Search results: journal nature

I’m having trouble keeping up with industry-sponsored nutrition research so will use this week’s posts to catch up.  I’ll start with this one.

Nutrition journals often publish supplements on specific themes that are paid for by outside parties, food industry groups among them.  The February 2016 issue of the Journal of Nutrition contains a supplement with the papers from the 2014 International Garlic Symposium: “Role of Garlic in Cardiovascular Disease Prevention, Metabolic Syndrome, and Immunology.”

To distinguish supplement papers from peer-reviewed journal articles, citations give page numbers with the letter S.  The Journal of Nutrition’s exceptionally clear policy on supplement publications explains that organizers are expected to pay page charges of $75 per article and $300 per published page plus additional editorial costs as needed.  It views supplements as paid advertisements and requires full disclosure of funding sources.

Here’s the disclosure for the garlic supplement.

The symposium was sponsored by the University of California, Los Angeles School of Medicine and the University of Florida and co-sponsored by the American Botanical Council; the American Herbal Products Association; the ASN [American Society for Nutrition]; the Japanese Society for Food Factors; the Japan Society for Bioscience, Biotechnology, and Agrochemistry; the Japan Society of Nutrition and Food Science; and the Natural Products Association. The symposium was supported by Agencias Motta S.A.; Bionam; Eco-Nutraceuticos; Healthy U 2000 Ltd.; Magna; Mannavita Bvba; MaxiPharma; Medica Nord A.S.; Nature’s Farm Pte. Ltd.; Nature Valley W.L.L.; Organic Health Ltd.; Oy Valioravinto Ab; Purity Life Health Products L.P.; PT Nutriprima Jayasakti; Vitaco Health Ltd.; Vitae Natural Nutrition; Sanofi Consumer Health Care; Wakunaga Pharmaceutical Co., Ltd.; and Wakunaga of America Co., Ltd. The Chair of the conference and Scientific Program Coordinator for the supplement publication was Matthew J Budoff, Harbor-UCLA Medical Center, Torrance, CA. Scientific Program Coordinator disclosures: MJ Budoff has been awarded research grants from Wakunaga of America Co., Ltd., and received an honorarium for serving as Chair of the conference. Vice-Chair and Supplement Coordinator for the supplement publication was Susan S Percival, University of Florida, Gainesville, FL. Supplement Coordinator disclosures: SS Percival has been awarded research grants from Wakunaga of America Co., Ltd., and received an honorarium for serving as Vice-Chair of the conference. Publication costs for this supplement were defrayed in part by the payment of page charges. This publication must therefore be hereby marked “advertisement” in accordance with 18 USC section 1734 solely to indicate this fact. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, Editor, or Editorial Board of The Journal of Nutrition [my emphasis].

Comment on scoring: Because they were presented at a symposium sponsored by food and supplement companies, all papers raise questions about industry sponsorship.  That is why the Journal requires every paper in the supplement to repeat this funding disclosure in its entirety.

But for this particular symposium, some of the papers report additional funding by Wakunaga of America, a company that, no surprise, manufactures garlic supplements.

All of the papers produced results useful to the sponsor.  Some of them, however, were independently funded and the authors report no links to the sponsor other than having given a talk at the meeting.  They did not disclose who paid for travel and hotels and without any way to check, I must assume that they paid their own expenses to the meeting in San Diego.  For the purposes of scoring, I’m not counting them as industry-funded, even though their presence at the symposium made it seem more scientifically credible.

Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review.  Karin Ried.  J Nutr. 2016; 146:389S-396S doi:10.3945/jn.114.202192.

• Conclusions: Our review suggests that garlic supplements have the potential to lower blood pressure in hypertensive individuals, to regulate slightly elevated cholesterol concentrations, and to stimulate the immune system. Garlic supplements are highly tolerated and may be considered as a complementary treatment option for hypertension, slightly elevated cholesterol, and stimulation of immunity.
• Author disclosures: K Ried, no conflicts of interest. K Ried received travel sponsorship from Wakunaga of America Co. Ltd. to attend the 2014 International Garlic Symposium.
• Score: industry-positive

Chemical Assignment of Structural Isomers of Sulfur-Containing Metabolites in Garlic by Liquid Chromatography−Fourier Transform Ion Cyclotron Resonance−Mass Spectrometry.  Ryo Nakabayashi, Yuji Sawada, Morihiro Aoyagi, Yutaka Yamada, Masami Yokota Hirai, Tetsuya Sakurai, Takahiro Kamoi, Daryl D Rowan, and Kazuki Saito.  J. Nutr. 2016; 146:397S-402S doi:10.3945/jn.114.202317.

• Conclusion: The ability to discriminate between such geometric isomers will be extremely useful for the chemical assignment of unknown metabolites in MS-based metabolomics.
• Supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; Japan Advanced Plant Science Network; Japan Science Technology Agency (JST), Strategic International Collaborative Research Program (SICORP); and JST, Strategic International Research Cooperative Program (SICP).
• Score: industry-neutral

Garlic-Derived Organic Polysulfides and Myocardial Protection.  Jessica M Bradley, Chelsea L Organ, and David J Lefer.  J. Nutr. 2016; 146:403S-409S doi:10.3945/jn.114.208066.

• Conclusion: The beneficial health effects of garlic on cardiovascular health are dependent on multiple mechanisms. Furthermore, the mechanisms of action may be mediated by the active components in garlic.
• Supported by grants from the National Heart, Lung, and Blood Institute (1R01 HL092141, 1R01 HL093579, 1U24 HL 094373, and 1P20 HL113452; to DJL) and by the Louisiana State University Health Foundation in New Orleans.
• Score: Industry-neutral

Aged Garlic Extract Inhibits Human Platelet Aggregation by Altering Intracellular Signaling and Platelet Shape Change.  Khalid Rahman, Gordon M Lowe, and Sarah Smith.  J. Nutr. 2016; 146:410S-415S doi:10.3945/jn.114.202408

• Conclusion: These results indicate that AGE [Aged Garlic Extract] inhibits platelet aggregation by increasing cyclic nucleotides and inhibiting fibrinogen binding and platelet shape change.
• Funding: Supported by a grant from Wakunaga of America Co. Ltd.  K Rahman and GM Lowe were in receipt of a grant from Wakunaga of America Co., Ltd. S Smith, no conflicts of interest.
• Score: industry-positive

Garlic and Heart Disease.  Ravi Varshney and Matthew J Budoff.  J. Nutr. 2016; 146:416S-421S doi:10.3945/jn.114.202333

• Conclusion: We conclude that garlic supplementation has the potential for cardiovascular protection based on risk factor reduction (hypertension and total cholesterol) and surrogate markers (CRP, PWV, and CAC) of atherosclerosis.
• Disclosures: The authors report no funding received for this study.  R Varshney, no conflicts of interest. MJ Budoff receives funding from Wakunaga of America Co., Ltd.
• Score: industry-positive

The Role of Adiponectin in Cardiometabolic Diseases: Effects of Nutritional Interventions.  Patricio Lopez-Jaramillo.  J. Nutr. 2016; 146:422S-426S doi:10.3945/jn.114.202432

• Conclusions: Recently, it was reported that the administration of aged garlic extract and a single food intervention with pistachios can increase adiponectin concentrations in individuals with metabolic syndrome. Moreover, the Mediterranean diet is associated with higher adiponectin concentrations. Additional studies are needed to evaluate the potential benefits of increasing adiponectin by nutritional interventions in the treatment and prevention of cardiometabolic diseases.
• Funding: The author reports no funding received for this study.
• Score:  Industry-neutral

Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study.  Suguru Matsumoto, Rine Nakanishi, Dong Li, Anas Alani, Panteha Rezaeian, Sach Prabhu, Jeby Abraham, Michael A Fahmy, Christopher Dailing, Ferdinand Flores, Sajad Hamal, Alexander Broersen, Pieter H Kitslaar, and Matthew J Budoff.  J. Nutr. 2016; 146:427S-432S doi:10.3945/jn.114.202424

• Conclusions: This study indicates that the %LAP [Low Attenuation Plaque] change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.
• Disclosures: While the study was funded by Wakunaga of America Co., Ltd., the authors are solely responsible for the design, all study analyses, the drafting and editing of the paper and its final contents…S Matsumoto, R Nakanishi, D Li, A Alani, P Rezaeian, S Prabhu, J Abraham, MA Fahmy, C Dailing, F Flores, S Hamal, and A Broersen, no conflicts of interest. PH Kitslaar is employed by Medis Medical Imaging Systems and has a research appointment at the Leiden University Medical Center. MJ Budoff receives funding from Wakunaga of America Co., Ltd.
• Score: industry-positive

Aged Garlic Extract Modifies Human Immunity.  Susan S Percival.  J.  Nutr. 2016; 146:433S-436S doi:10.3945/jn.115.210427

• Conclusions: These results suggest that AGE supplementation may enhance immune cell function and may be partly responsible for the reduced severity of colds and flu reported. The results also suggest that the immune system functions well with AGE supplementation, perhaps with less accompanying inflammation.
• Funding: Support for this research was provided by Wakunaga of America Co., Ltd.  Author disclosures: SS Percival received travel expenses to the conference where this work was presented.
• Score: industry-positive

Bioavailability of Alfrutamide and Caffedymine and Their P-Selectin Suppression and Platelet-Leukocyte Aggregation Mechanisms in Mice.  Jae B Park.  J. Nutr. 2016; 146:437S-443S doi:10.3945/jn.114.202473

• Conclusions: These data show the adequate bioavailability of alfrutamide and caffedymine and their different mechanisms of suppressing PSE and PLA: alfrutamide exerts its effects only via COX inhibition, whereas caffedymine works through both COX inhibition and cAMP amplification.
• Funding: Supported by the USDA (project 8040-51000-057-00).
• Score: Industry-neutral

Garlic Influences Gene Expression In Vivo and In Vitro.  Craig S Charron, Harry D Dawson, and Janet A Novotny.  J. Nutr. 2016; 146:444S-449S doi:10.3945/jn.114.202481

• Conclusion: Measuring mRNA gene expression in whole blood may provide a unique window to understanding how garlic intake affects human health.
• Support: CSC, HDD, and JAN were supported by the USDA.
• Score: Industry-neutral.

Development of an Analytic Method for Sulfur Compounds in Aged Garlic Extract with the Use of a Postcolumn High Performance Liquid Chromatography Method with Sulfur-Specific Detection.  Toshiaki Matsutomo and Yukihiro Kodera.  J. Nutr. 2016; 146:450S-455S doi:10.3945/jn.114.208520

• Conclusion: We developed a rapid postcolumn HPLC method for both qualitative and quantitative analyses of sulfur compounds, and this method helped elucidate a potential mechanism of cis-S1PC and SAMC action in AGE.
• Acknowledgment: The authors thank Takami Oka of Wakunaga Pharmaceutical Co., Ltd. for his kind guidance for this study and critical review of the manuscript.
• Score: Industry-positive

Pharmacokinetics of S-Allyl-L-cysteine in Rats Is Characterized by High Oral Absorption and Extensive Renal Reabsorption.  Hirotaka Amano, Daichi Kazamori, and Kenji Itoh.  J. Nutr. 2016; 146:456S-459S doi:10.3945/jn.114.201749

• Conclusion: The pharmacokinetics of SAC in rats were characterized by high oral absorption, limited metabolism, and extensive renal reabsorption, all of which potentially contribute to its high and relatively long-lasting plasma concentrations.
• Acknowledgment: We thank Takami Oka of Wakunaga Pharmaceutical Co. for his valuable advice, critical reading of the manuscript, and helpful suggestions.
• Score: Industry-positive

Aged Garlic Extract Suppresses the Development of Atherosclerosis in Apolipoprotein E–Knockout Mice.  Naoaki Morihara, Atsuko Hino, Takako Yamaguchi, and Jun-ichiro Suzuki. J. Nutr. 2016; 146:460S-463S doi:10.3945/jn.114.206953

• Conclusion: These data suggest that the antiatherosclerotic activity of AGE is at least partly due to the suppression of inflammation and lipid deposition in the vessels during the early stage of atherosclerotic development in ApoE-KO mice.
• Acknowledgment: We thank Takami Oka of Wakunaga Pharmaceutical Co., Ltd., for his helpful advice, encouragement, and critical reading of this manuscript; Yukihiro Kodera of Wakunaga Pharmaceutical Co., Ltd., for the preparation of AGE; and Tadamitsu Tsuneyoshi of Wakunaga Pharmaceutical Co., Ltd., for his technical advice.
• Score: Industry-positive

This makes 8 industry-positives from this journal supplement.

But let me add one more on this topic, sent by a reader:

The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: the AGE at Heart trial.  Karin Ried Nikolaj Travica, Avni Sali.  Integrated Blood Pressure Control, 27 January 2016.

• Conclusion: Our trial suggests that aged garlic extract is effective in reducing peripheral and central blood pressure in a large proportion of patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and other cardiovascular markers in patients with elevated levels. Aged garlic extract was highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment.
• Funding: This trial was supported by a grant from Wakunaga of America Co Ltd, who sup­plied trial capsules and provided funding for costs of tests and research assistance. Wakunaga of America was not involved in study design, data collection, analysis, or prepa­ration of the manuscript…The authors report no conflicts of interest in this work.
• Score: industry-positive, of course.

This brings the score since last March to 119 industry-positives/11 industry-negatives.

Systematic Review of Pears and Health. Holly Reiland, BS Joanne Slavin, PhD, RD.  Nutrition Today November/December 2015 – Volume 50 – Issue 6 – p 301–305.  doi: 10.1097/NT.0000000000000112.  

• Conclusions: Animal studies with pears suggest that pears may regulate alcohol metabolism, protect against ulcers, and lower plasma lipids. Human feeding studies with pears have not been conducted. In epidemiological studies, pears are combined with all fresh fruits or with apples, because they are most similar in composition. The high content of dietary fiber in pears and their effects on gut health set pears apart from other fruit and deserves study.
• Funding: The authors received a grant from USA Pears in the past. The authors provided their own funding to allow this article to publish as Open Access.
• Comment: Pears are a great fruit but the marketing purpose of this study is evident from this press release from the Pear Bureau Northwest: “While the body of evidence connecting pear intake and health outcomes is still limited, USA Pears has been contributing to research efforts by commissioning independent studies to learn and affirm the heath attributes of pears. Visit www.usapears.org for additional pear research, nutrition resources and recipes.”

Whole Grain Intakes in the Diets Of Malaysian Children and Adolescents – Findings from the MyBreakfast Study.  Norimah AK , H. C. Koo, Hamid Jan JM, Mohd Nasir MT, S. Y. Tan, Mahendran Appukutty, Nurliyana AR, Frank Thielecke, Sinead Hopkins, M. K. Ong, C. Ning, E. S. Tee.  PLoS ONE 10(10): e0138247. doi:10.1371/journal.pone.0138247

• Conclusion: Whole grain is consumed by only a minority of Malaysian children and adolescents and even among consumers, intakes are well below recommendations. Efforts are needed to firstly understand the barriers to whole grain consumption among Malaysian children in order to design effective health promotion initiatives to promote an increase in whole grain consumption.
• Funding: The Nutrition Society of Malaysia received an unrestricted research grant from Cereal Partners Worldwide, Switzerland and Nestleé R&D Center, Singapore. This financial support was provided in the form of salaries for authors but the funders did not have any additional role in the study design, data collection and analysis or decision to publish. Frank Thielecke was an employee of Cereal Partners Worldwide at the time this study was conducted. He now works for Nestec SA. Sinead Hopkins is employed by Cereal Partners Worldwide (CPW), Switzerland and Moi Kim Ong and Celila Ning are employed by Nestleé R&D Center, Singapore….Nestlé and Cereal Partners Worldwide have a commercial interest in breakfast cereals.
• Comment: I learned about this study from a comment on Retraction Watch, which reported that PLoS One had filed a correction to the funding section.  The correction says that the salaries were for research assistants, not authors.

Walnuts Consumed by Healthy Adults Provide Less Available Energy than Predicted by the Atwater Factors.  David J Baer*, Sarah K Gebauer, and Janet A Novotny. J Nutrition First published November 18, 2015, doi: 10.3945/​jn.115.217372.

• Conclusion: Consistent with other tree nuts, Atwater factors overestimate the metabolizable energy value of walnuts. These results could help explain the observations that consumers of nuts do not gain excessive weight and could improve the accuracy of food labeling.
• Funding: This research was funded by the USDA and the California Walnut Commission… DJ Baer was funded by the USDA and the California Walnut Commission.

Cardiorespiratory Fitness, Body Fatness, and Submaximal Systolic Blood Pressure Among Young Adult Women.  Prasad Vivek Kumar, Drenowatz Clemens, Hand Gregory A., Lavie Carl J., Sui Xuemei, Demello Madison, and Blair Steven N.  Journal of Women’s Health, 2015 ahead of print. doi:10.1089/jwh.2015.5307.

• Conclusion: CRF, BF%, and BMI seem to have critical roles in determining SSBP with CRF and BF% being more potent at lower intensity exercise, whereas BMI was more strongly associated at higher intensity exercise.
• Funding for this project was provided through an unrestricted grant from The Coca-Cola Company. The sponsor played no role in the study design, data collection, analysis, and interpretation, or preparation and submission of this article. The authors thank the Energy Balance staff and study participants for their contributions. No competing financial interests exist. 
• Comment: This is one of the papers produced by participants in the now defunct Global Energy Balance Network formerly sponsored by Coca-Cola.

Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including metaanalyses, of the evidence from human and animal studies. PJ Rogers, PS Hogenkamp, C de Graaf , S Higgs , A Lluch , AR Ness , C Penfold , R Perry , P Putz , MR Yeomans and DJ Mela.  International Journal of Obesity advance online publication, 10 November 2015; doi:10.1038/ijo.2015.177

• Conclusion¨The preponderance of evidence from all human randomized controlled trials indicates that LES [low-energy sweeteners] do not increase EI [energy intake] or BW [body weight], whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.
• Conflict: This work was conducted by an expert group of the European branch of the International Life Science Institute (ILSI Europe). The expert group received funding from the ILSI Europe Eating Behaviour and Energy Balance Task Force. Industry members of this task force are listed on the ILSI Europe website at www.ilsi.eu.
• Comment: ILSI is funded by food companies.

In case you haven’t been following this saga, I’ve been collecting studies funded by food companies since last March and posting them according to whether the results do or do not favor the sponsor’s interests.  So far, I’ve reported 80 that do, versus 6 that don’t (although I have a couple more saved up for posting soon).

The point of this exercise is to demonstrate that sponsored studies are far more likely to favor the interests of the sponsor than are studies funded by government agencies or foundations, and to argue for more independent funding of food and nutrition research (see my recent Viewpoint on this topic in JAMA Internal Medicine).

Here are five more examples.

Is consuming yoghurt associated with weight management outcomes? Results from a systematic review. J Eales, I Lenoir-Wijnkoop, S King, H Wood, F J Kok, R Shamir, A Prentice, M Edwards, J Glanville, R L Atkinson. Int’l J Obesity 2015 ahead of print.

• Conclusions: Yoghurt consumption is associated with lower BMI, lower body weight/weight gain, smaller waist circumference and lower body fat in epidemiological studies. RCTs [randomized controlled trials] suggest weight reduction effects, but do not permit determination of a cause/effect relationship. Well-controlled, adequately powered trials in research and community settings appear likely to identify a modest but beneficial effect of yoghurt consumption for prevention of weight gain and management of obesity. The ready availability of yoghurt (a nutrient dense food) and its ease of introduction to most diets, suggests that educating the public to eat yoghurt as part of a balanced and healthy diet may potentially contribute to improved public health.
• Funding: This project was funded by Danone Institute International.
• Conflict of interest statement: York Health Economics Consortium received funding from Danone Institute International to conduct this review. York Health Economics Consortium has received funding from the Global Alliance for Probiotics, Danone and the European Food Safety Agency for projects involving food and health topics. FJK is member of the Scientific Advisory Board Global Dairy Platform, Chicago USA RS is President of Danone Institute International ILW is employed by the Danone Company, France.

Red Meat and Colorectal Cancer: A Quantitative Update on the State of the Epidemiologic Science.  Dominik D. Alexander PhD, MSPHab*, Douglas L. Weed MD, PhDc, Paula E. Miller MPHb & Muhima A. Mohamed M PHd. J Am College Nutrition 2015;34: 521-43.  DOI:10.1080/07315724.2014.992553

• Conclusion:  The state of the epidemiologic science on red meat consumption and CRC [colorectal cancer] is best described in terms of weak associations, heterogeneity, an inability to disentangle effects from other dietary and lifestyle factors, lack of a clear dose-response effect, and weakening evidence over time.
• Funding: This manuscript was partially funded by Meat & Livestock Australia (MLA). MLA did not contribute to the writing, analysis, or interpretation of study findings.
• Comment: The conclusion of this industry-funded study contradicts the findings of the WHO International Agency for Research on Cancer, which finds processed meats to be carcinogenic, and red meat to be a probable carcinogen.

The challenges of nutrition policymaking. Joanne Slavin.  Nutrition Journal (2015) 14:15 DOI 10.1186/s12937-015-0001-8.

• Thrust of paper: As every DGAC [Dietary Guidelines Advisory Committee] wants to be bold and set new direction, nutrition science would support that first we must do no harm with our dietary guidance. Moderation and variety must be kept front and center…A suggestion that all Americans should reduce sodium intakes is not sound and is potentially dangerous. Targeting certain foods and beverages, including chocolate milk, processed meats, added sugars, and even the noble potato as villains in the nutrition wars is not a science-based strategy and may need to be countered on the political front if appointed scientific review committees continue to take this approach.
• Competing interests: In the past 5 years Dr. Slavin has received research grants from Minnesota Beef Council, Minnesota Cultivated Wild Rice Council, Novartis Consumer Health, USA Rice, Nestle Nutrition, Tate and Lyle, General Mills, Inc., USA Pears and American Pulse Association. In the past 5 years Dr. Slavin has received speaking fees from food companies and commodity groups with interests in processed foods, dairy products, meat, pulses, fruits, vegetables, fiber, grains, and carbohydrates. Dr. Slavin has participated in scientific panels and advisory boards that are funded by food companies, ingredient companies, commodity groups, scientific societies, and trade groups. She holds a third interest in the Slavin Sisters LLC, a 119-acre farm in Southern Wisconsin.

Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies PJ Rogers, PS Hogenkam , C de Graaf, S Higgs, A Lluch, AR Ness, C Penfold, R Perry, P Putz, MR Yeomansand DJ Mela.International Journal of Obesity (2015), 1–14 10 November 2015; doi:10.1038/ijo.2015.177

• Conclusions: Overall, the balance of evidence indicates that use of LES [low-energy sweeteners] in place of sugar, in children and adults, leads to reduced EI [energy intake] and BW [body weight], and possibly also when compared with water.
• Conflict of interest: Peter J Rogers has received grants from Sugar Nutrition, UK in support of research on the effects of sugar on human appetite. Cees de Graaf has received grants from the Dutch Sugar Bureau in support of a study on brain responses to sugars and low energy sweeteners. Suzanne Higgs has received a grant from Canderel in support of research on the effects of low-energy sweeteners on human appetite. Anne Lluch and David J Mela are employees and shareholders of companies that manufacture products containing sugars and low-energy sweeteners. Peter Putz is an employee of ILSI Europe.

Walnut ingestion in adults at risk for diabetes: effects on body composition, diet quality, and cardiac risk measures Valentine Yanchou Njike, Rockiy Ayettey, Paul Petraro, Judith A Treu, David L Katz.  . BMJ Open Diabetes Research and Care 2015;3:e000115. doi:10.1136/bmjdrc-2015- 000115.

• Conclusions: The inclusion of walnuts in an ad libitum diet for 6 months, with or without dietary counseling to adjust calorie intake, significantly improved diet quality, endothelial function, total and LDL cholesterol, but had no effects on anthropometric measures, blood glucose level, and blood pressure.
• Funding: Funding for this study has been provided by the California Walnut Commission.
• Competing interests. DLK has been compensated for public speaking by the California Walnut Commission.

The Journal of Public Health Policy (JPHP) will soon announce the retraction of a Viewpoint—an opinion piece—I co-authored with a Guatemalan physician, Dr. Joaquin Barnoya, “The food industry and conflicts of interest in nutrition research: A Latin American perspective.” Because of factual errors in the piece, and in response to valid objections about the errors from its subjects, they and we requested its retraction and JPHP is doing so.

I believe it is useful to explain how this happened.  In late summer, Dr. Barnoya brought to my attention an advertorial, a sponsored news account, published in el Periódico and other Guatemalan newspapers announcing an alliance among the Central American Bottling Corporation (cbc), the largest beverage distributor in Guatemala and bottler for PepsiCo; the Guatemala-based Institute of Nutrition of Central America and Panama (INCAP); and the U.S.-based Shalom Christian Foundation to distribute a supplemental food product, Mani+, to chronically malnourished children in rural areas (here is a translation of the advertorial).  Mani+ is a sweetened, peanut-based, nutrient-fortified supplemental food made from local ingredients in Guatemala, used to prevent malnutrition in young children.  The advertorial displayed a photograph of the directors of the three organizations holding the agreement.  It also displayed statements from all three directors emphasizing the alliance’s importance in addressing childhood malnutrition.

As readers of this blog should know, I have long been concerned about the conflicts of interest that arise when food companies—especially soda companies—enter into alliances with public health organizations.   The New York Times made the consequences of such alliances clear in its recent revelations of Coca-Cola sponsorship of the Global Energy Balance Network and the fallout from those revelations.  The announced alliance between cbc and INCAP raises similar concerns, particularly in the light of more general food industry partnerships with research and health institutions in Latin America.  Our intention in writing the Viewpoint was to question the appropriateness of this alliance, as well as of other such partnerships and alliances.

We should, however, have exercised more care.  Shortly after publication of the Viewpoint, Carolina Siu Bermúdez, the director of INCAP who appears in the advertorial, wrote to object that our piece incorrectly implied a financial relationship with cbc, and that Dr. Barnoya had failed to disclose that INCAP paid a substantial portion of his salary via a grant from yet another organization.  We also received letters from Dr. Edward Fischer, the founder of NutriPlus/Mani+, Professor of Anthropology and Director of the Center for Latin American Studies at Vanderbilt University, objecting to our statement that the alliance was responsible for manufacturing (rather than just distributing) the product.   Both asked us to retract the Viewpoint.

Upon investigation, we realized their objections had merit.  Indeed, further investigation by us and by the editors of the JPHP exposed additional errors.  Together, these include the following clarifications and corrections:

• The alliance is involved only in the distribution of Mani+, not its manufacture (as we had asserted).
• The actual nature of the alliance between cbc, INCAP, and the Shalom Christian Foundation—who does what—is, in fact, unclear. The Viewpoint should have characterized the relationship with less certainty and specified that cbc has no financial relationship with either INCAP or the Foundation.
• Dr. Barnoya should have disclosed his financial relationship with INCAP, and I should have insisted that he do so.
• The Viewpoint was triggered by the advertorial, and we should have made this connection more explicit.
• The reference in the Viewpoint to the advertorial is incorrect. It is listed as (2015) cbc co. Unidos contra la desnutricion. INCAP, cbc y Fundacion Crisitiana Shalom Firman Convenio 23(July): 9.  The correct reference is Alianza Contra la Desnutricion. elPeriódico. July 23, 2015;Advertorial: 9.

To correct and clarify these issues, we would need to revise the Viewpoint.  Doing so, however, is not possible once a paper is published.  That left us no choice but to request a retraction, which I believe is the right course of action in this situation.

In my books and other writing, I try as hard as I can to be precise and accurate.  This incident is a lapse that I regret deeply, for which I take responsibility, and for which I apologize to Carolina Siu Bermúdez, to Dr. Fischer, and to my readers.  I also apologize to Phyllis Freeman and Anthony Robbins, the editors of JPHP, and to Lucy Wheeler of Palgrave, who have set an exemplary standard of ethics and integrity throughout these investigations and discussions.

As for lessons learned: Although I fully intend to continue to write critically about alliances between food companies and public health organizations, I also intend to use this experience to recommit myself to accountability and to diligence in checking and double-checking facts and disclosures going forward.   Again, my deepest apologies.

Addition, December 14: The actual retraction notice is published here.  The discussion on Retraction Watch is here.

Nutrition research studies funded by food companies are pouring in and here’s another set of five with expected results.  The first one is notable for its extensive revelations, a case of TMI (too much information) if I’ve ever seen one.  As usual, if you run across more of these—and especially industry-funded studies that do not favor the sponsor’s interest, please send.  The roundup since mid-March: 60 with favorable results, 3 without.

Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta‐Analysis of Controlled Feeding Trials.  Laura Chiavaroli, Russell J. de Souza, Vanessa Ha, Adrian I. Cozma, Arash Mirrahimi, David D. Wang, Matthew Yu, Amanda J. Carleton, Marco Di Buono, Alexandra L. Jenkins, Lawrence A. Leiter, Thomas M. S. Wolever, Joseph Beyene, Cyril W. C. Kendall, David J. A. Jenkins, and John L. Sievenpiper.  J Am Heart Assoc. 2015;4: originally published September 10, 2015, doi:10.1161/JAHA.114.001700.

• Conclusion: Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids.
• Conflicts:  The disclosures cover two full pages in the journal.  These authors report every source of income—honoraria, prizes, travel funds—including those of their spouses.  They apparently work for every food company imaginable, including any number with interests in minimizing a harmful role of fructose in health.
• Comment:  I do not know why the editors of this journal decided that the conflict-of-interest statement was worth two pages of journal space.  Perhaps they don’t think such statements necessary and were being ironic?  Or perhaps they wanted to make sure that these highly conflicted authors were fully exposed?  Yoni Freedhoff of Weighty Matters consulted an ethicist about this question but did not get a clear answer.  I wrote the journal editor and asked what this was about, but have not received a response.

Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. Ana N. Paiva, Josivan G. de Lima, Anna C.Q. de Medeiros, Heverton A.O. Figueiredo, Raiana L. de Andrade, Marcela A.G. Ururahye, Adriana A. Rezende, José Brandão-Neto, Maria das G. Almeida.   Journal of Trace Elements in Medicine and Biology 32 (2015) 66–72.

• Conclusions: CrPic supplementation had a beneficial effect on glycemic control in patients with poorly controlled T2DM, without affecting the lipid profile.
• Conflict: Manipulation Pharmacy Companhia da Fórmula donated the chromium picolinate supplement.
• Comment: Without knowing more about this situation, it’s not possible to say whether donation of a supplement is enough to raise concerns.  This study raises questions because most independently funded studies of chromium and diabetes have shown minimal or no benefits (see, for example this one).

Oat consumption reduced intestinal fat deposition and improved health span in Caenorhabditis elegans model. Chenfei Gao, Zhanguo Gao, Frank L. Greenway, Jeffrey H. Burton, William D. Johnson, Michael J. Keenan, Frederick M. Enright, Roy J. Martin, YiFang Chu, Jolene Zheng.  Nutrition Research September 2015 Volume 35, Issue 9, Pages 834–843.

• Conclusion: Oat consumption may be a beneficial dietary intervention for reducing fat accumulation, augmenting health span, and improving hyperglycemia-impaired lipid metabolism [in nematodes].
• Conflict: This research was supported by a nonrestricted donation from PepsiCo Inc. Oats used in this study were a gift of PepsiCo Inc. Y. Chu is an employee of PepsiCo, Inc, which manufactures oatmeal products under the brand name Quaker Oats.

A pilot study examining the effects of consuming a high-protein vs normal-protein breakfast on free-living glycemic control in overweight/obese ‘breakfast skipping’ adolescents. L B Bauer, L J Reynolds, S M Douglas, M L Kearney, H A Hoertel, R S Shafer, J P Thyfault and H J Leidy.  International Journal of Obesity (2015) 39, 1421–1424; doi:10.1038/ijo.2015.101; published online 7 July 2015

• Conclusion: These data suggest that the daily addition of a HP breakfast, containing 35 g of high-quality protein, has better efficacy at improving free-living glycemic control compared with a NP breakfast in overweight/obese, but otherwise healthy, ‘breakfast skipping’ adolescents.
• Disclosure: The authors declare no conflict of interest, but the study was funded by the Pork Checkoff.

Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast.  Arpita Basu, Nancy M Betts, Misti J Leyva, Dongxu Fu, Christopher E Aston, and Timothy J Lyons.  J Nutr September 2, 2015, doi: 10.3945/​jn.115.215772

• Conclusions: Acute cocoa supplementation showed no clear overall benefit in T2D patients after a high-fat fast-food–style meal challenge. Although HDL cholesterol and insulin remained higher throughout the 6-h postprandial period, an overall decrease in large artery elasticity was found after cocoa consumption.
• Funding: Among other sources, the lead author receiveda grant from The Hershey Company.
• Comment: This is a negative study (no benefit) with a positive spin (higher HDL, decrease in large artery elasticity).

 

Sunday’s New York Times story on academic conflicts of interest focused on scientists with financial ties to Monsanto.  The ties were revealed by open-records requests for e-mails and other information.

The Times was not the only one to make these requests.  U.S. Right to Know, a group devoted to investigating Big Food and its front groups had already done so.  U.S. Right to Know is funded primarily by the Organic Consumers Association, a national grassroots network advocating for organics, sustainability, and food safety—but against GMOs.

U.S. Right to Know rightfully takes credit for establishing the basis of the Times’ story.  It sent open-records requests to scientists working for public institutions who seemed likely to have financial ties to Monsanto.  Bingo.  Some of the e-mails revealed such ties.*

But should government-funded scientists be subjected to open records requests?  Couldn’t these requests amount to open season on academics—a modern-day version of witchhunts?  This question is now under active debate (and see comments on my previous post).

While these debates are raging, here is one aspect of this story that the New York Times did not tell.

Earlier this month, Paul Thacker and my NYU colleague Charles Seife, wrote a piece for PLoS [Public Library of Science] Blogs arguing that Freedom of Information Act (FOIA) requests “for personal correspondence are not just appropriate, but crucial to ensuring transparency.”   They argue that the benefits of transparency outweigh the costs.

But transparency laws remain a fundamental tool for monitoring possible scientific misbehavior. And it would be a mistake to believe that scientists should not be subject to a high level of outside scrutiny. So long as scientists receive government money, they are subject to government oversight; so long as their work affects the public, journalists and other watchdogs are simply doing their jobs when they seek out possible misconduct and questionable practices that could threaten the public interest.

Thacker and Seife explain:

Last week, Nature reported that the University of Florida had provided them with emails that U.S. Right to Know had FOIA’d on one of their researchers…the [Nature] story noted that the researcher has received money from Monsanto to fund expenses incurred while giving educational talks on GMOs.  The article also noted that the PR Firm Ketchum had provided the scientist with canned answers to respond to GMO critics, although it is unclear if he used them [the Times story says he did but now regrets it].

The article does not report that the scientist has repeatedly denied having a financial relationship with Monsanto. The article also does not report on an email titled “CONFIDENTIAL: Coalition Update” from the researcher to Monsanto in which the scientist advised Monsanto on ways to defeat a political campaign in California to require labeling of GMO products.

Some readers of PLoS were outraged that this online journal would publish an article supporting open-records requests of scientists (see, for example, this from the American Council on Science and Health).

Here’s where things get interesting.

PLoS responded to the criticism by, of all things, retracting the article.

Seife and Thacker explained their views in an op-ed in the Los Angeles Times.

If the public pays your salary, citizens have the right — within limits — to see what you’re doing. That’s the principle at the core of the federal Freedom of Information Act and of the many similar state freedom of information laws… “snooping” on scientists’ inboxes by journalists, watchdogs and government officials has revealed significant problems that would never have come to light via other means.

That, of course, is the basis of the New York Times’ exposé of Monsanto’s funding of scientists to testify on the company’s behalf to reporters, Congress, and the public.

Bottom line: Because industry-funded science and scientists almost invariably provide data and testimony that favors the sponsors interests, the press and public need to know about sponsorship.

One more comment:  A substantial body of literature exists on industry sponsorship of science, particularly on the effects of pharmaceutical industry funding of medical professionals.  Conflicts-of-interest researchers conclude that such conflicts are generally unconscious, unintentional, and unrecognized by participants.  The remedy is increased government spending for research, an unlikely possibility these days.  This means journalists will be kept busy exposing the many problems that arise when scientists take industry funding.

*The documents collected by the New York Times

• David Shaw
• Bruce Chassy
• Kevin Folta

Additions:

• Note: My previous post on organic-industry funding gives the link to the e-mails for Charles Benbrook
• Jonathan Latham provides further details on GMO public relations efforts

This is the latest in a series of Q & A’s written by Kerry Trueman.   It appeared on Civil Eats, August 12, 2015.  And please note references added at the end.

Despite my long interest in and dubious opinion about the benefits of Golden Rice (genetically modified to contain the beta-carotene precursor of vitamin A), I somehow completely missed the huge and highly embarrassing uproar over a study demonstrating the effectiveness of this rice in raising vitamin A levels in young children.

This particular uproar began with publication of the study in the American Journal of Clinical Nutrition in 2012.  Last week the journal announced that it has retracted the study—on ethical, not scientific, grounds.

To explain:  Dr. Guangwen Tang, a long-time researcher at Tufts University, and her colleagues at Tufts, in China, and at Baylor and the NIH, compared the effectiveness of vitamin A capsules, Golden Rice, and spinach in raising vitamin A levels in the blood of Chinese schoolchildren.  They reported that Golden Rice proved just as effective as capsules, and somewhat better than spinach, in inducing higher vitamin A levels, just as it is supposed to do.

Golden Rice, of course, is the poster child for the benefits of GMOs, extolled by many as the solution to the developing world’s high prevalence of vitamin A deficiency (I’m dubious because I view vitamin A deficiency as a social problem requiring policy and cultural shifts).

Soon after, Greenpeace, which is decidedly anti-GMO, challenged the ethics of the study, charging that the children were being used as “guinea pigs.”

As reported in Nature,

none of the children, their parents or school teachers was aware that Golden Rice was involved, according to a 45-minute investigative news programme broadcast on 8 December on CCTV, China’s state television channel.  The informed-consent form said that the rice contained β-carotene, but not that it was genetically modified or that it was Golden Rice. Nor did it highlight uncertainty around any potential risks of ingesting such rice…Moreover, Wang didn’t apply for ethical evaluation of the trial, instead fabricating the approval documents, according to CDC. And Tang brought Golden Rice from the United States to China illegally, without due declaration to the relevant Chinese authorities, it said.

According to a report on NPR, Tufts University did a year-long investigation and agreed that ethical standards had been violated:

the study was not “conducted in full compliance with … policy or federal regulations”… the researchers did not adequately explain the nature of golden rice and made some changes in the study without getting approval from the committee at Tufts that is supposed to review all research involving human subjects.  Guangwen Tang will be banned from conducting research on human subjects for two years. For two years after that, any research that she conducts will be under the direct supervision of another investigator.

A report on the case in ScienceInsider explains the ethical problem raised by the study’s informed consent form :

U.S. guidelines stipulate that such forms use plain language understandable to lay people, and the IRB [the Tufts Institutional Review Board] agreed to let Tang say that “Golden Rice is a new rice which makes beta-carotene,” without using the loaded words “genetically modified.” (The consent form for a very similar study by Tang among adults in Boston, published in 2009, didn’t use that term either.) Given the sensitivities over transgenic food, which existed in China as well, that was the wrong decision, according to the external panel.

In 2014,  Dr. Tang sued the ASN:

ASN twice asked Tang and her six co-authors to withdraw the paper voluntarily, which they declined to do. The society recently decided to retract the paper on its own…but it has agreed to a 90-day stay after Tang filed her lawsuit, to see if the matter can be settled out of court.

But the court ruled in favor of ASN.  Hence, the retraction.  ASN issued a press release:

In a ruling by the Massachusetts Superior Court, Judge Salinger…cleared the way for the American Society for Nutrition (ASN) to retract the article “β-Carotene in Golden Rice is as good as β-carotene in oil at providing vitamin A to children”…ASN is very pleased that the Massachusetts courts have upheld the organization’s First Amendment rights and have allowed ASN to move forward with the retraction of the article.

In its online retraction notice, ASN states the reasons:

1. The authors are unable to provide sufficient evidence that the study had been reviewed and approved by a local ethics committee in China in a manner fully consistent with NIH guidelines….
2. The authors are unable to substantiate through documentary evidence that all parents or children involved in the study were provided with the full consent form for the study.
3. Specific eligibility issues were identified in regard to 2 subjects in the study.

Last week, Retraction Watch published a lengthy summary of this case that includes a long statement from Tufts University:

No questions were raised about the integrity of the study data, accuracy of the research results or safety of the research subjects…Tufts University has always been and remains deeply committed to the highest ethical and scientific standards in research.  In September 2012, w …convened an external review committee to interview those involved and to review documentation of the study…There was no evidence found of falsification or fabrication of the data that underlie the study’s primary findings. Those reviews did, however, determine that the research had not been conducted in full compliance with Tufts research policies and federal research regulations.

The retraction is a huge embarrassment, not only for the researchers involved but also for Tufts University’s Friedman School of Nutrition Science and Policy, Tufts’ Institutional Review Board, the American Journal of Clinical Nutrition, and the American Society for Clinical Nutrition.

The study was funded by NIH, USDA, as well as a program in China.  NIH takes research ethics very seriously and expects the researchers it funds to adhere to the highest possible standards for research on human subjects.  Because the study did not follow standard ethical guidelines, especially with regard to research on children, Tufts had no choice but to investigate and impose sanctions, and the journal had no choice but to retract the paper.

This case reinforces my views about GMOs in general and Golden Rice in particular.

The controversies are not (or not usually) about the science.  They are very much about ethics and other questions of values.