Biomarkers of immune tolerance in kidney transplantation: an overview.

Kidney failure, one of the most prevalent diseases in the world and with increasing incidence, is associated with substantial morbidity and mortality. Currently available modes of kidney replacement therapy include dialysis and kidney transplantation. Though kidney transplantation is the preferred and ideal mode of kidney replacement therapy, this modality, however, is not without its risks. Kidney transplant recipients are constantly at risk of complications associated with immunosuppression, namely, opportunistic infections (e.g., Epstein-Barr virus and cytomegalovirus infections), post-transplant lymphoproliferative disorder, and complications associated with immunosuppressants (e.g., calcineurin inhibitor- and corticosteroid-associated new onset diabetes after transplantation and calcineurin inhibitor-associated nephrotoxicity). Transplantation tolerance, an acquired state in which immunocompetent recipients have developed donor-specific unresponsiveness, may be the Holy Grail in enabling optimal allograft survival and obviating the risks associated with immunosuppression in kidney transplant recipients. This review aims to discuss the biomarkers available to predict, identify, and define the transplant immune tolerant state and various tolerance induction strategies. Regrettably, pediatric patients have not been included in any tolerance studies and this should be the focus of future studies.

A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction.

Many developed countries are experiencing a rapidly "greying" population, and cognitive decline is common in the elderly. There is no cure for dementia, and pharmacotherapy options to treat cognitive dysfunction provide limited symptomatic improvements. Withania somnifera (Ashwagandha), a popular herb highly valued in Ayurvedic medicine, has often been used to aid memory and cognition. This systematic review thus aimed to evaluate the clinical evidence base and investigate the potential role of W. somnifera in managing cognitive dysfunction. Using the following keywords [withania somnifera OR indian ginseng OR Ashwagandha OR winter cherry] AND [brain OR cognit* OR mental OR dementia OR memory], a comprehensive search of PubMed, EMBASE, Medline, PsycINFO and Clinicaltrials.gov databases found five clinical studies that met the study's eligibility criteria. Overall, there is some early clinical evidence, in the form of randomized, placebo-controlled, double-blind trials, to support the cognitive benefits of W. somnifera supplementation. However, a rather heterogeneous study population was sampled, including older adults with mild cognitive impairment and adults with schizophrenia, schizoaffective disorder, or bipolar disorder. In most instances, W. somnifera extract improved performance on cognitive tasks, executive function, attention, and reaction time. It also appears to be well tolerated, with good adherence and minimal side effects.

MeSsAGe risk score: tool for renal biopsy decision in steroid-dependent nephrotic syndrome.

BACKGROUND: A lack of consensus exists as to the timing of kidney biopsy in children with steroid-dependent nephrotic syndrome (SDNS) where minimal change disease (MCD) predominates. This study aimed at examining the applicability of a biomarker-assisted risk score model to select SDNS patients at high risk of focal segmental glomerulosclerosis (FSGS) for biopsy. METHODS: Fifty-five patients with SDNS and biopsy-proven MCD (n = 40) or FSGS (n = 15) were studied. A risk score model was developed with variables consisting of age, sex, eGFR, suPAR levels and percentage of CD8+ memory T cells. Following multivariate regression analysis, total risk score was calculated as sum of the products of odds ratios and corresponding variables. Predictive cut-off point was determined using receiver operator characteristics (ROC) curve analysis. RESULTS: Plasma suPAR levels in FSGS patients were significantly higher, while percentage of CD45RO+CD8+CD3+ was significantly lower than in MCD patients and controls. ROC analysis suggests the risk score model with threshold score of 16.7 (AUC 0.84, 95% CI 0.72-0.96) was a good predictor of FSGS on biopsy. The 100% PPV cut-off was >24.0, while the 100% NPV was <13.3. CONCLUSION: A suPAR and CD8+ memory T cell percentage-based risk score model was developed to stratify SDNS patients for biopsy and for predicting FSGS.

A Systematic Review of the Effect of Probiotic Supplementation on Schizophrenia Symptoms.

BACKGROUND: Derangements of the gut microbiome have been linked to increased systemic inflammation and central nervous system disorders, including schizophrenia. This systematic review thus aimed to investigate the hypothesis that probiotic supplementation improves schizophrenia symptoms. METHODS: By using the keywords (probiotic OR gut OR microbiota OR microbiome OR yogurt OR yoghurt OR lactobacillus OR bifidobacterium) AND (schizophrenia OR psychosis), a preliminary search of the PubMed, Medline, Embase, Google Scholar, ClinicalTrials.gov, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), and Cochrane Field for Complementary Medicine databases yielded 329 papers published in English between January 1, 1960 and May 1, 2018. Attempts were made to search grey literature as well. RESULTS: Three clinical studies were reviewed, comparing the use of probiotics to placebo controls. Applying per-protocol analysis and a fixed-effects model, there was no significant difference in schizophrenia symptoms between the group that received probiotic supplementation and the placebo group post-intervention as the standardized mean difference was -0.0884 (95% CI -0.380 to 0.204, p = 0.551). Separate analyses were performed to investigate the effect of probiotic supplementation on positive or negative symptoms of schizophrenia alone. In both instances, no significant difference was observed as well. CONCLUSION: Based on current evidence, limited inferences can be made regarding the efficacy of probiotics in schizophrenia. Although probiotics may have other benefits, for example to regulate bowel movement and ameliorate the metabolic effects of antipsychotic medications, the clinical utility of probiotics in the treatment of schizophrenia patients remains to be validated by future clinical studies.

Systematic review with meta-analysis: The association between post-traumatic stress disorder and irritable bowel syndrome.

BACKGROUND AND AIM: Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by symptoms of hyperarousal and hypervigilance. Increasing research on the "gut-brain" axis (bidirectional signaling between the gut and the brain) has drawn links between PTSD and irritable bowel syndrome (IBS), an exceedingly common yet incompletely understood gastrointestinal condition. This meta-analysis thus aimed to examine the body of evidence and extent of association of PTSD with IBS. METHODS: Using the keywords [early abuse OR childhood abuse OR violence OR trauma OR PTSD] AND [irritable bowel syndrome or IBS], a preliminary search on the PubMed, Medline, Embase, ScienceDirect, PsychINFO, Web of Science, and Google Scholar databases yielded 11,257 papers published in English between January 1, 1988, and May 1, 2018. Of these, only eight studies were included in the final meta-analysis. RESULTS: The eight studies (four cross-sectional and four cohort) contained a total of 648,375 subjects. Most studies were from the USA and conducted on army veterans. The funnel plot revealed a roughly symmetrical distribution of studies, and Egger test was not significant for publication bias (P = 0.583). Random-effects meta-analysis found PTSD to be a significant risk factor for IBS (pooled odds ratio 2.80, 95% confidence interval: 2.06 to 3.54, P < 0.001). CONCLUSIONS: Overall, PTSD is associated with an increased likelihood of IBS. This is the first meta-analysis to specifically examine the association between PTSD and IBS, and it provides insights into the probable (patho)physiology and management of IBS, supporting a holistic consideration of the psychosocial aspects of IBS and further research into effective multi-modal therapeutics.

A systematic review of the use of rifaximin for Clostridium difficile infections.

Clostridium difficile infection (CDI) is an increasingly common occurrence in the hospital setting, and it is associated with significant morbidity and mortality. In vitro studies have found that rifaximin, a nonabsorbable rifamycin antibiotic, displays potent antimicrobial activity against C. difficile. This systematic review thus aimed to examine the clinical role of rifaximin in CDI. Using the keywords [clostridium OR difficile OR colitis] AND [rifaximin OR xifaxan OR rifagut], a preliminary search on the PubMed, EMBASE, Medline, Clinicaltrials.gov and Google Scholar databases yielded 6210 papers published in English between 1-Jan-1988 and 1-Jul-2018. A total of eight clinical trials were systematically reviewed. Of these, only two were randomized, controlled trials. In the treatment of mild-moderate CDI, rifaximin is a viable alternative to existing therapies (metronidazole or vancomycin). More importantly, rifaximin has a potential role in conjunction with other therapies, showing to be efficacious in reducing the rate of CDI recurrence. However, clinical studies have reported a resistance rate in the range of 29.1-48.9%, with a geographical variance in the distribution of rifaximin-resistant C. difficile strains. With its unique eubiotic properties and positive modulation of the gut flora, rifaximin has a potential therapeutic role in the management of CDI, especially in CDI recurrences. As there is a paucity of randomized, controlled trials to support its use, studies with larger and more diverse populations should be conducted before the efficacy of rifaximin can be conclusively stated. Rifaximin is also a relatively expensive antimicrobial, further studies should include cost-benefit analyses.

A Meta-Analysis of the Utility of Preoperative Intravenous Paracetamol for Post-Caesarean Analgesia.

Background and objectives: Worldwide, the number of caesarean sections performed has increased exponentially. Some studies have reported better pain control and lower postoperative requirements for opioids when intravenous (IV) paracetamol was administered preoperatively. This meta-analysis thus aimed to investigate the utility of preoperative IV paracetamol for post-caesarean analgesia. Materials and Methods: By using the keywords (paracetamol OR acetaminophen) AND [cesarea* OR caesarea* OR cesaria* OR caesaria*], a systematic literature search was conducted using PubMed, Medline, Embase, Google Scholar and ClinicalTrials.gov databases for papers published in English between January 1, 1960 and March 1, 2019. Grey literature was searched as well. Results: Seven clinical trials were reviewed, while five randomized, placebo-controlled, double-blind studies were included in the final meta-analysis. Applying per-protocol analysis and a random-effects model, there was a significant reduction in postoperative opioid consumption and pain score in the group that received preoperative IV paracetamol, compared to placebo, as the standardized mean difference (SMD) were -0.460 (95% CI -0.828 to -0.092, p = 0.014) and -0.719 (95% CI: -1.31 to -0.13, p = 0.018), respectively. However, there was significant heterogeneity amongst the different studies included in the meta-analysis (I2 = 70.66%), perhaps owing to their diverse protocols. Some studies administered IV paracetamol 15 min before induction while others gave it before surgical incision. Conclusion: This is the first review on the topic. Overall, preoperative IV paracetamol has convincingly demonstrated useful opioid-sparing effects and it also appears safe for use at the time of delivery. It should be considered as a component of an effective multimodal analgesic regimen. Future studies could be conducted on other patient groups, e.g., those with multiple comorbidities or chronic pain disorders, and further delineate the optimal timing to administer the drug preoperatively.

A Systematic Review of the Role of Prebiotics and Probiotics in Autism Spectrum Disorders.

Background: Autism spectrum disorder (ASD) is a complex developmental condition typically characterized by deficits in social and communicative behaviors as well as repetitive patterns of behaviors. Despite its prevalence (affecting 0.1% to 1.8% of the global population), the pathogenesis of ASD remains incompletely understood. Patients with ASD are reported to have more frequent gastrointestinal (GI) complaints. There is some anecdotal evidence that probiotics are able to alleviate GI symptoms as well as improve behavioral issues in children with ASD. However, systematic reviews of the effect of prebiotics/probiotics on ASD and its associated symptoms are lacking. Methods: Using the keywords (prebiotics OR probiotics OR microbiota OR gut) AND (autism OR social OR ASD), a systematic literature search was conducted on PubMed, EMBASE, Medline, Clinicaltrials.gov and Google Scholar databases. The inclusion criteria were original clinical trials, published in English between the period 1st January 1988 and 1st February 2019. Results: A total of eight clinical trials were systematically reviewed. Two clinical trials examined the use of prebiotic and/or diet exclusion while six involved the use of probiotic supplementation in children with ASD. Most of these were prospective, open-label studies. Prebiotics only improved certain GI symptoms; however, when combined with an exclusion diet (gluten and casein free) showed a significant reduction in anti-sociability scores. As for probiotics, there is limited evidence to support the role of probiotics in alleviating the GI or behavioral symptoms in children with ASD. The two available double-blind, randomized, placebo-controlled trials found no significant difference in GI symptoms and behavior. Conclusion: Despite promising preclinical findings, prebiotics and probiotics have demonstrated an overall limited efficacy in the management of GI or behavioral symptoms in children with ASD. In addition, there was no standardized probiotics regimen, with multiple different strains and concentrations of probiotics, and variable duration of treatments.

A meta-analysis of the association between Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum remains a common, distressing, and significant yet poorly understood disorder during pregnancy. The association between maternal Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum has been increasingly recognized and investigated. This study thus aimed to provide an updated review and meta-analysis of the topic. METHODS: Using the search terms (H. pyloriOR Helicobacter ORHelicobacter pyloriOR infection) AND (pregnancy OR emesis OR hyperemesis gravidarum OR nausea OR vomiting), a preliminary search on the PubMed, Ovid, Web of Science, Google Scholar, and WanFang database yielded 372 papers published in English between January 1st, 1960 and June 1st, 2017. RESULTS: A total of 38 cross-sectional and case-control studies, with a total of 10 289 patients were eligible for review. Meta-analysis revealed a significant association between H. pylori infection and hyperemesis gravidarum during pregnancy, with a pooled odds ratio of 1.348 (95% CI: 1.156-1.539, P < .001). Subgroup analysis found that serologic and stool antigen tests were comparable methods of detecting H. pylori as they yielded similar odds ratios. LIMITATIONS: Although the studies did not have high heterogeneity (I2  = 28%), publication bias was observed, and interstudy discrepancies in the diagnostic criteria adopted for hyperemesis gravidarum limit the reliability of findings. Also, 15 of the included studies were from the same country (Turkey), which could limit the generalizability of current findings. The prevalence of H. pylori infection varies throughout the world, and there may also be pathogenic differences as most strains of H. pylori in East Asia carry the cytotoxin-associated gene A gene. CONCLUSION: H. pylori infection was associated with an increased likelihood of hyperemesis gravidarum during pregnancy. Given the high prevalence of H. pylori infections worldwide, detecting H. pylori infection and the eradication of maternal H. pylori infection could be part of maternal hyperemesis gravidarum management. Further confirmation with robust longitudinal studies and mechanistic investigations are needed.

Disruptive technological advances in vascular access for dialysis: an overview.

End-stage kidney disease (ESKD), one of the most prevalent diseases in the world and with increasing incidence, is associated with significant morbidity and mortality. Current available modes of renal replacement therapy (RRT) include dialysis and renal transplantation. Though renal transplantation is the preferred and ideal mode of RRT, this modality may not be available to all patients with ESKD. Moreover, renal transplant recipients are constantly at risk of complications associated with immunosuppression and immunosuppressant use, and posttransplant lymphoproliferative disorder. Dialysis may be the only available modality in certain patients. However, dialysis has its limitations, which include issues associated with lack of vascular access, risks of infections and vascular thrombosis, decreased quality of life, and absence of biosynthetic functions of the kidney. In particular, the creation and maintenance of hemodialysis vascular access in children poses a unique set of challenges to the pediatric nephrologist owing to the smaller vessel diameters and vascular hyperreactivity compared with adult patients. Vascular access issues continue to be one of the major limiting factors prohibiting the delivery of adequate dialysis in ESKD patients and is the Achilles' heel of hemodialysis. This review aims to provide a critical overview of disruptive technological advances and innovations for vascular access. Novel strategies in preventing neointimal hyperplasia, novel bioengineered products, grafts and devices for vascular access will be discussed. The potential impact of these solutions on improving the morbidity encountered by dialysis patients will also be examined.

Bioengineering in renal transplantation: technological advances and novel options.

End-stage kidney disease (ESKD) is one of the most prevalent diseases in the world with significant morbidity and mortality. Current modes of renal replacement therapy include dialysis and renal transplantation. Although dialysis is an acceptable mode of renal replacement therapy, it does have its shortcomings, which include poorer life expectancy compared with renal transplantation, risk of infections and vascular thrombosis, lack of vascular access and absence of biosynthetic functions of the kidney. Renal transplantation, in contrast, is the preferred option of renal replacement therapy, with improved morbidity and mortality rates and quality of life, compared with dialysis. Renal transplantation, however, may not be available to all patients with ESKD. Some of the key factors limiting the availability and efficiency of renal transplantation include shortage of donor organs and the constant risk of rejection with complications associated with over-immunosuppression respectively. This review focuses chiefly on the potential roles of bioengineering in overcoming limitations in renal transplantation via the development of cell-based bioartificial dialysis devices as bridging options before renal transplantation, and the development of new sources of organs utilizing cell and organ engineering.

Agomelatine, a novel therapeutic option for the management of irritable bowel syndrome.

WHAT IS KNOWN AND OBJECTIVE: Irritable bowel syndrome (IBS) is a complex and chronic, relapsing gastrointestinal condition that affects more than 10% of the population worldwide. There is a pressing need for new therapeutic strategies in the management of IBS. Increasing research has shed light on the modulatory functions of melatonin on pain, local inflammation and motility in the gastrointestinal tract. However, melatonin's effects are limited by its extensive first-pass metabolism and short half-life. COMMENT: Agomelatine, a naphthalene analog of melatonin, is a novel melatonergic drug with a longer half-life and a comparatively greater affinity for MT1 and MT2 melatonin receptors than melatonin itself. Agomelatine also shows serotonin 5-HT3 receptor antagonist activity, which is theoretically of benefit for patients with IBS with diarrhoea (IBS-D) as it regulates gastrointestinal motility and visceral sensory mechanisms. Although only one clinical study of agomelatine use in patients with IBS exists, we believe that agomelatine is a safe and efficacious multimodal agent with untapped potential in the management of IBS. WHAT IS NEW AND CONCLUSION: Numerous comorbidities are associated with IBS, including chronic pain syndromes and psychiatric disorders. Coupled with its antidepressant actions, agomelatine could serve as an effective adjunct therapeutic. Agomelatine should be considered in our therapeutic armamentarium for IBS management.

Recurrent white thrombi formation in hemodialysis tubing: a case report.

BACKGROUND: While the appearance of red clots in the dialyzer is a common phenomenon in every hemodialysis unit, the occurrence of white thrombi in the tubing is relatively rare. CASE PRESENTATION: We describe an adolescent male with recurrent white thrombi formation in the hemodialysis tubing. This patient had chronic renal failure from focal segmental glomerulosclerosis, but was no longer nephrotic at the time of the thrombi formation. He had a history of recurrent thrombosis of his vascular access. However, no pro-thrombotic risk factors could be identified. White particulate matter, measuring 1 to 3mm in size, and adherent to the arterial and venous blood tubing lines was found during the rinse back of a hemodialysis session. This was associated with a 60% decrease in his platelet count. Light microscopic examination of the deposits revealed the presence of platelet aggregates. He subsequently developed thrombosis of his arteriovenous graft six hours later. The white thrombi recurred at the next dialysis session, as well as six months later. These episodes occurred regardless of the type of dialysis machine or tubing, and appeared to resolve with an increase in heparin dose. CONCLUSION: Recurrent white thrombi formation can occur in the hemodialysis tubing of a patient with no identifiable pro-thrombotic factors. The white thrombi may be a harbinger of arteriovenous graft thrombosis and may be prevented by an increase in heparin dose.

Use of HF20 membrane in critically ill unstable low-body-weight infants on inotropic support.

BACKGROUND: Initiating continuous renal replacement therapy (CRRT) in infants exposes them to the dual hemodynamic challenges of high circuit extracorporeal volumes and potential membrane reactions, in the case of acrylonitrile AN69 membranes. The use of the new Prismaflex HF20 membrane in hemodynamically unstable low-body-weight infants on inotropic support has not been reported. TREATMENT: We describe the use of the HF20 (Gambro Lundia AB, Lund, Sweden) membrane in four low-body-weight infants (2.3 to 5.4 kg) with multi-organ dysfunction syndrome who were critically ill in the Pediatric Intensive Care Unit (PICU), hemodynamically unstable, and on inotropes. We were able to achieve target volume loss in all infants without compromising their hemodynamic status. Mean arterial pressures were maintained between 39 and 57 mmHg. The relatively low circuit volume of the HF20 set (60 ml) obviated the need for blood prime in the majority; however, when blood prime was required, there was no adverse reaction with the polyarylethersulfone (PAES) membrane. Solute clearance in these small infants was efficient with correction of metabolic acidosis and electrolyte abnormalities. Excellent circuit lifespan (56.3 ± 32.3 h) was observed. CONCLUSIONS: CRRT using the HF20 membrane is safe and hemodynamically well tolerated in high-risk, unstable low-body-weight infants with cardiac dysfunction on multiple inotropes.

A Systematic Review and Meta-Analysis of the Clinical Use of Megestrol Acetate for Cancer-Related Anorexia/Cachexia.

Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol acetate (MA) is often used off-label to stimulate appetite and improve anorexia/cachexia in patients with advanced cancers, the benefits are controversial. The present meta-analysis aimed to better elucidate the clinical benefits of MA in patients with cancer-related anorexia/cachexia. A systematic search of PubMed, EMBASE, OVID Medline, Clinicaltrials.gov, and Google Scholar databases found 23 clinical trials examining the use of MA in cancer-related anorexia. The available randomized, controlled trials were appraised using Version 2 of the Cochrane risk-of-bias tool (RoB 2) and they had moderate-to-high risk of bias. A total of eight studies provided sufficient data on weight change for meta-analysis. The studies were divided into high-dose treatment (>320 mg/day) and low-dose treatment (≤320 mg/day). The overall pooled mean change in weight among cancer patients treated with MA, regardless of dosage was 0.75 kg (95% CI = −1.64 to 3.15, τ2 = 9.35, I2 = 96%). Patients who received high-dose MA tended to have weight loss rather than weight gain. There were insufficient studies to perform a meta-analysis for the change in tricep skinfold, midarm circumference, or quality of life measures. MA was generally well-tolerated, except for a clear thromboembolic risk, especially with higher doses. On balance, MA did not appear to be effective in providing the symptomatic improvement of anorexia/cachexia in patients with advanced cancer.

Obsessive-Compulsive Disorders and Functional Urinary Disorders: A Fortuitous Association?

Although psychological factors are known to affect bladder and bowel control, the occurrence of functional urinary disorders in patients with psychiatric disorders has not been well-studied or described. A higher prevalence of functional lower urinary tract disorders have also been reported amongst patients with obsessive-compulsive (OC) disorders. A systematic literature search of PubMed, EMBASE, OVID Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found five observational studies on the topic. Unfortunately, as only one study had a (healthy) control group, a meta-analytic approach was not possible. Overall, patients with OC symptoms appeared to have increased occurrence of functional urinary symptoms, e.g., overactive bladder, increase in urgency, frequency, incontinence and enuresis. This was even more common amongst patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS) or Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) as opposed to patients with OCD alone. Several biological and behavioural mechanisms and treatment approaches were discussed. However, as the current evidence base was significantly limited and had moderate to serious risk of bias, no strong inferences could be drawn. Further well-designed cohort studies are necessary to better elucidate the observed associations and their management.

Effects of Astaxanthin Supplementation on Skin Health: A Systematic Review of Clinical Studies.

Astaxanthin (AST), a naturally-occurring keto-carotenoid found in several species of bacteria and microalgae, has demonstrated diverse biological activities in vitro and in vivo. There is growing commercial interest in the application of astaxanthin in nutraceuticals and cosmeceuticals, due to its purported photoprotective, DNA repair, antioxidant, and anti-inflammatory benefits. This systematic review therefore aimed to summarize current clinical evidence on the effects of astaxanthin supplementation on skin health. Using the following combinations of broad Major Exploded Subject Headings (MesH) terms or text words [astaxanthin OR AST OR ASX OR carotenoid OR xanthophyll] AND [skin OR derm*], a comprehensive search of PubMed, EMBASE, Medline, Clinicaltrials.gov, and Google Scholar databases found a total of eleven clinical studies. There were six randomized, placebo-controlled, double-blind trials, while the rest were prospective, open-label studies. In many of the randomized, controlled trials reviewed, AST supplementation improved skin texture, appearance (wrinkles), and moisture content at the end of the study period. AST also appeared to protect against UV-induced skin damage. No serious adverse events were reported in any of the studies. However, most available studies had a relatively small sample size and were conducted on healthy Japanese females. Many of the studies were also funded by commercial entities, with potential conflicts of interests. This was difficult to account for in our analyses. Overall, there is some clinical data to support the benefits of astaxanthin supplementation (in the range of 3 to 6 mg/d) on skin health, especially for photoaged skin.