Continued from Yesterday
Prevention Vs. Treatment - Continued
The case of beta-carotene is an excellent example of inappropriate application of a therapeutic study design to address a prevention question. Decades ago, observational studies suggested that diets and/or serum high in beta-carotene were associated with a lower risk of certain cancers, including lung cancer. This lead to RCTs published in the mid-1990s (the famous “Finnish trials”19,20) in which lifelong smokers or asbestos workers were supplemented with high doses of antioxidants, such as beta-carotene. The results at the time were shocking: compared to placebo, supplementation with beta-carotene significantly increased the risk of lung cancer in these smokers and asbestos workers. To this day, some people misuse this example is misused to demonstrate that the results of a RCT invalidated earlier epidemiological data. Some clinicians guided by EBM conclude that beta-carotene presents a similar risk of increased lung cancer to all patients, including those who do not smoke or have asbestos exposure, and discontinued its use altogether. Indeed, in its evidence-based review system guidance document, FDA touts this example as one that justifies the EBM approach to data evaluation, stating that the results of RCTs “trump” those of observational studies.3 Ignored is the fact that the RCTs in smokers and asbestos workers asked and answered questions different from those of the earlier epidemiological studies. Assessing the effect of lifelong exposure to a modest amount of a nutrient in the context of the whole diet in a general population that is healthy at baseline is completely different from administering a high dose of a single, purified, and isolated nutrient to a very specific population (eg, lifelong smokers) that is not healthy at baseline (because lung cancer was likely well on its way). In the latter case, beta-carotene was studied as a therapeutic drug, not a nutrient. Asking the question of whether beta-carotene can behave like a drug is certainly worthwhile, sometimes necessary. But the design and interpretation of such a study should be vastly different from one that studies a nutritive effect.
A quote from a recent editorial on nutrition and cancer summarizes the well intended, but misguided, beta-carotene trials: “By analogy, when keys are missing, it is common to look for them under the lamppost where there is light rather than in the murky location where the keys were more likely dropped.”21
Continued Tomorrow
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com/
Showing posts with label Evidence Based Nutrition. Show all posts
Showing posts with label Evidence Based Nutrition. Show all posts
Saturday, March 26, 2011
Thursday, March 24, 2011
New Paradigm of Evidence-Based Nutrition
Continued from Yesterday
A more recent example of inappropriate application of EBM to nutrition research comes from the recent study of the effect of antioxidant supplementation on preeclampsia.17
Investigators randomized more than 10,000 women to receive 1,000 mg vitamin C and 400 IU vitamin E daily or placebo between the 9th and 16th weeks of pregnancy and concluded there was no effect of antioxidants on preeclampsia. Analysis of the findings reveals that the majority of the women enrolled in the study (80%) were using multivitamins, which could have affected their baseline nutritional status and, therefore, their response to the supplemental vitamin C and E. Furthermore, vitamin C and E status was not assessed at baseline or during the study, so one cannot know whether these women were truly in need of supplementation.
Finally, the premise of the study is that oxidative stress may induce preeclampsia.
However, oxidative stress was neither measured at baseline nor during the study, so the “oxidative stress status” of these women was not known; if they were not oxidatively stressed in the first place, it follows that the antioxidant supplements would fail to have an effect. These critical nutritional nuances were overlooked by the investigators and the publishing journal as well. Clinicians should not take the results from this RCT at face value and abandon antioxidant supplementation among this target population, but instead should determine what level of confidence they have that the data from this trial are transferable to the individual patients sitting in their offices.
This “blind faith” in RCTs without consideration of study limitations and quality should be of greater concern than it currently is. A well-designed RCT eliminates variables such as comorbid conditions, concomitant interventions, and assumes individual variability in treatment response will be randomly allocated if the trial is large enough. Conversely, a clinician must carefully consider these same variables when deciding if a particular treatment is suited for an individual patient. From the clinician’s perspective, an RCT may be the best way to determine if a treatment works; however, it reveals little about which individuals will benefit. EBM applies a hierarchy of evidence (with the RCT as the “gold” standard) to guide clinical judgment rather than using clinical judgment as a guide to evidence that is relevant to an individual patient.18 Recommendations, whether they be public health-based or practitioner-patient-based, should be developed from the totality of the available evidence, not on a single study or study design.
Continued Tomorrow
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com/
A more recent example of inappropriate application of EBM to nutrition research comes from the recent study of the effect of antioxidant supplementation on preeclampsia.17
Investigators randomized more than 10,000 women to receive 1,000 mg vitamin C and 400 IU vitamin E daily or placebo between the 9th and 16th weeks of pregnancy and concluded there was no effect of antioxidants on preeclampsia. Analysis of the findings reveals that the majority of the women enrolled in the study (80%) were using multivitamins, which could have affected their baseline nutritional status and, therefore, their response to the supplemental vitamin C and E. Furthermore, vitamin C and E status was not assessed at baseline or during the study, so one cannot know whether these women were truly in need of supplementation.
Finally, the premise of the study is that oxidative stress may induce preeclampsia.
However, oxidative stress was neither measured at baseline nor during the study, so the “oxidative stress status” of these women was not known; if they were not oxidatively stressed in the first place, it follows that the antioxidant supplements would fail to have an effect. These critical nutritional nuances were overlooked by the investigators and the publishing journal as well. Clinicians should not take the results from this RCT at face value and abandon antioxidant supplementation among this target population, but instead should determine what level of confidence they have that the data from this trial are transferable to the individual patients sitting in their offices.
This “blind faith” in RCTs without consideration of study limitations and quality should be of greater concern than it currently is. A well-designed RCT eliminates variables such as comorbid conditions, concomitant interventions, and assumes individual variability in treatment response will be randomly allocated if the trial is large enough. Conversely, a clinician must carefully consider these same variables when deciding if a particular treatment is suited for an individual patient. From the clinician’s perspective, an RCT may be the best way to determine if a treatment works; however, it reveals little about which individuals will benefit. EBM applies a hierarchy of evidence (with the RCT as the “gold” standard) to guide clinical judgment rather than using clinical judgment as a guide to evidence that is relevant to an individual patient.18 Recommendations, whether they be public health-based or practitioner-patient-based, should be developed from the totality of the available evidence, not on a single study or study design.
Continued Tomorrow
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com/
Tuesday, March 22, 2011
New Paradigm of Evidence-Based Nutrition
A Commentary on the Nutrient-Chronic Disease Relationship and the New Paradigm of Evidence-Based Nutrition
A discussion regarding the relationship between predisposition to many chronic diseases and the diet, nutritional status, and lifestyle of an individual.
Continued from Yesterday
Evidence-Based Medicine Vs. Evidence-Based Nutrition
* A PubMed search for “evidence-based medicine” resulted in 41,096 publications; the same search for “evidence-based nutrition” resulted in 37 publications. http://www.ncbi.nlm.nih.gov/sites/entrez Accessed August 10, 2010.
Figure 1. Pyramid describing the hierarchy of evidencebased medicine, the c cornerstone of which is its strong reliance on the randomized, controlled trial as the “gold standard” of evidence.
These nuances, while seemingly apparent, have been largely overlooked in the design and/or interpretation of some of the most resource-intensive, high-profile RCTs conducted in recent years. The results of these recently published trials9–13 by EBM criteria has led to conclusions that there is no evidence to support the supplemental nutrient-chronic disease relationship. But given the clear, yet under-appreciated differences between drugs and nutrients, one must ask a series of importantquestions regarding study design, the questions intended to be addressed, and the questions that were actually addressed and whether broad conclusions can be drawn from these studies to serve as the basis for recommendations (or lack thereof ). If blind application of EBM to nutrition questions is inappropriate, the scientific paradigm within which nutrients should be evaluated needs to be defined.
The Women’s Health Initiative (WHI) trial13 is a glaring example of the difficulties researchers face when conducting large-scale, long-term RCTs examining the effect of supplemental nutrients on chronic disease risk, even when adequate resources are readily available. While well intentioned, the trial (which included multiple arms: calcium and vitamin D supplementation;low-fat diet; hormone replacement therapy) suffered from a host of logistical limitations, including poor compliance, extensive use of supplemental nutrients in the placebo arm (due to ethical constraints), and other administrative difficulties associated with multicenter trials. Because the investigators found themselves caught in an ethical dilemma (WHI was initiated when awareness of the bone-protecting benefits of calcium was just becoming widespread), they could not prevent the use of calcium supplements by the placebo group. The result was a median calcium intake in the placebo group of nearly 1,100 mg/day. Thus, the hypothesis ostensibly tested in the WHI trial was not “low vs. high calcium intake” but “high vs. higher calcium intake.” The erroneous message sent from this multimillion dollar ($625 million), NIH-sponsored trial was that calcium and vitamin D supplementation is not useful for maintaining bone health in post-menopausal women, which is counter to the overwhelming majority of evidence. This has prompted some to question the value of large and expensive RCTs: “The results of the WHI add further evidence that clear answers to questions about the long-term effects of diet on risks of cancers and other major diseases may not be obtainable by large randomized intervention trials, no matter how much money is spent conducting them.”14
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com/
Monday, March 21, 2011
New Paradigm of Evidence-Based Nutrition
A Commentary on the Nutrient-Chronic Disease Relationship and the New Paradigm of Evidence-Based Nutrition
A discussion regarding the relationship between predisposition to many chronic diseases and the diet, nutritional status, and lifestyle of an individual.
Continued from Yesterday
Evidence-Based Medicine Vs. Evidence-Based Nutrition
Unlike pharmaceuticals, which have long been studied under the principles of EBM, nutrition and chronic disease research is in a relative state of infancy. Nutrition researchers have yet to establish clear criteria and guidelines for how best to study the effects of nutrients in humans, and subsequently how to evaluate those findings—in other words, what constitutes evidencebased nutrition (EBN).
In the absence of such guidelines, the long-established principles of EBM and its strong reliance on randomized, controlled trials (RCTs) have been applied to fill this void (Figure 1). Within this paradigm, expert opinion is given the least weight, while practitioners’ clinical experiences are not even considered part of the evidence base.
The traditional RCT is viewed in the EBM hierarchy as the gold standard for research on cause-and-effect relationships, and its design has been more suited to assess the efficacy and safety of drugs, not nutrients. When designed, executed, and analyzed properly, the results of RCTs can be persuasive and provide a high level of certainty.
Such certainty, one could argue, is necessary when assessing the effects of expensive, potent, and potentially dangerous drug therapies. This cost-benefit-risk equation,while appropriate for drugs, is substantially different for nutrients. Several nutrition researchers have, in recent years, raised concerns over what is perceived to be the misapplication of drug-based trials to assess nutrition questions, without taking into account the totality of the evidence or the complexitiesand nuances of nutrition.5–8
Drugs tend generally to have single, targeted effects; drugs are not homeostatically controlled by the body and can easily be contrasted with a true “placebo” group; drugs can act within a relatively short therapeutic window of time, often with large effect sizes. In contrast, nutrients tend to work in complex systems in concert with other nutrients and affect multiple cells and organs; nutrients are homeostatically controlled, and thus the body’s baseline nutrient “status” affects the response to a nutrient intervention; a nutrient intervention group cannot be contrasted with a true placebo group (ie, “zero”exposure group); and with respect to chronic disease prevention,nutrient effect sizes tend to be small and may take decades to manifest. Finally, the very absence (or inadequacy) of a given nutrient produces disease, which is a fundamental differencecompared to drugs (summarized in Table 1).
Continued Tomorrow
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com
A discussion regarding the relationship between predisposition to many chronic diseases and the diet, nutritional status, and lifestyle of an individual.
Continued from Yesterday
Evidence-Based Medicine Vs. Evidence-Based Nutrition
Unlike pharmaceuticals, which have long been studied under the principles of EBM, nutrition and chronic disease research is in a relative state of infancy. Nutrition researchers have yet to establish clear criteria and guidelines for how best to study the effects of nutrients in humans, and subsequently how to evaluate those findings—in other words, what constitutes evidencebased nutrition (EBN).
In the absence of such guidelines, the long-established principles of EBM and its strong reliance on randomized, controlled trials (RCTs) have been applied to fill this void (Figure 1). Within this paradigm, expert opinion is given the least weight, while practitioners’ clinical experiences are not even considered part of the evidence base.
The traditional RCT is viewed in the EBM hierarchy as the gold standard for research on cause-and-effect relationships, and its design has been more suited to assess the efficacy and safety of drugs, not nutrients. When designed, executed, and analyzed properly, the results of RCTs can be persuasive and provide a high level of certainty.
Such certainty, one could argue, is necessary when assessing the effects of expensive, potent, and potentially dangerous drug therapies. This cost-benefit-risk equation,while appropriate for drugs, is substantially different for nutrients. Several nutrition researchers have, in recent years, raised concerns over what is perceived to be the misapplication of drug-based trials to assess nutrition questions, without taking into account the totality of the evidence or the complexitiesand nuances of nutrition.5–8
Drugs tend generally to have single, targeted effects; drugs are not homeostatically controlled by the body and can easily be contrasted with a true “placebo” group; drugs can act within a relatively short therapeutic window of time, often with large effect sizes. In contrast, nutrients tend to work in complex systems in concert with other nutrients and affect multiple cells and organs; nutrients are homeostatically controlled, and thus the body’s baseline nutrient “status” affects the response to a nutrient intervention; a nutrient intervention group cannot be contrasted with a true placebo group (ie, “zero”exposure group); and with respect to chronic disease prevention,nutrient effect sizes tend to be small and may take decades to manifest. Finally, the very absence (or inadequacy) of a given nutrient produces disease, which is a fundamental differencecompared to drugs (summarized in Table 1).
Continued Tomorrow
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com
Sunday, March 20, 2011
New Paradigm of Evidence-Based Nutrition
A Commentary on the Nutrient-Chronic Disease Relationship and the New Paradigm of Evidence-Based Nutrition
A discussion regarding the relationship between predisposition to many chronic diseases and the diet, nutritional status, and lifestyle of an individual.
Abstract
Understanding the role of nutrition in the prevention of long-latency chronic disease is one of the greatest challenges facing the health sciences field today.
The scientific community lacks consensus around how to appropriately generate and/or evaluate the available nutrition data to inform treatment recommendations and public policy decisions.
Evidence-based medicine (EBM) is a well-established research paradigm for the evaluation of drug effects. Currently, EBM is arguably being misapplied in order to establish the relationship between nutrients and human health. Nutrients and other bioactive food components are not drugs, and several distinguishing characteristics are overlooked in the design and/or interpretation of nutrition research. Unlike drugs, nutrients work in complex networks, are homeostatically controlled, and cannot be contrasted to a true placebo group. The beneficial effects of nutrients are small and can take decades to manifest. A new paradigm of evidence-based nutrition (EBN) needs to be established that sets criteria and guidelines for how to best study the effects of nutrients in humans. EBN must consider the complex nuances of nutrients and bioactive food components to better inform the design and interpretation of nutrition research. Practitioners, researchers, and policy makers will be better served by a nutrition-centered framework suited to assess the totality of the available evidence and inform treatment and policy decisions. Several recommendations for guidelines and criteria that could help define the EBN research paradigm are discussed.
Introduction
There is general agreement within the nutrition science and practitioner communities that one’s diet, nutritional status, and lifestyle can substantially predispose one to (or protect against) many chronic diseases and other conditions, including heart disease, diabetes, and cardiovascular disease.
For decades, the US government has invested, and continues to invest, enormous resources to support programs such as the Dietary Guidelines for Americans1 and the Institute of Medicine’s (IOM) Dietary Reference Intakes2 to develop recommendations for diet and nutrient intake levels that will, among other things, reduce chronic disease risk within the population.
The nutrient-chronic disease relationship is also addressed by the Food and Drug Administration (FDA) when it reviews Health Claim and Qualified Health Claim petitions,3 both of which are viewed as broad public health statements. But many questions unique to nutrition still remain when it comes to evaluating the evidence on which these and other recommendations are based. Although a research paradigm for the evaluation of drug effects—evidence-based medicine (EBM)—has been established for years,1 the amount, level, and scope of scientific evidence, and the interpretation needed to support nutrition recommendations, continue to be of intense debate.4–6 Obtaining this evidence has proved to be challenging due to resource and feasibility limitations. Consensus does not yet exist about how to appropriately generate and/or evaluate the available data to inform clinical and/or public policy decision making. These and other important issues are currently being debated by scientists from government (FDA, NIH, USDA), academia, and industry, as well as among practitioners.
Continued Tomorrow
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com
A discussion regarding the relationship between predisposition to many chronic diseases and the diet, nutritional status, and lifestyle of an individual.
Abstract
Understanding the role of nutrition in the prevention of long-latency chronic disease is one of the greatest challenges facing the health sciences field today.
The scientific community lacks consensus around how to appropriately generate and/or evaluate the available nutrition data to inform treatment recommendations and public policy decisions.
Evidence-based medicine (EBM) is a well-established research paradigm for the evaluation of drug effects. Currently, EBM is arguably being misapplied in order to establish the relationship between nutrients and human health. Nutrients and other bioactive food components are not drugs, and several distinguishing characteristics are overlooked in the design and/or interpretation of nutrition research. Unlike drugs, nutrients work in complex networks, are homeostatically controlled, and cannot be contrasted to a true placebo group. The beneficial effects of nutrients are small and can take decades to manifest. A new paradigm of evidence-based nutrition (EBN) needs to be established that sets criteria and guidelines for how to best study the effects of nutrients in humans. EBN must consider the complex nuances of nutrients and bioactive food components to better inform the design and interpretation of nutrition research. Practitioners, researchers, and policy makers will be better served by a nutrition-centered framework suited to assess the totality of the available evidence and inform treatment and policy decisions. Several recommendations for guidelines and criteria that could help define the EBN research paradigm are discussed.
Introduction
There is general agreement within the nutrition science and practitioner communities that one’s diet, nutritional status, and lifestyle can substantially predispose one to (or protect against) many chronic diseases and other conditions, including heart disease, diabetes, and cardiovascular disease.
For decades, the US government has invested, and continues to invest, enormous resources to support programs such as the Dietary Guidelines for Americans1 and the Institute of Medicine’s (IOM) Dietary Reference Intakes2 to develop recommendations for diet and nutrient intake levels that will, among other things, reduce chronic disease risk within the population.
The nutrient-chronic disease relationship is also addressed by the Food and Drug Administration (FDA) when it reviews Health Claim and Qualified Health Claim petitions,3 both of which are viewed as broad public health statements. But many questions unique to nutrition still remain when it comes to evaluating the evidence on which these and other recommendations are based. Although a research paradigm for the evaluation of drug effects—evidence-based medicine (EBM)—has been established for years,1 the amount, level, and scope of scientific evidence, and the interpretation needed to support nutrition recommendations, continue to be of intense debate.4–6 Obtaining this evidence has proved to be challenging due to resource and feasibility limitations. Consensus does not yet exist about how to appropriately generate and/or evaluate the available data to inform clinical and/or public policy decision making. These and other important issues are currently being debated by scientists from government (FDA, NIH, USDA), academia, and industry, as well as among practitioners.
Continued Tomorrow
http://www.naturalmedicinejournal.com/article_content.asp?article=117
http://www.depsyl.com/
http://back2basicnutrition.com/
http://bionutritionalresearch.olhblogspace.com
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