Establish a Network of Centers of Excellence in Human Nutrition (CEHN) to Overcome the Data Drought in Nutrition Science Research
NIH needs to invest in both the infrastructure and funding to undertake rigorous nutrition clinical trials, so that we can rapidly improve food and make progress on obesity and nutrition-related chronic disease.
The notion that ‘what we eat impacts our health’ has risen to national prominence with the rise of the “Make America Healthy Again” movement, placing nutrition at the center of American politics. This high degree of interest and enthusiasm is starkly contrasted by the limited high quality data to inform many key nutrition questions, a result of the limited and waning investment in controlled, experimental research on diet’s impact on health and disease. With heightened public interest and increasing societal costs due to diet-related diseases (>$250 billion), it is imperative to re-envision a nutrition research ecosystem that is capable of rapidly producing robust evidence relevant to policymakers, regulators and the food industry. This begins with establishing a network of clinical research centers capable of undertaking controlled human nutrition intervention studies at scale. Such a network, combined with enhanced commitment to nutrition research funding, will revolutionize nutrition science and our understanding of how food impacts obesity and metabolic health.
The proposed clinical trial network would be endowed with high capacity metabolic wards and kitchens, with the ability to oversee the long-term stay of large numbers of participants. The network would be capable of deeply phenotyping body composition, metabolic status, clinical risk factors, and the molecular mediators of diet. Such a clinical trial network would publish numerous rigorous clinical trials per year, testing the leading hypotheses that exist in the literature that lack meaningful clinical trials. Such a network would produce evidence of direct relevance to policy makers and the food industry, to inform how to best make long-overdue progress on reforming the food system and reducing the burden of diet-related diseases like obesity and Type 2 diabetes.
Challenge and Opportunity
While commonly viewed in the modern era as a medical science, nutrition research historically began as an agricultural science. Early researchers sought to define food composition of common agricultural products and ensure the food system supplied adequate levels of nutrients at affordable prices to meet nutrient requirements. This history firmly established the field of nutrition in universities embedded in the agricultural extension network and funded in large part by the United States Department of Agriculture (USDA) and relevant food industries. It took decades, until the late 1980s and early 1990s, for nutrition’s impact on chronic diseases like obesity and cardiometabolic to be taken seriously and viewed through a more medicalized lens. Despite this updated view of nutrition as ostensibly a serious medical science, the study of food has arguably never received the level of attention and resources commensurate with both its importance and the challenges in its rigorous study.
Our understanding of obesity and related chronic diseases has increased dramatically over the past 30 years. Despite improved understanding, many nutrition questions remain. For example, what is the impact of food processing and additives on health? What is the role of factors such as genetics and the microbiome (“Precision Nutrition”) in determining the effect of diet? These and more have emerged as key questions facing the field, policymakers and industry. Unfortunately during this time, the capacity to undertake controlled nutrition interventions, the strongest form of evidence generating causal relationships, has atrophied substantially.
Early research examining nutrition and its relationship to chronic diseases (e.g. type of fat and blood cholesterol responses). benefited from the availability of the general clinical research center (GCRCs). GCRCs were largely extramurally funded clinical research infrastructure that provided the medical and laboratory services, as well as metabolic kitchens and staff funding, to conduct controlled dietary interventions. This model produced evidence that continues to serve as the backbone of existing nutritional recommendations. In the mid-2000s, the GCRC infrastructure was largely defunded and replaced with the Clinical Translational Science Awards (CTSAs). CTSAs’ funding model is significantly less generous and provides limited if any funds for key infrastructure such as metabolic kitchens, nursing and laboratory services, and registered dietitian staff, all essential for undertaking controlled nutrition research. The model outsources the burden of cost from the NIH to the funder, a price tag that the pharmaceutical and medical device industries can bear but is simply not met by the food and supplement industry and is beyond the limited research budgets of academic or government research. Without public investment, there is simply no way for nutrition science to keep up with other fields of biomedicine, exacerbating a perception of the American medical system ignoring preventive measures like nutrition and ensuring that nutrition research is rated as ‘low quality’ in systematic reviews of the evidence.
The results attributed to this funding model are strikingly evident, and were readily predicted in two high profile commentaries mourning the loss of the GCRC model. When the field systematically reviews the data, the evidence from controlled feeding trials and chronic disease risk factors are largely published between the 1980s-2000s. More modern data is overwhelmingly observational in nature or relies on dietary interventions that educate individuals to consume a specific diet, rather than providing food – both types of evidence significantly reduce the confidence in results and introduce various biases that downgrade the certainty of evidence. The reality of the limited ability to generate high quality controlled feeding trial data was most evident in the last edition of the Dietary Guidelines Advisory Committee’s report, which conducted a systematic review of ultraprocessed foods (UFPs) and obesity. This review identified only a single, small experimental study, a two-week clinical trial in 20 adults, with the rest of the literature being observational in nature and graded as too limited to draw firm conclusions about UPFs and obesity risk. This state of the literature is the expected reality for all forthcoming questions in the field of nutrition until the field receives a massive infusion of resources. Without funding for infrastructure and research, the situation will worsen, as both the facilities and investigators trained in this work continue to wither, and academic tenure track lines are filled instead by areas currently prioritized by funders (e.g., basic science, global health). How can we expect ‘high certainty’ conclusions in the evidence to inform dietary guidelines when we simply don’t fund research with the capability of producing such evidence? While the GCRCs were far from perfect, the impact of their defunding on nutrition science over the past two decades is apparent from the quality of evidence on emerging topics and an even cursory look at the faculty at legacy academic nutrition departments. Legislators and policymakers should be alarmed at what the trajectory of the field over the last two decades means for public health.
As we deal with crisis levels of obesity and nutrition-related chronic diseases, we must face the realities of our failures to fund nutrition science seriously over the last two decades, and the data drought a lack of funding has caused. It is a critical failure of the biomedical research infrastructure in the United States that controlled nutrition interventions have fallen by the wayside while rates of diet-related chronic diseases have only worsened. It is essential for the health of our nation and our economy to reinvest in nutrition research to a degree never-before-seen in American history, and produce a state-of-the-art network of clinical trial centers capable of elucidating how food impacts health.
Several key challenges exist to produce a coordinated clinical research center network capable of producing evidence that transforms our understanding of diet’s impact on health:
Challenge 1. Few Existing Research Centers Have the Existing Interdisciplinary Expertise Needed to Tackle Pressing Food and Nutrition Challenges
Both food and health are wildly interdisciplinary in nature, requiring the right mix of expertises across plant and animal agriculture, food science, human nutrition, and various fields of medicine to adequately tackle the pressing nutrition-related challenges facing society. However, the current ‘nutrition’ research landscape of the United States reflects its natural, uncoordinated evolution across diverse agricultural colleges and medical centers.
Any proposed clinical research network needs to harmonize the divides and bring together the broad expertises needed to conduct rigorous experimental human nutrition studies into a coordinated network. Conquering this divide will require funding to intentionally build out research centers with the appropriate mix of researchers, staff, infrastructure and equipment necessary to tackle key questions on large cohorts of study participants consuming controlled diets for extended time periods.
Challenge 2. The Study of Food and Nutrition is Intrinsically Challenging
Despite less investment relative to pharmaceuticals and medical devices, the conduct of rigorous nutrition science is often more cost burdensome due to its unique methodological burdens. Typical gold-standard pharmaceutical designs of placebo-controlled randomized double blind trials are impossible for most research questions. Many interventions cannot be blinded. Placebos do not exist for foods, necessitating comparisons between active interventions, of which there are many viable options. Foods are complex interventions, serving as vehicles for many bioactive compounds, making isolating causal factors challenging in the setting of a single study. Researchers must often make zero-sum decisions that balance internal versus external validity, often trading off between rigorous inference and ‘real-world’ application.
Challenge 3. The Study of Food and Nutrition Is Practically Challenging
Historically, controlled trials, including those conducted in GCRC facilities, have been restricted to shorter term interventions (e.g. 1-4 weeks in duration). These short-term trials are the subject of relevant critique, for both failing to capture long-term adaptations to diet as well as relying on surrogate endpoints, of which there are few with significant prognostic capacity. Observing differences in actual disease endpoints in response to food interventions is ideal but investment in such studies has historically been limited. Attempts at a definitive ‘National Diet Heart Study’ trial to address diet-cardiovascular disease hypotheses in the 1960s were ultimately not funded beyond pilot trials. These challenges have long been used to justify underinvestment in experimental nutrition research and exacerbated the field’s reliance on observational data. While presenting real challenges, investment and innovation are needed to tackle these challenges rather than continue avoiding.
These challenges presented by investing in a nutrition clinical research center network pale in comparison to the benefits of its successful implementation. We need only look at the current state of the scientific literature on how to modify diets and food composition to prevent obesity to understand the harms of not investing. The opportunities from doing so are many:
Benefit 1. Build Back Trust in the Scientific Process Surrounding Dietary Recommendation
The deep distrust of the scientific process and in the dietary recommendations from the federal government should be impetus alone for investing heavily in rigorous nutrition research. It is essential for the public to see that the government is taking nutrition seriously. Data alone will not fix public trust but investing in nutrition research, engaging citizens in the process, and ensuring transparency in the conduct of studies and their results will begin to make a dent in the deep distrust that underlies the MAHA movement and that of many food activists over the past several decades.
Benefit 2. Produce Policy- and Formulator-relevant Data
The atrophying of the clinical research network, limited funding and historical separation of expertises in nutrition have led to a situation where we know little about how food influences disease risk, beyond oft-cited links between sodium and blood pressure and saturated fats and LDL-cholesterol. It should be evident from these two long-standing recommendations that have survived many politicized criticisms that controlled human intervention research is the critical foundation of rigorous policy.
In two decades, we need to look back and be able to say the same things about the discoveries ultimately made from studying the next generation of topics around food and food processing. Such findings will be critical for not only policy makers but also from the food industry, who have shown a willingness to reformulate products but often lack the policy guidance and level of evidence needed to do so in an informed manner, leaving their actions to chase trends over science.
Benefit 3. Enhanced Discovery in Emerging Health Research Topics, such as the Microbiome
The potential to rigorously control and manipulate diets to understand their impact on health and disease holds great promise to improve not only public policy and dietary guidance but also shape our fundamental understanding of human physiology, the gut microbiome, diet-x-gene interactions, and impact of environmental chemicals. The previous GCRC network expired prior to numerous technical revolutions in nucleotide (DNA, RNA) sequencing, mass spectrometry, and cell biology that have left nutrition decades behind other advances in medicine.
Benefit 4. Improved Public Health and Reduced Societal Costs
Ultimately, the funding of a clinical research center network that supports the production of rigorous data on links between diet and disease will address the substantial degree of morbidity and mortality caused by obesity and related chronic conditions. This research can be applied to reduce health risks, improve patient outcomes, and lessen the costly burden of an unhealthy nation.
Plan of Action
Congress must pass legislation that mandates the revival and revolution of experimental human nutrition research through the appropriation of funds to establish a network of Centers of Excellence in Human Nutrition (CEHN) research across the country.
Recommendation 1. Congressional Mandate to Review Historical Human Nutrition Research Funding in America and the GCRCs, and:
- Examine of the current landscape of nutrition research happening across the United States;
- Investigate of the deficiencies in the current funding models and clinical research infrastructure;
- Identify key existing infrastructure and infrastructure needs;
- Establish a 10 year timeline to coordinate and fund high priority nutrition research, appropriating at least $5,000,000,000 per year to the CEHN (representing 200% of the current NIH investment in nutrition research, spanning basic to clinical and epidemiological studies).
Congress should seek NIH, USDA, university, industry and public input to inform the establishment of the CEHN and the initial rounds of projects it ultimately funds. Within six months, Congress should have a clear roadmap for the CEHN, including participating centers and researchers, feasibility analyses and cost estimates, and three initial approved proposals. At least (1) proposal should advance existing intramurally funded work on processed foods that has identified several characteristics, including energy density and palatability, as potential drivers of energy intake.
Recommendation 2. Congress Should Mandate that CEHN establish an Operating Charter that Details a Governing Council for the Network Composed of Multi-sector Stakeholders.
This charter will oversee the network’s management and coordination. Specifically, it will:
- Identify key nutrition science stakeholders, including those with perceived contrasting viewpoints, to guide trial design and prioritization efforts;
- Engage non-nutrition science trialists and form partnerships with contract research organizations (CROs) with experience and demonstrated success managing large pharmaceutical trials to ensure innovative and rigorous trial designs are undertaken and CEHN operations are rigorous;
- Identify methods for public involvement in the proposal and funding of proposals, and; issue quarterly mandates to inform the public on updated progress on studies operating within the CEHN,providing new results from its studies and ways for the public to actively participate in this research.
CEHN should be initiated by Congress. It should also explore novel funding mechanisms that pools resources from specific NIH institutes that have historically supported nutrition research (such as the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Heart, Lung, and Blood Institute (NHLBI), NIA, National Institute of Child Health and Human Development (NICHD), the USDA, the Department of Defense, agricultural commodity boards and the food industry to ensure cost-sharing across relevant sectors and a robust, sustainable CEHN. CEHN will ultimately study topics that may produce results that are perceived as adversarial to the food industry and its independence should be protected. However, it is clear that America is not going back to a world where the majority of food is produced in the home in resource scarce settings as occurred when rates of overweight and obesity were low. Thus, engagement with industry actors across the food system will be critical, including food product formulators and manufacturers, restaurants and food delivery companies. Funds should be appropriated to facilitate collaboration between the CEHN and these industries to study effective reformulations and modifications that impact the health of the population.
Conclusion
The current health, social and economic burden of obesity and nutrition-related diseases are indefensible, and necessitate a multi-sector, coordinated approach to reenvisioning our food environment. Such a reenvisioning needs to be based on rigorous science that describes causal links between food and health, and serves innovative solutions to address food and nutrition-related problems. Investment in an intentional, coordinated and well-funded research network capable of conducting rigorous and long-term nutrition intervention trials is long overdue and holds substantial capacity to revolutionize nutritional guidance, food formulation and policy. It is imperative that visionary political leaders overhaul our nutrition research landscape and invest in a network of Centers of Excellence in Human Nutrition that can meet the demands for rigorous nutrition evidence, build back trust in public health, and dramatically mitigate the impacts of nutrition- and obesity-related chronic disease.
This memo produced as part of the Federation of American Scientists and Good Science Project sprint. Find more ideas at Good Science Project x FAS
To better understand what might drive the way we live, learn, and work in 2050, we’re asking the community to share their expertise and thoughts about how key factors like research and development infrastructure and automation will shape the trajectory of the ecosystem.
Recognizing the power of the national transportation infrastructure expert community and its distributed expertise, ARPA-I took a different route that would instead bring the full collective brainpower to bear around appropriately ambitious ideas.
NIH needs to seriously invest in both the infrastructure and funding to undertake rigorous nutrition clinical trials, so that we can rapidly improve food and make progress on obesity.
Modernizing ClinicalTrials.gov will empower patients, oncologists, and others to better understand what trials are available, where they are available, and their up-to-date eligibility criteria, using standardized search categories to make them more easily discoverable.