Currently browsing posts about: Supplements

Happy new year to all.!

And now, back to my Monday postings of industry-funded studies.  Today’s is about the popular herbal supplement, ashwagandha.   This is typically taken to reduce stress and improve a wide variety of health problems, but little science backs up those contentions.  Hence, this study, which I learned about from reading an account of it: Single ashwagandha dose may exert cognitive performance: Study.  That headline was all it took to get me to ask my usual question: Who paid for this?

The study: Effects of Acute Ashwagandha Ingestion on Cognitive Function. Int. J. Environ. Res. Public Health 2022, 19(19), 11852; https://doi.org/10.3390/ijerph191911852

Methods: The study assessed performance on the Berg–Wisconsin Card Sorting (BCST), Go/No-Go (GNG), Sternberg Task (STT), and Psychomotor Vigilance Task (PVTT) tests.   Participants took a placebo or ashwagandha (ASH) extract (NooGandha^®, Specnova Inc., Boca Raton, FL, USA).

Conclusions: Acute supplementation with 400 mg of ashwagandha improved selected measures of executive function, helped sustain attention, and increased short-term/working memory.

Funding: “This study was funded as a fee-for-service project awarded to the Human Clinical Research Facility at Texas A&M University from Specnova, Inc. (Boca Raton, FL, USA)…Specnova was not involved in any way in data collection, analysis of the data, or the writing of the manuscript.”

Comment: Specnova, you will not be surprised to learn, is a supplier of supplement ingredients.  The company ordered the study to its specifications.  It got the result it wanted, as funders almost invariably do.  Despite booming sales of ashwagandha, so little is known about its properties that the National Center for Complementary and Integrative Medicine does not even have a fact sheet for it among its reviews of herbal supplements.  Industry-sponsored research to the rescue!  And of course it “was not involved in any way…”  It didn’t have to be.  Funding is usually enough to induce unconscious bias on its own.

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The FDA’s food operations are under siege over problems with infant formula, the Fresh Harvest recall, and all its other food safety and regulatory problems.

As you saw yesterday, it has plenty of time for educational initiatives.

This one is called “Supplement Your Knowledge.”  Its purpose is to help inform health care professionals, consumers, and educators about the hazards of dietary supplements.

How is the FDA helping with this?

• For consumers: Public education videos and fact sheets.
• For educators: Curriculum guide, Science and Our Food Supply: Examining Dietary Supplements (2021 Edition).
• For healthcare professionals: In collaboration with the American Medical Association (AMA), a continuing medical education (CME) program, free.  This includes three videos and companion education materials available on the FDA’s Healthcare Professionals website.  Physicians should go to the AMA Ed Hub^TM

The FDA is worried about harm from thousands of products that are largely unregulated, thanks to the Dietary Supplement Health and Education Act of 1994 (DSHEA).  This act took the FDA out of the business of regulating supplements, allowed supplement manufacturers to claim pretty much anything they want about supplements (regardless of evidence), and left ghe matter of what’s actually in the bottles as a matter of faith.

More than half of American adults take supplements of one kind or another, despite lack of evidence that they do any good at all for reasonably healthy people.  Fortunately, most are harmless.

The FDA wants to encourage supplement users to report adverse effects from the ones that aren’t.

I’m guessing the AMA wants to discourage physicians from inappropriately suggesting supplements and encourage them to recognize adverse events when they see them.

Congress passed DSHEA.  It will take another act of Congress to  protect the public from supplements that contain what they shouldn’t, don’t contain what they should, and otherwise mislead the public about what they can do.

Related Information

• To report a problem: the Safety Reporting Portal.
• Dietary Supplements Social Media Toolkit
• Additional information on dietary supplements:  www.fda.gov/dietarysupplements.
• Constituent Update 
• Dietary Supplements Education Initiative  
• Information for Consumers on Using Dietary Supplements
• Dietary Supplements

I found this discussion on David Allison’s remarkably useful weekly collection of articles about obesity and energetics.  His listings include articles in categories, one of them “Scientific Rigor & Scholarly Dialogue.”

I was particularly interested in this example:

• Article: Efficacy of Vitamin C for the Prevention and Treatment of Upper Respiratory Tract Infection. A Meta-Analysis in Children.
• Letter: Meta-Analysis on Vitamin C and the Common Cold in Children May Be Misleading.
• Reply: Authors’ Response to Letter to the Editor: “Meta-Analysis on Vitamin C and the Common Cold in Children May Be Misleading”.
• Retraction: Efficacy of Vitamin C for the Prevention and Treatment of Upper Respiratory Tract Infection. A Meta-Analysis in Children.
• Summary: Vitamin C and the Common Cold in Children: Severe Flaws in the Meta-Analyses by Vorilhon et al. (2019).

This took me back to one of my all-time-favorite research studies: Ascorbic Acid for the Common Cold: A Prophylactic and Therapeutic Trial.  JAMA;1975;231:1038-1942.

Linus Pauling wrote Vitamin C and the Common Cold in 1970.  NIH investigators wondered if there was anything to it.  They got 300 volunteers to take vitamin C or a placebo and measured the number of colds and their duration in both groups.

When they first looked at the data, it looked like the volunteers who were taking vitamin C had fewer and shorter colds.   Exciting!

But these were highly rigorous investigators.

They examined the data closely and noticed that an unusually large number of participants had dropped out of the trial, especially those in the placebo group (44%).  They guessed that participants thought they knew what they were taking and dropped out if they “knew” they were taking the placebo.

They reanalyzed the data to account for participants thought they were taking.

The final result: volunteers who thought they were taking vitamin C reported fewer and shorter colds, regardless of whether they were taking vitamin C or the placebo.

Those who thought they were taking the placebo had more and longer colds, regardless of whether they were taking the placebo or vitamin C.

Comment: This study provides compelling evidence for the placebo effects of vitamin C.  Placebo effects are powerful. I’m all for them.  The authors of the recently retracted study should have read this one first.

I am not much of a fan of dietary supplements and have to admit to confirmation bias; I collect studies that provide evidence for skepticism about how well they work.

So when a reader, Arya Afrashteh, sent this study, I gave it some attention.

The study:  Dietary Supplements as Source of Unintentional Doping.  Vanya Rangelov Kozhuharov, Kalin Ivanov, and Stanislava Ivanova.  Biomed Res Int. 2022; 2022: 8387271. Published online 2022 Apr 22. doi: 10.1155/2022/8387271

The rationale:  Athletes are not supposed to take performance-enhancing drugs but they are permitted to take dietary supplements.  Are these safe?

Method: A review of the literature on unapproved substances found in dietary supplements.

Results: 875 of 3132 supplements contained undeclared substances.

Conclusion: ~28% of the analyzed dietary supplements pose a potential risk of unintentional doping.

Comment:  Between one-quarter and one-third of dietary supplements taken for performance enhancement contained unlabled substances that could test as unapproved drugs.

This is a result of the Dietary Supplement Health and Education Act of 1994 (DSHEA) that basically deregulated dietary supplements.  It took supplements out from under the control of the FDA.

All the FDA can do is write warning letters, which it occasionally does.

But unless the FDA is checking, you cannot be sure that what is in the supplements is accurately reflected by their labels.  Sports supplements, it seems, are prime examples of why this is a problem.

Caveat emptor.

 

The New York Times’ obituary for the late Utah Senator Orrin Hatch, “Orrin Hatch, Seven-Term Senator and a Republican Force, Dies at 88,” filled an entire page of the newspaper.  That’s how important he was.

I was surprised that the obituary said not one word about Senator’s Hatch’s responsibility for the Dietary Supplement Health and Education Act of 1994 (DSHEA, pronounced d’shay).  The purpose of this act was to boost the supplement industry, which is well represented in Utah, by taking it out from under the regulatory authority of the FDA.

As a reminder, DSHEA:

• Assumed that dietary supplements were safe.
• Essentially deregulated them by weakening the FDA’s regulatory power.
• Permitted structure/function health claims on supplements, (e.g., supports a healthy immune system), regardless of level of scientific substantiation.
• Labeled supplements with Supplement Facts rather than Nutrition Facts.
• Forced the FDA to take manufacturers to court if agency regulators had concerns about safety, misleading claims, or inconsistent contents.
• Caused the FDA to lose court cases on First Amendment grounds.

The results:

• The supplement industry expanded rapidly, achieving DSHEA’s purpose.
• You cannot be sure that what you are buying is actually waht the label says you are buying.
• You cannot be sure that claimed benefits have any science behind them.
• Food manufacturers demanded the right to make struture/function claims.
• Use of the First Amendment to protect commercial (rather than personal, political, or religious) speech has gotten stronger.

We have Orrin Hatch to thank for turning the supplement industry into one based on faith, not science.

Why would he do this?

The obituary suggests one possibility:

During the opioid crisis in 2015, he introduced a bill to narrow the authority of government regulators to halt the marketing of drugs by predatory pharmaceutical companies. It later emerged that he had received $2.3 million in donations from the drug industry over 25 years.

For a more direct explanation, check out this article about Senator Hatch from the New York Times in 2011, “Support Is Mutual for Senator and Utah Industry.“

“Senator Hatch — he’s our natural ally,” said Marc S. Ullman, a lawyer for several supplement companies. Mr. Hatch, who credits a daily regimen of nutritional supplements for his vigor at 77, has spent his career in Washington helping the $25-billion-a-year industry thrive….Mr. Hatch has been rewarded with hundreds of thousands of dollars in campaign contributions, political loyalty and corporate sponsorship of his favorite causes back home.  His family and friends have benefited, too, from links to the supplement industry.

Hatch’s efforts to deregulate supplements did no good for public health or trust in science.  As the obituary said,

But there were no political repercussions. The senator was re-elected in 1982, 1988, 1994, 2000, 2006 and 2012, averaging nearly 65 percent of the vote.

Requiescat in pace.

Yesterday I reported about the COSMOS clinical trial demonstrating reductions in mortality among people taking cocoa flavanol supplements.

That trial had another arm: multivitamin supplements.

The study: Multivitamins in the Prevention of Cancer and Cardiovascular Disease: The COSMOS Randomized Clinical Trial.  Sesso HD et al.  The American Journal of Clinical Nutrition, nqac056, https://doi.org/10.1093/ajcn/nqac056

Conclusion: The supplements did not reduce cardiovascular disease, cancer, or all-cause mortality in older men and women.

Funding: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge, a segment of Mars dedicated to nutrition research and products, which included infrastructure support and the donation of study pills and packaging. Pfizer Consumer Healthcare (now part of GSK Consumer Healthcare) provided support through the partial provision of study pills and packaging.

Conflicts of interest: Drs. Sesso and Manson reported receiving investigatorinitiated grants from Mars Edge, a segment of Mars Incorporated dedicated to nutrition research and products, for infrastructure support and donation of COSMOS study pills and packaging,
Pfizer Consumer Healthcare (now part of GSK Consumer Healthcare) for donation of COSMOS study pills and packaging during the conduct of the study. Dr. Sesso additionally reported receiving investigator-initiated grants from Pure Encapsulations and Pfizer Inc. and honoraria
and/or travel for lectures from the Council for Responsible Nutrition, BASF, NIH, and American Society of Nutrition during the conduct of the study. No other authors reported any conflicts of interest.

Comment: Pfizer, of course, makes Centrum multivitamin supplements aimed at older adults.

I was surprised by this part of the trial because previous studies have also shown no consistently beneficial effect of supplementation of individual vitamins or multivitamins on disease risk.  Pfizer must have hoped to find benefits for Centrum.  This is a rare industry-supported study that showed no benefits and is, therefore, worth attention.

Thanks to Lynn Ripley for this gem.

Who knew that herbal dietary supplements are now marketed for cows, with claims that they improve milk quality and yield and reduce methane emissions at the same time?  Not me, for sure.

The producer of this supplement says feeding a dairy cow one gram a day will produce these benefits. That’s not much for a 1500-2000 pound dairy cow, even feeding the gram a day for at least four weeks (which is what the manufacturer says you have to do).

This, to say the least, is hard to believe.

As evidence, the manufacturer, Agolin Ruminant, cites three studies of its supplement.   Want to take a guess as to who funded all three of them?  Bingo!  Agolin Ruminant.

My first question: what is in Agolin Ruminant that is so powerful that only one gram a day will produce measurable benefits?

This question is not easy to answer.

The manufacturer’s statement of product information says only:

AGOLIN RUMINANT L is a carefully balanced combination of essential oil compounds in their natural / nature-identical form. All active substances are of high purity and are accepted for use under current European animal feed and human food legislation.

In the meta-analysis summarized below, the authors say:

The main active compounds of this product are food grade and chemically-defined plant extracts including coriander (Coriandrum sativum) seed oil (up to 10%), eugenol (up to 7%), geranyl acetate (up to 7%) and geraniol (up to 6%) along with some preservatives such as fumaric acid.

Those account for 30% of what’s in the product.  The other 70%?  A mystery.

This supplement is a feed additive.  Animal feed products do not require the level of ingredient disclosure required for dietary supplements.  The manufacturer says all ingredients are either FDA-approved or Generally Recognized as Safe (GRAS).  All are plant extracts (available from cloves or geraniums, for example).   Great.  I’d like to know what they are.

The manufacturer points to an endorsement from the Carbon Trust for the value of this product for reducing methane emissions.

This opinion is based on academic references, published scientific papers and field reports and joins the conclusions of the independent meta analyses from A. Belanche et al.

Oh dear.  The Carbon Trust did not do its homework.  The article by Belanche et al, is anything but independent.

Here are the key studies attesting to the purported benefits of this supplement for cows, starting with Belanche et al.

I.  A Meta-analysis Describing the Effects of the Essential oils Blend Agolin Ruminant on Performance, Rumen Fermentation and Methane Emissions in Dairy Cows. Alejandro Belanche, Charles J. Newbold, Diego P. Morgavi, Alex Bach, Beatrice Zweifel and David R. Yáñez-Ruiz.  Animals 2020, 10, 620; doi:10.3390/ani10040620

Conclusion: This meta-analysis combining 23 experimental and farm studies across 10 different countries indicated that supplementation of lactating dairy cows with the essential oils blend Agolin Ruminant® (at 1g/d per cow) exerted positive effects on milk production whereas it decreased enteric methane emissions in comparison to un-supplemented cows. These effects mostly appeared after an adaptation period of approximately 4 weeks of treatment and consisted in an increase in fat and protein corrected milk suggesting an improved feed utilization.

Funding: This research received no external funding.

Acknowledgments: This study was supported by Agolin SA (Bière, Switzerland).

Conflicts of Interest: Author B.Z. was employed by the company Agolin SA but had no role in the design, execution, interpretation, or writing of the meta-analysis. 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:  Really?  Even though the authors cite support by Agolin SA?

II.  The Impact of Essential Oil Feed Supplementation on Enteric Gas Emissions and Production Parameters from Dairy Cattle Angelica V. Carrazco, Carlyn B. Peterson, Yongjing Zhao, Yuee Pan , John J. McGlone, Edward J. DePeters and Frank M. Mitloehner.  Sustainability 2020, 12, 10347; doi:10.3390/su122410347

Conclusion: Cows supplemented with Agolin versus the control had less methane intensity (g/period/kg
energy-corrected milk (ECM); p = 0.025).

Funding: This study was funded by Agolin (Agolin SA, Bière, Switzerland) and by Feedworks USA Ltd. (Ohio, USA).

Conflicts of Interest: The sponsor played no role in the execution and interpretation of the data and preparation of the present manuscript. The authors declare no conflict of interest.

III.  Evaluation of Agolin®, an Essential Oil Blend, as a Feed Additive for High Producing Cows.  Peter Williams1, John Clark, Kelly Bean  Open Journal of Animal Sciences, 11, 231-237. https://doi.org/10.4236/ojas.2021.112018

Conclusion: The trial showed that Agolin assisted in improving production parameters of economic importance to dairy producers.

Conflict of Interest: Mr. John Clark and Mr. Peter Williams market Agolin in the United States of America. Both were involved in the design but not the analysis of data or interpretation of results.

Comment

These are industry-funded supplement studies designed to sell a supplement of dubious benefit (my interpretation) to dairy producers to convince the public that they are doing all they can to reduce methane emissions.

The supplement doesn’t cost much per dose, but there are lots of dairy cows that have to be given the supplement for at least four weeks.

Without even getting into the details of the measurement difficulties or the overall science, two things are particularly troubling:

• The lack of transparency about ingredients
• The lack of a convincing mechanism of action

Call me skeptical.  I don’t see this supplement as a solution to the methane emission problem caused by ruminants.

A reader, Philly Nassau, sent me the ingredient list of several “immune-boosting” supplements, in quotes because I am a supplement skeptic in general, and of immune supplements in particular (I favor eating healthfully and staying active).

Immune supplements claim to be “Nootropics and Brain Supplement for Memory, Brain Support, Clarity, Focus, Mood Boost, Anti Anxiety & Stress Relief.”  Nootropics?  These are defined as drugs or supplements capable of enhancing memory, concentration, or other cognitive functions and of preventing cognitive decline.  How I wish.

But first, the science.

• Gut-microbiota-targeted diets modulate human immune status.  “The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.”
• The Stanford press release on this paper. A fermented-food diet increases microbiome diversity and lowers inflammation, Stanford study finds.  Stanford researchers discover that a 10-week diet high in fermented foods boosts microbiome diversity and improves immune responses.
• The New York Times account: How Fermented Foods May Alter Your Microbiome and Improve Your Health.  Foods like yogurt, kimchi, sauerkraut and kombucha increased the diversity of gut microbes and led to lower levels of inflammation.

Beyond eating healthfully and including fermented foods in the diet, here’s what’s being said about diet and immunity.

• Immune health is a marketing opportunity: Given current events, it’s likely that there has been no greater focus on immune health amongst consumers than right now. The market opportunity in this space is staggering, with immunity supplements showing an explosive 72.3% growth in 2020.
• Euromonitor Immunity Report: How to appeal to the holistic health shopper:  As consumers search for holistic and natural ways to improve their immunity, Euromonitor has published a new white paper examining how brands can appeal in a competitive and confusing market…. Read more
• Is immunity really the top functional choice for consumers in a pandemic era?  It sounds pretty logical – the pandemic has prompted increased interest in immunity across F&B. But is it really top dog in the world of functional beverages – or are there other claims consumers are more interested in?… Read more
• Parents are looking for immune-boosting options for school kids. Grocery retailers and packaged food and beverage brands should brace for another significant shift in consumer shopping habits this month as many families with students returning to in-person school after a year or more of distance or hybrid learning look for more on-the-go, budget-conscious and immune-boosting breakfast and lunch solutions.
• Immunity in a glass: Orange juice bioactives may bolster immunity and reduce inflammation:  The micronutrients and other bioactives contained in a glass of orange juice is sufficient enough to shore up the immune response and tackle oxidative stress and inflammation, a review concludes…. Read more  
• Beyond immunity: What ‘superpowers’ do today’s consumers want from their beverages?  The pandemic has propelled immunity to the top of the functional beverage agenda. But that doesn’t mean interest in other functional beverages has disappeared. We ask the experts what trends are bubbling away beneath the pandemic headlines – and will become all the more important to everyday heros in the coming years…. Read more  
• Shiitake happens: Mushrooms to play key role in immunity nutrition and health, concludes report:  Concerns over immune health and the pandemic has thrust the humble mushroom into the spotlight as experts hail the fungi’s ability to interact with gut microbes that influence healthy immune and inflammatory responses…. Read more