Apple polyphenols each day may help keep intestinal inflammation away

Posted on December 19, 2011 by Dr. Jonathan

Summary: phenolic compounds in apples have beneficial effects for autoimmune inflammatory bowel disease.

A paper just published in the Journal of Leukocyte Biology demonstrates the mechanism by which polyphenols in apples help quell the inflammation of the autoimmune diseases ulcerative colitis and Crohn’s disease. The authors state:

“Human IBD, including UC and Crohn’s disease, is characterized by a chronic, relapsing, and remitting condition that exhibits various features of immunological inflammation and affects at least one/1000 people in Western countries. Polyphenol extracts from a variety of plants have been shown to have immunomodulatory and anti-inflammatory effects. In this study, treatment with APP [apple polyphenols] was investigated to ameliorate chemically induced colitis.”

The authors administered APP to study animals genetically predisposed to autoimmune inflammatory bowel disease win whom inflammation as induced by chemical irritation. Their findings documented an protective effect:

“Oral but not peritoneal administration of APP during colitis induction significantly protected C57BL/6 mice against disease, as evidenced by the lack of weight loss, colonic inflammation, and shortening of the colon. APP administration dampened the mRNA expression of IL-1β, TNF-α, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, and IFN-γ in the colons of mice with colitis.”

A rational treatment strategy for autoimmune disease requires an assessment of the factors involved in the loss of self-tolerance, including integrity of barrier systems, glutathione production and recycling, nitric oxide synthase production, regulatory T cell function, cytokine regulation, antigenic environmental triggering agents, lifestyle factors that modulate genetic expression, etc. For palliation, however, interventions that can reduce inflammation without side effects are desirable. Although an extract concentrates polyphenols more than is obtained by eating apples, compounds like this and resveratrol are worthy of consideration for adjunctive use. The authors conclude:

“…these results show that oral administration of APP protects against experimental colitis and diminishes proinflammatory cytokine expression via T cells.”

SSRI antidepressant use during pregnancy may increase the risk of autism

Posted on December 17, 2011 by Dr. Jonathan

Summary: The use of selective serotonin reuptake inhibitors (SSRIs, such as Prozac®, Celexa®, Lexapro®, Luvox® and Paxil®) taken during pregnancy—especially the first trimester—appears to increase the risk of autism spectrum disorders. There are evidence-based alternatives to SSRIs that support brain health without putting the fetus at risk.

A study recently published in the journal Archives of General Psychiatry draws attention to a risk of autism spectrum disorders (ASDs) born to mothers who took SSRI antidepressants during their pregnancy. The authors observe:

“The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.”

Therefore they set out to…

“…systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.”

In order to do so they compared the data for 298 children with ASD to 1507 randomly selected control children, along with the data for both their mothers. Their findings support a cautionary approach to the prenatal use of SSRIs:

“Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8).”

In other words, the increase in risk for the whole year before delivery was 220%, but limiting the investigation to the first trimester it was 380%. Interestingly…

“No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.”

Meaning that it wasn’t a history of mental health treatment the year before delivery but specifically the use of SSRIs that accounted for the increased risk of ASDs. The authors conclude:

“Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders.”

This would be a troubling dilemma were it not for the fact that therapies supporting brain health are available to treat depression. Serotonin production and signaling, when indicated, can be supported in a physiological and sustainable manner that promotes the brain health of mother and fetus. A categorization and description of key resources that applies to adults as well as children is available in the Parents’ Guide To Brain Health.

Stroke risk is greater with both higher and lower than normal blood pressure

Posted on December 15, 2011 by Dr. Jonathan

Summary: lower than normal blood pressure results from underlying causes that need investigation and treatment. These underlying factors can increase the risk of stroke comparable to higher than normal blood pressure.

An important study recently published in the JAMA (The Journal of the American Medical Association) offers evidence that lower than normal blood pressure is a risk factor for stroke comparable to blood pressure that is higher than normal. The authors state:

“Recurrent stroke prevention guidelines suggest that larger reductions in systolic blood pressure (SBP) are positively associated with a greater reduction in the risk of recurrent stroke and define an SBP level of less than 120 mm Hg as normal. However, the association of SBP maintained at such levels with risk of vascular events after a recent ischemic stroke is unclear.”

So they set out to…

“…assess the association of maintaining low-normal vs high-normal SBP levels with risk of recurrent stroke.”

They examined two and a half years of data for 20,330 patients from 35 countries who had recently had an ischemic stroke. Patients were categorized based on their average systolic blood pressure as very low–normal (<120 mm Hg), low-normal (120-<130 mm Hg), high-normal (130-<140 mm Hg), high (140-<150 mm Hg), and very high (≥150 mm Hg). Their primary outcome measure was a stroke of any kind, and the secondary outcome was a composite of stroke, heart attack, or death from any other vascular cause. What did the data show?

“The recurrent stroke rates were 8.0% for the very low–normal SBP level group, 7.2% for the low-normal SBP group, 6.8% for the high-normal SBP group, 8.7% for the high SBP group, and 14.1% for the very high SBP group. Compared with patients in the high-normal SBP group, the risk of the primary outcome was higher for patients in the very low–normal SBP group (adjusted hazard ratio [AHR], 1.29), in the high SBP group (AHR, 1.23), and in the very high SBP group (AHR, 2.08). Compared with patients in the high-normal SBP group, the risk of secondary outcome was higher for patients in the very low–normal SBP group (AHR, 1.31), in the low-normal SBP group (AHR, 1.16), in the high SBP group (AHR, 1.24), and in the very high SBP group (AHR, 1.94).”

In other words, while the very high systolic blood pressure was the worst for both primary and secondary outcomes, the very low-normal group was the ‘runner up’ for both recurrent stroke (29%) and the secondary outcomes of heart attack or death from other vascular causes (31%). The authors conclude:

“Among patients with recent non–cardioembolic ischemic stroke, SBP levels during follow-up in the very low–normal (<120 mm Hg), high (140-<150 mm Hg), or very high (≥150 mm Hg) range were associated with increased risk of recurrent stroke.”

It’s important for both clinicians and patients to understand that lower than normal blood pressure is an indicator that things ‘under the surface’ are not working as they should. For example, autoimmune disorders that are Th1 dominant can be associated with lower adrenocortical activity due to the effect on the brain’s paraventricular nucleus—while promoting vascular inflammation.

Overdose with acetaminophen is more deadly divided over a day than all at once

Posted on December 13, 2011 by Dr. Jonathan

Summary: great care must be taken to avoid overdose when using acetaminophen (Tylenol®, Paracetamol®), especially for pain relief. Doses staggered over a day are more harmful than downing the whole amount at once.

Acetaminophen overdose is a leading cause of severe liver injury. It might seem that more than 4000 mg of acetaminophen taken all at once would be more toxic than the same amount divided over the course of a day, but a paper just published in the British Journal of Clinical Pharmacology presents evidence that the opposite is true. The authors state:

“Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose.”

They investigated the cases of 663 patients admitted to hospital with acetaminophen-induced severe liver injury between 1992 and 2008. 161 of them (24.3%) had taken a staggered overdose, most commonly for relief of pain. These tragic events led to a compelling observation:

“Despite lower total ingested paracetamol doses, and lower admission serum alanine aminotransferase levels, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation, and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%)…”

In other words, spacing out the dosage of Tylenol® is not only an ineffective strategy for avoiding overdose, it is more likely to lead to liver failure, kidney failure and death. Additionally, going to the hospital more than 24 hours after ingestion of a single time overdose was associated with worse outcomes. What is the first-line therapy for acetaminophen overdose?

“Patients presenting with these overdose patterns should be treated as high-risk for progression to acute liver failure, and should receive N-acetyl cysteine in their presenting hospital whilst awaiting serial alanine aminotransferase (ALT) and prothrombin time levels.”

Over-the-counter pain medication, including both non-steroidal antiinflammatory drugs (NSAIDs) and acetaminophen, can do severe harm and must be handled with respect. My practice has included patients whose autoimmune disease was triggered or aggravated by the effect of too enthusiastic NSAID use on the intestinal epithelial lining that functions as a barrier between the intestinal contents and the immune lymphoid tissue. The authors conclude:

“Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multiorgan failure and should be considered for early transfer to specialist liver centres.”

Antibiotic prescribing for kids is frequently inappropriate

Posted on December 12, 2011 by Dr. Jonathan

Summary: Broad-spectrum antibiotics are very commonly prescribed for kids, especially with respiratory conditions, when they are not indicated.

A study just published in the journal Pediatrics disappointingly documents that antibiotics are still grossly overused in pediatric practice. The authors state:

“Antibiotics are commonly prescribed for children with conditions for which they provide no benefit, including viral respiratory infections. Broad-spectrum antibiotic use is increasing, which adds unnecessary cost and promotes the development of antibiotic resistance.”

This is more than a matter of promoting antibiotic-resistant pathogens. As more insight emerges into the profound importance of the human microbiome (indigenous microbial flora), the serious immune and metabolic consequences implications of damaging the microbial flora are becoming more apparent. The authors set out to…

“…provide a nationally representative analysis of antibiotic prescribing in ambulatory pediatrics according to antibiotic classes and diagnostic categories and identify factors associated with broad-spectrum antibiotic prescribing.”

They examined data from the National Ambulatory and National Hospital Ambulatory Medical Care surveys from 2006 to 2008 for the percentage of visits for patients younger than 18 years for whom antibiotics were prescribed, their category, and the associated diagnoses. The guidelines for judicious use of broad-spectrum antibiotics have obviously not hit home:

“Antibiotics were prescribed during 21% of pediatric ambulatory visits; 50% were broad-spectrum, most commonly macrolides. Respiratory conditions accounted for >70% of visits in which both antibiotics and broad-spectrum antibiotics were prescribed. Twenty-three percent of the visits in which antibiotics were prescribed were for respiratory conditions for which antibiotics are not clearly indicated, which accounts for >10 million visits annually.”

Research is needed to investigate to what degree this may contribute to the rising tide of autoimmune disease and allergy. The authors conclude:

“Broad-spectrum antibiotic prescribing in ambulatory pediatrics is extremely common and frequently inappropriate.”

Depression as a dysfunction of the immune system

Posted on December 7, 2011 by Dr. Jonathan

Summary: chronic inflammation due to immune system dysregulation, with or without a diagnosed autoimmune disease, plays a fundamental role in chronic depression. This offers sustainable and evidence-based treatments for depression and brain health.

The authors of an important paper published in Current Immunology Reviews state:

…current antidepressants do not effectively target all of the pathological processes that are responsible for the major symptoms of depression…However, in recent years greater attention has been directed to the inter-relationship between the brain and peripheral organs (the” body-mind” connection) in which changes in the endocrine and immune systems play a major role in the pathological changes that occur in depression. Thus inflammation is beginning to emerge as a major contributing factor not only to depression and other major psychiatric disorders…”

Two major ways that immune dysfunction promotes depression are emphasized: the direct effect of inflammation on the brain, and the brain effects of the hormonal response to inflammation. Regarding the former:

“…in the past 30 years or so that clinical and experimental evidence has been obtained clearly demonstrating that aspects of both cellular and humoral immunity were dysfunctional in major depression…in particular the pro- and anti-inflammatory cytokines…Such clinical observations suggest that proinflammatory cytokines contribute to the major symptoms of depression and now forms the basis of the inflammation, cytokine or inflammatory response hypothesis of depression.”

It’s now known that peripherally derived inflammatory cytokines have access to the brain, including areas involved in depression…

“Once in the brain, the proinflammatory cytokines activated both neuronal and non-neuronal (for example, the microglia, astrocytes and oligodendroglia) cells via the nuclear factor-kappa-beta (NF-kB) cascade in a similar manner to that occurring in the peripheral inflammatory response…

Also, the production of serotonin and dopamine is adversely affected by inflammation:

“Recently much attention has been paid to the activation of the tryptophan-kynurenine pathway by these cytokines whereby tryptophan is shunted from the synthesis of serotonin to that of kynurenine…clearly this is an important mechanism whereby serotonergic function is decreased in depression. The activity of the dopaminergic system is also reduced in response to inflammation. For example, IFN reduces the synthesis of dopamine by decreasing the concentration of the co-factor tetrahydrobiopterin (BH4)…As IFN increases the synthesis of nitric oxide by activating the BH4 dependent enzyme nitric oxide synthase in the microglia it seems likely that the reduction in dopaminergic function is linked to the increase in nitric oxide. This gaseous neurotransmitter is known to activate the glutamatergic system which, when this exceeds physiologically limits, enhances apoptosis and neurodegeneration.”

In other words, an increase in inflammatory cytokines derails the production of serotonin and dopamine, and activates the excitatory (glutamatergic) system to the point of cell death.

Additionally, proinflammatory cytokines activate the HPA (hypothalamo-pituitary-adrenal) axis causing excessive cortisol production which is lethal to brain cells at high levels…

“In addition to the modulation of neurotransmitter function, proinflammatory cytokines contribute to the major symptoms of depression by activating the HPA axis by increasing the release of CRF, thereby contributing to hypercortisolaemia, a feature of major depression. The mechanism whereby the cytokines induce hypercortisolaemia involves a decreased sensitivity of the glucocorticoid receptors thereby leading to glucocorticoid resistance…”

The inflammation model also sheds light on the role of stress in depression:

“…as major depression is often accompanied by inflammatory diseases (such as irritable bowel syndrome, type 2 diabetes, arthritis and autoimmune disorders) that can activate the peripheral and central inflammatory response, it is possible that such inflammatory disorders initiate the inflammatory changes that precipitate depression….[But] it is evident that inflammation also occurs in depressed patients who are not suffering from concurrent inflammatory disorders. Thus the increased vulnerability of depressed patients to psychosocial stress is probably the key factor that leads to the activation of the immune and endocrine axes in depression. It is known, for example, that even the relatively mild acute stress of public speaking causes an increase in NF-kB activity, a key element in the induction of the inflammatory cascade. In this regard, it is also known that patients with major depression frequently show an enhanced responsiveness of IL-6 and NF-kB to an antigen challenge…such changes appear to be associated with activation of the microglia thereby suggestion that the inflammatory changes are also occurring in the brain.”

In other words, patients with major depression have a more pronounced inflammatory response to substances to which they are sensitized or allergic to (antigens). This is in addition to an increased immune and hormonal response to psychosocial stress.

Of special significance for the use of heart rate variability analysis for evaluation of the autonomic nervous system and therapies that increase parasympathetic tone…

“The mechanism whereby psychological stress influences both the peripheral and central inflammatory cascade is co-ordinated by the autonomic nervous system. Thus the release of noradrenaline and adrenaline following the activation of the sympathetic system results in the activation of both alpha and beta adrenoceptors on immune cells thereby initiating the release of proinflammatory cytokines, via the activation of the NF-kB cascade, particularly on macrophages and monocytes in peripheral blood…Conversely stimulation of the parasympathetic system has the opposite effect on the stress induced inflammatory response…It is possible that the anti-depressant-like action of vagal nerve stimulation, occasionally used to treat resistant depression, is associated with such an anti-inflammatory action.”

Brain inflammation associated with depression actually causes the death of brain cells (apoptosis):

“Thus in major depression, the prolonged activation of the inflammatory network in the brain results in a decrease in neurotrophins, leading to reduced neuronal repair, a decrease in neurogenesis, and an increased activation of the glutamatergic pathway that contributes to neuronal apoptosis, oxidative stress and the induction of apoptosis in astrocytes and oligodendrocytes.”

On top of all this, inflammation causes the biochemical pathway that produces serotonin from tryptophan to converted to the production of neurotoxins instead through the tryptophan-kynurenine pathway and the production of quinolinic acid.

“As both the cytokines and cortisol are raised in major depression, it is not surprising to find that the tryptophan-kynurenine pathway is increased….Kynurenine hydroxylase metabolises kynurenine first to 3-hydroxykynurenine and then to 3-hydroxyanthranilic acid and quinolinic acid. This pathway is increased in depression and dementia…In chronic depression…the activated microglia produce an excess of the neurotoxin…Furthermore quinolinic acid can cause apoptosis of the astrocytes. This results in a reduction in the metabolic and physical buffer to the neurons that is usually provided by the astrocytes and thereby further exposes the neurons to the neurodegenerative actions of quinolinic acid.”

Inflammation in the brain over the long term causes neurodegeneration that appear as brain shrinkage:

“The structural changes observed in the brain of patients with chronic depression lends support to the neurodegenerative hypothesis of depression. It is known that there is a shrinkage of the hippocampus in patients with major depression and a decrease in the number of astrocytes and a neuronal loss in the prefrontal cortex and in the striatum. Such changes could be the consequence of chronic low grade inflammation in which the proinflammatory cytokines, nitric oxide, prostaglandin E2 and other inflammatory mediators play key roles; the cytokines are known to induce the cyclo-oxygenase and nitric oxide sythase pathways in the brain and thereby increase the inflammatory insult. The inhibition of neurotrophin synthesis in the brain by glucocorticoids, and the neurotoxic action of quinolinic acid, add further to the impact of the inflammatory changes.”

There are indications that patients who respond poorly to neurotransmitter-manipulating medications have markers for increased inflammation:

“Further evidence for the relationship between inflammation and depression is provided by the observation that depressed patients with a history of partial or lack of response to antidepressant treatments have elevated plasma concentrations of IL-6 and acute phase proteins that persist despite antidepressant treatment. It has been suggested that patients who are resistant to conventional antidepressant treatment possess abnormal alleles of the IL-1 and TNF genes, and possibly for T-cell function.”

Moreover, even when there is some relief from a depressed mood or anxiety with these medications…

“…there is abundant clinical evidence that the available antidepressants…are far less effective in treating the memory and cognitive dysfunction (fatigue, psychomotor retardation) that commonly affect middle aged and elderly depressed patients.”

There is mounting evidence that modulating inflammation can improve the inflammatory response:

“There are already indications from the clinical literature that TNF antagonists…reduce the symptoms of depression in a variety of patients with autoimmune diseases…the mood state of the patients improving before the signs of improvement of the autoimmune disorder…IL-10, and insulin-like growth factor that has prominent anti-inflammatory activity, have been shown to attenuate the depressive-like behaviour in rodents induced by an inflammatory challenge.”

IL-10 is increased by correcting suboptimal levels of vitamin D.

“Perhaps the most obvious step to the reduction of inflammation both centrally and peripherally is to reduce the activity of the prostenoid pathway and thereby reduce the synthesis of inflammatory prostaglandins such as PGE2.”

This is exactly what is accomplished by correcting an omega-3 fatty acid deficiency with a low 3:6 ratio.

The best chance for a sustainable program for helping depression by treating the inflammation is to determine with the appropriate tests why the excessive inflammation is happening in the first place. Then physiological and sustainable treatments can address those underlying causes properly. That brings up the very large topic of the functional management of autoimmune disease and chronic inflammation, a subject of many posts here and deserving of a weighty textbook. See posts forthcoming in the next week on the role of gastrointestinal inflammation as a contributing cause and treatment target for depression and the effectiveness of the omega-3 fatty acid EPA as a PGE2 reducer for depression.

Modest doses of resveratrol produce metabolic changes similar to caloric restriction

Posted on December 5, 2011 by Dr. Jonathan

Summary: In a double-blind crossover study 140 mg per day of resveratrol improved a cluster of markers for metabolism and inflammation that corresponded to the known benefits of caloric restriction.

A study published recently in the journal Cell Metabolism adds more evidence for the beneficial metabolic effects of resveratrol. The authors state:

“Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity.”

They gave 150 mg/day of resveratrol alternating with placebo to eleven obese men in a randomized double-blind crossover study for 30 days. This is quite a small dose (in practice 500 mg two times per day is common). Nonetheless, the benefits were robust:

“Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased.”

In other words, there were meaningful improvements in cellular energy metabolism, liver and blood fats, blood sugar, inflammation, blood pressure and insulin sensitivity (HOMA index). These benefits are similar to those gained from restricting calories. The authors conclude:

“…we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.”

Elevated blood sugar is associated with colorectal cancer in postmenopausal women

Posted on December 3, 2011 by Dr. Jonathan

Summary: women in the highest third of blood glucose levels were almost twice as likely to develop colorectal cancer over the course of the study.

More evidence that high blood sugar contributes to cancer is presented in a study just published in the British Journal of Cancer that examines the link between elevated fasting glucose and colorectal cancer in postmenopausal women. The authors state:

“It is unclear whether circulating insulin or glucose levels are associated with increased risk of colorectal cancer. Few prospective studies have examined this question, and only one study had repeated measurements.”

So they examined baseline fasting serum insulin and glucose values for 4902 non-diabetic women over 12 years, during which 81 cases of colorectal cancer turned up. The data showed a significant trend:

“Baseline glucose levels were positively associated with colorectal cancer and colon cancer risk: multivariable-adjusted hazard ratio (HR) comparing the highest (greater than or equal to 99.5 mg dl−1) with the lowest tertile (<89.5 mg dl−1): 1.74 and 2.25, respectively. Serum insulin and homeostasis model assessment were not associated with risk.”

In other words, glucose in the highest third almost doubles the risk. In this non-diabetic group an association with fasting insulin levels was not observed. However, I can say through extensive experience over 2-3 years having patients suffer through an extended glucose + insulin tolerance test that insulin can be often elevated later in the test but not in the fasting sample. The authors conclude:

“These data suggest that elevated serum glucose levels may be a risk factor for colorectal cancer in postmenopausal women.”

The use of any non-aspirin NSAIDs during pregnancy increases the risk of spontaneous abortion

Posted on November 30, 2011 by Dr. Jonathan

Summary: any type of non-aspirin NSAID must be used only with great caution during pregnancy because they may significantly increase the risk of spontaneous abortion.

Research recently published in the Canadian Medical Association Journal alerts practitioners and pregnant women to the risk for spontaneous abortions caused by the gestational use of any non-aspirin non-steroidal anti-inflammatory drug (NSAID). The authors state:

“We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women.”

They examined data for 4705 women who had a spontaneous abortion compared to ten times as many matched controls, and correlated associations between different types and dosages of non-aspirin NSAIDs with having the spontaneous abortion. Their data raises some serious alarm:

“Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43). Specifically, use of diclofenac (OR 3.09), naproxen (OR 2.64), celecoxib (OR 2.21), ibuprofen (OR 2.19) and rofecoxib (OR 1.83) alone, and combinations thereof (OR 2.64), were all associated with increased risk of spontaneous abortion. No dose–response effect was seen.”

In other words, there as an overall 243% increase in the risk for spontaneous abortion. The increase was over 300% for diclofenac (Voltaren®) and more than 200% for ibuprofen. The authors express the gravity of their concern supported by the data in their conclusion:

“Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy.”

Anemia before surgery increases the risk of serious complications

Posted on November 28, 2011 by Dr. Jonathan

Summary: anemia at the time of surgery, even mild anemia, increases the risk of serious complications including death.

There is a large body of evidence that even borderline anemia has profound implications (see earlier posts). Anemia affects the ability of every cell in the body to do perform its functions by diminishing the amount of oxygen available. A study recently published in The Lancet documents the serious effects of anemia on surgical outcomes. The authors state:

“Preoperative anaemia is associated with adverse outcomes after cardiac surgery but outcomes after non-cardiac surgery are not well established. We aimed to assess the effect of preoperative anaemia on 30-day postoperative morbidity and mortality in patients undergoing major non-cardiac surgery.”

They analyzed data for 227,425 patients, of whom 69,229 had preoperative anaemia, undergoing surgery in 2008 from The American College of Surgeons’ National Surgical Quality Improvement Program database from 211 hospitals worldwide with reference to mortality and morbidity due to cardiac, respiratory, CNS, urinary tract, wound, sepsis, and venous thromboembolism complications. This was correlated with anaemia, defined as mild with a hematocrit or more than 29d% to 39% in men and 29 to 36% in women, or moderate-to-severe, less than 29% in both sexes. What did the data show?

“After adjustment, postoperative mortality at 30 days was higher in patients with anaemia than in those without anaemia; this difference was consistent in mild anaemia and moderate-to-severe anaemia. Composite postoperative morbidity at 30 days was also higher in patients with anaemia than in those without anaemia, again consistent in patients with mild anaemia and moderate-to-severe anaemia. When compared with patients without anaemia or a defined risk factor, patients with anaemia and most risk factors had a higher adjusted OR for 30-day mortality and morbidity than did patients with either anaemia or the risk factor alone.”

The preoperative diagnosis and treatment of anemia is rarely undertaken before surgery. Indeed, I often find on delving into the medical histories of complex chronic cases that anemia, whose causes can be a significant clue to unlocking a case, is ‘swept under the rug’. The authors state:

“Our findings should lead to a careful consideration of appropriate interventions aimed at correction of preoperative anemia in the most patients…At least in elective surgical cases, the treatment of preoperative anemia before surgical intervention should be strongly considered.”

This should be the standard of care for patients undergoing elective surgery. The authors conclude:

“Preoperative anaemia, even to a mild degree, is independently associated with an increased risk of 30-day morbidity and mortality in patients undergoing major non-cardiac surgery.”

Even mild anemia is a complicating factor, impediment to improvement, and important clue to underlying causation in many chronic conditions.