Aspirin Modes of Action and Clinical Benefits: What We Know Today

From Medscape Education
Aspirin Modes of Action and Clinical Benefits: What We Know Today CME

Karsten Schrör, MD


Introduction

Aspirin (acetylsalicylic acid) is among the most widely used anti-inflammatory analgesics and its benefits at doses of ≥300 mg are well established. It is also effective at lower doses (≤100 mg/day) in the secondary prevention of cardiovascular disease (CVD).[1-12]
Its use is widely recommended in treatment guidelines. Furthermore, aspirin has shown significant benefit in patients with gastrointestinal (GI) cancers, most notably colorectal cancer (CRC),[13] and the United States Preventive Services Task Force (USPSTF) has recently made a draft recommendation for the use of aspirin in the prevention of CVD and cancer.[14]

Randomized studies suggest that low-dose aspirin is beneficial in the primary prevention of CVD, and evidence is growing for a role in the prevention of other cancers of the Gl tract and improving survival after a cancer diagnosis.[3-7,15-17] This article will review the modes of action of aspirin and describe its benefits in various conventional and new therapeutic indications.

Mechanism of Action

Aspirin acetylates and thereby modifies the activity of enzymes. This acetylation is irreversible; ie, it changes the enzymatic properties of the targeted enzyme throughout its lifetime, which is in most cases much longer than the half-life of unmetabolized aspirin in blood -- approximately 30 minutes.

This acetylating property of aspirin is unique among nonsteroidal anti-inflammatory drugs (NSAIDs).[3,18-21] Cyclooxygenases (COXs) are the major target of aspirin at low, antiplatelet doses (75 to 325 mg/day). The acetylation of COX-1 prevents the production of prostaglandins (PGs) and thromboxane A2 from arachidonic acid. The acetylation of COX-2 also reduces PG production, but mainly changes the activity of the enzyme from a COX to a lipoxygenase that produces "aspirin-triggered lipoxin" (ATL) through interaction with white cell lipoxygenases.[22] 15-epi-lipoxin A4 is a constitutive protective lipid that helps to maintain a healthy cardiovascular (CV) system, to reduce acute inflammatory responses, and to improve tissue healing.[21] Aspirin is more potent at inhibiting COX-1 than COX-2.

The ability of aspirin to acetylate (inhibit) COX-1 and subsequent thromboxane formation has been suggested as the primary mechanism of antiplatelet action.[23,24] However, the clinical effects of aspirin cannot be solely ascribed to the inhibition of COX-1 in platelets, and subsequent platelet secretion and aggregation.
They also involve paracrine actions of platelet secretion products, such as sphingosine-1-phosphate (S1-P), inflammatory mediators, or mitogens on other cells; for example, white cells and endothelial cells, as well as other acetylation targets relevant for inflammation, thrombosis, and tumorigenesis (Figure 1).[19,20,25-30]

Figure 1. Antiplatelet Aspirin Doses Result in Multiple Effects.[31]

AA = arachidonic acid; ATL = aspirin-triggered lipoxin; COX = cyclooxygenase; eNOS = endothelial nitric oxide synthase; HO-1 = heme oxygenase-1; NO = nitric oxide; PG = prostaglandin; TxA2= thromboxane A2.

Role of Asprin in Cardiovascular Disease
Secondary Prevention of Cardiovascular Disease

The benefits of low-dose aspirin (≤100 mg once daily) in the secondary prevention of CVD are well established, and it has been shown to reduce the risk of major CV events -- nonfatal myocardial infarction (MI), nonfatal stroke, or death from vascular causes -- by approximately 22%.[6]

Low-dose aspirin is widely recommended in treatment guidelines as first-line therapy for the secondary prevention of CVD following MI, acute coronary syndrome (ACS), and interventions such as the insertion of stents.[1-12] There is an increased risk of GI and extracranial bleeding with aspirin.
The mechanisms for upper GI bleeding are not well understood, but are essentially related to the antiplatelet effects of aspirin and its interference with the coagulation process that is initiated by platelets.
Whether enhanced GI bleeding is also affected by the local irritating effects of aspirin on the stomach mucosa and the inhibition of local PG biosynthesis remains a matter of discussion.[32]

However, in secondary prevention, the number of patients who avoid a serious CV event is significantly greater than those who experience bleeding (risk/benefit ratio 10:1).[20,33] Recommended dosages are mostly in the range of 75 mg to 100 mg aspirin/day. Aspirin is also an integral part of dual antiplatelet therapy with prasugrel, ticagrelor, or clopidogrel.[3,12,34]

Research is ongoing into the optimal aspirin dosage and new approaches to antithrombotic prevention. In this context, new and exciting findings have been reported for aspirin in the prevention of primary and secondary venous thromboembolism (VTE; EPCAT and INSPIRE studies).[35, 36]
The EINSTEIN-CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing 2 doses of rivaroxaban with aspirin.[37]

Primary Prevention of Cardiovascular Disease

The benefits of low-dose aspirin in the primary prevention of CV events are less clear than for secondary prevention because the risk of a CV event is lower than in secondary prevention, whereas the risk of bleeding is similar.[3-7,15,16]
Therefore,in order to optimize the risk/benefit ratio, physicians need to assess the patient's baseline risk of future CV events and balance it against the risk of future bleeding.
The most important risk factors include preexisting diseases, in particular hypertension, hypercholesterolemia, and diabetes, a history of peptic ulcers, older age, and concomitant use of NSAIDs.
Preventive strategies to reduce the risk of bleeding in the upper GI tract include the use of gastroprotective agents, such as proton pump inhibitors, and debatably, the eradication of Helicobacter pylori.

Several guidelines recommend the use of low-dose aspirin in patients with an increased risk for CV events[4,17,38]; for example, the European Society of Cardiology recommends that those with a 10-year CVD risk of >20% take daily aspirin (Figure 2).

If the risk is <10%, other factors should be taken into account. The beneficial effects of aspirin are similar in patients with or without diabetes, and between sexes, and 'aspirin-resistance' due to an insufficient pharmacological activity of aspirin is thought to occur rarely.[17,20] However, clinical treatment failures may occur for several reasons, including delayed absorption with enteric-coated tablets allowing for enhanced metabolic degradation of aspirin especially at low doses,[39] drug interactions with NSAIDs, and platelet stimulation by non-aspirin-sensitive stimuli are thought to account for most instances of 'aspirin resistance'.[40] In addition, in situations with increased platelet turnover rates, such as diabetes, twice-daily dosing has been shown to be more effective than once-daily dosing, probably because of more rapid replacement of aspirinized platelet COX-1 by fresh platelets from the bone marrow.[41,42]

Figure 2. Stepwise Approach to the Use of Low-Dose (≤100 mg/day) Aspirin Recommended by the European Society of Cardiology Guidelines.[17]

Three ongoing larger-scale trials are evaluating the effects of aspirin use in higher-risk populations: ASPirin in Reducing Events in the Elderly (ASPREE),[43] A Study of Cardiovascular Events iN Diabetes (ASCEND),[44] and Aspirin to Reduce the Risk of Vascular Events (ARRIVE).[45]

Primary Prevention of Cancer

There is increasing evidence of the benefits of low-dose aspirin in the prevention of cancers, in particular CRC, but also other solid tumors of the GI tract (Table).
The majority of the data come from secondary analyses of trials that studied the role of aspirin in reducing the risk of CV events.[13,15]

In September 2015, the USPSTF has made a draft recommendation for the use of aspirin in the primary prevention of CVD and CRC in people aged 50 to 59 years whose 10-year CVD risk is 10% or greater, who are not at increased risk for bleeding, who have a life expectancy of at least 10 years, and who are willing to take daily low-dose aspirin for at least 10 years.[14]

However, most guidelines do not reflect the growing evidence base, so physicians should take the individual patient risk/benefit ratio into account when deciding whether or not to prescribe aspirin in primary prevention.[3]

Colorectal Cancer

Evidence for the chemopreventive effects of aspirin is strongest for CRC; for example, a randomized controlled trial (RCT) of patients with Lynch syndrome, an inherited condition that increases the risk for developing CRC, found that 600 mg aspirin once daily reduced the incidence of CRC.
A first tendency for this became apparent 3 to 4 years after the start of aspirin therapy and became significant in an "on treatment" analysis after 56 months.[46]

Numerous observational trials suggest that regular, long-term intake of low-dose aspirin (≤100 mg/day) significantly reduces the risk of CRC and may also prevent the appearance of distal metastases and prolong survival in certain patient subpopulations.[47]

Aspirin has demonstrated a delayed action (at least 3 to 5 years) for reducing the risk of colon cancer.[15,48] Aspirin treatment for up to 20 years reduced the risk of proximal colon cancer by 55%, but did not change the incidence of distal colon cancer.[48]

Importantly, low-dose aspirin (75 mg daily) was just as effective as higher doses in reducing the risk of cancer.[48] The reason why aspirin may affect proximal colon cancer preferentially may be due to its less complete inhibition of COX-2 in distal tumors.[48]
Another interesting finding was a reduced total mortality that was due to reduced non-CV mortality; ie, probably due to reduced cancer mortality.[13]

COX-1 inhibition prevents thromboxane formation as well as the secretion of several platelet-derived products that might act as paracrine mediators on other cells.[20]
Sphingosine-1-phosphate (S1-P) is a lipid mediator with proinflammatory and oncogenic activities that also induces COX-2 in nucleated cells.[49]
In blood, S1-P is stored in platelets and released during platelet stimulation in a thromboxane-dependent manner, and may be involved in tumor growth.

Low-dose aspirin treatment prevents S1-P release from human platelets.[50] It is unlikely that all of the chemopreventive effects of aspirin in CRC are solely due to platelet-related actions. One mechanism proposed for aspirin's antitumor activity involves the mammalian target of rapamycin (mTOR) pathway, which is progressively dysregulated in colorectal tumorigenesis, suggesting that aspirin's antitumor activity is due to its potent inhibition of mTOR signaling and its activation of AMP-activated kinase, which also inhibits mTOR and protein synthesis.[51]

However, it should be noted that these and many other antitumor effects of aspirin, such as interaction with certain transcription factors (eg, NFkB or S56-kinase), are mainly seen in cell culture studies at high aspirin/salicylate levels that might completely block cellular oxidative phosphorylation (ie, energy metabolism and all ATP-dependent cellular signaling).[52] If the full chemopreventive action of aspirin is seen at 75 mg/day, these actions are probably not involved.

COX-2 is an inducible enzyme that is upregulated in CRC. Of the various PGs produced by COX-2, PGE2 is involved in tumorigenesis, inhibits apoptosis, and has proinflammatory and immunosuppressive effects.[18] PGE2 stimulates tumor angiogenesis and proliferation, as well as distant metastasis, possibly via vascular endothelial growth factor (VEGF). VEGF is the most relevant angiogenic factor with more than 80% of VEGF in blood being stored in platelets.[53]

Aspirin also upregulates NSAID-activated gene-1 (NAG-1), which may act as an inhibitor of tumor formation.[18] Some cancer cell lines do not have COX-2, but aspirin is able to inhibit proliferation and induce apoptosis associated with an inhibition of β-catenin-dependent gene transcription, although only at extremely high concentrations.[18] Thus, the antiapoptotic/antitumor actions of aspirin may be a combination of effects, with acetylation of COX-1, COX-2, and perhaps, additional factors inhibiting carcinogenesis and tumor metastases.[20, 21]

Other Cancers

Aspirin reduced cancer deaths by approximately 15% when 51 RCTs assessed the time course of the risk/benefit profile of daily, low-dose aspirin on cancer incidence, mortality, and non-vascular death.[13] This was particularly noticeable from 5 years onwards (37% reduction).
The effect of aspirin on cancer incidence increased with the length of therapy. In contrast, the effect of aspirin on major vascular events and major extracranial bleeding diminished over time.[13] Aspirin also reduced cancer metastasis, which could account for the early reduction in cancer deaths observed in some clinical trials.[54]

Observational studies suggest that aspirin reduces the risk for several other cancers (esophageal, gastric, biliary, prostate, lung, and breast cancer) and the risk for distant metastasis (Table).[14,55,56] However, the effects on non-GI cancers were very small and not seen in all trials (eg, breast cancer).[57] Thus, until interventional studies are conducted with low-dose aspirin, the data remain inconclusive.[56]
Condition Incidence Estimated Risk Ratio Mortality Estimated Risk Ratio
Myocardial infarction 0.82 0.95
Stroke 0.95 1.21
Colorectal cancer 0.65 0.60
Esophageal cancer 0.70 0.50
Gastric cancer 0.70 0.65
Lung cancer 0.95 0.85
Prostate cancer 0.90 0.85
Breast cancer 0.90 0.95

Best estimates of incidence and mortality are shown. Refer to original article for conservative estimates.[15]

Aspirin for the Treatment of Cancer

There is growing epidemiological evidence to support the beneficial effects of taking aspirin after a cancer diagnosis in order to prevent metastases and prolong survival, in particular for CRC and GI cancers.[58-61]
A number of trials are ongoing or planned that aim to establish a role for aspirin in the treatment of cancer.[62,63] Research is also ongoing into specific tumor mutations as potential biomarkers of aspirin response.[64]

Prevention of Other Diseases/Conditions
Patients With Cognitive Decline

Observational studies have suggested that the use of long-term NSAIDs may delay the progression of dementia. By reducing the number of sub-clinical brain infarcts/ischemia, aspirin could have a beneficial role in delaying cognitive decline.[65-68] Also, platelets are a major storage site for amyloid-ß and are hyperactive in Alzheimer’s disease.[69,70] However,the data are currently inconclusive.
Additional well-designed studies will help elucidate the role of aspirin in cognitive function.

Patients With HIV-1 Infection

Patients with human immunodeficiency-1 virus (HIV-1) infection have an elevated CV risk, and platelet activation causing a prothrombotic state may be a significant factor in these patients. Aspirin is likely to have a beneficial role by inhibiting platelet activation.

Between 6% and 15% of HIV deaths are due to CVD, including coronary heart disease and MI.[71-74] In addition to pathological immune reactions, patients with HIV infection also have platelet hyperreactivity and endothelial dysfunction, which can be attenuated after low-dose aspirin.[71,75].
There is also a growing body of evidence that HIV infection is associated with heightened immune activation and a chronic inflammatory state.[76-78]
Short-term studies suggest that low-dose aspirin may therefore have a role in attenuating platelet activity and immune activation, and longer-term studies on this are ongoing.[79,80]

Patients With SIRS

Patients with systemic inflammatory response syndrome (SIRS) may also benefit from early aspirin treatment. As with other indications, platelets are likely to have a key role in these pathologies, and there is evidence of the beneficial effects of aspirin and other antiplatelet agents in these critically ill patients.[81-83]

Pre-eclampsia

Aspirin has been shown to reduce the risk of developing pre-eclampsia in women at high risk for the condition, and early low-dose aspirin is recommended by both the United States Preventive Services Task Force and the World Health Organization for such women.[38,84,85] Recently, it has been suggested that women at modestly elevated risk (6% to 10%) should also be considered for aspirin treatment. RCTs are needed to establish clear evidence of a benefit.[86]

Summary

Aspirin has shown benefits in the treatment of a wide range of conditions.
The evidence today is most robust for the secondary prevention of CVD, and although the use of aspirin for primary prevention is an area of intense debate, several treatment guidelines recommend its use in higher risk patients with a low risk for bleeding.
Clinical trial data also support the use of aspirin for the prevention of colorectal and other GI cancers, and data are emerging for a role for aspirin in the prevention of metastases after a cancer diagnosis in certain subpopulations of patients.
Although the USPSTF has made a draft recommendation for the use of aspirin in the primary prevention of CVD and CRC, the chemopreventive benefits of aspirin are not yet addressed in most treatment guidelines. A range of possible mechanisms for aspirin's anticancer action have been proposed.

An involvement of the antiplatelet effect is not unlikely as current evidence suggests a full chemopreventive effect already at antiplatelet doses. Aspirin also has a role in the management of other conditions, including immunomodulation in HIV, prevention of pre-eclampsia, treatment of SIRS, and possibly, prevention of cognitive decline.

The results of ongoing studies on the effects of aspirin across various conditions may help physicians to more accurately assess the risk/benefit ratios of aspirin use in individual patients and may also lead to the inclusion of aspirin in treatment guidelines for CRC.

Precision Medicine Modeling Helps Advance Colorectal Cancer

Precision Medicine Modeling Helps Advance Colorectal Cancer Care
Dustin A. Deming, MD

Published Online: Sunday, August 30, 2015
Carbone Cancer CenterMelissa A. Wilson, MD, PhD
Dustin A. Deming, MD
Assistant Professor
University of Wisconsin Carbone Cancer Center
Madison, WI

My Own Cancer Diagnosis: A Doctor’s Story

In treating my patients with colorectal cancer, I see daily how research can provide hope and impact patient outcomes in the clinic. But my understanding goes beyond what I’ve learned as a gastrointestinal oncologist and translational researcher.

Two weeks after starting as a medical oncologist specializing in the treatment of colorectal cancer, I was diagnosed with colorectal cancer at age 31. Having completed radiation, surgery, and chemotherapy, I now understand how a colorectal cancer diagnosis changes every aspect of your life.

I am honored to care for people diagnosed with cancer. In addition, I now better understand the importance of research and the urgency with which further advances in cancer treatment are needed.

With this urgency in mind, my laboratory focuses on fundamentally changing the way in which colon cancer is treated to a more individualized approach. Our lab has developed multiple models to investigate novel therapies and we are now examining rational combinations of therapeutic agents that are already in clinical development for the treatment of subtypes of colon cancer.
Dr. Catherine M. Diefenbach

Although significant progress has been made during the last 20 years, colorectal cancer (CRC) is a leading cause of cancer-related death in the United States, accounting for nearly 50,000 deaths every year.1 Improved treatment options and biologic markers to predict treatment response are clearly needed.

At the University of Wisconsin Carbone Cancer Center, we are developing improved preclinical models that will help precision medicine become a reality for patients with CRC, as we aim to identify the patient populations most likely to benefit from new therapies.

Colorectal Cancer Mutations

Several key mutations are important in tumor initiation, progression, metastasis, and the response to some therapeutic agents. These mutations include APC (found in 80% of CRC tumors), TP53 (50%), KRAS (35%-45%), PIK3CA (20%-30%), and BRAF (10%), among others.2 Each CRC has been shown to possess two to six driver mutations per tumor.3 To date, KRAS, NRAS, and BRAF mutations are utilized clinically because their presence predicts resistance to the anti-epidermal growth factor receptor antibodies cetuximab and panitumumab.4

With advances in our ability to perform clinical genomic profiling, each histological type of cancer is now better understood as a collection of multiple subtypes characterized by unique mutation profiles.

To make precision medicine a reality for patients with CRC, a better understanding of how the molecular profile can help select the best therapies is needed. Giant strides toward achieving this goal have been made with improvements in the CRC preclinical models used for developing treatment strategies.

Colon cancers in mice can be identified with an endoscope and monitored for response to therapeutics (A and B). Fluorescent murine colon cancer spheroids can be generated with specific mutation profiles for translational studies (C and D). We have now generated human CRC spheroids to grow cells that are not able to otherwise be cultured (E and F).
Clinical advancements in targeting subtypes of CRC are starting to be realized as recent advances have been described for tumors that are BRAF mutant, HER2 expressing, or demonstrate microsatellite instability (MSI).

The combination of vemurafenib, cetuximab, and irinotecan demonstrated a 35% response rate in a phase I study in patients with BRAF mutant CRC (5%-10% of all patients).5

The combination of trastuzumab and lapatinib resulted in a 34.7% response rate in patients with HER2-overexpressing CRC.6

In addition, pembrolizumab demonstrated a 40% response rate for patients with high-MSI CRC.7 These exciting studies are demonstrating the promise of targeting subtypes of CRC, and these early results will be investigated further in upcoming clinical trials.

Improved Preclinical Modeling
Genetically Engineered Murine Model

Mouse models have been vital in studying the biology and response to pharmacologic agents in CRCs. However, ApcMin mouse and models using tissue-specific promoters, which are commonly utilized for preclinical studies, are limited in their abilities to address the genetic complexity seen in human cancers.

Our laboratory has developed an innovative adaptable transgenic mouse model of CRC that allows for multiple combinations of mutations to be expressed, thus enabling multiple mutations to be initiated within a single colon cancer.8
Using this model system, we are able to control when, where, and with which mutations the cancers form. These cancers can be followed by murine colonoscopy, and biopsies can be performed pre- and posttreatment for biomarker identification (Figure A and B).

This model has already proved effective in developing targeted strategies that exploit the cancer's mutation profile. Our laboratory has demonstrated benefit for targeting the PI3K pathway in colon cancers with PIK3CA mutations and these therapies are now being evaluated in new clinical trials.9-11

Spheroid Cultures

The capability to investigate subtypes of CRC has also been limited by classic cell culture techniques. The commonly utilized cell lines were selected for their ability to be grown in adherent cultures and not based upon their mutation profile.

To further our investigations into subtypes of CRC, we are developing a library of CRC spheroids in 3-dimensional culture media.
We are culturing colon cancers from our novel murine models (Figure C and D), as well as human cancers (Figure E and F). The cancer cells in these cultures form hollow spheres, develop infolding, and can even develop crypt-like structures.

We have now developed multiple lines of spheroids derived from colon cancers with defined mutation profiles. These cells cannot be cultured using adherent cell culture techniques, but can be grown in spheroid culture. This is important because the commonly utilized panels of colon cancer cells do not fully represent the mutation profiles of human cancers.
- See more at: http://www.onclive.com/publications/Oncology-live/2015/September-2015/precision-medicine-modeling-helps-advance-colorectal-cancer-care#sthash.Fb00ALdx.dpuf

Lung Cancer: Stereotactic Body Radiotherapy for Early-Stage NSCLC

Stereotactic Body Radiation Therapy an Effective Option for Early-Stage Lung Cancer Patients

By Caroline Helwick
September 1, 2014, Volume 5, Issue 14

Roy Decker, MD, PhD

Stereotactic Body Radiotherapy for Early-Stage NSCLC

In high-risk patients, SBRT appears to offer approximately equivalent control and survival when compared to surgical resection, in retrospective series. I can say that SBRT is approximately as good as surgery.
—Roy Decker, MD, PhD

Stereotactic body radiation therapy (SBRT) is safe and effective in early-stage non–small cell lung cancer (NSCLC), as it confers local control in 90% or more patients with T1 disease, according to Roy Decker, MD, PhD, Associate Professor in the Department of Therapeutic Radiology at Yale Cancer Center, New Haven, Connecticut. Dr. Decker described the use of SBRT in high-risk early-stage NSCLC patients at the 15th Annual International Lung Cancer Congress in Huntington Beach, California.

“In high-risk patients, SBRT appears to offer approximately equivalent control and survival when compared to surgical resection, in retrospective series,” he said. “I can say that SBRT is approximately as good as surgery.”

Transformative Study

Dr. Decker said that a multidisciplinary approach is always ideal. “Our guidelines state that all patients having SBRT who are at high risk should be evaluated by an experienced thoracic surgeon for minimally invasive surgery,” he said. “I never call a patient ‘inoperable’ without that consultation.”

However, results with stereotactic body radiotherapy are essentially equivalent to surgery, and may be preferred over surgery for some patients. The technique has been used in practice for 2 decades, and based on mature prospective trial data, the appropriate and inappropriate candidates for SBRT can now be identified, he said.

Several important studies have informed current SBRT practice in the United States. A number of years ago, phase II studies suggested that the failure pattern is primarily nodal or distant, and toxicity is more likely in the case of centrally located tumors, vs peripheral. This information formed the basis of the well-known Radiation Therapy Oncology Group (RTOG) 0236 trial, which enrolled 59 patients with T1 and T2 peripheral lesions outside of the zone of the proximal tracheobronchial tree.1

The study showed that patients with inoperable NSCLC receiving stereotactic body radiotherapy had a 3-year survival of 55.8%, high rates of local tumor control, and moderate treatment-related morbidity. Only one patient had a primary tumor failure, producing a 3-year primary tumor control rate of 97.6%. Three patients had a recurrence within the involved lobe, producing a 3-year primary tumor and involved lobe control rate of 90.6%. Median overall survival was 48 months. Rates of adverse events were 12.7% for grade 3 and 3.6% for grade 4. More patients died of other causes than of lung cancer.

“This study was transformative,” Dr. Decker said. “The findings are probably the best argument I can make for treating some high-risk patients with radiation.”

A subsequent population-based analysis from the Netherlands Cancer Registry examined the survival of early-stage NSCLC patients during three time periods, concluding the increase in survival between 2001 and 2009 was at least in part due to the increased use of SBRT over fractionated radiation.2

SBRT vis à vis Surgery

The issue of SBRT vs surgery has been examined through several comparative analyses. A retrospective comparison of patients with stage I NSCLC deemed ineligible for lobectomy found no significant difference in outcomes between stereotactic body radiotherapy and wedge resection.3 There were no differences in regional recurrence, locoregional recurrence, distant metastasis, or freedom from any failure. Risk of local recurrence was less with SBRT (4% vs 20%, P = .07), and while overall survival was higher with resection (87% vs 72%, P = .01), cause-specific survival was identical (94% with wedge, 93% with SBRT).

A similar finding was reached in another study of patients with stage I disease, 462 of whom underwent surgery and 76 who had SBRT. A propensity-matched analysis revealed similar rates of local recurrence and disease-specific survival between the two groups. Four-year local control was 90%, and there was no difference in cancer-specific survival.4

Japanese investigators conducted a retrospective review of 87 stage I patients who declined surgery and were treated with stereotactic radiotherapy, and found local control rates for T1 and T2 tumors at 5 years to be 92% and 73%, respectively. Five-year overall survival rates for stage IA and IB subgroups were 72% and 62%, respectively. The researchers concluded that the survival rate for SBRT is “potentially comparable to that of surgery.”

The most recent data come from a propensity-matched analysis of 64 patients treated with SBRT and 64 treated with minimally invasive surgery.5 Post-SBRT locoregional control rates were superior to surgery at 1 year (96.8% vs 86.9%) and 3 years (86.9% vs 82.6%, P = .04), but distant recurrences and overall survival were similar.

“None of these studies found that SBRT and surgery were the same, but they do tell us that outcomes with SBRT are in the same ballpark as those we get with surgery,” Dr. Decker concluded.

Prospective Trials

Only two prospective trials have been reported for operable patients—and remain unpublished. Their results are not as favorable, he noted.

RTOG 0618 was a small study of 26 patients with T1 and T2 disease in which the 2-year local and lobar failure rate was 19%.6 “This local failure rate is concerningly high,” Dr. Decker commented. “We await the publication, before we know what to make of this.”

Japan Clinical Oncology Group (JCOG) 0403 was a single-arm study of 64 operable patients.7 The 3-year local control rate was 86%, and overall survival rate was 76%. “This local control is not as good as expected, although we do not know how this was defined,” he remarked.

Unfortunately several randomized studies comparing surgery to SBRT have closed early due to poor accrual, including ROSEL (lobectomy vs SBRT), STARS (lobectomy vs SBRT with cyberknife) and ACOSOG Z4099/RTOG1021 (sublobar resection vs SBRT).

Pulmonary Function and Quality of Life

“The decision could come down to, ‘What’s the effect of SBRT on the patient’s quality of life and pulmonary function?’” Dr. Decker said. “The thoracic surgeon and I discuss whether the patient is a candidate for surgery or SBRT, and we try to parse out what the patient’s life will be like after treatment.”

In RTOG 0236, an analysis of patients’ pulmonary function following SBRT found no significant effect overall, but there were nonsignificant declines in both forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide. This is consistent with what retrospective series have shown, and the impact of this could vary among patients, he said.

Quality of life has been examined in some studies. One from the Cleveland also revealed small declines in diffusing capacity of the lung for carbon monoxide, but no degradation in quality-of-life, no reductions in 6-minute walking distance, and no increase in patient-reported dyspnea.8

Few ‘Poor Candidates’ for SBRT

Not all patients with early-stage lung cancer are optimal candidates for stereotactic radiotherapy, though even suboptimal patients can have good outcomes, with caveats.

“Patients with centrally located tumors can be treated effectively, but they are at higher risk for side effects. And we think it’s safe to treat patients with larger tumors, but we have lower expectations of control,” he said.

For centrally located tumors that are small, reduced-dose SBRT can be effective, retrospective studies suggest. Even with a lower dose, however, grade 5 toxicities can occur.

In a study from Yale, in which 47 patients with central lesions received stereotactic body radiotherapy, four patients had grade 3 dyspnea and one developed hemoptysis that contributed to respiratory failure and death. Patients who developed grade 3 or more toxicity had larger tumors than those without toxicity (median diameter = 4.3 vs 2.9 cm, P = .02).

The 2-year lobar local control rate overall was 94%; this rose to 100% for patients receiving a biologic equivalent dose of 100 Gy or more and diminished to 80% among those receiving a lower dose. The authors concluded that SBRT for central lung tumors seems safe, but treatment of larger tumors carries an increased risk of high-grade toxicity.

Accrual is complete for RTOG 0813, which will treat patients at the highest dose levels and should be informative, he predicted.

For larger (T2) tumors in general—ie, those that are 4 to 5 cm—evidence is emerging that SBRT is effective, though local control is somewhat less than that seen with smaller tumors. A series of patients treated at Yale showed local control rates to be 75% to 80% in this population.

“This is no surprise. With a 5-cm tumor, you won’t get 90% local control,” he added. “If this patient has a good surgical option, that’s a better choice.”

Patients with poor pulmonary function at baseline also need not be excluded. A review of 423 patients, stratified by pretreatment pulmonary function, found that pulmonary function declined by 3.6% at 6 months and by 6.8% at 24 months.9 Interestingly, the largest loss was observed among patients with the best pulmonary function pretreatment; pulmonary function actually improved the most among patients with the worst baseline function. ■

Disclosure: Dr. Decker reported no potential conflicts of interest.

Guide for Appropriate Use of PICCs

Medscape Medical News
Panel Releases Guide for Appropriate Use of PICCs

Susan London
September 15, 2015


Clinicians can now refer to a new tool, the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC), to help determine when and how to use peripherally inserted central catheters (PICCs) and related venous access devices. The guide is published as a supplement to the Annals of Internal Medicine.

"[Intravenous] access and getting an [intravenous drip] is the most commonly performed procedure in any hospitalized patient in the world. And yet it's the least studied, for a number of different reasons," lead author Vineet Chopra, MD, an assistant professor of medicine at the University of Michigan and a research scientist with the VA Ann Arbor Healthcare System, told Medscape Medical News.

Meanwhile, "the use of PICCs in hospitalized patients has just exploded," he said. In addition, "there was really no good...unifying document that instructed physicians or provided guidance as to when one device is better than the other, or when the use of one device is potentially harmful. All of that exists in fragmented spaces and in different disciplines, but not in the mainstream view of a typical inpatient doctor.

"We thought it was really important, given the growing use of PICCs and other devices in mainstream medicine, to have something that would help coordinate the literature in a way that was a lot more systematic and a lot more practical for the everyday doctor," Dr Chopra summarized. "I think there was a huge need that never existed before, especially with the rise of hospitalists and the rise of PICCs in hospitalized patients."

To create MAGIC, he and other members of an international, multispecialty panel of experts applied the RAND/University of California, Los Angeles, Appropriateness Method to develop criteria for the use, care, and management of PICCs and related venous access devices in adults. They performed a systematic review of the literature and created clinical scenarios based on patient population, indication for insertion, and duration of use. For each scenario, they compared the appropriateness of PICC use with that of other venous access devices.

A noteworthy aspect of the panel was inclusion of a patient who had undergone placement of several different venous access devices over time and was able to contribute that perspective, which is a rare practice in guideline development, according to Dr Chopra.

"We wanted to be different, first, because the evidence here is not very mature, there are very few randomized trials to guide us on our decision making and, second, because when there is uncertainty, it's imperative to have that conversation with the patient," he elaborated. "A lot of the recommendations that we ended up with that were not evidence driven were really based on the patient being on our panel, who actually [said], 'Listen, if this were me, this is what I would want.' "

Dr Chopra enumerated three key take-home points from MAGIC for clinicians. First, "think about the device before you place it," he recommended. "Too often, in medicine we are so focused on the clinical moment or moving the patient through processes of care, and we don't think of the device as being potentially harmful. So I think that a moment of pause needs to be interjected right before an operation, to slow down and...reflect, 'Is this the right choice for the patient?' "

Second, "choose wisely," Dr Chopra advised. To that end, the guide details specific risks and benefits of each device. Clinicians can then consider their individual patient and goals of treatment in deciding the best way to move forward.

"Third, I am hoping this will become a tool that will actually help improve quality of care," he said. "I am hoping MAGIC becomes an instrument that can be tested in real-world scenarios, whether it's through [electronic medical records] or through quality improvement initiatives like we have in Michigan, where we can actually think about how can you utilize this in an everyday fashion, so that it doesn't become more of an obstacle, but rather a great benefit to have on your side."

The MAGIC panelists reviewed a daunting 665 scenarios for the use of PICCs, rating 38% as appropriate, 19% as neutral/uncertain, and 43% as inappropriate. But time-strapped clinicians can simply refer to the color-coded figures that summarize the findings in a way that makes them easy to apply at the bedside, according to Dr Chopra.

"Think of those as pocket cards," he suggested. "All that physicians need to do is have those in your pocket because you can literally think about your patient and what you need, and run through that list of devices and how long you will need it for to come up with a handy way of saying, 'Yup, these are my options, and this one seems to be the preferred device or the best device.' "

"We are working on creating smart phone apps and other handy dandy tools that make this a lot easier, so hopefully this will become a lot more manageable when you are taking care of many patients, so that you don't have to dig through the paper or find the [figures]," Dr Chopra added.

The timing of MAGIC's publication works out well for teaching institutions, as it coincides with the beginning of the academic year, he noted. "It's a great educational tool that I would sort of love to be able to walk around with the new interns and say, 'Look, this is a new tool out there for you to start thinking about,' " he elaborated.

Dr Chopra reports receiving grants from the Society of Hospital Medicine and Agency for Healthcare Research and Quality during the conduct of the study. Several coauthors report various financial relationships with Blue Cross Blue Shield of Michigan, the Institute for Healthcare Improvement, the Society of Hospital Medicine, the University of Michigan, the CDC Foundation, Michigan Hospital Association, Agency for Healthcare Research and Quality, Wiley Publishing, Doximity, Jvion, BMS, Vascular Pathways, Bard Peripheral Vascular, B. Braun, Orbimed, Teleflex, Cook, W.L. Gore, Lutonix, PICC Excellence Inc, Greenville Hospital System, Alliance for Vascular Access Device Training and Research, Griffith University, Teleflex, Ethicon, Bard International, SonoSite, 3M, Department of Veterans Affairs National Center for Patient Safety, University of Michigan Medical Group.

Ann Intern Med. 2015;163:S1-S42. Abstract

Pesticide Exposure Linked to Childhood Blood Cancers

Medscape Medical News > Oncology
Pesticide Exposure Linked to Childhood Blood Cancers

Roxanne Nelson RN, BSN
September 21, 2015


Exposure to pesticides that are used inside the home was associated with an increased risk of developing childhood leukemia and lymphoma, according to new data.

The study was published in the October issue of Pediatrics.

In this meta-analysis of 16 epidemiologic studies, researchers from the Harvard TH Chan School of Public Health in Boston, Massachusetts, examined the possible association between residential pesticide exposure during childhood and childhood cancers.

They found that exposure to indoor insecticides was associated with a significant increase in the risk for childhood leukemia (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.26 - 1.72; I 2 = 30%) and lymphomas (OR, 1.43; 95% CI, 1.15 - 1.78; I 2 = 0%).

In addition, the authors found that there was a positive association between childhood home pesticide or herbicide exposure and childhood brain tumors, but it did not reach statistical significance.

"Using pesticides in the indoor environment where young children live is the most unwise decision that parents can make, because of the close proximity, lack to adequate ventilation, and deposition of residues on the surface in which children come into contact with," said senior author Chensheng Lu, PhD, associate professor of environmental exposure biology in the department of environmental health, Harvard School of Public Health.

While the data isn't conclusive and additional research is needed to confirm the association between residential indoor pesticide exposures and childhood cancers, the findings of this meta-analysis should prompt more attention to childhood exposure, explained Dr Lu.

Preventive measures should be considered to reduce children's exposure to pesticides at home, he said.

"Making your homes pest-proof or pest-free is the best way to prevent your children from developing childhood cancers," Dr Lu told Medscape Medical News. "Also there are so many non-chemical treatments that can be used, such as using screen windows or fixing cracks and crevices to prevent insects from getting inside."

There are also safer types of chemical treatments that can be used for pest control. "Parents also should be aware of whether the school, playground, sports field, or parks have been treated with pesticides because children often spend many hours in these environments," he pointed out.

AAP Statement Urges Caution

In 2012, the American Academy of Pediatrics (AAP) issued a policy statement and an accompanying technical report noting that prenatal and early childhood exposure to pesticides is associated with several childhood cancers as well as with decreased cognitive function and behavioral problems (Pediatrics. 2012;130(6):e1757-1763).

In their statement, they recommended that pediatricians become familiar with the effects of acute and chronic exposures to pesticides, and learn what resources are available for both treatment of acute poisoning and addressing lower-dose chronic exposures in children.

In an interview with Medscape at the time, James Roberts, MD, MPH, professor of pediatrics at Medical University of South Carolina in Charleston and lead author of the AAP documents, noted that "this report really has been a long time in coming."

"Most people think of pesticide poisoning as happening in an agricultural area," he said. "Certainly, to some extent, these are high-use areas, and there may be some more exposure both through proximity to the fields and take-home exposure from parents who work in the fields."

"However, poisonings in the home do occur as a result of treatment for nuisance pests such as cockroaches, mice, ants, and other kinds of insects," Dr Roberts pointed out. "Other sources at home include the application of herbicides used for weed control on lawns and the application of tick and flea control products to household pets."

Links to Pesticides and Herbicides

In the current paper, Dr Lu and colleagues looked primarily at exposure to indoor pesticide use. They reviewed all observational studies published in PubMed before February 2014 and reviewed reference sections of articles derived from searches. The search yielded 277 studies that met inclusion criteria, and of those, 16 were included in the meta-analysis.

A subgroup analysis that combined studies on acute leukemia showed elevated risks for exposure to both home pesticides (OR, 1.55; 95% CI, 1.38 - 1.75) and indoor insecticides (OR, 1.59; 95% CI, 1.39 - 1.81).

When studies were combined for both leukemia and lymphoma risks, the authors observed a statistically significant association between childhood hematopoietic malignancies and home pesticide exposure during childhood (11 out of 12 data were from indoor insecticides).

A positive but a statistically insignificant association was observed between home pesticide exposure and childhood brain tumors (OR, 1.22; 95% CI, 0.83 - 1.81; I 2 = 23%).

The use of outdoor pesticides, including insecticides, herbicides, and fungicides also showed a statistically significant association between childhood leukemia and exposure to herbicides (OR, 1.26; 95% CI, 1.10 - 1.44, I 2 = 0%), but the association with lymphoma was not statistically significant. There was also no apparent association between herbicide exposure and brain tumors.

When studies on all types of childhood cancers were combined, including neuroblastoma and Wilms' tumor, a statistically significant association with residential herbicide exposure was observed (OR, 1.35; 95% CI, 1.16 - 1.55; I 2 = 23%), but no association was observed between exposure to outdoor pesticides or outdoor insecticides and any types of childhood cancers.

"Overall, the results suggest that cancer risks are related to the type of pesticide and where it was used," write the authors.

The study was supported by the Department of Energy and Environmental Protection, State of Connecticut. The authors have no disclosures.

Pediatrics. Published online September 14, 2015.

Ultraviolet (UV) Radiation and Your Eyes

Ultraviolet (UV) Radiation and Your Eyes

By Gary Heiting, OD



The UV Index developed by the U.S. Environmental Protection Agency (EPA) and the National Weather Service (NWS) has made many Americans more aware of the risks of sunburn and skin cancer from the sun's ultraviolet (UV) radiation.

But did you know UV and other radiation from the sun also can harm your eyes?

Extended exposure to the sun's UV rays has been linked to eye damage, including cataracts, macular degeneration, pingueculae, pterygia and photokeratitis that can cause temporary vision loss.

And new research suggests the sun's high-energy visible (HEV) radiation — also called "blue light" — may increase your long-term risk of macular degeneration. People with low blood plasma levels of vitamin C and other antioxidants especially appear at risk of retinal damage from HEV radiation.

Dangers of Ultraviolet Radiation to Your Eyes

To protect your eyes from harmful solar radiation, sunglasses should block 100 percent of UV rays and also absorb most HEV rays.

Frames with a close-fitting wraparound style provide the best protection because they limit how much stray sunlight reaches your eyes from above and beyond the periphery of your sunglass lenses.

While many people refer to ultraviolet radiation as UV light, the term technically is incorrect because you cannot see UV rays.

The three categories of invisible high-energy UV rays are:

UVC rays. These are the highest-energy UV rays and potentially could be the most harmful to your eyes and skin. Fortunately, the atmosphere's ozone layer blocks virtually all UVC rays.

But this also means depletion of the ozone layer potentially could allow high-energy UVC rays to reach the earth's surface and cause serious UV-related health problems. UVC rays have wavelengths of 100-280 nanometer (nm).
UVB rays. These have slightly longer wavelengths (280-315 nm) and lower energy than UVC rays. These rays are filtered partially by the ozone layer, but some still reach the earth's surface.

In low doses, UVB radiation stimulates the production of melanin (a skin pigment), causing the skin to darken, creating a suntan.

But in higher doses, UVB rays cause sunburn that increases the risk of skin cancer. UVB rays also cause skin discolorations, wrinkles and other signs of premature aging of the skin.


Ultraviolet (UV) rays are higher in energy and do not fall within the realm of visible light, as shown here. In the electromagnetic spectrum, radio waves have the lowest energy, and gamma rays have the highest energy.

UVA rays. These are closer to visible light rays and have lower energy than UVB and UVC rays. But UVA rays can pass through the cornea and reach the lens and retina inside the eye.

Overexposure to UVA radiation has been linked to the development of certain types of cataracts, and research suggests UVA rays may play a role in development of macular degeneration.

Various eye problems have been associated with overexposure to UV radiation. As an example, UVB rays are thought to help cause pingueculae and pterygia. These growths on the eye's surface can become unsightly and cause corneal problems as well as distorted vision.

In high short-term doses, UVB rays also can cause photokeratitis, a painful inflammation of the cornea. "Snow blindness" is the common term for severe photokeratitis, which causes temporary vision loss usually lasting 24-48 hours.

The risk for snow blindness is greatest at high altitudes, but it can occur anywhere there is snow if you don't protect your eyes with UV-blocking sunglasses.

Because the cornea appears to absorb 100 percent of UVB rays, this type of UV radiation is unlikely to cause cataracts and macular degeneration, which instead are linked to UVA exposure.

HEV Radiation Risks

As the name suggests, high-energy visible (HEV) radiation, or blue light, is visible. Although HEV rays have longer wavelengths (400-500 nm) and lower energy than UV rays, they penetrate deeply into the eye and can cause retinal damage.

According to a European study published in the October 2008 issue of Archives of Ophthalmology, HEV radiation — especially when combined with low blood plasma levels of vitamin C and other antioxidants — is associated with the development of macular degeneration.

Sun Safety Essentials

Clip-on and Fit-over Sunglasses: Eyeglasses and Sunglasses in One!

Do you wear prescription eyeglasses? If so, you also need to wear sunglasses while outside; standard glasses won't shield your eyes from harmful UV and HEV radiation.

Man and woman wearing Solar Shield fit-over sunglasses

"Fits Over" sunglasses by Solar Shield

Despite this, many people go without proper sun protection because of the extra cost for prescription sunglasses or the inconvenience of having to switch glasses when they move from indoors to outdoors. If this sounds familiar, fit-over or clip-on sunglasses may be an ideal solution for you.

Fit-over sunglasses, such as Solar Shield "Fits Over" sunglasses shown in the image above, are designed to be worn over prescription frames, while clip-on lenses can attach to most contemporary prescription eyeglasses. Both of these "2-in-1" options offer a great value alternative to prescription sunglasses.

As with regular sunglasses, always look for lenses that block 100 percent of UV rays. — A.S.

Outdoor Risk Factors

Anyone who spends time outdoors is at risk for eye problems from UV radiation. Risks of eye damage from UV and HEV exposure change from day to day and depend on a number of factors, including:

Geographic location. UV levels are greater in tropical areas near the earth's equator. The farther you are from the equator, the smaller your risk.
Altitude. UV levels are greater at higher altitudes.
Time of day. UV and HEV levels are greater when the sun is high in the sky, typically from 10 a.m. to 2 p.m.
Setting. UV and HEV levels are greater in wide open spaces, especially when highly reflective surfaces are present, like snow and sand.
In fact, UV exposure can nearly double when UV rays are reflected from the snow. UV exposure is less likely in urban settings, where tall buildings shade the streets.
Medications. Certain medications, such as tetracycline, sulfa drugs, birth control pills, diuretics and tranquilizers, can increase your body's sensitivity to UV and HEV radiation.

Surprisingly, cloud cover doesn't affect UV levels significantly. Your risk of UV exposure can be quite high even on hazy or overcast days. This is because UV is invisible radiation, not visible light, and can penetrate clouds.

Measuring Ultraviolet Rays

In the United States, the risk for UV exposure is measured using the UV Index.

Developed by the NWS and EPA, the UV Index predicts each day's ultraviolet radiation levels on a simple 1 to 11+ scale.

In addition to publishing the UV Index daily, the EPA also issues a UV Alert when the level of solar UV radiation that day is expected to be unusually high.
UV Protection Recommendations UV Index Risk Level Recommendations
2 or less Low 1. Wear sunglasses.
2. If you burn easily, use sunscreen with an SPF* of 15+.
3 - 5 Moderate 1. Wear sunglasses.
2. Cover up and use sunscreen.
3. Stay in the shade near midday, when the sun is strongest.
6 - 7 High 1. Wear a hat and sunglasses.
2. Cover up and use sunscreen.
3. Reduce time in the sun between 10 a.m. and 4 p.m.
8 - 10 Very high 1. Wear a hat and sunglasses.
2. Cover up and use sunscreen.
3. Minimize sun exposure between 10 a.m. and 4 p.m.
11+ Extreme 1. Wear a hat and sunglasses.
2. Apply sunscreen (SPF 15+) liberally every two hours.
3. Try to avoid sun exposure between 10 a.m. and 4 p.m.
*SPF = sun protection factor
Information based on U.S. Environmental Protection Agency standards.

If you're wondering how high today's UV light levels are where you live, here's a handy UV index map for the United States.

Kids Need UV Protection Even More Than Adults

The risk of damage to our eyes and skin from solar UV radiation is cumulative, meaning the danger continues to grow as we spend time in the sun throughout our lifetime.
Real Kids Shades sunglasses, style RKS Flex
These rubber frames are soft and flexible, so your kids won't break them, and the polycarbonate lenses offer 100 percent UV protection. RKS Flex, by Real Kids Shades.

With this in mind, it's especially important for kids to protect their eyes from the sun. Children generally spend much more time outdoors than adults.

In fact, some experts say that because children tend to spend significantly more time outdoors than most adults, up to half of a person's lifetime exposure to UV radiation can occur by age 18. (Other research cited by The Skin Cancer Foundation says slightly less than 25 percent of our lifetime exposure to UV radiation is sustained during childhood.)

Also, children are more susceptible to retinal damage from UV rays because the lens inside a child's eye is clearer than an adult lens, enabling more UV to penetrate deep into the eye.

Therefore, make sure your kids' eyes are protected from the sun with good quality sunglasses. Also, encourage your child to wear a hat on sunny days to further reduce UV exposure.

Sunglasses That Protect Your Eyes From UV and HEV Rays

To best protect your eyes from the sun's harmful UV and HEV rays, always wear good quality sunglasses when you are outdoors.

News About UV Light

New Report on How UV Light Affects the Eyes, With Prevention Tips
Please click here for a copy of Protection for the Naked Eye: Sunglasses as a Health Necessity

June 2015 — The Vision Council has released its 2015 report on UV protection, called Protection for the Naked Eye: Sunglasses as a Health Necessity.

The report includes information on how UV light harms eye health and vision, a map of the most vulnerable U.S. cities, and results from a survey that show differing sunglass use among Millennials, Generation X, Baby Boomers and Beyond Boomers.

The report also includes helpful suggestions on choosing the right sunglasses for UV protection, plus an interesting history of sunglasses. It's in a PDF format, and you can access it here.

For more booklets and reports on eye health and vision topics, please visit our Downloads page.

Look for sunglasses that block 100 percent of UV rays and that also absorb most HEV rays. Your optician can help you choose the best sunglass lenses for your needs.

To protect as much of the delicate skin around your eyes as possible, try at least one pair of sunglasses with large lenses or a close-fitting wraparound style.

Depending on your outdoor lifestyle, you also may want to explore performance sunglasses or sport sunglasses.

The amount of UV protection sunglasses provide is unrelated to the color and darkness of the lenses.

For example, a light amber-colored lens can provide the same UV protection as a dark gray lens. Your optician can verify that the lenses you choose provide 100 percent UV protection.

But for HEV protection, color does matter. Most sunglass lenses that block a significant amount of blue light will be bronze, copper or reddish-brown (see lens tint guide).

Again, your optician can help you choose the best "blue-blocking" lenses.

In addition to sunglasses, wearing a wide-brimmed hat on sunny days can reduce your eyes' exposure to UV and HEV rays by up to 50 percent.
More Tips About Sunglasses and UV Exposure

Many misconceptions exist about the right sun protection for your eyes. Keep these tips in mind:

This UV Index devised by the Environmental Protection Agency and National Weather Service provides a color-coded warning system to alert people to the dangers of being outdoors on certain days.

Not all sunglasses block 100 percent of UV rays. If you're unsure about the level of UV protection your sunglasses provide, take them to your eye doctor or optician for an evaluation. Many eye care professionals have instruments such as spectrophotometers that can measure the amount of visible light and UV radiation your lenses block.

Almost all sunglasses block a portion of HEV rays, but some tints block more blue light than others. Blue-blocking sunglass lenses usually are bronze, copper or reddish-brown in color.
Remember to wear sunglasses even when you're in the shade. Although shade reduces your UV and HEV exposure to some degree, your eyes still will be exposed to UV rays reflected from buildings, roadways and other surfaces.
Sunglasses are important especially in winter, because fresh snow can reflect 80 percent of UV rays, nearly doubling your overall exposure to solar UV radiation. If you ski or snowboard, choosing the right ski goggles is essential for adequate UV protection on the slopes.
Even if your contact lenses block UV rays, you still need sunglasses. UV-blocking contacts shield only the part of your eye under the lens. UV rays still can damage your conjunctiva and other tissues not covered by the lens.

Wearing sunglasses protects these delicate tissues and the skin around your eyes from UV damage.
If you have dark skin and eyes, you still need to wear sunglasses.

Although your dark skin may give you a lower risk of skin cancer from UV radiation, your risk of eye damage from UV and HEV rays is the same as that of someone with fair skin.

You need not fear the outdoors and sunny days, as long as you are equipped with the right eye and skin protection to reduce your UV exposure.
Home » Sunglasses » UV Rays and Vision

Dr. Gary HeitingAbout the Author: Gary Heiting, OD, is senior editor of AllAboutVision.com. Dr. Heiting has more than 25 years of experience as an eye care provider, health educator and consultant to the eyewear industry. His special interests include contact lenses, nutrition and preventive vision care. Connect with Dr. Heiting via Google+.

UK cancer survival rates below European average

UK cancer survival rates below European average

Behind the Headlines

Thursday December 5 2013
Researchers looked at data from over 10 million patients

The good news is that cancer survival rates are improving

“Cancer survival in Britain the worst in Europe,” The Daily Telegraph reports.

This and many other similar headlines are prompted by a major new study on cancer survival rates in Europe from 1997 to 2007.

While survival rates have tended to improve, cancer survival still varies widely between European countries. The lowest survival rates for most cancers were found in eastern Europe.

The study also found that the UK and Ireland has lower survival rates than the European average for many cancers, particularly of the colon, ovary, kidney, stomach and lung. The lung cancer survival rate in particular was far lower than for other regions. The UK has about average survival rates for cancer of the rectum, breast, prostate, melanoma of the skin and lymphomas.

Researchers say the main reason for low survival rates in the UK seems to be delayed diagnosis, underuse of successful treatments and unequal access to treatment, particularly among elderly people.

However, patient factors are not accounted for, such as the level of smoking, alcohol misuse and poor diet in the UK.

It could be the case that poor cancer care in the UK is not solely to blame for the below average cancer survival rates, but may also be related to the factors listed above.

Good news on children’s cancers

A related report from the EUROCARE study looked at survival rates for childhood cancers had better news. Figures for 2005-2007 show that survival for all childhood cancers combined is about 79%, up from 76% in 1999-2001, with the most striking increase being in eastern Europe.
Where did the story come from?

The study was carried out by researchers from a number of centres across Europe including the London School of Hygiene and Tropical Medicine in the UK. It was funded by the European Commission, Italian Ministry of Health and the Cariplo Foundation.

The study was published in the peer-reviewed medical journal Lancet Oncology.

Unsurprisingly, the research got wide coverage in the UK press, with the Mail Online pointing out that cancer survival rates in the UK were often on a par with former states of the eastern bloc and below comparable countries such as France and Germany. The Mail also included comments from NHS England as well as cancer charities, while The Guardian linked the study to a story about reported moves to raise awareness of cancer among older people.

The good news about the improvements in childhood cancer rates appears to have been ignored.

The types of cancers studied

As there are 100s of different cancers the researchers, out of necessity, limited their main analysis to the 10 most common cancers in terms of causing deaths:

Breast cancer
Colon cancer
Kidney cancer
Lung cancer
Non-Hodgkin lymphoma
Ovarian cancer
Prostate cancer
Rectal cancer
Skin cancer – melanomas
Stomach cancer

What kind of research was this?

The findings on both adult and childhood cancer survival rates come from an ongoing population based study called EUROCARE which provides regular updates of cancer survival in Europe.

EUROCARE’s findings are important since they can be used to improve national cancer plans and organise better cancer care.

The researchers point out that cancer diagnosis and treatment have changed greatly in recent decades, with screening for breast cancer and cervical cancer, and to a lesser extent colorectal cancer, being widely adopted. They also say there have been advances in diagnostic imaging, genetic profiling, and cancer treatments.

The latter includes the introduction of targeted drugs, multidisciplinary care and a growing concentration of treatment in specialist centres.

The EUROCARE-5 database contains about 22 million records of patients diagnosed from 1978 to 2007 and followed up to Dec 31, 2008. The participation of additional countries, especially from eastern Europe, has increased coverage.
What did the research involve?

The researchers analysed data for more than 10 million adult patients (aged 15 and over) who had been diagnosed with cancer up to 2007 and followed up to 2008.

The data came from 107 population-based cancer registries from 29 countries, grouped into five regions:

Denmark, Finland, Iceland, Norway, Sweden (northern Europe)
England, Ireland, Northern Ireland, Scotland, Wales (UK and Ireland)
Austria, Belgium, France, Germany, Netherlands, Switzerland (central Europe)
Croatia, Italy, Malta, Portugal, Slovenia, Spain (southern Europe)
Bulgaria, Czech Republic, Estonia, Latvia, Lithuania, Poland, Slovakia (eastern Europe)

All invasive, primary cancers, except non-melanoma skin cancer (which is rarely lethal), were eligible for inclusion and were defined according to international guidelines. Patients who had more than one type of cancer were included in each of the counts.

The researchers used anonymised cancer registration records, which had to contain information about each patient’s:

date of birth
diagnosis
whether they were dead or alive at the last record
sex
the site and characteristics of the cancer
the basis for diagnosis

Cases diagnosed at autopsy or registered only from a death certificate were excluded.

The researchers applied standard quality control procedures to detect missing or invalid information and possible errors in patients’ records. About 68,000 records with major or probable errors were returned to registries for correction or confirmation. From this information they calculated the five year survival rate for 46 cancers, weighted by age and country.

They also calculated country-specific and age-specific survival for 10 common cancers, together with survival differences between the time periods 1999-2001, 2002-4, and 2005-7.

What were the basic results?

The researchers found that overall, the five year survival rates increased steadily over time for all European regions. Cancers with the largest increases in survival rates were:

Prostate cancer – 81.7% in 2005-7, compared to 73.4% in 1999 to 2001
Non-Hodgkin lymphoma – 60.4% in 2005-7, compared to 53.8% in 1999-2001
Rectal cancer – 57.6% in 2005-7 compared to 52.1% in 1999-2001

They say that survival rates in eastern Europe were generally low and below the European average, with survival rates highest for northern, central, and southern Europe.

In the UK and Ireland survival rates were:

Around the European average for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma.
Low for kidney, stomach, ovarian, colon, and lung cancers.
Much lower for lung cancer than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) may be affected by overestimation.

Generally survival usually decreased with age, although to different degrees depending on region and cancer type.

Looking specifically at the UK and Ireland compared to neighbouring countries, the study found that:

For breast cancer, survival rate in the UK was 79.2%, slightly below the European average (81.8%) and lower than France (86.1%), Germany (83.6%) and Austria (82.1%).
For colon cancer, survival rate was 51.8%, lower than the European average (57%) and lower than Germany (62.2%), Austria (61.2%) and France (59.7%).
For lung cancer survival was 9%, below the European average (13%) and Austria (16.7%), Germany (15.6%) and France (13.8%).
For prostate cancer survival was 80.6%, below the European average and below Austria (90.4%), Germany (89.4%) and France (88.9%).
For ovarian cancer, survival was 31%, below the European average (37.6%) and below Austria (41.4%), Germany (40.3%) and France (40.1%).
For melanoma, survival was 85.6%, higher than the European average (83.2%) and Austria (83.1%) but below Germany (89.4%) and France (87.2%).

How did the researchers interpret the results?

The researchers say that the major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. The differences in survival between countries are probably explained by differences in stage at diagnosis and accessibility to good care, different diagnostic and screening approaches, and differences in cancer biology.

Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities, they say.

Conclusion

The results of this large study on cancer survival are likely to be reliable. There may be some errors or omissions in the information obtained from cancer registries but the researchers took steps to minimise these and they are unlikely to have affected the overall results.

Findings of slightly lower survival rates of some cancers in the UK compared to similar countries are likely to raise concerns.

The findings have already provoked a media debate in the UK, with one charity executive reportedly calling them “truly depressing” and Sean Duffy, National Clinical Director for Cancer at NHS England saying that “real inroads” have been made into improving cancer survival in England.

However, writing in a linked commentary article in the same journal, Professor Alastair Munro from the University of Dundee School of Medicine, points out that to understand the patterns that emerge we need more detailed information.

"Registries should record more sociodemographic information and more details about investigation, staging, treatment, recurrences, and second-line treatment,” he argues. “Until more is known about the individual attributes of patients, the interpretation of the EUROCARE studies will be far from straightforward."

As Prof Munro says, there are no details about the rates of risk taking behaviour for the UK compared to the European studies in terms of smoking, alcohol use, diet and sun exposure.

And the UK may have more in common with countries such as Poland, Bulgaria and the Czech Republic, rather than France, Germany and Sweden, when it comes to our smoking, eating, drinking and exercising habits.

It would be premature and unjust to purely attribute the difference to the level of care received in the UK.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Analysis by Bazian

Edited by NHS Choices

Food additives

National Institutes of Health U.S. National Library of Medicine
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Food additives

Food additives are substances that become part of a food product when they are added during the processing or making of that food.

"Direct" food additives are often added during processing to:

Add nutrients
Help process or prepare the food
Keep the product fresh
Make the food more appealing

Direct food additives may be man-made or natural.

Natural food additives include:

Herbs or spices to add flavor to foods
Vinegar for pickling foods
Salt, to preserve meats

"Indirect" food additives are substances that may be found in food during or after it is processed. They were not used or placed in the food on purpose. These additives are present in small amounts in the final product.

Function

Food additives serve five main functions.

Give the food a smooth and consistent texture:

Emulsifiers prevent liquid products from separating.
Stabilizers and thickeners provide an even texture.
Anticaking agents allow substances to flow freely.

Improve or preserve the nutrient value:

Many foods and drinks are fortified and enriched to provide vitamins, minerals, and other nutrients. Examples of commonly fortified foods are flour, cereal, margarine, and milk. This helps to make up for vitamins or minerals that may be low or lacking in a person's diet.
All products that contain added nutrients must be labeled.

Maintain the wholesomeness of foods:

Bacteria and other germs can cause foodborne illnesses. Preservatives reduce the spoilage that these germs can cause.
Certain preservatives help preserve the flavor in baked goods by preventing the fats and oils from going bad.
Preservatives also keep fresh fruits from turning brown when they are exposed to the air.

Control the acid-base balance of foods and provide leavening:

Certain additives help change the acid-base balance of foods to get a certain flavor or color.
Leavening agents that release acids when they are heated react with baking soda to help biscuits, cakes, and other baked goods rise.

Provide color and enhance flavor:

Certain colors improve the appearance of foods.
Many spices, as well as natural and man-made flavors, bring out the taste of food.

Side Effects

Most concerns about food additives have to do with man-made ingredients that are added to foods. Some of these are:

Antibiotics given to food-producing animals, such as chickens and cows
Antioxidants in oily or fatty foods
Artificial sweeteners, such as aspartame, saccharine, and sodium cyclamate
Benzoic acid in fruit juices
Lecithin, gelatins, corn starch, waxes, gums, and propylene glycol in food stabilizers and emulsifiers
Many different dyes and coloring substances
Monosodium glutamate (MSG)
Nitrates and nitrites in hot dogs and other processed meat products
Sulfites in beer, wine, and packaged vegetables

The U.S. Food and Drug Administration (FDA) has a list of food additives that are thought to be safe. Many have not been tested, but most scientists consider them to be safe. These substances are put on the "generally recognized as safe (GRAS)" list. This list contains about 700 items.

Congress defines safe as "reasonable certainty that no harm will result from use" of an additive. Examples of items on this list are: guar gum, sugar, salt, and vinegar. The list is reviewed regularly.

Some substances that are found to be harmful to people or animals may still be allowed, but only at the level of 1/100th of the amount that is considered harmful. For their own protection, people with any allergies or food intolerances should always check the ingredient list on the label. Reactions to any additive can be mild or severe.

It is still important to gather information about the safety of food additives. Tell the FDA Center for Food Safety and Applied Nutrition (CFSAN) about any reactions you have to food or food additives. Information about reporting a reaction is available at http://www.fda.gov/AboutFDA/CentersOffices/OfficeofFoods/CFSAN/ContactCFSAN/default.htm.

Recommendations

The FDA and the United States Department of Agriculture (USDA) supervise and regulate the use of additives in food products sold in the United States. However, people who have special diets or intolerances should be careful when choosing products in the grocery store.
Alternative Names

Additives in food; Artificial flavors and color

References

Food Ingredients and Colors. International Food Information Council (IFIC) and U.S. Food and Drug Administration. November 2004; revised April 2010. Page last updated May 23, 2011. Available at: www.fda.gov/downloads/Food/FoodIngredientsPackaging/ucm094249.pdf.
Update Date 5/6/2014

Updated by: Stuart I. Henochowicz, MD, FACP, Associate Clinical Professor of Medicine, Division of Allergy, Immunology, and Rheumatology, Georgetown University Medical School, Washington, DC. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.

Food Coloring and Health

Colors To Die For: The Dangerous Impact of Food Coloring

dangers-of-food-dye


Source: Special-Education-Degree.net">

The Dangerous Impact of Food Coloring

Americans are now eating 5 times more food dye than in 1955.

Many parents have observed their child’s behavior improve drastically when taken off food dyes, especially Red #40. Because of this widespread anecdotal evidence, the editors at Special Education Degree decided to do an investigative report on the negative effects of food dye’s in human beings.

The hidden dangers of food coloring dyes:

Blue #1 Brilliant Blue

Known Dangers:

Caused kidney tumors in mice
May induce an allergic reaction in individuals with pre-existing asthma

Commonly found in: baked goods, beverages, candies, cereal

Blue #2 Indigo Carmine

Known Dangers:

Causes significant occurrence of tumors, particularly brain gliomas, in male rats

Commonly found in: beverages, candies, dog food

Citrus Red #2

Known Dangers:

Toxic to rats and mice at modest levels
Bladder and other tumors found in mice
Labeled “possibly carcinogenic to humans”by the IARC

Commonly found in: skin of Florida oranges

Green #3 Fast Green

Known Dangers:

As a food dye it is prohibited in the EU and some other countries
Caused significant increases in bladder tumors in male rats

Commonly found in: beverages, candies, ice cream, cosmetics

Red #40 Allura Red

Known Dangers:

Accelerates the appearance of immune system tumors in mice
Suspected trigger of hyperactivity in children
Causes allergy-like reactions in some people

Commonly found in: beverages, candies, cereal, cosmetics

Red #3 Erythrosine

Known Dangers:

Suspected trigger of hyperactivity in children
Thyroid carcinogen in animals
Issued a partial ban by the FDA in 1990

Commonly found in: baked goods, candies, sausage, maraschino cherries

Yellow #5 Tartrazine

Known Dangers:

Can cause allergy-like reactions
May cause mild to severe hypersensitiviy reactions

Commonly found in: baked goods, candies, cereal, beverages

Yellow #6 Sunset Yellow

Known Dangers:

May cause hyperactivity in some children
Causes adrenal tumors in animals

Commonly found in: baked goods, sausage, cereal, cosmetics

“Our daughter Emma is a completely different person since we cleared her diet of food dye. No more meltdowns or shouting matches. And we just realized that her reading, writing, and math have accelerated tremendously in these few short weeks. Coincidence?”

Alternatives to Artificial Dyes Include:

Beets

Carrots

Spinach

Pumpkin

Berries

Red cabbage

Turmeric powder

Saffron powder

Paprika

Natural dyes do not have as concentrated color as artificial ones. Thus, more must be used, which may affect taste. They’re also more sensitive to heat, so colors may vary.

Now, 30%-40% of the nation’s food is colored with naturally-derived food dyes.Organic food has no added dyes or preservatives.

On food labels, artificial dyes are often identified by their alternative names.

Food Dyes and Children

In 2009, Great Britain asked its food companies to stop using artificial dyes in food.They worried about the link between artificial dyes and hyperactivity and cancer.

Today, companies like Kellogg’s and Kraft Foods no longer use artificial dyes in their UK products.

Dyes Red #40 and Yellow #5 have come under fire. However, the FDA has found no conclusive evidence to link these dyes to child behavior or ADHD.

Researchers at Southampton University found that consuming certain synthetic dyes with preservative sodium benzoate increased hyperactivity in kids ages 3-9. Those studied had never been diagnosed with ADHD.

A US study published in Science found that children score worse on tests that measure after consuming a food-dye blend than when they drank a placebo

A U.S. study published in Science found that when children who scored high on a scale measuring hyperactivity consumed a food-dye blend they performed worse on tests that measured their ability to recall images than when they drank a placebo.

Artificial sweeteners and Health. Mayo Clinic

Artificial sweeteners and other sugar substitutes

Bewildered by the variety of sugar substitutes available these days? Understand the pros and cons to make an informed choice.
By Mayo Clinic Staff

If you're trying to reduce the sugar and calories in your diet, you may be turning to artificial sweeteners or other sugar substitutes. You aren't alone.

Today artificial sweeteners and other sugar substitutes are found in a variety of food and beverages; they're marketed as "sugar-free" or "diet," including soft drinks, chewing gum, jellies, baked goods, candy, fruit juice, and ice cream and yogurt.

Just what are all these sweeteners? And what's their role in your diet?
Understanding artificial sweeteners and other sugar substitutes

Sugar substitutes are loosely considered any sweetener that you use instead of regular table sugar (sucrose). Artificial sweeteners are just one type of sugar substitute.

The topic of sugar substitutes can be confusing. One problem is that the terminology is often open to interpretation. For instance, some manufacturers call their sweeteners "natural" even though they're processed or refined, as is the case with stevia preparations. And some artificial sweeteners are derived from naturally occurring substances — sucralose comes from sugar, for example.

Regardless of how they're classified, sugar substitutes aren't magic bullets for weight loss. Take a closer look.

Artificial sweeteners

Artificial sweeteners are synthetic sugar substitutes, but may be derived from naturally occurring substances, including herbs or sugar itself. Artificial sweeteners are also known as intense sweeteners because they are many times sweeter than regular sugar.

Uses for artificial sweeteners

Artificial sweeteners are attractive alternatives to sugar because they add virtually no calories to your diet. In addition, you need only a fraction compared with the amount of sugar you would normally use for sweetness.

Artificial sweeteners are widely used in processed foods, including baked goods, soft drinks, powdered drink mixes, candy, puddings, canned foods, jams and jellies, dairy products, and scores of other foods and beverages.

Artificial sweeteners are also popular for home use. Some can even be used in baking or cooking. Certain recipes may need modification, though, because artificial sweeteners provide no bulk or volume, as does sugar. Check the labels on artificial sweeteners for appropriate home use.

Some artificial sweeteners may leave an aftertaste. Try different artificial sweeteners to find one or a combination that you enjoy.

Possible health benefits of artificial sweeteners

One benefit of artificial sweeteners is that they don't contribute to tooth decay and cavities. They may also help with the following:

Weight control. One of the most appealing aspects of artificial sweeteners is that they are non-nutritive — they have virtually no calories. In contrast, each gram of regular table sugar contains 4 calories. A teaspoon of sugar is about 4 grams. For perspective, consider that one 12-ounce can of a sweetened cola contains 10 teaspoons of added sugar, or about 150 calories. If you're trying to lose weight or prevent weight gain, products sweetened with artificial sweeteners, rather than with higher calorie table sugar, may be an attractive option. On the other hand, some research has suggested that consuming artificial sweeteners may be associated with increased weight, but the cause is not yet known.
Diabetes. Artificial sweeteners may be a good alternative to sugar if you have diabetes. Unlike sugar, artificial sweeteners generally don't raise blood sugar levels because they are not carbohydrates. But because of concerns about how sugar substitutes are labeled and categorized, always check with your doctor or dietitian about using any sugar substitutes if you have diabetes.

Possible health concerns with artificial sweeteners

Artificial sweeteners have been scrutinized intensely for decades. Critics of artificial sweeteners say that they cause a variety of health problems, including cancer. That's largely because of studies dating to the 1970s that linked saccharin to bladder cancer in laboratory rats. Because of those studies, saccharin once carried a warning label that it may be hazardous to your health.

But according to the National Cancer Institute and other health agencies, there's no sound scientific evidence that any of the artificial sweeteners approved for use in the U.S. cause cancer or other serious health problems. And numerous research studies confirm that artificial sweeteners are generally safe in limited quantities, even for pregnant women. As a result of the newer studies, the warning label for saccharin was dropped.

Artificial sweeteners are regulated by the Food and Drug Administration (FDA) as food additives. They must be reviewed and approved by the FDA before being made available for sale.

In some cases, the FDA declares a substance "generally recognized as safe" (GRAS). These GRAS substances, including highly refined stevia preparations, are deemed by qualified professionals based on scientific data as being safe for their intended use, or they have such a lengthy history of common use in food that they're considered generally safe and don't require FDA approval before sale.

The FDA has also established an acceptable daily intake (ADI) for each artificial sweetener. This is the maximum amount considered safe to consume each day over the course of your lifetime. ADIs are intended to be about 100 times less than the smallest amount that might cause health concerns.
Sugar alcohols and novel sweeteners

Sugar alcohols (polyols) are carbohydrates that occur naturally in certain fruits and vegetables, but they also can be manufactured. They're not considered intense sweeteners, because they aren't sweeter than sugar. In fact, some are less sweet than sugar. As with artificial sweeteners, the FDA regulates the use of sugar alcohols.

Sugar alcohols aren't considered noncaloric or non-nutritive sweeteners because they contain calories. But they're lower in calories than is regular sugar, making them an attractive alternative. Despite their name, sugar alcohols aren't alcoholic. They don't contain ethanol, which is found in alcoholic beverages.

Novel sweeteners are combinations of various types of sweeteners. Novel sweeteners, such as stevia, are hard to fit into one particular category because of what they're made from and how they're made. Note that although the FDA has approved highly refined stevia preparations as a novel sweetener, it has not approved whole-leaf stevia or crude stevia extracts for this use.

Tagatose and trehalose are considered novel sweeteners because of their chemical structure. The FDA categorizes them as GRAS substances. Tagatose is a low-carbohydrate sweetener similar to fructose that occurs naturally, but is also manufactured from lactose in dairy products. Trehalose is found naturally in honey and mushrooms.
Uses for sugar alcohols

Sugar alcohols generally aren't used when you prepare food at home. Rather, they are found in many processed foods and other products, including chocolate, candy, frozen desserts, chewing gum, toothpaste, mouthwash, baked goods and fruit spreads, usually replacing sugar on an equal basis.

When added to foods, sugar alcohols add sweetness, bulk and texture. They also help food stay moist, prevent browning when heated and add a cooling sensation to products.

Sugar alcohols are often combined with artificial sweeteners to enhance sweetness. Check the food label to help see if a product contains sugar alcohols. Food labels may list the specific name, such as xylitol, or simply use the general term "sugar alcohol."

Possible health benefits of sugar alcohols

One benefit of sugar alcohols is that they don't contribute to tooth decay and cavities. They may also help with the following:

Weight control. Sugar alcohols are considered nutritive sweeteners because they contribute calories to your diet. Still, sugar alcohols have fewer calories than does regular sugar — about 2 calories per gram on average. This means that sugar alcohols can be considered lower calorie sweeteners, and they may aid weight-control efforts.
Diabetes. Unlike artificial sweeteners, sugar alcohols can raise blood sugar levels because they're carbohydrates. But because your body doesn't completely absorb sugar alcohols, their effect on blood sugar is less than that of other sugars. Different sugar alcohols can affect blood sugar differently. You can consume sugar alcohols if you have diabetes, but you still must pay attention to the total amount of carbohydrates in your meals and snacks. Talk to your doctor or dietitian for guidance.

Possible health concerns with sugar alcohols

As with artificial sweeteners, the FDA regulates sugar alcohols as food additives. Sugar alcohols used in U.S. manufactured food generally have GRAS status.

There are few health concerns associated with sugar alcohols. When eaten in large amounts, usually more than 50 grams, but sometimes as little as 10 grams, sugar alcohols can have a laxative effect, causing bloating, intestinal gas and diarrhea. Product labels may carry a warning about this potential laxative effect.

Natural sweeteners

Natural sweeteners are sugar substitutes that are often promoted as healthier options than processed table sugar or other sugar substitutes. But even these so-called natural sweeteners often undergo processing and refining, including agave nectar.

Among the natural sweeteners that the FDA recognizes as being generally safe for consumption are fruit juices and nectars, honey, molasses, and maple syrup.

Uses for natural sweeteners

Natural sweeteners have a variety of uses both at home and in processed foods. They are sometimes known as added sugars because they're added to foods during processing. They may be used, for example, in tea and cocktails to sweeten drinks, in desserts, as pancake and waffle toppings, on cereals, and for baking.
Possible health benefits of natural sweeteners

Although natural sugar substitutes may seem healthier than processed table sugar, their vitamin and mineral content isn't significantly different from that of sugar. Honey and sugar, for instance, are nutritionally similar, and both end up in your body as glucose and fructose. Choose a natural sweetener based on how it tastes and its uses, rather than on its health claims, and use it sparingly.

Possible health concerns with natural sweeteners

So-called natural sweeteners are generally safe. But there's no health advantage to consuming any type of added sugar. And consuming too much added sugar, even natural sweeteners, can lead to health problems, such as tooth decay, poor nutrition, weight gain and increased triglycerides. Also, be aware that honey can contain small amounts of bacterial spores that can produce botulism toxin. Because of that, honey shouldn't be given to children younger than than 1 year old.

Moderation is key with sugar substitutes

When choosing sugar substitutes, it pays to be a savvy consumer. Get informed and look beyond the hype. While artificial sweeteners and sugar substitutes may help with weight management, they aren't a magic bullet and should be used only in moderation. If you use sugar substitutes to save calories, be careful not to eat higher calorie foods as a reward for the calories you saved.

Just because a food is marketed as sugar-free doesn't mean it's free of calories. If you eat too many sugar-free foods, you can still gain weight if they have other ingredients that contain calories. And remember that processed foods, which often contain sugar substitutes, generally don't offer the same health benefits as do whole foods, such as fruits and vegetables.