• Probiotics Show Benefits for Nonalcoholic Fatty Liver Disease
• Vitamin D Supplementation Does Little to Improve Asthma Control
• The Placental Microbiome
• Changes in Vaginal Microorganisms During the Menopausal Transition
• Successful Nonoperative Management of Uncomplicated Acute Appendicitis with
Antibiotic Therapy
• More Evidence for Anti-Aging Effects of a Mammalian Molecule
• Irritable Bowel Syndrome Runs in Families
• Statins Disappoint in COPD and ARDS
MM: This is a very important study that demonstrates some of the benefits of high dose probiotics. The strains contained in VSL#3 are similar to those contained in all of the Synergy Blends Products and that are recommended in conjunction with the HCG Metabolic Syndrome Protocol.
Aliment Pharmacol Ther 2014 Jun; 39:1276
Probiotics Show Benefits for Nonalcoholic Fatty Liver Disease
A 4-month course of VSL#3 reduced the severity of fatty liver in obese children.
Few treatment options are available for non-alcoholic fatty liver disease (NAFLD). However, recent evidence suggests that modulation of the gut microbiome with probiotics may have a therapeutic role in NAFLD.
In the current parallel-arm, double-blind trial, investigators assessed the efficacy of VSL#3, a mixture of eight probiotic strains that has been studied in experimental models of NAFLD. Forty-eight obese (body-mass index >85th percentile) children with biopsy-proven NAFLD and abnormal liver tests were randomized to receive VSL#3 daily (1 packet if aged <10 years; 2 packets if aged ≥10 years) or placebo for 4 months. The main study outcome was the change in fatty liver severity by ultrasonography at 4 months.
At baseline, moderate and severe NAFLD were present in 55% and 45% of the patients in the VSL#3 group and 64% and 36% in the placebo group. The odds ratio of more severe versus less severe steatosis after 4 months of treatment was 0.001 (95% confidence interval, 0.0001–0.02) for the VSL#3 group versus the placebo group. The probabilities of moderate and severe fatty liver after treatment were 9% and 0% in the VSL#3 group compared with 76% and 17% in the placebo group.
Comment: In this small, randomized, placebo-controlled study, fatty liver improved with a relatively short course of probiotics in children. These results appear to be the first evidence in humans of the potential therapeutic role of probiotics in NAFLD. Further studies are needed with larger sample sizes, longer follow-up, and histologic and clinical primary endpoints.
Citation(s): Alisi A et al. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with nonalcoholic steatohepatitis. Aliment Pharmacol Ther 2014 Jun; 39:1276.
(http://dx.doi.org/10.1111/apt.12758)
http://www.ncbi.nlm.nih.gov/pubmed/24738701?access_num=
24738701&link_type=MED&dopt=Abstract
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MM: I still have to argue with this study. My clinical experience over the past decade with my direct patients has demonstrated fewer asthmatic exacerbations and those that have occurred are less intense and did not typically result in the patients entering the hospital. In general, we see fewer incidences of colds, flu, allergies or asthmatic attacks when patients have vitamin D levels in the 60-80ng/ml range.
JAMA 2014 May 28; 311:2083
Vitamin D Supplementation Does Little to Improve Asthma Control
No need to check vitamin D levels in patients with uncontrolled asthma.
In patients with asthma, lower serum levels of 25-hydroxyvitamin D have been associated with more-frequent exacerbations, airway hyper-responsiveness, and decreased lung function. Low vitamin D levels theoretically could exacerbate pro-inflammatory states and reduce corticosteroid responsiveness. To determine whether vitamin D supplementation improves responsiveness to corticosteroid therapy, investigators randomized 408 adults (mean age, 40) with asthma and 25-hydroxyvitamin D levels <30 ng/mL (mean, 18.8 ng/mL) to high-dose oral vitamin D3 supplementation (initial dose of 100,000 IU followed by 4000 IU daily) or placebo for 28 weeks. All participants received the inhaled corticosteroid ciclesonide (320 μg daily). During the study period, ciclesonide use was tapered in those whose asthma was controlled.
At 28 weeks, 82% of patients had achieved vitamin D levels of ≥30 ng/mL. No differences were observed overall between the supplementation and placebo groups in the primary outcome of asthma treatment failure (e.g., decline in lung function, increased use of rescue medications). In addition, no clinically meaningful differences were observed between groups in various secondary outcomes.
Comment: This is yet another study that shows that, although low vitamin D levels are associated with many diseases, supplementation does not affect clinical outcomes meaningfully. We should not check vitamin D levels or supplement vitamin D in hopes of improving asthma control.
Citation(s): Castro M et al. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: The VIDA randomized clinical trial. JAMA 2014 May 28; 311:2083.
(http://dx.doi.org/10.1001/jama.2014.5052)
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MM: I merely found this article interesting. It got me thinking... Periodontal disease tends to accompany inflammation and has further been related to cardiovascular illness. It would be interesting to see if these two conditions could be reduced over a lifetime if moms or infants were administered probiotics either in partum to the mother or post-partum to the newborn.
Sci Transl Med 2014 May 21; 6:237ra65
The Placental Microbiome
Analysis of placentas from healthy pregnancies revealed a distinct microbiome that is most similar to the oral microbiome.
It has been commonly accepted that the intrauterine environment during pregnancy is relatively sterile and that the introduction of bacteria could lead to the development of chorioamnionitis. However, several recent studies have found both gram-positive and gram-negative bacteria — including taxa not associated with the urogenital tract — in placental tissue showing no evidence of chorioamnionitis. To explore this issue further, researchers in Texas undertook a comprehensive metagenomic analysis of the microbiome of sterilely processed placental tissue from 48 women (about one third each with healthy pregnancies, spontaneous preterm deliveries, or histories of clinically symptomatic infections during the first or early second trimester).
The microbiome was relatively similar across the 48 placental samples, with Escherichia coli the most abundant species followed by other organisms normally considered part of the oral microbiome (e.g., Prevotella tannerae, nonpathogenic Neisseria species). The taxonomic profile of the placental microbiome was similar to that of the oral microbiome and quite distinct from that of the vaginal microbiome. Certain variations in the placental microbiome were associated with preterm birth (and week of delivery) and with a remote antenatal infection.
Comment: If these findings are confirmed, they will fundamentally affect our understanding of the intrauterine environment in pregnancy. They also raise numerous questions: What is the origin of this vaginal microbiome? Could it develop hematogenously? If so, could such transmission explain the known association of preterm birth with periodontal disease?
Citation(s): Aagaard K et al. The placenta harbors a unique microbiome. Sci Transl Med 2014 May 21; 6:237ra65.
(http://dx.doi.org/10.1126/scitranslmed.3008599)
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MM: The introduction of estriol (E3) to vaginal tissues has been demonstrated to be beneficial for bacterial vaginosis, vulvar atrophy and vaginal dryness. The actual mechanism of action is a valid question and worthy of added investigation but the bottom line is that it consistently works and appears to have very little down side tothe treatment approach.
Menopause 2014 May; 21:450
Changes in Vaginal Microorganisms During the Menopausal Transition
Do bad bugs contribute to vulvovaginal atrophy
In premenopausal women, the vaginal microorganism population (microbiota or microbiome) is dominated by various Lactobacillus species, which are thought to be important in protecting the reproductive tract against pathogens. Investigators explored the relations among the vaginal microbiome, menopausal status, and vulvovaginal atrophy in 87 women classified as pre-, peri-, or postmenopausal.
Lactobacillus crispatus and L. iners predominated in premenopausal women. Perimenopausal women were more likely to have vaginal microbiota characterized by L. gasseri or bacteria from the genera Streptococcus and Prevotella, the latter of which was also common in postmenopausal women. Streptococcus and Prevotella predominated in 7 of 19 women with vulvovaginal atrophy (37%) but only 2 of 60 women without atrophy (3%; P=0.002).
Comment: Because lactobacilli depend on glycogen — which is deposited under the influence of estrogen — these changes in microbiota observed during the menopausal transition are not surprising. However, the contributions of specific microbial communities to the development of vulvovaginal atrophy are difficult to evaluate, as the direction of causality remains unknown: Does vulvovaginal atrophy result from lack of estrogen (which also interferes with Lactobacillus colonization), or do disturbances in bacterial communities result in atrophy? Clinical trials of approaches that reverse atrophy (e.g., estrogen therapy) or that restore Lactobacillus will help tease apart this relation. Until such trials are completed, I would not recommend probiotic therapy for vulvovaginal atrophy.
Citation(s): Brotman RM et al. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 2014 May; 21:450.
(http://dx.doi.org/10.1097/GME.0b013e3182a4690b)
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MM: We have discussed in the past that the appendix is most likely not simply a vestigial organ as has been long supposed by the general medical community, but a storehouse for healthy bacteria that supports and re-populates the gut on demand. This approach to treating inflamed appendix supports that theory and offers an added possible treatment of high dose probiotics to treat low grade appendicitis or more likely as a preventative measure.
J Am Coll Surg 2014 Apr 12
Successful Nonoperative Management of Uncomplicated Acute Appendicitis with Antibiotic Therapy
90% of children managed nonoperatively had no progression within 30 days.
Urgent appendectomy has been the mainstay of therapy for acute appendicitis. A nonrandomized, prospective trial compared two therapies determined by parental choice: intravenous piperacillin-tazobactam or ciprofloxacin/metronidazole therapy for at least 24 hours followed by oral antibiotics for 10 days (30 children) versus appendectomy (47 children).
Patients were between ages 7 and 17 years, with ≤48 hours of abdominal pain, white blood cell counts <18,000/µL, and no radiographic evidence of rupture, abscess, or appendiceal fecalith. Immediate and 30-day success rates for nonoperative management were 93% and 90%, respectively. None of the three patients who progressed and underwent subsequent appendectomy had a ruptured appendix. Nonoperative management was associated with significantly longer length of stay (38 vs. 20 hours), but shorter delay before return to school (3 vs. 5 days) and higher scores on parent assessment of child quality of life.
Comment: With careful selection and follow-up of uncomplicated patients with appendicitis, nonoperative treatment with antibiotic therapy is successful and can avoid surgery, longer hospitalizations, and longer school absences. Although no cost analysis was performed, it is highly likely that the cost of nonoperative care is much lower than appendectomy. Long-term follow-up of the nonoperative group will be important to assess risk for relapse.
Citation(s): Minneci PC et al. Feasibility of a nonoperative management strategy for uncomplicated acute appendicitis in children. J Am Coll Surg 2014 Apr 12; [e-pub ahead of print].
(http://dx.doi.org/10.1016/j.jamcollsurg.2014.02.031)
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MM: For centuries man has searched for the fountain of youth and we continue to this day. The entire anti-aging and cosmetic industries serve to assist us in our denial of the aging process and eventually leaving this mortal environment. On the other hand, perhaps the late James Dean was more of a philosopher than he realized when he proposed that we should live fast and leave a beautiful corpse.
Science 2014 May 9; 344:649
More Evidence for Anti-Aging Effects of a Mammalian Molecule
Supplemental growth differentiation factor 11 improved muscle mass and brain function in old mice.
In 2013, a Harvard research group reported that linking the circulation of an old mouse to that of a young mouse reversed age-related diastolic dysfunction in the old mouse. The team also identified a molecule that appeared to be responsible for this effect: growth differentiation factor 11 (GDF11; NEJM JW Gen Med May 23 2013). High levels of GDF11 occur in the blood of young animals, but these levels drop as animals age.
Researchers now report that, when GDF11 is administered systemically to old mice, it reverses age-related degeneration of skeletal muscle and improves exercise endurance. The muscle cells in treated old animals had much less nuclear and mitochondrial DNA damage. Treated old animals had markedly improved exercise endurance. GDF11 caused no changes in young animals, presumably because their natural GDF11 levels were high.
The investigators also studied the effect of systemically administered GDF11 on the brains of old mice. Treatment increased volume of blood vessels, cortical blood flow, and number of neural stem cells, and it improved cognition and olfaction. Simply joining the circulation of young mice to that of old mice had even more positive effects than did administration of GDF11 itself, indicating that other anti-aging factors besides GDF11 might be present in the blood of young mammals.
In another study, investigators from California also looked at the effect of blood from young mice on the aging process. Instead of linking the circulatory systems of young and old animals, they simply injected plasma from young mice into old mice. This infusion led to better synaptic plasticity (more dendritic spines creating synapses) and improved the ability of the old mice to learn.
Comment: The blood of young mice contains substances that reverse aging processes in heart muscle, skeletal muscle, and brain. Clearly, one of these substances is GDF11. Whether this molecule also reverses aging in other organs and has therapeutic value in humans remains to be determined.
Citation(s): Sinha M et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 2014 May 9; 344:649.
(http://dx.doi.org/10.1126/science.1251152)
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MM: The question/debate of Nature vs. Nurture in various medical conditions is a recurring one. The consistent response is that if we can continually improve our lifestyle habits then we have a greater chance of improving our overall health.
Gut 2014 Apr 2
Irritable Bowel Syndrome Runs in Families
Not just in siblings and cousins, but in spouses too, implicating both genetic and environmental risk factors
The relative contributions of genetic and environmental factors to the etiology of irritable bowel syndrome (IBS) are uncertain.
To determine the risk for IBS in relatives of patients with IBS, researchers conducted a case-control study using linked data from multiple population-based databases in Sweden. Using diagnostic data from a hospital registry and an outpatient registry, they identified 52,000 patients diagnosed with IBS between 1987 and 2010 (cases). The risk for IBS in relatives of cases was compared with the risk in relatives of individuals unaffected by IBS (controls), who were matched to cases based on year of birth, residency in Sweden, and other demographic factors (controls).The odds ratios for IBS were as follows: 1.75 in siblings, 1.82 in offspring, 1.90 in parents, 1.10 in maternal half-siblings, 1.78 in paternal half-siblings, 1.27 in nieces and nephews, 1.11 in cousins, and 1.51 in spouses. All risks were statistically significant.
The increased risk for IBS in first-degree, second-degree, and third-degree relatives was interpreted as evidence of a genetic component, whereas the increased risk in spouses indicated an environmental component.
Comment: It is interesting to know that IBS runs in families, even though both genetic and environmental factors underlie the observation. Another recent study demonstrated that diverticular disease also has a genetic component.
Citation(s): Waehrens R et al. Risk of irritable bowel syndrome in first-degree, second-degree and third-degree relatives of affected individuals: A nationwide family study in Sweden. Gut 2014 Apr 2; [e-pub ahead of print].
(http://dx.doi.org/10.1136/gutjnl-2013-305705)
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Statins Disappoint in COPD and ARDS
By Larry Husten
Two NHLBI studies have failed to find any benefit for statins in patients with chronic obstructive pulmonary disease and acute respiratory distress syndrome. Both trials were stopped early by their data and safety monitoring boards for futility. The results were presented at American Thoracic Society's meeting and published in the New England Journal of Medicine.
Although the trials were negative, they needed to be performed, write editorialists. "We needed to bridge the gap between information gleaned by deduction from observation ... and something gleaned from interventional experimentation... It would have been a big mistake to accept the findings without a test... Had we accepted the observational data at face value, we might have spent the cost of the trials many times over in useless treatments before recognizing our errors. That raises a hard question: With the advent of big data, which observational associations should we test in rigorous trials?"
Adapted from CardioExchange.
http://www.nejm.org/doi/full/10.1056/NEJMoa1403086?query=featured_home
http://www.nejm.org/doi/full/10.1056/NEJMoa1401520?query=featured_home
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