A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice.

The Western diet (WD) predisposes to bodyweight gain and obesity and is linked to mitochondrial dysfunction, oxidative damage, inflammation, and multisystem disease, even affecting the reproductive organs, fertility, and pregnancy outcomes. In this study, we investigated the effects of multi-ingredient supplementation (MIS) with antioxidants, phytonutrients, and vitamins ('Fertility Enhancer'; FE) on white adipose tissue (WAT) expansion, nonalcoholic fatty liver disease (NAFLD), and infertility in WD-fed C57BL/6J mice. Five-month-old male (M) and female (F) mice were fed a low-fat diet (LF) or a high fat/sucrose WD (HF) for six weeks, followed by six weeks of LF (3.64 kcal/g), HF (4.56 kcal/g), or HF combined with FE (4.50 kcal/g). A sub-set of animals were sacrificed at 12 weeks, while the remainder were harem-mated in a 1:2 male-to-female ratio, and singly housed during the gestational period. Two-way, factorial ANOVA analysis revealed a main effect of diet on bodyweight (BW), total body fat, % body fat, white adipose tissue mass, and liver lipid content (all p < 0.001), driven by the anti-obesogenic effects of the 'Fertility Enhancer'. Similarly, a main effect of diet was found on PGC1-α mRNA levels (p < 0.05) and mitochondrial protein content (p < 0.001) in perigonadal WAT, with PGC1-α induction and higher complex II and complex III expression in FE vs. HF animals. Copulatory plug counts were higher in FE vs. HE couples (30% vs. 6%), resulting in more litters (4 vs. 0) and higher copulatory success (67% vs. 0%). Although the trends of all histology outcomes were suggestive of a benefit from the FE diet, only the number of atretic follicles and testicular mass were significant. Ovarian IL-1ß mRNA induction was significantly attenuated in the FE group (p < 0.05 vs. HF) with CASP1 attenuation trending lower (p = 0.09 vs. HF), which is indicative of anti-inflammatory benefits of the 'Fertility Enhancer.' We conclude that supplementation with specific phytonutrients, antioxidants, and vitamins may have utility as an adjunctive therapy for weight management, fatty liver disease, and infertility in overweight and obese couples.

The Acute Effect of Multi-Ingredient Antioxidant Supplementation following Ionizing Radiation.

Radiation exposure is an undeniable health threat encountered in various occupations and procedures. High energy waves in ionizing radiation cause DNA damage and induce reactive oxygen species (ROS) production, which further exacerbate DNA, protein, and lipid damage, increasing risk of mutations. Although endogenous antioxidants such as superoxide dismutase have evolved to upregulate and neutralize ROS, exogenous dietary antioxidants also have the potential to combat ionizing radiation (IR)-induced ROS production. We evaluated a cocktail of ingredients (AOX) purported to have antioxidant and mitochondrial protective properties on the acute effects of IR. We show that IR stimulates DNA damage through phosphorylation of DNA repair proteins in the heart, brain, and liver of mice. AOX showed partial protection in brain and liver, through a lack of significant activation in given repair proteins. In addition, AOX attenuated the IR-induced increase in NF-kß mRNA and protein expression in brain and liver. Lastly, cytochrome c oxidase complex transcripts were significantly higher in heart and brain following radiation, which was also diminished by prior ingestion of AOX. Together, our findings suggest that a multi-ingredient AOX supplement may attenuate the IR-induced cellular damage response and represents a feasible and cost-effective preventative supplement for at-risk populations of radiation exposure.

Maternal Aerobic Exercise, but Not Blood Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations, during Pregnancy Influence Infant Body Composition.

Although discrete maternal exercise and polyunsaturated fatty acid (PUFA) supplementation individually are beneficial for infant body composition, the effects of exercise and PUFA during pregnancy on infant body composition have not been studied. This study evaluated the body composition of infants born to women participating in a randomized control exercise intervention study. Participants were randomized to aerobic exercise (n = 25) or control (stretching and breathing) groups (n = 10). From 16 weeks of gestation until delivery, the groups met 3×/week. At 16 and 36 weeks of gestation, maternal blood was collected and analyzed for Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA). At 1 month postnatal, infant body composition was assessed via skinfolds (SFs) and circumferences. Data from 35 pregnant women and infants were analyzed via t-tests, correlations, and regression. In a per protocol analysis, infants born to aerobic exercisers exhibited lower SF thicknesses of triceps (p = 0.008), subscapular (p = 0.04), SF sum (p = 0.01), and body fat (BF) percentage (%) (p = 0.006) compared with controls. After controlling for 36-week DHA and EPA levels, exercise dose was determined to be a negative predictor for infant skinfolds of triceps (p = 0.001, r2 = 0.27), subscapular (p = 0.008, r2 = 0.19), SF sum (p = 0.001, r2 = 0.28), mid-upper arm circumference (p = 0.049, r2 = 0.11), and BF% (p = 0.001, r2 = 0.32). There were no significant findings for PUFAs and infant measures: during pregnancy, exercise dose, but not blood DHA or EPA levels, reduces infant adiposity.

The Influence of Maternal Aerobic Exercise, Blood DHA and EPA Concentrations on Maternal Lipid Profiles.

Exercise and polyunsaturated fatty acid (PUFA) supplementation independently improve lipid profiles. The influence of both exercise and PUFAs on lipids during pregnancy remains unknown. This study evaluated exercise, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations on lipids during pregnancy. Participants were randomized to aerobic exercise or control groups. From 16 weeks gestation until delivery, groups met 3x/week; exercisers performed moderate-intensity aerobic activity, controls performed low-intensity stretching and breathing. At 16 and 36 weeks' gestation, maternal blood was analyzed for lipids (total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG)), DHA and EPA. In intent-to-treat analysis, the aerobic group (n = 20), relative to controls (n = 10), exhibited a higher HDL change across gestation (p = 0.03). In a per protocol analysis, the aerobic group, relative to controls, exhibited 21.2% lower TG at 36 weeks (p = 0.04). After controlling for 36-week DHA and EPA, exercise dose predicts 36 weeks' TG (F (1,36) = 6.977, p = 0.012, r2 = 0.16). Aerobic exercise normalizes late pregnancy TG. During pregnancy, exercise dose controls the rise in TG, therefore maintaining normal levels. DHA and EPA do not have measurable effects on lipids. Regardless of PUFA levels, exercise at recommended levels maintains appropriate TG levels in pregnant women. Normal TG levels are critical for pregnancy outcomes, and further studies are warranted to investigate this association in broader populations.

A Five-Ingredient Nutritional Supplement and Home-Based Resistance Exercise Improve Lean Mass and Strength in Free-Living Elderly.

Old age is associated with lower physical activity levels, suboptimal protein intake, and desensitization to anabolic stimuli, predisposing for age-related muscle loss (sarcopenia). Although resistance exercise (RE) and protein supplementation partially protect against sarcopenia under controlled conditions, the efficacy of home-based, unsupervised RE (HBRE) and multi-ingredient supplementation (MIS) is largely unknown. In this randomized, placebo-controlled and double-blind trial, we examined the effects of HBRE/MIS on muscle mass, strength, and function in free-living, older men. Thirty-two sedentary men underwent twelve weeks of home-based resistance band training (3 d/week), in combination with daily intake of a novel five-nutrient supplement ('Muscle5'; M5, n = 16, 77.4 ± 2.8 y) containing whey, micellar casein, creatine, vitamin D, and omega-3 fatty acids, or an isocaloric/isonitrogenous placebo (PLA; n = 16, 74.4 ± 1.3 y), containing collagen and sunflower oil. Appendicular and total lean mass (ASM; +3%, TLM; +2%), lean mass to fat ratios (ASM/% body fat; +6%, TLM/% body fat; +5%), maximal strength (grip; +8%, leg press; +17%), and function (5-Times Sit-to-Stand time; -9%) were significantly improved in the M5 group following HBRE/MIS therapy (pre vs. post tests; p < 0.05). Fast-twitch muscle fiber cross-sectional areas of the quadriceps muscle were also significantly increased in the M5 group post intervention (Type IIa; +30.9%, Type IIx, +28.5%, p < 0.05). Sub-group analysis indicated even greater gains in total lean mass in sarcopenic individuals following HBRE/MIS therapy (TLM; +1.65 kg/+3.4%, p < 0.05). We conclude that the Muscle5 supplement is a safe, well-tolerated, and effective complement to low-intensity, home-based resistance exercise and improves lean mass, strength, and overall muscle quality in old age.

An Assessment of the Performance of the PLUS+ Tool in Supporting the Evaluation of Water Framework Directive Compliance in Scottish Standing Waters.

Phosphorus is one of the main causes of waterbodies in Scotland being at less than good ecological status (GES) in terms of the water framework directive (WFD). In Scotland, there are more than 8000 standing waters, defined as lakes and reservoirs that have a surface area of more than 0.5 km2. Only about 330 of these are monitored routinely to assess compliance with the WFD. The export coefficient tool PLUS+ (phosphorus land use and slope) has been developed to estimate total phosphorus (TP) concentrations in the unmonitored sites; modelled values are then compared to WFD target concentrations for high, good, moderate, poor, and bad status to assess compliance. These type-specific or site-specific targets are set by the regulatory authority and form part of a suite of physical, chemical, and ecological targets that are used to assess GES, all of which must be met. During development, the PLUS+ tool was applied to 323 monitored catchments and 7471 unmonitored catchments. The efficacy of the tool was assessed against TP concentrations observed in 2014 and found to perform well in the rural catchments. 51% of standing waters had the same modelled and observed WFD class (i.e., High, Good, Moderate, Poor, Bad), and a further 40% of standing waters had a modelled WFD class that was within one class of observed water quality. The tool performed less well in catchments with larger inputs of TP from urban sources (e.g., sewage). The greatest deviations between measured and modelled classes were explained by the shortage of information on wastewater treatment works, fish farms, migratory birds, levels of uncertainty in TP measurements, and the amount of in-lake re-cycling of P. The limitations of the tool are assessed using data from six well documented case study sites and recommendations for improving the model performance are proposed.

The potential role of sediment organic phosphorus in algal growth in a low nutrient lake.

The role of sediment-bound organic phosphorus (Po) as an additional nutrient source is a component of internal P budgets in lake system that is usually neglected. Here we examined the relative importance of sediment Po to internal P load and the role of bioavailable Po in algal growth in Lake Erhai, China. Lake Erhai sediment extractable Po accounted for 11-43% (27% average) of extractable total P, and bioavailable Po accounted for 21-66% (40%) of Po. The massive storage of bioavailable Po represents an important form of available P, essential to internal loads. The bioavailable Po includes mainnly labile monoester P and diester P was identified in the sequential extractions by H2O, NaHCO3, NaOH, and HCl. 40% of H2O-Po, 39% of NaHCO3-Po, 43% of NaOH-Po, and 56% of HCl-Po can be hydrolyzed to labile monoester and diester P, suggesting that the bioavailability of Po fractions was in decreasing order as follows: HCl-Po > NaOH-Po > H2O-Po > NaHCO3-Po. It is implied that traditional sequential fractionation of Po might overestimate the availability of labile Po in sediments. Furthermore, analysis of the environmental processes of bioavailable Po showed that the stabler structure of dissloved organic matter (DOM) alleviated the degradation and release of diester P, abundant alkaline phosphatase due to higher algal biomass promoted the degradation of diester P. The stability of DOM structure and the degradation of diester P might responsible for the spatial differences of labile monoester P. The biogeochemical cycle of bioavailable Po replenishs available P pools in overlying water and further facilitate algal growth during the algal blooms. Therefore, to control the algal blooms in Lake Erhai, an effective action is urgently required to reduce the accumulation of Po in sediments and interrupt the supply cycle of bioavailable Po to algal growth.

Nutrient fluxes from domestic wastewater: A national-scale historical perspective for the UK 1800-2010.

Nutrient emissions in human waste and wastewater effluent fluxes from domestic sources are quantified for the UK over the period 1800-2010 based on population data from UK Census returns. The most important drivers of change have been the introduction of the water closet (flush toilet) along with population growth, urbanization, connection to sewer, improvements in wastewater treatment and use of phosphorus in detergents. In 1800, the population of the UK was about 12 million and estimated emissions in human waste were 37kt N, 6.2kt P and 205ktorganicC/year. This would have been recycled to land with little or no sewage going directly to rivers or coastal waters. By 1900, population had increased to 35.6 million and some 145kt N were emitted in human waste but, with only the major urban areas connected to sewers, only about 19kt N were discharged in sewage effluent. With the use of phosphorus in detergents, estimated phosphorus emissions peaked at around 63.5ktP/year in the 1980s, with about 28ktP/year being discharged in sewage effluent. By 2010, population had increased to 63 million with estimated emissions of 263kt N, 43.6kt P and 1460ktorganicC/year, and an estimated effluent flux of 104kt N, 14.8kt P and 63kt organic C. Despite improvements in wastewater treatment, current levels of nutrient fluxes in sewage effluent are substantially higher than those in the early 20th century.

Phosphorus legacy: overcoming the effects of past management practices to mitigate future water quality impairment.

The water quality response to implementation of conservation measures across watersheds has been slower and smaller than expected. This has led many to question the efficacy of these measures and to call for stricter land and nutrient management strategies. In many cases, this limited response has been due to the legacies of past management activities, where sinks and stores of P along the land-freshwater continuum mask the effects of reductions in edge-of-field losses of P. Accounting for legacy P along this continuum is important to correctly apportion sources and to develop successful watershed remediation. In this study, we examined the drivers of legacy P at the watershed scale, specifically in relation to the physical cascades and biogeochemical spirals of P along the continuum from soils to rivers and lakes and via surface and subsurface flow pathways. Terrestrial P legacies encompass prior nutrient and land management activities that have built up soil P to levels that exceed crop requirements and modified the connectivity between terrestrial P sources and fluvial transport. River and lake P legacies encompass a range of processes that control retention and remobilization of P, and these are linked to water and sediment residence times. We provide case studies that highlight the major processes and varying timescales across which legacy P continues to contribute P to receiving waters and undermine restoration efforts, and we discuss how these P legacies could be managed in future conservation programs.

The effect of three-monthly albendazole treatment on malarial parasitemia and allergy: a household-based cluster-randomized, double-blind, placebo-controlled trial.

BACKGROUND: Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy. METHODS AND FINDINGS: A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5-15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35-12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74-1.86) at 9 months or 1.37 (0.93-2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported. CONCLUSIONS: The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN83830814.

Variation in chlorophyll a to total phosphorus ratio across 94 UK and Irish lakes: implications for lake management.

Eutrophication is the most widespread pressure impacting on lakes worldwide and, in general, its control is underpinned by the premise that algal biomass is regulated by phosphorus availability. This paper aims to demonstrate that not all lakes will conform to the underlying principle of the Chl:TP relationships using variables collected widely in lake monitoring programmes across the world (i.e. total phosphorus (TP) and chlorophyll a (Chl) concentrations). The ratio of annual mean Chl and TP concentrations in 94 lakes (2007 and 2008) was used as a measure of the efficiency with which TP is transferred into algal biomass (i.e. as an indicator of P limitation) to investigate the validity of the phosphorus reduction approach. Chl:TP ratios ranged from 0.02 to 0.84 in 2007 and from 0.03 to 0.96 in 2008. Chl and TP values were positively correlated (p < 0.05) with alkalinity, and negatively correlated with depth and surface area, in both years. In general, mean annual Chl and TP concentrations increased as alkalinity increased and depth decreased. However, Chl:TP ratio was highest in high alkalinity lakes in 2007, and moderate alkalinity lakes in 2008. Our results indicate that the use of TP water quality targets alone is insufficient to accurately manage eutrophication pressures at the lake specific scale, and that a wider range of ecological and ecosystem service evaluation targets would provide a more comprehensive assessment of management needs. The wide range of Chl:TP ratio values reported in this study suggests that, although reducing TP concentrations in lakes is undoubtedly a sensible approach to eutrophication management in many cases, TP reductions alone may not result in the expected reductions in phytoplankton biomass in all lakes.

Bibliometric measures and National Institutes of Health funding at colleges of osteopathic medicine, 2006-2010.

CONTEXT: During the past 20 years, colleges of osteopathic medicine (COMs) have made several advances in research that have substantially improved the osteopathic medical profession and the health of the US population. Furthering the understanding of research at COMs, particularly the factors influencing the attainment of extramural funds, is highly warranted and coincides with the missions of most COMs and national osteopathic organizations. OBJECTIVES: To describe bibliometric measures (numbers of peer-reviewed publications [ie, published articles] and citations of these publications, impact indices) at COMs from 2006 through 2010 and to examine statistical associations between these measures and the amount of National Institutes of Health (NIH) research funds awarded to COMs in 2006 and 2010. METHODS: A customized, systematic search of the Web of Science database was used to obtain bibliometric measures for 28 COMs. For the analyses, the bibliometric measures were summed or averaged over a 5-year period (2006 through 2010). The NIH database was used to obtain the amount of NIH funds for research grants and contracts received by the 28 COMs. Bivariate and multivariate statistical procedures were used to explore relationships between bibliometric measures and NIH funding amounts. RESULTS: The COMs with 2010 NIH funding, compared with COMs without NIH funding, had greater numbers of publications and citations and higher yearly average impact indices. Funding from the NIH in 2006 and 2010 was positively and significantly correlated with the numbers of publications, citations, and citations per publication and impact indices. The regression analysis indicated that 63.2% and 38.5% of the total variance in 2010 NIH funding explained by the model (adjusted R(2)=0.74) was accounted for by 2006 NIH funding and the combined bibliometric (ie, publications plus citations), respectively. CONCLUSION: Greater scholarly output leads to the procurement of more NIH funds for research at COMs.

Research funding at colleges of osteopathic medicine in the United States.

CONTEXT: Research is a vital component of a college of osteopathic medicine (COM) portfolio. Previous studies have described research activity at COMs from 1989 through 2004 using data from surveys of COM administrators conducted by the American Association of Colleges of Osteopathic Medicine (AACOM). However, these studies had limitations. OBJECTIVES: To address the limitations of previous studies and to provide more depth of understanding regarding research activity at COMs by (1) documenting changes in research funding at COMs from 2004 to 2009 according to the funding agencies, principal investigators' degrees, and areas of study after considering inflation and (2) examining predictors of research funding at COMs. METHODS: Information about 2004 and 2009 active research grants and contracts, research expenditures, and COM characteristics was obtained from AACOM databases. Descriptive statistics are presented for 20 COMs that completed the survey in both years. The 2004 dollar values were adjusted for the rate of inflation (13.57%). Bivariate and multivariate analyses were used to explore associations between school characteristics (eg, number of faculty), research expenditures, and research funding outcomes (total amount and number of awards) for all COMs completing the survey in 2009 (n=26). RESULTS: From 2004 to 2009, the total amount of awards increased from 115.2 million to 216.6 million, and the number of awards increased from 450 to 665. Funding rose substantially from foundations (336%), to PhD-DO principal investigators (909%), and for osteopathic manipulative medicine (60%). Total award amounts were positively associated with both research expenditures (P<.001) and the number of faculty (P<.001). Larger research expenditures also were related to securing a greater number of awards (P<.001). CONCLUSION: Research activity at COMs continues to advance partly because of investments in research and faculty made by COMs.

A longitudinal study of allergy and intestinal helminth infections in semi urban and rural areas of Flores, Indonesia (ImmunoSPIN Study).

BACKGROUND: The prevalence of asthma and atopic disease has been reported to be low in low income countries, however helminth infections are likely to be high among these communities. The question of whether helminth infections play a role in allergic diseases can best be addressed by intervention studies. None of the studies so far have been based on a large scale placebo-controlled trial. METHOD/DESIGN: This study was designed to assess how intestinal helminth infections can influence the immune response and atopic and allergic disorders in children in Indonesia. The relations between allergic outcomes and infection and lifestyle factors will be addressed. This study was set up among school-age children in semi urban and rural areas, located in Ende District of Flores Island, Indonesia. A randomized placebo-controlled anthelmintic treatment trial to elucidate the impact of helminth infections on the prevalence of skin prick test (SPT) reactivity and symptoms of allergic diseases will be performed. The children living in these semi-urban and rural areas will be assessed for SPT to allergens before and after 1 and 2 years of treatment as the primary outcome of the study; the secondary outcome is symptoms (asthma and atopic dermatitis); while the tertiary outcome is immune responses (both antibody levels to allergens and cellular immune responses). DISCUSSION: The study will provide information on the influence of helminth infections and anthelmintic treatment on immune response, atopy and allergic disorders. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: ISRCTN83830814.

Does treatment of intestinal helminth infections influence malaria? Background and methodology of a longitudinal study of clinical, parasitological and immunological parameters in Nangapanda, Flores, Indonesia (ImmunoSPIN Study).

BACKGROUND: Given that helminth infections are thought to have strong immunomodulatory activity, the question whether helminth infections might affect responses to malaria antigens needs to be addressed. Different cross-sectional studies using diverse methodologies have reported that helminth infections might either exacerbate or reduce the severity of malaria attacks. The same discrepancies have been reported for parasitemia. METHODS/DESIGN: To determine the effect of geohelminth infections and their treatment on malaria infection and disease outcome, as well as on immunological parameters, the area of Nangapanda on Flores Island, Indonesia, where malaria and helminth parasites are co-endemic was selected for a longitudinal study. Here a Double-blind randomized trial will be performed, incorporating repeated treatment with albendazole (400 mg) or placebo at three monthly intervals. Household characteristic data, anthropometry, the presence of intestinal helminth and Plasmodium spp infections, and the incidence of malaria episodes are recorded. In vitro cultures of whole blood, stimulated with a number of antigens, mitogens and toll like receptor ligands provide relevant immunological parameters at baseline and following 1 and 2 years of treatment rounds. The primary outcome of the study is the prevalence of Plasmodium falciparum and P. vivax infection. The secondary outcome will be incidence and severity of malaria episodes detected via both passive and active follow-up. The tertiary outcome is the inflammatory cytokine profile in response to parasite antigens. The project also facilitates the transfer of state of the art methodologies and technologies, molecular diagnosis of parasitic diseases, immunology and epidemiology from Europe to Indonesia. DISCUSSION: The study will provide data on the effect of helminth infections on malaria. It will also give information on anthelminthic treatment efficacy and effectiveness and could help develop evidence-based policymaking. TRIAL REGISTRATION: This study was approved by The Ethical Committee of Faculty of Medicine, University of Indonesia, ref:194/PT02.FK/Etik/2006 and has been filed by ethics committee of the Leiden University Medical Center. CLINICAL TRIAL NUMBER: ISRCTN83830814. The study is reported in accordance with the CONSORT guidelines for cluster-randomized studies.

The importance of nitrogen limitation in the restoration of Llangorse Lake, Wales, UK.

Llangorse Lake is the largest natural lake in South Wales, UK, and is of European conservation importance. The site has a long history of eutrophication problems and, in recent years, significant efforts have been made to meet water quality restoration targets at this site by reducing the input of phosphorus (P) from external sources. Although the lake has improved substantially in quality since the late 1970s, it is still not meeting its ecological targets. Phosphorus concentrations have remained high and there has been little reduction in algal biomass. Management decisions to reduce P input were originally based on the widely held assumption that shallow lakes are P-limited in summer. However, this study clearly shows that this is not always the case; Llangorse Lake, at least, is strongly nitrogen (N) limited over the summer months. As a result, bio-available P released from the sediments cannot be used by the phytoplankton population. So, it accumulates in the water column, causing very high concentrations to occur in late summer. This puts the lake at very high risk of developing algal blooms when N availability increases, usually in early autumn. The study also found that the hydrology of the lake was strongly affected by sub-surface flow. This suggested that nutrients and water could be delivered to the lake from areas beyond the topographically defined surface water catchment. These findings have widespread implications for the successful management of external inputs to lakes, which currently tends to focus on management of the surface water catchment only. The results are discussed in relation to the restoration and management of nitrogen-limited lakes, and of those that are significantly affected by sub-surface flow.