Currently browsing posts about: Supplements

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.

I am indebted to NutraIngredients-Europe for this collection of articles on the trendy herbal supplement, ashwagandha.

Ashwaganda is one of those supplements said to do wonders for stress and anxiety (of which we all have lots these days) and sleep (also a common problem).

The Ashwagandha plant is native to India, northern Africa, and the Middle East—but is now grown around the world. While the whole plant is cultivated, the root and leaf are used in extracts. Ashwagandha is a traditional herb long used for its adaptogenic properties to help your body adapt to stressors. Adaptogens are plants that facilitate your body’s ability to adapt to stress.

The NIH Office of Dietary Supplements says

Ashwagandha appears to be well tolerated for up to 3 months of use. However, the efficacy and safety of long-term ashwagandha use over months or years for stress, anxiety, or sleep is not known. In addition, ashwagandha may have potential adverse effects on the liver and thyroid and might not be safe for people with prostate cancer or those who are pregnant or nursing.

What is especially interesting are the contradictory views of this supplement.  Some see benefits.  Others see risks.

The purported benefits

• Study: Ashwagandha effectively relieves chronic stress: Standardized root and leaf aqueous ashwagandha extract safely and effectively reduces stress in chronically stressed people, according to a new study…. Read more
• Ashwagandha intake linked to memory and attention benefits: Acute and repeated supplementation with liposomal ashwagandha may boost select cognitive effects, including memory, attention, vigilance and reaction time in healthy adults, says a new study…. Read more
• Review reveals benefits of ashwagandha on ‘inflammaging’: A new synthetic review on ashwagandha (Withania somnifera, or WS) has underlined the herb’s potential for treating ‘inflammaging’—persistent low-grade inflammation linked to aging…. Read more

The risks

• French agency warns ashwagandha unsafe in specific populations: The French Agency for Food, Environmental and Occupational Health & Safety (ANSES) has warned against the use of ashwagandha in a number of specific populations, making it likely operators will be advised to use label warnings…. Read more
• European food safety report ‘taking pot shots’ at popular botanicals: A working group of 26 member states has published a report suggesting the need to ban or restrict 12 ‘critical’ ingredients such as ashwagandha, curcumin, maca and substances like melatonin…. Read more

The debate

• AHP responds to claims of ashwagandha abortifacient effects: The American Herbal Pharmacopoeia (AHP) has responded to the growing number of European authorities reporting ashwagandha as an abortificient, arguing they have incorrectly cited the WHO monograph and AHP review…. Read more
• Ashwagandha concerns branded pure ‘horse s**t’: On-trend herb thrives despite authority unease: While ashwagandha investment and innovation is surging, some European authorities are showing signs of safety concern, leading industry experts to criticize a spread of “complete misinformation” across the continent…. Read more
• UK launches ashwagandha safety consultation as Indian experts step up defense:  Ashwagandha suppliers are being urged to invest in defense as the UK Food Safety Agency (FSA) launches a consultation into the herb and Indian experts refute safety concerns…. Read more

Comment

I, as you undoubtedly have guessed, am a supplement skeptic.  If European agencies are warning against it, I vote for avoiding it, especially if you are in one of the risk categories: pregnant or breastfeeding women, people under the age of 18, and those with endocrine disorders (particularly dysthyroidism and hyperandrogenism), liver or heart problems or undergoing treatment with a central nervous system depressant action.

Supplement sellers can fight back all they like; I urge caution.

I saw this on FoodNavigator–Asia, a newsletter to which I subscribe.

Red yeast rice impact: Kobayashi Pharmaceutical records nearly US$25m losses in Q1: Kobayashi Pharmaceutical reported an “extraordinary loss” of nearly US$25m (JPY$3.86bn) in its Q1 results due to the recall of its contaminated red yeast rice products, raw materials, and compensation of medical expenses. Read more

Red yeast rice is a dietary supplement with a statin-like component observed to reduce blood cholesterol levels, although not nearly to the same extent as statin drugs.  Consumer Lab tests show at least half not to contain what they say they do.

Now, on top of that, the supplements were associated with kidney disease (at least 50 cases) and deaths (at least 2) among takers in Japan.

Comment: Dietary supplements are the wild west of the food supply.  Anyone can make and sell them.  Because they are mainly harmless, nobody much bothers to test them, even major pharmaceutical companies.  Problems with red yeast rice supplements have been known for a long time.  As a result, supplements are risky.  How risky?  Nobody knows.  I don’t recommend them.

The title of this article triggered my usual question: Who paid for this?  I cannot think of any reason other than marketing this supplement for doing a study like this.

Multi-nutrient supplementation of astaxanthin, vitamin E and grape juice improves episodic memory, cognitive performance – RCT:  A study has found that 12 weeks of multi-nutrient supplementation, comprising astaxanthin, vitamin E and grape juice extract, resulted in improved episodic memory and several biomarkers associated with cognitive health…. Read more

The study: Lopresti AL, Smith SJ, Riggs ML, Major RA, Gibb TG, Wood SM, Hester SN, Knaggs HE. An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2024; 16(11):1770. https://doi.org/10.3390/nu16111770

Method: adults aged 40 to 70 years with subjective memory complaints were randomized to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo.

Outcomes:  Changes in cognitive tasks assessing episodic memory, working memory, and verbal memory., speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health.

Results: “Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures.”

Conclusions: “The results from this 12-week study provide some support for the cognitive-enhancing effects of a nutraceutical containing astaxanthin, vitamin E, and grape juice extract in adults with self-reported memory complaints. This was demonstrated by improvements in one primary outcome measure (episodic memory) but not working memory or verbal learning.”

I saw this one in a newsletter:

Ashwagandha intake linked to memory and attention benefits: Acute and repeated supplementation with liposomal ashwagandha may boost select cognitive effects, including memory, attention, vigilance and reaction time in healthy adults, says a new study…. Read more

The NIH Office of Dietary Supplements says

Several randomized, placebo-controlled clinical trials, most of them fairly small in size and of short duration, have found that ashwagandha may reduce perceived stress and anxiety and improve the quality and duration of sleep [6,7,31]. Because studies have used various ashwagandha preparations (with different extraction and standardization processes) and doses, it is difficult to identify specific extracts or recommended amounts [6,32]…In addition, ashwagandha may have potential adverse effects on the liver and thyroid and might not be safe for people with prostate cancer or those who are pregnant or nursing.

The National Center for Complementary and Integrative Health says:

• Research shows that some ashwagandha preparations may be effective for insomnia and stress. However, evidence is unclear about its effects on anxiety.
• There is some limited evidence that suggests that taking ashwagandha for 2 to 4 months may increase testosterone levels and sperm quality.
• There isn’t enough evidence to determine if ashwagandha is helpful for any other health conditions, such as asthma, athletic performance, cognitive function, diabetes, menopause, and female infertility.
• There is not enough high-quality evidence suggesting that ashwagandha is helpful in treating COVID-19.

When it comes to supplements, evidence is not the issue.  Belief is what matters.  The mere suggestion that a supplement might work is all it takes to convince people to buy it.  And if nothing else, supplements have powerful placebo effects.  We could all use some of those these days.

I learned about this one from FoodNavigator-Europe.

Ashwagandha has ‘tremendous potential’ for promoting healthy aging: Review:  Ashwagandha could serve as a potent anti-aging ingredient by improving immune system function and acting as an antioxidant, according to a review published in Frontiers in Nutrition…. Read more

This is the kind of headline that makes me ask: “Who paid for this?”

FoodNavigator usually provides references, so I could easily look this one up.

The study: Current insights into transcriptional role(s) for the nutraceutical Withania somnifera in inflammation and aging.  Praful Saha, Saiprasad Ajgaonkar,  Dishant Maniar, Simran Sahare, , Dilip Mehta,  Sujit Nair. Front. Nutr., 03 May 2024. Volume 11 – 2024 | https://doi.org/10.3389/fnut.2024.1370951.

Conclusions: “Management of aging is difficult due to its progressive and irreversible nature, as well as the comorbidities associated with aging. However, the quality of biological aging can be improvised by recent advancements including intervention with nutraceuticals that can modulate the transcriptional activity of different genes implicated in aging and age-related complications…Taken together, given the modulation of key RNA markers in aging and inflammation pathways, there is tremendous potential for harnessing the beneficial effects of Withania for achieving healthy aging.”

Funding: “The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.”

Conflict of interest: “PS, SA, DMa, SS, DMe, and SN were employed by PhytoVeda Pvt. Ltd. and Viridis Biopharma Pvt. Ltd., Mumbai, India. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.”

Comment:  I looked up Viridis BioPharma.

Viridis BioPharma is a marketing, manufacturing and research company that deals with active ingredients for the pharmaceutical, nutraceuticals, food and cosmetic industries, medicated dressings and formulations to treat wounds, burns and other novel clinically proven topical formulations.  What drives us is the desire to extend lifespans and, more than that, to extend health and wellbeing at every stage of life.

Employees of this and the other company developed this quite comprehensive review.  The authors state its purpose explicitly.

WS [Withania somnifera] is known for its versatility in treating a range of conditions, such as immunomodulation, rejuvenation, enhancement of cognitive function, inflammation, enhancing concentration, etc. However, a synthetic review exploring its potential role in ameliorating aging and aging-related disorders is currently lacking…This may facilitate the development of various preventive and therapeutic strategies employing WS as a nutraceutical for healthy aging.

Their funding statement is accurate; they weren’t paid particularly to write this article; they are just on salary generally.  And they are members of the editorial board of this journal.  Oh dear.

Here’s what the NIH says about ashwagandha.  It finds some evidence for use but concludes “most studies have been conducted as part of a traditional medical system, so the potential effects of ashwagandha when used as a dietary supplement outside of that approach remain unclear.”

The headline caught my eye: 5 dead and over 100 hospitalized from recalled Japanese health supplements

The supplement is benikoji.

Kobayashi Pharmaceutical had been selling benikoji products for years, with a million packages sold over the past three fiscal years, but a problem crept up with the supplements produced in 2023. Kobayashi Pharmaceutical said it produced 18.5 tons of benikoji last year.

Apparently, the company knew there was a problem but delayed the recall.

What, you may well ask, is benikoji?   The answer: Red yeast rice.

Red yeast rice is a well known dietary supplement.  it contains lovastatin.  Like other statins, it lowers blood cholesterol levels.

Consumer Lab, which tests and evaluates dietary supplements, says,

Red yeast rice can be very effective in lowering elevated levels of cholesterol, as shown in several clinical trials (see What It Does). However, not all red yeast rice supplements contain the amount of lovastatin needed to lower cholesterol, and products normally do not list the amount of lovastatin they contain on their labels.

Of additional concern is that CL found a potential kidney toxin, citrinin, in 30% of products, one of which contained citrinin at a level 65 times the limit allowed in Europe (there is no established limit in the U.S.).

Like other dietary supplements, nobody is minding the store.  Nobody makes sure the contents of a supplement reflect what is on the label or that labels are accurate.  The FDA says adding lovastatin to red yeast rice, which some manufacturors do, apparently, is illegal in the U.S.  But how would you know?

The study:  Lactobacillus paragasseri OLL2809 Improves Premenstrual Psychological Symptoms in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2023; 15(23):4985. https://doi.org/10.3390/nu15234985

Methods: “This study employed a randomized, placebo-controlled, double-blind, parallel-group design to assess the efficacy of continuous ingestion of OLL2809 [the supplement] for managing menstrual symptoms in healthy women.”

Conclusion: “This study suggests that the consumption of OLL2809 over three menstrual cycles in healthy women can alleviate premenstrual ‘decline in activity’ and ‘irritability’, thereby indicating the potential of OLL2809 to enhance women’s QOL [Quality of Life].

Conflicts of Interest:  All authors are employees of Meiji Co., Ltd. The company funded this research. All authors are the inventors of pending patent (Japanese Patent Application No. 2023-182470).

Comment: The supplement is a bacterial probiotic.  The authors are employed by its maker and hold a patent for it, which they fully disclose.  Just as a reminder, industry-funded studies tend to come out with results favoring the sponsor’s interest, as is certainly the case here.

I need to say something about the journal, Nutrients, since many of the studies I post on industry-funded Mondays appear in that journal.  It charges authors €2900 (about $3300) to publish their articles.  It’s an open-access journal, so all authors have to pay to publish their articles.  More rigorous journals do not usually require page charges from authors unless they want open access.  Nutrients gives me the impression of pay to play.