Currently browsing posts about: Conflicts-of-interest

Last week, my industry-influenced study of the week involved kombucha, although the involvement appeared minimal.

All kombucha and placebo drinks were donated by Craft Kombucha. Craft Kombucha did not have any access to data reported in this study. No author has any financial ties with Craft Kombucha. SD was employed by MedStar Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

One of the authors of the study, Daniel Merenstein, wrote to object to the way I characterized it (quoted with his permission).

…But you do make it very clear in the article that all industry did was donate free drinks and had no access to data. Not sure how that really deserves being called influence. But my much larger point is this statement, ” It’s easy to find claims for its health benefits if you search for them, but much harder to find science to back them up.  IIf you can demonstrate benefits, you can sell more products.  Hence, this study.”

I think it is exactly the opposite. It is much easier to just say your product works or even better yet to get an influencer to drink your product.

But to actually put your product into scientist’s hands and have no access to data or publication is a huge step forward in food science. Look at JAMA every week, almost all the drug studies are -. The kombucha maker should be applauded for their bravery.

We didn’t going looking for a + outcome but registered our trial and stated a priori exactly what we would be looking at and reporting. This study has many limitations but not the ones you mentioned.

Dan

I appreciate thoughtful and respectful letters like this .  This one especially deserves a response.  Dr. Merenstein implies that this is an investigator-initiated study designed to test an investigator-initiated hypothesis.  Such things do happen.  Unfortunately, they are not the norm.

Here’ what concerned me about the study:

• It involved a kombucha company, even if lightly.  Much evidence demonstrates that company involvement in research ia highly correlated with positive outcomes, so much so that it has a name, the “funding effect.”
• Funding influence is thorougly demonstrated to occur at an unconscious level; investigators do not intend to be influenced, are unaware of the influence, do not recognize it, and deny it (even in the face of much research to the contrary).  The unconscious influence usually shows up in the way the research question is asked or in the interpretation of the results.
• Statements that funders have no involvement in the research have coften been shown to be false.  Exceptions do occur; this may well be one of them.
• This is a one-food study.  It is impossible to control such studies for dietary and other lifestyle confounders unless done in a locked metabolic ward.

On this last point, I am always suspicious of one-food studies because I find it hard to believe that a single food can make a measureable difference in chronic disease outcome.

I would like to know a lot more about how the microbiome works before being convinced that kombucha has any special health benefits (I do think it is delicious).

To their great credit, these authors fully disclose the limitations of their study (it was small) .

Dr. Merenstein says this study is really about the science.  In this case then, the bias is one shared by all scientists—a belief and the desire to prove it,–in this case that kombucha has particular health benefits .  If scientists didn’t have such beliefs and desires, no science would ever get done.

Such personal biases are indeed quite different from bias induced by financial interests with a company making a product.

Perhaps I misjudged this one.  If so, I owe Dr. Merenstein and his colleagues a sincere apology, here offered.

I thank him for writing and giving me the opportunity to discuss these issues again.

(For detailed discussion and references on issues related to industry research funding, see my book, Unsavory Truth: How the Food Industry Skews the Science of What We Eat).

At least five readers recently sent me items about research funding by pecan trade associations and I especially thank Lisa Young and Matthew Rees.

But I will begin with Headline vs. Study from the weekly newsletter (invaluable) Obesity & Energetics Offerings (8-18-23).

• Headline: New Research: Regular Pecan Consumption Could Curb Obesity and Reduce Inflammation.
• University News Article: Adding Pecans to Your Diet Could Help Prevent Obesity and Reduce Inflammation.
• Press-Release: Pecans Give Obesity and Diabetes a Slim Chance: Study Shows the Health Benefits of Pecans, Which May Curb Obesity and Reduce Inflammation.
• Study: Pecans and Its Polyphenols Prevent Obesity, Hepatic Steatosis and Diabetes by Reducing Dysbiosis, Inflammation, and Increasing Energy Expenditure in Mice Fed a High-Fat Diet.

Guess who funded this:

• Funding: We acknowledge funding from the Texas Pecan Board and a grant from the Texas Department of Agriculture.
• Conflicts of Interest: The authors declare no conflict of interest.

Comment: Acknowledged or not, the funding establishes a conflicted interest.  Industry funding influences the outcome of research, whether the researchers recognize it or not.  I will say more about that this week in response to a comment from a reader.

In the meantime, here is another one.

• The study: McKay DL, Eliasziw M, Chen CYO, Blumberg JB. A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial. Nutrients. 2018 Mar 11;10(3):339. doi: 10.3390/nu10030339.
• Acknowledgments: This work was supported by the U.S. Department of Agriculture (USDA) Agricultural Research Service under Cooperative Agreement No. 58-1950-014 and the National Pecan Shellers Association. The National Pecan Shellers Association provided the pecans for the intervention.
• Conflicts of Interest: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Comment:  The role of the National Pecan Sheller sAssociation is not clear (to me) from these acknowledgments.  Did the trade association initiate or fund the study, or was its involvement strictly in providing pecans?   Is there a difference?  Perhaps.  It is possible for studies involving vested financial interests to be done objectively, but studies of the “funding effect”—a higher probability of favorable outcomes—to be the norm.  Again, I will speak to this point later this week.

In the meantime, for detailed discussion and references of this issue, see my book, Unsavory Truth: How the Food Industry Skews the Science of What We Eat.

The study: Kombucha tea as an anti-hyperglycemic agent in humans with diabetes – a randomized controlled pilot investigation.  Mendelson Chagai, Sparkes Sabrina, Merenstein Daniel J., Christensen Chloe, Sharma Varun, Desale Sameer, Auchtung Jennifer M., Kok Car Reen, Hallen-Adams Heather E., Hutkins Robert.  Frontiers in Nutrition.  2023;10.  DOI=10.3389/fnut.2023.1190248.

Purpose: “Kombucha is a popular fermented tea that has attracted considerable attention due, in part, to its suggested health benefits. Previous results from animal models led us to hypothesize kombucha may reduce blood sugar levels in humans with diabetes. The objective of this pilot clinical study was to evaluate kombucha for its anti-hyperglycemic activities in adults with diabetes mellitus type II.”

Method: 12 study subjects were instructed to consume kombucha or a placebo (240 ml each) for 4 weeks, then later switch to the other one.

Results: “Kombucha lowered average fasting blood glucose levels at 4 weeks compared to baseline (164 vs. 116 mg/dL, p = 0.035), whereas the placebo did not (162 vs. 141 mg/dL, p = 0.078).”

Conclusion: “In this pilot study, the effect of kombucha consumption on blood glucose levels in adult T2D subjects revealed positive effects. Nonetheless, this study was not sufficiently powered to provide more definitive conclusions.”

Acknowledgment: “We thank Craft Kombucha, Kombucha Brewery in Washington, DC, and especially founder Tanya Maynigo-Loucks for donating the kombucha and for creating and donating the placebo drink for this study.”

Conflicts of interest: “RH is a co-founder of Synbiotic Health; JA has a financial interest in Synbiotic Health. DM serves as President of the Board of Directors of the International Scientific Association for Probiotics and Prebiotics, a non-paid position. All kombucha and placebo drinks were donated by Craft Kombucha. Craft Kombucha did not have any access to data reported in this study. No author has any financial ties with Craft Kombucha. SD was employed by MedStar Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Comment: Synbiotic Health develops and sells probiotic ingredients.  Its “mission is to harness the power of the human microbiome, using the best science to develop precise, scientifically validated microbiome ingredients that support optimal health in every age group.”  Craft Kombucha sells its products in classy cans.  Kombucha is a fermented sweet tea; it contains bacteria and yeast (probiotics).   It’s easy to find claims for its health benefits if you search for them, but much harder to find science to back them up.  IIf you can demonstrate benefits, you can sell more products.  Hence, this study.  High marks to the authors for including the disclaimer: “this study was not sufficiently powered to provide more definitive conclusions.”  Indeed.

My bottom line: drink kombucha if you like it, but don’t expect miracles.

Thanks to Laura Schmidt for this one.  Both of us like kombucha drinks, by the way.

My thanks to Paola Baratto for sending this one.

The study: . Intakes of Added Sugars, with a Focus on Beverages and the Associations with Micronutrient Adequacy in US Children, Adolescents, and Teens (NHANES 2003–2018).  Ricciuto L, Fulgoni VL III, Gaine PC, Scott MO, DiFrancesco L.   Nutrients. 2023; 15(15):3285. https://doi.org/10.3390/nu15153285.

Method: This is an analysis of links between added sugars from different kinds of drinks and nutrient adequacy in children using combined data from 8 consecutive NHANES surveys (2003-2018).

Results: I found the results hard to understand because they are presented selectively by age, and they compare nutrient intakes to estimated average requirements.  Here is what I think they mean:

• 2 to 8 year olds: If they got their sugar from flavored milk, they had better calcium intake.
• 9 to 18 year olds: If they got their sugar from soft drinks, coffee, or tea, thei had worse intakes of magnesium and vitamins A and C.  But if they got their sugars from fruit drinks or flavored milk, they had better intake of vitamin C (from the fruit drinks), and of calcium, magnesium, phosphorus, vitamin A, and potassium (from the flavored milk).
• 9 to 18 year olds: Higher intake of added sugars in the overall diet was associated with bettter intake of vitamins and minerals.

Conclusion: The results suggest that the relationship between added sugars intake and micronutrient adequacy depends on the added sugar sources and their nutrient composition.

Funding: The funding for this research was provided by The Sugar Association, Inc. P.C.G. and M.O.S. are employed by The Sugar Association Inc., had input in the study design, and reviewed and edited the manuscript.

Comment: The Sugar Association’s purpose in sponsoring this study is to buttress its argument that sugary drinks and foods have nutrients and, therefore, do not warrant restrictions.  If you get the idea from this study that the more sugary foods you eat, the more nutrients you and your kids get, the Association will be even happier.  Sorry Sugar Association, but it is quite possible to consume adequate intakes of vitamins and minerals without eating sugary foods and doing so will make calories easier to control.  With this study, the Sugar Association got what it paid for.

I posted several examples of industry-funded studies this week in part to reduce my backlog but also because of charges that (1) doing so constitites ad hominem (personal) attacks on authors, (2) I should be focusing on the science, not who paid for it, and (3) I have my own ideological biases.

To the first point:

I do not see industry funding of research as a personal matter.  I see it as a systematic problem.

If I see a study titled “Effect of food product X on disease Y,” I can often guess that

• The food’s manufacturer or trade association paid for it
• The study outcome will be favorable to the funder’s commercial interests

This phenomenon is so systematic that it has a name: The Funding Effect.

To the second point

Researchers who study funding effects, and there are many, note that the scientific conduct of the studies is not usually an issue.  Instead, the influence of the funders shows up in the way the research question is framed or the results are interpreted.

The easiest way to explain the research question bias is to cite the requests for research proposals I often receive from food trade associations.  These say: “we have (this much money) for research to demonstrate the benefits of our product on (one or more of these conditions).”

These groups will not fund research proposals unlikely to show benefits.

As for interpretation, industry-funded studies tend to report null results as positive; I posted several such examples this week.

To the third point

Yes, I have ideological or opinion biases and I try to be as clear as I can about them.  All investigators have such biases; otherwise they wouldn’t be doing science.  We all have something we believe in that we would like to prove.  Such biases are not discretionary; everyone has them.  In contrast, industry funding is about selling products, not science and is completely discretionary; investigators can do science without it.

The evidence?

I review the evidence for what I’ve just said here in my book, Unsavory Truth: How Food Companies Skew the Science of What We Eat.

In it, I cite many other books and papers addressing these points.

We all come to the same conclusions:

• Industry funding biases research.  But funded investigators do not recognize the influence, and deny it.
• The statement that accompanies many disclosure statements—“The funder had no influence on the design, conduct, interpretation, or publication of the results,”—is often untrue and must be taken with some degree of skepticism.

I see industry funding of food and nutrition research as a serious problem for public perception.  Even when the research is not conflicted, it appears conflicted.  That alone is a systematic problem.

Thanks to Arjan van Groningen for this one.

The study:  The Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-analysis. Zhang, R.; Noronha, J.C.; Khan, T.A.; McGlynn, N.; Back, S.; Grant, S.M.; Kendall, C.W.C.; Sievenpiper, J.L. Nutrients 2023, 15, 1050. https://doi.org/10.3390/nu15041050.

Conclusions: The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.

Funding: This work was supported by an unrestricted grant from the Institute for the Advancement of Food and Nutrition Sciences (IAFNS). The grant was awarded through a competitive request for the proposal process. The sponsor was not involved in the development of the study protocol and design, execution, analyses, interpretation of the data, or decision to publish. The protocol and results were presented to the Low- And No-Calorie Sweeteners Scientific Committee of IAFNS on several occasions with an opportunity for scientific dialogue.

Comment:  IAFNS is the new name for ILSI North America, a classic industry front group.  To its credit, the authors disclose the involvement of IAFNS in this review.  Check out the Conflict-of-Interest declarations from this group; they are legendary.

Conflicts of Interest: J.C.N. has worked as a clinical research coordinator at INQUIS Clinical Research. He has also received research support from Glycemia Consulting Inc. T.A.K. has received research support from the Canadian Institutes of Health Research (CIHR), the International Life Science Institute (ILSI), and the National Honey Board. He has taken honorariums for lectures from the International Food Information Council (IFIC) and the Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America). He is funded by the National Honey Board. N.M., was a former employee of Loblaw Companies Limited, and is a current employee of Enhanced Medical Nutrition. She has completed consulting work for contract research organizations, restaurants, start-ups, the International Food Information Council, and the American Beverage Association, all of which occurred outside of the submitted work. S.M.G. has received honoraria from Dietitians of Canada and Diabetes Canada for the development and delivery of educational resources on the glycemic index in the past five years. C.W.C.K has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada (AAFC), the Almond Board of California, Barilla, the Canadian Institutes of Health Research (CIHR), the Canola Council of Canada, the International Nut and Dried Fruit Council, the International Tree Nut Council Research and Education Foundation, Loblaw Brands Ltd., the Peanut Institute, Pulse Canada, and Unilever. He has received in-kind research support from the Almond Board of California, Barilla, the CaliforniaWalnut Commission, Kellogg Canada, Loblaw Companies, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo, Unico, Unilever, and WhiteWave Foods/Danone. He has received travel support and/or honoraria from Barilla, the CaliforniaWalnut Commission, the Canola Council of Canada, General Mills, the International Nut and Dried Fruit Council, the International Pasta Organization, Lantmannen, Loblaw Brands Ltd., the Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate & Lyle, Unilever, and White Wave Foods/Danone. He has served on the scientific advisory board for the International Tree Nut Council, the International Pasta Organization, the McCormick Science Institute, and Oldways Preservation Trust. He is a founding member of the International Carbohydrate Quality Consortium (ICQC), the Chair of the Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the EASD, and is a Director of Glycemia Consulting and the  Toronto 3D Knowledge Synthesis and Clinical Trials foundation. J.L.S. has received research support from the Canadian Foundation for Innovation, the Ontario Research Fund, the Province of Ontario
Ministry of Research and Innovation and Science, the Canadian Institutes of health Research (CIHR),  Diabetes Canada, the American Society for Nutrition (ASN), the International Nut and Dried Fruit Council (INC) Foundation, the National Honey Board (U.S. Department of Agriculture [USDA] honey “Checkoff” program), the Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, the Quaker Oats Center of Excellence, the United Soybean Board (USDA soy “Checkoff” program), the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), the Plant Protein Fund at the University of Toronto (a fund which has received contributions from IFF), and the Nutrition Trialists Network Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received food donations to support randomized controlled trials from the Almond Board of California, the California Walnut Commission, the Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods/Danone, Nutrartis, and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from ASN, Danone, Dairy Farmers of Canada, FoodMinds LLC, Nestlé, Abbott, General Mills, Nutrition Communications, the International Food Information Council (IFIC), the Calorie Control Council, the International Sweeteners Association, and the International Glutamate Technical Committee. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, Phynova, and Inquis Clinical Research. He is a former member of the European Fruit Juice Association Scientific Expert Panel and a former member of the Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, the European Association for the study of Diabetes (EASD), the Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid member of the Board of Trustees and an unpaid scientific advisor for the Carbohydrates Committee of IAFNS. He is a member of the International Carbohydrate Quality Consortium (ICQC), an Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and a Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. R.Z. and S.B. have no conflicts of interest to declare.

I have been sent so many examples of industry-funded studies that I can’t keep up with them.  This is a slow news week and I’m traveling, so how about I post several.  Here’s the first.

My thanks to Katie Iwanowski for sending this one.

The study: The Relationship of Ready-to-Eat Cereal Intake and Body Weight in Adults: A Systematic Review of Observational Studies and Controlled Trials Lisa M. Sanders, Mary R. Dicklin, Yong Zhu, Kevin C. Maki.  Advances in Nutrition, Volume 14, Issue 4, 2023, Pages 671-684.  https://doi.org/10.1016/j.advnut.2023.05.001.

Results:  RTEC[Ready to Eat Cereal] consumers (2 – 4 servings a week), as compared with non- and less frequent consumers have lower BMI, lower prevalence of overweight/obesity, less weight gain over time,  less anthropometric evidence of abdominal adiposity.

Conclusions:

• RTEC may be used as a meal or snack replacement as part of a hypocaloric diet, but this approach is not superior to other options for those attempting to achieve an energy deficit.
• RTEC consumption was not associated with significantly less loss of body weight, or with weight gain, in any of the RCTs.
• RTEC intake is associated with favorable body weight outcomes in adults in observational studies.
• RTEC does not hinder weight loss when used as a meal or snack replacement within a hypocaloric diet.

Funding: This research was funded by Bell Institute of Health and Nutrition, General Mills Inc. The funding sponsor commented on the study design’s early aspects, reviewed the final data, and provided input to the manuscript.

Author disclosures: LMS is a consulting scientist, and MRD and KCM are employees of Midwest Biomedical Research, which has received research funding from General Mills Inc and Kellogg Company. LMS has received funding from Kellogg Company. YZ is an employee of General Mills Inc.

Comment: This cereal study was funded by a cereal company which—this is quite unusual—disclosed its involvement in the study’s design, interpretation, and writing.  The study results are a classic example of interpretation bias.  Basically, breakfast cereals don’t make much difference to body weight (it’s overall calorie balance that counts), but the conclusions are spun positively.  I especially like the double negative, “not associated with significantly less loss….”

The British journal, Public Health Nutrition, published a debate about ultra-processed foods this month.

Invited commentaries

CON:  Michael Gibney.  Ultra-processed foods in public health nutrition: the unanswered questions,

Several definitions of the degree of processing have been proposed. However, when each of these is used on a common database of nutritional, clinical and anthropometric variables, the observed effect of high intakes of highly processed food, varies considerably.. Moreover, assigning a given food by nutritional experts, to its appropriate level of processing, has been shown to be variable. Thus, the subjective definitions of the degree of food processing and the coding of foods according to these classifications is prone to error…Another issue that need[s] resolution is the relative importance of the degree of food processing and the formulation of a processed food. Although correlational studies linking processed food and obesity abound, there is a need for more investigative studies.

PRO: Mark Lawrence.  Ultra-processed foods: a fit-for-purpose concept for nutrition policy activities to tackle unhealthy and unsustainable diets.  Also an addendum: Ultra-processed foods: a fit-for-purpose concept for nutrition policy activities to tackle unhealthy and unsustainable diets.

This commentary describes the UPF concept as being fit-for-purpose in providing guidance to inform policy activities to tackle unhealthy and unsustainable diets. There is now a substantial body of evidence linking UPF exposure with adverse population and planetary health outcomes. The UPF concept is increasingly being used in the development of food-based dietary guidelines and nutrition policy actions. It challenges many conventional nutrition research and policy activities as well as the political economy of the industrial food system. Inevitably, there are politicised debates associated with UPF and it is apparent a disproportionate number of articles claiming the concept is controversial originate from a small number of researchers with declared associations with UPF manufacturers.

Letters to the editor

CON: Mark J Messina, John L Sievenpiper, Patricia Williamson, Jessica Kiel, John W Erdman.  Ultra-processed foods: a concept in need of revision to avoid targeting healthful and sustainable plant-based foods

we take issue with his perspective on our recently published article in which we make two fundamental points. First, the common criticisms of ultra-processed foods (UPF) do not apply to soya-based meat and dairy alternatives more so than they do to their animal-based counterparts, meat and cows’ milk, despite the former being classified as UPF and the latter as unprocessed/minimally processed foods. Second, NOVA is overly simplistic and does not adequately evaluate the nutritional attributes of meat and dairy alternatives based on soya….We therefore stand by our opinion that NOVA does a disservice to the public by suggesting that because soya burgers and soyamilk are NOVA-classified as UPF, they should be avoided. These foods can aid in the transition to and maintenance of plant-based diets.

PRO:  Mark Lawrence. The need for particular scrutiny of claims made by researchers associated with ultra-processed food manufacturers.

In this Commentary, I referred to challenges the UPF concept presents to researchers with declared associations with UPF manufacturers. The interplay between nutrition research and commercial interests is a widely recognised phenomenon in the commercial determinants of health literature…UPF-related research has become highly politicised and the integrity of the claims presented by researchers associated with UPF manufacturers demands close scrutiny.

Comment

In his letter, Mark Lawrence noted my having included the paper by Messina et al as one of my “industry-funded studies of the week” on this website.  In it, I reproduced the unusually long conflict of interest declaration of the authors, many of them disclosing ties to companies making ultra-processed foods.  Again, the ultra-processed concept is backed up by an extraordinary amount of research far beyond the point where it can be ignored or dismissed out of hand.

Professor Lawrence explains why there is so much pushback: “It [the UPF concept] challenges many conventional nutrition research and policy activities as well as the political economy of the industrial food system.”