Mechanistic insights into the aetiology of post-prandial decline in testosterone in reproductive-aged men.

Obesity is known to be associated with impaired testicular function potentially resulting in androgen deficiency and subfertility. While the underlying cause of obesity-related male hypogonadism is multi-factorial, here, we investigated the impact of dietary fat on testicular endocrine function. Ingestion of a high-fat "fast food" mixed meal, a common practice for obese men, produced a 25% fall in serum testosterone within an hour of eating, with levels remaining suppressed below fasting baseline for up to 4 hr. These changes in serum testosterone were not associated with any significant changes in serum gonadotrophins. The nadir in serum testosterone preceded the post-prandial increase in serum IL-6/IL-17 by several hours, suggesting that inflammation was unlikely the cause. Furthermore, intravenous administration of fat (Intralipid) had no impact on testosterone levels, while an identical oral dose of fat did suppress testosterone. These results suggest that fat does not directly impair Leydig cell function, but rather the passage of fat through the intestinal tract elicits a response that indirectly elicits a post-prandial fall in testosterone.

Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age.

Inflammation, both acute and chronic, is associated with testosterone deficiency, raising the possibility of a direct causal link. One potential trigger for inflammation in obese men is the passage of intestinal bacteria into the circulation due to a breakdown in mucosal barrier integrity. Recently, we hypothesized that this endotoxin exposure may cause androgen deficiency in obese men. To test this hypothesis, we analyzed the relationship between serum levels of lipopolysaccharide-binding protein (LBP), an indirect measure of endotoxin exposure, against male reproductive hormones, inflammatory markers (C-reactive protein, IL-1ß, IL-6, TNF-α), and adiposity in 75 men. Adiposity was positively correlated with endotoxin exposure (LBP) and inflammation (C-reactive protein, IL-6) and negatively correlated with testosterone. Furthermore, endotoxemia (LBP) was negatively correlated with serum testosterone but positively correlated with IL-6. Multivariate analysis revealed a significant, negative correlation between serum IL-6 and free testosterone. In a second interventional study, low-dose endotoxin challenge in lean men produced a transient inflammatory response that was followed by a decline in serum testosterone, without changes in LH or FSH, providing further evidence that endotoxin-driven inflammation may result in impaired Leydig cell function.

Increased miscarriage of euploid pregnancies in obese women undergoing cryopreserved embryo transfer.

Obesity is known to be associated with an increased risk of miscarriage after natural and assisted conception. Although most sporadic miscarriages are caused by genetic abnormalities, it is presently uncertain if genetics is also the underlying mechanism leading to increased pregnancy loss seen in obese women. Karyotyping of the products of conception suggests a reduced rate of fetal aneuploidy in miscarriages from obese compared with lean individuals. Karyotype analysis, however, is prone to false negative results because of inadvertent culture of maternal rather than fetal tissue. Therefore, to better analyse the effect of the genetic status on obesity-related miscarriage, we retrospectively analysed the outcomes 125 consecutive cryopreserved embryo transfer cycles resulting in a pregnancy after screening for genetic normality using comparative genomic hydridization. Lean individuals (body mass index 18.5-24.9 kg/m2) had a significantly lower rate of miscarriages (14.2%) than overweight (29.1%) or obese (41.9%) women (P = 0.001); this relationship remained significant (P = 0.023) even after adjusting for relevant confounders, e.g. maternal age, cause of infertility, number of previous IVF cycles, type of frozen embryo transfer cycle or past obstetric history. These results support a non-genetic cause for obesity-related miscarriage.

Disparity in the micronutrient content of diets high or low in advanced glycation end products (AGEs) does not explain changes in insulin sensitivity.

We have previously shown that an isoenergetic low advanced glycation end products (AGEs) diet matched for macronutrient content improved insulin sensitivity compared to high AGE diet. Here, we evaluated the differences in micronutrient intake of these two dietary patterns and if they could explain differences in insulin sensitivity. Participants consumed the intervention diets each for 2 weeks with 4 weeks of habitual dietary intake (washout) in-between. Dietary analysis revealed that the high AGE diet contained greater levels of retinol equivalents (RE) (478.9 + 151.3 µg/day versus 329.0 + 170.0 µg/day; p < .006), vitamin A (806.3 + 223.5 (µg RE)/day versus 649.1 + 235.8 (µg RE)/day; p < .05) and thiamine (2.3 + 0.6 mg/day versus 1.6 + 0.4 mg/day; p = .014) compared to the low AGE diet. The changes in polyunsaturated fat, retinol, vitamin A and thiamine did not correlate with changes in insulin sensitivity (all p > .1) therefore are unlikely to explain observed changes in insulin sensitivity. (clinicaltrials.gov:NCT00422253).

Serum anti-Mullerian hormone production is not correlated with seasonal fluctuations of vitamin D status in ovulatory or PCOS women.

STUDY QUESTION: Is there a relationship between serum anti-Mullerian hormone (AMH) levels and seasonal variations in serum vitamin D in ovulatory and polycystic ovary syndrome (PCOS) women? STUDY ANSWER: Serum AMH levels were not associated with serum vitamin D status even after controlling for relevant co-variants, with this finding being consistent for all causes of infertility. As expected, seasonal variations in serum vitamin D were observed between summer and winter. WHAT IS KNOWN ALREADY: AMH plays an important role in maintaining ovarian reserve and modifying follicle sensitivity to FSH stimulation. Studies suggest that vitamin D has the ability to modify AMH production in vitro, yet only one clinical study reports the influence of vitamin D on AMH levels. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study analyzing the potential interaction of AMH and vitamin D for 340 women (58 PCOS and 282 ovulatory women) aged less than 40 years collected as part of their routine fertility assessment between January and December 2013 at a private fertility clinic in Adelaide, South Australia. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patient data including age, BMI, cause of infertility, antral follicle counts (AFC), serum AMH and vitamin D levels, smoking status, and menstrual cycle length for women aged less than 40 years of age, with serum AMH and vitamin D sampled within the same 4-week period were retrieved from a database. The hours of sunlight per day and daily UV index were extracted from a database at the South Australian Bureau of Meteorology, South Australia. Serum vitamin D (25-hydroxyvitamin D) levels were analyzed against seasonal variation in sunlight and UV exposure and serum AMH levels, while controlling for relevant co-variants. MAIN RESULTS AND THE ROLE OF CHANCE: Seasonal variations in serum vitamin D were observed between summer and winter (30% variance; P < 0.001), while serum AMH levels (mean ± SEM) remained unaffected by season status (36.9 ± 3.3 versus 38.5 ± 2.7 pmol/l; P > 0.05), even after controlling for relevant co-variants. Overall, no correlation was observed between serum AMH and vitamin D levels, in either the PCOS or ovulatory cohort. Serum vitamin D levels were not significantly related to the underlying cause of infertility (PCOS, diminished ovarian reserve, 'fertile' ovulatory controls). LIMITATIONS, REASONS FOR CAUTION: The data used to generate the study findings are cross sectional in nature. While we acknowledge that a longitudinal study monitoring the relationship between serum AMH and vitamin D in individuals over the four seasons would have been ideal, we believe the current findings are robust as our four seasonal groups did not differ for any significant co-variant for serum AMH or vitamin D (age, BMI, PCOS status or AFC) and that there is no significant association between serum vitamin D concentration and AMH production. WIDER IMPLICATIONS OF THE FINDINGS: At present, while in vitro studies suggest vitamin D has the potential to modify AMH production, clinical study findings are conflicting. If vitamin D does influence AMH production, this could have important therapeutic implications. STUDY FUNDING/COMPETING INTERESTS: K.G. was supported through a University of South Australia summer scholarship. The authors have no competing interests.

Metabolic endotoxaemia--a potential novel link between ovarian inflammation and impaired progesterone production.

INTRODUCTION: Medical conditions such as obesity and inflammatory bowel disease are associated with impaired luteal function, menstrual disturbance and infertility. It is proposed that the disturbance in gut wall integrity ("leaky gut") seen in these conditions may result in the passage of bacterial endotoxin (LPS) from the colonic lumen into the circulation that may initiate inflammation in the ovary and subsequently impair hormone production. METHODS: Quantify the association between systemic levels of LBP, a marker of endotoxin exposure, and levels of inflammation in the ovary (follicular fluid IL-6), plus steroid hormone production in 45 women undergoing IVF treatment. RESULTS: Endotoxaemia (LBP) were positively correlated with plasma CRP and inflammation within the ovary (follicular fluid IL-6). Furthermore, endotoxaemia was negatively correlated with progesterone production. CONCLUSION: The observed correlations, together with previously published animal studies linking endotoxin exposure to impaired luteal function, suggest that the translocation of bacterial endotoxin from the gut lumen into the circulation has the potential to interfere with progesterone production and result in luteal deficiency.

Primary School Educators' Perspectives and Experiences of Nature-Based Play and Learning and Its Benefits, Barriers, and Enablers: A Qualitative Descriptive Study.

Nature-based play and learning is of increasing interest to primary schools and research suggests that it has many potential benefits for children's health and development. However, little is known about educators' perspectives and experiences of nature-based play and learning, particularly the barriers, benefits and enablers, despite their direct relevance to the uptake of nature-based play and learning in schools. A qualitative descriptive methodology was employed to uncover these. Individual, semi-structured interviews were conducted with 12 principals and educators from South Australian public primary schools, recruited via a participant contact list from a previous study. The participants were two principals, eight educators and two individuals with dual principal and educator positions. Metropolitan and rural schools were equally represented. Interviews were audio-taped, transcribed verbatim and analysed using thematic analysis. Analysis identified four overarching themes: the practice, perceived benefits, barriers and enablers of nature-based play and learning. Children's learning, enjoyment, creativity, and a relaxed and flexible environment were clear benefits. Meanwhile educator knowledge and confidence and the crowded curriculum were barriers. Enablers were nature-based play and learning champions and support from school leadership. The findings suggest that schools can help engage students with nature-based play and learning activities by mitigating these barriers and promoting these enablers.

Egg consumption as part of an energy-restricted high-protein diet improves blood lipid and blood glucose profiles in individuals with type 2 diabetes.

The role of dietary cholesterol in people with diabetes has been little studied. We investigated the effect of a hypoenergetic high-protein high-cholesterol (HPHchol) diet compared to a similar amount of animal protein (high-protein low-cholesterol, HPLchol) on plasma lipids, glycaemic control and cardiovascular risk markers in individuals with type 2 diabetes. A total of sixty-five participants with type 2 diabetes or impaired glucose tolerance (age 54·4 (sd 8·2) years; BMI 34·1 (sd 4·8) kg/m2; LDL-cholesterol (LDL-C) 2·67 (sd 0·10) mmol/l) were randomised to either HPHchol or HPLchol. Both hypoenergetic dietary interventions (6-7 MJ; 1·4-1·7 Mcal) and total carbohydrate:protein:fat ratio of 40:30:30 % were similar but differed in cholesterol content (HPHchol, 590 mg cholesterol; HPLchol, 213 mg cholesterol). HPHchol participants consumed two eggs per d, whereas HPHchol participants replaced the eggs with 100 g of lean animal protein. After 12 weeks, weight loss was 6·0 (sd 0·4) kg (P < 0·001). LDL-C and homocysteine remained unchanged. All the subjects reduced total cholesterol ( - 0·3 (sd 0·1) mmol/l, P < 0·001), TAG ( - 0·4 (sd 0·1) mmol/l, P < 0·001), non-HDL-cholesterol (HDL-C, - 0·4 (sd 0·1) mmol/l, P < 0·001), apo-B ( - 0·04 (sd 0·02) mmol/l, P < 0·01), HbA1c ( - 0·6 (sd 0·1) %, P < 0·001), fasting blood glucose ( - 0·5 (sd 0·2) mmol/l, P < 0·01), fasting insulin ( - 1·7 (sd 0·7) mIU/l, P < 0·01), systolic blood pressure ( - 7·6 (sd 1·7) mmHg, P < 0·001) and diastolic blood pressure ( - 4·6 (sd 1·0) mmHg; P < 0·001). Significance was not altered by diet, sex, medication or amount of weight loss. HDL-C increased on HPHchol (+0·02 (sd 0·02) mmol/l) and decreased on HPLchol ( - 0·07 (sd 0·03) mmol/l, P < 0·05). Plasma folate and lutein increased more on HPHchol (P < 0·05). These results suggest that a high-protein energy-restricted diet high in cholesterol from eggs improved glycaemic and lipid profiles, blood pressure and apo-B in individuals with type 2 diabetes.

Investigating Australian Consumers' Perceptions of and Preferences for Different Styles of Sparkling Wine Using the Fine Wine Instrument.

This study investigated consumer preferences for different styles of sparkling wine and the influence of wine style and occasion on sparkling wine purchasing and consumption behavior. Australian consumers (n = 203) completed an online survey and blind tasting of representative styles of commercial sparkling wines, including Champagne. Wine sensory profiles were determined by descriptive analysis using a trained panel (n = 12) and consumers were segmented into 'No Frills', 'Aspirant' and 'Enthusiast' clusters using the Fine Wine Instrument. Consumer perceptions, preferences and liking were measured using 9-point hedonic scales and compared via statistical analysis. Consumers anticipated liking Champagne and sparkling white wine the most, and Moscato and Prosecco the least, but on tasting, could only readily identify the Moscato and sparkling red wines, as the most contrasting wine styles. As such, liking scores for the Champagne and sparkling white wine were significantly lower based on tasting (median scores were 6.0, compared with 9.0 and 8.0 for survey responses, respectively). Consumers' preconceived expectations of different sparkling wine styles clearly influenced purchasing and consumption behavior. Aspirants and Enthusiasts were more likely to spend more per bottle for Champagne and sparkling white wine, and consumption of these sparkling wines was most frequently associated with celebratory occasions, such as anniversaries, birthdays, Christmas, New Year and weddings.

Influence of Βeta-Cryptoxanthin Supplementation on Ovarian Reserve and Fertility Status in Aged Wistar Rats.

Previous observational studies have suggested that ß-cryptoxanthin, a micronutrient present in yellow and orange fruit and vegetables, may help delay the onset of menopause. Given the widespread social trend of delaying pregnancy, the possibility that ß-cryptoxanthin supplementation may delay age-related loss of fertility and onset of menopause is of significant interest. In a parallel study, either saline or ß-cryptoxanthin (5 µg/kg rat/day) was delivered to Wistar albino rats via an osmotic pump from 4 to 7 months of age. All control and ß-cryptoxanthin-treated dams were fertile at 7 months of age, with no differences in litter size, sex ratio, or pup viability at the time of mating at 7, 9, 11, and 15 months of age (p ≥ .05 for all). As expected, over time there was a pronounced decrease in litter size and serum anti-Müllerian hormone (AMH), but with no significant differences between the two groups at any time point. Overall, there was a positive correlation between litter size and AMH (r = 0.324, p = .012), confirming a link between this serum marker of ovarian reserve status and fertility potential. At 16 months, bilateral oophorectomies were performed at necropsy, before conducting follicle density assessments of ovarian reserve. The total number and stage of follicle development were similar between the ß-cryptoxanthin and control groups (13.8 ± 3.2 cf 10.2 ± 4.8, respectively, p > .05). ß-cryptoxanthin supplementation for 3 months early in reproductive life was not effective in delaying ovarian senescence or enhancing fertility in rats later in life, contrary to the association suggested by observational studies in humans.

Metabolic Endotoxemia, Feeding Studies and the Use of the Limulus Amebocyte (LAL) Assay; Is It Fit for Purpose?

The Limulus amebocyte assay (LAL) is increasingly used to quantify metabolic endotoxemia (ME), particularly in feeding studies. However, the assay was not intended to assess plasma at levels typically seen in ME. We aimed to optimize and validate the LAL assay under a range of pre-treatment conditions against the well-established lipopolysaccharide binding protein assay (LBP). Fifteen healthy overweight and obese males aged 28.8 ± 9.1years provided plasma. The LAL assay employed a range of pre-treatments; 70 °C for 15 and 30 min and 80 °C for 15 and 30 min, ultrasonication (70 °C for 10 min and then 40 °C for 10 min), and dilution (1:50, 1:75, 1:100, and 1:200 parts) or diluted using 0.5% pyrosperse. Seventeen different plasma pre-treatment methods employed prior to the use of the LAL analytical technique failed to show any relationships with either LBP, or body mass index (BMI; obesity), the biological trigger for ME (p > 0.05 for all). As expected, BMI positively correlated with LBP (r = 0.523, p = 0.052. No relationships were observed between LAL with any of the sample pre-treatments and LBP or BMI. In its current form, the LAL assay is unsuitable for detecting levels of endotoxin typically seen in ME.

Healthy for Life Pilot Study: A Multicomponent School and Home Based Physical Activity Intervention for Disadvantaged Children.

The study aimed to develop and evaluate a multicomponent school and home based physical activity (PA) intervention in children in grades 3-7 (aged 8-13 years) and determine the psychological variables that influence PA; 10 × 1 h school-based training sessions, a home-based activity program and 4 × 1 h lifestyle workshops for parents. PA was assessed at an intervention and nearby control school using accelerometers and self-report at 3-time points: baseline, post intervention and 10-week follow-up. Self-efficacy, self-management strategies, enjoyment, perceived barriers to PA, outcome-expectancy and social support were evaluated. The study showed 73% of the children with complete data sets at the intervention school (n = 27) did not increase device measured moderate to vigorous PA (MVPA) in the after-school period (3 p.m. to 6 p.m.) or over the whole day or during school break time immediately following the intervention or at follow-up, as compared to 70% of children with complete data sets at the control school (n = 35; p > 0.05 for all). Overall, 59% of boys attained more than double the recommended 120 min of MVPA each day compared to 42% of girls (p = 0.013). At the baseline, children's self-reported PA in the intervention school positively correlated with: outcome expectancy (R = 0.240, p = 0.015), enjoyment (R = 0.339, p < 0.001), self-efficacy (R = 0.399, p < 0.001), self-management (R = 0.617, p < 0.001), social support at home (R = 0.406, p < 0.001), and social support at school (R = 0.407, p < 0.001). Similar relationships were observed after the intervention and at follow-up. Focus groups with the children, parents and interviews with teachers identified areas for improvement of the intervention. In conclusion, while the multifaceted approach to improve PA was ineffective over the time span of the study, important predictors of PA in this sample of disadvantaged children were identified.

The Effect of Macronutrients on Reproductive Hormones in Overweight and Obese Men: A Pilot Study.

Hypogonadal obese men find it difficult to lose weight. We investigated whether the modification of macronutrient intake can alter testosterone levels independently of the body mass index. Fasted overweight or obese fertile men were asked to consume meals of polyunsaturated fats (PUFA), monounsaturated fats (MUFA), refined carbohydrates (CHO, orange juice, OJ), whey and egg albumin and mixed meals of PUFA and CHO, PUFA and egg albumin, and CHO and egg albumin. Blood was collected at fasting, then hourly for 5 h and analysed to determine the levels of testosterone and other hormones. We found PUFA and MUFA or a mixed meal of PUFA and CHO significantly reduced serum testosterone production to a similar degree over a 5 h period. PUFA decreased serum testosterone levels by 3.2 nmol/L after 1 h compared to baseline (p = 0.023), with this suppression remaining significant up to 5 h postprandially (2.1 nmol/L; p = 0.012). The net overall testosterone levels were reduced by approximately 10 nmol/L × h by PUFA, MUFA and PUFA combined with CHO. CHO alone had little effect on testosterone levels, whereas egg albumin was able to increase them (7.4 cf 2.0 nmol/L × h). Therefore, for men wishing to optimize their testosterone levels, it may be wise to avoid a high fat intake, drink liquids such as water or OJ or even consider fasting. ANZCTR, Australia; ACTRN12617001034325.

Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity.

BACKGROUND: Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Importantly, obesity is also reported to be associated with an increase in intestinal permeability with the passage of intestinal bacteria into the circulation (metabolic endotoxemia) that triggers a systemic state of inflammation and resultant oxidative stress. Therefore, we hypothesised that this obesity related increase in intestinal permeability and resultant metabolic endotoxemia (ME) may activate inflammation within the male reproductive tract, leading to increased reactive oxygen species production, sperm oxidative stress and a decline in DNA integrity. RESULTS: Our pilot study of 37 infertile men confirmed a significant positive correlation between body mass index (BMI), increased intestinal permeability (serum zonulin), metabolic endotoxaemia (LBP), sperm DNA oxidative damage (seminal 8 OhDG) and increasing levels of sperm DNA fragmentation (Halosperm). Metabolic endotoxemia was positively correlated with increasing levels of sperm DNA oxidative damage with this relationship remaining significant, even after adjustment for relevant confounders such as age, BMI and days of abstinence. These observations suggest that metabolic endotoxemia and its associated oxidative stress may be a key driver of sperm DNA damage in obese men. CONCLUSION: This study confirms a link between obesity, increasing intestinal permeability and endotoxin exposure, and oxidative mediated sperm DNA damage. This warrants further investigation to fully understand the effect of metabolic endotoxemia on male reproductive function which could result in the new therapies to improve male fertility potential.

The Apples of Academic Performance: Associations Between Dietary Patterns and Academic Performance in Australian Children.

BACKGROUND: The purpose of this study was to determine whether there was an association between dietary patterns and children's academic performance. METHODS: This cross-sectional study involved 315 children aged 9-11 years from 26 schools in Australia. Academic performance was measured in 4 domains (reading, writing, numeracy, and language-subdomains: spelling, grammarm and punctuation) using the National Assessment Program in Literacy and Numeracy (NAPLAN). A self-reported child questionnaire collected dietary intake data. "Core" (healthy) and "noncore" (unhealthy) dietary patterns were derived using principal components analysis. RESULTS: The noncore pattern was associated with lower NAPLAN scores across all academic domains (mean: -12.6, 95% CI: -18.7 to -6.4, r2 = .073, p < .001) except writing, while the core foods pattern was not associated with NAPLAN scores across all domains. When the noncore model was adjusted for sociodemographic covariates (child body mass index, ethnicity, sex, parental education, household income, marital status, mother's employment hours, and number of siblings), the association was attenuated but remained statistically significant (NAPLAN summary score: -8.5, 95% CI -15.0 to -1.9, r2 = .123, p = .011). CONCLUSIONS: Academic performance was deleteriously associated with a nutrient-poor, energy-dense diet, yet not associated with a nutritious diet.

Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men.

BACKGROUND: Obesity is associated with both impaired testosterone production and a chronic state of low grade inflammation. Previously it was believed that this inflammation was mediated by a decline in the immunosuppressive action of testosterone. However, more recently an alternative hypothesis (GELDING theory) has suggested that inflammation originating from the passage of intestinal bacteria into the circulation (metabolic endotoxaemia) may actually be the cause of impaired testicular function in obese men. The aim of this study is to investigate if metabolic endotoxaemia, as quantified by serum Lipopolysaccharide Binding Protein (LBP), is associated with impaired testicular endocrine function. METHODS: A total of 50 men aged between 21 and 50 years (mean 35.1 ± 6.8 years) were assessed for adiposity (BMI, waist circumference and % body fat using bio-impedance), inflammatory status (serum CRP, IL-1ß, IL-6, TNFα and LBP) and testicular endocrine function (serum testosterone, estradiol, AMH, LH and FSH). Statistical analysis was performed using Pearson correlation analysis, with log transformation of data where appropriate, and multi-variate regression. RESULTS: Overall increasing adiposity (% body fat) was positively associated with metabolic endotoxaemia (LBP, r = 0.366, p = 0.009) and inflammation (CRP r = 0.531, p < 0.001; IL-6 r = 0.463, p = 0.001), while also being negatively correlated with serum testosterone (r = -0.403, p = 0.004). Serum testosterone levels were significantly negatively correlated with inflammation (CRP r = -0.471, p = 0.001; IL-6 r = -0.516, p < 0.001) and endotoxaemia (LBP) after adjusting for serum LH levels (p = -0.317, p = 0.03). Furthermore, serum IL-6 was negatively associated with AMH levels (r = -0.324, p = 0.023), with a negative trend between LBP and AMH also approaching significance (r = -0.267, p = 0.064). CONCLUSIONS: Obesity and its associated metabolic endotoxaemia helps initiate a pro-inflammatory state characterised by raised serum IL-6 levels, which in turn is correlated with impairment of both Leydig (testosterone) and Sertoli cell function (AMH). These results open up the potential for new treatments of obesity related male hypogonadism that focus on preventing the endotoxaemia associated chronic inflammatory state.

Influence of nutrition on the decline of ovarian reserve and subsequent onset of natural menopause.

The early loss of ovarian reserve and subsequent menopause has a major impact on fertility potential and increases the risk of cardiovascular disease, osteoporosis, cognitive decline and mortality later in life. While many studies have reported that lifestyle factors such as diet can influence the age of onset of natural menopause, their results are often contradictory. Therefore, the aim of this study was to examine the influence of diet on the onset of natural menopause using a self-reported food frequency questionnaire in a cohort of 1146 pre-menopausal women followed up for an average of 12.5 years. The primary finding was that the age of natural menopause was positively correlated with dietary intake of the micronutrient ß-cryptoxanthin (r(2 )=( )0.105, p < 0.001) and fruit (r(2 )=( )0.07, p = 0.01), with these relationships remaining significant even after adjustment for other known co-variants for onset of menopause (parity, BMI, physical activity level, education, smoking, energy and alcohol intake). Kaplan-Meier survival analysis confirmed that both ß-cryptoxanthin and fruit intake was associated with a significant delay in the onset of natural menopause. While still acknowledging that further research is required, in the interim we would advocate that a diet containing ∼400 mcg of ß-cryptoxanthin per day from fruits (mandarins, oranges and peaches) has significant potential to delay ovarian senescence by 1.3 years.

A 4-week nutrition and therapeutics course in an undergraduate pharmacy program.

OBJECTIVE: To determine the effectiveness of an intensive 4-week nutrition course in increasing the knowledge of undergraduate pharmacy students. DESIGN: A Nutrition and Therapeutics elective course was developed that covered the Australian Guide to Healthy Eating, as well as nutrition labeling, food composition, functional foods, diabetes, cardiovascular disease, nutrition and cancer, osteoporosis, nutrient-drug interactions, nutritional supplements, weight management, and infant feeding. The course was taught using lectures, student-focused tutorials featuring evidence-based practice, problem-based learning exercises, case-based scenarios, media examples, video clips from the lay press, and articles from the professional/scientific literature. ASSESSMENT: A self-administered, validated questionnaire on dietary recommendations, sources of nutrients, choosing everyday foods, and diet-disease relationship was administered prior to and after completion of the course. Students' scores in all 4 areas improved significantly; however, their knowledge of the national dietary recommendations, sources of nutrients, and everyday foods high in nutrients was below that of members of the community. CONCLUSIONS: Nutritional education courses can increase the nutrition knowledge of undergraduate pharmacy students. The need for pharmacists to advise patients regarding nutritional supplements continues to increase the need for incorporating nutrition courses within curriculum.

Dysbiosis of Gut Microbiota (DOGMA)--a novel theory for the development of Polycystic Ovarian Syndrome.

Polycystic Ovarian Syndrome (PCOS) is the most common cause for menstrual disturbance and impaired ovulation, effecting one in twenty women of reproductive age. As the majority of women with PCOS are either overweight or obese, a dietary or adipose tissue related trigger for the development of the syndrome is quite possible. It has now well established that PCOS is characterised by a chronic state of inflammation and insulin resistance, but the precise underlying triggers for these two key biochemical disturbances is presently unknown. In this paper we present support for a microbiological hypothesis for the development of PCOS. This novel paradigm in PCOS aetiology suggests that disturbances in bowel bacterial flora ("Dysbiosis of Gut Microbiota") brought about by a poor diet creates an increase in gut mucosal permeability, with a resultant increase in the passage of lipopolysaccaride (LPS) from Gram negative colonic bacteria into the systemic circulation. The resultant activation of the immune system interferes with insulin receptor function, driving up serum insulin levels, which in turn increases the ovaries production of androgens and interferes with normal follicle development. Thus, the Dysbiosis of Gut Microbiota (DOGMA) theory of PCOS can account for all three components of the syndrome-anovulation/menstrual irregularity, hyper-androgenism (acne, hirsutism) and the development of multiple small ovarian cysts.