Inform–Discover–Translate: Knowledge about the needs of the elderly from geriatrics is used to inform basic research on the biology of aging and translated through clinical research into interventions to improve the aging human condition.
As it becomes increasingly evident that many diseases are profoundly influenced by age, more and more medical scientists around the world recognize the importance of understanding the biology of aging.
The Brown Biology of Aging Initiative brings together a group of faculty in an organized effort to study the basic biological processes that are associated with aging. In addition to our own research programs we have mounted educational and outreach activities, the cornerstone of which is the Molecular Biology of Aging (MBoA) graduate curriculum track leading to a Ph.D. degree.
The Initiative also runs a monthly Providence Area Aging Research Forum, an extramural Aging Seminar Series, and the annual Colloquium on the Biology of Human Aging.
Biology of Aging
Aging is accompanied by gradual changes in most body systems. Research on the biology of aging focuses on understanding the cellular and molecular processes underlying these changes as well as those accompanying the onset of age-related diseases. As scientists learn more about these processes, experiments can be designed to understand when and how pathological changes begin, providing important clues toward developing interventions to prevent or treat disease. A great deal has been learned about structural and functional changes that occur in different body systems. Research has expanded our knowledge, too, of the biologic factors associated with extended longevity in humans and animal models.
Extending the Lifespan
Identification of the factors that affect the overall lifespan of an organism will help us better understand the aging process, and will also help us develop interventions to keep older people healthy and free of disease and/or disability as long as possible. Over the last ten years, the NIA Longevity Assurance Gene (LAG) Initiative has been pivotal in the identification of multiple genes, pathways, and biological processes involved in the regulation of longevity and aging in multiple organisms (yeast, nematode, fruit fly, mouse, human). Through the use of both invertebrate and mammalian models, the LAG Initiative has identified common factors and mechanisms that mediate longevity and extend health span.
Scientific advances in model systems provide the critical scientific foundation to extend NIA-supported studies to humans. In addition, they provide the knowledge base necessary to guide the rational development and testing of intervention strategies to delay aging, promote longevity, and extend human health span in the near future. For example, researchers recently used RNA interference (RNAi), a technique to inactivate individual genes one at a time, to identify genes involved in longevity regulation in the worm C. elegans. They found that inactivation of many genes involved in mitochondrial function extended longevity; in fact, 15 per cent of the genes influencing longevity were specific for mitochondrial function. These results reinforce the idea that energy metabolism is important in determining animal longevity.
Increased evidence of familial and genetic factors in exceptionally long and healthy life. Three recent studies of exceptionally long-lived individuals and their children suggest that a tendency for exceptionally long and healthy life to run in families may be related to exceptionally favorable risk factor profiles for cardiovascular and other diseases over the life span. In the first study, middle-aged sons of long-lived parents had lower systolic pressures, better cholesterol levels, and decreased frequencies of the APOE-e4 allele (a gene variant commonly associated with cardiovascular disease and Alzheimer’s disease) compared to middle-aged sons of shorter-lived parents. The second group found that compared to controls, children of centenarians had markedly reduced prevalence of some age-related diseases, including heart disease, hypertension, and diabetes. In the third study, researchers found that Ashkenazi Jewish centenarians and their offspring were more likely than a control group to have a variant form of a gene for a cholesterol regulating protein. This form of the gene is associated with larger-than-average cholesterol-carrying particles in the blood, and with higher levels of HDL (“good”) cholesterol, both of which were found in the centenarians’ offspring. These findings suggest that larger lipoprotein particle sizes may be one of the familial factors that promote long and healthy survival.
Together these findings add to growing evidence that the good health profiles that occur in centenarians and their children differ markedly from age-matched counterparts in the general population, and that there are familial and possibly genetic components that most likely influence protective factors against age-related disease and promote exceptionally healthy human survival. Identification of these factors earlier in life could lead to new interventions to prevent age-related diseases and disabilities, and extend healthy lifespan.
Selected Future Research Directions in the Biology of Aging
The identification of “longevity genes” is complex and necessarily interdisciplinary, involving ongoing interactions between basic and epidemiologic researchers to accelerate discovery of and confirm translational findings. To facilitate identification and understanding of longevity genes, the NIA has formed a Longevity Consortium, a self-sufficient system for rapid generation, review, and funding of new projects. Components of the Consortium include:
Multiple basic laboratories addressing relevant disciplines including cell and molecular biology, physiology, and biochemistry
A collaborative group of major epidemiologic studies with data on multiple outcomes in established study populations
Diverse populations and large sample sizes to allow analyses of subgroups and covariates
Registry and/or database capacity to allow rapid identification of possible cases and controls, and genotype and phenotype information
Genotyping, genomics, computational, and cell line repository facilities to allow standardization and economies of scale
System for rapid information exchange among basic and epidemiologic researchers to convey new findings and conduct follow-up studies
Members of the Consortium include epidemiologists, geneticists, population biologists, statisticians, and others with an interest in the genetic and molecular basis for longevity, and the Consortium draws on the study populations of 15 of the largest human aging studies, including the Cardiovascular Health Study, the Women’s Health Initiative, Health ABC, the Study of Osteoporotic Fractures, the Rotterdam Study, the Honolulu Heart Study, and the New England Centenarian Study. Altogether, Consortium researchers will have access to data on some 200,000 study subjects.
National Institute on Aging
Understanding how we age
Since the 1980s, when the first “longevity” gene was mapped by scientist Tom Johnson, there’s been more progress made in understanding how we age and how we can slow it down.
Moreover, the similarity between aging and age-related diseases is increasingly becoming the focus for many of these longevity research initiatives — many researchers studying age-related diseases like Alzheimer’s are now collaborating with researchers looking at aging more broadly.
THE BIOLOGY OF AGING
Biogerontology is the scientific discipline dedicated to the biology of aging.
Recent studies have identified key traits — referred to as hallmarks of aging — that attempt to define what aging is.
Genomic instability: Throughout one’s life, both internal and external factors that cause genetic damage start to build up in the body. This is known to accelerate aging.
Telomere attrition: Telomeres – the protective “caps” located at the ends of our chromosomes (which house our genetic material) – start getting shorter each time a cell divides. Over time, this results in cells not being able to divide anymore, which can lead to disease.
Epigenetic alterations: There are changes in gene expression (not changes to the DNA itself) via an individual’s life experiences or environmental factors which affect aging.
Loss of proteostasis: With age, cellular proteins become misfolded and therefore, lose their homeostatic functions. A build up of these damaged proteins is observed with aging or age-related diseases.
Deregulated nutrient-sensing: There are metabolism-regulating pathways, whose proteins (e.g. mTOR, sirtuins) are influenced by nutrient levels and also implicated in promoting aging.
Mitochondrial dysfunction: When the mitochondria (considered the energy powerhouse responsible for regulating metabolism in our bodies) starts to malfunction with age.
Cellular senescence: “Older” cells can’t be cleared out as fast and their build up can lead to harmful health effects.
Stem cell exhaustion: Activities of the 4 types of stem cells, which all help in regenerating new tissue cells, decline with aging.
Altered intercellular communication: Communication between cells is disrupted with age, resulting in inflammation and tissue damage.
Companies focused on aging or age-related diseases are tackling one or more of these biological traits to find promising therapeutic candidates. In the next sections, we’ll explore how each of these are being targeted.
THE RELATIONSHIP BETWEEN AGING & AGE-RELATED DISEASES
Longevity research on its own has seen a lot of progress, especially as we learn more about the biological processes that underlie aging.
But it’s also become more intertwined with research studies focused on major diseases due to similar traits at the cellular and molecular level.
For example, there’s a higher probability of lethal gene mutations as one ages that can result in diseases such as cancer or Alzheimer’s. This is a big reason why many drug companies are targeting aging in an attempt to stave off other degenerative diseases.
Major Health Risks Associated with Aging
Understanding the Dynamics of the Aging Process
Aging is associated with changes in dynamic biological, physiological, environmental, psychological, behavioral, and social processes. Some age-related changes are benign, such as graying hair. Others result in declines in function of the senses and activities of daily life and increased susceptibility to and frequency of disease, frailty, or disability. In fact, advancing age is the major risk factor for a number of chronic diseases in humans.
Studies from the basic biology of aging using laboratory animals—and now extended to human populations—have led to the emergence of theories to explain aging. While there is no single 'key' to explain aging, these studies have demonstrated that while the passage of time is not altered, the rate of aging can be slowed. These studies suggest that targeting aging will coincidentally slow the appearance and/or lessen the burden of numerous diseases and increase health span (the portion of life spent in good health).
NIA-supported researchers are engaged in basic science at all levels of analysis, from molecular to social, to understand the processes of aging and the factors that determine who ages well and who ages poorly. Research is also ongoing to identify the interactions among genetic, environmental, lifestyle, behavioral, and social factors and their influence on the initiation and progression of age-related diseases and degenerative conditions.
To develop new interventions for the prevention, early detection, diagnosis, and treatment of aging related diseases, disorders, and disabilities, we must first understand their causes and the factors that place people at increased risk for their initiation and progression. NIA has established two goals in the basic science of aging:
Many things cause our skin to age. Some things we cannot do anything about; others we can influence.
One thing that we cannot change is the natural aging process. It plays a key role. With time, we all get visible lines on our face. It is natural for our face to lose some of its youthful fullness. We notice our skin becoming thinner and drier. Our genes largely control when these changes occur. The medical term for this type of aging is “intrinsic aging.”
We can influence another type of aging that affects our skin. Our environment and lifestyle choices can cause our skin to age prematurely. The medical term for this type of aging is “extrinsic aging.” By taking some preventive actions, we can slow the effects that this type of aging has on our skin.
11 ways to reduce premature skin aging
The sun plays a major role in prematurely aging our skin. Other things that we do also can age our skin more quickly than it naturally would. To help their patients prevent premature skin aging, dermatologists offer their patients the following tips.
Protect your skin from the sun every day. Whether spending a day at the beach or running errands, sun protection is essential. You can protect your skin by seeking shade, covering up with clothing, and using sunscreen that is broad-spectrum, SPF 30 (or higher), and water-resistant. You should apply sunscreen every day to all skin that is not covered by clothing.
Apply self-tanner rather than get a tan. Every time you get a tan, you prematurely age your skin. This holds true if you get a tan from the sun, a tanning bed, or other indoor tanning equipment. All emit harmful UV rays that accelerate how quickly your skin ages.
If you smoke, stop. Smoking greatly speeds up how quickly skin ages. It causes wrinkles and a dull, sallow complexion.
Avoid repetitive facial expressions. When you make a facial expression, you contract the underlying muscles. If you repeatedly contract the same muscles for many years, these lines become permanent. Wearing sunglasses can help reduce lines caused by squinting.
Eat a healthy, well-balanced diet. Findings from a few studies suggest that eating plenty of fresh fruits and vegetables may help prevent damage that leads to premature skin aging. Findings from research studies also suggest that a diet containing lots of sugar or other refined carbohydrates can accelerate aging.
Drink less alcohol. Alcohol is rough on the skin. It dehydrates the skin, and in time, damages the skin. This can make us look older.
Exercise most days of the week. Findings from a few studies suggest that moderate exercise can improve circulation and boost the immune system. This, in turn, may give the skin a more-youthful appearance.
Cleanse your skin gently. Scrubbing your skin clean can irritate your skin. Irritating your skin accelerates skin aging. Gentle washing helps to remove pollution, makeup, and other substances without irritating your skin.
Wash your face twice a day and after sweating heavily. Perspiration, especially when wearing a hat or helmet, irritates the skin, so you want to wash your skin as soon as possible after sweating.
Apply a facial moisturizer every day. Moisturizer traps water in our skin, giving it a more youthful appearance.
Stop using skin care products that sting or burn. When your skin burns or stings, it means your skin is irritated. Irritating your skin can make it look older.
Note: Some anti-aging products prescribed by a dermatologist may burn or sting. When using a prescription anti-aging product, this can be okay. Just be sure to let your dermatologist know.
Never too late to benefit
Even people who already have signs of premature skin aging can benefit from making lifestyle changes. By protecting your skin from the sun, you give it a chance to repair some of the damage. Smokers who stop often notice that their skin looks healthier.
If signs of aging skin bother you, you may want to see a dermatologist. New treatments and less-invasive procedures for smoothing wrinkles, tightening skin, and improving one’s complexion are giving many people younger-looking skin.
The National Institute on Aging (NIA), part of the National Institutes of Health at the U.S. Department of Health and Human Services, was established to help improve the health and well-being of older people through research. NIA conducts and supports research on the medical, social, and behavioral aspects of aging. This mission is carried out through NIA’s Intramural Research Program composed of staff scientists in Baltimore and Bethesda, Maryland, and through its Extramural Research Program, which funds researchers at major institutions across the United States and internationally. Biology of Aging: Research Today for a Healthier Tomorrow describes some of NIA’s exciting findings about the basic biology of aging and points to directions for future investigation.
AGING UNDER THE MICROSCOPE
We marvel at the 90-year-old who still gets up every day and goes to work. And, it is a genuine thrill to celebrate a relative’s 100th birthday. Yet our feelings about aging are complex.
We may want to live forever, but who looks forward to getting old? We hope we’re vigorous right up until the very end. Still, day-to-day, many of us make unhealthy choices that could put our future at risk.
From the beginning of time, people have tried to understand aging. Almost every culture has a mythology to explain it. As we grow up, tales of eternal youth pique our curiosity. And, it is these musings that may provide just the spark needed to ignite a budding scientist. There’s the little girl, excited to visit her grandmother, who asks her parents how someone so spunky and fun could be so old. Or, the 3rd grader who, after watching in awe as a caterpillar spins a cocoon and then days later emerges as a butterfly, peppers the teacher with questions about this magical transformation. These are the types of questions and kinds of experiences that could stimulate a lifelong quest to explore what happens as we age.
Since the National Institute on Aging (NIA) was established at the National Institutes of Health (NIH) in 1974, scientists asking just such questions have learned a great deal about the processes associated with the biology of aging. For scientists who study aging—called gerontologists—this is an exciting time. Technology today supports research that years ago would have seemed possible only in a science fiction novel. And, a scientific community that values active collaboration as well as individual scientific achievement has helped to move research forward faster than ever before.
Over centuries, theories about aging have emerged and faded, but the true nature of the aging process is still uncertain. The fact is—aging is a part of everyone’s life. But the facts of aging—what is happening on a biochemical, genetic, and physiological level—remain rich for exploration.
This booklet introduces some key areas of research into the biology of aging. Each area is a part of a larger field of scientific inquiry. You can look at each topic individually, or you can step back to see how they fit together in a lattice-work, interwoven to help us better understand aging processes. Research on aging is dynamic, constantly evolving based on new discoveries, and so this booklet also keeps an open eye on the future, as today’s research provides the strongest hints of things to come.
What is aging?
In the broadest sense, aging reflects all the changes that occur over the course of life. You grow. You develop. You reach maturity. To the young, aging is exciting—it leads to later bedtimes and curfews, and more independence. By middle age, another candle seems to fill up the top of the birthday cake. It’s hard not to notice some harmless cosmetic changes like gray hair and wrinkles. Middle age also is the time when people begin to notice a fair amount of physical decline. Even the most athletically fit cannot escape these changes. Take marathon runners, for example. An NIA-funded study found that their record times increased with age—aging literally slowed down the runners. Although some physical decline may be a normal result of aging, the reasons for these changes are of particular interest to gerontologists.
Gerontologists look for what distinguishes normal aging from disease, as well as explore why older adults are increasingly vulnerable to disease and disability. They also try to understand why these health threats take a higher toll on older bodies. Since 1958, NIA’s Baltimore Longitudinal Study of Aging (BLSA) has been observing and reporting on these kinds of questions. As with any longitudinal study, the BLSA repeatedly evaluates people over time rather than comparing a group of young people to a group of old people, as in a cross-sectional study. Using this approach, BLSA scientists have observed, for example, that people who have no evidence of ear problems or noise-induced hearing loss still lose some of their hearing with age—that’s normal. Using brain scans to learn if cognitive changes can be related to structural changes in the brain, BLSA scientists discovered that even people who remain healthy and maintain good brain function late in life lose a significant amount of brain volume during normal aging.
However, some changes that we have long thought of as normal aging can be, in fact, the signs of a potential disease. Take, for example, sudden changes in personality. A common belief is that people become cranky, depressed, and withdrawn as they get older. But an analysis of long-term data from the BLSA showed that an adult’s personality generally does not change much after age 30. People who are cheerful and assertive when they are younger will likely be the same when they are age 80. The BLSA finding suggests that significant changes in personality are not due to normal aging, but instead may be early signs of disease or dementia.
The rate and progression of cellular aging can vary greatly from person to person. But generally, over time, aging affects the cells of every major organ of the body. Changes can start early. Some impact our health and function more seriously than others. For instance, around the age of 20, lung tissue starts to lose elasticity, and the muscles of the rib cage slowly begin to shrink. As a result, the maximum amount of air you can inhale decreases. In the gut, production of digestive enzymes diminishes, affecting your ability to absorb foods properly and maintain a nutritional balance. Blood vessels in your heart accumulate fatty deposits and lose flexibility to varying degrees, resulting in what used to be called “hardening of the arteries” or atherosclerosis. Over time, women’s vaginal fluid production decreases, and sexual tissues atrophy. In men, aging decreases sperm production, and the prostate can become enlarged.
Scientists are increasingly successful at detailing these age-related differences because of studies like the BLSA. Yet studies that observe aging do not identify the reasons for age-related changes, and, therefore, can only go so far toward explaining aging. Questions remain at the most basic level about what triggers aging in our tissues and cells, why it occurs, and what are the biological processes underlying these changes. Scientists look deep into our cells and the cells of laboratory animals to find answers. What they learn today about aging at the cellular and molecular levels may, ultimately, lead to new and better ways to live a longer, healthier life.
Possible Pathways Leading to Aging Illustration and information adapted from www.genome.com
To answer questions about why and how we age, some scientists look for mechanisms or pathways in the body that lead to aging. Our cells constantly receive cues from both inside and outside the body, prompted by such things as injury, infection, stress, or even food. To react and adjust to these cues, cells send and receive signals through biological pathways. Some of the most common are involved in metabolism, the regulation of genes, and the transmission of signals. These pathways may also be important to aging.
Living long and well: Can we do both? Are they the same?
You can hardly turn on your computer these days without being bombarded with advertisements that pop up trying to convince you of the power of a pill that will make you live longer or a cream that will help to revive your youthful vigor and appearance. The search for ways to stop or reverse the aging process is a near-obsession in popular culture. The likelihood of discovering a scientifically proven “anti-aging” elixir is slim, but researchers believe their work will reveal ways to improve a person’s ability to live a longer, healthier life. They express these goals in terms of “lifespan” and “health span,” respectively.
Lifespan is the length of life for an organism. For instance, if you live to age 99, that would be your lifespan. Maximal lifespan is the maximum number of years of life observed in a specific population. It differs from species to species. The maximum recorded lifespan for humans, reported in 2010, was 122.5 years for females and 116 years for males.
Lifespan is a common measurement in aging research. That’s because it is clear-cut and easy to measure—an organism is either alive or dead. Scientists look for factors such as genes, environment, and behavioral traits (including diet) that may contribute to an organism’s lifespan. Altering a factor to see if it changes lifespan can provide evidence about whether or not that specific factor is important for aging. For instance, when researchers suspect that a specific gene has an effect on lifespan, they may test their hypothesis by modifying the activity of that gene (perhaps lower its activity by deleting the gene or increase its activity by adding an extra copy of it). If the life of the animal with the modified gene activity is longer or shorter, then the gene probably does play a role in lifespan.
Researchers are finding that lifespan may be influenced by external factors, as well. This has been demonstrated in animal studies. NIA’s Interventions Testing Program (ITP) examines a variety of compounds for their effects on the lifespan of mice. Compounds studied include dietary supplements, hormones, and anti-inflammatory drugs. In one ITP study, male mice treated with aspirin, an anti-inflammatory drug, displayed a moderately increased lifespan. In another ITP study, masoprocol, an anti-inflammatory drug that has antioxidant properties, was found to increase longevity of male, but not female, mice. These and other findings may help scientists identify compounds to test in humans for their effects on aging. While some of the compounds tested in the ITP already have a clinical use for humans, scientists are clear: These compounds should be used only as prescribed and not for lifespan extension at this time.
The ability to withstand disease could also be central to lifespan. Studies of exceptionally long-lived people are helping to establish patterns of health decline and increased disease (called morbidity) with old age. For example, do health problems start around the same age in all people and expand over extra years of life for the long-lived, or are the problems delayed, occurring closer to the end of life among exceptional agers? Evidence from a Danish longitudinal study of 92- to 100-year-olds found that health problems seem to be delayed, appearing closer to the end of life. This is not a certain outcome, but in many studies, the average centenarian seems to be in better health than the average 80-year-old. However, living to 100 does not mean never having any health issues. In the New England Centenarian Study, researchers have developed three categories for their long-lived participants. They are characterized as “survivors,” “delayers,” or “escapers,” depending on whether they have survived a life-threatening disease, delayed a serious health problem until much later in life, and/or escaped any serious health events.
Scientists used to think that long life was a good indicator of health span, or years of good health and function. However, some experiments, particularly in mice, demonstrate significant improvements in health, without actually increasing lifespan. For example, NIA scientists and grantees (that is, scientists at a university or other institution whose research is funded by NIA) examining the effects of the wine-derived compound resveratrol in mice on a normal diet found the compound positively influenced the health of the mice—resveratrol-treated mice had better bone health, heart function, strength, vision, coordination, and cholesterol than the control group. But, resveratrol did not increase lifespan. (Lifespan was increased, however, in mice on a high-fat diet supplemented with resveratrol.)
Understanding how to extend health span—apart from its impact on longevity—is a growing focus of many studies, and for good reason. Imagine a society where a majority of people live to be 100, but along with the added years comes considerably more physical decline. While there is still a place for lifespan research, health span research holds promise for revealing ways to delay or prevent disease and disability so that we can live healthier longer.
Uncovering Family Secrets to a Long Life
Most of what we know about factors that can contribute to a long lifespan and health span is based on research in animal models. However, NIA-funded research like the Long Life Family Study is taking what we’ve learned in animals and seeing if it applies to human aging. This study is collecting data from families with at least two siblings who have lived to a very old age in relatively good health. Along with asking questions about their family and health history, the researchers conduct physical assessments and health screenings and collect a small blood sample for genetic tests. What researchers learn about common characteristics shared by these families could one day be used to guide lifestyle advice and medical treatments.
Is what's good for mice good for men?
A lot of research findings seem to tell us what is good—or bad—for yeast, mice, roundworms (C. elegans), or fruit flies (Drosophila melanogaster). Does that mean it will work for you? Animal models are essential to research in the biology of aging. Fruit flies and roundworms, along with more complex organisms like mice, rats, and nonhuman primates, have many biological mechanisms and genes that are similar to humans. They also experience many of the same physiological changes (changes in the body) with aging. Therefore, these animals can be used as models of human aging and human physiology, despite the obvious differences in appearance. Scientists can use some exploratory approaches (like modifying a gene to measure its effects on health or longevity) in animal models such as worms, flies, and mice that would not be possible in humans. They also can better isolate the variable they want to investigate because animal studies are conducted in tightly controlled environments. The animals typically have a very structured daily regimen with limited exposure to pollutants, stressors, or other elements that could otherwise affect lifespan and health span.
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Different types of studies use different animal models. Animal models with a short lifespan take less time and fewer resources to study from birth to death and to test interventions that might affect the aging process. Scientists might favor a fruit fly when studying a possible genetic target for an intervention to increase longevity, for example, because their average lifespan is only 30 days. This allows researchers to measure the effects in about a month. The roundworm’s 2- to 3-week lifespan makes it another ideal model for identifying and studying genes that might affect longevity. In a landmark study, NIA-funded researchers found that reducing the activity of a set of genes, called daf, increased roundworm lifespan by three- or even fourfold. Daf genes are involved in the roundworm’s ability to enter a type of hibernation stage, called diapause, to survive periods of food scarcity. This research would not have been as feasible if conducted using an animal model with an average lifespan of 10 or 20 years.
After scientists establish a possible intervention in one animal model, they then apply the intervention to increasingly complex organisms. They might work their way up from worms or flies to mice and then to larger mammals, such as nonhuman primates. At each step, researchers carefully study if the intervention has the same effect on the comparable biological pathway. Sometimes it does not. Part of the reason might be that while mice, for example, have only a slightly larger number of genes than worms, and the genes in mice and worms serve similar functions, the activity of mouse genes is different and somewhat more complex than that of worms. As a result, a genetic intervention that increases a worm’s lifespan by fourfold might have a significantly less impressive effect on a mouse’s lifespan. For similar reasons, an intervention might be promising in mice, but that does not mean it will work the same way or at all in humans.
Studies in animal models closer to humans, such as monkeys or other nonhuman primates, can be key to understanding how basic discoveries might apply to humans. They are essential for pre-clinical studies, an intermediary step between research in animal models like mice and clinical studies in humans. Studies in nonhuman primates, for example, have demonstrated to NIA researchers how normal age-related changes in the heart influence risk of heart disease. They have also been important for testing interventions to lower risks of heart disease, such as drugs to decrease blood vessel stiffness.
So, if something works to slow aging in mice, worms, fruit flies, or monkeys, does that mean it will definitely work for you? The answer is no. Certainly, data from animal studies provide critical insights to the aging process and can form the basis for testing potential interventions. But direct testing in humans is essential before an intervention can be considered safe and effective.
Geroscience: The intersection of basic aging biology, chronic disease, and health
As we grow older, we are more likely to be diagnosed with one or more chronic ailments. These ailments include life-threatening diseases such as cardiovascular disease, diabetes, and cancer, as well as debilitating conditions like arthritis, fatigue, and frailty. These ailments rob us of our quality of life. The question is: How does the aging process affect the disease process and susceptibility—and vice versa?
Over the years, researchers studying the basic science of aging have sought to answer this question, but their work was confined primarily to investigations of the specific activities and mechanisms that contribute to the aging process, and not as much on the effects of the aging process on various diseases. While aging itself isn't a disease, the aging process represents a major risk factor for several chronic diseases and conditions, including frailty and lack of resilience.
Geroscience takes a different approach, seeking to understand the genetic, molecular, and cellular mechanisms that make aging a major risk factor and driver of common chronic conditions and diseases of older people.
An NIH-wide initiative
One of the first steps in advancing geroscience was to demonstrate that this approach is likely to affect research in many fields. Traditionally, biomedical research has focused primarily on specific diseases such as cancer, diabetes, heart disease, and, more recently, Alzheimer's and related dementias. But aging affects the onset and progression of all of these diseases and is a common risk factor for them. By studying what happens during aging at the genetic, molecular, and cellular levels, investigators hope to discover the similarities and differences among these conditions as they relate to aging.
Drs. Felipe Sierra and Ronald Kohanski, director and deputy director, respectively, of NIA's Division of Aging Biology, were a moving force behind the establishment of the Trans-NIH Geroscience Interest Group (GSIG) in 2012. The goal of the group is to stimulate interest and involvement in the basic science of aging across Institutes, Centers, and Offices at NIH. The group, which now includes 21 of NIH's 27 Institutes and Centers, hosts three seminars on the NIH campus each year and convenes workshops and summits on topics of interest to the geroscience community on a regular basis.
A meeting of the minds on geroscience
In 2013, nearly 500 scientists, advocates, and others interested in health and aging gathered on the NIH campus for a first Summit meeting, Advances in Geroscience: Impact on Healthspan and Chronic Disease. Hosted by the GSIG, the Summit was supported by the Alliance for Aging Research, Gerontological Society of America, and private foundations and companies through gifts to the Foundation for the National Institutes of Health.
The Summit's primary goal was to look at new ways to understand how common mechanisms governing aging might underlie the occurrence and pathology of diverse chronic diseases. A second goal was to promote new pathways for collaboration among researchers of these varied diseases, specifically in the context of aging. The meeting offered participants an opportunity to explore the interplay between chronic disease and aging in the hope of eventually identifying new avenues for prevention and treatment.
About 50 renowned investigators from various disciplines addressed topics in aging and chronic disease that have come to be known as the Pillars of Geroscience: inflammation, immunity, adaptation to stress, epigenetics, metabolism, macromolecular damage, proteostasis, and senescence.
Geroscience accelerates research into the basic biological mechanisms driving aging, which could lead to improved clinical interventions for the diseases and conditions experienced by many older people.
Recommendations from the session focused on expanding the field of geroscience and laying the groundwork for new research initiatives on the relationship among aging, chronic disease, and degenerative conditions (Kennedy et al., 2014). For example, six NIH Institutes (NIA, NIAID, NIDCR, NINDS, NIEHS, and NCI) combined efforts to support research that evaluates age as a variable when studying animal models of specific diseases (RFA AG-16-020). In addition, a group of researchers used the R24 NIH grant mechanism to form a Geroscience Consortium, with the goal of discussing approaches to bring geroscience to fruition. An overview of the Summit sessions was published in June 2014 in a supplemental issue of The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences.
Geroscience advances
With growing interest in geroscience, by 2015 researchers from several disciplines were eager to discuss the progress to date and identify new directions for investigations. The GSIG planned a second Summit, with important collaboration and support from the New York Academy of Sciences, the American Federation for Aging Research, and the Gerontological Society of America.
The Disease Drivers of Aging: 2016 Advances in Geroscience Summit, held at the New York Academy of Sciences in April 2016, focused on three chronic diseases—cancer, HIV/AIDS, and diabetes—and how their negative effects (and sometimes their treatments) might accelerate the onset of age-related physical decline and disease. Molecular explorations, along with well-established epidemiological data, were key to focusing on the connection between these diseases and the major pillars of aging. Basic, translational, and clinical researchers identified knowledge gaps and future directions of research needed to better understand the molecular pathways that might accelerate the aging process in people exposed to early forms of chronic diseases. Their efforts resulted in a series of papers published as a special issue of the Journal of Gerontology: Series A in November 2016.
Planning for a third geroscience summit in spring 2019 is underway.
Future research directions
People are living longer today because of progress in medical care. But many people suffer from debilitating conditions because research has focused on curing life-threatening diseases such as cancer and cardiovascular disease. For the growing population of older adults, geroscience may provide novel preventive or diagnostic measures that can reduce the burden of age-related disease and disability.
Resilience at the molecular, cellular, and systems levels is one key to these types of studies. Some diseases can speed the loss of function and resilience associated with aging, leading to increased susceptibility to further disease and disability. By exploring accurate and predictive measurements of resilience, researchers hope to discover how these measures can be adapted to benefit people. With that in mind, NIA has recently published twin Funding Opportunity Announcements to accelerate research in this field, both in mice (RFA AG-17-040) and in people (RFA AG 17-014), as research in this area is ongoing.
Investigators also seek to determine how particular chronic diseases affect not only the primary organ involved in a disease, but also, how additional organs and systems may be impaired. In Alzheimer's disease, for example, studies focus on what happens in the brain—the primary affected organ—while researchers also look at the bones, vascular system, and overall metabolism. Such studies provide a more holistic view of individual diseases and conditions, which could lead to interventions on a number of levels. For any chronic disease or lost function that increases with age, geroscience proposes that slowing the rate of aging will improve health.
The ultimate goal of geroscience is to accelerate research into the basic mechanisms driving aging, which could lead to improved clinical interventions. Toward that goal, the GSIG remains focused on discovering the basic biology at the intersection among aging, chronic disease, frailty, and resilience. Basic biology renders the process of aging the major risk factor for the age-related decline in health, threatening an increasingly older population.
Reference
Kennedy BK, et al. Geroscience: linking aging to chronic disease. Cell 2014;159(4): 709-713.
Is longevity determined by genetics?
The duration of human life (longevity) is influenced by genetics, the environment, and lifestyle. Environmental improvements beginning in the 1900s extended the average life span dramatically with significant improvements in the availability of food and clean water, better housing and living conditions, reduced exposure to infectious diseases, and access to medical care. Most significant were public health advances that reduced premature death by decreasing the risk of infant mortality, increasing the chances of surviving childhood, and avoiding infection and communicable disease. Now people in the United States live about 80 years on average, but some individuals survive for much longer.
Scientists are studying people in their nineties (called nonagenarians) and hundreds (called centenarians, including semi-supercentenarians of ages 105-109 years and supercentenarians, ages 110+) to determine what contributes to their long lives. They have found that long-lived individuals have little in common with one another in education, income, or profession. The similarities they do share, however, reflect their lifestyles—many are nonsmokers, are not obese, and cope well with stress. Also, most are women. Because of their healthy habits, these older adults are less likely to develop age-related chronic diseases, such as high blood pressure, heart disease, cancer, and diabetes, than their same-age peers.
The siblings and children (collectively called first-degree relatives) of long-lived individuals are more likely to remain healthy longer and to live to an older age than their peers. People with centenarian parents are less likely at age 70 to have the age-related diseases that are common among older adults. The brothers and sisters of centenarians typically have long lives, and if they develop age-related diseases (such as high blood pressure, heart disease, cancer, or type 2 diabetes), these diseases appear later than they do in the general population. Longer life spans tend to run in families, which suggests that shared genetics, lifestyle, or both play an important role in determining longevity.
The study of longevity genes is a developing science. It is estimated that about 25 percent of the variation in human life span is determined by genetics, but which genes, and how they contribute to longevity, are not well understood. A few of the common variations (called polymorphisms) associated with long life spans are found in the APOE, FOXO3, and CETP genes, but they are not found in all individuals with exceptional longevity. It is likely that variants in multiple genes, some of which are unidentified, act together to contribute to a long life.
Whole genome sequencing studies of supercentenarians have identified the same gene variants that increase disease risk in people who have average life spans. The supercentenarians, however, also have many other newly identified gene variants that possibly promote longevity. Scientists speculate that for the first seven or eight decades, lifestyle is a stronger determinant of health and life span than genetics. Eating well, not drinking too much alcohol, avoiding tobacco, and staying physically active enable some individuals to attain a healthy old age; genetics then appears to play a progressively important role in keeping individuals healthy as they age into their eighties and beyond. Many nonagenarians and centenarians are able to live independently and avoid age-related diseases until the very last years of their lives.
Some of the gene variants that contribute to a long life are involved with the basic maintenance and function of the body’s cells. These cellular functions include DNA repair, maintenance of the ends of chromosomes (regions called telomeres), and protection of cells from damage caused by unstable oxygen-containing molecules (free radicals). Other genes that are associated with blood fat (lipid) levels, inflammation, and the cardiovascular and immune systems contribute significantly to longevity because they reduce the risk of heart disease (the main cause of death in older people), stroke, and insulin resistance.
In addition to studying the very old in the United States, scientists are also studying a handful of communities in other parts of the world where people often live into their nineties and older—Okinawa (Japan), Ikaria (Greece), and Sardinia (Italy). These three regions are similar in that they are relatively isolated from the broader population in their countries, are lower income, have little industrialization, and tend to follow a traditional (non-Western) lifestyle. Unlike other populations of the very old, the centenarians on Sardinia include a significant proportion of men. Researchers are studying whether hormones, sex-specific genes, or other factors may contribute to longer lives among men as well as women on this island.
Scientific journal articles for further reading
Martin GM, Bergman A, Barzilai N. Genetic determinants of human health span and life span: progress and new opportunities. PLoS Genet. 2007 Jul;3(7):e125. PubMed: 17677003. Free full-text available from PubMed Central: PMC1934400.
Sebastiani P, Gurinovich A, Bae H, Andersen S, Malovini A, Atzmon G, Villa F, Kraja AT, Ben-Avraham D, Barzilai N, Puca A, Perls TT. Four genome-wide association studies identify new extreme longevity variants. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1453-1464. doi: 10.1093/gerona/glx027. PubMed: 28329165.
Your skin works hard to keep you healthy, and you can return the favour by taking care of it. Here are some tips to help you keep your skin looking and feeling good.
Skin is made up of an outer layer, the epidermis, and a layer of soft tissue underneath called the dermis. The epidermis constantly grows up towards the outer surface of the skin and sheds dead cells.
The skin acts as a barrier to protect our body from the environment. It also regulates temperature and detects and fights off infections. Nerves in the skin let us feel things such as touch. The skin is one of the biggest and most complex organs of the body, and contains hair follicles, oil glands, sweat glands, nerves and blood vessels.
Hermione Lawson of the British Skin Foundation says: "If you look after your skin, it will be able to do its job better. There are a number of ways you can protect your skin to maintain health."
Sun care
Sunlight contains ultraviolet (UV) rays, which are the main cause of skin ageing and can cause skin cancer. It's important to protect skin against sun damage at any age, but take special care with babies, children and young people. A blistering sunburn before the age of 20 may double the risk of malignant melanoma, the most serious type of skin cancer.
To protect yourself, spend time in the shade between 11am and 3pm, cover up with clothing, hat and sunglasses, and use suncream with a sun protection factor (SPF) of at least 15.
You need to spend some time in sunlight so your body can make vitamin D, which is essential for healthy bones. To find out more about balancing the need for getting vitamin D and protecting your skin from sun damage, see how to get vitamin D from sunlight.
Smoking
"Strong evidence links smoking to ageing of the skin, and it's one of the main environmental factors in premature skin ageing," says Lawson. "It causes wrinkles and a leathery complexion, which makes the skin look old before it should."
It is thought smoking reduces the skin's natural elasticity by causing the breakdown of collagen and reducing collagen production (collagen is a protein that supports skin strength).
Collagen naturally degrades as we get older, leading to the formation of wrinkles. Smoking makes this happen sooner. "Smoking also causes the tiny blood vessels in the skin to constrict, reducing the supply of oxygen to the skin," says Lawson.
Get help to stop smoking.
Alcohol
When you drink alcohol, your body and skin can become dehydrated, leaving the skin looking older and tired. "Drink plenty of water to avoid drying out your skin," says Lawson. When you're drinking alcohol, try to drink within recommended limits and have a non-alcoholic drink, such as soda water or fruit juice, between alcoholic drinks.
Facts from the British Association of Dermatologists
The average adult has 21 sq ft (2 sq m) of skin.
On average, each square half-inch of skin contains:
10 hairs
5 sebaceous (oil) glands
100 sweat glands
3.2ft (1m) of tiny blood vessels
Keeping skin clean
Washing the skin can help prevent smells and infections, but too much washing or using harsh soaps can wash away the natural oils we need to keep our skin healthy. Use mild soaps or bath oils.
"Moisturising protects your skin from the elements as well as preventing it from drying," says Lawson. "An expensive moisturiser is not necessarily more effective than a cheaper one. It all comes down to personal preference."
If you have dry skin, don't use harsh, alcohol-based products as these can irritate skin and dry it out. If you have oily skin, avoid oil-based products and choose water-based ones instead.
People who work in jobs where they frequently have to put their hands in water or come into contact with certain chemicals can sometimes experience inflammation and itchiness on their hands. This is known as contact dermatitis or contact eczema. A doctor can advise on treatment, which usually includes special creams.
Sleep
Don't let late nights ruin your skin. "If you're deprived of sleep, this will make your skin look older and tired," says Lawson. "It can also cause anxiety, irritation and depression. This can cause more sleeplessness and the cycle continues. Make sure you get enough sleep to keep your skin looking healthy."
If you wear make-up, always wash it off before going to bed to reduce the risk of bacteria building up on your skin.
Feeling stressed can disrupt sleeping patterns, which can leave you looking tired and feeling run-down and irritable. Consider taking up an activity, such as running, swimming or yoga.
"Regular exercise is a great outlet for stress," says Lawson. "This leaves the skin looking and feeling vibrant."
How to apply sunscreen
An expert explains why it is important to protect your skin from sunburn to help avoid skin cancer. She also gives advice on how to apply sunscreen correctly and what to look out for when buying sun cream.
Source: NHS Choices, UK
Botox injection 'leads to rejection'
Muscle-freezing botox injections have grown in popularity
"Botox can lose you your friends,” according to the Metro, which said that the anti-wrinkle injections could “damage your social life and emotions”. According to the newspaper, using the popular cosmetic jab could make users “take longer to frown or look sad” and that they “may be unable to show empathy when told of the death of a friend”.
The small study behind this and other news reports found that people who have had Botox treatment for frown lines read angry and sad sentences slower after treatment than before it. Conversely, the treatment had no effect on the reading speed of happy sentences.
Overall, it is questionable whether these findings, based on reading speed, can be interpreted to imply that a volunteer’s emotional processing was different before and after treatment. What is more certain is that this study does not provide evidence that people who have Botox will lose their friends, as many media reports have implied.
Where did the story come from?
The study was carried out by Dr David Havas and colleagues from the University of Wisconsin-Madison, Arizona State University and the University of Chicago. The US study was funded by the National Science Foundation, National Institute of Mental Health and Research to Prevent Blindness. The study is available prior to full publication in the peer-reviewed medical journal Psychological Science.
Newspapers have generally overstated the findings of this study. This research provides no evidence that people who have Botox treatment have fewer friends or a poorer social life.
What kind of research was this?
This observational study looked at a theoretical measure of emotional response time in 41 healthy people who received Botox injections for the first time. Researchers observed the time the group took to read sentences describing angry, happy and sad situations before and after Botox treatment for frown lines. The researchers say that by measuring the change in reading times, they could comment on how Botox affects processing of angry, happy and sad sentences.
What did the research involve?
The 41 female participants were recruited through cosmetic surgery clinics. They were given $50 towards the cost of their treatment for participation in two study sessions. In the first session, immediately before their Botox treatment, the women were given 20 happy, 20 sad and 20 angry sentences to read on a computer. They were instructed to press a key on the keyboard when they had finished reading the sentence. Some sentences were followed by a yes or no question, which the researchers say was inserted to encourage comprehension.
A second study session was scheduled for two weeks after the Botox treatment, in which the participants read 60 remaining sentences. At each session, the last 16 participants also completed a questionnaire that assessed their positive and negative emotions.
The researchers used a technique called regression analysis to assess the contribution of different factors to reading time, namely in which session a question was asked and the emotion it reflected. The researchers also undertook a separate analysis to determine whether treatment-related anxiety might be responsible for any change in the way the sentences were read.
What were the basic results?
The study found that, on average, overall reading times were longer for angry sentences than for happy or sad ones. Response time was also linked to both session number and the sentence emotion, suggesting that performance was different before and after the Botox treatment.
Angry and sad sentence reading times increased by about 0.2 to 0.3 seconds following Botox treatment. There was no difference in happy sentence reading time. Pre-treatment anxiety was not significantly related to the change in reading times between the sessions.
The researchers discuss reasons why Botox may affect the processing of emotions, drawing on the findings of other researchers, both in animal and human studies.
How did the researchers interpret the results?
The researchers concluded that their study shows that paralysis of facial muscles “selectively hinders emotional language processing”. They say that the reading time of sentences was increased if the sentiment they conveyed would usually be expressed using the muscles paralysed by Botox.
Conclusion
This small observational study measured reading time which, the researchers say, is a proxy for emotional processing. They say that previous research has linked the ability to interpret a negative emotion, such as sadness and anger, to the ability to physically express the emotion facially. Based on this theory, they investigated whether the interpretation of these negative emotions was affected if physical expression was paralysed by Botox.
Overall, this research has some limitation, principally the assumption by the researchers that reading time is the same as emotional processing. It is not clear that this has been conclusively established by previous studies. Other points to consider when interpreting these findings include the small sample size and the potential for unmeasured confounders, which may have affected the outcome. Equally, while the researchers attempted to rule out pre-treatment anxiety as a cause of faster reading times before treatment, other emotions may have been at play that would be difficult to measure.
The findings of this research have been overstated by the media. The researchers say that their study “raises questions about the effects of Botox on […] emotional reactivity”, whereas news coverage interpreted this to suggest that Botox could damage personal relationships. Such claims seem unfounded given that the research did not assess sociability or popularity of the participants (either before or after treatment), nor did it ask other people to rate the facial expressions of the people treated with Botox.
Analysis by
Edited by NHS Choices
Botox eases urinary incontinence
Botox can ease incontinence by freezing bladder muscles
Botox injections may help women with urinary incontinence, The Daily Telegraph has today reported. The newspaper said that injecting the muscle-freezing toxin into the wall of the bladder can have a long-lasting impact on overactive bladder syndrome, a major cause of incontinence.
The newspaper’s story is based on a UK medical trial that investigated whether the paralysing properties of botox were effective at reducing the symptoms such as frequently using the toilet, feeling an urgent need to urinate, and leakage in patients with overactive bladder syndrome.
The trial featured 240 women who had not responded to medical treatments for overactive balder syndrome. The researchers found that women who received the botox injection experienced these symptoms significantly less frequently than women who received a dummy injection of saltwater. However, women given botox were more likely to get urinary tract infections.
The results of the study indicate that botox may be effective in treating a common and upsetting health condition. However, if it does get adopted into use in this way there are several other treatment options (including lifestyle measures, bladder training exercises and medication that would be considered first. Botox may be considered as an option only if these treatments fail, and the benefits would have to be considered in relation to its potential harms.
Where did the story come from?
The study was carried out by researchers from the University of Leicester and was funded by the Moulton Charitable Trust and the women’s health charity Wellbeing of Women.
The study was published in the peer-reviewed medical journal European Urology.
The Telegraph covered this study appropriately, covering the study size and design, as well as the treatment benefits and harms.
What kind of research was this?
While it is hard to gauge the true scale of the problem, research suggests that around 13% of women in the UK may have some form of urinary incontinence. Although many conditions and factors can cause urinary incontinence, one major cause is overactive bladder syndrome. The condition is marked by uncontrolled contraction of the bladder that results in an urgent need to pass urine. While this can lead women to need the toilet frequently, some also experience a form of leakage called urge incontinence.
An overactive bladder can be a cause of urge incontinence, which is when urine leaks at the same time or just after you feel an intense urge to pass urine. Urge incontinence differs from stress incontinence, where the pelvic floor muscles are too weak to prevent urination. This causes urine to leak when your bladder is placed under pressure from actions such as coughing or laughing.
This was a placebo-controlled randomised controlled trial that examined the effectiveness and safety of using botulinum toxin (botox) as a treatment for overactive bladder syndrome. A randomised controlled trial is the best way to measure the effectiveness of a treatment, as the randomisation process helps to ensure that any patient characteristics that may influence the outcome have an equal chance of appearing in either treatment group. This allows researchers to be confident that any observed effect is due to the treatment under study.
What did the research involve?
The researchers enrolled 240 women with bladder muscle overactivity, or overactive bladder syndrome, that had not responded to previous treatment. The women were randomly allocated injections of either Botulinum toxin A (botox) or placebo (saltwater) into the wall of the bladder. Women with another common type of incontinence, stress incontinence, were not included in the study.
The participants kept a diary over three days, recording the number of times they:
emptied their bladder
felt an urgent need to empty their bladder
experienced an unintentional passing of urine (or leakage)
The women also completed a questionnaire that assessed their quality of life, as overactive bladder syndrome often has a significant negative impact on patient quality of life.
The researchers conducted follow-up sessions with the women on average at six weeks, three months and six months after treatment. They assessed differences in the frequency of the above three symptoms between the two treatment groups. They also compared quality of life scores, treatment complications and time until troubling symptoms returned between the two groups.
The researchers used appropriate statistical methods to assess differences in frequency of symptoms between the two groups.
What were the basic results?
There were 122 women allocated to the botox treatment group and 118 women allocated to the placebo group.
The researchers compared the outcomes in the botox and placebo groups at the six-month follow-up. They found that in any 24-hour period women in the botox group:
emptied their bladders less often: 8.33 times versus 9.67 times, a difference of 1.34 (95% confidence interval [CI] 1.00 to 2.33, p=0.0001)
experienced fewer leakage episodes: 1.67 versus 6.00, a difference of 4.33 episodes (95% CI 3.33 to 5.67, p<0.0001)
experienced fewer episodes of urgency to urinate: 3.83 versus 6.33, a difference of 2.50 episodes (95% CI 1.33 to 3.33, p<0.0001)
Almost a one-third of women in the botox group (31.3%) developed bladder control (or continence) following their treatment, compared to 12.0% in the placebo group (Odds Ratio [OR] 3.12, 95% CI 1.49 to 6.52, p=0.002).
However, urinary tract infection was reported at least once during six months by a one-third of women in the botox treatment group, compared to 10% in the placebo group (OR 3.68, 95% CI 1.72 to 8.25, p=0.0003).
Those given botox also reported greater difficulty emptying their bladders, which required self-catheterisation to remove their urine: 16% of the botox group compared to 4% of the placebo group (OR 4.87, 95% CI 1.52 to 20.33, p=0.003).
How did the researchers interpret the results?
The researchers concluded that injections of botulinum toxin A into the bladder wall is an effective and safe treatment for overactive bladder syndrome in women who have not responded to previous treatment.
Conclusion
Urinary incontinence can be a distressing and problematic condition, and although we cannot be sure of the number of people affected, research suggests it is surprisingly common.
While there is a range of potential treatments and ways to manage urinary incontinence (including medication, bladder training, lifestyle changes and surgery) not all people respond to them, and they can have problems. This randomised controlled trial provided good evidence that botox injections may be a useful treatment option for women with incontinence due to overactive bladder syndrome that has proven difficult to treat with other methods.
The researchers say that the relief of symptoms reported by the participants was considerably better than those who used oral anticholinergic drugs. These drugs act on the nerve supply to the bladder and are the standard medical treatment used for this condition. They add that other randomised controlled trials have reported similar effects.
The researchers say that since they designed their trial, other studies have published results that support using a lower recommended dose of botox for this type of treatment. Therefore, it is unclear if the same results would be found at this reduced dose. They also say that their study recruited participants with severe cases of overactive bladder syndrome, and that it is unclear if the treatment would be as effective in less severe cases.
It is important to note that the study participants did not have stress incontinence, which is a common cause of urinary incontinence. Therefore, the results of this study cannot be generalised to all women with symptoms of overactive bladder or incontinence, but can only be applied to those with diagnosed overactive bladder syndrome (or detrusor overactivity).
Botox is not routinely used by the NHS in this way, but if it were then it would probably be considered as an option only among women who have required specialist referral for their condition. This would be given after they had tried other treatment options first, which may include lifestyle measures and bladder training exercises in addition to oral medications. If these treatments fail, the benefits of botox would have to be considered in relation to its potential harms.
Analysis by
Edited by NHS Choices
Could Botox be used to treat severe asthma?
Botox – not just for wrinkles
“Botox is commonly used to smooth out wrinkles, but new research suggests it could be used to help asthma sufferers,” the Mail Online reports.
While early results seem encouraging, the research being reported on is still at proof of concept stage.
For most people, asthma can be controlled using conventional treatments such as inhalers. However, some people's asthma symptoms are resistant to treatment (intractable).
The researchers make the case that abnormal vocal cord movement, caused by muscle spasms, may be responsible for some of these intractable asthma cases.
So they tested Botox (botulinum toxin) – a powerful neurotoxin that can cause temporary partial paralysis – on 11 people with severe intractable asthma who had abnormal vocal cord movements that had failed to respond to speech therapy.
After injecting a course of Botox into their vocal cords, participants reported better asthma control, and airway size at the level of the vocal cords was increased. However, there were no changes in measures of lung function.
While the results seem promising it is important to point out that there was no control group in this small study. So any improvement in symptoms could be due to the placebo effect.
As the treatment appears to be relatively safe it should lead to further randomised controlled trials, which will help assess whether a placebo effect influenced the results.
Botox – handle with care
Botox, aka botulinum toxin, is only safe in minute doses. Above a certain level it is extremely deadly.
It is estimated that a teaspoon of botulinum toxin is enough to kill the entire population of India (1.2 billion people).
Where did the story come from?
The study was carried out by researchers from Monash University in Australia. It was funded by Monash Medical Centre.
The study was published in the peer-reviewed journal Respirology.
The results of this study were poorly reported by the Mail Online. The story headline read “injections into the vocal cords proven to help patients breathe”. Although the study did find that people reported better asthma control, there were no improvements in lung function after the treatment.
In addition, as the study was not a randomised controlled trial, it cannot prove that the improvements in asthma control were due to the injections.
Finally, the article appears to have been “cut in half” as it has no proper ending and just peters out.
What kind of research was this?
This study was a case-series of 11 people who still had severe asthma symptoms despite optimised treatment and who had abnormal vocal cord movement which was not improved by speech therapy.
All 11 were treated with vocal cord injections of Botox. The researchers wanted to see whether Botox is an effective treatment that improves asthma control.
A small study like this, often referred to as a phase I trial, can provide some indication of whether Botox may be a safe and effective treatment. However a randomised controlled trial is required to determine whether any improvements seen are actually due to the treatment and are not just due to people reporting improved symptoms because they have been treated (the placebo effect).
What did the research involve?
The study involved 11 people who had severe asthma symptoms despite optimised treatment and who had abnormal vocal cord movement which was not improved by speech therapy. They were treated with Botox injections into one of their vocal cords. If people didn’t have improved symptoms they were given additional injections.
After treatment, response was assessed using the following:
asthma control test scores – a self-reported “scorecard” that is based on the severity and frequency of symptoms (minimum five points for poor control, maximum 25 points for good control)
spirometry (where the amount and/or speed of air that can be inhaled or exhaled is measured)
measuring vocal cord narrowing using computerised tomography (CT) scans, where a series of X-rays are taken to create a detailed image of the larynx
The researchers also collected information on any side-effects that were experienced by the participants.
What were the basic results?
Four people had a single Botox injection, and the other seven received repeat injections, with two people receiving four injections. In total, 24 injections were given.
Asthma control test scores one month after each injection were significantly improved, from an average of 9.1 before treatment to 13.5 after treatment. The researchers state that changes of three or more on this score are clinically important.
Airway size was measured by computerised tomography in 10 patients. Some patients had received multiple injections when it was measured. Compared to before treatment, the amount of time the airway was narrowed below the lower limit of normal significantly improved from 39.4% to 17.6%.
There was no change in lung function as assessed by spirometry.
Side effects were noted after 17 of the 24 injections. Dysphonia (voice disorder) occurred after 16 injections and lasted for up to six weeks in five of the cases, though they were still able to have normal conversations. Dysphagia (difficulty swallowing) was reported after six of the 24 injections. All cases were categorised as ‘mild’.
One person with severe asthma required hospital admission and steroids after having the injection under general anaesthetic. The study fails to make clear whether this was due to an adverse reaction to the Botox or to the general anaesthetic (or to something else entirely).
How did the researchers interpret the results?
The researchers conclude that “although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.”
Conclusion
This small study involved 11 people who had severe asthma symptoms despite optimised treatment and who had abnormal vocal cord movement which was not improved by speech therapy. The results suggest that Botox injections into one of the vocal cords improved asthma control and the airway size at the level of the vocal cords was increased. However, there were no changes in measures of lung function.
As the researchers point out, this study was not controlled or blinded and a placebo effect cannot be excluded.
It is also not known how long any effect would last, as participants were only assessed for one to three months after treatment.
It is also currently unclear how common the problem of abnormal vocal cord movements is in people with poorly controlled asthma.
In conclusion, although Botox could be a promising treatment for people with asthma who also have abnormal vocal cord movement, further randomised controlled trials are needed.
If you do feel that your asthma symptoms are poorly controlled then speak to your GP or the doctor in charge of your care. There are a range of treatments that may be of benefit.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.
Analysis by
Edited by NHS Choices
Botox may be useful in treating stomach cancers
Botox can block nerve signals
"Botox may have cancer fighting role," BBC News reports after research involving mice found using Botox to block nerve signals to the stomach may help slow the growth of stomach cancers. Botox, short for botulinum toxin, is a powerful neurotoxin that can block nerve signals.
The researchers studied genetically modified mice designed to develop stomach cancer as they grew older.
They found that mice treated with Botox injections had improved survival rates, because the cancer spread at a reduced rate or was prevented from developing in the first place.
Cutting the nerve supply to the stomach during an operation called a vagotomy had a similar effect.
In mice that had already developed stomach cancer, Botox injections reduced cancer growth and improved survival rates when combined with chemotherapy.
Further studies of human stomach cancer samples confirmed the finding that nerves play a role in tumour growth.
An early-phase human trial is now underway in Norway to determine the safety of such a procedure and to work out how many people would need to be treated in trials, to see whether the treatment is effective.
Botox: not just for wrinkles
Botulinum toxin is a toxin produced by the bacterium Clostridium botulinum and is thought to be the most powerful toxin on the planet. It is estimated that a single gram of Botox would be enough to kill one million people, though it is safe to use in very small doses.
Aside from its cosmetic uses, Botox is useful medically, as it can help relax muscles and block nerve signals. This means it has a wide range of potential applications, from treating excessive sweating to uncontrollable muscle contractions (dystonia) and migraines.
Where did the story come from?
The study was carried out by researchers from the Norwegian University of Science and Technology in Trondheim, Columbia University College of Physicians and Surgeons in New York, and universities and institutes of technology in Boston, Germany and Japan.
It was funded by the Research Council of Norway, the Norwegian University of Science and Technology, St Olav's University Hospital, the Central Norway Regional Health Authority, the US National Institutes of Health, the Clyde Wu Family Foundation, the Mitsukoshi Health and Welfare Foundation, the Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad, the Uehara Memorial Foundation, the European Union Seventh Framework Programme, the Max Eder Program of the Deutsche Krebshilfe and the German Research Foundation.
The study was published in the peer-reviewed medical journal Science Translational Medicine.
The study was reported accurately by the UK media, making it clear that this potential treatment is not yet available and will take years to assess its potential.
What kind of research was this?
This research was a collection of experiments on mice and studies of human tissue samples. Previous research had shown that cutting the main nerve to the stomach (vagus) in a procedure called a vagotomy reduces the thickness of the stomach wall and decreases cell division.
Another research study found people who had a vagotomy had a 50% reduced risk of developing stomach cancer 10 to 20 years later. The researchers wanted to see if targeting the nerve would reduce stomach cancer growth.
What did the research involve?
Genetically modified mice designed to develop stomach cancer by 12 months of age were studied to see if there was a link between the density of nerves and stomach cancer.
One of four different types of operation was then performed on the vagus nerve of 107 genetically modified mice at the age of six months to see if this made a difference in the development of stomach cancer. This was either:
a sham operation
pyloroplasty (PP) – surgery to widen the valve at the bottom of the stomach so the stomach can empty food more easily
bilateral vagotomy with pyloroplasty (VTPP) – cutting both sections of the vagus nerve and widening the valve
anterior unilateral vagotomy (UVT) – cutting just the front section of the vagus nerve
The researchers then performed a Botox procedure on another set of mice by injecting the anterior vagus nerve (front section) when they were six months old to see if this reduced the development of stomach cancer.
To see if cutting or injecting the nerve had any effect after stomach cancer had developed, the researchers performed UVT on mice aged 8, 10 or 12 months and compared their survival rate with mice who had not had the intervention.
They then injected Botox into the stomach cancer of mice aged 12 months and looked at the subsequent cancer growth. They also compared survival rates for chemotherapy with saline injection, chemotherapy with Botox and chemotherapy with UVT.
The researchers then examined human stomach samples from 137 people who had undergone an operation for stomach cancer, to look at how active the nerves were in the sections of cancer compared with normal tissue.
They also compared tissue samples of 37 people who had already had an operation for stomach cancer, but then developed stomach cancer in the base portion of the stomach. The vagus nerve had been cut in 13 of these people.
What were the basic results?
The genetically modified mice mostly developed stomach cancer in the section of the stomach that had the highest density of nerves.
Cutting the vagus nerve supply reduced the incidence of tumours developing. The percentage of mice that had tumours six months after the operation was:
78% after the sham surgery
86% after PP
17% after VTPP
14% in the front section of the stomach (where the nerve had been cut) and 76% in the back section (where the vagus nerve was still intact) after UVT
Six months after the Botox injection into the anterior vagus nerve, the mice still developed stomach cancer. However, the size of the tumour and number of dividing cancer cells in the front section of the stomach was less than half that of the back section.
In mice that had already developed stomach cancer, the normal survival rate was 53% by 18 months, but this was increased by the UVT to:
71% if the UVT was performed at 8 months
64% if the UVT was performed at 10 months
67% if the UVT was performed at 12 months
Botox injection into the stomach tumours of mice reduced the growth by roughly half. Botox and chemotherapy improved mouse survival compared with chemotherapy on its own, as did UVT and chemotherapy.
In the human samples, there was evidence of increased nerve activity in the cancer sections of tissue compared with the normal tissues. This was higher in more advanced tumours.
All 24 people who had not had the vagus nerve cut developed stomach cancer in the base, as well as the remaining front and back sections of the stomach. Only one of the 13 people who had had the vagus nerve cut developed cancer in the front or back section of the stomach, suggesting that the nerve needed to be intact for cancer to develop.
How did the researchers interpret the results?
The researchers say that their "finding that nerves play an important role in cancer initiation and progression highlights a component of the tumour microenvironment contributing to the cancer stem cell niche.
"The data strongly supports the notion that denervation and cholinergic antagonism, in combination with other therapies, could represent a viable approach for the treatment of gastric cancer and possibly other solid malignancies."
Conclusion
These laboratory experiments show that nerves have a role in the development and advancement of stomach cancer. The early experiments in mice found that stopping the nervous supply by either cutting the vagus nerve or injecting it with Botox improved survival rates and reduced cancer growth.
The Botox injections were not performed on any humans in this study. However, an early-phase clinical trial in humans with inoperable stomach cancer began in Norway in January 2013, with the results expected in 2016.
This will determine the safety of such a procedure and work out the number of people who would need to be treated in a larger controlled trial to see whether the treatment is effective.
You can reduce your risk of stomach cancer by quitting smoking if you smoke and moderating your consumption of salt and smoked meats, such as pastrami.
Stomach cancer has also been linked to a chronic infection by H. pylori bacteria, a common cause of stomach ulcers.
If you find yourself having persistent bouts of indigestion or stomach pain, you should contact your GP for advice. The symptoms could be caused by a H. pylori infection, which is relatively straightforward to treat.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.
Analysis by
Edited by NHS Choices
Cancer Cream and Wrinkles
Researchers claim that “a cream used to treat early signs of skin cancer can erase wrinkles and make skin look younger,” the Daily Mail reported. It said that the cream, used to treat a form of pre-cancer called actinic keratoses, could also reverse signs of ageing.
The cream was tested on 21 healthy people between the ages of 56 and 85. All of them experienced irritation with red, scaly skin at the beginning of the treatment, but after ten weeks they rated their skin as improved. This result was also confirmed through clinical assessment.
The researchers say that many people would find the cream’s side effects unacceptable if used for cosmetic purposes. As the Daily Mail said, the volunteers’ skin looked like “raw hamburger meat” during therapy. The researchers say that the cream’s restorative effects may be seen as an additional benefit for people with actinic keratoses and could give them extra motivation to undergo the treatment.
Where did the story come from?
This research was carried out by Dr Dana L Sachs and colleagues from dermatology departments at the University of Michigan and Johns Hopkins University. The study was supported by Valeant Pharmaceuticals International, the maker of the cream being studied. The study was published in the peer-reviewed medical journal Archives of Dermatology.
What kind of scientific study was this?
The study investigated what effects a course of skin cream for treating actinic keratoses would have on the wrinkles, texture and pigmentation of the skin. Actinic keratoses (also known as solar keratosis) are thick, scaly or crusty patches on the skin that are caused by exposure to sunlight. They are most common in fair-skinned people and those who have been frequently exposed to the sun. While they are usually harmless, actinic keratoses sometimes develop into a type of skin cancer called squamous cell carcinoma.
The cream investigated by this study contains the chemical fluorouracil, which is usually used to treat cancers of the colon, head and neck, pancreas and other organs. Since 1963, it has been used in creams to treat actinic keratoses.
In this case series, the researchers enrolled 13 men and eight women in a 24-week study. All the volunteers were between 56 and 85 years of age with moderate to severe sun damage and actinic keratoses on the face. The volunteers needed to be in general good health and willing to have skin biopsies taken from the face. They could not be pregnant, breast-feeding or have a history of allergy to any ingredients of the cream.
All volunteers were given the same 5% cream to be applied to the whole of the face twice a day to for two weeks. The study was an open-label study with no control group for comparison. All participants knew they were getting the active cream.
The researchers measured the cream’s effects with before-and-after photos of the volunteers’ faces, close-up photos of any actinic keratoses, and 3mm punch biopsy specimens of sun-damaged skin from behind the ears and forehead. The biopsies were repeated at two weeks (24 hours after the last cream was applied), four weeks, 10 weeks and 24 weeks. Various molecular markers of inflammation and protein levels in the skin were estimated from the tissue samples.
The volunteers’ skin was clinically assessed at the same intervals using scores for a global assessment of overall photoageing severity, coarse wrinkling, fine wrinkling, dark spots, mottled hyperpigmentation, sallowness and tactile roughness. The researchers counted the actinic keratoses at the beginning of the study and at subsequent visits. They asked the volunteers to complete a questionnaire at 10 weeks.
What were the results of the study?
The researchers reported that the day after the final fluorouracil treatment was applied, there were significant increases in the molecular markers of inflammation and cellular damage. At week four, there was evidence of increases in the production of procollagen (a forerunner to collagen).
Actinic keratoses and photoaging were improved and this was statistically significant. Most patients rated photoaging as improved and said they would be willing to have the therapy again.
What interpretations did the researchers draw from these results?
The researchers say that the fluorouracil cream applied to the face causes skin injury, which leads to healing and then skin remodelling, resulting in improved appearance. They suggest that this mechanism is “reminiscent of that seen with laser treatment of photoageing”.
What does the NHS Knowledge Service make of this study?
This study has shown that some molecular changes attributed to this cream are linked to a sequence of events that results in improved skin appearance. Although the subjective improvements in appearance have been observed by people using this cream before, this study has clarified how these improvements occurs. There are some notes of caution:
The clearance of sun damage spots was predictable and the cream is licensed for this purpose. Its application to skin that has only wrinkles and no sun damage is not currently a licensed use.
After two weeks of applying the cream, the average number of actinic keratoses had significantly increased from 11.6 to 59.5 per patient. This may be the result of miscounting, as the researchers suggest, but it also suggests that this cream makes the condition worse before it gets better. The degree of reddening and scaliness of the skin at two weeks was substantial.
There are good reasons why researchers and volunteers would have realised they were getting an inert control cream, if one had been used. For example, their skin would not have gone red or flaky with the inert cream. However, it is still important that a control group is used where possible. Without one, it is not possible to say if this cream is any better than other creams or laser treatment.
Long-term results, safety or side effects were not reported by the researchers.
Overall, this small study improves our understanding of the repair mechanisms in sun-damaged skin in people over 50. The results do not suggest that the cream should be routinely used for cosmetic purposes as its side effects are considerable. The researchers say that the cream’s restorative effects may be seen by people with actinic keratoses as an additional benefit and give them extra motivation to undergo the treatment. They also say that while the cream may be cheaper than laser treatment, many people would not think that the cream’s side effects and length of treatment were acceptable, and it may not achieve the same degree of improvement as laser treatment.
Analysis by
Edited by NHS Choices
Nail Care Products
It is important to use nail products safely, following labeled directions and paying attention to any warning statements. The following information answers common questions about some nail products and ingredients.
How Nail Products Are Regulated
Nail Product Ingredient Safety
Some Common Nail Product Ingredients
Acetonitrile
Formaldehyde
Methacrylate Monomers
Methacrylic Acid
Phthalates
Toluene in Nail Polishes and Other Products
Reporting Adverse Nail Product Reactions
How Nail Products Are Regulated
Nail products for both home and salon use are regulated by the Food and Drug Administration. Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), these products are cosmetics [FD&C Act, section 201(i)].
By law, nail products sold in the United States must be free of poisonous or deleterious (harmful) substances that might injure users when used as labeled or under the usual or customary conditions of use (see Key Legal Concepts: Interstate Commerce, Adulteration and Misbranding). Many nail products contain potentially harmful ingredients, but are allowed on the market because they are safe when used as directed. For example, some nail ingredients are harmful only when ingested, which is not their intended use.
The labels of all cosmetics, whether marketed to consumers or salons, must include a warning statement whenever necessary or appropriate to prevent a health hazard that may occur with use of the product (21 CFR 740.1). Cosmetics sold on a retail basis to consumers also must bear an ingredient declaration, with the names of the ingredients listed in descending order of predominance. The requirement for an ingredient declaration does not apply, for example, to products used at professional establishments or samples distributed free of charge. However, the requirement does apply if these products are also sold at retail, even if they are labeled "For professional use only" (see Cosmetic Labeling: An Overview).
Under the law, cosmetic products and ingredients, including nail products, are not subject to FDA premarket approval authority, with the exception of most color additives. However, FDA may pursue enforcement action against violative products, or against firms or individuals who violate the law (See FDA Authority Over Cosmetics).
While FDA regulates the nail products intended for use at home and in salons, the operation of nail salons and the licensing of their technicians are regulated by state and local authorities. Also, the Occupational Safety and Health Administration has addressed the safety of employees in nail salons.
Nail Product Ingredient Safety
Infections and allergic reactions can occur with some nail products. As mentioned previously, some ingredients in nail products may be harmful if ingested. Some can easily catch fire if exposed to the flame of the pilot light of a stove, a lit cigarette, or other heat source, such as the heating element of a curling iron. Nail products also can be dangerous if they get in the eyes. Consumers should read labels of nail products carefully and heed any warnings.
Acetonitrile in Artificial Nail Removers
Artificial nail removers consist primarily of acetonitrile. Child-resistant packaging is required for all household glue removers in liquid form containing more than 500 milligrams of acetonitrile in a single container [16 CFR 1700.14 (18)]. The Consumer Product Safety Commission (CPSC) enforces this requirement under authority of the Poison Prevention Packaging Act [15 U.S.C. 1471-1476]. However, the fact that a product is in "child-resistant" packaging does not mean that a child could not open it.
Like any cosmetic product that may be hazardous if misused, it is important for these artificial nail removers to carry an appropriate warning on the label, along with directions for safe use.
Formaldehyde in Nail Hardeners
Formaldehyde is used in many different products, some of which are regulated as cosmetics. For example, formaldehyde is an important component of nail hardeners. Formaldehyde and formaldehyde-releasing ingredients are often used in other cosmetics as preservatives to protect against harmful bacteria, and formaldehyde also has been used in certain hair-smoothing or hair-straightening products. Different forms of formaldehyde have different names, such as "formalin" and "methylene glycol."
The Cosmetic Ingredient Review (CIR) Expert Panel concluded in December 2011 that formaldehyde and methylene glycol are safe for use in cosmetics when formulated to ensure use at the minimal effective concentration, but in no case should formalin concentration exceed 0.2% by weight. (This would be 0.074% by weight calculated as formaldehyde or 0.118% by weight calculated as methylene glycol.) CIR also found that formaldehyde and methylene glycol are safe under present practices of use and concentration in nail hardening products, where the concentration of formaldehyde is typically higher than the 0.2% level noted for cosmetics generally. "Present practices of use" include instructions to avoid skin contact. However, CIR found that formaldehyde and methylene glycol are unsafe in the present practices of use and concentration in hair smoothing products; see FDA, OSHA Act on Brazilian Blowout and the related Warning Letter.
Nail hardeners that contain formaldehyde may cause an irritation or allergic reaction to those sensitized to this compound. There is also some evidence that certain individuals may become allergic to toluene sulfonamide–formaldehyde resin, a common ingredient in nail preparations. If you are allergic to formaldehyde, have previously experienced an allergic reaction to nail preparations, or for any other reason wish to avoid this ingredient, be sure to read the product ingredient statement on the label to determine whether formaldehyde or related ingredients, such as formalin and toluene sulfonamide-formaldehyde resin, are present.
Methacrylate Monomers in Artificial Nails ("Acrylics")
Artificial nails are composed primarily of acrylic polymers and are made by reacting together acrylic monomers, such as ethyl methacrylate monomer, with acrylic polymers, such as polymethylmethacrylate. When the reaction is completed, traces of the monomer are likely to remain in the polymer. For example, traces of methacrylate monomers remain after artificail nails are formed. The polymers themselves are typically quite safe, but traces of the reactive monomers could result in an adverse reaction, such as redness, swelling, and pain in the nail bed, among people who have become sensitive (allergic) to methacrylates.
Ethyl methacrylate monomer is commonly used today in acrylic nails, although methyl methacrylate monomer may still be found in some artificial nail products. In the early 1970s, FDA received a number of complaints of injury associated with the use of artificial nails containing methyl methacrylate monomer. Among these injuries were reports of fingernail damage and deformity, as well as contact dermatitis. Unlike methyl methacrylate monomer, ethyl methacrylate polymers were not associated with these injuries. Based on its investigations of the injuries and discussions with medical experts in the field of dermatology, the agency chose to remove from the market products containing 100 percent methyl methacrylate monomer through court proceedings, which resulted in a preliminary injunction against one firm as well as several seizure actions and voluntary recalls. No regulation specifically prohibits the use of methyl methacrylate monomer in cosmetic products.
The CIR Expert Panel determined in 2002 that ethyl methacrylate is safe as used when application is accompanied by directions to avoid skin contact because of its sensitizing potential (that is, the possibility that a person might develop an allergy to this material).
Methacrylic Acid in Nail Primers
Despite the similar names, methacrylic acid is different from methacrylate monomers. It also is used differently and raises different safety concerns. Methacrylic acid (MAA) has been used in nail primers to help acrylic nails adhere to the nail surfaces. In response to cases of poisoning and injury, the CPSC issued a regulation [16 CFR 1700.14 (29)] requiring child-resistant packaging for household products containing MAA. A number of serious injuries have occurred to children who ingested such products or spilled them, receiving burns to their skin.
Nail primers that contain MAA are most commonly distributed through wholesale suppliers to nail salons and retail beauty supply stores, and they usually are labeled "For Professional Use Only." However, some of these retail stores sell to both professionals and consumers.
The CPSC regulation, established in accordance with the Poison Prevention Packaging Act, requires child- resistant packaging for liquid household products containing more than 5 percent MAA, weight to volume, in a single retail package. That means that it applies, for example, to a product containing more than 5 grams of MAA per 100 milliliters.
MAA products applied by means of absorbent material in a dispenser, such as a pen-like marker, are exempt from this requirement if there is no free liquid in the device and if, under any reasonably foreseeable conditions of use, the methacrylic acid will emerge only through the tip of the device. For more information regarding the child-resistant packaging requirements for MAA, contact the Office of Compliance, CPSC, at (301) 504-0608.
Phthalates
Phthalates are a group of chemicals used in a wide variety of products, from toys to carpeting and medical tubing. In nail polishes, they are used primarily at concentrations of less than 10% as plasticizers, to reduce cracking by making them less brittle. Dibutylphthalate (DBP) has been used most commonly in nail polishes, but dimethylphthalate (DMP) and diethylphthalate (DEP) have been used occasionally. According to FDA's latest survey of cosmetics, conducted in 2010, however, DBP and DMP are now used rarely. For information on health questions related to phthalates in cosmetics, please see Phthalates.
Toluene in Nail Polishes and Other Products
Toluene is used as a solvent in a variety of nail products, such as nail polish, nail hardeners, and polish removers. Toluene was reviewed by the CIR Expert Panel in 1987, when the Panel determined that it was safe for cosmetic use in nail products when limited to concentrations no greater than 50 percent. The Panel re-evaluated the safety of toluene in 2005 and confirmed its original conclusion.
Reporting Adverse Nail Product Reactions
Consumers, nail technicians, and healthcare providers can report adverse reactions from nail products using the contact information in Bad Reaction to Cosmetics? Tell FDA.
* The Cosmetic Ingredient Review (CIR) Expert Panel is an independent, industry-funded panel of medical and toxicology experts that meets quarterly to conduct safety assessments of cosmetic ingredients and publishes its findings in peer-review journals. FDA participates in the CIR in a non-voting capacity. FDA takes the results of CIR reviews into consideration when evaluating safety, but the results of FDA safety assessments may differ from those of CIR.
February 29, 2000; Updated December 13, 2006, March 9, 2010, December 6, 2012, and March 11, 2013
What ingredients are prohibited or restricted from use in cosmetics? You can find the information on what the law and FDA regulations say about cosmetic ingredients and safety below.
Are harmful ingredients allowed in cosmetics?
What ingredients are prohibited or restricted by regulation?
What about color additives?
What about drug ingredients?
Why are different ingredients prohibited in some other countries?
More Resources
Are harmful ingredients allowed in cosmetics?
It’s against the law for a cosmetic to contain any ingredient that makes the product harmful when consumers use it according to directions on the label, or in the customary or expected way. This is true whether or not there is a regulation that specifically prohibits or restricts the use of the ingredient in cosmetics.
The one exception is for coal-tar hair dyes, which the law treats differently. Under the law, FDA cannot take action against a coal-tar hair dye for safety reasons as long as it has a special warning statement on the label and directions for a skin test. The caution statement reads as follows:
Caution - This product contains ingredients which may cause skin irritation on certain individuals and a preliminary test according to accompanying directions should first be made. This product must not be used for dyeing the eyelashes or eyebrows; to do may cause blindness.
It’s also important to understand that some cosmetics that are safe when people use them correctly may be unsafe when used the wrong way. Cosmetics must have any directions for use or warning statements needed to make sure people use the products safely. For example, some ingredients may be safe in products such as cleansers that we wash off the skin immediately, but not in products that we leave on the skin for hours. Similarly, ingredients that are safe for use on the hair or nails may be unsafe when used on the skin or near the eyes.
Under U.S. law, cosmetic products and ingredients, other than color additives, do not need FDA approval before they go on the market. Cosmetic manufacturers have a legal responsibility for the safety and labeling of their products. FDA can and does take action against cosmetics on the market that do not comply with the law.
What ingredients are prohibited or restricted by FDA regulations?
Although it’s against the law to use any ingredient that makes a cosmetic harmful when used as intended, FDA has regulations that specifically prohibit or restrict the use of the following ingredients in cosmetics:
Bithionol. The use of bithionol is prohibited because it may cause photocontact sensitization (21 CFR 700.11).
Chlorofluorocarbon propellants. The use of chlorofluorocarbon propellants in cosmetic aerosol products intended for domestic consumption is prohibited (21 CFR 700.23).
Chloroform. The use of chloroform in cosmetic products is prohibited because it causes cancer in animals and is likely to be harmful to human health, too. The regulation makes an exception for residual amounts from its use as a processing solvent during manufacture, or as a byproduct from the synthesis of an ingredient (21 CFR 700.18).
Halogenated salicylanilides (di-, tri-, metabromsalan and tetrachlorosalicylanilide). These are prohibited in cosmetic products because they may cause serious skin disorders (21 CFR 700.15).
Hexachlorophene. Because of its toxic effect and ability to penetrate human skin, hexachlorophene (HCP) may be used only when no other preservative has been shown to be as effective. The HCP concentration in a cosmetic may not exceed 0.1 percent, and it may not be used in cosmetics that are applied to mucous membranes, such as the lips (21 CFR 250.250).
Mercury compounds. Mercury compounds are readily absorbed through the skin on topical application and tend to accumulate in the body. They may cause allergic reactions, skin irritation, or neurotoxic problems. The use of mercury compounds in cosmetics is limited to eye area products at no more than 65 parts per million (0.0065 percent) of mercury calculated as the metal and is permitted only if no other effective and safe preservative is available. All other cosmetics containing mercury are adulterated and subject to regulatory action unless it occurs in a trace amount of less than 1 part per million (0.0001 percent) calculated as the metal and its presence is unavoidable under conditions of good manufacturing practice (21 CFR 700.13).
Methylene chloride. It causes cancer in animals and is likely to be harmful to human health, too (21 CFR 700.19).
Prohibited cattle materials. To protect against bovine spongiform encephalopathy (BSE), also known as "mad cow disease," cosmetics may not be manufactured from, processed with, or otherwise contain, prohibited cattle materials. These materials include specified risk materials*, material from nonambulatory cattle, material from cattle not inspected and passed, or mechanically separated beef. Prohibited cattle materials do not include tallow that contains no more than 0.15 percent insoluble impurities, tallow derivatives, and hides and hide-derived products, and milk and milk products** (21 CFR 700.27).
Sunscreens in cosmetics. Use of the term "sunscreen" or similar sun protection wording in a product's labeling generally causes the product to be subject to regulation as a drug or a drug/cosmetic, depending on the claims. However, sunscreen ingredients may also be used in some cosmetic products to protect the products’ color. The labelling must also state why the sunscreen ingredient is used, for example, "Contains a sunscreen to protect product color." If this explanation isn’t present, the product may be subject to regulation as a drug (21 CFR 700.35). For more information on sunscreens, refer to Tanning Products.
Vinyl chloride. The use of vinyl chloride is prohibited as an ingredient of aerosol products, because it causes cancer and other health problems (21 CFR 700.14).
Zirconium-containing complexes. The use of zirconium-containing complexes in aerosol cosmetic products is prohibited because of their toxic effect on lungs of animals, as well as the formation of granulomas in human skin (21 CFR 700.16).
What about color additives?
Color additives are permitted in cosmetics only if FDA has approved them for the intended use. In addition, some may be used only if they are from batches that FDA has tested and certified. To learn more, see “Color Additives and Cosmetics.”
What about drug ingredients?
If a product is intended for a therapeutic purpose, such as treating or preventing disease, it’s a drug under the law and must meet those requirements, such as premarket approval by FDA, even if it affects the appearance. The presence of certain ingredients with a therapeutic use that is well-known to the public and industry is one factor that can determine whether a product is intended for use as a drug. FDA makes these decisions on a case-by-case basis. To learn more, see “Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?).”
Why are different ingredients prohibited in some other countries?
Different countries and regions regulate cosmetics under different legal frameworks.
Under U.S. law, FDA does not have the authority to require cosmetic manufacturers to submit their safety data to FDA, and the burden is on FDA to prove that a particular product or ingredient is harmful when used as intended. We make these decisions based on reliable scientific information available to us. FDA can take other countries’ decisions into consideration, but we can only take action within the legal and regulatory framework for cosmetics in the United States.
More Resources
Color Additives and Cosmetics
FDA Authority Over Cosmetics
Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?)
Key Legal Concepts: Interstate Commerce, Adulteration, and Misbranding
Regulations Related to Cosmetics
Science & Research
* "Specified risk material" means the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months and older and the tonsils and distal ileum of the small intestine of all cattle.
** Tallow must be produced from tissues that are not prohibited cattle materials or must contain not more than 0.15 percent insoluble impurities as determined by the method entitled "Insoluble Impurities" (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS Official Method Ca 3a-46. You may obtain copies of the method from AOCS , 2211 W. Bradley Ave. Champaign, IL 61821
Laws & Regulations
Key Legal Concepts: Interstate Commerce, Adulterated, and MisbrandedRegulations Related to CosmeticsProhibited & Restricted IngredientsCosmetics & U.S. Law
Resources for You
Color Additives Permitted for Use in Cosmetics
Page Last Updated: 01/26/2015
Source: FDA, HHS
Color Additives and Cosmetics
Color additives are subject to a strict system of approval under U.S. law [Federal Food, Drug, and Cosmetic Act (FD&C Act), sec. 721; 21 U.S.C. 379e]. Except in the case of coal-tar hair dyes, failure to meet U.S. color additive requirements causes a cosmetic to be adulterated [FD&C Act, sec. 601(e); 21 U.S. Code 361(e)]. Color additive violations are a common reason for detaining imported cosmetic products offered for entry into this country.
Some Basic Requirements
If your product (except coal-tar hair dyes) contains a color additive, by law [FD&C Act, Sec. 721; 21 U.S.C. 379e; 21 CFR Parts 70 and 80] you must adhere to requirements for:
Approval. All color additives used in cosmetics (or any other FDA-regulated product) must be approved by FDA. There must be a regulation specifically addressing a substance's use as a color additive, specifications, and restrictions.
Certification. In addition to approval, a number of color additives must be batch certified by FDA if they are to be used in cosmetics (or any other FDA-regulated product) marketed in the U.S.
Identity and specifications. All color additives must meet the requirements for identity and specifications stated in the Code of Federal Regulations (CFR).
Use and restrictions. Color additives may be used only for the intended uses stated in the regulations that pertain to them. The regulations also specify other restrictions for certain colors, such as the maximum permissible concentration in the finished product.
How are color additives categorized?
The FD&C Act Section 721(c) [21 U.S. C. 379e(c)] and color additive regulations [21 CFR Parts 70 and 80] separate approved color additives into two main categories: those subject to certification (sometimes called "certifiable") and those exempt from certification. In addition, the regulations refer to other classifications, such as straight colors and lakes.
Colors subject to certification. These color additives are derived primarily from petroleum and are sometimes known as "coal-tar dyes" or "synthetic-organic" colors. (NOTE: Coal-tar colors are materials consisting of one or more substances that either are made from coal-tar or can be derived from intermediates of the same identity as coal-tar intermediates. They may also include diluents or substrata. (See Federal Register, May 9, 1939, page 1922.) Today, most are made from petroleum.)Colors exempt from certification. These color additives are obtained primarily from mineral, plant, or animal sources. They are not subject to batch certification requirements. However, they still are considered artificial colors, and when used in cosmetics or other FDA-regulated products, they must comply with the identity, specifications, uses, restrictions, and labeling requirements stated in the regulations [21 CFR 73].
Except in the case of coal-tar hair dyes, these colors must not be used unless FDA has certified that the batch in question has passed analysis of its composition and purity in FDA's own labs. If the batch is not FDA-certified, don't use it.
These certified colors generally have three-part names. The names include a prefix FD&C, D&C, or External D&C; a color; and a number. An example is "FD&C Yellow No. 5." Certified colors also may be identified in cosmetic ingredient declarations by color and number alone, without a prefix (such as "Yellow 5").
Straight color. "Straight color" refers to any color additive listed in 21 CFR 73, 74, and 81 [21 CFR 70.3(j)].
Lake. A lake is a straight color extended on a substratum by adsorption, coprecipitation, or chemical combination that does not include any combination of ingredients made by a simple mixing process [21 CFR 70.3(l)]. Because lakes are not soluble in water, they often are used when it is important to keep a color from "bleeding," as in lipstick. In some cases, special restrictions apply to their use. As with any color additive, it is important to check the Summary of Color Additives Listed for Use in the United States in Foods, Drugs, Cosmetics and Medical Devices and the regulations themselves [21 CFR 82, Subparts B and C] to be sure you are using lakes only for their approved uses.
How can I guard against color additive violations?
Several precautions can help you avoid color additive violations that will cause your cosmetic to be adulterated:
Do not confuse certified colors with their uncertified counterparts. For example, FD&C Yellow No. 5 is the certified form of tartrazine, and is approved for use in cosmetics generally. But tartrazine, which has not undergone FDA analysis and received FDA certification, must not be substituted for or identified in an ingredient declaration as FD&C Yellow No. 5.
Do not confuse certified colors with colors identified only by a Colour Index (CI) number, or by the E number sometimes used in European color identification. You must not use a color subject to certification unless FDA has certified the batch in question [FD&C Act, sec. 721(a)(1)(A). A CI or E number does not indicate FDA certification.
When purchasing color additives subject to certification, check the label. If the lot is certified, the color's label must state the legal name for the color (such as "FD&C Yellow No. 5"), or, if it is a mixture, the name of each ingredient; the FDA lot certification number; and the color's uses and restrictions as stated in the CFR [21 CFR 70.25).
Check the Summary of Color Additives on FDA's Web site. Although this table is not a substitute for the regulations, it is an easy-to-use reference that introduces you to FDA-approved color additives and directs you to the regulations addressing specific color additives.
Become familiar with the regulations themselves. The color additive regulations are in 21 CFR Parts 70 through 82. Specific color additives are addressed in Parts 73, 74, and 82. The color additive regulations are posted on FDA's Web site. To purchase printed copies of the CFR by credit card, call the Government Printing Office at (202) 512-1800, Monday through Friday, from 8:00 a.m. to 4:00 p.m., Eastern Standard Time. To pay by check, write to the Superintendent of Documents, Attn: New Orders, P.O. Box 371954, Pittsburgh, PA 15250-7954. Contact the Government Printing Office directly for current costs.
Confirm the status of color additives before use. There may be changes in color additive approvals and changes in the uses and restrictions that apply to a color additive. Such changes may affect colors subject to certification as well as colors exempt from certification. To stay current with the regulations, you can check the latest edition of the CFR and FDA Dockets. You also may contact FDA at .
When purchasing colors subject to certification, confirm that the manufacturer has requested certification. For example, you can choose a manufacturer from FDA's list of companies that have requested color certification within the past two years. If the company that appears on the color additive label is not on this list, you may contact FDA at to determine whether the company has in fact requested certification of its color additives.
Must I match colors with intended use?
Yes. No matter whether a particular color is subject to certification or exempt from certification, U.S. law prohibits its use in cosmetics (or any other FDA-regulated product) unless it is approved specifically for the intended use [FD&C Act, sec. 721(a)(1)(A); 21 U.S.C. 379e(a)(1)(A)].
The regulations also restrict intended use as follows:
Eye-area use: You may not use a color additive in the area of the eye unless the regulation for that additive specifically permits such use [21 CFR 70.5(a)]. The "area of the eye" includes "the area enclosed within the circumference of the supra-orbital ridge and the infra-orbital ridge, including the eyebrow, the skin below the eyebrow, the eyelids and the eyelashes, and conjunctival sac of the eye, the eyeball, and the soft areolar tissue that lies within the perimeter of the infra-orbital ridge" [21 CFR 70.3(s)]. Although there are color additives approved for use in products such as mascara and eyebrow pencils, none is approved for dyeing the eyebrows or eyelashes.
Externally applied cosmetics: This term does not apply to the lips or any body surface covered by mucous membrane. For instance, if a color additive is approved for use in externally applied cosmetics, you may not use it in products such as lipsticks unless the regulation specifically permits this use [21 CFR 70.3 (v)].
Injection: No color additive may be used in injections unless its listing in the regulations specifically provides for such use. This includes injection into the skin for tattooing or permanent makeup. The fact that a color additive is listed for any other use does not mean that it may be used for injections [21 CFR 70.5(b)]. There are no color additives listed in the regulations as approved for injections.
What about special effects and novelty use?
No matter how exotic or novel the color additive or its intended use, it is subject to the same regulations as the more everyday colors and products. The following items are a sampling of some out-of-the-ordinary color additives. This list is not exhaustive. Rather, it is intended to show how the regulations apply to such colors:
Color-changing pigments: Colors that change in response to such factors as change in pH or exposure to oxygen or temperature are subject to the same regulations as all other color additives.
Composite pigments: Color additives used in combination to achieve variable effects, such as those found in pearlescent products, are subject to the same regulations as all other color additives. Some color additives, when used in combination, may form new pigments, which may not be approved for the intended use. An example is a "holographic" glitter, consisting of aluminum, an approved color additive, bonded to an etched plastic film.
Fluorescent colors: Only the following fluorescent colors are approved for use in cosmetics, and there are limits on their intended uses: D&C Orange No. 5, No. 10, and No. 11; and D&C Red No. 21, No. 22, No. 27, and No. 28 [21 CFR 74.2254, 74.2260, 74.2261, 74.2321, 74.2322, 74.2327, and 74.2328].
Glow-in-the-dark colors: Luminescent zinc sulfide is the only approved glow-in-the-dark color additive [21 CFR 73.2995].
Halloween makeup: These products are considered cosmetics [FD&C Act, sec. 201(i); 21 U.S.C. 321(i)] and are therefore subject to the same regulations as other cosmetics, including the same restrictions on color additives.
Liquid crystal colors: These additives, which produce color motifs in a product through diffraction, are unapproved color additives. Their use in cosmetics is therefore illegal [FD&C Act, sec. 601(e); 21 U.S.C. 361(e)].
Tattoo pigments: As noted above, no color additives are approved for injection into the skin, as in tattoos and permanent makeup.
Theatrical makeup: Like Halloween makeup, these products are considered cosmetics [FD&C Act, sec. 201(i); 21 U.S.C. 321(i)] and are therefore subject to the same regulations as other cosmetics, including the same restrictions on color additives.
February 3, 2006; Updated April 29, 2007. This information is current. It is updated only when necessary.
In Cosmetics
Resources for You
Color Additives Listed for Use in Cosmetics (From the Code of Federal Regulations)
Color Additives Permitted for Use in Cosmetics: Quick-Reference Table
Untitled Letter to BASF Regarding Mica-Based Pearlescent Pigments
Color Additive Petitions: Information on the Color Additive Approval Process
Follow FDA Cosmetics on Twitter
Page Last Updated: 01/27/2015
Source: FDA, HHS
Lipstick & Lead: Questions & Answers
FDA has received a number of inquiries from consumers concerned about the amount of lead present in lipstick. FDA's studies have found no lead levels that would pose safety concerns when lipstick is used as intended.
FDA scientists developed an analytical method, published in 2009, for measuring the amount of lead in lipstick. Our initial findings, as well as our expanded findings posted in December 2011, confirm that the amount of lead found in lipstick is very low and does not pose safety concerns.
The following information is drawn from responses to inquiries we have received, along with information on our latest findings.
What is FDA's legal authority over cosmetic safety?
Has FDA set limits for lead in cosmetics?
What are FDA's limits for lead in color additives?
Has FDA been aware of concerns about lead in lipstick?
How did FDA follow up on the October 2007 report on lead in lipstick?
How did FDA follow up on its initial survey of lead in lipstick?
What did FDA's expanded survey reveal about lipsticks on the market?
Is there a safety concern about the lead levels FDA found in lipsticks?
It has been reported that levels of lead in certain lipsticks exceed those for candy. Is this a fair comparison?
What are FDA's next steps for lead in lipstick?
FDA Analyses of Lead in Lipsticks – Initial Survey (Table)
FDA Analyses of Lead in Lipsticks – Expanded Survey (Table)
What is FDA's legal authority over cosmetic safety?
FDA regulates cosmetic safety under the authority of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The FD&C Act requires that cosmetics marketed in interstate commerce be safe when used as directed in the labeling or under customary conditions of use. Cosmetics are not subject to pre-market approval by FDA. However, pre-market approval is required for the color additives used in cosmetics (including those in lipsticks), with the exception of coal-tar hair dyes. To learn more, see FDA Authority Over Cosmetics.
Has FDA set limits for lead in cosmetics?
No, FDA has not set limits for lead in cosmetics. FDA has set specifications for lead in color additives used in cosmetics. FDA approval of color additives is based on safety evaluations that consider the color additives’ intended uses and estimated consumer exposure resulting from those uses. FDA-approved color additives are listed in Title 21 of the U.S. Code of Federal Regulations (CFR). To learn more about FDA-approved color additives, see Color Additives.
What are FDA's limits for lead in color additives?
FDA limits lead in color additives to maximum specified levels, typically no more than 20 parts per million (ppm) for color additives approved for use in cosmetics. In addition, the color additives listed under regulations in 21 CFR Parts 74 and 82 are required to be batch-certified by FDA, which includes testing each batch for lead, before they may be used in cosmetics.
Has FDA been aware of concerns about lead in lipstick?
Yes, reports about lead in lipstick are not new. In the 1990s, reports of analytical results from a commercial testing laboratory suggested that traces of lead in lipstick might be of concern. The Campaign for Safe Cosmetics (CSC), in October 2007, reported finding lead in a selection of lipsticks on the market. Because reports about lead in lipstick have surfaced periodically and because of the time that had elapsed since we last examined information on lipsticks in the marketplace, we decided that further follow-up was needed.
How did FDA follow up on the October 2007 report on lead in lipstick?
FDA scientists developed and validated a highly sensitive method for the analysis of total lead content in lipstick and applied the method to the same lipsticks, that were still available on the market, previously evaluated by the CSC. FDA scientists found lead in all of the 20 lipsticks tested, ranging from 0.09 ppm to 3.06 ppm, with an average value of 1.07 ppm. The detection limit was estimated to be 0.04 ppm. FDA concluded that the lead levels found are within the range that would be expected from lipsticks formulated with permitted color additives and other ingredients that had been prepared under good manufacturing practice conditions.
An article on FDA's testing method, published in the July/August 2009 issue of the peer-reviewed Journal of Cosmetic Science, is available online.1 The article includes results for lead in all the lipsticks we tested. For a table of the results, see FDA Analyses of Lead in Lipsticks – Initial Survey. FDA's testing method is now available for use by any suitable analytical laboratory for the determination of total lead content in lipstick.
How did FDA follow up on its initial survey of lead in lipstick?
FDA conducted an expanded survey of lipsticks, covering a wide variety of shades, prices, and manufacturers. Four hundred lipsticks available on the U.S. market in the spring of 2010 were tested for total lead content. The selection of lipsticks tested was based on the parent company’s market share. We also included some lipsticks from niche markets in an effort to capture lipsticks with unusual characteristics.
Frontier Global Sciences, Inc., a private laboratory based in Seattle, WA, performed the analyses in the expanded survey, following a protocol consistent with FDA’s validated method.1 The laboratory was required to show continued reliability of the results using specific quality control procedures.
What did FDA's expanded survey reveal about lipsticks on the market?
The expanded survey found that the average lead concentration in the 400 lipsticks tested was 1.11 ppm, very close to the average of 1.07 ppm obtained in our initial survey. The results ranged from the detection limit of 0.026 ppm to the highest value of 7.19 ppm. For a table of the results, see FDA Analyses of Lead in Lipsticks – Expanded Survey. The expanded survey will be published in the May/June, 2012, issue of the Journal of Cosmetic Science.2
Is there a safety concern about the lead levels FDA found in lipsticks?
No. We have assessed the potential for harm to consumers from use of lipstick containing lead at the levels found in both rounds of testing. Lipstick, as a product intended for topical use with limited absorption, is ingested only in very small quantities. We do not consider the lead levels we found in the lipsticks to be a safety concern. The lead levels we found are within the limits recommended by other public health authorities for lead in cosmetics, including lipstick.3,4
It has been reported that levels of lead in certain lipsticks exceed those for candy. Is this a fair comparison?
No. The FDA-recommended upper limit for lead in candy is 0.1 ppm. It is not scientifically valid to equate the risk to consumers presented by lead levels in candy, a product intended for ingestion, with that associated with lead levels in lipstick, a product intended for topical use and ingested in much smaller quantities than candy.
What are FDA's next steps for lead in lipstick?
Although we do not believe that the lead content found in our recent lipstick analyses poses a safety concern, we are evaluating whether there may be a need to recommend an upper limit for lead in lipstick in order to further protect the health and welfare of consumers.
References:
1Hepp, N. M., Mindak, W. R., and Cheng, J., "Determination of Total Lead in Lipstick: Development and Single Lab Validation of a Microwave-Assisted Digestion, Inductively Coupled Plasma–Mass Spectrometric Method," Journal of Cosmetic Science, Vol. 60, No. 4, July/August, 2009.
2Hepp, N.M.., “Determination of Total Lead in 400 Lipsticks on the U.S. Market Using a Validated Microwave-Assisted Digestion, Inductively Coupled Plasma–Mass Spectrometric Method,” Journal of Cosmetic Science, accepted for publication in May/June, 2012, issue.
3Letter from Edmund G. Brown, Jr., Attorney General, State of California to J. L. Sean Slattery, David Lavine, and Laralei Paras regarding Proposition 65 claims concerning lead in lipstick, March 3, 2008.
4Health Canada, Draft Guidance on Heavy Metal Impurities in Cosmetics.
Sunlamps and Sunlamp Products (Tanning Beds/Booths)
Description
Risks/Benefits
Information for the Public
Laws, Regulations & Standards
Industry Guidance
Other Resources
The FDA wants consumers to know that UV radiation in tanning devices poses serious health risks. A recent report by the International Agency for Research on Cancer, (IARC), part of the World Health Organization, concludes that tanning devices are more dangerous than previously thought. Exposure to UV radiation, whether from the sun or indoor tanning beds, can cause:
Skin cancer
Skin burns
Premature skin aging
Eye damage (both short- and long-term)
Description
Sunlamp products are electronic products designed to use one or more ultraviolet lamp(s) and are intended for irradiation of any part of the living human body, by ultraviolet radiation with wavelengths in air between 200 and 400 nanometers, to induce skin tanning. Sunlamp products include portable home units, table top models, tanning beds and tanning booths.
The ultraviolet lamps, subject to the performance standard, produce radiation within a prescribed range of wavelengths and are intended for use in sunlamp products.
Risks/Benefits
Sunlamp products for indoor UV tanning may incorporate different types of fluorescent lamps, reflector spot (RS) or High Intensity Discharge (HID) with different levels of energy output and radiation at different wavelengths.
These products are recognized as hazardous and produce over 3,000 hospital emergency room cases a year. This number is based on the average yearly estimate of injuries for 2003 and 2012 (the most recent years for which data are available). It is likely that the actual number of injuries may be higher because this estimate only includes cases that are initially treated in US hospital emergency departments and reported to a central database. This estimate does not include cases that are treated in outpatient clinics, physicians' offices, not medically treated, or not reported.
(Source: National estimates for tanning bed/booth-related injuries, 2003 and 2012 are from the National Electronic Injury Surveillance System – All Injury Program operated by the US Consumer Product Safety Commission in collaboration with the National Center for Injury Prevention and Control (NCIPC), CDC. Estimates were computed by the Office of Statistics and Programming, NCIPC, CDC.)
Overexposure to sunlamps and/or sunlamp products can cause eye and skin injury and allergic reactions. Repeated exposure may cause premature aging of skin and skin cancer.
Information for the Public
The term "suntanning preparations" includes gels, creams, liquids, and other topical products that are intended to provide cosmetic effects on the skin while tanning through exposure to ultraviolet (UV) radiation (such as moisturizing or conditioning products) or to give the appearance of a tan by imparting color to the skin through the application of approved color additives, such as dihydroxyacetone, without the need for exposure to UV radiation.
Because such products include those sold for use at the beach or for use in tanning salons, consumers are strongly encouraged to read carefully the labeling of all tanning products to determine whether or not they provide protection against the harmful effects of UV radiation.
Source: FDA, HHS
Tanning Pills
In their quest for the perfect tan, some people may look for a "magic pill" that will help them achieve this with minimal exposure to ultraviolet (UV) radiation. There are no such pills approved for this purpose. Nevertheless, pills bearing tanning claims continue to appear on the market. Consumers should be aware of risks associated with such products, as well as doubts about their efficacy.
The Claim: Tinting the Skin by Ingesting a Color Additive
So-called tanning pills are promoted for tinting the skin by ingesting massive doses of color additives, usually canthaxanthin. When taken at these large doses - many times greater than the amount normally ingested in food - this substance is deposited in various parts of the body, including the skin, where it imparts a color. The color varies with each individual, ranging from orange to brownish. This coloration is not the result of an increase in the skin's supply of melanin, the substance produced naturally in the skin to help protect it against UV radiation.
'Tanning Pills' Are Not FDA-Approved
Although canthaxanthin is approved by FDA for use as a color additive in foods, where it is used in small amounts, its use in so-called tanning pills is not approved. Imported tanning pills containing canthaxanthin are subject to automatic detention as products containing unsafe color additives.
Adverse Effects Have Been Reported
At least one company submitted an application for the approval of canthaxanthin-containing pills as a tanning agent, but withdrew the application when side effects, such as the deposition of crystals in the eye, were discovered. In the August 1993 issue of American Pharmacy, Darrell Hulisz, Pharm.D., and pharmacist Ginger Boles described this condition - called "canthaxanthin-induced retinopathy" - as "a common adverse effect associated with canthaxanthin use," adding: "The patient experiencing this form of retinopathy rarely is symptomatic, although decreased visual acuity has been reported."
According to the article, the condition is reversible, "although it may take 25 to 60 months for complete resolution, and deposits have been detected for up to seven years following discontinuation of canthaxanthin." Hulisz and Boles also referred to reports of "nausea, cramping, diarrhea, severe itching, and welts" associated with the use of canthaxanthin "tanning" pills.
The following article appeared in the February 1990 issue of FDA Consumer:
Tanning Pills: U.S. Court of Appeals Decision
"French Bronze" Fades Away
You no longer can order a "French Bronze tan" by dialing 1-800-544-1300. U.S. Court of Appeals Judges Irving Kaufman, Richard Cardamone, and Daniel Friedman last October rejected an appeal by a tanning pill distributor to keep her product on the market by claiming its sale was legal under the Food, Drug, and Cosmetic Act.
The distributor, Diane Alberti, was challenging an earlier order by Judge Israel Glasser of the U.S. District Court for the Eastern District of New York. At a Feb. 17, 1989, hearing, the judge had instructed Alberti to stop distributing the "special European formulae" French Bronze Tablets because they contained an unapproved ingredient.
Alberti acknowledged that each tablet contained 30 milligrams of the color additive canthaxanthin, which has not been approved for use in cosmetics. But she claimed that because small amounts of canthaxanthin are used legally in foods and drugs, the Food, Drug, and Cosmetic Act approval extended to use in cosmetics.
As a matter of "statutory construction and simple logic," the appellate court ruled that - because of factors such as varying concentrations - use of substances must be regulated separately for foods, drugs, and cosmetics. An average daily intake of canthaxanthin is only 5.6 milligrams (mostly from foods such as ketchup and salad dressings). But a person taking four French Bronze Tablets a day, the recommended dosage, would consume an additional 120 milligrams.
FDA became suspicious of Alberti's product after an investigator from the agency's Raleigh district office saw a magazine advertisement for the tablets, guaranteeing a "golden tan" in just three weeks. The tablets were available through both telephone order and a New York city mail-order address.
Andrea Latish, an investigator with FDA's New York district office, visited the New York address in January 1988 and found it to be a mail drop location. Letters sent to "French Bronze Tablets," a clerk told Latish, were forwarded to Diane Alberti, president of FBNH Ent., Inc., at 8000 Fourth Avenue in Brooklyn. Alberti distributed the tablets from her home.
Latish made an appointment with Alberti and her lawyer and learned in the meeting that Alberti ordered approximately 1,500 bottles of 80 tablets every month from the manufacturer, Universal Labs, in New Brunswick, N.J. Universal's label lists the ingredients and carries a statement that no nutritional claims are made and the ingredients are for use as a food coloring. Nevertheless, the labels also carry the name "French Bronze Tablets" and a picture of a palm tree.
Alberti developed an instruction brochure for using the pills as tanning tablets and advertised in muscle and fitness magazines. The ads claimed that the pills would help prevent skin blistering and peeling and even skin cancer because they were "Safer than UV ¢ultraviolet| radiation from the sun."
Latish inspected Alberti's home in late January 1988 and found 141 bottles - an estimated $1,615 worth of tanning pills - bearing the label "French Bronze Tablets." Laboratory analysis of samples collected during the inspection confirmed that the tablets contained 30 milligrams of canthaxanthin.
FDA's New York district compliance officer Ira Flaum then wrote FDA headquarters recommending seizure of the tanning pills, based on both the use of an unapproved ingredient and the unsubstantitated drug claims. Before sending a formal seizure request to the U.S. attorney's office in New York, FDA again inspected Alberti's home and found 192 bottles of the pills labeled "French Bronze Tablets." Alberti was continuing to receive shipments from Universal and distribute the tablets as tanning pills.
At FDA's request, U.S. marshals seized 15 cases (24 bottles each) of tanning pills from Alberti's home on June 24, 1988. The pills, valued at more than $4,000, were ordered destroyed in the October 1989 court decision.
October 18, 2000; Updated January 12, 2005. This information is current. It is updated only when necessary.
