Significant Scientific Agreement Research Articles

Introduction

Since its passage in 1990, the Nutrition Labeling and Education Act (NLEA)has become well integrated into federal food policy, although its provisions regarding health claims have generated considerable controversy, and such claims so far are little used. Health claims appear to be a good way of delivering nutritional messages, so it is prudent that we try to resolve differences over the regulation of these claims. Now is the time for constructive dialogue, because the question of whether the health claims provisions of NLEA are good legisla tion probably could be back on the national agenda given the current congressional review of the programs of all regulatory agencies. The Center for Food and Nutrition Policy convened this symposium to initiate constructive dialogue on the health claims provisions of NLEA.Over the past 2 years, we at Georgetown University’s Center for Food and Nutrition Policy have examined the public record on health claims for foods and on national food fortification policy by focusing on the B-vitamin, folate. The basic metabolism of folate is well understood. Moreover, the research needed in this case to establish the “significant scientific agreement” mandated by statute is also less complicated to obtain than other health claims because of the relatively short time between the preventive measure, folate administration in early pregnancy, and the outcome, birth. Compare folate in this regard with the relationship between calcium intake and the development of osteoporosis in the elderly, for example. Thus, assessing folate’s ability to reduce the risk of having infants with neural tube defects (NTDs) should provide a comparatively straightforward case to study in the problems of implementing health claims under NLEA.

Life Is Quantum Biology Effects Explained from the Schrödinger Equation, Serious or Life-Threatening Conditions or Diseases, and COVID-19 Results

Background: A plant based approach was undertaken to ascertain the efficacy of the Technology/Innovation of a new medical Technology based on similar activity to the circulatory system of plants. Basic Technology formulations were introduced into plant structures to evaluate the responses for cell division and plant growth which ultimately lead to the final product. This Technology/Innovation transforms and enhances common botanical/herb products such that they can be used to treat COVID-19 infection and Serious or Life-threatening conditions or diseases. They can restore the diseased cell’s abnormal metabolism to homeostasis and return it to normal function by slowing or reversing the cell’s malfunctioning metabolism, or in other words, slowing or reversing the disease process. Methods: A systematic treatment for COVID-19 infection and Serious or Life-threatening illness in patients is based on theories of traditional Chinese medicine. The Technology/Innovation is developed as dietary supplement products for treatment of Serious or Life-threatening conditions or diseases. Results: The results consist of over one hundred Serious or Life-threatening patient medical records. The U.S. Food and Drug Administration (FDA) reviewed/evaluated/accepted the Technology/Innovation patient medical record results, which included fifty-four COVID-19 patients with Prioritized Review Expedited No.: 2020-2867 CR2020-2596 information on September 16, 2020 and twenty-seven cancer patients Cancer Survival Rate Results in (Table 1) with FDA Establishment Identification No.: 3012327979 information on March 25, 2019 as FDA-Regulated medical products and meet the requirement under FDA Significant Scientific Agreement standards.

Psyllium husk intake and risk of type 2 diabetes: an evidence-based scientific and regulatory review of a qualified health claim conducted by the US Food and Drug Administration.

The US Food and Drug Administration (FDA) received a petition from a company requesting that FDA issue an authorized health claim for the relationship between psyllium husk and a reduced risk of type 2 diabetes. After an initial assessment of the available scientific evidence, FDA determined that significant scientific agreement was lacking for this substance-disease relationship, whereupon the company agreed to have its petition reviewed as a qualified health claim. This article describes the process FDA used in conducting an evidence-based review of the science underpinning the proposed claim and addresses certain safety issues associated with psyllium husk that FDA considered in its review of the petition. Of the 6 studies from which scientific conclusions could be drawn, as identified through FDA's review, psyllium husk significantly improved plasma glucose levels and insulin sensitivity in only 1 study. Therefore, FDA's enforcement discretion letter for this qualified health claim stated: "Psyllium husk may reduce the risk of type 2 diabetes, although the FDA has concluded that there is very little scientific evidence for this claim."

Perspective: Structure-Function Claims on Infant Formula.

In the context of a food product label, the term "claim" refers to information that attributes value to the product. The term extends to many different types of information, from product identity, descriptors of intended use, and identification of characteristic properties to the physiologic effects in the body of substances in the food, including the reduction of risk of disease. Food labeling, which includes claims, provides information that consumers want and use to improve their diets. Consumers prefer short statements on the front label claims to longer, more detailed information, including ingredients statements and a nutrition panel. Three types of claims are permitted in the United States. Nutrient content claims describe the level of the nutrient in the food relative to an established daily value, e.g., "Excellent source of choline," and are subject to composition limits for other nutrients, such as total fat, saturated fat, and cholesterol. Health claims describe the relation between a food substance and the risk of disease, e.g., "Adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis." They must undergo a premarket evaluation by the FDA to ensure that there is significant scientific agreement about the relation in question. The third type of claim, structure-function (SF) claims, has recently come under scrutiny, particularly regarding their use on infant formula. Such claims represent a food's effect on the structure or function of the body for maintenance of good health and nutrition. These claims must be truthful and not misleading, but are not subject to premarket approval before use. The purpose of this perspective is to describe the origins and unique niche of SF claims, and to comment on recent proposals to further regulate such claims on infant formula.

Cholesterol-lowering effects of oat β-glucan

Elevated total and low-density lipoprotein (LDL) cholesterol levels are considered major risk factors for cardiovascular disease. Oat β-glucan, a soluble dietary fiber that is found in the endosperm cell walls of oats, has generated considerable interest due to its cholesterol-lowering properties. The United States Food and Drug Administration (FDA) approved a health claim for β-glucan soluble fiber from oats for reducing plasma cholesterol levels and risk of heart disease in 1997. Similarly, in 2004 the United Kingdom Joint Health Claims Initiative (JHCI) allowed a cholesterol-lowering health claim for oat β-glucan. The present review aims to investigate if results from more recent studies are consistent with the original conclusions reached by the FDA and JHCI. Results of this analysis show that studies conducted during the past 13 years support the suggestion that intake of oat β-glucan at daily doses of at least 3 g may reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 5-10% in normocholesterolemic or hypercholesterolemic subjects. Studies described herein have shown that, on average, oat consumption is associated with 5% and 7% reductions in total and LDL cholesterol levels, respectively. Significant scientific agreement continues to support a relationship between oat β-glucan and blood cholesterol levels, with newer data being consistent with earlier conclusions made by the FDA and JHCI.

Application of Epidemiological Data for Decision Making: Health Claims

The Nutrition Labeling and Education Act (NLEA), which amended the Federal Food, Drug, and Cosmetic Act in 1990, authorized the use of health claims that are based on significant scientific agreement in food labeling. In 1994, the Dietary Supplement Health and Education Act (DSHEA) defined dietary supplements and created a legal framework for use of claims that is similar to the regulation of foods. Health claims describe the relationship between a substance (food or food component) and reduction of the risk of a disease or health-related condition; they are not intended as claims to cure, treat, mitigate, or prevent disease, which are considered drug claims. Since the enactment of the NLEA, the FDA has developed a process to evaluate scientific evidence in support of health claims. In 1999, the FDA published Guidance for Industry: Significant Scientific Agreement in the Review of Health Claims for Conventional Foods and Dietary Supplements. As a result of a series of court cases, the agency developed a process for qualified health claims that characterizes the quality and strength of scientific evidence because these claims are not based on significant scientific agreement. Since 2003, the FDA has published several letters of enforcement discretion for qualified health claims that illustrate the agency's approach to evaluating the scientific literature when the strength of the evidence is not consistent with significant scientific agreement. In 2007, the agency published the draft Guidance for Industry: Evidence-Based Review System for the Scientific Evaluation of Health Claims that further outlined the FDA's approach to evaluating scientific evidence for health claims. In January 2009, the final guidance was posted and replaced the 1999 guidance document as well as the interim guidance related to qualified health claims. The final guidance specifically addresses the use of observational data in the evaluation of health claims and describes the criteria used by the agency in the evaluation of such data. A copy of the guidance can be found on the FDA Web site (http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/ucm073332.htm). The guidance highlights some of the challenges that must be considered for the agency to use observational data to draw scientific conclusions on the relationship between a specific substance and disease or health-related condition for the health claim under review. This article is not subject to US copyright law.

How the US Food and Drug Administration evaluates the scientific evidence for health claims

Health claims describe the relationship between a substance (food or component of food) and a disease or health-related condition. They were first authorized through the Nutrition Labeling and Education Act of 1990. The standard set by the US Congress for the scientific evidence required to authorize a claim was the significant scientific agreement standard. This strong standard was challenged by several manufacturers of dietary supplements. Several court decisions directed the US Food and Drug Administration (FDA) to provide for dietary supplement claims not meeting the significant scientific agreement standard by adding a disclaimer to the claim that would eliminate the claim's potential to be misleading. In December 2002, the FDA announced a major new initiative, "The Consumer Health Information for Better Nutrition Initiative," which, among other things, provided for the use of qualified health claims for both conventional foods and dietary supplements. The process for reviewing the scientific evidence for a claim reaching significant scientific agreement and for those that require qualifying language is the same. In January 2009, the FDA issued a guidance document entitled "Evidence-Based Review System for the Scientific Evaluation of Health Claims." The process used by the FDA to review the scientific evidence for health claims and qualified health claims are described in this article.

Supplemental Calcium and Risk Reduction of Hypertension, Pregnancy-Induced Hypertension, and Preeclampsia: An Evidence-Based Review by the US Food and Drug Administration

The labeling of health claims that meet the significant scientific agreement (SSA) standard (authorized health claims) and qualified health claims on conventional foods and dietary supplements requires premarket approval by the US Food and Drug Administration (FDA). FDA conducts an evidence-based review to determine whether there is sufficient evidence to support an authorized or qualified health claim. An evidence-based review was conducted on the human intervention and observational studies evaluating the role of supplemental calcium in reducing the risk of hypertension, pregnancy-induced hypertension, and preeclampsia. This review provides FDA's evaluation of the current scientific evidence on the role of supplemental calcium in reducing the risk of these three end points. Based on this evidence-based review, the agency concluded that the relationship between calcium and risk of hypertension is inconsistent and inconclusive, and the relationship between calcium and risk of pregnancy-induced hypertension and preeclampsia is highly unlikely.

Health Claims in the United States: An Aid to the Public or a Source of Confusion? 3

Health claims in the United States have been a topic of intense controversy since the mid-1980s. Three categories of claims can currently be used on food and dietary supplement labels in the United States: 1) health claims, 2) nutrient content claims, and 3) structure/function claims. Structure/function claims were authorized under the Dietary Supplement Health and Education Act and describe the effect of a dietary supplement on the structure or function of the body. Nutrient content claims are used to describe the percentage of a nutrient in a product relative to the daily value. Health claims describe a relation between a food, food component, or dietary supplement ingredient and reducing risk of a disease or health-related condition. Health claims are based on a very high standard of scientific evidence and significant scientific agreement. Are U.S. health claims really benefitting public health? Recent evidence suggests that this mode of communication has had limited success and in fact may be misleading to consumers.

Health Claims on Foods in Canada

Interest in the health effects of foods by both industry and consumers has put a spotlight on the role of health claims on foods in Canada. The current regulatory framework governing the use of different health claims on foods in Canada is described and compared with international approaches. Similarities were observed in how risk-reduction claims for serious diseases are managed in the United States, European Union and proposed by Food Standards Australia New Zealand, including the need for premarket authorization and the requirement for a high level of certainty based on the totality of evidence in substantiating this type of claim. However, approaches to permitting function claims other than those for the well-established functions of known nutrients are divergent among the jurisdictions compared. Canada also differs from other jurisdictions in not establishing core nutritional criteria for foods carrying disease risk-reduction claims. A brief overview of the status in Canada of a number of disease risk-reduction claims that have been approved in the United States, based on significant scientific agreement under the Nutrition Labeling and Education Act or through authoritative statements under the Food and Drug Administration Modernization Act, is also provided.

FDA’s Review of Scientific Evidence for Health Claims

AbstractUnder the Federal Food, Drug, and Cosmetic Act health claims on foods or dietary supplements must be authorized by the FDA. Health claims describe the relationship between a food, food component, or dietary supplement and reducing the risk of a disease or health-related condition. Under interim guidance and enforcement discretion, certain qualified health claims have been provided for on foods and dietary supplements; these claims contain language to qualify the quality and strength of scientific evidence to support the claim because they are not based on significant scientific agreement, which is the standard for health claims authorized by the Federal Food, Drug, and Cosmetic Act. In order to meet its statutory responsibility for evaluation of health claims, the agency has developed guidelines for review of scientific evidence in support of a health claim.

Lutein and zeaxanthin intakes and risk of age-related macular degeneration and cataracts: an evaluation using the Food and Drug Administration’s evidence-based review system for health claims

The labeling of health claims that meet the significant scientific agreement standard and of qualified health claims on conventional foods and dietary supplements requires premarket approval by the Food and Drug Administration (FDA). The FDA conducts an evidence-based review to ascertain whether sufficient evidence exists to support a significant scientific agreement standard or a qualified health claim. The FDA recently reviewed intervention and observational studies that evaluated the role of lutein and zeaxanthin in reducing the risk of age-related macular degeneration and cataracts. On the basis of this evidence-based review, the FDA concluded that no credible evidence exists for a health claim about the intake of lutein or zeaxanthin (or both) and the risk of age-related macular degeneration or cataracts.

Chromium Picolinate Intake and Risk of Type 2 Diabetes: An Evidence-Based Review by the United States Food and Drug Administration

The labeling of both health claims that meet significant scientific agreement (SSA) and qualified health claims on conventional foods and dietary supplements requires pre-market approval by the US Food and Drug Administration (FDA). Approval by the FDA involves, in part, a thorough review of the scientific evidence to support an SSA or a qualified health claim. This article discusses FDA's evidence-based review of the scientific evidence on the role of chromium picolinate supplements in reducing the risk of type 2 diabetes. Based on this evidence-based review, FDA issued a letter of enforcement discretion for one qualified health claim on chromium picolinate and risk of insulin resistance, a surrogate endpoint for type 2 diabetes. The agency concluded that the relationship between chromium picolinate intake and insulin resistance is highly uncertain.

Chromium Picolinate Intake and Risk of Type 2 Diabetes: An Evidence-Based Review by the United States Food and Drug Administration

The labeling of both health claims that meet significant scientific agreement (SSA) and qualified health claims on conventional foods and dietary supplements requires pre-market approval by the US Food and Drug Administration (FDA). Approval by the FDA involves, in part, a thorough review of the scientific evidence to support an SSA or a qualified health claim. This article discusses FDA's evidence-based review of the scientific evidence on the role of chromium picolinate supplements in reducing the risk of type 2 diabetes. Based on this evidence-based review, FDA issued a letter of enforcement discretion for one qualified health claim on chromium picolinate and risk of insulin resistance, a surrogate endpoint for type 2 diabetes. The agency concluded that the relationship between chromium picolinate intake and insulin resistance is highly uncertain. SUMMARY In summary (Table 1), there was one intervention study that showed a beneficial effect of chromium picolinate intake on risk of insulin resistance. One other intervention study that provided chromium chloride showed no beneficial effect on insulin resistance. None of the five intervention studies showed a statistically significant beneficial effect of chromium picolinate on FBS and/or OGTT. Furthermore, none of the 10 intervention studies using other forms of chromium showed a beneficial effect of on FBS or OGTT in individuals with normal glucose tolerance. Based on FDA's evidence-based review, the agency concluded that there is very limited credible evidence for a qualified health claim for chromium picolinate and reduced risk of insulin resistance, and therefore reduced risk of type 2 diabetes. The findings of Cefalu et al. have not been replicated, and replication of scientific findings is important to substantiate results. For these reasons, FDA concluded that the existence of a relationship between chromium picolinate intake and reduced risk of either insulin resistance or type 2 diabetes is highly uncertain. On August 25, 2005, FDA issued a letter of enforcement discretion for the labeling of dietary supplements with the following qualified health claim: “One small study suggests that chromium picolinate may reduce the risk of insulin resistance, and therefore possibly may reduce the risk of type 2 diabetes. FDA concludes, however, that the existence of such a relationship between chromium picolinate and either insulin resistance or type 2 diabetes is highly uncertain.” The agency concluded that there was no credible evidence to suggest that chromium picolinate intake may reduce the risk of elevated blood glucose levels.

FDA perspectives on health claims for food labels

The U.S. Food and Drug Administration's regulatory authority over health claims was clarified in 1990 legislation known as the Nutrition Labeling and Education Act (NLEA). This law established mandatory nutrition labeling for most foods and placed restrictions on the use of food label claims characterizing the levels or health benefits of nutrients in foods. NLEA set a high threshold for the scientific standard under which the U.S. Food and Drug Administration (FDA) may authorize health claims, this standard is known as the significant scientific agreement (SSA) standard. Subsequent legislation known as the Food and Drug Administration Modernization Act (FDAMA) provided an alternative to FDA review of the health claim where an U.S. government scientific body other than FDA concluded that there is SSA for a substance/disease relationship. Courts have since extended the scope of health claims to include qualified health claims (QHC) that are health claims not substantiated on evidence that meets the level of SSA standard, but include a qualifying statement intended to convey to the consumer the level of evidence for the claim. FDA has responded by developing an evidence-based ranking system for scientific data to determine the level of evidence substantiating a health claim. The following is an overview of FDA's regulations and evidence-based method for evaluating health claims.

Label Claims for Foods and Supplements: A Review of the Regulations

Consumers are confronted with a vast array of food and dietary supplement products claiming to improve health, manage conditions, and reduce disease risks. Most consumers are unaware of the legal requirements, regulatory processes, and scientific evaluation that underlie these label statements. Labeling for foods and dietary supplements is regulated by the US Food and Drug Administration (FDA). Regulations cover 3 main types of health-related statements: health claims, structure/function claims, and nutrient content claims. Health claims must be supported by "significant scientific agreement" among experts that the claimed benefit of a food or food component on a disease or health-related condition is true. When significant scientific agreement is lacking, qualifying statements may be required on the label to describe the strength of the evidence that supports the claim. Structure/function claims describe an effect of a product on body structure or function, and whereas these claims must be truthful and not misleading, they are not subject to premarket scientific review and approval. Nutrient content claims describe the level of a nutrient in a food or supplement and require FDA approval. By understanding the regulatory framework behind label statements and claims, health care professionals can better assist their patients and clients in making informed decisions.

The Level of Evidence for Permitting a Qualified Health Claim: FDA's Review of the Evidence for Selenium and Cancer and Vitamin E and Heart Disease

Health claims are authorized for the labeling of foods when there is significant scientific agreement among qualified experts on the evidence for a relationship between a food or food component (substance) and a disease. Qualified health claims are permitted when there is less scientific evidence for a substance-disease relationship, therefore requiring qualifying language. The evidence for a relationship between vitamin E and heart disease and selenium and cancer was reviewed by the U.S. FDA. It was determined that there was insufficient evidence to permit a qualified health claim for vitamin E and cancer, whereas there was some evidence for permitting a qualified health claim for selenium and cancer. The rationale for these conclusions is discussed below.

Introduction to and Perspectives from the Symposium on Nutrient Disease Relationships: Closing the Scientific Knowledge Gap

The U.S. Congress through the Nutrition Labeling and Education Act of 1990 authorized the use of health claims on food labels. These claims describe the relationship between a substance and a disease or health-related condition. In addition, Congress directed the U.S. FDA to apply a significant scientific agreement standard in approving these claims. Since 1990, the FDA has approved several health claims, but has also denied claims that did not meet this standard. The purpose of The Nutrient Disease Relationships: Closing the Scientific Knowledge Gap symposium was to provide researchers with perspectives to keep in mind when designing studies that examine the relationship between a nutrient and a disease or health-related condition, to help close the scientific knowledge gap for nutrient-disease relationships of scientific, consumer, and public health interest.

Wholegrain health claims in Europe.

Wholegrain foods are important sources of nutrients and phyto-protective components, which are in short supply in many member states of the EU, including the UK. Encouraging the public to increase consumption of wholegrain foods is a positive health message that has critical public health implications. In February 2002 the UK Joint Health Claims Initiative (JHCI) published its authoritative endorsement that wholegrain foods are associated with a healthy heart (Joint Health Claims Initiative, 2002). This new health claim reflects a similar one in the USA based on the accumulation of epidemiological evidence between 1996 and 2001 from several very large cohort studies in the USA, Finland and Norway, which show a consistent protective effect of whole grain and reduced risk of CHD. The JHCI code of practice on health claims requires that the claimed benefit must be scientifically valid, with evidence supporting efficacy of the food in human consumers, under typical conditions of use. The evidence-based approach consists of the identification of studies, an evaluation of individual references, a critical evaluation of the totality of the evidence and a statement that there is significant scientific agreement to establish the validity of the claim. The studies suggest that an intake of three servings per d may have an important cardio-protective effect. The development of a process for the substantiation of health claims in the UK and in the EU is important to underpin regulatory developments, which should protect the consumer, promote fair trade and encourage innovation in the food industry. The present paper sets out the format of the scientific dossier that was presented to the JHCI and includes a call to promote further research to identify the important protective components in the whole grain 'package' and the biological mechanisms behind the observed beneficial effects on health. The major sources of whole grain in the UK are bread and breakfast cereals, and > 90 % of adults in the UK consume less than three servings per d. Increasing the variety and availability of acceptable wholegrain foods could lead to greater consumption levels, which has important public health implications and offers an attractive and food-based dietary strategy for targeting the whole population.

Health Claims and Disclaimers: Extended Boundaries and Research Opportunities in Consumer Interpretation

In Pearson v. Shalala, the court restricts FDA authority by allowing sellers of dietary supplements to make health claims based on less than “significant scientific agreement” when these claims are accompanied by a disclaimer. The authors raise issues regarding the lack of standards for substantiation and the effectiveness of disclaimers in light of the untested nature of some supplements and the vulnerabilities of some supplement consumers.