Currently browsing posts about: Conflicts-of-interest

A reader, Emma Calvert, a Senior Food Policy Officerfor the European Union in Brussels, sent me “this article.  She also pointed me to the article Food Navigator wrote about it: “Review hails health benefits of beer-gut alliance.”

Eager to find out what the “beer-gut alliance” might be, I went right to it.

The study: Beer-gut microbiome alliance: a discussion of beer-mediated immunomodulation via the gut microbiome.” Silu Zhang, Shuo Jin, Cui Zhang, Shumin Hu, Huajun Li.  Front. Nutr., 25 July 2023.  Volume 10. https://doi.org/10.3389/fnut.2023.1186927

Background: “As a long-established fermented beverage, beer is rich in many essential amino acids, vitamins, trace elements, and bioactive substances that are involved in the regulation of many human physiological functions.  The polyphenols in the malt and hops of beer are also important active compounds that interact in both directions with the gut microbiome.”

Methods: “This review summarizes the mechanisms by which polyphenols, fiber, and other beneficial components of beer are fermentatively broken down by the intestinal microbiome to initiate the mucosal immune barrier and thus participate in immune regulation.”

Conclusion: “Beer degradation products have anti-inflammatory, anticoagulant, antioxidant, and glucolipid metabolism-modulating potential. ..The positive effects of bioactive substances in beer in cancer prevention, reduction of cardiovascular events, and modulation of metabolic syndrome make it one of the candidates for microecological modulators.”

Funding: “This study was supported by the Open Research Fund of State Key Laboratory of Biological Fermentation Engineering of Beer, under grant no. K202101.”

Conflict of interest: “CZ and SH were employed by Tsingtao Brewery Co. Ltd.  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: This seems like a lot to claim for beer.  Vested interest?  Yes.  The State Key Beer Lab is part of the Tsingtao Brewery Co. Ltd, Qingdao, 266100, China and two of the authors work for the company.  Why do this study?  To distract attention from the harmful effects of alcohol consumption (where do I begin?) and from its calories, and instead give beer a health aura.

Beer, alas, is not a health food, best consumed in moderation if at all.

Sorry.

One of the most viewed articles in The Guardian last week was this one on possible conflicts of interest among WHO panelists dealing with the health effects of the artificial sweetener, aspartame.

The headline: Revealed: WHO aspartame safety panel linked to alleged Coca-Cola front group

The article refers to the release last month of two somewhat contradictory reports on the potential carcinogenicity of the artificial sweetener, aspartame, a situation I referred to in this space as crazy-making.

To review:

• The WHO’s International Agency for Research on Cancer (IARC) classified aspartame as possibly carcinogenic to humans.
• But in the same report, the WHO and FAO Joint Expert Committee on Food Additives (JECFA) said a daily aspartame intake of 40 mg/kg body weight was acceptable.

A  report from US Right to Know poses a possible explanation: “Did a Coca-Cola front group sway a WHO review of aspartame?”

One possible answer: at least six out of 13 JECFA panel members have ties to ILSI, a longtime Coca-Cola front group. [In addition] Both the chair and vice chair of the JECFA panel have ties to ILSI.

I’ve written repeatedly about ILSI actions on behalf of the food industry, most recently about how it tracked responses to my book Unsavory Truth (in which I discuss the organization as a front group).

Just because committee members have affiliations with an industry front group does not mean they cannot be objective about the science of aspartame, and I have certainly heard arguments that anyone who has any stature in nutrition cannot avoid such ties (full disclosure: in the late 1980s, ILSI attempted—unsuccessfully, no surprise—to recruit me for a job).

But it is striking that 8 of 13 members had such an affiliation, a (perhaps) coincidence that got The Guardian’s attention.

At the very least, the membership gives the appearance of a conflict of interest, which is one reason why such things matter.

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.