MODERN DISEASE PREVENTION
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Turn your face to the sun and the shadows fall behind you. — Maori Proverb
BENEFITS OF SUNLIGHT
Each day, Apollo’s fiery chariot makes its way across the sky, bringing life-giving light to the planet. For the ancient Greeks and Romans, Apollo was the god of medicine and healing as well as of sun and light—but Apollo could bring sickness as well as cure. Today’s scientists have come to a similarly dichotomous recognition that exposure to the Ultraviolet Radiation (UVR) in sunlight has both beneficial and deleterious effects on human health.
Most public health messages of the past century have focused on the hazards of too much sun exposure. Ultraviolet A (UVA) radiation (95–97% of the UVR that reaches Earth’s surface) penetrates deeply into the skin, where it can contribute to skin cancer indirectly via generation of DNA-damaging molecules such as hydroxyl and oxygen radicals. Sunburn is caused by too much Ultraviolet B (UVB) radiation; this form also leads to direct DNA damage and promotes various skin cancers. Both forms can damage collagen fibers, destroy vitamin A in skin, accelerate aging of the skin, and increase the risk of skin cancers. Excessive sun exposure can also cause cataracts and diseases aggravated by UVR-induced immunosuppression such as reactivation of some latent viruses.
However, excessive Ultraviolet Radiation exposure accounts for only 0.1% of the total global burden of disease in Disability-Adjusted Life Years (DALYs), according to the 2006 World Health Organization (WHO) report The Global Burden of Disease Due to Ultraviolet Radiation. DALYs measure how much a person’s expectancy of healthy life is reduced by premature death or disability caused by disease. Coauthor Robyn Lucas, an epidemiologist at the National Centre for Epidemiology and Population Health in Canberra, Australia, explains that many diseases linked to excessive UVR exposure tend to be relatively benign—apart from malignant melanoma—and occur in older age groups, due mainly to the long lag between exposure and manifestation, the requirement of cumulative exposures, or both. Therefore, when measuring by DALYs, these diseases incur a relatively low disease burden despite their high prevalence.
In contrast, the same WHO report noted that a markedly larger annual disease burden of 3.3 billion DALYs worldwide might result from very low levels of UVR exposure. This burden subsumes major disorders of the musculoskeletal system and possibly an increased risk of various autoimmune diseases and life-threatening cancers.
The best-known benefit of sunlight is its ability to boost the body’s vitamin D supply; most cases of vitamin D deficiency are due to lack of outdoor sun exposure. At least 1,000 different genes governing virtually every tissue in the body are now thought to be regulated by 1,25-dihydroxyvitamin D3 (1,25[OH]D), the active form of the vitamin, including several involved in calcium metabolism and neuromuscular and immune system functioning.
Although most of the health-promoting benefits of sun exposure are thought to occur through vitamin D photosynthesis, there may be other health benefits that have gone largely overlooked in the debate over how much sun is needed for good health [see “Other Sun-Dependent Pathways,” p. A165]. As for what constitutes “excessive” UVR exposure, there is no one-size-fits-all answer, says Robyn Lucas: “‘Excessive’ really means inappropriately high for your skin type under a particular level of ambient UVR.”
Unlike other essential vitamins, which must be obtained from food, vitamin D can be synthesized in the skin through a photosynthetic reaction triggered by exposure to UVB radiation. The efficiency of production depends on the number of UVB photons that penetrate the skin, a process that can be curtailed by clothing, excess body fat, sunscreen, and the skin pigment melanin. For most white people, a half-hour in the summer sun in a bathing suit can initiate the release of 50,000 IU (1.25 mg) vitamin D into the circulation within 24 hours of exposure; this same amount of exposure yields 20,000–30,000 IU in tanned individuals and 8,000–10,000 IU in dark-skinned people.
The initial photosynthesis produces vitamin D3, most of which undergoes additional transformations, starting with the production of 25-hydroxyvitamin D (25[OH]D), the major form of vitamin D circulating in the bloodstream and the form that is routinely measured to determine a person’s vitamin D status. Although various cell types within the skin can carry out this transformation locally, the conversion takes place primarily in the liver. Another set of transformations occurs in the kidney and other tissues, forming 1,25(OH)D. This form of the vitamin is actually a hormone, chemically akin to the steroid hormones.
1,25(OH)D accumulates in cell nuclei of the intestine, where it enhances calcium and phosphorus absorption, controlling the flow of calcium into and out of bones to regulate bone-calcium metabolism. Michael Holick, a medical professor and director of the Bone Health Care Clinic at Boston University Medical Center, says, “The primary physiologic function of vitamin D is to maintain serum calcium and phosphorous levels within the normal physiologic range to support most metabolic functions, neuromuscular transmission, and bone mineralization.”
Without sufficient vitamin D, bones will not form properly. In children, this causes rickets, a disease characterized by growth retardation and various skeletal deformities, including the hallmark bowed legs. More recently, there has been a growing appreciation for vitamin D’s impact on bone health in adults. In August 2007, the Agency for Health Care Policy and Research published Effectiveness and Safety of Vitamin D in Relation to Bone Health, a systematic review of 167 studies that found “fair evidence” of an association between circulating 25(OH)D concentrations and either increased bone-mineral density or reduced falls in older people (a result of strengthened muscles as well as strengthened bones). “Low vitamin D levels will precipitate and exacerbate osteoporosis in both men and women and cause the painful bone disease osteomalacia,” says Professor Holick.
...
Various studies have linked low 25(OH)D levels to diseases other than cancer, raising the possibility that vitamin D insufficiency is contributing to many major illnesses. For example, there is substantial though not definitive evidence that high levels of vitamin D either from diet or from UVR exposure may decrease the risk of developing multiple sclerosis (MS). Populations at higher latitudes have a higher incidence and prevalence of MS; a review in the December 2002 issue of Toxicology by epidemiology professor Anne-Louise Ponsonby and colleagues from The Australian National University revealed that living at a latitude above 37° increased the risk of developing MS throughout life by greater than 100%.
Still to be resolved, however, is the question of what levels of vitamin D are optimal for preventing the disease—and whether the statistical associations reflect different gene pools rather than different levels of 25(OH)D. (Interestingly, Dr. Michael Holick reported in the August 1988 issue of The Journal of Clinical Endocrinology & Metabolism that no previtamin D3 formed when human skin was exposed to sunlight on cloudless days in Boston, at 42.2°N, from November through February or in Edmonton, at 52°N, from October through March.)
“Scientific evidence on specific effects of vitamin D in preventing MS or slowing its progression is not sufficient,” says Alberto Ascherio, a nutritional epidemiologist at the Harvard School of Public Health. “Nevertheless, considering the safety of vitamin D even in high doses, there is no clear contraindication, and because vitamin D deficiency is very prevalent, especially among MS patients, taking vitamin D supplements and getting moderate sun exposure is more likely to be beneficial than not.”
As with multiple sclerosis, there appears to be a latitudinal gradient for type 1 diabetes, with a higher incidence at higher latitudes. A Swedish epidemiologic study published in the December 2006 issue of Diabetologia found that sufficient vitamin D status in early life was associated with a lower risk of developing type 1 diabetes. Nonobese mice of a strain predisposed to develop type 1 diabetes showed an 80% reduced risk of developing the disease when they received a daily dietary dose of 1,25(OH)D, according to research published in the June 1994 issue of the same journal. And a Finnish study published 3 November 2001 in The Lancet showed that children who received 2,000 IU vitamin D per day from 1 year of age on had an 80% decreased risk of developing type 1 diabetes later in life, whereas children who were vitamin D deficient had a fourfold increased risk. Researchers are now seeking to understand how much UVR/vitamin D is needed to lower the risk of diabetes and whether this is a factor only in high-risk groups.
There is also a connection with metabolic syndrome, a cluster of conditions that increases one’s risk for type 2 diabetes and cardiovascular disease. A study in the September 2006 issue of Progress in Biophysics and Molecular Biology demonstrated that in young and elderly adults, serum 25(OH)D was inversely correlated with blood glucose concentrations and insulin resistance. Some studies have demonstrated high prevalence of low vitamin D levels in people with type 2 diabetes, although it is not clear whether this is a cause of the disease or an effect of another causative factor—for example, lower levels of physical activity (in this case, outdoor activity in particular).
People living at higher latitudes throughout the world are at higher risk of hypertension, and patients with cardiovascular disease are often found to be deficient in vitamin D, according to research by Harvard Medical School professor Thomas J. Wang and colleagues in the 29 January 2008 issue of Circulation. “Although the exact mechanisms are poorly understood, it is known that 1,25(OH)D is among the most potent hormones for down-regulating the blood pressure hormone renin in the kidneys,” says Professor Holick. “Moreover, there is an inflammatory component to atherosclerosis, and vascular smooth muscle cells have a vitamin D receptor and relax in the presence of 1,25(OH)D, suggesting a multitude of mechanisms by which vitamin D may be cardioprotective.”
To determine the potential link betwen sun exposure and the protective effect in preventing hypertension, Rolfdieter Krause of the Free University of Berlin Department of Natural Medicine and colleagues exposed a group of hypertensive adults to a tanning bed that emitted full-spectrum UVR similar to summer sunlight. Another group of hypertensive adults was exposed to a tanning bed that emitted UVA-only radiation similar to winter sunlight. After three months, those who used the full-spectrum tanning bed had an average 180% increase in their 25(OH)D levels and an average 6 mm Hg decrease in their systolic and diastolic blood pressures, bringing them into the normal range. In constrast, the group that used the UVA-only tanning bed showed no change in either 25(OH)D or blood pressure. These results were published in the 29 August 1998 issue of The Lancet. According to Krause, who currently heads the Heliotherapy Research Group at the Medical University of Berlin, a serum 25(OH)D level of at least 40 ng/mL should be adequate to protect against hypertension and other forms of cardiovascular disease (as well as cancers of the prostate and colon).
William Grant, who directs the Sunlight, Nutrition, and Health Research Center, a research and education organization based in San Francisco, suspects that sun exposure and higher 25(OH)D levels may confer protection against other illnesses such as rheumatoid arthritis (RA), asthma, and infectious diseases. “Vitamin D induces cathelicidin, a polypeptide that effectively combats both bacterial and viral infections,” Grant says. “This mechanism explains much of the seasonality of such viral infections as influenza, bronchitis, and gastroenteritis, and bacterial infections such as tuberculosis and septicemia.” For example, rheumatoid arthritis is more severe in winter, when 25(OH)D levels tend to be lower, and is also more prevalent in the higher latitudes. In addition, 25(OH)D levels are inversely associated with the clinical status of rheumatoid arthritis patients, and greater intake of vitamin D has been linked with lower RA risk, as reported in January 2004 in Arthritis & Rheumatism.
Some reports, including an article in the October–December 2007 issue of Acta Medica Indonesiana, indicate that sufficient 1,25(OH)D inhibits induction of disease in rheumatoid arthritis, collagen-induced arthritis, Lyme arthritis, autoimmune encephalomyelitis, thyroiditis, inflammatory bowel disease, and systemic lupus erythematosus. Nonetheless, interventional data are lacking for most autoimmune disorders and infectious diseases, with the exception of TB.
Mark Nathaniel Mead, MSc. Benefits of Sunlight: A Bright Spot for Human Health. 2008. Environmental Health Perspectives (EHP) 116(4): doi:10.1289/ehp.116-a160
Each day, Apollo’s fiery chariot makes its way across the sky, bringing life-giving light to the planet. For the ancient Greeks and Romans, Apollo was the god of medicine and healing as well as of sun and light—but Apollo could bring sickness as well as cure. Today’s scientists have come to a similarly dichotomous recognition that exposure to the Ultraviolet Radiation (UVR) in sunlight has both beneficial and deleterious effects on human health.
Most public health messages of the past century have focused on the hazards of too much sun exposure. Ultraviolet A (UVA) radiation (95–97% of the UVR that reaches Earth’s surface) penetrates deeply into the skin, where it can contribute to skin cancer indirectly via generation of DNA-damaging molecules such as hydroxyl and oxygen radicals. Sunburn is caused by too much Ultraviolet B (UVB) radiation; this form also leads to direct DNA damage and promotes various skin cancers. Both forms can damage collagen fibers, destroy vitamin A in skin, accelerate aging of the skin, and increase the risk of skin cancers. Excessive sun exposure can also cause cataracts and diseases aggravated by UVR-induced immunosuppression such as reactivation of some latent viruses.
However, excessive Ultraviolet Radiation exposure accounts for only 0.1% of the total global burden of disease in Disability-Adjusted Life Years (DALYs), according to the 2006 World Health Organization (WHO) report The Global Burden of Disease Due to Ultraviolet Radiation. DALYs measure how much a person’s expectancy of healthy life is reduced by premature death or disability caused by disease. Coauthor Robyn Lucas, an epidemiologist at the National Centre for Epidemiology and Population Health in Canberra, Australia, explains that many diseases linked to excessive UVR exposure tend to be relatively benign—apart from malignant melanoma—and occur in older age groups, due mainly to the long lag between exposure and manifestation, the requirement of cumulative exposures, or both. Therefore, when measuring by DALYs, these diseases incur a relatively low disease burden despite their high prevalence.
In contrast, the same WHO report noted that a markedly larger annual disease burden of 3.3 billion DALYs worldwide might result from very low levels of UVR exposure. This burden subsumes major disorders of the musculoskeletal system and possibly an increased risk of various autoimmune diseases and life-threatening cancers.
The best-known benefit of sunlight is its ability to boost the body’s vitamin D supply; most cases of vitamin D deficiency are due to lack of outdoor sun exposure. At least 1,000 different genes governing virtually every tissue in the body are now thought to be regulated by 1,25-dihydroxyvitamin D3 (1,25[OH]D), the active form of the vitamin, including several involved in calcium metabolism and neuromuscular and immune system functioning.
Although most of the health-promoting benefits of sun exposure are thought to occur through vitamin D photosynthesis, there may be other health benefits that have gone largely overlooked in the debate over how much sun is needed for good health [see “Other Sun-Dependent Pathways,” p. A165]. As for what constitutes “excessive” UVR exposure, there is no one-size-fits-all answer, says Robyn Lucas: “‘Excessive’ really means inappropriately high for your skin type under a particular level of ambient UVR.”
Unlike other essential vitamins, which must be obtained from food, vitamin D can be synthesized in the skin through a photosynthetic reaction triggered by exposure to UVB radiation. The efficiency of production depends on the number of UVB photons that penetrate the skin, a process that can be curtailed by clothing, excess body fat, sunscreen, and the skin pigment melanin. For most white people, a half-hour in the summer sun in a bathing suit can initiate the release of 50,000 IU (1.25 mg) vitamin D into the circulation within 24 hours of exposure; this same amount of exposure yields 20,000–30,000 IU in tanned individuals and 8,000–10,000 IU in dark-skinned people.
The initial photosynthesis produces vitamin D3, most of which undergoes additional transformations, starting with the production of 25-hydroxyvitamin D (25[OH]D), the major form of vitamin D circulating in the bloodstream and the form that is routinely measured to determine a person’s vitamin D status. Although various cell types within the skin can carry out this transformation locally, the conversion takes place primarily in the liver. Another set of transformations occurs in the kidney and other tissues, forming 1,25(OH)D. This form of the vitamin is actually a hormone, chemically akin to the steroid hormones.
1,25(OH)D accumulates in cell nuclei of the intestine, where it enhances calcium and phosphorus absorption, controlling the flow of calcium into and out of bones to regulate bone-calcium metabolism. Michael Holick, a medical professor and director of the Bone Health Care Clinic at Boston University Medical Center, says, “The primary physiologic function of vitamin D is to maintain serum calcium and phosphorous levels within the normal physiologic range to support most metabolic functions, neuromuscular transmission, and bone mineralization.”
Without sufficient vitamin D, bones will not form properly. In children, this causes rickets, a disease characterized by growth retardation and various skeletal deformities, including the hallmark bowed legs. More recently, there has been a growing appreciation for vitamin D’s impact on bone health in adults. In August 2007, the Agency for Health Care Policy and Research published Effectiveness and Safety of Vitamin D in Relation to Bone Health, a systematic review of 167 studies that found “fair evidence” of an association between circulating 25(OH)D concentrations and either increased bone-mineral density or reduced falls in older people (a result of strengthened muscles as well as strengthened bones). “Low vitamin D levels will precipitate and exacerbate osteoporosis in both men and women and cause the painful bone disease osteomalacia,” says Professor Holick.
...
Various studies have linked low 25(OH)D levels to diseases other than cancer, raising the possibility that vitamin D insufficiency is contributing to many major illnesses. For example, there is substantial though not definitive evidence that high levels of vitamin D either from diet or from UVR exposure may decrease the risk of developing multiple sclerosis (MS). Populations at higher latitudes have a higher incidence and prevalence of MS; a review in the December 2002 issue of Toxicology by epidemiology professor Anne-Louise Ponsonby and colleagues from The Australian National University revealed that living at a latitude above 37° increased the risk of developing MS throughout life by greater than 100%.
Still to be resolved, however, is the question of what levels of vitamin D are optimal for preventing the disease—and whether the statistical associations reflect different gene pools rather than different levels of 25(OH)D. (Interestingly, Dr. Michael Holick reported in the August 1988 issue of The Journal of Clinical Endocrinology & Metabolism that no previtamin D3 formed when human skin was exposed to sunlight on cloudless days in Boston, at 42.2°N, from November through February or in Edmonton, at 52°N, from October through March.)
“Scientific evidence on specific effects of vitamin D in preventing MS or slowing its progression is not sufficient,” says Alberto Ascherio, a nutritional epidemiologist at the Harvard School of Public Health. “Nevertheless, considering the safety of vitamin D even in high doses, there is no clear contraindication, and because vitamin D deficiency is very prevalent, especially among MS patients, taking vitamin D supplements and getting moderate sun exposure is more likely to be beneficial than not.”
As with multiple sclerosis, there appears to be a latitudinal gradient for type 1 diabetes, with a higher incidence at higher latitudes. A Swedish epidemiologic study published in the December 2006 issue of Diabetologia found that sufficient vitamin D status in early life was associated with a lower risk of developing type 1 diabetes. Nonobese mice of a strain predisposed to develop type 1 diabetes showed an 80% reduced risk of developing the disease when they received a daily dietary dose of 1,25(OH)D, according to research published in the June 1994 issue of the same journal. And a Finnish study published 3 November 2001 in The Lancet showed that children who received 2,000 IU vitamin D per day from 1 year of age on had an 80% decreased risk of developing type 1 diabetes later in life, whereas children who were vitamin D deficient had a fourfold increased risk. Researchers are now seeking to understand how much UVR/vitamin D is needed to lower the risk of diabetes and whether this is a factor only in high-risk groups.
There is also a connection with metabolic syndrome, a cluster of conditions that increases one’s risk for type 2 diabetes and cardiovascular disease. A study in the September 2006 issue of Progress in Biophysics and Molecular Biology demonstrated that in young and elderly adults, serum 25(OH)D was inversely correlated with blood glucose concentrations and insulin resistance. Some studies have demonstrated high prevalence of low vitamin D levels in people with type 2 diabetes, although it is not clear whether this is a cause of the disease or an effect of another causative factor—for example, lower levels of physical activity (in this case, outdoor activity in particular).
People living at higher latitudes throughout the world are at higher risk of hypertension, and patients with cardiovascular disease are often found to be deficient in vitamin D, according to research by Harvard Medical School professor Thomas J. Wang and colleagues in the 29 January 2008 issue of Circulation. “Although the exact mechanisms are poorly understood, it is known that 1,25(OH)D is among the most potent hormones for down-regulating the blood pressure hormone renin in the kidneys,” says Professor Holick. “Moreover, there is an inflammatory component to atherosclerosis, and vascular smooth muscle cells have a vitamin D receptor and relax in the presence of 1,25(OH)D, suggesting a multitude of mechanisms by which vitamin D may be cardioprotective.”
To determine the potential link betwen sun exposure and the protective effect in preventing hypertension, Rolfdieter Krause of the Free University of Berlin Department of Natural Medicine and colleagues exposed a group of hypertensive adults to a tanning bed that emitted full-spectrum UVR similar to summer sunlight. Another group of hypertensive adults was exposed to a tanning bed that emitted UVA-only radiation similar to winter sunlight. After three months, those who used the full-spectrum tanning bed had an average 180% increase in their 25(OH)D levels and an average 6 mm Hg decrease in their systolic and diastolic blood pressures, bringing them into the normal range. In constrast, the group that used the UVA-only tanning bed showed no change in either 25(OH)D or blood pressure. These results were published in the 29 August 1998 issue of The Lancet. According to Krause, who currently heads the Heliotherapy Research Group at the Medical University of Berlin, a serum 25(OH)D level of at least 40 ng/mL should be adequate to protect against hypertension and other forms of cardiovascular disease (as well as cancers of the prostate and colon).
William Grant, who directs the Sunlight, Nutrition, and Health Research Center, a research and education organization based in San Francisco, suspects that sun exposure and higher 25(OH)D levels may confer protection against other illnesses such as rheumatoid arthritis (RA), asthma, and infectious diseases. “Vitamin D induces cathelicidin, a polypeptide that effectively combats both bacterial and viral infections,” Grant says. “This mechanism explains much of the seasonality of such viral infections as influenza, bronchitis, and gastroenteritis, and bacterial infections such as tuberculosis and septicemia.” For example, rheumatoid arthritis is more severe in winter, when 25(OH)D levels tend to be lower, and is also more prevalent in the higher latitudes. In addition, 25(OH)D levels are inversely associated with the clinical status of rheumatoid arthritis patients, and greater intake of vitamin D has been linked with lower RA risk, as reported in January 2004 in Arthritis & Rheumatism.
Some reports, including an article in the October–December 2007 issue of Acta Medica Indonesiana, indicate that sufficient 1,25(OH)D inhibits induction of disease in rheumatoid arthritis, collagen-induced arthritis, Lyme arthritis, autoimmune encephalomyelitis, thyroiditis, inflammatory bowel disease, and systemic lupus erythematosus. Nonetheless, interventional data are lacking for most autoimmune disorders and infectious diseases, with the exception of TB.
Mark Nathaniel Mead, MSc. Benefits of Sunlight: A Bright Spot for Human Health. 2008. Environmental Health Perspectives (EHP) 116(4): doi:10.1289/ehp.116-a160
INSTITUTE OF MEDICINE 2011 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D
A new public health report on dietary intake requirements for calcium and vitamin D from the Institute of Medicine, released on 30 November 2010, updates the Institute of Medicine report of 1997. In light of the growing body of research on these nutrients over the past 10–15 yr, the three central questions addressed by the report are:
1) Which health outcomes are influenced by vitamin D and/or calcium intake?
2) How much calcium and vitamin D are needed to achieve desirable health outcomes?
3) How much is too much?
The Institute of Medicine, at the request of agencies of the U.S. and Canadian governments, assembled a committee to update the Dietary Reference Intakes for calcium and vitamin D based upon a rigorous and comprehensive review of the scientific data. The Institute of Medicine Committee included 14 scientists with a broad range of expertise, assisted by experienced Institute of Medicine staff members.
After careful consideration of the evidence, the Institute of Medicine Committee concluded that bone health was the only outcome that satisfied criteria for use as an “indicator” whereby causality was established and the available evidence on dose-response was sufficient to support its use for Dietary Reference Intake development. In addition, serum 25-hydroxyvitamin D (25OHD) levels were considered to be the most useful marker of vitamin D exposure, incorporating endogenous synthesis from solar exposure, dietary intake from foods, fortified products, and/or supplements, and other factors.
For cancer, cardiovascular disease, diabetes, falls, physical performance, autoimmune disorders, and other extraskeletal chronic disease outcomes, the evidence was deemed to be inconsistent, inconclusive as to causality, and insufficient to serve as a basis for Dietary Reference Intake development. Importantly, randomized trial evidence was sparse, and few clinical trials of calcium and/or vitamin D had been done with these extraskeletal outcomes as the primary prespecified outcomes.
The available scientific evidence supports a key role for calcium and vitamin D in skeletal health, providing a sound basis for Dietary Reference Intakes. The evidence, however, is not yet compelling that either nutrient confers benefits for, or is causally related to, extraskeletal health outcomes. Moreover, existing evidence suggests that nearly all individuals meet their needs at intake levels (Recommended Dietary Allowances) provided in this report and, for vitamin D, at 25OHD levels of at least 20 ng/ml (50 nmol/liter) even under conditions of minimal sun exposure. Furthermore, higher levels have not been shown consistently to confer greater benefits, challenging the concept that “more is better.”
The Committee finds that the prevalence of vitamin D inadequacy in the North American population has been overestimated by some groups due to the use of inappropriate cut-points that greatly exceed the levels identified in this report. Serum concentrations of 25-hydroxyvitamin D (25OHD) above 30 ng/ml (75 nmol/liter) are not consistently associated with increased benefit, and risks have been identified for some outcomes at 25OHD levels above 50 ng/ml (125 nmol/liter). Additional research, including large-scale, randomized clinical trials, is needed. In the meantime, however, we believe that there is an urgent clinical and public health need for consensus cut-points for serum 25-hydroxyvitamin D inadequacy to avoid problems of both under-treatment and overtreatment.
Review the full report at www.iom.edu/vitamind for a fuller understanding of the process and the pertinent evidence base. This article was edited for length.
The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know. The Journal of Clinical Endocrinology & Metabolism January 1, 2011 vol. 96 no. 1 53-58.
ALPHA HYDROXY ACIDS IN COSMETICS
Products containing alpha hydroxy acids, also known as AHAs, are marketed for a variety of purposes, such as smoothing fine lines and surface wrinkles, improving skin texture and tone, unblocking and cleansing pores, and improving skin condition in general. Sometimes AHAs are used in cosmetics for other purposes, such as to adjust the pH (the degree of acidity or alkalinity). AHAs used as ingredients in cosmetic and drug products applied to the skin cause exfoliation, or shedding of the surface skin. The extent of exfoliation depends on the type and concentration of the AHA, its pH, and other ingredients in the product.
Some products containing AHAs have been marketed for uses such as treating acne, removing scars, and lightening discolorations. Among these are some products marketed as "skin peelers," which may contain relatively high concentrations of AHAs or other acids and are designed to remove the outer layer of the skin. Products that are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body are drugs under the law (Federal Food, Drug, and Cosmetic Act, Sec. 201(g)). For example, products intended for use as acne treatments or skin lighteners are considered drugs.
The Food and Drug Administration (FDA) received a total of 114 adverse dermatologic experience reports for AHA-containing skin care products between 1992 and February 2004, with the maximum number in 1994. The reported adverse experiences included burning (45), dermatitis or rash (35), swelling (29), pigmentary changes (15), blisters or welts (14), skin peeling (13), itching (12), irritation or tenderness (8), chemical burns (6), and increased sunburn (3). The frequency of such reports for skin exfoliating products that contain AHAs has been considerably lower in subsequent years. The more serious adverse reactions appear to occur most often with products that cause the greatest degree of exfoliation, such as "skin peelers."
FDA research on the safety of AHAs (1) compared the effect of AHAs, topically applied in a cream, on the sensitivity of human skin to ultraviolet (UV) radiation with the effect of the same cream containing no AHAs, (2) measured how fast the skin returns to normal after use of the AHA-containing cream is discontinued, and (3) investigated whether AHAs enhance UV-induced damage to DNA in the skin (Kays Kaidbey, Betsy Sutherland, Paula Bennett, Wayne G. Wamer, Curtis Barton, Donna Dennis, and Andrija Kornhauser, Topical glycolic acid enhances photodamage by ultraviolet light, Photodermatology, Photoimmunology and Photomedicine, vol. 19 (2003), issue 1, pages 21-27).
These studies confirmed previous industry studies indicating that applying AHAs to the skin results in increased UV sensitivity. After four weeks of AHA application, volunteers' sensitivity to skin reddening produced by UV increased by 18 percent. Similarly, the volunteers' sensitivity to UV-induced cellular damage doubled, on average, with considerable differences among individuals. However, the studies also indicated that this increase in sensitivity is reversible and does not last long after discontinuing use of the AHA cream. One week after the treatments were halted, researchers found no significant differences in UV sensitivity among the various skin sites. The FDA studies did not identify exactly how AHAs bring about the increased UV sensitivity, although the effects did not appear to involve dramatic increases in UV-induced damage to DNA in the skin.
Previous FDA studies have indicated that a cosmetic-type cream base caused an AHA to penetrate more deeply into the skin when compared to an AHA solution without the usual cosmetic ingredients. However, further studies will be needed to learn how much, if at all, those cosmetic-type ingredients influence the AHA-related effects on UV sensitivity. The most common AHAs in cosmetic products are glycolic acid and lactic acid. Among others are citric acid, hydroxycaprylic acid, and hydroxycapric acid.
Alpha Hydroxy Acids in Cosmetics. U.S. Department of Health and Human Services, Food and Drug Administration. 07/06/2011. Accessed 07/13/2011. http://www.fda.gov/Cosmetics/ProductandIngredientSafety/SelectedCosmeticIngredients/ucm107940.htm
Products containing alpha hydroxy acids, also known as AHAs, are marketed for a variety of purposes, such as smoothing fine lines and surface wrinkles, improving skin texture and tone, unblocking and cleansing pores, and improving skin condition in general. Sometimes AHAs are used in cosmetics for other purposes, such as to adjust the pH (the degree of acidity or alkalinity). AHAs used as ingredients in cosmetic and drug products applied to the skin cause exfoliation, or shedding of the surface skin. The extent of exfoliation depends on the type and concentration of the AHA, its pH, and other ingredients in the product.
Some products containing AHAs have been marketed for uses such as treating acne, removing scars, and lightening discolorations. Among these are some products marketed as "skin peelers," which may contain relatively high concentrations of AHAs or other acids and are designed to remove the outer layer of the skin. Products that are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body are drugs under the law (Federal Food, Drug, and Cosmetic Act, Sec. 201(g)). For example, products intended for use as acne treatments or skin lighteners are considered drugs.
The Food and Drug Administration (FDA) received a total of 114 adverse dermatologic experience reports for AHA-containing skin care products between 1992 and February 2004, with the maximum number in 1994. The reported adverse experiences included burning (45), dermatitis or rash (35), swelling (29), pigmentary changes (15), blisters or welts (14), skin peeling (13), itching (12), irritation or tenderness (8), chemical burns (6), and increased sunburn (3). The frequency of such reports for skin exfoliating products that contain AHAs has been considerably lower in subsequent years. The more serious adverse reactions appear to occur most often with products that cause the greatest degree of exfoliation, such as "skin peelers."
FDA research on the safety of AHAs (1) compared the effect of AHAs, topically applied in a cream, on the sensitivity of human skin to ultraviolet (UV) radiation with the effect of the same cream containing no AHAs, (2) measured how fast the skin returns to normal after use of the AHA-containing cream is discontinued, and (3) investigated whether AHAs enhance UV-induced damage to DNA in the skin (Kays Kaidbey, Betsy Sutherland, Paula Bennett, Wayne G. Wamer, Curtis Barton, Donna Dennis, and Andrija Kornhauser, Topical glycolic acid enhances photodamage by ultraviolet light, Photodermatology, Photoimmunology and Photomedicine, vol. 19 (2003), issue 1, pages 21-27).
These studies confirmed previous industry studies indicating that applying AHAs to the skin results in increased UV sensitivity. After four weeks of AHA application, volunteers' sensitivity to skin reddening produced by UV increased by 18 percent. Similarly, the volunteers' sensitivity to UV-induced cellular damage doubled, on average, with considerable differences among individuals. However, the studies also indicated that this increase in sensitivity is reversible and does not last long after discontinuing use of the AHA cream. One week after the treatments were halted, researchers found no significant differences in UV sensitivity among the various skin sites. The FDA studies did not identify exactly how AHAs bring about the increased UV sensitivity, although the effects did not appear to involve dramatic increases in UV-induced damage to DNA in the skin.
Previous FDA studies have indicated that a cosmetic-type cream base caused an AHA to penetrate more deeply into the skin when compared to an AHA solution without the usual cosmetic ingredients. However, further studies will be needed to learn how much, if at all, those cosmetic-type ingredients influence the AHA-related effects on UV sensitivity. The most common AHAs in cosmetic products are glycolic acid and lactic acid. Among others are citric acid, hydroxycaprylic acid, and hydroxycapric acid.
Alpha Hydroxy Acids in Cosmetics. U.S. Department of Health and Human Services, Food and Drug Administration. 07/06/2011. Accessed 07/13/2011. http://www.fda.gov/Cosmetics/ProductandIngredientSafety/SelectedCosmeticIngredients/ucm107940.htm
