in adequately nourished older adults

Epigallocatechin gallate, a major component of green tea polyphenols, protects against the oxidation of fat-soluble antioxidants including lutein. The current study determined the effect of a relatively high but a dietary achievable dose of lutein or lutein plus green tea extract on antioxidant status. Healthy subjects (50–70 years) were randomly assigned to one of two groups (n=20 in each group): (1) a lutein (12 mg/day) supplemented group or (2) a lutein (12 mg/day) plus green tea extract (200 mg/day) supplemented group. After 2 weeks of run-in period consuming less than two servings of lightly colored fruits and vegetables in their diet, each group was treated for 112 days while on their customary regular diets. Plasma carotenoids including lutein, tocopherols, flavanols and ascorbic acid were analyzed by HPLC-UVD and HPLC-electrochemical detector systems; total antioxidant capacity by fluorometry; lipid peroxidation by malondialdehyde using a HPLC system with a fluorescent detector and by total hydroxyoctadecadienoic acids using a GC/MS. Plasma lutein, total carotenoids and ascorbic acid concentrations of subjects in either the lutein group or the lutein plus green tea extract group were significantly increased (P<.05) at 4 weeks and throughout the 16-week study period. However, no significant changes from baseline in any biomarker of overall antioxidant activity or lipid peroxidation of the subjects were seen in either group. Our results indicate that an increase of antioxidant concentrations within a range that could readily be achieved in a healthful diet does not affect in vivo antioxidant status in normal healthy subjects when sufficient amounts of antioxidants already exist.     

Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements

Purpose

To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used.

Methods

Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured.

Results

The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. “retinal responders”, who had an increase of both MPOD levels and serum lutein concentrations (n = 13), “retinal non-responders”, who had only increased serum concentrations and no change in MPOD levels (n = 20), and “retinal and serum non-responders”, who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in contrast sensitivity.

Conclusions

No statistically significant differences could be detected for MPOD levels and serum lutein concentrations between the two investigated lutein supplement formulations. Responses to lutein supplementation regarding MPOD levels and serum lutein concentrations varied between subjects. Subjects with lower MPOD levels at baseline responded well to lutein supplementation. However, since the number of subjects was low, a further study with more subjects is needed to prove that subjects with low MPOD levels will benefit from lutein supplementation.

Trial Registration

UMIN-CTR UMIN000004593     

Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin - the LUXEA (LUtein Xanthophyll Eye Accumulation) study

The xanthophylls lutein (L) and zeaxanthin (Z) form the macular pigment with the highest density in the macula lutea. We investigated Macular Pigment Optical Density (MPOD) responses to supplementation with identically formulated (Actilease™) L or Z (OPTISHARP™) or L + Z over 6-12 months using doses of 10 or 20 mg/day. MPOD as well as blue light sensitivity in fovea and parafovea were measured monthly by heterochromatic flicker photometry. Average xanthophyll plasma concentrations, analysed monthly by HPLC, increased up to 27-fold. MPOD increased by 15% upon L or L + Z supplementation. Supplementation of Z alone produced similar pigment accumulation in fovea and parafovea, which confounded MPOD measurements. After correction for this, a 14% MPOD increase resulted for Z. Thus, during supplementation with xanthophylls, L is predominantly deposited in the fovea while Z deposition appears to cover a wider retinal area. This may be relevant to health and disease of the retina.     

Lutein bioavailability from lutein ester-fortified fermented milk: in vivo and in vitro study

We assessed the bioavailability of lutein from lutein-fortified fermented milk using in vivo and in vitro approaches. Twenty-four volunteers were randomized to take lutein-fortified fermented milk at two levels of fortification. Single-dose bioavailability study (2×100 ml, ca. 8 or 16 mg of lutein) was performed using a three-point approach (baseline, 3.5 and 6.5 h). Multiple-dose study consisted of consuming one serving/day (ca. 4 or 8 mg/100 ml) for 14 days. Blood samples for biochemical, hematological and lutein analysis were drawn at baseline, Day 7 and Day 14. In vitro bioaccessibility was assessed by a static gastrointestinal digestion model. Lutein content, in vitro ester hydrolysis and micellarization, and lutein concentrations achieved in serum were analyzed by HPLC. In vivo, post-prandial response was higher using the high content fermented milk, but the percentage of absorption was not different according to the dose consumed. Net increments at Day 7 and Day 14 were significantly higher on consuming the high-dose milk as well. In vitro, lutein ester hydrolysis was incomplete regardless of the amount initially present. Free lutein released was higher using the high-dose fermented milk, but the percentage of hydrolysis was similar at both levels of fortification. In the micellar phase, the percentage of free and total lutein was not different according to the dose. Our results support the suitability of the fermented milk as a carrier of lutein esters and an in vivo dose-dependent effect upon regular consumption and suggest the usefulness of in vitro models to provide relevant information to predict in vivo responses.     

Possible degradation/biotransformation of lutein in vitro and in vivo: isolation and structural elucidation of lutein metabolites by HPLC and LC-MS (atmospheric pressure chemical ionization)

Metabolites of lutein are highly concentrated in the human macula and are known to provide protection against age-related macular degeneration. The aim of this investigation was to characterize the in vitro oxidation products of lutein obtained through photo-oxidation and to compare them with biologically transformed dietary lutein in intestine, plasma, liver, and eyes of rats. In vivo studies involved feeding rats a diet devoid of lutein for 2 weeks to induce deficiency. Rats were divided into two equal groups (n=6/group) and received either micellar lutein by gavage for 10 days or diet supplemented with fenugreek leaves as a lutein source for 4 weeks. Lutein metabolites/oxidation products obtained from in vivo and in vitro studies were characterized by HPLC and LC-MS (APCI) techniques to elucidate their structure. The characteristic fragmented ions resulting from photo-oxidation of lutein were identified as 523 (M(+)+H(+)-3CH(3)), 476 (M(+)+H(+)-6CH(3)), and 551 (M(+)+H(+)-H(2)O). In the eyes, the fragmented molecules resulting from lutein were 13-Z lutein, 13'-Z lutein, 13-Z zeaxanthin, all-E zeaxanthin, 9-Z lutein, 9'-Z lutein, and 3'-oxolutein. Epoxycarotenoids were identified in liver and plasma, whereas anhydrolutein was identified in intestine. This study emphasizes the essentiality of dietary lutein to maintain its status in the retina.     

The roles of prolactin and testosterone in the development and function of granulosa lutein tissue in the rat

The luteotropic roles of prolactin and testosterone (or estradiol formed in luteal tissue) were investigated in hypophysectomized rats with homografts of granulosa lutein tissue. Using this approach, we could determine the effects of prolactin independently of estrogen, since granulosa lutein tissue does not produce estrogen de novo under these conditions. Luteinizing granulosa cells were expressed from the ovaries of immature pregnant mare's serum gonadotropin-primed Fischer 344 rats 6 h after injection of human chorionic gonadotropin. The cells were transplanted beneath the kidney capsule of adult, hypophysectomized, ovariectomized Fischer 344 recipients, which were treated with hormones daily for 12 or 14 days. In rats without treatment (no hormones, n = 3) and in rats treated with only testosterone (Silastic capsule, n = 6), only small amounts of luteal tissue (less than 5 mg/rat) were found and serum progesterone remained at low concentrations (10 ng or less) throughout the experiment. In contrast, in rats treated either with ovine prolactin (300 micrograms/day, n = 10) or with the combination of prolactin and testosterone (n = 12), serum progesterone increased to 43 ng/ml by Day 8. Beyond Day 8, serum progesterone continued to rise in rats treated with the combination of prolactin and testosterone to reach a mean value of 87 ng/ml by Day 14, and mean homograft wet weight was 49 mg/rat; in rats treated with only prolactin, serum progesterone decreased to 25 ng/ml by Day 14 and homograft wet weight was lower (24 mg/rat). Prolactin and testosterone together stimulated more homograft aromatase activity in vivo than did prolactin alone, but the in vitro production of progesterone was not different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropsychological and biochemical investigations in heterozygotes for phenylketonuria during ingestion of high dose aspartame (a sweetener containing phenylalanine)

Aspartame, a high intensity sweetener, is used extensively worldwide in over 5,000 products. Upon ingestion, aspartame is completely metabolized to two amino acids and methanol (approximately 50% phenylalanine, 40% aspartic acid, and 10% methanol). The effects of aspartame on cognitive function, electroencephalograms (EEGs) and biochemical parameters were evaluated in 48 adult (21 men, 27 women) heterozygotes for phenylketonuria (PKUH). PKUH subjects whose carrier status had been proven by DNA analysis ingested aspartame (either 15 or 45 mg/kg/day) and placebo for 12 weeks on each treatment using a randomized, doubleblind, placebo-controlled, crossover study. A computerized battery of neuropsychological tests was administered at baseline weeks -2 and -1, and during treatment at weeks 6, 12, 18, and 24. Samples for plasma amino acids and urinary organic acids were also collected during these visits. EEGs were evaluated by conventional and spectral analysis at baseline week -1 and treatment weeks 12 and 24. The results of the neuropsychological tests demonstrated that aspartame had no effect on cognitive function. Plasma phenylalanine significantly increased, within the normal range for PKUH, at 1 and 3 h following the morning dose of aspartame in the group receiving the 45 mg/kg per day dose only. There were no significant differences in the conventional or spectral EEG analyses, urinary organic acid concentrations, and adverse experiences when aspartame was compared with placebo. This study reaffirms the safety of aspartame in PKUH and refutes the speculation that aspartame affects cognitive performance, EEGs, and urinary organic acids.     

Fluoxetine: A Randomized Clinical Trial in the Maintenance of Weight Loss

Because current weight-reduction treatments have considerable recidivism, a therapy that could help patients maintain weight loss would be of benefit. A six-center, randomized, double-blind trial compared the effects of the specific serotonin uptake inhibitor, fluoxetine hydrochloride, and placebo on maintenance of weight loss. Obese outpatients who had lost ≤3.6 kg after 8 weeks of single-blind fluoxetine 60 mg/day in the qualification phase (N=317 [70.4% of patients entered]; mean ± standard deviation [SD] weight loss, 6.8 ± 2.8 kg) were randomly assigned to fluoxetine 20 mg/day (N=104), fluoxetine 60 mg/day (N=106), or placebo (N=107) for 40 weeks (maintenance phase). Patients received minimal nutrition/dietary counseling. Qualification phase clinic visits were biweekly; maintenance phase visits were monthly for 4 months, then bimonthly for 6 months. Patients treated with fluoxetine 60 mg/day continued to lose weight for 8 additional weeks (16 weeks total; maximum mean ± SD weight loss, 7.2 ± 4.6 kg); those treated with fluoxetine 20 mg/day or placebo began to regain weight. Mean weights remained below baseline values at week 48 (all groups); treatment differences were not statistically significant. Study completion rates were comparable (fluoxetine 20 mg/day, 67.3%; fluoxetine 60 mg/day, 56.6%; placebo, 67.3%; p = 0.175). Among commonly reported adverse events (>10% incidence), only asthenia was reported statistically significantly (p< 0.050) more frequently with fluoxetine than with placebo. Few patients discontinued for any single adverse event. Fluoxetine 60 mg/day was effective for a longer period than fluoxetine 20 mg/day or placebo in maintaining weight loss. Overall, fluoxetine was safe and well tolerated.     

Immune enhancement activities of silk lutein extract from Bombyx mori cocoons

Background

Declining immune function poses an important clinical challenge worldwide and supplementation with natural products that possessing immune enhancing properties is a promising approach for preventing or delaying immune function decline. Cocoons from yellow silkworms are a significant source of lutein, and this unexplored silk extract could be a viable alternative source for dietary lutein. This study assessed immunomodulatory activities of the silk lutein extract. Female BALB/c mice orally received lutein, either as silk or marigold extracts (10 or 20 mg/kg daily), or vehicle only (1% tween 80 in PBS pH 7.4) for 4 weeks. Natural killer (NK) cell activity, specific antibody production, lymphocyte subpopulations, mitogen-induced lymphocyte proliferation, and cytokine production were examined.

Results

Silk lutein extract increased NK cell activity, and the effect was dose-related whereas marigold lutein extract was ineffective. Silk lutein extract dose-dependently enhanced antibody production in pre-immunized mice but marigold lutein extract had no effect. Feeding with silk lutein extract increased the populations of CD3+ and CD4 + CD3 + cells. Silk lutein extract also stimulated concanavalin A- and lipopolysaccharide-induced proliferations of T and B lymphocytes, respectively. Moreover, silk lutein extract increased IL-2 and IFN-γ production while the effect of marigold lutein extract was undetectable.

Conclusions

Together, silk lutein extract enhanced both innate and adaptive immune functions. This preparation may prove to be an effective supplement for strengthened immunity.     

Zinc supplementation increases the level of serum insulin-like growth factor-I but does not promote growth in infants with nonorganic failure to thrive

We investigated in a randomized double-blind placebo-controlled study the effects of zinc supplementation (2 mg/kg/day) for 12 weeks on growth, serum insulin-like growth factor-I (IGF-I) and insulin-like factor binding protein-3 (IGFBP-3) on 3- to 9-month-old infants with nonorganic failure to thrive (NOFTT). 25 infants completed the study, 14 received zinc supplementation (group A), and 11 received placebo (group B). The control group for baseline measurements was composed of 10 age-matched normal growing infants. There were no significant changes in weight for age, length for age, or weight for length during the entire study period in either group A or B. Serum IGF-I levels at baseline were similar in all the groups. After 12 weeks of therapy, serum IFG-I levels increased significantly only in the zinc-supplemented group, from 40.3 +/- 7 ng/ml at baseline to 65 +/- 8 ng/ml (p < 0.05). There was a marked difference in serum IGF-I levels between the zinc-supplemented group and the placebo group after 12 weeks: 65 +/- 8 vs. 49.4 +/- 5 ng/ml (p = 0.058, 95% CI of difference 9.88-21.31). No change was demonstrated in serum IGFBP-3 levels in either study group. We conclude that although zinc supplementation increased serum IGF-I levels, it did not improve the growth parameters of infants with NOFTT.     

Isolation, structural elucidation, and partial synthesis of lutein dehydration products in extracts from human plasma

All-E-(3R,6′R)-3-hydroxy-3′,4′-didehydro-β,γ-carotene (anhydrolutein I) and all-E-(3R,6′R)-3-hydroxy-2′,3′-didehydro-β,ε-carotene (2′,3′-anhydrolutein II) have been isolated and characterized from extracts of human plasma using semipreparative high-performance liquid chromatography (HPLC) on a C₁₈ reversed-phase column. The identification of anhydroluteins was accomplished by comparison of the UV-Vis absorption and mass spectral data as well as HPLC-UV-Vis-mass spectrometry (MS) spiking experiments using fully characterized synthetic compounds. Partial synthesis of anhydroluteins from the reaction of lutein with 2% H₂SO₄ in acetone, in addition to anhydrolutein I (54%) and 2′,3′-anhydrolutein II (19%), also gave (3′R)-3′-hydroxy-3,4-dehydro-β-carotene (3′,4′-anhydrolutein III, 19%). While anhydrolutein I has been shown to be usually accompanied by minute quantities of 2′,3′-anhydrolutein II (ca. 7–10%) in human plasma, 3′,4′-anhydrolutein III has not been detected. The presence of anhydrolutein I and II in human plasma is postulated to be due to acid catalyzed dehydration of the dietary lutein as it passes through the stomach. These anhydroluteins have also been prepared by conversion of lutein diacetate to the corresponding anhydrolutein acetates followed by alkaline hydrolysis. However, under identical acidic conditions, loss of acetic acid from lutein diacetate proceeded at a much slower rate than dehydration of lutein. The structures of the synthetic anhydroluteins, including their absolute configuration at C(3) and C(6′) have been unambiguously established by ¹H NMR and in part by ¹³C NMR, and circular dichroism.     

Bioavailability of lutein in humans from intrinsically labeled vegetables determined by LC-APCI-MS

The aim of the investigation was to assess a stable isotope method for determining the relative bioavailability of food-derived lutein in humans. Subjects were administered a single dose of deuterium-labeled carotenoids from intrinsically labeled spinach or collard green; 10 mL blood samples were drawn at various time points over a 34 days period. The vegetables had been hydroponically grown using 25 atom-% deuterated water. Lutein molecules in the vegetables were partially deuterated with a highest abundance isotopomer at M(0) + 8 (unlabeled molecular mass, M(0,) plus 8 additional mass units from 8 deuterium atoms in the molecules). This allowed labeled lutein to be distinguished from endogenous lutein in serum samples after consuming the labeled meal. The presence of labeled lutein in the circulation was determined by liquid chromatography-mass spectrometry (LC/MS) equipped with an atmospheric pressure chemical ionization (APCI) interface. The quantification of the labeled lutein in serum samples enabled the calculation of the enrichment for each time point after the dose; these values were plotted vs. time to generate absorption-clearance curves for each of the subjects. Area under the curve analyses of four different subjects (integrated over 29 days) yielded serum lutein responses of 128, 145, 149, and 262 microg-day/mg dietary lutein, following an acute dose of spinach containing 15.4, 18.8, 18.8 and 9.8 mg labeled lutein, respectively. This technique will facilitate the study of lutein bioavailability from different foods of diverse carotenoid composition and/or following various food preparation procedures.     

The Effects of Rosuvastatin on the Serum Cortisol,Serum Lipid,and Serum Mevalonic Acid Levels in the Healthy Indian Male Population

In this open-label, balanced, randomized, placebo-controlled, parallel study, healthy male volunteers were randomly divided into two groups. Each group received either a single oral dose of rosuvastatin 20 mg or placebo. Estimations were done at predose on day 1 of dosing (baseline) and 24 h postdose after days 7 and 14. Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid (MVA) levels were measured using validated liquid chromatography–tandem mass spectrometry method. Rosuvastatin produced a statistically significant (P < 0.05) decrease in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides. However, the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group. The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol-lowering agent, without any significant change in serum cortisol level in the healthy Indian male population.     

Effect of imipramine on the circadian rhythm of plasma melatonin in unipolar depression

The authors took a series of 20 serum samples over a 24-hr period for measurement of melatonin in four men and six women with Major Depressive Disorder (DSM-III), at baseline (depressed) and after 4 weeks on imipramine (150-200 mg/day) after achieving clinical remission. After successful treatment with imipramine, 24-hr secretion and peak levels of melatonin were significantly higher than at baseline, with no difference in time of peak level. Testing after 2 weeks of treatment (four subjects), with only a partial or no clinical response, revealed no differences compared with baseline. The therapeutic efficacy of imipramine may be associated with an enhancement of noradrenergic activity.     

High dietary intake of phytosterol esters decreases carotenoids and increases plasma plant sterol levels with no additional cholesterol lowering

The objective of this study was to measure the effects on serum lipids and plasma phytosterols of 6.6 g/day phytosterols from three foods (bread, breakfast cereal, and spread) consumed for 12 weeks compared with a diet that was not enriched with phytosterols. Thirty-five subjects undertook a nonrandomized, single-blind study consisting of a 2 week baseline period, 6 weeks on high-phytosterol intake, 6 weeks on high-phytosterol intake plus increased fruit and vegetable intake, and a final 2 week washout period. Serum total cholesterol decreased by 8.3% from 6.59 to 6.04 mmol/l, and LDL cholesterol decreased by 12.6% from 4.44 to 3.88 mmol/l. Plasma phytosterol levels increased by 45% (sitosterol) and 105% (campesterol). Cholesterol-adjusted plasma alpha- and beta-carotene levels decreased by 19-23%, lutein by 14%, and lycopene by 11%. Levels of alpha-carotene and lutein increased with extra fruit and vegetables. Only lycopene failed to increase during the washout phase. There were no significant changes in biochemical parameters. Serum LDL cholesterol lowering with 6.6 g/day ingested phytosterols was in the range seen with 1.6-3.2 g/day phytosterols. Lowering of plasma carotenoids was greater than that seen with lower phytosterol intake and was partially reversed by increased fruit and vegetable intake.     

拉米夫定与IFNα-1b序贯治疗HBeAg阳性慢性乙肝患者临床疗效观察

目的：观察比较拉米夫定联合IFNα-1b的序贯疗法与拉米夫定,IFNα-1b的单药疗法在治疗HBeAg阳性的慢性乙型肝炎方面的疗效差异。方法：将98例HBeAg阳性慢乙肝患者随机分为序贯治疗组、拉米夫定治疗组和IFNα-1b治疗组。序贯治疗组33例,年龄37．85±7．70岁,男／女：18／15,首先使用拉米夫定（100mg—El一次口服疗程24周）,序贯使用IFNα-1b（60ug隔日一次皮下注射疗程28用1,在第20周至24同同时使用拉米夫定和IFNα-1b,总疗程48周;拉米夫定治疗组34例,年龄39．42＋6．88岁．男／女：20／14,仅口服拉米夫定,100mg一日一次口服,疗程48周;IFNα-1b治疗组31例,年龄35．71±6．14岁,男／女：14／17,仅皮下注射IFNα-1b,60ug隔日一次,疗程48周。治疗12周、24周、48周时检测肝功能、乙肝两对半、HBV—DNA等指标变化。结果：在治疗12周、24周时三组间肝功复常率、HBeAg阴转率无差异,序贯治疗组、拉米夫定组HBV·DNA阴转率优于IFNα-1b治疗组;实验疗程结束时序贯治疗组HBeAg阴转率、抗-HBe转换率及HBV—DNA阴转率显著高于其他两组,P〈0．05,但在HBV-DNA阴转率方面序贯治疗组与拉米夫定治疗组差异不显著。结论：拉米夫定和IFNα-1b序贯疗法在HBV—DNA阴转率、HBeAg阴转率和抗HBe转换率三方面的疗效优于拉米夫定、IFNα-1b单一用药。     

Antioxidant activity of carotenoid lutein in vitro and in vivo

Carotenoid lutein was evaluated for its antioxidant potential both in vitro and in vivo. Lutein was found to scavenge superoxide radicals, hydroxyl radicals and inhibited in vitro lipid peroxidation. Concentrations needed for 50% inhibition (IC50) were 21, 1.75 and 2.2 microg/mL respectively. It scavenged 2,2-diphenyl-1-picryl hydrazyl (IC50 35 microg/mL) and nitric oxide radicals (IC50 3.8 microg/mL) while 2,2-azobis-3-ethylbenzthiozoline-6-sulfonic acid radicals were inhibited at higher concentration. Ferric reducing power (50%) of lutein was found to be equal 0.3 micromols/mL of FeSO4.7H2O. Its oral administration inhibited superoxide generation in macrophages in vivo by 34.18, 64.32 and 70.22% at doses of 50, 100 and 250 mg/kg body weight. The oral administration of lutein in mice for 1 month significantly increased the activity of catalase, superoxide dismutase, glutathione reductase and glutathione in blood and liver while the activity of glutathione peroxidase and glutathione-S-transferase were found to be increased in the liver tissue. Implication of these results in terms of its role in reducing degenerative diseases is discussed.     

The effect of short-term use of testosterone enanthate on muscular strength and power in healthy young men

Use of testosterone enanthate has been shown to significantly increase strength within 6-12 weeks of administration (2, 9), however, it is unclear if the ergogenic benefits are evident in less than 6 weeks. Testosterone enanthate is classified as a prohibited substance by the World Anti-Doping Agency (WADA) and its use may be detected by way of the urinary testosterone/epitestosterone (T/E) ratio (16). The two objectives of this study were to establish (a) if injection of 3.5 mg.kg(-1) testosterone enanthate once per week could increase muscular strength and cycle sprint performance in 3-6 weeks; and (b) if the WADA-imposed urinary T/E ratio of 4:1 could identify all subjects being administered 3.5 mg.kg(-1) testosterone enanthate. Sixteen healthy young men were match-paired and were assigned randomly in a double-blind manner to either a testosterone enanthate or a placebo group. All subjects performed a structured heavy resistance training program while receiving either testosterone enanthate (3.5 mg.kg(-1)) or saline injections once weekly for 6 weeks. One repetition maximum (1RM) strength measures and 10-second cycle sprint performance were monitored at the pre (week 0), mid (week 3), and post (week 6) time points. Body mass and the urinary T/E ratio were measured at the pre (week 0) and post (week 6) time points. When compared with baseline (pre), 1RM bench press strength and total work during the cycle sprint increased significantly at week 3 (p < 0.01) and week 6 (p < 0.01) in the testosterone enanthate group, but not in the placebo group. Body mass at week 6 was significantly greater than at baseline in the testosterone enanthate group (p < 0.01), but not in the placebo group. Despite the clear ergogenic effects of testosterone enanthate in as little as 3 weeks, 4 of the 9 subjects in the testosterone enanthate group ( approximately 44%) did not test positive to testosterone under current WADA urinary T/E ratio criteria.     

Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial

ObjectivesTo assess the effects of rivastigmine on the core domains of Alzheimer’s disease.DesignProspective, randomised, multicentre, double blind, placebo controlled, parallel group trial. Patients received either placebo, 1-4 mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) over the first 12 weeks with a subsequent assessment period of 14 weeks.Setting45 centres in Europe and North America.Participants725 patients with mild to moderately severe probable Alzheimer’s disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association.ResultsAt the end of the study cognitive function had deteriorated among those in the placebo group. Scores on the Alzheimer’s disease assessment scale improved in patients in the higher dose group when compared with patients taking placebo (P<0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global function as rated by the clinician interview scale had significantly improved among those in the higher dose group compared with those taking placebo (P<0.001), and significantly more patients in the higher dose group showed improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved from baseline in patients in the higher dose group but fell in the placebo group. Adverse events were predominantly gastrointestinal, of mild to moderate severity, transient, and occurred mainly during escalation of the dose. 23% (55/242) of those in the higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those in the placebo group discontinued treatment because of adverse events.ConclusionsRivastigmine is well tolerated and effective. It improves cognition, participation in activities of daily living, and global evaluation ratings in patients with mild to moderately severe Alzheimer’s disease. This is the first treatment to show compelling evidence of efficacy in a predominantly European population.

Key messages

• In a 6 month trial rivastigmine was effective in treating the core cognitive and functional symptoms of patients with mild to moderate Alzheimer’s disease
• Rivastigmine at doses of 6-12 mg/day produces clinically relevant and statistically significant improvements in cognitive and global assessments, and in activities of daily living
• The effects of rivastigmine are dose dependent
• Rivastigmine was well tolerated in this population of elderly patients