Currently browsing posts about: Conflicts-of-interest

The Associated Press reporter Candice Choi has a special interest in industry-funded research (as I do) and has been using emails obtained through FOIA requests to document connections between funders and researchers that otherwise would not come to light.

Yesterday, she reported some follow up on the article I was surprised to see published in the Annals of Internal Medicine—the one I wrote about in my last post.

Ms. Choi came up with these delicious tidbits:

• Mars Inc., which is one of the companies that funds ILSI (the International Life Sciences Institute, which funded the study in the Annals charging that dietary guidelines for sugar are based on weak evidence), is now denouncing the study on the grounds that “the paper undermines the work of public health officials and makes all industry-funded research look bad…[and] creates more doubt for consumers rather than helping them make better choices.”
• Mars is saying this even though emails show that two Mars executives knew about the study last year.
• Mars now said it will make clear to ILSI hat it does not support such work.
• ILSI’s executive director says ILSI devised the concept for the study, but the paper originally said that the authors wrote the protocol and conducted the study independently from the funder. Oops.  When confronted with the Associated Press emails “showing the group sent the authors ‘requested revisions’ on the proposal last year,” the journal corrected that statement to make clear that ILSI “reviewed and approved” the protocol.
• One of the authors did not fully disclose her consulting and research agreements with companies that make high-sugar foods.  The AP had emails demonstrating this author’s financial ties to Coca-Cola and to ILSI for a previous grant on the same topic.  The Annals now show a more complete disclosure statement.

The point of all this is that when food companies sponsor research, they sometimes are much more involved in it than they would like to let on.

Mars is right.  These kinds of incidents make all industry-funded research look bad.  Mars should know.  It funds research to make chocolate look like a health food.

I haven’t posted an industry-funded study for a while, but here’s a good one.  This is a systematic review published in the Annals of Internal Medicine attacking dietary advice to eat less sugar on the grounds that such advice is not scientifically justified.

This one doesn’t pass the laugh test.

What are dietary guidelines supposed to do?  Tell people to eat more sugar?

This review is particularly peculiar:

• It was funded by the International Life Sciences Institute (ILSI), a food-industry front group.
• Two of the four authors consult for ILSI, and one of the two is on the scientific advisory board of Tate & Lyle, the British sugar company.
• The authors admit that “given our funding source, our study team has a financial conflict of interest and readers should consider our results carefully.”  No kidding.
• It was published by a prestigious medical journal.  Why?
• It is accompanied by an editorial that thoroughly demolishes every single one of the authors’ arguments.

I can understand why ILSI wanted this review.  Many of its funders make sugary foods and drinks.  They would like to:

• Cast doubt on the vast amounts of research linking excessive sugar intake to poor health.
• Discredit dietary guidelines aimed at reducing sugar consumption.
• Head off regulatory attempts to tax or label added sugars.

In funding this study, ILSI is following the tobacco industry playbook to the letter.  Strategy #1 is to cast doubt on the science.

When the 2015 Dietary Guidelines came out with a recommendation to restrict sugar intake to 10% of calories or less, the Sugar Association called it“agenda-based, not science-based.”  The Annals review says international sugar guidelines do not “meet criteria for trustworthy recommendations and are based on low-quality evidence.”

I detect a theme here.

But I ask again: what are dietary guidelines supposed to do?  We cannot lock up large numbers of people and feed them controlled amounts of sugar for decades and see what happens.  Short of that, we have to do the best we can with observational and intervention studies, none of which can ever meet rigorous standards for proof.  So this review is stating the obvious.

Take a look at the accompanying editorial.  After destroying each of the flawed premises of this review, it concludes:

Industry documents show that the F&B [Food & Beverage] industry has manipulated research on sugars for public relations purposes….Accordingly, high quality journals could refrain from publishing studies on health effects of added sugars funded by entities with commercial interests in the outcome. In summary, our concerns about the funding source and methods of the current review preclude us from accepting its conclusion that recommendations to limit added sugar consumption to less than 10% of calories are not trustworthy. Policymakers, when confronted with claims that sugar guidelines are based on “junk science,” should consider whether “junk food” was the source.

I don’t ever remember seeing a paper accompanied by an invited editorial that trashes it, as this one did, but this incident suggests a useful caution.

Whenever you hear that something isn’t “science-based,” look carefully to see who is paying for it.

The press coverage

• The New York Times: A Food Industry Study Tries to Discredit Advice About Sugar (I’m quoted)
• NPR: How Much Is Too Much? New Study Casts Doubts On Sugar Guidelines (I’m quoted)
• EurekAlert: Dietary sugar guidelines are based on low quality evidence
• WTKR:The debate continues on how much sugar is OK
• Time: Should You Trust the New Research About Sugar?
• CSPI: Industry-funded Study Designed to Cast Doubt on Sugar Advice
• Daily Mail (Reuters): So we CAN eat more sugar? Controversy as top journal publishes Coca Cola-funded study claiming sweets are NOT as bad as feds claim (I’m quoted)

I wrote a commentary for a study published this morning in JAMA Internal Medicine: “Food industry funding of nutrition research: The relevance of history for current debates.”

The study, by UCSF investigators Cristin Kearns, Laura Schmidt and Stanton Glantz, is based on their archival research.  They found documentary evidence of shocking manipulation by the sugar industry of a Harvard review of studies on dietary factors and heart disease published in the New England Journal of Medicine in 1967.

Kearns et al. discovered that the sugar industry trade association paid investigators at Harvard an impressive amount of money ($48,000 in today’s dollars) to produce research demonstrating that saturated fat—not sugar—raises the risk of heart disease.

In my commentary, I reproduced a figure from the sugar-funded 1967 reviews.  This summarizes the epidemiology showing that both sugar and saturated fat intake were then indistinguishably associated with increased mortality in 14 countries.

Nevertheless, the reviews exonerated sugars and blamed saturated fat.

Yes, I know that association does not necessarily mean causation, but I’m guessing that the epidemiology still shows that both sugars and saturated fats are associated with increased heart disease risk.

My interpretation: We would all be healthier eating less of sugary foods and fatty meats.

Here are the relevant documents for your reading pleasure:

• The press release from JAMA Internal Medicine
• The press release from UCSF
• The article by Kearns et al.
• Kearns et al.’s online tables analyzing the studies (look for Supplement in their paper)
• The New England Journal of Medicine articles from 1967: Part 1 and Part 2
• My commentary on Kearns et al.’s paper
• NYU’s blog post about my commentary
• JAMA Internal Medicine’s podcast interview with me and Stan Glantz (find it under Related Multimedia on the right side of the page)

The Sugar Association issued a response to today’s article by Kearns et al.:

We acknowledge that the Sugar Research Foundation should have exercised greater transparency in all of its research activities…Generally speaking, it is not only unfortunate but a disservice that industry-funded research is branded as tainted…We question this author’s continued attempts to reframe historical occurrences to conveniently align with the currently trending anti-sugar narrative, particularly when the last several decades of research have concluded that sugar does not have a unique role in heart disease.  Most concerning is the growing use of headline-baiting articles to trump quality scientific research—we’re disappointed to see a journal of JAMA’s stature being drawn into this trend.

I will post press accounts as they appear (I’m quoted in most of these):

•  Vox 
• New York Times
• STAT (a particularly detailed account)
• CSPI’s comment on Kearns et al.
• Reuters 
• Live Science
• Bloomberg News 
• Healthy Food America comment
• Business Insider
• Associated Press 
• NBC
• Time
• Quartz
• CNN
• Forbes
• United Press International
• Good Food
• Fortune
• Daily Mail
• Helio
• The Guardian
• US News
• CBS News
• Glamour
• Smithsonian
• Huffington Post
• Union of Concerned Scientists

While in Israel, I kept hearing that peanut allergies are virtually unknown in that country.  Nobody I met knows anyone with problems with peanuts—not Jews, Arabs, children, nor adults.

The explanation?

Bamba (and its Arabic equivalent).

These things are peanut puffs.

Because they melt in the mouth, they are often fed to babies as a first food.  Apparently, babies love them.

How do they taste?  Just as you might expect (peanut-flavored straw?  peanut-flavored Cheetos?).  They are sold everywhere as a snack and I met adults who love them too.

Do they really prevent peanut allergies?  Indeed, there might be something to this idea.

Introduction of peanut products into the diets of infants at high risk of developing peanut allergy was safe and led to an 81 percent reduction in the subsequent development of the allergy, a clinical trial has found…Researchers led by Gideon Lack, M.D., of King’s College London, designed a study called Learning Early About Peanut Allergy (LEAP), based on observations that Israeli children have lower rates of peanut allergy compared to Jewish children of similar ancestry residing in the United Kingdom. Unlike children in the UK, Israeli children begin consuming peanut-containing foods early in life.

Translation:  Bamba.

These researchers also found that allergic reactions did not return even if the children in that trial stopped eating Bamba for a year.

Their studies were funded mainly by NIH and the UK Department of Health, but the researchers also report that their clinical trials unit was supported by the National Peanut Board, Atlanta, and that the manufacturer of Bamba supplied the products.  The lead author, Gideon Lack, reports holding stock in DBV Technologies, the maker of Viaskin Peanut, a product that helps people with peanut allergies tolerate exposure to peanuts.

I’d like to see these studies repeated by fully independent researchers.

In the meantime, pediatric allergists are advising parents to let their babies eat peanut butter (but not peanuts because babies can choke on them).

These allergists—and the authors of the Bamba studies—participated in an American Academy of Pediatrics consensus statement:

There is now scientific evidence (Level 1 evidence from a randomized controlled trial) that health care providers should recommend introducing peanut-containing products into the diets of ‘‘high-risk’’ infants early on in life (between 4 and 11 months of age) in countries where peanut allergy is prevalent because delaying the introduction of peanut can be associated with an increased risk of peanut allergy.

If these studies are right, introducing babies to the widest possible variety of foods as soon as they can handle solid foods (usually at 4 to 5 months) may well help prevent allergies later on.

Addition

A reader just sent another paper from the same authors, this one a randomized trial of six allergenic foods given to breastfed babies at 3 or 6 months of age.  By one analysis, allergies developed 1 to 3 years later in 7.1% of the later-introduction group and 5.6% of the earlier-introduction group—a result that was not statistically significant.  By another, allergies were much lower in the early-introduction group (2.4% vs 7.3%), especially with respect to peanut and milk allergies.  

The USDA has just done a write up on a study it funded in collaboration with the National Honey Board:  Consumption of Honey, Sucrose, and High-Fructose Corn Syrup Produces Similar Metabolic Effects in Glucose-Tolerant and -Intolerant Individuals.

This was one of the 12 industry-negative studies I posted to my collection of 168 industry-funded studies from March 2015 to March 2016.

The USDA article explains:

Controversy exists over whether all sweeteners produce the same metabolic effects in consumers despite the sweeteners’ chemical similarities. A study conducted by U.S. Department of Agriculture (USDA) researchers indicates that consuming lower amounts of added sugars is a more effective approach to health than finding a sugar that is more neutral in terms of its health effects…Volunteers [consuming honey, white cane sugar, or HFCS] did not show any differences in blood sugar levels based on the dietary sugar source. In addition, blood levels of triglyceride, an indicator of blood fat concentrations (a marker for heart disease risk), increased in response to all three sugars tested.

White cane sugar is 50% glucose and 50% fructose, linked together (but quickly separated in the body).  Honey and High Fructose Corn Syrup are glucose and fructose, already separated, but with slightly higher percentages of fructose.  Biochemically, they are not all that different.

So the results of this study, disappointing as they may have been to the Honey Board, were predictable on the basis of basic sugar biochemistry.

Since March 16, 2015, I’ve been collecting research studies funded by industry or conducted by investigators with food industry connections.  These are studies that I’ve either run across in the course of my reading or that were sent to me by readers (thanks especially to Cole Adams).

It has now been a year since I started doing this.  If I have counted correctly, this somewhat haphazard collection comes to a grand total of 168 funded studies, 156 of them with results favorable to the sponsor’s interests, but only 12 industry-funded studies with unfavorable results.

That’s more than enough to make this point: it’s a lot easier to find industry-funded studies with results favorable to the sponsor’s interest than against it.

I will do a more accurate count and see what other conclusions, if any, can be drawn from this collection as soon as I can get to its analysis.

In the meantime, I’m stopping the collection.  From now on, I will only post sponsored studies that raise particular issues or that I find particularly amusing.

Here’s the last bunch:

Missing Lunch Is Associated with Lower Intakes of Micronutrients from Foods and Beverages among Children and Adolescents in the United States.  Kevin C. Mathias, PhD, Emma Jacquier, MMedSci, Alison L. Eldridge, PhD, RD.  DOI: http://dx.doi.org/10.1016/j.jand.2015.12.021.

• Conclusions: This study identifies potential concerns for children missing lunch with respect to micronutrient intakes and shows that the lunches consumed by children in the United States are an important source of essential nutrients, but also less healthful dietary components.
• Disclosures: All authors are employed by the Nestlé Research Center, Lausanne Switzerland (Nestec Ltd). Funding was provided by Nestec Ltd (Vevey, Switzerland) 

Higher-protein diets improve indexes of sleep in energy-restricted overweight and obese adults: results from 2 randomized controlled trials.  Jing Zhou, Jung Eun Kim, Cheryl LH Armstrong, Ningning Chen, and Wayne W Campbell.   Am J Clin Nutr March 2016;vol. 103 no. 3 766-774. doi: 10.3945/​ajcn.115.124669.

• Conclusion: The consumption of a greater proportion of energy from protein while dieting may improve sleep in overweight and obese adults.
• Disclosures: WWC was a member of the National Dairy Council Whey Protein Advisory Panel while the research was being conducted. The other authors reported no conflicts of interest related to the study.

A randomized trial of high-dairy-protein, variable-carbohydrate diets and exercise on body composition in adults with obesity.  Evelyn B. Parr, Vernon G. Coffey, Louise E. Cato, Stuart M. Phillips, Louise M. Burke andJohn A. Hawley. Obesity.  Article first published online: 2 MAR 2016.  DOI: 10.1002/oby.21451

• Conclusions: Compared to a healthy control diet, energy-restricted high-protein diets containing different proportions of fat and CHO confer no advantage to weight loss or change in body composition in the presence of an appropriate exercise stimulus.
• Funding agencies: Supported by a grant from the Dairy Health and Nutrition Consortium, Dairy Innovation Australia Ltd…to JAH, VGC, SMP, and LMB).  Disclosure: The authors declared no conflict of interest.

Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial.  Betsy Foxman, PhD; Anna E. W. Cronenwett, BA; Cathie Spino, DSc; Mitchell B. Berger, MD, PhD; Daniel M. Morgan, MD.  Am J Obstet Gynecol 2015;213:194.e1-8.

• Conclusion: Among women undergoing elective benign gynecological surgery involving urinary catheterization, the use of cranberry extract capsules during the postoperative period reduced the rate of UTI by half.
• Disclosure: The authors report no conflicts of interest… We also thank Theralogix, LLC (Rockville, MD) for providing cranberry juice capsules and placebo for use in this study.
• Comment: With respect to herbal medications, JAMA says “Only the use of cranberry for prevention of recurrent urinary tract infections in women is supported by some scientific evidence.”  It does not say whether that evidence was obtained by cranberry or cranberry supplement producers.

Coffee Consumption Increases the Antioxidant Capacity of Plasma and Has No Effect on the Lipid Profile or Vascular Function in Healthy Adults in a Randomized Controlled Trial. Gloria M Agudelo-Ochoa, Isabel C Pulgar´ın-Zapata, Claudia M Velasquez-Rodriguez, ´  Mauricio Duque-Ramirez, Mauricio Naranjo-Cano, Monica M Quintero-Ortiz, Oscar J Lara-Guzman, and Katalina Munoz-Durango.  J Nutr 2016;146:524–31.

• Conclusions: Both coffees, which contained CGAs [chlorogenic acids] and were low in diterpenes and caffeine, provided bioavailable CGAs and had a positive acute effect on the plasma AC [antioxidant capacity] in healthy adults and no effect on blood lipids or vascular function. The group that did not drink coffee showed no improvement in serum lipid profile, FMD [flow-mediated dilatation], BP [blood pressure], or NO [nitrous oxide] plasma metabolites.
• Funding: Supported by Vidarium, Nutrition, Health and Wellness Research Center, Nutresa Business Group; CES University; and the University of Antioquia.
• Author disclosures: GM Agudelo-Ochoa, IC Pulgarın-Zapata, OJ Lara-Guzman, ´ and K Munoz-Durango are researchers at Vidarium, Nutrition, Health and Wellness Research Center, Nutresa Business Group. M Naranjo-Cano and M Quintero-Ortiz are researchers at the Colcafe Research Coffee Group, Colcafe S.A.S. CM Velasquez-Rodrıguez and M Duque-Ramırez, no conflicts of interest.

Consumption of Fish Oil Providing Amounts of Eicosapentaenoic Acid and Docosahexaenoic Acid That Can Be Obtained from the Diet Reduces Blood Pressure in Adults with Systolic Hypertension: A Retrospective Analysis. Anne M Minihane, Christopher K Armah, Elizabeth A Miles, Jacqueline M Madden, Allan B Clark, Muriel J Caslake, Chris J Packard, Bettina M Kofler, Georg Lietz, Peter J Curtis, John C Mathers, Christine M Williams, and Philip C Calder.  J. Nutr. March 1, 2016 vol. 146 no. 3 516-523

• Conclusions: These findings indicate that in adults with isolated systolic hypertension, daily doses of EPA+DHA as low as 0.7 g show clinically meaningful BP reductions, which, at a population level, could be associated with lower cardiovascular disease risk. Confirmation of findings in an RCT in which participants are prospectively recruited on the basis of BP status is required to draw definite conclusions.
• Author disclosures: CK Armah, EA Miles, JM Madden, AB Clark, MJ Caslake, CJ Packard, BM Kofler, G Lietz, PJ Curtis, JC Mathers, and CM Williams, no conflicts of interest. AM Minihane is academic advisor for International Life Sciences Institute (ILSI) Europe Obesity and Diabetes Task Force and receives funding from Abbott Nutrition, USA. PC Calder serves on advisory boards of Pronova BioPharma, Aker Biomarine, Danone/Nutricia, Smartfish, Sancilio, DSM, Solutex, and ILSI Europe.

Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial.  Thomas M Longland, Sara Y Oikawa, Cameron J Mitchell, Michaela C Devries, and Stuart M Phillips.  Am J Clin Nutr  March 2016  vol. 103 no. 3 738-746. doi: 10.3945/​ajcn.115.119339

• Conclusion: Our results showed that, during a marked energy deficit, consumption of a diet containing 2.4 g protein · kg⁻¹ · d⁻¹ was more effective than consumption of a diet containing 1.2 g protein · kg⁻¹ · d⁻¹ in promoting increases in LBM [lean body mass] and losses of fat mass when combined with a high volume of resistance and anaerobic exercise.
• Conflicts of interest: SMP has received research funding, travel allowances, and honoraria from the US National Dairy Council and Dairy Farmers of Canada. None of the other authors reported a conflict of interest related to the study.
• Comment: Dairy, of course, is a source of protein.

Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies. Gijsbers L, Ding EL, Malik VS, de Goede J, Geleijnse JM, Soedamah-Muthu SS. Am J Clin Nutr. 2016 Feb 24. pii: ajcn123216. [Epub ahead of print]

• Conclusion: This dose-response meta-analysis of observational studies suggests a possible role for dairy foods, particularly yogurt, in the prevention of T2D. Results should be considered in the context of the observed heterogeneity.
• Funding: This meta-analysis project on dairy products and incident diabetes was funded by Wageningen University.  SSS-M previously received funding from Global Dairy Platform, Dairy Research Institute, and Dairy Australia for projects related to dairy effects on lipoproteins and mortality; JMG previously received funding from the Global Dairy Platform and Dutch Dairy Association for projects related to dairy and cardiovascular diseases; and ELD previously consulted for the Dairy Research Institute. LG, VSM, and JdG reported no conflicts of interest related to the study. Any prior sponsors had no role in the design and conduct of the study, data collection and analysis, interpretation of the data, decision to publish, or preparation of this manuscript. The current funder had no role in design and conduct of the study, data collection and analysis, interpretation of the data, or decision to publish.
• Comment: The conclusions put a positive spin on results that can also be considered equivocal.

Plenary Lecture 2: Milk and dairy produce and CVD: new perspectives on dairy and cardiovascular health. Julie A. Lovegrove* and Ditte A. Hobbs.  Proceedings of the Nutrition Society, Page 1 of 12 doi:10.1017/S002966511600001X.

• Conclusion: These apparent benefits of milk and dairy foods have been attributed to their unique nutritional composition, and suggest that the elimination of milk and dairy may not be the optimum strategy for CVD risk reduction.
• Conflicts of Interest: The authors have previously received funding for research from AHDB Dairy. J. A. L. has acted as an advisor to the Dairy Council. J. A. L. has received funding for research from Volac for BBSRC case studentship and ‘in kind’ foods from Arla for an MRC funded study.

Multivitamin/mineral supplements: rationale and safety – A systematic review. Hans K. Biesalski, Jana Tinz.  Nutrition, in press 2016.  doi:10.1016/j.nut.2016.02.013

• Conclusion: Taken together, these findings indicate that MVM can be safe for long-term use (more than 10 years).
• Funding: Editorial support was provided by Peloton Advantage and funded by Pfizer.

The challenges of vitamin and mineral supplementation in children with inherited metabolic disorders: a prospective trial.  A. Daly, S. Evans, S. Chahal, I. Surplice, S. Vijay, S. Santra and A. MacDonald.  J Human Nutrition and Dietetics.  Article first published online: 18 JAN 2016. DOI: 10.1111/jhn.12354 (thanks to Cole Adams for sending).

• Conclusions: Despite improvements in some nutritional markers, overall use of the vitamin and mineral supplement was less than prescribed. New methods are needed to guarantee delivery of micronutrients in children at risk of deficiencies as a result of an essential manipulation of diet in inborn disorders of metabolism.
• Funding: Anita MacDonald has received research funding from Merck Serono, Vitaflo Ltd and Nutricia. She is on Advisory Boards for Arla, Merck Serono and Nutricia. Anne Daly and Sharon Evans have received research funding from Vitaflo Ltd, and Nutricia. Research funding was obtained from Vitaflo International for the funding of this project.