What Research Should Be Funded?

In November 2018 through December 15, 2018, the NIH invited public comments to guide the kind of research they will support for the next decade. This comment period was short but critical. Historically, the NIH has been influenced tremendously by business interests that provide huge chucks of financial support to the government and thereby to the NIH. Thus there has ever been any unbiased research funding for nutrition research. This may also be true of other research areas–I am no familiar with them.

I found it very important to submit my commentary, which I did on the 11th of December, so a few days before the deadline. Here I copy-paste my commentary so you can see what I see as weakness in the NIH funding process through my recommendations. There is no way to know if the NIH considers anyone’s recommendations at all. However, it cannot hurt to try. Right? Right. So here is my comment, which starts with the greeting letter. I copy-paste the whole thing. I also attach it in a PDF in case you want to download it–it is a public document now: NIH–comment–AAStanton–12-11-2018

12/11/2018

To: Christopher J. Lynch, Ph.D.
Executive Secretary of the NIH Nutrition Research Task Force
301-827-3988
Email: nutritionresearch@niddk.nih.gov
Input for the Draft Strategic Plan for NIH Nutrition research
Notice Number: NOT-DK-19-004
Response sent to: nutritionresearch@niddk.nih.gov
From: Angela A Stanton, Ph.D.
angela@angelastanton.com

Greetings,

Unlike a private organization, the NIH is funded by tax payers. Its activities are governed by the public interest, that is, its support of research subjects is not guided by special interests or entrenched gate keepers. Therefore, it is expected that all suggested research topics are evaluated without bias and that no arbitrary exclusions can be made when a project approval/rejection is at stake. Over the past several decades, NIH-funded nutrition research has shown funding preference toward certain nutritional-paradigms while continuously ignored others. This is unacceptable. It is important to redirect NIH funding in a way that they are allocated to all areas that can benefit the health of the population. Like in all areas of research, in nutritional research as well, the challenge is to accept and support research that, perhaps, the majority of funding committee members disagree with on a personal level.

This note aims to highlight some areas where NIH funding has historically been lacking, showing bias. Given the high percentage of the population experimenting on its own with various nutritional paradigms without medical guidance, potentially endangering their health, it is of utmost importance that the NIH promotes those research areas for funding as priority that the public now needs. The research must protect and support the public, which is embarking on untested nutritional methods, to provide appropriate evidence-based research for professional guidance and public education.

In the commentary I cover selected areas following the outline of the draft proposal with the same titles and subheadings and quotes for easy reference.

Areas quoting the original draft, where changes are recommended, are in bold-italic-underlined followed by the proposed directions.

PROPOSAL

When I started to work on this proposal, I mentioned this commentary opportunity to a colleague, who said the following:

“When a belief is an axiom, not a hypothesis, no amount of evidence can change it. Rather, evidence simply changes the argument. This is why the evidence against our nutrition beliefs starting in the 1950s and 60s has been impervious to data”

–Vernon L. Smith, 2002 Nobel Laureate of Economics

No one has put the experience the people have with the NIH’s project funding selection process better. How the NIH selects its projects has been questionable—at best. Major revisions are required, indeed must be made, owing to the taxpayers in the interest of the general public. Here I detail some of them.

• Explore Individual Variability in Response to Diet Interventions to Inform Nutrition Science, Improve Health, and Prevent Disease

Studies have shown that individuals respond to the same nutrition differently based on their health status and genetics¹. Research also shows that where the food gets metabolized matters greatly in how the nutrition affects the individual². Since people with type 2 diabetes (T2D) have impaired insulin, their carbohydrate and fat metabolism differ significantly from healthy individuals. There is nearly no research at all comparing the healthy to the metabolically challenged to various nutritional paradigms. The current guidelines all place every single individual into one bucket, the Dietary Guidelines for Americans, which clearly cannot fit both metabolic types. The goal should be to evaluate not one type of nutrition for all, but to explore and utilize findings with all their differences. For example, studies show that there is a significant harm to glucose sensitive, metabolically sick individuals when they are recommended a high carbohydrate diet^3-5, so effort should be made to “Inform Nutrition Science” by dietary interventions such that the metabolically challenged can receive a different nutritional recommendation from the metabolically healthy. This necessitates the establishment of what a metabolically healthy and one who is challenged should consume. Currently, neither of these goals has satisfactorily been met by evidence-based science.

What is recommended:

1. Select all health conditions affected by nutrition
2. Examine which one of them responds and how to a particular proposed nutritional change
3. Decide to fund those research areas where the least amount of information is available and/or where the most areas of controversies are found
4. Spell out in the draft each and every health condition that will be funded for research—leave nothing for the guess-work of the specialist who evaluates the individual proposal for approval.

• The Diabetes Prevention Program (DPP) clinical trial demonstrated that diet and exercise changes designed to achieve 7 percent weight loss can prevent or delay the onset of type 2 diabetes

While the DPP is certainly achieving 7% weight loss and delays the onset of type 2 diabetes, it is rather modest compared to other research that demonstrated more success. For example, a privately funded clinical trial, in which participants have achieved type 2 diabetes reversal, were also able to stop insulin and other medicines, and lost significant weight as well—showing much more promise and benefit³. Research like this should be funded by the NIH and not by private funds. The taxpayers expect meaningful results, not modest improvements, when such results can be shown to be achievable. More research—specifically clinical trials—is needed to evaluate the efficacy of the low carbohydrate diets for all populations afflicted with type 2 diabetes, not just the obese. Obesity is not a prerequisite to T2D similarly how T2D is not a prerequisite for obesity^6,7. Furthermore, there are very few clinical trials evaluating type 1 diabetes management assisted by nutritional means; more research is needed evaluating if the same methods applicable to type 2 diabetes management may also work for type 1 diabetes—current research indicates that this might be the case but findings are mixed⁸.

It is ethically and fundamentally unacceptable for the NIH, a tax-payer funded government organization, to skip/ignore/or deliberately avoid funding research that opposes what its experts support.

Additionally, the NIH experts may not be aware—though should be—that millions of their fellow citizens with metabolic diseases have taken their health into their own hands, without any medical guidance, and by moving against the Dietary Guidelines for Americans embarked on the road to reverse their metabolic disease. The blame for this—should anything harm these people—falls on the NIH for refusing to fund research the people need.

What the grass-root practices of ordinary people clearly suggest for an action plan?

1. Research on all forms of the low carbohydrate diets, including the carnivore diet, which is only animal products, seafood, eggs and dairy
2. Research on the gut flora’s response to the low carbohydrate diets
3. Research on the gut flora’s response to the no-carbohydrate carnivore diets
4. Research why inflammatory markers improve on high-fat low-carbohydrate diets^9-12

• Nutrition as a Relevant Variable Influencing all Biological Responses

Funds supporting research from the NIH affects many researchers. Here is an example:

…I sent the protocol to CAM which flipped it to NIDDK. NIDDK then gave it a truly ignorant review– there wasn’t a single person on the study section whose name I recognized; indeed not one who had either knowledge or even sympathy for a nutritional and metabolic approach vs. a drug trial. The very first review denied the proposal’s credibility on grounds that ‘…didn’t even measure ketone bodies in the urine.’ This was strictly true, because I measured [ketone bodies] in the blood, a far more accurate and precise measure of ketosis. However, the reviewer didn’t know this because he didn’t know that beta-hydroxybutyrate was a ketone body.

The NIH proposal reviewing experts must have enough experience to evaluate a proposal. It is not acceptable to have a reviewer evaluate a research proposal on the ketogenic diet when he/she is not familiar with even the basics of what ketone bodies are.

Recommendations:

1. The NIH should select review experts according to the topics approved for funding
2. Since all reviewers are not masters in all nutritional processes, specialists need to be added to the expert group for the nutritional methods selected for funding
3. It is the NIH’s responsibility to select a lead expert for the evaluation of a paper whose expertise is within the area of expertise required to evaluate the proposed research

• To obtain information about research gaps and opportunities that should be addressed by this Strategic Plan
• Dietary pattern research may focus on specific types of diets (e.g., Western, Mediterranean, vegetarian)

The NIH selection team of experts needs to be able to understand a wide-breath of nutritional topics and be able to make their decisions based on strict detailed guidelines of what is within the budget and what is not. Vague comments, like “Dietary pattern research may focus on specific types of diets (e.g., Western, Mediterranean, vegetarian)” have no room in a tax-payer funded program.

Example:

1. Areas of research must fully be specified, such as:
   1. Western Diet
   2. Paleo Diet
   3. Low carbohydrate Diet
   4. Vegetarian Diet
   5. Vegan Diet
   6. Dash
   7. Very low carbohydrate diet (ketogenic)
   8. SAD (Standard American Diet)
   9. Mediterranean Diet
   10. Carnivore Diet
2. Once this list exists, the committee needs to allocate funds per category such that the funds fill in the current gaps. For example, a quick PubMed search yielded the following already existing research in the above noted nutrition types:
   1. Western Diet: 17433 documents, 8232 on humans
   2. Paleo Diet: 262 documents, 191 on humans
   3. Low Carb Diet (search terms: “low carb”, “very low carb”, LC, and VLC): 104 documents, 78 in humans;
   4. Vegetarian: 3868 documents, 3448 on humans
   5. Vegan Diet: 660 documents, 551 on humans
   6. DASH: 9607 documents, 5428 on humans
   7. Ketogenic Diet (search term: “ketogenic diet” AND “nutrition” NOT “seizure” NOT “cancer”) yielded 129 documents, 73 on humans
   8. SAD: 171 documents, 109 on humans
   9. Mediterranean: 5824 documents, 2166 on humans
   10. Carnivore Diet: 0 documents on humans

Based on this quick review, it is clear that there is no point of further funding research on the Western Diet, the Mediterranean Diet, the Vegetarian Diet, and DASH. However, there is major need to fund the Carnivore Diet, Paleo Diet, Low Carb diet, Vegan Diet, Ketogenic Diet, and the SAD Diet.

Funds should be allocated only to those research areas where additional research will enhance our understanding of how nutrition affects our health before we get sick—e.g. to be able to really establish the “evidence base” for the real Dietary Guideline for Americans of 2020, so that it is based on solid data and not estimations.

Research types brought up as examples in the draft document (such as the three nutrition types listed in the draft) are the most likely to be funded for research by the NIH experts—they must demonstrate clear bias following the examples given in the document.

An organization, such as the NIH, that aims at precision in scientific research must be precise itself in its definitions.

Recommended steps:

1. Evaluate each nutritional areas and name each separately if funds are to be allocated
2. List all “gap areas” of research to be funded, such as carnivore Diet, Paleo Diet, Low Carb diet, Vegan Diet, Ketogenic Diet, and SAD Diet as listed above
3. Publish the precise list of the gap looked for in research by the NIH so the application for funds is streamlined, no researcher is misdirected by vague non-information, and no reviewer has to work on proposals that are not covered by the allocated plan
4. NIH must be as precise in its definitions as what it requires from its researchers who apply for funds

• The Dietary Guidelines for Americans provides evidence-based recommendations for a healthy diet

I personally find this to be the most interesting request made in the NIH Draft. The Dietary Guideline for Americans has no evidence on which it is based—it is not an evidence-based dietary guideline. The Dietary Guideline for Americans is based on an assumed range of studies that don’t exist in PubMed: the SAD (Standard American Diet) currently has 171 documents and only 109 of those are on humans. Clearly, much more research is needed to establish what the NIH can call the Dietary Guideline for Americans.

There have been lots of assumptions made in the creation of the current dietary guideline, such as the importance of heart health by reducing LDL cholesterol via reducing dietary saturated fats. There are no properly conducted human clinical trials that compare the benefits of a diet poor or rich in saturated fats. Furthermore, research evaluating heart health is based on an underlying assumption that lowering LDLc is the most important factor in heart and cardiovascular health. However, to date, no research (that used statistics correctly) has been able to show that reduced LDLc was of heart-health benefit and that the reduction of LDLc by way of a diet low in saturated fat has any heart-health benefit—in fact, it appears that the opposite is true. Several research studies have come to the findings that higher LDLc appears to be protective against heart disease^13,14.

Recommendations:

1. The priority should be to evaluate nutritional gaps and the associated heart and metabolic health to establish a real evidence-based plan for the 2020 Dietary Guidelines of Americans.
2. Make zero assumptions that are based on faulty hypotheses of a previous era.
3. Fund research that proposes to oppose the current heart and metabolic health paradigm so that we can extend our knowledge.
4. Encourage disagreement. Knowledge doesn’t advance by agreement but by disagreement.

Sources

1          Zeevi, D. et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell 163, 1079-1094, doi:10.1016/j.cell.2015.11.001 (2015).
2          Wong, J. M. W. & Jenkins, D. J. A. Carbohydrate Digestibility and Metabolic Effects. The Journal of Nutrition 137, 2539S-2546S, doi:10.1093/jn/137.11.2539S (2007).
3          Hallberg, S. J. et al. Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study. Diabetes Ther. 9 (2018).
4          McKenzie, A. et al. A novel intervention including individualized nutritional recommendations reduces hemoglobin A1c level, medication use, and weight in type 2 diabetes. JMIR Diabetes 2, doi:10.2196/diabetes.6981 (2017).
5          Lennerz, B. S. et al. Management of Type 1 Diabetes With a Very Low–Carbohydrate Diet. Pediatrics 141, doi:10.1542/peds.2017-3349 (2018).
6          Ding, C., Chan, Z. & Magkos, F. Lean, but not healthy: the ‘metabolically obese, normal-weight’ phenotype. Current Opinion in Clinical Nutrition & Metabolic Care 19, 408-417, doi:10.1097/mco.0000000000000317 (2016).
7          Dobson, R. et al. Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity. International Journal Of Obesity 40, 153, doi:10.1038/ijo.2015.151 (2015).
8          Turton, J. L., Raab, R. & Rooney, K. B. Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. PloS One 13, e0194987-e0194987, doi:10.1371/journal.pone.0194987 (2018).
9          Volek, J. S., Fernandez, M. L., Feinman, R. D. & Phinney, S. D. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res 47, doi:10.1016/j.plipres.2008.02.003 (2008).
10        Feinman, R. D. & Volek, J. S. Low carbohydrate diets improve atherogenic dyslipidemia even in the absence of weight loss. Nutr Metab (Lond) 3, doi:10.1186/1743-7075-3-24 (2006).
11        Jonasson, L., Guldbrand, H., Lundberg, A. K. & Nystrom, F. H. Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet. Annals of medicine 46, 182-187, doi:10.3109/07853890.2014.894286 (2014).
12        Ruth, M. R. et al. Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects. Metabolism: clinical and experimental 62, 1779-1787, doi:10.1016/j.metabol.2013.07.006 (2013).
13        Sachdeva, A. et al. Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines. American Heart Journal 157, 111-117.e112, doi:https://doi.org/10.1016/j.ahj.2008.08.010 (2009).
14        Ravnskov, U. et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open 6, doi:10.1136/bmjopen-2015-010401 (2016).

Comments are welcome, as usual, and are moderated for appropriateness.

Angela