Currently browsing posts about: Sponsored-research

When I saw this article—Study: Orange and pomegranate extract impacts major marker for healthy ageing—my first thought was “Who paid for this?”  Bingo.

The study: Ahles, S., Cuijpers, I., Hartgens, F. et al. The Effect of a Citrus and Pomegranate Complex on Physical Fitness and Mental Well-Being in Healthy Elderly: A Randomized Placebo-Controlled Trial. J Nutr Health Aging 26, 839–846 (2022). https://doi.org/10.1007/s12603-022-1834-4

• Objectives: This study investigates whether a citrus and pomegranate complex (CPC) improves physical fitness, mental well-being, and blood biomarkers for oxidative stress and endothelial function in healthy elderly.
• Design: A randomized placebo-controlled cross-over trial.
• Participants: The study included 36 healthy elderly aged 60–75 years old.
• Intervention and Measurements: Participants received four weeks of CPC supplementation and performed the handgrip strength and senior fitness test. Quality of life (QOL) was assessed and blood samples were analyzed for oxidative stress and endothelial function markers.
• Results: After four weeks of CPC supplementation, handgrip strength significantly improved (p=0.019), compared to placebo. Moreover, the thinking, memory, learning, and concentration facets were improved (p=0.042), compared to placebo, and plasma malondialdehyde decreased, compared to placebo (p=0.033). The intervention did not affect senior fitness and the other QOL domains and blood parameters.
• Conclusion: Four weeks of daily CPC supplementation significantly improves handgrip strength and self-evaluated measures of psychological function in healthy older adults. Further research should focus on mechanisms associated with physical performance.
• Funding: Funding: Authors IC and FT are supported by the Province of Limburg, The Netherlands [grant number HEFI-2]. This research project was supported by BioActor B.V.
• Ethics declarations: Conflict of interest: S.A. is an employee of BioActor BV. F.H. is a sports medicine consultant and owner of Sports Medicine Center Maastricht*Parkstad. All other authors declare no conflict of interest. The funders had no role in the design of the study, in the preparation of the manuscript, or in the decision to publish the results.

Comment: This is a classic example of a study nobody but the product maker would ever do.  The statement that the funders had nothing to do with the study design or anything else may or may not be true—there have been too many examples of its not being true to take any such statement seriously without much further discussion.  Even with that assurance, researchers who accept industry funding rarely recognize industry influence—it seems to occur at some unconscious level.

I missed posting these last week (oops).

Blueberries set the standard for industry-funded studies (I discussed the origins of blueberry-industry funding in my book, Unsavory Truth).  Blueberry producers are still at it.  Here are two examples.

I.  This one started with a press release sent to my email:

From: Blueberries <updates@blueberrycouncil.org>
Date: August 29, 2023 at 11:59:59 AM EDT
Subject: Study Alert: New Research Links Blueberries to Gut Health Benefits

A new study published in Nutrients suggests blueberries may hold benefits for those suffering from functional gastrointestinal disorders (FGID). In this study, FGID patients saw greater abdominal symptom relief and improved markers of well-being, quality of life, and life functioning after consuming freeze-dried blueberry powder for 6 weeks as compared to a placebo treatment.

The study: Wilder-Smith CH, Materna A, Olesen SS. Blueberries Improve Abdominal Symptoms, Well-Being and Functioning in Patients with Functional Gastrointestinal Disorders. Nutrients. 2023; 15(10):2396. https://doi.org/10.3390/nu15102396.

Conclusion: Blueberries relieved abdominal symptoms and improved general markers of well-being, quality of life, and life functioning more than placebo in patients with FGID. Consequently, the polyphenol and fiber components of blueberries exert broad beneficial effects separate from the sugars present in both treatments.

Funding: This research was funded by a grant from the US Highbush Blueberry Council.

Comment: Of course it was.

II.  I read about this one in ConscienHealth.

Burning Fat with Wild Blueberries in 11 Athletes

This is nearly perfect clickbait that is just about meaningless for an average person in real life. Researchers did a study of fat oxidation after consuming freeze-dried powder from wild blueberries. They found an increased oxidation rate associated with consuming that powder in the 11 aerobically trained males they studied. So the press office at Cal Poly Humboldt, where the researchers work, issued a release saying wild blueberries help with burning fat.  From there, twitter and health reporters take the next leap, writing headlines like “eating wild blueberries can help you lose weight.”

The study: Pilolla KD, Armendariz J, Burrus BM, Baston DS, McCarthy KA, Bloedon TK. Effects of Wild Blueberries on Fat Oxidation Rates in Aerobically Trained Males. Nutrients. 2023; 15(6):1339. https://doi.org/10.3390/nu15061339.

Conclusion: “Results indicate that WBs may increase the rate of FAT-ox during moderate-intensity activity in healthy, active males.”

Funding: “This research was funded by Cal Poly Humboldt’s Dean of Research.* Freeze-dried Wild blueberry powder was donated by the Wild Blueberry Association of North America (WBANA).“

Comment: I agree that simply providing product to be tested is not an earth-shaking conflict of interest, but because the powder came from the WBANA the ties seem closer.  In any case, the idea that blueberry powder—not nearly as delicious as the real thing—can have these kinds of effects should raise eyebrows from the get go.  Studies of the health effects of one sincle food always require critical thinking and more than a modicum of skepticism.

As for the asterisk*:  My son went to Humboldt State College (long before it was taken over by Cal Poly) so I was especially interested in this.

I want to end the week with this unusual example.

Yes, avocados are fruits (hint: fruits have seeds).

This story begins with an emailed ad from an avocado trade association to subscribers to Today’s Dietitian.

In the largest study of its kind, published in the Journal of the American Heart Association, researchers across multiple institutions looked at the impact of consuming one avocado per day on weight-related measures, markers of cardiometabolic risk and diet quality—insights you won’t want to miss.

If you click around to further discussion, you get this:

Daily avocado consumption led to reductions in total and LDL cholesterol and improved diet quality compared to the control group. The Avocado Nutrition Center supported this study, and although the findings from one study cannot be generalized to larger populations, this study supports a growing body of evidence that suggests consuming heart-healthy avocados is associated with better diet quality.

Let’s take a look:

• The study: Effect of Incorporating 1 Avocado Per Day Versus Habitual Diet on Visceral Adiposity: A Randomized Trial. J Am Heart Assoc. . 2022 Jul 19;11(14):e025657.  doi: 10.1161/JAHA.122.025657. Epub 2022 Jul 5.  Authors: Alice H Lichtenstein ¹, Penny M Kris-Etherton ², Kristina S Petersen ³, Nirupa R Matthan ¹, Samuel Barnes ⁴, Mara Z Vitolins ⁵, Zhaoping Li ⁶, Joan Sabaté ⁷, Sujatha Rajaram ⁷, Shilpy Chowdhury ⁴, Kristin M Davis ⁸, Jean Galluccio ¹, Cheryl H Gilhooly ¹, Richard S Legro ⁹, Jason Li ⁶, Laura Lovato ¹⁰, Letitia H Perdue ¹⁰, Gayle Petty ¹, Anna M Rasmussen ⁶, Gina Segovia-Siapco ⁷, Rawiwan Sirirat ⁷, April Sun ⁶, David M Reboussin ¹⁰
• Conclusions: “In conclusion, in this randomized controlled multicenter parallel trial, the addition of 1 avocado per day to the habitual diet for 6 months in individuals with visceral adiposity did not reduce VAT and had minimal effect on risk factors associated with cardiometabolic disorders.”
• Funding: This work was supported by the Avocado Nutrition Center.

Comment: I don’t usually include the names of authors of industry-funded studies because I don’t see the “funding effect” (a higher probability of positive results) as personal to individual investigators; I see it as systematic.  But I listed these authors because they produced something quite rare: an industry-funded study that did not find positive results.  And they said so explicitly, without hedging or trying to spin the results so they looked  more favorable.

The avocado marketers did the spinning.  This, alas, is yet another hazard of  doing studies funded by food trade associations with vested interests in research outcome.  Investigators have no control over how the sponsor will use or spin their research results, as we see in this example.

Addition, September 16

I often hear criticisms that I don’t deal with the science when I post industry-funded studies.  I don’t because how the science is conducted is rarely the problem.  Instead, industry influence turns up most frequently in the study design or in the interpretation of the results.  That’s what’s happening here, as a reader, mrpicasso2, writes:

Wow! This is astounding how the Avocado marketers try to spin the results in their favor. “Changes in most secondary and additional outcome measures (cardiometabolic risk factors), except for modest decreases in total cholesterol and LDL‐C concentrations, were not statistically significant” became “Daily avocado consumption led to reductions in total and LDL cholesterol and improved diet quality compared to the control group.”

And even the “improved diet quality” is a big stretch because the Healthy Eating Index (HEI) values (even when split into below and above the median subgroups) were not significantly different. It’s true the avocado arm values were numerically higher (0.064 vs 0.044, and 0.083 vs 0.069) but without reaching statistical significance they are indistinguishable.

Of course the Avocado marketers don’t mention that there were 9 adverse events in the Avocado diet arm compared with none in the habitual diet group.

This reminds me of the story of the boy who was so excited to get a pile of horse manure for his birthday because he reasoned that with so much manure there had to be a pony near by.

The study:  Martinez-Canton M, Galvan-Alvarez V, Garcia-Gonzalez E, Gallego-Selles A, Gelabert-Rebato M, Garcia-Perez G, Santana A, Lopez-Rios L, Vega-Morales T, Martin-Rincon M, et al. A Mango Leaf Extract (Zynamite^®) Combined with Quercetin Has Exercise-Mimetic Properties in Human Skeletal Muscle. Nutrients. 2023; 15(13):2848. https://doi.org/10.3390/nu15132848

Hypothesis:  Zynamite PX^®, a mango leaf extract combined with quercetin, enhances exercise performance by unknown molecular mechanisms.

Conclusion: Zynamite PX^® elicits muscle signaling changes in resting skeletal muscle resembling those described for exercise training and partly abrogates the stress kinases responses to exercise as observed in trained muscles.

Funding: This investigation was co-financed in part by Nektium Pharma S.L., Ministerio de Economía y Competitividad…Consejo Superior de Deportes de España (EXP_75097), FEDER and Cabildo de Gran Canaria…and FDCAN (Fondo de Desarrollo de Canarias).

Conflicts of Interest: The present investigation was partially financed by Nektium Pharma S.L, who provided the polyphenolic compounds and participated in the experimental design, although they were fully excluded from participation in experimental data collection, data analysis and interpretation of results. The remaining funding agencies had no role in study design, data collection, management, data analysis, interpretation of data, writing of the report, and the decision to submit the report for publication.

Comment: This is a classic example of an industry-funded supplement study with favorable interpreted favorably.  The manufacturer paid for the study as part of a private-public partnership to aid businesses in the Canary Islands.

For this one I thank Jerry Hagstrom, who writes The Hagstrom Report (Ag news as it happens) to which I subscribe.

This too begins with a press release: “REDISCOVER FIGS: THE ANCIENT FRUIT WITH MODERN APPEAL: Newly Published Literature Review Suggests the Intake of Figs Regularly in the Diet, Alone or with Other Dried Fruits, Increases Select Micronutrient Intake and is Associated with Higher Diet Quality.”

I am way behind on posting all the industry-funded studies sent to me and collected, so will share a week’s worth of fruit studies .  This is to emphasize the obvious point that fruit is good for you, but one is not necessarily better than another–except to its marketers.  Enjoy!

Here’s the first: strawberries.

I heard about this from two news releases, and because it was sent to me by Charles Platkin, Executive Director, Center for Food as Medicine  and Distinguished Lecturer at Hunter College, City University of New York.

• From CBS News, Boston:  “Strawberries could improve heart and brain health, researchers say.“
• From Neuroscience News: “Berry Good News: Daily Strawberries Boost Cognitive & Cardio Health.”

Wow.  This is exciting.  I had strawberries with my cereal for breakfast this morning.

I could not wait to read the study.

Uh oh.  Not yet published.  But given in a poster session at the American Society for Nutrition meetings in Boston last month.

• Title: The Impact of Strawberries on Cognition and Cardiovascular Health of Older Healthy Adults: A Randomized, Crossover, Double-Blind, Placebo-Controlled Clinical Trial .
• Objectives: The polyphenolic compounds in strawberries may improve cognitive function and cardiovascular health due to their antioxidant capacities. This study aimed to examine the effects of strawberries on cognitive function and cardiometabolic health in healthy aging adults.
• Methods:  This was a randomized, crossover, double-blind, placebo-controlled clinical trial with 35 healthy older adults  given 26 grams of freeze-dried strawberry powder (not strawberries) and a control powder daily for 8 weeks each.
• Results:  The strawberry powder group increased processing speed.  The control group increased episodic memory.  : The powder also had other effects: “Strawberry consumption reduced systolic blood pressure…Total antioxidant capacity significantly decreased during the control trial …and significantly increased with strawberry consumption.”
• Conclusions: This study demonstrates that daily consumption of 26 grams of freeze-dried strawberry powder moderately improves cognitive processing speed, lowers systolic blood pressure, and increases total-antioxidant capacity, potentially promoting cognitive function and improving cardiovascular risk factors.
• Funding Sources: This study was funded by California Strawberry Commission.

Comment: Of course it was.  Who else would care about the effects of strawberry powder.  Not that no other fruit powders were tested; I would expect all of them to produce similar effects, whatever those effects might be.  Given that the control group performed better on memory tests, you could interpret the results as not particularly meaningful.  But one characteristic of industry funded studies is to put a positive spin on whatever results occur.  We can argue about the methods when the study is actually published.  In the meantime, we have press releases.

Oh.  And my morning strawberries were somewhat local, red all the way through, and tasted like strawberries.  Do I feel smarter as a result?  Sure, why not.

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.

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).