Currently browsing posts about: Vitamins

Much fuss is being made over this study: Loftfield E, O’Connell CP, Abnet CC, Graubard BI, Liao LM, Beane Freeman LE, Hofmann JN, Freedman ND, Sinha R. Multivitamin Use and Mortality Risk in 3 Prospective US Cohorts. JAMA Netw Open. 2024 Jun 3;7(6):e2418729. doi: 10.1001/jamanetworkopen.2024.18729.

Key Points

Question  What is the association between long-term, daily multivitamin use and mortality in generally healthy adults?

Findings  In this cohort study of 390 124 generally healthy adults with more than 20 years of follow-up, daily multivitamin use was not associated with a mortality benefit.

Meaning  These findings suggest that multivitamin use to improve longevity is not supported.

Here’s the summary:

The investigators did not find any associated benefit of multivitamins for mortality.  If anything, there is a slight association with increased risk.

In this cohort study of 390 124 generally healthy US adults with more than 20 years of follow-up, daily MV use was not associated with a mortality benefit. In contrast, we found that daily MV use vs nonuse was associated with 4% higher mortality risk.

Comment

Nobody should be surprised by this result.  Lots of other studies also suggest that multivitamin supplements do not make healthy people healthier.  Healthy people are most likely to take such supplements in the belief that they might help and can’t hurt.

This study says they won’t help.  If they do hurt, it won’t be by much.

I doubt the study will make much difference to supplement takers.  Supplements are about belief, not science.

Here’s another one that several readers have asked me about: Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial.  Authors: Lok-Kin Yeung, Daniel M. Alschuler, Melanie Wall, Howard D. Sesso, JoAnn E. Manson, Adam M. Brickman.  American Journal of Clinical Nutrition. DOI:https://doi.org/10.1016/j.ajcnut.2023.05.011

The study: “Participants were randomly assigned to a daily multivitamin supplement (Centrum Silver) or placebo and evaluated annually with an Internet-based battery of neuropsychological tests for 3 y.”  Primary outcome measure: change in episodic memory (immediate recall performance on the ModRey test, after 1 y of intervention).  Secondary outcome measures: changes in episodic memory over 3 y of follow-up,  and in performance on neuropsychological tasks of novel object recognition and executive function over 3 y.

Results: “Compared with placebo, participants randomly assigned to multivitamin supplementation had significantly better ModRey immediate recall at 1 y, the primary endpoint (t(5889) = 2.25, P = 0.025), as well as across the 3 y of follow-up on average (t(5889) = 2.54, P = 0.011). Multivitamin supplementation had no significant effects on secondary outcomes…we estimated that the effect of the multivitamin intervention improved memory performance above placebo by the equivalent of 3.1 y of age-related memory change.”

Conflict of interest: HDS, JEM, and AMB received investigator-initiated grant support to their institutions from Mars Edge. Pfizer Consumer Healthcare (now Haleon) provided support through the partial provision of study pills and packaging. HDS received 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 the
American Society of Nutrition during the conduct of the study. No funding sources had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Funding: This work was supported by an investigator-initiated grant from Mars Edge, a segment of Mars Inc dedicated to nutrition research. Pfizer Consumer Healthcare (now Haleon) provided support through the
partial provision of study pills and packaging.

Comment:  This study continues to surprise me.  As I’ve written before, it is part of the COSMOS trial, which is also supported by grants from NIH and a private foundation.  In my previous post on it, I noted that despite being funded by Pfizer (which makes Centrum Silver multivitamin supplements), the study did not show benefits of the supplement for prevention of cardiovascular disease or cancer—a rare exception to the rule that industry-funded studies tend to favor the sponsor’s interests.  But here we go again, this time with an equally surprising result but for a different reason: most multivitamin studies have shown no benefits whereas this one says if you take Centrum Silver, it will give you another three years of no loss in memory.  Wow!  I’ll be Pfizer is thrilled.

Here’s what the NIH National Center for Complementary and Integrative Health says about multivitamins:

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.

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.

I cannot believe that we are still talking about whether vitamin C prevents colds.  No such luck.

What triggered this is a recent and quite detailed critique of a 2018 meta-analysis of studies of this question: “Extra Dose of Vitamin C Based on a Daily Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized Controlled Trials.”

Its conclusion:  “The combination of supplemental and therapeutic doses of vitamin C is capable of relieving chest pain, fever, and chills, as well as shortening the time of confinement indoors and mean duration.”

You can read the detailed critique of this study for yourself, but I thought this was settled years ago by one of my all-time favorite nutrition studies: Karlowski TR, Chalmers TC, Frenkel LD, Kapikian AZ, Lewis TL, Lynch JM. Ascorbic acid for the common cold. A prophylactic and therapeutic trial. JAMA 1975; 231: 1038–1042.

This fabulous study was done at NIH using NIH employees.  As the abstract puts it,

Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months. At the onset of a cold, the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid.

The initial analysis of the data showed a highly significant effect of vitamin C in preventing colds or reducing symptoms.  But the trial had one major flaw: it had an usually big dropout rate.

One hundred ninety volunteers completed the study. Dropouts were defined as those who missed at least one month of drug ingestion. They represented 44% of the placebo group and 34% of those taking ascorbic acid.

These were good investigators.  They asked the dropouts why they had dropped out.  The reason: the study subjects knew (well, they thought they knew) whether they were taking vitamin C or the placebo.

The investigators reanalyzed the data according to what the study subjects thought they were taking.  Those who thought they were taking vitamin C had fewer colds and reduced symptoms—regardless of whether they were taking vitamin C or the placebo.  And those who thought they were taking the placebo had more colds and worse symptoms regardless of whether they really were taking the placebo or were actually taking vitamin C.

The authors’ cautious conclusion:

Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds, and that the effects demonstrated might be explained equally well by a break in the double blind.

My conclusion: Vitamin C is one terrific placebo.

Nothing wrong with that, but that’s why I can’t believe investigators are still arguing about it.

My latest book, Unsavory Truth: How Food Companies Skew the Science of What We Eat, is about food industry funding of nutrition research and why it’s not good for science, public health, or trust.

The book is full of examples, easily recognized by their titles.

I can’t resist showing you the latest example:

The title: Vitamin-supplemented chewing gum can increase salivary and plasma levels of a panel of vitamins in healthy human participants.  Journal of Functional Foods Volume 50, November 2018, Pages 37-44.

The conclusion: “our study demonstrates the potential usefulness of chewing gum as a delivery vehicle for both water- and fat-soluble vitamins.”

Guess who funded this study?  “This work was supported by Vitaball, Inc. (FT. Thomas, KY, USA) and the United States Department of Agriculture.”

Vitaball, you can probably guess, makes vitamin-fortified chewing gum, and one of the study’s authors works for the company.

Want vitamins?  Try food.

I was surprised by FoodNavigator-USA’s story about “SmartCandy,”—a “vitamin-infused snack.”

Could the name and contents of this candy be violating the FDA’s “jelly bean” rule?

The “jelly bean” rule refers to FDA’s fortification policy,* which aims to discourage food and beverage makers from adding vitamins to “foods of minimal nutritional value” (a.k.a. junk foods) so they can be marketed as healthy.

The policy is explicit.  The FDA does not consider it appropriate to add nutrients to candies and beverages.

Here’s what the article says about what’s in it:

Smartcandy is formulated with a blend of Vitamin A for eye health, three B vitamins to support converting sugar and carbohydrates into sustained energy, and vitamin C for immunity. The trans fat-, high-fructose corn syrup-free candies come in four varieties: sweet and sour gummies; and Froot, a proprietary snack with a candy shell and a layer of yogurt encasing a strawberry or orange center.

Here’s the Nutrition Facts label (thanks to a reader for sending).

Here’s what the website says Orange Froot candy can do:

This is the visionary leader of the snacking world, it’s the one they listen to and admire. He can make a three point shot with his eyes closed, build the best fort you’ve ever seen, or solve an algebra question like it was a nursery rhyme, this flavor packed snack will push you to achieve anything!

If SmartCandy can get away with this, won’t Coca-Cola and Pepsi be next?

Candy is candy and has an place in kids’s diets—occasionally.  But a health food that makes kids do better in school?  I’d like to see the evidence for that.

FDA: take a look please.

*Thanks to Michael Jacobson for forwarding.

Update, April 13: The New York State Attorney General has filed a complaint.

Catherine Price.  Vitamania: Our Obsessive Quest for Nutritional Perfection.  Penguin Press, 2015.

I blurbed this one:

Catherine Price gives us a journalist’s entertaining romp through the fascinating history of the discovery of vitamins, and their use and marketing as objects of health obsession.  Faith in vitamins, she advises, should be tempered by scientific uncertainty and dietary complexity, and the understanding that foods are better sources than pills.

This is the second excellent book I know of with that title.  This one came out in 1996.  It focused on supplements and their marketing.

Both have interesting things to say about why so many of us take vitamin supplements, regardless of the lack of evidence that they do us much good.

As I keep observing, there just isn’t much evidence that vitamin supplements make healthy people healthier.